Contraction-induced injury to single permeabilized muscle fibers from normal and congenitally-clefted goat palates.

PubMed

Rader, Erik P; Cederna, Paul S; Weinzweig, Jeffrey; Panter, Kip E; Yu, Deborah; Buchman, Steven R; Larkin, Lisa M; Faulkner, John A

2007-03-01

Levator veli palatini muscles from normal palates of adult humans and goats are predominantly slow oxidative (type 1) fibers. However, 85% of levator veli palatini fibers from cleft palates of adult goats are physiologically fast (type 2). This fiber composition difference between cleft and normal palates may have implications in palatal function. For limb muscles, type 2 muscle fibers are more susceptible to lengthening contraction-induced injury than are type 1 fibers. We tested the hypothesis that, compared with single permeabilized levator veli palatini muscle fibers from normal palates of adult goats, those from cleft palates are more susceptible to lengthening contraction-induced injury. Congenital cleft palates were the result of chemically-induced decreased movement of the fetal head and tongue causing obstruction of palatal closure. Each muscle fiber was maximally activated and lengthened. Fiber type was determined by contractile properties and gel electrophoresis. Susceptibility to injury was assessed by measuring the decrease in maximum force following the lengthening contraction, expressed as a percentage of the initial force. Compared with fibers from normal palates that were all type 1 and had force deficits of 23 +/- 1%, fibers from cleft palates were all type 2 and sustained twofold greater deficits, 40 +/- 1% (p = .001). Levator veli palatini muscles from cleft palates of goats contain predominantly type 2 fibers that are highly susceptible to lengthening contraction-induced injury. This finding may have implications regarding palatal function and the incidence of velopharyngeal incompetence.

Muscle dysmorphia in male weightlifters: a case-control study.

PubMed

Olivardia, R; Pope, H G; Hudson, J I

2000-08-01

Muscle dysmorphia is a form of body dysmorphic disorder in which individuals develop a pathological preoccupation with their muscularity. The authors interviewed 24 men with muscle dysmorphia and 30 normal comparison weightlifters, recruited from gymnasiums in the Boston area, using a battery of demographic, psychiatric, and physical measures. The men with muscle dysmorphia differed significantly from the normal comparison weightlifters on numerous measures, including body dissatisfaction, eating attitudes, prevalence of anabolic steroid use, and lifetime prevalence of DSM-IV mood, anxiety, and eating disorders. The men with muscle dysmorphia frequently described shame, embarrassment, and impairment of social and occupational functioning in association with their condition. By contrast, normal weightlifters displayed little pathology. Indeed, in an a posteriori analysis, the normal weightlifters proved closely comparable to a group of male college students recruited as a normal comparison group in an earlier study. Muscle dysmorphia appears to be a valid diagnostic entity, possibly related to a larger group of disorders, and is associated with striking and stereotypical features. Men with muscle dysmorphia differ sharply from normal weightlifters, most of whom display little psychopathology. Further research is necessary to characterize the nosology and potential treatment of this syndrome.

Muscle abnormalities in osteogenesis imperfecta

PubMed Central

Veilleux, L-N.; Trejo, P.; Rauch, F.

2017-01-01

Osteogenesis imperfecta (OI) is mainly characterized by bone fragility but muscle abnormalities have been reported both in OI mouse models and in children with OI. Muscle mass is decreased in OI, even when short stature is taken into account. Dynamic muscle tests aiming at maximal eccentric force production reveal functional deficits that can not be explained by low muscle mass alone. However, it appears that diaphyseal bone mass is normally adapted to muscle force. At present the determinants of muscle mass and function in OI have not been clearly defined. Physiotherapy interventions and bisphosphonate treatment appear to have some effect on muscle function in OI. Interventions targeting muscle mass have shown encouraging results in OI animal models and are an interesting area for further research. PMID:28574406

Targeted Deletion of the Muscular Dystrophy Gene myotilin Does Not Perturb Muscle Structure or Function in Mice▿

PubMed Central

Moza, Monica; Mologni, Luca; Trokovic, Ras; Faulkner, Georgine; Partanen, Juha; Carpén, Olli

2007-01-01

Myotilin, palladin, and myopalladin form a novel small subfamily of cytoskeletal proteins that contain immunoglobulin-like domains. Myotilin is a thin filament-associated protein localized at the Z-disk of skeletal and cardiac muscle cells. The direct binding to F-actin, efficient cross-linking of actin filaments, and prevention of induced disassembly of filaments are key roles of myotilin that are thought to be involved in structural maintenance and function of the sarcomere. Missense mutations in the myotilin-encoding gene cause dominant limb girdle muscular dystrophy type 1A and spheroid body myopathy and are the molecular defect that can cause myofibrillar myopathy. Here we describe the generation and analysis of mice that lack myotilin, myo−/− mice. Surprisingly, myo−/− mice maintain normal muscle sarcomeric and sarcolemmal integrity. Also, loss of myotilin does not cause alterations in the heart or other organs of newborn or adult myo−/− mice. The mice develop normally and have a normal life span, and their muscle capacity does not significantly differ from wild-type mice even after prolonged physical stress. The results suggest that either myotilin does not participate in muscle development and basal function maintenance or other proteins serve as structural and functional compensatory molecules when myotilin is absent. PMID:17074808

Effect of rapid rigor mortis processes on protein functionality in pectoralis major muscle of domestic turkeys.

PubMed

Pietrzak, M; Greaser, M L; Sosnicki, A A

1997-08-01

The pale, soft, exudative (PSE) phenomenon in turkey pectoralis major (breast) muscle was studied using a combination of biochemical, meat quality, microscopic, and gel electrophoresis techniques. Breast muscle samples were collected from turkeys characterized by slow vs fast postmortem glycolysis assessed by muscle pH at 20 min after death. The PSE group was characterized by lower muscle ATP (P < .05) and higher lactate levels (P < .05) compared with the normal group. Excess water-holding capacity and cooking yield were significantly lower (P < .05) in the PSE group than in normal turkeys. Breast muscle of the PSE group was also lighter (P < .05) than that in the normal group as determined by Minolta L* values. The SDS-PAGE, Western blotting, and immunofluorescence microscopy revealed that phosphorylase, a soluble enzyme, became tightly associated with the myofibrils in muscle from the PSE group. Also, less myosin could be solubilized from PSE vs normal myofibril samples. The results indicate that irreversible myosin insolubility due to low pH and high-temperature conditions is decisive in the development of PSE turkey breast muscle.

Role of pelvic floor in lower urinary tract function.

PubMed

Chermansky, Christopher J; Moalli, Pamela A

2016-10-01

The pelvic floor plays an integral part in lower urinary tract storage and evacuation. Normal urine storage necessitates that continence be maintained with normal urethral closure and urethral support. The endopelvic fascia of the anterior vaginal wall, its connections to the arcus tendineous fascia pelvis (ATFP), and the medial portion of the levator ani muscles must remain intact to provide normal urethral support. Thus, normal pelvic floor function is required for urine storage. Normal urine evacuation involves a series of coordinated events, the first of which involves complete relaxation of the external urethral sphincter and levator ani muscles. Acquired dysfunction of these muscles will initially result in sensory urgency and detrusor overactivity; however, with time the acquired voiding dysfunction can result in intermittent urine flow and incomplete bladder emptying, progressing to urinary retention in severe cases. This review will start with a discussion of normal pelvic floor anatomy and function. Next various injuries to the pelvic floor will be reviewed. The dysfunctional pelvic floor will be covered subsequently, with a focus on levator ani spasticity and stress urinary incontinence (SUI). Finally, future research directions of the interaction between the pelvic floor and lower urinary tract function will be discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Muscle anatomy and dynamic muscle function in osteogenesis imperfecta type I.

PubMed

Veilleux, Louis-Nicolas; Lemay, Martin; Pouliot-Laforte, Annie; Cheung, Moira S; Glorieux, Francis H; Rauch, Frank

2014-02-01

Results of previous studies suggested that children and adolescents with osteogenesis imperfecta (OI) type I have a muscle force deficit. However, muscle function has only been assessed by static isometric force tests and not in more natural conditions such as dynamic force and power tests. The purpose of this study was to assess lower extremity dynamic muscle function and muscle anatomy in OI type I. The study was performed in the outpatient department of a pediatric orthopedic hospital. A total of 54 individuals with OI type I (6-21 years; 20 male) and 54 age- and sex-matched controls took part in this study. Calf muscle cross-sectional area and density were measured by peripheral quantitative computed tomography. Lower extremity muscle function (peak force per body weight and peak power per body mass) was measured by jumping mechanography through 5 tests: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, chair-rise test, and heel-rise test. Compared with age- and sex-matched controls, patients with OI type I had smaller muscle size (P = .04) but normal muscle density (P = .21). They also had lower average peak force and lower specific force (peak force/muscle cross-sectional area; all P < .008). Average peak power was lower in patients with OI type I but not significantly so (all P > .054). Children and adolescents with OI type I have, on average, a significant force deficit in the lower limb as measured by dynamic force tests. Nonetheless, these data also show that OI type I is compatible with normal muscle performance in some individuals.

The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

NASA Technical Reports Server (NTRS)

Adams, G. R.; Haddad, F.

1996-01-01

Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P < 0.05). Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

The role of muscle spindles in the development of the monosynaptic stretch reflex

PubMed Central

Wang, Zhi; Li, LingYing

2012-01-01

Muscle sensory axons induce the development of specialized intrafusal muscle fibers in muscle spindles during development, but the role that the intrafusal fibers may play in the development of the central projections of these Ia sensory axons is unclear. In the present study, we assessed the influence of intrafusal fibers in muscle spindles on the formation of monosynaptic connections between Ia (muscle spindle) sensory axons and motoneurons (MNs) using two transgenic strains of mice. Deletion of the ErbB2 receptor from developing myotubes disrupts the formation of intrafusal muscle fibers and causes a nearly complete absence of functional synaptic connections between Ia axons and MNs. Monosynaptic connectivity can be fully restored by postnatal administration of neurotrophin-3 (NT-3), and the synaptic connections in NT-3-treated mice are as specific as in wild-type mice. Deletion of the Egr3 transcription factor also impairs the development of intrafusal muscle fibers and disrupts synaptic connectivity between Ia axons and MNs. Postnatal injections of NT-3 restore the normal strengths and specificity of Ia–motoneuronal connections in these mice as well. Severe deficits in intrafusal fiber development, therefore, do not disrupt the establishment of normal, selective patterns of connections between Ia axons and MNs, although these connections require the presence of NT-3, normally supplied by intrafusal fibers, to be functional. PMID:22490553

Normal muscle oxygen consumption and fatigability in sickle cell patients despite reduced microvascular oxygenation and hemorheological abnormalities.

PubMed

Waltz, Xavier; Pichon, Aurélien; Lemonne, Nathalie; Mougenel, Danièle; Lalanne-Mistrih, Marie-Laure; Lamarre, Yann; Tarer, Vanessa; Tressières, Benoit; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique; Hue, Olivier; Connes, Philippe

2012-01-01

Although it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue. We compared muscle metabolism and function (muscle microvascular oxygenation, microvascular blood flow, muscle oxygen consumption and muscle microvascular oxygenation variability, which reflects vasomotion activity, maximal muscle force and local muscle fatigability) and the hemorheological profile at rest between 16 healthy subjects (AA), 20 sickle cell-hemoglobin C disease (SC) patients and 16 sickle cell anemia (SS) patients. Muscle microvascular oxygenation was reduced in SS patients compared to the SC and AA groups and this reduction was not related to hemorhelogical abnormalities. No difference was observed between the three groups for oxygen consumption and vasomotion activity. Muscle microvascular blood flow was higher in SS patients compared to the AA group, and tended to be higher compared to the SC group. Multivariate analysis revealed that muscle oxygen consumption was independently associated with muscle microvascular blood flow in the two sickle cell groups (SC and SS). Finally, despite reduced muscle force in sickle cell patients, their local muscle fatigability was similar to that of the healthy subjects. Sickle cell patients have normal resting muscle oxygen consumption and fatigability despite hemorheological alterations and, for SS patients only, reduced muscle microvascular oxygenation and increased microvascular blood flow. Two alternative mechanisms can be proposed for SS patients: 1) the increased muscle microvascular blood flow is a way to compensate for the lower muscle microvascular oxygenation to maintain muscle oxygen consumption to normal values or 2) the reduced microvascular oxygenation coupled with a normal resting muscle oxygen consumption could indicate that there is slight hypoxia within the muscle which is not sufficient to limit mitochondrial respiration but increases muscle microvascular blood flow.

Abdicating power for control: a precision timing strategy to modulate function of flight power muscles.

PubMed

Sponberg, S; Daniel, T L

2012-10-07

Muscles driving rhythmic locomotion typically show strong dependence of power on the timing or phase of activation. This is particularly true in insects' main flight muscles, canonical examples of muscles thought to have a dedicated power function. However, in the moth (Manduca sexta), these muscles normally activate at a phase where the instantaneous slope of the power-phase curve is steep and well below maximum power. We provide four lines of evidence demonstrating that, contrary to the current paradigm, the moth's nervous system establishes significant control authority in these muscles through precise timing modulation: (i) left-right pairs of flight muscles normally fire precisely, within 0.5-0.6 ms of each other; (ii) during a yawing optomotor response, left-right muscle timing differences shift throughout a wider 8 ms timing window, enabling at least a 50 per cent left-right power differential; (iii) timing differences correlate with turning torque; and (iv) the downstroke power muscles alone causally account for 47 per cent of turning torque. To establish (iv), we altered muscle activation during intact behaviour by stimulating individual muscle potentials to impose left-right timing differences. Because many organisms also have muscles operating with high power-phase gains (Δ(power)/Δ(phase)), this motor control strategy may be ubiquitous in locomotor systems.

Abdicating power for control: a precision timing strategy to modulate function of flight power muscles

PubMed Central

Sponberg, S.; Daniel, T. L.

2012-01-01

Muscles driving rhythmic locomotion typically show strong dependence of power on the timing or phase of activation. This is particularly true in insects' main flight muscles, canonical examples of muscles thought to have a dedicated power function. However, in the moth (Manduca sexta), these muscles normally activate at a phase where the instantaneous slope of the power–phase curve is steep and well below maximum power. We provide four lines of evidence demonstrating that, contrary to the current paradigm, the moth's nervous system establishes significant control authority in these muscles through precise timing modulation: (i) left–right pairs of flight muscles normally fire precisely, within 0.5–0.6 ms of each other; (ii) during a yawing optomotor response, left—right muscle timing differences shift throughout a wider 8 ms timing window, enabling at least a 50 per cent left–right power differential; (iii) timing differences correlate with turning torque; and (iv) the downstroke power muscles alone causally account for 47 per cent of turning torque. To establish (iv), we altered muscle activation during intact behaviour by stimulating individual muscle potentials to impose left—right timing differences. Because many organisms also have muscles operating with high power–phase gains (Δpower/Δphase), this motor control strategy may be ubiquitous in locomotor systems. PMID:22833272

Measurement of Maximum Isometric Force Generated by Permeabilized Skeletal Muscle Fibers.

PubMed

Roche, Stuart M; Gumucio, Jonathan P; Brooks, Susan V; Mendias, Christopher L; Claflin, Dennis R

2015-06-16

Analysis of the contractile properties of chemically skinned, or permeabilized, skeletal muscle fibers offers a powerful means by which to assess muscle function at the level of the single muscle cell. Single muscle fiber studies are useful in both basic science and clinical studies. For basic studies, single muscle fiber contractility measurements allow investigation of fundamental mechanisms of force production, and analysis of muscle function in the context of genetic manipulations. Clinically, single muscle fiber studies provide useful insight into the impact of injury and disease on muscle function, and may be used to guide the understanding of muscular pathologies. In this video article we outline the steps required to prepare and isolate an individual skeletal muscle fiber segment, attach it to force-measuring apparatus, activate it to produce maximum isometric force, and estimate its cross-sectional area for the purpose of normalizing the force produced.

Piezo channels and GsMTx4: Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology.

PubMed

Suchyna, Thomas M

2017-11-01

Discovery of Piezo channels and the reporting of their sensitivity to the inhibitor GsMTx4 were important milestones in the study of non-selective cationic mechanosensitive channels (MSCs) in normal physiology and pathogenesis. GsMTx4 had been used for years to investigate the functional role of cationic MSCs, especially in muscle tissue, but with little understanding of its target or inhibitory mechanism. The sensitivity of Piezo channels to bilayer stress and its robust mechanosensitivity when expressed in heterologous systems were keys to determining GsMTx4's mechanism of action. However, questions remain regarding Piezo's role in muscle function due to the non-selective nature of GsMTx4 inhibition toward membrane mechanoenzymes and the implication of MCS channel types by genetic knockdown. Evidence supporting Piezo like activity, at least in the developmental stages of muscle, is presented. While the MSC targets of GsMTx4 in muscle pathology are unclear, its muscle protective effects are clearly demonstrated in two recent in situ studies on normal cardiomyocytes and dystrophic skeletal muscle. The muscle protective function may be due to the combined effect of GsMTx4's inhibitory action on cationic MSCs like Piezo and TRP, and its potentiation of repolarizing K + selective MSCs like K2P and SAKCa. Paradoxically, the potent in vitro action of GsMTx4 on many physiological functions seems to conflict with its lack of in situ side-effects on normal animal physiology. Future investigations into cytoskeletal control of sarcolemma mechanics and the suspected inclusion of MSCs in membrane micro/nano sized domains with distinct mechanical properties will aide our understanding of this dichotomy. Published by Elsevier Ltd.

Association between muscle function, cognitive state, depression symptoms and quality of life of older people: evidence from clinical practice.

PubMed

Gariballa, Salah; Alessa, Awad

2018-04-01

Although low muscle function/strength is an important predictor of poor clinical outcome in older patients, information on its impact on mental health in clinical practice is still lacking. The aim of this report is to measure the impact of low muscle function measured by handgrip strength on mental health of older people during both acute illness and recovery. Four hundred and thirty-two randomly selected hospitalized older patients had their baseline demographic and clinical characteristics assessed within 72 h of admission, at 6 weeks and at 6 months. Low muscle strength-handgrip was defined using the European Working Group criteria. Mental health outcome measures including cognitive state, depression symptoms and quality of life were also measured. Among the 432 patients recruited, 308 (79%) had low muscle strength at baseline. Corresponding figures at 6 weeks and at 6 months were 140 (73%) and 158 (75%). Patients with poor muscle strength were significantly older with increased disability and poor nutritional status compared with those with normal muscle strength. After adjustment for age, gender, disability, comorbidity including severity of acute illness and body mass index patients with low muscle strength had worse cognitive function, quality of life and higher depression symptoms compared with those with normal muscle strength over a 6-month period (p < 0.05). Poor muscle strength in older people is associated with poor cognitive state and quality of life and increased depression symptoms during both acute illness and recovery.

Assessment of the maximum voluntary arm muscle contraction in sign language for the deaf.

PubMed

Regalo, S C H; Teixeira, V R; Vitti, M; Chaves, T C; Hallak, J E C; Bevilaqua-Grossi, D; Siriani de Oliveira, A

2006-01-01

The purpose of this study was to investigate the levels of upper member muscles' activation of deaf individuals, who use the Brazilian sign language - LIBRAS, comparing these findings to volunteers with no postural deviations and normal hearing Forty eight volunteers divided into two groups comprising healthy and deaf subjects (24 volunteers for each group). The signs of rest were obtained with the volunteer maintaining the upper member in an anatomical position, but with the forearm flexed and sustained by the lower member. Maximum voluntary isometric contractions (MVIC) of the biceps, triceps, deltoid, and trapezius muscles were performed in the position of muscular function testing. Statistical analysis was performed using the SPSS-10.0. Continuous data with normal distribution were analyzed by ANOVA with the significance level of p < 0.01. The normalized electromyographic muscle data obtained in muscular rest do not show statistically significant differences among the studies muscles, in both groups. In the comparison of normalized RMS values obtained in MVIC, the mean values for the trapezius muscle of deaf group were statistically lower than control group. This study's results indicate there are no differences between the levels of muscular activation for arm biceps, arm triceps, and the anterior portion of the deltoid muscle between the mean normalized RMS values of deaf and healthy individuals.

GSNOR Deficiency Enhances In Situ Skeletal Muscle Strength, Fatigue Resistance, and RyR1 S-Nitrosylation Without Impacting Mitochondrial Content and Activity

PubMed Central

Moon, Younghye; Cao, Yenong; Zhu, Jingjing; Xu, Yuanyuan; Balkan, Wayne; Buys, Emmanuel S.; Diaz, Francisca; Kerrick, W. Glenn; Hare, Joshua M.

2017-01-01

Abstract Aim: Nitric oxide (NO) plays important, but incompletely defined roles in skeletal muscle. NO exerts its regulatory effects partly though S-nitrosylation, which is balanced by denitrosylation by enzymes such as S-nitrosoglutathione reductase (GSNOR), whose functions in skeletal muscle remain to be fully deciphered. Results: GSNOR null (GSNOR−/−) tibialis anterior (TA) muscles showed normal growth and were stronger and more fatigue resistant than controls in situ. However, GSNOR−/− lumbrical muscles showed normal contractility and Ca2+ handling in vitro, suggesting important differences in GSNOR function between muscles or between in vitro and in situ environments. GSNOR−/− TA muscles exhibited normal mitochondrial content, and capillary densities, but reduced type IIA fiber content. GSNOR inhibition did not impact mitochondrial respiratory complex I, III, or IV activities. These findings argue that enhanced GSNOR−/− TA contractility is not driven by changes in mitochondrial content or activity, fiber type, or blood vessel density. However, loss of GSNOR led to RyR1 hypernitrosylation, which is believed to increase muscle force output under physiological conditions. cGMP synthesis by soluble guanylate cyclase (sGC) was decreased in resting GSNOR−/− muscle and was more responsive to agonist (DETANO, BAY 41, and BAY 58) stimulation, suggesting that GSNOR modulates cGMP production in skeletal muscle. Innovation: GSNOR may act as a “brake” on skeletal muscle contractile performance under physiological conditions by modulating nitrosylation/denitrosylation balance. Conclusions: GSNOR may play important roles in skeletal muscle contractility, RyR1 S-nitrosylation, fiber type specification, and sGC activity. Antioxid. Redox Signal. 26, 165–181. PMID:27412893

[Effect of biological electric stimulation on free muscle transfer].

PubMed

Yuang, F; Guan, W; Cao, Y

1997-01-01

The rectus femoris muscles of rabbits were used as muscle model. The electrical stimulation which resembled the normal motor-unit activity was used to observe its effects on free transferred muscle. After three months, the moist muscle weight (MW), its maximum cross-section area, its contractility and its histochemical characteristics were examined. The results showed that the function and morphology of the muscles were well preserved. These findings might encourage its clinical application.

Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears.

PubMed

Mendias, Christopher L; Roche, Stuart M; Harning, Julie A; Davis, Max E; Lynch, Evan B; Sibilsky Enselman, Elizabeth R; Jacobson, Jon A; Claflin, Dennis R; Calve, Sarah; Bedi, Asheesh

2015-01-01

A persistent atrophy of muscle fibers and an accumulation of fat, collectively referred to as fatty degeneration, commonly occur in patients with chronic rotator cuff tears. The etiology of fatty degeneration and function of the residual rotator cuff musculature have not been well characterized in humans. We hypothesized that muscles from patients with chronic rotator cuff tears have reduced muscle fiber force production, disordered myofibrils, and an accumulation of fat vacuoles. The contractility of muscle fibers from biopsy specimens of supraspinatus muscles of 13 patients with chronic full-thickness posterosuperior rotator cuff tears was measured and compared with data from healthy vastus lateralis muscle fibers. Correlations between muscle fiber contractility, American Shoulder and Elbow Surgeons (ASES) scores, and tear size were analyzed. Histology and electron microscopy were also performed. Torn supraspinatus muscles had a 30% reduction in maximum isometric force production and a 29% reduction in normalized force compared with controls. Normalized supraspinatus fiber force positively correlated with ASES score and negatively correlated with tear size. Disordered sarcomeres were noted, along with an accumulation of lipid-laden macrophages in the extracellular matrix surrounding supraspinatus muscle fibers. Patients with chronic supraspinatus tears have significant reductions in muscle fiber force production. Force production also correlates with ASES scores and tear size. The structural and functional muscle dysfunction of the residual muscle fibers is independent of the additional area taken up by fibrotic tissue. This work may help establish future therapies to restore muscle function after the repair of chronically torn rotator cuff muscles. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Neutrophilic infiltration within the airway smooth muscle in patients with COPD

PubMed Central

Baraldo, S; Turato, G; Badin, C; Bazzan, E; Beghe, B; Zuin, R; Calabrese, F; Casoni, G; Maestrelli, P; Papi, A; Fabbri, L; Saetta, M

2004-01-01

Background: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. Methods: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. Results: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). Conclusions: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation. PMID:15047950

The origin and development of malocclusions. When, where and how dental malocclusions develop.

PubMed

Loudon, Merle E

2013-01-01

This article describes the forces of the muscles from the stomatonathic system and how they interact in many children to change the normal forces of growth. Because of this change in muscle forces there is a change from normal teeth and bone growth positions to abnormal positions. These normal and/or abnormal changes in muscle forces are the basis for development into class one, class two and class three occlusions. This is very valuable information for the orthodontic clinician because these muscle forces are the fundamental basis for all orthodontic treatment. By knowing this an orthodontic clinician will be more able to diagnose and treat a malocclusion. This is exceptionally important for the dentist who is just starting to learn diagnosis, treatment planning, functional and fixed orthodontic treatment.

Contractile properties of single permeabilized muscle fibers from congenital cleft palates and normal palates of Spanish goats.

PubMed

Hanes, Michael C; Weinzweig, Jeffrey; Kuzon, William M; Panter, Kip E; Buchman, Steven R; Faulkner, John A; Yu, Deborah; Cederna, Paul S; Larkin, Lisa M

2007-05-01

Analysis of the composition of muscle fibers constituent to a cleft palate could provide significant insight into the cause of velopharyngeal inadequacy. The authors hypothesized that levator veli palatini muscle dysfunction inherent to cleft palates could affect the timing and outcome of cleft palate repair. Single, permeabilized muscle fibers from levator veli palatini muscles of three normal (n = 19 fibers) and three chemically induced congenital cleft palates (n = 21 fibers) of 14-month-old goats were isolated, and contractile properties were evaluated. The maximum isometric force and rate constants of tension redevelopment (ktr) were measured, and the specific force and normalized power were calculated for each fiber. The ktr measures indicate that cleft fibers are predominantly fast-fatigable; normal fibers are slow fatigue-resistant: after a 10-minute isometric contraction, fibers from cleft palates had a loss of force 16 percent greater than that from normal palates (p = 0.0001). The cross-sectional areas of the fibers from cleft palates (2750 +/- 209 microm2) were greater (p = 0.05) than those from normal palates (2226 +/- 143 microm2). Specific forces did not differ between the two groups. Maximum normalized power of fibers from cleft palates (11.05 +/- 1.82 W/l) was greater (p = 0.0001) than fibers from normal palates (1.60 +/- 0.12 W/l). There are clear physiologic differences in single muscle fibers from cleft palates and normal palates: cleft palate fibers are physiologically fast, have greater fatigability, and have greater power production. Detection of functional and/or fiber type differences in muscles of cleft palates may provide preoperative identification of a patient's susceptibility to velopharyngeal inadequacy and permit early surgical intervention to correct this clinical condition.

Skeletal and cardiac muscle pericytes: Functions and therapeutic potential

PubMed Central

Murray, Iain R.; Baily, James E.; Chen, William C.W.; Dar, Ayelet; Gonzalez, Zaniah N.; Jensen, Andrew R.; Petrigliano, Frank A.; Deb, Arjun; Henderson, Neil C.

2017-01-01

Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease. PMID:27595928

Functional aspects of cross-legged sitting with special attention to piriformis muscles and sacroiliac joints.

PubMed

Snijders, Chris J; Hermans, Paul F G; Kleinrensink, Gerrit Jan

2006-02-01

Transversely oriented pelvic muscles such as the internal abdominal oblique, transversus abdominis, piriformis and pelvic floor muscles may contribute to sacroiliac joint stability by pressing the sacrum between the hipbones. Surface electromyographic measurements showed that leg crossing lowers the activity of the internal oblique abdominal muscle significantly. This suggests that leg crossing is a substitute for abdominal muscle activity. No previous studies addressed piriformis muscle and related pelvic structures in cross-legged sitting. Angles of pelvis and femur were measured in healthy subjects in standing, normal sitting and cross-legged sitting, and were used to simulate these postures on embalmed pelvises and measure piriformis muscle elongation. Deformations of pelvic ring and iliolumbar ligament caused by piriformis muscle force were measured on embalmed pelvises. Cross-legged sitting resulted in a relative elongation of the piriformis muscle of 11.7% compared to normal sitting and even 21.4% compared to standing. Application of piriformis muscle force resulted in inward deformation of the pelvic ring and compression of the sacroiliac joints and the dorsal side of the pubic symphysis. Cross-legged sitting is common. We believe that it contributes to sacroiliac joint stability. This study demonstrates the influence of the piriformis muscle on sacroiliac joint compression. The elongation of the piriformis muscle bilaterally by crossing the legs may be functional in the build-up of active or passive tension between sacrum and femur.

Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

NASA Technical Reports Server (NTRS)

Adams, Gregory A.; Haddad, Fadia; Baldwin, Kenneth M.

2003-01-01

Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4) Fast IIb MHC gene expression was enhanced in fast-twitch muscles of normal thyroid animals exposed to spaceflight; however, thyroid deficiency markedly repressed expression of this gene independently of spaceflight. In summary, the absence of gravity, when imposed at critical stages of development, impaired body and skeletal muscle growth, as well as expression of the MHC gene family of motor proteins. This suggests that normal weightbearing activity is essential for establishing body and muscle growth in neonatal animals, and for expressing the motor gene essential for supporting antigravity functions.

Recovery of peripheral muscle function from fatiguing exercise and daily physical activity level in patients with multiple sclerosis: a case-control study.

PubMed

Ickmans, Kelly; Simoens, Fauve; Nijs, Jo; Kos, Daphne; Cras, Patrick; Willekens, Barbara; Meeus, Mira

2014-07-01

Delayed recovery of muscle function following exercise has been demonstrated in the lower limbs of patients with multiple sclerosis (MS). However, studies examining this in the upper limbs are currently lacking. This study compared physical activity level (PAL) and recovery of upper limb muscle function following exercise between MS patients and healthy inactive controls. Furthermore, the relationship between PAL and muscle recovery was examined. PAL of 19 MS patients and 32 controls was measured using an accelerometer for 7 consecutive days. Afterwards, recovery of muscle function was assessed by performing a fatiguing upper limb exercise test with subsequent recovery measures. Muscle recovery of the upper limb muscles was similar in both groups. Average activity counts were significantly lower in MS patients than in the control group. MS patients spent significantly more time being sedentary and less time on activities of moderate intensity compared with the control group. No significant correlation between PAL and recovery of muscle function was found in MS patients. Recovery of upper limb muscle function following exercise is normal in MS patients. MS patients are less physically active than healthy inactive controls. PAL and recovery of upper limb muscle function appear unrelated in MS patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Cardiac mechanics: Physiological, clinical, and mathematical considerations

NASA Technical Reports Server (NTRS)

Mirsky, I. (Editor); Ghista, D. N.; Sandler, H.

1974-01-01

Recent studies concerning the basic physiological and biochemical principles underlying cardiac muscle contraction, methods for the assessment of cardiac function in the clinical situation, and mathematical approaches to cardiac mechanics are presented. Some of the topics covered include: cardiac ultrastructure and function in the normal and failing heart, myocardial energetics, clinical applications of angiocardiography, use of echocardiography for evaluating cardiac performance, systolic time intervals in the noninvasive assessment of left ventricular performance in man, evaluation of passive elastic stiffness for the left ventricle and isolated heart muscle, a conceptual model of myocardial infarction and cardiogenic shock, application of Huxley's sliding-filament theory to the mechanics of normal and hypertrophied cardiac muscle, and a rheological modeling of the intact left ventricle. Individual items are announced in this issue.

Effect of α{sub 7} nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

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

Welch, Kevin D., E-mail: kevin.welch@ars.usda.gov; Pfister, James A.; Lima, Flavia G.

2013-02-01

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscularmore » paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. -- Highlights: ► Mice treated with nAChR agonists and antagonists have a loss in motor function. ► These deficits are temporary as near normal motor function returns within 10 min. ► There are compound-specific differences in the effects on motor function.« less

Cytoskeletal tropomyosin Tm5NM1 is required for normal excitation-contraction coupling in skeletal muscle.

PubMed

Vlahovich, Nicole; Kee, Anthony J; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S; Parton, Robert G; Gunning, Peter W; Hardeman, Edna C

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation-contraction coupling in skeletal muscle.

Cytoskeletal Tropomyosin Tm5NM1 Is Required for Normal Excitation–Contraction Coupling in Skeletal Muscle

PubMed Central

Vlahovich, Nicole; Kee, Anthony J.; Van der Poel, Chris; Kettle, Emma; Hernandez-Deviez, Delia; Lucas, Christine; Lynch, Gordon S.; Parton, Robert G.; Gunning, Peter W.

2009-01-01

The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation–contraction coupling in skeletal muscle. PMID:19005216

Normal Muscle Oxygen Consumption and Fatigability in Sickle Cell Patients Despite Reduced Microvascular Oxygenation and Hemorheological Abnormalities

PubMed Central

Waltz, Xavier; Pichon, Aurélien; Lemonne, Nathalie; Mougenel, Danièle; Lalanne-Mistrih, Marie-Laure; Lamarre, Yann; Tarer, Vanessa; Tressières, Benoit; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique; Hue, Olivier; Connes, Philippe

2012-01-01

Background/Aim Although it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue. Methods We compared muscle metabolism and function (muscle microvascular oxygenation, microvascular blood flow, muscle oxygen consumption and muscle microvascular oxygenation variability, which reflects vasomotion activity, maximal muscle force and local muscle fatigability) and the hemorheological profile at rest between 16 healthy subjects (AA), 20 sickle cell-hemoglobin C disease (SC) patients and 16 sickle cell anemia (SS) patients. Results Muscle microvascular oxygenation was reduced in SS patients compared to the SC and AA groups and this reduction was not related to hemorhelogical abnormalities. No difference was observed between the three groups for oxygen consumption and vasomotion activity. Muscle microvascular blood flow was higher in SS patients compared to the AA group, and tended to be higher compared to the SC group. Multivariate analysis revealed that muscle oxygen consumption was independently associated with muscle microvascular blood flow in the two sickle cell groups (SC and SS). Finally, despite reduced muscle force in sickle cell patients, their local muscle fatigability was similar to that of the healthy subjects. Conclusions Sickle cell patients have normal resting muscle oxygen consumption and fatigability despite hemorheological alterations and, for SS patients only, reduced muscle microvascular oxygenation and increased microvascular blood flow. Two alternative mechanisms can be proposed for SS patients: 1) the increased muscle microvascular blood flow is a way to compensate for the lower muscle microvascular oxygenation to maintain muscle oxygen consumption to normal values or 2) the reduced microvascular oxygenation coupled with a normal resting muscle oxygen consumption could indicate that there is slight hypoxia within the muscle which is not sufficient to limit mitochondrial respiration but increases muscle microvascular blood flow. PMID:23285055

A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys.

PubMed

St Andre, Michael; Johnson, Mark; Bansal, Prashant N; Wellen, Jeremy; Robertson, Andrew; Opsahl, Alan; Burch, Peter M; Bialek, Peter; Morris, Carl; Owens, Jane

2017-11-09

The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice. Therefore, myostatin blockade via a specific antibody could ameliorate the muscle weakness in DMD patients by increasing skeletal muscle mass and function, thereby reducing patients' functional decline. A murine anti-myostatin antibody, mRK35, and its humanized analog, domagrozumab, were developed and their ability to inhibit several TGB-β ligands was measured using a cell-based Smad-activity reporter system. Normal and mdx mice were treated with mRK35 to examine the antibody's effect on body weight, lean mass, muscle weights, grip strength, ex vivo force production, and fiber size. The humanized analog (domagrozumab) was tested in non-human primates (NHPs) for changes in skeletal muscle mass and volume as well as target engagement via modulation of circulating myostatin. Both the murine and human antibodies are specific and potent inhibitors of myostatin and GDF11. mRK35 is able to increase body weight, lean mass, and muscle weights in normal mice. In mdx mice, mRK35 significantly increased body weight, muscle weights, grip strength, and ex vivo force production in the extensor digitorum longus (EDL) muscle. Further, tibialis anterior (TA) fiber size was significantly increased. NHPs treated with domagrozumab demonstrated a dose-dependent increase in lean mass and muscle volume and exhibited increased circulating levels of myostatin demonstrating target engagement. We demonstrated that the potent anti-myostatin antibody mRK35 and its clinical analog, domagrozumab, were able to induce muscle anabolic activity in both rodents, including the mdx mouse model of DMD, and non-human primates. A Phase 2, potentially registrational, clinical study with domagrozumab in DMD patients is currently underway.

Effect of inaction on function of fast and slow muscle spindles

NASA Technical Reports Server (NTRS)

Arutyunyan, R. S.

1980-01-01

There is no data on the comparative effect of tenotomy on the function of the muscle spindles of fast and slow muscles. This study covers this question. The experiments were conducted on cats. The musuculus extensor digitorum longus (m. EDL) was selected as the fast muscle, and the musculus soleus (m. Sol.) as the slow. In a comparison of the spontaneous activity of primary and secondary endings of the fast and slow muscle spindles (i.e., the activity with complete relaxation of the muscles) normally no difference between them was successfully found. The authors recorded the integrative, and not the individual activity, and secondly, under conditions of such recording technique, those slight changes that are observed in the fast muscle receptors could remain unnoticed.

Muscle function in Turner syndrome: normal force but decreased power.

PubMed

Soucek, Ondrej; Lebl, Jan; Matyskova, Jana; Snajderova, Marta; Kolouskova, Stanislava; Pruhova, Stepanka; Hlavka, Zdenek; Sumnik, Zdenek

2015-02-01

Although hypogonadism and SHOX gene haploinsufficiency likely cause the decreased bone mineral density and increased fracture rate associated with Turner syndrome (TS), the exact mechanism remains unclear. We tested the hypothesis that muscle dysfunction in patients with TS contributes to increased fracture risk. The secondary aim was to determine whether menarche, hormone therapy duration, positive fracture history and genotype influence muscle function parameters in patients with TS. A cross-sectional study was conducted in a single university hospital referral centre between March 2012 and October 2013. Sixty patients with TS (mean age of 13·7 ± 4·5 years) were compared to the control group of 432 healthy girls. A Leonardo Mechanograph(®) Ground Reaction Force Platform was used to assess muscle force (Fmax ) by the multiple one-legged hopping test and muscle power (Pmax ) by the single two-legged jump test. While the Fmax was normal (mean weight-specific Z-score of 0·11 ± 0·77, P = 0·27), the Pmax was decreased in patients with TS (Z-score of -0·93 ± 1·5, P < 0·001) compared with healthy controls. The muscle function parameters were not significantly influenced by menarcheal stage, hormone therapy duration, fracture history or genotype (linear regression adjusted for age, weight and height; P > 0·05 for all). Fmax , a principal determinant of bone strength, is normal in patients with TS. Previously described changes in bone quality and structure in TS are thus not likely related to inadequate mechanical loading but rather represent a primary bone deficit. A decreased Pmax indicates impaired muscle coordination in patients with TS. © 2014 John Wiley & Sons Ltd.

Evaluating Swallowing Muscles Essential for Hyolaryngeal Elevation by Using Muscle Functional Magnetic Resonance Imaging

PubMed Central

Pearson, William G.; Hindson, David F.; Langmore, Susan E.; Zumwalt, Ann C.

2012-01-01

Summary Elevation of the larynx is critical to swallowing function, an observation supported by the fact that radiation therapy-induced dysphagia is associated with reduced laryngeal elevation. We investigated muscles underlying hyolaryngeal elevation by using muscle functional MRI. We acquired scans from 11 healthy subjects to determine whole-muscle T2 signal profiles pre-swallowing, post-swallowing, and after performing swallowing exercises. Results demonstrate muscles essential to laryngeal elevation and exercises that target them. Purpose Reduced hyolaryngeal elevation, a critical event in swallowing, is associated with radiation therapy. Two muscle groups that suspend the hyoid, larynx, and pharynx have been proposed to elevate the hyolaryngeal complex: the suprahyoid and longitudinal pharyngeal muscles. Thought to assist both groups is the thyrohyoid, a muscle intrinsic to the hyolaryngeal complex. Intensity modulated radiation therapy guidelines designed to preserve structures important to swallowing currently exclude the suprahyoid and thyrohyoid muscles. This study used muscle functional magnetic resonance imaging (mfMRI) in normal healthy adults to determine whether both muscle groups are active in swallowing and to test therapeutic exercises thought to be specific to hyolaryngeal elevation. Methods and Materials mfMRI data were acquired from 11 healthy subjects before and after normal swallowing and after swallowing exercise regimens (the Mendelsohn maneuver and effortful pitch glide). Whole-muscle transverse relaxation time (T2 signal, measured in milliseconds) profiles of 7 test muscles were used to evaluate the physiologic response of each muscle to each condition. Changes in effect size (using the Cohen d measure) of whole-muscle T2 profiles were used to determine which muscles underlie swallowing and swallowing exercises. Results Post-swallowing effect size changes (where a d value of >0.20 indicates significant activity during swallowing) for the T2 signal profile of the thyrohyoid was a d value of 0.09; a d value of 0.40 for the mylohyoid, 0.80 for the geniohyoid, 0.04 for the anterior digastric, and 0.25 for the posterior digastric-stylohyoid in the suprahyoid muscle group; and d values of 0.47 for the palatopharyngeus and 0.28 for the stylopharyngeus muscles in the longitudinal pharyngeal muscle group. The Mendelsohn maneuver and effortful pitch glide swallowing exercises showed significant effect size changes for all muscles tested, except for the thyrohyoid. Conclusions Muscles of both the suprahyoid and the longitudinal pharyngeal muscle groups are active in swallowing, and both swallowing exercises effectively target muscles elevating the hyolaryngeal complex. mfMRI is useful in testing swallowing muscle function. PMID:22995662

Evaluation of respiratory muscles activity by means of cross mutual information function at different levels of ventilatory effort.

PubMed

Alonso, Joan Francesc; Mañanas, Miguel A; Hoyer, Dirk; Topor, Zbigniew L; Bruce, Eugene N

2007-09-01

Analysis of respiratory muscles activity is an effective technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Respiratory diseases, especially those associated with changes in the mechanical properties of the respiratory apparatus, are often associated with disruptions of the normally highly coordinated contractions of respiratory muscles. Due to the complexity of the respiratory control, the assessment of OSAS related dysfunctions by linear methods are not sufficient. Therefore, the objective of this study was the detection of diagnostically relevant nonlinear complex respiratory mechanisms. Two aims of this work were: (1) to assess coordination of respiratory muscles contractions through evaluation of interactions between respiratory signals and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF); (2) to differentiate between functioning of respiratory muscles in patients with OSAS and in normal subjects. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from three respiratory muscles: genioglossus, sternomastoid and diaphragm. Inspiratory pressure and flow were also acquired. All signals were measured in eight patients with OSAS and eight healthy subjects during an increased respiratory effort while awake. Several variables were defined and calculated from CMIF in order to describe correlation between signals. The results indicate different nonlinear couplings of respiratory muscles in both populations. This effect is progressively more evident at higher levels of respiratory effort.

Gastrocnemius mitochondrial respiration: are there any differences between men and women?

PubMed

Thompson, Jonathan R; Swanson, Stanley A; Casale, George P; Johanning, Jason M; Papoutsi, Evlampia; Koutakis, Panagiotis; Miserlis, Dimitrios; Zhu, Zhen; Pipinos, Iraklis I

2013-11-01

Work on human and mouse skeletal muscle by our group and others has demonstrated that aging and age-related degenerative diseases are associated with mitochondrial dysfunction, which may be more prevalent in males. There have been, however, no studies that specifically examine the influence of male or female sex on human skeletal muscle mitochondrial respiration. The purpose of this study was to compare mitochondrial respiration in the gastrocnemius of adult men and women. Gastrocnemius muscle was obtained from male (n = 19) and female (n = 11) human subjects with healthy lower-extremity musculoskeletal and arterial systems and normal ambulatory function. All patients were undergoing operations for the treatment of varicose veins in their legs. Mitochondrial respiration was determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Complex I-, II-, III-, and IV-dependent respiration was measured individually and normalized to muscle weight, total protein content, and citrate synthase (CS, index of mitochondrial content). Male and female patients had no evidence of musculoskeletal or arterial disease and did not differ with regard to age, race, body mass index, or other clinical characteristics. Complex I-, II-, III-, and IV-dependent respiration normalized to muscle weight, total protein content, and CS did not statistically differ for males compared with females. Our study evaluates, for the first time, gastrocnemius mitochondrial respiration of adult men and women who have healthy musculoskeletal and arterial systems and normal ambulatory function. Our data demonstrate there are no differences in the respiration of gastrocnemius mitochondria between men and women. Copyright © 2013 Elsevier Inc. All rights reserved.

Strain map of the tongue in normal and ALS speech patterns from tagged and diffusion MRI

NASA Astrophysics Data System (ADS)

Xing, Fangxu; Prince, Jerry L.; Stone, Maureen; Reese, Timothy G.; Atassi, Nazem; Wedeen, Van J.; El Fakhri, Georges; Woo, Jonghye

2018-03-01

Amyotrophic Lateral Sclerosis (ALS) is a neurological disease that causes death of neurons controlling muscle movements. Loss of speech and swallowing functions is a major impact due to degeneration of the tongue muscles. In speech studies using magnetic resonance (MR) techniques, diffusion tensor imaging (DTI) is used to capture internal tongue muscle fiber structures in three-dimensions (3D) in a non-invasive manner. Tagged magnetic resonance images (tMRI) are used to record tongue motion during speech. In this work, we aim to combine information obtained with both MR imaging techniques to compare the functionality characteristics of the tongue between normal and ALS subjects. We first extracted 3D motion of the tongue using tMRI from fourteen normal subjects in speech. The estimated motion sequences were then warped using diffeomorphic registration into the b0 spaces of the DTI data of two normal subjects and an ALS patient. We then constructed motion atlases by averaging all warped motion fields in each b0 space, and computed strain in the line of action along the muscle fiber directions provided by tractography. Strain in line with the fiber directions provides a quantitative map of the potential active region of the tongue during speech. Comparison between normal and ALS subjects explores the changing volume of compressing tongue tissues in speech facing the situation of muscle degradation. The proposed framework provides for the first time a dynamic map of contracting fibers in ALS speech patterns, and has the potential to provide more insight into the detrimental effects of ALS on speech.

Strain Map of the Tongue in Normal and ALS Speech Patterns from Tagged and Diffusion MRI.

PubMed

Xing, Fangxu; Prince, Jerry L; Stone, Maureen; Reese, Timothy G; Atassi, Nazem; Wedeen, Van J; El Fakhri, Georges; Woo, Jonghye

2018-02-01

Amyotrophic Lateral Sclerosis (ALS) is a neurological disease that causes death of neurons controlling muscle movements. Loss of speech and swallowing functions is a major impact due to degeneration of the tongue muscles. In speech studies using magnetic resonance (MR) techniques, diffusion tensor imaging (DTI) is used to capture internal tongue muscle fiber structures in three-dimensions (3D) in a non-invasive manner. Tagged magnetic resonance images (tMRI) are used to record tongue motion during speech. In this work, we aim to combine information obtained with both MR imaging techniques to compare the functionality characteristics of the tongue between normal and ALS subjects. We first extracted 3D motion of the tongue using tMRI from fourteen normal subjects in speech. The estimated motion sequences were then warped using diffeomorphic registration into the b0 spaces of the DTI data of two normal subjects and an ALS patient. We then constructed motion atlases by averaging all warped motion fields in each b0 space, and computed strain in the line of action along the muscle fiber directions provided by tractography. Strain in line with the fiber directions provides a quantitative map of the potential active region of the tongue during speech. Comparison between normal and ALS subjects explores the changing volume of compressing tongue tissues in speech facing the situation of muscle degradation. The proposed framework provides for the first time a dynamic map of contracting fibers in ALS speech patterns, and has the potential to provide more insight into the detrimental effects of ALS on speech.

Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest.

PubMed

Manderfield, Lauren J; Aghajanian, Haig; Engleka, Kurt A; Lim, Lillian Y; Liu, Feiyan; Jain, Rajan; Li, Li; Olson, Eric N; Epstein, Jonathan A

2015-09-01

Notch signaling has well-defined roles in the assembly of arterial walls and in the development of the endothelium and smooth muscle of the vasculature. Hippo signaling regulates cellular growth in many tissues, and contributes to regulation of organ size, in addition to other functions. Here, we show that the Notch and Hippo pathways converge to regulate smooth muscle differentiation of the neural crest, which is crucial for normal development of the aortic arch arteries and cranial vasculature during embryonic development. Neural crest-specific deletion of the Hippo effectors Yap and Taz produces neural crest precursors that migrate normally, but fail to produce vascular smooth muscle, and Notch target genes such as Jagged1 fail to activate normally. We show that Yap is normally recruited to a tissue-specific Jagged1 enhancer by directly interacting with the Notch intracellular domain (NICD). The Yap-NICD complex is recruited to chromatin by the DNA-binding protein Rbp-J in a Tead-independent fashion. Thus, Hippo signaling can modulate Notch signaling outputs, and components of the Hippo and Notch pathways physically interact. Convergence of Hippo and Notch pathways by the mechanisms described here might be relevant for the function of these signaling cascades in many tissues and in diseases such as cancer. © 2015. Published by The Company of Biologists Ltd.

Overview of Minerals

MedlinePlus

... and dark green vegetables Required for metabolism of nitrogen, the activation of certain enzymes, and normal cell ... normal nerve and muscle function Involved in electrolyte balance 3.5 grams — Selenium Meats, seafood, nuts, and ...

Extraocular muscle function testing

MedlinePlus

... may result in double vision or rapid, uncontrolled eye movements . Normal Results Normal movement of the eyes in all directions. What Abnormal Results Mean Eye movement disorders may be due to abnormalities of the ...

The effect of obesity on the contractile performance of isolated mouse soleus, EDL, and diaphragm muscles.

PubMed

Tallis, Jason; Hill, Cameron; James, Rob S; Cox, Val M; Seebacher, Frank

2017-01-01

Obesity affects the major metabolic and cellular processes involved in skeletal muscle contractility. Surprisingly, the effect of obesity on isolated skeletal muscle performance remains unresolved. The present study is the first to examine the muscle-specific changes in contractility following dietary-induced obesity using an isolated muscle work-loop (WL) model that more closely represents in vivo muscle performance. Following 16-wk high-calorific feeding, soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) were isolated from female (CD-1) mice, and contractile performance was compared against a lean control group. Obese SOL produced greater isometric force; however, isometric stress (force per unit muscle area), absolute WL power, and normalized WL power (watts per kilogram muscle mass) were unaffected. Maximal isometric force and absolute WL power of the EDL were similar between groups. For both EDL and DIA, isometric stress and normalized WL power were reduced in the obese groups. Obesity caused a significant reduction in fatigue resistance in all cases. Our findings demonstrate a muscle-specific reduction in contractile performance and muscle quality that is likely related to in vivo mechanical role, fiber type, and metabolic profile, which may in part be related to changes in myosin heavy chain expression and AMP-activated protein kinase activity. These results infer that, beyond the additional requirement of moving a larger body mass, functional performance and quality of life may be further limited by poor muscle function in obese individuals. As such, a reduction in muscle performance may be a substantial contributor to the negative cycle of obesity. The effect of obesity on isolated muscle function is surprisingly underresearched. The present study is the first to examine the effects of obesity on isolated muscle performance using a method that more closely represents real-world muscle function. This work uniquely establishes a muscle-specific profile of mechanical changes in relation to underpinning mechanisms. These findings may be important to understanding the negative cycle of obesity and in designing interventions for improving weight status. Copyright © 2017 the American Physiological Society.

Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia

PubMed Central

Roberts, Edward W.; Deonarine, Andrew; Jones, James O.; Denton, Alice E.; Feig, Christine; Lyons, Scott K.; Espeli, Marion; Kraman, Matthew; McKenna, Brendan; Wells, Richard J.B.; Zhao, Qi; Caballero, Otavia L.; Larder, Rachel; Coll, Anthony P.; O’Rahilly, Stephen; Brindle, Kevin M.; Teichmann, Sarah A.; Tuveson, David A.

2013-01-01

Fibroblast activation protein-α (FAP) identifies stromal cells of mesenchymal origin in human cancers and chronic inflammatory lesions. In mouse models of cancer, they have been shown to be immune suppressive, but studies of their occurrence and function in normal tissues have been limited. With a transgenic mouse line permitting the bioluminescent imaging of FAP+ cells, we find that they reside in most tissues of the adult mouse. FAP+ cells from three sites, skeletal muscle, adipose tissue, and pancreas, have highly similar transcriptomes, suggesting a shared lineage. FAP+ cells of skeletal muscle are the major local source of follistatin, and in bone marrow they express Cxcl12 and KitL. Experimental ablation of these cells causes loss of muscle mass and a reduction of B-lymphopoiesis and erythropoiesis, revealing their essential functions in maintaining normal muscle mass and hematopoiesis, respectively. Remarkably, these cells are altered at these sites in transplantable and spontaneous mouse models of cancer-induced cachexia and anemia. Thus, the FAP+ stromal cell may have roles in two adverse consequences of cancer: their acquisition by tumors may cause failure of immunosurveillance, and their alteration in normal tissues contributes to the paraneoplastic syndromes of cachexia and anemia. PMID:23712428

Recovery time course in contractile function of fast and slow skeletal muscle after hindlimb immobilization

NASA Technical Reports Server (NTRS)

Witzmann, F. A.; Kim, D. H.; Fitts, R. H.

1982-01-01

The present study was undertaken to characterize the time course and extent of recovery in the isometric and isotonic contractile properties of fast and slow skeletal muscle following 6 wk of hindlimb immobilization. Female Sprague-Dawley rats were randomly assigned to an immobilized group or a control group. The results of the study show that fast and slow skeletal muscles possess the ability to completely recover normal contractile function following 6 wk of hindlimb immobilization. The rate of recovery is dependent on the fiber type composition of the affected muscle.

Restricting calcium currents is required for correct fiber type specification in skeletal muscle

PubMed Central

Sultana, Nasreen; Dienes, Beatrix; Benedetti, Ariane; Tuluc, Petronel; Szentesi, Peter; Sztretye, Monika; Rainer, Johannes; Hess, Michael W.; Schwarzer, Christoph; Obermair, Gerald J.; Csernoch, Laszlo

2016-01-01

ABSTRACT Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted CaV1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental CaV1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease. PMID:26965373

Eccentric activation and muscle damage: biomechanical and physiological considerations during downhill running.

PubMed Central

Eston, R G; Mickleborough, J; Baltzopoulos, V

1995-01-01

An eccentric muscle activation is the controlled lengthening of the muscle under tension. Functionally, most leg muscles work eccentrically for some part of a normal gait cycle, to support the weight of the body against gravity and to absorb shock. During downhill running the role of eccentric work of the 'anti-gravity' muscles--knee extensors, muscles of the anterior and posterior tibial compartments and hip extensors--is accentuated. The purpose of this paper is to review the relationship between eccentric muscle activation and muscle damage, particularly as it relates to running, and specifically, downhill running. PMID:7551767

Functional heterogeneity of side population cells in skeletal muscle

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

Uezumi, Akiyoshi; Ojima, Koichi; Fukada, So-ichiro

2006-03-17

Skeletal muscle regeneration has been exclusively attributed to myogenic precursors, satellite cells. A stem cell-rich fraction referred to as side population (SP) cells also resides in skeletal muscle, but its roles in muscle regeneration remain unclear. We found that muscle SP cells could be subdivided into three sub-fractions using CD31 and CD45 markers. The majority of SP cells in normal non-regenerating muscle expressed CD31 and had endothelial characteristics. However, CD31{sup -}CD45{sup -} SP cells, which are a minor subpopulation in normal muscle, actively proliferated upon muscle injury and expressed not only several regulatory genes for muscle regeneration but also somemore » mesenchymal lineage markers. CD31{sup -}CD45{sup -} SP cells showed the greatest myogenic potential among three SP sub-fractions, but indeed revealed mesenchymal potentials in vitro. These SP cells preferentially differentiated into myofibers after intramuscular transplantation in vivo. Our results revealed the heterogeneity of muscle SP cells and suggest that CD31{sup -}CD45{sup -} SP cells participate in muscle regeneration.« less

The effect of muscle contraction level on the cervical vestibular evoked myogenic potential (cVEMP): usefulness of amplitude normalization.

PubMed

Bogle, Jamie M; Zapala, David A; Criter, Robin; Burkard, Robert

2013-02-01

The cervical vestibular evoked myogenic potential (cVEMP) is a reflexive change in sternocleidomastoid (SCM) muscle contraction activity thought to be mediated by a saccular vestibulo-collic reflex. CVEMP amplitude varies with the state of the afferent (vestibular) limb of the vestibulo-collic reflex pathway, as well as with the level of SCM muscle contraction. It follows that in order for cVEMP amplitude to reflect the status of the afferent portion of the reflex pathway, muscle contraction level must be controlled. Historically, this has been accomplished by volitionally controlling muscle contraction level either with the aid of a biofeedback method, or by an a posteriori method that normalizes cVEMP amplitude by the level of muscle contraction. A posteriori normalization methods make the implicit assumption that mathematical normalization precisely removes the influence of the efferent limb of the vestibulo-collic pathway. With the cVEMP, however, we are violating basic assumptions of signal averaging: specifically, the background noise and the response are not independent. The influence of this signal-averaging violation on our ability to normalize cVEMP amplitude using a posteriori methods is not well understood. The aims of this investigation were to describe the effect of muscle contraction, as measured by a prestimulus electromyogenic estimate, on cVEMP amplitude and interaural amplitude asymmetry ratio, and to evaluate the benefit of using a commonly advocated a posteriori normalization method on cVEMP amplitude and asymmetry ratio variability. Prospective, repeated-measures design using a convenience sample. Ten healthy adult participants between 25 and 61 yr of age. cVEMP responses to 500 Hz tone bursts (120 dB pSPL) for three conditions describing maximum, moderate, and minimal muscle contraction. Mean (standard deviation) cVEMP amplitude and asymmetry ratios were calculated for each muscle-contraction condition. Repeated measures analysis of variance and t-tests compared the variability in cVEMP amplitude between sides and conditions. Linear regression analyses compared asymmetry ratios. Polynomial regression analyses described the corrected and uncorrected cVEMP amplitude growth functions. While cVEMP amplitude increased with increased muscle contraction, the relationship was not linear or even proportionate. In the majority of cases, once muscle contraction reached a certain "threshold" level, cVEMP amplitude increased rapidly and then saturated. Normalizing cVEMP amplitudes did not remove the relationship between cVEMP amplitude and muscle contraction level. As muscle contraction increased, the normalized amplitude increased, and then decreased, corresponding with the observed amplitude saturation. Abnormal asymmetry ratios (based on values reported in the literature) were noted for four instances of uncorrected amplitude asymmetry at less than maximum muscle contraction levels. Amplitude normalization did not substantially change the number of observed asymmetry ratios. Because cVEMP amplitude did not typically grow proportionally with muscle contraction level, amplitude normalization did not lead to stable cVEMP amplitudes or asymmetry ratios across varying muscle contraction levels. Until we better understand the relationships between muscle contraction level, surface electromyography (EMG) estimates of muscle contraction level, and cVEMP amplitude, the application of normalization methods to correct cVEMP amplitude appears unjustified. American Academy of Audiology.

Vitamin D and muscle function in the elderly: the elixir of youth?

PubMed

Girgis, Christian M

2014-11-01

Circumstantial evidence suggests that vitamin D deficiency may contribute to age-related changes in skeletal muscle. This review discusses recent clinical trials examining effects of vitamin D on muscle function in the elderly, and poses the important question: can vitamin D reverse muscle ageing? Observational studies report an association between vitamin D and muscle atrophy/weakness in elderly subjects. Interventional studies suggest that frail, elderly subjects may benefit from vitamin D supplementation by displaying reduced falls, improved muscle function and increased muscle fibre size. However, meta-analyses do not report convincing effects of vitamin D in the elderly. This may be because of multiple factors including lack of standardized endpoints for muscle function, variable study design and different doses of vitamin D supplementation amongst these studies. The evidence base is therefore inconsistent. Vitamin D deficiency may exacerbate ageing of skeletal muscle. However, current evidence that vitamin D supplementation reverses age-related muscle dysfunction is equivocal and does not justify stringent vitamin D targets in the elderly. Until these issues are clarified, the safest option is to aim for conservative vitamin D targets that are sufficient for normal calcium homeostasis.

Decreased Muscle Strength Relates to Self-Reported Stooping, Crouching, or Kneeling Difficulty in Older Adults

PubMed Central

Goldberg, Allon; Alexander, Neil B.

2010-01-01

Background Bending down and kneeling are fundamental tasks of daily living, yet nearly a quarter of older adults report having difficulty performing or being unable to perform these movements. Older adults with stooping, crouching, or kneeling (SCK) difficulty have demonstrated an increased fall risk. Strength (force-generating capacity) measures may be useful for determining both SCK difficulty and fall risk. Objective The purposes of this study were: (1) to examine muscle strength differences in older adults with and without SCK difficulty and (2) to examine the relative contributions of trunk and leg muscle strength to SCK difficulty. Design This was a cross-sectional observational study. Methods Community-dwelling older adults (age [X̅±SD]=75.5±6.0 years) with SCK difficulty (n=27) or without SCK difficulty (n=21) were tested for leg and trunk strength and functional mobility. Isometric strength at the trunk, hip, knee, and ankle also was normalized by body weight and height. Results Compared with older adults with no SCK difficulty, those with SCK difficulty had significant decreases in normalized trunk extensor, knee extensor, and ankle dorsiflexor and plantar-flexor strength. In 2 separate multivariate analyses, raw ankle plantar-flexor strength (odds ratio [OR]=0.97, 95% confidence interval [CI]=0.95–0.99) and normalized knee extensor strength (OR=0.61, 95% CI=0.44–0.82) were significantly associated with SCK difficulty. Stooping, crouching, and kneeling difficulty also correlated with measures of functional balance and falls. Limitations Although muscle groups that were key to rising from SCK were examined, there are other muscle groups that may contribute to safe SCK performance. Conclusions Decreased muscle strength, particularly when normalized for body size, predicts SCK difficulty. These data emphasize the importance of strength measurement at multiple levels in predicting self-reported functional impairment. PMID:19942678

Evaluating swallowing muscles essential for hyolaryngeal elevation by using muscle functional magnetic resonance imaging.

PubMed

Pearson, William G; Hindson, David F; Langmore, Susan E; Zumwalt, Ann C

2013-03-01

Reduced hyolaryngeal elevation, a critical event in swallowing, is associated with radiation therapy. Two muscle groups that suspend the hyoid, larynx, and pharynx have been proposed to elevate the hyolaryngeal complex: the suprahyoid and longitudinal pharyngeal muscles. Thought to assist both groups is the thyrohyoid, a muscle intrinsic to the hyolaryngeal complex. Intensity modulated radiation therapy guidelines designed to preserve structures important to swallowing currently exclude the suprahyoid and thyrohyoid muscles. This study used muscle functional magnetic resonance imaging (mfMRI) in normal healthy adults to determine whether both muscle groups are active in swallowing and to test therapeutic exercises thought to be specific to hyolaryngeal elevation. mfMRI data were acquired from 11 healthy subjects before and after normal swallowing and after swallowing exercise regimens (the Mendelsohn maneuver and effortful pitch glide). Whole-muscle transverse relaxation time (T2 signal, measured in milliseconds) profiles of 7 test muscles were used to evaluate the physiologic response of each muscle to each condition. Changes in effect size (using the Cohen d measure) of whole-muscle T2 profiles were used to determine which muscles underlie swallowing and swallowing exercises. Post-swallowing effect size changes (where a d value of >0.20 indicates significant activity during swallowing) for the T2 signal profile of the thyrohyoid was a d value of 0.09; a d value of 0.40 for the mylohyoid, 0.80 for the geniohyoid, 0.04 for the anterior digastric, and 0.25 for the posterior digastric-stylohyoid in the suprahyoid muscle group; and d values of 0.47 for the palatopharyngeus and 0.28 for the stylopharyngeus muscles in the longitudinal pharyngeal muscle group. The Mendelsohn maneuver and effortful pitch glide swallowing exercises showed significant effect size changes for all muscles tested, except for the thyrohyoid. Muscles of both the suprahyoid and the longitudinal pharyngeal muscle groups are active in swallowing, and both swallowing exercises effectively target muscles elevating the hyolaryngeal complex. mfMRI is useful in testing swallowing muscle function. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluating Swallowing Muscles Essential for Hyolaryngeal Elevation by Using Muscle Functional Magnetic Resonance Imaging

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

Pearson, William G., E-mail: bp1@bu.edu; Hindson, David F.; Langmore, Susan E.

2013-03-01

Purpose: Reduced hyolaryngeal elevation, a critical event in swallowing, is associated with radiation therapy. Two muscle groups that suspend the hyoid, larynx, and pharynx have been proposed to elevate the hyolaryngeal complex: the suprahyoid and longitudinal pharyngeal muscles. Thought to assist both groups is the thyrohyoid, a muscle intrinsic to the hyolaryngeal complex. Intensity modulated radiation therapy guidelines designed to preserve structures important to swallowing currently exclude the suprahyoid and thyrohyoid muscles. This study used muscle functional magnetic resonance imaging (mfMRI) in normal healthy adults to determine whether both muscle groups are active in swallowing and to test therapeutic exercisesmore » thought to be specific to hyolaryngeal elevation. Methods and Materials: mfMRI data were acquired from 11 healthy subjects before and after normal swallowing and after swallowing exercise regimens (the Mendelsohn maneuver and effortful pitch glide). Whole-muscle transverse relaxation time (T2 signal, measured in milliseconds) profiles of 7 test muscles were used to evaluate the physiologic response of each muscle to each condition. Changes in effect size (using the Cohen d measure) of whole-muscle T2 profiles were used to determine which muscles underlie swallowing and swallowing exercises. Results: Post-swallowing effect size changes (where a d value of >0.20 indicates significant activity during swallowing) for the T2 signal profile of the thyrohyoid was a d value of 0.09; a d value of 0.40 for the mylohyoid, 0.80 for the geniohyoid, 0.04 for the anterior digastric, and 0.25 for the posterior digastric-stylohyoid in the suprahyoid muscle group; and d values of 0.47 for the palatopharyngeus and 0.28 for the stylopharyngeus muscles in the longitudinal pharyngeal muscle group. The Mendelsohn maneuver and effortful pitch glide swallowing exercises showed significant effect size changes for all muscles tested, except for the thyrohyoid. Conclusions: Muscles of both the suprahyoid and the longitudinal pharyngeal muscle groups are active in swallowing, and both swallowing exercises effectively target muscles elevating the hyolaryngeal complex. mfMRI is useful in testing swallowing muscle function.« less

Structural and functional characteristics of the thoracolumbar multifidus muscle in horses.

PubMed

García Liñeiro, J A; Graziotti, G H; Rodríguez Menéndez, J M; Ríos, C M; Affricano, N O; Victorica, C L

2017-03-01

The multifidus muscle fascicles of horses attach to vertebral spinous processes after crossing between one to six metameres. The fascicles within one or two metameres are difficult to distinguish in horses. A vertebral motion segment is anatomically formed by two adjacent vertebrae and the interposed soft tissue structures, and excessive mobility of a vertebral motion segment frequently causes osteoarthropathies in sport horses. The importance of the equine multifidus muscle as a vertebral motion segment stabilizer has been demonstrated; however, there is scant documentation of the structure and function of this muscle. By studying six sport horses postmortem, the normalized muscle fibre lengths of the the multifidus muscle attached to the thoracic (T)4, T9, T12, T17 and lumbar (L)3 vertebral motion segments were determined and the relative areas occupied by fibre types I, IIA and IIX were measured in the same muscles after immunohistochemical typying. The values for the normalized muscle fibre lengths and the relative areas were analysed as completely randomized blocks using an anova (P ≤ 0.05). The vertebral motion segments of the T4 vertebra include multifidus bundles extending between two and eight metameres; the vertebral motion segments of the T9, T12, T17 and L3 vertebrae contain fascicles extending between two and four metameres The muscle fibres with high normalized lengths that insert into the T4 (three and eight metameres) vertebral motion segment tend to have smaller physiological cross-sectional areas, indicating their diminished capacity to generate isometric force. In contrast, the significantly decreased normalized muscle fibre lengths and the increased physiological cross-sectional areas of the fascicles of three metameres with insertions on T9, T17, T12, L3 and the fascicles of four metameres with insertions on L3 increase their capacities to generate isometric muscle force and neutralize excessive movements of the vertebral segments with great mobility. There were no significant differences in the values of relative areas occupied by fibre types I, IIA and IIX. In considering the relative areas occupied by the fibre types in the multifidus muscle fascicles attached to each vertebral motion segment examined, the relative area occupied by the type I fibres was found to be significantly higher in the T4 vertebral motion segment than in the other segments. It can be concluded that the equine multifidus muscle in horses is an immunohistochemically homogeneous muscle with various architectural designs that have functional significance according to the vertebral motion segments considered. The results obtained in this study can serve as a basis for future research aimed at understanding the posture and dynamics of the equine spine. © 2016 Anatomical Society.

Computer-aided mechanogenesis of skeletal muscle organs from single cells in vitro

NASA Technical Reports Server (NTRS)

Vanderburgh, Herman H.; Swasdison, Somporn; Karlisch, Patricia

1991-01-01

Complex mechanical forces generated in the growing embryo play an important role in organogenesis. Computerized application of similar forces to differentiating skeletal muscle myoblasts in vitro generate three dimensional artificial muscle organs. These organs contain parallel networks of long unbranched myofibers organized into fascicle-like structures. Tendon development is initiated and the muscles are capable of performing directed, functional work. Kinetically engineered organs provide a new method for studying the growth and development of normal and diseased skeletal muscle.

Computer aided mechanogenesis of skeletal muscle organs from single cells in vitro

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.; Swasdison, Somporn; Karlisch, Patricia

1990-01-01

Complex mechanical forces generated in the growing embryo play an important role in organogenesis. Computerized application of similar forces to differentiating skeletal muscle myoblasts in vitro generate three dimensional artificial muscle organs. These organs contain parallel networks of long unbranched myofibers organized into fascicle-like structures. Tendon development is initiated and the muscles are capable of performing directed, functional work. Kinetically engineered organs provide a new method for studying the growth and development of normal and diseased skeletal muscle.

Relationships of muscle strength and bone mineral density in ambulatory children with cerebral palsy.

PubMed

Chen, C-L; Lin, K-C; Wu, C-Y; Ke, J-Y; Wang, C-J; Chen, C-Y

2012-02-01

This work explores the relationships of muscle strength and areal bone mineral density (aBMD) in ambulatory children with cerebral palsy (CP). The knee extensor strength, but not motor function, was related to aBMD. Thus, muscle strength, especially antigravity muscle strength, was more associated with aBMD in these children than motor function. Muscle strength is related to bone density in normal children. However, no studies have examined these relationships in ambulatory children with CP. This work explores the relationships of muscle strength and aBMD in ambulatory children with CP. Forty-eight ambulatory children with spastic CP, aged 5-15 years, were classified into two groups based on Gross Motor Function Classification System levels: I (n = 28) and II (n = 20). Another 31 normal development (ND) children were recruited as the comparison group for the aBMD. Children with CP underwent assessments of growth, lumbar and distal femur aBMD, Gross Motor Function Measure-66 (GMFM-66), and muscle strength of knee extensor and flexor by isokinetic dynamometer. The distal femur aBMD, but not lumbar aBMD, was lower in children with CP than in ND children (p < 0.05). Children with level I had greater knee flexor strength and GMFM-66 scores than those with level II (p < 0.001). However, the knee extensor strength and distal femur and lumbar aBMD did not differ between two groups. Regression analysis revealed the weight and knee extensor strength, but not GMFM-66 scores, were related positively to the distal femur and lumbar aBMD (adjusted r (2) = 0.56-0.65, p < 0.001). These results suggest the muscle strength, especially antigravity muscle strength, were more associated with the bone density of ambulatory children with CP than motor function. The data may allow clinicians for early identifying the ambulatory CP children of potential low bone density.

Identification and functional characterization of muscle satellite cells in Drosophila

PubMed Central

Reichert, Heinrich

2017-01-01

Work on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly, however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates. In this study, we show that lineal descendants of muscle stem cells are present in adult muscle of Drosophila as small, unfused cells observed at the surface and in close proximity to the mature muscle fibers. Normally quiescent, following muscle fiber injury, we show that these cells express Zfh1 and engage in Notch-Delta-dependent proliferative activity and generate lineal descendant populations, which fuse with the injured muscle fiber. In view of strikingly similar morphological and functional features, we consider these novel cells to be the Drosophila equivalent of vertebrate muscle satellite cells. PMID:29072161

THE COMPARISON OF THE LUMBAR MULTIFIDUS MUSCLES FUNCTION BETWEEN GYMNASTIC ATHLETES WITH SWAY-BACK POSTURE AND NORMAL POSTURE.

PubMed

Mahdavie, Elnaz; Rezasoltani, Asghar; Simorgh, Leila

2017-08-01

The prevalence of sway back posture (SBP) is very high among elite gymnasts. This posture may be partly due to the improper function of lumbar multifidus muscles (LMM) as lumbar stabilizers muscles. The aim of this study was to compare the thicknesses of LMM measured at rest and during the contraction elicited during an arm lift between elite gymnasts with SBP and normal posture. Observational, descriptive, comparative. The participants consist of twenty gymnasts between the ages of 17 and 30 who had trained in gymnastics for more than ten years. They were assigned to two groups: SBP (n=10) and control (n=10). Posture analysis with grid paper and plumb line was performed for all subjects. The thickness of LMM on dominant side of spinal column was measured by a real-time ultrasound at five lumbar levels. The thickness of the LMM was measured both at rest and during the contraction elicited during an arm lift. The variation between the LMM thickness between the muscle at rest and muscle at the peak of contraction was regarded as LMM muscle function. The thickness of LMM was less in SBP group than the control group at all lumbar segments. The variation in LMM thickness between the state of rest and muscle contraction was significantly less in athletes with SBP than controls when compared at all levels of the lumbar spine (p < 0.05). The function of LMM may be disturbed in athletes with SBP as demonstrated by decreased thicknesses of LMM found in gymnasts with SBP. Additionally, the thickness of the LMM as a strong antigravity and stabilizing muscle group was decreased during arm raising in gymnasts with SBP. 3a.

Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

PubMed

Mitchell, Jere H

2017-06-01

During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

Drosophila small heat shock protein CryAB ensures structural integrity of developing muscles, and proper muscle and heart performance.

PubMed

Wójtowicz, Inga; Jabłońska, Jadwiga; Zmojdzian, Monika; Taghli-Lamallem, Ouarda; Renaud, Yoan; Junion, Guillaume; Daczewska, Malgorzata; Huelsmann, Sven; Jagla, Krzysztof; Jagla, Teresa

2015-03-01

Molecular chaperones, such as the small heat shock proteins (sHsps), maintain normal cellular function by controlling protein homeostasis in stress conditions. However, sHsps are not only activated in response to environmental insults, but also exert developmental and tissue-specific functions that are much less known. Here, we show that during normal development the Drosophila sHsp CryAB [L(2)efl] is specifically expressed in larval body wall muscles and accumulates at the level of Z-bands and around myonuclei. CryAB features a conserved actin-binding domain and, when attenuated, leads to clustering of myonuclei and an altered pattern of sarcomeric actin and the Z-band-associated actin crosslinker Cheerio (filamin). Our data suggest that CryAB and Cheerio form a complex essential for muscle integrity: CryAB colocalizes with Cheerio and, as revealed by mass spectrometry and co-immunoprecipitation experiments, binds to Cheerio, and the muscle-specific attenuation of cheerio leads to CryAB-like sarcomeric phenotypes. Furthermore, muscle-targeted expression of CryAB(R120G), which carries a mutation associated with desmin-related myopathy (DRM), results in an altered sarcomeric actin pattern, in affected myofibrillar integrity and in Z-band breaks, leading to reduced muscle performance and to marked cardiac arrhythmia. Taken together, we demonstrate that CryAB ensures myofibrillar integrity in Drosophila muscles during development and propose that it does so by interacting with the actin crosslinker Cheerio. The evidence that a DRM-causing mutation affects CryAB muscle function and leads to DRM-like phenotypes in the fly reveals a conserved stress-independent role of CryAB in maintaining muscle cell cytoarchitecture. © 2015. Published by The Company of Biologists Ltd.

The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

PubMed

Dorchies, Olivier M; Reutenauer-Patte, Julie; Dahmane, Elyes; Ismail, Heham M; Petermann, Olivier; Patthey- Vuadens, Ophélie; Comyn, Sophie A; Gayi, Elinam; Piacenza, Tony; Handa, Robert J; Décosterd, Laurent A; Ruegg, Urs T

2013-02-01

Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.

Functional evaluation of anterolateral thigh flap donor sites: isokinetic torque comparisons for knee function.

