WorldWideScience

Sample records for vivo mechanical muscle

  1. In vivo passive mechanical behaviour of muscle fascicles and tendons in human gastrocnemius muscle-tendon units.

    Science.gov (United States)

    Herbert, Robert D; Clarke, Jillian; Kwah, Li Khim; Diong, Joanna; Martin, Josh; Clarke, Elizabeth C; Bilston, Lynne E; Gandevia, Simon C

    2011-11-01

    Ultrasound imaging was used to measure the length of muscle fascicles in human gastrocnemius muscles while the muscle was passively lengthened and shortened by moving the ankle. In some subjects the muscle belly 'buckled' at short lengths. When the gastrocnemius muscle-tendon unit was passively lengthened from its shortest in vivo length by dorsiflexing the ankle, increases in muscle-tendon length were not initially accompanied by increases in muscle fascicle lengths (fascicle length remained constant), indicating muscle fascicles were slack at short muscle-tendon lengths. The muscle-tendon length at which slack is taken up differs among fascicles: some fascicles begin to lengthen at very short muscle-tendon lengths whereas other fascicles remain slack over a large range of muscle-tendon lengths. This suggests muscle fascicles are progressively 'recruited' and contribute sequentially to muscle-tendon stiffness during passive lengthening of the muscle-tendon unit. Even above their slack lengths muscle fascicles contribute only a small part (tendon length. The contribution of muscle fascicles to muscle-tendon length increases with muscle length. The novelty of this work is that it reveals a previously unrecognised phenomenon (buckling at short lengths), posits a new mechanism of passive mechanical properties of muscle (recruitment of muscle fascicles), and confirms with high-resolution measurements that the passive compliance of human gastrocnemius muscle-tendon units is due largely to the tendon. It would be interesting to investigate if adaptations of passive properties of muscles are associated with changes in the distribution of muscle lengths at which fascicles fall slack.

  2. Magnetic resonance imaging assessment of mechanical interactions between human lower leg muscles in vivo.

    Science.gov (United States)

    Yaman, Alper; Ozturk, Cengizhan; Huijing, Peter A; Yucesoy, Can A

    2013-09-01

    Evidence on epimuscular myofascial force transmission (EMFT) was shown for undissected muscle in situ. We hypothesize that global length changes of gastrocnemius muscle-tendon complex in vivo will cause sizable and heterogeneous local strains within all muscles of the human lower leg. Our goal is to test this hypothesis. A method was developed and validated using high-resolution 3D magnetic resonance image sets and Demons nonrigid registration algorithm for performing large deformation analyses. Calculation of strain tensors per voxel in human muscles in vivo allowed quantifying local heterogeneous tissue deformations and volume changes. After hip and knee movement (Δ knee angle ≈ 25 deg) but without any ankle movement, local lengthening within m. gastrocnemius was shown to occur simultaneously with local shortening (maximally by +34.2% and -32.6%, respectively) at different locations. Moreover, similar local strains occur also within other muscles, despite being kept at constant muscle-tendon complex length. This is shown for synergistic m. soleus and deep flexors, as well as for antagonistic anterior crural and peroneal muscle groups: minimum peak lengthening and shortening equaled 23.3% and 25.54%, respectively despite global isometric conditions. These findings confirm our hypothesis and show that in vivo, muscles are in principle not independent mechanically.

  3. Amplified Mechanically Gated Currents in Distinct Subsets of Myelinated Sensory Neurons following In Vivo Inflammation of Skin and Muscle.

    Science.gov (United States)

    Weyer, Andy D; O'Hara, Crystal L; Stucky, Cheryl L

    2015-06-24

    Primary afferents are sensitized to mechanical stimuli following in vivo inflammation, but whether sensitization of mechanically gated ion channels contributes to this phenomenon is unknown. Here we identified two populations of murine A fiber-type sensory neurons that display markedly different responses to focal mechanical stimuli of the membrane based on their expression of calcitonin gene-related peptide (CGRP). Following inflammation of the hindpaw, myelinated, CGRP-positive neurons projecting to the paw skin displayed elevated mechanical currents in response to mechanical stimuli. Conversely, muscle inflammation markedly amplified mechanical currents in myelinated, CGRP-negative neurons projecting to muscle. These data show, for the first time, that mechanically gated currents are amplified following in vivo tissue inflammation, and also suggest that mechanical sensitization can occur in myelinated neurons after inflammation. Copyright © 2015 the authors 0270-6474/15/359456-07$15.00/0.

  4. The mechanical power output of the pectoralis muscle of cockatiel (Nymphicus hollandicus): the in vivo muscle length trajectory and activity patterns and their implications for power modulation.

    Science.gov (United States)

    Morris, Charlotte R; Askew, Graham N

    2010-08-15

    In order to meet the varying demands of flight, pectoralis muscle power output must be modulated. In birds with pectoralis muscles with a homogeneous fibre type composition, power output can be modulated at the level of the motor unit (via changes in muscle length trajectory and the pattern of activation), at the level of the muscle (via changes in the number of motor units recruited), and at the level of the whole animal (through the use of intermittent flight). Pectoralis muscle length trajectory and activity patterns were measured in vivo in the cockatiel (Nymphicus hollandicus) at a range of flight speeds (0-16 m s(-1)) using sonomicrometry and electromyography. The work loop technique was used to measure the mechanical power output of a bundle of fascicles isolated from the pectoralis muscle during simulated in vivo length change and activity patterns. The mechanical power-speed relationship was U-shaped, with a 2.97-fold variation in power output (40-120 W kg(-1)). In this species, modulation of neuromuscular activation is the primary strategy utilised to modulate pectoralis muscle power output. Maximum in vivo power output was 22% of the maximum isotonic power output (533 W kg(-1)) and was generated at a lower relative shortening velocity (0.28 V(max)) than the maximum power output during isotonic contractions (0.34 V(max)). It seems probable that the large pectoralis muscle strains result in a shift in the optimal relative shortening velocity in comparison with the optimum during isotonic contractions as a result of length-force effects.

  5. ASSESSMENT OF IN VIVO MECHANICAL MUSCLE FUNCTION IN PATIENTS WITH OSTEOARTHRITIS (OA) OF THE HIP; RELIABILITY

    DEFF Research Database (Denmark)

    Jensen, Carsten; Overgaard, Søren; Aagaard, Per

    2009-01-01

    hip OA participated in a test-retest after 8w at 10w post op.   RESULTS   Table 1: Patient test - retest reliability (Maximal Isometric Muscle Torque) for aff-side AFF-leg Test (8W) Mean ± SD (Nmkg-1) Test (10W) Mean ± SD (Nmkg-1) Δmean (Nmkg-1)   CVws   Spearman ± SE   LoA   Knee EXT 1.32 ± 0.38 1......INTRODUCTION Muscle function in patients with hip OA is not well-studied. We established a new setup of tests in order to monitor patients before and after surgery with total hip arthroplasty (THA). A test-retest protocol was designed to evaluate the reproducibility of single- and multi......-joint strength and power a novel setup. MATERIAL AND METHODS Isokinetic contractions for both knee and hip muscles were performed. Reliability for isometric muscle contractions in vivo was recorded and evaluated by use of within subject variability (CVW-S), Spearman correlation and Limits of Agreement (Lo...

  6. Mechanisms of in vivo muscle fatigue in humans: investigating age‐related fatigue resistance with a computational model

    Science.gov (United States)

    Callahan, Damien M.; Umberger, Brian R.

    2016-01-01

    Key points Muscle fatigue can be defined as the transient decrease in maximal force that occurs in response to muscle use. Fatigue develops because of a complex set of changes within the neuromuscular system that are difficult to evaluate simultaneously in humans.The skeletal muscle of older adults fatigues less than that of young adults during static contractions. The potential sources of this difference are multiple and intertwined.To evaluate the individual mechanisms of fatigue, we developed an integrative computational model based on neural, biochemical, morphological and physiological properties of human skeletal muscle.Our results indicate first that the model provides accurate predictions of fatigue and second that the age‐related resistance to fatigue is due largely to a lower reliance on glycolytic metabolism during contraction.This model should prove useful for generating hypotheses for future experimental studies into the mechanisms of muscle fatigue. Abstract During repeated or sustained muscle activation, force‐generating capacity becomes limited in a process referred to as fatigue. Multiple factors, including motor unit activation patterns, muscle fibre contractile properties and bioenergetic function, can impact force‐generating capacity and thus the potential to resist fatigue. Given that neuromuscular fatigue depends on interrelated factors, quantifying their independent effects on force‐generating capacity is not possible in vivo. Computational models can provide insight into complex systems in which multiple inputs determine discrete outputs. However, few computational models to date have investigated neuromuscular fatigue by incorporating the multiple levels of neuromuscular function known to impact human in vivo function. To address this limitation, we present a computational model that predicts neural activation, biomechanical forces, intracellular metabolic perturbations and, ultimately, fatigue during repeated isometric contractions

  7. In vivo passive mechanical properties of skeletal muscle improve with massage-like loading following eccentric exercise.

    Science.gov (United States)

    Haas, Caroline; Best, Thomas M; Wang, Qian; Butterfield, Timothy A; Zhao, Yi

    2012-10-11

    A quasi-linear viscoelasticity (QLV) model was used to study passive time-dependent responses of skeletal muscle to repeated massage-like compressive loading (MLL) following damaging eccentric exercise. Six skeletally mature rabbits were surgically instrumented with bilateral peroneal nerve cuffs for stimulation of the hindlimb tibialis anterior (TA) muscles. Following the eccentric exercise, rabbits were randomly assigned to a four-day MLL protocol mimicking deep effleurage (0.5 Hz, 10 N for 15 min or for 30 min). The contralateral hindlimb served as the exercised, no-MLL control for both MLL conditions. Viscoelastic properties of the muscle pre-exercise, post-exercise on Day 1, and pre- and post-MLL Day 1 through Day 4 were determined with ramp-and-hold tests. The instantaneous elastic response (AG(0)) increased following exercise (p0.05). This is the first experimental evidence of the effect of both acute (daily) and cumulative changes in viscoelastic properties of intensely exercised muscle due to ex vivo MLL. It provides a starting point for correlating passive muscle properties with mechanical effects of manual therapies, and may shed light on design and optimization of massage protocols. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Mechanical forces during muscle development.

    Science.gov (United States)

    Lemke, Sandra B; Schnorrer, Frank

    2017-04-01

    Muscles are the major force producing tissue in the human body. While certain muscle types specialize in producing maximum forces, others are very enduring. An extreme example is the heart, which continuously beats for the entire life. Despite being specialized, all body muscles share similar contractile mini-machines called sarcomeres that are organized into regular higher order structures called myofibrils. The major sarcomeric components and their organizational principles are conserved throughout most of the animal kingdom. In this review, we discuss recent progress in the understanding of myofibril and sarcomere development largely obtained from in vivo models. We focus on the role of mechanical forces during muscle and myofibril development and propose a tension driven self-organization mechanism for myofibril formation. We discuss recent technological advances that allow quantification of forces across tissues or molecules in vitro and in vivo. Although their application towards muscle development is still in its infancy, these technologies are likely to provide fundamental new insights into the mechanobiology of muscle and myofibril development in the near future. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Passive mechanics of canine internal abdominal muscles.

    Science.gov (United States)

    Hwang, Willy; Carvalho, Jason C; Tarlovsky, Isaac; Boriek, Aladin M

    2005-05-01

    The internal abdominal muscles are biaxially loaded in vivo, and therefore length-tension relations along and transverse to the directions of the muscle fibers are important in understanding their mechanical properties. We hypothesized that 1) internal oblique and transversus abdominis form an internal abdominal composite muscle with altered compliance than that of either muscle individually, and 2) anisotropy, different compliances in orthogonal directions, of internal abdominal composite muscle is less pronounced than that of its individual muscles. To test these hypotheses, in vitro mechanical testing was performed on 5 x 5 cm squares of transversus abdominis, internal oblique, and the two muscles together as a composite. These tissues were harvested from the left lateral side of abdominal muscles of eleven mongrel dogs (15-23 kg) and placed in a bath of oxygenated Krebs solution. Each tissue strip was attached to a biaxial mechanical testing device. Each muscle was passively lengthened and shortened along muscle fibers, transverse to fibers, or simultaneously along and transverse to muscle fibers. Both transversus abdominis and internal oblique muscles demonstrated less extensibility in the direction transverse to muscle fibers than along fibers. Biaxial loading caused a stiffening effect that was greater in the direction along the fibers than transverse to the fibers. Furthermore, the abdominal muscle composite was less compliant than either muscle alone in the direction of the muscle fibers. Taken together, our data suggested that the internal abdominal composite tissue has complex mechanical properties that are dependent on the mechanical properties of internal oblique and transversus abdominis muscles.

  10. An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo.

    Directory of Open Access Journals (Sweden)

    Cameron B Williams

    Full Text Available The current study tested the hypothesis that a single, moderate dose of RSV would activate the AMPK/SIRT1 axis in human skeletal muscle and adipose tissue. Additionally, the effects of RSV on mitochondrial respiration in PmFBs were examined. Eight sedentary men (23.8±2.4 yrs; BMI: 32.7±7.1 reported to the lab on two occasions where they were provided a meal supplemented with 300 mg of RSV or a placebo. Blood samples, and a muscle biopsy were obtained in the fasted state and again, with the addition of an adipose tissue biopsy, two hours post-prandial. The effect of RSV on mitochondrial respiration was examined in PmFBs taken from muscle biopsies from an additional eight men (23.4±5.4 yrs; BMI: 24.4±2.8. No effect of RSV was observed on nuclear SIRT1 activity, acetylation of p53, or phosphorylation of AMPK, ACC or PKA in either skeletal muscle or adipose tissue. A decrease in post absorptive insulin levels was accompanied by elevated skeletal muscle phosphorylation of p38 MAPK, but no change in either skeletal muscle or adipose tissue insulin signalling. Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100-300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production.

  11. Development of an inverse approach for the characterization of in vivo mechanical properties of the lower limb muscles.

    Science.gov (United States)

    Affagard, Jean-Sébastien; Bensamoun, Sabine F; Feissel, Pierre

    2014-11-01

    The purpose of this study was to develop an inverse method, coupling imaging techniques with numerical methods, to identify the muscle mechanical behavior. A finite element model updating (FEMU) was developed in three main interdependent steps. First, a 2D FE modeling, parameterized by a Neo-Hookean behavior (C10 and D), was developed from a segmented thigh muscle 1.5T MRI (magnetic resonance imaging). Thus, a displacement field was simulated for different static loadings (contention, compression, and indentation). Subsequently, the optimal mechanical test was determined from a sensitivity analysis. Second, ultrasound parameters (gain, dynamic, and frequency) were optimized on the thigh muscles in order to apply the digital image correlation (DIC), allowing the measurement of an experimental displacement field. Third, an inverse method was developed to identify the Neo-Hookean parameters (C10 and D) by performing a minimization of the distance between the simulated and measured displacement fields. To replace the experimental data and to quantify the identification error, a numerical example was developed. The result of the sensitivity analysis showed that the compression test was more adapted to identify the Neo-Hookean parameters. Ultrasound images were recorded with a frequency, gain, and dynamic of 9 MHz, 34 dB, 42 dB, respectively. In addition, the experimental noise on displacement field measurement was estimated to be 0.2 mm. The identification performed on the numerical example revealed a low error for the C10 (muscle behavior will help to follow treatment and to ensure accurate medical procedures during the use of robotic devices.

  12. Intermuscular force transmission between human plantarflexor muscles in vivo

    DEFF Research Database (Denmark)

    Bojsen-Møller, Jens; Bojsen-Møller, Jens; Schwartz, Sidse

    2010-01-01

    The exact mechanical function of synergist muscles within a human limb in vivo is not well described. Recent studies indicate the existence of a mechanical interaction between muscle actuators that may have functional significance and further play a role for injury mechanisms. The purpose...... of the present study was to investigate if intermuscular force transmission occurs within and between human plantarflexor muscles in vivo. Seven subjects performed four types of either active contractile tasks or passive joint manipulations: passive knee extension, voluntary isometric plantarflexion, voluntary...... task-induced tissue displacement (which is assumed to represent loading) for the plantarflexor muscles [MG, soleus (SOL), and flexor hallucis longus (FHL)]. Selective MG stimulation and passive knee extension resulted in displacement of both the MG and SOL muscles. Minimal displacement of the triceps...

  13. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

    Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

    2012-01-01

    Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... and adipose tissue leptin release in vivo. We recruited 16 healthy male human participants. Catheters were inserted into the femoral artery and vein draining skeletal muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose tissue. By combining the veno-arterial differences in plasma...... leptin with measurements of blood flow, leptin release from both tissues was quantified. To induce changes in leptin, the participants were infused with either saline or adrenaline in normo-physiological concentrations. The presence of leptin in skeletal muscle was confirmed by western blotting. Leptin...

  14. Mechanical Properties of Respiratory Muscles

    Science.gov (United States)

    Sieck, Gary C.; Ferreira, Leonardo F.; Reid, Michael B.; Mantilla, Carlos B.

    2014-01-01

    Striated respiratory muscles are necessary for lung ventilation and to maintain the patency of the upper airway. The basic structural and functional properties of respiratory muscles are similar to those of other striated muscles (both skeletal and cardiac). The sarcomere is the fundamental organizational unit of striated muscles and sarcomeric proteins underlie the passive and active mechanical properties of muscle fibers. In this respect, the functional categorization of different fiber types provides a conceptual framework to understand the physiological properties of respiratory muscles. Within the sarcomere, the interaction between the thick and thin filaments at the level of cross-bridges provides the elementary unit of force generation and contraction. Key to an understanding of the unique functional differences across muscle fiber types are differences in cross-bridge recruitment and cycling that relate to the expression of different myosin heavy chain isoforms in the thick filament. The active mechanical properties of muscle fibers are characterized by the relationship between myoplasmic Ca2+ and cross-bridge recruitment, force generation and sarcomere length (also cross-bridge recruitment), external load and shortening velocity (cross-bridge cycling rate), and cross-bridge cycling rate and ATP consumption. Passive mechanical properties are also important reflecting viscoelastic elements within sarcomeres as well as the extracellular matrix. Conditions that affect respiratory muscle performance may have a range of underlying pathophysiological causes, but their manifestations will depend on their impact on these basic elemental structures. PMID:24265238

  15. Mechanics of the respiratory muscles.

    Science.gov (United States)

    De Troyer, André; Boriek, Aladin M

    2011-07-01

    This article examines the mechanics of the muscles that drive expansion or contraction of the chest wall during breathing. The diaphragm is the main inspiratory muscle. When its muscle fibers are activated in isolation, they shorten, the dome of the diaphragm descends, pleural pressure (P(pl)) falls, and abdominal pressure (P(ab)) rises. As a result, the ventral abdominal wall expands, but a large fraction of the rib cage contracts. Expansion of the rib cage during inspiration is produced by the external intercostals in the dorsal portion of the rostral interspaces, the intercartilaginous portion of the internal intercostals (the so-called parasternal intercostals), and, in humans, the scalenes. By elevating the ribs and causing an additional fall in P(pl), these muscles not only help the diaphragm expand the chest wall and the lung, but they also increase the load on the diaphragm and reduce the shortening of the diaphragmatic muscle fibers. The capacity of the diaphragm to generate pressure is therefore enhanced. In contrast, during expiratory efforts, activation of the abdominal muscles produces a rise in P(ab) that leads to a cranial displacement of the diaphragm into the pleural cavity and a rise in P(pl). Concomitant activation of the internal interosseous intercostals in the caudal interspaces and the triangularis sterni during such efforts contracts the rib cage and helps the abdominal muscles deflate the lung. © 2011 American Physiological Society.

  16. Skeletal muscle mechanics: questions, problems and possible solutions.

    Science.gov (United States)

    Herzog, Walter

    2017-09-16

    Skeletal muscle mechanics have been studied ever since people have shown an interest in human movement. However, our understanding of muscle contraction and muscle mechanical properties has changed fundamentally with the discovery of the sliding filament theory in 1954 and associated cross-bridge theory in 1957. Nevertheless, experimental evidence suggests that our knowledge of the mechanisms of contraction is far from complete, and muscle properties and muscle function in human movement remain largely unknown.In this manuscript, I am trying to identify some of the crucial challenges we are faced with in muscle mechanics, offer possible solutions to questions, and identify problems that might be worthwhile exploring in the future. Since it is impossible to tackle all (worthwhile) problems in a single manuscript, I identified three problems that are controversial, important, and close to my heart. They may be identified as follows: (i) mechanisms of muscle contraction, (ii) in vivo whole muscle mechanics and properties, and (iii) force-sharing among synergistic muscles. These topics are fundamental to our understanding of human movement and movement control, and they contain a series of unknowns and challenges to be explored in the future.It is my hope that this paper may serve as an inspiration for some, may challenge current beliefs in selected areas, tackle important problems in the area of muscle mechanics, physiology and movement control, and may guide and focus some of the thinking of future muscle mechanics research.

  17. Mechanically induced alterations in cultured skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

    1991-01-01

    Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

  18. In vivo muscle force and muscle power during near-maximal frog jumps.

    Science.gov (United States)

    Moo, Eng Kuan; Peterson, Daniel R; Leonard, Timothy R; Kaya, Motoshi; Herzog, Walter

    2017-01-01

    Frogs' outstanding jumping ability has been associated with a high power output from the leg extensor muscles. Two main theories have emerged to explain the high power output of the frog leg extensor muscles, either (i) the contractile conditions of all leg extensor muscles are optimized in terms of muscle length and speed of shortening, or (ii) maximal power is achieved through a dynamic catch mechanism that uncouples fibre shortening from the corresponding muscle-tendon unit shortening. As in vivo instantaneous power generation in frog hind limb muscles during jumping has never been measured directly, it is hard to distinguish between the two theories. In this study, we determined the instantaneous variable power output of the plantaris longus (PL) of Lithobates pipiens (also known as Rana pipiens), by directly measuring the in vivo force, length change, and speed of muscle and fibre shortening in near maximal jumps. Fifteen near maximal jumps (> 50cm in horizontal distance) were analyzed. High instantaneous peak power in PL (536 ± 47 W/kg) was achieved by optimizing the contractile conditions in terms of the force-length but not the force-velocity relationship, and by a dynamic catch mechanism that decouples fascicle shortening from muscle-tendon unit shortening. We also found that the extra-muscular free tendon likely amplifies the peak power output of the PL by modulating fascicle shortening length and shortening velocity for optimum power output, but not by releasing stored energy through recoiling as the tendon only started recoiling after peak PL power had been achieved.

  19. In Vivo Assessment of Muscle Contractility in Animal Studies.

    Science.gov (United States)

    Iyer, Shama R; Valencia, Ana P; Hernández-Ochoa, Erick O; Lovering, Richard M

    2016-01-01

    In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Animal models provide unmitigated access to histological samples, which provide a "direct measure" of damage. However, even with unconstrained access to tissue morphology and biochemistry assays, the findings typically do not account for loss of muscle function. Thus, the most comprehensive measure of the overall health of the muscle is assessment of its primary function, which is to produce contractile force. The majority of animal models testing contractile force have been limited to the muscle groups moving the ankle, with advantages and disadvantages depending on the equipment. Here, we describe in vivo methods to measure torque, to produce a reliable muscle injury, and to follow muscle function within the same animal over time. We also describe in vivo methods to measure tension in the leg and thigh muscles.

  20. Optical clearing mechanisms characterization in muscle

    Directory of Open Access Journals (Sweden)

    Luís Oliveira

    2016-09-01

    Full Text Available Optical immersion clearing is a technique that has been widely studied for more than two decades and that is used to originate a temporary transparency effect in biological tissues. If applied in cooperation with clinical methods it provides optimization of diagnosis and treatment procedures. This technique turns biological tissues more transparent through two main mechanisms — tissue dehydration and refractive index (RI matching between tissue components. Such matching is obtained by partial replacement of interstitial water by a biocompatible agent that presents higher RI and it can be completely reversible by natural rehydration in vivo or by assisted rehydration in ex vivo tissues. Experimental data to characterize and discriminate between the two mechanisms and to find new ones are necessary. Using a simple method, based on collimated transmittance and thickness measurements made from muscle samples under treatment, we have estimated the diffusion properties of glucose, ethylene glycol (EG and water that were used to perform such characterization and discrimination. Comparing these properties with data from literature that characterize their diffusion in water we have observed that muscle cell membrane permeability limits agent and water diffusion in the muscle. The same experimental data has allowed to calculate the optical clearing (OC efficiency and make an interpretation of the internal changes that occurred in muscle during the treatments. The same methodology can now be used to perform similar studies with other agents and in other tissues in order to solve engineering problems at design of inexpensive and robust technologies for a considerable improvement of optical tomographic techniques with better contrast and in-depth imaging.

  1. Effects of knee joint angle on global and local strains within human triceps surae muscle: MRI analysis indicating in vivo myofascial force transmission between synergistic muscles

    NARCIS (Netherlands)

    Huijing, P.A.J.B.M.; Yaman, A.; Ozturk, C.; Yucesoy, C.A.

    2011-01-01

    Purpose Mechanical interactions between muscles have been shown for in situ conditions. In vivo data for humans is unavailable. Global and local length changes of calf muscles were studied to test the hypothesis that local strains may occur also within muscle for which global strain equals zero.

  2. Human skeletal muscle fibroblasts stimulate in vitro myogenesis and in vivo muscle regeneration

    DEFF Research Database (Denmark)

    Mackey, Abigail L.; Magnan, Mélanie; Chazaud, Bénédicte

    2017-01-01

    Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence...... and strongly stimulate both MPC differentiation and MPC fusion. It thus appears, in humans, that fibroblasts exert a strong positive regulatory influence on MPC activity, in line with observations during in vivo skeletal muscle regeneration....

