Healthy Adult Muscle Research Articles

Absence of RAGE in an animal experimental model of Duchenne muscular dystrophy results in reduced muscle necrosis and inflammation

Duchenne muscular dystrophy (DMD) is a lethal X-linked neuromuscular disorder characterized by progressive muscle degeneration due to lack of dystrophin, a protein essential for the integrity of sarcolemma during contraction. Chronic inflammation is a hallmark of muscles in DMD subjects, and contributes to progressive muscle wasting. RAGE (receptor for advanced glycation end-products) is a multiligand receptor of the immunoglobulin superfamily involved in physiological and pathological processes including inflammation and myogenesis [1]. While absent in healthy adult muscle tissue, RAGE is expressed in regenerating myofibers during muscle regeneration [2,3], in dystrophic muscles and activated immune cells. To have information about the role of RAGE in the pathophysiology of DMD we generated a double mutant mouse lacking dystrophin and RAGE (mdx/Ager–/– mouse) by cross-breeding dystrophic (mdx) mice with RAGE-null (Ager-/-) mice. Comparison of Quadriceps femoris of mdx and mdx/Ager–/– mice at different ages (i.e., 2, 3, 4 and 5 weeks, and 6 and 12 months of age) showed that the absence of RAGE in dystrophic mice did not affect the onset of the pathology. However, compared with age-matched mdx mice, muscles of 5 week- and 6 and 12 month-old mdx/Ager–/– mice showed i) significantly reduced numbers of necrotic myofibers, ii) a shift towards higher values of the cross-sectional areas (CSA) of myofibers, which was also evident in regenerating (centrally-nucleated) myofibers, and iii) reduced areas of immune cell infiltrate. The expression of MAC3, a marker of activated macrophages, was strongly reduced in muscles of mdx/Ager–/– mice compared with mdx mice. Moreover, muscles of mdx/Ager–/– mice exhibited significantly reduced PAX7+ve and myogenin+ve cell numbers, suggesting a reduced recruitment of muscle precursor cells and more efficient regeneration in dystrophic mice lacking RAGE. Our results suggest that RAGE may sustain inflammatory and degenerative processes in dystrophic muscles, and the inhibition of its expression/activity might represent a potential therapeutic approach in DMD patients.This work was supported by grants from MIUR 2012N8YJC3, AFM-Telethon 16812 and Fondazione CRP 2015.0325.021.

Continuous passive movement does not influence motor maps in healthy adults

Hand weakness following stroke is often associated with a reduced representation of the hand in the primary motor cortex. Meaningful sensory input can induce sensorimotor reorganization in the brain, but the after-effect of continuous passive motion (CPM) on the cortical representation is unknown. The purpose of this study was to determine whether repeated sessions of continuous passive movement of the thumb induce a lasting increase in the motor cortical representation of a thumb muscle in healthy adults. Thirteen right-handed healthy adults (mean age 24.3 ± 4.3 years) participated in the study. Single-pulse Transcranial Magnetic Stimulation (TMS) was delivered over the motor area of the target muscle (abductor pollicis brevis) before and/or after a thirty minute session of thumb CPM administered on three consecutive days. TMS was also delivered 5 days after cessation of the CPM intervention. The response to TMS (motor evoked potential) was recorded in the target muscle with surface EMG. Resting motor threshold (RMT), motor evoked potential amplitude at a specified intensity, and the area and volume of the cortical representation of the target muscle were measured. Thumb CPM had no significant effect on TMS parameters (p > 0.05 all measures) and performance of an attention task remained unchanged within and across CPM sessions. The results suggest that three sessions of repetitive passive thumb movement is not sufficient to induce a change in the cortical representation of the thumb and is unlikely to reverse the decreased representation of the affected hand following stroke.

Intrinsic and extrinsic mechanisms regulating satellite cell function.