PubMed

Tsuji, Naoko; Suga, Hirotaka; Uda, Koichi; Sugawara, Yasushi

2008-01-01

The anterolateral thigh flap is thought to have minor donor site morbidity, but muscle dissection is unavoidable when skin perforator vessels run through the vastus lateralis muscle. The purpose of this study was to investigate the functional problems associated with the anterolateral thigh flap donor site. We evaluated 12 patients who underwent free anterolateral thigh flap transfer between March 2003 and November 2005. A questionnaire and dynamic functional evaluation of the knee joint using the Biodex System were performed preoperatively and 6 months postoperatively. No patients reported any disturbance in their daily life. No significant differences were found between donor and normal thighs on isokinetic power tests of the quadriceps muscle. The function of the donor site after harvesting the anterolateral thigh flap was maintained. Damage to or functional disturbance of the donor site is minimal even if muscle is injured when harvesting the flap. (c) 2008 Wiley-Liss, Inc. Microsurgery, 2008

Effect of changes of femoral offset on abductor and joint reaction forces in total hip arthroplasty.

PubMed

Rüdiger, Hannes A; Guillemin, Maïka; Latypova, Adeliya; Terrier, Alexandre

2017-11-01

Anatomical reconstruction in total hip arthroplasty (THA) allows for physiological muscle function, good functional outcome and implant longevity. Quantitative data on the effect of a loss or gain of femoral offset (FO) are scarce. The aim of this study was to quantitatively describe the effect of FO changes on abductor moment arms, muscle and joint reactions forces. THA was virtually performed on 3D models built from preoperative CT scans of 15 patients undergoing THA. Virtual THA was performed with a perfectly anatomical reconstruction, a loss of 20% of FO (-FO), and a gain of 20% of FO (+FO). These models were combined with a generic musculoskeletal model (OpenSim) to predict moment arms, muscle and joint reaction forces during normal gait cycles. In average, with -FO reconstructions, muscle moment arms decreased, while muscle and hip forces increased significantly (p < 0.001). We observed the opposite with +FO reconstructions. Gluteus medius was more affected than gluteus minimus. -FO had more effect than +FO. A change of 20% of FO induced an average change 8% of abductor moment arms, 16% of their forces, and 6% of the joint reaction force. To our knowledge, this is the first report providing quantitative data on the effect of FO changes on muscle and joint forces during normal gait. A decrease of FO necessitates an increase of abductor muscle force to maintain normal gait, which in turn increases the joint reaction force. This effect underscores the importance of an accurate reconstruction of the femoral offset.

Low levels of Survival Motor Neuron protein are sufficient for normal muscle function in the SMNΔ7 mouse model of SMA.

PubMed

Iyer, Chitra C; McGovern, Vicki L; Murray, Jason D; Gombash, Sara E; Zaworski, Phillip G; Foust, Kevin D; Janssen, Paul M L; Burghes, Arthur H M

2015-11-01

Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by loss of lower motor neurons. SMA is caused by deletion or mutation of the Survival Motor Neuron 1 (SMN1) gene and retention of the SMN2 gene. The loss of SMN1 results in reduced levels of the SMN protein. SMN levels appear to be particularly important in motor neurons; however SMN levels above that produced by two copies of SMN2 have been suggested to be important in muscle. Studying the spatial requirement of SMN is important in both understanding how SMN deficiency causes SMA and in the development of effective therapies. Using Myf5-Cre, a muscle-specific Cre driver, and the Cre-loxP recombination system, we deleted mouse Smn in the muscle of mice with SMN2 and SMNΔ7 transgenes in the background, thus providing low level of SMN in the muscle. As a reciprocal experiment, we restored normal levels of SMN in the muscle with low SMN levels in all other tissues. We observed that decreasing SMN in the muscle has no phenotypic effect. This was corroborated by muscle physiology studies with twitch force, tetanic and eccentric contraction all being normal. In addition, electrocardiogram and muscle fiber size distribution were also normal. Replacement of Smn in muscle did not rescue SMA mice. Thus the muscle does not appear to require high levels of SMN above what is produced by two copies of SMN2 (and SMNΔ7). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2016-04-01

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

Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction.

PubMed

Eberli, Daniel; Horst, Maya; Mortezavi, Ashkan; Andersson, Karl-Erik; Gobet, Rita; Sulser, Tullio; Simon, Hans-Uwe; Salemi, Souzan

2018-05-24

To explore whether autophagy plays a role in the remodeling of bladder smooth muscle cells (SMCs) in children with neurogenic lower urinary tract dysfunction (NLUTD), we investigated the effect of autophagy in NLUTD in the paediatric population. Bladder biopsies were taken from children with NLUTD and healthy donors as controls. Samples were labeled with the SMC markers calponin, smoothelin, and the autophagy proteins LC3, ATG5, and Beclin1. The contractile ability of bladder derived SMCs was investigated. ATG5 gene and protein was upregulated in NLUTD muscle tissue compared to normal bladder. NLUTD muscle exhibited a punctated immunostaining pattern for LC3 in a subset of the SMCs, confirming the accumulation of autophagosomes. Pronounced elevation of ATG5 in the SMC in NLUTD tissue was associated with a downregulation of the key contractile proteins smoothelin and calponin. Pharmacological blocking of autophagy completely stopped the cells growth in normal bladder SMCs. Inhibition of autophagy in the NLUTD SMCs, with already elevated levels of ATG5, resulted in a reduction of ATG5 protein expression to the basal level found in normal controls. Our study suggests that autophagy is an important factor affecting the remodeling of SMCs and the alteration of functionality in bladder smooth muscle tissue in the NLUTD. Since autophagy can be influenced by oral medication, this finding might lead to novel strategies preventing the deterioration of NLUTD muscle. © 2018 Wiley Periodicals, Inc.

Relationship between PPARα mRNA expression and mitochondrial respiratory function and ultrastructure of the skeletal muscle of patients with COPD.

PubMed

Zhang, Jian-Qing; Long, Xiang-Yu; Xie, Yu; Zhao, Zhi-Huan; Fang, Li-Zhou; Liu, Ling; Fu, Wei-Ping; Shu, Jing-Kui; Wu, Jiang-Hai; Dai, Lu-Ming

2017-11-02

Peripheral muscle dysfunction is an important complication in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to explore the relationship between the levels of peroxisome proliferator-activated receptor α (PPARα) mRNA expression and the respiratory function and ultrastructure of mitochondria in the vastus lateralis of patients with COPD. Vastus lateralis biopsies were performed on 14 patients with COPD and 6 control subjects with normal lung function. PPARα mRNA levels in the muscle tissue were detected by real-time PCR. A Clark oxygen electrode was used to assess mitochondrial respiratory function. Mitochondrial number, fractional area in skeletal muscle cross-sections, and Z-line width were observed via transmission electron microscopy. The PPARα mRNA expression was significantly lower in COPD patients with low body mass index (BMIL) than in both COPD patients with normal body mass index (BMIN) and controls. Mitochondrial respiratory function (assessed by respiratory control ratio) was impaired in COPD patients, particularly in BMIL. Compared with that in the control group, mitochondrial number and fractional area were lower in the BMIL group, but were maintained in the BMIN group. Further, the Z-line became narrow in the BMIL group. PPARα mRNA expression was positively related to mitochondrial respiratory function and volume density. In COPD patients with BMIN, mitochondria volume density was maintained, while respiratory function decreased, whereas both volume density and respiratory function decreased in COPD patients with BMIL. PPARα mRNA expression levels are associated with decreased mitochondrial respiratory function and volume density, which may contribute to muscle dysfunction in COPD patients.

Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens

PubMed Central

Luo, Wen; Lin, Shumao; Li, Guihuan; Nie, Qinghua; Zhang, Xiquan

2016-01-01

The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. PMID:26927061

Evaluation of normal swallowing functions by using dynamic high-density surface electromyography maps.

PubMed

Zhu, Mingxing; Yu, Bin; Yang, Wanzhang; Jiang, Yanbing; Lu, Lin; Huang, Zhen; Chen, Shixiong; Li, Guanglin

2017-11-21

Swallowing is a continuous process with substantive interdependencies among different muscles, and it plays a significant role in our daily life. The aim of this study was to propose a novel technique based on high-density surface electromyography (HD sEMG) for the evaluation of normal swallowing functions. A total of 96 electrodes were placed on the front neck to acquire myoelectric signals from 12 healthy subjects while they were performing different swallowing tasks. HD sEMG energy maps were constructed based on the root mean square values to visualize muscular activities during swallowing. The effects of different volumes, viscosities, and head postures on the normal swallowing process were systemically investigated by using the energy maps. The results showed that the HD sEMG energy maps could provide detailed spatial and temporal properties of the muscle electrical activity, and visualize the muscle contractions that closely related to the swallowing function. The energy maps also showed that the swallowing time and effort was also explicitly affected by the volume and viscosity of the bolus. The concentration of the muscular activities shifted to the opposite side when the subjects turned their head to either side. The proposed method could provide an alternative method to physiologically evaluate the dynamic characteristics of normal swallowing and had the advantage of providing a full picture of how different muscle activities cooperate in time and location. The findings from this study suggested that the HD sEMG technique might be a useful tool for fast screening and objective assessment of swallowing disorders or dysphagia.

Cardiopulmonary fitness and muscle strength in patients with osteogenesis imperfecta type I.

PubMed

Takken, Tim; Terlingen, Heike C; Helders, Paul J M; Pruijs, Hans; Van der Ent, Cornelis K; Engelbert, Raoul H H

2004-12-01

To evaluate cardiopulmonary function, muscle strength, and cardiopulmonary fitness (VO 2 peak) in patients with osteogenesis imperfecta (OI). In 17 patients with OI type I (mean age 13.3 +/- 3.9 years) cardiopulmonary function was assessed at rest using spirometry, plethysmography, electrocardiography, and echocardiography. Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Muscle strength in shoulder abductors, hip flexors, ankle dorsal flexor, and grip strength were measured. All results were compared with reference values. Cardiopulmonary function at rest was within normal ranges, but when it was compared with normal height for age and sex, vital capacities were reduced. Mean absolute and relative VO 2 peak were respectively -1.17 (+/- 0.67) and -1.41 (+/- 1.52) standard deviations lower compared with reference values ( P < .01). Muscle strength also was significantly reduced in patients with OI, ranging from -1.24 +/- 1.40 to -2.88 +/- 2.67 standard deviations lower compared with reference values. In patients with OI type I, no pulmonary or cardiac abnormalities at rest were found. The exercise tolerance and muscle strength were significantly reduced in patients with OI, which might account for their increased levels of fatigue during activities of daily living.

Mapping Interactions between Myosin Relay and Converter Domains That Power Muscle Function*

PubMed Central

Kronert, William A.; Melkani, Girish C.; Melkani, Anju; Bernstein, Sanford I.

2014-01-01

Intramolecular communication within myosin is essential for its function as motor, but the specific amino acid residue interactions required are unexplored within muscle cells. Using Drosophila melanogaster skeletal muscle myosin, we performed a novel in vivo molecular suppression analysis to define the importance of three relay loop amino acid residues (Ile508, Asn509, and Asp511) in communicating with converter domain residue Arg759. We found that the N509K relay mutation suppressed defects in myosin ATPase, in vitro motility, myofibril stability, and muscle function associated with the R759E converter mutation. Through molecular modeling, we define a mechanism for this interaction and suggest why the I508K and D511K relay mutations fail to suppress R759E. Interestingly, I508K disabled motor function and myofibril assembly, suggesting that productive relay-converter interaction is essential for both processes. We conclude that the putative relay-converter interaction mediated by myosin residues 509 and 759 is critical for the biochemical and biophysical function of skeletal muscle myosin and the normal ultrastructural and mechanical properties of muscle. PMID:24627474

HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise.

PubMed

Park, Bong-Sup; Henning, Paul C; Grant, Samuel C; Lee, Won Jun; Lee, Sang-Rok; Arjmandi, Bahram H; Kim, Jeong-Su

2013-12-01

To investigate the efficacy and underlying mechanisms of β-hydroxy-β-methylbutyrate (HMB) on body composition, muscle mass and physical performance under catabolic versus normal training conditions. Mice were divided into four groups (n=10/group): (1) ALT=ad libitum+trained (1 h/d for 3 d/wk); (2) ALTH=ALT+HMB (0.5 g/kg BW/d); (3) C=calorie restricted (-30%)+trained (6 h/d, 6 d/wk); and (4) CH=C+HMB. Repeated in vivo assessments included body composition, grip strength and sensorimotor coordination before and after the experimental protocol, while in vitro analyses included muscle wet weights, expression of selected genes and proteins regulating muscle mass, and myofiber cross-sectional area. ANOVAs were used with significance set at p<0.05. ALTH had greater lean mass than ALT and sensorimotor function increased in ALTH, but decreased in ALT under normal training conditions. Grip strength decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber CSA were greater in CH than C following catabolic conditions. Gastrocnemius atrogin-1 mRNA expression was elevated in C but not in CH compared to all other groups whereas atrogin-1 protein levels showed no significant changes. HMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions. © 2013.

Effects of Combined Spinal-Epidural Analgesia during Labor on Postpartum Electrophysiological Function of Maternal Pelvic Floor Muscle: A Randomized Controlled Trial.

PubMed

Xing, Ji-Juan; Liu, Xiu-Fen; Xiong, Xiao-Ming; Huang, Li; Lao, Cheng-Yi; Yang, Mei; Gao, Shan; Huang, Qiong-Yan; Yang, Wei; Zhu, Yun-Feng; Zhang, Di-Hua

2015-01-01

Combined spinal-epidural analgesia (CSEA) is sometimes used for difficult births, but whether it contributes to postpartum pelvic muscle disorder is unclear. This randomized controlled trial examined whether CSEA given during labor affects the electrophysiological index of postpartum pelvic floor muscle function. A consecutive sample of primiparous women who delivered vaginally at term were randomly assigned to a CSEA group (n = 143) and control group (n = 142) between June 2013 and June 2014. All were assessed 6-8 weeks later for electrophysiological function of pelvic floor muscle. The two groups were similar in the degree of muscle strength, muscle fatigue, and pelvic dynamic pressure of pelvic floor muscle. The CSEA and control groups showed similar proportions of women with normal muscle strength (score ≥4) in type I pelvic fibers (23.1% vs. 14.1%, P = 0.051) and type II pelvic fibers (28.0% vs. 24.6%, P = 0.524). The groups also contained similar proportions of women who showed no fatigue in type I fibers (54.5% vs. 48.6%, P = 0.315) or type II fibers (88.8% vs. 87.3%, P = 0.699). Similarly low proportions of women in the CSEA group and control group showed normal pelvic dynamic pressure (11.2% vs. 7.7%, P = 0.321). However, women in the CSEA group spent significantly less time in labor than those in the control group (7.25 vs. 9.52 h, P <0.001). CSEA did not affect the risk of postpartum pelvic muscle disorder in this cohort of primiparous women who gave birth vaginally. A significant shorter duration of labour was observed in the CSEA-group. ClinicalTrials.gov NCT02334150.

Slow- and fast-twitch rat hind limb skeletal muscle phenotypes 8 months after spinal cord transection and olfactory ensheathing glia transplantation

PubMed Central

Negredo, Pilar; Rivero, José-Luis L; González, Beatriz; Ramón-Cueto, Almudena; Manso, Rafael

2008-01-01

Paralysed skeletal muscle of rats with spinal cord injury (SCI) undergoes atrophy and a switch in gene expression pattern which leads to faster, more fatigable phenotypes. Olfactory ensheathing glia (OEG) transplants have been reported to promote axonal regeneration and to restore sensory-motor function in animals with SCI. We hypothesized that OEG transplants could attenuate skeletal muscle phenotypic deterioration and that this effect could underlie the functional recovery observed in behavioural tests. A variety of morphological, metabolic and molecular markers were assessed in soleus (SOL) and extensor digitorum longus (EDL) muscles of spinal cord transected (SCT), OEG-transplanted rats 8 months after the intervention and compared with non-transplanted SCT rats and sham-operated (without SCT) controls (C). A multivariate analysis encompassing all the parameters indicated that OEG-transplanted rats displayed skeletal muscle phenotypes intermediate between non-transplanted and sham-operated controls, but different from both. A high correlation was observed between behaviourally tested sensory-motor functional capacity and expression level of slow- and fast-twitch hind limb skeletal muscle phenotypic markers, particularly the histochemical glycerol-3-phosphate dehydrogenase activity (−0.843, P < 0.0001) and the fraction of variant 2s of the slow regulatory myosin light chain isoform (0.848, P < 0.0001) in SOL. Despite the mean overall effect of OEG transplants in patterning skeletal muscle protein expression towards normal, in 6 out of 9 animals they appeared insufficient to overcome fibre type switching and to support a consistent and generalized long-term maintenance of normal skeletal muscle characteristics. The interplay of OEG and exercise-mediated neurotrophic actions is a plausible mechanism underlying OEG transplantation effects on paralysed skeletal muscle. PMID:18372308

Effects of Combined Spinal-Epidural Analgesia during Labor on Postpartum Electrophysiological Function of Maternal Pelvic Floor Muscle: A Randomized Controlled Trial

PubMed Central

Xiong, Xiao-Ming; Huang, Li; Lao, Cheng-Yi; Yang, Mei; Gao, Shan; Huang, Qiong-Yan; Yang, Wei; Zhu, Yun-Feng; Zhang, Di-Hua

2015-01-01

Objective Combined spinal-epidural analgesia (CSEA) is sometimes used for difficult births, but whether it contributes to postpartum pelvic muscle disorder is unclear. This randomized controlled trial examined whether CSEA given during labor affects the electrophysiological index of postpartum pelvic floor muscle function. Methods A consecutive sample of primiparous women who delivered vaginally at term were randomly assigned to a CSEA group (n = 143) and control group (n = 142) between June 2013 and June 2014. All were assessed 6–8 weeks later for electrophysiological function of pelvic floor muscle. Results The two groups were similar in the degree of muscle strength, muscle fatigue, and pelvic dynamic pressure of pelvic floor muscle. The CSEA and control groups showed similar proportions of women with normal muscle strength (score ≥4) in type I pelvic fibers (23.1% vs. 14.1%, P = 0.051) and type II pelvic fibers (28.0% vs. 24.6%, P = 0.524). The groups also contained similar proportions of women who showed no fatigue in type I fibers (54.5% vs. 48.6%, P = 0.315) or type II fibers (88.8% vs. 87.3%, P = 0.699). Similarly low proportions of women in the CSEA group and control group showed normal pelvic dynamic pressure (11.2% vs. 7.7%, P = 0.321). However, women in the CSEA group spent significantly less time in labor than those in the control group (7.25 vs. 9.52 h, P <0.001). Conclusions CSEA did not affect the risk of postpartum pelvic muscle disorder in this cohort of primiparous women who gave birth vaginally. A significant shorter duration of labour was observed in the CSEA-group. Trial Registration ClinicalTrials.gov NCT02334150 PMID:26340002

Ultrasound Assessment of the Transverse Abdominis During Functional Movement.

PubMed

Mangum, L Colby; Henderson, Kaitlin; Murray, Kyle P; Saliba, Susan A

2018-05-01

The traditional activation ratio divides contracted muscle thickness by resting muscle thickness while an abdominal draw-in maneuver is performed during hook lying. Ultrasound imaging during function, such as standing or gait, or peak knee flexion in a single-leg squat allows for further visualization of muscle activity. The goal of this study was to examine activation ratio calculations for transverse abdominis function in supine versus loaded conditions to determine the most informative normalization strategy for muscle activity based on thickness values. Transverse abdominis thickness was measured via ultrasound in 35 healthy participants under 4 different conditions. Comparisons were made between the traditional activation ratio tabletop, standing activation ratio (standing abdominal draw-in maneuver thickness/quiet standing thickness), and functional activation ratio (single-leg squat thickness/quiet standing thickness). Additionally, a cued activation ratio (single-leg squat with cued abdominal draw-in maneuver thickness/single-leg squat thickness) during the single-leg squat was obtained. Activation ratios of greater than 1.0 indicated that participants could activate the muscle during activity, and values were compared by analysis of variance. The participants included 23 women and 12 men with a mean age ± SD of 21.3 ± 2.7 years, mass of 66.1 ± 14.4 kg, and height of 168.5 ± 10.1 cm. Activation ratios exceeded 1.0 in 94.3% for the traditional activation ratio, 85.7% for the standing activation ratio, 82.9% for the cued activation ratio, and 82.9% for the functional activation ratio. With groups defined as tabletop activated or not, the standing, cued, and functional activation ratios were all significantly different (all P < .05). Normalizing muscle thickness to the corresponding functional position quiet value provides a useful functional activation ratio and may help clinicians better understand the transverse abdominis role during complex functional tasks. Assessment techniques using various formulas for activation ratios reveal that the muscle functions differently during weight bearing compared to traditional measures. © 2017 by the American Institute of Ultrasound in Medicine.

Optimal Normalization Tests for Muscle Activation of the Levator Scapulae, Pectoralis Minor, and Rhomboid Major: An Electromyography Study Using Maximum Voluntary Isometric Contractions.

PubMed

Castelein, Birgit; Cagnie, Barbara; Parlevliet, Thierry; Danneels, Lieven; Cools, Ann

2015-10-01

To identify maximum voluntary isometric contraction (MVIC) test positions for the deeper-lying scapulothoracic muscles (ie, levator scapulae, pectoralis minor, rhomboid major), and to provide a standard set of a limited number of test positions that generate an MVIC in all scapulothoracic muscles. Cross-sectional study. Physical and rehabilitation medicine department. Healthy subjects (N=21). Not applicable. Mean peak electromyographic activity from levator scapulae, pectoralis minor, and rhomboid major (investigated with fine-wire electromyography) and from upper trapezius, middle trapezius, lower trapezius, and serratus anterior (investigated with surface electromyography) during the performance of 12 different MVICs. The results indicated that various test positions generated similar high mean electromyographic activity and that no single test generated maximum activity for a specific muscle in all subjects. The results of this study support using a series of test positions for normalization procedures rather than a single exercise to increase the likelihood of recruiting the highest activity in the scapulothoracic muscles. A standard set of 5 test positions was identified as being sufficient for generating an MVIC of all scapulothoracic muscles: seated T, seated U 135°, prone T-thumbs up, prone V-thumbs up, and supine V-thumbs up. A standard set of test positions for normalization of scapulothoracic electromyographic data that also incorporates the levator scapulae, pectoralis minor, and rhomboid major muscles is 1 step toward a more comprehensive understanding of normal and abnormal muscle function of these muscles and will help to standardize the presentation of scapulothoracic electromyographic muscle activity. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

NASA Technical Reports Server (NTRS)

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, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

Knee Muscle Strength at Varying Angular Velocities and Associations with Gross Motor Function in Ambulatory Children with Cerebral Palsy

ERIC Educational Resources Information Center

Hong, Wei-Hsien; Chen, Hseih-Ching; Shen, I-Hsuan; Chen, Chung-Yao; Chen, Chia-Ling; Chung, Chia-Ying

2012-01-01

The aim of this study was to evaluate the relationships of muscle strength at different angular velocities and gross motor functions in ambulatory children with cerebral palsy (CP). This study included 33 ambulatory children with spastic CP aged 6-15 years and 15 children with normal development. Children with CP were categorized into level I (n =…

Preserving Healthy Muscle during Weight Loss123

PubMed Central

Cava, Edda; Yeat, Nai Chien; Mittendorfer, Bettina

2017-01-01

Weight loss is the cornerstone of therapy for people with obesity because it can ameliorate or completely resolve the metabolic risk factors for diabetes, coronary artery disease, and obesity-associated cancers. The potential health benefits of diet-induced weight loss are thought to be compromised by the weight-loss–associated loss of lean body mass, which could increase the risk of sarcopenia (low muscle mass and impaired muscle function). The objective of this review is to provide an overview of what is known about weight-loss–induced muscle loss and its implications for overall physical function (e.g., ability to lift items, walk, and climb stairs). The currently available data in the literature show the following: 1) compared with persons with normal weight, those with obesity have more muscle mass but poor muscle quality; 2) diet-induced weight loss reduces muscle mass without adversely affecting muscle strength; 3) weight loss improves global physical function, most likely because of reduced fat mass; 4) high protein intake helps preserve lean body and muscle mass during weight loss but does not improve muscle strength and could have adverse effects on metabolic function; 5) both endurance- and resistance-type exercise help preserve muscle mass during weight loss, and resistance-type exercise also improves muscle strength. We therefore conclude that weight-loss therapy, including a hypocaloric diet with adequate (but not excessive) protein intake and increased physical activity (particularly resistance-type exercise), should be promoted to maintain muscle mass and improve muscle strength and physical function in persons with obesity. PMID:28507015

Velopharyngeal closure and the longus capitis muscle.

PubMed

Yamawaki, Y; Nishimura, Y; Suzuki, Y

1996-09-01

The dynamic mechanism of velopharyngeal function not only in normal individuals but also in patients with velopharyngeal insufficiency, which is mainly related to cleft palate, has been the subject of considerable interest and controversy. Recently, in order to clarify velopharyngeal movement in the valvular action on phonation we examined dynamic MR images of this area taken in the transverse plane in parallel with the muscle sling of levator veli palatini. In cases in whom the closure pattern in that plane is circular, detailed observation revealed a very interesting result; that is, the longus capitis muscle, one of the group of anterior vertebral muscles, is directly involved in velopharyngeal valving function. It has not previously been reported that the longus capitis muscle acts as one of the velopharyngeal closure muscles, in addition to levator veli palatini. The present study demonstrated that contraction of the muscle contributed to velopharyngeal closure by forward movement of the pharyngeal wall.

Development of a nitric oxide-releasing analogue of the muscle relaxant guaifenesin for skeletal muscle satellite cell myogenesis.

PubMed

Wang, Guqi; Burczynski, Frank J; Hasinoff, Brian B; Zhang, Kaidong; Lu, Qilong; Anderson, Judy E

2009-01-01

Nitric oxide (NO) mediates activation of satellite precursor cells to enter the cell cycle. This provides new precursor cells for skeletal muscle growth and muscle repair from injury or disease. Targeting a new drug that specifically delivers NO to muscle has the potential to promote normal function and treat neuromuscular disease, and would also help to avoid side effects of NO from other treatment modalities. In this research, we examined the effectiveness of the NO donor, iosorbide dinitrate (ISDN), and a muscle relaxant, methocarbamol, in promoting satellite cell activation assayed by muscle cell DNA synthesis in normal adult mice. The work led to the development of guaifenesin dinitrate (GDN) as a new NO donor for delivering nitric oxide to muscle. The results revealed that there was a strong increase in muscle satellite cell activation and proliferation, demonstrated by a significant 38% rise in DNA synthesis after a single transdermal treatment with the new compound for 24 h. Western blot and immunohistochemistry analyses showed that the markers of satellite cell myogenesis, expression of myf5, myogenin, and follistatin, were increased after 24 h oral administration of the compound in adult mice. This research extends our understanding of the outcomes of NO-based treatments aimed at promoting muscle regeneration in normal tissue. The potential use of such treatment for conditions such as muscle atrophy in disuse and aging, and for the promotion of muscle tissue repair as required after injury or in neuromuscular diseases such as muscular dystrophy, is highlighted.

Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

PubMed Central

Gokhin, David S.; Lewis, Raymond A.; McKeown, Caroline R.; Nowak, Roberta B.; Kim, Nancy E.; Littlefield, Ryan S.; Lieber, Richard L.

2010-01-01

During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology. PMID:20368620

Morphological variations of papillary muscles in the mitral valve complex in human cadaveric hearts.

PubMed

Gunnal, Sandhya Arvind; Wabale, Rajendra Namdeo; Farooqui, Mujeebuddin Samsamuddin

2013-01-01

Papillary muscle rupture and dysfunction can lead to complications of prolapsed mitral valve and mitral regurgitation. Multiple operative procedures of the papillary muscles, such as resection, repositioning and realignment, are carried out to restore normal physiological function. Therefore, it is important to know both the variations and the normal anatomy of papillary muscles. This study was carried out on 116 human cadaveric hearts. The left ventricles were opened along the left border in order to view the papillary muscles. The number, shape, position and pattern of the papillary muscles were observed. In this series, the papillary muscles were mostly found in groups instead of in twos, as is described in standard textbooks. Four different shapes of papillary muscles were identified - conical, broad-apexed, pyramidal and fan-shaped. We also discovered various patterns of papillary muscles. No two mitral valve complexes have the same architectural arrangement. Each case seems to be unique. Therefore, it is important for scientists worldwide to study the variations in the mitral valve complex in order to ascertain the reason behind each specific architectural arrangement. This will enable cardiothoracic surgeons to tailor the surgical procedures according to the individual papillary muscle pattern.

Human skeletal muscle responses to spaceflight and possible countermeasures

NASA Technical Reports Server (NTRS)

Gollnick, Philip D.; Edgerton, V. Reggie; Saltin, Bengt

1990-01-01

The current status of knowledge concerning the effects of unweighting skeletal muscle is summarized. The results of both ground-based and space-based animal studies are reviewed which show that there is rapid loss in muscle mass, primarily in slow-twitch muscle, of the rat during unweighting of muscle. There is also a shift in the myosin isoforms with muscles such that slow-twitch muscles take on many of the characteristics of fast-twitch muscles. Ground-based studies in human suggest that programs of electrical stimulation can be developed to simulate normal muscular contractions. Attempts to develop countermeasures to the adverse effects of space travel on muscular functions in humans have not been successful to date.

Knockdown of desmin in zebrafish larvae affects interfilament spacing and mechanical properties of skeletal muscle.

PubMed

Li, Mei; Andersson-Lendahl, Monika; Sejersen, Thomas; Arner, Anders

2013-03-01

Skeletal muscle was examined in zebrafish larvae in order to address questions related to the function of the intermediate filament protein desmin and its role in the pathogenesis of human desminopathy. A novel approach including mechanical and structural studies of 4-6-d-old larvae was applied. Morpholino antisense oligonucleotides were used to knock down desmin. Expression was assessed using messenger RNA and protein analyses. Histology and synchrotron light-based small angle x-ray diffraction were applied. Functional properties were analyzed with in vivo studies of swimming behavior and with in vitro mechanical examinations of muscle. The two desmin genes normally expressed in zebrafish could be knocked down by ~50%. This resulted in a phenotype with disorganized muscles with altered attachments to the myosepta. The knockdown larvae were smaller and had diminished swimming activity. Active tension was lowered and muscles were less vulnerable to acute stretch-induced injury. X-ray diffraction revealed wider interfilament spacing. In conclusion, desmin intermediate filaments are required for normal active force generation and affect vulnerability during eccentric work. This is related to the role of desmin in anchoring sarcomeres for optimal force transmission. The results also show that a partial lack of desmin, without protein aggregates, is sufficient to cause muscle pathology resembling that in human desminopathy.

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.

PubMed

Martin, Elizabeth A; Barresi, Rita; Byrne, Barry J; Tsimerinov, Evgeny I; Scott, Bryan L; Walker, Ashley E; Gurudevan, Swaminatha V; Anene, Francine; Elashoff, Robert M; Thomas, Gail D; Victor, Ronald G

2012-11-28

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy

PubMed Central

Martin, Elizabeth A.; Barresi, Rita; Byrne, Barry J.; Tsimerinov, Evgeny I.; Scott, Bryan L.; Walker, Ashley E.; Gurudevan, Swaminatha V.; Anene, Francine; Elashoff, Robert M.; Thomas, Gail D.; Victor, Ronald G.

2013-01-01

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates local α-adrenergic vasoconstriction thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. Here, we report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled cross-over trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation fully restored in the muscles of men with BMD by boosting NO-cGMP signaling with a single dose of the drug tadalafil, a phosphodiesterase (PDE5A) inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD. PMID:23197572

Impaired Organization and Function of Myofilaments in Single Muscle Fibers from a Mouse Model of Pompe Disease

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

Xu, S.; Galperin, M; Melvin, G

Pompe disease, a deficiency of lysosomal acid {alpha}-glucosidase, is a disorder of glycogen metabolism that can affect infants, children, or adults. In all forms of the disease, there is progressive muscle pathology leading to premature death. The pathology is characterized by accumulation of glycogen in lysosomes, autophagic buildup, and muscle atrophy. The purpose of the present investigation was to determine if myofibrillar dysfunction in Pompe disease contributes to muscle weakness beyond that attributed to atrophy. The study was performed on isolated myofibers dissected from severely affected fast glycolytic muscle in the {alpha}-glucosidase knockout mouse model. Psoas muscle fibers were firstmore » permeabilized, so that the contractile proteins could be directly relaxed or activated by control of the composition of the bathing solution. When normalized by cross-sectional area, single fibers from knockout mice produced 6.3 N/cm{sup 2} of maximum Ca{sup 2+}-activated tension compared with 12.0 N/cm{sup 2} produced by wild-type fibers. The total protein concentration was slightly higher in the knockout mice, but concentrations of the contractile proteins myosin and actin remained unchanged. Structurally, X-ray diffraction showed that the actin and myosin filaments, normally arranged in hexagonal arrays, were disordered in the knockout muscle, and a lower fraction of myosin cross bridges was near the actin filaments in the relaxed muscle. The results are consistent with a disruption of actin and myosin interactions in the knockout muscles, demonstrating that impaired myofibrillar function contributes to weakness in the diseased muscle fibers.« less

Dependence of normal development of skeletal muscle in neonatal rats on load bearing

NASA Technical Reports Server (NTRS)

Ohira, Y.; Tanaka, T.; Yoshinaga, T.; Kawano, F.; Nomura, T.; Nonaka, I.; Allen, D. L.; Roy, R. R.; Edgerton, V. R.

2000-01-01

Antigravity function plays an important role in determining the morphological and physiological properties of the neuromuscular system. Inhibition of the normal development of the neuromuscular system is induced by hindlimb unloading during the neonatal period in rats. However, the role of gravitational loading on the development of skeletal muscle in rats is not well understood. It could be hypothesized that during the early postnatal period, i.e. when minimal weight-supporting activity occurs, the activity imposed by gravity would be of little consequence in directing the normal development of the skeletal musculature. We have addressed this issue by limiting the amount of postnatal weight-support activity of the hindlimbs of rats during the lactation period. We have focused on the development of three characteristics of the muscle fibers, i.e. size, myonuclear number and myosin heavy chain expression.

The relationship of choline acetyltransferase activity at the neuromuscular junction to changes in muscle mass and function

PubMed Central

Diamond, Ivan; Franklin, Gary M.; Milfay, Dale

1974-01-01

1. The role of muscle mass and function in the regulation of choline acetyltransferase activity at the neuromuscular junction has been investigated in the rat. 2. Choline acetyltransferase (ChAc) is located in presynaptic nerve terminals and is a specific enzymatic marker of cholinergic innervation in muscle. 3. ChAc activity increased co-ordinately with developmental growth of the soleus muscle. However, another form of muscle growth, work hypertrophy, did not produce an increase in ChAc. 4. Growth arrest of muscle by hypophysectomy did not alter the normal development of ChAc activity, and cortisone-induced muscle atrophy did not reduce ChAc activity in the soleus or plantaris. 5. Tenotomy-induced muscle atrophy provoked a significant fall in ChAc in the soleus and plantaris. 6. The tonic soleus had significantly greater ChAc activity than the phasic plantaris. 7. These observations suggest that muscle mass per se does not influence the development and regulation of ChAc in muscle but that the quality of muscle contraction may modulate enzyme activity. PMID:4818500

[Regulatory mechanism for lncRNAs in skeletal muscle development and progress on its research in domestic animals].

PubMed

Zhou, Rui; Wang, Yi Xin; Long, Ke Ren; Jiang, An An; Jin, Long

2018-04-20

Skeletal muscle is an essential tissue to maintain the normal functions of an organism. It is also closely associated with important economic performance, such as carcass weight, of domestic animals. In recent years, studies using high-throughput sequencing techniques have identified numerous long non-coding RNAs (lncRNAs) with myogenic functions involved in regulation of gene expression at multiple levels, including epigenetic, transcriptional and post-transcriptional regulation. These lncRNAs target myogenic factors, which participate in all processes of skeletal muscle development, including proliferation, migration and differentiation of skeletal muscle stem cells, proliferation, differentiation and fusion of myocytes, muscle hypertrophy and conversion of muscle fiber types. In this review, we summarize the functional roles of lncRNAs in regulation of myogenesis in humans and mice, describe the methods for the analysis of lncRNA function, discuss the progress of lncRNA research in domestic animals, and highlight the current problems and challenges in lncRNA research on livestock production. We hope to provide a useful reference for research on lncRNA in domestic animals, thereby further identifying the molecular regulatory mechanisms in skeletal muscle growth and development.

Motor and sensory function of the esophagus: revelations through ultrasound imaging.

PubMed

Mittal, Ravinder K

2005-04-01

Catheter based high frequency intraluminal ultrasound (HFIUS) imaging is a powerful tool to study esophageal sensory and motor function and dysfunction in vivo in humans. It has provided a number of important insights into the longitudinal muscle function of the esophagus. Based on the ultrasound images and intraluminal pressure recordings, it is clear that there is synchrony in the timing as well as the amplitude of contraction between the circular and the longitudinal muscle layers of the esophagus in normal subjects. On the other hand, in patients with spastic disorders of the esophagus, there is an asynchrony of contraction related to the timing and amplitude of contraction of the two muscle layers during peristalsis. Achalasia, diffuse esophageal spasm, and nutcracker esophagus (spastic motor disorders of the esophagus) are associated with hypertrophy of the circular as well as longitudinal muscle layers. A sustained contraction of the longitudinal muscle of the esophagus is temporally related to chest pain and heartburn and may very well be the cause of symptoms. Longitudinal muscle function of the esophagus can be studied in vivo in humans using dynamic ultrasound imaging. Longitudinal muscle dysfunction appears to be important in the motor and sensory disorders of the esophagus.

Long-term effect of prednisolone on functional blink recovery after transient peripheral facial motor paralysis.

PubMed

VanderWerf, Frans; Reits, Dik; Metselaar, Mick; De Zeeuw, Chris I

2012-03-01

To determine the functional recovery in patients with severe transient peripheral facial motor paralysis (Bell palsy). Prospective controlled trial. Academic medical center. Blink recovery was studied in 2 groups of severely affected Bell palsy patients during a follow-up period of 84 weeks. The patients in one group received prednisolone within the first week after the onset of symptoms. No medication was given to the other group. A control group of healthy subjects was also included. Simultaneous orbicularis oculi muscle activity and eyelid kinematics were recorded by surface electromyographic (EMG) recording and eyelid search coils, respectively. At the beginning of the paralysis, very little integrated orbicularis oculi muscle activity and eyelid movement was measured at the palsied side of the face. Thirteen weeks later, the integrated orbicularis oculi EMG and functional blink recovery gradually improved until 39 weeks. Beyond, only the integrated orbicularis oculi EMG slightly increased. At 84 weeks, the integrated orbicularis oculi EMG was significantly larger in the prednisolone group compared with the control group. The integrated EMG of the nonmedicated group recovered to normal values. Curiously enough, the functional blink recovery at the palsied side remained reduced to 64% compared with the healthy controls in the prednisolone-treated group and to 36% in the nonmedicated group. The authors demonstrate that prednisolone significantly increased the orbicularis oculi muscle activity and significantly improved functional blink recovery in severely affected Bell palsy patients. However, the increase of muscle activity was insufficient to restore functional blinking to normal values.

A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy.

PubMed

Whitehead, Nicholas P; Kim, Min Jeong; Bible, Kenneth L; Adams, Marvin E; Froehner, Stanley C

2015-10-13

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases.

A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy

PubMed Central

Whitehead, Nicholas P.; Kim, Min Jeong; Bible, Kenneth L.; Adams, Marvin E.; Froehner, Stanley C.

2015-01-01

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases. PMID:26417069

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance.

PubMed

Guinan, Emer M; Doyle, S L; Bennett, A E; O'Neill, L; Gannon, J; Elliott, J A; O'Sullivan, J; Reynolds, J V; Hussey, J

2018-05-01

Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.

Effect of α₇ nicotinic acetylcholine receptor agonists and antagonists on motor function in mice.

PubMed

Welch, Kevin D; Pfister, James A; Lima, Flavia G; Green, Benedict T; Gardner, Dale R

2013-02-01

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. Published by Elsevier Inc.

Satellite Cells and the Muscle Stem Cell Niche

PubMed Central

Yin, Hang; Price, Feodor

2013-01-01

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. PMID:23303905

AMPK Agonist AICAR Improves Cognition and Motor Coordination in Young and Aged Mice

ERIC Educational Resources Information Center

Kobilo, Tali; Guerrieri, Davide; Zhang, Yongqing; Collica, Sarah C.; Becker, Kevin G.; van Praag, Henriette

2014-01-01

Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging-associated frailty can preclude physical activity. In young sedentary animals, pharmacological activation of AMP-activated protein kinase (AMPK), a transcriptional regulator important for muscle physiology, enhanced…

Contributions of muscle imbalance and impaired growth to postural and osseous shoulder deformity following brachial plexus birth palsy: a computational simulation analysis.

PubMed

Cheng, Wei; Cornwall, Roger; Crouch, Dustin L; Li, Zhongyu; Saul, Katherine R

2015-06-01

Two potential mechanisms leading to postural and osseous shoulder deformity after brachial plexus birth palsy are muscle imbalance between functioning internal rotators and paralyzed external rotators and impaired longitudinal growth of paralyzed muscles. Our goal was to evaluate the combined and isolated effects of these 2 mechanisms on transverse plane shoulder forces using a computational model of C5-6 brachial plexus injury. We modeled a C5-6 injury using a computational musculoskeletal upper limb model. Muscles expected to be denervated by C5-6 injury were classified as affected, with the remaining shoulder muscles classified as unaffected. To model muscle imbalance, affected muscles were given no resting tone whereas unaffected muscles were given resting tone at 30% of maximal activation. To model impaired growth, affected muscles were reduced in length by 30% compared with normal whereas unaffected muscles remained normal in length. Four scenarios were simulated: normal, muscle imbalance only, impaired growth only, and both muscle imbalance and impaired growth. Passive shoulder rotation range of motion and glenohumeral joint reaction forces were evaluated to assess postural and osseous deformity. All impaired scenarios exhibited restricted range of motion and increased and posteriorly directed compressive glenohumeral joint forces. Individually, impaired muscle growth caused worse restriction in range of motion and higher and more posteriorly directed glenohumeral forces than did muscle imbalance. Combined muscle imbalance and impaired growth caused the most restricted joint range of motion and the highest joint reaction force of all scenarios. Both muscle imbalance and impaired longitudinal growth contributed to range of motion and force changes consistent with clinically observed deformity, although the most substantial effects resulted from impaired muscle growth. Simulations suggest that treatment strategies emphasizing treatment of impaired longitudinal growth are warranted for reducing deformity after brachial plexus birth palsy. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Longitudinal in vivo muscle function analysis of the DMSXL mouse model of myotonic dystrophy type 1.

PubMed

Decostre, Valérie; Vignaud, Alban; Matot, Béatrice; Huguet, Aline; Ledoux, Isabelle; Bertil, Emilie; Gjata, Bernard; Carlier, Pierre G; Gourdon, Geneviève; Hogrel, Jean-Yves

2013-12-01

Myotonic dystrophy is the most common adult muscle dystrophy. In view of emerging therapies, which use animal models as a proof of principle, the development of reliable outcome measures for in vivo longitudinal study of mouse skeletal muscle function is becoming crucial. To satisfy this need, we have developed a device to measure ankle dorsi- and plantarflexion torque in rodents. We present an in vivo 8-month longitudinal study of the contractile properties of the skeletal muscles of the DMSXL mouse model of myotonic dystrophy type 1. Between 4 and 12 months of age, we observed a reduction in muscle strength in the ankle dorsi- and plantarflexors of DMSXL compared to control mice although the strength per muscle cross-section was normal. Mild steady myotonia but no abnormal muscle fatigue was also observed in the DMSXL mice. Magnetic resonance imaging and histological analysis performed at the end of the study showed respectively reduced muscle cross-section area and smaller muscle fibre diameter in DMSXL mice. In conclusion, our study demonstrates the feasibility of carrying out longitudinal in vivo studies of muscle function over several months in a mouse model of myotonic dystrophy confirming the feasibility of this method to test preclinical therapeutics. Copyright © 2013 Elsevier B.V. All rights reserved.

The Effect of Functional Mandibular Shift on the Muscle Spindle Systems in Head-Neck Muscles and the Related Neurotransmitter Histamine.

PubMed

Du, Bing-Li; Li, Jiang-Ning; Guo, Hong-Ming; Li, Song; Liu, Biao

2017-09-01

The aim of this study is to explore the effects of abnormal occlusion and functional recovery caused by functional mandible deviation on the head and neck muscles and muscle spindle sensory-motor system by electrophysiological response and endogenous monoamine neurotransmitters' distribution in the nucleus of the spinal tract. Seven-week-old male Wistar rats were randomly divided into 7 groups: normal control group, 2W experimental control group, 2W functional mandible deviation group, 2W functional mandible deviation recovery group, 4W experimental control group, 4W functional mandible deviation group, 4W functional mandible deviation recovery group. Chewing muscles, digastric muscle, splenius, and trapezius muscle spindles electrophysiological response activities at the opening and closing state were recorded. And then the chewing muscles, digastric, splenius, trapezius, and neck trigeminal nucleus were taken for histidine decarboxylase (HDC) detection by high performance liquid chromatography (HPLC), immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR). Histamine receptor proteins in the neck nucleus of the spinal tract were also examined by immunofluorescence and RT-PCR. Electromyography activity of chewing muscles, digastric, and splenius muscle was significantly asymmetric; the abnormal muscle electromyography activity was mainly detected at the ipsilateral side. After functional mandibular deviation, muscle sensitivity on the ipsilateral sides of the chewing muscle and splenius decreased, muscle excitement weakened, modulation depth decreased, and the muscle spindle afferent impulses of excitation transmission speed slowed down. Changes for digastric muscle electrical activity were contrary. The functions recovered at different extents after removing the deflector. However, trapezius in all the experimental groups and recovery groups exhibited bilateral symmetry electrophysiological responses, and no significant difference compared with the control group. After functional mandibular deviation, HDC protein and messenger ribonucleic acid (mRNA) levels on the ipsilateral sides of the chewing muscle and splenius increased significantly. HDC level changes for digastric muscle were contrary. After the removal of the mandibular position deflector, HDC protein and mRNA levels decreased on the ipsilateral sides of the chewing muscle and splenius while they increased in the digastric muscle. The difference of histamine decarboxylase content in the bilateral trapezius in each experimental group was small. After functional mandibular deviation, the temporomandibular joint mechanical receptors not only caused the fusimotor fiber hypoallergenic fatigue slow response on the ipsilateral sides of splenius, but also increased the injury neurotransmitter histamine release. The authors' results further support the opinion that the temporomandibular joint receptors may be involved in the mechanical theory of the head and neck muscles nervous system regulation.

The effect of subtalar inversion/eversion on the dynamic function of the tibialis anterior, soleus, and gastrocnemius during the stance phase of gait.

PubMed

Wang, Ruoli; Gutierrez-Farewik, Elena M

2011-05-01

The purpose of this study was to determine how gait deviation in one plane (i.e. excessive subtalar inversion/eversion) can affect the dynamic function of the tibialis anterior, gastrocnemius, and soleus to accelerate the subtalar, ankle, knee and hip joints, as well as the body center of mass. Induced acceleration analysis was performed based on a subject-specific three-dimensional linkage model configured by stance phase gait data and driven by one unit of muscle force. Eight healthy adult subjects were examined in gait analysis. The subtalar inversion/eversion was modeled by offsetting up to 20° from the normal subtalar angle while other configurations remained unaltered. This study showed that the gastrocnemius, soleus and tibialis anterior generally functioned as their anatomical definition in normal gait, but counterintuitive function was occasionally found in the bi-articular gastrocnemius. The plantarflexors play important roles in the body support and forward progression. Excessive subtalar eversion was found to enlarge the plantarflexors and tibialis anterior's function. Induced acceleration analysis demonstrated its ability to isolate the contributions of individual muscle to a given factor, and as a means of studying effect of pathological gait on the dynamic muscle functions. Copyright © 2011 Elsevier B.V. All rights reserved.

Innovative strength training-induced neuroplasticity and increased muscle size and strength in children with spastic cerebral palsy: an experimenter-blind case study--three-month follow-up.

PubMed

Lee, Dong Ryul; Kim, Yun Hee; Kim, Dong A; Lee, Jung Ah; Hwang, Pil Woo; Lee, Min Jin; You, Sung Hyun

2014-01-01

In children with cerebral palsy (CP), the never-learned-to-use (NLTU) effect and underutilization suppress the normal development of cortical plasticity in the paretic limb, which further inhibits its functional use and increases associated muscle weakness. To highlight the effects of a novel comprehensive hand repetitive intensive strengthening training system on neuroplastic changes associated with upper extremity (UE) muscle strength and motor performance in children with spastic hemiplegic CP. Two children with spastic hemiplegic CP were recruited. Intervention with the comprehensive hand repetitive intensive strengthening training system was provided for 60 min a day, three times a week, for 10 weeks. Neuroplastic changes, muscle size, strength, and associated motor function were measured using functional magnetic resonance imaging (MRI), ultrasound imaging, and standardized motor tests, respectively. The functional MRI data showed that the comprehensive hand repetitive intensive strengthening training intervention produced measurable neuroplastic changes in the neural substrates associated with motor control and learning. These neuroplastic changes were associated with increased muscle size, strength and motor function. These results provide compelling evidence of neuroplastic changes and associated improvements in muscle size and motor function following innovative upper extremity strengthening exercise.

Impaired Insulin Signaling is Associated with Hepatic Mitochondrial Dysfunction in IR+/−-IRS-1+/− Double Heterozygous (IR-IRS1dh) Mice

PubMed Central

Franko, Andras; Kunze, Alexander; Böse, Marlen; von Kleist-Retzow, Jürgen-Christoph; Paulsson, Mats; Hartmann, Ursula; Wiesner, Rudolf J.

2017-01-01

Mitochondria play a pivotal role in energy metabolism, but whether insulin signaling per se could regulate mitochondrial function has not been identified yet. To investigate whether mitochondrial function is regulated by insulin signaling, we analyzed muscle and liver of insulin receptor (IR)+/−-insulin receptor substrate-1 (IRS-1)+/− double heterozygous (IR-IRS1dh) mice, a well described model for insulin resistance. IR-IRS1dh mice were studied at the age of 6 and 12 months and glucose metabolism was determined by glucose and insulin tolerance tests. Mitochondrial enzyme activities, oxygen consumption, and membrane potential were assessed using spectrophotometric, respirometric, and proton motive force analysis, respectively. IR-IRS1dh mice showed elevated serum insulin levels. Hepatic mitochondrial oxygen consumption was reduced in IR-IRS1dh animals at 12 months of age. Furthermore, 6-month-old IR-IRS1dh mice demonstrated enhanced mitochondrial respiration in skeletal muscle, but a tendency of impaired glucose tolerance. On the other hand, 12-month-old IR-IRS1dh mice showed improved glucose tolerance, but normal muscle mitochondrial function. Our data revealed that deficiency in IR/IRS-1 resulted in normal or even elevated skeletal muscle, but impaired hepatic mitochondrial function, suggesting a direct cross-talk between insulin signaling and mitochondria in the liver. PMID:28556799

Impaired Insulin Signaling is Associated with Hepatic Mitochondrial Dysfunction in IR+/--IRS-1+/- Double Heterozygous (IR-IRS1dh) Mice.

PubMed

Franko, Andras; Kunze, Alexander; Böse, Marlen; von Kleist-Retzow, Jürgen-Christoph; Paulsson, Mats; Hartmann, Ursula; Wiesner, Rudolf J

2017-05-30

Mitochondria play a pivotal role in energy metabolism, but whether insulin signaling per se could regulate mitochondrial function has not been identified yet. To investigate whether mitochondrial function is regulated by insulin signaling, we analyzed muscle and liver of insulin receptor (IR) +/- -insulin receptor substrate-1 (IRS-1) +/- double heterozygous (IR-IRS1dh) mice, a well described model for insulin resistance. IR-IRS1dh mice were studied at the age of 6 and 12 months and glucose metabolism was determined by glucose and insulin tolerance tests. Mitochondrial enzyme activities, oxygen consumption, and membrane potential were assessed using spectrophotometric, respirometric, and proton motive force analysis, respectively. IR-IRS1dh mice showed elevated serum insulin levels. Hepatic mitochondrial oxygen consumption was reduced in IR-IRS1dh animals at 12 months of age. Furthermore, 6-month-old IR-IRS1dh mice demonstrated enhanced mitochondrial respiration in skeletal muscle, but a tendency of impaired glucose tolerance. On the other hand, 12-month-old IR-IRS1dh mice showed improved glucose tolerance, but normal muscle mitochondrial function. Our data revealed that deficiency in IR/IRS-1 resulted in normal or even elevated skeletal muscle, but impaired hepatic mitochondrial function, suggesting a direct cross-talk between insulin signaling and mitochondria in the liver.

The Development of an Accelerometer System for Measuring Pelvic Motion During Walking.

DTIC Science & Technology

1979-01-01

9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT, T ASK AFIT STUDENT AT: University of Oxford CONTROLLING OFFICE NAME AND...bones, joints or muscles and physiotherapy to improve the functioning of impaired lower limbs. When irreparable damage occurs, the normal locomotor system...restoring near normal functioning of the locomotor system. Any improvement in surgical procedures, physiotherapy techniques, orthoses or prostheses

Stem cell antigen-1 in skeletal muscle function.

PubMed

Bernstein, Harold S; Samad, Tahmina; Cholsiripunlert, Sompob; Khalifian, Saami; Gong, Wenhui; Ritner, Carissa; Aurigui, Julian; Ling, Vivian; Wilschut, Karlijn J; Bennett, Stephen; Hoffman, Julien; Oishi, Peter

2013-08-15

Stem cell antigen-1 (Sca-1) is a member of the Ly-6 multigene family encoding highly homologous, glycosyl-phosphatidylinositol-anchored membrane proteins. Sca-1 is expressed on muscle-derived stem cells and myogenic precursors recruited to sites of muscle injury. We previously reported that inhibition of Sca-1 expression stimulated myoblast proliferation in vitro and regulated the tempo of muscle repair in vivo. Despite its function in myoblast expansion during muscle repair, a role for Sca-1 in normal, post-natal muscle has not been thoroughly investigated. We systematically compared Sca-1-/- (KO) and Sca-1+/+ (WT) mice and hindlimb muscles to elucidate the tissue, contractile, and functional effects of Sca-1 in young and aging animals. Comparison of muscle volume, fibrosis, myofiber cross-sectional area, and Pax7+ myoblast number showed little differences between ages or genotypes. Exercise protocols, however, demonstrated decreased stamina in KO versus WT mice, with young KO mice achieving results similar to aging WT animals. In addition, KO mice did not improve with practice, while WT animals demonstrated conditioning over time. Surprisingly, myomechanical analysis of isolated muscles showed that KO young muscle generated more force and experienced less fatigue. However, KO muscle also demonstrated incomplete relaxation with fatigue. These findings suggest that Sca-1 is necessary for muscle conditioning with exercise, and that deficient conditioning in Sca-1 KO animals becomes more pronounced with age.

Why the chameleon has spiral-shaped muscle fibres in its tongue

PubMed Central

Leeuwen, J. L. van

1997-01-01

The intralingual accelerator muscle is the primary actuator for the remarkable ballistic tongue projection of the chameleon. At rest, this muscle envelopes the elongated entoglossal process, a cylindrically shaped bone with a tapering distal end. During tongue projection, the accelerator muscle elongates and slides forward along the entoglossal process until the entire muscle extends beyond the distal end of the process. The accelerator muscle fibres are arranged in transverse planes (small deviations are possible), and form (hitherto unexplained) spiral-shaped arcs from the peripheral to the internal boundary. To initiate tongue projection, the muscle fibres probably generate a high intramuscular pressure. The resulting negative pressure gradient (from base to tip) causes the muscle to elongate and to accelerate forward. Effective forward sliding is made possible by a lubricant and a relatively low normal stress exerted on the proximal cylindrical part of the entoglossal process. A relatively high normal stress is, however, probably required for an effective acceleration of muscle tissue over the tapered end of the process. For optimal performance, the fast extension movement should occur without significant (energy absorbing) torsional motion of the tongue. In addition, the tongue extension movement is aided by a close packing of the muscles fibres (required for a high power density) and a uniform strain and work output in every cross-section of the muscle. A quantitative model of the accelerator muscle was developed that predicts internal muscle fibre arrangements based on the functional requirements above and the physical principle of mechanical stability. The curved shapes and orientations of the muscle fibres typically found in the accelerator muscle were accurately predicted by the model. Furthermore, the model predicts that the reduction of the entoglossal radius towards the tip (and thus the internal radius of the muscle) tends to increase the normal stress on the entoglossal bone.

Skeletal muscle contractile properties in a novel murine model for limb girdle muscular dystrophy 2i.

PubMed

Rehwaldt, Jordan D; Rodgers, Buel D; Lin, David C

2017-12-01

Limb-girdle muscular dystrophy (LGMD) 2i results from mutations in fukutin-related protein and aberrant α-dystroglycan glycosylation. Although this significantly compromises muscle function and ambulation, the comprehensive characteristics of contractile dysfunction are unknown. Therefore, we quantified the in situ contractile properties of the medial gastrocnemius in young adult P448L mice, an affected muscle of a novel model of LGMD2i. Normalized maximal twitch force, tetanic force, and power were significantly smaller in P448L mice, compared with sex-matched, wild-type mice. These differences were consistent with the replacement of contractile fibers by passive tissue. The shape of the active force-length relationships were similar in both groups, regardless of sex, consistent with an intact sarcomeric structure in P448L mice. Passive force-length curves normalized to maximal isometric force were steeper in P448L mice, and passive elements contribute disproportionately more to total contractile force in P448L mice. Sex differences were mostly noted in the force-velocity curves, as normalized values for maximal and optimal velocities were significantly slower in P448L males, compared with wild-type, but not in P448L females. This suggests that the dystrophic phenotype, which may include possible changes in cross-bridge kinetics and fiber-type proportions, progresses more quickly in P448L males. These results together indicate that active force and power generation are compromised in both sexes of P448L mice, while passive forces increase. More importantly, the results identified several functional markers of disease pathophysiology that could aid in developing and assessment of novel therapeutics for LGMD2i and possibly other dystroglycanopathies as well. NEW & NOTEWORTHY Comprehensive assessments of muscle contractile function have, until now, never been performed in an animal model for any dystroglycanopathy. This study suggests that skeletal muscle contractile properties are significantly compromised in a recently developed model for limb-girdle muscular dystrophy 2i, the P448L mouse. It further identifies novel pathological markers of muscle function that are suitable for developing therapeutics and for better understanding of disease pathogenesis.

Strength training in the elderly: effects on risk factors for age-related diseases.

PubMed

Hurley, B F; Roth, S M

2000-10-01

Strength training (ST) is considered a promising intervention for reversing the loss of muscle function and the deterioration of muscle structure that is associated with advanced age. This reversal is thought to result in improvements in functional abilities and health status in the elderly by increasing muscle mass, strength and power and by increasing bone mineral density (BMD). In the past couple of decades, many studies have examined the effects of ST on risk factors for age-related diseases or disabilities. Collectively, these studies indicate that ST in the elderly: (i) is an effective intervention against sarcopenia because it produces substantial increases in the strength, mass, power and quality of skeletal muscle; (ii) can increase endurance performance; (iii) normalises blood pressure in those with high normal values; (iv) reduces insulin resistance; (v) decreases both total and intra-abdominal fat; (vi) increases resting metabolic rate in older men; (vii) prevents the loss of BMD with age; (viii) reduces risk factors for falls; and (ix) may reduce pain and improve function in those with osteoarthritis in the knee region. However, contrary to popular belief, ST does not increase maximal oxygen uptake beyond normal variations, improve lipoprotein or lipid profiles, or improve flexibility in the elderly.

Defective mitochondrial dynamics is an early event in skeletal muscle of an amyotrophic lateral sclerosis mouse model.

PubMed

Luo, Guo; Yi, Jianxun; Ma, Changling; Xiao, Yajuan; Yi, Frank; Yu, Tian; Zhou, Jingsong

2013-01-01

Mitochondria are dynamic organelles that constantly undergo fusion and fission to maintain their normal functionality. Impairment of mitochondrial dynamics is implicated in various neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is an adult-onset neuromuscular degenerative disorder characterized by motor neuron death and muscle atrophy. ALS onset and progression clearly involve motor neuron degeneration but accumulating evidence suggests primary muscle pathology may also be involved. Here, we examined mitochondrial dynamics in live skeletal muscle of an ALS mouse model (G93A) harboring a superoxide dismutase mutation (SOD1(G93A)). Using confocal microscopy combined with overexpression of mitochondria-targeted photoactivatable fluorescent proteins, we discovered abnormal mitochondrial dynamics in skeletal muscle of young G93A mice before disease onset. We further demonstrated that similar abnormalities in mitochondrial dynamics were induced by overexpression of mutant SOD1(G93A) in skeletal muscle of normal mice, indicating the SOD1 mutation drives ALS-like muscle pathology in the absence of motor neuron degeneration. Mutant SOD1(G93A) forms aggregates inside muscle mitochondria and leads to fragmentation of the mitochondrial network as well as mitochondrial depolarization. Partial depolarization of mitochondrial membrane potential in normal muscle by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) caused abnormalities in mitochondrial dynamics similar to that in the SOD1(G93A) model muscle. A specific mitochondrial fission inhibitor (Mdivi-1) reversed the SOD1(G93A) action on mitochondrial dynamics, indicating SOD1(G93A) likely promotes mitochondrial fission process. Our results suggest that accumulation of mutant SOD1(G93A) inside mitochondria, depolarization of mitochondrial membrane potential and abnormal mitochondrial dynamics are causally linked and cause intrinsic muscle pathology, which occurs early in the course of ALS and may actively promote ALS progression.

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

PubMed

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 incontinence.

Ultrasound evaluation of foot muscles and plantar fascia in pes planus.

PubMed

Angin, Salih; Crofts, Gillian; Mickle, Karen J; Nester, Christopher J

2014-01-01

Multiple intrinsic and extrinsic soft tissue structures that apply forces and support the medial longitudinal arch have been implicated in pes planus. These structures have common functions but their interaction in pes planus is not fully understood. The aim of this study was to compare the cross-sectional area (CSA) and thickness of the intrinsic and extrinsic foot muscles and plantar fascia thickness between normal and pes planus feet. Forty-nine adults with a normal foot posture and 49 individuals with pes planus feet were recruited from a university population. Images of the flexor digitorum longus (FDL), flexor hallucis longus (FHL), peroneus longus and brevis (PER), flexor hallucis brevis (FHB), flexor digitorum brevis (FDB) and abductor hallucis (AbH) muscles and the plantar fascia were obtained using a Venue 40 ultrasound system with a 5-13 MHz transducer. The CSA and thickness of AbH, FHB and PER muscles were significantly smaller (AbH -12.8% and -6.8%, FHB -8.9% and -7.6%, PER -14.7% and -10%), whilst FDL (28.3% and 15.2%) and FHL (24% and 9.8%) were significantly larger in the pes planus group. The middle (-10.6%) and anterior (-21.7%) portions of the plantar fascia were thinner in pes planus group. Greater CSA and thickness of the extrinsic muscles might reflect compensatory activity to support the MLA if the intrinsic foot muscle function has been compromised by altered foot structure. A thinner plantar fascia suggests reduced load bearing, and regional variations in structure and function in feet with pes planus. Copyright © 2014 Elsevier B.V. All rights reserved.

Long-term Effects of Combat Ready Clamp Application to Control Junctional Hemorrhage in Swine

DTIC Science & Technology

2014-01-01

wounds were equally affected in the CRoC-treated and control groups and showed only normal regenerative changes. Muscle (peroneus tertius) fiber ...full function in 3 days ( p 0.001). At 2 weeks, muscle strength of CRoC-applied legs was diminished ( p G 0.05 vs. baselines or controls). Injury...necrosis of lumbar muscles with significant disabilities. CONCLUSION: Two-hour inguinal application of CRoC caused mild and reversible ischemic injuries

Sarcoplasmic reticulum function in slow- and fast-twitch skeletal muscles from mdx mice.

PubMed

Divet, Alexandra; Huchet-Cadiou, Corinne

2002-08-01

The aim of the present study was to establish whether alterations in sarcoplasmic reticulum function are involved in the abnormal Ca(2+) homeostasis of skeletal muscle in mice with muscular dystrophy ( mdx). The properties of the sarcoplasmic reticulum and contractile proteins of fast- and slow-twitch muscles were therefore investigated in chemically skinned fibres isolated from the extensor digitorum longus (EDL) and soleus muscles of normal (C57BL/10) and mdx mice at 4 and 11 weeks of development. Sarcoplasmic reticulum Ca(2+) uptake, estimated by the Ca(2+) release following exposure to caffeine, was significantly slower in mdx mice, while the maximal Ca(2+) quantity did not differ in either type of skeletal muscle at either stage of development. In 4-week-old mice spontaneous sarcoplasmic reticulum Ca(2+) leakage was observed in EDL and soleus fibres and this was more pronounced in mdx mice. In addition, the maximal Ca(2+)-activated tension was smaller in mdx than in normal fibres, while the Ca(2+) sensitivity of the contractile apparatus was not significantly different. These results indicate that mdx hindlimb muscles are affected differently by the disease process and suggest that a reduced ability of the Ca(2+)-ATPase to load Ca(2+) and a leaky sarcoplasmic reticulum membrane may be involved in the altered intracellular Ca(2+) homeostasis.

Neurotrophin expression and laryngeal muscle pathophysiology following recurrent laryngeal nerve transection

PubMed Central

WANG, BAOXIN; YUAN, JUNJIE; XU, JIAFENG; XIE, JIN; WANG, GUOLIANG; DONG, PIN

2016-01-01

Laryngeal palsy often occurs as a result of recurrent laryngeal or vagal nerve injury during oncological surgery of the head and neck, affecting quality of life and increasing economic burden. Reinnervation following recurrent laryngeal nerve (RLN) injury is difficult despite development of techniques, such as neural anastomosis, nerve grafting and creation of a laryngeal muscle pedicle. In the present study, due to the limited availability of human nerve tissue for research, a rat model was used to investigate neurotrophin expression and laryngeal muscle pathophysiology in RLN injury. Twenty-five male Sprague-Dawley rats underwent right RLN transection with the excision of a 5-mm segment. Vocal fold movements, vocalization, histology and immunostaining were evaluated at different time-points (3, 6, 10 and 16 weeks). Although vocalization was restored, movement of the vocal fold failed to return to normal levels following RLN injury. The expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor differed in the thyroarytenoid (TA) and posterior cricoarytenoid muscles. The number of axons did not increase to baseline levels over time. Furthermore, normal muscle function was unlikely with spontaneous reinnervation. During regeneration following RLN injury, differences in the expression levels of neurotrophic factors may have resulted in preferential reinnervation of the TA muscles. Data from the present study indicated that neurotrophic factors may be applied for restoring the function of the laryngeal nerve following recurrent injury. PMID:26677138

Neurotrophin expression and laryngeal muscle pathophysiology following recurrent laryngeal nerve transection.

PubMed

Wang, Baoxin; Yuan, Junjie; Xu, Jiafeng; Xie, Jin; Wang, Guoliang; Dong, Pin

2016-02-01

Laryngeal palsy often occurs as a result of recurrent laryngeal or vagal nerve injury during oncological surgery of the head and neck, affecting quality of life and increasing economic burden. Reinnervation following recurrent laryngeal nerve (RLN) injury is difficult despite development of techniques, such as neural anastomosis, nerve grafting and creation of a laryngeal muscle pedicle. In the present study, due to the limited availability of human nerve tissue for research, a rat model was used to investigate neurotrophin expression and laryngeal muscle pathophysiology in RLN injury. Twenty-five male Sprague-Dawley rats underwent right RLN transection with the excision of a 5-mm segment. Vocal fold movements, vocalization, histology and immunostaining were evaluated at different time-points (3, 6, 10 and 16 weeks). Although vocalization was restored, movement of the vocal fold failed to return to normal levels following RLN injury. The expression of brain‑derived neurotrophic factor and glial cell line-derived neurotrophic factor differed in the thyroarytenoid (TA) and posterior cricoarytenoid muscles. The number of axons did not increase to baseline levels over time. Furthermore, normal muscle function was unlikely with spontaneous reinnervation. During regeneration following RLN injury, differences in the expression levels of neurotrophic factors may have resulted in preferential reinnervation of the TA muscles. Data from the present study indicated that neurotrophic factors may be applied for restoring the function of the laryngeal nerve following recurrent injury.

Treatment with a nitric oxide-donating NSAID alleviates functional muscle ischemia in the mouse model of Duchenne muscular dystrophy.

PubMed

Thomas, Gail D; Ye, Jianfeng; De Nardi, Claudio; Monopoli, Angela; Ongini, Ennio; Victor, Ronald G

2012-01-01

In patients with Duchenne muscular dystrophy (DMD) and the standard mdx mouse model of DMD, dystrophin deficiency causes loss of neuronal nitric oxide synthase (nNOSμ) from the sarcolemma, producing functional ischemia when the muscles are exercised. We asked if functional muscle ischemia would be eliminated and normal blood flow regulation restored by treatment with an exogenous nitric oxide (NO)-donating drug. Beginning at 8 weeks of age, mdx mice were fed a standard diet supplemented with 1% soybean oil alone or in combination with a low (15 mg/kg) or high (45 mg/kg) dose of HCT 1026, a NO-donating nonsteroidal anti-inflammatory agent which has previously been shown to slow disease progression in the mdx model. After 1 month of treatment, vasoconstrictor responses to intra-arterial norepinephrine (NE) were compared in resting and contracting hindlimbs. In untreated mdx mice, the usual effect of muscle contraction to attenuate NE-mediated vasoconstriction was impaired, resulting in functional ischemia: NE evoked similar decreases in femoral blood flow velocity and femoral vascular conductance (FVC) in the contracting compared to resting hindlimbs (ΔFVC contraction/ΔFVC rest=0.88 ± 0.03). NE-induced functional ischemia was unaffected by low dose HCT 1026 (ΔFVC ratio=0.92 ± 0.04; P>0.05 vs untreated), but was alleviated by the high dose of the drug (ΔFVC ratio=0.22 ± 0.03; P<0.05 vs untreated or low dose). The beneficial effect of high dose HCT 1026 was maintained with treatment up to 3 months. The effect of the NO-donating drug HCT 1026 to normalize blood flow regulation in contracting mdx mouse hindlimb muscles suggests a putative novel treatment for DMD. Further translational research is warranted.

Long-term effects of systemic gene therapy in a canine model of myotubular myopathy.

PubMed

Elverman, Matthew; Goddard, Melissa A; Mack, David; Snyder, Jessica M; Lawlor, Michael W; Meng, Hui; Beggs, Alan H; Buj-Bello, Ana; Poulard, Karine; Marsh, Anthony P; Grange, Robert W; Kelly, Valerie E; Childers, Martin K

2017-11-01

X-linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of the protein myotubularin, results from mutations in the MTM1 gene. While there is no cure for XLMTM, we previously reported effects of MTM1 gene therapy using adeno-associated virus (AAV) vector on muscle weakness and pathology in MTM1-mutant dogs. Here, we followed 2 AAV-infused dogs over 4 years. We evaluated gait, strength, respiration, neurological function, muscle pathology, AAV vector copy number (VCN), and transgene expression. Four years following AAV-mediated gene therapy, gait, respiratory performance, neurological function and pathology in AAV-infused XLMTM dogs remained comparable to their healthy littermate controls despite a decline in VCN and muscle strength. AAV-mediated gene transfer of MTM1 in young XLMTM dogs results in long-term expression of myotubularin transgene with normal muscular performance and neurological function in the absence of muscle pathology. These findings support a clinical trial in patients. Muscle Nerve 56: 943-953, 2017. © 2017 Wiley Periodicals, Inc.

Muscle strength and endurance following lowerlimb suspension in man

NASA Technical Reports Server (NTRS)

Tesch, Per A.; Berg, Hans E.; Haggmark, Tom; Ohlsen, Hans; Dudley, Gary A.

1991-01-01

The effect of lower-limb suspension on the muscle strength and muscle endurance was investigated in six men subjected to four weeks of unilateral unloading of a lower limb (using of a harness attached to a modified shoe), followed by seven weeks of weight-bearing recovery. Results showed a decrease in the cross-sectional area (CSA) of the thigh muscle and in the average peak torque (APT) during three bouts of 30 concentric knee extensions. While the the thigh muscle CSA returned to normal after seven weeks of recovery, the APT recovery was still reduced by 11 percent, suggesting that muscle metabolic function was severely affected by unloading and was not restored by ambulation.

Greater understanding of normal hip physical function may guide clinicians in providing targeted rehabilitation programmes.

PubMed

Kemp, Joanne L; Schache, Anthony G; Makdissi, Michael; Sims, Kevin J; Crossley, Kay M

2013-07-01

This study investigated tests of hip muscle strength and functional performance. The specific objectives were to: (i) establish intra- and inter-rater reliability; (ii) compare differences between dominant and non-dominant limbs; (iii) compare agonist and antagonist muscle strength ratios; (iv) compare differences between genders; and (v) examine relationships between hip muscle strength, baseline measures and functional performance. Reliability study and cross-sectional analysis of hip strength and functional performance. In healthy adults aged 18-50years, normalised hip muscle peak torque and functional performance were evaluated to: (i) establish intra-rater and inter-rater reliability; (ii) analyse differences between limbs, between antagonistic muscle groups and genders; and (iii) associations between strength and functional performance. Excellent reliability (intra-rater ICC=0.77-0.96; inter-rater ICC=0.82-0.95) was observed. No difference existed between dominant and non-dominant limbs. Differences in strength existed between antagonistic pairs of muscles: hip abduction was greater than adduction (p<0.001) and hip ER was greater than IR (p<0.001). Men had greater ER strength (p=0.006) and hop for distance (p<0.001) than women. Strong associations were observed between measures of hip muscle strength (except hip flexion) and age, height, and functional performance. Deficits in hip muscle strength or functional performance may influence hip pain. In order to provide targeted rehabilitation programmes to address patient-specific impairments, and determine when individuals are ready to return to physical activity, clinicians are increasingly utilising tests of hip strength and functional performance. This study provides a battery of reliable, clinically applicable tests which can be used for these purposes. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model.

PubMed

Isaacs, Jonathan; Feher, Joseph; Shall, Mary; Vota, Scott; Fox, Michael A; Mallu, Satya; Razavi, Ashkon; Friebe, Ilvy; Shah, Sagar; Spita, Nathalie

2013-10-01

Suboptimal recovery following repair of major peripheral nerves has been partially attributed to denervation atrophy. Administration of anabolic steroids in conjunction with neurotization may improve functional recovery of chronically denervated muscle. The purpose of this study was to evaluate the effect of the administration of nandrolone on muscle recovery following prolonged denervation in a rat model. Eight groups of female Sprague-Dawley rats (15 rats per group, 120 in all) were divided into 3- or 6-month denervated hind limb and sham surgery groups and, then, nandrolone treatment groups and sham treatment groups. Evaluation of treatment effects included nerve conduction, force of contraction, comparative morphology, histology (of muscle fibers), protein electrophoresis (for muscle fiber grouping), and immunohistochemical evaluation. Although a positive trend was noted, neither reinnervated nor normal muscle showed a statistically significant increase in peak muscle force following nandrolone treatment. Indirect measures, including muscle mass (weight and diameter), muscle cell size, muscle fiber type, and satellite cell counts, all failed to support significant anabolic effect. There does not seem to be a functional benefit from nandrolone treatment following reinnervation of either mild or moderately atrophic muscle (related to prolonged denervation) in a rodent model.

Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

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

Zhang, Pengpeng; Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907

Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor{sup flox/flox} mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leadsmore » to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor{sup flox/flox} mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.« less

Cardiac Electrophysiology: Normal and Ischemic Ionic Currents and the ECG

ERIC Educational Resources Information Center

Klabunde, Richard E.

2017-01-01

Basic cardiac electrophysiology is foundational to understanding normal cardiac function in terms of rate and rhythm and initiation of cardiac muscle contraction. The primary clinical tool for assessing cardiac electrical events is the electrocardiogram (ECG), which provides global and regional information on rate, rhythm, and electrical…

Correlation between cardiac remodelling, function, and myocardial contractility in rat hearts 5 weeks after myocardial infarction.

PubMed

Gosselin, H; Qi, X; Rouleau, J L

1998-01-01

Early after infarction, ventricular dysfunction occurs as a result of loss of myocardial tissue. Although papillary muscle studies suggest that reduced myocardial contractility contributes to this ventricular dysfunction, in vivo studies indicate that at rest, cardiac output is normal or near normal, suggesting that contractility of the remaining viable myocardium of the ventricular wall is preserved. However, this has never been verified. To explore this further, 100 rats with various-sized myocardial infarctions had ventricular function assessed by Langendorff preparation or by isolated papillary muscle studies 5 weeks after infarction. Morphologic studies were also done. Rats with large infarctions (54%) had marked ventricular dilatation (dilatation index from 0.23 to 0.75, p < 0.01) and papillary muscle dysfunction (total tension from 6.7 to 3.2 g/mm2, p < 0.01) but only moderate left ventricular dysfunction (maximum developed tension from 206 to 151 mmHg (1 mmHg = 133.3 Pa), p < 0.01), a decrease less than one would expect with an infarct size of 54%. The contractility of the remaining viable myocardium of the ventricle was also moderately depressed (peak systolic midwall stress 91 to 60 mmHg, p < 0.01). Rats with moderate infarctions (32%) had less marked but still moderate ventricular dilatation (dilatation index 0.37, p < 0.001) and moderate papillary muscle dysfunction (total tension 4.2 g/mm2, p < 0.01). However, their decrease in ventricular function was only mild (maximum developed pressure 178 mmHg, p < 0.01) and less than one would expect with an infarct size of 32%. The remaining viable myocardium of the ventricular wall appeared to have normal contractility (peak systolic midwall stress = 86 mmHg, ns). We conclude that in this postinfarction model, in large myocardial infarctions, a loss of contractility of the remaining viable myocardium of the ventricular wall occurs as early as 5 weeks after infarction and that papillary muscle studies slightly overestimate the degree of ventricular dysfunction. In moderate infarctions, the remaining viable myocardium of the ventricular wall has preserved contractility while papillary muscle function is depressed. In this relatively early postinfarction phase, ventricular remodelling appears to help maintain left ventricular function in both moderate and large infarctions.

Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fibers, and at neuromuscular junctions.

PubMed

Askanas, V; Engel, W K; Alvarez, R B; McFerrin, J; Broccolini, A

2000-07-01

Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer disease brain. A distinct feature of s-IBM pathology is specific vacuolar degeneration of muscle fibers characterized by intracellular amyloid inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies of s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn was strongly immunoreactive at the postsynaptic region of the neuromuscular junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating and necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study provides the first demonstration that alpha-syn participates in normal and pathologic processes of human muscle. Therefore. its function is not exclusive to the brain and neurodegenerative diseases.

Reactive oxygen species and calcium signals in skeletal muscle: A crosstalk involved in both normal signaling and disease.

PubMed

Espinosa, Alejandra; Henríquez-Olguín, Carlos; Jaimovich, Enrique

2016-09-01

Reactive Oxygen Species (ROS) have been profusely studied as agents of potential damage to living cells and they have been related to a number of pathological processes. Increasing evidence points to a more positive role of ROS in cell signaling and the detailed mechanism that regulates the precise amount of ROS needed for cell functioning without the deleterious effects of excess ROS still needs to be resolved in detail. In skeletal muscle the main source of ROS during normal functioning appears to be NADPH oxidase 2 (NOX2), which is activated by electrical stimuli (or exercise) through a cascade of events that include ATP release through pannexin1 channels. NOX2 is a protein complex that assembles in the T-tubule membrane before activation and ROS production by NOX2 appears to be important for muscle adaptation through gene expression and mitochondrial biogenesis as well as for improving glucose transport after insulin action. Excess ROS production (or diminished antioxidant defenses) plays a role in a number of pathological processes in skeletal muscle. Together with increased reactive nitrogen species, an increase in ROS appears to have a deleterious role in a model of Duchenne muscular dystrophy as well as muscle wasting in other diseases such as aging sarcopenia and cancer cachexia. In addition, ROS is involved in obesity and muscle insulin resistance, both of which are causally related to type 2 diabetes. A detailed description of the fine-tuning of ROS (including all sources of ROS) in skeletal muscle in health and disease will significantly contribute to our knowledge of both muscle adaptation and muscle related pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

PubMed

Todman, M G; Baines, R A; Stebbings, L A; Davies, J A; Bacon, J P

1999-01-01

Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.

Dual AAV therapy ameliorates exercise-induced muscle injury and functional ischemia in murine models of Duchenne muscular dystrophy.

PubMed

Zhang, Yadong; Yue, Yongping; Li, Liang; Hakim, Chady H; Zhang, Keqing; Thomas, Gail D; Duan, Dongsheng

2013-09-15

Neuronal nitric oxide synthase (nNOS) membrane delocalization contributes to the pathogenesis of Duchenne muscular dystrophy (DMD) by promoting functional muscle ischemia and exacerbating muscle injury during exercise. We have previously shown that supra-physiological expression of nNOS-binding mini-dystrophin restores normal blood flow regulation and prevents functional ischemia in transgenic mdx mice, a DMD model. A critical next issue is whether systemic dual adeno-associated virus (AAV) gene therapy can restore nNOS-binding mini-dystrophin expression and mitigate muscle activity-related functional ischemia and injury. Here, we performed systemic gene transfer in mdx and mdx4cv mice using a pair of dual AAV vectors that expressed a 6 kb nNOS-binding mini-dystrophin gene. Vectors were packaged in tyrosine mutant AAV-9 and co-injected (5 × 10(12) viral genome particles/vector/mouse) via the tail vein to 1-month-old dystrophin-null mice. Four months later, we observed 30-50% mini-dystrophin positive myofibers in limb muscles. Treatment ameliorated histopathology, increased muscle force and protected against eccentric contraction-induced injury. Importantly, dual AAV therapy successfully prevented chronic exercise-induced muscle force drop. Doppler hemodynamic assay further showed that therapy attenuated adrenergic vasoconstriction in contracting muscle. Our results suggest that partial transduction can still ameliorate nNOS delocalization-associated functional deficiency. Further evaluation of nNOS binding mini-dystrophin dual AAV vectors is warranted in dystrophic dogs and eventually in human patients.

Neural and Muscular Contributions to the Age-Related Reductions in Rapid Strength.

PubMed

Gerstner, Gena R; Thompson, Brennan J; Rosenberg, Joseph G; Sobolewski, Eric J; Scharville, Michael J; Ryan, Eric D

2017-07-01

The purposes of this study were to investigate the age-related differences in absolute and normalized plantarflexion rate of torque development (RTD) at early (0-50 ms) and late (100-200 ms) time intervals and to examine specific neural and muscular mechanisms contributing to these differences. Thirty-two young (20.0 ± 2.1 yr) and 20 older (69.5 ± 3.3 yr) recreationally active men performed rapid plantarflexion isometric muscle actions to examine absolute and normalized RTD and muscle activation using EMG at early and late time intervals. Ultrasonography was used to examine medial gastrocnemius muscle size, echo intensity (EI), and muscle architecture (fascicle length [FL] and pennation angle [PA]). The older men were weaker (23.9%, P < 0.001) and had lower later absolute and normalized RTD (P = 0.001-0.034) variables when compared with the young men. The older men also had higher EI (P < 0.001), smaller PA (P = 0.004), and lower later EMG amplitude values (P = 0.009-0.046). However, there were no differences in early RTD and EMG amplitude values, muscle size, or FL between groups (P = 0.097-0.914). Lower late RTD values were related to higher EI, smaller PA, and lower EMG amplitude values (r = -0.28-0.59, P = 0.001-0.044); however, late RTD values were no longer related to PA after normalizing to peak torque. Age-related alterations in muscle quality (EI), architecture, and muscle activation may influence rapid torque production at late time intervals (≥100 ms) from contraction onset. These findings highlight specific neuromuscular factors that influence the age-related reductions in RTD, which has been shown to significantly influence function and performance in older adults.

[Study on the 3D mathematical mode of the muscle groups applied to human mandible by a linear programming method].

PubMed

Wang, Dongmei; Yu, Liniu; Zhou, Xianlian; Wang, Chengtao

2004-02-01

Four types of 3D mathematical mode of the muscle groups applied to the human mandible have been developed. One is based on electromyography (EMG) and the others are based on linear programming with different objective function. Each model contains 26 muscle forces and two joint forces, allowing simulation of static bite forces and concomitant joint reaction forces for various bite point locations and mandibular positions. In this paper, the method of image processing to measure the position and direction of muscle forces according to 3D CAD model was built with CT data. Matlab optimization toolbox is applied to solve the three modes based on linear programming. Results show that the model with an objective function requiring a minimum sum of the tensions in the muscles is reasonable and agrees very well with the normal physiology activity.

Continued Expression of Neonatal Myosin Heavy Chain in Adult Dystrophic Skeletal Muscle

NASA Astrophysics Data System (ADS)

Bandman, Everett

1985-02-01

The expression of myosin heavy chain isoforms was examined in normal and dystrophic chicken muscle with a monoclonal antibody specific for neonatal myosin. Adult dystrophic muscle continued to contain neonatal myosin long after it disappeared from adult normal muscle. A new technique involving western blotting and peptide mapping demonstrated that the immunoreactive myosin in adult dystrophic muscle was identical to that found in neonatal normal muscle. Immunocytochemistry revealed that all fibers in the dystrophic muscle failed to repress neonatal myosin heavy chain. These studies suggest that muscular dystrophy inhibits the myosin gene switching that normally occurs during muscle maturation.

[Muscle regeneration in mdx mouse, and a trial of normal myoblast transfer into regenerating dystrophic muscle].

PubMed

Takemitsu, M; Arahata, K; Nonaka, I

1990-10-01

The most ideal therapeutic trial on Duchenne muscular dystrophy (DMD) is a transfer of normal myoblasts into dystrophic muscle which has been attempted on animal models in several institutes. In the process of muscle regeneration, the transferred normal myoblasts are expected to incorporate into the regenerating fibers in host dystrophic mouse. To know the capacity of muscle regeneration in dystrophic muscle, we compared the regenerating process of the normal muscle with that of the dystrophic muscle after myonecrosis induced by 0.25% bupivacaine hydrochloride (BPVC) chronologically. In the present study, C57BL/10ScSn-mdx (mdx) mouse was used as an animal model of DMD and C57BL/10ScSn (B10) mouse as a control. There was no definite difference in the behavior of muscle fiber regeneration between normal and dystrophic muscles. The dystrophic muscle regenerated rapidly at the similar tempo to the normal as to their size and fiber type differentiation. The variation in fiber size diameter of dystrophic muscle, however, was more obvious than that of normal. To promote successful myoblast transfer from B10 mouse into dystrophic mdx mouse at higher ratio, cultured normal myoblasts were transferred into the regenerating dystrophic muscle on the first and the second day after myonecrosis induced by BPVC. Two weeks after the myoblast injection, the muscles were examined with immunohistochemical stain using anti dystrophin antibody. Although dystrophin-positive fibers appeared in dystrophic muscle, the positive fibers were unexpectedly small in number (3.86 +/- 1.50%).(ABSTRACT TRUNCATED AT 250 WORDS)

Factors that influence muscle shear modulus during passive stretch.

PubMed

Koo, Terry K; Hug, François

2015-09-18

Although elastography has been increasingly used for evaluating muscle shear modulus associated with age, sex, musculoskeletal, and neurological conditions, its physiological meaning is largely unknown. This knowledge gap may hinder data interpretation, limiting the potential of using elastography to gain insights into muscle biomechanics in health and disease. We derived a mathematical model from a widely-accepted Hill-type passive force-length relationship to gain insight about the physiological meaning of resting shear modulus of skeletal muscles under passive stretching, and validated the model by comparing against the ex-vivo animal data reported in our recent work (Koo et al. 2013). The model suggested that resting shear modulus of a slack muscle is a function of specific tension and parameters that govern the normalized passive muscle force-length relationship as well as the degree of muscle anisotropy. The model also suggested that although the slope of the linear shear modulus-passive force relationship is primarily related to muscle anatomical cross-sectional area (i.e. the smaller the muscle cross-sectional area, the more the increase in shear modulus to result in the same passive muscle force), it is also governed by the normalized passive muscle force-length relationship and the degree of muscle anisotropy. Taken together, although muscle shear modulus under passive stretching has a strong linear relationship with passive muscle force, its actual value appears to be affected by muscle's mechanical, material, and architectural properties. This should be taken into consideration when interpreting the muscle shear modulus values. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling length-tension properties of RCPm muscles during voluntary retraction of the head.

PubMed

Hallgren, Richard C

2014-08-01

Head retraction exercises are one of several commonly used clinical tools that are used to assess and treat patients with head and neck pain and to aid in restoration of a normal neutral head posture. Retraction of the head results in flexion of the occipitoatlantal (OA) joint and stretching of rectus capitis posterior minor (RCPm) muscles. The role that retraction of the head might have in treating head and neck pain patients is currently unknown. RCPm muscles arise from the posterior tubercle of the posterior arch of C1 and insert into the occipital bone inferior to the inferior nuchal line and lateral to the midline. RCPm muscles are the only muscles that attach to the posterior arch of C1. The functional role of RCPm muscles has not been clearly defined. The goal of this project was to develop a three-dimensional, computer-based biomechanical model of the posterior aspect of the OA joint. This model should help clarify why voluntary head retraction exercises seem to contribute to the resolution of head and neck pain and restoration of a normal head posture in some patients. The model documents that length-tension properties of RCPm muscles are significantly affected by variations in the physical properties of the musculotendonous unit. The model suggests that variations in the cross sectional area of RCPm muscles due to pathologies that weaken the muscle, such as muscle atrophy, may reduce the ability of these muscles to generate levels of force that are necessary for the performance of normal, daily activities. The model suggests that the main benefit of the initial phase of head retraction exercises may be to strengthen RCPm muscles through eccentric contractions, and that the main benefit of the final phase of retraction may be to stretch the muscles as the final position is held. Copyright © 2014 Elsevier Ltd. All rights reserved.

Naked mole-rats maintain healthy skeletal muscle and Complex IV mitochondrial enzyme function into old age

PubMed Central

Stoll, Elizabeth A; Karapavlovic, Nevena; Rosa, Hannah; Woodmass, Michael; Rygiel, Karolina; White, Kathryn; Turnbull, Douglass M; Faulkes, Chris G

2016-01-01

The naked mole-rat (NMR) Heterocephalus glaber is an exceptionally long-lived rodent, living up to 32 years in captivity. This extended lifespan is accompanied by a phenotype of negligible senescence, a phenomenon of very slow changes in the expected physiological characteristics with age. One of the many consequences of normal aging in mammals is the devastating and progressive loss of skeletal muscle, termed sarcopenia, caused in part by respiratory enzyme dysfunction within the mitochondria of skeletal muscle fibers. Here we report that NMRs avoid sarcopenia for decades. Muscle fiber integrity and mitochondrial ultrastructure are largely maintained in aged animals. While mitochondrial Complex IV expression and activity remains stable, Complex I expression is significantly decreased. We show that aged naked mole-rat skeletal muscle tissue contains some mitochondrial DNA rearrangements, although the common mitochondrial DNA deletions associated with aging in human and other rodent skeletal muscles are not present. Interestingly, NMR skeletal muscle fibers demonstrate a significant increase in mitochondrial DNA copy number. These results have intriguing implications for the role of mitochondria in aging, suggesting Complex IV, but not Complex I, function is maintained in the long-lived naked mole rat, where sarcopenia is avoided and healthy muscle function is maintained for decades. PMID:27997359

Surgical and conservative methods for restoring impaired motor function - facial nerve, spinal accessory nerve, hypoglossal nerve (not including vagal nerve or swallowing)

PubMed Central

Laskawi, R.; Rohrbach, S.

2005-01-01

The present review gives a survey of rehabilitative measures for disorders of the motor function of the mimetic muscles (facial nerve), and muscles innervated by the spinal accessory and hypoglossal nerves. The dysfunction can present either as paralysis or hyperkinesis (hyperkinesia). Conservative and surgical treatment options aimed at restoring normal motor function and correcting the movement disorders are described. Static reanimation techniques are not dealt with. The final section describes the use of botulinum toxin in the therapy of dysphagia. PMID:22073058

Effects of aging on mitochondrial function in skeletal muscle of American Quarter Horses

PubMed Central

Li, Chengcheng; White, Sarah H.; Warren, Lori K.

2016-01-01

Skeletal muscle function, aerobic capacity, and mitochondrial (Mt) function have been found to decline with age in humans and rodents. However, not much is known about age-related changes in Mt function in equine skeletal muscle. Here, we compared fiber-type composition and Mt function in gluteus medius and triceps brachii muscle between young (age 1.8 ± 0.1 yr, n = 24) and aged (age 17-25 yr, n = 10) American Quarter Horses. The percentage of myosin heavy chain (MHC) IIX was lower in aged compared with young muscles (gluteus, P = 0.092; triceps, P = 0.012), while the percentages of MHC I (gluteus; P < 0.001) and MHC IIA (triceps; P = 0.023) were increased. Mass-specific Mt density, indicated by citrate synthase activity, was unaffected by age in gluteus, but decreased in aged triceps (P = 0.023). Cytochrome-c oxidase (COX) activity per milligram tissue and per Mt unit decreased with age in gluteus (P < 0.001 for both) and triceps (P < 0.001 and P = 0.003, respectively). Activity of 3-hydroxyacyl-CoA dehydrogenase per milligram tissue was unaffected by age, but increased per Mt unit in aged gluteus and triceps (P = 0.023 and P < 0.001, respectively). Mt respiration of permeabilized muscle fibers per milligram tissue was unaffected by age in both muscles. Main effects of age appeared when respiration was normalized to Mt content, with increases in LEAK, oxidative phosphorylation capacity, and electron transport system capacity (P = 0.038, P = 0.045, and P = 0.007, respectively), independent of muscle. In conclusion, equine skeletal muscle aging was accompanied by a shift in fiber-type composition, decrease in Mt density and COX activity, but preserved Mt respiratory function. PMID:27283918

The microprotein Minion controls cell fusion and muscle formation

PubMed Central

Zhang, Qiao; Vashisht, Ajay A.; O'Rourke, Jason; Corbel, Stéphane Y; Moran, Rita; Romero, Angelica; Miraglia, Loren; Zhang, Jia; Durrant, Eric; Schmedt, Christian; Sampath, Srinath C.; Sampath, Srihari C.

2017-01-01

Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, their function remains to be determined. Skeletal muscle development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process. Here we report the identification of Minion (microprotein inducer of fusion), a smORF encoding an essential skeletal muscle specific microprotein. Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally and demonstrate a marked reduction in fused muscle fibres. The fusogenic activity of Minion is conserved in the human orthologue, and co-expression of Minion and the transmembrane protein Myomaker is sufficient to induce cellular fusion accompanied by rapid cytoskeletal rearrangement, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component programme for the induction of mammalian cell fusion. Moreover, these data also significantly expand the known functions of smORF-encoded microproteins. PMID:28569745

Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization

NASA Technical Reports Server (NTRS)

Fitts, R. H.; Brimmer, C. J.

1985-01-01

The effect of three-month hindlimb immobilization (IM) in rats on contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus, and fast-twitch superficial region of the vastus lateralis were measured after 0, 14, 28, 60, and 90 days of recovery on excized, horizontally suspended muscles stimulated electrically to maximal twitch tension. IM caused decreases in muscle-to-body weight ratios for all muscles, with no complete recovery even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than those of the slow-twitch SOL. The SOL isometric twitch duration was shortened, due to reduced contraction and half-relaxation time, both of which returned to control levels after 14 days of recovery. The peak tetanic tension, P(O), g/sq cm,, decreased with IM by 46 percent in the SOL, but recovered by the 28th day. The maximum shortening velocity was not altered by IM in any of the muscles. Thus, normal contractile function could recover after prolonged limb IM.

Prolonged central motor conduction time of lower limb muscle in spinocerebellar ataxia 6.

PubMed

Chen, Jen-Tse; Lin, Yung-Yang; Lee, Yi-Chung; Soong, Bing-Wen; Wu, Zin-An; Liao, Kwong-Kum

2004-05-01

We investigated the function of corticospinal tract in spinocerebellar ataxia 6 (SCA6) by measuring the central motor conduction time (CMCT). Motor evoked potentials (MEP) of tibialis anterior (TA) muscle were elicited by magnetic stimulation to motor cortex and spinal cord in 9 SCA6 patients and 10 normal height- and age-matched subjects. CMCT in lower limb of SCA6 patients (18.1+/-1.9 ms) was significantly prolonged than that of the normal subjects (15.0+/-1.0 ms) ((p < 0.001). The prolonged CMCT was well correlated with the duration of disease (p = 0.005), but MEP amplitudes and stimulation intensities were not significantly different. These results indicate that the corticospinal tract function is also impaired and correlate with the disease duration in SCA6.

Magnesium and the Athlete.

PubMed

Volpe, Stella Lucia

2015-01-01

Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation in the body. It is a required mineral that is involved in more than 300 metabolic reactions in the body. Magnesium helps maintain normal nerve and muscle function, heart rhythm (cardiac excitability), vasomotor tone, blood pressure, immune system, bone integrity, and blood glucose levels and promotes calcium absorption. Because of magnesium's role in energy production and storage, normal muscle function, and maintenance of blood glucose levels, it has been studied as an ergogenic aid for athletes. This article will cover the general roles of magnesium, magnesium requirements, and assessment of magnesium status as well as the dietary intake of magnesium and its effects on exercise performance. The research articles cited were limited from those published in 2003 through 2014.

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

PubMed Central

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 simulation of muscle packages. PMID:26114955

Detailed characterization of a long-term rodent model of critical illness and recovery.

PubMed

Hill, Neil E; Saeed, Saima; Phadke, Rahul; Ellis, Matthew J; Chambers, Darren; Wilson, Duncan R; Castells, Josiane; Morel, Jerome; Freysennet, Damien G; Brett, Stephen J; Murphy, Kevin G; Singer, Mervyn

2015-03-01

To characterize a long-term model of recovery from critical illness, with particular emphasis on cardiorespiratory, metabolic, and muscle function. Randomized controlled animal study. University research laboratory. Male Wistar rats. Intraperitoneal injection of the fungal cell wall constituent, zymosan or n-saline. Following intervention, rats were followed for up to 2 weeks. Animals with zymosan peritonitis reached a clinical and biochemical nadir on day 2. Initial reductions were seen in body weight, total body protein and fat, and muscle mass. Leg muscle fiber diameter remained subnormal at 14 days with evidence of persisting myonecrosis, even though gene expression of regulators of muscle mass (e.g., MAFbx, MURF1, and myostatin) had peaked on days 2-4 but normalized by day 7. Treadmill exercise capacity, forelimb grip strength, and in vivo maximum tetanic force were also reduced. Food intake was minimal until day 4 but increased thereafter. This did not relate to appetite hormone levels with early (6 hr) rises in plasma insulin and leptin followed by persisting subnormal levels; ghrelin levels did not change. Serum interleukin-6 level peaked at 6 hours but had normalized by day 2, whereas interleukin-10 remained persistently elevated and high-density lipoprotein cholesterol persistently depressed. There was an early myocardial depression and rise in core temperature, yet reduced oxygen consumption and respiratory exchange ratio with a loss of diurnal rhythmicity that showed a gradual but incomplete recovery by day 7. This detailed physiological, metabolic, hormonal, functional, and histological muscle characterization of a model of critical illness and recovery reproduces many of the findings reported in human critical illness. It can be used to assess putative therapies that may attenuate loss, or enhance recovery, of muscle mass and function.

Role of microtubules in the contractile dysfunction of hypertrophied myocardium

NASA Technical Reports Server (NTRS)

Zile, M. R.; Koide, M.; Sato, H.; Ishiguro, Y.; Conrad, C. H.; Buckley, J. M.; Morgan, J. P.; Cooper, G. 4th

1999-01-01

OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles

PubMed Central

Valdez, Gregorio; Tapia, Juan C.; Lichtman, Jeff W.; Fox, Michael A.; Sanes, Joshua R.

2012-01-01

Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to change. A third set of muscles, including several muscles of facial expression and the external anal sphinter, succumb to aging but not until the third postnatal year. We asked whether susceptible and resistant muscles differed in rostrocaudal or proximodistal position, source of innervation, motor unit size, or fiber type composition. Of these factors, muscle innervation by brainstem motor neurons correlated best with resistance to age-related decline. Finally, we compared synaptic alterations in normally aging muscles to those in a mouse model of amyotrophic lateral sclerosis (ALS). Patterns of resistance and susceptibility were strikingly correlated in the two conditions. Moreover, damage to NMJs in aged muscles correlated with altered expression and distribution of CRMP4a and TDP-43, which are both altered in motor neurons affected by ALS. Together, these results reveal novel structural, regional and molecular parallels between aging and ALS. PMID:22485182

Utility of Cystatin C to monitor renal function in Duchenne muscular dystrophy

PubMed Central

Viollet, Laurence; Gailey, Susan; Thornton, David J.; Friedman, Neil R.; Flanigan, Kevin M.; Mahan, John D.; Mendell, Jerry R.

2009-01-01

Introduction: Creatinine as a marker of renal function has limited value in Duchenne muscular dystrophy (DMD) because of reduced muscle mass. Alternative methods of assessing renal function are sorely needed. Cystatin C, a nonglycosylated protein unaffected by muscle mass, is potentially an ideal biomarker of nephrotoxicity for this population but requires validation. Methods: 75 subjects were recruited: 35 DMD (mean age 10.8 ± 5.4 years, corticosteroids n = 19, ambulatory n = 26), 29 healthy controls, 10 with renal disease, and one DMD with renal failure. Results: Cystatin C levels in DMD were normal irrespective of age, ambulation or corticosteroid treatment. Serum cystatin C was 0.67 ± 0.11 mg/L compared to normal controls 0.69 ± 0.09. mg/L. In these same individuals serum creatinine was severely reduced (0.27 ± 0.12 mg/dL) versus normals (0.75 ± 0.15 mg/dL, p < 0.01). In one DMD subject in renal failure, cystatin C was elevated. Discussion: This study demonstrates the potential value of cystatin C as a biomarker for monitoring renal function in DMD. Its applicability extends to other neuromuscular diseases. PMID:19623638

Daily Supplementation of D-ribose Shows No Therapeutic Benefits in the MHC-I Transgenic Mouse Model of Inflammatory Myositis

PubMed Central

Coley, William; Rayavarapu, Sree; van der Meulen, Jack H.; Duba, Ayyappa S.; Nagaraju, Kanneboyina

2013-01-01

Background Current treatments for idiopathic inflammatory myopathies (collectively called myositis) focus on the suppression of an autoimmune inflammatory response within the skeletal muscle. However, it has been observed that there is a poor correlation between the successful suppression of muscle inflammation and an improvement in muscle function. Some evidence in the literature suggests that metabolic abnormalities in the skeletal muscle underlie the weakness that continues despite successful immunosuppression. We have previously shown that decreased expression of a purine nucleotide cycle enzyme, adenosine monophosphate deaminase (AMPD1), leads to muscle weakness in a mouse model of myositis and may provide a mechanistic basis for muscle weakness. One of the downstream metabolites of this pathway, D-ribose, has been reported to alleviate symptoms of myalgia in patients with a congenital loss of AMPD1. Therefore, we hypothesized that supplementing exogenous D-ribose would improve muscle function in the mouse model of myositis. We treated normal and myositis mice with daily doses of D-ribose (4 mg/kg) over a 6-week time period and assessed its effects using a battery of behavioral, functional, histological and molecular measures. Results Treatment with D-ribose was found to have no statistically significant effects on body weight, grip strength, open field behavioral activity, maximal and specific forces of EDL, soleus muscles, or histological features. Histological and gene expression analysis indicated that muscle tissues remained inflamed despite treatment. Gene expression analysis also suggested that low levels of the ribokinase enzyme in the skeletal muscle might prevent skeletal muscle tissue from effectively utilizing D-ribose. Conclusions Treatment with daily oral doses of D-ribose showed no significant effect on either disease progression or muscle function in the mouse model of myositis. PMID:23785461

Daily supplementation of D-ribose shows no therapeutic benefits in the MHC-I transgenic mouse model of inflammatory myositis.

PubMed

Coley, William; Rayavarapu, Sree; van der Meulen, Jack H; Duba, Ayyappa S; Nagaraju, Kanneboyina

2013-01-01

Current treatments for idiopathic inflammatory myopathies (collectively called myositis) focus on the suppression of an autoimmune inflammatory response within the skeletal muscle. However, it has been observed that there is a poor correlation between the successful suppression of muscle inflammation and an improvement in muscle function. Some evidence in the literature suggests that metabolic abnormalities in the skeletal muscle underlie the weakness that continues despite successful immunosuppression. We have previously shown that decreased expression of a purine nucleotide cycle enzyme, adenosine monophosphate deaminase (AMPD1), leads to muscle weakness in a mouse model of myositis and may provide a mechanistic basis for muscle weakness. One of the downstream metabolites of this pathway, D-ribose, has been reported to alleviate symptoms of myalgia in patients with a congenital loss of AMPD1. Therefore, we hypothesized that supplementing exogenous D-ribose would improve muscle function in the mouse model of myositis. We treated normal and myositis mice with daily doses of D-ribose (4 mg/kg) over a 6-week time period and assessed its effects using a battery of behavioral, functional, histological and molecular measures. Treatment with D-ribose was found to have no statistically significant effects on body weight, grip strength, open field behavioral activity, maximal and specific forces of EDL, soleus muscles, or histological features. Histological and gene expression analysis indicated that muscle tissues remained inflamed despite treatment. Gene expression analysis also suggested that low levels of the ribokinase enzyme in the skeletal muscle might prevent skeletal muscle tissue from effectively utilizing D-ribose. Treatment with daily oral doses of D-ribose showed no significant effect on either disease progression or muscle function in the mouse model of myositis.

Myosin Va Plays a Role in Nitrergic Smooth Muscle Relaxation in Gastric Fundus and Corpora Cavernosa of Penis

PubMed Central

Carew, Josephine A.; Goyal, Raj K.; Sullivan, Maryrose P.

2014-01-01

The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction. PMID:24516539

Caspase-12 ablation preserves muscle function in the mdx mouse

PubMed Central

Moorwood, Catherine; Barton, Elisabeth R.

2014-01-01

Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin. Several downstream consequences of dystrophin deficiency are triggers of endoplasmic reticulum (ER) stress, including loss of calcium homeostasis, hypoxia and oxidative stress. During ER stress, misfolded proteins accumulate in the ER lumen and the unfolded protein response (UPR) is triggered, leading to adaptation or apoptosis. We hypothesized that ER stress is heightened in dystrophic muscles and contributes to the pathology of DMD. We observed increases in the ER stress markers BiP and cleaved caspase-4 in DMD patient biopsies, compared with controls, and an increase in multiple UPR pathways in muscles of the dystrophin-deficient mdx mouse. We then crossed mdx mice with mice null for caspase-12, the murine equivalent of human caspase-4, which are resistant to ER stress. We found that deleting caspase-12 preserved mdx muscle function, resulting in a 75% recovery of both specific force generation and resistance to eccentric contractions. The compensatory hypertrophy normally found in mdx muscles was normalized in the absence of caspase-12; this was found to be due to decreased fibre sizes, and not to a fibre type shift or a decrease in fibrosis. Fibre central nucleation was not significantly altered in the absence of caspase-12, but muscle fibre degeneration found in the mdx mouse was reduced almost to wild-type levels. In conclusion, we have identified heightened ER stress and abnormal UPR signalling as novel contributors to the dystrophic phenotype. Caspase-4 is therefore a potential therapeutic target for DMD. PMID:24879640

Correction of the enzymatic and functional deficits in a model of Pompe disease using adeno-associated virus vectors.

PubMed

Fraites, Thomas J; Schleissing, Mary R; Shanely, R Andrew; Walter, Glenn A; Cloutier, Denise A; Zolotukhin, Irene; Pauly, Daniel F; Raben, Nina; Plotz, Paul H; Powers, Scott K; Kessler, Paul D; Byrne, Barry J

2002-05-01

Pompe disease is a lysosomal storage disease caused by the absence of acid alpha-1,4 glucosidase (GAA). The pathophysiology of Pompe disease includes generalized myopathy of both cardiac and skeletal muscle. We sought to use recombinant adeno-associated virus (rAAV) vectors to deliver functional GAA genes in vitro and in vivo. Myotubes and fibroblasts from Pompe patients were transduced in vitro with rAAV2-GAA. At 14 days postinfection, GAA activities were at least fourfold higher than in their respective untransduced controls, with a 10-fold increase observed in GAA-deficient myotubes. BALB/c and Gaa(-/-) mice were also treated with rAAV vectors. Persistent expression of vector-derived human GAA was observed in BALB/c mice up to 6 months after treatment. In Gaa(-/-) mice, intramuscular and intramyocardial delivery of rAAV2-Gaa (carrying the mouse Gaa cDNA) resulted in near-normal enzyme activities. Skeletal muscle contractility was partially restored in the soleus muscles of treated Gaa(-/-) mice, indicating the potential for vector-mediated restoration of both enzymatic activity and muscle function. Furthermore, intramuscular treatment with a recombinant AAV serotype 1 vector (rAAV1-Gaa) led to nearly eight times normal enzymatic activity in Gaa(-/-) mice, with concomitant glycogen clearance as assessed in vitro and by proton magnetic resonance spectroscopy.

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

PubMed

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

2016-12-01

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

Normal reference values of strength in pelvic floor muscle of women: a descriptive and inferential study.

PubMed

Chevalier, Francine; Fernandez-Lao, Carolina; Cuesta-Vargas, Antonio Ignacio

2014-11-25

To describe the clinical, functional and quality of life characteristics in women with Stress Urinary Incontinence (SUI). In addition, to analyse the relationship between the variables reported by the patients and those informed by the clinicians, and the relationship between instrumented variables and the manual pelvic floor strength assessment. Two hundred and eighteen women participated in this observational, analytical study. An interview about Urinary Incontinence and the quality of life questionnaires (EuroQoL-5D and SF-12) were developed as outcomes reported by the patients. Manual muscle testing and perineometry as outcomes informed by the clinician were assessed. Descriptive and correlation analysis were carried out. The average age of the subjects was (39.93 ± 12.27 years), (24.49 ± 3.54 BMI). The strength evaluated by manual testing of the right levator ani muscles was 7.79 ± 2.88, the strength of left levator ani muscles was 7.51 ± 2.91 and the strength assessed with the perineometer was 7.64 ± 2.55. A positive correlation was found between manual muscle testing and perineometry of the pelvic floor muscles (p < .001). No correlation was found between outcomes of quality of life reported by the patients and outcomes of functional capacity informed by the physiotherapist. A stratification of the strength of pelvic floor muscles in a normal distribution of a large sample of women with SUI was done, which provided the clinic with a baseline. There is a relationship between the strength of the pelvic muscles assessed manually and that obtained by a perineometer in women with SUI. There was no relationship between these values of strength and quality of life perceived.

Severe rhabdomyolysis and acute renal failure in an adolescent with hypothyroidism.

PubMed

Comak, Elif; Koyun, Mustafa; Kiliçarslan-Akkaya, Bahar; Bircan, Iffet; Akman, Sema

2011-01-01

Hypothyroidism has been reported rarely as the cause of rhabdomyolysis in adults and children. We present here a non-compliant adolescent with a diagnosis of hypothyroidism who developed rhabdomyolysis and acute renal failure with no additional predisposing factor. A 13-year-old girl with a previous history of hypothyroidism due to thyroid hypoplasia presented with generalized myalgia, malaise, vomiting, and oliguria lasting for three days. Neurological examination revealed bilateral marked weakness and tenderness of muscles of both lower and upper extremities. Urine had bloody appearance and urine analysis showed blood reaction with dipstick test, but there were no erythrocytes on microscopic examination. Serum creatine phosphokinase and myoglobin levels were elevated. Thyroid stimulating hormone (TSH) levels were high, and free thyroxine (T4) and triiodothyronine (T3) levels were low, compatible with uncontrolled hypothyroidism. Renal function tests showed acute renal failure. Other causes of rhabdomyolysis such as muscular trauma, drugs, toxins, infections, vigorous exercise, and electrolyte abnormalities were excluded. Hemodialysis was administered for 24 sessions. After L-thyroxine therapy, thyroid function tests normalized, muscle strength improved, serum muscle enzyme levels returned to normal levels, and renal function tests recovered. One must be aware that rhabdomyolysis may develop in a non-compliant patient with hypothyroidism.

How do deltoid muscle moment arms change after reverse total shoulder arthroplasty?

PubMed

Walker, David R; Struk, Aimee M; Matsuki, Keisuke; Wright, Thomas W; Banks, Scott A

2016-04-01

Although many advantages of reverse total shoulder arthroplasty (RTSA) have been demonstrated, a variety of complications indicate there is much to learn about how RTSA modifies normal shoulder function. This study used a subject-specific computational model driven by in vivo kinematic data to assess how RTSA affects deltoid muscle moment arms after surgery. A subject-specific 12 degree-of-freedom musculoskeletal model was used to analyze the shoulders of 26 individuals (14 RTSA and 12 normal). The model was modified from the work of Holzbaur to directly input 6 degree-of-freedom humeral and scapular kinematics obtained using fluoroscopy. The moment arms of the anterior, lateral, and posterior aspects of the deltoid were significantly different when RTSA and normal cohorts were compared at different abduction angles. Anterior and lateral deltoid moment arms were significantly larger in the RTSA group at the initial elevation of the arm. The posterior deltoid was significantly larger at maximum elevation. There was large intersubject variability within the RTSA group. Placement of implant components during RTSA can directly affect the geometric relationship between the humerus and scapula and the muscle moment arms in the RTSA shoulder. RTSA shoulders maintain the same anterior and posterior deltoid muscle moment-arm patterns as healthy shoulders but show much greater intersubject variation and larger moment-arm magnitudes. These observations provide a basis for determining optimal implant configuration and surgical placement to maximize RTSA function in a patient-specific manner. Published by Elsevier Inc.

Duchenne Muscular Dystrophy Gene Expression in Normal and Diseased Human Muscle

NASA Astrophysics Data System (ADS)

Oronzi Scott, M.; Sylvester, J. E.; Heiman-Patterson, T.; Shi, Y.-J.; Fieles, W.; Stedman, H.; Burghes, A.; Ray, P.; Worton, R.; Fischbeck, K. H.

1988-03-01

A probe for the 5' end of the Duchenne muscular dystrophy (DMD) gene was used to study expression of the gene in normal human muscle, myogenic cell cultures, and muscle from patients with DMD. Expression was found in RNA from normal fetal muscle, adult cardiac and skeletal muscle, and cultured muscle after myoblast fusion. In DMD muscle, expression of this portion of the gene was also revealed by in situ RNA hybridization, particularly in regenerating muscle fibers.

Proteomic Changes in Rat Thyroarytenoid Muscle Induced by Botulinum Neurotoxin Injection

PubMed Central

Welham, Nathan V.; Marriott, Gerard; Tateya, Ichiro; Bless, Diane M.

2009-01-01

Botulinum neurotoxin (BoNT) injection into the thyroarytenoid (TA) muscle is a commonly performed medical intervention for adductor spasmodic dysphonia. The mechanism of action of BoNT at the neuromuscular junction is well understood, however, aside from reports focused on myosin heavy chain isoform abundance, there is a paucity of data addressing the effects of therapeutic BoNT injection on the TA muscle proteome. In this study, 12 adult Sprague Dawley rats underwent unilateral TA muscle BoNT serotype A injection followed by tissue harvest at 72 hrs, 7 days, 14 days, and 56 days post-injection. Three additional rats were reserved as controls. Proteomic analysis was performed using 2D SDS-PAGE followed by MALDI-MS. Vocal fold movement was significantly reduced by 72 hrs, with complete return of function by 56 days. Twenty-five protein spots demonstrated significant protein abundance changes following BoNT injection, and were associated with alterations in energy metabolism, muscle contractile function, cellular stress response, transcription, translation, and cell proliferation. A number of protein abundance changes persisted beyond the return of gross physiologic TA function. These findings represent the first report of BoNT induced changes in any skeletal muscle proteome, and reinforce the utility of applying proteomic tools to the study of system-wide biological processes in normal and perturbed TA muscle function. PMID:18442174

Mouse forepaw lumbrical muscles are resistant to age-related declines in force production.

PubMed

Russell, Katelyn A; Ng, Rainer; Faulkner, John A; Claflin, Dennis R; Mendias, Christopher L

2015-05-01

A progressive loss of skeletal muscle mass and force generating capacity occurs with aging. Mice are commonly used in the study of aging-associated changes in muscle size and strength, with most models of aging demonstrating 15-35% reductions in muscle mass, cross-sectional area (CSA), maximum isometric force production (Po) and specific force (sPo), which is Po/CSA. The lumbrical muscle of the mouse forepaw is exceptionally small, with corresponding short diffusion distances that make it ideal for in vitro pharmacological studies and measurements of contractile properties. However, the aging-associated changes in lumbrical function have not previously been reported. To address this, we tested the hypothesis that compared to adult (12month old) mice, the forepaw lumbrical muscles of old (30month old) mice exhibit aging-related declines in size and force production similar to those observed in larger limb muscles. We found that the forepaw lumbricals were composed exclusively of fibers with type II myosin heavy chain isoforms, and that the muscles accumulated connective tissue with aging. There were no differences in the number of fibers per whole-muscle cross-section or in muscle fiber CSA. The whole muscle CSA in old mice was increased by 17%, but the total CSA of all muscle fibers in a whole-muscle cross-section was not different. No difference in Po was observed, and while sPo normalized to total muscle CSA was decreased in old mice by 22%, normalizing Po by the total muscle fiber CSA resulted in no difference in sPo. Combined, these results indicate that forepaw lumbrical muscles from 30month old mice are largely protected from the aging-associated declines in size and force production that are typically observed in larger limb muscles. Copyright © 2015 Elsevier Inc. All rights reserved.

Introduction and historical perspective.

PubMed

Gunning, Peter

2008-01-01

Tropomyosin is a coiled coil dimer which forms a polymer along the major groove of the majority of actin filaments. It is therefore one of the two primary components of the actin filament. Our understanding of the biological function of tropomyosin has been driven almost entirely by its role in striated muscle. This reflects both its original discovery as part of the thin filament in skeletal muscle and its pivotal role in regulating muscle contraction. In contrast, its role in the function of the cytoskeleton of all cells has been poorly understood due, at least in part, to the technical challenge of deciphering the function of a large number of isoforms. This book has brought together many of the leading researchers who have defined the function of tropomyosin in both normal and pathological conditions. Each author brings their own perspective in a series of stand alone reviews of the areas of tropomyosin research they have played a major role in defining.

Augmented sympathetic vasoconstriction in exercising forearms of postmenopausal women is reversed by oestrogen therapy

PubMed Central

Fadel, Paul J; Wang, Zhongyun; Watanabe, Hitoshi; Arbique, Debbie; Vongpatanasin, Wanpen; Thomas, Gail D

2004-01-01

Sympathetic vasoconstriction is normally attenuated in exercising muscles of young men and women. Recent evidence indicates that such modulation, termed functional sympatholysis, may be impaired in older men. Whether a similar impairment occurs in older women, and what role oestrogen deficiency might play in this impairment, are not known. Based on the strong positive correlation between circulating oestrogen levels and functional sympatholysis previously reported in female rats, we hypothesized that sympatholysis would be impaired in oestrogen-deficient postmenopausal women, and that this impairment would be reversed by oestrogen replacement. To test these hypotheses, we measured vasoconstrictor responses in the forearms of pre- and postmenopausal women using near infrared spectroscopy to detect decreases in muscle oxygenation in response to reflex activation of sympathetic nerves evoked by lower body negative pressure (LBNP). In eight premenopausal women, LBNP decreased muscle oxygenation by 20 ± 1% in resting forearm, but only by 3 ± 2% in exercising forearm (P < 0.05). In contrast, in eight postmenopausal women, LBNP decreased muscle oxygenation by 15 ± 3% in resting forearm, and by 12 ± 4% in exercising forearm (P > 0.05). After 1 month of transdermal oestradiol replacement in these women, the normal effect of exercise to blunt sympathetic vasoconstriction was restored (rest, −19 ± 3%; exercise, −2 ± 3%; P < 0.05). These data indicate that functional sympatholysis is impaired in oestrogen-deficient postmenopausal women. The effect of short-term unopposed oestrogen replacement to correct this impairment implicates a role for oestrogen in the sympathetic neural control of muscle haemodynamics during exercise. PMID:15498809

Quadriceps Muscle Function After Rehabilitation With Cryotherapy in Patients With Anterior Cruciate Ligament Reconstruction

PubMed Central

Hart, Joseph M.; Kuenze, Christopher M.; Diduch, David R.; Ingersoll, Christopher D.

2014-01-01

Context: Persistent muscle weakness after anterior cruciate ligament (ACL) reconstruction may be due to underlying activation failure and arthrogenic muscle inhibition (AMI). Knee-joint cryotherapy has been shown to improve quadriceps function transiently in those with AMI, thereby providing an opportunity to improve quadriceps muscle activation and strength in patients with a reconstructed ACL. Objective: To compare quadriceps muscle function in patients with a reconstructed ACL who completed a 2-week intervention including daily cryotherapy (ice bag), daily exercises, or both. Design: Cross-sectional study. Setting: Laboratory. Patients or Other Participants: A total of 30 patients with reconstructed ACLs who were at least 6 months post-index surgery and had measurable quadriceps AMI. Intervention(s): The patients attended 4 supervised visits over a 2-week period. They were randomly assigned to receive 20 minutes of knee-joint cryotherapy, 1 hour of therapeutic rehabilitation exercises, or cryotherapy followed by exercises. Main Outcome Measure(s): We measured quadriceps Hoffmann reflex, normalized maximal voluntary isometric contraction torque, central activation ratio using the superimposed-burst technique, and patient-reported outcomes before and after the intervention period. Results: After the 2-week intervention period, patients who performed rehabilitation exercises immediately after cryotherapy had higher normalized maximal voluntary isometric contraction torques (P = .002, Cohen d effect size = 1.4) compared with those who received cryotherapy alone (P = .16, d = 0.58) or performed exercise alone (P = .16, d = 0.30). Conclusions: After ACL reconstruction, patients with AMI who performed rehabilitation exercises immediately after cryotherapy experienced greater strength gains than those who performed cryotherapy or exercises alone. PMID:25299442

Immortalization of cat iris sphincter smooth muscle cells by SV40 virus: growth, morphological, biochemical and pharmacological characteristics.

PubMed

Ocklind, A; Yousufzai, S Y; Ghosh, S; Coca-Prados, M; St Jernschantz, J; Abdel-Latif, A A

1995-11-01

The purpose of this study was to establish immortalized cell cultures of cat iris sphincter smooth muscle cells for a model investigating ocular receptors and their signal transduction pathways. Cultured cat iris sphincter muscle cells were immortalized by viral transformation with SV40 virus and the morphological and immunocytochemical properties of the normal and immortalized cells were investigated. The transformed cell clone, SV-CISM-2, was further characterized biochemically and pharmacologically. The normal muscle cells showed characteristics of smooth muscle cells, as judged by their growth and the presence of smooth muscle alpha-actin and desmin. After seven passages the normal cells ceased to proliferate. In contrast, the immortalized cells retained their proliferative ability for more than 220 population doublings over 55 passages. The transformation phenotype in these cells was confirmed by their expression of the large T-antigen, the incorporation of viral DNA into cellular DNA, growth in agarose and in low-serum medium, and complete loss of contact inhibition. The immortalized cells expressed smooth muscle alpha-actin, desmin and MLC protein. Biochemical and pharmacological studies on the SV-CISM cells revealed the presence of several functional receptors including muscarinic cholinergic, beta-adrenergic, peptidergic (substance P and endothelin). Platelet-activating factor, and prostaglandin (PG). Muscarinic stimulation of these cells resulted in: (a) a dose-dependent increase in the release of arachidonic acid (AA) and (PGs) and enhancement in the production of inositol trisphosphate (IP3); and (b) a substantial increase in MLC phosphorylation (118%), an indicator of smooth muscle contractility. The stimulatory effects of carbachol on these responses were completely blocked by atropine, a muscarinic receptor antagonist. This study constitutes the first successful immortalization of iris sphincter smooth muscle cells. The SV-CISM-2 cells can serve as an important model system for investigations on the biochemical and pharmacological properties of receptors and their signal transduction pathways in smooth muscle. The advantage of these cells over normal iris sphincter cells is that they can be propagated over many generations without alterations in their morphological, biochemical and physiological characteristics.

Dmpk gene deletion or antisense knockdown does not compromise cardiac or skeletal muscle function in mice

PubMed Central

Carrell, Samuel T.; Carrell, Ellie M.; Auerbach, David; Pandey, Sanjay K.; Bennett, C. Frank; Dirksen, Robert T.; Thornton, Charles A.

2016-01-01

Myotonic dystrophy type 1 (DM1) is a genetic disorder in which dominant-active DM protein kinase (DMPK) transcripts accumulate in nuclear foci, leading to abnormal regulation of RNA processing. A leading approach to treat DM1 uses DMPK-targeting antisense oligonucleotides (ASOs) to reduce levels of toxic RNA. However, basal levels of DMPK protein are reduced by half in DM1 patients. This raises concern that intolerance for further DMPK loss may limit ASO therapy, especially since mice with Dmpk gene deletion reportedly show cardiac defects and skeletal myopathy. We re-examined cardiac and muscle function in mice with Dmpk gene deletion, and studied post-maturity knockdown using Dmpk-targeting ASOs in mice with heterozygous deletion. Contrary to previous reports, we found no effect of Dmpk gene deletion on cardiac or muscle function, when studied on two genetic backgrounds. In heterozygous knockouts, the administration of ASOs reduced Dmpk expression in cardiac and skeletal muscle by > 90%, yet survival, electrocardiogram intervals, cardiac ejection fraction and muscle strength remained normal. The imposition of cardiac stress by pressure overload, or muscle stress by myotonia, did not unmask a requirement for DMPK. Our results support the feasibility and safety of using ASOs for post-transcriptional silencing of DMPK in muscle and heart. PMID:27522499

Effect of spaceflight on the functional, biochemical, and metabolic properties of skeletal muscle

NASA Technical Reports Server (NTRS)

Baldwin, K. M.

1996-01-01

This paper summarizes the effects of spaceflight on the functional, morphological, and biochemical properties of human and rodent skeletal muscle. The findings suggest that following as little as 5-6 in space there are deficits in both human and rodent motor capacity, strength, and endurance properties of skeletal muscle. The reduced strength is associated, in part, with a reduction in muscle mass as reflected in smaller cross-sectional areas of both fast- and slow-twitch fibers. Available evidence in animal models suggests that slow-twitch fibers are more sensitive to the atrophying process. Accompanying the atrophy is a transformation of slow to fast protein phenotype involving myosin heavy chain and sarcoplasmic reticulum protein isoforms. These transformations appear to be regulated, in part, by pretranslational processes. Data on the oxidative capacity of rodent skeletal muscle suggest a bias toward preferential utilization of carbohydrate as the primary substrate. These collective findings suggest that skeletal muscles comprised chiefly of slow fibers are highly dependent on gravity for the normal expression of protein mass and slow phenotype. Future studies need to focus on elucidating the mechanisms associated with the atrophy response, as well as identifying suitable exercise and other countermeasures capable of preserving the structural and functional integrity of skeletal muscle.

Study of the trapezius muscle region pressure pain threshold and latency time in young people with and without depressed scapula.

PubMed

Lee, Kuan-Ting; Chuang, Chiung-Cheng; Lai, Chien-Hung; Ye, Jing-Jhao; Wu, Chien-Lung

2015-02-01

The scapula is stabilized in or moved to a certain position to coordinate shoulder function and achieve shoulder and arm movement during the athletic and daily activities. An alteration in the scapular position both at rest and during arm movements is commonly associated with shoulder injury or dysfunction. The purpose of this study was to assess the influence of the depressed scapular position using pressure pain threshold (PPT) and delayed muscle activation of the upper and middle trapezius muscles. The study included 20 subjects who were divided into normal shoulder (n = 12) and depressed shoulder (n = 8) group. PPT was measured in a relaxed position. Muscle activity was recorded using surface electromyography and by calculating each shrug's muscle latency time (MLT). The results revealed that the healthy young subjects with depressed scapular position had significantly lower PPT levels than those with normal scapular position both in the upper and middle trapezius muscle (P < 0.05). MLT of the upper trapezius was significantly delayed in both sides during the shoulder shrugs (P < 0.05). Copyright © 2014 Elsevier Ltd. All rights reserved.

Troponin T3 expression in skeletal and smooth muscle is required for growth and postnatal survival: characterization of Tnnt3(tm2a(KOMP)Wtsi) mice.

PubMed

Ju, Yawen; Li, Jie; Xie, Chao; Ritchlin, Christopher T; Xing, Lianping; Hilton, Matthew J; Schwarz, Edward M

2013-09-01

The troponin complex, which consists of three regulatory proteins (troponin C, troponin I, and troponin T), is known to regulate muscle contraction in skeletal and cardiac muscle, but its role in smooth muscle remains controversial. Troponin T3 (TnnT3) is a fast skeletal muscle troponin believed to be expressed only in skeletal muscle cells. To determine the in vivo function and tissue-specific expression of Tnnt3, we obtained the heterozygous Tnnt3+/flox/lacZ mice from Knockout Mouse Project (KOMP) Repository. Tnnt3(lacZ/+) mice are smaller than their WT littermates throughout development but do not display any gross phenotypes. Tnnt3(lacZ/lacZ) embryos are smaller than heterozygotes and die shortly after birth. Histology revealed hemorrhagic tissue in Tnnt3(lacZ/lacZ) liver and kidney, which was not present in Tnnt3(lacZ/+) or WT, but no other gross tissue abnormalities. X-gal staining for Tnnt3 promoter-driven lacZ transgene expression revealed positive staining in skeletal muscle and diaphragm and smooth muscle cells located in the aorta, bladder, and bronchus. Collectively, these findings suggest that troponins are expressed in smooth muscle and are required for normal growth and breathing for postnatal survival. Moreover, future studies with this mouse model can explore TnnT3 function in adult muscle function using the conditional-inducible gene deletion approach Copyright © 2013 Wiley Periodicals, Inc.

Role of the middle ear muscle apparatus in mechanisms of speech signal discrimination

NASA Technical Reports Server (NTRS)

Moroz, B. S.; Bazarov, V. G.; Sachenko, S. V.

1980-01-01

A method of impedance reflexometry was used to examine 101 students with hearing impairment in order to clarify the interrelation between speech discrimination and the state of the middle ear muscles. Ability to discriminate speech signals depends to some extent on the functional state of intraaural muscles. Speech discrimination was greatly impaired in the absence of stapedial muscle acoustic reflex, in the presence of low thresholds of stimulation and in very small values of reflex amplitude increase. Discrimination was not impeded in positive AR, high values of relative thresholds and normal increase of reflex amplitude in response to speech signals with augmenting intensity.

Muscle-Tendon-Enthesis Unit.

PubMed

Tadros, Anthony S; Huang, Brady K; Pathria, Mini N

2018-07-01

Injuries to the muscle-tendon-enthesis unit are common and a significant source of pain and loss of function. This article focuses on the important anatomical and biomechanical considerations for each component of the muscle-tendon-enthesis unit. We review normal and pathologic conditions affecting this unit, illustrating the imaging appearance of common disorders on magnetic resonance imaging and ultrasound. Knowledge of the anatomy and biomechanics of these structures is crucial for the radiologist to make accurate diagnoses and provide clinically relevant assessments. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The foot core system: a new paradigm for understanding intrinsic foot muscle function.

PubMed

McKeon, Patrick O; Hertel, Jay; Bramble, Dennis; Davis, Irene

2015-03-01

The foot is a complex structure with many articulations and multiple degrees of freedom that play an important role in static posture and dynamic activities. The evolutionary development of the arch of the foot was coincident with the greater demands placed on the foot as humans began to run. The movement and stability of the arch is controlled by intrinsic and extrinsic muscles. However, the intrinsic muscles are largely ignored by clinicians and researchers. As such, these muscles are seldom addressed in rehabilitation programmes. Interventions for foot-related problems are more often directed at externally supporting the foot rather than training these muscles to function as they are designed. In this paper, we propose a novel paradigm for understanding the function of the foot. We begin with an overview of the evolution of the human foot with a focus on the development of the arch. This is followed by a description of the foot intrinsic muscles and their relationship to the extrinsic muscles. We draw the parallels between the small muscles of the trunk region that make up the lumbopelvic core and the intrinsic foot muscles, introducing the concept of the foot core. We then integrate the concept of the foot core into the assessment and treatment of the foot. Finally, we call for an increased awareness of the importance of the foot core stability to normal foot and lower extremity function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of step length and step frequency on lower-limb muscle function in human gait.

PubMed

Lim, Yoong Ping; Lin, Yi-Chung; Pandy, Marcus G

2017-05-24

The aim of this study was to quantify the effects of step length and step frequency on lower-limb muscle function in walking. Three-dimensional gait data were used in conjunction with musculoskeletal modeling techniques to evaluate muscle function over a range of walking speeds using prescribed combinations of step length and step frequency. The body was modeled as a 10-segment, 21-degree-of-freedom skeleton actuated by 54 muscle-tendon units. Lower-limb muscle forces were calculated using inverse dynamics and static optimization. We found that five muscles - GMAX, GMED, VAS, GAS, and SOL - dominated vertical support and forward progression independent of changes made to either step length or step frequency, and that, overall, changes in step length had a greater influence on lower-limb joint motion, net joint moments and muscle function than step frequency. Peak forces developed by the uniarticular hip and knee extensors, as well as the normalized fiber lengths at which these muscles developed their peak forces, correlated more closely with changes in step length than step frequency. Increasing step length resulted in larger contributions from the hip and knee extensors and smaller contributions from gravitational forces (limb posture) to vertical support. These results provide insight into why older people with weak hip and knee extensors walk more slowly by reducing step length rather than step frequency and also help to identify the key muscle groups that ought to be targeted in exercise programs designed to improve gait biomechanics in older adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Strength characterization of knee flexor and extensor muscles in Prader-Willi and obese patients.

PubMed

Capodaglio, Paolo; Vismara, Luca; Menegoni, Francesco; Baccalaro, Gabriele; Galli, Manuela; Grugni, Graziano

2009-05-06

despite evidence of an obesity-related disability, there is a lack of objective muscle functional data in overweight subjects. Only few studies provide instrumental strength measurements in non-syndromal obesity, whereas no data about Prader-Willi syndrome (PWS) are reported. The aim of our study was to characterize the lower limb muscle function of patients affected by PWS as compared to non-syndromal obesity and normal-weight subjects. We enrolled 20 obese (O) females (age: 29.1 +/- 6.5 years; BMI: 38.1 +/- 3.1), 6 PWS females (age: 27.2 +/- 4.9 years; BMI: 45.8 +/- 4.4) and 14 healthy normal-weight (H) females (age: 30.1 +/- 4.7 years; BMI: 21 +/- 1.6). Isokinetic strength during knee flexion and extension in both lower limbs at the fixed angular velocities of 60 degrees /s, 180 degrees /s, 240 degrees /s was measured with a Cybex Norm dynamometer. the H, O and PWS populations appear to be clearly stratified with regard to muscle strength.: PWS showed the lowest absolute peak torque (PT) for knee flexor and extensor muscles as compared to O (-55%) and H (-47%) (P = 0.00001). O showed significantly higher strength values than H as regard to knee extension only (P = 0.0014). When strength data were normalised by body weight, PWS showed a 50% and a 70% reduction in PT as compared to O and H, respectively. Knee flexors strength values were on average half of those reported for extension in all of the three populations. the novel aspect of our study is the determination of objective measures of muscle strength in PWS and the comparison with O and H patients. The objective characterization of muscle function performed in this study provides baseline and outcome measures that may quantify specific strength deficits amendable with tailored rehabilitation programs and monitor effectiveness of treatments.

Strength characterization of knee flexor and extensor muscles in Prader-Willi and obese patients

PubMed Central

Capodaglio, Paolo; Vismara, Luca; Menegoni, Francesco; Baccalaro, Gabriele; Galli, Manuela; Grugni, Graziano

2009-01-01

Background despite evidence of an obesity-related disability, there is a lack of objective muscle functional data in overweight subjects. Only few studies provide instrumental strength measurements in non-syndromal obesity, whereas no data about Prader-Willi syndrome (PWS) are reported. The aim of our study was to characterize the lower limb muscle function of patients affected by PWS as compared to non-syndromal obesity and normal-weight subjects. Methods We enrolled 20 obese (O) females (age: 29.1 ± 6.5 years; BMI: 38.1 ± 3.1), 6 PWS females (age: 27.2 ± 4.9 years; BMI: 45.8 ± 4.4) and 14 healthy normal-weight (H) females (age: 30.1 ± 4.7 years; BMI: 21 ± 1.6). Isokinetic strength during knee flexion and extension in both lower limbs at the fixed angular velocities of 60°/s, 180°/s, 240°/s was measured with a Cybex Norm dynamometer. Results the H, O and PWS populations appear to be clearly stratified with regard to muscle strength.: PWS showed the lowest absolute peak torque (PT) for knee flexor and extensor muscles as compared to O (-55%) and H (-47%) (P = 0.00001). O showed significantly higher strength values than H as regard to knee extension only (P = 0.0014). When strength data were normalised by body weight, PWS showed a 50% and a 70% reduction in PT as compared to O and H, respectively. Knee flexors strength values were on average half of those reported for extension in all of the three populations. Conclusion the novel aspect of our study is the determination of objective measures of muscle strength in PWS and the comparison with O and H patients. The objective characterization of muscle function performed in this study provides baseline and outcome measures that may quantify specific strength deficits amendable with tailored rehabilitation programs and monitor effectiveness of treatments. PMID:19419559

Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis.

PubMed

Lansey, Melissa N; Walker, Natalie N; Hargett, Stefan R; Stevens, Joseph R; Keller, Susanna R

2012-11-15

Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160(-/-)) mice. We observed increased and normal basal glucose uptake in isolated AS160(-/-) adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160(-/-) extensor digitorum longus muscles. In plasma membranes isolated from AS160(-/-) adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160(-/-) adipocytes and normal in AS160(-/-) soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160(-/-) skeletal muscles and liver but not in AS160(-/-) adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis.

Association of sarcopenia with functional decline in community-dwelling elderly subjects in Japan.

PubMed

Tanimoto, Yoshimi; Watanabe, Misuzu; Sun, Wei; Tanimoto, Keiji; Shishikura, Kanako; Sugiura, Yumiko; Kusabiraki, Toshiyuki; Kono, Koichi

2013-10-01

The present study aimed to determine the association of sarcopenia, defined by muscle mass, muscle strength and physical performance, with functional disability from a 2-year cohort study of community-dwelling elderly Japanese people. Participants were 743 community-dwelling elderly Japanese people aged 65 years or older. We used bioelectrical impedance analysis (BIA) to measure muscle mass, grip strength to measure muscle strength, and usual walking speed to measure physical performance in a baseline study. Functional disability was defined using an activities of daily living (ADL) scale and instrumental activities of daily living (IADL) scale at baseline and during follow-up examinations 2 years later. Logistic regression analysis, adjusted for age and body mass index, was used to examine the association between sarcopenia and the occurrence of functional disability. In the present study, 7.8% of men and 10.2% of women were classified as having sarcopenia. Among sarcopenia patients in the baseline study, 36.8% of men and 18.8% of women became dependent in ADL at 2-year follow up. From the logistic regression analysis adjusted by age and body mass index, sarcopenia was significantly associated with the occurrences of physical disability compared with normal subjects in both men and women. Sarcopenia, defined by muscle mass, muscle strength and physical performance, was associated with functional decline over a 2-year period in elderly Japanese. Interventions to prevent sarcopenia are very important to prevent functional decline among elderly individuals. © 2013 Japan Geriatrics Society.

Partial Reductions in Mechanical Loading Yield Proportional Changes in Bone Density, Bone Architecture, and Muscle Mass

PubMed Central

Ellman, Rachel; Spatz, Jordan; Cloutier, Alison; Palme, Rupert; Christiansen, Blaine A; Bouxsein, Mary L

2014-01-01

Although the musculoskeletal system is known to be sensitive to changes in its mechanical environment, the relationship between functional adaptation and below-normal mechanical stimuli is not well defined. We investigated bone and muscle adaptation to a range of reduced loading using the partial weight suspension (PWS) system, in which a two-point harness is used to offload a tunable amount of body weight while maintaining quadrupedal locomotion. Skeletally mature female C57Bl/6 mice were exposed to partial weight bearing at 20%, 40%, 70%, or 100% of body weight for 21 days. A hindlimb unloaded (HLU) group was included for comparison in addition to age-matched controls in normal housing. Gait kinematics was measured across the full range of weight bearing, and some minor alterations in gait from PWS were identified. With PWS, bone and muscle changes were generally proportional to the degree of unloading. Specifically, total body and hindlimb bone mineral density, calf muscle mass, trabecular bone volume of the distal femur, and cortical area of the femur midshaft were all linearly related to the degree of unloading. Even a load reduction to 70% of normal weight bearing was associated with significant bone deterioration and muscle atrophy. Weight bearing at 20% did not lead to better bone outcomes than HLU despite less muscle atrophy and presumably greater mechanical stimulus, requiring further investigation. These data confirm that the PWS model is highly effective in applying controllable, reduced, long-term loading that produces predictable, discrete adaptive changes in muscle and bone of the hindlimb. PMID:23165526

Funktionelle Elektrostimulation Paraplegischer Patienten.

PubMed

Kern, Helmut

2014-07-08

Functional Electrical Stimulation on Paraplegic Patients. We report on clinical and physiological effects of 8 months Functional Electrical Stimulation (FES) of quadriceps femoris muscle on 16 paraplegic patients. Each patient had muscle biopsies, CT-muscle diameter measurements, knee extension strength testing carried out before and after 8 months FES training. Skin perfusion was documented through infrared telethermography and xenon clearance, muscle perfusion was recorded through thallium scintigraphy. After 8 months FES training baseline skin perfusion showed 86 % increase, muscle perfusion was augmented by 87 %. Muscle fiber diameters showed an average increase of 59 % after 8 months FES training. Muscles in patients with spastic paresis as well as in patients with denervation showed an increase in aerob and anaerob muscle enzymes up to the normal range. Even without axonal neurotropic substances FES was able to demonstrate fiberhypertrophy, enzyme adaptation and intracellular structural benefits in denervated muscles. The increment in muscle area as visible on CT-scans of quadriceps femoris was 30 % in spastic paraplegia and 10 % in denervated patients respectively. FES induced changes were less in areas not directly underneath the surface electrodes. We strongly recommend the use of Kern's current for FES in denervated muscles to induce tetanic muscle contractions as we formed a very critical opinion of conventional exponential current. In patients with conus-cauda-lesions FES must be integrated into modern rehabilitation to prevent extreme muscle degeneration and decubital ulcers. Using FES we are able to improve metabolism and induce positive trophic changes in our patients lower extremities. In spastic paraplegics the functions "rising and walking" achieved through FES are much better training than FES ergometers. Larger muscle masses are activated and an increased heart rate is measured, therefore the impact on cardiovascular fitness and metabolism is much greater. This effectively addresses and prevents all problems which result from inactivity in paraplegic patients.

Proximal muscle weakness as a result of osteomalacia associated with celiac disease: a case report.

PubMed

Oz, B; Akan, O; Kocyigit, H; Gürgan, H A

2016-02-01

A 24-year-old woman suffering from back and hip pain with difficulty in walking was reported. She had proximal muscle weakness. Laboratory findings led to the diagnosis of osteomalacia. Positivity of antibodies strengthened suspicion of celiac disease. In patients with proximal muscle weakness, osteomalacia should be considered in differential diagnosis even in a young woman. A 24-year-old woman suffering from back pain, bilateral hip pain, and difficulty in walking was reported. Her symptoms had started in the first trimester of pregnancy. In her physical examination, proximal muscle weakness and waddling gait pattern were determined. Her lumbar spine and hip MRI revealed no obvious pathological findings. Electromyography showed a myophatic pattern. Physical examination, normal values of creatine kinase, and muscle biopsy were supplied to exclude the diagnosis of primer muscle diseases. Laboratory findings led to the diagnosis of osteomalacia with normal renal function. Gastrointestinal symptoms and positivity of anti-gliadin and anti-endomysium antibodies strengthened the suspicion of celiac disease as a cause of the osteomalacia. The diagnosis of celiac disease was confirmed with duodenal mucosal biopsy. In patients with proximal muscle weakness and waddling gait pattern, osteomalacia should be considered in differential diagnosis even in a young woman and underlying disease should be investigated.

Molecular mechanism of sarcopenia and cachexia: recent research advances.

PubMed

Sakuma, Kunihiro; Aoi, Wataru; Yamaguchi, Akihiko

2017-06-01

Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Muscle loss occurs as a consequence of several chronic diseases (cachexia) and normal aging (sarcopenia). Although many negative regulators (atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.) have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of these mediators markedly differs within both conditions. Sarcopenia and cachectic muscles have been demonstrated to be abundant in myostatin-linked molecules. The ubiquitin-proteasome system (UPS) is activated during rapid atrophy model (cancer cachexia), but few mediators of the UPS change during sarcopenia. NF-κB signaling is activated in cachectic, but not in sarcopenic, muscle. Recent studies have indicated the age-related defect of autophagy signaling in skeletal muscle, whereas autophagic activation occurs in cachectic muscle. This review provides recent research advances dealing with molecular mediators modulating muscle mass in both sarcopenia and cachexia.

GREG cells, a dysferlin-deficient myogenic mouse cell line

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

Humphrey, Glen W.; Mekhedov, Elena; Blank, Paul S.

2012-01-15

The dysferlinopathies (e.g. LGMD2b, Myoshi myopathy) are progressive, adult-onset muscle wasting syndromes caused by mutations in the gene coding for dysferlin. Dysferlin is a large ({approx} 200 kDa) membrane-anchored protein, required for maintenance of plasmalemmal integrity in muscle fibers. To facilitate analysis of dysferlin function in muscle cells, we have established a dysferlin-deficient myogenic cell line (GREG cells) from the A/J mouse, a genetic model for dysferlinopathy. GREG cells have no detectable dysferlin expression, but proliferate normally in growth medium and fuse into functional myotubes in differentiation medium. GREG myotubes exhibit deficiencies in plasma membrane repair, as measured by lasermore » wounding in the presence of FM1-43 dye. Under the wounding conditions used, the majority ({approx} 66%) of GREG myotubes lack membrane repair capacity, while no membrane repair deficiency was observed in dysferlin-normal C2C12 myotubes, assayed under the same conditions. We discuss the possibility that the observed heterogeneity in membrane resealing represents genetic compensation for dysferlin deficiency.« less

Changes in interhemispheric motor connectivity after muscle fatigue

NASA Astrophysics Data System (ADS)

Peltier, Scott; LaConte, Stephen M.; Niyazov, Dmitriy; Liu, Jing; Sahgal, Vinod; Yue, Guang; Hu, Xiaoping

2005-04-01

Synchronized oscillations in resting state timecourses have been detected in recent fMRI studies. These oscillations are low frequency in nature (< 0.08 Hz), and seem to be a property of symmetric cortices. These fluctuations are important as a potential signal of interest, which could indicate connectivity between functionally related areas of the brain. It has also been shown that the synchronized oscillations decrease in some spontaneous pathological states. Thus, detection of these functional connectivity patterns may help to serve as a gauge of normal brain activity. The cognitive effects of muscle fatigue are not well characterized. Sustained fatigue has the potential to dynamically alter activity in brain networks. In this work, we examined the interhemispheric correlations in the left and right primary motor cortices and how they change with muscle fatigue. Resting-state functional MRI imaging was done before and after a repetitive unilateral fatigue task. We find that the number of significant correlations in the bilateral motor network decreases with fatigue. These results suggest that resting-state interhemispheric motor cortex functional connectivity is affected by muscle fatigue.

Influence of fixed muscle length and contractile properties on atrophy and subsequent recovery in the rat soleus and plantaris muscles.

PubMed

Fujita, Naoto; Arakawa, Takamitsu; Matsubara, Takako; Ando, Hiroshi; Miki, Akinori

2009-01-01

This study examined muscular atrophy and the recovery process induced by hindlimb unloading and joint immobilization in the rat soleus and plantaris muscles. Rats were divided into control, hindlimb unloading (HU), hindlimb unloading with ankle joint immobilization at the maximum dorsiflexion (HUD), and maximum plantarflexion (HUP) groups. The hindlimb was reloaded after fourteen days of unloading, and muscle atrophy and walking ability were assessed at 0, 3, and 7 days of reloading. A cross sectional area of muscle fibers in the soleus muscle on day 0 of reloading revealed sizes in order from the control, HUD, HUP down to the HU group, indicating that the HU group was the most atrophied among the four groups. These values in the plantaris muscle ranged in order from the control, HU, HUD, to HUP groups, the HUP group being the most atrophied among the four groups. These muscles recovered from atrophy in the same descending order, and the values in the HUD and HUP groups slowly recovered during the reloading periods. The HUD and HUP groups showed a central core lesion and reloading-induced lesions in some type I muscle fibers after the immobilization and reloading, one possible reason for the delayed recovery in these groups. The muscle atrophy in the HU, HUD, and HUP groups remained at day 7 although the walking ability appeared to be normal. Accordingly, further rehabilitation therapy might be necessary even if the functional ability appears to be normal.

Treatment with a Nitric Oxide-Donating NSAID Alleviates Functional Muscle Ischemia in the Mouse Model of Duchenne Muscular Dystrophy

PubMed Central

Thomas, Gail D.; Ye, Jianfeng; De Nardi, Claudio; Monopoli, Angela; Ongini, Ennio; Victor, Ronald G.

2012-01-01

In patients with Duchenne muscular dystrophy (DMD) and the standard mdx mouse model of DMD, dystrophin deficiency causes loss of neuronal nitric oxide synthase (nNOSμ) from the sarcolemma, producing functional ischemia when the muscles are exercised. We asked if functional muscle ischemia would be eliminated and normal blood flow regulation restored by treatment with an exogenous nitric oxide (NO)-donating drug. Beginning at 8 weeks of age, mdx mice were fed a standard diet supplemented with 1% soybean oil alone or in combination with a low (15 mg/kg) or high (45 mg/kg) dose of HCT 1026, a NO-donating nonsteroidal anti-inflammatory agent which has previously been shown to slow disease progression in the mdx model. After 1 month of treatment, vasoconstrictor responses to intra-arterial norepinephrine (NE) were compared in resting and contracting hindlimbs. In untreated mdx mice, the usual effect of muscle contraction to attenuate NE-mediated vasoconstriction was impaired, resulting in functional ischemia: NE evoked similar decreases in femoral blood flow velocity and femoral vascular conductance (FVC) in the contracting compared to resting hindlimbs (ΔFVC contraction/ΔFVC rest = 0.88±0.03). NE-induced functional ischemia was unaffected by low dose HCT 1026 (ΔFVC ratio = 0.92±0.04; P>0.05 vs untreated), but was alleviated by the high dose of the drug (ΔFVC ratio = 0.22±0.03; P<0.05 vs untreated or low dose). The beneficial effect of high dose HCT 1026 was maintained with treatment up to 3 months. The effect of the NO-donating drug HCT 1026 to normalize blood flow regulation in contracting mdx mouse hindlimb muscles suggests a putative novel treatment for DMD. Further translational research is warranted. PMID:23139842

Contractile properties of rat fast-twitch skeletal muscle during reinnervation - Effects of testosterone and castration

NASA Technical Reports Server (NTRS)

Yeagle, S. P.; Mayer, R. F.; Max, S. R.

1983-01-01

The peroneal nerve of subject rats were crushed 1 cm from the muscle in order to examine the isometric contractile properties of skeletal muscle in the recovery sequency during reinnervation of normal, castrated, and testosterone-treated rats. The particular muscle studied was the extensor digitorum longus, with functional reinnervation first observed 8-9 days after nerve crush. No evidence was found that either castration or testosterone injections altered the process of reinnervation after the nerve crush, with the conclusion being valid at the 0.05 p level. The most reliable index of reinnervation was found to be the twitch:tetanus ratio, a factor of use in future studies of the reinnervation of skeletal muscle.

Relationship between peripheral muscle structure and function in patients with chronic obstructive pulmonary disease with different nutritional status.

PubMed

Malaguti, Carla; Napolis, Lara M; Villaça, Débora; Neder, José A; Nery, Luiz E; Dal Corso, Simone

2011-07-01

The purpose of this study was to investigate the relationships between peripheral muscle structure (mass) and function (strength, endurance, and maximal aerobic capacity) in patients with chronic obstructive pulmonary disease (COPD) with different nutritional states. Thirty-nine patients (31 male) with moderate-severe COPD (63.5 ± 7.3 [SD] years) and 17 controls (14 male; 64.7 ± 5.5 [SD] years) underwent isokinetic (peak torque [PT]), isometric (isometric torque [IT]), and endurance strength (total work [TW]) measurements of the knee extensor muscles and a maximal cardiopulmonary exercise test to evaluate the maximal aerobic capacity (peak oxygen uptake [VO(2)] peak). Muscle mass (MM) was determined using dual-energy x-ray absorptiometry. Patients with COPD presented with reduced muscle function as compared with the healthy controls: PT (105.9 ± 33.9 vs. 134.3 ± 30.9, N·m(-1), respectively, p < 0.05), TW (1,446.3 ± 550.8 vs. 1,792.9 ± 469.1 kJ, respectively, p < 0.05), and VO(2)peak (68.1 ± 15.1 vs. 93.7 ± 14.5, % pred, respectively, p < 0.05). Significant relationships were found between muscle structure and function (strength and endurance) in the patient subgroup with preserved MM and in the control group: PT·MM(r(2) = 0.36; p = 0.01 vs. r(2) = 0.32; p = 0.01, respectively) and TW·MM (r(2) = 0.32; p = 0.01 vs. r(2) = 0.22; p = 0.05, respectively). Strength corrected for mass normalized this function in both patient subgroups, whereas endurance was normalized only in the patient subgroup without muscle depletion. Maximal aerobic capacity remained reduced, despite the correction, in both patient subgroups (depleted or nondepleted) compared with the healthy controls (VO(2)peak.MM: 9.1 ± 3.7 vs. 21.8 ± 4.9 vs. 28.5 ± 4.2 ml·min·kg, respectively, with p < 0.01 among groups). Muscle atrophy seems to be the main determinant of strength reduction among patients with moderate-severe COPD, whereas endurance reduction seems to be more related to imbalance between oxygen delivery and consumption than to the local muscle structure itself. Peripheral MM did not constitute a good predictor for maximal aerobic capacity in this population. The main practical application of this study is to point out a crucial role for the strategies able to ameliorate cardiorespiratory and muscular fitness in patients with COPD, even in those patients with preserved MM.