  3. The Mitochondrial Calcium Uniporter controls skeletal muscle trophism in vivo

    Science.gov (United States)

    Mammucari, Cristina; Gherardi, Gaia; Zamparo, Ilaria; Raffaello, Anna; Boncompagni, Simona; Chemello, Francesco; Cagnin, Stefano; Braga, Alessandra; Zanin, Sofia; Pallafacchina, Giorgia; Zentilin, Lorena; Sandri, Marco; De Stefani, Diego; Protasi, Feliciano; Lanfranchi, Gerolamo; Rizzuto, Rosario

    2015-01-01

    Summary Muscle atrophy contributes to the poor prognosis of many pathophysiological conditions, but pharmacological therapies are still limited. Muscle activity leads to major swings in mitochondrial [Ca2+] which control aerobic metabolism, cell death and survival pathways. We have investigated in vivo the effects of mitochondrial Ca2+ homeostasis in skeletal muscle function and trophism, by overexpressing or silencing the Mitochondrial Calcium Uniporter (MCU). The results demonstrate that both in developing and in adult muscles MCU-dependent mitochondrial Ca2+ uptake has a marked trophic effect that does not depend on aerobic control, but impinges on two major hypertrophic pathways of skeletal muscle, PGC-1α4 and IGF1-AKT/PKB. In addition, MCU overexpression protects from denervation-induced atrophy. These data reveal a novel Ca2+-dependent organelle-to-nucleus signaling route, which links mitochondrial function to the control of muscle mass and may represent a possible pharmacological target in conditions of muscle loss. PMID:25732818

  4. Mechanical modeling of skeletal muscle functioning.

    NARCIS (Netherlands)

    van der Linden, B.J.J.J.

    1998-01-01

    For movement of body or body segments is combined effort needed of the central nervous system and the muscular-skeletal system. This thesis deals with the mechanical functioning of skeletal muscle. That muscles come in a large variety of geometries, suggest the existence of a relation between muscle

  5. Muscle-Driven In Vivo Nanogenerator

    KAUST Repository

    Li, Zhou

    2010-05-05

    (Figure Presented) A nanogenerator based on a single piezoelectric fine wire producing an alternating current (AC) is successfully used for the harvesting of biomechanical energy under in vivo conditions. We demonstrate the implanting and working of such a nanogenerator in a live rat where it harvests energy generated by its breathing or heart beating. This study shows the potential of applying these nanogenerators for driving in vivo nanodevices. © 2010 WILEY-VCH Verlag GmbH & Co. KCaA, Weinheim.

  6. Cellular and molecular mechanisms of muscle atrophy

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo

    2013-01-01

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

  7. Effects of knee joint angle on global and local strains within human triceps surae muscle: MRI analysis indicating in vivo myofascial force transmission between synergistic muscles

    OpenAIRE

    Huijing, Peter A.; Yaman, Alper; Ozturk, Cengizhan; Yucesoy, Can A.

    2011-01-01

    Purpose Mechanical interactions between muscles have been shown for in situ conditions. In vivo data for humans is unavailable. Global and local length changes of calf muscles were studied to test the hypothesis that local strains may occur also within muscle for which global strain equals zero. Methods For determination of globally induced strain in m. gastrocnemius in dissected human cadavers several knee joint angles were imposed, while keeping ankle joint angle constant and measuring its ...

  8. Mechanism for Mechanical Wave Break in the Heart Muscle

    Science.gov (United States)

    Weise, L. D.; Panfilov, A. V.

    2017-09-01

    Using a reaction-diffusion-mechanics model we identify a mechanism for mechanical wave break in the heart muscle. For a wide range of strengths and durations an external mechanical load causes wave front dissipation leading to formation and breakup of spiral waves. We explain the mechanism, and discuss under which conditions it can cause or abolish cardiac arrhythmias.

  9. Effects of knee joint angle on global and local strains within human triceps surae muscle: MRI analysis indicating in vivo myofascial force transmission between synergistic muscles.

    Science.gov (United States)

    Huijing, Peter A; Yaman, Alper; Ozturk, Cengizhan; Yucesoy, Can A

    2011-12-01

    Mechanical interactions between muscles have been shown for in situ conditions. In vivo data for humans is unavailable. Global and local length changes of calf muscles were studied to test the hypothesis that local strains may occur also within muscle for which global strain equals zero. For determination of globally induced strain in m. gastrocnemius in dissected human cadavers several knee joint angles were imposed, while keeping ankle joint angle constant and measuring its muscle-tendon complex length changes. In vivo local strains in both gastrocnemius and soleus muscles were calculated using MRI techniques in healthy human volunteers comparing images taken at static knee angles of 173° and 150°. Imposed global strains on gastrocnemius were much smaller than local strains. High distributions of strains were encountered, e.g. overall lengthened muscle contains locally lengthened, as well as shortened areas within it. Substantial strains were not limited to gastrocnemius, but were found also in synergistic soleus muscle, despite the latter muscle-tendon complex length remaining isometric (constant ankle angle: i.e. global strain = 0), as it does not cross the knee. Based on results of animal experiments this effect is ascribed to myofascial connections between these synergistic muscles. The most likely pathway is the neurovascular tract within the anterior crural compartment (i.e. the collagen reinforcements of blood vessels, lymphatics and nerves). However, direct intermuscular transmission of force may also occur via the perimysium shared between the two muscles. Global strains imposed on muscle (joint movement) are not good estimators of in vivo local strains within it: differing in magnitude, as well as direction of length change. Substantial mechanical interaction occurs between calf muscles, which is mediated by myofascial force transmission between these synergistic muscles. This confirms conclusions of previous in situ studies in experimental animals

  10. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  11. Membrane-stabilizing copolymers confer marked protection to dystrophic skeletal muscle in vivo

    Directory of Open Access Journals (Sweden)

    Evelyne M Houang

    Full Text Available Duchenne muscular dystrophy (DMD is a fatal disease of striated muscle deterioration. A unique therapeutic approach for DMD is the use of synthetic membrane stabilizers to protect the fragile dystrophic sarcolemma against contraction-induced mechanical stress. Block copolymer-based membrane stabilizer poloxamer 188 (P188 has been shown to protect the dystrophic myocardium. In comparison, the ability of synthetic membrane stabilizers to protect fragile DMD skeletal muscles has been less clear. Because cardiac and skeletal muscles have distinct structural and functional features, including differences in the mechanism of activation, variance in sarcolemma phospholipid composition, and differences in the magnitude and types of forces generated, we speculated that optimized membrane stabilization could be inherently different. Our objective here is to use principles of pharmacodynamics to evaluate membrane stabilization therapy for DMD skeletal muscles. Results show a dramatic differential effect of membrane stabilization by optimization of pharmacodynamic-guided route of poloxamer delivery. Data show that subcutaneous P188 delivery, but not intravascular or intraperitoneal routes, conferred significant protection to dystrophic limb skeletal muscles undergoing mechanical stress in vivo. In addition, structure-function examination of synthetic membrane stabilizers further underscores the importance of copolymer composition, molecular weight, and dosage in optimization of poloxamer pharmacodynamics in vivo.

  12. Artificial Muscles: Mechanisms, Applications, and Challenges.

    Science.gov (United States)

    Mirvakili, Seyed M; Hunter, Ian W

    2017-12-18

    The area of artificial muscle is a highly interdisciplinary field of research that has evolved rapidly in the last 30 years. Recent advances in nanomaterial fabrication and characterization, specifically carbon nanotubes and nanowires, have had major contributions in the development of artificial muscles. However, what can artificial muscles really do for humans? This question is considered here by first examining nature's solutions to this design problem and then discussing the structure, actuation mechanism, applications, and limitations of recently developed artificial muscles, including highly oriented semicrystalline polymer fibers; nanocomposite actuators; twisted nanofiber yarns; thermally activated shape-memory alloys; ionic-polymer/metal composites; dielectric-elastomer actuators; conducting polymers; stimuli-responsive gels; piezoelectric, electrostrictive, magnetostrictive, and photostrictive actuators; photoexcited actuators; electrostatic actuators; and pneumatic actuators. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Making muscle: skeletal myogenesis in vivo and in vitro.

    Science.gov (United States)

    Chal, Jérome; Pourquié, Olivier

    2017-06-15

    Skeletal muscle is the largest tissue in the body and loss of its function or its regenerative properties results in debilitating musculoskeletal disorders. Understanding the mechanisms that drive skeletal muscle formation will not only help to unravel the molecular basis of skeletal muscle diseases, but also provide a roadmap for recapitulating skeletal myogenesis in vitro from pluripotent stem cells (PSCs). PSCs have become an important tool for probing developmental questions, while differentiated cell types allow the development of novel therapeutic strategies. In this Review, we provide a comprehensive overview of skeletal myogenesis from the earliest premyogenic progenitor stage to terminally differentiated myofibers, and discuss how this knowledge has been applied to differentiate PSCs into muscle fibers and their progenitors in vitro. © 2017. Published by The Company of Biologists Ltd.

  14. In Vivo Microscopy Reveals Extensive Embedding of Capillaries within the Sarcolemma of Skeletal Muscle Fibers

    Science.gov (United States)

    Glancy, Brian; Hsu, Li-Yueh; Dao, Lam; Bakalar, Matthew; French, Stephanie; Chess, David J.; Taylor, Joni L.; Picard, Martin; Aponte, Angel; Daniels, Mathew P.; Esfahani, Shervin; Cushman, Samuel; Balaban, Robert S.

    2013-01-01

    Objective To provide insight into mitochondrial function in vivo, we evaluated the 3D spatial relationship between capillaries, mitochondria, and muscle fibers in live mice. Methods 3D volumes of in vivo murine Tibialis anterior muscles were imaged by multi-photon microscopy (MPM). Muscle fiber type, mitochondrial distribution, number of capillaries, and capillary-to-fiber contact were assessed. The role of myoglobin-facilitated diffusion was examined in myoglobin knockout mice. Distribution of GLUT4 was also evaluated in the context of the capillary and mitochondrial network. Results MPM revealed that 43.6 ± 3.3% of oxidative fiber capillaries had ≥ 50% of their circumference embedded in a groove in the sarcolemma, in vivo. Embedded capillaries were tightly associated with dense mitochondrial populations lateral to capillary grooves and nearly absent below the groove. Mitochondrial distribution, number of embedded capillaries, and capillary-to-fiber contact were proportional to fiber oxidative capacity and unaffected by myoglobin knockout. GLUT4 did not preferentially localize to embedded capillaries. Conclusions Embedding capillaries in the sarcolemma may provide a regulatory mechanism to optimize delivery of oxygen to heterogeneous groups of muscle fibers. We hypothesize that mitochondria locate to paravascular regions due to myofibril voids created by embedded capillaries, not to enhance the delivery of oxygen to the mitochondria. PMID:25279425

  15. Mechanisms of cisplatin-induced muscle atrophy

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-15

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

  16. β-alanine supplementation improves in-vivo fresh and fatigued skeletal muscle relaxation speed.

    Science.gov (United States)

    Jones, Rebecca Louise; Barnett, Cleveland Thomas; Davidson, Joel; Maritza, Billy; Fraser, William D; Harris, Roger; Sale, Craig

    2017-05-01

    In fresh muscle, supplementation with the rate-limiting precursor of carnosine, β-alanine (BA), results in a decline in muscle half-relaxation time (HRT) potentially via alterations to calcium (Ca2+) handling. Accumulation of hydrogen cation (H+) has been shown to impact Ca2+ signalling during muscular contraction, carnosine has the potential to serve as a cytoplasmic regulator of Ca2+ and H+ coupling, since it binds to both ions. The present study examined the effect of BA supplementation on intrinsic in-vivo isometric knee extensor force production and muscle contractility in both fresh and fatigued human skeletal muscle assessed during voluntary and electrically evoked (nerve and superficial muscle stimulation) contractions. Twenty-three males completed two experimental sessions, pre- and post- 28 day supplementation with 6.4 g.day-1 of BA (n = 12) or placebo (PLA; n = 11). Isometric force was recorded during a series of voluntary and electrically evoked knee extensor contractions. BA supplementation had no effect on voluntary or electrically evoked isometric force production, or twitch electromechanical delay and time-to-peak tension. There was a significant decline in muscle HRT in fresh and fatigued muscle conditions during both resting (3 ± 13%; 19 ± 26%) and potentiated (1 ± 15%; 2 ± 20%) twitch contractions. The mechanism for reduced HRT in fresh and fatigued skeletal muscle following BA supplementation is unclear. Due to the importance of muscle relaxation on total energy consumption, especially during short, repeated contractions, BA supplementation may prove to be beneficial in minimising contractile slowing induced by fatigue. The trial is registered with Clinicaltrials.gov, ID number NCT02819505.

  17. Capsiate supplementation reduces oxidative cost of contraction in exercising mouse skeletal muscle in vivo.

    Directory of Open Access Journals (Sweden)

    Kazuya Yashiro

    Full Text Available Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control or purified capsiate (at 10- or 100-mg/kg body weight on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR imaging and 31-phosphorus MR spectroscopy (31P-MRS. Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz, both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.

  18. Fast Motion of Plants through mechanical instability: Mechanics without Muscles

    Science.gov (United States)

    Guo, Qiaohang; Chen, Zi; Zheng, Huang; Chen, Wenzhe

    2012-02-01

    Plants are not well known for fast motions, yet some plants such as the Venus flytrap can move in a fraction of a second to capture insects, even though they do not have nerves or muscles. This type of rapid motion has intrigued scientists for centuries. Darwin did a first systematic study on the trap closure mechanism, and considered the plant as ``one of the most wonderful in the world". Thereafter, several physical mechanisms have been proposed, such as the rapid loss of turgor pressure, an irreversible acid-induced wall loosening mechanism, and the snap-through model by mechanical instability, but with no unanimous agreement among researchers. Here we propose a coupled mechanical bistable mechanism that explains the rapid closure of the Venus flytrap in a comprehensive manner, consistent with a series of experimental observations. Such bistabile behaviors are theoretically modeled and validated with table-top experiments. Based on the principles learnt from the Venus flytrap, we are also able to manufacture a preliminary ``flytrap robot''. Hence, it is promising to design smart bio-mimetic materials and devices with snapping mechanisms as sensors, actuators, artificial muscles and biomedical devices.

  19. In vivo longitudinal study of rodent skeletal muscle atrophy using ultrasonography.

    Science.gov (United States)

    Mele, Antonietta; Fonzino, Adriano; Rana, Francesco; Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Giustino, Arcangela; Conte Camerino, Diana; Desaphy, Jean-François

    2016-02-01

    Muscle atrophy is a widespread ill condition occurring in many diseases, which can reduce quality of life and increase morbidity and mortality. We developed a new method using non-invasive ultrasonography to measure soleus and gastrocnemius lateralis muscle atrophy in the hindlimb-unloaded rat, a well-accepted model of muscle disuse. Soleus and gastrocnemius volumes were calculated using the conventional truncated-cone method and a newly-designed sinusoidal method. For Soleus muscle, the ultrasonographic volume determined in vivo with either method was linearly correlated to the volume determined ex-vivo from excised muscles as muscle weight-to-density ratio. For both soleus and gastrocnemius muscles, a strong linear correlation was obtained between the ultrasonographic volume and the muscle fiber cross-sectional area determined ex-vivo on muscle cryosections. Thus ultrasonography allowed the longitudinal in vivo evaluation of muscle atrophy progression during hindlimb unloading. This study validates ultrasonography as a powerful method for the evaluation of rodent muscle atrophy in vivo, which would prove useful in disease models and therapeutic trials.

  20. In situ muscle power differs without varying in vitro mechanical properties in two insect leg muscles innervated by the same motor neuron.

    Science.gov (United States)

    Ahn, A N; Meijer, K; Full, R J

    2006-09-01

    The mechanical behavior of muscle during locomotion is often predicted by its anatomy, kinematics, activation pattern and contractile properties. The neuromuscular design of the cockroach leg provides a model system to examine these assumptions, because a single motor neuron innervates two extensor muscles operating at a single joint. Comparisons of the in situ measurements under in vivo running conditions of muscle 178 to a previously examined muscle (179) demonstrate that the same inputs (e.g. neural signal and kinematics) can result in different mechanical outputs. The same neural signal and kinematics, as determined during running, can result in different mechanical functions, even when the two anatomically similar muscles possess the same contraction kinetics, force-velocity properties and tetanic force-length properties. Although active shortening greatly depressed force under in vivo-like strain and stimulation conditions, force depression was similarly proportional to strain, similarly inversely proportional to stimulation level, and similarly independent of initial length and shortening velocity between the two muscles. Lastly, passive pre-stretch enhanced force similarly between the two muscles. The forces generated by the two muscles when stimulated with their in vivo pattern at lengths equal to or shorter than rest length differed, however. Overall, differences between the two muscles in their submaximal force-length relationships can account for up to 75% of the difference between the two muscles in peak force generated at short lengths observed during oscillatory contractions. Despite the fact that these muscles act at the same joint, are stimulated by the same motor neuron with an identical pattern, and possess many of the same in vitro mechanical properties, the mechanical outputs of two leg extensor muscles can be vastly different.

  1. Mechanical analysis of Drosophila indirect flight and jump muscles.

    Science.gov (United States)

    Swank, Douglas M

    2012-01-01

    The genetic advantages of Drosophila make it a very appealing choice for investigating muscle development, muscle physiology and muscle protein structure and function. To take full advantage of this model organism, it has been vital to develop isolated Drosophila muscle preparations that can be mechanically evaluated. We describe techniques to isolate, prepare and mechanically analyze skinned muscle fibers from two Drosophila muscle types, the indirect flight muscle and the jump muscle. The function of the indirect flight muscle is similar to vertebrate cardiac muscle, to generate power in an oscillatory manner. The indirect flight muscle is ideal for evaluating the influence of protein mutations on muscle and cross-bridge stiffness, oscillatory power, and deriving cross-bridge rate constants. Jump muscle physiology and structure are more similar to skeletal vertebrate muscle than indirect flight muscle, and it is ideal for measuring maximum shortening velocity, force-velocity characteristics and steady-state power generation. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Contractile efficiency of dystrophic mdx mouse muscle: in vivo and ex vivo assessment of adaptation to exercise of functional end points.

    Science.gov (United States)

    Capogrosso, Roberta Francesca; Mantuano, Paola; Cozzoli, Anna; Sanarica, Francesca; Massari, Ada Maria; Conte, Elena; Fonzino, Adriano; Giustino, Arcangela; Rolland, Jean-Francois; Quaranta, Angelo; De Bellis, Michela; Camerino, Giulia Maria; Grange, Robert W; De Luca, Annamaria

    2017-04-01

    Progressive weakness is a typical feature of Duchenne muscular dystrophy (DMD) patients and is exacerbated in the benign mdx mouse model by in vivo treadmill exercise. We hypothesized a different threshold for functional adaptation of mdx muscles in response to the duration of the exercise protocol. In vivo weakness was confirmed by grip strength after 4, 8, and 12 wk of exercise in mdx mice. Torque measurements revealed that exercise-related weakness in mdx mice correlated with the duration of the protocol, while wild-type (WT) mice were stronger. Twitch and tetanic forces of isolated diaphragm and extensor digitorum longus (EDL) muscles were lower in mdx compared with WT mice. In mdx, both muscle types exhibited greater weakness after a single exercise bout, but only in EDL after a long exercise protocol. As opposite to WT muscles, mdx EDL ones did not show any exercise-induced adaptations against eccentric contraction force drop. qRT-PCR analysis confirmed the maladaptation of genes involved in metabolic and structural remodeling, while damage-related genes remained significantly upregulated and angiogenesis impaired. Phosphorylated AMP kinase level increased only in exercised WT muscle. The severe histopathology and the high levels of muscular TGF-β1 and of plasma matrix metalloproteinase-9 confirmed the persistence of muscle damage in mdx mice. Therefore, dystrophic muscles showed a partial degree of functional adaptation to chronic exercise, although not sufficient to overcome weakness nor signs of damage. The improved understanding of the complex mechanisms underlying maladaptation of dystrophic muscle paves the way to a better managment of DMD patients.NEW & NOTEWORTHY We focused on the adaptation/maladaptation of dystrophic mdx mouse muscles to a standard protocol of exercise to provide guidance in the development of more effective drug and physical therapies in Duchenne muscular dystrophy. The mdx muscles showed a modest functional adaptation to chronic

  3. In Vivo Assessment of Muscle Contractility in Animal Studies

    OpenAIRE

    Iyer, Shama R.; Valencia, Ana P.; Hern?ndez-Ochoa, Erick O.; Richard M Lovering

    2016-01-01

    In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Animal models provide unmitigated access to histological samples, which provide a ?direct measure? of damage. However, even with unconstrained access to tissue morphology and biochemistry assays, the findings typically do not account for loss of muscle function. Thus, the most comprehensive meas...

  4. In vivo evidence of altered skeletal muscle blood flow in chronic tension-type headache

    National Research Council Canada - National Science Library

    Ashina, M; Stallknecht, B; Bendtsen, L; Pedersen, J F; Galbo, H; Dalgaard, P; Olesen, J

    2002-01-01

    .... Using a microdialysis technique, we aimed to estimate in vivo blood flow and interstitial lactate concentrations in the trapezius muscle at rest and during static exercise in patients with chronic...

  5. Activation and aponeurosis morphology affect in vivo muscle tissue strains near the myotendinous junction.

    Science.gov (United States)

    Fiorentino, Niccolo M; Epstein, Frederick H; Blemker, Silvia S

    2012-02-23

    Hamstring strain injury is one of the most common injuries in athletes, particularly for sports that involve high speed running. The aims of this study were to determine whether muscle activation and internal morphology influence in vivo muscle behavior and strain injury susceptibility. We measured tissue displacement and strains in the hamstring muscle injured most often, the biceps femoris long head muscle (BFLH), using cine DENSE dynamic magnetic resonance imaging. Strain measurements were used to test whether strain magnitudes are (i) larger during active lengthening than during passive lengthening and (ii) larger for subjects with a relatively narrow proximal aponeurosis than a wide proximal aponeurosis. Displacement color maps showed higher tissue displacement with increasing lateral distance from the proximal aponeurosis for both active lengthening and passive lengthening, and higher tissue displacement for active lengthening than passive lengthening. First principal strain magnitudes were averaged in a 1cm region near the myotendinous junction, where injury is most frequently observed. It was found that strains are significantly larger during active lengthening (0.19 SD 0.09) than passive lengthening (0.13 SD 0.06) (p<0.05), which suggests that elevated localized strains may be a mechanism for increased injury risk during active as opposed to passive lengthening. First principal strains were higher for subjects with a relatively narrow aponeurosis width (0.26 SD 0.15) than wide (0.14 SD 0.04) (p<0.05). This result suggests that athletes who have BFLH muscles with narrow proximal aponeuroses may have an increased risk for BFLH strain injuries. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Mechanisms of exertional fatigue in muscle glycogenoses

    DEFF Research Database (Denmark)

    Vissing, John; Haller, Ronald G

    2012-01-01

    Exertional fatigue early in exercise is a clinical hallmark of muscle glycogenoses, which is often coupled with painful muscle contractures and episodes of myoglobinuria. A fundamental biochemical problem in these conditions is the impaired generation of ATP to fuel muscle contractions, which...... relates directly to the metabolic defect, but also to substrate-limited energy deficiency, as exemplified by the "second wind" phenomenon in McArdle disease. A number of secondary events may also play a role in inducing premature fatigue in glycogenoses, including (1) absent or blunted muscle acidosis...... and aerobic energy for muscle contraction; and the pathological fatigue that occurs when glycogenolysis and/or glycolysis is blocked imply an important role for theses metabolic pathways in normal muscle fatigue....

  7. Mechanical properties of the human Achilles tendon, in vivo

    DEFF Research Database (Denmark)

    Kongsgaard, M; Nielsen, C H; Hegnsvad, S

    2011-01-01

    Ultrasonography has been widely applied for in vivo measurements of tendon mechanical properties. Assessments of human Achilles tendon mechanical properties have received great interest. Achilles tendon injuries predominantly occur in the tendon region between the Achilles-soleus myotendinous...... Achilles tendon in vivo by the use of ultrasonography and 2) assess the between-day reproducibility of these measurements....

  8. In vivo measurement of the series elasticity release curve of human triceps surae muscle

    NARCIS (Netherlands)

    Hof, AL

    The force-extension characteristic of the series-elastic component of the human triceps surae muscle has been measured in vivo by means of a hydraulic controlled-release ergometer in 12 subjects. The SEC characteristic can be described by a linear relation between muscle moment and extension, with a

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

    Science.gov (United States)

    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.

  10. Electrical conductivity of skeletal muscle tissue: Experimental results from different musclesin vivo

    NARCIS (Netherlands)

    Gielen, F.L.H.; Wallinga, W.; Boon, K.L.