Muscle stem cells, termed satellite cells, are crucial for skeletal muscle growth and regeneration. In healthy adult muscle, satellite cells are quiescent but poised for activation. During muscle regeneration, activated satellite cells transiently re-enter the cell cycle to proliferate and subsequently exit the cell cycle to differentiate or self-renew. Recent studies have demonstrated that satellite cells are heterogeneous and that subpopulations of satellite stem cells are able to perform asymmetric divisions to generate myogenic progenitors or symmetric divisions to expand the satellite cell pool. Thus, a complex balance between extrinsic cues and intrinsic regulatory mechanisms is needed to tightly control satellite cell cycle progression and cell fate determination. Defects in satellite cell regulation or in their niche, as observed in degenerative conditions such as aging, can impair muscle regeneration. Here, we review recent discoveries of the intrinsic and extrinsic factors that regulate satellite cell behaviour in regenerating and degenerating muscles.

Afferent inhibition and cortical silent periods in shoulder primary motor cortex and effect of a suprascapular nerve block in people experiencing chronic shoulder pain

ObjectiveTo characterise short afferent inhibition (SAI) and the cortical silent period (CSP) in the primary motor cortex representations of the infraspinatus muscle in healthy adults and people experiencing chronic shoulder pain, to determine the impact of a suprascapular nerve block (SSNB). MethodsNeurophysiological measures were obtained in 18 controls and 8 patients with chronic shoulder pain, pre and post SSNB and 1week later. Pain intensity was assessed by a visual analogue scale. ResultsSAI was apparent in controls (all P<0.03) and a CSP was observed which reduced in the presence of SAI (all P<0.0001). Compared to controls, shoulder pain patients demonstrated higher active motor threshold (P=0.046), less SAI (P=0.044), a longer CSP (P=0.048) and less modulation of the CSP by SAI (P=0.045). Higher motor thresholds were related to higher pain scores (P=0.009). The SSNB immediately restored SAI (P=0.013), with a positive relationship between increased SAI and reduced pain (P=0.031). The SSNB further reduced modulation of CSP by SAI at 1week post injection (P=0.006). ConclusionsSAI and the CSP were present and demonstrated robust interaction in controls, which was aberrant in patients. The SSNB transiently restored SAI but had no effect on the CSP; however CSP modulation by SAI was further attenuated 1week post injection. SignificanceThe current findings improve understanding of the neurophysiology of the shoulder motor cortex and its modulation by chronic pain. The effect of SSNB in shoulder pain patients should be interpreted with caution until proven in a larger population. Interventions that target intracortical inhibition might increase efficacy in people with chronic shoulder pain.

Effect of workstation height and distance on upper extremity muscle activity during repetitive below-the-knee assembly work.

To determine the activity of the upper trapezius, serratus anterior, anterior deltoid, biceps brachii. and lower trapezius muscles in healthy adults during below-the-knee assembly work. Fifteen right-handed male subjects participated in this study. The electrical activities, measured by EMG, of the right upper trapezius, serratus anterior, anterior deltoid, biceps brachii. and lower trapezius were measured during below-the-knee assembly work at four workstations of varying height and distance from the participant (workstation 1, below-the-knee assembly work with a height of 15 cm above the floor and a reach distance of 30 cm; workstation 2, height of 15 cm and distance of 45 cm; workstation 3, height of 30 cm and distance of 30 cm; workstation 4, height of 30 cm and distance of 45 cm). Muscle activity at the four workstations was represented as a percentage of the reference voluntary isometric contraction (RVIC). Height: Upper and lower trapezius activity increased significantly during below the knee assembly work as height above the floor increased. The activities of the serratus anterior and biceps brachii muscles increased significantly during low-height below-the-knee assembly work. Distance: The activities of the upper trapezius, serratus anterior, anterior deltoid and biceps brachii increased significantly during below-the-knee assembly work at a far distance (45 cm). The lower trapezius muscle activity increased significantly during below-the-knee assembly work at a close distance (30 cm). Below-knee workers should engage in work close to themselves, since distance appears to be a stronger risk factor for injury than height above the floor.