Peroneus quartus and functional ankle instability.

PubMed

Lotito, G; Pruvost, J; Collado, H; Coudreuse, J-M; Bensoussan, L; Curvale, G; Viton, J-M; Delarque, A

2011-07-01

Physical and rehabilitation medicine physicians commonly see patients with chronic functional ankle instability. The main anatomical structures involved in ankle stability are the peroneus (fibularis) brevis and peroneus longus muscles. Several anatomical muscle-tendon variations have been described in the literature as being sometimes responsible for this instability, the peroneus quartus muscle being the most frequent. The objective of this clinical study is to discuss the implication of the bilateral peroneus quartus muscle in functional ankle instability. This 26-year-old patient was seen in PM&R consultation for recurrent episodes of lateral ankle sprains. The clinical examination found a moderate hyperlaxity on the right side in bilateral ankle varus. We also noted a bilateral weakness of the peroneus muscles. Additional imaging examinations showed a supernumerary bilateral peroneus quartus. The electroneuromyogram of the peroneus muscles was normal. In the literature the incidence of a supernumerary peroneus quartus muscle varies from 0 to 21.7%. Most times this muscle is asymptomatic and is only fortuitously discovered. However some cases of chronic ankle pain or instability have been reported in the literature. It seems relevant to discuss, around the clinical case of this patient, the impact of this muscle on ankle instability especially when faced with lingering weakness of the peroneus brevis and longus muscles in spite of eccentric strength training and in the absence of any neurological impairment. One of the hypotheses, previously described in the literature, would be the overcrowding effect resulting in a true conflict by reducing the available space for the peroneal muscles in the peroneal sheath. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism.

PubMed

Blanchet, Emilie; Annicotte, Jean-Sébastien; Pradelli, Ludivine A; Hugon, Gérald; Matecki, Stéfan; Mornet, Dominique; Rivier, François; Fajas, Lluis

2012-09-01

E2F1 deletion leads to increased mitochondrial number and function, increased body temperature in response to cold and increased resistance to fatigue with exercise. Since E2f1-/- mice show increased muscle performance, we examined the effect of E2f1 genetic inactivation in the mdx background, a mouse model of Duchenne muscular dystrophy (DMD). E2f1-/-;mdx mice demonstrated a strong reduction of physiopathological signs of DMD, including preservation of muscle structure, decreased inflammatory profile, increased utrophin expression, resulting in better endurance and muscle contractile parameters, comparable to normal mdx mice. E2f1 deficiency in the mdx genetic background increased the oxidative metabolic gene program, mitochondrial activity and improved muscle functions. Interestingly, we observed increased E2F1 protein levels in DMD patients, suggesting that E2F1 might represent a promising target for the treatment of DMD.

Effect of transforming growth factor-beta1 on embryonic and posthatch muscle growth and development in normal and low score normal chicken.

PubMed

Li, X; Velleman, S G

2009-02-01

During skeletal muscle development, transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of muscle cell proliferation and differentiation. The TGF-beta1 signal is carried by Smad proteins into the cell nucleus, inhibiting the expression of key myogenic regulatory factors including MyoD and myogenin. However, the molecular mechanism by which TGF-beta1 inhibits muscle cell proliferation and differentiation has not been well documented in vivo. The present study investigated the effect of TGF-beta1 on in vivo skeletal muscle growth and development. A chicken line, Low Score Normal (LSN) with reduced muscling and upregulated TGF-beta1 expression, was used and compared to a normal chicken line. The injection of TGF-beta1 at embryonic day (ED) 3 significantly reduced the pectoralis major (p. major) muscle weight in the normal birds at 1 wk posthatch, whereas no significant difference was observed in the LSN birds. The difference between normal and LSN birds in response to TGF-beta1 is likely due to different levels of endogenous TGF-beta1 where the LSN birds have increased TGF-beta1 expression in their p. major muscle at both 17 ED and 6 wk posthatch. Smad3 expression was reduced by TGF-beta1 from 10 ED to 1 wk posthatch in normal p. major muscle. Unlike Smad3, Smad7 expression was not significantly affected by TGF-beta1 until posthatch in both normal and LSN p. major muscle. Expression of MyoD was reduced 35% by TGF-beta1 during embryonic development in normal p. major muscle, whereas LSN p. major muscle showed a delayed decrease at 1 d posthatch in MyoD expression in response to the TGF-beta1 treatment. Myogenin expression was reduced 29% by TGF-beta1 after hatch in normal p. major muscle. In LSN p. major muscle, TGF-beta1 treatment significantly decreased myogenin expression by 43% at 1 d posthatch and 32% at 1 wk posthatch. These data suggested that TGF-beta1 reduced p. major muscle growth by inhibiting MyoD and myogenin expression during both embryonic and posthatch development. Furthermore, TGF-beta1 also reduced the expression of the cell adhesion receptor beta1 integrin subunit during embryonic and posthatch muscle growth in normal and LSN chickens. Therefore, the reduction of beta1 integrin in response to TGF-beta1 is also associated with decreased posthatch muscle growth. The results from this study indicate that TGF-beta1 inhibits skeletal muscle growth by regulating MyoD and myogenin expression. These data also suggest that a beta1 integrin-mediated alternative pathway is likely involved in the TGF-beta1-induced reduction of muscle growth.

Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: from sarcopenic obesity to cachexia.

PubMed

Biolo, Gianni; Cederholm, Tommy; Muscaritoli, Maurizio

2014-10-01

Skeletal muscle is the most abundant body tissue accounting for many physiological functions. However, muscle mass and functions are not routinely assessed. Sarcopenia is defined as skeletal muscle loss and dysfunction in aging and chronic diseases. Inactivity, inflammation, age-related factors, anorexia and unbalanced nutrition affect changes in skeletal muscle. Mechanisms are difficult to distinguish in individual subjects due to the multifactorial character of the condition. Sarcopenia includes both muscle loss and dysfunction which induce contractile impairment and metabolic and endocrine abnormalities, affecting whole-body metabolism and immune/inflammatory response. There are different metabolic trajectories for muscle loss versus fat changes in aging and chronic diseases. Appetite regulation and physical activity affect energy balance and changes in body fat mass. Appetite regulation by inflammatory mediators is poorly understood. In some patients, inflammation induces anorexia and fat loss in combination with sarcopenia. In others, appetite is maintained, despite activation of systemic inflammation, leading to sarcopenia with normal or increased BMI. Inactivity contributes to sarcopenia and increased fat tissue in aging and diseases. At the end of the metabolic trajectories, cachexia and sarcopenic obesity are paradigms of the two patient categories. Pre-cachexia and cachexia are observed in patients with cancer, chronic heart failure or liver cirrhosis. Sarcopenic obesity and sarcopenia with normal/increased BMI are observed in rheumatoid arthritis, breast cancer patients with adjuvant chemotherapy and in most of patients with COPD or chronic kidney disease. In these conditions, sarcopenia is a powerful prognostic factor for morbidity and mortality, independent of BMI. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Histochemical and morphometric characteristics of the normal human vastus medialis longus and vastus medialis obliquus muscles.

PubMed Central

Travnik, L; Pernus, F; Erzen, I

1995-01-01

The histochemical and morphometric characteristics of the vastus medialis longus and vastus medialis obliquus muscles were studied and compared with data on vastus lateralis. Cross-sections of autopsied muscles from 9 healthy men, aged 18-44 y, who had died suddenly were analysed. Data were obtained on proportions, cross-sectional diameter, and on atrophy and hypertrophy factors, of type 1, 2a, 2b, and 2c fibres. The analysis showed that the anatomical differences and the different functional demands placed on vastus medialis longus and vastus medialis obliquus are also expressed in different proportions and sizes of fibre types in the two muscles. The proportion of type 1 fibres was significantly higher (P < 0.01), and the proportion of 2b fibres was significantly lower (P < 0.01) in vastus medialis longus than in vastus medialis obliquus. The diameters of type 1 and type 2a fibres were significantly smaller (P < 0.01) in vastus medialis longus than in vastus medialis obliquus, although the differences were small. Within muscles a nonrandom arrangement of fibre types existed with the deeper portions of the muscles having more type 1 fibres than the more superficial portions. The histochemical and morphometric characteristics of vastus lateralis and vastus medialis obliquus show great similarity, reflecting the common function of both muscles which is taking part in transverse knee stability. Estimates of the limits of normality of the proportion, diameter, atrophy and hypertrophy factors of type 1, 2a, 2b, and 2c fibres might be useful in obtaining information on how different physiological and pathological conditions influence the proportion and size of different fibre types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7592003

A Restrictive Cardiomyopathy Mutation in an Invariant Proline at the Myosin Head/Rod Junction Enhances Head Flexibility and Function, Yielding Muscle Defects in Drosophila

PubMed Central

Achal, Madhulika; Trujillo, Adriana S.; Melkani, Girish C.; Farman, Gerrie P.; Ocorr, Karen; Viswanathan, Meera C.; Kaushik, Gaurav; Newhard, Christopher S.; Glasheen, Bernadette M.; Melkani, Anju; Suggs, Jennifer A.; Moore, Jeffrey R.; Swank, Douglas M.; Bodmer, Rolf; Cammarato, Anthony; Bernstein, Sanford I.

2016-01-01

An “invariant proline” separates the myosin S1 head from its S2 tail and is proposed to be critical for orienting S1 during its interaction with actin, a process that leads to muscle contraction. Mutation of the invariant proline to leucine (P838L) caused dominant restrictive cardiomyopathy in a pediatric patient (Karam et al., Congenit. Heart Dis. 3:138–43, 2008). Here, we use Drosophila melanogaster to model this mutation and dissect its effects on the biochemical and biophysical properties of myosin, as well as on the structure and physiology of skeletal and cardiac muscles. P838L mutant myosin isolated from indirect flight muscles of transgenic Drosophila showed elevated ATPase and actin sliding velocity in vitro. Furthermore, the mutant heads exhibited increased rotational flexibility, and there was an increase in the average angle between the two heads. Indirect flight muscle myofibril assembly was minimally affected in mutant homozygotes, and isolated fibers displayed normal mechanical properties. However, myofibrils degraded during aging, correlating with reduced flight abilities. In contrast, hearts from homozygotes and heterozygotes showed normal morphology, myofibrillar arrays, and contractile parameters. When P838L was placed in trans to Mhc5, an allele known to cause cardiac restriction in flies, it did not yield the constricted phenotype. Overall, our studies suggest that increased rotational flexibility of myosin S1 enhances myosin ATPase and actin sliding. Moreover, instability of P838L myofibrils leads to decreased function during aging of Drosophila skeletal muscle, but not cardiac muscle, despite the strong evolutionary conservation of the P838 residue. PMID:27107639

Lactate dehydrogenase regulation in aged skeletal muscle: Regulation by anabolic steroids and functional overload.

PubMed

Washington, Tyrone A; Healey, Julie M; Thompson, Raymond W; Lowe, Larry L; Carson, James A

2014-09-01

Aging alters the skeletal muscle response to overload-induced growth. The onset of functional overload is characterized by increased myoblast proliferation and an altered muscle metabolic profile. The onset of functional overload is associated with increased energy demands that are met through the interconversion of lactate and pyruvate via the activity of lactate dehydrogenase (LDH). Testosterone targets many of the processes activated at the onset of functional overload. However, the effect of aging on this metabolic plasticity at the onset of functional overload and how anabolic steroid administration modulates this response is not well understood. The purpose of this study was to determine if aging would alter overload-induced LDH activity and expression at the onset of functional overload and whether anabolic steroid administration would modulate this response. Five-month and 25-month male Fischer 344xF1 BRN were given nandrolone decanoate (ND) or sham injections for 14days and then the plantaris was functionally overloaded (OV) for 3days by synergist ablation. Aging reduced muscle LDH-A & LDH-B activity 70% (p<0.05). Aging also reduced LDH-A mRNA abundance, however there was no age effect on LDH-B mRNA abundance. In 5-month muscle, both ND and OV decreased LDH-A and LDH-B activity. However, there was no synergistic or additive effect. In 5-month muscle, ND and OV decreased LDH-A mRNA expression with no change in LDH-B expression. In 25-month muscle, ND and OV increased LDH-A and LDH-B activity. LDH-A mRNA expression was not altered by ND or OV in aged muscle. However, there was a main effect of OV to decrease LDH-B mRNA expression. There was also an age-induced LDH isoform shift. ND and OV treatment increased the "fast" LDH isoforms in aged muscle, whereas ND and OV increased the "slow" isoforms in young muscle. Our study provides evidence that aging alters aspects of skeletal muscle metabolic plasticity normally induced by overload and anabolic steroid administration. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of maternal hypothyroidism during pregnancy on insulin resistance, lipid accumulation and mitochondrial dysfunction in skeletal muscle of fetal rats.

PubMed

Xia, Tongjia; Zhang, Xue; Wang, Youmin; Deng, Datong

2018-05-21

This study aimed to investigate the effect of maternal hypothyroidism during pregnancy on thyroid function of the fetal rat. Female Sprague-Dawley rats were randomized into two groups. PTU group received propylthiouracil (PTU) in drinking water for 6 weeks (n = 90), normal group received drinking normal water (n = 50). The pregnant rats were obtained and had a cesarean-section to get at gestational age of 8.5 d, 13d and 21 d, following blood samples and skeletal muscle were obtained from fetal rats. Levels of thyroid hormone, insulin, mitochondrial protein and adipokines were detected using ELISA. Western blotting was performed to analyze mitochondria and insulin signal transduction-related protein in fetal rat skeletal muscle. Immunostaining of periodic acid-Schiff (PAS) and Oil Red O was used to observe accumulation of muscle glycogen and lipid in the fetal rat. The results showed that levels of thyroid hormone, insulin, insulin signal transduction-related protein, mitochondrial protein and adipokines increased with the fetus developed, but had no statistical differences in PTU the group compared to the normal group. In conclusion, pregnant rats with hypothyroidism have not an influence on insulin resistance, lipid accumulation and mitochondrial dysfunction in skeletal muscle of fetal rats. ©2018 The Author(s).

The role of the inspiratory muscle weakness in functional capacity in hemodialysis patients

PubMed Central

Gomes, Rosalina Tossige; Neves, Camila Danielle Cunha; de Oliveira, Evandro Silveira; Alves, Frederico Lopes; Rodrigues, Vanessa Gomes Brandão; Maciel, Emílio Henrique Barroso

2017-01-01

Introduction Inspiratory muscle function may be affected in patients with End-Stage Renal Disease (ESRD), further worsening the functional loss in these individuals. However, the impact of inspiratory muscle weakness (IMW) on the functional capacity (FC) of hemodialysis patients remains unknown. Thus, the present study aimed to evaluate the impact of IMW on FC in ESRD patients undergoing hemodialysis. Materials and methods ESRD patients on hemodialysis treatment for more than six months were evaluated for inspiratory muscle strength and FC. Inspiratory muscle strength was evaluated based on maximal inspiratory pressure (MIP). IMW was defined as MIP values less than 70% of the predicted value. FC was evaluated using the Incremental Shuttle Walk test (ISWT). Patients whose predicted peak oxygen uptake (VO2peak) over the distance walked during the ISWT was less than 16mL/kg/min were considered to have FC impairment. Associations between variables were assessed by linear and logistic regression, with adjustment for age, sex, body mass index (BMI), presence of diabetes and hemoglobin level. Receiver-operating characteristic (ROC) analysis was used to determine different cutoff values of the MIP for normal inspiratory muscle strength and FC. Results Sixty-five ERSD patients (67.7% male), aged 48.2 (44.5–51.9) years were evaluated. MIP was an independent predictor of the distance walked during the ISWT (R2 = 0.44). IMW was an independent predictor of VO2peak < 16mL/kg/min. (OR = 5.7; p = 0.048) in adjusted logistic regression models. ROC curves showed that the MIP cutoff value of 82cmH2O had a sensitivity of 73.5% and specificity of 93.7% in predicting normal inspiratory strength and a sensitivity and specificity of 76.3% and 70.4%, respectively, in predicting VO2peak ≥ 16mL/kg/min. Conclusions IMW is associated with reduced FC in hemodialysis patients. Evaluation of the MIP may be important to functional monitoring in clinical practice and can help in the stratification of patients eligible to perform exercise testing. PMID:28278163

The role of the inspiratory muscle weakness in functional capacity in hemodialysis patients.

PubMed

Figueiredo, Pedro Henrique Scheidt; Lima, Márcia Maria Oliveira; Costa, Henrique Silveira; Gomes, Rosalina Tossige; Neves, Camila Danielle Cunha; Oliveira, Evandro Silveira de; Alves, Frederico Lopes; Rodrigues, Vanessa Gomes Brandão; Maciel, Emílio Henrique Barroso; Balthazar, Cláudio Heitor

2017-01-01

Inspiratory muscle function may be affected in patients with End-Stage Renal Disease (ESRD), further worsening the functional loss in these individuals. However, the impact of inspiratory muscle weakness (IMW) on the functional capacity (FC) of hemodialysis patients remains unknown. Thus, the present study aimed to evaluate the impact of IMW on FC in ESRD patients undergoing hemodialysis. ESRD patients on hemodialysis treatment for more than six months were evaluated for inspiratory muscle strength and FC. Inspiratory muscle strength was evaluated based on maximal inspiratory pressure (MIP). IMW was defined as MIP values less than 70% of the predicted value. FC was evaluated using the Incremental Shuttle Walk test (ISWT). Patients whose predicted peak oxygen uptake (VO2peak) over the distance walked during the ISWT was less than 16mL/kg/min were considered to have FC impairment. Associations between variables were assessed by linear and logistic regression, with adjustment for age, sex, body mass index (BMI), presence of diabetes and hemoglobin level. Receiver-operating characteristic (ROC) analysis was used to determine different cutoff values of the MIP for normal inspiratory muscle strength and FC. Sixty-five ERSD patients (67.7% male), aged 48.2 (44.5-51.9) years were evaluated. MIP was an independent predictor of the distance walked during the ISWT (R2 = 0.44). IMW was an independent predictor of VO2peak < 16mL/kg/min. (OR = 5.7; p = 0.048) in adjusted logistic regression models. ROC curves showed that the MIP cutoff value of 82cmH2O had a sensitivity of 73.5% and specificity of 93.7% in predicting normal inspiratory strength and a sensitivity and specificity of 76.3% and 70.4%, respectively, in predicting VO2peak ≥ 16mL/kg/min. IMW is associated with reduced FC in hemodialysis patients. Evaluation of the MIP may be important to functional monitoring in clinical practice and can help in the stratification of patients eligible to perform exercise testing.

Partial rupture of the pectoralis major muscle in athletes.

PubMed

Roi, G S; Respizzi, S; Dworzak, F

1990-02-01

Partial rupture of the pectoralis major muscle is quite a rare event in sports traumatology and information about its treatment is lacking in literature. In this paper the long term effect of conservative non-surgical treatment in two body-builders and one shot-putter is discussed, who reported the partial rupture while performing bench lifts with barbells. Functional recovery was evaluated a few years after the injury (from 4 to 7) with an isokinetic dynamometer (Cybex II, Lumex INC N.Y.), measuring maximal shoulder adduction-abduction torques at different angular speeds (60, 180, and 300 degrees/s). The results were compared with those of five healthy athletes practicing either body-building or weight-lifting. From the present study we conclude the following: the non-invasive treatment of a partial rupture of the pectoralis major muscle may produce almost complete functional recovery; in normal subjects adduction muscles are advantageous in comparison to the abduction ones.

PubMed Central

Descarreaux, Martin; Blouin, Jean-Sébastien; Normand, Martin C; Hudon, Daniel

2001-01-01

Background: Ankylosing spondylitis (AS) produces gradual ossification in articular components of the sacro-iliac joints, spine, thoracic and scapular region. This pathology features a diminution of range of motion, muscle force and extensibility as well as functional capacities. Actual treatment of ankylosing spondylitis includes exercise program aimed at pain control, restoration of normal muscle force and extensibility and improvement in functional capacities. These programs are designed to adapt to the special characteristics of ankylosing spondylitis population. Case study: We present the case of a 30 years old man suffering from AS who participated in a 10 week exercise program based on his personal characteristics. We evaluated changes in trunk and hip muscle force and extensibility, pain level (visual pain scale) and disability level (Modified Oswerstry questionnaire). Conclusion: He showed improvement of some physical characteristics that were deficient in the initial evaluation. Improvement were noted in trunk range of motion, some muscular group forces and extensibility of certain muscles too.

Group-level variations in motor representation areas of thenar and anterior tibial muscles: Navigated Transcranial Magnetic Stimulation Study.

PubMed

Niskanen, Eini; Julkunen, Petro; Säisänen, Laura; Vanninen, Ritva; Karjalainen, Pasi; Könönen, Mervi

2010-08-01

Navigated transcranial magnetic stimulation (TMS) can be used to stimulate functional cortical areas at precise anatomical location to induce measurable responses. The stimulation has commonly been focused on anatomically predefined motor areas: TMS of that area elicits a measurable muscle response, the motor evoked potential. In clinical pathologies, however, the well-known homunculus somatotopy theory may not be straightforward, and the representation area of the muscle is not fixed. Traditionally, the anatomical locations of TMS stimulations have not been reported at the group level in standard space. This study describes a methodology for group-level analysis by investigating the normal representation areas of thenar and anterior tibial muscle in the primary motor cortex. The optimal representation area for these muscles was mapped in 59 healthy right-handed subjects using navigated TMS. The coordinates of the optimal stimulation sites were then normalized into standard space to determine the representation areas of these muscles at the group-level in healthy subjects. Furthermore, 95% confidence interval ellipsoids were fitted into the optimal stimulation site clusters to define the variation between subjects in optimal stimulation sites. The variation was found to be highest in the anteroposterior direction along the superior margin of the precentral gyrus. These results provide important normative information for clinical studies assessing changes in the functional cortical areas because of plasticity of the brain. Furthermore, it is proposed that the presented methodology to study TMS locations at the group level on standard space will be a suitable tool for research purposes in population studies. 2010 Wiley-Liss, Inc.

Preferential reduction of quadriceps over respiratory muscle strength and bulk after lung transplantation for cystic fibrosis.

PubMed

Pinet, C; Scillia, P; Cassart, M; Lamotte, M; Knoop, C; Mélot, C; Estenne, M

2004-09-01

In the absence of complications, recipients of lung transplants for cystic fibrosis have normal pulmonary function but the impact of the procedure on the strength and bulk of respiratory and limb muscles has not been studied. Twelve stable patients who had undergone lung transplantation for cystic fibrosis 48 months earlier (range 8-95) and 12 normal subjects matched for age, height, and sex were studied. The following parameters were measured: standard lung function, peak oxygen uptake by cycle ergometry, diaphragm surface area by computed tomographic (CT) scanning, diaphragm and abdominal muscle thickness by ultrasonography, twitch transdiaphragmatic and gastric pressures, quadriceps isokinetic strength, and quadriceps cross section by CT scanning, and lean body mass. Diaphragm mass was computed from diaphragm surface area and thickness. Twitch transdiaphragmatic and gastric pressures, diaphragm mass, and abdominal muscle thickness were similar in the two groups but quadriceps strength and cross section were decreased by nearly 30% in the patients. Patients had preserved quadriceps strength per unit cross section but reduced quadriceps cross section per unit lean body mass. The cumulative dose of corticosteroids was an independent predictor of quadriceps atrophy. Peak oxygen uptake showed positive correlations with quadriceps strength and cross section in the two groups, but peak oxygen uptake per unit quadriceps strength or cross section was reduced in the patient group. The diaphragm and abdominal muscles have preserved strength and bulk in patients transplanted for cystic fibrosis but the quadriceps is weak due to muscle atrophy. This atrophy is caused in part by corticosteroid therapy and correlates with the reduction in exercise capacity.

Laminin and Matrix metalloproteinase 11 regulate Fibronectin levels in the zebrafish myotendinous junction.

PubMed

Jenkins, Molly H; Alrowaished, Sarah S; Goody, Michelle F; Crawford, Bryan D; Henry, Clarissa A

2016-01-01

Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition. We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture. These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.

Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone.

PubMed

Wijnhoven, Hanneke J H; Ennen, Leo; Rodenburg, Richard J T; Dekhuijzen, P N Richard

2006-01-01

Respiratory failure in patients with COPD may be caused by insufficient force production or insufficient endurance capacity of the respiratory muscles. Anabolic steroids may improve respiratory muscle function in COPD. The effect of anabolic steroids on mitochondrial function in the diaphragm in emphysema is unknown. In an emphysematous male hamster model, we investigated whether administration of the anabolic steroid nandrolone decanoate (ND) altered the activity of mitochondrial respiratory chain complexes in the diaphragm. The bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and serum testosterone levels were significantly lower in hamsters treated with ND than in control hamsters. No difference in the activity of mitochondrial respiratory chain complexes in the diaphragm between normal and emphysematous hamsters was observed. Treatment with ND did not change the activity of mitochondrial respiratory chain complexes in the diaphragm of both normal and emphysematous hamsters. In emphysematous hamsters, administration of ND decreased the activity of succinate:cytochrome c oxidoreductase compared with ND treatment in normal hamsters. We conclude that anabolic steroids have negative effects on the activity of succinate:cytochrome c oxidoreductase and anabolic status in this emphysematous hamster model.

Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone

PubMed Central

Wijnhoven, Hanneke JH; Ennen, Leo; Rodenburg, Richard JT; Dekhuijzen, PN Richard

2006-01-01

Respiratory failure in patients with COPD may be caused by insufficient force production or insufficient endurance capacity of the respiratory muscles. Anabolic steroids may improve respiratory muscle function in COPD. The effect of anabolic steroids on mitochondrial function in the diaphragm in emphysema is unknown. In an emphysematous male hamster model, we investigated whether administration of the anabolic steroid nandrolone decanoate (ND) altered the activity of mitochondrial respiratory chain complexes in the diaphragm. The bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and serum testosterone levels were significantly lower in hamsters treated with ND than in control hamsters. No difference in the activity of mitochondrial respiratory chain complexes in the diaphragm between normal and emphysematous hamsters was observed. Treatment with ND did not change the activity of mitochondrial respiratory chain complexes in the diaphragm of both normal and emphysematous hamsters. In emphysematous hamsters, administration of ND decreased the activity of succinate:cytochrome c oxidoreductase compared with ND treatment in normal hamsters. We conclude that anabolic steroids have negative effects on the activity of succinate:cytochrome c oxidoreductase and anabolic status in this emphysematous hamster model. PMID:18046906

Muscle force modification strategies are not consistent for gait retraining to reduce the knee adduction moment in individuals with knee osteoarthritis.

PubMed

Shull, Peter B; Huang, Yangjian; Schlotman, Taylor; Reinbolt, Jeffrey A

2015-09-18

While gait retraining paradigms that alter knee loads typically focus on modifying kinematics, the underlying muscle force modifications responsible for these kinematic changes remain largely unknown. As humans are generally thought to select uniform gait muscle patterns such as strategies based on fatigue cost functions or energy minimization, we hypothesized that a kinematic gait change known to reduce the knee adduction moment (i.e. toe-in gait) would be accompanied by a uniform muscle force modification strategy for individuals with symptomatic knee osteoarthritis. Ten subjects with self-reported knee pain and radiographic evidence of medial compartment knee osteoarthritis performed normal gait and toe-in gait modification walking trials. Two hundred muscle-actuated dynamic simulations (10 steps for normal gait and 10 steps from toe-in gait for each subject) were performed to determine muscle forces for each gait. Results showed that subjects internally rotated their feet during toe-in gait, which decreased the foot progression angle by 7° (p<0.01) and reduced the first peak knee adduction moment by 20% (p<0.01). While significant muscle force modifications were evidenced within individuals, there were no consistent muscle force modifications across all subjects. It may be that self-selected muscle pattern changes are not uniform for gait modification particularly for individuals with knee pain. Future studies focused on altering knee loads should not assume consistent muscle force modifications for a given kinematic gait change across subjects and should consider muscle forces in addition to kinematics in gait retraining paradigms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pilot study on quantitative assessment of muscle imbalance: differences of muscle synergies, equilibrium-point trajectories, and endpoint stiffness in normal and pathological upper-limb movements.

PubMed

Oku, Takanori; Uno, Kanna; Nishi, Tomoki; Kageyama, Masayuki; Phatiwuttipat, Pipatthana; Koba, Keitaro; Yamashita, Yuto; Murakami, Kenta; Uemura, Mitsunori; Hirai, Hiroaki; Miyazaki, Fumio; Naritomi, Hiroaki

2014-01-01

This paper proposes a novel method for assessment of muscle imbalance based on muscle synergy hypothesis and equilibrium point (EP) hypothesis of motor control. We explain in detail the method for extracting muscle synergies under the concept of agonist-antagonist (AA) muscle pairs and for estimating EP trajectories and endpoint stiffness of human upper limbs in a horizontal plane using an electromyogram. The results of applying this method to the reaching movement of one normal subject and one hemiplegic subject suggest that (1) muscle synergies (the balance among coactivation of AA muscle pairs), particularly the synergies that contributes to the angular directional kinematics of EP and the limb stiffness, are quite different between the normal subject and the hemiplegic subject; (2) the concomitant EP trajectory is also different between the normal and hemiplegic subjects, corresponding to the difference of muscle synergies; and (3) the endpoint (hand) stiffness ellipse of the hemiplegic subject becomes more elongated and orientation of the major axis rotates clockwise more than that of the normal subject. The level of motor impairment would be expected to be assessed from a comparison of these differences of muscle synergies, EP trajectories, and endpoint stiffness among normal and pathological subjects using the method.

Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

PubMed

Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I; Trinity, Joel D; Hyngstrom, John R; Garten, Ryan S; Diakos, Nikolaos A; Ives, Stephen J; Dela, Flemming; Larsen, Steen; Drakos, Stavros; Richardson, Russell S

2014-08-01

Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s(-1)·mg(-1), P < 0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·g(-1)·min(-1), P < 0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s(-1)·mg(-1), P < 0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.

Muscle quality characteristics of muscles in the thigh, upper arm and lower back in elderly men and women.

PubMed

Yoshiko, Akito; Kaji, Takashi; Sugiyama, Hiroki; Koike, Teruhiko; Oshida, Yoshiharu; Akima, Hiroshi

2018-04-23

The ratio of fat within skeletal muscle is an important parameter that is indicative of muscle quality, and can be assessed using ultrasonography to measure echo intensity (EI). Muscle EI indicates muscle strength and risk of physical dysfunction; however, this observation was determined following examinations of only selected muscle. The purpose of this study was to investigate the EI characteristics of muscles in several regions in elderly men and women, using physical function tests and serum cholesterol levels. Twenty-two men and women (age 78 ± 8 years) participated in this study. The EIs were calculated from rectus femoris (RF), biceps femoris (BF) triceps brachii (TB) and multifidus (MF) using B-mode transverse ultrasound images. Seven functional tests (isometric knee-extension peak torque, functional reach, sit-to-stand, 5-m normal/maximal speed walking, handgrip strength and timed up-and-go) and blood lipid components including adipocytokines were measured in all participants. A statistically significant correlation between EI of the RF, TB and BF was observed (r = 0.46-0.50, P < 0.05), but not between EI of the MF and that of other muscles. EI of muscles of the limbs, which was averaged EI for RF, TB and BF, was negatively correlated with leptin levels (adjusted R 2  = 0.27, P < 0.01), and EI of the MF was correlated with muscle mass and performance in the timed up-and-go test (adjusted R 2  = 0.61, P < 0.01). These results suggest that EI might be influenced by specific parameters depending on the location of the muscle.

Parvalbumin Gene Transfer Impairs Skeletal Muscle Contractility in Old Mice

PubMed Central

Murphy, Kate T.; Ham, Daniel J.; Church, Jarrod E.; Naim, Timur; Trieu, Jennifer; Williams, David A.

2012-01-01

Abstract Sarcopenia is the progressive age-related loss of skeletal muscle mass associated with functional impairments that reduce mobility and quality of life. Overt muscle wasting with sarcopenia is usually preceded by a slowing of the rate of relaxation and a reduction in maximum force production. Parvalbumin (PV) is a cytosolic Ca2+ buffer thought to facilitate relaxation in muscle. We tested the hypothesis that restoration of PV levels in muscles of old mice would increase the magnitude and hasten relaxation of submaximal and maximal force responses. The tibialis anterior (TA) muscles of young (6 month), adult (13 month), and old (26 month) C57BL/6 mice received electroporation-assisted gene transfer of plasmid encoding PV or empty plasmid (pcDNA3.1). Contractile properties of TA muscles were assessed in situ 14 days after transfer. In old mice, muscles with increased PV expression had a 40% slower rate of tetanic force development (p<0.01), and maximum twitch and tetanic force were 22% and 16% lower than control values, respectively (p<0.05). Muscles with increased PV expression from old mice had an 18% lower maximum specific (normalized) force than controls, and absolute force was ∼26% lower at higher stimulation frequencies (150–300 Hz, p<0.05). In contrast, there was no effect of increased PV expression on TA muscle contractile properties in young and adult mice. The impairments in skeletal muscle function in old mice argue against PV overexpression as a therapeutic strategy for ameliorating aspects of contractile dysfunction with sarcopenia and help clarify directions for therapeutic interventions for age-related changes in skeletal muscle structure and function. PMID:22455364

Antibody-directed myostatin inhibition enhances muscle mass and function in tumor-bearing mice.

PubMed

Murphy, Kate T; Chee, Annabel; Gleeson, Ben G; Naim, Timur; Swiderski, Kristy; Koopman, René; Lynch, Gordon S

2011-09-01

Cancer cachexia describes the progressive skeletal muscle wasting and weakness in many cancer patients and accounts for >20% of cancer-related deaths. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the atrophy and loss of function in muscles of tumor-bearing mice. Twelve-week-old C57BL/6 mice received a subcutaneous injection of saline (control) or Lewis lung carcinoma (LLC) tumor cells. One week later, mice received either once weekly injections of saline (control, n = 12; LLC, n = 9) or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg·kg⁻¹·wk⁻¹, LLC+PF-354, n = 11) for 5 wk. Injection of LLC cells reduced muscle mass and maximum force of tibialis anterior (TA) muscles by 8-10% (P < 0.05), but the muscle atrophy and weakness were prevented with PF-354 treatment (P > 0.05). Maximum specific (normalized) force of diaphragm muscle strips was reduced with LLC injection (P < 0.05) but was not improved with PF-354 treatment (P > 0.05). PF-354 enhanced activity of oxidative enzymes in TA and diaphragm muscles of tumor-bearing mice by 118% and 89%, respectively (P < 0.05). Compared with controls, apoptosis that was not of myofibrillar or satellite cell origin was 140% higher in TA muscle cross sections from saline-treated LLC tumor-bearing mice (P < 0.05) but was not different in PF-354-treated tumor-bearing mice (P > 0.05). Antibody-directed myostatin inhibition attenuated the skeletal muscle atrophy and loss of muscle force-producing capacity in a murine model of cancer cachexia, in part by reducing apoptosis. The improvements in limb muscle mass and function highlight the therapeutic potential of antibody-directed myostatin inhibition for cancer cachexia.

What is the most suitable MR signal index for quantitative evaluation of placental function using Half-Fourier acquisition single-shot turbo spin-echo compared with T2-relaxation time?

PubMed

Kameyama, Kyoko Nakao; Kido, Aki; Himoto, Yuki; Moribata, Yusaku; Minamiguchi, Sachiko; Konishi, Ikuo; Togashi, Kaori

2018-06-01

Background Half-Fourier acquisition single-shot turbo spin-echo (HASTE) imaging is now widely used for placental and fetal imaging because of its rapidity and low sensitivity to fetal movement. If placental dysfunction is also predicted by quantitative value obtained from HASTE image, then it might be beneficial for evaluating placental wellbeing. Purpose To ascertain the most suitable magnetic resonance (MR) signal indexes reflecting placental function using HASTE imaging. Material and Methods This retrospective study included 37 consequent patients who had given informed consent to MR imaging (MRI) examinations. All had undergone MRI examinations between February 2014 and June 2015. First, the correlation between T2-relaxation time of normal placenta and gestational age (GA) was examined. Second, correlation between signal intensity ratios (SIRs) using HASTE imaging and placental T2-relaxation time were assessed. The SIRs were calculated using placental signal intensity (SI) relative to the SI of the amniotic fluid, fetal ocular globes, gastric fluid, bladder, maternal psoas major muscles, and abdominal subcutaneous adipose tissue. Results Among the 37 patients, the correlation between T2-relaxation time of the 25 normal placentas and GA showed a moderately strong correlation (Spearman rho = -0.447, P = 0.0250). The most significant correlation with placental T2-relaxation time was observed with the placental SIR relative to the maternal psoas major muscles (SIR pl./psoas muscle ) (Spearman rho = -0.531, P = 0.0007). Conclusion This study revealed that SIR pl./psoas muscle showed the best correlation to placental T2-relaxation time. Results show that SIR pl./psoas muscle might be optimal as a clinically available quantitative index of placental function.

Human spinal cord injury: motor unit properties and behaviour.

PubMed

Thomas, C K; Bakels, R; Klein, C S; Zijdewind, I

2014-01-01

Spinal cord injury (SCI) results in widespread variation in muscle function. Review of motor unit data shows that changes in the amount and balance of excitatory and inhibitory inputs after SCI alter management of motoneurons. Not only are units recruited up to higher than usual relative forces when SCI leaves few units under voluntary control, the force contribution from recruitment increases due to elevation of twitch/tetanic force ratios. Force gradation and precision are also coarser with reduced unit numbers. Maximal unit firing rates are low in hand muscles, limiting voluntary strength, but are low, normal or high in limb muscles. Unit firing rates during spasms can exceed voluntary rates, emphasizing that deficits in descending drive limit force production. SCI also changes muscle properties. Motor unit weakness and fatigability seem universal across muscles and species, increasing the muscle weakness that arises from paralysis of units, motoneuron death and sensory impairment. Motor axon conduction velocity decreases after human SCI. Muscle contractile speed is also reduced, which lowers the stimulation frequencies needed to grade force when paralysed muscles are activated with patterned electrical stimulation. This slowing does not necessarily occur in hind limb muscles after cord transection in cats and rats. The nature, duration and level of SCI underlie some of these species differences, as do variations in muscle function, daily usage, tract control and fibre-type composition. Exploring this diversity is important to promote recovery of the hand, bowel, bladder and locomotor function most wanted by people with SCI. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

ERIC Educational Resources Information Center

Ianuzzo, C. D.; Chen, V.

1977-01-01

Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

[Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions].

PubMed

Neuhaus, J; Heinrich, M; Schlichting, N; Oberbach, A; Fitzl, G; Schwalenberg, T; Horn, L-C; Stolzenburg, J-U

2007-09-01

Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders. Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells. Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes. Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the etiology of urge incontinence. A multi-step model is presented as a working hypothesis.

Is visual assessment of thyroid attenuation on unenhanced CT of the chest useful for detecting hypothyroidism?

PubMed

Maldjian, P D; Chen, T

2016-11-01

To determine if visual assessment of the attenuation of morphologically normal appearing thyroid glands on unenhanced computed tomography (CT) of the chest is useful for identifying patients with decreased thyroid function. This was a retrospective study of 765 patients who underwent both unenhanced CT of the chest and thyroid function tests performed within 1 year of the CT examination. Attenuation of the thyroid gland was visually assessed in each patient relative to the attenuation of the surrounding muscles to categorise the gland as "low attenuation" (attenuation similar to surrounding muscles) or "high attenuation" (attenuation greater than surrounding muscles). Thyroid attenuation was quantitatively measured in each case to determine the validity of the visual assessment. Results of thyroid function tests were used to classify thyroid function as hypothyroid, euthyroid, or hyperthyroid. Data were analysed to determine the relationship between visual assessment of thyroid attenuation and status of thyroid function. Thyroid glands of low attenuation were present in 4.2% (32/765) of the patients. Nearly half (47%) of the patients with low-attenuation thyroids had hypofunctioning thyroid glands. Compared to patients with high-attenuation thyroids, patients with low-attenuation thyroids were significantly more likely to have decreased thyroid function (clinical and subclinical hypothyroidism) and significantly less likely to be euthyroid (p<0.0001). Quantitative measurement of thyroid attenuation confirmed the validity of the visual assessment. Low attenuation of an otherwise normal-appearing thyroid gland on unenhanced CT of the chest is strongly associated with decreased thyroid function. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Renal function alterations during skeletal muscle disuse in simulated microgravity

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.

1992-01-01

This project was to examine the alterations in renal functions during skeletal muscle disuse in simulated microgravity. Although this area could cover a wide range of investigative efforts, the limited funding resulted in the selection of two projects. These projects would result in data contributing to an area of research deemed high priority by NASA and would address issues of the alterations in renal response to vasoactive stimuli during conditions of skeletal muscle disuse as well as investigate the contribution of skeletal muscle disuse, conditions normally found in long term human exposure to microgravity, to the balance of fluid and macromolecules within the vasculature versus the interstitium. These two projects selected are as follows: investigate the role of angiotensin 2 on renal function during periods of simulated microgravity and skeletal muscle disuse to determine if the renal response is altered to changes in circulating concentrations of angiotensin 2 compared to appropriate controls; and determine if the shift of fluid balance from vasculature to the interstitium, the two components of extracellular fluid volume, that occur during prolonged exposure to microgravity and skeletal muscle disuse is a result, in part, to alterations in the fluid and macromolecular balance in the peripheral capillary beds, of which the skeletal muscle contains the majority of recruitment capillaries. A recruitment capillary bed would be most sensitive to alterations in Starling forces and fluid and macromolecular permeability.

Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

PubMed

Lustgarten, Michael S; Fielding, Roger A

2017-12-15

Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p≤0.05 and q<0.30) associated with NDM/LDM. Decreased renal function and the immune response have been previously linked with reduced muscle density, but the mechanisms underlying these connections are less clear. Metabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (β±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle may be a compensatory antimicrobial response to protect against an elevated microbial burden. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of statins on skeletal muscle function.

PubMed

Parker, Beth A; Capizzi, Jeffrey A; Grimaldi, Adam S; Clarkson, Priscilla M; Cole, Stephanie M; Keadle, Justin; Chipkin, Stuart; Pescatello, Linda S; Simpson, Kathleen; White, C Michael; Thompson, Paul D

2013-01-01

Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (P<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

Architectural and biochemical adaptations in skeletal muscle and bone following rotator cuff injury in a rat model.

PubMed

Sato, Eugene J; Killian, Megan L; Choi, Anthony J; Lin, Evie; Choo, Alexander D; Rodriguez-Soto, Ana E; Lim, Chanteak T; Thomopoulos, Stavros; Galatz, Leesa M; Ward, Samuel R

2015-04-01

Injury to the rotator cuff can cause irreversible changes to the structure and function of the associated muscles and bones. The temporal progression and pathomechanisms associated with these adaptations are unclear. The purpose of this study was to investigate the time course of structural muscle and osseous changes in a rat model of a massive rotator cuff tear. Supraspinatus and infraspinatus muscle architecture and biochemistry and humeral and scapular morphological parameters were measured three days, eight weeks, and sixteen weeks after dual tenotomy with and without chemical paralysis via botulinum toxin A (BTX). Muscle mass and physiological cross-sectional area increased over time in the age-matched control animals, decreased over time in the tenotomy+BTX group, and remained nearly the same in the tenotomy-alone group. Tenotomy+BTX led to increased extracellular collagen in the muscle. Changes in scapular bone morphology were observed in both experimental groups, consistent with reductions in load transmission across the joint. These data suggest that tenotomy alone interferes with normal age-related muscle growth. The addition of chemical paralysis yielded profound structural changes to the muscle and bone, potentially leading to impaired muscle function, increased muscle stiffness, and decreased bone strength. Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Muscle categorization using PDF estimation and Naive Bayes classification.

PubMed

Adel, Tameem M; Smith, Benn E; Stashuk, Daniel W

2012-01-01

The structure of motor unit potentials (MUPs) and their times of occurrence provide information about the motor units (MUs) that created them. As such, electromyographic (EMG) data can be used to categorize muscles as normal or suffering from a neuromuscular disease. Using pattern discovery (PD) allows clinicians to understand the rationale underlying a certain muscle characterization; i.e. it is transparent. Discretization is required in PD, which leads to some loss in accuracy. In this work, characterization techniques that are based on estimating probability density functions (PDFs) for each muscle category are implemented. Characterization probabilities of each motor unit potential train (MUPT) are obtained from these PDFs and then Bayes rule is used to aggregate the MUPT characterization probabilities to calculate muscle level probabilities. Even though this technique is not as transparent as PD, its accuracy is higher than the discrete PD. Ultimately, the goal is to use a technique that is based on both PDFs and PD and make it as transparent and as efficient as possible, but first it was necessary to thoroughly assess how accurate a fully continuous approach can be. Using gaussian PDF estimation achieved improvements in muscle categorization accuracy over PD and further improvements resulted from using feature value histograms to choose more representative PDFs; for instance, using log-normal distribution to represent skewed histograms.

Isometric contractions of motor units and immunohistochemistry of mouse soleus muscle.

PubMed Central

Lewis, D M; Parry, D J; Rowlerson, A

1982-01-01

1. Isometric contractions of motor units, isolated functionally by ventral root splitting in vivo, were recorded from mouse soleus muscle. 2. Motor unit tensions varied over a narrow symmetrical range and averaged 4.7% of whole muscle tension, corresponding to twenty-one motor units per muscle. 3. There was considerable variation between muscles in isometric twitch times-to-peak and even greater variation for the motor units. The distribution of motor unit times-to-peak was apparently unimodal and could be fitted by a single normal population. A slightly better fit was, however, obtained with two normal populations, as suggested by the histochemistry. 4. Twitch time-to-peak decreased in proportion to axonal conduction velocity in individual animals. The whole population of motor units could be fitted by a linear relation between time-to-peak and the reciprocal of conduction time in the motor axon. Motor unit tension was also linearly related to the reciprocal of conduction time. 5. Histochemistry showed clear division between Type I and Type IIa fibres. Type I fibres reacted strongly with antibody against slow myosin of cat soleus muscle; Type IIa gave a reaction no stronger than the background. The division was as clear as in the cat or rat. Images Fig. 2 Plate 1 PMID:7050345

Modified high-sucrose diet-induced abdominally obese and normal-weight rats developed high plasma free fatty acid and insulin resistance.

PubMed

Cao, Li; Liu, Xuehui; Cao, Hongyi; Lv, Qingguo; Tong, Nanwei

2012-01-01

Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle.

Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine.

PubMed

Wang, Huiling; Liu, Dajun; Cao, Peirang; Lecker, Stewart; Hu, Zhaoyong

2010-08-01

Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses. We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism. Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented. Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.

Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo.

PubMed

Keramaris-Vrantsis, Elizabeth; Lu, Pei J; Doran, Timothy; Zillmer, Allen; Ashar, Jignya; Esapa, Christopher T; Benson, Matthew A; Blake, Derek J; Rosenfeld, Jeffrey; Lu, Qi L

2007-10-01

Mutations in the fukutin-related protein gene (FKRP) are associated with a spectrum of diseases from mild limb-girdle muscular dystrophy type 2I to severe congenital muscular dystrophy type 1C, muscle-eye-brain disease (MEB), and Walker-Warburg syndrome (WWS). The effect of mutations on the transportation of the mutant proteins may constitute the underlying mechanisms for the pathogenesis of these diseases. Here we examined the subcellular localization of mouse and human normal and mutant FKRP proteins in cells and in muscle in vivo. Both normal human and mouse FKRPs localize in part of the Golgi apparatus in muscle fibers. Mutations in the FKRP gene invariably altered the localization of the protein, leading to endoplasmic reticulum retention within cells and diminished Golgi localization in muscle fibers. Our results therefore suggest that an individual missense point mutation can confer at least two independent effects on the protein, causing (1) reduction or loss of the presumed glycosyltransferase activity directly and (2) mislocalization that could further alter the function of the protein. The complexity of the effect of individual missense point mutations may partly explain the wide variation of the FKRP-related myopathies.

The Toll pathway is required in the epidermis for muscle development in the Drosophila embryo

NASA Technical Reports Server (NTRS)

Halfon, M. S.; Keshishian, H.

1998-01-01

The Toll signaling pathway functions in several Drosophila processes, including dorsal-ventral pattern formation and the immune response. Here, we demonstrate that this pathway is required in the epidermis for proper muscle development. Previously, we showed that the zygotic Toll protein is necessary for normal muscle development; in the absence of zygotic Toll, close to 50% of hemisegments have muscle patterning defects consisting of missing, duplicated and misinserted muscle fibers (Halfon, M.S., Hashimoto, C., and Keshishian, H., Dev. Biol. 169, 151-167, 1995). We have now also analyzed the requirements for easter, spatzle, tube, and pelle, all of which function in the Toll-mediated dorsal-ventral patterning pathway. We find that spatzle, tube, and pelle, but not easter, are necessary for muscle development. Mutations in these genes give a phenotype identical to that seen in Toll mutants, suggesting that elements of the same pathway used for Toll signaling in dorsal-ventral development are used during muscle development. By expressing the Toll cDNA under the control of distinct Toll enhancer elements in Toll mutant flies, we have examined the spatial requirements for Toll expression during muscle development. Expression of Toll in a subset of epidermal cells that includes the epidermal muscle attachment cells, but not Toll expression in the musculature, is necessary for proper muscle development. Our results suggest that signals received by the epidermis early during muscle development are an important part of the muscle patterning process.

Excess TGF-β mediates muscle weakness associated with bone metastases in mice

PubMed Central

Reiken, Steven; Xie, Wenjun; Andersson, Daniel C.; John, Sutha; Chiechi, Antonella; Wright, Laura E.; Umanskaya, Alisa; Niewolna, Maria; Trivedi, Trupti; Charkhzarrin, Sahba; Khatiwada, Pooja; Wronska, Anetta; Haynes, Ashley; Benassi, Maria Serena; Witzmann, Frank A.; Zhen, Gehua; Wang, Xiao; Cao, Xu; Roodman, G. David; Marks, Andrew R.; Guise, Theresa A.

2015-01-01

Cancer-associated muscle weakness is poorly understood and there is no effective treatment. Here, we find that seven different mouse models of human osteolytic bone metastases, representing breast, lung and prostate cancers, as well as multiple myeloma exhibited impaired muscle function, implicating a role for the tumor-bone microenvironment in cancer-associated muscle weakness. We found that TGF-β, released from the bone surface as a result of metastasis-induced bone destruction upregulated NADPH oxidase 4 (Nox4), resulting in elevated oxidization of skeletal muscle proteins, including the ryanodine receptor/calcium (Ca2+) release channel (RyR1). The oxidized RyR1 channels leaked Ca2+, resulting in lower intracellular signaling required for proper muscle contraction. We found that inhibiting RyR1 leak, TGF-β signaling, TGF-β release from bone or Nox4 all improved muscle function in mice with MDA-MB-231 bone metastases. Humans with breast cancer- or lung cancer-associated bone metastases also had oxidized skeletal muscle RyR1 that is not seen in normal muscle. Similarly, skeletal muscle weakness, higher levels of Nox4 protein and Nox4 binding to RyR1, and oxidation of RyR1 were present in a mouse model of Camurati-Engelmann disease, a non-malignant metabolic bone disorder associated with increased TGF-β activity. Thus, metastasis-induced TGF-β release from bone contributes to muscle weakness by decreasing Ca2+-induced muscle force production. PMID:26457758

Aging Gut Microbiota at the Cross-Road between Nutrition, Physical Frailty, and Sarcopenia: Is There a Gut–Muscle Axis?

PubMed Central

Ticinesi, Andrea; Lauretani, Fulvio; Milani, Christian; Tana, Claudio; Maggio, Marcello; Ventura, Marco; Meschi, Tiziana

2017-01-01

Inadequate nutrition and physical inactivity are the mainstays of primary sarcopenia–physiopathology in older individuals. Gut microbiota composition is strongly dependent on both of these elements, and conversely, can also influence the host physiology by modulating systemic inflammation, anabolism, insulin sensitivity, and energy production. The bacterial metabolism of nutrients theoretically influences skeletal muscle cell functionality through producing mediators that drive all of these systemic effects. In this study, we review the scientific literature supporting the concept of the involvement of gut microbiota in primary sarcopenia physiopathology. First, we examine studies associating fecal microbiota alterations with physical frailty, i.e., the loss of muscle performance and normal muscle mass. Then, we consider studies exploring the effects of exercise on gut microbiota composition. Finally, we examine studies demonstrating the possible effects of mediators produced by gut microbiota on skeletal muscle, and intervention studies considering the effects of prebiotic or probiotic administration on muscle function. Even if there is no evidence of a distinct gut microbiota composition in older sarcopenic patients, we conclude that the literature supports the possible presence of a “gut–muscle axis”, whereby gut microbiota may act as the mediator of the effects of nutrition on muscle cells. PMID:29189738

Changes in shoulder muscle activity pattern on surface electromyography after breast cancer surgery.

PubMed

Yang, Eun Joo; Kwon, YoungOk

2018-02-01

Alterations in muscle activation and restricted shoulder mobility, which are common in breast cancer patients, have been found to affect upper limb function. The purpose of this study was to determine muscle activity patterns, and to compare the prevalence of abnormal patterns among the type of breast surgery. In total, 274 breast cancer patients were recruited after surgery. Type of breast surgery was divided into mastectomy without reconstruction (Mastectomy), reconstruction with tissue expander/implant (TEI), latissimus dorsi (LD) flap, or transverse rectus abdominis flap (TRAM). Activities of shoulder muscles were measured using surface electromyography. Experimental analysis was conducted using a Gaussian filter smoothing method with regression. Patients demonstrated different patterns of muscle activation, such as normal, lower muscle electrical activity, and tightness. After adjusting for BMI and breast surgery, the odds of lower muscle electrical activity and tightness in the TRAM are 40.2% and 38.4% less than in the Mastectomy only group. The prevalence of abnormal patterns was significantly greater in the ALND than SLNB in all except TRAM. Alterations in muscle activity patterns differed by breast surgery and reconstruction type. For breast cancer patients with ALND, TRAM may be the best choice for maintaining upper limb function. © 2017 Wiley Periodicals, Inc.

The evaluation of relationship between vitamin D and muscle power by micro manual muscle tester in end-stage renal disease patients.

PubMed

Zahed, Nargesosadat; Chehrazi, Saghar; Falaknasi, Kianosh

2014-09-01

Muscle force of lower limb is a major factor for sustaining physical activity. Decreased muscle force can limit physical activity, which can increase mortality and morbidity in end-stage renal disease (ESRD) patients. Muscle force depends on several factors. One of the most important factors is 25-hydroxy vitamin D (25-OHD) that affects muscle function in both uremic and non-uremic patients. The aim of this study was to investigate the association between serum level of 25-OHD and muscle force of lower extremities in hemodialysis patients estimated by a Micro Manual Muscle Tester, a digital instrument that measures muscle force in kilograms This cross-sectional study was performed on 135 adult patients, 69 male (51%) and 66 female (69%) (mean: 1.4, standard deviation: 0.5), undergoing hemodialysis. Standard biochemistry parameters were measured before hemodialysis, including 25-OHD, calcium, albumin, para-hyroid hormone and C-reactive protein (CRP). Based on the result of serum level of 25-OHD, patients were classified into the following three groups: 85 patients (63%) were 25-OHD deficient (25-OHD <30), 43 patients (32%) had a normal level of 25-OHD (30-70) and seven patients (5%) had a toxic level of 25-OHD (>70) (mean: 1.42, standard deviation: 0.59). Also, based on the result of muscle force, patients were classified into the following three groups: 84/133 patients (62%) had weak muscle force (<5 kg), 46/133 patients (34%) had normal muscle force (5-10 kg) and three patients (21%) had strong muscle force (>10 kg) (mean: 1.39, standard deviation: 0.53). There was a significant relation between 25-OHD level and muscle force (P = 0.02), between age and muscle force (P = 0.002) and between gender and muscle force (P <0.001). In our opinion, 25-OHD can be a useful drug in ESRD patients to improve muscle force and physical activity.

Transcranial electric stimulation for intraoperative motor evoked potential monitoring: dependence of required stimulation current on interstimulus interval value.

PubMed

Joksimovic, Boban; Szelenyi, Andrea; Seifert, Volker; Damjanovic, Aleksandar; Damjanovic, Aleksandra; Rasulic, Lukas

2015-05-01

To evaluate the relationship between stimulus intensity by constant current transcranial electric stimulation and interstimulus interval (ISI) for eliciting muscle motor evoked potentials (MEPs) in three different hand muscles and the tibialis anterior muscles. We tested intraoperatively different monophasic constant current pulses and ISIs in 22 patients with clinically normal motor function. Motor thresholds of contralateral muscle MEPs were determined at 0.5 milliseconds (ms) pulse duration and ISIs of 1, 2, 3, 4, 5, and 10 ms using a train of 2, 3, and 5 monophasic constant current pulses of 62 to 104 mA before craniotomy and after closure of the dura mater. The lowest stimulation threshold to elicit MEPs in the examined muscles was achieved with a train of 5 pulses (ISI: 3 ms) before craniotomy, which was statistically significant compared with 2 pulses (ISI: 3 ms) as well as 3 pulses (ISIs: 3 and 10 ms). An ISI of 3 ms gave the lowest motor thresholds with statistical significance compared with the ISIs of 4 ms (2 pulses) and of 1 ms (3 pulses). All current intensity (mA) and ISI (ms) relationship graphs had a trend of the exponential function as y = a + bx + c ρ (x), where y is intensity (mA) and x is ISI (ms). The minimum of the function was determined for each patient and each muscle. The difference was statistically significant between 3 and 5 pulses before craniotomy and between 3 and 5 pulses and 2 and 5 pulses after closure of the dura mater. In adult neurosurgical patients with a normal motor status, a train of 5 pulses and an ISI of 3 ms provide the lowest motor thresholds. We provided evidence of the dependence of required stimulation current on ISI. Georg Thieme Verlag KG Stuttgart · New York.

A child with a difficult airway: what do I do next?

PubMed

Engelhardt, Thomas; Weiss, Markus

2012-06-01

Difficulties in pediatric airway management are common and continue to result in significant morbidity and mortality. This review reports on current concepts in approaching a child with a difficult airway. Routine airway management in healthy children with normal airways is simple in experienced hands. Mask ventilation (oxygenation) is always possible and tracheal intubation normally simple. However, transient hypoxia is common in these children usually due to unexpected anatomical and functional airway problems or failure to ventilate during rapid sequence induction. Anatomical airway problems (upper airway collapse and adenoid hypertrophy) and functional airway problems (laryngospasm, bronchospasm, insufficient depth of anesthesia and muscle rigidity, gastric hyperinflation, and alveolar collapse) require urgent recognition and treatment algorithms due to insufficient oxygen reserves. Early muscle paralysis and epinephrine administration aids resolution of these functional airway obstructions. Children with an 'impaired' normal (foreign body, allergy, and inflammation) or an expected difficult (scars, tumors, and congenital) airway require careful planning and expertise. Training in the recognition and management of these different situations as well as a suitably equipped anesthesia workstation and trained personnel are essential. The healthy child with an unexpected airway problem requires clear strategies. The 'impaired' normal pediatric airway may be handled by anesthetists experienced with children, whereas the expected difficult pediatric airway requires dedicated pediatric anesthesia specialist care and should only be managed in specialized centers.

Electromyographic evaluation of abdominal-muscle function with and without concomitant pelvic-floor-muscle contraction.

PubMed

Tahan, Nahid; Arab, Amir Massoud; Vaseghi, Bita; Khademi, Khosro

2013-05-01

Coactivation of abdominal and pelvic-floor muscles (PFM) is an issue considered by researchers recently. Electromyography (EMG) studies have shown that the abdominal-muscle activity is a normal response to PFM activity, and increase in EMG activity of the PFM concomitant with abdominal-muscle contraction was also reported. The purpose of this study was to compare the changes in EMG activity of the deep abdominal muscles during abdominal-muscle contraction (abdominal hollowing and bracing) with and without concomitant PFM contraction in healthy and low-back-pain (LBP) subjects. A 2 × 2 repeated-measures design. Laboratory. 30 subjects (15 with LBP, 15 without LBP). Peak rectified EMG of abdominal muscles. No difference in EMG of abdominal muscles with and without concomitant PFM contraction in abdominal hollowing (P = .84) and abdominal bracing (P = .53). No difference in EMG signal of abdominal muscles with and without PFM contraction between LBP and healthy subjects in both abdominal hollowing (P = .88) and abdominal bracing (P = .98) maneuvers. Adding PFM contraction had no significant effect on abdominal-muscle contraction in subjects with and without LBP.

Isolation and maintenance-free culture of contractile myotubes from Manduca sexta embryos.

PubMed

Baryshyan, Amanda L; Woods, William; Trimmer, Barry A; Kaplan, David L

2012-01-01

Skeletal muscle tissue engineering has the potential to treat tissue loss and degenerative diseases. However, these systems are also applicable for a variety of devices where actuation is needed, such as microelectromechanical systems (MEMS) and robotics. Most current efforts to generate muscle bioactuators are focused on using mammalian cells, which require exacting conditions for survival and function. In contrast, invertebrate cells are more environmentally robust, metabolically adaptable and relatively autonomous. Our hypothesis is that the use of invertebrate muscle cells will obviate many of the limitations encountered when mammalian cells are used for bioactuation. We focus on the tobacco hornworm, Manduca sexta, due to its easy availability, large size and well-characterized muscle contractile properties. Using isolated embryonic cells, we have developed culture conditions to grow and characterize contractile M. sexta muscles. The insect hormone 20-hydroxyecdysone was used to induce differentiation in the system, resulting in cells that stained positive for myosin, contract spontaneously for the duration of the culture, and do not require media changes over periods of more than a month. These cells proliferate under normal conditions, but the application of juvenile hormone induced further proliferation and inhibited differentiation. Cellular metabolism under normal and low glucose conditions was compared for C2C12 mouse and M. sexta myoblast cells. While differentiated C2C12 cells consumed glucose and produced lactate over one week as expected, M. sexta muscle did not consume significant glucose, and lactate production exceeded mammalian muscle production on a per cell basis. Contractile properties were evaluated using index of movement analysis, which demonstrated the potential of these cells to perform mechanical work. The ability of cultured M. sexta muscle to continuously function at ambient conditions without medium replenishment, combined with the interesting metabolic properties, suggests that this cell source is a promising candidate for further investigation toward bioactuator applications.

Systemic SMAD7 Gene Therapy Increases Striated Muscle Mass and Enhances Exercise Capacity in a Dose-Dependent Manner.

PubMed

Maricelli, Joseph W; Bishaw, Yemeserach M; Wang, Bo; Du, Min; Rodgers, Buel D

2018-03-01

Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated virus (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and, as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to improve systemic muscle function similarly, especially exercise capacity. A 2-month-long dose-escalation study was therefore conducted using 5 × 10 11 , 1 × 10 12 , and 5 × 10 12 vg/mouse and different tests of systemic muscle function. Body mass, skeletal muscle mass, heart mass, and forelimb grip strength were all increased in a dose-dependent manner, as was the fiber cross-sectional area of tibialis anterior muscles. Maximal oxygen consumption (VO 2 max), a measure of metabolic rate, was similarly enhanced during forced treadmill running, and although the total distance traveled was only elevated by the highest dose, all doses reduced the energy expenditure rate compared to control mice injected with an empty vector. Such improvements in VO 2 max are consistent with physiological cardiac hypertrophy, which is highly beneficial and a normal adaptive response to exercise. This was particularly evident at the lowest dose tested, which had minimal significant effects on skeletal muscle mass and/or function, but increased heart weight and exercise capacity. These results together suggest that AVGN7 enhances striated muscle mass and systemic muscle function. They also define minimally effective and optimal doses for future preclinical trials and toxicology studies and in turn will aid in establishing dose ranges for clinical trials.

Quadriceps muscle use in the flywheel and barbell squat.

PubMed

Norrbrand, Lena; Tous-Fajardo, Julio; Vargas, Roberto; Tesch, Per A

2011-01-01

Resistance exercise has been proposed as an aid to counteract quadriceps muscle atrophy in astronauts during extended missions in orbit. While space authorities have advocated the squat exercise should be prescribed, no exercise system suitable for in-flight use has been validated with regard to quadriceps muscle use. We compared muscle involvement in the terrestrial "gold standard" squat using free weights and a nongravity dependent flywheel resistance exercise device designed for use in space. The subjects were 10 strength-trained men who performed 5 sets of 10 repetitions using the barbell squat (BS; 10 repetition maximum) or flywheel squat (FS; each repetition maximal), respectively. Functional magnetic resonance imaging (MRI) and surface electromyography (EMG) techniques assessed quadriceps muscle use. Exercise-induced contrast shift of MR images was measured by means of transverse relaxation time (T2). EMG root mean square (RMS) was measured during concentric (CON) and eccentric (ECC) actions and normalized to EMG RMS determined during maximal voluntary contraction. The quadriceps muscle group showed greater exercise-induced T2 increase following FS compared with BS. Among individual muscles, the rectus femoris displayed greater T2 increase with FS (+24 +/- 14%) than BS (+8 +/- 4%). Normalized quadriceps EMG showed no difference across exercise modes. Collectively, the results of this study suggest that quadriceps muscle use in the squat is comparable, if not greater, with flywheel compared with free weight resistance exercise. Data appear to provide support for use of flywheel squat resistance exercise as a countermeasures adjunct during spaceflight.

The role of hormones, cytokines and heat shock proteins during age-related muscle loss.

PubMed

Lee, Claire E; McArdle, Anne; Griffiths, Richard D

2007-10-01

Ageing is associated with a progressive decline of muscle mass, strength, and quality, a condition known as sarcopenia. Due to the progressive ageing of western populations, age-related sarcopenia is a major public health problem. Several possible mechanisms for age-related muscle atrophy have been described; however the precise contribution of each is unknown. Age-related muscle loss is thought to be a multi-factoral process composed of events such as physical activity, nutritional intake, oxidative stress, inflammatory insults and hormonal changes. There is a need for a greater understanding of the loss of muscle mass with age as this could have a dramatic impact on the elderly and critically ill if this research leads to maintenance or improvement in functional ability. This review aims to outline the process of skeletal muscle degeneration with ageing, normal and aberrant skeletal muscle regeneration, and to address recent research on the effects of gender and sex steroid hormones during the process of age-related muscle loss.

Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension

NASA Technical Reports Server (NTRS)

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.

Myoelectric Response of Back Muscles to Vertical Random Whole-Body Vibration with Different Magnitudes at Different Postures

NASA Astrophysics Data System (ADS)

BLÜTHNER, R.; SEIDEL, H.; HINZ, B.

2002-05-01

Back muscle forces contribute essentially to the whole-body vibration-induced spinal load. The electromyogram (EMG) can help to estimate these forces during whole-body vibration (WBV). Thirty-eight subjects were exposed to identical random low-frequency WBV (0·7, 1·0 and 1·4 m/s-2 r.m.s. weighted acceleration) at a relaxed, erect and bent forward postures. The acceleration of the seat and the force between the seat and the buttocks were measured. Six EMGs were derived from the right side of the m. trapezius pars descendens, m. ileocostalis lumborum pars thoracis, m. ileocostalis lumborum pars lumborum; m. longissimus thoracis pars thoracis, m. longissimus thoracis pars lumborum, and lumbar multifidus muscle. All data were filtered for anti-aliasing and sampled with 1000 Hz. Artefacts caused by the ECG in the EMG were identified and eliminated in the time domain using wavelets. The individually rectified and normalized EMGs were averaged across subjects. The EMGs without WBV exhibited characteristic patterns for the three postures examined. The coherence and transfer functions indicated characteristic myoelectric responses to random WBV with several effects of posture and WBV magnitude. A comprehensive set of transfer functions from the seat acceleration or the mean normalized input force to the mean processed EMG was presented.The results can be used for the development of more sophisticated models with a separate control of various back muscle groups. However, the EMG-force relationship under dynamic conditions needs to be examined in more detail before the results can be implemented. Since different reflex mechanisms depending on the frequency of WBV are linked with different types of active muscle fibres, various time delays between the EMG and muscle force may be necessary.

Computer modeling of siRNA knockdown effects indicates an essential role of the Ca2+ channel alpha2delta-1 subunit in cardiac excitation-contraction coupling.

PubMed

Tuluc, Petronel; Kern, Georg; Obermair, Gerald J; Flucher, Bernhard E

2007-06-26

L-type Ca(2+) currents determine the shape of cardiac action potentials (AP) and the magnitude of the myoplasmic Ca(2+) signal, which regulates the contraction force. The auxiliary Ca(2+) channel subunits alpha(2)delta-1 and beta(2) are important regulators of membrane expression and current properties of the cardiac Ca(2+) channel (Ca(V)1.2). However, their role in cardiac excitation-contraction coupling is still elusive. Here we addressed this question by combining siRNA knockdown of the alpha(2)delta-1 subunit in a muscle expression system with simulation of APs and Ca(2+) transients by using a quantitative computer model of ventricular myocytes. Reconstitution of dysgenic muscle cells with Ca(V)1.2 (GFP-alpha(1C)) recapitulates key properties of cardiac excitation-contraction coupling. Concomitant depletion of the alpha(2)delta-1 subunit did not perturb membrane expression or targeting of the pore-forming GFP-alpha(1C) subunit into junctions between the outer membrane and the sarcoplasmic reticulum. However, alpha(2)delta-1 depletion shifted the voltage dependence of Ca(2+) current activation by 9 mV to more positive potentials, and it slowed down activation and inactivation kinetics approximately 2-fold. Computer modeling revealed that the altered voltage dependence and current kinetics exert opposing effects on the function of ventricular myocytes that in total cause a 60% prolongation of the AP and a 2-fold increase of the myoplasmic Ca(2+) concentration during each contraction. Thus, the Ca(2+) channel alpha(2)delta-1 subunit is not essential for normal Ca(2+) channel targeting in muscle but is a key determinant of normal excitation and contraction of cardiac muscle cells, and a reduction of alpha(2)delta-1 function is predicted to severely perturb normal heart function.

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

NASA Technical Reports Server (NTRS)

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.

Electromyographic assessment of muscle activity between genders during unilateral weight-bearing tasks using adjusted distances.

PubMed

Bouillon, Lucinda E; Wilhelm, Jacqueline; Eisel, Patricia; Wiesner, Jessica; Rachow, Megan; Hatteberg, Lindsay

2012-12-01

Researchers have observed differences in muscle activity patterns between males and females during functional exercises. The research methods employed have used various step heights and lunge distances to assess functional exercise making gender comparisons difficult. The purpose of this study was to examine core and lower extremity muscle activity between genders during single-limb exercises using adjusted distances and step heights based on a percentage of the participant's height. Twenty men and 20 women who were recreationally active and healthy participated in the study. Two-dimensional video and surface electromyography (SEMG) were used to assess performance during three exercise maneuvers (step down, forward lunge, and side-step lunge). Eight muscles were assessed using SEMG (rectus abdominus, external oblique, erector spinae, rectus femoris, tensor fascia latae, gluteus medius, gluteus maximus, biceps femoris). Maximal voluntary isometric contractions (MVIC) were used for each muscle and expressed as %MVIC to normalize SEMG to account for body mass differences. Exercises were randomized and distances were normalized to the participant's lower limb length. Descriptive statistics, mixed-model ANOVA, and ICCs with 95% confidence intervals were calculated. Males were taller, heavier, and had longer leg length when compared to the females. No differences in %MVIC activity were found between genders by task across the eight muscles. For both males and females, the step down task resulted in higher %MVIC for gluteus maximus compared to lunge, (p=0.002). Step down exercise produced higher %MVIC for gluteus medius than lunge (p=0.002) and side step (p=0.006). ICC(3,3) ranged from moderate to high (0.74 to 0.97) for the three tasks. Muscle activation among the eight muscles was similar between females and males during the lunge, side-step, and step down tasks, with distances adjusted to leg length. Both males and females elicited higher muscle activity for gluteus maximus and gluteus medius as compared to the trunk, hip flexors, or hamstring muscles. However these values were well below the recruitment levels necessary for strengthening in both genders. 4.

ELECTROMYOGRAPHIC ASSESSMENT OF MUSCLE ACTIVITY BETWEEN GENDERS DURING UNILATERAL WEIGHT‐BEARING TASKS USING ADJUSTED DISTANCES

PubMed Central

Wilhelm, Jacqueline; Eisel, Patricia; Wiesner, Jessica; Rachow, Megan; Hatteberg, Lindsay

2012-01-01

Purpose/Background: Researchers have observed differences in muscle activity patterns between males and females during functional exercises. The research methods employed have used various step heights and lunge distances to assess functional exercise making gender comparisons difficult. The purpose of this study was to examine core and lower extremity muscle activity between genders during single‐limb exercises using adjusted distances and step heights based on a percentage of the participant's height. Methods: Twenty men and 20 women who were recreationally active and healthy participated in the study. Two‐dimensional video and surface electromyography (SEMG) were used to assess performance during three exercise maneuvers (step down, forward lunge, and side‐step lunge). Eight muscles were assessed using SEMG (rectus abdominus, external oblique, erector spinae, rectus femoris, tensor fascia latae, gluteus medius, gluteus maximus, biceps femoris). Maximal voluntary isometric contractions (MVIC) were used for each muscle and expressed as %MVIC to normalize SEMG to account for body mass differences. Exercises were randomized and distances were normalized to the participant's lower limb length. Descriptive statistics, mixed‐model ANOVA, and ICCs with 95% confidence intervals were calculated. Results: Males were taller, heavier, and had longer leg length when compared to the females. No differences in %MVIC activity were found between genders by task across the eight muscles. For both males and females, the step down task resulted in higher %MVIC for gluteus maximus compared to lunge, (p=0.002). Step down exercise produced higher %MVIC for gluteus medius than lunge (p=0.002) and side step (p=0.006). ICC3,3 ranged from moderate to high (0.74 to 0.97) for the three tasks. Conclusions: Muscle activation among the eight muscles was similar between females and males during the lunge, side‐step, and step down tasks, with distances adjusted to leg length. Both males and females elicited higher muscle activity for gluteus maximus and gluteus medius as compared to the trunk, hip flexors, or hamstring muscles. However these values were well below the recruitment levels necessary for strengthening in both genders. Level of evidence: 4 PMID:23316423

Deregulation of the Protocadherin Gene FAT1 Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy

PubMed Central

Caruso, Nathalie; Herberth, Balàzs; Bartoli, Marc; Puppo, Francesca; Dumonceaux, Julie; Zimmermann, Angela; Denadai, Simon; Lebossé, Marie; Roche, Stephane; Geng, Linda; Magdinier, Frederique; Attarian, Shahram; Bernard, Rafaelle; Maina, Flavio; Levy, Nicolas; Helmbacher, Françoise

2013-01-01

Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts. Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains, altering the shape of selective groups of muscles in the shoulder and face. These shape abnormalities were followed by early onset regionalised muscle defects in adult Fat1-deficient mice. Tissue-specific ablation of Fat1 driven by Pax3-cre reproduced muscle shape defects in limb but not face muscles, indicating a cell-autonomous contribution of Fat1 in migrating muscle precursors. Strikingly, the topography of muscle abnormalities caused by Fat1 loss-of-function resembles that of human patients with facioscapulohumeral dystrophy (FSHD). FAT1 lies near the critical locus involved in causing FSHD, and Fat1 mutant mice also show retinal vasculopathy, mimicking another symptom of FSHD, and showed abnormal inner ear patterning, predictive of deafness, reminiscent of another burden of FSHD. Muscle-specific reduction of FAT1 expression and promoter silencing was observed in foetal FSHD1 cases. CGH array-based studies identified deletion polymorphisms within a putative regulatory enhancer of FAT1, predictive of tissue-specific depletion of FAT1 expression, which preferentially segregate with FSHD. Our study identifies FAT1 as a critical determinant of muscle form, misregulation of which associates with FSHD. PMID:23785297

Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells.

PubMed

Fletcher, Rachel S; Ratajczak, Joanna; Doig, Craig L; Oakey, Lucy A; Callingham, Rebecca; Da Silva Xavier, Gabriella; Garten, Antje; Elhassan, Yasir S; Redpath, Philip; Migaud, Marie E; Philp, Andrew; Brenner, Charles; Canto, Carles; Lavery, Gareth G

2017-08-01

Augmenting nicotinamide adenine dinucleotide (NAD + ) availability may protect skeletal muscle from age-related metabolic decline. Dietary supplementation of NAD + precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating muscle NAD + . Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD + from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis. We exploited expression profiling of muscle NAD + biosynthetic pathways, single and double nicotinamide riboside kinase 1/2 (NRK1/2) loss-of-function mice, and pharmacological inhibition of muscle NAD + recycling to evaluate NMN and NR utilization. Skeletal muscle cells primarily rely on nicotinamide phosphoribosyltransferase (NAMPT), NRK1, and NRK2 for salvage biosynthesis of NAD + . NAMPT inhibition depletes muscle NAD + availability and can be rescued by NR and NMN as the preferred precursors for elevating muscle cell NAD + in a pathway that depends on NRK1 and NRK2. Nrk2 knockout mice develop normally and show subtle alterations to their NAD+ metabolome and expression of related genes. NRK1, NRK2, and double KO myotubes revealed redundancy in the NRK dependent metabolism of NR to NAD + . Significantly, these models revealed that NMN supplementation is also dependent upon NRK activity to enhance NAD + availability. These results identify skeletal muscle cells as requiring NAMPT to maintain NAD + availability and reveal that NRK1 and 2 display overlapping function in salvage of exogenous NR and NMN to augment intracellular NAD + availability.