    1984-01-01

    For a quantitative EMG analysis reliable and unique values of the electrical conductivities of skeletal muscle tissuein vivo are indispensable. Literature values do not satisfy these criteria. In the paper experimental results of conductivity measurements (four-electrode technique) on musclesin vivo

  11. Complex myograph allows the examination of complex muscle contractions for the assessment of muscle force, shortening, velocity, and work in vivo

    Directory of Open Access Journals (Sweden)

    Ruhschulte Hainer

    2008-07-01

    Full Text Available Abstract Background The devices used for in vivo examination of muscle contractions assess only pure force contractions and the so-called isokinetic contractions. In isokinetic experiments, the extremity and its muscle are artificially moved with constant velocity by the measuring device, while a tetanic contraction is induced in the muscle, either by electrical stimulation or by maximal voluntary activation. With these systems, experiments cannot be performed at pre-defined, constant muscle length, single contractions cannot be evaluated individually and the separate examination of the isometric and the isotonic components of single contractions is not possible. Methods The myograph presented in our study has two newly developed technical units, i.e. a. a counterforce unit which can load the muscle with an adjustable, but constant force and b. a length-adjusting unit which allows for both the stretching and the contraction length to be infinitely adjustable independently of one another. The two units support the examination of complex types of contraction and store the counterforce and length-adjusting settings, so that these conditions may be accurately reapplied in later sessions. Results The measurement examples presented show that the muscle can be brought to every possible pre-stretching length and that single isotonic or complex isometric-isotonic contractions may be performed at every length. The applied forces act during different phases of contraction, resulting into different pre- and after-loads that can be kept constant – uninfluenced by the contraction. Maximal values for force, shortening, velocity and work may be obtained for individual muscles. This offers the possibility to obtain information on the muscle status and to monitor its changes under non-invasive measurement conditions. Conclusion With the Complex Myograph, the whole spectrum of a muscle's mechanical characteristics may be assessed.

  12. Exercise-induced muscle cramp. Proposed mechanisms and management.

    Science.gov (United States)

    Bentley, S

    1996-06-01

    Muscle cramp is a common, painful, physiological disturbance of skeletal muscle. Many athletes are regularly frustrated by exercise-induced muscle cramp yet the pathogenesis remains speculative with little scientific research on the subject. This has resulted in a perpetuation of myths as to the cause and treatment of it. There is a need for scientifically based protocols for the management of athletes who suffer exercise-related muscle cramp. This article reviews the literature and neurophysiology of muscle cramp occurring during exercise. Disturbances at various levels of the central and peripheral nervous system and skeletal muscle are likely to be involved in the mechanism of cramp and may explain the diverse range of conditions in which cramp occurs. The activity of the motor neuron is subject to a multitude of influences including peripheral receptor sensory input, spinal reflexes, inhibitory interneurons in the spinal cord, synaptic and neurotransmitter modulation and descending CNS input. The muscle spindle and golgi tendon organ proprioceptors are fundamental to the control of muscle length and tone and the maintenance of posture. Disturbance in the activity of these receptors may occur through faulty posture, shortened muscle length, intense exercise and exercise to fatigue, resulting in increased motor neuron activity and motor unit recruitment. The relaxation phase of muscle contraction is prolonged in a fatigued muscle, raising the likelihood of fused summation of action potentials if motor neuron activity delivers a sustained high firing frequency. Treatment of cramp is directed at reducing muscle spindle and motor neuron activity by reflex inhibition and afferent stimulation. There are no proven strategies for the prevention of exercise-induced muscle cramp but regular muscle stretching using post-isometric relaxation techniques, correction of muscle balance and posture, adequate conditioning for the activity, mental preparation for competition and

  13. Vasodilatory mechanisms in contracting skeletal muscle

    DEFF Research Database (Denmark)

    Clifford, Philip S.; Hellsten, Ylva

    2004-01-01

    Skeletal muscle blood flow is closely coupled to metabolic demand, and its regulation is believed to be mainly the result of the interplay of neural vasoconstrictor activity and locally derived vasoactive substances. Muscle blood flow is increased within the first second after a single contraction...... and stabilizes within 30 s during dynamic exercise under normal conditions. Vasodilator substances may be released from contracting skeletal muscle, vascular endothelium, or red blood cells. The importance of specific vasodilators is likely to vary over the time course of flow, from the initial rapid rise...

  14. The breaking and making of healthy adult human skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Mackey, Abigail L.; Kjaer, Michael

    2017-01-01

    Background While muscle regeneration has been extensively studied in animal and cell culture models, in vivo myogenesis in adult human skeletal muscle has not been investigated in detail. Methods Using forced lengthening contractions induced by electrical stimulation, we induced myofibre injury...... in young healthy males. Muscle biopsies were collected from the injured leg 7 and 30 days after muscle injury and from the uninjured leg as a control. Immuno-stained single muscle fibres and muscle cross sections were studied by wide-field and confocal microscopy. Samples were also studied at the ultra......-structural level by electron microscopy. Results Microscopy of single muscle fibres in 3 dimensions revealed a repeating pattern of necrotic and regenerating zones along the length of the same myofibre, characterised by extensive macrophage infiltration alongside differentiating myogenic progenitor cells...

  15. Mechanical properties and fiber type composition of chronically inactive muscles

    Science.gov (United States)

    Roy, R. R.; Zhong, H.; Monti, R. J.; Vallance, K. A.; Kim, J. A.; Edgerton, V. R.

    2000-01-01

    A role for neuromuscular activity in the maintenance of skeletal muscle properties has been well established. However, the role of activity-independent factors is more difficult to evaluate. We have used the spinal cord isolation model to study the effects of chronic inactivity on the mechanical properties of the hindlimb musculature in cats and rats. This model maintains the connectivity between the motoneurons and the muscle fibers they innervate, but the muscle unit is electrically "silent". Consequently, the measured muscle properties are activity-independent and thus the advantage of using this model is that it provides a baseline level (zero activity) from which regulatory factors that affect muscle cell homeostasis can be defined. In the present paper, we will present a brief review of our findings using the spinal cord isolation model related to muscle mechanical and fiber type properties.

  16. Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Christensen, Britt; Lundby, Carsten; Jessen, Niels

    2012-01-01

    as activation of Epo signalling pathways (STAT5, MAPK, Akt, IKK) were analysed by western blotting. Changes in muscle protein profiles after prolonged erythropoietin treatment were evaluated by 2D gel-electrophoresis and mass spectrometry. The presence of the erythropoietin receptor in skeletal muscle......Background: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle. Methodology/Principal Findings: The protocols...... involved 1) acute effects of a single bolus injection of erythropoietin followed by consecutive muscle biopsies for 1-10 hours, and 2) a separate study with prolonged administration for 16 days with biopsies obtained before and after. The presence of erythropoietin receptors in muscle tissue as well...

  17. Skeletal muscle mechanics: questions, problems and possible solutions

    National Research Council Canada - National Science Library

    Walter Herzog

    2017-01-01

    .... In this manuscript, I am trying to identify some of the crucial challenges we are faced with in muscle mechanics, offer possible solutions to questions, and identify problems that might be worthwhile...

  18. Mechanisms of muscle growth and atrophy in mammals and Drosophila

    National Research Council Canada - National Science Library

    Piccirillo, Rosanna; Demontis, Fabio; Perrimon, Norbert; Goldberg, Alfred L

    2014-01-01

    .... Although the pathogenesis of this condition has been primarily studied in mammals, Drosophila is emerging as an attractive system to investigate some of the mechanisms involved in muscle growth and atrophy. Results...

  19. Peroxisome Proliferator-activated Receptor γ Coactivator 1α (PGC-1α) Promotes Skeletal Muscle Lipid Refueling in Vivo by Activating de Novo Lipogenesis and the Pentose Phosphate Pathway*

    OpenAIRE

    S. Summermatter; Baum, O; Santos, G.; Hoppeler, H.; Handschin, C.

    2010-01-01

    Exercise induces a pleiotropic adaptive response in skeletal muscle, largely through peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). PGC-1α enhances lipid oxidation and thereby provides energy for sustained muscle contraction. Its potential implication in promoting muscle refueling remains unresolved, however. Here, we investigated a possible role of elevated PGC-1α levels in skeletal muscle lipogenesis in vivo and the molecular mechanisms that underlie PGC-1α-mediated d...

  20. Muscle and motor neuron ciliary neurotrophic factor receptor α together maintain adult motor neuron axons in vivo.

    Science.gov (United States)

    Lee, Nancy; Serbinski, Carolyn R; Braunlin, Makayla R; Rasch, Matthew S; Rydyznski, Carolyn E; MacLennan, A John

    2016-12-01

    The molecular mechanisms maintaining adult motor innervation are comparatively unexplored relative to those involved during development. In addition to the fundamental neuroscience question, this area has important clinical ramifications given that loss of neuromuscular contact is thought to underlie several adult onset human neuromuscular diseases including amyotrophic lateral sclerosis. Indirect evidence suggests that ciliary neurotrophic factor (CNTF) receptors may contribute to adult motor neuron axon maintenance. To directly address this in vivo, we used adult onset mouse genetic disruption techniques to deplete motor neuron and muscle CNTF receptor α (CNTFRα), the essential ligand binding subunit of the receptor, and incorporated reporters labelling affected motor neuron axons and terminals. The combined depletion of motor neuron and muscle CNTFRα produced a large loss of motor neuron terminals and retrograde labelling of motor neurons with FluoroGold indicated axon die-back well beyond muscle, together revealing an essential role for CNTFRα in adult motor axon maintenance. In contrast, selective depletion of motor neuron CNTFRα did not affect motor innervation. These data, along with our previous work indicating no effect of muscle specific CNTFRα depletion on motor innervation, suggest that motor neuron and muscle CNTFRα function in concert to maintain motor neuron axons. The data also raise the possibility of motor neuron and/or muscle CNTFRα as therapeutic targets for adult neuromuscular denervating diseases. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Evaluation of a simple method for determining muscle volume in vivo.

    Science.gov (United States)

    Infantolino, Benjamin W; Challis, John H

    2016-06-14

    The quantification in vivo of muscle volume is important, for example, to understand how muscles change with aging, and respond to rehabilitation. Albracht et al. (2008) suggested that muscle volume can be estimated in vivo from the measurement of muscle cross-sectional area and muscle belly length only. The purpose of this study was to evaluate this proposed relationship for determining muscle volume for both the Vastus Lateralis (VL) and First Dorsal Interosseous (FDI) using ultrasound imaging. The cross-sectional area and length of 22 cadaver FDI and 6 VL muscles in cadavers were imaged using ultrasound, these muscles were then dissected and muscle volumes measured directly using the water displacement technique. Estimated muscle volumes were compared with their direct measurement, and for the VL the percentage root mean square error in the estimation of muscle volume was 5.0%, and the Bland-Altman analysis had all volume estimates within the 95% confidence interval, with no evidence of bias (proportional or constant) in the volume estimates. In contrast, percentage root mean square error for the FDI was 18.8%, with the Bland-Altman analysis showing volume estimates outside of the 95% confidence interval and proportional bias. These results indicate that the simple method proposed by Albracht et al. (2008) for the estimation of muscle volume is appropriate the VL but not the FDI using ultrasound imaging. Morphological disparities likely account for these differences, if accurate and fast measures of the volume of the FDI are required other approaches should be explored. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. In vivo mechanisms of acquired thymic tolerance

    DEFF Research Database (Denmark)

    Chen, W; Issazadeh-Navikas, Shohreh; Sayegh, M H

    1997-01-01

    Injection of antigen into the thymus of adult animals induces specific systemic tolerance, but the mechanisms of acquired thymic tolerance are not well understood. To investigate these mechanisms we used a model of intrathymic injection of ovalbumin (OVA) in BALB/c mice. We show an antigen-specif...

  3. The force-length curves of the human rectus femoris and gastrocnemius muscles in vivo.

    Science.gov (United States)

    Winter, Samantha L; Challis, John H

    2010-02-01

    For a physiologically realistic joint range of motion and therefore range of muscle fiber lengths, only part of the whole muscle force-length curve can be used in vivo; that is, only a section of the force-length curve is expressed. Previous work has determined that the expressed section of the force-length curve for individual muscles can vary between subjects; however, the degree of intersubject variability is different for different muscles. This study determined the expressed section of both the rectus femoris and gastrocnemius--muscles with very different ratios of tendon slack length to muscle fiber optimum length--for 28 nonspecifically trained subjects to test the hypothesis that the value of this ratio affects the amount of variability in the expressed section. The force-length curves of the two muscles were reconstructed from moment-angle data using the method of Herzog & ter Keurs (1988). There was no relationship between the expressed sections of the force-length curve for the two muscles. Less variability was found in the expressed section of the gastrocnemius compared with the rectus femoris, supporting the hypothesis. The lack of relationship between the expressed sections of the two muscles has implications for motor control and for training muscle for rehabilitation.

  4. In Vivo Imaging of Far-red Fluorescent Proteins after DNA Electrotransfer to Muscle Tissue

    DEFF Research Database (Denmark)

    Hojman, Pernille; Eriksen, Jens; Gehl, Julie

    2009-01-01

    DNA electrotransfer to muscle tissue yields long-term, high levels of gene expression; showing great promise for future gene therapy. We want to characterize the novel far-red fluorescent protein Katushka as a marker for gene expression using time domain fluorescence in vivo imaging. Highly effic...... weeks. Depth and 3D analysis proved that the expression was located in the target muscle. In vivo bio-imaging using the novel Katushka fluorescent protein enables excellent evaluation of the transfection efficacy, and spatial distribution, but lacks long-term stability....

  5. Implantation of in vitro tissue engineered muscle repair constructs and bladder acellular matrices partially restore in vivo skeletal muscle function in a rat model of volumetric muscle loss injury.

    Science.gov (United States)

    Corona, Benjamin T; Ward, Catherine L; Baker, Hannah B; Walters, Thomas J; Christ, George J

    2014-02-01

    The frank loss of a large volume of skeletal muscle (i.e., volumetric muscle loss [VML]) can lead to functional debilitation and presents a significant problem to civilian and military medicine. Current clinical treatment for VML involves the use of free muscle flaps and physical rehabilitation; however, neither are effective in promoting regeneration of skeletal muscle to replace the tissue that was lost. Toward this end, skeletal muscle tissue engineering therapies have recently shown great promise in offering an unprecedented treatment option for VML. In the current study, we further extend our recent progress (Machingal et al., 2011, Tissue Eng; Corona et al., 2012, Tissue Eng) in the development of tissue engineered muscle repair (TEMR) constructs (i.e., muscle-derived cells [MDCs] seeded on a bladder acellular matrix (BAM) preconditioned with uniaxial mechanical strain) for the treatment of VML. TEMR constructs were implanted into a VML defect in a tibialis anterior (TA) muscle of Lewis rats and observed up to 12 weeks postinjury. The salient findings of the study were (1) TEMR constructs exhibited a highly variable capacity to restore in vivo function of injured TA muscles, wherein TEMR-positive responders (n=6) promoted an ≈61% improvement, but negative responders (n=7) resulted in no improvement compared to nonrepaired controls, (2) TEMR-positive and -negative responders exhibited differential immune responses that may underlie these variant responses, (3) BAM scaffolds (n=7) without cells promoted an ≈26% functional improvement compared to uninjured muscles, (4) TEMR-positive responders promoted muscle fiber regeneration within the initial defect area, while BAM scaffolds did so only sparingly. These findings indicate that TEMR constructs can improve the in vivo functional capacity of the injured musculature at least, in part, by promoting generation of functional skeletal muscle fibers. In short, the degree of functional recovery observed following

  6. The mechanisms of muscle wasting in COPD and heart failure

    Directory of Open Access Journals (Sweden)

    Giorgio Vescovo

    2012-10-01

    Full Text Available Many of the mechanisms leading to skeletal muscle wasting in COPD and heart failure are common to both conditions. These encompass neurohormonal activation and systemic inflammation. The mechanisms leading to muscle dysfunction are both qualitative and quantitative. Qualitative changes comprise the transition from aerobic metabolism and prevalent slow fibers composition toward anaerobic metabolism and fast fibers synthesis. Quantitative changes are mainly linked to muscle loss. These changes occur not only in the major muscles bulks of the body but also in respiratory muscles. The mechanisms leading to muscle wastage include cytokine-triggered skeletal muscle apoptosis and ubiquitin-proteasomeand non-ubiquitin-dependent pathways. The regulation of fiber type involves the growth hormone/insulin-like growth factor 1/calcineurin/transcriptional coactivator PGC1 cascade. The imbalance between protein synthesis and degradation plays an important role. Protein degradation can occur through ubiquitin-dependent and non-ubiquitin-dependent pathways. Very recently, two systems controlling ubiquitin-proteasome activation have been described: FOXO-ubiquitin ligase and NFkB ubiquitin ligase. These are triggered by TNFα and growth hormone/insulin-like growth factor 1. Moreover, apoptosis, which is triggered by tumor necrosis factor α, plays an important role. Another mechanism acting on muscle wastage is malnutrition, with an imbalance between catabolic and anabolic factors toward the catabolic component. Catabolism is also worsened by the activation of the adrenergic system and alteration of the cortisol/DEHA ratio toward cortisol production. Sarcomeric protein oxidation and its consequent contractile impairment can be another cause of skeletal muscle dysfunction in CHF.

  7. Partial rescue of in vivo insulin signalling in skeletal muscle by impaired insulin clearance in heterozygous carriers of a mutation in the insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Wojtaszewski, Jørgen F.P.; Birk, J.

    2006-01-01

    AIMS/HYPOTHESIS: Recently we reported the coexistence of postprandial hypoglycaemia and moderate insulin resistance in heterozygous carriers of the Arg1174Gln mutation in the insulin receptor gene (INSR). Controlled studies of in vivo insulin signalling in humans with mutant INSR are unavailable...... in vivo insulin signalling in muscle in these carriers of a mutant INSR, probably by increasing insulin action on the non-mutated insulin receptors......., and therefore the cellular mechanisms underlying insulin resistance in Arg1174Gln carriers remain to be clarified. SUBJECTS, MATERIALS AND METHODS: We studied glucose metabolism and insulin signalling in skeletal muscle from six Arg1174Gln carriers and matched control subjects during a euglycaemic...

  8. Muscle force loss and soreness subsequent to maximal eccentric contractions depend on the amount of fascicle strain in vivo.

    Science.gov (United States)

    Guilhem, G; Doguet, V; Hauraix, H; Lacourpaille, L; Jubeau, M; Nordez, A; Dorel, S

    2016-06-01

    Defining the origins of muscle injury has important rehabilitation and exercise applications. However, current knowledge of muscle damage mechanics in human remains unclear in vivo. This study aimed to determine the relationships between muscle-tendon unit mechanics during maximal eccentric contractions and the extent of subsequent functional impairments induced by muscle damage. The length of the muscle-tendon unit, fascicles and tendinous tissues was continuously measured on the gastrocnemius medialis using ultrasonography, in time with torque, during 10 sets of 30 maximal eccentric contractions of plantar flexors at 45°s(-1) , in seventeen participants. Muscle-tendon unit, fascicles and tendinous tissues were stretched up to 4.44 ± 0.33 cm, 2.31 ± 0.64 cm and 1.92 ± 0.61 cm respectively. Fascicle stretch length, lengthening amplitude and negative fascicle work beyond slack length were significantly correlated with the force decrease 48 h post-exercise (r = 0.51, 0.47 and 0.68, respectively; P muscle fibres during eccentric contractions strongly influences the magnitude of muscle damage in vivo. Achilles tendon compliance decreases the amount of strain, while architectural gear ratio may moderately contribute to attenuating muscle fascicle lengthening and hence muscle damage. Further studies are necessary to explore the impact of various types of task to fully understand the contribution of muscle-tendon interactions during active lengthening to muscle damage. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  9. Imaging two-dimensional mechanical waves of skeletal muscle contraction.

    Science.gov (United States)

    Grönlund, Christer; Claesson, Kenji; Holtermann, Andreas

    2013-02-01

    Skeletal muscle contraction is related to rapid mechanical shortening and thickening. Recently, specialized ultrasound systems have been applied to demonstrate and quantify transient tissue velocities and one-dimensional (1-D) propagation of mechanical waves during muscle contraction. Such waves could potentially provide novel information on musculoskeletal characteristics, function and disorders. In this work, we demonstrate two-dimensional (2-D) mechanical wave imaging following the skeletal muscle contraction. B-mode image acquisition during multiple consecutive electrostimulations, speckle-tracking and a time-stamp sorting protocol were used to obtain 1.4 kHz frame rate 2-D tissue velocity imaging of the biceps brachii muscle contraction. The results present novel information on tissue velocity profiles and mechanical wave propagation. In particular, counter-propagating compressional and shear waves in the longitudinal direction were observed in the contracting tissue (speed 2.8-4.4 m/s) and a compressional wave in the transverse direction of the non-contracting muscle tissue (1.2-1.9 m/s). In conclusion, analysing transient 2-D tissue velocity allows simultaneous assessment of both active and passive muscle tissue properties. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  10. Robotic Powered Transfer Mechanism modeling on Human Muscle Structure

    Science.gov (United States)

    Saito, Yukio

    It is considered in engineering that one power source can operate one joint. However, support movement mechanism of living organism is multi joint movement mechanism. Considerably different from mechanical movement mechanism, two pairs of uni-articular muscles and a pair of bi-articular muscles are involved in it. In leg, movements observed in short run including leg idling, heel contact and toeing are operated by bi-articular muscles of the thigh showing strong legs to support body weight. Pursuit of versatility in welfare robot brings its comparison with conventional machinery or industrial robot to the fore. Request for safety and technology allowing elderly people to operate the robot is getting stronger in the society. The robot must be safe when it is used together with other welfare equipment and simpler system avoiding difficult operation has to be constructed. Appearance of recent care and assistance robot is getting similar to human arm in comparison with industrial robot. Being easily able to imagine from industrial robot, mid-heavyweight articulated robot to support 60-70kgf combined with large output motor and reduction gears is next to impossible to be installed in the bath room. This research indicated that upper limb arm and lower limb thigh of human and animals are holding coalitional muscles and movement of uni-artcular muscle and bi-articular muscle conjure the image of new actuators.

  11. Myofiber ellipticity as an explanation for transverse asymmetry of skeletal muscle diffusion MRI in vivo signal.

    Science.gov (United States)

    Karampinos, Dimitrios C; King, Kevin F; Sutton, Bradley P; Georgiadis, John G

    2009-12-01

    Due to its unique non-invasive microstructure probing capabilities, diffusion tensor imaging (DTI) constitutes a valuable tool in the study of fiber orientation in skeletal muscles. By implementing a DTI sequence with judiciously chosen directional encoding to quantify in vivo the microarchitectural properties in the calf muscles of three healthy volunteers at rest, we report that the secondary eigenvalue is significantly higher than the tertiary eigenvalue, a phenomenon corroborated by prior DTI findings. Toward a physics-based explanation of this phenomenon, we propose a composite medium model that accounts for water diffusion in the space within the muscle fiber and the extracellular space. The muscle fibers are abstracted as cylinders of infinite length with an elliptical cross section, the latter closely approximating microstructural features well documented in prior histological studies of excised muscle. The range of values of fiber ellipticity predicted by our model agrees with these studies, and the spatial orientation of the cross-sectional ellipses is consistent with local muscle strain fields and the putative direction of lateral transmission of stress between fibers in certain regions in three antigravity muscles (Tibialis Anterior, Soleus, and Gastrocnemius), as well as independent measurements of deformation in active calf muscles. As a metric, fiber cross-sectional ellipticity may be useful for quantifying morphological changes in skeletal muscle fibers with aging, hypertrophy, or sarcopenia.

  12. Validation of Hill-Type Muscle Models in Relation to Neuromuscular Recruitment and Force-Velocity Properties: Predicting Patterns of In Vivo Muscle Force

    OpenAIRE

    Biewener, Andrew Austin; Wakeling, James; Lee, Sabrina S.; Arnold, Allison

    2014-01-01

    We review here the use and reliability of Hill-type muscle models to predict muscle performance under varying conditions, ranging from in situ production of isometric force to in vivo dynamics of muscle length change and force in response to activation. Muscle models are frequently used in musculoskeletal simulations of movement, particularly when applied to studies of human motor performance in which surgically implanted transducers have limited use. Musculoskeletal simulations of different ...

  13. Non-local muscle fatigue: effects and possible mechanisms.

    Science.gov (United States)

    Halperin, Israel; Chapman, Dale W; Behm, David G

    2015-10-01

    Non-local muscle fatigue (NLMF) is characterized by muscle performance impairments in a contralateral or remote non-exercised muscle(s) following a fatiguing protocol of a different muscle group(s). This topic is of interest as it affords insights into physiological determinants of muscle fatigue and may provide practical applications concerning the order of exercises in training and rehabilitation programs. A literature review was conducted using Web of Science, PubMed, and Google Scholar databases to evaluate the NLMF effects and possible underlying mechanisms. Overall, 35 studies with 58 outcome measures that met the inclusion criteria were identified. The literature is conflicting with approximately half of the studies reporting NLMF effects (32 of 58 measurements). However, on closer examination 76% of outcome measures of the lower limbs reported NLMF effects (23 of 30 measurements) compared to only 32% in the upper body (9 of 28 measurements). Thus, it appears that NLMF effects may be muscle group dependent. Also, tests that involve prolonged or repetitive contractions provide clearer evidence of NLMF. Other variables potentially influencing the size of the NLMF effect include the fatigued muscle groups, the protocols used to elicit the fatigue, gender and training background of participants. While the NLMF literature is conflicting, certain variables appear to affect NLMF responses which can account for some of the discrepancies. Furthermore, the NLMF effects may be attributed to four different but interconnected pathways: neurological, biochemical, biomechanical and psychological.

  14. Lower limb asymmetry in mechanical muscle function

    DEFF Research Database (Denmark)

    Jordan, M J; Aagaard, Per; Herzog, W

    2015-01-01

    Due to a high incidence of anterior cruciate ligament (ACL) re-injury in alpine ski racers, this study aims to assess functional asymmetry in the countermovement jump (CMJ), squat jump (SJ), and leg muscle mass in elite ski racers with and without anterior cruciate ligament reconstruction (ACL......-R). Elite alpine skiers with ACL-R (n = 9; 26.2 ± 11.8 months post-op) and uninjured skiers (n = 9) participated in neuromuscular screening. Vertical ground reaction force during the CMJ and SJ was assessed using dual force plate methodology to obtain phase-specific bilateral asymmetry indices (AIs...... as a part of a multifaceted approach for improving outcome following ACL-R in elite ski racers....