Does Neuromuscular Electrical Stimulation Improve Muscular Strength Gains of the Vastus Medialis Muscle

Background: Neuromuscular electrical stimulation is currently being used for treatment in rehabilitation situations. Studies indicate that neuromuscular electrical stimulation increases muscle strength in weakened muscles; however few studies have examined the effect of neuromuscular electrical stimulation and muscle strength on healthy muscles or compared combinations of NMES and exercise. Objective: To compare the effectiveness of three methods in strengthening the vastus medialis muscle in healthy adults. Methods: Fifteen healthy male participants between the ages of 18-25 participated in this randomized repeated measures study. The participants were randomly assigned into three (neuromuscular electrical stimulation, neuromuscular electrical stimulation + exercise or exercise only) groups of five. They performed eccentric stepdowns for 5 minutes, 3 times a week for 4 weeks. The force of the vastus medialis muscle was measured with an isometric leg extension at 60 degrees, using the Biodex force dynamometer (Model 820-110). This test was performed a total of three times on each participant: pre-testing, mid-testing and final-testing. Results: A two-way analysis of variance and a post hoc Scheffe’s test revealed a significant test interaction difference between group and test time. In the neuromuscular electrical stimulation group the mean force from the pre-test (121.4Nm), to the final-test (165.8Nm) significantly increased compared to the pre and post-tests in the other groups. Conclusion: Neuromuscular electrical stimulation training was most effective in increasing muscle strength of the vastus medialis muscle in healthy participants after four weeks.

건강한 성인의 슬개건 반사 시 무릎 감쇠효과를 고려한 대퇴사두근의 근력 및 근활성도 예측

Most analytical models of the human body have focused on conscious responses. A patellar tendon reflex, a representative example of spinal reflexes, occurs without a neural command. Muscle forces and activation of the quadriceps femoris muscles in healthy adults during patellar tendon reflex are identified in this study. The model is assumed to move in the sagittal plane, and the thigh and the trunk are assumed to be fixed in a sitting position so that the shank can move similar to a pendulum. The knee joint is modeled as a revolute joint, and the ankle joint is modeled as a fixed joint so that the shank and the foot can be regarded as one rigid body. Muscle forces are calculated following the inverse dynamic approach. Kinematic data obtained from an experiment (Mamizuka, 2007) are used as input data. Muscle activations are identified using a Hill-type muscle model. The obtained simulation results are compared with experimental results for validating the model and the underlying assumptions. † Corresponding Author, hhyoo@hanyang.ac.kr C 2014 The Korean Society of Mechanical Engineers

Aging Decreases the Strength of Suprahyoid Muscles Involved in Swallowing Movements

Swallowing disorders are common in the elderly, and aging is a factor that affects swallowing function. The elevation of the hyoid bone is important for swallowing and is controlled by the suprahyoid muscles. The hyoid and laryngeal elevation allows the bolus to enter the esophagus. The suprahyoid muscles, therefore, play an important role in swallowing. The effects of aging on suprahyoid muscle strength are unclear. In this study, we analyzed the effects of aging on suprahyoid muscle strength by comparing the jaw opening functions of healthy adults and elderly adults. The subjects were 150 healthy volunteers consisting of 76 adults aged < 70 years (38 men and 38 women; mean age, 48.8 ± 13.8 years; range, 23-69) and 74 elderly adults aged > 70 years (37 men and 37 women; mean age, 78.1 ± 4.8 years; range, 70-92). The jaw opening force (JOF) was measured with a jaw opening sthenometer and compared between the healthy adult and elderly groups. The mean JOF of healthy adults was about 10 kg in men and about 6 kg in women, which was significantly greater than the mean JOF of the healthy elderly subjects (about 7 kg in men and about 4 kg in women). The JOF of the men was significantly greater than that of the women in the healthy adult and elderly groups. We thus propose that aging decreases the strength of suprahyoid muscles in healthy adults. The swallowing function may decrease even in healthy adults, aged over 70 years.