Macrophage Plasticity and the Role of Inflammation in Skeletal Muscle Repair

PubMed Central

Kharraz, Yacine; Guerra, Joana; Mann, Christopher J.; Serrano, Antonio L.; Muñoz-Cánoves, Pura

2013-01-01

Effective repair of damaged tissues and organs requires the coordinated action of several cell types, including infiltrating inflammatory cells and resident cells. Recent findings have uncovered a central role for macrophages in the repair of skeletal muscle after acute damage. If damage persists, as in skeletal muscle pathologies such as Duchenne muscular dystrophy (DMD), macrophage infiltration perpetuates and leads to progressive fibrosis, thus exacerbating disease severity. Here we discuss how dynamic changes in macrophage populations and activation states in the damaged muscle tissue contribute to its efficient regeneration. We describe how ordered changes in macrophage polarization, from M1 to M2 subtypes, can differently affect muscle stem cell (satellite cell) functions. Finally, we also highlight some of the new mechanisms underlying macrophage plasticity and briefly discuss the emerging implications of lymphocytes and other inflammatory cell types in normal versus pathological muscle repair. PMID:23509419

Muscle velocity recovery cycles: effects of repetitive stimulation on two muscles.

PubMed

Boërio, Delphine; Z'Graggen, Werner J; Tan, S Veronica; Guetg, Andri; Ackermann, Karin; Bostock, Hugh

2012-07-01

We sought to characterize the excitability properties of tibialis anterior (TA) and brachioradialis (BR) muscles at rest and during electrically induced muscle activation in normal subjects. Two centers recruited 10 subjects each. Multi-fiber velocity recovery cycles (VRCs) were recorded from TA (both centers) and BR (one center). VRCs were assessed at rest and during repetitive stimulation (intermittent 20 Hz for 6 min). Changes in latency and peak amplitude of the muscle action potential induced by a frequency ramp to 30 Hz were also characterized. Excitability properties recorded from TA were very similar between centers. Repetitive stimulation generated marked excitability changes, which were similar between TA and BR. Standardized tests of muscle VRCs and responses to repetitive stimulation can provide consistent measures of membrane function and may encourage their wider use in clinical neurophysiology to investigate the pathophysiology of neuromuscular disorders. Copyright © 2012 Wiley Periodicals, Inc.

[Muscle efficiency in total shoulder prosthesis implantation: dependence on position of the humeral head and rotator cuff function].

PubMed

Klages, A; Hurschler, C; Wülker, N; Windhagen, H

2001-09-01

Modern shoulder prostheses permit an anatomic reconstruction of the joint, although the biomechanical advantages are not proven. The goal of this study was to investigate the relationship between position of the humeral head and function of the shoulder prosthesis (muscle efficiency). Shoulder elevation-motion and rotator cuff defects were simulated in vitro in a robot-assisted shoulder simulator. The EPOCA Custom Offset shoulder prosthesis (Argomedical AG, Cham, CH) was implanted in seven normal shoulders (77 +/- 20 kg, 55 +/- 14 years). Active elevation was simulated by hydraulic cylinders, and scapulothoratic motion by a specially programmed industrial robot. Muscle efficiency (elevation-angle/muscle-force of the deltoid muscle) was measured in anatomic (ANA), medialised (MED) and lateralised (LAT) positions of the humeral head, with or without rotator cuff muscle deficiency. Medialisation increased efficiency by 0.03 +/- 0.04 deg/N (p = 0.022), lateralisation decreased it by 0.04 +/- 0.06 deg/N (p = 0.009). Supraspinatus muscle deficiency increased the deltoid force required to elevate the arm, and thus decreased efficiency (ANA p = 0.091, MED p = 0.018, LAT p = 0.028). The data confirm that the position of the humeral head affects the mechanics of total shoulder arthroplasty. Medialisation increases efficiency of the deltoid muscle and may prove useful in compensating isolated supraspinatus muscle deficiency. Lateralisation, in contrast, leads to an unfavorable situation.

Muscle quality, aerobic fitness and fat mass predict lower-extremity physical function in community-dwelling older adults.

PubMed

Misic, Mark M; Rosengren, Karl S; Woods, Jeffrey A; Evans, Ellen M

2007-01-01

Muscle mass, strength and fitness play a role in lower-extremity physical function (LEPF) in older adults; however, the relationships remain inadequately characterized. This study aimed to examine the relationships between leg mineral free lean mass (MFLM(LEG)), leg muscle quality (leg strength normalized for MFLM(LEG)), adiposity, aerobic fitness and LEPF in community-dwelling healthy elderly subjects. Fifty-five older adults (69.3 +/- 5.5 years, 36 females, 19 males) were assessed for leg strength using an isokinetic dynamometer, body composition by dual energy X-ray absorptiometry and aerobic fitness via a treadmill maximal oxygen consumption test. LEPF was assessed using computerized dynamic posturography and stair ascent/descent, a timed up-and-go task and a 7-meter walk with and without an obstacle. Muscle strength, muscle quality and aerobic fitness were similarly correlated with static LEPF tests (r range 0.27-0.40, p < 0.05); however, the strength of the independent predictors was not robust with explained variance ranging from 9 to 16%. Muscle quality was the strongest correlate of all dynamic LEPF tests (r range 0.54-0.65, p < 0.001). Using stepwise linear regression analysis, muscle quality was the strongest independent predictor of dynamic physical function explaining 29-42% of the variance (p < 0.001), whereas aerobic fitness or body fat mass explained 5-6% of the variance (p < 0.05) depending on performance measure. Muscle quality is the most important predictor, and aerobic fitness and fat mass are secondary predictors of LEPF in community-dwelling older adults. These findings support the importance of exercise, especially strength training, for optimal body composition, and maintenance of strength and physical function in older adults.

Funktionelle Elektrostimulation Paraplegischer Patienten

PubMed Central

2014-01-01

Functional Electrical Stimulation on Paraplegic Patients. We report on clinical and physiological effects of 8 months Functional Electrical Stimulation (FES) of quadriceps femoris muscle on 16 paraplegic patients. Each patient had muscle biopsies, CT-muscle diameter measurements, knee extension strength testing carried out before and after 8 months FES training. Skin perfusion was documented through infrared telethermography and xenon clearance, muscle perfusion was recorded through thallium scintigraphy. After 8 months FES training baseline skin perfusion showed 86 % increase, muscle perfusion was augmented by 87 %. Muscle fiber diameters showed an average increase of 59 % after 8 months FES training. Muscles in patients with spastic paresis as well as in patients with denervation showed an increase in aerob and anaerob muscle enzymes up to the normal range. Even without axonal neurotropic substances FES was able to demonstrate fiberhypertrophy, enzyme adaptation and intracellular structural benefits in denervated muscles. The increment in muscle area as visible on CT-scans of quadriceps femoris was 30 % in spastic paraplegia and 10 % in denervated patients respectively. FES induced changes were less in areas not directly underneath the surface electrodes. We strongly recommend the use of Kern’s current for FES in denervated muscles to induce tetanic muscle contractions as we formed a very critical opinion of conventional exponential current. In patients with conus-cauda-lesions FES must be integrated into modern rehabilitation to prevent extreme muscle degeneration and decubital ulcers. Using FES we are able to improve metabolism and induce positive trophic changes in our patients lower extremities. In spastic paraplegics the functions „rising and walking“ achieved through FES are much better training than FES ergometers. Larger muscle masses are activated and an increased heart rate is measured, therefore the impact on cardiovascular fitness and metabolism is much greater. This effectively addresses and prevents all problems which result from inactivity in paraplegic patients. PMID:26913132

PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy.

PubMed

Nelson, Michael D; Rader, Florian; Tang, Xiu; Tavyev, Jane; Nelson, Stanley F; Miceli, M Carrie; Elashoff, Robert M; Sweeney, H Lee; Victor, Ronald G

2014-06-10

To determine whether phosphodiesterase type 5 (PDE5) inhibition can alleviate exercise-induced skeletal muscle ischemia in boys with Duchenne muscular dystrophy (DMD). In 10 boys with DMD and 10 healthy age-matched male controls, we assessed exercise-induced attenuation of reflex sympathetic vasoconstriction, i.e., functional sympatholysis, a protective mechanism that matches oxygen delivery to metabolic demand. Reflex vasoconstriction was induced by simulated orthostatic stress, measured as the decrease in forearm muscle oxygenation with near-infrared spectroscopy, and performed when the forearm muscles were rested or lightly exercised with rhythmic handgrip exercise. Then, the patients underwent an open-label, dose-escalation, crossover trial with single oral doses of tadalafil or sildenafil. The major new findings are 2-fold: first, sympatholysis is impaired in boys with DMD-producing functional muscle ischemia-despite contemporary background therapy with corticosteroids alone or in combination with cardioprotective medication. Second, PDE5 inhibition with standard clinical doses of either tadalafil or sildenafil alleviates this ischemia in a dose-dependent manner. Furthermore, PDE5 inhibition also normalizes the exercise-induced increase in skeletal muscle blood flow (measured by Doppler ultrasound), which is markedly blunted in boys with DMD. These data provide in-human proof of concept for PDE5 inhibition as a putative new therapeutic strategy for DMD. This study provides Class IV evidence that in patients with DMD, PDE5 inhibition restores functional sympatholysis. © 2014 American Academy of Neurology.

Response of mitochondrial function to hypothyroidism in normal and regenerated rat skeletal muscle.

PubMed

Zoll, J; Ventura-Clapier, R; Serrurier, B; Bigard, A X

2001-01-01

Although thyroid hormones induce a well known decrease in muscle oxidative capacity, nothing is known concerning their effects on mitochondrial function and regulation in situ. Similarly, the influence of regeneration process is not completely understood. We investigated the effects of hypothyroidism on mitochondrial function in fast gastrocnemius (GS) and slow soleus (SOL) muscles either intact or having undergone a cycle of degeneration/regeneration (Rg SOL) following a local injection of myotoxin. Thyroid hormone deficiency was induced by thyroidectomy and propylthiouracyl via drinking water. Respiration was measured in muscle fibres permeabilised by saponin in order to assess the oxidative capacity of the muscles and the regulation of mitochondria in situ. Oxidative capacities were 8.9 in SOL, 8.5 in Rg SOL and 5.9 micromol O2/min/g dry weight in GS and decreased by 52, 42 and 39% respectively (P < 0.001) in hypothyroid rats. Moreover, the Km of mitochondrial respiration for the phosphate acceptor ADP exhibited a two-fold decrease in Rg SOL and intact SOL by hypothyroidism (P < 0.01), while mitochondrial creatine kinase activity and sensitivity of mitochondrial respiration to creatine were not altered. The results of this study demonstrate that hypothyroidism markedly altered the sensitivity of mitochondrial respiration to ADP but not to creatine in SOL muscles, suggesting that mitochondrial regulation could be partially controlled by thyroid hormones. On the other hand, mitochondrial function completely recovered following regeneration/degeneration, suggesting that thyroid hormones are not involved in the regeneration process per se.

The ICM research agenda on intensive care unit-acquired weakness.

PubMed

Latronico, Nicola; Herridge, Margaret; Hopkins, Ramona O; Angus, Derek; Hart, Nicholas; Hermans, Greet; Iwashyna, Theodore; Arabi, Yaseen; Citerio, Giuseppe; Wesley Ely, E; Hall, Jesse; Mehta, Sangeeta; Puntillo, Kathleen; Van den Hoeven, Johannes; Wunsch, Hannah; Cook, Deborah; Dos Santos, Claudia; Rubenfeld, Gordon; Vincent, Jean-Louis; Van den Berghe, Greet; Azoulay, Elie; Needham, Dale M

2017-09-01

We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, amplifying the effects of each individual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.

Arterial Smooth Muscle Mitochondria Amplify Hydrogen Peroxide Microdomains Functionally Coupled to L-Type Calcium Channels

PubMed Central

Chaplin, Nathan L.; Nieves-Cintrón, Madeline; Fresquez, Adriana M.; Navedo, Manuel F.; Amberg, Gregory C.

2015-01-01

Rationale Mitochondria are key integrators of convergent intracellular signaling pathways. Two important second messengers modulated by mitochondria are calcium and reactive oxygen species. To date, coherent mechanisms describing mitochondrial integration of calcium and oxidative signaling in arterial smooth muscle are incomplete. Objective To address and add clarity to this issue we tested the hypothesis that mitochondria regulate subplasmalemmal calcium and hydrogen peroxide microdomain signaling in cerebral arterial smooth muscle. Methods and Results Using an image-based approach we investigated the impact of mitochondrial regulation of L-type calcium channels on subcellular calcium and ROS signaling microdomains in isolated arterial smooth muscle cells. Our single cell observations were then related experimentally to intact arterial segments and to living animals. We found that subplasmalemmal mitochondrial amplification of hydrogen peroxide microdomain signaling stimulates L-type calcium channels and that this mechanism strongly impacts the functional capacity of the vasoconstrictor angiotensin II. Importantly, we also found that disrupting this mitochondrial amplification mechanism in vivo normalized arterial function and attenuated the hypertensive response to systemic endothelial dysfunction. Conclusions From these observations we conclude that mitochondrial amplification of subplasmalemmal calcium and hydrogen peroxide microdomain signaling is a fundamental mechanism regulating arterial smooth muscle function. As the principle components involved are fairly ubiquitous and positioning of mitochondria near the plasma membrane is not restricted to arterial smooth muscle, this mechanism could occur in many cell types and contribute to pathological elevations of intracellular calcium and increased oxidative stress associated with many diseases. PMID:26390880

Myosin Transducer Mutations Differentially Affect Motor Function, Myofibril Structure, and the Performance of Skeletal and Cardiac Muscles

PubMed Central

Cammarato, Anthony; Dambacher, Corey M.; Knowles, Aileen F.; Kronert, William A.; Bodmer, Rolf

2008-01-01

Striated muscle myosin is a multidomain ATP-dependent molecular motor. Alterations to various domains affect the chemomechanical properties of the motor, and they are associated with skeletal and cardiac myopathies. The myosin transducer domain is located near the nucleotide-binding site. Here, we helped define the role of the transducer by using an integrative approach to study how Drosophila melanogaster transducer mutations D45 and Mhc5 affect myosin function and skeletal and cardiac muscle structure and performance. We found D45 (A261T) myosin has depressed ATPase activity and in vitro actin motility, whereas Mhc5 (G200D) myosin has these properties enhanced. Depressed D45 myosin activity protects against age-associated dysfunction in metabolically demanding skeletal muscles. In contrast, enhanced Mhc5 myosin function allows normal skeletal myofibril assembly, but it induces degradation of the myofibrillar apparatus, probably as a result of contractile disinhibition. Analysis of beating hearts demonstrates depressed motor function evokes a dilatory response, similar to that seen with vertebrate dilated cardiomyopathy myosin mutations, and it disrupts contractile rhythmicity. Enhanced myosin performance generates a phenotype apparently analogous to that of human restrictive cardiomyopathy, possibly indicating myosin-based origins for the disease. The D45 and Mhc5 mutations illustrate the transducer's role in influencing the chemomechanical properties of myosin and produce unique pathologies in distinct muscles. Our data suggest Drosophila is a valuable system for identifying and modeling mutations analogous to those associated with specific human muscle disorders. PMID:18045988

Symptom characteristics and psychiatric comorbidity among males with muscle dysmorphia.

PubMed

Cafri, Guy; Olivardia, Roberto; Thompson, J Kevin

2008-01-01

Muscle dysmorphia has been described as a disorder in which individuals are pathologically preoccupied with their muscularity. This study was designed to further investigate the symptom characteristics and psychiatric conditions associated with the disorder. Weight lifting males meeting current criteria for muscle dysmorphia (n = 15), past muscle dysmorphia (n = 8), and no history of muscle dysmorphia (n = 28) responded to advertisements placed in gymnasium and nutrition stores. Structured and semistructured interviews were administered, as well as survey measures. Relative to controls, males with current muscle dysmorphia experienced more aversive symptoms related to the appearance of their bodies, including more often thinking about their muscularity, dissatisfaction with appearance, appearance checking, bodybuilding dependence, and functional impairment. Higher rates of mood and anxiety disorders were found among individuals with a history of muscle dysmorphia relative to individuals with no history of muscle dysmorphia. The findings suggest that muscle dysmorphia can be distinguished from normal weight lifting on a number of clinical dimensions. Muscle dysmorphia appears to be comorbid with other psychiatric conditions. Limitations of the current study and directions for future research are considered.

Robust functional statistics applied to Probability Density Function shape screening of sEMG data.

PubMed

Boudaoud, S; Rix, H; Al Harrach, M; Marin, F

2014-01-01

Recent studies pointed out possible shape modifications of the Probability Density Function (PDF) of surface electromyographical (sEMG) data according to several contexts like fatigue and muscle force increase. Following this idea, criteria have been proposed to monitor these shape modifications mainly using High Order Statistics (HOS) parameters like skewness and kurtosis. In experimental conditions, these parameters are confronted with small sample size in the estimation process. This small sample size induces errors in the estimated HOS parameters restraining real-time and precise sEMG PDF shape monitoring. Recently, a functional formalism, the Core Shape Model (CSM), has been used to analyse shape modifications of PDF curves. In this work, taking inspiration from CSM method, robust functional statistics are proposed to emulate both skewness and kurtosis behaviors. These functional statistics combine both kernel density estimation and PDF shape distances to evaluate shape modifications even in presence of small sample size. Then, the proposed statistics are tested, using Monte Carlo simulations, on both normal and Log-normal PDFs that mimic observed sEMG PDF shape behavior during muscle contraction. According to the obtained results, the functional statistics seem to be more robust than HOS parameters to small sample size effect and more accurate in sEMG PDF shape screening applications.

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

PubMed

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

2015-08-01

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

Tibial and fibular nerves evaluation using intraoperative electromyography in rats.

PubMed

Nepomuceno, André Coelho; Politani, Elisa Landucci; Silva, Eduardo Guandelini da; Salomone, Raquel; Longo, Marco Vinicius Losso; Salles, Alessandra Grassi; Faria, José Carlos Marques de; Gemperli, Rolf

2016-08-01

To evaluate a new model of intraoperative electromyographic (EMG) assessment of the tibial and fibular nerves, and its respectives motor units in rats. Eight Wistar rats underwent intraoperative EMG on both hind limbs at two different moments: week 0 and week 12. Supramaximal electrical stimulation applied on sciatic nerve, and compound muscle action potential recorded on the gastrocnemius muscle (GM) and the extensor digitorum longus muscle (EDLM) through electrodes at specifics points. Motor function assessment was performaced through Walking Track Test. Exposing the muscles and nerves for examination did not alter tibial (p=0.918) or fibular (p=0.877) function between the evaluation moments. Electromyography of the GM, innervated by the tibial nerve, revealed similar amplitude (p=0.069) and latency (p=0.256) at week 0 and at 12 weeks, creating a standard of normality. Meanwhile, electromyography of the EDLM, innervated by the fibular nerve, showed significant differences between the amplitudes (p=0.003) and latencies (p=0.021) at the two different moments of observation. Intraoperative electromyography determined and quantified gastrocnemius muscle motor unit integrity, innervated by tibial nerve. Although this study was not useful to, objectively, assess extensor digitorum longus muscle motor unit, innervated by fibular nerve.

Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles.

PubMed

Tasca, Giorgio; Pescatori, Mario; Monforte, Mauro; Mirabella, Massimiliano; Iannaccone, Elisabetta; Frusciante, Roberto; Cubeddu, Tiziana; Laschena, Francesco; Ottaviani, Pierfrancesco; Ricci, Enzo

2012-01-01

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease.

Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or ‘classical’ congenital myopathy

PubMed Central

Zaharieva, Irina T.; Thor, Michael G.; Oates, Emily C.; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T.; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D’Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R.; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A.; Morgan, Jennifer E.; Laing, Nigel G.; Vallance, Hilary; Ruben, Peter; Hanna, Michael G.; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope

2016-01-01

Abstract See Cannon (doi: 10.1093/brain/awv400 ) for a scientific commentary on this article. Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Na v 1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero - or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro functional assessment in HEK293 cells of the impact of the identified SCN4A mutations showed loss-of-function of the mutant Na v 1.4 channels. All, apart from one, of the mutations either caused fully non-functional channels, or resulted in a reduced channel activity. Each of the affected cases carried at least one full loss-of-function mutation. In five out of six families, a second loss-of-function mutation was present on the trans allele. These functional results provide convincing evidence for the pathogenicity of the identified mutations and suggest that different degrees of loss-of-function in mutant Na v 1.4 channels are associated with attenuation of the skeletal muscle action potential amplitude to a level insufficient to support normal muscle function. The results demonstrate that recessive loss-of-function SCN4A mutations should be considered in patients with a congenital myopathy. PMID:26700687

Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.

PubMed

Zaharieva, Irina T; Thor, Michael G; Oates, Emily C; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D'Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A; Morgan, Jennifer E; Laing, Nigel G; Vallance, Hilary; Ruben, Peter; Hanna, Michael G; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope; Muntoni, Francesco

2016-03-01

Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro functional assessment in HEK293 cells of the impact of the identified SCN4A mutations showed loss-of-function of the mutant Nav1.4 channels. All, apart from one, of the mutations either caused fully non-functional channels, or resulted in a reduced channel activity. Each of the affected cases carried at least one full loss-of-function mutation. In five out of six families, a second loss-of-function mutation was present on the trans allele. These functional results provide convincing evidence for the pathogenicity of the identified mutations and suggest that different degrees of loss-of-function in mutant Nav1.4 channels are associated with attenuation of the skeletal muscle action potential amplitude to a level insufficient to support normal muscle function. The results demonstrate that recessive loss-of-function SCN4A mutations should be considered in patients with a congenital myopathy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

[Myonuclear domain and microtubule proteome during skeletal muscle maturation].

PubMed

Couturier, Nathalie; Gache, Vincent

2017-11-01

In the normal course of muscle fiber development, myonuclei actively position and adapt a precise localization in mature fibers, shaping MyoNuclear Domains (MNDs). Myonuclei positioning in fibers appears to be essential for muscle function as defects in MNDs settings are always associated with dysfunction (i.e., centronuclear myopathy, sarcopenia). Previous studies have shown that myonuclei positioning in fibers is reversible, suggesting that in pathologies presenting MNDs impairment, myonuclei could be re-addressed to the "correct" position in fibers and this could benefit to muscle function. Cytoskeleton networks, and particularly microtubules, have been implicated in early nuclei localization in myotubes. As the microtubule network is completely redesigned during muscle maturation, we hypothesized that "microtubules associated proteomes" would change between immature and mature fibers and contribute to a microtubule-dependent process resulting in MNDs setting and maintenance in mature fibers. We performed an in vitro biochemical approach to isolate microtubules partners in immature (myotubes) and mature myofibers. Using mass-spectrometry identification, we selected 244 candidates, differentially associated/expressed with microtubules during myofiber maturation and potentially controlling MNDs settings. We are currently conducting a siRNA screen approach on these candidates to decipher their respective implication in early and late phases of MNDs establishment, using an unbiased assay developed by our team allowing statistical analysis of MNDs regarding myonuclei content. This approach will lead to the identification of new pathways related to nuclear positioning and MNDs setting in normal condition and in myopathies associated to MNDs impairment such as CNMs. © 2017 médecine/sciences – Inserm.

Prolonged stretching of the ankle plantarflexors elicits muscle-tendon adaptations relevant to ankle gait kinetics in children with spastic cerebral palsy.

PubMed

Martín Lorenzo, Teresa; Rocon, Eduardo; Martínez Caballero, Ignacio; Ramírez Barragán, Ana; Lerma Lara, Sergio

2017-11-01

Tissue related ankle hyper-resistance has been reported to contribute to equinus gait in children with spastic cerebral palsy. Hence, ankle plantarflexor stretching programs have been developed in order to restore passive ankle dorsiflexion. Despite high quality evidence on the limited effects of stretching on passive joint mobility, further muscle-tendon adaptations have been reported which may impact gait performance. As such, children with spastic cerebral palsy subject to long-term manual static stretching achieved dorsiflexion gains through the reduction of muscle and fascicle strain whilst preserving tendon strain, and prolonged use of ankle-foot orthoses achieved similar dorsiflexion gains through increased tendon strain whilst preserving muscle and fascicle strain. The latter concurred with normalization of early stance plantarflexor moment yet reductions in push-off plantarflexor moment given the increase in tendon compliance. Therefore, similar limited gains in passive ankle joint mobility in response to stretching may be achieved either by preserving/restoring optimal muscle-tendon function, or at the expense of muscle-tendon function and thus contributing gait impairments. The largest increase in ankle passive joint mobility in children with SCP has been obtained through prolonged plantarflexor stretching through ankle casting combined with botulinum neurotoxin type A. However, to our knowledge, there are no published studies on muscle-tendinous adaptations to ankle casting combined with botulinum toxin type A and its effect on ankle joint gait kinetics. Therefore, we hypothesized that ankle casting elicits muscle-tendon adaptations which concur with altered ankle joint kinetics during the stance phase of gait in children with SCP. More information is needed about the relationships between muscle structure and function, and the effect of specific interventions designed to alter muscle properties and associated functional outcomes in children with spastic cerebral palsy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Compensatory strategies during walking in response to excessive muscle co-contraction at the ankle joint.

PubMed

Wang, Ruoli; Gutierrez-Farewik, Elena M

2014-03-01

Excessive co-contraction causes inefficient or abnormal movement in several neuromuscular pathologies. How synergistic muscles spanning the ankle, knee and hip adapt to co-contraction of ankle muscles is not well understood. This study aimed to identify the compensation strategies required to retain normal walking with excessive antagonistic ankle muscle co-contraction. Muscle-actuated simulations of normal walking were performed to quantify compensatory mechanisms of ankle and knee muscles during stance in the presence of normal, medium and high levels of co-contraction of antagonistic pairs gastrocnemius+tibialis anterior and soleus+tibialis anterior. The study showed that if co-contraction increases, the synergistic ankle muscles can compensate; with gastrocmemius+tibialis anterior co-contraction, the soleus will increase its contribution to ankle plantarflexion acceleration. At the knee, however, almost all muscles spanning the knee and hip are involved in compensation. We also found that ankle and knee muscles alone can provide sufficient compensation at the ankle joint, but hip muscles must be involved to generate sufficient knee moment. Our findings imply that subjects with a rather high level of dorsiflexor+plantarflexor co-contraction can still perform normal walking. This also suggests that capacity of other lower limb muscles to compensate is important to retain normal walking in co-contracted persons. The compensatory mechanisms can be useful in clinical interpretation of motion analyses, when secondary muscle co-contraction or other deficits may present simultaneously in subjects with motion disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Muscles within muscles: a tensiomyographic and histochemical analysis of the normal human vastus medialis longus and vastus medialis obliquus muscles

PubMed Central

Travnik, Ludvik; Djordjevič, Srdjan; Rozman, Sergej; Hribernik, Marija; Dahmane, Raja

2013-01-01

The aim of this study was to show the connection between structure (anatomical and histochemical) and function (muscle contraction properties) of vastus medialis obliquus (VMO) and vastus medialis longus (VML). The non-invasive tensiomyography (TMG) method was used to determine the contractile properties (contraction time; Tc) of VML and VMO muscle, as a reflection of the ratio between the slow and fast fibers in two groups of nine young men. VML and VMO significantly (P < 0.01) differ in the proportion of type 1 (59.6: 44%) and type 2b (6.3: 15%) fibers. The VML muscle is almost entirely composed of type 1 and type 2a fibers. In many samples of this muscle no type 2b fibers were found. The proportion of slow-twitch type 1 fibers is nearly twice as high as the proportion of fast-twitch type 2a fibers. These observations indicate that VML is a slower and more fatigue-resistant muscle than VMO muscle. These characteristics correspond to the different functions of the VML, which is an extensor of the knee, and to the VMO, which maintains the stable position of the patella in the femoral groove. Our results obtained by TMG provided additional evidence that muscle fibers within the segments of VM muscle were not homogenous with regard to their contractile properties, thereby confirming the histochemical results. Tc can be attributed to the higher percentage of slow-twitch fibers – type 1. The statistically shorter Tc (P ≤ 0.001) of VMO (22.8 ± 4.0 ms) compared with VML (26.7 ± 4.0 ms) in our study is consistent with previously found differences in histochemical, morphological and electrophysiological data. In conclusion, the results of this study provide evidence that the VML and VMO muscles are not only anatomically and histochemically different muscles, but also functionally different biological structures. PMID:23586984

Neuronal Nitric Oxide Synthase Is Dislocated in Type I Fibers of Myalgic Muscle but Can Recover with Physical Exercise Training

PubMed Central

Jensen, L.; Andersen, L. L.; Schrøder, H. D.; Frandsen, U.; Sjøgaard, G.

2015-01-01

Trapezius myalgia is the most common type of chronic neck pain. While physical exercise reduces pain and improves muscle function, the underlying mechanisms remain unclear. Nitric oxide (NO) signaling is important in modulating cellular function, and a dysfunctional neuronal NO synthase (nNOS) may contribute to an ineffective muscle function. This study investigated nNOS expression and localization in chronically painful muscle. Forty-one women clinically diagnosed with trapezius myalgia (MYA) and 18 healthy controls (CON) were included in the case-control study. Subsequently, MYA were randomly assigned to either 10 weeks of specific strength training (SST, n = 18), general fitness training (GFT, n = 15), or health information (REF, n = 8). Distribution of fiber type, cross-sectional area, and sarcolemmal nNOS expression did not differ between MYA and CON. However, MYA showed increased sarcoplasmic nNOS localization (18.8 ± 12 versus 12.8 ± 8%, P = 0.049) compared with CON. SST resulted in a decrease of sarcoplasm-localized nNOS following training (before 18.1 ± 12 versus after 12.0 ± 12%; P = 0,027). We demonstrate that myalgic muscle displays altered nNOS localization and that 10 weeks of strength training normalize these disruptions, which supports previous findings of impaired muscle oxygenation during work tasks and reduced pain following exercise. PMID:25853139

Neuromuscular adaptation to actual and simulated weightlessness

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Roy, R. R.

1994-01-01

The chronic "unloading" of the neuromuscular system during spaceflight has detrimental functional and morphological effects. Changes in the metabolic and mechanical properties of the musculature can be attributed largely to the loss of muscle protein and the alteration in the relative proportion of the proteins in skeletal muscle, particularly in the muscles that have an antigravity function under normal loading conditions. These adaptations could result in decrements in the performance of routine or specialized motor tasks, both of which may be critical for survival in an altered gravitational field, i.e., during spaceflight and during return to 1 G. For example, the loss in extensor muscle mass requires a higher percentage of recruitment of the motor pools for any specific motor task. Thus, a faster rate of fatigue will occur in the activated muscles. These consequences emphasize the importance of developing techniques for minimizing muscle loss during spaceflight, at least in preparation for the return to 1 G after spaceflight. New insights into the complexity and the interactive elements that contribute to the neuromuscular adaptations to space have been gained from studies of the role of exercise and/or growth factors as countermeasures of atrophy. The present chapter illustrates the inevitable interactive effects of neural and muscular systems in adapting to space. It also describes the considerable progress that has been made toward the goal of minimizing the functional impact of the stimuli that induce the neuromuscular adaptations to space.

NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation

PubMed Central

Ryu, Dongryeol; Zhang, Hongbo; Ropelle, Eduardo R.; Sorrentino, Vincenzo; Mázala, Davi A. G.; Mouchiroud, Laurent; Marshall, Philip L.; Campbell, Matthew D.; Ali, Amir Safi; Knowels, Gary M.; Bellemin, Stéphanie; Iyer, Shama R.; Wang, Xu; Gariani, Karim; Sauve, Anthony A.; Cantó, Carles; Conley, Kevin E.; Walter, Ludivine; Lovering, Richard M.; Chin, Eva R.; Jasmin, Bernard J.; Marcinek, David J.; Menzies, Keir J.; Auwerx, Johan

2017-01-01

Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD+) synthesis, consistent with a potential role for the essential cofactor NAD+ in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene’s muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5’-diphosphate (ADP)–ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD+ and are involved in pleiotropic events, including inflammation. In the mdx mouse model of DMD, we observed significant reductions in muscle NAD+ levels, concurrent increases in PARP activity, and reduced expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD+ biosynthesis. Replenishing NAD+ stores with dietary nicotinamide riboside supplementation improved muscle function and heart pathology in mdx and mdx/Utr−/− mice and reversed pathology in Caenorhabditis elegans models of DMD. The effects of NAD+ repletion in mdx mice relied on the improvement in mitochondrial function and structural protein expression (α-dystrobrevin and δ-sarcoglycan) and on the reductions in general poly(ADP)-ribosylation, inflammation, and fibrosis. In combination, these studies suggest that the replenishment of NAD+ may benefit patients with muscular dystrophies or other neuromuscular degenerative conditions characterized by the PARP/NNMT gene expression signatures. PMID:27798264

Motor cortical representation of the pelvic floor muscles.

PubMed

Schrum, A; Wolff, S; van der Horst, C; Kuhtz-Buschbeck, J P

2011-07-01

Pelvic floor muscle training involves rhythmical voluntary contractions of the external urethral sphincter and ancillary pelvic floor muscles. The representation of these muscles in the motor cortex has not been located precisely and unambiguously. We used functional magnetic resonance imaging to determine brain activity during slow and fast pelvic floor contractions. Cerebral responses were recorded in 17 healthy male volunteers, 21 to 47 years old, with normal bladder control. Functional magnetic resonance imaging was performed during metronome paced slow (0.25 Hertz) and fast (0.7 Hertz) contractions of the pelvic floor that mimicked the interruption of voiding. To study the somatotopy of the cortical representations, flexion-extension movements of the right toes were performed as a control task. Functional magnetic resonance imaging during pelvic floor contractions detected activity of the supplementary motor area in the medial wall and of the midcingulate cortex, insula, posterior parietal cortex, putamen, thalamus, cerebellar vermis and upper ventral pons. There were no significant differences in activation between slow and fast contractions. Toe movements involved significantly stronger activity of the paracentral lobule (ie the medial primary motor cortex) than did the pelvic floor contractions. Otherwise the areas active during pelvic floor and leg muscle contractions overlapped considerably. The motor cortical representation of pelvic floor muscles is located mostly in the supplementary motor area. It extends further ventrally and anteriorly than the representation of distal leg muscles. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Relative differences in strength and power from slow to fast isokinetic velocities may reflect dynapenia.

PubMed

Jenkins, Nathaniel D M; Housh, Terry J; Palmer, Ty B; Cochrane, Kristen C; Bergstrom, Haley C; Johnson, Glen O; Schmidt, Richard J; Cramer, Joel T

2015-07-01

We compared absolute and normalized values for peak torque (PT), mean power (MP), rate of velocity development, and electromyography (EMG) amplitude during maximal isometric and concentric isokinetic leg extension muscle actions, as well as the %decrease in PT and %increase in MP from 1.05 to 3.14 rad·s(-1) in younger versus older men. Measurements were performed twice for reliability. Isokinetic measurements were normalized to the isometric muscle actions. Absolute isometric PT, isokinetic PT and MP, and EMG amplitudes at 1.05 and 3.14 rad·s(-1) were greater in the younger men, although normalizing to isometric PT eliminated the age differences. The older men exhibited greater %decrease in PT (37.2% vs. 31.3%) and lower %increase in MP (87.6% vs. 126.4%) regardless of normalization. Normalization eliminated absolute differences in isokinetic strength and power, but the relative differences from slow to fast velocities may reflect dynapenia characterized by age-related decreases in fast-twitch fiber function. © 2014 Wiley Periodicals, Inc.

The Effect of Statins on Skeletal Muscle Function

PubMed Central

Parker, Beth A.; Capizzi, Jeffrey A.; Grimaldi, Adam S.; Clarkson, Priscilla M.; Cole, Stephanie M.; Keadle, Justin; Chipkin, Stuart; Pescatello, Linda S.; Simpson, Kathleen; White, C. Michael; Thompson, Paul D.

2015-01-01

Background Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials and the effect of statins on muscle performance has not been carefully studied. Methods and Results The Effect of STatins On Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase (CK), exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo were administered for 6 months to 420 healthy, statin-naive subjects. No individual CK value exceeded 10 times normal, but average CK increased 20.8 ± 141.1 U/L (p<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 vs 10; p = 0.05). Myalgic subjects on atorvastatin or placebo decreased muscle strength in 5 of 14 and 4 of 14 variables respectively (p = 0.69). Conclusions These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average CK suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in CK should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. Clinical Trial Registration Information: www.clinicaltrials.gov; Identifier: NCT00609063. PMID:23183941

Prevalence of sarcopenia among older community-dwelling people with normal health and nutritional state.

PubMed

Hedayati, Kerstin Khalaj; Dittmar, Manuela

2010-01-01

This study analyzed whether sarcopenia, a risk factor for disability in the aged, also occurs in healthy community-dwelling elders with normal nutritional state. As indicators, body cell mass (BCM) and lean body mass (LBM) were determined in 110 Germans (ages 60-83) using bioimpedance analysis. Nutritional status, muscle function, anthropometry, and physical activity level were investigated. Sarcopenia was already present in well nourished healthy elders. Its prevalence depended on the measure of muscle mass used (BCM percent, 22 percent males, 20 percent females; LBM percent, 4 percent males, 11 percent females). In conclusion, screening for presence of sarcopenia is needed in healthy, well-nourished elderly populations requiring an international standardization. Copyright © Taylor & Francis Group, LLC

Morphology of the lumbar transversospinal muscles examined in a mouse bearing a muscle fiber-specific nuclear marker.

PubMed

Cornwall, Jon; Deries, Marianne; Duxson, Marilyn

2010-12-01

Although the morphology of human lumbar transversospinal (TSP) muscles has been studied, little is known about the structure of these muscles in the mouse (Mus musculus). Such information is relevant given mice are often used as a "normal" phenotype for studies modeling human development. This study describes the gross morphology, muscle fiber arrangement, and innervation pattern of the mouse lumbar TSP muscles. A unique feature of the study is the use of a transgenic mouse line bearing a muscle-specific nuclear marker that allows clear delineation of muscle fiber and connective tissue boundaries. The lumbar TSP muscles of five mice were examined bilaterally; at each spinal level muscles attached to the caudal edge of the spinous process and passed caudally as a single complex unit. Fibers progressively terminated over the four vertebral segments caudad, with multiple points of muscle fiber attachment on each vertebra. Motor endplates, defined with acetylcholinesterase histochemistry, were consistently located half way along each muscle fiber, regardless of length, with all muscle fibers arranged in-parallel rather than in-series. These results provide information relevant to interpretation of developmental and functional studies involving this muscle group in the mouse and show mouse lumbar TSP muscles are different in form to descriptions of equivalent muscles in humans and horses.

Haploinsufficiency for Translation Elongation Factor eEF1A2 in Aged Mouse Muscle and Neurons Is Compatible with Normal Function

PubMed Central

Griffiths, Lowri A.; Doig, Jennifer; Churchhouse, Antonia M. D.; Davies, Faith C. J.; Squires, Charlotte E.; Newbery, Helen J.; Abbott, Catherine M.

2012-01-01

Translation elongation factor isoform eEF1A2 is expressed in muscle and neurons. Deletion of eEF1A2 in mice gives rise to the neurodegenerative phenotype “wasted” (wst). Mice homozygous for the wasted mutation die of muscle wasting and neurodegeneration at four weeks post-natal. Although the mutation is said to be recessive, aged heterozygous mice have never been examined in detail; a number of other mouse models of motor neuron degeneration have recently been shown to have similar, albeit less severe, phenotypic abnormalities in the heterozygous state. We therefore examined the effects of ageing on a cohort of heterozygous +/wst mice and control mice, in order to establish whether a presumed 50% reduction in eEF1A2 expression was compatible with normal function. We evaluated the grip strength assay as a way of distinguishing between wasted and wild-type mice at 3–4 weeks, and then performed the same assay in older +/wst and wild-type mice. We also used rotarod performance and immunohistochemistry of spinal cord sections to evaluate the phenotype of aged heterozygous mice. Heterozygous mutant mice showed no deficit in neuromuscular function or signs of spinal cord pathology, in spite of the low levels of eEF1A2. PMID:22848658

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats

PubMed Central

Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun

2015-01-01

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1 × 106 cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. Significance This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. PMID:26315571

Expression of Hsp27 correlated with rat detrusor contraction after acute urinary retention.

PubMed

Xiong, Zhiyong; Wang, Yongquan; Gong, Wei; Zhou, Zhansong; Lu, Gensheng

2013-09-01

Heat shock protein 27 (Hsp27) can regulate actin cytoskeleton dynamics and contractile protein activation. This study investigates whether Hsp27 expression is related to bladder contractile dysfunction after acute urinary retention (AUR). Female rats were randomized either to AUR by urethral ligation or to normal control group. Bladder and smooth muscle strip contraction at time points from 0 h to 7 days after AUR were estimated by cystometric and organ bath studies. Hsp27 expression in bladder tissue at each time point was detected with immunofluorescence, Western blots, and real-time PCR. Expression of the three phosphorylated forms of Hsp27 was detected by Western blots. Smooth muscle ultrastructure was observed by transmission electron microscopy. Data suggest that maximum detrusor pressure and both carbachol-induced and spontaneous detrusor strip contraction amplitude decreased gradually for the duration from 0 to 6 h, and then increased gradually to near-normal values at 24 h. Treatment of muscle strips with the p38MAK inhibitor, SB203580, inhibited carbachol-induced contractions. Smooth muscle ultrastructure damage was the highest at 6 h after AUR, and then lessened gradually during next 7 days, and ultrastructure was close to normal. Expressions of Hsp27 mRNA and protein and the proteins of the three phosphorylated forms were higher at 0 h, decreased to lower levels up to 6 h, and then gradually increased. Therefore, we conclude that rat bladder contractile function after AUR worsens during 0-6 h, and then gradually recovers. The findings of the current study suggest that Hsp27 modulates bladder smooth muscle contraction after AUR, and that phosphorylation of Hsp27 may be an important pathway modulating actin cytoskeleton dynamics in bladder smooth muscle contraction and reconstruction after injury.

Reductions in muscle quality and quantity in CIDP patients assessed by magnetic resonance imaging.

PubMed

Gilmore, Kevin J; Doherty, Timothy J; Kimpinski, Kurt; Rice, Charles L

2018-05-09

Weakness in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) may be caused by decreases in muscle quantity and quality, but these have not been explored. Twelve patients with CIDP (mean 61 years) and ten age- matched (mean 59 years) control subjects were assessed for ankle dorsiflexion strength, and two different MRI scans (T1 and T2) of leg musculature. Isometric strength was lower in CIDP patients by 36% compared with controls. Tibialis anterior muscle volumes of CIDP patients were smaller by ∼17% than controls, and non-contractile tissue volume was ∼58% greater in CIDP patients. When normalized to total muscle or corrected contractile volume, strength was ∼ 29% and ∼18% lower, respectively in CIDP patients DISCUSSION: These results provide insight into structural integrity of muscle contractile proteins and pathological changes to whole-muscle tissue composition that contribute to impaired muscle function in CIDP. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Green tea extract attenuates muscle loss and improves muscle function during disuse, but fails to improve muscle recovery following unloading in aged rats.

PubMed

Alway, Stephen E; Bennett, Brian T; Wilson, Joseph C; Sperringer, Justin; Mohamed, Junaith S; Edens, Neile K; Pereira, Suzette L

2015-02-01

In this study we tested the hypothesis that green tea extract (GTE) would improve muscle recovery after reloading following disuse. Aged (32 mo) Fischer 344 Brown Norway rats were randomly assigned to receive either 14 days of hindlimb suspension (HLS) or 14 days of HLS followed by normal ambulatory function for 14 days (recovery). Additional animals served as cage controls. The rats were given GTE (50 mg/kg body wt) or water (vehicle) by gavage 7 days before and throughout the experimental periods. Compared with vehicle treatment, GTE significantly attenuated the loss of hindlimb plantaris muscle mass (-24.8% vs. -10.7%, P < 0.05) and tetanic force (-43.7% vs. -25.9%, P <0.05) during HLS. Although GTE failed to further improve recovery of muscle function or mass compared with vehicle treatment, animals given green tea via gavage maintained the lower losses of muscle mass that were found during HLS (-25.2% vs. -16.0%, P < 0.05) and force (-45.7 vs. -34.4%, P < 0.05) after the reloading periods. In addition, compared with vehicle treatment, GTE attenuated muscle fiber cross-sectional area loss in both plantaris (-39.9% vs. -23.9%, P < 0.05) and soleus (-37.2% vs. -17.6%) muscles after HLS. This green tea-induced difference was not transient but was maintained over the reloading period for plantaris (-45.6% vs. -21.5%, P <0.05) and soleus muscle fiber cross-sectional area (-38.7% vs. -10.9%, P <0.05). GTE increased satellite cell proliferation and differentiation in plantaris and soleus muscles during recovery from HLS compared with vehicle-treated muscles and decreased oxidative stress and abundance of the Bcl-2-associated X protein (Bax), yet this did not further improve muscle recovery in reloaded muscles. These data suggest that muscle recovery following disuse in aging is complex. Although satellite cell proliferation and differentiation are critical for muscle repair to occur, green tea-induced changes in satellite cell number is by itself insufficient to improve muscle recovery following a period of atrophy in old rats. Copyright © 2015 the American Physiological Society.

Paraplegic patients: how to measure balance and what is normal or functional?

PubMed

Barkoh, Kaku; Lucas, Joshua W; Lee, Larry; Hsieh, Patrick C; Wang, Jeffrey C; Rolfe, Kevin

2018-02-01

To review the current understanding and data of sagittal balance and alignment considerations in paraplegic patients. A PubMed literature search was conducted to identify all relevant articles relating to sagittal alignment and sagittal balance considerations in paraplegic and spinal cord injury patients. While there are numerous studies and publications on sagittal balance in the ambulatory patient with spinal deformity or complex spine disorders, there is paucity of the literature on "normal" sagittal balance in the paraplegic patients. Studies have reported significantly alterations of the sagittal alignment parameters in the non-ambulatory paraplegic patients compared to ambulatory patients. The variability of the alignment changes is related to the differences in the level of the spinal cord injury and their differences in the activations of truncal muscles to allow functional movements in those patients, particularly in optimizing sitting and transferring. Surgical goal in treating paraplegic patients with complex pathologies should not be solely directed to achieve the "normal" radiographic parameters of sagittal alignment in the ambulatory patients. The goal should be to maintain good coronal balance to allow ideal sitting position and to preserve motion segment to optimize functions of paraplegia patients. Current available literature data have not defined normal sagittal parameters for paraplegic patients. There are significant differences in postural sagittal parameters and muscle activations in paraplegic and non-spinal cord injury patients that can lead to differences in sagittal alignment and balance. Treatment goal in spine surgery for paraplegic patients should address their global function, sitting balance, and ability to perform self-care rather than the accepted radiographic parameters for adult spinal deformity in ambulatory patients.

Functional anorectal disorders.

PubMed

Bharucha, Adil E; Wald, Arnold; Enck, Paul; Rao, Satish

2006-04-01

This report defines criteria for diagnosing functional anorectal disorders (ie, fecal incontinence, anorectal pain, and disorders of defecation). Functional fecal incontinence is defined as the uncontrolled passage of fecal material recurring for > or =3 months in an individual with a developmental age of > or =4 years that is associated with: (1) abnormal functioning of normally innervated and structurally intact muscles, and/or (2) no or minor abnormalities of sphincter structure and/or innervation insufficient to explain fecal incontinence, and/or (3) normal or disordered bowel habits (ie, fecal retention or diarrhea), and/or (4) psychological causes. However, conditions wherein structural and/or neurogenic abnormalities explain the symptom, or are part of a generalized process (eg, diabetic neuropathy) are not included within functional fecal incontinence. Functional fecal incontinence is a common, but underrecognized symptom, which is equally prevalent in men and women, and can often cause considerable distress. The clinical features are useful for guiding diagnostic testing and therapy. Functional anorectal pain syndromes include proctalgia fugax (fleeting pain) and chronic proctalgia; chronic proctalgia may be subdivided into levator ani syndrome and unspecified anorectal pain, which are defined by arbitrary clinical criteria. Functional defecation disorders are characterized by 2 or more symptoms of constipation, with > or =2 of the following features during defecation: impaired evacuation, inappropriate contraction of the pelvic floor muscles, and inadequate propulsive forces. Functional disorders of defecation may be amenable to pelvic floor retraining by biofeedback therapy (such as dyssynergic defecation).

Early Mitochondrial Adaptations in Skeletal Muscle to Diet-Induced Obesity Are Strain Dependent and Determine Oxidative Stress and Energy Expenditure But Not Insulin Sensitivity

PubMed Central

Sena, Sandra; Sloan, Crystal; Tebbi, Ali; Han, Yong Hwan; O'Neill, Brian T.; Cooksey, Robert C.; Jones, Deborah; Holland, William L.; McClain, Donald A.; Abel, E. Dale

2012-01-01

This study sought to elucidate the relationship between skeletal muscle mitochondrial dysfunction, oxidative stress, and insulin resistance in two mouse models with differential susceptibility to diet-induced obesity. We examined the time course of mitochondrial dysfunction and insulin resistance in obesity-prone C57B and obesity-resistant FVB mouse strains in response to high-fat feeding. After 5 wk, impaired insulin-mediated glucose uptake in skeletal muscle developed in both strains in the absence of any impairment in proximal insulin signaling. Impaired mitochondrial oxidative capacity preceded the development of insulin resistant glucose uptake in C57B mice in concert with increased oxidative stress in skeletal muscle. By contrast, mitochondrial uncoupling in FVB mice, which prevented oxidative stress and increased energy expenditure, did not prevent insulin resistant glucose uptake in skeletal muscle. Preventing oxidative stress in C57B mice treated systemically with an antioxidant normalized skeletal muscle mitochondrial function but failed to normalize glucose tolerance and insulin sensitivity. Furthermore, high fat-fed uncoupling protein 3 knockout mice developed increased oxidative stress that did not worsen glucose tolerance. In the evolution of diet-induced obesity and insulin resistance, initial but divergent strain-dependent mitochondrial adaptations modulate oxidative stress and energy expenditure without influencing the onset of impaired insulin-mediated glucose uptake. PMID:22510273

BRE facilitates skeletal muscle regeneration by promoting satellite cell motility and differentiation

PubMed Central

Xiao, Lihai; Lee, Kenneth Ka Ho

2016-01-01

ABSTRACT The function of the Bre gene in satellite cells was investigated during skeletal muscle regeneration. The tibialis anterior leg muscle was experimentally injured in Bre knockout mutant (BRE-KO) mice. It was established that the accompanying muscle regeneration was impaired as compared with their normal wild-type counterparts (BRE-WT). There were significantly fewer pax7+ satellite cells and smaller newly formed myofibers present in the injury sites of BRE-KO mice. Bre was required for satellite cell fusion and myofiber formation. The cell fusion index and average length of newly-formed BRE-KO myofibers were found to be significantly reduced as compared with BRE-WT myofibers. It is well established that satellite cells are highly invasive which confers on them the homing ability to reach the muscle injury sites. Hence, we tracked the migratory behavior of these cells using time-lapse microscopy. Image analysis revealed no difference in directionality of movement between BRE-KO and BRE-WT satellite cells but there was a significant decrease in the velocity of BRE-KO cell movement. Moreover, chemotactic migration assays indicated that BRE-KO satellite cells were significantly less responsive to chemoattractant SDF-1α than BRE-WT satellite cells. We also established that BRE normally protects CXCR4 from SDF-1α-induced degradation. In sum, BRE facilitates skeletal muscle regeneration by enhancing satellite cell motility, homing and fusion. PMID:26740569

Biomechanical paradigm and interpretation of female pelvic floor conditions before a treatment

PubMed Central

Lucente, Vincent; van Raalte, Heather; Murphy, Miles; Egorov, Vladimir

2017-01-01

Background Further progress in restoring a woman’s health may be possible if a patient with a damaged pelvic floor could undergo medical imaging and biomechanical diagnostic tests. The results of such tests could contribute to the analysis of multiple treatment options and suggest the optimal one for that patient. Aim To develop a new approach for the biomechanical characterization of vaginal conditions, muscles, and connective tissues in the female pelvic floor. Methods Vaginal tactile imaging (VTI) allows biomechanical assessment of the soft tissue along the entire length of the anterior, posterior, and lateral vaginal walls at rest, with manually applied deflection pressures and with muscle contraction, muscle relaxation, and Valsalva maneuver. VTI allows a large body of measurements to evaluate individual variations in tissue elasticity, support defects, as well as pelvic muscle function. Presuming that 1) the female pelvic floor organs are suspended by ligaments against which muscles contract to open or close the outlets and 2) damaged ligaments weaken the support and may reduce the force of muscle contraction, we made an attempt to characterize multiple pelvic floor structures from VTI data. Results All of the 138 women enrolled in the study were successfully examined with the VTI. The study subjects have had normal pelvic support or pelvic organ prolapse (stages I–IV). The average age of this group of subjects was 60±15 years. We transposed a set of 31 VTI parameters into a quantitative characterization of pelvic muscles and ligamentous structures. Interpretation of the acquired VTI data for normal pelvic floor support and prolapse conditions is proposed based on biomechanical assessment of the functional anatomy. Conclusion Vaginal tactile imaging allows biomechanical characterization of female pelvic floor structures and tissues in vivo, which may help to optimize treatment of the diseased conditions such as prolapse, incontinence, atrophy, and some forms of pelvic pain. PMID:28831274

Modified High-Sucrose Diet-Induced Abdominally Obese and Normal-Weight Rats Developed High Plasma Free Fatty Acid and Insulin Resistance

PubMed Central

Cao, Li; Liu, Xuehui; Cao, Hongyi; Lv, Qingguo; Tong, Nanwei

2012-01-01

Introduction. Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Methods and Results. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. Conclusion. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle. PMID:23320128

Arsenic Promotes NF-Kb-Mediated Fibroblast Dysfunction and Matrix Remodeling to Impair Muscle Stem Cell Function

PubMed Central

Zhang, Changqing; Ferrari, Ricardo; Beezhold, Kevin; Stearns-Reider, Kristen; D’Amore, Antonio; Haschak, Martin; Stolz, Donna; Robbins, Paul D.; Barchowsky, Aaron; Ambrosio, Fabrisia

2016-01-01

Arsenic is a global health hazard that impacts over 140 million individuals worldwide. Epidemiological studies reveal prominent muscle dysfunction and mobility declines following arsenic exposure; yet, mechanisms underlying such declines are unknown. The objective of this study was to test the novel hypothesis that arsenic drives a maladaptive fibroblast phenotype to promote pathogenic myomatrix remodeling and compromise the muscle stem (satellite) cell (MuSC) niche. Mice were exposed to environmentally relevant levels of arsenic in drinking water before receiving a local muscle injury. Arsenic-exposed muscles displayed pathogenic matrix remodeling, defective myofiber regeneration and impaired functional recovery, relative to controls. When naïve human MuSCs were seeded onto three-dimensional decellularized muscle constructs derived from arsenic-exposed muscles, cells displayed an increased fibrogenic conversion and decreased myogenicity, compared with cells seeded onto control constructs. Consistent with myomatrix alterations, fibroblasts isolated from arsenic-exposed muscle displayed sustained expression of matrix remodeling genes, the majority of which were mediated by NF-κB. Inhibition of NF-κB during arsenic exposure preserved normal myofiber structure and functional recovery after injury, suggesting that NF-κB signaling serves as an important mechanism of action for the deleterious effects of arsenic on tissue healing. Taken together, the results from this study implicate myomatrix biophysical and/or biochemical characteristics as culprits in arsenic-induced MuSC dysfunction and impaired muscle regeneration. It is anticipated that these findings may aid in the development of strategies to prevent or revert the effects of arsenic on tissue healing and, more broadly, provide insight into the influence of the native myomatrix on stem cell behavior. PMID:26537186

Masseter and temporalis muscle electromyography findings after lower third molar extraction

PubMed Central

Buesa-Bárez, José-María; Martínez-Rodríguez, Natalia; Barona-Dorado, Cristina; Sanz-Alonso, Javier; Cortés-Bretón-Brinkmann, Jorge; Martínez-González, José-María

2018-01-01

Background The main clinical application of electromyography is to detect abnormalities in muscle function, to assess muscle activity for purposes of recruitment, and in the biomechanics of movement. Objectives To analyze electromyography (EMG) findings for masticatory muscles during chewing following surgical extraction of lower third molars, and to determine any correlation between pain, inflammation, trismus, and the EMG data registered. Material and Methods This prospective study included 31 patients. Surface EMG was used to study masseter and temporalis muscle function before lower third molar extraction and 72 hours and seven days after surgery. Clinical variables, pain, inflammation, and trismus were registered before and after surgery. Results Studying the area and size of the masticatory muscles, higher values were found for temporalis than masseter muscles, regardless of the surgical side, which points to the greater involvement of the temporalis muscle in mastication. Comparing the side where surgery had been performed with the non-surgical side, a sharp and statistically significant reduction in amplitude and area were noted on the surgical side reflecting major functional affectation. One week after surgery, amplitude and area had almost returned to base-line values, indicating almost complete recovery. While pain decreased progressively after surgery, inflammation peaked at 72 hours, while mouth opening reached a minimum at this time, returning to normality within the week. Conclusions Surgical extraction of lower third molars produces changes to electromyography activity that are more evident during the first hours after surgery and closely related to the intensity of pain suffered and the patient’s inflammatory responses, although they are not related to mouth opening capacity. Key words:Third molar surgery, electromyography, pain, inflammation, trismus, masticatory muscles. PMID:29274163

[EMG activities of the head, neck and upper trunk muscles with mandibular movements in healthy adults and mandibular asymmetry patients].

PubMed

Jiang, Ting; Zhang, Zhenkang; Yang, Zhaohui; Yi, Biao; Feng, Hailan; Wang, Xing

2002-03-25

To study the activities of head, neck and upper trunk muscles during mandibular movements in healthy adults and mandibular asymmetry patients. Electromyographic integrogram was used to record and analyze the electromyographic activities of the anterior temporal (Ta), posterior temporal (Tp), sternocleidomastoid (SCM), and trapezius (TRAP) muscles in rest position and during mandibular movement among 10 normal adults and 10 mandibular asymmetry patients. All the four muscles showed constant electromyographic activities when the mandible was in the rest position. The activities of Ta, Tp, and SCM muscles increased with protrusion of mandible, mouth opening, tapping, maximum clenching, and chewing. The activities of Ta and Tp muscles of the patients were 1.7 times greater than that of the normal adults during mandibular movement without occlusion, and were weaker by 50% during mandibular movement with occlusion. The difference between electromyographic activities during mandibular movement and in rest position was less among patients than among normal adults. The TRAP muscle of the patients showed constant electromyographic activities with the activity volume nearly 1.8 times that of the normal adults. The difference between the muscle and its namesake at the opposite side was greater among the patients (21%) than among the normal adults (8%). All the four muscles participate in the maintenance of rest position of mandible and the realization of mandibular movements. The coordination of muscular activities among mandibular asymmetry patients is poorer than that among normal adults.

The application of muscle wrapping to voxel-based finite element models of skeletal structures.

PubMed

Liu, Jia; Shi, Junfen; Fitton, Laura C; Phillips, Roger; O'Higgins, Paul; Fagan, Michael J

2012-01-01

Finite elements analysis (FEA) is now used routinely to interpret skeletal form in terms of function in both medical and biological applications. To produce accurate predictions from FEA models, it is essential that the loading due to muscle action is applied in a physiologically reasonable manner. However, it is common for muscle forces to be represented as simple force vectors applied at a few nodes on the model's surface. It is certainly rare for any wrapping of the muscles to be considered, and yet wrapping not only alters the directions of muscle forces but also applies an additional compressive load from the muscle belly directly to the underlying bone surface. This paper presents a method of applying muscle wrapping to high-resolution voxel-based finite element (FE) models. Such voxel-based models have a number of advantages over standard (geometry-based) FE models, but the increased resolution with which the load can be distributed over a model's surface is particularly advantageous, reflecting more closely how muscle fibre attachments are distributed. In this paper, the development, application and validation of a muscle wrapping method is illustrated using a simple cylinder. The algorithm: (1) calculates the shortest path over the surface of a bone given the points of origin and ultimate attachment of the muscle fibres; (2) fits a Non-Uniform Rational B-Spline (NURBS) curve from the shortest path and calculates its tangent, normal vectors and curvatures so that normal and tangential components of the muscle force can be calculated and applied along the fibre; and (3) automatically distributes the loads between adjacent fibres to cover the bone surface with a fully distributed muscle force, as is observed in vivo. Finally, we present a practical application of this approach to the wrapping of the temporalis muscle around the cranium of a macaque skull.

Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

PubMed Central

Park, Song-Young; Gifford, Jayson R.; Andtbacka, Robert H. I.; Trinity, Joel D.; Hyngstrom, John R.; Garten, Ryan S.; Diakos, Nikolaos A.; Ives, Stephen J.; Dela, Flemming; Larsen, Steen; Drakos, Stavros

2014-01-01

Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s−1·mg−1, P < 0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·g−1·min−1, P < 0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s−1·mg−1, P < 0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production. PMID:24906913

Increased pain sensitivity but normal function of exercise induced analgesia in hip and knee osteoarthritis--treatment effects of neuromuscular exercise and total joint replacement.

PubMed

Kosek, E; Roos, E M; Ageberg, E; Nilsdotter, A

2013-09-01

To assess exercise induced analgesia (EIA) and pain sensitivity in hip and knee osteoarthritis (OA) and to study the effects of neuromuscular exercise and surgery on these parameters. The dataset consisted of knee (n = 66) and hip (n = 47) OA patients assigned for total joint replacement at Lund University Hospital undergoing pre-operative neuromuscular exercise and 43 matched controls. Sensitivity to pressure pain was assessed by pressure algometry at 10 sites. Subjects were then instructed to perform a standardized static knee extension. Pressure pain thresholds (PPTs) were assessed at the contracting quadriceps muscle (Q) and at the resting deltoid muscle (D) before and during contraction. The relative increase in PPTs during contraction was taken as a measure of localized (Q) or generalized (D) EIA. Patients were assessed at baseline, following on average 12 weeks of neuromuscular exercise and 3 months following surgery. We found a normal function of EIA in OA patients at baseline. Previous studies have reported beneficial effects of physical exercise on pain modulation in healthy subjects. However, no treatment effects on EIA were seen in OA patients despite the increase in muscle strength following neuromuscular exercise and reduced pain following surgery. Compared to controls, OA patients had increased pain sensitivity and no beneficial effects on pain sensitivity were seen following treatment. To our knowledge, this is the first study of EIA in OA patients. Despite increased pain sensitivity, OA patients had a normal function of EIA. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Surgical relocation of the papillary muscles in functional ischemic mitral regurgitation: what are the forces of the relocation stitches acting on the myocardium?

PubMed

Jensen, Henrik; Jensen, Morten O; Vind-Kezunovic, Stefan; Vestergaard, Rikke; Ringgaard, Steffen; Smerup, Morten H; Hønge, Jesper L; Hasenkam, J Michael; Nielsen, Sten L

2013-07-01

In patients with chronic functional ischemic mitral regurgitation (FIMR), papillary muscle relocation has the potential to induce reverse left ventricular remodeling. However, in order to optimize function and durability, the forces imposed on the left ventricular myocardium by papillary muscle relocation should be assessed. Eight pigs with FIMR were subjected to down-sized ring annuloplasty in combination with relocation of the anterior (5 mm) and posterior (15 mm) papillary muscles towards the respective trigone. Papillary muscle relocation was obtained by a 2-0 expanded polytetrafluoroethylene stitch fixed to the trigone, exteriorized through the myocardium overlying the papillary muscle, and fixed to an epicardial disc. Tension in these stitches was measured at a systolic blood pressure > 80 mmHg using a custom-made sliding caliper with a strain gauge mounted in line. This allowed assessment of the cyclic change from minimal diastolic to maximum systolic papillary muscle relocation stitch tension. Maximum cyclic change in the posterior papillary muscle (PPM) stitch tension was 1.1 N at 15 mm relocation. In comparison, the anterior papillary muscle (APM) tension was increased to a maximum of 1.4 N with only 5 mm relocation. Surprisingly, during each step of isolated PPM relocation, the APM stitch tension increased concomitantly, but in contrast APM relocation did not influence the magnitude of PPM stitch tension. There was no statistically significant difference between cyclic changes in APM and PPM stitch tension at any step of relocation. Papillary muscle relocation using stitches attached between epicardial discs and respective trigones induced a cyclic change in papillary muscle relocation stitch tension of 1.1-1.4 N. These values were in the range of normal tension in the mitral valve apparatus, and equivalent to only 19-24% of the total papillary muscle forces. Therefore, this technique does not appear to induce a non-physiologically high cyclic load on the mitral valve complex.

Big-conductance Ca2+-activated K+ channels in physiological and pathophysiological urinary bladder smooth muscle cells

PubMed Central

Parajuli, Shankar P.; Zheng, Yun-Min; Levin, Robert; Wang, Yong-Xiao

2016-01-01

ABSTRACT Contraction and relaxation of urinary bladder smooth muscle cells (UBSMCs) represent the important physiological functions of the bladder. Contractile responses in UBSMCs are regulated by a number of ion channels including big-conductance Ca2+- activated K+ (BK) channels. Great progress has been made in studies of BK channels in UBSMCs. The intent of this review is to summarize recent exciting findings with respect to the functional interactions of BK channels with muscarinic receptors, ryanodine receptors (RyRs) and inositol triphosphate receptors (IP3Rs) as well as their functional importance under normal and pathophysiological conditions. BK channels are highly expressed in UBSMCs. Activation of muscarinic M3 receptors inhibits the BK channel activity, facilitates opening of voltage-dependent Ca2+ (CaV) channels, and thereby enhances excitability and contractility of UBSMCs. Signaling molecules and regulatory mechanisms involving RyRs and IP3Rs have a significant effect on functions of BK channels and thereby regulate cellular responses in UBSMCs under normal and pathophysiological conditions including overactive bladders. Moreover, BK channels may represent a novel target for the treatment of bladder dysfunctions. PMID:27101440

beta. -adrenergic relaxation of smooth muscle: differences between cells and tissues

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

Scheid, C.R.

1987-09-01

The present studies were carried out in an attempt to resolve the controversy about the Na/sup +/ dependence of ..beta..-adrenergic relaxation in smooth muscle. Previous studies on isolated smooth muscle cells from the toad stomach had suggested that at least some of the actions of ..beta..-adrenergic agents, including a stimulatory effect on /sup 45/Ca efflux, were dependent on the presence of a normal transmembrane Na/sup +/ gradient. Studies by other investigators using tissues derived from mammalian sources had suggested that the relaxing effect of ..beta..-adrenergic agents was Na/sup +/ independent. Uncertainty remained as to whether these discrepancies reflected differences betweenmore » cells and tissues or differences between species. Thus, in the present studies, the authors utilized both tissues and cells from the same source, the stomach muscle of the toad Bufo marinus, and assessed the Na/sup +/ dependence of ..beta..-adrenergic relaxation. They found that elimination of a normal Na/sup +/ gradient abolished ..beta..-adrenergic relaxation of isolated cells. In tissues, however, similar manipulations had no effect on relaxation. The reasons for this discrepancy are unclear but do not appear to be attributable to changes in smooth muscle function following enzymatic dispersion. Thus the controversy concerning the mechanisms of ..beta..-adrenergic relaxation may reflect inherent differences between tissues and cells.« less

Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia

PubMed Central

Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

2013-01-01

Familial dysautonomia (Riley–Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement. PMID:23165765

Mechanism of valvular regurgitation.

PubMed

Khoo, Nee S; Smallhorn, Jeffery F

2011-10-01

Despite improvements in surgical techniques, valvular regurgitation results in major morbidity in children with heart disease. Functional anatomy, mechanisms of valve closure and adaptation to changing hemodynamic stress in normal mitral and tricuspid valves are complex and only partially understood. As well, pathology of atrioventricular valve regurgitation is further complicated by congenital valve abnormalities involving leaflet tissue, supporting chordal apparatus and displaced papillary muscles. This review provides a current understanding of the mechanisms that result in atrioventricular valve failure. Mitral valve leaflets have contractile elements, in addition to atrial muscle modulation of leaflet tension. When placed under mechanical tethering stress, the mitral valve adapts by leaflet expansion, which increases coaptation surface reserve and chordal thickening. Both pediatric and adult studies are increasingly reporting on the importance of subvalvar apparatus function in maintaining valve competency. The maintenance of efficient valve function is accomplished by a complex series of events involving atrial and annular contraction, annular deformation, active leaflet tension, chordal transmission of papillary muscle contractions and ventricular contraction.

Myostatin induces interstitial fibrosis in the heart via TAK1 and p38.

PubMed

Biesemann, Nadine; Mendler, Luca; Kostin, Sawa; Wietelmann, Astrid; Borchardt, Thilo; Braun, Thomas

2015-09-01

Myostatin, a member of the TGF-β superfamily of secreted growth factors, is a negative regulator of skeletal muscle growth. In the heart, it is expressed at lower levels compared to skeletal muscle but up-regulated under disease conditions. Cre recombinase-mediated inactivation of myostatin in adult cardiomyocytes leads to heart failure and increased mortality but cardiac function of surviving mice is restored after several weeks probably due to compensatory expression in non-cardiomyocytes. To study long-term effects of increased myostatin expression in the heart and to analyze the putative crosstalk between cardiomyocytes and fibroblasts, we overexpressed myostatin in cardiomyocytes. Increased expression of myostatin in heart muscle cells caused interstitial fibrosis via activation of the TAK-1-MKK3/6-p38 signaling pathway, compromising cardiac function in older mice. Our results uncover a novel role of myostatin in the heart and highlight the necessity for tight regulation of myostatin to maintain normal heart function.

Functional studies of RYR1 mutations in the skeletal muscle ryanodine receptor using human RYR1 complementary DNA.

PubMed

Sato, Keisaku; Pollock, Neil; Stowell, Kathryn M

2010-06-01

Malignant hyperthermia is associated with mutations within the gene encoding the skeletal muscle ryanodine receptor, the calcium channel that releases Ca from sarcoplasmic reticulum stores triggering muscle contraction, and other metabolic activities. More than 200 variants have been identified in the ryanodine receptor, but only some of these have been shown to functionally affect the calcium channel. To implement genetic testing for malignant hyperthermia, variants must be shown to alter the function of the channel. A number of different ex vivo methods can be used to demonstrate functionality, as long as cells from human patients can be obtained and cultured from at least two unrelated families. Because malignant hyperthermia is an uncommon disorder and many variants seem to be private, including the newly identified H4833Y mutation, these approaches are limited. The authors cloned the human skeletal muscle ryanodine receptor complementary DNA and expressed both normal and mutated forms in HEK-293 cells and carried out functional analysis using ryanodine binding assays in the presence of a specific agonist, 4-chloro-m-cresol, and the antagonist Mg. Transiently expressed human ryanodine receptor proteins colocalized with an endoplasmic reticulum marker in HEK-293 cells. Ryanodine binding assays confirmed that mutations causing malignant hyperthermia resulted in a hypersensitive channel, while those causing central core disease resulted in a hyposensitive channel. The functional assays validate recombinant human skeletal muscle ryanodine receptor for analysis of variants and add an additional mutation (H4833Y) to the repertoire of mutations that can be used for the genetic diagnosis of malignant hyperthermia.

Tong Xie Yao Fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P

PubMed Central

Yin, Yue; Zhong, Lei; Wang, Jian-Wei; Zhao, Xue-Ying; Zhao, Wen-Jing; Kuang, Hai-Xue

2015-01-01

AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang (TXYF) improves dysfunction in an irritable bowel syndrome (IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats (1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine (5-HT) and substance P (SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity. RESULTS: Defecation frequency was 1.8 ± 1.03 in normal rats and 4.5 ± 1.58 in IBS model rats (P < 0.001). However, the defecation frequency was significantly decreased (3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time (in seconds) of colon transit function was significantly increased (256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS. PMID:25914462

Tong Xie Yao Fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P.

PubMed

Yin, Yue; Zhong, Lei; Wang, Jian-Wei; Zhao, Xue-Ying; Zhao, Wen-Jing; Kuang, Hai-Xue

2015-04-21

To investigate whether the Chinese medicine Tong Xie Yao Fang (TXYF) improves dysfunction in an irritable bowel syndrome (IBS) rat model. Thirty baby rats for IBS modeling were separated from mother rats (1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine (5-HT) and substance P (SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity. Defecation frequency was 1.8 ± 1.03 in normal rats and 4.5 ± 1.58 in IBS model rats (P < 0.001). However, the defecation frequency was significantly decreased (3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time (in seconds) of colon transit function was significantly increased (256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.

Mechanical ventilation and sepsis impair protein metabolism in the diaphragm of neonatal pigs

USDA-ARS?s Scientific Manuscript database

Mechanical ventilation (MV) impairs diaphragmatic function and diminishes the ability to wean from ventilatory support in adult humans. In normal neonatal pigs, animals that are highly anabolic, endotoxin (LPS) infusion induces sepsis, reduces peripheral skeletal muscle protein synthesis rates, but ...

Skeletal muscle growth and fiber composition in mice are regulated through the transcription factors STAT5a/b: linking growth hormone to the androgen receptor.

PubMed

Klover, Peter; Chen, Weiping; Zhu, Bing-Mei; Hennighausen, Lothar

2009-09-01

In skeletal muscle, STAT5a/b transcription factors are critical for normal postnatal growth, whole-animal glucose homeostasis, and local IGF-1 production. These observations have led us to hypothesize that STAT5a/b are critical for maintenance of normal muscle mass and function. To investigate this, mice with a skeletal muscle-specific deletion of the Stat5a/b genes (Stat5MKO) were used. Stat5MKO mice displayed reduced muscle mass, altered fiber-type distribution and reduced activity. On a molecular level, gene expression in skeletal muscle of Stat5MKO and control mice was analyzed by microarrays and real-time PCR, both in the presence and absence of growth hormone (GH) stimulation. Expression of several genes involved in muscle growth and fiber type were significantly changed. Specifically, in the quadriceps, a muscle almost exclusively composed of type II fibers, the absence of STAT5a/b led to increased expression of several genes associated with type I fibers and the de novo appearance of type I fibers. In addition, it is shown here that expression of the androgen receptor gene (Ar) is controlled by GH through STAT5a/b. The link between STAT5a/b and Ar gene is likely through direct transcriptional regulation, as chromatin immunoprecipitaion of the Ar promoter region in C2C12 myoblasts was accomplished by antibodies against STAT5a. These experiments demonstrate an important role for STAT5a/b in skeletal muscle physiology, and they provide a direct link to androgen signaling.

Toward Optimizing Vestibular Evoked Myogenic Potentials: Normalization Reduces the Need for Strong Neck Muscle Contraction.

PubMed

Noij, Kimberley S; Herrmann, Barbara S; Rauch, Steven D; Guinan, John J

2017-01-01

The cervical vestibular evoked myogenic potential (cVEMP) represents an inhibitory reflex of the saccule measured in the ipsilateral sternocleidomastoid muscle (SCM) in response to acoustic or vibrational stimulation. Since the cVEMP is a modulation of SCM electromyographic (EMG) activity, cVEMP amplitude is proportional to muscle EMG amplitude. We sought to evaluate muscle contraction influences on cVEMP peak-to-peak amplitudes (VEMPpp), normalized cVEMP amplitudes (VEMPn), and inhibition depth (VEMPid). cVEMPs at 500 Hz were measured in 25 healthy subjects for 3 SCM EMG contraction ranges: 45-65, 65-105, and 105-500 μV root mean square (r.m.s.). For each range, we measured cVEMP sound level functions (93-123 dB peSPL) and sound off, meaning that muscle contraction was measured without acoustic stimulation. The effect of muscle contraction amplitude on VEMPpp, VEMPn, and VEMPid and the ability to distinguish cVEMP presence/absence were evaluated. VEMPpp amplitudes were significantly greater at higher muscle contractions. In contrast, VEMPn and VEMPid showed no significant effect of muscle contraction. Cohen's d indicated that for all 3 cVEMP metrics contraction amplitude variations produced little change in the ability to distinguish cVEMP presence/absence. VEMPid more clearly indicated saccular output because when no acoustic stimulus was presented the saccular inhibition estimated by VEMPid was zero, unlike those by VEMPpp and VEMPn. Muscle contraction amplitude strongly affects VEMPpp amplitude, but contractions 45-300 μV r.m.s. produce stable VEMPn and VEMPid values. Clinically, there may be no need for subjects to exert high contraction effort. This is especially beneficial in patients for whom maintaining high SCM contraction amplitudes is challenging. © 2018 S. Karger AG, Basel.

Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective

NASA Astrophysics Data System (ADS)

Grassi, Bruno; Quaresima, Valentina

2016-09-01

In most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.

Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective.

PubMed

Grassi, Bruno; Quaresima, Valentina

2016-09-01

In most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.

Asymmetric activation of temporalis, masseter, and sternocleidomastoid muscles in temporomandibular disorder patients.

PubMed

Ries, Lilian Gerdi Kittel; Alves, Marcelo Correa; Bérzin, Fausto

2008-01-01

The aim of this study was to analyze the symmetry of the electromyographic (EMG) activity of the temporalis, masseter, and sternocleidomastoid (SCM) muscles in volunteers divided into a control group and a temporomandibular disorder (TMD) group. The surface EMG recordings were made during mandibular rest position, maximal intercuspal position, and during the chewing cycle. Normalized EMG waves of paired muscles were compared by computing a percentage overlapping coefficient (POC). The difference between the groups and between the static and dynamic clenching tests was analyzed through repeated measures, ANOVA. Symmetry of the temporalis, masseter, and SCM muscles activity was smaller in the TMD group compared to the control group. The mandibular postures were also significantly different among themselves. The asymmetric activation of jaw and neck muscles was interpreted as a compensatory strategy to achieve stability for the mandibular and cervical systems during masticatory function.