  15. Polypyrrole for Artificial Muscles: Ionic Mechanisms

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2006-01-01

    Some conjugated polymers can convert electrical energy to mechanical energy (via chemical energy), thereby acting as electro-chemo-mechanical actuators or “artificial muscles”. The advantage of this type of actuator is that the process can be driven by the application of a small potential (1-5 V...

  16. Combined in vivo and ex vivo analysis of mesh mechanics in a porcine hernia model.

    Science.gov (United States)

    Kahan, Lindsey G; Lake, Spencer P; McAllister, Jared M; Tan, Wen Hui; Yu, Jennifer; Thompson, Dominic; Brunt, L Michael; Blatnik, Jeffrey A

    2017-07-21

    Hernia meshes exhibit variability in mechanical properties, and their mechanical match to tissue has not been comprehensively studied. We used an innovative imaging model of in vivo strain tracking and ex vivo mechanical analysis to assess effects of mesh properties on repaired abdominal walls in a porcine model. We hypothesized that meshes with dissimilar mechanical properties compared to native tissue would alter abdominal wall mechanics more than better-matched meshes. Seven mini-pigs underwent ventral hernia creation and subsequent open repair with one of two heavyweight polypropylene meshes. Following mesh implantation with attached radio-opaque beads, fluoroscopic images were taken at insufflation pressures from 5 to 30 mmHg on postoperative days 0, 7, and 28. At 28 days, animals were euthanized and ex vivo mechanical testing performed on full-thickness samples across repaired abdominal walls. Testing was conducted on 13 mini-pig controls, and on meshes separately. Stiffness and anisotropy (the ratio of stiffness in the transverse versus craniocaudal directions) were assessed. 3D reconstructions of repaired abdominal walls showed stretch patterns. As pressure increased, both meshes expanded, with no differences between groups. Over time, meshes contracted 17.65% (Mesh A) and 0.12% (Mesh B; p = 0.06). Mesh mechanics showed that Mesh A deviated from anisotropic native tissue more than Mesh B. Compared to native tissue, Mesh A was stiffer both transversely and craniocaudally. Explanted repaired abdominal walls of both treatment groups were stiffer than native tissue. Repaired tissue became less anisotropic over time, as mesh properties prevailed over native abdominal wall properties. This technique assessed 3D stretch at the mesh level in vivo in a porcine model. While the abdominal wall expanded, mesh-ingrown areas contracted, potentially indicating stresses at mesh edges. Ex vivo mechanics demonstrate that repaired tissue adopts mesh properties, suggesting

  17. In-Vivo Measurement of Muscle Tension: Dynamic Properties of the MC Sensor during Isometric Muscle Contraction

    Directory of Open Access Journals (Sweden)

    Srđan Đorđević

    2014-09-01

    Full Text Available Skeletal muscle is the largest tissue structure in our body and plays an essential role for producing motion through integrated action with bones, tendons, ligaments and joints, for stabilizing body position, for generation of heat through cell respiration and for blood glucose disposal. A key function of skeletal muscle is force generation. Non-invasive and selective measurement of muscle contraction force in the field and in clinical settings has always been challenging. The aim of our work has been to develop a sensor that can overcome these difficulties and therefore enable measurement of muscle force during different contraction conditions. In this study, we tested the mechanical properties of a “Muscle Contraction” (MC sensor during isometric muscle contraction in different length/tension conditions. The MC sensor is attached so that it indents the skin overlying a muscle group and detects varying degrees of tension during muscular contraction. We compared MC sensor readings over the biceps brachii (BB muscle to dynamometric measurements of force of elbow flexion, together with recordings of surface EMG signal of BB during isometric contractions at 15° and 90° of elbow flexion. Statistical correlation between MC signal and force was very high at 15° (r = 0.976 and 90° (r = 0.966 across the complete time domain. Normalized SD or σN = σ/max(FMC was used as a measure of linearity of MC signal and elbow flexion force in dynamic conditions. The average was 8.24% for an elbow angle of 90° and 10.01% for an elbow of angle 15°, which indicates high linearity and good dynamic properties of MC sensor signal when compared to elbow flexion force. The next step of testing MC sensor potential will be to measure tension of muscle-tendon complex in conditions when length and tension change simultaneously during human motion.

  18. In vivo alterations in skeletal muscle form and function after disuse atrophy.

    Science.gov (United States)

    Clark, Brian C

    2009-10-01

    Prolonged reductions in muscle activity and mechanical loading (e.g., bed rest, cast immobilization) result in alterations in skeletal muscle form and function. The purpose of this review article was to synthesize recent findings from several studies on the dramatic effects of disuse on skeletal muscle morphology and muscle performance in humans. Specifically, the following are discussed: 1) how the antigravity muscles are most susceptible to atrophy and how the degree of atrophy varies between muscle groups; 2) how disuse alters muscle composition by increasing intermuscular adipose tissue; 3) the influence of different disuse models on regulating the loss of muscle mass and strength, with immobilization causing greater reductions than bed rest and limb suspension do; 4) the observation that disuse decreases strength to a greater extent than muscle mass and the role of adaptations in both neural and contractile properties that influences this excessive loss of strength; 5) the equivocal findings on the effect of disuse on muscle fatigue resistance; and 6) the reduction in motor control after prolonged disuse. Lastly, emerging data warranting further inquiry into the modulating role of biological sex on disuse-induced adaptations are also discussed.

  19. In Vivo Pediatric Shoulder Muscle Volumes and Their Relationship to 3D Strength

    Science.gov (United States)

    Im, Hyun Soo; Alter, Katharine E.; Brochard, Sylvain; Pons, Christelle; Sheehan, Frances T.

    2017-01-01

    In the pediatric shoulder, injury and pathology can disrupt the muscle force balance, resulting in severe functional losses. As little data exists pertaining to in vivo pediatric shoulder muscle function, musculoskeletal data are crucially needed to advance the treatment of pediatric shoulder pathology/injury. Therefore, the purpose of this study was to develop a pediatric database of in vivo volumes for the major shoulder muscles and correlate these volumes to maximum isometric flexion/extension, internal/external rotation, and abduction/adduction joint moments. A methodology was developed to derive 3D shoulder muscle volumes and to divide the deltoid into sub-units with unique torque producing capabilities, based on segmentation of three-dimensional magnetic resonance images. Eleven typically developing children/adolescents (4F/7M, 12.0±3.2years, 150.8±16.7cm, 49.2±16.4kg) participated. Correlation and regression analyses were used to evaluate the relationship between volume and maximum, voluntary, isometric joint torques. The deltoid demonstrated the largest (30.4 ±1.2%) and the supraspinatus the smallest (4.8 ± 0.5%) percent of the total summed volume of all six muscles evaluated. The anterior and posterior deltoid sections were 43.4±3.9% and 56.6±3.9% of the total deltoid volume. The percent volumes were highly consistent across subjects. Individual muscle volumes demonstrated moderate-high correlations with torque values (0.70–0.94, pshoulder muscle volume. Using these data a clear relationship between shoulder volume and the torques they produce was established in all three rotational degrees-of-freedom. This study furthers the understanding of shoulder muscle function and serves as a foundation for evaluating shoulder injury/pathology in the pediatric/adolescent population. PMID:24925254

  20. Peripheral muscle strength and correlates of muscle weakness in patients receiving mechanical ventilation.

    Science.gov (United States)

    Chlan, Linda L; Tracy, Mary Fran; Guttormson, Jill; Savik, Kay

    2015-11-01

    Intensive care unit-acquired weakness is a frequent complication of critical illness because of patients' immobility and prolonged use of mechanical ventilation. To describe daily measurements of peripheral muscle strength in patients receiving mechanical ventilation and explore relationships among factors that influence intensive care unit-acquired weakness. Peripheral muscle strength of 120 critically ill patients receiving mechanical ventilation was measured daily by using a standardized handgrip dynamometry protocol. Three grip measurements for each hand were recorded in pounds-force; the mean of these 3 assessments was used in the analysis. Correlates of intensive care unit-acquired weakness (age, sex, illness severity, duration of mechanical ventilation, medications) were analyzed by using mixed models to explore the relationship to grip strength. Median baseline grip strength was variable yet diminished (7.7 pounds-force), with either a pattern of diminishing grip strength or maintenance of the baseline low grip strength over time. With controls for days of measurement, female sex (β = -10.4; P mechanical ventilation (β = -0.34; P = .005) explained a significant amount of variance in grip strength over time. Patients receiving prolonged mechanical ventilation had marked decrements in grip strength, measured by hand dynamometry, a marker for peripheral muscle strength. Hand dynamometry is a reliable method for measuring muscle strength in cooperative critically ill patients and can be used to develop interventions to prevent intensive care unit-acquired weakness. ©2015 American Association of Critical-Care Nurses.

  1. Keratin Hydrogel Enhances In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss.

    Science.gov (United States)

    Passipieri, J A; Baker, H B; Siriwardane, Mevan; Ellenburg, Mary D; Vadhavkar, Manasi; Saul, Justin M; Tomblyn, Seth; Burnett, Luke; Christ, George J

    2017-06-01

    Volumetric muscle loss (VML) injuries exceed the considerable intrinsic regenerative capacity of skeletal muscle, resulting in permanent functional and cosmetic deficits. VML and VML-like injuries occur in military and civilian populations, due to trauma and surgery as well as due to a host of congenital and acquired diseases/syndromes. Current therapeutic options are limited, and new approaches are needed for a more complete functional regeneration of muscle. A potential solution is human hair-derived keratin (KN) biomaterials that may have significant potential for regenerative therapy. The goal of these studies was to evaluate the utility of keratin hydrogel formulations as a cell and/or growth factor delivery vehicle for functional muscle regeneration in a surgically created VML injury in the rat tibialis anterior (TA) muscle. VML injuries were treated with KN hydrogels in the absence and presence of skeletal muscle progenitor cells (MPCs), and/or insulin-like growth factor 1 (IGF-1), and/or basic fibroblast growth factor (bFGF). Controls included VML injuries with no repair (NR), and implantation of bladder acellular matrix (BAM, without cells). Initial studies conducted 8 weeks post-VML injury indicated that application of keratin hydrogels with growth factors (KN, KN+IGF-1, KN+bFGF, and KN+IGF-1+bFGF, n = 8 each) enabled a significantly greater functional recovery than NR (n = 7), BAM (n = 8), or the addition of MPCs to the keratin hydrogel (KN+MPC, KN+MPC+IGF-1, KN+MPC+bFGF, and KN+MPC+IGF-1+bFGF, n = 8 each) (p functional recovery for as many as 12 weeks post-VML injury after application of keratin hydrogels in the absence of cells. A significant time-dependent increase in functional recovery of the KN, KN+bFGF, and KN+IGF+bFGF groups was observed, relative to NR and BAM implantation, achieving as much as 90% of the maximum possible functional recovery. Histological findings from harvested tissue at 12 weeks post-VML injury documented

  2. Considerations for ex vivo thermal tissue testing exemplified using the fresh porcine longissimus muscle model for endometrial ablation

    Science.gov (United States)

    Fugett, James H.; Bennett, Haydon E.; Shrout, Joshua L.; Coad, James E.

    2017-02-01

    Expansions in minimally invasive medical devices and technologies with thermal mechanisms of action are continuing to advance the practice of medicine. These expansions have led to an increasing need for appropriate animal models to validate and quantify device performance. The planning of these studies should take into consideration a variety of parameters, including the appropriate animal model (test system - ex vivo or in vivo; species; tissue type), treatment conditions (test conditions), predicate device selection (as appropriate, control article), study timing (Day 0 acute to more than Day 90 chronic survival studies), and methods of tissue analysis (tissue dissection - staining methods). These considerations are discussed and illustrated using the fresh extirpated porcine longissimus muscle model for endometrial ablation.

  3. Classical and adaptive control of ex vivo skeletal muscle contractions using Functional Electrical Stimulation (FES.

    Directory of Open Access Journals (Sweden)

    Paola Jaramillo Cienfuegos

    Full Text Available Functional Electrical Stimulation is a promising approach to treat patients by stimulating the peripheral nerves and their corresponding motor neurons using electrical current. This technique helps maintain muscle mass and promote blood flow in the absence of a functioning nervous system. The goal of this work is to control muscle contractions from FES via three different algorithms and assess the most appropriate controller providing effective stimulation of the muscle. An open-loop system and a closed-loop system with three types of model-free feedback controllers were assessed for tracking control of skeletal muscle contractions: a Proportional-Integral (PI controller, a Model Reference Adaptive Control algorithm, and an Adaptive Augmented PI system. Furthermore, a mathematical model of a muscle-mass-spring system was implemented in simulation to test the open-loop case and closed-loop controllers. These simulations were carried out and then validated through experiments ex vivo. The experiments included muscle contractions following four distinct trajectories: a step, sine, ramp, and square wave. Overall, the closed-loop controllers followed the stimulation trajectories set for all the simulated and tested muscles. When comparing the experimental outcomes of each controller, we concluded that the Adaptive Augmented PI algorithm provided the best closed-loop performance for speed of convergence and disturbance rejection.

  4. Mechanical properties of the human Achilles tendon, in vivo

    DEFF Research Database (Denmark)

    Kongsgaard, M; Nielsen, C H; Hegnsvad, S

    2011-01-01

    Ultrasonography has been widely applied for in vivo measurements of tendon mechanical properties. Assessments of human Achilles tendon mechanical properties have received great interest. Achilles tendon injuries predominantly occur in the tendon region between the Achilles-soleus myotendinous...... junction and Achilles-calcaneus osteotendinous junction i.e. in the free Achilles tendon. However, there has been no adequate ultrasound based method for quantifying the mechanical properties of the free human Achilles tendon. This study aimed to: 1) examine the mechanical properties of the free human...

  5. Mimicking exercise in three-dimensional bioengineered skeletal muscle to investigate cellular and molecular mechanisms of physiological adaptation.

    Science.gov (United States)

    Kasper, Andreas M; Turner, Daniel C; Martin, Neil R W; Sharples, Adam P

    2018-03-01

    Bioengineering of skeletal muscle in vitro in order to produce highly aligned myofibres in relevant three dimensional (3D) matrices have allowed scientists to model the in vivo skeletal muscle niche. This review discusses essential experimental considerations for developing bioengineered muscle in order to investigate exercise mimicking stimuli. We identify current knowledge for the use of electrical stimulation and co-culture with motor neurons to enhance skeletal muscle maturation and contractile function in bioengineered systems in vitro. Importantly, we provide a current opinion on the use of acute and chronic exercise mimicking stimuli (electrical stimulation and mechanical overload) and the subsequent mechanisms underlying physiological adaptation in 3D bioengineered muscle. We also identify that future studies using the latest bioreactor technology, providing simultaneous electrical and mechanical loading and flow perfusion in vitro, may provide the basis for advancing knowledge in the future. We also envisage, that more studies using genetic, pharmacological, and hormonal modifications applied in human 3D bioengineered skeletal muscle may allow for an enhanced discovery of the in-depth mechanisms underlying the response to exercise in relevant human testing systems. Finally, 3D bioengineered skeletal muscle may provide an opportunity to be used as a pre-clinical in vitro test-bed to investigate the mechanisms underlying catabolic disease, while modelling disease itself via the use of cells derived from human patients without exposing animals or humans (in phase I trials) to the side effects of potential therapies. © 2017 Wiley Periodicals, Inc.

  6. Unloaded shortening velocity of voluntarily and electrically activated human dorsiflexor muscles in vivo.

    Directory of Open Access Journals (Sweden)

    Kazushige Sasaki

    Full Text Available We have previously shown that unloaded shortening velocity (V(0 of human plantar flexors can be determined in vivo, by applying the "slack test" to submaximal voluntary contractions (J Physiol 567:1047-1056, 2005. In the present study, to investigate the effect of motor unit recruitment pattern on V(0 of human muscle, we modified the slack test and applied this method to both voluntary and electrically elicited contractions of dorsiflexors. A series of quick releases (i.e., rapid ankle joint rotation driven by an electrical dynamometer was applied to voluntarily activated dorsiflexor muscles at three different contraction intensities (15, 50, and 85% of maximal voluntary contraction; MVC. The quick-release trials were also performed on electrically activated dorsiflexor muscles, in which three stimulus conditions were used: submaximal (equal to 15%MVC 50-Hz stimulation, supramaximal 50-Hz stimulation, and supramaximal 20-Hz stimulation. Modification of the slack test in vivo resulted in good reproducibility of V(0, with an intraclass correlation coefficient of 0.87 (95% confidence interval: 0.68-0.95. Regression analysis showed that V(0 of voluntarily activated dorsiflexor muscles significantly increased with increasing contraction intensity (R(2 = 0.52, P<0.001. By contrast, V(0 of electrically activated dorsiflexor muscles remained unchanged (R(2<0.001, P = 0.98 among three different stimulus conditions showing a large variation of tetanic torque. These results suggest that the recruitment pattern of motor units, which is quite different between voluntary and electrically elicited contractions, plays an important role in determining shortening velocity of human skeletal muscle in vivo.

  7. Mechanism of attenuation of skeletal muscle atrophy by zinc-alpha2-glycoprotein.

    Science.gov (United States)

    Russell, Steven T; Tisdale, Michael J

    2010-10-01

    The mechanism by which the adipokine zinc-α2-glycoprotein (ZAG) increases the mass of gastrocnemius, but not soleus muscle of diabetic mice, has been evaluated both in vivo and in vitro. There was an increased phosphorylation of both double-stranded RNA-dependent protein kinase and its substrate, eukaryotic initiation factor-2α, which was attenuated by about two-thirds in gastrocnemius but not soleus muscle of ob/ob mice treated with ZAG (50 μg, iv daily) for 5 d. ZAG also reduced the expression of the phospho forms of p38MAPK and phospholipase A2, as well as expression of the ubiquitin ligases (E3) muscle atrophy F-box/atrogin-1 and muscle RING finger protein, and the increased activity of both caspase-3 and casapse-8 to values found in nonobese controls. ZAG also increased the levels of phospho serine-threonine kinase and mammalian target of rapamycin in gastrocnemius muscle and reduced the phosphorylation of insulin receptor substrate-1 (Ser307) associated with insulin resistance. Similar changes were seen with ZAG when murine myotubes were incubated with high glucose concentrations (10 and 25 mm), showing that the effect of ZAG was direct. ZAG produced an increase in cAMP in murine myotubes, and the effects of ZAG on protein synthesis and degradation in vitro could be replicated by dibutyryl cAMP. ZAG increased cAMP levels of gastrocnemius but not soleus muscle. These results suggest that protein accretion in skeletal muscle in response to ZAG may be due to changes in intracellular cAMP and also that ZAG may have a therapeutic application in the treatment of muscle wasting conditions.

  8. Postoperative Recovery of Mechanical Muscle Function in Hip Replacement Patients

    DEFF Research Database (Denmark)

    Jensen, Carsten; Aagaard, Per; Overgaard, Søren

    2011-01-01

    formal training. Parameters: In vivo isometric peak strength/torque (Tmax) and rate of torque development (RTD) were measured during unilateral knee extension and flexion but also extension, flexion, adduction and abduction of the hip muscle groups were evaluated. Data was obtained pre, 8, 26 and 52......INTRODUCTION Muscle function in patients with hip osteoarthritis (OA) is not well-studied. We established a new setup of tests in order to monitor patients before and after surgery. Our novel setup was used to evaluate single- and multi-joint strength (torque) and power in a group of 40 – 65 year...... old hip patients.   MATERIAL AND METHODS Patients: Forty elderly patients (age 55 ± 6, BMI 27.5 ± 4.1) with unilateral osteoarthritis participated in this prospectively study and were randomized to either total or resurfacing hip replacement. All implants inserted by two senior surgeons using only...

  9. The effect of in vivo rotator cuff muscle contraction on glenohumeral joint translation: An ultrasonographic and electromyographic study.

    Science.gov (United States)

    Rathi, Sangeeta; Taylor, Nicholas F; Green, Rodney A

    2016-12-08

    The proposed stabilizing mechanism of rotator cuff muscles is to limit excessive humeral head translation. However, an accurate measurement of glenohumeral joint translation in vivo has been challenging. We aimed to measure the effect of rotator cuff muscle contraction on glenohumeral joint translation using real time ultrasound (RTUS) and electromyography. Twenty healthy adults with no history of shoulder pathology were recruited. Six intramuscular electrodes were inserted in the rotator cuff muscles (supraspinatus, upper and lower infraspinatus, teres minor, upper and lower subscapularis). Anterior and posterior glenohumeral translations were measured in testing conditions (with and without translation force, with and without isometric internal and external rotation), in two positions (shoulder neutral, abduction) and views (anterior, posterior). There was reduced glenohumeral translation with rotator cuff muscle contraction in the neutral anterior (F 2,38 =17.8, pmuscles in response to anterior and posterior translation forces (pmuscles, infraspinatus and teres minor, appeared to tether anterior translation of the humeral head. Our results confirm that the rotator cuff functions as a stabilizer of the glenohumeral joint by limiting humeral head translation and this is likely to be in a direction-specific manner. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. In vivo pediatric shoulder muscle volumes and their relationship to 3D strength.

    Science.gov (United States)

    Im, Hyun Soo; Alter, Katharine E; Brochard, Sylvain; Pons, Christelle; Sheehan, Frances T

    2014-08-22

    In the pediatric shoulder, injury and pathology can disrupt the muscle force balance, resulting in severe functional losses. As little data exists pertaining to in vivo pediatric shoulder muscle function, musculoskeletal data are crucially needed to advance the treatment of pediatric shoulder pathology/injury. Therefore, the purpose of this study was to develop a pediatric database of in vivo volumes for the major shoulder muscles and correlate these volumes with maximum isometric flexion/extension, internal/external rotation, and abduction/adduction joint moments. A methodology was developed to derive 3D shoulder muscle volumes and to divide the deltoid into sub-units with unique torque producing capabilities, based on segmentation of three-dimensional magnetic resonance images. Eleven typically developing children/adolescents (4F/7M, 12.0 ± 3.2 years, 150.8 ± 16.7 cm, 49.2 ± 16.4 kg) participated. Correlation and regression analyses were used to evaluate the relationship between volume and maximum, voluntary, isometric joint torques. The deltoid demonstrated the largest (30.4 ± 1.2%) and the supraspinatus the smallest (4.8 ± 0.5%) percent of the total summed volume of all six muscles evaluated. The anterior and posterior deltoid sections were 43.4 ± 3.9% and 56.6 ± 3.9% of the total deltoid volume. The percent volumes were highly consistent across subjects. Individual muscle volumes demonstrated moderate-high correlations with torque values (0.70-0.94, pmuscle volume. Using these data a clear relationship between shoulder volume and the torques they produce was established in all three rotational degrees-of-freedom. This study furthers the understanding of shoulder muscle function and serves as a foundation for evaluating shoulder injury/pathology in the pediatric/adolescent population. Copyright © 2014. Published by Elsevier Ltd.

  11. Antisense c-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo

    Science.gov (United States)

    Simons, Michael; Edelman, Elazer R.; Dekeyser, Jean-Luc; Langer, Robert; Rosenberg, Robert D.

    1992-09-01

    SYNTHETIC antisense oligonucleotides have been used to dissect gene function in vitro. Technical difficulties prevented the use of this approach for investigating the effect of gene products in vivo. Here we report the use of local delivery of antisense c-myb oligonu-cleotide to suppress intimal accumulation of rat carotid arterial smooth muscle cells. Our results suggest that antisense oligonucleotides can be used to define the in vivo biological role of specific macromolecules in the blood vessel wall and could potentially serve as a new class of therapeutic agents for cardiovascular disorders.

  12. In vivo assessment of contractile strength distinguishes differential gene function in skeletal muscle of zebrafish larvae.

    Science.gov (United States)

    Martin, Brit L; Gallagher, Thomas L; Rastogi, Neha; Davis, Jonathan P; Beattie, Christine E; Amacher, Sharon L; Janssen, Paul M L

    2015-10-01

    The accessible genetics and extensive skeletal musculature of the zebrafish make it a versatile and increasingly used model for studying muscle contraction. We here describe the development of an in vivo assay for measuring the contractile force of intact zebrafish at the larval stage. In addition, as proof of applicability, we have used this assay to quantify contractile strength of zebrafish larvae in a morphant model of deranged rbfox function. Average maximum tetanic (180 Hz) whole body forces produced by wild-type larvae at 2, 3, 4, and 5 days postfertilization amounted to 3.0, 7.2, 9.1, and 10.8 mN, respectively. To compare at potentially different stages of muscle development, we developed an immunohistological assay for empirically determining the cross-sectional area of larval trunk skeletal muscle to quantify muscle-specific force per cross-sectional area. At 4-5 days postfertilization, specific force amounts to ∼ 300 mN/mm(2), which is similar to fully developed adult mammalian skeletal muscle. We used these assays to measure contractile strength in zebrafish singly or doubly deficient for two rbfox paralogs, rbfox1l and rbfox2, which encode RNA-binding factors shown previously to modulate muscle function and muscle-specific splicing. We found rbfox2 morphants produce maximal tetanic forces similar to wild-type larvae, whereas rbfox1l morphants demonstrate significantly impaired function. rbfox1l/rbfox2 morphants are paralyzed, and their lack of contractile force production in our assay suggests that paralysis is a muscle-autonomous defect. These quantitative functional results allow measurement of muscle-specific phenotypes independent of neural input. Copyright © 2015 the American Physiological Society.