Botulinum toxin within the muscle – MRI follow up in children with spastic cerebral palsy supports neurogenic atrophy in healthy muscle one year after a single injection of botulinum toxin

Botulinum toxin is widely used as a therapeutic option to reduce (multi-) focal muscle hypertension as well as for cosmetic indications. Recommendations on reinjection intervals (3-12months) are based on clinical observation and basic science research using animal models. Morphologic long-term alterations following a single injection of botulinum toxin are scarce. With the development of short tau inversion recovery (STIR) sequences Magnetic resonance imaging (MRI) is able to detect neurogenic muscle atrophy over the course of time. The aim of this study was to investigate the neurogenic atrophy induced by a single injection of botulinum toxin in healthy adult muscle and the induced atrophy in primarily altered spastic muscle in children with cerebral palsy (CP).

Lumbar Paraspinal Muscle Activation During Back Extension Exercise On A New Home Exercise Device

Progressive resistance exercise on machines that stabilize the pelvis in the seated position is effective in improving lumbar extensor muscle function in healthy adults and symptoms in patients with low back pain. Existing lumbar extension machines with these features are not intended for home exercise programs, however. PURPOSE: To assess the lumbar paraspinal surface EMG activity during slow movement, full range of motion exercise on a new home exercise device. METHODS: 10 individuals (5M/5F, age 33.0+/−8.1 yr) in good general health performed lumbar extension exercise on the new home exercise device at 3 loads (1X, 1.25X, 1.5X bodyweight). Loads were increased by attaching metal plates to the device. At each load, 1 set of 3 repetitions was performed using a slow movement full range of motion protocol (i.e. 10 second concentric, 10 second eccentric). Exercise order was balanced among subjects. Surface EMG activity was collected from the L3/4 paraspinal region during exercise. The effect of exercise load and phase of movement on lumbar paraspinal surface EMG activity (normalized based on % of peak strength) was assessed with ANOVA and post hoc Tukey's procedure. RESULTS: No adverse events were reported. 30% (3/10) of subjects reported mild delayed onset muscle soreness in the low back. During full repetition exercise, group means for lumbar paraspinal surface EMG activity increased with load (1X: 34.9+/−16.0%; 1.25X: 42.1+/−11.8%: 1.5X: 47.1+/−9.8%; p < 0.05). 50% (5/10) of subjects did not display a progressive increase in EMG activity with exercise load. During the concentric phase, EMG activity increased from 1X to 1.25X (p < 0.05), but not from 1.25X to 1.5X (p > 0.05) (1X: 41.2+/−17.9%; 1.25X: 50.5+/−16.2%; 1.5X: 52.8+/−10.3%). During the eccentric phase, EMG activity increased with load (1X: 28.7+/−16.0%; 1.25X: 33.6+/−12.7%; 1.5X: 41.4+/−13.8%). CONCLUSION: Slow movement, full range of motion lumbar extension exercise on a new home exercise device safely activates the lumbar paraspinal muscles in healthy adults. Lumbar paraspinal surface EMG activity during exercise is variable among subjects and throughout the range of motion. Design modifications to the device may be needed to address this variability. Supported in part by a unrestricted research grant from MedX Corp, Altamonte Springs, FL.

Central fatigue of the first dorsal interosseous muscle during low‐force and high‐force sustained submaximal contractions

The aim of this study was to compare the extent of central fatigue in the first dorsal interosseous (FDI) muscle of healthy adults in low, moderate and high-force submaximal contractions. Nine healthy adults completed four experimental sessions where index finger abduction force was recorded during voluntary contractions and in response to brief trains (five pulses at 100 Hz) of electrical stimulation. The ability to maximally activate FDI under volition, or voluntary activation, and its change with sustained activity (central fatigue) was assessed using the twitch interpolation technique. The fatigue tasks consisted of continuous isometric index finger abduction contractions held until exhaustion at four target force levels: 30%, 45%, 60% and 75% of the maximal voluntary contraction. The main finding was the presence of central fatigue for the 30% task, but not for the three other fatigue tasks. The extent of central fatigue was also associated with changes in a measure reflecting the status of peripheral structures/mechanisms. It appears that central fatigue contributed to task failure for the lowest force fatigue task (30%), but not for the other (higher) contraction intensities.