Analysis of Skeletal Muscle Metrics as Predictors of Functional Task Performance

NASA Technical Reports Server (NTRS)

Ryder, Jeffrey W.; Buxton, Roxanne E.; Redd, Elizabeth; Scott-Pandorf, Melissa; Hackney, Kyle J.; Fiedler, James; Ploutz-Snyder, Robert J.; Bloomberg, Jacob J.; Ploutz-Snyder, Lori L.

2010-01-01

PURPOSE: The ability to predict task performance using physiological performance metrics is vital to ensure that astronauts can execute their jobs safely and effectively. This investigation used a weighted suit to evaluate task performance at various ratios of strength, power, and endurance to body weight. METHODS: Twenty subjects completed muscle performance tests and functional tasks representative of those that would be required of astronauts during planetary exploration (see table for specific tests/tasks). Subjects performed functional tasks while wearing a weighted suit with additional loads ranging from 0-120% of initial body weight. Performance metrics were time to completion for all tasks except hatch opening, which consisted of total work. Task performance metrics were plotted against muscle metrics normalized to "body weight" (subject weight + external load; BW) for each trial. Fractional polynomial regression was used to model the relationship between muscle and task performance. CONCLUSION: LPMIF/BW is the best predictor of performance for predominantly lower-body tasks that are ambulatory and of short duration. LPMIF/BW is a very practical predictor of occupational task performance as it is quick and relatively safe to perform. Accordingly, bench press work best predicts hatch-opening work performance.

Effect of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres.

PubMed

Simon, Magda; Porter, Rebecca; Brown, Robert; Coulton, Gary R; Terenghi, Giorgio

2003-11-01

We investigated whether neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) affected the reinnervation of slow and fast motor units. Neurotrophin-impregnated or plain fibronectin (FN) conduits were inserted into a sciatic nerve gap. Fast extensor digitorum longus (EDL) and slow soleus muscles were collected 4 months postsurgery. Muscles were weighed and fibre type proportion and mean fibre diameters were derived from muscle cross-sections. All fibre types in muscles from FN animals were severely atrophied and this correlated well with type 1 fibre loss and atrophy in soleus and type 2b loss and atrophy in EDL. Treatment with NT-4 reversed soleus but not EDL mass loss above the FN group by significantly restoring type 1 muscle fibre proportion and diameters towards those of normal unoperated animals. BDNF did not increase muscle mass but did have minor effects on fibre type and diameter. Thus, NT-4 significantly improved slow motor unit recovery, and provides a basis for therapies intended to aid the functional recovery of muscles after denervating injury.

Role of nitric oxide in skeletal muscle glucose uptake during exercise.

PubMed

Hong, Yet Hoi; Betik, Andrew C; McConell, Glenn K

2014-12-01

Nitric oxide is produced within skeletal muscle fibres and has various functions in skeletal muscle. There is evidence that NO may be essential for normal increases in skeletal muscle glucose uptake during contraction/exercise. Although there have been some discrepant results, it has been consistently demonstrated that inhibition of NO synthase (NOS) attenuates the increase in skeletal muscle glucose uptake during contraction in mouse and rat muscle ex vivo, during in situ contraction in rats and during exercise in humans. The NO-mediated increase in skeletal muscle glucose uptake during contraction/exercise is probably due to the modulation of intramuscular signalling that ultimately increases glucose transporter 4 (GLUT4) translocation and is, surprisingly, independent of blood flow. In this review, we discuss the evidence for and against a role of NO in regulating skeletal muscle glucose uptake during contraction/exercise and outline the possible mechanism(s) involved. Emerging findings regarding the role of neuronal NOS mu (nNOSμ) in this process are also discussed. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Quadriceps muscle strength and voluntary activation after polio.

PubMed

Beelen, Anita; Nollet, Frans; de Visser, Marianne; de Jong, Bareld A; Lankhorst, Gustaaf J; Sargeant, Anthony J

2003-08-01

Quadriceps strength, maximal anatomical cross-sectional area (CSA), maximal voluntary activation (MVA), and maximal relaxation rate (MRR) were studied in 48 subjects with a past history of polio, 26 with and 22 without postpoliomyelitis syndrome (PPS), and in 13 control subjects. It was also investigated whether, apart from CSA, MVA and MRR were determinants of muscle strength. Polio subjects had significantly less strength, CSA, and MRR in the more-affected quadriceps than control subjects. MVA was reduced in 18 polio subjects and normal in all controls. PPS subjects differed from non-PPS subjects only in that the MVA of the more-affected quadriceps was significantly lower. Both CSA and MVA were found to be associated with muscle strength. Quadriceps strength in polio subjects was dependent not only on muscle mass, but also on the ability to activate the muscles. Since impaired activation was more pronounced in PPS subjects, the new muscle weakness and functional decline in PPS may be due not only to a gradual loss of muscle fibers, but also to an increasing inability to activate the muscles.

Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy

PubMed Central

2014-01-01

Background Fibrosis, an excessive collagen accumulation, results in scar formation, impairing function of vital organs and tissues. Fibrosis is a hallmark of muscular dystrophies, including the lethal Duchenne muscular dystrophy (DMD), which remains incurable. Substitution of muscle by fibrotic tissue also complicates gene/cell therapies for DMD. Yet, no optimal models to study muscle fibrosis are available. In the widely used mdx mouse model for DMD, extensive fibrosis develops in the diaphragm only at advanced adulthood, and at about two years of age in the ‘easy-to-access’ limb muscles, thus precluding fibrosis research and the testing of novel therapies. Methods We developed distinct experimental strategies, ranging from chronic exercise to increasing muscle damage on limb muscles of young mdx mice, by myotoxin injection, surgically induced trauma (laceration or denervation) or intramuscular delivery of profibrotic growth factors (such as TGFβ). We also extended these approaches to muscle of normal non-dystrophic mice. Results These strategies resulted in advanced and enhanced muscle fibrosis in young mdx mice, which persisted over time, and correlated with reduced muscle force, thus mimicking the severe DMD phenotype. Furthermore, increased fibrosis was also obtained by combining these procedures in muscles of normal mice, mirroring aberrant repair after severe trauma. Conclusions We have developed new and improved experimental strategies to accelerate and enhance muscle fibrosis in vivo. These strategies will allow rapidly assessing fibrosis in the easily accessible limb muscles of young mdx mice, without necessarily having to use old animals. The extension of these fibrogenic regimes to the muscle of non-dystrophic wild-type mice will allow fibrosis assessment in a wide array of pre-existing transgenic mouse lines, which in turn will facilitate understanding the mechanisms of fibrogenesis. These strategies should improve our ability to combat fibrosis-driven dystrophy progression and aberrant regeneration. PMID:25157321

Benefits of pulmonary rehabilitation in patients with COPD and normal exercise capacity.

PubMed

Lan, Chou-Chin; Chu, Wen-Hua; Yang, Mei-Chen; Lee, Chih-Hsin; Wu, Yao-Kuang; Wu, Chin-Pyng

2013-09-01

Pulmonary rehabilitation (PR) is beneficial for patients with COPD, with improvement in exercise capacity and health-related quality of life. Despite these overall benefits, the responses to PR vary significantly among different individuals. It is not clear if PR is beneficial for patients with COPD and normal exercise capacity. We aimed to investigate the effects of PR in patients with normal exercise capacity on health-related quality of life and exercise capacity. Twenty-six subjects with COPD and normal exercise capacity were studied. All subjects participated in 12-week, 2 sessions per week, hospital-based, out-patient PR. Baseline and post-PR status were evaluated by spirometry, the St George's Respiratory Questionnaire, cardiopulmonary exercise test, respiratory muscle strength, and dyspnea scores. The mean FEV1 in the subjects was 1.29 ± 0.47 L/min, 64.8 ± 23.0% of predicted. After PR there was significant improvement in maximal oxygen uptake and work rate. Improvements in St George's Respiratory Questionnaire scores of total, symptoms, activity, and impact were accompanied by improvements of exercise capacity, respiratory muscle strength, maximum oxygen pulse, and exertional dyspnea scores (all P < .05). There were no significant changes in pulmonary function test results (FEV1, FVC, and FEV1/FVC), minute ventilation, breathing frequency, or tidal volume at rest or exercise after PR. Exercise training can result in significant improvement in health-related quality of life, exercise capacity, respiratory muscle strength, and exertional dyspnea in subjects with COPD and normal exercise capacity. Exercise training is still indicated for patients with normal exercise capacity.

Identification of disease specific pathways using in vivo SILAC proteomics in dystrophin deficient mdx mouse.

PubMed

Rayavarapu, Sree; Coley, William; Cakir, Erdinc; Jahnke, Vanessa; Takeda, Shin'ichi; Aoki, Yoshitsugu; Grodish-Dressman, Heather; Jaiswal, Jyoti K; Hoffman, Eric P; Brown, Kristy J; Hathout, Yetrib; Nagaraju, Kanneboyina

2013-05-01

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by a mutation in the dystrophin gene. DMD is characterized by progressive weakness of skeletal, cardiac, and respiratory muscles. The molecular mechanisms underlying dystrophy-associated muscle weakness and damage are not well understood. Quantitative proteomics techniques could help to identify disease-specific pathways. Recent advances in the in vivo labeling strategies such as stable isotope labeling in mouse (SILAC mouse) with (13)C6-lysine or stable isotope labeling in mammals (SILAM) with (15)N have enabled accurate quantitative analysis of the proteomes of whole organs and tissues as a function of disease. Here we describe the use of the SILAC mouse strategy to define the underlying pathological mechanisms in dystrophin-deficient skeletal muscle. Differential SILAC proteome profiling was performed on the gastrocnemius muscles of 3-week-old (early stage) dystrophin-deficient mdx mice and wild-type (normal) mice. The generated data were further confirmed in an independent set of mdx and normal mice using a SILAC spike-in strategy. A total of 789 proteins were quantified; of these, 73 were found to be significantly altered between mdx and normal mice (p < 0.05). Bioinformatics analyses using Ingenuity Pathway software established that the integrin-linked kinase pathway, actin cytoskeleton signaling, mitochondrial energy metabolism, and calcium homeostasis are the pathways initially affected in dystrophin-deficient muscle at early stages of pathogenesis. The key proteins involved in these pathways were validated by means of immunoblotting and immunohistochemistry in independent sets of mdx mice and in human DMD muscle biopsies. The specific involvement of these molecular networks early in dystrophic pathology makes them potential therapeutic targets. In sum, our findings indicate that SILAC mouse strategy has uncovered previously unidentified pathological pathways in mouse models of human skeletal muscle disease.

Identification of Disease Specific Pathways Using in Vivo SILAC Proteomics in Dystrophin Deficient mdx Mouse*

PubMed Central

Rayavarapu, Sree; Coley, William; Cakir, Erdinc; Jahnke, Vanessa; Takeda, Shin'ichi; Aoki, Yoshitsugu; Grodish-Dressman, Heather; Jaiswal, Jyoti K.; Hoffman, Eric P.; Brown, Kristy J.; Hathout, Yetrib; Nagaraju, Kanneboyina

2013-01-01

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by a mutation in the dystrophin gene. DMD is characterized by progressive weakness of skeletal, cardiac, and respiratory muscles. The molecular mechanisms underlying dystrophy-associated muscle weakness and damage are not well understood. Quantitative proteomics techniques could help to identify disease-specific pathways. Recent advances in the in vivo labeling strategies such as stable isotope labeling in mouse (SILAC mouse) with 13C6-lysine or stable isotope labeling in mammals (SILAM) with 15N have enabled accurate quantitative analysis of the proteomes of whole organs and tissues as a function of disease. Here we describe the use of the SILAC mouse strategy to define the underlying pathological mechanisms in dystrophin-deficient skeletal muscle. Differential SILAC proteome profiling was performed on the gastrocnemius muscles of 3-week-old (early stage) dystrophin-deficient mdx mice and wild-type (normal) mice. The generated data were further confirmed in an independent set of mdx and normal mice using a SILAC spike-in strategy. A total of 789 proteins were quantified; of these, 73 were found to be significantly altered between mdx and normal mice (p < 0.05). Bioinformatics analyses using Ingenuity Pathway software established that the integrin-linked kinase pathway, actin cytoskeleton signaling, mitochondrial energy metabolism, and calcium homeostasis are the pathways initially affected in dystrophin-deficient muscle at early stages of pathogenesis. The key proteins involved in these pathways were validated by means of immunoblotting and immunohistochemistry in independent sets of mdx mice and in human DMD muscle biopsies. The specific involvement of these molecular networks early in dystrophic pathology makes them potential therapeutic targets. In sum, our findings indicate that SILAC mouse strategy has uncovered previously unidentified pathological pathways in mouse models of human skeletal muscle disease. PMID:23297347

Difference in muscle activation patterns during high-speed versus standard-speed yoga: A randomized sequence crossover study.

PubMed

Potiaumpai, Melanie; Martins, Maria Carolina Massoni; Wong, Claudia; Desai, Trusha; Rodriguez, Roberto; Mooney, Kiersten; Signorile, Joseph F

2017-02-01

To compare the difference in muscle activation between high-speed yoga and standard-speed yoga and to compare muscle activation of the transitions between poses and the held phases of a yoga pose. Randomized sequence crossover trial SETTING: A laboratory of neuromuscular research and active aging Interventions: Eight minutes of continuous Sun Salutation B was performed, at a high speed versus a standard-speed, separately. Electromyography was used to quantify normalized muscle activation patterns of eight upper and lower body muscles (pectoralis major, medial deltoids, lateral head of the triceps, middle fibers of the trapezius, vastus medialis, medial gastrocnemius, thoracic extensor spinae, and external obliques) during the high-speed and standard-speed yoga protocols. Difference in normalized muscle activation between high-speed yoga and standard-speed yoga. Normalized muscle activity signals were significantly higher in all eight muscles during the transition phases of poses compared to the held phases (p<0.01). There was no significant interaction between speed×phase; however, greater normalized muscle activity was seen for highspeed yoga across the entire session. Our results show that transitions from one held phase of a pose to another produces higher normalized muscle activity than the held phases of the poses and that overall activity is greater during highspeed yoga than standard-speed yoga. Therefore, the transition speed and associated number of poses should be considered when targeting specific improvements in performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Architectural analysis and predicted functional capability of the human latissimus dorsi muscle.

PubMed

Gerling, Michael E; Brown, Stephen H M

2013-08-01

The latissimus dorsi is primarily considered a muscle with actions at the shoulder, despite its widespread attachments at the spine. There is some dispute regarding the potential contribution of this muscle to lumbar spine function. The architectural design of a muscle is one of the most accurate predictors of muscle function; however, detailed architectural data on the latissimus dorsi muscle are limited. Therefore, the aim of this study was to quantify the architectural properties of the latissimus dorsi muscle and model mechanical function in light of these new data. One latissimus dorsi muscle was removed from each of 12 human cadavers, separated into regions, and micro-dissected for quantification of fascicle length, sarcomere length, and physiological cross-sectional area. From these data, sarcomere length operating ranges were modelled to determine the force-length characteristics of latissimus dorsi across the spine and shoulder ranges of motion. The physiological cross-sectional area of latissimus dorsi was 5.6±0.5 cm2 and normalized fascicle length was 26.4±1.0 cm, indicating that this muscle is designed to produce a moderate amount of force over a large range of lengths. Measured sarcomere length in the post-mortem neutral spine posture was nearly optimal at 2.69±0.06 μm. Across spine range of motion, biomechanical modelling predicted latissimus dorsi acts across both the ascending and descending limbs of the force-length curve during lateral bend, and primarily at or near the plateau region (where maximum force generation is possible) during flexion/extension and axial twist. Across shoulder range of motion, latissimus dorsi acts primarily on the plateau region and descending limbs of the force length curve during both flexion/extension and abduction/adduction. These data provide novel insights into the ability of the latissimus dorsi muscle to generate force and change length throughout the spine and shoulder ranges of motion. In addition, these findings provide an improved understanding of the spine and shoulder positions at which the force-generating capacity of this muscle can become jeopardized, and consequently how this may affect its spine-stabilizing ability. © 2013 Anatomical Society.

Architectural analysis and predicted functional capability of the human latissimus dorsi muscle

PubMed Central

Gerling, Michael E; Brown, Stephen H M

2013-01-01

The latissimus dorsi is primarily considered a muscle with actions at the shoulder, despite its widespread attachments at the spine. There is some dispute regarding the potential contribution of this muscle to lumbar spine function. The architectural design of a muscle is one of the most accurate predictors of muscle function; however, detailed architectural data on the latissimus dorsi muscle are limited. Therefore, the aim of this study was to quantify the architectural properties of the latissimus dorsi muscle and model mechanical function in light of these new data. One latissimus dorsi muscle was removed from each of 12 human cadavers, separated into regions, and micro-dissected for quantification of fascicle length, sarcomere length, and physiological cross-sectional area. From these data, sarcomere length operating ranges were modelled to determine the force–length characteristics of latissimus dorsi across the spine and shoulder ranges of motion. The physiological cross-sectional area of latissimus dorsi was 5.6 ± 0.5 cm2 and normalized fascicle length was 26.4 ± 1.0 cm, indicating that this muscle is designed to produce a moderate amount of force over a large range of lengths. Measured sarcomere length in the post-mortem neutral spine posture was nearly optimal at 2.69 ± 0.06 μm. Across spine range of motion, biomechanical modelling predicted latissimus dorsi acts across both the ascending and descending limbs of the force–length curve during lateral bend, and primarily at or near the plateau region (where maximum force generation is possible) during flexion/extension and axial twist. Across shoulder range of motion, latissimus dorsi acts primarily on the plateau region and descending limbs of the force length curve during both flexion/extension and abduction/adduction. These data provide novel insights into the ability of the latissimus dorsi muscle to generate force and change length throughout the spine and shoulder ranges of motion. In addition, these findings provide an improved understanding of the spine and shoulder positions at which the force-generating capacity of this muscle can become jeopardized, and consequently how this may affect its spine-stabilizing ability. PMID:23758053

[Cleft palate repair with a combined method of mucosal flap pushback of the hard palate].

PubMed

Zhao, Z; Li, S; Xu, J

1996-03-01

From January of 1992, we applied a combined method to repair cleft palate in 20 patients and received satisfactory results. The method is characterized by pushing back the mucosal flap of the hard palate, a Z-plasty on the nasal mucosa, repositioning the levator muscle to lengthen the palate, circumferential pharyng oplasty using denervated extensor hallucis brevis muscle, without making relaxing incisions and elevating the mucoperiosteal flap, avoiding interference to the greater and lesser palatine vessels and nerves, without relaxing palatal aponeurosis. The advantages of this method are preserving the normal anatomy and function of the palate and nasopharyngeal cavity, improving the function of velopharyngeal closure and minimizing secondary deformities.

Drosophila Importin-α2 Is Involved in Synapse, Axon and Muscle Development

PubMed Central

Mosca, Timothy J.; Schwarz, Thomas L.

2010-01-01

Nuclear import is required for communication between the cytoplasm and the nucleus and to enact lasting changes in gene transcription following stimuli. Binding to an Importin-α molecule in the cytoplasm is often required to mediate nuclear entry of a signaling protein. As multiple isoforms of Importin-α exist, some may be responsible for the entry of distinct cargoes rather than general nuclear import. Indeed, in neuronal systems, Importin-α isoforms can mediate very specific processes such as axonal tiling and communication of an injury signal. To study nuclear import during development, we examined the expression and function of Importin-α2 in Drosophila melanogaster. We found that Importin-α2 was expressed in the nervous system where it was required for normal active zone density at the NMJ and axonal commissure formation in the central nervous system. Other aspects of synaptic morphology at the NMJ and the localization of other synaptic markers appeared normal in importin-α2 mutants. Importin-α2 also functioned in development of the body wall musculature. Mutants in importin-α2 exhibited errors in muscle patterning and organization that could be alleviated by restoring muscle expression of Importin-α2. Thus, Importin-α2 is needed for some processes in the development of both the nervous system and the larval musculature. PMID:21151903

Synemin acts as a regulator of signalling molecules during skeletal muscle hypertrophy.

PubMed

Li, Zhenlin; Parlakian, Ara; Coletti, Dario; Alonso-Martin, Sonia; Hourdé, Christophe; Joanne, Pierre; Gao-Li, Jacqueline; Blanc, Jocelyne; Ferry, Arnaud; Paulin, Denise; Xue, Zhigang; Agbulut, Onnik

2014-11-01

Synemin, a type IV intermediate filament (IF) protein, forms a bridge between IFs and cellular membranes. As an A-kinase-anchoring protein, it also provides temporal and spatial targeting of protein kinase A (PKA). However, little is known about its functional roles in either process. To better understand its functions in muscle tissue, we generated synemin-deficient (Synm(-) (/-)) mice. Synm(-) (/-) mice displayed normal development and fertility but showed a mild degeneration and regeneration phenotype in myofibres and defects in sarcolemma membranes. Following mechanical overload, Synm(-) (/-) mice muscles showed a higher hypertrophic capacity with increased maximal force and fatigue resistance compared with control mice. At the molecular level, increased remodelling capacity was accompanied by decreased myostatin (also known as GDF8) and atrogin (also known as FBXO32) expression, and increased follistatin expression. Furthermore, the activity of muscle-mass control molecules (the PKA RIIα subunit, p70S6K and CREB1) was increased in mutant mice. Finally, analysis of muscle satellite cell behaviour suggested that the absence of synemin could affect the balance between self-renewal and differentiation of these cells. Taken together, our results show that synemin is necessary to maintain membrane integrity and regulates signalling molecules during muscle hypertrophy. © 2014. Published by The Company of Biologists Ltd.

An FBXO40 knockout generated by CRISPR/Cas9 causes muscle hypertrophy in pigs without detectable pathological effects.

PubMed

Zou, Yunlong; Li, Zhiyuan; Zou, Yunjing; Hao, Haiyang; Li, Ning; Li, Qiuyan

2018-04-15

The regulatory function of Fbxo40 has been well characterized in mice. As a key component of the SCF-E3 ubiquitin ligase complex, Fbxo40 induces IRS1 ubiquitination, thus inactivating the IGF1/Akt pathway. The expression of Fbxo40 is restricted to muscle, and mice with an Fbxo40 null mutation exhibit muscle hypertrophy. However, the function of FBXO40 has not been elucidated in pigs, and it is not known whether FBXO40 mutations affect their health. We therefore generated FBXO40 knockout pigs using somatic cell nuclear transfer (SCNT) technology. CRISPR/Cas9 technology was combined with G418 selection, making it possible to generate donor cells at an efficiency of 75.86%. In muscle from FBXO40 knockout pigs, IRS1 levels were higher, and the IGF1/Akt pathway was stimulated. Mutant animals also had approximately 4% more muscle mass compared to WT controls. The knockout pigs developed normally and no pathological changes were found in major organs. These results demonstrate that FBXO40 is a promising candidate gene for improving production traits in agricultural livestock and for developing therapeutic interventions for muscle diseases. Copyright © 2018. Published by Elsevier Inc.

Two years of Functional Electrical Stimulation by large surface electrodes for denervated muscles improve skin epidermis in SCI

PubMed Central

Albertin, Giovanna; Kern, Helmut; Hofer, Christian; Guidolin, Diego; Porzionato, Andrea; Rambaldo, Anna; Caro, Raffaele De; Piccione, Francesco; Marcante, Andrea; Zampieri, Sandra

2018-01-01

Our previous studies have shown that severely atrophic Quadriceps muscles of spinal cord injury (SCI) patients suffering with complete conus and cauda equina lesions, and thus with permanent denervation-induced atrophy and degeneration of muscle fibers, were almost completely rescued to normal size after two years of home-based Functional Electrical Stimulation (h-bFES). Since we used large surface electrodes to stimulate the thigh muscles, we wanted to know if the skin was affected by long-term treatment. Here we report preliminary data of morphometry of skin biopsies harvested from legs of 3 SCI patients before and after two years of h-bFES to determine the total area of epidermis in transverse skin sections. By this approach we support our recently published results obtained randomly measuring skin thickness in the same biopsies after H-E stain. The skin biopsies data of three subjects, taken together, present indeed a statistically significant 30% increase in the area of the epidermis after two years of h-bFES. In conclusion, we confirm a long term positive modulation of electrostimulated epidermis, that correlates with the impressive improvements of the FES-induced muscle strength and bulk, and of the size of the muscle fibers after 2-years of h-bFES. PMID:29686823

High resolution three-dimensional reconstruction of fibrotic skeletal muscle extracellular matrix.

PubMed

Gillies, Allison R; Chapman, Mark A; Bushong, Eric A; Deerinck, Thomas J; Ellisman, Mark H; Lieber, Richard L

2017-02-15

Fibrosis occurs secondary to many skeletal muscle diseases and injuries, and can alter muscle function. It is unknown how collagen, the most abundant extracellular structural protein, alters its organization during fibrosis. Quantitative and qualitative high-magnification electron microscopy shows that collagen is organized into perimysial cables which increase in number in a model of fibrosis, and cables have unique interactions with collagen-producing cells. Fibrotic muscles are stiffer and have a higher concentration of collagen-producing cells. These results improve our understanding of the organization of fibrotic skeletal muscle extracellular matrix and identify novel structures that might be targeted by antifibrotic therapy. Skeletal muscle extracellular matrix (ECM) structure and organization are not well understood, yet the ECM plays an important role in normal tissue homeostasis and disease processes. Fibrosis is common to many muscle diseases and is typically quantified based on an increase in ECM collagen. Through the use of multiple imaging modalities and quantitative stereology, we describe the structure and composition of wild-type and fibrotic ECM, we show that collagen in the ECM is organized into large bundles of fibrils, or collagen cables, and the number of these cables (but not their size) increases in desmin knockout muscle (a fibrosis model). The increase in cable number is accompanied by increased muscle stiffness and an increase in the number of collagen producing cells. Unique interactions between ECM cells and collagen cables were also observed and reconstructed by serial block face scanning electron microscopy. These results demonstrate that the muscle ECM is more highly organized than previously reported. Therapeutic strategies for skeletal muscle fibrosis should consider the organization of the ECM to target the structures and cells contributing to fibrotic muscle function. © 2016 Rehabilitation Institute of Chicago. The Journal of Physiology © 2016 The Physiological Society.

High resolution three‐dimensional reconstruction of fibrotic skeletal muscle extracellular matrix

PubMed Central

Gillies, Allison R.; Chapman, Mark A.; Bushong, Eric A.; Deerinck, Thomas J.; Ellisman, Mark H.

2016-01-01

Key points Fibrosis occurs secondary to many skeletal muscle diseases and injuries, and can alter muscle function.It is unknown how collagen, the most abundant extracellular structural protein, alters its organization during fibrosis.Quantitative and qualitative high‐magnification electron microscopy shows that collagen is organized into perimysial cables which increase in number in a model of fibrosis, and cables have unique interactions with collagen‐producing cells.Fibrotic muscles are stiffer and have a higher concentration of collagen‐producing cells.These results improve our understanding of the organization of fibrotic skeletal muscle extracellular matrix and identify novel structures that might be targeted by antifibrotic therapy. Abstract Skeletal muscle extracellular matrix (ECM) structure and organization are not well understood, yet the ECM plays an important role in normal tissue homeostasis and disease processes. Fibrosis is common to many muscle diseases and is typically quantified based on an increase in ECM collagen. Through the use of multiple imaging modalities and quantitative stereology, we describe the structure and composition of wild‐type and fibrotic ECM, we show that collagen in the ECM is organized into large bundles of fibrils, or collagen cables, and the number of these cables (but not their size) increases in desmin knockout muscle (a fibrosis model). The increase in cable number is accompanied by increased muscle stiffness and an increase in the number of collagen producing cells. Unique interactions between ECM cells and collagen cables were also observed and reconstructed by serial block face scanning electron microscopy. These results demonstrate that the muscle ECM is more highly organized than previously reported. Therapeutic strategies for skeletal muscle fibrosis should consider the organization of the ECM to target the structures and cells contributing to fibrotic muscle function. PMID:27859324

Glucocorticoid Steroid and Alendronate Treatment Alleviates Dystrophic Phenotype with Enhanced Functional Glycosylation of α-Dystroglycan in Mouse Model of Limb-Girdle Muscular Dystrophy with FKRPP448L Mutation.

PubMed

Wu, Bo; Shah, Sapana N; Lu, Peijuan; Richardson, Stephanie M; Bollinger, Lauren E; Blaeser, Anthony; Madden, Kyle L; Sun, Yubo; Luckie, Taylor M; Cox, Michael D; Sparks, Susan; Harper, Amy D; Lu, Qi Long

2016-06-01

Fukutin-related protein-muscular dystrophy is characterized by defects in glycosylation of α-dystroglycan with variable clinical phenotypes, most commonly as limb-girdle muscular dystrophy 2I. There is no effective therapy available. Glucocorticoid steroids have become the standard treatment for Duchenne and other muscular dystrophies with serious adverse effects, including excessive weight gain, immune suppression, and bone loss. Bisphosphonates have been used to treat Duchenne muscular dystrophy for prevention of osteoporosis. Herein, we evaluated prednisolone and alendronate for their therapeutic potential in the FKRPP448L-mutant mouse representing moderate limb-girdle muscular dystrophy 2I. Mice were treated with prednisolone, alendronate, and both in combination for up to 6 months. Prednisolone improved muscle pathology with significant reduction in muscle degeneration, but had no effect on serum creatine kinase levels and muscle strength. Alendronate treatment did not ameliorate muscle degeneration, but demonstrated a limited enhancement on muscle function test. Combined treatment of prednisolone and alendronate provided best improvement in muscle pathology with normalized fiber size distribution and significantly reduced serum creatine kinase levels, but had limited effect on muscle force generation. The use of alendronate significantly mitigated the bone loss. Prednisolone alone and in combination with alendronate enhance functionally glycosylated α-dystroglycan. These results, for the first time, demonstrate the efficacy and feasibility of this alliance treatment of the two drugs for fukutin-related protein-muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation.

PubMed

Ryu, Dongryeol; Zhang, Hongbo; Ropelle, Eduardo R; Sorrentino, Vincenzo; Mázala, Davi A G; Mouchiroud, Laurent; Marshall, Philip L; Campbell, Matthew D; Ali, Amir Safi; Knowels, Gary M; Bellemin, Stéphanie; Iyer, Shama R; Wang, Xu; Gariani, Karim; Sauve, Anthony A; Cantó, Carles; Conley, Kevin E; Walter, Ludivine; Lovering, Richard M; Chin, Eva R; Jasmin, Bernard J; Marcinek, David J; Menzies, Keir J; Auwerx, Johan

2016-10-19

Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD + ) synthesis, consistent with a potential role for the essential cofactor NAD + in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene's muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5'-diphosphate (ADP)-ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD + and are involved in pleiotropic events, including inflammation. In the mdx mouse model of DMD, we observed significant reductions in muscle NAD + levels, concurrent increases in PARP activity, and reduced expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD + biosynthesis. Replenishing NAD + stores with dietary nicotinamide riboside supplementation improved muscle function and heart pathology in mdx and mdx/Utr -/- mice and reversed pathology in Caenorhabditis elegans models of DMD. The effects of NAD + repletion in mdx mice relied on the improvement in mitochondrial function and structural protein expression (α-dystrobrevin and δ-sarcoglycan) and on the reductions in general poly(ADP)-ribosylation, inflammation, and fibrosis. In combination, these studies suggest that the replenishment of NAD + may benefit patients with muscular dystrophies or other neuromuscular degenerative conditions characterized by the PARP/NNMT gene expression signatures. Copyright © 2016, American Association for the Advancement of Science.

Non-Glycanated Biglycan and LTBP4: Leveraging the extracellular matrix for Duchenne Muscular Dystrophy therapeutics.

PubMed

Fallon, Justin R; McNally, Elizabeth M

2018-08-01

The extracellular matrix (ECM) plays key roles in normal and diseased skeletal and cardiac muscle. In healthy muscle the ECM is essential for transmitting contractile force, maintaining myofiber integrity and orchestrating cellular signaling. Duchenne Muscular Dystrophy (DMD) is caused by loss of dystrophin, a cytosolic protein that anchors a transmembrane complex and serves as a vital link between the actin cytoskeleton and the basal lamina. Loss of dystrophin leads to membrane fragility and impaired signaling, resulting in myofiber death and cycles of inflammation and regeneration. Fibrosis is also a cardinal feature of DMD. In this review, we will focus on two cases where understanding the normal function and regulation of ECM in muscle has led to the discovery of candidate therapeutics for DMD. Biglycan is a small leucine rich repeat ECM protein present as two glycoforms in muscle that have dramatically different functions. One widely expressed form is biglycan proteoglycan (PG) that bears two chondroitin sulfate GAG chains (typically chondroitin sulfate) and two N-linked carbohydrates. The second glycoform, referred to as 'NG' (non-glycanated) biglycan, lacks the GAG side chains. NG, but not PG biglycan recruits utrophin, an autosomal paralog of dystrophin, and an NOS-containing signaling complex to the muscle cell membrane. Recombinant NG biglycan can be systemically delivered to dystrophic mice where it upregulates utrophin at the membrane and improves muscle health and function. An optimized version of NG biglycan, 'TVN-102', is under development as a candidate therapeutic for DMD. A second matrix-embedded protein being evaluated for therapeutic potential is latent TGFβ binding protein 4 (LTBP4). Identified in a genomic screen for modifiers of muscular dystrophy, LTBP4 binds both TGFβ and myostatin. Genetic studies identified the hinge region of LTBP4 as linked to TGFβ release and contributing to the "hyper-TGFβ" signaling state that promotes fibrosis in muscular dystrophy. This hinge region can be stabilized by antibodies directed towards this domain. Stabilizing the hinge region of LTBP4 is expected to reduce latent TGFβ release and thus reduce fibrosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of the callipyge phenotype and cooking method on tenderness of several major lamb muscles.

PubMed

Shackelford, S D; Wheeler, T L; Koohmaraie, M

1997-08-01

We conducted three experiments to determine the effects of the callipyge phenotype on the tenderness of several major lamb muscles and to determine the effect of method of cookery on the tenderness of callipyge lamb at 7 d postmortem. In Exp. 1, chops from normal (n = 23) and callipyge (n = 16) carcasses were open-hearth-broiled. Warner-Bratzler shear force values of longissimus, gluteus medius, semimembranosus, biceps femoris, semitendinosus, adductor, and quadriceps femoris were 123, 44, 28, 26, 19, 16, and 13% greater, respectively, for callipyge (P < .05). In Exp. 2, muscles from normal (n = 18) and callipyge (n = 18) carcasses were oven-roasted. Shear force of triceps brachii was 11% greater for callipyge (P < .001); however, phenotype did not affect shear force of supraspinatus (P = .87) or psoas major (P = .64). In Exp. 3, a trained sensory panel evaluated leg roasts and open-hearth-broiled leg chops from normal (n = 60) and callipyge lamb carcasses (n = 60). Callipyge chops were less tender than normal chops (P < .05). Regardless of callipyge phenotype, muscles were more (P < .05) tender when roasted; however, the effect of method of cookery on tenderness scores was greater for callipyge muscles than for normal muscles. Callipyge roasts and normal roasts had similar tenderness (P = .58), and callipyge roasts were more tender than normal chops (P < .05). Regardless of cooking method, callipyge samples were less juicy than normal samples (P < .05). These data demonstrate that the callipyge phenotype will likely reduce consumer satisfaction due to reduced tenderness and juiciness; however, reduced tenderness in callipyge leg muscles could be prevented by ovenroasting.

Hedgehog signaling and laminin play unique and synergistic roles in muscle development.

PubMed

Peterson, Matthew T; Henry, Clarissa A

2010-03-01

Hedgehog (Hh) signaling and laminin-111, a basement membrane protein, are required for early muscle development. Hh signaling specifies different populations of muscle fibers and laminin-111 is critical for early muscle morphogenesis. However, additional requirements for Hh signaling and laminin during later phases of muscle development are not known. Furthermore, interactions between Hh signaling and laminin in this context are unknown. We used laminin gamma1 mutant zebrafish and cyclopamine to block Hh signal transduction separately and in combination to investigate their functions and interactions. We found that both Hh signaling and laminin are required for normal myosin chain expression. In addition, Hh signaling and laminin act synergistically during fast-twitch fiber elongation: fast muscle cells do not elongate in embryos deficient for both Hh signaling and laminin. Finally, we present evidence that suggests that Hh signaling is indirectly required via slow fiber specification for recovery of fast fiber elongation in laminin gamma1 mutant embryos. Copyright (c) 2010 Wiley-Liss, Inc.

Photothermal imaging of skeletal muscle mitochondria.

PubMed

Tomimatsu, Toru; Miyazaki, Jun; Kano, Yutaka; Kobayashi, Takayoshi

2017-06-01

The morphology and topology of mitochondria provide useful information about the physiological function of skeletal muscle. Previous studies of skeletal muscle mitochondria are based on observation with transmission, scanning electron microscopy or fluorescence microscopy. In contrast, photothermal (PT) microscopy has advantages over the above commonly used microscopic techniques because of no requirement for complex sample preparation by fixation or fluorescent-dye staining. Here, we employed the PT technique using a simple diode laser to visualize skeletal muscle mitochondria in unstained and stained tissues. The fine mitochondrial network structures in muscle fibers could be imaged with the PT imaging system, even in unstained tissues. PT imaging of tissues stained with toluidine blue revealed the structures of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria and the swelling behavior of mitochondria in damaged muscle fibers with sufficient image quality. PT image analyses based on fast Fourier transform (FFT) and Grey-level co-occurrence matrix (GLCM) were performed to derive the characteristic size of mitochondria and to discriminate the image patterns of normal and damaged fibers.

Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle

PubMed Central

Hernández, Andrés; Schiffer, Tomas A; Ivarsson, Niklas; Cheng, Arthur J; Bruton, Joseph D; Lundberg, Jon O; Weitzberg, Eddie; Westerblad, Håkan

2012-01-01

Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca2+ handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca2+] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca2+ handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca2+ handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness. PMID:22687611

Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle.

PubMed

Hernández, Andrés; Schiffer, Tomas A; Ivarsson, Niklas; Cheng, Arthur J; Bruton, Joseph D; Lundberg, Jon O; Weitzberg, Eddie; Westerblad, Håkan

2012-08-01

Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca(2+) handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca(2+)] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤ 50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca(2+) handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca(2+) handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness.

A comparison between handgrip strength, upper limb fat free mass by segmental bioelectrical impedance analysis (SBIA) and anthropometric measurements in young males

NASA Astrophysics Data System (ADS)

Gonzalez-Correa, C. H.; Caicedo-Eraso, J. C.; Varon-Serna, D. R.

2013-04-01

The mechanical function and size of a muscle may be closely linked. Handgrip strength (HGS) has been used as a predictor of functional performing. Anthropometric measurements have been made to estimate arm muscle area (AMA) and physical muscle mass volume of upper limb (ULMMV). Electrical volume estimation is possible by segmental BIA measurements of fat free mass (SBIA-FFM), mainly muscle-mass. Relationship among these variables is not well established. We aimed to determine if physical and electrical muscle mass estimations relate to each other and to what extent HGS is to be related to its size measured by both methods in normal or overweight young males. Regression analysis was used to determine association between these variables. Subjects showed a decreased HGS (65.5%), FFM, (85.5%) and AMA (74.5%). It was found an acceptable association between SBIA-FFM and AMA (r2 = 0.60) and poorer between physical and electrical volume (r2 = 0.55). However, a paired Student t-test and Bland and Altman plot showed that physical and electrical models were not interchangeable (pt<0.0001). HGS showed a very weak association with anthropometric (r2 = 0.07) and electrical (r2 = 0.192) ULMMV showing that muscle mass quantity does not mean muscle strength. Other factors influencing HGS like physical training or nutrition require more research.

Increased Muscle Stress-Sensitivity Induced by Selenoprotein N Inactivation in Mouse: A Mammalian Model for SEPN1-Related Myopathy

PubMed Central

Arbogast, Sandrine; Lainé, Jeanne; Vassilopoulos, Stéphane; Beuvin, Maud; Dubourg, Odile; Vignaud, Alban; Ferry, Arnaud; Krol, Alain; Allamand, Valérie; Guicheney, Pascale; Ferreiro, Ana; Lescure, Alain

2011-01-01

Selenium is an essential trace element and selenoprotein N (SelN) was the first selenium-containing protein shown to be directly involved in human inherited diseases. Mutations in the SEPN1 gene, encoding SelN, cause a group of muscular disorders characterized by predominant affection of axial muscles. SelN has been shown to participate in calcium and redox homeostasis, but its pathophysiological role in skeletal muscle remains largely unknown. To address SelN function in vivo, we generated a Sepn1-null mouse model by gene targeting. The Sepn1−/− mice had normal growth and lifespan, and were macroscopically indistinguishable from wild-type littermates. Only minor defects were observed in muscle morphology and contractile properties in SelN-deficient mice in basal conditions. However, when subjected to challenging physical exercise and stress conditions (forced swimming test), Sepn1−/− mice developed an obvious phenotype, characterized by limited motility and body rigidity during the swimming session, as well as a progressive curvature of the spine and predominant alteration of paravertebral muscles. This induced phenotype recapitulates the distribution of muscle involvement in patients with SEPN1-Related Myopathy, hence positioning this new animal model as a valuable tool to dissect the role of SelN in muscle function and to characterize the pathophysiological process. PMID:21858002

Protein O-Mannosyltransferases Affect Sensory Axon Wiring and Dynamic Chirality of Body Posture in the Drosophila Embryo.

PubMed

Baker, Ryan; Nakamura, Naosuke; Chandel, Ishita; Howell, Brooke; Lyalin, Dmitry; Panin, Vladislav M

2018-02-14

Genetic defects in protein O-mannosyltransferase 1 (POMT1) and POMT2 underlie severe muscular dystrophies. POMT genes are evolutionarily conserved in metazoan organisms. In Drosophila , both male and female POMT mutants show a clockwise rotation of adult abdominal segments, suggesting a chirality of underlying pathogenic mechanisms. Here we described and analyzed a similar phenotype in POMT mutant embryos that shows left-handed body torsion. Our experiments demonstrated that coordinated muscle contraction waves are associated with asymmetric embryo rolling, unveiling a new chirality marker in Drosophila development. Using genetic and live-imaging approaches, we revealed that the torsion phenotype results from differential rolling and aberrant patterning of peristaltic waves of muscle contractions. Our results demonstrated that peripheral sensory neurons are required for normal contractions that prevent the accumulation of torsion. We found that POMT mutants show abnormal axonal connections of sensory neurons. POMT transgenic expression limited to sensory neurons significantly rescued the torsion phenotype, axonal connectivity defects, and abnormal contractions in POMT mutant embryos. Together, our data suggested that protein O-mannosylation is required for normal sensory feedback to control coordinated muscle contractions and body posture. This mechanism may shed light on analogous functions of POMT genes in mammals and help to elucidate the etiology of neurological defects in muscular dystrophies. SIGNIFICANCE STATEMENT Protein O-mannosyltransferases (POMTs) are evolutionarily conserved in metazoans. Mutations in POMTs cause severe muscular dystrophies associated with pronounced neurological defects. However, neurological functions of POMTs remain poorly understood. We demonstrated that POMT mutations in Drosophila result in abnormal muscle contractions and cause embryo torsion. Our experiments uncovered a chirality of embryo movements and a unique POMT -dependent mechanism that maintains symmetry of a developing system affected by chiral forces. Furthermore, POMTs were found to be required for proper axon connectivity of sensory neurons, suggesting that O-mannosylation regulates the sensory feedback controlling muscle contractions. This novel POMT function in the peripheral nervous system may shed light on analogous functions in mammals and help to elucidate pathomechanisms of neurological abnormalities in muscular dystrophies. Copyright © 2018 the authors 0270-6474/18/381850-16$15.00/0.

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

PubMed

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.

Quantification of functional hand grip using electromyography and inertial sensor-derived accelerations: clinical implications.

PubMed

Martin-Martin, Jaime; Cuesta-Vargas, Antonio I

2014-12-11

Assessing hand injury is of great interest given the level of involvement of the hand with the environment. Knowing different assessment systems and their limitations generates new perspectives. The integration of digital systems (accelerometry and electromyography) as a tool to supplement functional assessment allows the clinician to know more about the motor component and its relation to movement. Therefore, the purpose of this study was the kinematic and electromyography analysis during functional hand movements. Ten subjects carried out six functional movements (terminal pinch, termino-lateral pinch, tripod pinch, power grip, extension grip and ball grip). Muscle activity (hand and forearm) was measured in real time using electromyograms, acquired with the Mega ME 6000, whilst acceleration was measured using the AcceleGlove. Electrical activity and acceleration variables were recorded simultaneously during the carrying out of the functional movements. The acceleration outcome variables were the modular vectors of each finger of the hand and the palm. In the electromyography, the main variables were normalized by the mean and by the maximum muscle activity of the thenar region, hypothenar, first interosseous dorsal, wrist flexors, carpal flexors and wrist extensors. Knowing muscle behavior allows the clinician to take a more direct approach in the treatment. Based on the results, the tripod grip shows greater kinetic activity and the middle finger is the most relevant in this regard. Ball grip involves most muscle activity, with the thenar region playing a fundamental role in hand activity. Relating muscle activation, movements, individual load and displacement offers the possibility to proceed with rehabilitation by individual component.

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

PubMed

Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

Activity of upper limb muscles during human walking.

PubMed

Kuhtz-Buschbeck, Johann P; Jing, Bo

2012-04-01

The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

Papillary Muscle Repositioning as a Subvalvular Apparatus Preservation Technique in Mitral Stenosis Patients with Normal Left Ventricular Systolic Function

PubMed Central

Lafci, Gokhan; Cagli, Kerim; Korkmaz, Kemal; Turak, Osman; Uzun, Alper; Yalcinkaya, Adnan; Diken, Adem; Gunertem, Eren; Cagli, Kumral

2014-01-01

Subvalvular apparatus preservation is an important concept in mitral valve replacement (MVR) surgery that is performed to remedy mitral regurgitation. In this study, we sought to determine the effects of papillary muscle repositioning (PMR) on clinical outcomes and echocardiographic left ventricular function in rheumatic mitral stenosis patients who had normal left ventricular systolic function. We prospectively assigned 115 patients who were scheduled for MVR surgery with mechanical prosthesis to either PMR or MVR-only groups. Functional class and echocardiographic variables were evaluated at baseline and at early and late postoperative follow-up examinations. All values were compared between the 2 groups. The PMR group consisted of 48 patients and the MVR-only group of 67 patients. The 2 groups’ baseline characteristics and surgery-related factors (including perioperative mortality) were similar. During the 18-month follow-up, all echocardiographic variables showed a consistent improvement in the PMR group; the mean left ventricular ejection fraction deteriorated significantly in the MVR-only group. Comparison during follow-up of the magnitude of longitudinal changes revealed that decreases in left ventricular end-diastolic and end-systolic diameters and in left ventricular sphericity indices, and increases in left ventricular ejection fractions, were significantly higher in the PMR group than in the MVR-only group. This study suggests that, in patients with rheumatic mitral stenosis and preserved left ventricular systolic function, the addition of papillary muscle repositioning to valve replacement with a mechanical prosthesis improves left ventricular dimensions, ejection fraction, and sphericity index at the 18-month follow-up with no substantial undesirable effect on the surgery-related factors. PMID:24512397

Reduced exercise capacity in untreated adults with primary growth hormone resistance (Laron syndrome).

PubMed

Ben-Dov, Issahar; Gaides, Mark; Scheinowitz, Mickey; Wagner, Rivka; Laron, Zvi

2003-12-01

Primary IGF-I deficiency (Laron syndrome, LS) may decrease exercise capacity as a result of a lack of an IGF-I effect on heart, peripheral muscle or lung structure and/or function. Eight patients (six females) who had never received treatment with IGF-I, with mean age of 36 +/- 10 (SD) years (range 21-48), weight 47 +/- 9 kg (31-61), height 126 +/- 12 cm (112-140) and body mass index of 29 +/- 4 kg/m2 (24-34), and 12 age-matched controls, underwent lung function tests and incremental cycling to the limit of tolerance (CPX, MedGraphics). Predicted values for the patients were derived from adult equations based on height. In LS patients, lung function was near normal; vital capacity was 84 +/- 11% of expected (66-103). Peak exercise O2-uptake and the anaerobic threshold were reduced, 57 +/- 20% of predicted and 33 +/- 9% of predicted peak (P = 0.005 vs. controls), despite normal mean exercise breathing reserve. All parameters were normal in the controls. Exercise capacity in untreated adults with LS is significantly reduced. The limitation for most patients was not ventilatory but resulted either from low cardiac output and/or from dysfunction of the peripheral muscles. However, the relative contribution of each of these elements and/or the role of poor fitness needs further study.

Scapulohumeral rhythm in shoulders with reverse shoulder arthroplasty.

PubMed

Walker, David; Matsuki, Keisuke; Struk, Aimee M; Wright, Thomas W; Banks, Scott A

2015-07-01

Little is known about kinematic function of reverse total shoulder arthroplasty (RTSA). Scapulohumeral rhythm (SHR) is a common metric for assessing muscle function and shoulder joint motion. The purpose of this study was to compare SHR in shoulders with RTSA to normal shoulders. Twenty-eight subjects, more than 12 months after unilateral RTSA, were recruited for an Institutional Review Board-approved study. Subjects performed arm abduction in the coronal plane with and without a 1.4-kg hand-held weight. Three-dimensional model-image registration techniques were used to measure orientation and position for the humerus and scapula from fluoroscopic images. Analysis of variance and Tukey tests were used to assess groupwise and pairwise differences. SHR in RTSA shoulders (1.3:1) was significantly lower than in normal shoulders (3:1). Below 30° abduction, RTSA and normal shoulders show a wide range of SHR (1.3:1 to 17:1). Above 30° abduction, SHR in RTSA shoulders was 1.3:1 for unweighted abduction and 1.3:1 for weighted abduction. Maximum RTSA shoulder abduction in weighted trials was lower than in unweighted trials. SHR variability in RTSA shoulders decreased with increasing arm elevation. RTSA shoulders show kinematics that are significantly different from normal shoulders. SHR in RTSA shoulders was significantly lower than in normal shoulders, indicating that RTSA shoulders use more scapulothoracic motion and less glenohumeral motion to elevate the arm. With these observations, it may be possible to improve rehabilitation protocols, with particular attention to the periscapular muscles, and implant design or placement to optimize functional outcomes in shoulders with RTSA. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment.

PubMed

Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M; Mustari, Michael J; McLoon, Linda K

2015-06-01

Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity. Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls. Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density. Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus.

Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment

PubMed Central

Willoughby, Christy L.; Fleuriet, Jérome; Walton, Mark M.; Mustari, Michael J.; McLoon, Linda K.

2015-01-01

Purpose. Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity. Methods. Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls. Results. Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density. Conclusions. Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus. PMID:26030103

Reflexes in the shoulder muscles elicited from the human coracoacromial ligament.

PubMed

Diederichsen, Louise Pyndt; Nørregaard, Jesper; Krogsgaard, Michael; Fischer-Rasmussen, Torsten; Dyhre-Poulsen, Poul

2004-09-01

Morphological studies have demonstrated mechanoreceptors in the capsuloligamentous structures of the shoulder joint, however knowledge of the role these joint receptors play in the control of shoulder stability is limited. We therefore investigated the effect of electrically induced afferent activity from mechanoreceptors in the coracoacromial ligament (CAL) on the activity of voluntary activated shoulder muscles in healthy humans. In study I, wire electrodes, for electrical stimulation, were inserted into the CAL in eight normal shoulders. In study II, a needle electrode was inserted into the CAL in seven normal shoulders. Electric activity was recorded from eight shoulder muscles by surface and intramuscular electrodes. During isometric contractions, electrical stimulation was applied to the CAL at two different stimulus intensities, a weak stimulus (stim-1) and a stronger stimulus (stim-2). In both experiments, electrical stimulation of the CAL elicited a general inhibition in the voluntary activated shoulder muscles. In study I the average latencies (mean+/-SE) of the muscular inhibition were 66+/-4 ms (stim-1) and 62+/-4 ms (stim-2) during isometric flexion and 73+/-3 ms (stim-1) and 73+/-5 ms (stim-2) during isometric extension. In study II the average latency (mean+/-SE) of the response was 66+/-4 ms (stim-1) during isometric flexion. Our results demonstrated a response, probably of reflex origin, from mechanoreceptors in the CAL to the shoulder muscles. The existence of this synaptic connection between mechanoreceptors in CAL and the shoulder muscles suggest a role of these receptors in muscle coordination and in the functional joint stability.

MRI-based registration of pelvic alignment affected by altered pelvic floor muscle characteristics.

PubMed

Bendová, Petra; Růzicka, Pavel; Peterová, Vera; Fricová, Martina; Springrová, Ingrid

2007-11-01

Pelvic floor muscles have potential to influence relative pelvic alignment. Side asymmetry in pelvic floor muscle tension is claimed to induce pelvic malalignment. However, its nature and amplitude are not clear. There is a need for non-invasive and reliable assessment method. An intervention experiment of unilateral pelvic floor muscle activation on healthy females was performed using image data for intra-subject comparison of normal and altered configuration of bony pelvis. Sequent magnetic resonance imaging of 14 females in supine position was performed with 1.5 T static body coil in coronal orientation. The intervention, surface functional electrostimulation, was applied to activate pelvic floor muscles on the right side. Spatial coordinates of 23 pelvic landmarks were localized in each subject and registered by specially designed magnetic resonance image data processing tool (MPT2006), where individual error calculation; data registration, analysis and 3D visualization were interfaced. The effect of intervention was large (Cohen's d=1.34). We found significant differences in quantity (P<0.01) and quality (P=0.02) of normal and induced pelvic displacements. After pelvic floor muscle activation on the right side, pelvic structures shifted most frequently to the right side in ventro-caudal direction. The right femoral head, the right innominate and the coccyx showed the largest displacements. The consequences arising from the capacity of pelvic floor muscles to displace pelvic bony structures are important to consider not only in management of malalignment syndrome but also in treatment of incontinence. The study has demonstrated benefits associated with processing of magnetic resonance image data within pelvic region with high localization and registration reliability.

Comparison of range of motion and function of subjects with reverse anatomy Bayley-Walker shoulder replacement with those of normal subjects.

PubMed

Masjedi, Milad; Lovell, Cara; Johnson, Garth R

2011-12-01

Patients with rotator cuff tear and degenerative shoulder joint disease commonly experience severe pain and reduced performance during activities of daily living. A popular way to treat these patients is by means of reverse anatomy shoulder prosthesis. Studying the kinematics of subjects with reverse anatomy implant would be useful in order to gain knowledge about functionality of different designs. It is hypothesized that the kinematics of these subjects, in the absence of rotator cuff muscles, differs from that of normal subjects. In this study the upper limb kinematics of 12 subjects with a Bayley-Walker reverse anatomy shoulder prosthesis while performing tasks common in everyday activities and those that represent the range of motion was analyzed and compared to that of 12 normal subjects. Each patient also completed an Oxford Shoulder Score. Substantial reduction in the Bayley-Walker subjects' ranges of motion was observed compared to normal subjects. The mean abduction angle decreased from 109° (±20) for normal subjects to 64° (±25). A similar trend was observed during flexion and axial rotation tasks. Furthermore, the normal group showed less variable ranges of motion performing the standard tasks, whereas for the prosthetic group this varied greatly, which is likely to be dependent on muscle strength. Although the decreased range of motion was prominent, subjects were able to complete most of the tasks by compensating with their elbow and trunk. The most challenging task for Bayley-Walker subjects was lifting an object to head height. Copyright © 2010 Elsevier B.V. All rights reserved.

[Apoptosis and expression of apoptosis-related proteins in experimental different denervated guinea-pig facial muscle].

PubMed

Hui, Lian; Wei, Hong-Quan; Li, Xiao-Tian; Guan, Chao; Ren, Zhong

2005-02-01

To study apoptosis and expression of apoptosis-related proteins in experimental different denervated guinea-pig facial muscle. An experimental model was established with guinea pigs by compressing the facial nerve 30 second (reinnervated group) and resecting the facial nerve (denervated group). TUNEL method and immunohistochemical technique (SABC) were applied to detect the apoptosis and expression of apoptosis-related proteins bcl-2 and bax from 1st to 8th week after operation. Experimentally denervated facial muscle revealed consistently increase of DNA fragmentation, average from(34.4 +/- 4.6)% to (38.2 +/- 10.6)%, from 1st week to 8th week after operation; Reinnervated facial muscle showed a temporal increase of DNA fragmentation, and then the muscle fiber nuclei revealed decreased DNA fragmentation along with the function of facial nerve recovered, latterly normal, average from (32.0 +/- 8.03)% to (5.6 +/- 3.5)%, from 1st week to 8th week after operation. In denervated group, bcl-2 and bax were expressed strongly; in reinnervated group, bcl-2 expressed consistently, but bax disappeared latterly along with the function of facial nerve recovered. Expression of DNA fragmentation and apoptosis-related proteins in denervated muscle are general reaction to denervation. bcl-2 can prevent early apoptotic muscle fiber to survival until reinnervation. It is concluded that proteins control apoptosis may give information for possible therapeutic interventions to reduce the rate of muscle fiber death in denervated atrophy in absence of effective primary treatment.

Lipogenesis mitigates dysregulated sarcoplasmic reticulum calcium uptake in muscular dystrophy.

PubMed

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

2015-12-01

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

Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets.

PubMed

Wacker, Michael J; Touchberry, Chad D; Silswal, Neerupma; Brotto, Leticia; Elmore, Chris J; Bonewald, Lynda F; Andresen, Jon; Brotto, Marco

2016-01-01

Autosomal recessive hypophosphatemic rickets (ARHR) is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well-characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand in order to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL-fast-twitch muscle), soleus (SOL-slow-twitch muscle), heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum) which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2α or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In summary, these results indicate that there are deficiencies in both fast twitch and slow twitch muscle fiber type contractions in this model of ARHR, while there was less of a phenotype observed in cardiac muscle, and no differences observed in aortic function. These results may help explain skeletal muscle weakness reported by some patients with osteomalacia and need to be further investigated.

Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets

PubMed Central

Wacker, Michael J.; Touchberry, Chad D.; Silswal, Neerupma; Brotto, Leticia; Elmore, Chris J.; Bonewald, Lynda F.; Andresen, Jon; Brotto, Marco

2016-01-01

Autosomal recessive hypophosphatemic rickets (ARHR) is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well-characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand in order to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL-fast-twitch muscle), soleus (SOL–slow-twitch muscle), heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum) which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2α or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In summary, these results indicate that there are deficiencies in both fast twitch and slow twitch muscle fiber type contractions in this model of ARHR, while there was less of a phenotype observed in cardiac muscle, and no differences observed in aortic function. These results may help explain skeletal muscle weakness reported by some patients with osteomalacia and need to be further investigated. PMID:27242547

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats.

PubMed

Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun; Ra, Jeong Chan; Kim, Yun-Bae

2015-10-01

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1×10(6) cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. ©AlphaMed Press.

Test-Retest Reliability of Innovated Strength Tests for Hip Muscles

PubMed Central

Meyer, Christophe; Corten, Kristoff; Wesseling, Mariska; Peers, Koen; Simon, Jean-Pierre; Jonkers, Ilse; Desloovere, Kaat

2013-01-01

The burden of hip muscles weakness and its relation to other impairments has been well documented. It is therefore a pre-requisite to have a reliable method for clinical assessment of hip muscles function allowing the design and implementation of a proper strengthening program. Motor-driven dynamometry has been widely accepted as the gold-standard for lower limb muscle strength assessment but is mainly related to the knee joint. Studies focusing on the hip joint are less exhaustive and somewhat discrepant with regard to optimal participants position, consequently influencing outcome measures. Thus, we aimed to develop a standardized test setup for the assessment of hip muscles strength, i.e. flexors/extensors and abductors/adductors, with improved participant stability and to define its psychometric characteristics. Eighteen participants performed unilateral isokinetic and isometric contractions of the hip muscles in the sagittal and coronal plane at two separate occasions. Peak torque and normalized peak torque were measured for each contraction. Relative and absolute measures of reliability were calculated using the intraclass correlation coefficient and standard error of measurement, respectively. Results from this study revealed higher levels of between-day reliability of isokinetic/isometric hip abduction/flexion peak torque compared to existing literature. The least reliable measures were found for hip extension and adduction, which could be explained by a less efficient stabilization technique. Our study additionally provided a first set of reference normalized data which can be used in future research. PMID:24260550

Finite element modelling predicts changes in joint shape and cell behaviour due to loss of muscle strain in jaw development

PubMed Central

Brunt, Lucy H.; Norton, Joanna L.; Bright, Jen A.; Rayfield, Emily J.; Hammond, Chrissy L.

2015-01-01

Abnormal joint morphogenesis is linked to clinical conditions such as Developmental Dysplasia of the Hip (DDH) and to osteoarthritis (OA). Muscle activity is known to be important during the developmental process of joint morphogenesis. However, less is known about how this mechanical stimulus affects the behaviour of joint cells to generate altered morphology. Using zebrafish, in which we can image all joint musculoskeletal tissues at high resolution, we show that removal of muscle activity through anaesthetisation or genetic manipulation causes a change to the shape of the joint between the Meckel's cartilage and Palatoquadrate (the jaw joint), such that the joint develops asymmetrically leading to an overlap of the cartilage elements on the medial side which inhibits normal joint function. We identify the time during which muscle activity is critical to produce a normal joint. Using Finite Element Analysis (FEA), to model the strains exerted by muscle on the skeletal elements, we identify that minimum principal strains are located at the medial region of the joint and interzone during mouth opening. Then, by studying the cells immediately proximal to the joint, we demonstrate that biomechanical strain regulates cell orientation within the developing joint, such that when muscle-induced strain is removed, cells on the medial side of the joint notably change their orientation. Together, these data show that biomechanical forces are required to establish symmetry in the joint during development. PMID:26253758

Finite element modelling predicts changes in joint shape and cell behaviour due to loss of muscle strain in jaw development.

PubMed

Brunt, Lucy H; Norton, Joanna L; Bright, Jen A; Rayfield, Emily J; Hammond, Chrissy L

2015-09-18

Abnormal joint morphogenesis is linked to clinical conditions such as Developmental Dysplasia of the Hip (DDH) and to osteoarthritis (OA). Muscle activity is known to be important during the developmental process of joint morphogenesis. However, less is known about how this mechanical stimulus affects the behaviour of joint cells to generate altered morphology. Using zebrafish, in which we can image all joint musculoskeletal tissues at high resolution, we show that removal of muscle activity through anaesthetisation or genetic manipulation causes a change to the shape of the joint between the Meckel's cartilage and Palatoquadrate (the jaw joint), such that the joint develops asymmetrically leading to an overlap of the cartilage elements on the medial side which inhibits normal joint function. We identify the time during which muscle activity is critical to produce a normal joint. Using Finite Element Analysis (FEA), to model the strains exerted by muscle on the skeletal elements, we identify that minimum principal strains are located at the medial region of the joint and interzone during mouth opening. Then, by studying the cells immediately proximal to the joint, we demonstrate that biomechanical strain regulates cell orientation within the developing joint, such that when muscle-induced strain is removed, cells on the medial side of the joint notably change their orientation. Together, these data show that biomechanical forces are required to establish symmetry in the joint during development. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuromuscular electrical stimulation of the hindlimb muscles for movement therapy in a rodent model.

PubMed

Ichihara, Kazuhiko; Venkatasubramanian, Ganapriya; Abbas, James J; Jung, Ranu

2009-01-30

Neuromuscular electrical stimulation (NMES) can provide functional movements in people after central nervous system injury. The neuroplastic effects of long-term NMES-induced repetitive limb movement are not well understood. A rodent model of neurotrauma in which NMES can be implemented may be effective for such investigations. We present a rodent model for NMES of the flexor and extensor muscles of the hip, knee, and ankle hindlimb muscles. Custom fabricated intramuscular stimulating electrodes for rodents were implanted near identified motor points of targeted muscles in ten adult, female Long Evans rats. The effects of altering NMES pulse stimulation parameters were characterized using strength duration curves, isometric joint torque recruitment curves and joint angle measures. The data indicate that short pulse widths have the advantage of producing graded torque recruitment curves when current is used as the control parameter. A stimulus frequency of 75 Hz or more produces fused contractions. The data demonstrate ability to accurately implant the electrodes and obtain selective, graded, repeatable, strong muscle contractions. Knee and ankle angular excursions comparable to those obtained in normal treadmill walking in the same rodent species can be obtained by stimulating the target muscles. Joint torques (normalized to body weight) obtained were larger than those reported in the literature for small tailed therian mammals and for peak isometric ankle plantarflexion in a different rodent species. This model system could be used for investigations of NMES assisted hindlimb movement therapy.

Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy

NASA Technical Reports Server (NTRS)

Gomes, M. D.; Lecker, S. H.; Jagoe, R. T.; Navon, A.; Goldberg, A. L.

2001-01-01

Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and found a unique gene fragment that is induced more than ninefold in muscles of fasted mice. We cloned this gene, which is expressed specifically in striated muscles. Because this mRNA also markedly increases in muscles atrophying because of diabetes, cancer, and renal failure, we named it atrogin-1. It contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the other components of SCF-type Ub-protein ligases (E3s), as well as a nuclear localization sequence and PDZ-binding domain. On fasting, atrogin-1 mRNA levels increase specifically in skeletal muscle and before atrophy occurs. Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases.

Role of muscle spindle in weightlessness-induced amyotrophia and muscle pain.

PubMed

Ali, Umar; Fan, Xiao-Li; You, Hao-Jun

2009-10-01

To date, the medium and long-term space flight is urgent in need and has become a major task of our manned space flight program. There is no doubt that medium and long-term space flight has serious damaging impact upon human physiological systems. For instance, atrophy of the lower limb anti-gravity muscle can be induced during the space flight. Muscle atrophy significantly affects the flight of astronauts in space. Most importantly, it influences the precise manipulation of the astronauts and their response capacity to emergencies on returning to the atmosphere from space. Muscle atrophy caused by weightlessness may also seriously disrupt the normal life and work of the astronauts during the re-adaptation period. Here we summarize the corresponding research concentrating on weightlessness-induced changes of muscular structure and function. By combining research on muscle pain, which is a common clinical pain disease, we further provide a hypothesis concerning a dynamic feedback model of "weightlessness condition right triple arrow muscular atrophy <--> muscle pain". This may be useful to explore the neural mechanisms underlying the occurrence and development of muscular atrophy and muscle pain, through the key study of muscle spindle, and furthermore provide more effective therapy for clinical treatment.

Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy

PubMed Central

Fry, Christopher S.; Lee, Jonah D.; Jackson, Janna R.; Kirby, Tyler J.; Stasko, Shawn A.; Liu, Honglu; Dupont-Versteegden, Esther E.; McCarthy, John J.; Peterson, Charlotte A.

2014-01-01

Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.—Fry, C. S., Lee, J. D., Jackson, J. R., Kirby, T. J., Stasko, S. A., Liu, H., Dupont-Versteegden, E. E., McCarthy, J. J., Peterson, C. A. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy. PMID:24376025

Force estimation from ensembles of Golgi tendon organs

NASA Astrophysics Data System (ADS)

Mileusnic, M. P.; Loeb, G. E.

2009-06-01

Golgi tendon organs (GTOs) located in the skeletal muscles provide the central nervous system with information about muscle tension. The ensemble firing of all GTO receptors in the muscle has been hypothesized to represent a reliable measure of the whole muscle force but the precision and accuracy of that information are largely unknown because it is impossible to record activity simultaneously from all GTOs in a muscle. In this study, we combined a new mathematical model of force sampling and transduction in individual GTOs with various models of motor unit (MU) organization and recruitment simulating various normal, pathological and neural prosthetic conditions. Our study suggests that in the intact muscle the ensemble GTO activity accurately encodes force information according to a nonlinear, monotonic relationship that has its steepest slope for low force levels and tends to saturate at the highest force levels. The relationship between the aggregate GTO activity and whole muscle tension under some pathological conditions is similar to one seen in the intact muscle during rapidly modulated, phasic excitation of the motor pool (typical for many natural movements) but quite different when the muscle is activated slowly or held at a given force level. Substantial deviations were also observed during simulated functional electrical stimulation.

The pedicled masseter muscle transfer for smile reconstruction in facial paralysis: repositioning the origin and insertion.

PubMed

Matic, Damir B; Yoo, John

2012-08-01

The pedicled masseter muscle transfer (PMMT) is introduced as a new reconstructive option for dynamic smile restoration in patients with facial paralysis. The masseter muscle is detached from both its origin and insertion and transferred to a new position to imitate the function of the native zygomaticus major muscle. Part one of this study consisted of cadaveric dissections of 4 heads (eight sides) in order to determine whether the masseter muscle could be (a) pedicled solely by its dominant neurovascular bundle and (b) repositioned directly over the native zygomaticus major. The second part of the study consisted of clinical assessments in three patients in order to confirm the applicability of this muscle transfer. Commissure excursion and vector of contraction following PMMT were compared to the non-paralyzed side. In all eight sides, the masseter muscles were successfully isolated on their pedicle and transposed on top of and in-line with the ipsilateral zygomaticus major. The mean length of the masseter and its angle from Frankfurt's horizontal line after transposition compared favorably to the native zygomaticus major muscle. In the clinical cases, the mean commissure movements of the paralyzed and normal sides were 7 mm and 12 mm respectively. The mean angles of commissural movement for the paralyzed and normal sides were 62° and 59° respectively. The PMMT can be used as a dynamic reconstruction for patients with permanent facial paralysis. As we gain experience with the PMMT, it may be possible to use it as a first-line option for patients not eligible for free micro-neurovascular reconstruction. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Expression pattern and function of tyrosine receptor kinase B isoforms in rat mesenteric arterial smooth muscle cells

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

Otani, Kosuke; Okada, Muneyoshi; Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp

Tyrosine receptor kinaseB (TrkB) is a high affinity receptor for brain-derived neurotrophic factor (BDNF). TrkB isoforms involve full length TrkB (TrkB FL) and truncated TrkB type1 (TrkB T1) and type 2 (TrkB T2) in rats. The aim of present study was to explore their expression pattern and function in mesenteric arterial smooth muscle cells (MASMCs). The expression of TrkB isoform protein and mRNA was examined by Western blotting, immunofluorescence and quantitative RT-PCR analyses. Cell proliferation was measured by a bromodeoxyuridine (BrdU) incorporation assay. Cell migration was measured by a Boyden chamber assay. Cell morphology was observed with a phase-contrast microscope.more » Protein and mRNA expression of BDNF and TrkB isoforms was confirmed in MASMCs. Expression level of TrkB FL was less, while that of TrkB T1 was the highest in MASMCs. Although BDNF increased phosphorylation of ERK, it had no influence on migration and proliferation of MASMCs. TrkB T1 gene knockdown by a RNA interference induced morphological changes and reduced expression level of α-smooth muscle actin (α-SMA) in MASMCs. Similar morphological changes and reduced α-SMA expression were induced in MASMCs by a Rho kinase inhibitor, Y-27632. In conclusion, we for the first time demonstrate that TrkB T1 expressed highly in MASMCs contributes to maintain normal cell morphology possibly via regulation of Rho activity. This study firstly defined expression level of TrkB isoforms and partly revealed their functions in peripheral vascular cells. - Highlights: • BDNF-TrkB axis mediates neurogenesis, growth, differentiation and survival. • Expression pattern and function of TrkB in vascular smooth muscle remain unclear. • Expression of TrkB FL is low, while that of TrkB T1 is the highest. • TrkB T1 contributes to maintain normal morphology possibly via activating Rho.« less

Effect of age on changes in motor units functional connectivity.

PubMed

Arjunan, Sridhar P; Kumar, Dinesh

2015-08-01

With age, there is a change in functional connectivity of motor units in muscle. This leads to reduced muscle strength. This study has investigated the effect of age on the changes in the motor unit recruitment by measuring the mutual information between multiple channels of surface electromyogram (sEMG) of biceps brachii muscle. It is hypothesised that with ageing, there is a reduction in number of motor units, which can lead to an increase in the dependency of remaining motor units. This increase can be observed in the mutual information between the multiple channels of the muscle activity. Two channels of sEMG were recorded during the maximum level of isometric contraction. 28 healthy subjects (Young: age range 20-35years and Old: age range - 60-70years) participated in the experiments. The normalized mutual information (NMI), a measure of dependency factor, was computed for the sEMG recordings. Statistical analysis was performed to test the effect of age on NMI. The results show that the NMI among the older cohort was significantly higher when compared with the young adults.

Botulinum neurotoxin effects on masseter muscle fibre in WNIN obese rats-Scanning electron microscope analysis.

PubMed

Nemani, Shivaram; Putchha, Uday K; Periketi, Madhusudhanachary; Pothana, Sailaja; Nappanveettil, Giridharan; Nemani, Harishankar

2016-09-01

WNIN/Ob obese mutant rats are unique in comparison to similar rodent models of obesity established in the West. The present study is aimed to evaluate the masticatory function and histological changes in masseter muscle fibres treated with botulinum toxin type A (BoNT/A) in WNIN/Ob rats. Twelve WNIN/Ob obese rats and 12 lean rats at 35 days of age were taken and divided into four groups (6 rats in each group): Group-I (WNIN/Ob) and Group-II (lean) rats were injected with BoNT/A (1 unit) into right side of masseter muscle. For control left masseter of both phenotypes was injected with saline. Group-III (WNIN/Ob) and Group-IV (lean) rats were without any treatment. Growth and food intake was monitored daily for 45 days. Rats were euthanized and gross necropsy was carried out to check any abnormalities. Masseter muscles were dissected and mean muscle mass was recorded. Small portion of muscle was stored in 10% formalin for hematoxylin-eosin (H&E) staining and remaining tissue stored in gluteraldehyde for scanning electron microscopy (SEM). There is a significant decrease in the body weights and food intake of BoNT/A treated obese rats. The H&E staining of the masseter muscle in both groups showed normal morphology and orientation. The SEM analysis showed that, fibre size in BoNT/A treated masseter muscle of obese rats increased more than the saline treated side and in control rats. The increase in the muscle fibre size and transition of muscle fibre subtypes may be due to the reduced masticatory function of the masseter muscle. SCANNING 38:396-402, 2016. © 2015 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

Exercise training does not increase muscle FNDC5 protein or mRNA expression in pigs

PubMed Central

Fain, John N.; Company, Joseph M.; Booth, Frank W.; Laughlin, M. Harold; Padilla, Jaume; Jenkins, Nathan T.; Bahouth, Suleiman W.; Sacks, Harold S.

2013-01-01

Background Exercise training elevates circulating irisin and induces the expression of the FNDC5 gene in skeletal muscles of mice. Our objective was to determine whether exercise training also increases FNDC5 protein or mRNA expression in the skeletal muscles of pigs as well as plasma irisin. Methods Castrated male pigs of the Rapacz familial hypercholesterolemic (FHM) strain and normal (Yucatan miniature) pigs were sacrificed after 16–20 weeks of exercise training. Samples of cardiac muscle, deltoid and triceps brachii muscle, subcutaneous and epicardial fat were obtained and FNDC5 mRNA, along with that of 6 other genes, was measured in all tissues of FHM pigs by reverse transcription polymerase chain reaction. FNDC protein in deltoid and triceps brachii was determined by Western blotting in both FHM and normal pigs. Citrate synthase activity was measured in the muscle samples of all pigs as an index of exercise training. Irisin was measured by an ELISA assay. Results There was no statistically significant effect of exercise training on FNDC5 gene expression in epicardial or subcutaneous fat, deltoid muscle, triceps brachii muscle or heart muscle. Exercise-training elevated circulating levels of irisin in the FHM pigs and citrate synthase activity in deltoid and triceps brachii muscle. A similar increase in citrate synthase activity was seen in muscle extracts of exercise-trained normal pigs but there was no alteration in circulating irisin. Conclusion Exercise training in pigs does not increase FNDC5 mRNA or protein in the deltoid or triceps brachii of FHM or normal pigs while increasing circulating irisin only in the FHM pigs. These data indicate that the response to exercise training in normal pigs is not comparable to that seen in mice. PMID:23831442

Mechanical ventilation alone, and in the presence of sepsis, impair protein metabolism in the diaphragm of neonatal pigs

USDA-ARS?s Scientific Manuscript database

Mechanical ventilation (MV) impairs diaphragmatic function and diminishes the ability to wean from ventilatory support in adult humans. In normal neonatal pigs, animals that are highly anabolic, endotoxin (LPS) infusion induces sepsis, reduces peripheral skeletal muscle protein synthesis rates, but ...

What evidence implicates airway smooth muscle in the cause of BHR?

PubMed

Dulin, Nickolai O; Fernandes, Darren J; Dowell, Maria; Bellam, Shashi; McConville, John; Lakser, Oren; Mitchell, Richard; Camoretti-Mercado, Blanca; Kogut, Paul; Solway, Julian

2003-02-01

Bronchial hyperresponsiveness (BHR), the occurrence of excessive bronchoconstriction in response to relatively small constrictor stimuli, is a cardinal feature of asthma. Here, we consider the role that airway smooth muscle might play in the generation of BHR. The weight of evidence suggests that smooth muscle isolated from asthmatic tissues exhibits normal sensitivity to constrictor agonists when studied during isometric contraction, but the increased muscle mass within asthmatic airways might generate more total force than the lesser amount of muscle found in normal bronchi. Another salient difference between asthmatic and normal individuals lies in the effect of deep inhalation (DI) on bronchoconstriction. DI often substantially reverses induced bronchoconstriction in normals, while it often has much less effect on spontaneous or induced bronchoconstriction in asthmatics. It has been proposed that abnormal dynamic aspects of airway smooth muscle contraction velocity of contraction or plasticity- elasticity balance might underlie the abnormal DI response in asthma. We suggest a speculative model in which abnormally long actin filaments might account for abnormally increased elasticity of contracted airway smooth muscle.