  13. Rac1 and AMPK account for the majority of muscle glucose uptake stimulated by ex vivo contraction but not in vivo exercise

    DEFF Research Database (Denmark)

    Sylow, Lykke; Møller, Lisbeth Liliendal Valbjørn; Kleinert, Maximilian

    2017-01-01

    by Rac1 mKO with no additive effect of α2KD. It is concluded that Rac1 and α2AMPK together account for almost the entire ex vivo contraction-response in muscle glucose transport, while only Rac1, but not α2AMPK, regulates muscle glucose uptake during submaximal exercise in vivo....... but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss-of-function combined with either pharmacological inhibition or genetic...

  14. Arterial wall mechanics as a function of heart rate: role of vascular smooth muscle

    Science.gov (United States)

    Salvucci, Fernando Pablo; Schiavone, Jonathan; Craiem, Damian; Barra, Juan Gabriel

    2007-11-01

    Vascular wall viscoelasticity can be evaluated using a first-order lumped model. This model consists of a spring with elastic constant E and a dashpot with viscous constant η. More importantly, this viscoelastic model can be fitted in-vivo measuring arterial pressure and diameter. The aim of this work is to analyze the influence of heart rate over E and η. In two anesthetized sheep, diameter in thoracic aorta and intravascular pressure has been registered. The right atrium was connected to a programmable stimulator through a pair of pace-maker wires to produce changes in stimulation heart rate (HR) from 80 to 160 bpm. Additionally, local activation of vascular smooth muscle was induced with phenylephrine. After converting pressure and diameter signals into stress and strain respectively, E y η were calculated in control state and during muscle activation. The elastic modulus E did not present significant changes with heart rate. The viscous modulus η decreased 49% with a two-fold acceleration in heart rate from 80 to 160 bpm. However, the product η HR remained stable. The viscous modulus η increased 39% with smooth muscle activation. No significant pressure changes were registered during the experiment. The contractile action of vascular smooth muscle could contribute to increasing arterial wall viscosity. The decrease of η when HR increased might be related to smooth muscle relaxation mediated by endothelium activity, which was stimulated by flow increase. We conclude that HR can modulate arterial wall viscoelasticity through endothelium-dependent mechanisms.

  15. Activation of respiratory muscles during weaning from mechanical ventilation.

    Science.gov (United States)

    Walterspacher, Stephan; Gückler, Julia; Pietsch, Fabian; Walker, David Johannes; Kabitz, Hans-Joachim; Dreher, Michael

    2017-04-01

    Respiratory muscle dysfunction is a key component of weaning failure. Balancing respiratory muscle loading and unloading by applying different ventilation modes along with spontaneous breathing episodes are established weaning strategies. However, the effects of body positioning on the respiratory muscles during weaning remains unclear. This study aimed at assessing respiratory drive by surface electromyography (EMG) of the diaphragm (EMGdia) and parasternal muscles (EMGpara) in tracheotomized patients during prolonged weaning in 3 randomized body positions-supine, 30° semirecumbent, and 80° sitting-during mechanical ventilation and spontaneous breathing. Nine patients were included for analysis. Cardiorespiratory parameters (heart rate, blood pressure, arterial oxygen saturation, dyspnea) did not change under each condition (all P>.05). EMGpara and EMGdia did not change under mechanical ventilation (both P>.05). EMGdia changed under spontaneous breathing from supine to sitting (0.45±0.26 vs 0.32±0.19; P=.012) and between semirecumbent to sitting (0.41±0.23 vs 0.32±0.19; P=.039), whereas EMGpara did not change. This is the first study to show that body positioning influences respiratory drive to the diaphragm in tracheotomized patients with prolonged weaning from mechanical ventilation during unassisted breathing. Sitting position reduces respiratory drive compared with semirecumbent and supine positioning and might therefore be favored during spontaneous breathing trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Ex vivo measures of muscle mitochondrial capacity reveal quantitative limits of oxygen delivery by the circulation during exercise

    DEFF Research Database (Denmark)

    Boushel, Robert; Saltin, Bengt

    2013-01-01

    Muscle mitochondrial respiratory capacity measured ex vivo provides a physiological reference to assess cellular oxidative capacity as a component in the oxygen cascade in vivo. In this article, the magnitude of muscle blood flow and oxygen uptake during exercise involving a small-to-large fracti...... capacity measured ex vivo underestimates the maximal in vivo oxygen uptake of muscle by up to ∼2-fold. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.......Muscle mitochondrial respiratory capacity measured ex vivo provides a physiological reference to assess cellular oxidative capacity as a component in the oxygen cascade in vivo. In this article, the magnitude of muscle blood flow and oxygen uptake during exercise involving a small-to-large fraction...... of the body mass will be discussed in relation to mitochondrial capacity measured ex vivo. These analyses reveal that as the mass of muscle engaged in exercise increases from one-leg knee extension, to 2-arm cranking, to 2-leg cycling and x-country skiing, the magnitude of blood flow and oxygen delivery...

  17. Insulin increases phosphorylation of mitochondrial proteins in human skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Zhao, Xiaolu; Bak, Steffen; Pedersen, Andreas James Thestrup

    2014-01-01

    There is increasing evidence that multiple proteins involved in key regulatory processes in mitochondria are phosphorylated in mammalian tissues. Insulin regulates glucose metabolism by phosphorylation-dependent signaling and has been shown to stimulate ATP synthesis in human skeletal muscle. Here......, we investigated the effect of insulin on the phosphorylation of mitochondrial proteins in human skeletal muscle in vivo. Using a combination of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC−MS/MS, we compared the phosphoproteomes of isolated mitochondria from skeletal muscle samples...... obtained from healthy individuals before and after 4 h of insulin infusion. In total, we identified 207 phosphorylation sites in 95 mitochondrial proteins. Of these phosphorylation sites, 45% were identified in both basal and insulin-stimulated samples. Insulin caused a 2-fold increase in the number...

  18. In vivo (31)P MRS study of skeletal muscle metabolism in patients with postpolio residual paralysis.

    Science.gov (United States)

    Sharma, Uma; Kumar, Virendra; Wadhwa, Sanjay; Jagannathan, Naranamangalan R

    2007-02-01

    The muscle metabolism of at-rest patients with varying degrees of postpolio residual paralysis (PPRP) was studied and compared with that of controls using in vivo phosphorus magnetic resonance spectroscopy. The phosphocreatine (PCr)/inorganic phosphate (Pi) and PCr/adenosine triphosphate ratios were lower in patients than in controls. Reduction in PCr/Pi suggests abnormalities in oxidative phosphorylation. A significant increase was observed in the phosphomonoester/PCr ratio in patients, indicating the accumulation of intermediary compounds of the glycolytic pathway. Furthermore, the phosphodiester/PCr ratio was also significantly increased in patients. In general, the observed changes in metabolite ratios were found to be related to the degree of residual paralysis, suggesting that metabolic changes are secondary to chronic neurogenic processes. These metabolic alterations appear to be the possible cause of energy deficit and underlying muscle fatigue in PPRP patients. The present results provide an insight into the metabolic impairment and degree of muscle damage in patients with PPRP.

  19. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  20. Dietary Flaxseed Mitigates Impaired Skeletal Muscle Regeneration: in Vivo, in Vitro and in Silico Studies

    Science.gov (United States)

    Carotenuto, Felicia; Costa, Alessandra; Albertini, Maria Cristina; Rocchi, Marco Bruno Luigi; Rudov, Alexander; Coletti, Dario; Minieri, Marilena; Di Nardo, Paolo; Teodori, Laura

    2016-01-01

    Background: Diets enriched with n-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to exert a positive impact on muscle diseases. Flaxseed is one of the richest sources of n-3 PUFA acid α-linolenic acid (ALA). The aim of this study was to assess the effects of flaxseed and ALA in models of skeletal muscle degeneration characterized by high levels of Tumor Necrosis Factor-α (TNF). Methods: The in vivo studies were carried out on dystrophic hamsters affected by muscle damage associated with high TNF plasma levels and fed with a long-term 30% flaxseed-supplemented diet. Differentiating C2C12 myoblasts treated with TNF and challenged with ALA represented the in vitro model. Skeletal muscle morphology was scrutinized by applying the Principal Component Analysis statistical method. Apoptosis, inflammation and myogenesis were analyzed by immunofluorescence. Finally, an in silico analysis was carried out to predict the possible pathways underlying the effects of n-3 PUFAs. Results: The flaxseed-enriched diet protected the dystrophic muscle from apoptosis and preserved muscle myogenesis by increasing the myogenin and alpha myosin heavy chain. Moreover, it restored the normal expression pattern of caveolin-3 thereby allowing protein retention at the sarcolemma. ALA reduced TNF-induced apoptosis in differentiating myoblasts and prevented the TNF-induced inhibition of myogenesis, as demonstrated by the increased expression of myogenin, myosin heavy chain and caveolin-3, while promoting myotube fusion. The in silico investigation revealed that FAK pathways may play a central role in the protective effects of ALA on myogenesis. Conclusions: These findings indicate that flaxseed may exert potent beneficial effects by preserving skeletal muscle regeneration and homeostasis partly through an ALA-mediated action. Thus, dietary flaxseed and ALA may serve as a useful strategy for treating patients with muscle dystrophies. PMID:26941581

  1. Novel insights into the regulation of skeletal muscle protein synthesis as revealed by a new nonradioactive in vivo technique

    National Research Council Canada - National Science Library

    Goodman, Craig A; Mabrey, Danielle M; Frey, John W; Miu, Man Hing; Schmidt, Enrico K; Pierre, Philippe; Hornberger, Troy A

    2011-01-01

    ...). Compared with controls, we first demonstrate excellent agreement between SUnSET and a [(3)H]phenylalanine method when detecting synergist ablation-induced increases in skeletal muscle PS ex vivo...

  2. Real-time muscle deformation via decoupled modeling of solid and muscle fiber mechanics.

    Science.gov (United States)

    Berranen, Yacine; Hayashibe, Mitsuhiro; Guiraud, David; Gilles, Benjamin

    2014-01-01

    This paper presents a novel approach for simulating 3D muscle deformations with complex architectures. The approach consists in choosing the best model formulation in terms of computation cost and accuracy, that mixes a volumetric-tissue model based on finite element method (3D FEM), a muscle fiber model (Hill contractile 1D element) and a membrane model accounting for aponeurosis tissue (2D FEM). The separate models are mechanically binded using barycentric embeddings. Our approach allows the computation of several fiber directions in one coarse finite element, and thus, strongly decreases the required finite element resolution to predict muscle deformation during contraction. Using surface registration, fibers tracks of specific architecture can be transferred from a template to subject morphology, and then simulated. As a case study, three different architectures are simulated and compared to their equivalent one dimensional Hill wire model simulations.

  3. The effects of speed on the in vivo activity and length of a limb muscle during the locomotion of the iguanian lizard Dipsosaurus dorsalis.

    Science.gov (United States)

    Nelson, F E; Jayne, B C

    2001-10-01

    The caudofemoralis muscle is the largest muscle that inserts onto the hindlimb of most ectothermic tetrapods, and previous studies hypothesize that it causes several movements that characterize the locomotion of vertebrates with a sprawling limb posture. Predicting caudofemoralis function is complicated because the muscle spans multiple joints with movements that vary with speed. Furthermore, depending on when any muscle is active relative to its change in length, its function can change from actively generating mechanical work to absorbing externally applied forces. We used synchronized electromyography, sonomicrometry and three-dimensional kinematics to determine in vivo caudofemoralis function in the desert iguana Dipsosaurus dorsalis for a wide range of speeds of locomotion from a walk to nearly maximal sprinting (50-350 cm s(-1)). Strain of the caudofemoralis increased with increasing tail elevation and long-axis rotation and protraction of the femur. However, knee extension only increased caudofemoralis strain when the femur was protracted. The maximum and minimum length of the caudofemoralis muscle and its average shortening velocity increased from the slowest speed up to the walk-run transition, but changed little with further increases in speed. The times of muscle shortening and lengthening were often not equal at higher locomotor speeds. Some (20-25 ms) activity occurred during lengthening of the caudofemoralis muscle before footfall. However, most caudofemoralis activity was consistent with performing positive mechanical work to flex the knee shortly after foot contact and to retract and rotate the femur throughout the propulsive phase.

  4. Ex vivo measures of muscle mitochondrial capacity reveal quantitative limits of oxygen delivery by the circulation during exercise.

    Science.gov (United States)

    Boushel, Robert; Saltin, Bengt

    2013-01-01

    Muscle mitochondrial respiratory capacity measured ex vivo provides a physiological reference to assess cellular oxidative capacity as a component in the oxygen cascade in vivo. In this article, the magnitude of muscle blood flow and oxygen uptake during exercise involving a small-to-large fraction of the body mass will be discussed in relation to mitochondrial capacity measured ex vivo. These analyses reveal that as the mass of muscle engaged in exercise increases from one-leg knee extension, to 2-arm cranking, to 2-leg cycling and x-country skiing, the magnitude of blood flow and oxygen delivery decrease. Accordingly, a 2-fold higher oxygen delivery and oxygen uptake per unit muscle mass are seen in vivo during 1-leg exercise compared to 2-leg cycling indicating a significant limitation of the circulation during exercise with a large muscle mass. This analysis also reveals that mitochondrial capacity measured ex vivo underestimates the maximal in vivo oxygen uptake of muscle by up to ∼2-fold. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. ADAR1-Mediated RNA Editing, A Novel Mechanism Controlling Phenotypic Modulation of Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Fei, Jia; Cui, Xiao-Bing; Wang, Jia-Ning; Dong, Kun; Chen, Shi-You

    2016-07-22

    Vascular smooth muscle cell (SMC) phenotypic modulation is characterized by the downregulation of SMC contractile genes. Platelet-derived growth factor-BB, a well-known stimulator of SMC phenotypic modulation, downregulates SMC genes via posttranscriptional regulation. The underlying mechanisms, however, remain largely unknown. To establish RNA editing as a novel mechanism controlling SMC phenotypic modulation. Precursor mRNAs (pre-mRNA) of SMC myosin heavy chain and smooth muscle α-actin were accumulated while their mature mRNAs were downregulated during SMC phenotypic modulation, suggesting an abnormal splicing of the pre-mRNAs. The abnormal splicing resulted from SMC marker pre-mRNA editing that was facilitated by adenosine deaminase acting on RNA 1 (ADAR1), an enzyme converting adenosines to inosines (A→I editing) in RNA sequences. ADAR1 expression inversely correlated with SMC myosin heavy chain and smooth muscle α-actin levels; knockdown of ADAR1 restored SMC myosin heavy chain and smooth muscle α-actin expression in phenotypically modulated SMC, and editase domain mutation diminished the ADAR1-mediated abnormal splicing of SMC marker pre-mRNAs. Moreover, the abnormal splicing/editing of SMC myosin heavy chain and smooth muscle α-actin pre-mRNAs occurred during injury-induced vascular remodeling. Importantly, heterozygous knockout of ADAR1 dramatically inhibited injury-induced neointima formation and restored SMC marker expression, demonstrating a critical role of ADAR1 in SMC phenotypic modulation and vascular remodeling in vivo. Our results unraveled a novel molecular mechanism, that is, pre-mRNA editing, governing SMC phenotypic modulation. © 2016 American Heart Association, Inc.

  6. In vivo Phosphoproteome of Human Skeletal Muscle Revealed by Phosphopeptide Enrichment and HPLC-ESI-MS/MS

    DEFF Research Database (Denmark)

    Højlund, Kurt; Bowen, Benjamin P; Hwang, Hyonson

    2009-01-01

    Protein phosphorylation plays an essential role in signal transduction pathways that regulate substrate and energy metabolism, contractile function, and muscle mass in human skeletal muscle. Abnormal phosphorylation of signaling enzymes has been identified in insulin resistant muscle using...... volunteers. Trypsin digestion of 3-5 mg human skeletal muscle protein was followed by phosphopeptide enrichment using SCX and TiO2. The resulting phosphopeptides were analyzed by HPLC-ESI-MS/MS. Using this unbiased approach, we identified 306 distinct in vivo phosphorylation sites in 127 proteins, including...... phosphoepitope-specific antibodies, but its role in other skeletal muscle disorders remains largely unknown. This may be in part due to insufficient knowledge of relevant targets. Here, we therefore present the first large-scale in vivo phosphoproteomic study of human skeletal muscle from 3 lean, healthy...

  7. Mechanical characterization of artificial muscles with computer vision

    Science.gov (United States)

    Verdu, R.; Morales-Sanchez, Juan; Fernandez-Romero, Antonio J.; Cortes, M. T.; Otero, Toribio F.; Weruaga-Prieto, Luis

    2002-07-01

    Conducting polymers are new materials that were developed in the late 1970s as intrinsically electronic conductors at the molecular level. The presence of polymer, solvent, and ionic components reminds one of the composition of the materials chosen by nature to produce muscles, neurons, and skin in living creatures. The ability to transform electrical energy into mechanical energy through an electrochemical reaction, promoting film swelling and shrinking during oxidation or reduction, respectively, produces a macroscopic change in its volume. On specially designed bi-layer polymeric stripes this conformational change gives rise to stripe curl and bending, where the position or angle of the free end of the polymeric stripe is directly related to the degree of oxidation, or charged consumed. Study of these curvature variations has been currently performed only in a manual basis. In this paper we propose a preliminary study of the polymeric muscle electromechanical properties by using a computer vision system. The vision system required is simple: it is composed of cameras for tracking the muscle from different angles and special algorithms, based on active contours, to analyse the deformable motion. Graphical results support the validity of this approach, which opens the way for performing automatic testing on artificial muscles with commercial purposes.

  8. Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

    Science.gov (United States)

    Rosenthal, Nadia A.

    1999-01-01

    The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as

  9. Nanomaterials for in vivo imaging of mechanical forces and electrical fields

    Science.gov (United States)

    Mehlenbacher, Randy D.; Kolbl, Rea; Lay, Alice; Dionne, Jennifer A.

    2018-02-01

    Cellular signalling is governed in large part by mechanical forces and electromagnetic fields. Mechanical forces play a critical role in cell differentiation, tissue organization and diseases such as cancer and heart disease; electrical fields are essential for intercellular communication, muscle contraction, neural signalling and sensory perception. Therefore, quantifying a biological system's forces and fields is crucial for understanding physiology and disease pathology and for developing medical tools for repair and recovery. This Review highlights advances in sensing mechanical forces and electrical fields in vivo, focusing on optical probes. The emergence of biocompatible optical probes, such as genetically encoded voltage indicators, molecular rotors, fluorescent dyes, semiconducting nanoparticles, plasmonic nanoparticles and lanthanide-doped upconverting nanoparticles, offers exciting opportunities to push the limits of spatial and temporal resolution, stability, multi-modality and stimuli sensitivity in bioimaging. We further discuss the materials design principles behind these probes and compare them across various metrics to facilitate sensor selection. Finally, we examine which advances are necessary to fully unravel the role of mechanical forces and electrical fields in vivo, such as the ability to probe the vectorial nature of forces, the development of combined force and field sensors, and the design of efficient optical actuators.

  10. In vivo determination of muscle-derived stem cells in rat corpus cavernosum.

    Science.gov (United States)

    Xu, L J; Xue, B X; Shan, Y X; Chen, D; Gao, J; Yang, D R; Sun, C Y; Cui, Y

    2015-08-21

    The aim of this in vivo study was to determine the existence of muscle-derived stem cells (MDSCs) in rat corpus cavernosum. Immunohistochemical and RT-PCR analyses were performed to determine the expression of the stem cell markers (Sca-1, Oct4, and desmin) in Sprague-Dawley (SD) rats in different age groups (10 rats in each group). Sca-1 was mainly expressed in blood vessels and cavernous sinus and demonstrated primarily cytoplasmic staining. Desmin was expressed mainly in muscle tissues and staining occurred mainly in the cytoplasm but also partially in the nucleus. An extremely small amount of double-positive stained cells (Sca-1/desmin) were detected near the cavernous sinus. Expression of the markers was significantly and negatively correlated with the age of the rats (P corpus cavernosum. MDSCs may have therapeutic potential in the treatment of organic erectile dysfunction.

  11. Combined magnetic resonance and diffusion tensor imaging analyses provide a powerful tool for in vivo assessment of deformation along human muscle fibers.

    Science.gov (United States)

    Pamuk, Uluç; Karakuzu, Agah; Ozturk, Cengizhan; Acar, Burak; Yucesoy, Can A

    2016-10-01

    Muscle fiber direction strain provides invaluable information for characterizing muscle function. However, methods to study this for human muscles in vivo are lacking. Using magnetic resonance (MR) imaging based deformation analyses and diffusion tensor (DT) imaging based tractography combined, we aimed to assess muscle fiber direction local tissue deformations within the human medial gastrocnemius (GM) muscle. Healthy female subjects (n=5, age=27±1 years) were positioned prone within the MR scanner in a relaxed state with the ankle angle fixed at 90°. The knee was brought to flexion (140.8±3.0°) (undeformed state). Sets of 3D high resolution MR, and DT images were acquired. This protocol was repeated at extended knee joint position (177.0±1.0°) (deformed state). Tractography and Demons nonrigid registration algorithm was utilized to calculate local deformations along muscle fascicles. Undeformed state images were also transformed by a synthetic rigid body motion to calculate strain errors. Mean strain errors were significantly smaller then mean fiber direction strains (lengthening: 0.2±0.1% vs. 8.7±8.5%; shortening: 3.3±0.9% vs. 7.5±4.6%). Shortening and lengthening (up to 23.3% and 116.7%, respectively) occurs simultaneously along individual fascicles despite imposed GM lengthening. Along-fiber shear strains confirm the presence of much shearing between fascicles. Mean fiber direction strains of different tracts also show non-uniform distribution. Inhomogeneity of fiber strain indicates epimuscular myofascial force transmission. We conclude that MR and DT imaging analyses combined provide a powerful tool for quantifying deformation along human muscle fibers in vivo. This can help substantially achieving a better understanding of normal and pathological muscle function and mechanisms of treatment techniques. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Contraction and AICAR Stimulate IL-6 Vesicle Depletion From Skeletal Muscle Fibers In Vivo

    DEFF Research Database (Denmark)

    Lauritzen, Hans P M M; Brandauer, Josef; Schjerling, Peter

    2013-01-01

    Recent studies suggest that interleukin 6 (IL-6) is released from contracting skeletal muscles; however, the cellular origin, secretion kinetics, and signaling mechanisms regulating IL-6 secretion are unknown. To address these questions, we developed imaging methodology to study IL-6 in fixed mouse...

  13. Glycolysis is independent of oxygenation state in stimulated human skeletal muscle in vivo

    Science.gov (United States)

    Conley, Kevin E; Kushmerick, Martin J; Jubrias, Sharon A

    1998-01-01

    We tested the hypothesis that the cytoplasmic control mechanism for glycolysis is affected by the presence of oxygen during exercise. We used a comparison of maximal twitch stimulation under ischaemic and intact circulation in human wrist flexor and ankle dorsiflexor muscles. 31P magnetic resonance spectroscopy followed the phosphocreatine (PCr), Pi and pH dynamics at 6–9 s intervals. Glycolytic PCr synthesis was determined during stimulation from pH and tissue buffer capacity, as well as the oxidative phosphorylation rate. Ischaemic vs. aerobic stimulation resulted in similar glycolytic fluxes in the two muscles. The onset of glycolysis occured after fifty to seventy stimulations and the extent of glycolytic PCr synthesis was directly proportional to the number of stimulations thereafter. Two-fold differences in the putative feedback regulators of glycolysis, [Pi] and [ADP], were found between aerobic and ischaemic stimulation. The similar glycolytic fluxes in the face of these differences in metabolite levels eliminates feedback as a control mechanism in glycolysis. These results demonstrate that glycolytic flux is independent of oxygenation state and metabolic feedback, but proportional to muscle activation. These results show a key role for muscle stimulation in the activation and maintenance of glycolysis. Further, this glycolytic control mechanism is independent of the feedback control mechanism that governs oxidative phosphorylation. PMID:9714871

  14. Mechanical stimulation in the engineering of heart muscle.

    Science.gov (United States)

    Liaw, Norman Yu; Zimmermann, Wolfram-Hubertus

    2016-01-15

    Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loading of the ventricles (preload) and on the force generated by the preloaded ventricles to overcome arterial blood pressure (afterload). The rate of contraction is controlled by the spontaneously active sinus node and transmission of its electrical impulses into the ventricles. The underlying principles for these physiological processes are described by the Frank-Starling mechanism and Bowditch phenomenon. It is essential to consider these principles in the design and evaluation of tissue engineered myocardium. This review focuses on current strategies to evoke mechanical loading in hydrogel-based heart muscle engineering. Copyright © 2015. Published by Elsevier B.V.

  15. Effects of aging on muscle mechanical function and muscle fiber morphology during short-term immobilization and subsequent retraining

    DEFF Research Database (Denmark)

    Hvid, Lars; Aagaard, Per; Justesen, Lene

    2010-01-01

    (i.e., rate of force development, impulse) than YM (∼ 20-37 vs. ∼ 13-16%; P muscle fiber area decreased in YM for type I, IIA, and IIx fibers (∼ 15-30%; P type IIa area decreased in OM (13.2%; P muscle mechanical...... mechanical function (e.g., maximal strength and rapid force capacity) and muscle fiber morphology in 9 old (OM: 67.3 ± 1.3 yr) and 11 young healthy men (YM: 24.4 ± 0.5 yr) with comparable levels of physical activity. Following immobilization, OM demonstrated markedly larger decreases in rapid force capacity...... function and muscle fiber area in YM, whereas OM showed an attenuated recovery in muscle fiber area and rapid force capacity (tendency). Changes in maximal isometric and dynamic muscle strength were similar between OM and YM. In conclusion, the present data reveal that OM may be more susceptible...