Mitochondrial function, fibre types and ageing: new insights from human muscle in vivo

Mitochondrial changes are at the centre of a wide range of maladies, including diabetes, neurodegeneration and ageing‐related dysfunctions. Here we describe innovative optical and magnetic resonance spectroscopic methods that non‐invasively measure key mitochondrial fluxes, ATP synthesis and O2 uptake, to permit the determination of mitochondrial coupling efficiency in vivo (P/O: half the ratio of ATP flux to O2 uptake). Three new insights result. First, mitochondrial coupling can be measured in vivo with the rigor of a biochemical determination and provides a gold standard to define well‐coupled mitochondria (P/O ≈ 2.5). Second, mitochondrial coupling differs substantially among muscles in healthy adults, from values reflective of well‐coupled oxidative phosphorylation in a hand muscle (P/O = 2.7) to mild uncoupling in a leg muscle (P/O = 2.0). Third, these coupling differences have an important impact on cell ageing. We found substantial uncoupling and loss of cellular [ATP] in a hand muscle indicative of mitochondrial dysfunction with age. In contrast, stable mitochondrial function was found in a leg muscle, which supports the notion that mild uncoupling is protective against mitochondrial damage with age. Thus, greater mitochondrial dysfunction is evident in muscles with higher type II muscle fibre content, which may be at the root of the preferential loss of type II fibres found in the elderly. Our results demonstrate that mitochondrial function and the tempo of ageing varies among human muscles in the same individual. These technical advances, in combination with the range of mitochondrial properties available in human muscles, provide an ideal system for studying mitochondrial function in normal tissue and the link between mitochondrial defects and cell pathology in disease.

Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults

Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30-40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (-0.8 +/- 0.5 vs. +0.7 +/- 0.3 mg.kg(-1).min(-1), P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (-52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9). (31)P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r2 = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity.

Moment-generating capacity of upper limb muscles in healthy adults

Muscle strength and volume vary greatly among individuals. Maximum isometric joint moment, a standard measurement of strength, has typically been assessed in young, healthy subjects, whereas muscle volumes have generally been measured in cadavers. This has made it difficult to characterize the relationship between isometric strength and muscle size in humans. We measured maximum isometric moments about the shoulder, elbow, and wrist in 10 young, healthy subjects, ranging in size from a 20th percentile female to a 97th percentile male. The volumes of 32 upper limb muscles were determined from magnetic resonance images of these same subjects, and grouped according to their primary function. The maximum moments produced using the shoulder adductors (67.9±28.4 Nm) were largest, and were approximately 6.5(±1.2) times greater than those produced using the wrist extensors (10.2±4.6 Nm), which were smallest. While there were substantial differences in moment-generating capacity among these 10 subjects, moment significantly covaried with muscle volume of the appropriate functional group, explaining between 95% ( p<0.0001; shoulder adductors) and 68% ( p=0.004; wrist flexors) of the variation in the maximum isometric joint moments among subjects. While other factors, such as muscle moment arms or neural activation and coordination, can contribute to variation in strength among subjects, they either were relatively constant across these subjects compared to large differences in muscle volumes or they covaried with muscle volume. We conclude that differences in strength among healthy young adults are primarily a consequence of variation in muscle volume, as opposed to other factors.

Adductor pollicis muscle: a new anthropometric parameter.