Effect of virtual reality exercise using the nintendo wii fit on muscle activities of the trunk and lower extremities of normal adults.

PubMed

Park, Jungseo; Lee, Daehee; Lee, Sangyong

2014-02-01

[Purpose] The present study aimed to determine the effect of virtual reality exercise using the Nintendo Wii Fit on the muscle activities of the trunk and lower extremities of normal adults. [Subjects] The subjects of the study were 24 normal adults who were divided into a virtual reality exercise group (VREG, n=12) and a stable surface exercise group (SEG, n=12). [Methods] The exercises of the VREG using the Nintendo Wii Fit and the SEG using a stable surface were conducted three times a week for six weeks. Electromyography was used to measure the muscle activities of the tibialis anterior (TA), medial gastrocnemius (MG), erector spinae (ES), and rectus abdominal (RA) muscles. [Results] VREG showed significant within group differences in TA and MG muscle activities, while the SEG showed a significant difference in the muscle activity of the MG. [Conclusion] Virtual reality exercise using the Nintendo Wii Fit was an effective intervention for the muscle activities of the TA and MG of normal adults.

Effect of Virtual Reality Exercise Using the Nintendo Wii Fit on Muscle Activities of the Trunk and Lower Extremities of Normal Adults

PubMed Central

Park, Jungseo; Lee, Daehee; Lee, Sangyong

2014-01-01

[Purpose] The present study aimed to determine the effect of virtual reality exercise using the Nintendo Wii Fit on the muscle activities of the trunk and lower extremities of normal adults. [Subjects] The subjects of the study were 24 normal adults who were divided into a virtual reality exercise group (VREG, n=12) and a stable surface exercise group (SEG, n=12). [Methods] The exercises of the VREG using the Nintendo Wii Fit and the SEG using a stable surface were conducted three times a week for six weeks. Electromyography was used to measure the muscle activities of the tibialis anterior (TA), medial gastrocnemius (MG), erector spinae (ES), and rectus abdominal (RA) muscles. [Results] VREG showed significant within group differences in TA and MG muscle activities, while the SEG showed a significant difference in the muscle activity of the MG. [Conclusion] Virtual reality exercise using the Nintendo Wii Fit was an effective intervention for the muscle activities of the TA and MG of normal adults. PMID:24648647

Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy.

PubMed Central

Vachon, P H; Xu, H; Liu, L; Loechel, F; Hayashi, Y; Arahata, K; Reed, J C; Wewer, U M; Engvall, E

1997-01-01

Mutations in genes coding for dystrophin, for alpha, beta, gamma, and delta-sarcoglycans, or for the alpha2 chain of the basement membrane component merosin (laminin-2/4) cause various forms of muscular dystrophy. Analyses of integrins showed an abnormal expression and localization of alpha7beta1 isoforms in myofibers of merosin-deficient human patients and mice, but not in dystrophin-deficient or sarcoglycan-deficient humans and animals. It was shown previously that skeletal muscle fibers require merosin for survival and function (Vachon, P.H., F. Loechel, H. Xu, U.M. Wewer, and E. Engvall. 1996. J. Cell Biol. 134:1483-1497). Correction of merosin deficiency in vitro through cell transfection with the merosin alpha2 chain restored the normal localization of alpha7beta1D integrins as well as myotube survival. Overexpression of the apoptosis-suppressing molecule Bcl-2 also promoted the survival of merosin-deficient myotubes, but did not restore a normal expression of alpha7beta1D integrins. Blocking of beta1 integrins in normal myotubes induced apoptosis and severely reduced their survival. These findings (a) identify alpha7beta1D integrins as the de facto receptors for merosin in skeletal muscle; (b) indicate a merosin dependence for the accurate expression and membrane localization of alpha7beta1D integrins in myofibers; (c) provide a molecular basis for the critical role of merosin in myofiber survival; and (d) add new insights to the pathogenesis of neuromuscular disorders. PMID:9312189

Developing Normal Turns-Amplitude Clouds for Upper and Lower Limbs.

PubMed

Jabre, Joe F; Nikolayev, Sergey G; Babayev, Michael B; Chindilov, Denis V; Muravyov, Anatoly Y

2016-10-01

Turns and amplitude analysis (T&A) is a frequently used method for automatic EMG interference pattern analysis. The T&A normal values have only been developed for a limited number of muscles. Our objective was to obtain normal T&A clouds for upper and lower extremity muscles for which no normal values exist in the literature. The T&A normative data using concentric needle electrodes were obtained from 68 men and 56 women aged 20 to 60 years. Normal upper and lower extremity T&A clouds were obtained and presented in this article. The T&A normal values collected in this study maybe used to detect neurogenic and myopathic abnormalities in men and women at low-to-moderate muscle contractions. The effect of turns-amplitude data obtained at high force level of muscle contraction and its potential to falsely show neurogenic abnormalities are discussed.

Estimating Isometric Tension of Finger Muscle Using Needle EMG Signals and the Twitch Contraction Model

NASA Astrophysics Data System (ADS)

Tachibana, Hideyuki; Suzuki, Takafumi; Mabuchi, Kunihiko

We address an estimation method of isometric muscle tension of fingers, as fundamental research for a neural signal-based prosthesis of fingers. We utilize needle electromyogram (EMG) signals, which have approximately equivalent information to peripheral neural signals. The estimating algorithm comprised two convolution operations. The first convolution is between normal distribution and a spike array, which is detected by needle EMG signals. The convolution estimates the probability density of spike-invoking time in the muscle. In this convolution, we hypothesize that each motor unit in a muscle activates spikes independently based on a same probability density function. The second convolution is between the result of the previous convolution and isometric twitch, viz., the impulse response of the motor unit. The result of the calculation is the sum of all estimated tensions of whole muscle fibers, i.e., muscle tension. We confirmed that there is good correlation between the estimated tension of the muscle and the actual tension, with >0.9 correlation coefficients at 59%, and >0.8 at 89% of all trials.

Impact of placental insufficiency on fetal skeletal muscle growth

PubMed Central

Hay, William W.

2016-01-01

Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal “catch-up” growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID:26994511

Ex vivo pharmacology of surgical samples of the uterosacral ligament. Part I: Effects of carbachol and oxytocin on smooth muscle.

PubMed

Drews, Ulrich; Renz, Matthias; Busch, Christian; Reisenauer, Christl

2012-11-01

In a previous study we observed impaired smooth muscle in the uterosacral ligament (USL) of patients with pelvic organ prolapse. The aims of the study were to describe the method of the novel microperfusion system and to determine normal function and pharmacology of smooth muscle in the USL. Samples from the USL were obtained during hysterectomy for benign reasons. Small stretches of connective tissue were mounted in a perfusion chamber under the stereomicroscope. Isotonic contractions of smooth muscle were monitored by digital time-lapse video and quantified by image processing. Constant perfusion with carbachol elicited tonic and pulse stimulation with carbachol and oxytocin rhythmic contractions of smooth muscle in the ground reticulum. Under constant perfusion with relaxin the tonic contraction after carbachol was abolished. With the novel microperfusion system, isotonic contractions of smooth muscle in the USL can be recorded and quantified in the tissue microenvironment on the microscopic level. The USL smooth muscle is cholinergic, stimulated by oxytocin and modulated by relaxin. Copyright © 2012 Wiley Periodicals, Inc.

Green tea extract attenuates muscle loss and improves muscle function during disuse, but fails to improve muscle recovery following unloading in aged rats

PubMed Central

Bennett, Brian T.; Wilson, Joseph C.; Sperringer, Justin; Mohamed, Junaith S.; Edens, Neile K.; Pereira, Suzette L.

2014-01-01

In this study we tested the hypothesis that green tea extract (GTE) would improve muscle recovery after reloading following disuse. Aged (32 mo) Fischer 344 Brown Norway rats were randomly assigned to receive either 14 days of hindlimb suspension (HLS) or 14 days of HLS followed by normal ambulatory function for 14 days (recovery). Additional animals served as cage controls. The rats were given GTE (50 mg/kg body wt) or water (vehicle) by gavage 7 days before and throughout the experimental periods. Compared with vehicle treatment, GTE significantly attenuated the loss of hindlimb plantaris muscle mass (−24.8% vs. −10.7%, P < 0.05) and tetanic force (−43.7% vs. −25.9%, P <0.05) during HLS. Although GTE failed to further improve recovery of muscle function or mass compared with vehicle treatment, animals given green tea via gavage maintained the lower losses of muscle mass that were found during HLS (−25.2% vs. −16.0%, P < 0.05) and force (−45.7 vs. −34.4%, P < 0.05) after the reloading periods. In addition, compared with vehicle treatment, GTE attenuated muscle fiber cross-sectional area loss in both plantaris (−39.9% vs. −23.9%, P < 0.05) and soleus (−37.2% vs. −17.6%) muscles after HLS. This green tea-induced difference was not transient but was maintained over the reloading period for plantaris (−45.6% vs. −21.5%, P <0.05) and soleus muscle fiber cross-sectional area (−38.7% vs. −10.9%, P <0.05). GTE increased satellite cell proliferation and differentiation in plantaris and soleus muscles during recovery from HLS compared with vehicle-treated muscles and decreased oxidative stress and abundance of the Bcl-2-associated X protein (Bax), yet this did not further improve muscle recovery in reloaded muscles. These data suggest that muscle recovery following disuse in aging is complex. Although satellite cell proliferation and differentiation are critical for muscle repair to occur, green tea-induced changes in satellite cell number is by itself insufficient to improve muscle recovery following a period of atrophy in old rats. PMID:25414242

In vivo detection of exercised-induced ultrastructural changes in genetically-altered murine skeletal muscle using polarization-sensitive optical coherence tomography

NASA Astrophysics Data System (ADS)

Boppart, Stephen

2006-02-01

Skeletal muscle fibers are a known source of form birefringence in biological tissue. The birefringence present in skeletal muscle is associated with the ultrastructure of individual sarcomeres, specifically the arrangement of A-bands corresponding to the thick myosin filaments. Certain structural proteins that prevent damage and maintain the structural and functional health of the muscle fiber preserve the organization of the Abands in skeletal muscle. Therefore, the level of birefringence detected can estimate the health of the muscle as well as the damage incurred during exercise. Murine skeletal muscle from both genetically-altered (mdx) and normal (wild-type) specimens were imaged in vivo with a fiber-based PSOCT imaging system to quantitatively determine the level of birefringence present in the tissue before and after exercise. The mdx muscle lacks dystrophin, a structural protein that is mutated in Duchenne muscular dystrophy in humans. Muscle from these mdx mice exhibited a marked decrease in birefringence after exercise, whereas the wild-type muscle was highly birefringent before and after exercise. The quantitative results from this tissue optics study suggest for the first time that there is a distinct relationship between the degree of birefringence detected using PS-OCT and the sarcomeric ultrastructure present within skeletal muscle.

The physiopathologic interplay between stem cells and tissue niche in muscle regeneration and the role of IL-6 on muscle homeostasis and diseases.

PubMed

Forcina, Laura; Miano, Carmen; Musarò, Antonio

2018-06-01

Skeletal muscle is a complex, dynamic tissue characterized by an elevated plasticity. Although the adult muscle is mainly composed of multinucleated fibers with post mitotic nuclei, it retains a remarkable ability to regenerate in response to traumatic events. The regenerative potential of the adult skeletal muscle relies in the activity of satellite cells, mononucleated cells residing within the muscle in intimate association with myofibers. Satellite cells normally remain quiescent in their sublaminar position, sporadically entering the cell cycle to guarantee an efficient cellular turnover, by fusing with pre-existing myofibers, and to maintain the stem cell pool. However, after muscle injury satellite cells undergo an extensive increase of their activity in response to environmental stimuli, thereby participating to the regeneration of a functional muscle tissue. Nevertheless, regeneration is affected in several pathologic conditions and by a wide range of environmental signals that are highly variable, not only through time, but also depending on the physiological or pathological conditions of the musculature. Among these factors, the interleukin-6 (IL-6) plays a critical physiopathologic role on muscle homeostasis and diseases. The basis of muscle regeneration and the impact of IL-6 on the physiopathology of skeletal muscle will be discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

The importance of a normal breathing pattern for an effective abdominal-hollowing maneuver in healthy people: an experimental study.

PubMed

Ha, Sung-min; Kwon, Oh-yun; Kim, Su-jung; Choung, Sung-dae

2014-02-01

A normal breathing pattern while performing the abdominal-hollowing (AH) maneuver or spinal-stabilization exercise is essential for the success of rehabilitation programs and exercises. In previous studies, subjects were given standardized instructions to control the influence of respiration during the AH maneuver. However, the effect of breathing pattern on abdominal-muscle thickness during the AH maneuver has not been investigated. To compare abdominal-muscle thickness in subjects performing the AH maneuver under normal and abnormal breathing-pattern conditions and to investigate the effect of breathing pattern on the preferential contraction ratio (PCR) of the transverse abdominis. Comparative, repeated-measures experimental study. University research laboratory. 16 healthy subjects (8 male, 8 female) from a university population. A real-time ultrasound scanner was used to measure abdominal-muscle thickness during normal and abnormal breathing patterns. A paired t test was used to assess the effect of breathing pattern on abdominal-muscle thickness and PCR. Muscle thickness in the transverse abdominis and internal oblique muscles was significantly greater under the normal breathing pattern than under the abnormal pattern (P < .05). The PCR of the transverse abdominis was significantly higher under the normal breathing pattern compared with the abnormal pattern (P < .05). The results indicate that a normal breathing pattern is essential for performance of an effective AH maneuver. Thus, clinicians should ensure that patients adopt a normal breathing pattern before performing the AH maneuver and monitor transverse abdominis activation during the maneuver.

Spatial differences of cellular origins and in vivo hypoxia modify contractile properties of pulmonary artery smooth muscle cells: lessons for arterial tissue engineering.

PubMed

Hall, S M; Soueid, A; Smith, T; Brown, R A; Haworth, S G; Mudera, V

2007-01-01

Tissue engineering of functional arteries is challenging. Within the pulmonary artery wall, smooth muscle cells (PASMCs) have site-specific developmental and functional phenotypes, reflecting differing contractile roles. The force generated by PASMCs isolated from the inner 25% and outer 50% of the media of intrapulmonary elastic arteries from five normal and eight chronically hypoxic (hypertensive) 14 day-old piglets was quantified in a three-dimensional (3D) collagen construct, using a culture force monitor. Outer medial PASMCs from normal piglets exerted more force (528 +/- 50 dynes) than those of hypoxic piglets (177 +/- 42 dynes; p < 0.01). Force generation by inner medial PASMCs from normal and hypoxic piglets was similar (349 +/- 35 and 239 +/- 60 dynes). In response to agonist (thromboxane) stimulation, all PASMCs from normal and hypoxic piglets contracted, but the increase in force generated by outer and inner hypoxic PASMCs (ranges 13-72 and 14-56 dynes) was less than by normal PASMCs (ranges 27-154 and 34-159 dynes, respectively; p < 0.05 for both). All hypoxic PASMCs were unresponsive to antagonist (sodium nitroprusside) stimulation, all normal PASMCs relaxed (range - 87 to - 494 dynes). Myosin heavy chain expression by both hypoxic PASMC phenotypes was less than normal (p < 0.05 for both), as was the activity of focal adhesion kinase, regulating contraction, in hypoxic inner PASMCs (p < 0.01). Chronic hypoxia resulted in the development of abnormal PASMC phenotypes, which in collagen constructs exhibited a reduction in contractile force and reactivity to agonists. Characterization of the mechanical response of spatially distinct cells and modification of their behaviour by hypoxia is critical for successful tissue engineering of major blood vessels.

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

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

Roberts, B.M.; Frye, G.S.; Ahn, B.

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

The heart of the matter: from guided microtools to 3-D printing and precision genome editing, promising research could lead to new advances in pediatric cardiology.

PubMed

Chandler, David L

2015-01-01

The smooth, powerful muscles of a newborn baby?s heart are pulsing normally, squeezing in and letting go rhythmically as a 3-mm-wide catheter-like tube snakes its way through, entering via an artery and being guided slowly by a surgeon. When it reaches its target?a protruding knot of malformed muscle tissue within a ventricle that has been partly blocking the valve?the tip of the precisely controlled tube whirs into action, with tiny scissor-like rotating blades gently grinding up the excess tissue as those pieces are sucked back into the device, leaving no floating particles that could lead to a blockage elsewhere. The defect is fully removed, and the heart?s function is restored to normal, leaving the child with the prospect of a normal life. The whole minimally invasive process takes place inside a beating heart and would otherwise have required open-heart surgery, with the heart stopped for a cardiopulmonary bypass.

Treatment with Riluzole Restores Normal Control of Soleus and Extensor Digitorum Longus Muscles during Locomotion in Adult Rats after Sciatic Nerve Crush at Birth

PubMed Central

Cabaj, Anna M.; Sławińska, Urszula

2017-01-01

The effects of sciatic nerve crush (SNC) and treatment with Riluzole on muscle activity during unrestrained locomotion were identified in an animal model by analysis of the EMG activity recorded from soleus (Sol) and extensor digitorum longus (EDL) muscles of both hindlimbs; in intact rats (IN) and in groups of rats treated for 14 days with saline (S) or Riluzole (R) after right limb nerve crush at the 1st (1S and 1R) or 2nd (2S and 2R) day after birth. Changes in the locomotor pattern of EMG activity were correlated with the numbers of survived motor units (MUs) identified in investigated muscles. S rats with 2–8 and 10–28 MUs that survived in Sol and EDL muscles respectively showed increases in the duration and duty factor of muscle EMG activity and a loss of correlation between the duty factors of muscle activity, and abnormal flexor-extensor co-activation 3 months after SNC. R rats with 5, 6 (Sol) and 15–29 MUs (EDL) developed almost normal EMG activity of both Sol and control EDL muscles, whereas EDL muscles with SNC showed a lack of recovery. R rats with 8 (Sol) and 23–33 (EDL) MUs developed almost normal EMG activities of all four muscles. A subgroup of S rats with a lack of recovery and R rats with almost complete recovery that had similar number of MUs (8 and 24–28 vs 8 and 23–26), showed that the number of MUs was not the only determinant of treatment effectiveness. The results demonstrated that rats with SNC failed to develop normal muscle activity due to malfunction of neuronal circuits attenuating EDL muscle activity during the stance phase, whereas treatment with Riluzole enabled almost normal EMG activity of Sol and EDL muscles during locomotor movement. PMID:28095499

Treatment with Riluzole Restores Normal Control of Soleus and Extensor Digitorum Longus Muscles during Locomotion in Adult Rats after Sciatic Nerve Crush at Birth.

PubMed

Zmysłowski, Wojciech; Cabaj, Anna M; Sławińska, Urszula

2017-01-01

The effects of sciatic nerve crush (SNC) and treatment with Riluzole on muscle activity during unrestrained locomotion were identified in an animal model by analysis of the EMG activity recorded from soleus (Sol) and extensor digitorum longus (EDL) muscles of both hindlimbs; in intact rats (IN) and in groups of rats treated for 14 days with saline (S) or Riluzole (R) after right limb nerve crush at the 1st (1S and 1R) or 2nd (2S and 2R) day after birth. Changes in the locomotor pattern of EMG activity were correlated with the numbers of survived motor units (MUs) identified in investigated muscles. S rats with 2-8 and 10-28 MUs that survived in Sol and EDL muscles respectively showed increases in the duration and duty factor of muscle EMG activity and a loss of correlation between the duty factors of muscle activity, and abnormal flexor-extensor co-activation 3 months after SNC. R rats with 5, 6 (Sol) and 15-29 MUs (EDL) developed almost normal EMG activity of both Sol and control EDL muscles, whereas EDL muscles with SNC showed a lack of recovery. R rats with 8 (Sol) and 23-33 (EDL) MUs developed almost normal EMG activities of all four muscles. A subgroup of S rats with a lack of recovery and R rats with almost complete recovery that had similar number of MUs (8 and 24-28 vs 8 and 23-26), showed that the number of MUs was not the only determinant of treatment effectiveness. The results demonstrated that rats with SNC failed to develop normal muscle activity due to malfunction of neuronal circuits attenuating EDL muscle activity during the stance phase, whereas treatment with Riluzole enabled almost normal EMG activity of Sol and EDL muscles during locomotor movement.

Pelvic floor muscle exercise by biofeedback and electrical stimulation to reinforce the pelvic floor muscle after normal delivery.

PubMed

Lee, In Sook; Choi, Euy Soon

2006-12-01

This study was conducted to investigate the effectiveness of pelvic floor muscle exercise using biofeedback and electrical stimulation after normal delivery. The subjects of this study were 49 (experimental group: 25, control group: 24) postpartum women who passed 6 weeks after normal delivery without complication of pregnancy, delivery and postpartum. The experimental group was applied to the pelvic muscle enforcement program by biofeedback and electrical stimulation for 30 minutes per session, twice a week for 6 weeks, after then self-exercise of pelvic floor muscle was done 50-60 repetition per session, 3 times a day for 6 weeks. Maximum pressure of pelvic floor muscle contraction (MPPFMC), average pressure of pelvic floor muscle contraction (APPFMC), duration time of pelvic floor muscle contraction (DTPFMC) and the subjective lower urinary symptoms were measured by digital perineometer and Bristol Female Urinary Symptom Questionnaire and compared between two groups prior to trial, at the end of treatment and 6 weeks after treatment. The results of this study indicated that MPPFMC, APPFMC, DTPFMC were significantly increased and subjective lower urinary symptoms were significantly decreased after treatment in the experimental group than in the control group. This study suggested that the pelvic floor muscle exercise using biofeedback and electrical stimulation might be a safer and more effective program for reinforcing pelvic floor muscle after normal delivery.

Granulocyte colony-stimulating factor (G-CSF) positive effects on muscle fiber degeneration and gait recovery after nerve lesion in MDX mice

PubMed Central

Simões, Gustavo F; Benitez, Suzana U; Oliveira, Alexandre L R

2014-01-01

Background G-CSF has been shown to decrease inflammatory processes and to act positively on the process of peripheral nerve regeneration during the course of muscular dystrophy. Aims The aims of this study were to investigate the effects of treatment of G-CSF during sciatic nerve regeneration and histological analysis in the soleus muscle in MDX mice. Methods Six-week-old male MDX mice underwent left sciatic nerve crush and were G-CSF treated at 7 days prior to and 21 days after crush. Ten and twenty-one days after surgery, the mice were euthanized, and the sciatic nerves were processed for immunohistochemistry (anti-p75NTR and anti-neurofilament) and transmission electron microscopy. The soleus muscles were dissected out and processed for H&E staining and subsequent morphologic analysis. Motor function analyses were performed at 7 days prior to and 21 days after sciatic crush using the CatWalk system and the sciatic nerve index. Results Both groups treated with G-CSF showed increased p75NTR and neurofilament expression after sciatic crush. G-CSF treatment decreased the number of degenerated and regenerated muscle fibers, thereby increasing the number of normal muscle fibers. Conclusions The reduction in p75NTR and neurofilament indicates a decreased regenerative capacity in MDX mice following a lesion to a peripheral nerve. The reduction in motor function in the crushed group compared with the control groups may reflect the cycles of muscle degeneration/regeneration that occur postnatally. Thus, G-CSF treatment increases motor function in MDX mice. Nevertheless, the decrease in baseline motor function in these mice is not reversed completely by G-CSF. PMID:25328849

Combined Effects of Brain-Derived Neurotrophic Factor Immobilized Poly-Lactic-Co-Glycolic Acid Membrane with Human Adipose-Derived Stem Cells and Basic Fibroblast Growth Factor Hydrogel on Recovery of Erectile Dysfunction

PubMed Central

Lee, Seung Hwan; Kim, In Gul; Jung, Ae Ryang; Shrestha, Kshitiz Raj; Lee, Jin Ho; Park, Ki Dong; Chung, Byung Ha; Kim, Sae Woong; Kim, Ki Hean

2014-01-01

Erectile dysfunction (ED) is the most frequent long-term problem after radical prostatectomy. We aimed to evaluate whether the use of combination therapy with basic fibroblast growth factor (bFGF)-hydrogel on corpus cavernosum and with adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF)-immobilized poly-lactic-co-glycolic acid (PLGA) membrane on the cavernous nerve (CN) could improve erectile function in a rat model of bilateral cavernous nerve crush injury (BCNI). Rats were randomly divided into five groups (n=15 per group): a normal group (N group), a group receiving saline application after bilateral cavernous nerve crush injury (BCNI), a group undergoing bFGF-hydrogel injection in the corpus cavernosum after BCNI (bFGF), a group receiving ADSC application covered with BDNF-membrane after BCNI (ADSC/BDNF), and a group undergoing coadministration of bFGF-hydrogel injection and BDNF-membrane with ADSCs after BDNF (bFGF+ADSC/BDNF). Four weeks postoperatively, the erectile function was assessed by detecting the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP). Smooth muscle and collagen contents were measured using Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. The protein expression of the α-smooth muscle actin (α-SMA) and the cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by western blot and cGMP assay, respectively. In the bFGF+ADSC/BDNF group, the erectile function was significantly elevated compared with the BCNI and other treated groups and showed a significantly increased smooth muscle/collagen ratio, nNOS content, α-SMA expression, and cGMP level. In particular, there were no statistical differences in the ICP/MAP ratio, smooth muscle/collagen ratio, and α-SMA and cGMP levels between the bFGF+ADSC/BDNF group and normal group. Application of the BDNF-immobilized PLGA membrane with human ADSC into the CN and bFGF-incorporated hydrogel into the corpus carvernosum improved nearly normal erectile function in a rat model of postprostatectomy ED. This result suggests that a combined application of bFGF+ADSC/BDNF might be a promising treatment for postprostatectomy ED. PMID:24673637

EMG normalization method based on grade 3 of manual muscle testing: Within- and between-day reliability of normalization tasks and application to gait analysis.

PubMed

Tabard-Fougère, Anne; Rose-Dulcina, Kevin; Pittet, Vincent; Dayer, Romain; Vuillerme, Nicolas; Armand, Stéphane

2018-02-01

Electromyography (EMG) is an important parameter in Clinical Gait Analysis (CGA), and is generally interpreted with timing of activation. EMG amplitude comparisons between individuals, muscles or days need normalization. There is no consensus on existing methods. The gold standard, maximum voluntary isometric contraction (MVIC), is not adapted to pathological populations because patients are often unable to perform an MVIC. The normalization method inspired by the isometric grade 3 of manual muscle testing (isoMMT3), which is the ability of a muscle to maintain a position against gravity, could be an interesting alternative. The aim of this study was to evaluate the within- and between-day reliability of the isoMMT3 EMG normalizing method during gait compared with the conventional MVIC method. Lower limb muscles EMG (gluteus medius, rectus femoris, tibialis anterior, semitendinosus) were recorded bilaterally in nine healthy participants (five males, aged 29.7±6.2years, BMI 22.7±3.3kgm -2 ) giving a total of 18 independent legs. Three repeated measurements of the isoMMT3 and MVIC exercises were performed with an EMG recording. EMG amplitude of the muscles during gait was normalized by these two methods. This protocol was repeated one week later. Within- and between-day reliability of normalization tasks were similar for isoMMT3 and MVIC methods. Within- and between-day reliability of gait EMG normalized by isoMMT3 was higher than with MVIC normalization. These results indicate that EMG normalization using isoMMT3 is a reliable method with no special equipment needed and will support CGA interpretation. The next step will be to evaluate this method in pathological populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Aerodynamic profiles of women with muscle tension dysphonia/aphonia.

PubMed

Gillespie, Amanda I; Gartner-Schmidt, Jackie; Rubinstein, Elaine N; Abbott, Katherine Verdolini

2013-04-01

In this study, the authors aimed to (a) determine whether phonatory airflows and estimated subglottal pressures (est-Psub) for women with primary muscle tension dysphonia/aphonia (MTD/A) differ from those for healthy speakers; (b) identify different aerodynamic profile patterns within the MTD/A subject group; and (c) determine whether results suggest new understanding of pathogenesis in MTD/A. Retrospective review of aerodynamic data collected from 90 women at the time of primary MTD/A diagnosis. Aerodynamic profiles were significantly different for women with MTD/A as compared with healthy speakers. Five distinct profiles were identified: (a) normal flow, normal est-Psub; (b) high flow, high est-Psub; (c) low flow, normal est-Psub; (d) normal flow, high est-Psub; and (e) high flow, normal est-Psub. This study is the first to identify distinct subgroups of aerodynamic profiles in women with MTD/A and to quantitatively identify a clinical phenomenon sometimes described in association with it-"breath holding"-that is shown by low airflow with normal est-Psub. Results were consistent with clinical claims that diverse respiratory and laryngeal functions may underlie phonatory patterns associated with MTD/A. One potential mechanism, based in psychobiological theory, is introduced to explain some of the variability in aerodynamic profiles of women with MTD/A.

The expression of β3-adrenoceptors and their function in the human prostate.

PubMed

Suzuki, Takahisa; Otsuka, Atsushi; Matsumoto, Rikiya; Furuse, Hiroshi; Ozono, Seiichiro

2016-02-01

Little is known about β3-adrenoceptor (AR) expression and function in human prostate. We examined the expression and distribution of β-AR subtypes in normal prostate and benign prostatic hyperplasia (BPH) tissues, and investigated which selective β-AR subtype agonist was most involved in the relaxation of isolated human prostate strips. Messenger RNA (mRNA) expression for β1-, β2-, and β3 -ARs was investigated using reverse transcriptase-polymerase chain reactions (RT-PCR). Quantitative analysis of mRNA expression of β-AR subtypes between normal prostate and BPH tissues was performed using quantitative RT-PCR (qPCR). Distributions were examined by immunohistochemistry (IHC). Strips of human normal prostate or BPH were suspended in organ baths and exposed to isoproterenol, dobutamine, procaterol, and TRK-380 to investigate their relaxant effects on KCl-induced contractions, and their inhibitory effects on electrical field stimulation (EFS)-induced contractions. We confirmed the presence of mRNA for β1-, β2-, and β3-ARs both in normal prostate and in BPH tissues. For β3-AR, mRNA expression in BPH tissues was significantly higher than in normal prostate tissues, but there was no significant difference in β1- and β2-AR expression between normal and BPH tissues. IHC revealed differences in staining intensity between smooth muscle cells and glandular cells, with different proportions for different β-AR subtypes. Staining of β3-AR was particularly intense in smooth muscle cells as opposed to glandular cells. Isoproterenol and TRK-380 significantly decreased the tone of KCl-induced contractions of the normal prostate strips. The rank order of relaxant effects was isoproterenol > TRK-380 > procaterol > dobutamine. All selective β-AR agonists significantly decreased the amplitude of EFS-induced contractions of the normal prostate strips. The rank order of inhibitory effects was isoproterenol > dobutamine >TRK-380 > procaterol. In BPH strips, all selective β-AR agonists showed no significant relaxant or inhibitory effects on KCl- or EFS-induced contractions. β3 -AR is abundant in human prostate smooth muscle, whose relaxation is mediated by β1- and β3-AR stimulation. β3-AR agonists may have clinical use in the treatment of male non-BPH patients or neurogenic bladder patients with voiding dysfunction. © 2015 Wiley Periodicals, Inc.

Multibody system of the upper limb including a reverse shoulder prosthesis.

PubMed

Quental, C; Folgado, J; Ambrósio, J; Monteiro, J

2013-11-01

The reverse shoulder replacement, recommended for the treatment of several shoulder pathologies such as cuff tear arthropathy and fractures in elderly people, changes the biomechanics of the shoulder when compared to the normal anatomy. Although several musculoskeletal models of the upper limb have been presented to study the shoulder joint, only a few of them focus on the biomechanics of the reverse shoulder. This work presents a biomechanical model of the upper limb, including a reverse shoulder prosthesis, to evaluate the impact of the variation of the joint geometry and position on the biomechanical function of the shoulder. The biomechanical model of the reverse shoulder is based on a musculoskeletal model of the upper limb, which is modified to account for the properties of the DELTA® reverse prosthesis. Considering two biomechanical models, which simulate the anatomical and reverse shoulder joints, the changes in muscle lengths, muscle moment arms, and muscle and joint reaction forces are evaluated. The muscle force sharing problem is solved for motions of unloaded abduction in the coronal plane and unloaded anterior flexion in the sagittal plane, acquired using video-imaging, through the minimization of an objective function related to muscle metabolic energy consumption. After the replacement of the shoulder joint, significant changes in the length of the pectoralis major, latissimus dorsi, deltoid, teres major, teres minor, coracobrachialis, and biceps brachii muscles are observed for a reference position considered for the upper limb. The shortening of the teres major and teres minor is the most critical since they become unable to produce active force in this position. Substantial changes of muscle moment arms are also observed, which are consistent with the literature. As expected, there is a significant increase of the deltoid moment arms and more fibers are able to elevate the arm. The solutions to the muscle force sharing problem support the biomechanical advantages attributed to the reverse shoulder design and show an increase in activity from the deltoid, teres minor, and coracobrachialis muscles. The glenohumeral joint reaction forces estimated for the reverse shoulder are up to 15% lower than those in the normal shoulder anatomy. The data presented here complements previous publications, which, all together, allow researchers to build a biomechanical model of the upper limb including a reverse shoulder prosthesis.

Redox Control of Skeletal Muscle Regeneration.

PubMed

Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane; Chazaud, Bénédicte; Mounier, Rémi

2017-08-10

Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.

Redox Control of Skeletal Muscle Regeneration

PubMed Central

Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane

2017-01-01

Abstract Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276–310. PMID:28027662

Handgrip Strength Related to Long-Term Electromyography: Application for Assessing Functional Decline in Parkinson Disease.

PubMed

Jones, Gareth R; Roland, Kaitlyn P; Neubauer, Noelannah A; Jakobi, Jennifer M

2017-02-01

To determine which clinical measures of physical function (ie, gait, balance, and grip strength) best represent long-term electromyography in persons with Parkinson disease (PD) compared with those without PD. Cross-sectional study. Local community. A sample (N=37) of men and women with PD (n=23) and those without PD (n=14), living independently at home, older than 50 years of age, from the local community. Not applicable. Measures of gait, balance, and grip strength were completed, and electromyography was examined in biceps brachii, triceps brachii, vastus lateralis, and biceps femoris during a 6.5-hour day. Muscle activity was quantified through burst in electromyography (>2% of the normalized maximum voluntary exertion with a continuous activity period of >0.1s). Stepwise multiple regression models were used to determine the proportion of variance in burst characteristics explained by clinical measures of physical function in PD. Grip strength was the best predictor of muscle activity in persons with PD (R 2 =.17-.33; P<.04), whereas gait characteristics explained muscle activity in healthy controls (R 2 =.40-.82; P<.04). Grip strength could serve as an effective clinical assessment tool to determine changes in muscle activity, which is a precursor to functional loss in persons with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training.

PubMed

Griffiths, Derek; Clarkson, Becky; Tadic, Stasa D; Resnick, Neil M

2015-09-01

Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement in urge urinary incontinence induced by training while prefrontal deactivation may be a mechanism contributing to the success of training. In nonresponders the latter mechanism is unavailable, which may explain why another form of therapy is required. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A Multidisciplinary Evaluation of the Effectiveness of Cyclosporine A in Dystrophic Mdx Mice

PubMed Central

De Luca, Annamaria; Nico, Beatrice; Liantonio, Antonella; Paola Didonna, Maria; Fraysse, Bodvael; Pierno, Sabata; Burdi, Rosa; Mangieri, Domenica; Rolland, Jean-François; Camerino, Claudia; Zallone, Alberta; Confalonieri, Paolo; Andreetta, Francesca; Arnoldi, Elisa; Courdier-Fruh, Isabelle; Magyar, Josef P.; Frigeri, Antonio; Pisoni, Michela; Svelto, Maria; Conte-Camerino, Diana

2005-01-01

Chronic inflammation is a secondary reaction of Duchenne muscular dystrophy and may contribute to disease progression. To examine whether immunosuppressant therapies could benefit dystrophic patients, we analyzed the effects of cyclosporine A (CsA) on a dystrophic mouse model. Mdx mice were treated with 10 mg/kg of CsA for 4 to 8 weeks throughout a period of exercise on treadmill, a protocol that worsens the dystrophic condition. The CsA treatment fully prevented the 60% drop of forelimb strength induced by exercise. A significant amelioration (P < 0.05) was observed in histological profile of CsA-treated gastrocnemius muscle with reductions of nonmuscle area (20%), centronucleated fibers (12%), and degenerating area (50%) compared to untreated exercised mdx mice. Consequently, the percentage of normal fibers increased from 26 to 35% in CsA-treated mice. Decreases in creatine kinase and markers of fibrosis were also observed. By electrophysiological recordings ex vivo, we found that CsA counteracted the decrease in chloride conductance (gCl), a functional index of degeneration in diaphragm and extensor digitorum longus muscle fibers. However, electrophysiology and fura-2 calcium imaging did not show any amelioration of calcium homeostasis in extensor digitorum longus muscle fibers. No significant effect was observed on utrophin levels in diaphragm muscle. Our data show that the CsA treatment significantly normalized many functional, histological, and biochemical endpoints by acting on events that are independent or downstream of calcium homeostasis. The beneficial effect of CsA may involve different targets, reinforcing the usefulness of immunosuppressant drugs in muscular dystrophy. PMID:15681831

[A case of chronic multifocal myositis].

PubMed

Maruyama, T; Kondo, K; Tabata, K; Yanagisawa, N

1992-11-01

A 61-year-old civil engineer began to have slowly progressive muscle atrophy in the right shoulder and the left arm at 56 years of age. Muscle wasting became manifest in the left thigh at 59 years and in the right thigh at 60 years. He had mild difficulty in climbing and descending stairs. On examination, although he had notable muscle atrophy in the right trapezius and proximal muscles in the upper and lower extremities, his muscle strength was relatively well preserved. The muscle atrophy was asymmetrical; the right periscapular region and the left upper and lower extremities were more markedly atrophic. In addition, multiple foci of the striking muscle atrophy were noted in the upper trunk and the proximal limb muscles. Fasciculation was not present. Deep tendon reflexes were normal with no pathologic reflexes. Except for a moderately elevated serum creatine kinase level of 709 Ul/l (normal 40-170) and mildly elevated serum myoglobin level of 100 ng/ml (normal < 60), no laboratory tests showed abnormal values suggesting an inflammatory process. Motor and sensory nerve conduction velocities were within normal limits. Electromyography disclosed myopathic and neuropathic changes. Computed tomography (CT) of skeletal muscles showed asymmetrical muscle atrophy and patchy low-density foci. In biopsied left quadriceps and right gastrocnemius muscles which showed partially low density on CT, there was marked variation in muscle fiber size, with necrotic and regenerating fibers, an increased number of centrally placed nuclei, and interstitial fibrosis. There were numerous foci of mononuclear inflammatory cellular infiltration, especially around the blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigation of electroacupuncture and manual acupuncture on carnitine and glutathione in muscle.

PubMed

Toda, Shizuo

2011-01-01

Electroacupuncture (EA) and manual acupuncture (MA) have therapeutic effects on muscle fatigue in muscle disease. The deficiencies of carnitine and glutathione induce muscle fatigue. This report investigated the effects of EA and MA on carnitine and glutathione in muscle. After the mice of EA group were fixed in the animal cage, right Zusanli (ST36) and Jiexi (ST41) were acupunctured and stimulated with uniform reinforcing and reducing method by twirling the acupuncture needle for 15 min. And then, the needle handles were connected to an electric stimulator for stimulating the acupoint with dense-sparse waves. After the mice of MA group were fixed in an animal cage, right ST36 and ST41 were acupunctured and allowed for 15 min. The mice of normal control group were not acupunctured and stimulated for 15 min. The mice of all groups were killed for collecting muscle tissue 1 h after the final treatment. Carnitine and glutathione in homogenate of muscle tissue were determined with carnitine (Kainos Laboratories Co., Tokyo, Japan) and glutathione assay kit (Dojin Chemicals Co., Kumamoto, Japan). Carnitine level in muscle tissue of MA group was significantly higher than those of EA group and normal control group. Carnitine level in muscle tissue of EA group was not significantly different from that of normal control group. Glutathione levels in muscle tissue of EA group and MA group were significantly higher than that of normal control group. This report presented that carnitine in muscle is increased by MA, and not increased by EA, and that glutathione in muscle is increased by EA and MA.

Investigation of Electroacupuncture and Manual Acupuncture on Carnitine and Glutathione in Muscle

PubMed Central

Toda, Shizuo

2011-01-01

Electroacupuncture (EA) and manual acupuncture (MA) have therapeutic effects on muscle fatigue in muscle disease. The deficiencies of carnitine and glutathione induce muscle fatigue. This report investigated the effects of EA and MA on carnitine and glutathione in muscle. After the mice of EA group were fixed in the animal cage, right Zusanli (ST36) and Jiexi (ST41) were acupunctured and stimulated with uniform reinforcing and reducing method by twirling the acupuncture needle for 15 min. And then, the needle handles were connected to an electric stimulator for stimulating the acupoint with dense-sparse waves. After the mice of MA group were fixed in an animal cage, right ST36 and ST41 were acupunctured and allowed for 15 min. The mice of normal control group were not acupunctured and stimulated for 15 min. The mice of all groups were killed for collecting muscle tissue 1 h after the final treatment. Carnitine and glutathione in homogenate of muscle tissue were determined with carnitine (Kainos Laboratories Co., Tokyo, Japan) and glutathione assay kit (Dojin Chemicals Co., Kumamoto, Japan). Carnitine level in muscle tissue of MA group was significantly higher than those of EA group and normal control group. Carnitine level in muscle tissue of EA group was not significantly different from that of normal control group. Glutathione levels in muscle tissue of EA group and MA group were significantly higher than that of normal control group. This report presented that carnitine in muscle is increased by MA, and not increased by EA, and that glutathione in muscle is increased by EA and MA. PMID:19592478

Etiology and Progression of Acute Muscle Tension Related Low Back Pain Occurring During Sustained Activity Including Combat Training Exercises

DTIC Science & Technology

1992-01-31

pattern of paraspinal muscle contraction , and (3) onset of low back pain. (b) That patterns of muscle tension recorded throughout the normal day in the...intensity and duration of activity being performed, (b) the pattern of paraspinal muscle contraction , and (c) onset of low back pain. (2) To determine whether... muscle contraction , and activity by performing continuous recordings of these factors among groups of low back pain subjects in their normal

Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs.

PubMed

Barreto, Rafael; Waning, David L; Gao, Hongyu; Liu, Yunlong; Zimmers, Teresa A; Bonetto, Andrea

2016-07-12

Cachexia affects the majority of cancer patients, with currently no effective treatments. Cachexia is defined by increased fatigue and loss of muscle function resulting from muscle and fat depletion. Previous studies suggest that chemotherapy may contribute to cachexia, although the causes responsible for this association are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapy-related effects on body composition and muscle function. Normal mice were administered chemotherapy regimens used for the treatment of colorectal cancer, such as Folfox (5-FU, leucovorin, oxaliplatin) or Folfiri (5-FU, leucovorin, irinotecan) for 5 weeks. The animals that received chemotherapy exhibited concurrent loss of muscle mass and muscle weakness. Consistently with previous findings, muscle wasting was associated with up-regulation of ERK1/2 and p38 MAPKs. No changes in ubiquitin-dependent proteolysis or in the expression of TGFβ-family members were detected. Further, marked decreases in mitochondrial content, associated with abnormalities at the sarcomeric level and with increase in the number of glycolytic fibers were observed in the muscle of mice receiving chemotherapy. Finally, ACVR2B/Fc or PD98059 prevented Folfiri-associated ERK1/2 activation and myofiber atrophy in C2C12 cultures. Our findings demonstrate that chemotherapy promotes MAPK-dependent muscle atrophy as well as mitochondrial depletion and alterations of the sarcomeric units. Therefore, these findings suggest that chemotherapy potentially plays a causative role in the occurrence of muscle loss and weakness. Moreover, the present observations provide a strong rationale for testing ACVR2B/Fc or MEK1 inhibitors in combination with anticancer drugs as novel strategies aimed at preventing chemotherapy-associated muscle atrophy.

Orai1 enhances muscle endurance by promoting fatigue-resistant type I fiber content but not through acute store-operated Ca2+ entry

PubMed Central

Carrell, Ellie M.; Coppola, Aundrea R.; McBride, Helen J.; Dirksen, Robert T.

2016-01-01

Orai1 is a transmembrane protein that forms homomeric, calcium-selective channels activated by stromal interaction molecule 1 (STIM1) after depletion of intracellular calcium stores. In adult skeletal muscle, depletion of sarcoplasmic reticulum calcium activates STIM1/Orai1-dependent store-operated calcium entry. Here, we used constitutive and inducible muscle-specific Orai1-knockout (KO) mice to determine the acute and long-term developmental effects of Orai1 ablation on muscle structure and function. Skeletal muscles from constitutive, muscle-specific Orai-KO mice exhibited normal postnatal growth and fiber type differentiation. However, a significant reduction in fiber cross-sectional area occurred by 3 mo of age, with the most profound reduction observed in oxidative, fatigue-resistant fiber types. Soleus muscles of constitutive Orai-KO mice exhibited a reduction in unique type I fibers, concomitant with an increase in hybrid fibers expressing both type I and type IIA myosins. Additionally, ex vivo force measurements showed reduced maximal specific force and in vivo exercise assays revealed reduced endurance in constitutive muscle-specific Orai-KO mice. Using tamoxifen-inducible, muscle-specific Orai-KO mice, these functional deficits were found to be the result of the delayed fiber changes resulting from an early developmental loss of Orai1 and not the result of an acute loss of Orai1-dependent store-operated calcium entry.—Carrell, E. M., Coppola, A. R., McBride, H. J., Dirksen, R. T. Orai1 enhances muscle endurance by promoting fatigue-resistant type I fiber content but not through acute store-operated Ca2+ entry. PMID:27587568

Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs

PubMed Central

Barreto, Rafael; Waning, David L.; Gao, Hongyu; Liu, Yunlong; Zimmers, Teresa A.; Bonetto, Andrea

2016-01-01

Cachexia affects the majority of cancer patients, with currently no effective treatments. Cachexia is defined by increased fatigue and loss of muscle function resulting from muscle and fat depletion. Previous studies suggest that chemotherapy may contribute to cachexia, although the causes responsible for this association are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapy-related effects on body composition and muscle function. Normal mice were administered chemotherapy regimens used for the treatment of colorectal cancer, such as Folfox (5-FU, leucovorin, oxaliplatin) or Folfiri (5-FU, leucovorin, irinotecan) for 5 weeks. The animals that received chemotherapy exhibited concurrent loss of muscle mass and muscle weakness. Consistently with previous findings, muscle wasting was associated with up-regulation of ERK1/2 and p38 MAPKs. No changes in ubiquitin-dependent proteolysis or in the expression of TGFβ-family members were detected. Further, marked decreases in mitochondrial content, associated with abnormalities at the sarcomeric level and with increase in the number of glycolytic fibers were observed in the muscle of mice receiving chemotherapy. Finally, ACVR2B/Fc or PD98059 prevented Folfiri-associated ERK1/2 activation and myofiber atrophy in C2C12 cultures. Our findings demonstrate that chemotherapy promotes MAPK-dependent muscle atrophy as well as mitochondrial depletion and alterations of the sarcomeric units. Therefore, these findings suggest that chemotherapy potentially plays a causative role in the occurrence of muscle loss and weakness. Moreover, the present observations provide a strong rationale for testing ACVR2B/Fc or MEK1 inhibitors in combination with anticancer drugs as novel strategies aimed at preventing chemotherapy-associated muscle atrophy. PMID:27259276

Is dynamic two-dimensional anal ultrasonography useful in the assessment of anismus? A comparison with manometry.

PubMed

Murad-Regadas, Sthela Maria; Regadas, Francisco Sérgio P; Barreto, Rosilma Gorete Lima; Rodrigues, Lusmar Veras; Fernandes, Graziela Olivia da Silva; Lima, Doryane Maria dos Reis

2010-01-01

Anismus is a prevalent functional cause of outlet delay. It is characterized by symptoms of obstructed defecation associated with paradoxical contraction of the pelvic floor muscles. To evaluate the ability of two dimensional anal ultrasonography to identify anismus patients with paradoxical contraction or normal relaxation, comparing findings with manometric measurements. Forty-nine women presenting with outlet delay and a mean validated Wexner constipation score of 13.5 were included in a prospective study. Following screening with anal manometry, the patients were assigned to one of two groups: G-I -with normal relaxation and G-II -patients with anismus. Dynamic anorectal ultrasonography was used to quantifier the movement of the puborectalis muscle and to measure changes in the angle between two converging lines drawn from the 3 o'clock and the 9 o'clock positions of the endoprobe circumference to the internal border of the puborectalis muscle. The angle decreases during straining in patients with normal relaxation, but increases in patients with anismus. The agreement between the two techniques was verified with the Kappa index. In manometry, during straining the anal canal pressure decreased by 41.3% in G-I and increased by 168.6% in G-II, indicating a diagnosis of anismus for the second group. In US, during straining, the angle produced by the movement of the puborectalis muscle decreased from 63 ± 1.31 to 58 ± 1.509 degrees (P = 0.0135) in 23 of the 30 patients in G-I, indicating normal relaxation, and increased from 66 ± 0.972 to 72 ± 0.897 degrees (P = 0.0001) in 16 of the 19 patients in G-II, indicating anismus. The index of agreement between manometry and two dimensional anal ultrasonography was moderate: 77% (23/30) for G-I and 84% (16/19) for G-II. Two-dimensional dynamic anal ultrasonography showed similar results previously suggested by anal manometry at identifying patients with normal relaxation or paradoxical contraction.

Does long-term passive stretching alter muscle-tendon unit mechanics in children with spastic cerebral palsy?

PubMed

Theis, Nicola; Korff, Thomas; Mohagheghi, Amir A

2015-12-01

Cerebral palsy causes motor impairments during development and many children may experience excessive neural and mechanical muscle stiffness. The clinical assumption is that excessive stiffness is thought to be one of the main reasons for functional impairments in cerebral palsy. As such, passive stretching is widely used to reduce stiffness, with a view to improving function. However, current research evidence on passive stretching in cerebral palsy is not adequate to support or refute the effectiveness of stretching as a management strategy to reduce stiffness and/or improve function. The purpose was to identify the effect of six weeks passive ankle stretching on muscle-tendon unit parameters in children with spastic cerebral palsy. Thirteen children (8-14 y) with quadriplegic/diplegic cerebral palsy were randomly assigned to either an experimental group (n=7) or a control group (n=6). The experimental group underwent an additional six weeks of passive ankle dorsiflexion stretching for 15 min (per leg), four days per week, whilst the control group continued with their normal routine, which was similar for the two groups. Measures of muscle and tendon stiffness, strain and resting length were acquired pre- and post-intervention. The experimental group demonstrated a 3° increase in maximum ankle dorsiflexion. This was accompanied by a 13% reduction in triceps surae muscle stiffness, with no change in tendon stiffness. Additionally, there was an increase in fascicle strain with no changes in resting length, suggesting muscle stiffness reductions were a result of alterations in intra/extra-muscular connective tissue. The results demonstrate that stretching can reduce muscle stiffness by altering fascicle strain but not resting fascicle length. Copyright © 2015 Elsevier Ltd. All rights reserved.

Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice.

PubMed

Bal, Naresh C; Singh, Sushant; Reis, Felipe C G; Maurya, Santosh K; Pani, Sunil; Rowland, Leslie A; Periasamy, Muthu

2017-10-06

Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) ( i.e. uncoupling protein 1 (UCP1)-based) and skeletal muscle ( i.e. sarcolipin (SLN)-based) thermogenesis processes play important roles in temperature homeostasis, but their relative contributions differ from small to large mammals. In this study, we investigated the functional interplay between skeletal muscle- and BAT-based thermogenesis under mild versus severe cold adaptation by employing UCP1 -/- and SLN -/- mice. Interestingly, adaptation of SLN -/- mice to mild cold conditions (16 °C) significantly increased UCP1 expression, suggesting increased reliance on BAT-based thermogenesis. This was also evident from structural alterations in BAT morphology, including mitochondrial architecture, increased expression of electron transport chain proteins, and depletion of fat droplets. Similarly, UCP1 -/- mice adapted to mild cold up-regulated muscle-based thermogenesis, indicated by increases in muscle succinate dehydrogenase activity, SLN expression, mitochondrial content, and neovascularization, compared with WT mice. These results further confirm that SLN-based thermogenesis is a key player in muscle non-shivering thermogenesis (NST) and can compensate for loss of BAT activity. We also present evidence that the increased reliance on BAT-based NST depends on increased autonomic input, as indicated by abundant levels of tyrosine hydroxylase and neuropeptide Y. Our findings demonstrate that both BAT and muscle-based NST are equally recruited during mild and severe cold adaptation and that loss of heat production from one thermogenic pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic processes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles.

PubMed

Nesteruk, Monika; Hennig, Ewa E; Mikula, Michal; Karczmarski, Jakub; Dzwonek, Artur; Goryca, Krzysztof; Rubel, Tymon; Paziewska, Agnieszka; Woszczynski, Marek; Ledwon, Joanna; Dabrowska, Michalina; Dadlez, Michal; Ostrowski, Jerzy

2014-03-01

Although mitochondrial dysfunction is implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are not well established. We performed mitochondrial quantitative proteomic and whole transcriptome analysis followed by functional annotations within liver and skeletal muscles, using fasted and non-fasted 16- and 48-week-old high-fat diet (HFD)-fed and normal diet-fed (control group) wild-type C56BL/6J mice, and hyperphagic ob/ob and db/db obese mice. Our study identified 1,675 and 704 mitochondria-associated proteins with at least two peptides in liver and muscle, respectively. Of these, 221 liver and 44 muscle proteins were differentially expressed (adjusted p values ≤ 0.05) between control and all obese mice, while overnight fasting altered expression of 107 liver and 35 muscle proteins. In the liver, we distinguished a network of 27 proteins exhibiting opposite direction of expression changes in HFD-fed and hyperphagic mice when compared to control. The network centered on cytochromes P450 3a11 (Cyp3a11) and 4a14 (Cyp4a14), and fructose-bisphosphate aldolase B (Aldob) proteins which bridged proteins cluster involved in Metabolism of xenobiotics with proteins engaged in Fatty acid metabolism and PPAR signaling pathways. Functional annotations revealed that most of the hepatic molecular alterations, which characterized both obesity and fasting, related to different aspects of energy metabolism (such as Fatty acid metabolism, Peroxisome, and PPAR signaling); however, only a limited number of functional annotations could be selected from skeletal muscle data sets. Thus, our comprehensive molecular overview revealed that both obesity and fasting states induce more pronounced mitochondrial proteome changes in the liver than in the muscles.

Muscle response to leg lengthening during distraction osteogenesis.

PubMed

Thorey, Fritz; Bruenger, Jens; Windhagen, Henning; Witte, Frank

2009-04-01

Continuous lengthening of intact muscles during distraction osteogenesis leads to an increase of sarcomeres and enhances the regeneration of tendons and blood vessels. A high distraction rate leads to an excessive leg and muscle lengthening and might cause damages of muscle fibers with fibrosis, necrosis, and muscle weakness. Complications like muscle contractures or atrophy after postoperative immobilization emphazize the importance of muscles and their function in the clinical outcome. In an animal model of distraction osteogenesis, 18 sheep were operated with an external fixator followed by 4 days latency, 21 days distraction (1.25 mm per day) and 51 days consolidation. The anatomical location (gastrocnemius, peroneus tertius, and first flexor digitorum longus muscle), dimension and occurrence of muscular defects were characterized histologically. The callus formation and leg axis was monitored by weekly X-rays. Additionally, serum creatine kinase was analyzed during a distraction and consolidation period. Significant signs of muscle lesions in all three observed muscles can be found postoperatively, whereas normal callus formation and regular leg axis was observed radiologically. The peroneus tertius and first flexor digitorum longus muscles were found to have significantly more signs of fibrosis, inflammatory, and necrosis. Creatine kinase showed two peaks: 4 and 39 days postoperative as an indication of muscle damage and regeneration. The study implicates that muscle damages should be considered when a long-distance distraction osteogenesis is planned. The surgeon should consider these muscle responses and individually discuss a two-stage treatment or additional muscle tendon releases to minimize the risk of muscle damages.

Conditional Loss of Pten in Myogenic Progenitors Leads to Postnatal Skeletal Muscle Hypertrophy but Age-Dependent Exhaustion of Satellite Cells.

PubMed

Yue, Feng; Bi, Pengpeng; Wang, Chao; Li, Jie; Liu, Xiaoqi; Kuang, Shihuan

2016-11-22

Skeletal muscle stem cells (satellite cells [SCs]) are normally maintained in a quiescent (G 0 ) state. Muscle injury not only activates SCs locally, but also alerts SCs in distant uninjured muscles via circulating factors. The resulting G Alert SCs are adapted to regenerative cues and regenerate injured muscles more efficiently, but whether they provide any long-term benefits to SCs is unknown. Here, we report that embryonic myogenic progenitors lacking the phosphatase and tensin homolog (Pten) exhibit enhanced proliferation and differentiation, resulting in muscle hypertrophy but fewer SCs in adult muscles. Interestingly, Pten null SCs are predominantly in the G Alert state, even in the absence of an injury. The G Alert SCs are deficient in self-renewal and subjected to accelerated depletion during regeneration and aging and fail to repair muscle injury in old mice. Our findings demonstrate a key requirement of Pten in G 0 entry of SCs and provide functional evidence that prolonged G Alert leads to stem cell depletion and regenerative failure. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Effects of multidimensional pelvic floor muscle training in healthy young women.

PubMed

Talasz, Helena; Kalchschmid, Elisabeth; Kofler, Markus; Lechleitner, Monika

2012-03-01

Cross-sectional and interventional study to assess pelvic floor muscle (PFM) function in healthy young nulliparous women and to determine the effects of a 3-month PFM training program with emphasis on co-contraction of PFM and anterolateral abdominal muscles and on correctly performed coughing patterns. PFM function was assessed by digital vaginal palpation in 40 volunteers and graded according to the 6-point Oxford grading scale. The PFM training program was comprised theoretical instruction, as well as verbal feedback during hands-on instruction and repeated training sessions focussing on strengthening PFM and anterolateral abdominal muscle co-contraction during forced expiration and coughing. At baseline, 30 women (75%) were able to perform normal PFM contractions at rest (Oxford scale score ≥ 3); only 4 of them (10%) presented additional involuntary PFM contractions before and during coughing. The remaining 10 women (25%) were unable to perform voluntary or involuntary PFM contractions. Mean Oxford scale score in the whole group was 3.3 ± 1.7. After completing the PFM training program, 29 women (72.5%) performed cough-related PFM contractions and group mean Oxford scale score increased significantly to 4.2 ± 1.0. The study shows that PFM dysfunction may be detected even in healthy young women. Multidimensional training, however, may significantly improve PFM function.

Phasic Contractions of the Mouse Vagina and Cervix at Different Phases of the Estrus Cycle and during Late Pregnancy

PubMed Central

Gravina, Fernanda S.; van Helden, Dirk F.; Kerr, Karen P.; de Oliveira, Ramatis B.; Jobling, Phillip

2014-01-01

Background/Aims The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Methodology/Principal Findings Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Conclusions/Significance Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges. PMID:25337931

Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy.

PubMed

Gravina, Fernanda S; van Helden, Dirk F; Kerr, Karen P; de Oliveira, Ramatis B; Jobling, Phillip

2014-01-01

The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

[Simultaneous repairing defects of orbital floor and palate with the modified temporalis muscle flap after the maxillectomy].

PubMed

Zhong, Q; Huang, Z G; Fang, J G; Chen, X J; Chen, X H; Hou, L Z; Li, P D; Ma, H Z; He, S Z

2016-09-07

Objective: To evaluate the outcome of one-stage reconstruction of maxillary and orbital defects with modified temporalis muscle flap (TMF) following the removal of malignant neoplasms. Methods: In this retrospective study, 15 patients underwent the reconstruction of defects of orbital floor and palate after maxillectomy for malignant tumor were included from June 2008 to June 2014. The modified temporalis muscle flap was used to repair the defects after surgery, and functional outcomes were analyzed. Results: All the patients were followed up for 12-81 months. Three cases of them received preoperative radiotherapy and 12 cases underwent postoperative radiotherapy. All flaps were survived. Epithelization of the tissues in oral and nasal cavity was completed in 4-6 weeks. Good functional reconstruction on swallowing and speaking functional results were achieved with maxillary and orbital reconstruction and no secondary deformity of external nose was observed. The eye positions in all cases were normal. Diplopia, diminution and loss of vision were not found. Conclusion: The modified TMF can be used for simultaneous reconstruction for the defects of orbital floor and palate after maxillectomy in patients whom free tissue flap can not be applied to, showing better cosmetic and functional results.

Motor unit and muscle fiber type grouping after peripheral nerve injury in the rat.

PubMed

Gordon, Tessa; de Zepetnek, Joanne E Totosy

2016-11-01

Muscle unit (MU) fibers innervated by one motoneuron and corresponding muscle fiber types are normally distributed in a mosaic. We asked whether, 4-8months after common peroneal nerve transection and random surgical alignment of nerve stumps in rat tibialis anterior muscles 1) reinnervated MU muscle and muscle fiber type clumping is invariant and 2) slow and fast motoneurons regenerate their nerve fibers within original endoneurial pathways. MU contractile forces were recorded in vivo, the MUs classified into types according to their contractile speed and fatigability, and one MU subjected to alternate exhaustive stimulation-recovery cycles to deplete glycogen for histochemical MU fiber recognition and enumeration, and muscle fiber typing. MU muscle fibers occupied defined territories whose size increased with MU force and muscle fiber numbers in normal and reinnervated muscles. The reinnervated MU muscle fiber territories were significantly smaller, the fibers clumped within 1-3 groups in 90% of the MUs, and each fiber lying adjacent to another significantly more frequently. Most reinnervated slow muscle fibers were normally located in the deep muscle compartment but substantial numbers were located abnormally in the superficial compartment. Our findings that well reinnervated muscle fibers clump in small muscles contrast with our earlier findings of clumping in large muscles only when reinnervated MU numbers were significantly reduced. We conclude that fiber type clumping is predictive of muscle reinnervation in small but not large muscles. In the latter muscles, clumping is more indicative of sprouting after partial nerve injuries than of muscle reinnervation after complete nerve injuries. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional impairment of skeletal muscle oxidative metabolism during knee extension exercise after bed rest.

PubMed

Salvadego, Desy; Lazzer, Stefano; Marzorati, Mauro; Porcelli, Simone; Rejc, Enrico; Simunic, Bostjan; Pisot, Rado; di Prampero, Pietro Enrico; Grassi, Bruno

2011-12-01

A functional evaluation of skeletal muscle oxidative metabolism during dynamic knee extension (KE) incremental exercises was carried out following a 35-day bed rest (BR) (Valdoltra 2008 BR campaign). Nine young male volunteers (age: 23.5 ± 2.2 yr; mean ± SD) were evaluated. Pulmonary gas exchange, heart rate and cardiac output (by impedance cardiography), skeletal muscle (vastus lateralis) fractional O(2) extraction, and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined during incremental KE. Values at exhaustion were considered "peak". Peak heart rate (147 ± 18 beats/min before vs. 146 ± 17 beats/min after BR) and peak cardiac output (17.8 ± 3.3 l/min before vs. 16.1 ± 1.8 l/min after BR) were unaffected by BR. As expected, brain oxygenation did not decrease during KE. Peak O(2) uptake was lower after vs. before BR, both when expressed as liters per minute (0.99 ± 0.17 vs. 1.26 ± 0.27) and when normalized per unit of quadriceps muscle mass (46.5 ± 6.4 vs. 56.9 ± 11.0 ml·min(-1)·100 g(-1)). Skeletal muscle peak fractional O(2) extraction, expressed as a percentage of the maximal values obtained during a transient limb ischemia, was lower after (46.3 ± 12.1%) vs. before BR (66.5 ± 11.2%). After elimination, by the adopted exercise protocol, of constraints related to cardiovascular O(2) delivery, a decrease in peak O(2) uptake and muscle peak capacity of fractional O(2) extraction was found after 35 days of BR. These findings suggest a substantial impairment of oxidative function at the muscle level, "downstream" with respect to bulk blood flow to the exercising muscles, that is possibly at the level of blood flow distribution/O(2) utilization inside the muscle, peripheral O(2) diffusion, and intracellular oxidative metabolism.

The fungicide Pristine® inhibits mitochondrial function in vitro but not flight metabolic rates in honey bees.

PubMed

Campbell, Jacob B; Nath, Rachna; Gadau, Juergen; Fox, Trevor; DeGrandi-Hoffman, Gloria; Harrison, Jon F

2016-03-01

Honey bees and other pollinators are exposed to fungicides that act by inhibiting fungal mitochondria. Here we test whether a common fungicide (Pristine®) inhibits the function of mitochondria of honeybees, and whether consumption of ecologically-realistic concentrations can cause negative effects on the mitochondria of flight muscles, or the capability for flight, as judged by CO2 emission rates and thorax temperatures during flight. Direct exposure of mitochondria to Pristine® levels above 5 ppm strongly inhibited mitochondrial oxidation rates in vitro. However, bees that consumed pollen containing Pristine® at ecologically-realistic concentrations (≈ 1 ppm) had normal flight CO2 emission rates and thorax temperatures. Mitochondria isolated from the flight muscles of the Pristine®-consuming bees had higher state 3 oxygen consumption rates than control bees, suggesting that possibly Pristine®-consumption caused compensatory changes in mitochondria. It is likely that the lack of a strong functional effect of Pristine®-consumption on flight performance and the in vitro function of flight muscle mitochondria results from maintenance of Pristine® levels in the flight muscles at much lower levels than occur in the food, probably due to metabolism and detoxification. As Pristine® has been shown to negatively affect feeding rates and protein digestion of honey bees, it is plausible that Pristine® consumption negatively affects gut wall function (where mitochondria may be exposed to higher concentrations of Pristine®). Copyright © 2015 Elsevier Ltd. All rights reserved.

The early use of botulinum toxin in post-stroke spasticity: study protocol for a randomised controlled trial.

PubMed

Lindsay, Cameron; Simpson, Julie; Ispoglou, Sissi; Sturman, Steve G; Pandyan, Anand D

2014-01-08

Patients surviving stroke but who have significant impairment of function in the affected arm are at more risk of developing pain, stiffness and contractures. The abnormal muscle activity, associated with post-stroke spasticity, is thought to be causally associated with the development of these complications. Treatment of spasticity is currently delayed until a patient develops signs of these complications. This protocol is for a phase II study that aims to identify whether using OnabotulinumtoxinA (BoNT-A) in combination with physiotherapy early post stroke when initial abnormal muscle activity is neurophysiologically identified can prevent loss of range at joints and improve functional outcomes.The trial uses a screening phase to identify which people are appropriate to be included in a double blind randomised placebo-controlled trial. All patients admitted to Sandwell and West Birmingham NHS Trust Hospitals with a diagnosis of stroke will be screened to identify functional activity in the arm. Those who have no function will be appropriate for further screening. Patients who are screened and have abnormal muscle activity identified on EMG will be given electrical stimulation to forearm extensors for 3 months and randomised to have either injections of BoNT-A or normal saline. The primary outcome measure is the action research arm test - a measure of arm function. Further measures include spasticity, stiffness, muscle strength and fatigue as well as measures of quality of life, participation and caregiver strain. ISRCTN57435427, EudraCT2010-021257-39, NCT01882556.

Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia

PubMed Central

Murphy, Kate T.; Chee, Annabel; Trieu, Jennifer; Naim, Timur; Lynch, Gordon S.

2012-01-01

SUMMARY Cancer cachexia describes the progressive skeletal muscle wasting and weakness that is associated with many cancers. It impairs quality of life and accounts for >20% of all cancer-related deaths. The main outcome that affects quality of life and mortality is loss of skeletal muscle function and so preclinical models should exhibit similar functional impairments in order to maximize translational outcomes. Mice bearing colon-26 (C-26) tumors are commonly used in cancer cachexia studies but few studies have provided comprehensive assessments of physiological and metabolic impairment, especially those factors that impact quality of life. Our aim was to characterize functional impairments in mildly and severely affected cachectic mice, and determine the suitability of these mice as a preclinical model. Metabolic abnormalities are also evident in cachectic patients and we investigated whether C-26-tumor-bearing mice had similar metabolic aberrations. Twelve-week-old CD2F1 mice received a subcutaneous injection of PBS (control) or C-26 tumor cells. After 18–20 days, assessments were made of grip strength, rotarod performance, locomotor activity, whole body metabolism, and contractile properties of tibialis anterior (TA) muscles (in situ) and diaphragm muscle strips (in vitro). Injection of C-26 cells reduced body and muscle mass, and epididymal fat mass. C-26-tumor-bearing mice exhibited lower grip strength and rotarod performance. Locomotor activity was impaired following C-26 injection, with reductions in movement distance, duration and speed compared with controls. TA muscles from C-26-tumor-bearing mice had lower maximum force (−27%) and were more susceptible to fatigue. Maximum specific (normalized) force of diaphragm muscle strips was reduced (−10%) with C-26 injection, and force during fatiguing stimulation was also lower. C-26-tumor-bearing mice had reduced carbohydrate oxidation and increased fat oxidation compared with controls. The range and consistency of functional and metabolic impairments in C-26-tumor-bearing mice confirm their suitability as a preclinical model for cancer cachexia. We recommend the use of these comprehensive functional assessments to maximize the translation of findings to more accurately identify effective treatments for cancer cachexia. PMID:22563056

Immunological studies on the structure and function of the nicotinic acetylcholine receptor in mammalian muscle

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

Gu, Y.

1989-01-01

The specificity of the antibodies in the serum of a patient with myasthenia gravis for a the {alpha}-bungarotoxin binding sites of the acetylcholine receptor (AChR) was examined using AChRs in the C2 mouse muscle cell line as a model. The antibodies were shown to be specific for one of the two toxin-binding sites. The effect of the antibodies in this myasthenic serum on the functional response of the receptor to cholinergic agonists was also examined using carbamylcholine-induced {sup 22}Na uptake into C2 myotubes as a measured of the receptor function. Antibodies specific for the {gamma}, {delta}, and {epsilon} subunit, respectively,more » of mammalian muscle AChRs were developed using subunit-specific synthetic peptides as antigens. Using these antibodies and monoclonal antibodies for other subunits as probes, I have identified four ({alpha}, {beta}, {gamma}, and {delta}) subunits of mammalian muscle AChRs on immunoblots. When AChRs from embryonic, neonatal, normal and denervated adult muscles were compared on immunoblots, the {alpha}, {beta}, and {delta} subunits were identical in all four receptor preparations, with or without endoglycosidase digestion. The spatial and temporal distribution of the {gamma}- and {epsilon}- AChRs in developing and in denervated muscles corresponds to the distribution of AChRs with slow and fast channels, respectively, and that the development changes in the channel properties of the receptor arise from a change in the subunit composition of the receptor, in which the {gamma} is replaced by {epsilon}.« less

Experimental masseter muscle pain alters jaw-neck motor strategy.

PubMed

Wiesinger, B; Häggman-Henrikson, B; Hellström, F; Wänman, A

2013-08-01

A functional integration between the jaw and neck regions has been demonstrated during normal jaw function. The effect of masseter muscle pain on this integrated motor behaviour in man is unknown. The aim of this study was to investigate the effect of induced masseter muscle pain on jaw-neck movements during a continuous jaw opening-closing task. Sixteen healthy men performed continuous jaw opening-closing movements to a target position, defined as 75% of the maximum jaw opening. Each subject performed two trials without pain (controls) and two trials with masseter muscle pain, induced with hypertonic saline as a single injection. Simultaneous movements of the mandible and the head were registered with a wireless optoelectronic three-dimensional recording system. Differences in movement amplitudes between trials were analysed with Friedman's test and corrected Wilcoxon matched pairs test. The head movement amplitudes were significantly larger during masseter muscle pain trials compared with control. Jaw movement amplitudes did not differ significantly between any of the trials after corrected Wilcoxon tests. The ratio between head and jaw movement amplitudes was significantly larger during the first pain trial compared with control. Experimental masseter muscle pain in humans affected integrated jaw-neck movements by increasing the neck component during continuous jaw opening-closing tasks. The findings indicate that pain can alter the strategy for jaw-neck motor control, which further underlines the functional integration between the jaw and neck regions. This altered strategy may have consequences for development of musculoskeletal pain in the jaw and neck regions. © 2012 European Federation of International Association for the Study of Pain Chapters.

Exercise performance and peripheral vascular insufficiency improve with AMPK activation in high-fat diet-fed mice.

PubMed

Baltgalvis, Kristen A; White, Kathy; Li, Wei; Claypool, Mark D; Lang, Wayne; Alcantara, Raniel; Singh, Baljit K; Friera, Annabelle M; McLaughlin, John; Hansen, Derek; McCaughey, Kelly; Nguyen, Henry; Smith, Ira J; Godinez, Guillermo; Shaw, Simon J; Goff, Dane; Singh, Rajinder; Markovtsov, Vadim; Sun, Tian-Qiang; Jenkins, Yonchu; Uy, Gerald; Li, Yingwu; Pan, Alison; Gururaja, Tarikere; Lau, David; Park, Gary; Hitoshi, Yasumichi; Payan, Donald G; Kinsella, Todd M

2014-04-15

Intermittent claudication is a form of exercise intolerance characterized by muscle pain during walking in patients with peripheral artery disease (PAD). Endothelial cell and muscle dysfunction are thought to be important contributors to the etiology of this disease, but a lack of preclinical models that incorporate these elements and measure exercise performance as a primary end point has slowed progress in finding new treatment options for these patients. We sought to develop an animal model of peripheral vascular insufficiency in which microvascular dysfunction and exercise intolerance were defining features. We further set out to determine if pharmacological activation of 5'-AMP-activated protein kinase (AMPK) might counteract any of these functional deficits. Mice aged on a high-fat diet demonstrate many functional and molecular characteristics of PAD, including the sequential development of peripheral vascular insufficiency, increased muscle fatigability, and progressive exercise intolerance. These changes occur gradually and are associated with alterations in nitric oxide bioavailability. Treatment of animals with an AMPK activator, R118, increased voluntary wheel running activity, decreased muscle fatigability, and prevented the progressive decrease in treadmill exercise capacity. These functional performance benefits were accompanied by improved mitochondrial function, the normalization of perfusion in exercising muscle, increased nitric oxide bioavailability, and decreased circulating levels of the endogenous endothelial nitric oxide synthase inhibitor asymmetric dimethylarginine. These data suggest that aged, obese mice represent a novel model for studying exercise intolerance associated with peripheral vascular insufficiency, and pharmacological activation of AMPK may be a suitable treatment for intermittent claudication associated with PAD.

Amino acid mutations in the caldesmon COOH-terminal functional domain increase force generation in bladder smooth muscle

PubMed Central

Deng, Maoxian; Boopathi, Ettickan; Hypolite, Joseph A.; Raabe, Tobias; Chang, Shaohua; Zderic, Stephen; Wein, Alan J.

2013-01-01

Caldesmon (CaD), a component of smooth muscle thin filaments, binds actin, tropomyosin, calmodulin, and myosin and inhibits actin-activated ATP hydrolysis by smooth muscle myosin. Internal deletions of the chicken CaD functional domain that spans from amino acids (aa) 718 to 731, which corresponds to aa 512–530 including the adjacent aa sequence in mouse CaD, lead to diminished CaD-induced inhibition of actin-activated ATP hydrolysis by myosin. Transgenic mice with mutations of five aa residues (Lys523 to Gln, Val524 to Leu, Ser526 to Thr, Pro527 to Cys, and Lys529 to Ser), which encompass the ATPase inhibitory determinants located in exon 12, were generated by homologous recombination. Homozygous (−/−) animals did not develop, but heterozygous (+/−) mice carrying the expected mutations in the CaD ATPase inhibitory domain (CaD mutant) matured and reproduced normally. The peak force produced in response to KCl and electrical field stimulation by the detrusor smooth muscle from the CaD mutant was high compared with that of the wild type. CaD mutant mice revealed nonvoiding contractions during bladder filling on awake cystometry, suggesting that the CaD ATPase inhibitory domain suppresses force generation during the filling phase and this suppression is partially released by mutations in 50% of CaD in heterozygous. Our data show for the first time a functional phenotype, at the intact smooth muscle tissue and in vivo organ levels, following mutation of a functional domain at the COOH-terminal region of CaD. PMID:23986516

Relationships between eccentric hip isokinetic torque and functional performance.