  16. Effects of aging on muscle mechanical function and muscle fiber morphology during short-term immobilization and subsequent retraining

    DEFF Research Database (Denmark)

    Hvid, Lars; Aagaard, Per; Justesen, Lene

    2010-01-01

    (i.e., rate of force development, impulse) than YM (~ 20-37 vs. ~ 13-16%; P muscle fiber area decreased in YM for type I, IIA, and IIx fibers (~ 15-30%; P type IIa area decreased in OM (13.2%; P muscle mechanical...... mechanical function (e.g., maximal strength and rapid force capacity) and muscle fiber morphology in 9 old (OM: 67.3 ± 1.3 yr) and 11 young healthy men (YM: 24.4 ± 0.5 yr) with comparable levels of physical activity. Following immobilization, OM demonstrated markedly larger decreases in rapid force capacity...... function and muscle fiber area in YM, whereas OM showed an attenuated recovery in muscle fiber area and rapid force capacity (tendency). Changes in maximal isometric and dynamic muscle strength were similar between OM and YM. In conclusion, the present data reveal that OM may be more susceptible...

  17. Rac1 and AMPK Account for the Majority of Muscle Glucose Uptake Stimulated by Ex Vivo Contraction but Not In Vivo Exercise.

    Science.gov (United States)

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; D'Hulst, Gommaar; De Groote, Estelle; Schjerling, Peter; Steinberg, Gregory R; Jensen, Thomas E; Richter, Erik A

    2017-06-01

    Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin-resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake, but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss of function combined with either pharmacological inhibition or genetic deletion of Rac1.Muscle-specific knockout (mKO) of Rac1, a kinase-dead α2 AMPK (α2KD), and double knockout (KO) of β1 and β2 AMPK subunits (β1β2 KO) each partially decreased contraction-stimulated glucose transport in mouse soleus and extensor digitorum longus (EDL) muscle. Interestingly, when pharmacological Rac1 inhibition was combined with either AMPK β1β2 KO or α2KD, contraction-stimulated glucose transport was almost completely inhibited. Importantly, α2KD+Rac1 mKO double-transgenic mice also displayed severely impaired contraction-stimulated glucose transport, whereas exercise-stimulated glucose uptake in vivo was only partially reduced by Rac1 mKO with no additive effect of α2KD. It is concluded that Rac1 and AMPK together account for almost the entire ex vivo contraction response in muscle glucose transport, whereas only Rac1, but not α2 AMPK, regulates muscle glucose uptake during submaximal exercise in vivo. © 2017 by the American Diabetes Association.

  18. The PGC-1 coactivators promote an anti-inflammatory environment in skeletal muscle in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Eisele, Petra Sabine [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel (Switzerland); Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich (Switzerland); Furrer, Regula; Beer, Markus [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel (Switzerland); Handschin, Christoph, E-mail: christoph.handschin@unibas.ch [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel (Switzerland); Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich (Switzerland)

    2015-08-28

    The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is abundantly expressed in trained muscles and regulates muscle adaptation to endurance exercise. Inversely, mice lacking a functional PGC-1α allele in muscle exhibit reduced muscle functionality and increased inflammation. In isolated muscle cells, PGC-1α and the related PGC-1β counteract the induction of inflammation by reducing the activity of the nuclear factor κB (NFκB). We now tested the effects of these metabolic regulators on inflammatory reactions in muscle tissue of control and muscle-specific PGC-1α/-1β transgenic mice in vivo in the basal state as well as after an acute inflammatory insult. Surprisingly, we observed a PGC-1-dependent alteration of the cytokine profile characterized by an increase in anti-inflammatory factors and a strong suppression of the pro-inflammatory interleukin 12 (IL-12). In conclusion, the anti-inflammatory environment in muscle that is promoted by the PGC-1s might contribute to the beneficial effects of these coactivators on muscle function and provides a molecular link underlying the tight mutual regulation of metabolism and inflammation. - Highlights: • Muscle PGC-1s are insufficient to prevent acute systemic inflammation. • The muscle PGC-1s however promote a local anti-inflammatory environment. • This anti-inflammatory environment could contribute to the therapeutic effect of the PGC-1s.

  19. Do Stretch Durations Affect Muscle Mechanical and Neurophysiological Properties?

    Science.gov (United States)

    Opplert, J; Genty, J-B; Babault, N

    2016-08-01

    The aim of the study was to determine whether stretching durations influence acute changes of mechanical and neurophysiological properties of plantar flexor muscles. Plantar flexors of 10 active males were stretched in passive conditions on an isokinetic dynamometer. Different durations of static stretching were tested in 5 randomly ordered experimental trials (1, 2, 3, 4 and 10×30-s). Fascicle stiffness index, evoked contractile properties and spinal excitability (Hmax/Mmax) were examined before (PRE), immediately after (POST0) and 5 min after (POST5) stretching. No stretch duration effect was recorded for any variable. Moreover, whatever the stretching duration, stiffness index, peak twitch torque and rate of force development were significantly lower at POST0 and POST5 as compared to PRE (Pstretch duration, no significant changes of Hmax/Mmax ratio were recorded. In conclusion, 30 s of static stretching to maximum tolerated discomfort is sufficient enough to alter mechanical properties of plantar flexor muscles, but 10×30 s does not significantly affect these properties further. Stretching does not impair spinal excitability. © Georg Thieme Verlag KG Stuttgart · New York.

  20. The vascular morphology and in vivo muscle temperatures of thresher sharks (Alopiidae).

    Science.gov (United States)

    Patterson, James C; Sepulveda, Chugey A; Bernal, Diego

    2011-11-01

    The thresher sharks comprise a single family (Alopiidae) of pelagic sharks most easily recognized by the elongate dorsal lobe of their caudal fin. Despite morphological similarities among the alopiids, the common thresher (Alopias vulpinus) is unique in that its red, aerobic myotomal muscle (RM) is medially positioned (i.e., closer to the vertebrae), its systemic blood is supplied through a lateral circulation which give rise to counter-current heat exchanging retia, and it is capable of regional RM endothermy. Despite this information, it remains unknown if the other two alopiid species (bigeye thresher, Alopias superciliosus and pelagic thresher, Alopias pelagicus) also possess some or all of the characteristics related to regional RM endothermy. Thus, this study aimed to 1) document the presence of vascular specializations necessary for heat retention and RM endothermy and 2) measure the in vivo muscle temperatures of all three alopiid species. Laboratory dissections of the thresher species showed that only A. vulpinus possesses the lateral branching of the dorsal aorta giving rise to a lateral subcutaneous circulation and retial system, and that RM temperatures are elevated relative to ambient temperature. By contrast, both A. pelagicus and A. superciliosus have a similar systemic blood circulation pathway, in which the dorsal aorta and postcardinal vein form the basis for the central circulation and in vivo RM temperature measurements closely matched those of the ambient temperature at which the sharks were captured. Collectively, the vascular anatomy and in vivo temperature data suggest that only one species of thresher shark (A. vulpinus) possesses the requisite vascular specializations (i.e., lateral subcutaneous vessels and retia mirabilia) that facilitate RM endothermy. Copyright © 2011 Wiley-Liss, Inc.

  1. In vivo ATP synthesis rates in single human muscles during high intensity exercise

    Science.gov (United States)

    Walter, Glenn; Vandenborne, Krista; Elliott, Mark; Leigh, John S

    1999-01-01

    In vivo ATP synthesis rates were measured in the human medial gastrocnemius muscle during high intensity exercise using localized 31P-magnetic resonance spectroscopy (31P-MRS). Six-second localized spectra were acquired during and following a 30 s maximal voluntary rate exercise using a magnetic resonance image-guided spectral localization technique. During 30 s maximal voluntary rate exercise, ATPase fluxes were predominantly met by anaerobic ATP sources. Maximal in vivo glycogenolytic rates of 207 ± 48 mM ATP min−1 were obtained within 15 s, decreasing to 72 ± 34 mM ATP min−1 by the end of 30 s. In contrast, aerobic ATP synthesis rates achieved 85 ± 2 % of their maximal capacity within 9 s and did not change throughout the exercise. The ratio of peak glycolytic ATP synthesis rate to maximal oxidative ATP synthesis was 2.9 ± 0.9. The non-Pi, non-CO2 buffer capacity was calculated to be 27.0 ± 6.2 slykes (millimoles acid added per unit change in pH). At the cessation of exercise, Pi, phosphomonoesters and CO2 were predicted to account for 17.2 ± 1.5, 5.57 ± 0.97 and 2.24 ± 0.34 slykes of the total buffer capacity. Over the approximately linear range of intracellular pH recovery following the post-exercise acidification, pHi recovered at a rate of 0.19 ± 0.03 pH units min−1. Proton transport capacity was determined to be 16.4 ± 4.1 mM (pH unit)−1 min−1 and corresponded to a maximal proton efflux rate of 15.3 ± 2.7 mM min−1. These data support the observation that glycogenolytic and glycolytic rates are elevated in vivo in the presence of elevated Pi levels. The data do not support the hypothesis that glycogenolysis follows Michealis-Menten kinetics with an apparent Km for [Pi]in vivo. In vivo -measured ATP utilization rates and the initial dependence on PCr and glycolysis were similar to those previously reported in in situ studies involving short duration, high intensity exercise. This experimental approach presents a non

  2. Inhibitor of endocytosis impairs gene electrotransfer to mouse muscle in vivo.

    Science.gov (United States)

    Markelc, Bostjan; Skvarca, Eva; Dolinsek, Tanja; Kloboves, Veronika Prevodnik; Coer, Andrej; Sersa, Gregor; Cemazar, Maja

    2015-06-01

    Application of electric pulses (electroporation/electropermeabilization) is an effective method for gene transfer (i.e. gene electrotransfer (GET)) in vitro and in vivo. Currently, the mechanisms by which the DNA enters the cell are not yet fully understood. Experimental evidence is building up that endocytosis is the main mechanism by which the DNA, which is later expressed, enters the cell. Therefore the aim of our study was to elucidate whether inhibitors of endocytosis, methyl-β-cyclodextrin (MβCD), Concanavalin A (ConA) and Dynasore, can impair the transfection efficacy of GET in vitro in B16F1 murine melanoma and in vivo in m. tibialis cranialis in mice. We show that MβCD--general inhibitor of endocytosis--can almost prevent GET of EGFP-N1 plasmid in vitro, that ConA--inhibitor of clathrin mediated endocytosis--also abrogates GET but to a lesser extent, and when using Dynasore--reversible inhibitor of dynamin--there is no effect on GET efficacy, if endocytosis is blocked for only 5 min after GET. Moreover, MβCD also reduced GET efficacy in vivo in m. tibialis cranialis and this effect was long lasting. The results of this study show that endocytosis is probably the main mechanism of entrance of DNA after GET in vitro and also in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

    OpenAIRE

    Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

    2007-01-01

    This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via...

  4. The study of muscle remodeling in Drosophila metamorphosis using in vivo microscopy and bioimage informatics

    Science.gov (United States)

    2012-01-01

    Background Metamorphosis in insects transforms the larval into an adult body plan and comprises the destruction and remodeling of larval and the generation of adult tissues. The remodeling of larval into adult muscles promises to be a genetic model for human atrophy since it is associated with dramatic alteration in cell size. Furthermore, muscle development is amenable to 3D in vivo microscopy at high cellular resolution. However, multi-dimensional image acquisition leads to sizeable amounts of data that demand novel approaches in image processing and analysis. Results To handle, visualize and quantify time-lapse datasets recorded in multiple locations, we designed a workflow comprising three major modules. First, the previously introduced TLM-converter concatenates stacks of single time-points. The second module, TLM-2D-Explorer, creates maximum intensity projections for rapid inspection and allows the temporal alignment of multiple datasets. The transition between prepupal and pupal stage serves as reference point to compare datasets of different genotypes or treatments. We demonstrate how the temporal alignment can reveal novel insights into the east gene which is involved in muscle remodeling. The third module, TLM-3D-Segmenter, performs semi-automated segmentation of selected muscle fibers over multiple frames. 3D image segmentation consists of 3 stages. First, the user places a seed into a muscle of a key frame and performs surface detection based on level-set evolution. Second, the surface is propagated to subsequent frames. Third, automated segmentation detects nuclei inside the muscle fiber. The detected surfaces can be used to visualize and quantify the dynamics of cellular remodeling. To estimate the accuracy of our segmentation method, we performed a comparison with a manually created ground truth. Key and predicted frames achieved a performance of 84% and 80%, respectively. Conclusions We describe an analysis pipeline for the efficient handling and

  5. The study of muscle remodeling in Drosophila metamorphosis using in vivo microscopy and bioimage informatics.

    Science.gov (United States)

    Chinta, Rambabu; Tan, Joo Huang; Wasser, Martin

    2012-01-01

    Metamorphosis in insects transforms the larval into an adult body plan and comprises the destruction and remodeling of larval and the generation of adult tissues. The remodeling of larval into adult muscles promises to be a genetic model for human atrophy since it is associated with dramatic alteration in cell size. Furthermore, muscle development is amenable to 3D in vivo microscopy at high cellular resolution. However, multi-dimensional image acquisition leads to sizeable amounts of data that demand novel approaches in image processing and analysis. To handle, visualize and quantify time-lapse datasets recorded in multiple locations, we designed a workflow comprising three major modules. First, the previously introduced TLM-converter concatenates stacks of single time-points. The second module, TLM-2D-Explorer, creates maximum intensity projections for rapid inspection and allows the temporal alignment of multiple datasets. The transition between prepupal and pupal stage serves as reference point to compare datasets of different genotypes or treatments. We demonstrate how the temporal alignment can reveal novel insights into the east gene which is involved in muscle remodeling. The third module, TLM-3D-Segmenter, performs semi-automated segmentation of selected muscle fibers over multiple frames. 3D image segmentation consists of 3 stages. First, the user places a seed into a muscle of a key frame and performs surface detection based on level-set evolution. Second, the surface is propagated to subsequent frames. Third, automated segmentation detects nuclei inside the muscle fiber. The detected surfaces can be used to visualize and quantify the dynamics of cellular remodeling. To estimate the accuracy of our segmentation method, we performed a comparison with a manually created ground truth. Key and predicted frames achieved a performance of 84% and 80%, respectively. We describe an analysis pipeline for the efficient handling and analysis of time

  6. Effects of lipid-lowering drugs on irisin in human subjects in vivo and in human skeletal muscle cells ex vivo.

    Directory of Open Access Journals (Sweden)

    Ioanna Gouni-Berthold

    Full Text Available The myokine irisin has been proposed to regulate energy homeostasis. Little is known about its association with metabolic parameters and especially with parameters influencing pathways of lipid metabolism. In the context of a clinical trial, an exploratory post hoc analysis has been performed in healthy subjects to determine whether simvastatin and/or ezetimibe influence serum irisin levels. The direct effects of simvastatin on irisin were also examined in primary human skeletal muscle cells (HSKMCs.A randomized, parallel 3-group study was performed in 72 men with mild hypercholesterolemia and without apparent cardiovascular disease. Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination.Baseline irisin concentrations were not significantly correlated with age, BMI, estimated GFR, thyroid parameters, glucose, insulin, lipoproteins, non-cholesterol sterols, adipokines, inflammation markers and various molecular markers of cholesterol metabolism. Circulating irisin increased significantly in simvastatin-treated but not in ezetimibe-treated subjects. The changes were independent of changes in LDL-cholesterol and were not correlated with changes in creatine kinase levels. In HSKMCs, simvastatin significantly increased irisin secretion as well as mRNA expression of its parent peptide hormone FNDC5. Simvastatin significantly induced cellular reactive oxygen species levels along with expression of pro- and anti-oxidative genes such as Nox2, and MnSOD and catalase, respectively. Markers of cellular stress such as atrogin-1 mRNA and Bax protein expression were also induced by simvastatin. Decreased cell viability and increased irisin secretion by simvastatin was reversed by antioxidant mito-TEMPO, implying in part that irisin is secreted as a result of increased mitochondrial oxidative stress and subsequent myocyte damage.Simvastatin increases irisin concentrations in vivo and in vitro

  7. The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle.

    Science.gov (United States)

    Hornberger, T A; Chu, W K; Mak, Y W; Hsiung, J W; Huang, S A; Chien, S

    2006-03-21

    Signaling by the mammalian target of rapamycin (mTOR) has been reported to be necessary for mechanical load-induced growth of skeletal muscle. The mechanisms involved in the mechanical activation of mTOR signaling are not known, but several studies indicate that a unique [phosphotidylinositol-3-kinase (PI3K)- and nutrient-independent] mechanism is involved. In this study, we have demonstrated that a regulatory pathway for mTOR signaling that involves phospholipase D (PLD) and the lipid second messenger phosphatidic acid (PA) plays a critical role in the mechanical activation of mTOR signaling. First, an elevation in PA concentration was sufficient for the activation of mTOR signaling. Second, the isozymes of PLD (PLD1 and PLD2) are localized to the z-band in skeletal muscle (a critical site of mechanical force transmission). Third, mechanical stimulation of skeletal muscle with intermittent passive stretch ex vivo induced PLD activation, PA accumulation, and mTOR signaling. Finally, pharmacological inhibition of PLD blocked the mechanically induced increase in PA and the activation of mTOR signaling. Combined, these results indicate that mechanical stimuli activate mTOR signaling through a PLD-dependent increase in PA. Furthermore, we showed that mTOR signaling was partially resistant to rapamycin in muscles subjected to mechanical stimulation. Because rapamycin and PA compete for binding to the FRB domain on mTOR, these results suggest that mechanical stimuli activate mTOR signaling through an enhanced binding of PA to the FRB domain on mTOR.

  8. Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2017-04-01

    Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU50 = 3.5% ± 1.6%) or without insulin (GU50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

  9. Electrically-induced muscle fatigue affects feedforward mechanisms of control.

    Science.gov (United States)

    Monjo, F; Forestier, N

    2015-08-01

    To investigate the effects of focal muscle fatigue induced by electromyostimulation (EMS) on Anticipatory Postural Adjustments (APAs) during arm flexions performed at maximal velocity. Fifteen healthy subjects performed self-paced arm flexions at maximal velocity before and after the completion of fatiguing electromyostimulation programs involving the medial and anterior deltoids and aiming to degrade movement peak acceleration. APA timing and magnitude were measured using surface electromyography. Following muscle fatigue, despite a lower mechanical disturbance evidenced by significant decreased peak accelerations (-12%, p.11 for all analyses). The fatigue signals evoked by externally-generated contractions seem to be gated by the Central Nervous System and result in postural strategy changes which aim to increase the postural safety margin. EMS is widely used in rehabilitation and training programs for its neuromuscular function-related benefits. However and from a motor control viewpoint, the present results show that the use of EMS can lead to acute inaccuracies in predictive motor control. We propose that clinicians should investigate the chronic and global effects of EMS on motor control. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Acute and chronic effects of hyperbaric oxygen therapy on blood circulation of human muscle and tendon in vivo.

    Science.gov (United States)

    Kubo, Keitaro; Ikebukuro, Toshihiro

    2012-10-01

    This study aimed to investigate the acute and chronic effects of hyperbaric oxygen therapy on blood circulation of human muscle and tendon in vivo. Using near-infrared spectroscopy and red laser lights, we determined acute changes in blood volume (THb) and oxygen saturation (StO2) of the medial gastrocnemius muscle and Achilles tendon during 60 minutes of hyperbaric oxygen therapy (1.3 atm absolute and 50% O2, experiment 1). In addition, we determined the chronic effects of hyperbaric oxygen therapy (60 minutes, 2 times per week, 6 weeks) on THb and StO2 of muscle and tendon (experiment 2). In experiment 1, THb of the muscle increased gradually from resting level, but StO2 did not change. On the other hand, THb and StO2 of the tendon increased during hyperbaric oxygen therapy. In experiment 2, the pattern of changes in the measured variables during 60 minutes of therapy was similar for both the muscle and tendon between the first and last therapies. During resting, THb and StO2 of the tendon were significantly lower after 6 weeks of therapy, although those of the muscle were not. In conclusion, oxygen saturation of the tendon increased during hyperbaric oxygen therapy, whereas that of the muscle did not. This result would be related to the difference in the treated effects between muscle and tendon. However, oxygen saturation of the tendon, but not the muscle, during resting decreased after 6 weeks of therapy.

  11. Muscle pain induced by static contraction in rats is modulated by peripheral inflammatory mechanisms.

    Science.gov (United States)

    Santos, Diogo Francisco da Silva Dos; Melo Aquino, Bruna de; Jorge, Carolina Ocanha; Azambuja, Graciana de; Schiavuzzo, Jalile Garcia; Krimon, Suzy; Neves, Juliana Dos Santos; Parada, Carlos Amilcar; Oliveira-Fusaro, Maria Claudia Gonçalves

    2017-09-01

    Muscle pain is an important health issue and frequently related to static force exertion. The aim of this study is to evaluate whether peripheral inflammatory mechanisms are involved with static contraction-induced muscle pain in rats. To this end, we developed a model of muscle pain induced by static contraction performed by applying electrical pulses through electrodes inserted into muscle. We also evaluated the involvement of neutrophil migration, bradykinin, sympathetic amines and prostanoids. A single session of sustained static contraction of gastrocnemius muscle induced acute mechanical muscle hyperalgesia without affecting locomotor activity and with no evidence of structural damage in muscle tissue. Static contraction increased levels of creatine kinase but not lactate dehydrogenase, and induced neutrophil migration. Dexamethasone (glucocorticoid anti-inflammatory agent), DALBK (bradykinin B1 antagonist), Atenolol (β1 adrenoceptor antagonist), ICI 118,551 (β2 adrenoceptor antagonist), indomethacin (cyclooxygenase inhibitor), and fucoidan (non-specific selectin inhibitor) all reduced static contraction-induced muscle hyperalgesia; however, the bradykinin B2 antagonist, bradyzide, did not have an effect on static contraction-induced muscle hyperalgesia. Furthermore, an increased hyperalgesic response was observed when the selective bradykinin B1 agonist des-Arg9-bradykinin was injected into the previously stimulated muscle. Together, these findings demonstrate that static contraction induced mechanical muscle hyperalgesia in gastrocnemius muscle of rats is modulated through peripheral inflammatory mechanisms that are dependent on neutrophil migration, bradykinin, sympathetic amines and prostanoids. Considering the clinical relevance of muscle pain, we propose the present model of static contraction-induced mechanical muscle hyperalgesia as a useful tool for the study of mechanisms underlying static contraction-induced muscle pain. Copyright © 2017 IBRO

  12. In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract

    Science.gov (United States)

    Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

    2016-01-01

    Background: Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae. Objective: The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). Materials and Methods: The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. Results: The LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. Conclusion: The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. SUMMARY Anxiety is implicated in the number of psychiatric disordersIn vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening

  13. In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract.

    Science.gov (United States)

    Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

    2016-01-01

    Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae. The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. The LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. Anxiety is implicated in the number of psychiatric disordersIn vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening test in mice and Rota-.rod test.The GABAergic system plays a significant role

  14. MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--mechanism of growth hormone stimulation of skeletal muscle growth in cattle.

    Science.gov (United States)

    Jiang, H; Ge, X

    2014-01-01

    Growth hormone, also called somatotropin (ST), is a polypeptide hormone produced by the anterior pituitary. The major functions of GH include stimulating bone and skeletal muscle growth, lipolysis, milk production, and expression of the IGF-I gene in the liver. Based on these functions, recombinant bovine ST (bST) and recombinant porcine ST (pST) have been used to improve milk production in dairy cows and lean tissue growth in pigs, respectively. However, despite these applications, the mechanisms of action of GH are not fully understood. Indeed, there has been a lot of controversy over the role of liver-derived circulating IGF-I and locally produced IGF-I in mediating the growth-stimulatory effect of GH during the last 15 yr. It is in this context that we have conducted studies to further understand how GH stimulates skeletal muscle growth in cattle. Our results do not support a role of skeletal muscle-derived IGF-I in GH-stimulated skeletal muscle growth in cattle. Our results indicate that GH stimulates skeletal muscle growth in cattle, in part, by stimulating protein synthesis in muscle through a GH receptor-mediated, IGF-I-independent mechanism. In this review, besides discussing these results, we also argue that liver-derived circulating IGF-I should be still considered as the major mechanism that mediates the growth-stimulatory effect of GH on skeletal muscle in cattle and other domestic animals.