To measure the thickness of adductor pollicis muscle in healthy adults. This measurement will be used as a nutritional anthropometric parameter in further studies. Four hundred and twenty-one healthy adults were studied, 209 men and 212 women, with ages ranging from 18 to 87 years, living in Rio de Janeiro. The adductor pollicis muscle was also studied in the human anatomy lab as well as in normal healthy volunteers using CAT scans and nuclear magnetic resonance imaging to ensure that only the adductor pollicis was included in measurement of muscle thickness with a Lange caliper. To standardize the measurement, the methodology was detailed, with subjects sitting with the dominant hand dangling over the homolateral thigh and the elbow bent at approximately a 90 degrees angle. The Lange caliper was applied at a pressure of 10 g/mm2, pinching the adductor pollicis muscle at the vertex of an imaginary angle between the thumb and the index finger. The average of 3 consecutive measurements was considered to be the muscle thickness. This study provides the first estimates of adductor pollicis thickness in normal healthy subjects as an anthropometric parameter. The normal values in the dominant hand for men were 12.5 +/- 2.8 mm (mean +/- SD), median 12 mm, and for women were 10.5 +/- 2.3 mm, median 10 mm.

Intracompartmental pressure, PO2, PCO2 and blood flow in the human skeletal muscle.

Measurement of PO2, PCO2, and blood flow in skeletal muscle could be a supplement to examination in clinical practice. Mass spectrometry was utilized to measure these parameters in the resting anterior tibial muscle of healthy adults. The partial pressures of oxygen and carbon dioxide were 21 +/- 3.6 and 46 +/- 2.5 Torr, respectively. The intracompartmental pressure was 8 +/- 1.1 Torr. The oxygen tension in muscle varied only slightly when arterial partial pressure was increased. The blood flow (tissue perfusion coefficient) estimated by washout of an inert gas was 5.4 +/- 0.8 ml/100 g/min. The results are in accordance with those from animal studies of skeletal muscle. The study demonstrates the feasibility of measuring PO2, PCO2, and blood flow in skeletal muscle by mass spectrometry.

Shoulder joint load and muscular activity during lifting : Arborelius UP, Ekholm J. Németh G, Svensson O, Nisell R. Scand J Rehab Med 1986;18:71–82

The aim of this study was to investigate load on shoulder joint and muscles in healthy adults during four different ways of lifting a moderate burden (12.8 kg) from floor to table level. The methods used were surface electrode EMG with linear envelope, and calculation of loading moments of force using a static biomechanical model. The shoulder load at the beginning of the lift was lowest for the straight knee lift. The peak load occurred in the late phase of all lifts. On completion of the lift, load and activation were considerably lower when the subject was allowed to step forward before putting the box down. The most activated shoulder muscles were the anterior and lateral parts of the deltoid, and the serratus anterior. Around 80% of the shoulder load moment was caused by the weight of the burden. Some 75% of maximum shoulder strength was required for lifting the burden.

One Method for Assessing the Effectiveness of Fast Brushing

The purposes of this study were to determine if fast brushing of the skin overlying a muscle is effective in increasing the sensitivity of the stretch reflex of that muscle and to detect the optimal rate and duration of brushing to elicit this effect in healthy adults. The stretch sensitivity of the right lateral gastrocnemius muscle was measured by EMG activity and force produced by the abrupt tap of the Achilles tendon before and after fast brushing. Peak-to-peak EMG and force from 10 taps were established. Eight different conditions (two control and six experimental brushing) were applied to 10 healthy adult subjects (age range, 30 to 46 years). The experimental conditions included rotary brushing at 5 Hz, 180 Hz, or 360 Hz for 5 seconds or at 5 Hz, 180 Hz, or 360 Hz for 30 seconds. Postbrushing taps began 30 seconds after the brush was turned off and continued every 5 minutes for 30 minutes. This method of fast brushing did not increase the stretch sensitivity of the muscle in healthy adults. Possible factors influencing the results of the study and recommendations for future studies are presented.