PubMed

Baldon, Rodrigo de Marche; Lobato D, Ferreira Moreira; Carvalho, Lívia Pinheiro; Wun P, Yan Lam; Presotti, Cátia Valéria; Serrão, Fábio Viadanna

2012-02-01

Recently, attention in sports has been given to eccentric hip-muscle function, both in preventing musculoskeletal injuries and improving performance. To determine the key isokinetic variables of eccentric hip torque that predict the functional performance of women in the single-leg triple long jump (TLJ) and the timed 6-m single-leg hop (TH). Within-subject correlational study. Musculoskeletal laboratory. 32 healthy women age 18-25 y. The participants performed 2 sets of 5 eccentric hip-abductor/adductor and lateral/medial-rotator isokinetic contractions (30°/s) and 3 attempts in the TLJ and TH. The independent variables were the eccentric hip-abductor and -adductor and medial- and lateral-rotator isokinetic peak torque, normalized according to body mass (Nm/kg). The dependent variables were the longest distance achieved in the TLJ normalized according to body height and the shortest time spent during the execution of the TH. The forward-stepwise-regression analysis showed that the combination of the eccentric hip lateral-rotator and -abductor isokinetic peak torque provided the most efficient estimate of both functional tests, explaining 65% of the TLJ variance (P < .001) and 55% of the TH variance (P < .001). Higher values for eccentric hip lateral-rotator and hip-abductor torques reflected better performance. Thus, the eccentric action of these muscles should be considered in the development of physical training programs that aim to increase functional performance.

Muscle Activation Profiles and Co-Activation of Quadriceps and Hamstring Muscles around Knee Joint in Indian Primary Osteoarthritis Knee Patients.

PubMed

Sharma, Sanjeev Kumar; Yadav, Shiv Lal; Singh, U; Wadhwa, Sanjay

2017-05-01

Osteoarthritis (OA) of knee is a common joint disease. It is associated with reduced knee joint stability due to impaired quadriceps strength, pain, and an altered joint structure. There is altered muscle activation in knee OA patients, which interferes with normal load distribution around the knee and facilitates disease progression. Our primary aim was to determine activation patterns of the muscles i.e., quadriceps and hamstrings in knee OA patients during walking. We also studied co-activation of muscles around knee joint in primary OA knee patients including directed medial and lateral co-contractions. This observational study was done at Department of Physical Medicine and Rehabilitation, All India Institute of Medical Sciences, New Delhi, India. Fourty-four patients with medial compartment primary knee OA were included in study after satisfying inclusion and exclusion criteria. All the patients were assessed for mean, peak and integrated Root Mean Square (RMS), EMG values, muscle activation patterns and co-activation of muscles around knee joint by surface Electromyography (EMG) analysis of Vastus Medialis Obliques (VMO), Vastus Lateralis (VL), Semitendinosus (SMT) and Biceps Femoris (BF) muscles during gait cycle. The EMG waveform for each muscle was amplitude normalized and time normalized to 100% of gait cycle and plotted on graph. Quantitative variables were assessed for normal distribution and accordingly mean±SD or median (range), as appropriate, was computed. For primary OA knee, mean age 61±5 years, mean weight 63.7±10.1 kg, mean height 153.9±7.2 cm, and mean Body Mass Index (BMI) 26.8±3.0 kg/m 2 was found. The muscle activity of hamstrings (SMT muscle and BF) was increased during midstance, late stance and early swing phase of gait cycle as compared to quadriceps (VMO and VL) muscle activity respectively, suggesting co-contraction of opposing muscles around knee joint. Patients with knee OA walk with increased hamstring muscle activity (during late stance and early swing phase) and reduced quadriceps recruitment. Altered neuro-muscular control around knee interferes with normal load distribution and facilitates disease progression in knee joint.

Muscle Activation Profiles and Co-Activation of Quadriceps and Hamstring Muscles around Knee Joint in Indian Primary Osteoarthritis Knee Patients

PubMed Central

Yadav, Shiv Lal; Singh, U; Wadhwa, Sanjay

2017-01-01

Introduction Osteoarthritis (OA) of knee is a common joint disease. It is associated with reduced knee joint stability due to impaired quadriceps strength, pain, and an altered joint structure. There is altered muscle activation in knee OA patients, which interferes with normal load distribution around the knee and facilitates disease progression. Aim Our primary aim was to determine activation patterns of the muscles i.e., quadriceps and hamstrings in knee OA patients during walking. We also studied co-activation of muscles around knee joint in primary OA knee patients including directed medial and lateral co-contractions. Materials and Methods This observational study was done at Department of Physical Medicine and Rehabilitation, All India Institute of Medical Sciences, New Delhi, India. Fourty-four patients with medial compartment primary knee OA were included in study after satisfying inclusion and exclusion criteria. All the patients were assessed for mean, peak and integrated Root Mean Square (RMS), EMG values, muscle activation patterns and co-activation of muscles around knee joint by surface Electromyography (EMG) analysis of Vastus Medialis Obliques (VMO), Vastus Lateralis (VL), Semitendinosus (SMT) and Biceps Femoris (BF) muscles during gait cycle. The EMG waveform for each muscle was amplitude normalized and time normalized to 100% of gait cycle and plotted on graph. Quantitative variables were assessed for normal distribution and accordingly mean±SD or median (range), as appropriate, was computed. Results For primary OA knee, mean age 61±5 years, mean weight 63.7±10.1 kg, mean height 153.9±7.2 cm, and mean Body Mass Index (BMI) 26.8±3.0 kg/m2 was found. The muscle activity of hamstrings (SMT muscle and BF) was increased during midstance, late stance and early swing phase of gait cycle as compared to quadriceps (VMO and VL) muscle activity respectively, suggesting co-contraction of opposing muscles around knee joint. Conclusion Patients with knee OA walk with increased hamstring muscle activity (during late stance and early swing phase) and reduced quadriceps recruitment. Altered neuro-muscular control around knee interferes with normal load distribution and facilitates disease progression in knee joint. PMID:28658860

Continuous exposure to low amplitude extremely low frequency electrical fields characterizing the vascular streaming potential alters elastin accumulation in vascular smooth muscle cells.

PubMed

Bergethon, Peter R; Kindler, Dean D; Hallock, Kevin; Blease, Susan; Toselli, Paul

2013-07-01

In normal development and pathology, the vascular system depends on complex interactions between cellular elements, biochemical molecules, and physical forces. The electrokinetic vascular streaming potential (EVSP) is an endogenous extremely low frequency (ELF) electrical field resulting from blood flowing past the vessel wall. While generally unrecognized, it is a ubiquitous electrical biophysical force to which the vascular tree is exposed. Extracellular matrix elastin plays a central role in normal blood vessel function and in the development of atherosclerosis. It was hypothesized that ELF fields of low amplitude would alter elastin accumulation, supporting a link between the EVSP and the biology of vascular smooth muscle cells. Neonatal rat aortic smooth muscle cell cultures were exposed chronically to electrical fields characteristic of the EVSP. Extracellular protein accumulation, DNA content, and electron microscopic (EM) evaluation were performed after 2 weeks of exposure. Stimulated cultures showed no significant change in cellular proliferation as measured by the DNA concentration. The per-DNA normalized protein in the extracellular matrix was unchanged while extracellular elastin accumulation decreased 38% on average. EM analysis showed that the stimulated cells had a 2.85-fold increase in mitochondrial number. These results support the formulation that ELF fields are a potential factor in both normal vessel biology and in the pathogenesis of atherosclerotic diseases including heart disease, stroke, and peripheral vascular disease. Copyright © 2013 Wiley Periodicals, Inc.

Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation

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

Ostlund, Cecilia; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Guan, Tinglu

2009-11-13

Muscular dystrophy and peripheral neuropathy have been linked to mutations in genes encoding nuclear envelope proteins; however, the molecular mechanisms underlying these disorders remain unresolved. Nuclear envelope protein p19A is a protein of unknown function encoded by a gene at chromosome 4q35. p19A levels are significantly reduced in human muscle as cells differentiate from myoblasts to myotubes; however, its levels are not similarly reduced in all differentiation systems tested. Because 4q35 has been linked to facioscapulohumeral muscular dystrophy (FSHD) and some adjacent genes are reportedly misregulated in the disorder, levels of p19A were analyzed in muscle samples from patients withmore » FSHD. Although p19A was increased in most cases, an absolute correlation was not observed. Nonetheless, p19A downregulation in normal muscle differentiation suggests that in the cases where its gene is inappropriately re-activated it could affect muscle differentiation and contribute to disease pathology.« less

Skilled movements require non-apoptotic Bax/Bak pathway-mediated corticospinal circuit reorganization

PubMed Central

Gu, Zirong; Serradj, Najet; Ueno, Masaki; Liang, Mishi; Li, Jie; Baccei, Mark L.; Martin, John H.; Yoshida, Yutaka

2017-01-01

Early postnatal mammals, including human babies, can perform only basic motor tasks. The acquisition of skilled behaviors occurs later, requiring anatomical changes in neural circuitry to support the development of coordinated activation or suppression of functionally related muscle groups. How this circuit reorganization occurs during postnatal development remains poorly understood. Here we explore the connectivity between corticospinal (CS) neurons in the motor cortex and muscles in mice. Using trans-synaptic viral and electrophysiological assays, we identify the early postnatal reorganization of CS circuitry for antagonistic muscle pairs. We further show that this synaptic rearrangement requires the activity-dependent, non-apoptotic Bax/Bak-caspase signaling cascade. Adult Bax/Bak mutant mice exhibit aberrant co-activation of antagonistic muscle pairs and skilled grasping deficits but normal reaching and retrieval behaviors. Our findings reveal key cellular and molecular mechanisms driving postnatal motor circuit reorganization and the resulting impacts on muscle activation patterns and the execution of skilled movements. PMID:28472660

Cardiomyocyte-specific desmin rescue of desmin null cardiomyopathy excludes vascular involvement.

PubMed

Weisleder, Noah; Soumaka, Elisavet; Abbasi, Shahrzad; Taegtmeyer, Heinrich; Capetanaki, Yassemi

2004-01-01

Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals. To determine whether altered capillary function or an intrinsic cardiomyocyte defect is responsible for desmin null DCM, transgenic mice were generated to rescue desmin expression specifically to cardiomyocytes. Desmin rescue mice display a wild-type cardiac phenotype with no fibrosis or calcification in the myocardium and normalization of coronary flow. Cardiomyocyte ultrastructure is also restored to normal. Markers of hypertrophy upregulated in desmin null hearts return to wild-type levels in desmin rescue mice. Working hearts were perfused to assess coronary flow and cardiac power. Restoration of a wild-type cardiac phenotype in a desmin null background by expression of desmin specifically within cardiomyocyte indicates that defects in the desmin null heart are due to an intrinsic cardiomyocytes defect rather than compromised coronary circulation.

Low skeletal muscle mass index is associated with function and nutritional status in residents in a Turkish nursing home.

PubMed

Tufan, Asli; Bahat, Gulistan; Ozkaya, Hilal; Taşcıoğlu, Didem; Tufan, Fatih; Saka, Bülent; Akin, Sibel; Karan, Mehmet Akif

2016-09-01

To determine the prevalence of low muscle mass (LMM) and the relationship between LMM with functional and nutritional status as defined using the LMM evaluation method of European Working Group on Sarcopenia in Older People (EWGSOP) criteria among male residents in a nursing home. Male residents aged >60 years of a nursing home located in Turkey were included in our study. Their body mass index (BMI) kg/m 2 , skeletal muscle mass (SMM-kg) and skeletal muscle mass index (SMMI-kg/m 2 ) were calculated. The participants were regarded as having low SMMI if they had SMMI <9.2 kg/m 2 according to our population specific cut-off point. Functional status was evaluated with Katz activities of daily living (ADL) and Lawton Instrumental Activities of Daily Living (IADL). Nutritional assessment was performed using the Mini Nutritional Assessment (MNA). The number of drugs taken and chronic diseases were recorded. One hundred fifty-seven male residents were enrolled into the study. Their mean age was 73.1 ± 6.7 years with mean ADL score of 8.9 ± 2.0 and IADL score of 8.7 ± 4.6. One hundred twelve (71%) residents were aged >70 years. Thirty-five men (23%) had low SMMI in group aged >60 years, and twenty-eight subjects (25%) in the group aged >70 years. MNA scores were significantly lower in residents with low SMMI compared with having normal SMMI (17.1 ± 3.4 versus 19.6 ± 2.5, p = 0.005). BMI was significantly lower in the residents with low SMMI compared with normal SMMI (19.6 ± 2.7 versus 27.1 ± 4.1, p< 0.001). ADL scores were significantly different between residents with low SMMI and normal SMMI in those aged >70 years (8.1 ± 2.6 versus 9.1 ± 1.6, p = 0.014). In regression analyses, the only factor associated with better functional status was the lower age (p = 0.04) while the only factor associated with better nutrition was higher SMMI (p = 0.01). Low SMMI detected by LMM evaluation method of EWGSOP criteria is prevalent among male nursing home residents. There is association of low SMMI with nutritional status and probably with functional status within the nursing home setting using the EWGSOP criteria with Turkish normative reference cut-off value.

Effects of pituitary dwarfism in the mouse on fast and slow skeletal muscles.

PubMed

Stickland, N C; Crook, A R; Sutton, C M

1994-01-01

The Snell dwarf mouse exhibits impaired growth of the anterior pituitary resulting in reduced levels of growth hormone and thyroid stimulating hormone. Ten dwarf mice and 10 phenotypically normal littermates were killed at 33 days of age. M. biceps brachii (a predominantly fast muscle) and m. soleus (a relatively slow muscle) were removed from each animal and complete frozen transverse sections obtained. Serial sections were reacted for various enzyme activities in order to identify muscle fibre types. There was no difference in the total number of muscle fibres in m. biceps brachii but a small difference in m. soleus between normal and dwarf mice. There were marked differences in the size of all fibre types between normal and dwarf mice with the largest differences in m. soleus. The percentage of slow oxidative fibres was similar (about 32%) in both groups of mice for m. soleus but there was a marked difference for this fibre type in m. biceps brachii being about 1.5% in normal mice and 8.0% in dwarf mice. This may be related to a difference in levels of thyroid hormone. Nuclear density was very significantly greater in dwarf muscles although total nuclear numbers were less than in normal muscles. These differences are most likely due to growth hormone levels. Differences in nuclear content were much greater in m. soleus than in m. biceps brachii.

Muscle Coordination and Locomotion in Humans.

PubMed

Sylos-Labini, Francesca; Zago, Myrka; Guertin, Pierre A; Lacquaniti, Francesco; Ivanenko, Yury P

2017-01-01

Locomotion is a semi-automatic daily task. Several studies show that muscle activity is fairly stereotyped during normal walking. Nevertheless, each human leg contains over 50 muscles and locomotion requires flexibility in order to adapt to different conditions as, for instance, different speeds, gaits, turning, obstacle avoidance, altered gravity levels, etc. Therefore, locomotor control has to deal with a certain level of flexibility and non-linearity. In this review, we describe and discuss different findings dealing with both simplicity and variability of the muscular control, as well as with its maturation during development. Despite complexity and redundancy, muscle activity patterns and spatiotemporal maps of spinal motoneuron output during human locomotion show both stereotypical features as well as functional re-organization. Flexibility and different solutions to adjust motor patterns should be considered when considering new rehabilitation strategies to treat disorders involving deficits in gait. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Myf5 and Myogenin in the development of thymic myoid cells - Implications for a murine in vivo model of myasthenia gravis.

PubMed

Hu, Bo; Simon-Keller, Katja; Küffer, Stefan; Ströbel, Philipp; Braun, Thomas; Marx, Alexander; Porubsky, Stefan

2016-03-01

Myasthenia gravis (MG) is caused by autoantibodies against the neuromuscular junction of striated muscle. Most MG patients have autoreactive T- and B-cells directed to the acetylcholine receptor (AChR). To achieve immunologic tolerance, developing thymocytes are normally eliminated after recognition of self-antigen-derived peptides. Presentation of muscle-specific antigens is likely achieved through two pathways: on medullary thymic epithelial cells and on medullary dendritic cells cross-presenting peptides derived from a unique population of thymic myoid cells (TMC). Decades ago, it has been hypothesized that TMC play a key role in the induction of immunological tolerance towards skeletal muscle antigens. However, an experimental model to address this postulate has not been available. To generate such a model, we tested the hypothesis that the development of TMC depends on myogenic regulatory factors. To this end, we utilized Myf5-deficient mice, which lack the first wave of muscle cells but form normal skeletal muscles later during development, and Myogenin-deficient mice, which fail to form differentiated myofibers. We demonstrate for the first time that Myf5- and Myogenin-deficient mice showed a partial or complete, respectively, loss of TMC in an otherwise regularly structured thymus. To overcome early postnatal lethality of muscle-deficient, Myogenin-knockout mice we transplanted Myogenin-deficient fetal thymuses into Foxn1(nu/nu) mice that lack their own thymus anlage. We found that the transplants are functional but lack TMC. In combination with established immunization strategies (utilizing AChR or Titin), this model should enable us in the future testing the hypothesis that TMC play an indispensable role in the development of central tolerance towards striated muscle antigens. Copyright © 2015 Elsevier Inc. All rights reserved.

Distinct function of estrogen receptor α in smooth muscle and fibroblast cells in prostate development.

PubMed

Vitkus, Spencer; Yeh, Chiuan-Ren; Lin, Hsiu-Hsia; Hsu, Iawen; Yu, Jiangzhou; Chen, Ming; Yeh, Shuyuan

2013-01-01

Estrogen signaling, through estrogen receptor (ER)α, has been shown to cause hypertrophy in the prostate. Our recent report has shown that epithelial ERα knockout (KO) will not affect the normal prostate development or homeostasis. However, it remains unclear whether ERα in different types of stromal cells has distinct roles in prostate development. This study proposed to elucidate how KO of ERα in the stromal smooth muscle or fibroblast cells may interrupt cross talk between prostate stromal and epithelial cells. Smooth muscle ERαKO (smERαKO) mice showed decreased glandular infolding with the proximal area exhibiting a significant decrease. Fibroblast ERαKO mouse prostates did not exhibit this phenotype but showed a decrease in the number of ductal tips. Additionally, the amount of collagen observed in the basement membrane was reduced in smERαKO prostates. Interestingly, these phenotypes were found to be mutually exclusive among smERαKO or fibroblast ERαKO mice. Compound KO of ERα in both fibroblast and smooth muscle showed combined phenotypes from each of the single KO. Further mechanistic studies showed that IGF-I and epidermal growth factor were down-regulated in prostate smooth muscle PS-1 cells lacking ERα. Together, our results indicate the distinct functions of fibroblast vs. smERα in prostate development.

Renin-angiotensin-aldosterone system inhibitors improve membrane stability and change gene-expression profiles in dystrophic skeletal muscles.

PubMed

Chadwick, Jessica A; Bhattacharya, Sayak; Lowe, Jeovanna; Weisleder, Noah; Rafael-Fortney, Jill A

2017-02-01

Angiotensin-converting enzyme inhibitors (ACEi) and mineralocorticoid receptor (MR) antagonists are FDA-approved drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) and are used to treat heart failure. Combined treatment with the ACEi lisinopril and the nonspecific MR antagonist spironolactone surprisingly improves skeletal muscle, in addition to heart function and pathology in a Duchenne muscular dystrophy (DMD) mouse model. We recently demonstrated that MR is present in all limb and respiratory muscles and functions as a steroid hormone receptor in differentiated normal human skeletal muscle fibers. The goals of the current study were to begin to define cellular and molecular mechanisms mediating the skeletal muscle efficacy of RAAS inhibitor treatment. We also compared molecular changes resulting from RAAS inhibition with those resulting from the current DMD standard-of-care glucocorticoid treatment. Direct assessment of muscle membrane integrity demonstrated improvement in dystrophic mice treated with lisinopril and spironolactone compared with untreated mice. Short-term treatments of dystrophic mice with specific and nonspecific MR antagonists combined with lisinopril led to overlapping gene-expression profiles with beneficial regulation of metabolic processes and decreased inflammatory gene expression. Glucocorticoids increased apoptotic, proteolytic, and chemokine gene expression that was not changed by RAAS inhibitors in dystrophic mice. Microarray data identified potential genes that may underlie RAAS inhibitor treatment efficacy and the side effects of glucocorticoids. Direct effects of RAAS inhibitors on membrane integrity also contribute to improved pathology of dystrophic muscles. Together, these data will inform clinical development of MR antagonists for treating skeletal muscles in DMD. Copyright © 2017 the American Physiological Society.

Muscle activation behavior in a swimming exergame: Differences by experience and gaming velocity.

PubMed

Soltani, Pooya; Figueiredo, Pedro; Fernandes, Ricardo J; Vilas-Boas, João Paulo

2017-11-01

The effects of playing intensity and prior exergame and sport experience on the activation patterns of upper limb muscles during a swimming exergame were investigated. Surface electromyography of Biceps Brachii, Triceps Brachii, Latissimus Dorsi, Upper Trapezius, and Erector Spinae of twenty participants was recorded, and the game play was divided into normal and fast. Mean muscle activation, normalized to maximum voluntary isometric contraction (MVIC), ranged from 4.9 to 95.2%MVIC and differed between normal and fast swimming for all techniques (p<0.05), except for Latissimus Dorsi during backstroke. After normalizing the %MVIC to playing velocity, selective behaviors were observed between muscles which were sufficient for pragmatic game play. Moreover, prior exergame and real sport experience did not have any effect on the muscle activation changes between normal and fast swimming. These behaviors are likely to happen when players understand the game mechanics, even after a short exposure. Such evaluation might help in adjusting the physical demands of sport exergames, for safe and meaningful experiences. Copyright © 2017 Elsevier Inc. All rights reserved.

Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.

PubMed

Ehinger, Johannes K; Morota, Saori; Hansson, Magnus J; Paul, Gesine; Elmér, Eskil

2015-06-01

Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the disease.

Functional implications of muscle co-contraction during gait in advanced age.

PubMed

Lo, Justine; Lo, On-Yee; Olson, Erin A; Habtemariam, Daniel; Iloputaife, Ikechukwu; Gagnon, Margaret M; Manor, Brad; Lipsitz, Lewis A

2017-03-01

Older adults often exhibit high levels of lower extremity muscle co-contraction, which may be the cause or effect of age-related impairments in gait and associated falls. Normal gait requires intact executive function and thus can be slowed by challenging executive resources available to the neuromuscular system through the performance of a dual task. We therefore investigated associations between lower limb co-contraction and gait characteristics under normal and dual task conditions in healthy older adults (85.4±5.9years). We hypothesized that greater co-contraction is associated with slower gait speed during dual task conditions that stress executive and attentional abilities. Co-contraction was quantified during different phases of the gait cycle using surface electromyography (EMG) signals obtained from the anterior tibialis and lateral gastrocnemius while walking at preferred speed during normal and dual task conditions. Variables included the time difference to complete the Trail Making Test A and B (ΔTMT) and gait measures during normal or dual task walking. Higher co-contraction levels during the swing phase of both normal and dual task walking were associated with longer ΔTMT (normal: R 2 =0.25, p=0.02; dual task: R 2 =0.27, p=0.01). Co-contraction was associated with gait measures during dual task walking only; greater co-contraction levels during stride and stance were associated with slower gait speed (stride: R 2 =0.38, p=0.04; stance: R 2 =0.38, p=0.04), and greater co-contraction during stride was associated with longer stride time (R 2 =0.16, p=0.03). Our results suggest that relatively high lower limb co-contraction may explain some of the mobility impairments associated with the conduct of executive tasks in older adults. Copyright © 2017 Elsevier B.V. All rights reserved.

Responses of skeletal muscle to unloading, a review

NASA Technical Reports Server (NTRS)

Tischler, M. E.; Jaspers, S. R.; Henriksen, E. J.; Jacob, S.

1985-01-01

Suspension models were used to study muscle response to reduced activity. During 6 days of tail casting, the soleus (SOL) atrophies while the extensor digitorum longus grows relatively normally. After discounting those changes in both muscles due primarily to increased secretion of adrenal hormones, the following conclusions regarding the specific responses of the SOL could be drawn: (1) Atrophy is probably due primarily to increased protein degradation; (2) Decreased synthesis of glutamine may result from reduced availability of ammonia due to diminished use of ATP; (3) Greater muscle glycogen seems to reflect an increased response to insulin of glucose uptake which leads to greater glucose metabolism; and (4) Faster catabolism of branched-chain amino acids can be attributed to enhanced flux through ketoacid dehydrogenase. Studies by others using tail casted suspended rats showed in the SOL: (1) a gradual switch from type 1 to type 2 fibers; (2) increased acid protease activity; and (3) altered muscle function and contractile duration. Using harness suspended rats, others showed in the SOL: (1) significant atrophy; (2) increased numbers of glucocorticoid receptors; and (3) no change in muscle fatigability.

Responses of skeletal muscle to unloading - A review

NASA Technical Reports Server (NTRS)

Tischler, M. E.; Jaspers, S. R.; Henriksen, E. J.; Jacob, S.

1985-01-01

Suspension models were used to study muscle response to reduced activity. During 6 days of tail casting, the soleus (SOL) atrophies while the extensor digitorum longus grows relatively normally. After discounting those changes in both muscles due primarily to increased secretion of adrenal hormones, the following conclusions regarding the specific responses of the SOL could be drawn: (1) Atrophy is probably due primarily to increased protein degradation; (2) Decreased synthesis of glutamine may result from reduced availability of ammonia due to diminished use of ATP; (3) Greater muscle glycogen seems to reflect an increased response to insulin of glucose uptake which leads to greater glucose metabolism; and (4) Faster catabolism of branched-chain amino acids can be attributed to enhanced flux through ketoacid dehydrogenase. Studies by others using tail casted suspended rats showed in the SOL: (1) a gradual switch from type 1 to type 2 fibers; (2) increased acid protease activity; and (3) altered muscle function and contractile duration. Using harness suspended rats, others showed in the SOL: (1) significant atrophy; (2) increased numbers of glucocorticoid receptors; and (3) no change in muscle fatigability.

Regulators of Autophagosome Formation in Drosophila Muscles

PubMed Central

Zirin, Jonathan; Nieuwenhuis, Joppe; Samsonova, Anastasia; Tao, Rong; Perrimon, Norbert

2015-01-01

Given the diversity of autophagy targets and regulation, it is important to characterize autophagy in various cell types and conditions. We used a primary myocyte cell culture system to assay the role of putative autophagy regulators in the specific context of skeletal muscle. By treating the cultures with rapamycin (Rap) and chloroquine (CQ) we induced an autophagic response, fully suppressible by knockdown of core ATG genes. We screened D. melanogaster orthologs of a previously reported mammalian autophagy protein-protein interaction network, identifying several proteins required for autophagosome formation in muscle cells, including orthologs of the Rab regulators RabGap1 and Rab3Gap1. The screen also highlighted the critical roles of the proteasome and glycogen metabolism in regulating autophagy. Specifically, sustained proteasome inhibition inhibited autophagosome formation both in primary culture and larval skeletal muscle, even though autophagy normally acts to suppress ubiquitin aggregate formation in these tissues. In addition, analyses of glycogen metabolic genes in both primary cultured and larval muscles indicated that glycogen storage enhances the autophagic response to starvation, an important insight given the link between glycogen storage disorders, autophagy, and muscle function. PMID:25692684

Satellite cell depletion prevents fiber hypertrophy in skeletal muscle.

PubMed

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

2016-08-15

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

Evidence of isometric function of the flexor hallucis longus muscle in normal gait.

PubMed

Kirane, Y M; Michelson, J D; Sharkey, N A

2008-01-01

Studying mechanics of the muscles spanning multiple joints provides insights into intersegmental dynamics and movement coordination. Multiarticular muscles are thought to function at "near-isometric" lengths to transfer mechanical energy between the adjacent body segments. Flexor hallucis longus (FHL) is a multiarticular flexor of the great toe; however, its potential isometric function has received little attention. We used a robotic loading apparatus to investigate FHL mechanics during simulated walking in cadaver feet, and hypothesized that physiological force transmission across the foot can occur with isometric FHL function. The extrinsic foot tendons, stripped of the muscle fibers, were connected to computer-controlled linear actuators. The FHL activity was controlled using force-feedback (FC) based upon electromyographic data from healthy subjects, and subsequently, isometric positional feedback (PC), maintaining the FHL myotendinous junction stationary during simulated walking. Tendon forces and excursions were recorded, as were the strains within the first metatarsal. Forces in the metatarsal and metatarsophalangeal joint were derived from these strains. The FHL tendon excursion under FC was 6.57+/-3.13mm. The forces generated in the FHL tendon, metatarsal and metatarsophalangeal joint with the FHL under isometric PC were not significantly different in pattern from FC. These observations provide evidence that physiological forces could be generated along the great toe with isometric FHL function. A length servo mechanism such as the stretch reflex could likely control the isometric FHL function during in vivo locomotion; this could have interesting implications regarding the conditions of impaired stretch reflex such as spastic paresis and peripheral neuropathies.

Reversing Anoikis Resistance in Triple-Negative Breast Cancer

DTIC Science & Technology

2015-10-01

impaired function and therefore is not as efficient at inducing apoptosis. Supervillin is a protein involved in focal adhesions, and the shorter...splice variant archvillin is normally only expressed in muscle cells. GOLGA4 encodes a golgi protein involved in vesicle transport. It shuttles GPI...when miR-200c is induced and another more 3’ exon is retained, so we are still investigating the function of these regions. Figure 4. Alternative

Genetics Home Reference: nemaline myopathy

MedlinePlus

... nemaline myopathy interact within the sarcomere to facilitate muscle contraction. When the skeletal muscle cells of people with ... The disorganized proteins cannot interact normally, which disrupts muscle contraction. Inefficient muscle contraction leads to muscle weakness and ...

Calpain 3 is important for muscle regeneration: evidence from patients with limb girdle muscular dystrophies.

PubMed

Hauerslev, Simon; Sveen, Marie-Louise; Duno, Morten; Angelini, Corrado; Vissing, John; Krag, Thomas O

2012-03-23

Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutations in the CAPN3 gene and complete lack of functional calpain 3 leads to the most severe muscle wasting. Calpain 3 is suggested to be involved in maturation of contractile elements after muscle degeneration. The aim of this study was to investigate how mutations in the four functional domains of calpain 3 affect muscle regeneration. We studied muscle regeneration in 22 patients with LGMD2A with calpain 3 deficiency, in five patients with LGMD2I, with a secondary reduction in calpain 3, and in five patients with Becker muscular dystrophy (BMD) with normal calpain 3 levels. Regeneration was assessed by using the developmental markers neonatal myosin heavy chain (nMHC), vimentin, MyoD and myogenin and counting internally nucleated fibers. We found that the recent regeneration as determined by the number of nMHC/vimentin-positive fibers was greatly diminished in severely affected LGMD2A patients compared to similarly affected patients with LGMD2I and BMD. Whorled fibers, a sign of aberrant regeneration, was highly elevated in patients with a complete lack of calpain 3 compared to patients with residual calpain 3. Regeneration is not affected by location of the mutation in the CAPN3 gene. Our findings suggest that calpain 3 is needed for the regenerative process probably during sarcomere remodeling as the complete lack of functional calpain 3 leads to the most severe phenotypes.

The role of weight loss and exercise in correcting skeletal muscle mitochondrial abnormalities in obesity, diabetes and aging.

PubMed

Toledo, Frederico G S; Goodpaster, Bret H

2013-10-15

Mitochondria within skeletal muscle have been implicated in insulin resistance of obesity and type 2 diabetes mellitus as well as impaired muscle function with normal aging. Evaluating the potential of interventions to improve mitochondria is clearly relevant to the prevention or treatment of metabolic diseases and age-related dysfunction. This review provides an overview and critical evaluation of the effects of weight loss and exercise interventions on skeletal muscle mitochondria, along with implications for insulin resistance, obesity, type 2 diabetes and aging. The available literature strongly suggests that the lower mitochondrial capacity associated with obesity, type 2 diabetes and aging is not an irreversible lesion. However, weight loss does not appear to affect this response, even when the weight loss is extreme. In contrast, increasing physical activity improves mitochondrial content and perhaps the function of individual mitochondrion. Despite the consistent effect of exercise to improve mitochondrial capacity, studies mechanistically linking mitochondria to insulin resistance, reductions in intramyocellular lipid or improvement in muscle function remain inconclusive. In summary, studies of diet and exercise training have advanced our understanding of the link between mitochondrial oxidative capacity and insulin resistance in obesity, type 2 diabetes and aging. Nevertheless, additional inquiry is necessary to establish the significance and clinical relevance of those perturbations, which could lead to targeted therapies for a myriad of conditions and diseases involving mitochondria. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy

PubMed Central

Allen, David G.; Whitehead, Nicholas P.; Froehner, Stanley C.

2015-01-01

Dystrophin is a long rod-shaped protein that connects the subsarcolemmal cytoskeleton to a complex of proteins in the surface membrane (dystrophin protein complex, DPC), with further connections via laminin to other extracellular matrix proteins. Initially considered a structural complex that protected the sarcolemma from mechanical damage, the DPC is now known to serve as a scaffold for numerous signaling proteins. Absence or reduced expression of dystrophin or many of the DPC components cause the muscular dystrophies, a group of inherited diseases in which repeated bouts of muscle damage lead to atrophy and fibrosis, and eventually muscle degeneration. The normal function of dystrophin is poorly defined. In its absence a complex series of changes occur with multiple muscle proteins showing reduced or increased expression or being modified in various ways. In this review, we will consider the various proteins whose expression and function is changed in muscular dystrophies, focusing on Ca2+-permeable channels, nitric oxide synthase, NADPH oxidase, and caveolins. Excessive Ca2+ entry, increased membrane permeability, disordered caveolar function, and increased levels of reactive oxygen species are early changes in the disease, and the hypotheses for these phenomena will be critically considered. The aim of the review is to define the early damage pathways in muscular dystrophy which might be appropriate targets for therapy designed to minimize the muscle degeneration and slow the progression of the disease. PMID:26676145

Muscle-specific accumulation of Drosophila myosin heavy chains: a splicing mutation in an alternative exon results in an isoform substitution.

PubMed Central

Kronert, W A; Edwards, K A; Roche, E S; Wells, L; Bernstein, S I

1991-01-01

We show that the molecular lesions in two homozygousviable mutants of the Drosophila muscle myosin heavy chain gene affect an alternative exon (exon 9a) which encodes a portion of the myosin head that is highly conserved among both cytoplasmic and muscle myosins of all organisms. In situ hybridization and Northern blotting analysis in wild-type organisms indicates that exon 9a is used in indirect flight muscles whereas both exons 9a and 9b are utilized in jump muscles. Alternative exons 9b and 9c are used in other larval and adult muscles. One of the mutations in exon 9a is a nonsense allele that greatly reduces myosin RNA stability. It prevents thick filament accumulation in indirect flight muscles and severely reduces the number of thick filaments in a subset of cells of the jump muscles. The second mutation affects the 5' splice site of exon 9a. This results in production of an aberrantly spliced transcript in indirect flight muscles, which prevents thick filament accumulation. Jump muscles of this mutant substitute exon 9b for exon 9a and consequently have normal levels of thick filaments in this muscle type. This isoform substitution does not obviously affect the ultrastructure or function of the jump muscle. Analysis of this mutant illustrates that indirect flight muscles and jump muscles utilize different mechanisms for alternative RNA splicing. Images PMID:1907912

Texture-modified diets are associated with decreased muscle mass in older adults admitted to a rehabilitation ward.

PubMed

Shimizu, Akio; Maeda, Keisuke; Tanaka, Kei; Ogawa, Mei; Kayashita, Jun

2018-05-01

Texture-modified diets (TMD) have significantly lower energy and protein content than normal diets. Therefore, TMD can cause malnutrition and loss of muscle mass. However, few studies have reported the relationship between TMD and decreased skeletal muscle mass. The aim of the present study was to clarify the association between TMD and decreased skeletal muscle mass. We reviewed data of 188 older adult patients who were admitted to a rehabilitation hospital. TMD were defined based on the Japanese Dysphagia Diet Criteria 2013 proposed by the Japanese Society of Dysphagia Rehabilitation. The Mini Nutritional Assessment-Short Form was used to assess nutritional status; dual-energy X-ray absorptiometry was used to measure the skeletal muscle mass index, and the cut-off values for decreased skeletal muscle mass index were based on the Asian Working Group for Sarcopenia; the Functional Independence Measure was used to evaluate activities of daily living. The patients' mean age was 80.6 ± 7.5 years, and 62% were women. A total of 22 patients (11.7%) consumed TMD. A total of 104 patients (55.3%) had decreased skeletal muscle mass, and approximately 90% of them consumed TMD. Decreased skeletal muscle mass index (odds ratio 7.199, 95% confidence interval 1.489-34.805, P ≤ 0.01) and Functional Independence Measure scores (odds ratio 0.972, 95% confidence interval 0.952-0.992, P ≤ 0.01) were independently related to TMD in the multivariate analysis. The TMD group was associated with decreased skeletal muscle mass. Future, prospective studies are necessary to investigate causality. Geriatr Gerontol Int 2018; 18: 698-704. © 2017 Japan Geriatrics Society.

Differential regulation of myofilament protein isoforms underlying the contractility changes in skeletal muscle unloading

PubMed Central

Yu, Zhi-Bin; Gao, Fang; Feng, Han-Zhong; Jin, J-P

2006-01-01

Weight-bearing skeletal muscles change phenotype rapidly in response to unloading. Using the hind limb-suspension rat model, we investigated the regulation of myofilament protein isoforms in correlation to contractility. Four weeks of continuous hind limb unloading produced progressive atrophy and contractility changes in soleus but not extensor digitorum longus (EDL) muscle. The unloaded soleus muscle also had decreased fatigue resistance. Together with the decrease of myosin heavy chain (MHC) isoform I and IIa and increase of MHC IIb and IIx, coordinated regulation of thin filament regulatory protein isoforms were observed: γ- and β-tropomyosin decreased and α-tropomyosin increased, resulting in an α/β ratio similar to that in normal fast twitch skeletal muscle; troponin I and troponin T (TnT) both showed decrease in the slow isoform and increases in the fast isoform. The TnT isoform switching began after 7 days of unloading and TnI isoform showed detectable changes at 14 days while other protein isoform changes were not significant until 28 days of treatment. Correlating to the early changes in contractility, especially the resistance to fatigue, the early response of TnT isoform regulation may play a unique role in the adaptation of skeletal muscle to unloading. When the fast TnT gene expression was up-regulated in the unloaded soleus muscle, alternative RNA splicing switched to produce more high molecular weight acidic isoforms, reflecting a potential compensation for the decrease of slow TnT that is critical to skeletal muscle function. The results demonstrate that differential regulation of TnT isoforms is a sensitive mechanism in muscle adaptation to functional demands. PMID:17108008

Occlusion, sternocleidomastoid muscle activity, and body sway: a pilot study in male astronauts.

PubMed

Sforza, Chiarella; Tartaglia, Gianluca M; Solimene, Umberto; Morgun, Valery; Kaspranskiy, Rustem R; Ferrario, Virgilio F

2006-01-01

The modifications induced by microgravity on the coordinated patterns of movement of the head, trunk, and limbs are reported on extensively. However, apparently there is little data on the masticatory muscles. In normal gravitational conditions, information from the neck and stomatognathic apparatus play a role in maintaining the body's balance and equilibrium. The current pilot study used normal gravity conditions to investigate the hypothesis of a functional coupling between occlusion and neck muscles and body postural oscillations. The immediate effect of modified occlusal surfaces on the contraction pattern of the sternocleidomastoid muscles during maximum voluntary clenching and on the oscillation of the center of foot pressure was analyzed in 11 male astronauts (aged 31-54 yrs). All subjects were healthy and free from pathologies of the neck and stomatognathic apparatus. Occlusal splints were prepared using impressions of their dental arches. The splints were modeled on the mandibular arch, had only posterior contacts, and were modified to obtain a more symmetric, standardized contraction of the masseter and temporalis muscles during teeth clenching. Surface EMG activity of the sternocleidomastoid muscles was recorded during a maximal voluntary clench with and without the splint. Sternocleidomastoid potentials were standardized as percent of the mean potentials recorded during a maximum contralateral rotation of the head, and the symmetry of the EMG waves of left- and right-side muscles was measured. Body sway was assessed with and without the splint, either with eyes open or closed. The variations of the center of foot pressure were analyzed through bivariate analysis, and the area of the 90% standard ellipse was computed. Within each visual condition (eyes open or closed), the difference between the areas of oscillation measured with and without the splint was computed. Muscular activity was more symmetric with the splint. The area of oscillation of the center of foot pressure was larger without the splint than with the splint, both with eyes open and eyes closed. The modifications, induced by the occlusal splint in the sternocleidomastoid muscles' symmetry, and center of foot pressure differential area with closed eyes, were significantly related (p < 0.05): the larger the increment in muscular symmetry, the smaller the area of oscillation with the splint as compared to without the splint. A functionally more symmetric maxillo-mandibular position resulted in a more symmetric sternocleidomastoid muscle contraction pattern and less body sway. Modifications in the contraction of the masticatory muscles may therefore affect the whole body.

Is the urothelium intelligent?

PubMed

Birder, L A; Kanai, A J; Cruz, F; Moore, K; Fry, C H

2010-04-01

The urothelium separates the urinary tract lumen from underlying tissues of the tract wall. Previously considered as merely an effective barrier between these two compartments it is now recognized as a more active tissue that senses and transduces information about physical and chemical conditions within the urinary tract, such as luminal pressure, urine composition, etc. To understand this sensory function it is useful to consider the urothelium and suburothelium as a functional unit; containing uroepithelial cells, afferent and efferent nerve fibers and suburothelial interstitial cells. This structure responds to alterations in its external environment through the release of diffusible agents, such as ATP and acetylcholine, and eventually modulates the activity of afferent nerves and underlying smooth muscles. This review considers different stresses the urothelium/suburothelium responds to; the particular chemicals released; the cellular receptors that are consequently affected; and how nerve and muscle function is modulated. Brief consideration is also to regional differences in the urothelium/suburothelium along the urinary tract. The importance of different pathways in relaying sensory information in the normal urinary tract, or whether they are significant only in pathological conditions is also discussed. An operational definition of intelligence is used, whereby a system (urothelium/suburothelium) responds to external changes, to maximize the possibility of the urinary tract achieving its normal function. If so, the urothelium can be regarded as intelligent. The advantage of this approach is that input-output functions can be mathematically formulated, and the importance of different components contributing to abnormal urinary tract function can be calculated. (c) 2010 Wiley-Liss, Inc.

Exploring the Link between Serum Phosphate Levels and Low Muscle Strength, Dynapenia, and Sarcopenia.

PubMed

Chen, Yuan-Yuei; Kao, Tung-Wei; Chou, Cheng-Wai; Wu, Chen-Jung; Yang, Hui-Fang; Lai, Ching-Huang; Wu, Li-Wei; Chen, Wei-Liang

2018-02-23

Emerging evidences addressed an association between phosphate and muscle function. Because little attention was focused on this issue, the objective of our study was to explore the relationship of phosphate with muscle strength, dynapenia, and sarcopenia. From the National Health and Nutrition Examination Survey, a total of 7421 participants aged 20 years or older were included in our study with comprehensive examinations included anthropometric parameters, strength of the quadriceps muscle, and appendicular lean masses. Within the normal range of serum phosphate, we used quartile-based analyses to determine the potential relationships of serum phosphate with dynapenia, and sarcopenia through multivariate regression models. After adjusting for the pertinent variables, an inverse association between the serum phosphate quartiles and muscle strength was observed and the linear association was stronger than other anthropometric parameters. Notably, the significant association between phosphate and muscle strength was existed in >65 years old age group, not in 20-65 years old. The higher quartiles of phosphate had higher likelihood for predicting the presence of dynapenia rather than sarcopenia in entire population. Our study highlighted that higher quartiles of phosphate had significant association with lower muscle strength and higher risks for predicting the presence of dynapenia.

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

PubMed Central

Fessler, Henry E.; Scharf, Steven M.; Ingenito, Edward P.; McKenna, Robert J.; Sharafkhaneh, Amir

2008-01-01

It is not readily apparent how pulmonary function could be improved by resecting portions of the lung in patients with emphysema. In emphysema, elevation in residual volume relative to total lung capacity reduces forced expiratory volumes, increases inspiratory effort, and impairs inspiratory muscle mechanics. Lung volume reduction surgery (LVRS) better matches the size of the lungs to the size of the thorax containing them. This restores forced expiratory volumes and the mechanical advantage of the inspiratory muscles. In patients with heterogeneous emphysema, LVRS may also allow space occupied by cysts to be reclaimed by more normal lung. Newer, bronchoscopic methods for lung volume reduction seek to achieve similar ends by causing localized atelectasis, but may be hindered by the low collateral resistance of emphysematous lung. Understanding of the mechanisms of improved function after LVRS can help select patients more likely to benefit from this approach. PMID:18453348

What Is Orofacial Fatigue and How Does It Affect Function for Swallowing and Speech?

PubMed Central

Solomon, Nancy Pearl

2012-01-01

Speech-language pathologists are likely to encounter patients who report symptoms of fatigue, but there are few clinical procedures to assess this phenomenon. Furthermore, it is difficult to determine whether fatigue contributes to a patient's dysphagia or dysarthria. This article reviews orofacial muscles, including the muscles of the tongue, lips, and cheeks, highlighting in particular their role in swallowing and speaking. It provides definitions of fatigue and describes assessment procedures. The author's research has focused on assessing fatigue, especially of the tongue, and elucidating the effects of exercising the tongue on speech and nonspeech tasks. Most of this work involves people who have Parkinson's disease and neurologically normal adults; results generally support heightened fatigue in Parkinson's disease. However, the effect of fatigue on functional activities remains unclear. Literature regarding the effects of orofacial fatigue on swallowing and speaking is notably sparse, but preliminary evidence indicates that these functions are rather robust. PMID:17117353

Cystatin C a marker for renal function after exercise.

PubMed

Mingels, A; Jacobs, L; Kleijnen, V; Wodzig, W; Dieijen-Visser, M van

2009-09-01

Renal impairment is common during and after severe exercise. In clinical practice, renal function is evaluated using serum creatinine, urine parameters, and equations to estimate the Glomular Filtration Rate (GFR). However, creatinine levels may be biased by skeletal muscle damage and the GFR equations, requiring age, gender and body weight, are shown to be inadequate in normals. In the present study, we show that serum cystatin C and creatinine concentrations were elevated after marathon running in 26% and 46% of the 70 recreational male runners, respectively, possibly because of reduction in renal blood flow. The mean cystatin C increase was twice as low as compared to creatinine (21% and 41%, respectively), suggesting that cystatin C is indeed less biased by muscle damage. Future research has to reveal whether training diminishes the elevation in renal markers. Overall, cystatin C seems a more reliable method to establish renal function during and after extensive exercise. Georg Thieme Verlag KG Stuttgart.

Actin isoform specificity is required for the maintenance of lactation

PubMed Central

Weymouth, Nate; Shi, Zengdun; Rockey, Don C.

2014-01-01

Smooth muscle α-actin (Acta2) is one of six highly conserved mammalian actin isoforms that appear to exhibit functional redundancy. Nonetheless, we have postulated a specific functional role for the smooth muscle specific isoform. Here, we show that Acta2 deficient mice have a remarkable mammary phenotype such that dams lacking Acta2 are unable to nurse their offspring effectively. The phenotype was rescued in cross fostering experiments with wild type mice, excluding a developmental defect in Acta2 null pups. The mechanism for the underlying phenotype is due to myoepithelial dysfunction postpartum resulting in precocious involution. Further, we demonstrate a specific defect in myoepithelial cell contractility in Acta2 null mammary glands, despite normal expression of cytoplasmic actins. We conclude that Acta2 specifically mediates myoepithelial cell contraction during lactation and that this actin isoform therefore exhibits functional specificity. PMID:22123032

Exercise-induced muscle glucose uptake in mice with graded, muscle-specific GLUT-4 deletion.

PubMed

Howlett, Kirsten F; Andrikopoulos, Sofianos; Proietto, Joseph; Hargreaves, Mark

2013-08-01

To investigate the importance of the glucose transporter GLUT-4 for muscle glucose uptake during exercise, transgenic mice with skeletal muscle GLUT-4 expression approximately 30-60% of normal (CON) and approximately 5-10% of normal (KO) were generated using the Cre/Lox system and compared with wild-type (WT) mice during approximately 40 min of treadmill running (KO: 37.7 ± 1.3 min; WT: 40 min; CON: 40 min, P = 0.18). In WT and CON animals, exercise resulted in an overall increase in muscle glucose uptake. More specifically, glucose uptake was increased in red gastrocnemius of WT mice and in the soleus and red gastrocnemius of CON mice. In contrast, the exercise-induced increase in muscle glucose uptake in all muscles was completely abolished in KO mice. Muscle glucose uptake increased during exercise in both red and white quadriceps of WT mice, while the small increases in CON mice were not statistically significant. In KO mice, there was no change at all in quadriceps muscle glucose uptake. No differences in muscle glycogen use during exercise were observed between any of the groups. However, there was a significant increase in plasma glucose levels after exercise in KO mice. The results of this study demonstrated that a reduction in skeletal muscle GLUT-4 expression to approximately 10% of normal levels completely abolished the exercise-induced increase in muscle glucose uptake.

Functional disorders of the anus and rectum

PubMed Central

Whitehead, W; Wald, A; Diamant, N; Enck, P; Pemberton, J; Rao, S

1999-01-01

In this report the functional anorectal disorders, the etiology of which is currently unknown or related to the abnormal functioning of normally innervated and structurally intact muscles, are discussed. These disorders include functional fecal incontinence, functional anorectal pain, including levator ani syndrome and proctalgia fugax, and pelvic floor dyssynergia. The epidemiology of each disorder is defined and discussed, their pathophysiology is summarized and diagnostic approaches and treatment are suggested. Some suggestions for the direction of future research on these disorders are also given.


Keywords: fecal incontinence; pelvic floor dyssynergia; anismus; proctalgia fugax; levator ani syndrome; constipation; Rome II PMID:10457046

Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration.

PubMed

Harada, Akihito; Maehara, Kazumitsu; Ono, Yusuke; Taguchi, Hiroyuki; Yoshioka, Kiyoshi; Kitajima, Yasuo; Xie, Yan; Sato, Yuko; Iwasaki, Takeshi; Nogami, Jumpei; Okada, Seiji; Komatsu, Tetsuro; Semba, Yuichiro; Takemoto, Tatsuya; Kimura, Hiroshi; Kurumizaka, Hitoshi; Ohkawa, Yasuyuki

2018-04-11

Regulation of gene expression requires selective incorporation of histone H3 variant H3.3 into chromatin. Histone H3.3 has several subsidiary variants but their functions are unclear. Here we characterize the function of histone H3.3 sub-variant, H3mm7, which is expressed in skeletal muscle satellite cells. H3mm7 knockout mice demonstrate an essential role of H3mm7 in skeletal muscle regeneration. Chromatin analysis reveals that H3mm7 facilitates transcription by forming an open chromatin structure around promoter regions including those of myogenic genes. The crystal structure of the nucleosome containing H3mm7 reveals that, unlike the S57 residue of other H3 proteins, the H3mm7-specific A57 residue cannot form a hydrogen bond with the R40 residue of the cognate H4 molecule. Consequently, the H3mm7 nucleosome is unstable in vitro and exhibited higher mobility in vivo compared with the H3.3 nucleosome. We conclude that the unstable H3mm7 nucleosome may be required for proper skeletal muscle differentiation.

Arrangement of the orbicularis oris muscle in different types of cleft lips.

PubMed

Wijayaweera, C J; Amaratunga, N A; Angunawela, P

2000-05-01

A thorough knowledge of the anatomy of the labial region, especially the arrangement of the muscle fibers, is essential for the success of primary repair of the cleft lip. Pared lateral and medial edges from 20 unilateral incomplete cleft lips and 25 unilateral complete cleft lips were obtained during primary surgery. Three specimens of normal lips were taken from unclaimed infant cadavers as the controls. They were prepared for routine histological studies and were examined to study the direction of muscle fibers. Intrinsic and extrinsic bundles were identified in both lateral and medial sides of specimens of both cleft types. The intrinsic bundle was not displaced but was interrupted by the cleft. The extrinsic bundle in the lateral side of both cleft types ran upward along the lateral cleft margin, whereas in the medial side it ran horizontally to terminate close to the medial cleft margin. The extrinsic bundle is the retractor, which is associated with facial expression, whereas the intrinsic bundle is the constrictor of the mouth. Because there are two functional components in the orbicularis oris muscle, identifying and repairing them separately will enable each of them to accomplish their distinctive functions.

What's new in the functional anatomy of pelvic organ prolapse?

PubMed

DeLancey, John O L

2016-10-01

Provide an evidence-based review of pelvic floor functional anatomy related to pelvic organ prolapse. Pelvic organ support depends on interactions between the levator ani muscle and pelvic connective tissues. Muscle failure exposes the vaginal wall to a pressure differential producing abnormal tension on the attachments of the pelvic organs to the pelvic sidewall. Birth-induced injury to the pubococcygeal portion of the levator ani muscle is seen in 55% of women with prolapse and 16% of women with normal support. Failure of the lateral connective tissue attachments between the uterus and vagina to the pelvic wall (cardinal, uterosacral, and paravaginal) are strongly related with prolapse (effect sizes ∼2.5) and are also highly correlated with one another (r ∼ 0.85). Small differences exist with prolapse in factors involving the vaginal wall length and width (effect sizes ∼1). The primary difference in ligament properties between women with and without prolapse is found in ligament length. Only minor differences in ligament stiffness are seen. Pelvic organ prolapse occurs because of injury to the levator ani muscles and failure of the lateral connections between the pelvic organs to the pelvic sidewall. Abnormalities of the vaginal wall fascial tissues may play a minor role.

Vestibular evoked myogenic potential (Vemp): evaluation of responses in normal subjects.

PubMed

Felipe, Lilian; Santos, Marco Aurélio Rocha; Gonçalves, Denise Utsch

2008-01-01

the Vestibular Evoked Myogenic Potential (Vemp) is formed by myogenic neurophysiologic responses activated by high-intensity sound stimulation. The response is registered through surface electromyography of the cervical muscles during muscle contraction. The acoustic stimuli activate the saccular macula, the vestibular inferior nerve and the pathways related to the vestibule-spinal descendant nerves. to describe Vemp parameters in a normal population. thirty adults, 13 men and 17 women with no otoneurological complaints were selected. The stimuli were 200 tone burst, with a frequency of 1Hz and intensity of 118 dB Na, band-pass filter ranging from 10Hz to 1500Hz. The first potential biphasic P13-N23 wave was analyzed. no significant difference was observed between the sides of stimulation in terms of latency and amplitude. However, a statistically significant difference was found for amplitude between genders. Vemp demonstrated to be a reliable instrument in the clinical assessment of the vestibular function.

Physiology of the motor cortex in polio survivors.

PubMed

Lupu, Vitalie D; Danielian, Laura; Johnsen, Jacqueline A; Vasconcelos, Olavo M; Prokhorenko, Olga A; Jabbari, Bahman; Campbell, William W; Floeter, Mary Kay

2008-02-01

We hypothesized that the corticospinal system undergoes functional changes in long-term polio survivors. Central motor conduction times (CMCTs) to the four limbs were measured in 24 polio survivors using transcranial magnetic stimulation (TMS). Resting motor thresholds and CMCTs were normal. In 17 subjects whose legs were affected by polio and 13 healthy controls, single- and paired-pulse TMS was used to assess motor cortex excitability while recording from tibialis anterior (TA) muscles at rest and following maximal contraction until fatigue. In polio survivors the slope of the recruitment curve was normal, but maximal motor evoked potentials (MEPs) were larger than in controls. MEPs were depressed after fatiguing exercise. Three patients with central fatigue by twitch interpolation had a trend toward slower recovery. There was no association with symptoms of post-polio syndrome. These changes occurring after polio may allow the motor cortex to activate a greater proportion of the motor neurons innervating affected muscles.

Assessment of the rotation motion at the papillary muscle short-axis plane with normal subjects by two-dimensional speckle tracking imaging: a basic clinical study.

PubMed

Ni, Xian-Da; Huang, Jun; Hu, Yuan-Ping; Xu, Rui; Yang, Wei-Yu; Zhou, Li-Ming

2013-01-01

The aim of this study was to observe the rotation patterns at the papillary muscle plane in the Left Ventricle(LV) with normal subjects using two-dimensional speckle tracking imaging(2D-STI). We acquired standard of the basal, the papillary muscle and the apical short-axis images of the LV in 64 subjects to estimate the LV rotation motion by 2D-STI. The rotational degrees at the papillary muscle short-axis plane were measured at 15 different time points in the analysis of two heart cycles. There were counterclockwise rotation, clockwise rotation, and counterclockwise to clockwise rotation at the papillary muscle plane in the LV with normal subjects, respectively. The ROC analysis of the rotational degrees was performed at the papillary muscle short-axis plane at the peak LV torsion for predicting whether the turnaround point of twist to untwist motion pattern was located at the papillary muscle level. Sensitivity and specificity were 97% and 67%, respectively, with a cut-off value of 0.34°, and an area under the ROC curve of 0.8. At the peak LV torsion, there was no correlation between the rotational degrees at the papillary muscle short-axis plane and the LVEF in the normal subjects(r = 0.000, p = 0.998). In the study, we conclude that there were three rotation patterns at the papillary muscle short-axis levels, and the transition from basal clockwise rotation to apical counterclockwise rotation is located at the papillary muscle level.

Deletion of Galgt2 (B4Galnt2) Reduces Muscle Growth in Response to Acute Injury and Increases Muscle Inflammation and Pathology in Dystrophin-Deficient Mice

PubMed Central

Xu, Rui; Singhal, Neha; Serinagaoglu, Yelda; Chandrasekharan, Kumaran; Joshi, Mandar; Bauer, John A.; Janssen, Paulus M.L.; Martin, Paul T.

2016-01-01

Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2−/−mdx). Galgt2−/− mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice. PMID:26435413

Complex impairment of IA muscle proprioceptors following traumatic or neurotoxic injury.

PubMed

Vincent, Jacob A; Nardelli, Paul; Gabriel, Hanna M; Deardorff, Adam S; Cope, Timothy C

2015-08-01

The health of primary sensory afferents supplying muscle has to be a first consideration in assessing deficits in proprioception and related motor functions. Here we discuss the role of a particular proprioceptor, the IA muscle spindle proprioceptor in causing movement disorders in response to either regeneration of a sectioned peripheral nerve or damage from neurotoxic chemotherapy. For each condition, there is a single preferred and widely repeated explanation for disability of movements associated with proprioceptive function. We present a mix of published and preliminary findings from our laboratory, largely from in vivo electrophysiological study of treated rats to demonstrate newly discovered IA afferent defects that seem likely to make important contributions to movement disorders. First, we argue that reconnection of regenerated IA afferents with inappropriate targets, although often repeated as the reason for lost stretch-reflex contraction, is not a complete explanation. We present evidence that despite successful recovery of stretch-evoked sensory signaling, peripherally regenerated IA afferents retract synapses made with motoneurons in the spinal cord. Second, we point to evidence that movement disability suffered by human subjects months after discontinuation of oxaliplatin (OX) chemotherapy for some is not accompanied by peripheral neuropathy, which is the acknowledged primary cause of disability. Our studies of OX-treated rats suggest a novel additional explanation in showing the loss of sustained repetitive firing of IA afferents during static muscle stretch. Newly extended investigation reproduces this effect in normal rats with drugs that block Na(+) channels apparently involved in encoding static IA afferent firing. Overall, these findings highlight multiplicity in IA afferent deficits that must be taken into account in understanding proprioceptive disability, and that present new avenues and possible advantages for developing effective treatment. Extending the study of IA afferent deficits yielded the additional benefit of elucidating normal processes in IA afferent mechanosensory function. © 2015 Anatomical Society.

Fetal myosin immunoreactivity in human dystrophic muscle.

PubMed

Schiaffino, S; Gorza, L; Dones, I; Cornelio, F; Sartore, S

1986-01-01

We report immunofluorescence observations on normal and dystrophic human muscle using an antibody (anti-bF) raised against bovine fetal myosin and specific for fetal myosin heavy chains. In rat skeletal muscle, anti-bF was previously found to react selectively with myosin isoforms expressed during fetal and early postnatal development and in regenerating muscles. Anti-bF stained most fibers in human fetal and neonatal muscle, whereas only nuclear chain fibers of muscle spindles were labeled in normal adult muscle. In muscle biopsies from patients with Duchenne's muscular dystrophy, numerous extrafusal fibers were stained: some were small regenerating fibers, others were larger fibers presumably resulting from previous regenerative events. Fetal myosin immunoreactivity in Duchenne's dystrophy appears to reflect the reexpression of fetal-specific myosin isoforms and provides a new valuable tool for identifying regenerating fibers and following their destiny in dystrophic muscle.

Anabolic androgenic steroid-induced Takotsubo cardiomyopathy

PubMed Central

Sella, Gianluigi; Bellanti, Giancarlo; Margheri, Massimo

2015-01-01

Anabolic steroid abuse, aimed at increasing muscle mass, has been growing in recent years. We describe a case of a 25-year-old bodybuilder who, after taking nandrolone and stanozolol, presented with Takotsubo syndrome. The angiography showed a normal coronary anatomy with the absence of stenosis. The left ventricular function was completely normalised after 1 week. PMID:25804946

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with chronic cough and preserved muscle stretch reflexes: evidence for selective sparing of afferent Ia fibres.

PubMed

Infante, Jon; García, Antonio; Serrano-Cárdenas, Karla M; González-Aguado, Rocío; Gazulla, José; de Lucas, Enrique M; Berciano, José

2018-06-01

The aim of this study was to describe five patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) with chronic cough and preserved limb muscle stretch reflexes. All five patients were in the seventh decade of age, their gait imbalance having been initiated in the fifth decade. In four patients cough antedated gait imbalance between 15 and 29 years; cough was spasmodic and triggered by variable factors. Established clinical picture included severe hypopallesthesia predominating in the lower limbs with postural imbalance, and variable degree of cerebellar axial and appendicular ataxia, dysarthria and horizontal gaze-evoked nystagmus. Upper- and lower-limb tendon jerks were preserved, whereas jaw jerk was absent. Vestibular function testing showed bilateral impairment of the vestibulo-ocular reflex. Nerve conduction studies demonstrated normal motor conduction parameters and absence or severe attenuation of sensory nerve action potentials. Somatosensory evoked potentials were absent or severely attenuated. Biceps and femoral T-reflex recordings were normal, while masseter reflex was absent or attenuated. Sympathetic skin responses were normal. Cranial MRI showed vermian and hemispheric cerebellar atrophy predominating in lobules VI, VII and VIIa. We conclude that spasmodic cough may be an integral part of the clinical picture in CANVAS, antedating the appearance of imbalance in several decades and that sparing of muscle spindle afferents (Ia fibres) is probably the pathophysiological basis of normoreflexia.

Mesenchymal Stromal Cells for Sphincter Regeneration: Role of Laminin Isoforms upon Myogenic Differentiation

PubMed Central

Seeger, Tanja; Hart, Melanie; Patarroyo, Manuel; Rolauffs, Bernd; Aicher, Wilhelm K.; Klein, Gerd

2015-01-01

Multipotent mesenchymal stromal cells (MSCs) are well known for their tri-lineage potential and ability to differentiate in vitro into osteogenic, chondrogenic or adipogenic lineages. By selecting appropriate conditions MSCs can also be differentiated in vitro into the myogenic lineage and are therefore a promising option for cell-based regeneration of muscle tissue such as an aged or damaged sphincter muscle. For the differentiation into the myogenic lineage there is still a need to evaluate the effects of extracellular matrix proteins such as laminins (LM) which are crucial for different stem cell types and for normal muscle function. The laminin family consists of 16 functionally different isoforms with LM-211 being the most abundant isoform of adult muscle tissues. In the sphincter tissue a strong expression of the isoforms LM-211/221, LM-411/421 and LM-511/521 can be detected in the different cell layers. Bone marrow-derived MSCs in culture, however, mainly express the isoforms LM-411 and LM-511, but not LM-211. Even after myogenic differentiation, LM-211 can hardly be detected. All laminin isoforms tested (LM-211, LM-411, LM-511 and LM-521) showed a significant inhibition of the proliferation of undifferentiated MSCs but, with the exception of LM-521, they had no influence on the proliferation of MSCs cultivated in myogenic medium. The strongest cellular adhesion of MSCs was to LM-511 and LM-521, whereas LM-211 was only a weakly-adhesive substrate for MSCs. Myogenic differentiation of MSCs even reduced the interaction with LM-211, but it did not affect the interaction with LM-511 and LM-521. Since during normal myogenesis the latter two isoforms are the major laminins surrounding developing myogenic progenitors, α5 chain-containing laminins are recommended for further improvements of myogenic differentiation protocols of MSCs into smooth muscle cells. PMID:26406476

Detection of ultrastructural changes in genetically altered and exercised skeletal muscle using PS-OCT

NASA Astrophysics Data System (ADS)

Pasquesi, James J.; Schlachter, Simon C.; Boppart, Marni D.; Chaney, Eric; Kaufman, Stephen J.; Boppart, Stephen A.

2006-02-01

Birefringence of skeletal muscle has been associated with the ultrastructure of individual sarcomeres, specifically the arrangement of A-bands corresponding to the thick myosin filaments. Murine skeletal muscle (gastrocnemius) was imaged with a fiber-based PS-OCT imaging system to determine the level of birefringence present in the tissue under various conditions. In addition to muscle controls from wild-type mice, muscle from abnormal mice included: genetically-modified (mdx) mice which model human muscular dystrophy, transgenic mice exhibiting an overexpression of integrin (α7β1), and transgenic integrin (α7β1)knockout mice. Comparisons were also made between rested and exercised muscles to determine the effects of exercise on muscle birefringence for each of these normal and abnormal conditions. The PS-OCT images revealed that the presence of birefringence was similar in the rested muscle with dystrophy-like features (i.e., lacking the structural protein dystrophin - mdx) and in the integrin (α7β1)knockout muscle when compared to the normal (wild-type) control. However, exercising these abnormal muscle tissues drastically reduced the presence of birefringence detected by the PS-OCT system. The muscle exhibiting an overexpression of integrin (α7β1) remained heavily birefringent before and after exercise, similar to the normal (wild-type) muscle. These results suggest that there is a distinct relationship between the degree of birefringence detected using PS-OCT and the sarcomeric ultrastructure present within skeletal muscle.

A Comparison of a Maximum Exertion Method and a Model-Based, Sub-Maximum Exertion Method for Normalizing Trunk EMG

PubMed Central

Cholewicki, Jacek; van Dieën, Jaap; Lee, Angela S.; Reeves, N. Peter

2011-01-01

The problem with normalizing EMG data from patients with painful symptoms (e.g. low back pain) is that such patients may be unwilling or unable to perform maximum exertions. Furthermore, the normalization to a reference signal, obtained from a maximal or sub-maximal task, tends to mask differences that might exist as a result of pathology. Therefore, we presented a novel method (GAIN method) for normalizing trunk EMG data that overcomes both problems. The GAIN method does not require maximal exertions (MVC) and tends to preserve distinct features in the muscle recruitment patterns for various tasks. Ten healthy subjects performed various isometric trunk exertions, while EMG data from 10 muscles were recorded and later normalized using the GAIN and MVC methods. The MVC method resulted in smaller variation between subjects when tasks were executed at the three relative force levels (10%, 20%, and 30% MVC), while the GAIN method resulted in smaller variation between subjects when the tasks were executed at the three absolute force levels (50 N, 100 N, and 145 N). This outcome implies that the MVC method provides a relative measure of muscle effort, while the GAIN-normalized EMG data gives an estimate of the absolute muscle force. Therefore, the GAIN-normalized EMG data tends to preserve the EMG differences between subjects in the way they recruit their muscles to execute various tasks, while the MVC-normalized data will tend to suppress such differences. The appropriate choice of the EMG normalization method will depend on the specific question that an experimenter is attempting to answer. PMID:21665489

Normalized knee-extension strength or leg-press power after fast-track total knee arthroplasty: which measure is most closely associated with performance-based and self-reported function?

PubMed

Aalund, Peter K; Larsen, Kristian; Hansen, Torben B; Bandholm, Thomas

2013-02-01

To investigate which of the 2 muscle-impairment measures for the operated leg, normalized knee extension strength or leg press power, was most closely associated with performance-based and self-reported measures of function shortly after total knee arthroplasty (TKA). Cross-sectional, exploratory study. Laboratory at a regional hospital. Individuals (N=39) with an average age ± SD of 65.5±10.3 years, who all had unilateral TKA 28 days prior. None. The patients performed maximal isometric knee extensions and dynamic leg presses to determine their body-mass normalized knee extension strength and leg press power, respectively. The 10-meter fast speed walking- and 30-second chair stand tests were used to determine performance-based function, while the Western Ontario and McMaster Universities Osteoarthritis Index and Oxford Knee Scores were used to determine self-reported function. Normalized leg press power was more closely associated with both performance-based (r=.82, P<.001) and self-reported (r=.48, P=.002) measures of function compared with normalized knee extension strength (r=.51, P=.001 and r=.39, P=.015, respectively). Normalized leg press power was more closely associated with both performance-based and self-reported function early after TKA than normalized knee extension strength. It may be explained by the fact that performance-based measures of function are typically closed kinetic chain tasks, such as walking or rising from a chair, and self-reported measures of function typically include questions that address perceived difficulty with performing these same tasks. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Connexin 39.9 Protein Is Necessary for Coordinated Activation of Slow-twitch Muscle and Normal Behavior in Zebrafish*

PubMed Central

Hirata, Hiromi; Wen, Hua; Kawakami, Yu; Naganawa, Yuriko; Ogino, Kazutoyo; Yamada, Kenta; Saint-Amant, Louis; Low, Sean E.; Cui, Wilson W.; Zhou, Weibin; Sprague, Shawn M.; Asakawa, Kazuhide; Muto, Akira; Kawakami, Koichi; Kuwada, John Y.

2012-01-01

In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for myogenesis. Although gap junctions were once believed to be absent from differentiated skeletal muscle in mammals, recent studies in teleosts revealed that differentiated muscle does express connexins and is electrically coupled, at least at the larval stage. These findings raised questions regarding the functional significance of gap junctions in differentiated muscle. Our analysis of gap junctions in muscle began with the isolation of a zebrafish motor mutant that displayed weak coiling at day 1 of development, a behavior known to be driven by slow-twitch muscle (slow muscle). We identified a missense mutation in the gene encoding Connexin 39.9. In situ hybridization found connexin 39.9 to be expressed by slow muscle. Paired muscle recordings uncovered that wild-type slow muscles are electrically coupled, whereas mutant slow muscles are not. The further examination of cellular activity revealed aberrant, arrhythmic touch-evoked Ca2+ transients in mutant slow muscle and a reduction in the number of muscle fibers contracting in response to touch in mutants. These results indicate that Connexin 39.9 facilitates the spreading of neuronal inputs, which is irregular during motor development, beyond the muscle cells and that gap junctions play an essential role in the efficient recruitment of slow muscle fibers. PMID:22075003

Growth hormone transgenesis in coho salmon disrupts muscle immune function impacting cross-talk with growth systems.

PubMed

Alzaid, Abdullah; Kim, Jin-Hyoung; Devlin, Robert H; Martin, Samuel A M; Macqueen, Daniel J

2018-04-26

Suppression of growth during infection may aid resource allocation towards effective immune function. Past work supporting this hypothesis in salmonid fish revealed an immune-responsive regulation of the insulin-like growth factor (IGF) system, an endocrine pathway downstream of growth hormone (GH). Skeletal muscle is the main target for growth and energetic storage in fish, yet little is known about how its growth is regulated during an immune response. We addressed this knowledge gap by characterizing muscle immune responses in size-matched coho salmon ( Oncorhynchus kisutch ) achieving different growth rates. We compared a wild-type strain with two GH transgenic groups from the same genetic background achieving either maximal or suppressed growth, a design separating GH's direct effects from its influence on growth rate and nutritional state. Fish were sampled 30h post-injection with PBS (control) or mimics of bacterial or viral infection. We quantified mRNA expression levels for genes from the GH, GH receptor, IGF hormone, IGF1 receptor and IGF-binding protein families, along with immune genes involved in inflammatory or antiviral responses and muscle growth status marker genes. We demonstrate dampened immune function in GH transgenics compared to wild-type. The muscle of GH transgenics achieving rapid growth showed no detectable antiviral response, coupled with evidence of a constitutive inflammatory state. GH and IGF system gene expression was strongly altered by GH transgenesis and fast growth, both for baseline expression and responses to immune stimulation. Thus, GH transgenesis strongly disrupts muscle immune status and normal GH and IGF system expression responses to immune stimulation. © 2018. Published by The Company of Biologists Ltd.

Localization of survival motor neuron protein in human apoptotic-like and regenerating muscle fibers, and neuromuscular junctions.

PubMed

Broccolini, A; Engel, W K; Askanas, V

1999-06-03

Mutations in the gene encoding survival motor neuron (SMN) protein are found in > 98% of patients with autosomal-recessive spinal muscular atrophy. We investigated the possible role of SMN in normal and abnormal human muscle by immunostaining biopsies of 20 patients with various neuromuscular diseases using monoclonal antibodies against SMN. SMN was strongly expressed cytoplasmically in chronic peripheral neuropathies, in about 80% of chronically denervated, very atrophic muscle fibers containing clumps of TUNEL-positive pyknotic nuclei: about 60% of those fibers also had cytoplasmic Bcl-2 and Bax immunoreactivity. In regenerating muscle fibers of various myopathies SMN co-localized with desmin, Bcl-2 and Bax; it was also present at the postsynaptic domain of normal human neuromuscular junctions. Thus, SMN may play a role in normal and pathological processes of adult human muscle fibers.

Bilateral experimental neck pain reorganize axioscapular muscle coordination and pain sensitivity.

PubMed

Christensen, S W; Hirata, R P; Graven-Nielsen, T

2017-04-01

Neck pain is a large clinical problem where reorganized trunk and axioscapular muscle activities have been hypothesised contributing to pain persistence and pain hypersensitivity. This study investigated the effects of bilateral experimental neck pain on trunk and axioscapular muscle function and pain sensitivity. In 25 healthy volunteers, bilateral experimental neck pain was induced in the splenius capitis muscles by hypertonic saline injections. Isotonic saline was used as control. In sitting, subjects performed slow, fast and slow-resisted unilateral arm movements before, during and after injections. Electromyography (EMG) was recorded from eight shoulder and trunk muscles bilaterally. Pressure pain thresholds (PPTs) were assessed bilaterally at the neck, head and arm. Data were normalized to the before-measures. Compared with control and post measurements, experimental neck pain caused (1) decreased EMG activity of the ipsilateral upper trapezius muscles during all but slow-resisted down movements (p < 0.001), and (2) increased EMG activity in the ipsilateral erector spinae muscle during slow and fast movements (p < 0.02), and in the contralateral erector spinae muscle during all but fast up and slow-resisted down movements (p < 0.007). The PPTs in the painful condition increased at the head and arm compared with post measurements and the control condition (p < 0.001). In the post-pain condition, the neck PPT was decreased compared with the control condition (p < 0.001). Acute bilateral neck pain reorganized axioscapular and trunk muscle activity together with local hyperalgesia and widespread hypoalgesia indicating that acute neck pain immediately affects trunk and axioscapular function which may affect both assessment and treatment. Bilateral clinical neck pain alters axioscapular muscle coordination but only effects of unilateral experimental neck pain has been investigated. Bilateral experimental neck pain causes task-dependent reorganized axioscapular and trunk muscle activity in addition to widespread decrease in pressure pain sensitivity. © 2016 European Pain Federation - EFIC®.

Functional characterization of muscle fibres from patients with chronic fatigue syndrome: case-control study.

PubMed

Pietrangelo, T; Toniolo, L; Paoli, A; Fulle, S; Puglielli, C; Fanò, G; Reggiani, C

2009-01-01

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Although immunological and psychological aspects are present, symptoms related to skeletal muscles, such as muscle soreness, fatigability and increased lactate accumulation, are prominent in CFS patients. In this case-control study, the phenotype of the same biopsy samples was analyzed by determining i) fibre-type proportion using myosin isoforms as fibre type molecular marker and gel electrophoresis as a tool to separate and quantify myosin isoforms, and ii) contractile properties of manually dissected, chemically made permeable and calcium-activated single muscle fibres. The results showed that fibre-type proportion was significantly altered in CSF samples, which showed a shift from the slow- to the fast-twitch phenotype. Cross sectional area, force, maximum shortening velocity and calcium sensitivity were not significantly changed in single muscle fibres from CSF samples. Thus, the contractile properties of muscle fibres were preserved but their proportion was changed, with an increase in the more fatigue-prone, energetically expensive fast fibre type. Taken together, these results support the view that muscle tissue is directly involved in the pathogenesis of CSF and it might contribute to the early onset of fatigue typical of the skeletal muscles of CFS patients.

An EMG-CT method using multiple surface electrodes in the forearm.

PubMed

Nakajima, Yasuhiro; Keeratihattayakorn, Saran; Yoshinari, Satoshi; Tadano, Shigeru

2014-12-01

Electromyography computed tomography (EMG-CT) method is proposed for visualizing the individual muscle activities in the human forearm. An EMG conduction model was formulated for reverse-estimation of muscle activities using EMG signals obtained with multi surface electrodes. The optimization process was calculated using sequential quadratic programming by comparing the estimated EMG values from the model with the measured values. The individual muscle activities in the deep region were estimated and used to produce an EMG tomographic image. For validation of the method, isometric contractions of finger muscles were examined for three subjects, applying a flexion load (4.9, 7.4 and 9.8 N) to the proximal interphalangeal joint of the middle finger. EMG signals in the forearm were recorded during the tasks using multiple surface electrodes, which were bound around the subject's forearm. The EMG-CT method illustrates the distribution of muscle activities within the forearm. The change in amplitude and area of activated muscles can be observed. The normalized muscle activities of all three subjects appear to increase monotonically with increases in the load. Kinesiologically, this method was able to estimate individual muscle activation values and could provide a novel tool for studying hand function and development of an examination for evaluating rehabilitation. Copyright © 2014 Elsevier Ltd. All rights reserved.