  15. In vivo imaging of the time-dependent apparent diffusional kurtosis in the human calf muscle.

    Science.gov (United States)

    Marschar, Anja Maria; Kuder, Tristan Anselm; Stieltjes, Bram; Nagel, Armin Michael; Bachert, Peter; Laun, Frederik Bernd

    2015-06-01

    To evaluate the time dependency of apparent diffusion coefficient Dapp and apparent diffusional kurtosis Kapp in vivo in the human calf. Diffusion-weighted images of five healthy male volunteers were acquired using a 1.5T MR scanner. A stimulated echo sequence with echo planar imaging readout was used with diffusion gradients oriented along the three main axes. Mixing times (TM) of 100, 300, 500, and 700 ms and b-values ranging from 0 to 5600 s/mm(2) were used. Dapp and Kapp were determined. Dapp and Kapp decreased with increasing TM. As an example for absolute values, Dapp of the tibialis anterior drops from 1.18 ± 0.04 μm(2) /ms (TM = 100 ms) to 0.86 ± 0.02 μm(2) /ms (TM = 700 ms) (P = 0.001) and Kapp from 0.38 ± 0.06 to 0.32 ± 0.03 (P = 0.046) for a diffusion weighting along the left-right direction. Kapp was smaller than 0.43 in all muscles and at all TMs. The clearly observed time-dependence of Dapp and Kapp is an indicator of restricted diffusion in muscle tissue and may thus be a promising marker to investigate alterations of the microstructure. Compared to typical kurtosis values in white matter tissue of the brain, the kurtosis in muscle tissue is much smaller, which we attribute to the absence of the almost impermeable myelin sheath. © 2014 Wiley Periodicals, Inc.

  16. Mechanisms of muscle gene regulation in the electric organ of Sternopygus macrurus

    OpenAIRE

    Güth, Robert; Pinch, Matthew; Unguez, Graciela A.

    2013-01-01

    Animals perform a remarkable diversity of movements through the coordinated mechanical contraction of skeletal muscle. This capacity for a wide range of movements is due to the presence of muscle cells with a very plastic phenotype that display many different biochemical, physiological and morphological properties. What factors influence the maintenance and plasticity of differentiated muscle fibers is a fundamental question in muscle biology. We have exploited the remarkable potential of ske...

  17. Muscle mechanics. The effect of stretch and shortening on skeletal muscle force

    NARCIS (Netherlands)

    Meijer, K.

    1998-01-01

    The aim of the present thesis was to study systematically the impact of history dependent effects in intact muscles. For this purpose, experiments were performed on in situ medial gastrocnemius (GM) and soleus (SOL) muscles of the rat. Furthermore, mathematical muscle models were developed that

  18. Charge movement and mechanical repriming in skeletal muscle.

    Science.gov (United States)

    Adrian, R H; Chandler, W K; Rakowski, R F

    1976-01-01

    1. Muscles were placed in a solution which depolarized the membrane to -30 to -20 mV so that mechanical activation was made refractory. Mechanical repriming and the recovery of voltage dependent charge movement were studied using a voltage clamp technique. 2. Mechanical repriming was investigated by determining the duration of a hyperpolarizing pulse required to elicit a just-visible contraction for various post-pulse potentials. As the post-pulse potential was made more positive shorter repriming times were required to produce a threshold contraction. The relationship approached a minimum repriming time for very positive post-pulse potentials. 3. These results suggest that hyperpolarization gradually removes some component of the activation mechanism from a refractory state and that the effectiveness of the amount which has recovered depends on the post-pulse potential. A quantitative explanation is given using a simple model in which the essential component is assumed to be the charge movement process. 4. The rate of repriming contraction is voltage dependent; at -160 mV the rate is about twice that at -120 mV. Between 4 and 10 degrees C the rate has a Q10 of about 9. 5. Recovery of charge movement was studied using a repriming duration less than that required to produce a threshold contraction. The observed charge movement increased linearly with repriming time, consistent with the approximately linear initial segment of a slow exponential recovery process. Extrapolation of the recovery curve indicated that 2-5 n/CmuF of charge is reprimed in the time necessary to reprime a threshold contraction. 6. The charge which recovers during a subthreshold repriming pulse is distributed according to membrane potential in the same way as a fully reprimed charge. 7. These results are consistent with the hypothesis that voltage dependent charge movement is an intermediate step in excitation-contraction coupling. 8. The characteristics of a second type of charge movement are

  19. Aging interferes central control mechanism for eccentric muscle contraction.

    Science.gov (United States)

    Yao, Wan X; Li, Jinqi; Jiang, Zhiguo; Gao, Jia-Hong; Franklin, Crystal G; Huang, Yufei; Lancaster, Jack L; Yue, Guang H

    2014-01-01

    Previous studies report greater activation in the cortical motor network in controlling eccentric contraction (EC) than concentric contraction (CC) despite lower muscle activation level associated with EC vs. CC in healthy, young individuals. It is unknown, however, whether elderly people exhibiting increased difficulties in performing EC than CC possess this unique cortical control mechanism for EC movements. To address this question, we examined functional magnetic resonance imaging (fMRI) data acquired during EC and CC of the first dorsal interosseous (FDI) muscle in 11 young (20-32 years) and 9 old (67-73 years) individuals. During the fMRI experiment, all subjects performed 20 CC and 20 EC of the right FDI with the same angular distance and velocity. The major findings from the behavioral and fMRI data analysis were that (1) movement stability was poorer in EC than CC in the old but not the young group; (2) similar to previous electrophysiological and fMRI reports, the EC resulted in significantly stronger activation in the motor control network consisting of primary, secondary and association motor cortices than CC in the young and old groups; (3) the biased stronger activation towards EC was significantly greater in the old than the young group especially in the secondary and association cortices such as supplementary and premotor motor areas and anterior cingulate cortex; and (4) in the primary motor and sensory cortices, the biased activation towards EC was significantly greater in the young than the old group. Greater activation in higher-order cortical fields for controlling EC movement by elderly adults may reflect activities in these regions to compensate for aging-related impairments in the ability to control complex EC movements. Our finding is useful for potentially guiding the development of targeted therapies to counteract age-related movement deficits and to prevent injury.

  20. A novel outlier detection method for identifying torque-related transient patterns of in vivo muscle behavior.

    Science.gov (United States)

    Sheng Han; Xin Chen; Sheng Zhong; Yongjin Zhou; Zhiguo Zhang

    2014-01-01

    This paper proposed a novel outlier detection method, named l1-regularized outlier isolation and regression (LOIRE), to examine torque-related transient patterns of in vivo muscle behavior from multimodal signals, including electromyography (EMG), mechanomyography (MMG) and ultrasonography (US), during isometric muscle contraction. Eight subjects performed isometric ramp contraction of knee up to 90% of the maximal voluntary contraction, and EMG, MMG and US were simultaneously recorded from the rectus femoris muscle. Five features, including two root mean square amplitudes from EMG and MMG, muscle cross sectional area, muscle thickness and width from US were extracted. Then, local polynomial regression was used to obtain the signal-to-torque relationships and their derivatives. By assuming the signal-to-torque functions are basically quadratic, the LOIRE method is applied to identify transient torque-related patterns of EMG, MMG and US features as outliers of the linear derivative-to-torque functions. The results show that the LOIRE method can effectively reveal transient patterns in the signal-to-torque relationships (for example, sudden changes around 20% MVC can be observed from all features), providing important information about in vivo muscle behavior.

  1. Mechanical basis of bone strength: influence of bone material, bone structure and muscle action

    Science.gov (United States)

    Hart, N.H.; Nimphius, S.; Rantalainen, T.; Ireland, A.; Siafarikas, A.; Newton, R.U.

    2017-01-01

    This review summarises current understanding of how bone is sculpted through adaptive processes, designed to meet the mechanical challenges it faces in everyday life and athletic pursuits, serving as an update for clinicians, researchers and physical therapists. Bone’s ability to resist fracture under the large muscle and locomotory forces it experiences during movement and in falls or collisions is dependent on its established mechanical properties, determined by bone’s complex and multidimensional material and structural organisation. At all levels, bone is highly adaptive to habitual loading, regulating its structure according to components of its loading regime and mechanical environment, inclusive of strain magnitude, rate, frequency, distribution and deformation mode. Indeed, the greatest forces habitually applied to bone arise from muscular contractions, and the past two decades have seen substantial advances in our understanding of how these forces shape bone throughout life. Herein, we also highlight the limitations of in vivo methods to assess and understand bone collagen, and bone mineral at the material or tissue level. The inability to easily measure or closely regulate applied strain in humans is identified, limiting the translation of animal studies to human populations, and our exploration of how components of mechanical loading regimes influence mechanoadaptation. PMID:28860414

  2. Emerging new tools to study and treat muscle pathologies: genetics and molecular mechanisms underlying skeletal muscle development, regeneration, and disease.

    Science.gov (United States)

    Crist, Colin

    2017-01-01

    Skeletal muscle is the most abundant tissue in our body, is responsible for generating the force required for movement, and is also an important thermogenic organ. Skeletal muscle is an enigmatic tissue because while on the one hand, skeletal muscle regeneration after injury is arguably one of the best-studied stem cell-dependent regenerative processes, on the other hand, skeletal muscle is still subject to many degenerative disorders with few therapeutic options in the clinic. It is important to develop new regenerative medicine-based therapies for skeletal muscle. Future therapeutic strategies should take advantage of rapidly developing technologies enabling the differentiation of skeletal muscle from human pluripotent stem cells, along with precise genome editing, which will go hand in hand with a steady and focused approach to understanding underlying mechanisms of skeletal muscle development, regeneration, and disease. In this review, I focus on highlighting the recent advances that particularly have relied on developmental and molecular biology approaches to understanding muscle development and stem cell function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  3. Acute effects of static stretching on muscle-tendon mechanics of quadriceps and plantar flexor muscles.

    Science.gov (United States)

    Bouvier, Tom; Opplert, Jules; Cometti, Carole; Babault, Nicolas

    2017-07-01

    This study aimed to determine the acute effects of static stretching on stiffness indexes of two muscle groups with a contrasting difference in muscle-tendon proportion. Eleven active males were tested on an isokinetic dynamometer during four sessions randomly presented. Two sessions were dedicated to quadriceps and the two others to triceps surae muscles. Before and immediately after the stretching procedure (5 × 30 s), gastrocnemius medialis and rectus femoris fascicle length and myotendinous junction elongation were determined using ultrasonography. Passive and maximal voluntary torques were measured. Fascicle and myotendinous junction stiffness indexes were calculated. After stretching, maximal voluntary torque similarly decreased for both muscle groups. Passive torque significantly decreased on triceps surae and remained unchanged on quadriceps muscles. Fascicle length increased similarly for both muscles. However, myotendinous junction elongation remained unchanged for gastrocnemius medialis and increased significantly for rectus femoris muscle. Fascicle stiffness index significantly decreased on medial gastrocnemius and remained unchanged on rectus femoris muscle. In contrast, myotendinous junction stiffness index similarly decreased on both muscles. Depending on the muscle considered, the present results revealed different acute stretching effects. This muscle dependency appeared to affect primarily fascicle stiffness index rather than the myotendinous junction.

  4. Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia

    Science.gov (United States)

    Brzeszczyńska, Joanna; Meyer, Angelika; McGregor, Robin; Schilb, Alain; Degen, Simone; Tadini, Valentina; Johns, Neil; Langen, Ramon; Schols, Annemie; Glass, David J.; Roubenoff, Ronenn; Ross, James A.; Fearon, Kenneth C.H.; Greig, Carolyn A.

    2017-01-01

    Abstract Background Sarcopenia is defined as the age‐related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2–5% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults, with or without sarcopenia, compared with middle‐aged controls using both in vivo and in vitro approaches to explore potential biomarker or causative molecular pathways associated with sarcopenic versus non‐sarcopenic skeletal muscle phenotypes during ageing. Methods Biomarkers of multiple molecular pathways associated with muscle regeneration were analysed using quantitative polymerase chain reaction in quadriceps muscle samples obtained from healthy elderly sarcopenic (HSE, n = 7) or non‐sarcopenic (HENS, n = 21) and healthy middle‐aged control (HMC, n = 22) groups. An in vitro system of myogenesis (using myoblasts from human donors aged 17–83 years) was used to mimic the environmental challenges of muscle regeneration over time. Results The muscle biopsies showed evidence of satellite cell activation in HENS (Pax3, P HSE biopsy samples showed satellite cell activation (Pax7, P HSE group. In contrast, there was 10‐fold higher upregulation of HSPA1A a stress‐induced chaperone acting upon misfolded proteins in HSE compared with the HENS group. Conclusions Both pathological and adaptive processes are active in skeletal muscle during healthy ageing. Muscle regeneration pathways are activated during healthy ageing, but there is evidence of dysregulation in sarcopenia. In addition, increased cellular stress, with an impaired oxidative‐stress and mis‐folded protein response (HSPA1A), may be associated with the development of sarcopenia. The in vitro system of young and old myoblasts replicated some of the differences between young and old muscle. PMID:29214748

  5. Gestational protein restriction impairs insulin-regulated glucose transport mechanisms in gastrocnemius muscles of adult male offspring.

    Science.gov (United States)

    Blesson, Chellakkan S; Sathishkumar, Kunju; Chinnathambi, Vijayakumar; Yallampalli, Chandrasekhar

    2014-08-01

    Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet-exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet-fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor

  6. Fluvastatin and atorvastatin affect calcium homeostasis of rat skeletal muscle fibers in vivo and in vitro by impairing the sarcoplasmic reticulum/mitochondria Ca2+-release system.

    Science.gov (United States)

    Liantonio, Antonella; Giannuzzi, Viviana; Cippone, Valentina; Camerino, Giulia Maria; Pierno, Sabata; Camerino, Diana Conte

    2007-05-01

    The mechanism by which the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) induce skeletal muscle injury is still under debate. By using fura-2 cytofluorimetry on intact extensor digitorum longus muscle fibers, here we provided the first evidence that 2 months in vivo chronic treatment of rats with fluvastatin (5 and 20 mg kg-1) and atorvastatin (5 and 10 mg kg-1) caused an alteration of calcium homeostasis. All treated animals showed a significant increase of resting cytosolic calcium [Ca2+]i, up to 60% with the higher fluvastatin dose and up to 20% with the other treatments. The [Ca2+]i rise induced by statin administration was not due to an increase of sarcolemmal permeability to calcium. Furthermore, the treatments reduced caffeine responsiveness. In vitro application of fluvastatin caused changes of [Ca2+]i, resembling the effect obtained after the in vivo administration. Indeed, fluvastatin produced a shift of mechanical threshold for contraction toward negative potentials and an increase of resting [Ca2+]i. By using ruthenium red and cyclosporine A, we determined the sequence of the statin-induced Ca2+ release mechanism. Mitochondria appeared as the cellular structure responsible for the earlier event leading to a subsequent large sarcoplasmic reticulum Ca2+ release. In conclusion, we suggest that calcium homeostasis alteration may be a crucial event for myotoxicity induced by this widely used class of hypolipidemic drugs.

  7. Contribution of elastic tissues to the mechanics and energetics of muscle function during movement.

    Science.gov (United States)

    Roberts, Thomas J

    2016-01-01

    Muscle force production occurs within an environment of tissues that exhibit spring-like behavior, and this elasticity is a critical determinant of muscle performance during locomotion. Muscle force and power output both depend on the speed of contraction, as described by the isotonic force-velocity curve. By influencing the speed of contractile elements, elastic structures can have a profound effect on muscle force, power and work. In very rapid movements, elastic mechanisms can amplify muscle power by storing the work of muscle contraction slowly and releasing it rapidly. When energy must be dissipated rapidly, such as in landing from a jump, energy stored rapidly in elastic elements can be released more slowly to stretch muscle contractile elements, reducing the power input to muscle and possibly protecting it from damage. Elastic mechanisms identified so far rely primarily on in-series tendons, but many structures within muscles exhibit spring-like properties. Actomyosin cross-bridges, actin and myosin filaments, titin, and the connective tissue scaffolding of the extracellular matrix all have the potential to store and recover elastic energy during muscle contraction. The potential contribution of these elements can be assessed from their stiffness and estimates of the strain they undergo during muscle function. Such calculations provide boundaries for the possible roles these springs might play in locomotion, and may help to direct future studies of the uses of elastic elements in muscle. © 2016. Published by The Company of Biologists Ltd.

  8. Possible mechanism for changes in glycogen metabolism in unloaded soleus muscle

    Science.gov (United States)

    Henriksen, E. J.; Tischler, M. E.

    1985-01-01

    Carbohydrate metabolism has been shown to be affected in a number of ways by different models of hypokinesia. In vivo glycogen levels in the soleus muscle are known to be increased by short-term denervation and harness suspension. In addition, exposure to 7 days of hypogravity also caused a dramatic increase in glycogen concentration in this muscle. The biochemical alterations caused by unloading that may bring about these increases in glycogen storage in the soleus were sought.

  9. Defective mitochondrial function in vivo in skeletal muscle in adults with Down's syndrome: a 31P-MRS study.

    Directory of Open Access Journals (Sweden)

    Alexander C Phillips

    Full Text Available Down's syndrome (DS is a developmental disorder associated with intellectual disability (ID. We have previously shown that people with DS engage in very low levels of exercise compared to people with ID not due to DS. Many aspects of the DS phenotype, such as dementia, low activity levels and poor muscle tone, are shared with disorders of mitochondrial origin, and mitochondrial dysfunction has been demonstrated in cultured DS tissue. We undertook a phosphorus magnetic resonance spectroscopy ((31P-MRS study in the quadriceps muscle of 14 people with DS and 11 non-DS ID controls to investigate the post-exercise resynthesis kinetics of phosphocreatine (PCr, which relies on mitochondrial respiratory function and yields a measure of muscle mitochondrial function in vivo. We found that the PCr recovery rate constant was significantly decreased in adults with DS compared to non-DS ID controls (1.7 ± 0.1 min(-1 vs 2.1 ± 0.1 min(-1 respectively who were matched for physical activity levels, indicating that muscle mitochondrial function in vivo is impaired in DS. This is the first study to investigate mitochondrial function in vivo in DS using (31P-MRS. Our study is consistent with previous in vitro studies, supporting a theory of a global mitochondrial defect in DS.

  10. Altered neuromuscular control mechanisms of the trapezius muscle in fibromyalgia

    Directory of Open Access Journals (Sweden)

    Karlsson Stefan J

    2010-03-01

    Full Text Available Abstract Background fibromyalgia is a relatively common condition with widespread pain and pressure allodynia, but unknown aetiology. For decades, the association between motor control strategies and chronic pain has been a topic for debate. One long held functional neuromuscular control mechanism is differential activation between regions within a single muscle. The aim of this study was to investigate differences in neuromuscular control, i.e. differential activation, between myalgic trapezius in fibromyalgia patients and healthy controls. Methods 27 fibromyalgia patients and 30 healthy controls performed 3 minutes bilateral shoulder elevations with different loads (0-4 Kg with a high-density surface electromyographical (EMG grid placed above the upper trapezius. Differential activation was quantified by the power spectral median frequency of the difference in EMG amplitude between the cranial and caudal parts of the upper trapezius. The average duration of the differential activation was described by the inverse of the median frequency of the differential activations. Results the median frequency of the differential activations was significantly lower, and the average duration of the differential activations significantly longer in fibromyalgia compared with controls at the two lowest load levels (0-1 Kg (p Conclusion these findings illustrate a different neuromuscular control between fibromyalgia patients and healthy controls during a low load functional task, either sustaining or resulting from the chronic painful condition. The findings may have clinical relevance for rehabilitation strategies for fibromyalgia.

  11. Skeletal muscle contraction in protecting joints and bones by absorbing mechanical impacts

    Science.gov (United States)

    Rudenko, O. V.; Tsyuryupa, S.; Sarvazyan, A.

    2016-09-01

    We have previously hypothesized that the dissipation of mechanical energy of external impact is a fundamental function of skeletal muscle in addition to its primary function to convert chemical energy into mechanical energy. In this paper, a mathematical justification of this hypothesis is presented. First, a simple mechanical model, in which the muscle is considered as a simple Hookean spring, is considered. This analysis serves as an introduction to the consideration of a biomechanical model taking into account the molecular mechanism of muscle contraction, kinetics of myosin bridges, sarcomere dynamics, and tension of muscle fibers. It is shown that a muscle behaves like a nonlinear and adaptive spring tempering the force of impact and increasing the duration of the collision. The temporal profiles of muscle reaction to the impact as functions of the levels of muscle contraction, durations of the impact front, and the time constants of myosin bridges closing, are obtained. The absorption of mechanical shock energy is achieved due to the increased viscoelasticity of the contracting skeletal muscle. Controlling the contraction level allows for the optimization of the stiffness and viscosity of the muscle necessary for the protection of the joints and bones.

  12. Regulatory mechanisms of skeletal muscle protein turnover during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2009-01-01

    Skeletal muscle protein turnover is a relatively slow metabolic process that is altered by various physiological stimuli such as feeding/fasting and exercise. During exercise, catabolism of amino acids contributes very little to ATP turnover in working muscle. With regards to protein turnover......, there is now consistent data from tracer studies in rodents and humans showing that global protein synthesis is blunted in working skeletal muscle. Whether there is altered skeletal muscle protein breakdown during exercise remains unclear. The blunting of protein synthesis is believed to be mediated...... downstream of changes in intracellular Ca(2+) and energy turnover. In particular, a signaling cascade involving Ca(2+)-calmodulin-eEF2 kinase-eEF2 is implicated. The possible functional significance of altered protein turnover in working skeletal muscle during exercise is discussed. Further work...

  13. Alterations of the In Vivo Torque-Velocity Relationship of Human Skeletal Muscle Following 30 Days Exposure to Simulated Microgravity

    Science.gov (United States)

    Dudley, Gary A.; Duvoisin, Marc R.; Convertino, Victor A.; Buchanan, Paul

    1989-01-01

    The purpose of this study was to examine the effect of 30 d of 6 deg headdown bedrest (BR) on the in vivo strength of skeletal muscle. Peak angle specific (0.78 rad below horizontal) torque of the knee extensor (KE) and flexor (KF) muscle groups of both limbs was assessed during unilateral efforts at four speeds (0.52, 1.74, 2.97 and 4.19 rad/s) during concentric and at three speeds (0.52, 1.74 and 2.97 rad/s) during eccentric actions. The average decrease (P less than 0.05) of peak angle specific torque directly post-BR for the KE across speeds of concentric and eccentric actions was about 19% (n = 7). Recovery for 30 d following BR markedly improved strength to about 92% (P greater than 0.05) of 'normal'. Strength of the KF was not altered (P greater than 0.05) by BR (about a 6% decrease independent of speed and type of muscle action). Changes of strength were not affected by the type or speed of muscle action. The results indicate that strength of ex-tensor more than of flexor muscle groups of the lower limb is decreased by 30 d of bedrest and that this response does not alter the nature of the in vivo torque-velocity relation.

  14. The role of endothelial cells in myofiber differentiation and the vascularization and innervation of bioengineered muscle tissue in vivo.

    Science.gov (United States)

    Criswell, Tracy L; Corona, Benjamin T; Wang, Zhan; Zhou, Yu; Niu, Guoguang; Xu, Yong; Christ, George J; Soker, Shay

    2013-01-01

    Musculoskeletal disorders are a major cause of disability and effective treatments are currently lacking. Tissue engineering affords the possibility of new therapies utilizing cells and biomaterials for the recovery of muscle volume and function. A major consideration in skeletal muscle engineering is the integration of a functional vasculature within the regenerating tissue. In this study we employed fluorescent cell labels to track the location and differentiation of co-cultured cells in vivo and in vitro. We first utilized a co-culture of fluorescently labeled endothelial cells (ECs) and muscle progenitor cells (MPCs) to investigate the ability of ECs to enhance muscle tissue formation and vascularization in an in vivo model of bioengineered muscle. Scaffolds that had been seeded with both MPCs and ECs showed significantly greater vascularization, tissue formation and enhanced innervation as compared to scaffolds seeded with MPCs alone. Subsequently, we performed in vitro experiments using a 3-cell type system (ECs, MPCs, and pericytes (PCs)) to demonstrate the utility of fluorescent cell labeling for monitoring cell growth and differentiation. The growth and differentiation of individual cell types was determined using live cell fluorescent microscopy demonstrating the utility of fluorescent labels to monitor tissue organization in real time. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

    Science.gov (United States)

    Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

    2015-01-01

    This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R = 0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions. PMID:18241900

  16. In vivo MRI quantification of individual muscle and organ volumes for assessment of anabolic steroid growth effects.

    Science.gov (United States)

    Wu, Ed X; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B; Vasselli, Joseph R

    2008-04-01

    This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 T scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R=0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions.

  17. In vivo field dependence of proton relaxation times in human brain, liver and skeletal muscle: a multicenter study

    DEFF Research Database (Denmark)

    Henriksen, O; de Certaines, J D; Spisni, A

    1993-01-01

    and MRS, the in vivo field dispersion of T1 and T2 has been measured in order to evaluate whether ex vivo data are representative for the in vivo situation. Brain, skeletal muscle, and liver of healthy human volunteers were studied. Fifteen MR units with a field strength ranging from 0.08 T to 1.5 T took......T1 and T2 relaxation times are fundamental parameters for signal contrast behaviour in MRI. A number of ex vivo relaxometry studies have dealt with the magnetic field dispersion of T1. By means of multicenter study within the frame of the COMAC BME Concerted Action on Tissue Characterization by MRI...... part in the trial, which comprised 218 volunteers. All the MR systems were tested for measurement accuracy using the Eurospin TO5 test object. The measured relaxation data were subsequently corrected according to the obtained calibration curves. The results showed a clear field dispersion of T1...

  18. Effect of spaceflight on skeletal muscle: Mechanical properties and myosin isoform content of a slow muscle

    Science.gov (United States)

    Caiozzo, Vincent J.; Baker, Michael J.; Herrick, Robert E.; Tao, Ming; Baldwin, Kenneth M.

    1994-01-01

    This study examined changes in contractile, biochemical, and histochemical properties of slow antigravity skeletal muscle after a 6-day spaceflight mission. Twelve male Sprague-Dawley rats were randomly divided into two groups: flight and ground-based control. Approximately 3 h after the landing, in situ contractile measurements were made on the soleus muscles of the flight animals. The control animals were studied 24 h later. The contractile measurements included force-velocity relationship, force-frequency relationship, and fatigability. Biochemical measurements focused on the myosin heavy chain (MHC) and myosin light chain profiles. Adenosinetriphosphatase histochemistry was performed to identify cross-sectional area of slow and fast muscle fibers and to determine the percent fiber type distribution. The force-velocity relationships of the flight muscles were altered such that maximal isometric tension P(sub o) was decreased by 24% and maximal shortening velocity was increased by 14% (P less than 0.05). The force-frequency relationship of the flight muscles was shifted to the right of the control muscles. At the end of the 2-min fatigue test, the flight muscles generated only 34% of P(sub o), whereas the control muscles generated 64% of P(sub o). The flight muscles exhibited de novo expression of the type IIx MHC isoform as well as a slight decrease in the slow type I and fast type IIa MHC isoforms. Histochemical analyses of flight muscles demonstrated a small increase in the percentage of fast type II fibers and a greater atrophy of the slow type I fibers. The results demonstrate that contractile properties of slow antigravity skeletal muscle are sensitive to the microgravity environment and that changes begin to occur within the 1st wk. These changes were at least, in part, associated with changes in the amount and type of contractile protein expressed.

  19. Molecular and cellular mechanisms of muscle aging and sarcopenia and effects of electrical stimulation in seniors

    Directory of Open Access Journals (Sweden)

    Laura Barberi

    2015-08-01

    Full Text Available The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers, alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors.

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

    Science.gov (United States)

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

    2017-06-01

    The goal of this study was to gain insight into how ankle exoskeletons affect the behavior of the plantarflexor muscles during walking. Using data from previous experiments, we performed electromyography-driven simulations of musculoskeletal dynamics to explore how changes in exoskeleton assistance affected plantarflexor muscle-tendon mechanics, particularly for the soleus. We used a model of muscle energy consumption to estimate individual muscle metabolic rate. As average exoskeleton torque was increased, while no net exoskeleton work was provided, a reduction in tendon recoil led to an increase in positive mechanical work performed by the soleus muscle fibers. As net exoskeleton work was increased, both soleus muscle fiber force and positive mechanical work decreased. Trends in the sum of the metabolic rates of the simulated muscles correlated well with trends in experimentally observed whole-body metabolic rate (R2=0.9), providing confidence in our model estimates. Our simulation results suggest that different exoskeleton behaviors can alter the functioning of the muscles and tendons acting at the assisted joint. Furthermore, our results support the idea that the series tendon helps reduce positive work done by the muscle fibers by storing and returning energy elastically. We expect the results from this study to promote the use of electromyography-driven simulations to gain insight into the operation of muscle-tendon units and to guide the design and control of assistive devices. © 2017. Published by The Company of Biologists Ltd.

  1. Carnitine supplementation in high-fat diet-fed rats does not ameliorate lipid-induced skeletal muscle mitochondrial dysfunction in vivo.

    Science.gov (United States)

    Wessels, Bart; van den Broek, Nicole M A; Ciapaite, Jolita; Houten, Sander M; Wanders, Ronald J A; Nicolay, Klaas; Prompers, Jeanine J

    2015-10-01

    Muscle lipid overload and the associated accumulation of lipid intermediates play an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid intermediates out of the mitochondria. The aim of the present study was to test the hypothesis that carnitine supplementation reduces high-fat diet-induced lipotoxicity, improves muscle mitochondrial function, and ameliorates insulin resistance. Wistar rats were fed either normal chow or a high-fat diet for 15 wk. One group of high-fat diet-fed rats was supplemented with 300 mg·kg(-1)·day(-1) L-carnitine during the last 8 wk. Muscle mitochondrial function was measured in vivo by (31)P magnetic resonance spectroscopy (MRS) and ex vivo by high-resolution respirometry. Muscle lipid status was determined by (1)H MRS (intramyocellular lipids) and tandem mass spectrometry (acylcarnitines). High-fat diet feeding induced insulin resistance and was associated with decreases in muscle and blood free carnitine, elevated levels of muscle lipids and acylcarnitines, and an increased number of muscle mitochondria that showed an improved capacity to oxidize fat-derived substrates when tested ex vivo. This was, however, not accompanied by an increase in muscle oxidative capacity in vivo, indicating that in vivo mitochondrial function was compromised. Despite partial normalization of muscle and blood free carnitine content, carnitine supplementation did not induce improvements in muscle lipid status, in vivo mitochondrial function, or insulin sensitivity. Carnitine insufficiency, therefore, does not play a major role in high-fat diet-induced muscle mitochondrial dysfunction in vivo. Copyright © 2015 the American Physiological Society.

  2. A biomechanical approach for in vivo diaphragm muscle motion prediction during normal respiration

    Science.gov (United States)

    Coelho, Brett; Karami, Elham; Haddad, Seyyed M. H.; Seify, Behzad; Samani, Abbas

    2017-03-01

    Lung cancer is one of the leading causes of cancer death in men and women. External Beam Radiation Therapy (EBRT) is a commonly used primary treatment for the condition. A major challenge with such treatments is the delivery of sufficient radiation dose to the lung tumor while ensuring that surrounding healthy lung parenchyma receives only minimal dose. This can be achieved by coupling EBRT with respiratory computer models which can predict the tumour location as a function of phase during the breathing cycle1. The diaphragm muscle contraction is mainly responsible for a large portion of the lung tumor motion during normal breathing, especially when tumours are in the lower lobes, therefore the importance of accurately modelling the diaphragm is paramount in lung tumour motion prediction. The goal of this research is to develop a biomechanical model of the diaphragm, including its active and passive response, using detailed geometric, biomechanical and anatomical information that mimics the diaphragmatic behaviour in a patient specific manner. For this purpose, a Finite Element Model (FEM) of the diaphragm was developed in order to predict the in vivo motion of the diaphragm, paving the way for computer assisted lung cancer tumor tracking in EBRT. Preliminary results obtained from the proposed model are promising and they indicate that it can be used as a plausible tool for effective lung cancer EBRT to improve patient care.

  3. In vivo determination of muscle-derived stem cells in the rat corpus cavernosum.

    Science.gov (United States)

    Xu, Lijun; Xue, Boxin; Shan, Yuxi; Chen, Dong; Gao, Jie; Yang, Dongrong; Sun, Chuanyang; Cui, Yong

    2014-07-01

    The aim of the present in vivo study was to determine the presence of muscle-derived stem cells (MDSCs) in the corpus cavernosum of rats. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to detect the expression of the stem cell markers stem cell antigen-1 (Sca-1), Oct4 and Desmin in Sprague-Dawley rats aged 2, 5 and 20 months. Sca-1 was mainly expressed in the blood vessels and cavernous sinus and staining revealed that Sca-1 was predominantly expressed in the cytoplasm. Desmin was primarily expressed in muscular tissues and staining demonstrated that it was mainly expressed in the cytoplasm, however, Desmin was also partially expressed in the nuclei. A small number of double positive cells, expressing Sca-1 and Desmin, were also detected near the cavernous sinus. It was found that the expression of the markers was negatively correlated with the age of the rats (Pcorpus cavernosum. MDSCs may be a potential therapeutic treatment for organic erectile dysfunction.

  4. Heterogeneous effects of old age on human muscle oxidative capacity in vivo: a systematic review and meta-analysis.

    Science.gov (United States)

    Fitzgerald, Liam F; Christie, Anita D; Kent, Jane A

    2016-11-01

    Despite intensive efforts to understand the extent to which skeletal muscle mitochondrial capacity changes in older humans, the answer to this important question remains unclear. To determine what the preponderance of evidence from in vivo studies suggests, we conducted a systematic review and meta-analysis of the effects of age on muscle oxidative capacity as measured noninvasively by magnetic resonance spectroscopy. A secondary aim was to examine potential moderators contributing to differences in results across studies, including muscle group, physical activity status, and sex. Candidate papers were identified from PubMed searches (n = 3561 papers) and the reference lists of relevant papers. Standardized effects (Hedges' g) were calculated for age and each moderator using data from the 22 studies that met the inclusion criteria (n = 28 effects). Effects were coded as positive when older (age, ≥55 years) adults had higher muscle oxidative capacity than younger (age, 20-45 years) adults. The overall effect of age on oxidative capacity was positive (g = 0.171, p < 0.001), indicating modestly greater oxidative capacity in old. Notably, there was significant heterogeneity in this result (Q = 245.8, p < 0.001; I2 = ∼70%-90%). Muscle group, physical activity, and sex were all significant moderators of oxidative capacity (p ≤ 0.029). This analysis indicates that the current body of literature does not support a de facto decrease of in vivo muscle oxidative capacity in old age. The heterogeneity of study results and identification of significant moderators provide clarity regarding apparent discrepancies in the literature, and indicate the importance of accounting for these variables when examining purported age-related differences in muscle oxidative capacity.

  5. Use it or lose it: multiscale skeletal muscle adaptation to mechanical stimuli.

    Science.gov (United States)

    Wisdom, Katrina M; Delp, Scott L; Kuhl, Ellen

    2015-04-01

    Skeletal muscle undergoes continuous turnover to adapt to changes in its mechanical environment. Overload increases muscle mass, whereas underload decreases muscle mass. These changes are correlated with, and enabled by, structural alterations across the molecular, subcellular, cellular, tissue, and organ scales. Despite extensive research on muscle adaptation at the individual scales, the interaction of the underlying mechanisms across the scales remains poorly understood. Here, we present a thorough review and a broad classification of multiscale muscle adaptation in response to a variety of mechanical stimuli. From this classification, we suggest that a mathematical model for skeletal muscle adaptation should include the four major stimuli, overstretch, understretch, overload, and underload, and the five key players in skeletal muscle adaptation, myosin heavy chain isoform, serial sarcomere number, parallel sarcomere number, pennation angle, and extracellular matrix composition. Including this information in multiscale computational models of muscle will shape our understanding of the interacting mechanisms of skeletal muscle adaptation across the scales. Ultimately, this will allow us to rationalize the design of exercise and rehabilitation programs, and improve the long-term success of interventional treatment in musculoskeletal disease.

  6. Ca2+-Dependent Regulations and Signaling in Skeletal Muscle: From Electro-Mechanical Coupling to Adaptation

    Directory of Open Access Journals (Sweden)

    Sebastian Gehlert

    2015-01-01

    Full Text Available Calcium (Ca2+ plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca2+ is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca2+ regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca2+-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca2+ ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca2+ ions in adult muscle but also highlight recent findings of critical Ca2+-dependent mechanisms essential for skeletal muscle-regulation and maintenance.

  7. Skeletal muscle lipid quantification in lean and diabetic subjects using in vivo proton MR spectroscopy

    Directory of Open Access Journals (Sweden)

    Sunil K Valaparla

    2014-03-01

    : Valaparla SK, Boone GRE, Ripley EM, Giuseppe D, Duong TQ, Abdul-Ghani M, Clarke GD. Skeletal muscle lipid quantification in lean and diabetic subjects using in vivo proton MR spectroscopy. Int J Cancer Ther Oncol 2014; 2(2:020239. DOI: 10.14319/ijcto.0202.39

  8. In vivo time-resolved microtomography reveals the mechanics of the blowfly flight motor.

    Directory of Open Access Journals (Sweden)

    Simon M Walker

    2014-03-01

    Full Text Available Dipteran flies are amongst the smallest and most agile of flying animals. Their wings are driven indirectly by large power muscles, which cause cyclical deformations of the thorax that are amplified through the intricate wing hinge. Asymmetric flight manoeuvres are controlled by 13 pairs of steering muscles acting directly on the wing articulations. Collectively the steering muscles account for <3% of total flight muscle mass, raising the question of how they can modulate the vastly greater output of the power muscles during manoeuvres. Here we present the results of a synchrotron-based study performing micrometre-resolution, time-resolved microtomography on the 145 Hz wingbeat of blowflies. These data represent the first four-dimensional visualizations of an organism's internal movements on sub-millisecond and micrometre scales. This technique allows us to visualize and measure the three-dimensional movements of five of the largest steering muscles, and to place these in the context of the deforming thoracic mechanism that the muscles actuate. Our visualizations show that the steering muscles operate through a diverse range of nonlinear mechanisms, revealing several unexpected features that could not have been identified using any other technique. The tendons of some steering muscles buckle on every wingbeat to accommodate high amplitude movements of the wing hinge. Other steering muscles absorb kinetic energy from an oscillating control linkage, which rotates at low wingbeat amplitude but translates at high wingbeat amplitude. Kinetic energy is distributed differently in these two modes of oscillation, which may play a role in asymmetric power management during flight control. Structural flexibility is known to be important to the aerodynamic efficiency of insect wings, and to the function of their indirect power muscles. We show that it is integral also to the operation of the steering muscles, and so to the functional flexibility of the

  9. Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model.

    Science.gov (United States)

    Aare, Sudhakar; Ochala, Julien; Norman, Holly S; Radell, Peter; Eriksson, Lars I; Göransson, Hanna; Chen, Yi-Wen; Hoffman, Eric P; Larsson, Lars

    2011-12-16

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients that is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents, corticosteroids (CS), and sepsis for 5 days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after 5 days' exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to 5 days' exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle-specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements, and sarcomeric proteins underlying the relative sparing of cranial vs. spinal nerve innervated muscles during exposure to the ICU intervention.

  10. A muscle-reflex model that encodes principles of legged mechanics produces human walking dynamics and muscle activities.

    Science.gov (United States)

    Geyer, Hartmut; Herr, Hugh

    2010-06-01

    While neuroscientists identify increasingly complex neural circuits that control animal and human gait, biomechanists find that locomotion requires little control if principles of legged mechanics are heeded that shape and exploit the dynamics of legged systems. Here, we show that muscle reflexes could be vital to link these two observations. We develop a model of human locomotion that is controlled by muscle reflexes which encode principles of legged mechanics. Equipped with this reflex control, we find this model to stabilize into a walking gait from its dynamic interplay with the ground, reproduce human walking dynamics and leg kinematics, tolerate ground disturbances, and adapt to slopes without parameter interventions. In addition, we find this model to predict some individual muscle activation patterns known from walking experiments. The results suggest not only that the interplay between mechanics and motor control is essential to human locomotion, but also that human motor output could for some muscles be dominated by neural circuits that encode principles of legged mechanics.

  11. Vanadium and cadmium in vivo effects in teleost cardiac muscle: metal accumulation and oxidative stress markers.

    Science.gov (United States)

    Soares, S S; Martins, H; Gutiérrez-Merino, C; Aureliano, M

    2008-03-01

    Several biological studies associate vanadium and cadmium with the production of reactive oxygen species (ROS), leading to lipid peroxidation and antioxidant enzymes alterations. The present study aims to analyse and compare the oxidative stress responses induced by an acute intravenous exposure (1 and 7 days) to a sub-lethal concentration (5 mM) of two vanadium solutions, containing different vanadate n-oligomers (n=1-5 or n=10), and a cadmium solution on the cardiac muscle of the marine teleost Halobatrachus didactylus (Lusitanian toadfish). It was observed that vanadium is mainly accumulated in mitochondria (1.33+/-0.26 microM), primarily when this element was administrated as decameric vanadate, than when administrated as metavanadate (432+/-294 nM), while the highest content of cadmium was found in cytosol (365+/-231 nM). Indeed, decavanadate solution promotes stronger increases in mitochondrial antioxidant enzymes activities (catalase: +120%; superoxide dismutase: +140%) than metavanadate solution. On contrary, cadmium increases cytosolic catalase (+111%) and glutathione peroxidases (+50%) activities. It is also observed that vanadate oligomers induce in vitro prooxidant effects in toadfish heart, with stronger effects induced by metavanadate solution. In summary, vanadate and cadmium are differently accumulated in blood and cardiac subcellular fractions and induced different responses in enzymatic antioxidant defence mechanisms. In the present study, it is described for the first time the effects of equal doses of two different metals intravenously injected in the same fish species and upon the same exposure period allowing to understand the mechanisms of vanadate and cadmium toxicity in fish cardiac muscle.

  12. A benchtop biorobotic platform for in vitro observation of muscle-tendon dynamics with parallel mechanical assistance from an elastic exoskeleton.

    Science.gov (United States)

    Robertson, Benjamin D; Vadakkeveedu, Siddarth; Sawicki, Gregory S

    2017-05-24

    We present a novel biorobotic framework comprised of a biological muscle-tendon unit (MTU) mechanically coupled to a feedback controlled robotic environment simulation that mimics in vivo inertial/gravitational loading and mechanical assistance from a parallel elastic exoskeleton. Using this system, we applied select combinations of biological muscle activation (modulated with rate-coded direct neural stimulation) and parallel elastic assistance (applied via closed-loop mechanical environment simulation) hypothesized to mimic human behavior based on previously published modeling studies. These conditions resulted in constant system-level force-length dynamics (i.e., stiffness), reduced biological loads, increased muscle excursion, and constant muscle average positive power output-all consistent with laboratory experiments on intact humans during exoskeleton assisted hopping. Mechanical assistance led to reduced estimated metabolic cost and MTU apparent efficiency, but increased apparent efficiency for the MTU+Exo system as a whole. Findings from this study suggest that the increased natural resonant frequency of the artificially stiffened MTU+Exo system, along with invariant movement frequencies, may underlie observed limits on the benefits of exoskeleton assistance. Our novel approach demonstrates that it is possible to capture the salient features of human locomotion with exoskeleton assistance in an isolated muscle-tendon preparation, and introduces a powerful new tool for detailed, direct examination of how assistive devices affect muscle-level neuromechanics and energetics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Sites of Superoxide and Hydrogen Peroxide Production by Muscle Mitochondria Assessed ex Vivo under Conditions Mimicking Rest and Exercise*

    Science.gov (United States)

    Goncalves, Renata L. S.; Quinlan, Casey L.; Perevoshchikova, Irina V.; Hey-Mogensen, Martin; Brand, Martin D.

    2015-01-01

    The sites and rates of mitochondrial production of superoxide and H2O2 in vivo are not yet defined. At least 10 different mitochondrial sites can generate these species. Each site has a different maximum capacity (e.g. the outer quinol site in complex III (site IIIQo) has a very high capacity in rat skeletal muscle mitochondria, whereas the flavin site in complex I (site IF) has a very low capacity). The maximum capacities can greatly exceed the actual rates observed in the absence of electron transport chain inhibitors, so maximum capacities are a poor guide to actual rates. Here, we use new approaches to measure the rates at which different mitochondrial sites produce superoxide/H2O2 using isolated muscle mitochondria incubated in media mimicking the cytoplasmic substrate and effector mix of skeletal muscle during rest and exercise. We find that four or five sites dominate during rest in this ex vivo system. Remarkably, the quinol site in complex I (site IQ) and the flavin site in complex II (site IIF) each account for about a quarter of the total measured rate of H2O2 production. Site IF, site IIIQo, and perhaps site EF in the β-oxidation pathway account for most of the remainder. Under conditions mimicking mild and intense aerobic exercise, total production is much less, and the low capacity site IF dominates. These results give novel insights into which mitochondrial sites may produce superoxide/H2O2 in vivo. PMID:25389297

  14. Expression of perilipins in human skeletal muscle in vitro and in vivo in relation to diet, exercise and energy balance

    DEFF Research Database (Denmark)

    Gjelstad, I M F; Haugen, F; Gulseth, H L

    2011-01-01

    , enhanced the expression of perilipin 2 and 3. Perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity. In conclusion, all perilipins mRNAs were expressed in human skeletal muscle. Diet as well as endurance exercise modulated......The perilipin proteins enclose intracellular lipid droplets. We describe the mRNA expression of the five perilipins in human skeletal muscle in relation to fatty acid supply, exercise and energy balance. We observed that all perilipins were expressed in skeletal muscle biopsies with the highest m......RNA levels of perilipin 2, 4 and 5. Cultured myotubes predominantly expressed perilipin 2 and 3. In vitro, incubation of myotubes with fatty acids enhanced mRNA expression of perilipin 1, 2 and 4. In vivo, low fat diet increased mRNA levels of perilipin 3 and 4. Endurance training, but not strength training...

  15. VCP-dependent muscle degeneration is linked to defects in a dynamic tubular lysosomal network in vivo.

    Science.gov (United States)

    Johnson, Alyssa E; Shu, Huidy; Hauswirth, Anna G; Tong, Amy; Davis, Graeme W

    2015-07-13

    Lysosomes are classically viewed as vesicular structures to which cargos are delivered for degradation. Here, we identify a network of dynamic, tubular lysosomes that extends throughout Drosophila muscle, in vivo. Live imaging reveals that autophagosomes merge with tubular lysosomes and that lysosomal membranes undergo extension, retraction, fusion and fission. The dynamics and integrity of this tubular lysosomal network requires VCP, an AAA-ATPase that, when mutated, causes degenerative diseases of muscle, bone and neurons. We show that human VCP rescues the defects caused by loss of Drosophila VCP and overexpression of disease relevant VCP transgenes dismantles tubular lysosomes, linking tubular lysosome dysfunction to human VCP-related diseases. Finally, disruption of tubular lysosomes correlates with impaired autophagosome-lysosome fusion, increased cytoplasmic poly-ubiquitin aggregates, lipofuscin material, damaged mitochondria and impaired muscle function. We propose that VCP sustains sarcoplasmic proteostasis, in part, by controlling the integrity of a dynamic tubular lysosomal network.

  16. In vivo longitudinal study of rodent skeletal muscle atrophy using ultrasonography

    OpenAIRE

    Antonietta Mele; Adriano Fonzino; Francesco Rana; Giulia Maria Camerino; Michela De Bellis; Elena Conte; Arcangela Giustino; Diana Conte Camerino; Jean-François Desaphy

    2016-01-01

    Muscle atrophy is a widespread ill condition occurring in many diseases, which can reduce quality of life and increase morbidity and mortality. We developed a new method using non-invasive ultrasonography to measure soleus and gastrocnemius lateralis muscle atrophy in the hindlimb-unloaded rat, a well-accepted model of muscle disuse. Soleus and gastrocnemius volumes were calculated using the conventional truncated-cone method and a newly-designed sinusoidal method. For Soleus muscle, the ultr...

  17. Titanium Implant Impairment and Surrounding Muscle Cell Death Following High-Salt Diet: An In Vivo Study.

    Science.gov (United States)

    Lecocq, Mathieu; Felix, Marie-Solenne; Linares, Jean-Marc; Chaves-Jacob, Julien; Decherchi, Patrick; Dousset, Erick

    2016-01-01

    High-salt consumption has been widely described as a risk factor for cardiovascular, renal and bone functions. In the present study, the extent to which high-salt diet could influence Ti6Al4V implant surface characteristic, its adhesion to rat tibial crest, and could modify muscle cell viability of two surrounding muscles, was investigated in vivo. These parameters have also been assessed following a NMES (neuro-myoelectrostimulation) program similar to that currently used in human care following arthroplasty. After a three-week diet, a harmful effect on titanium implant surface and muscle cell viability was noted. This is probably due to salt corrosive effect on metal and then release of toxic substance around biologic tissue. Moreover, if the use of NMES with high-salt diet induced muscles damages, the latter were higher when implant was added. Unexpectedly, higher implant-to-bone adhesion was found for implanted animals receiving salt supplementation. Our in vivo study highlights the potential dangerous effect of high-salt diet in arthroplasty based on titanium prosthesis. This effect appears to be more important when high-salt diet is combined with NMES.

  18. Review of Modelling Techniques for In Vivo Muscle Force Estimation in the Lower Extremities during Strength Training.

    Science.gov (United States)

    Schellenberg, Florian; Oberhofer, Katja; Taylor, William R; Lorenzetti, Silvio

    2015-01-01

    Knowledge of the musculoskeletal loading conditions during strength training is essential for performance monitoring, injury prevention, rehabilitation, and training design. However, measuring muscle forces during exercise performance as a primary determinant of training efficacy and safety has remained challenging. In this paper we review existing computational techniques to determine muscle forces in the lower limbs during strength exercises in vivo and discuss their potential for uptake into sports training and rehabilitation. Muscle forces during exercise performance have almost exclusively been analysed using so-called forward dynamics simulations, inverse dynamics techniques, or alternative methods. Musculoskeletal models based on forward dynamics analyses have led to considerable new insights into muscular coordination, strength, and power during dynamic ballistic movement activities, resulting in, for example, improved techniques for optimal performance of the squat jump, while quasi-static inverse dynamics optimisation and EMG-driven modelling have helped to provide an understanding of low-speed exercises. The present review introduces the different computational techniques and outlines their advantages and disadvantages for the informed usage by nonexperts. With sufficient validation and widespread application, muscle force calculations during strength exercises in vivo are expected to provide biomechanically based evidence for clinicians and therapists to evaluate and improve training guidelines.

  19. Review of Modelling Techniques for In Vivo Muscle Force Estimation in the Lower Extremities during Strength Training

    Science.gov (United States)

    Schellenberg, Florian; Oberhofer, Katja; Taylor, William R.

    2015-01-01

    Background. Knowledge of the musculoskeletal loading conditions during strength training is essential for performance monitoring, injury prevention, rehabilitation, and training design. However, measuring muscle forces during exercise performance as a primary determinant of training efficacy and safety has remained challenging. Methods. In this paper we review existing computational techniques to determine muscle forces in the lower limbs during strength exercises in vivo and discuss their potential for uptake into sports training and rehabilitation. Results. Muscle forces during exercise performance have almost exclusively been analysed using so-called forward dynamics simulations, inverse dynamics techniques, or alternative methods. Musculoskeletal models based on forward dynamics analyses have led to considerable new insights into muscular coordination, strength, and power during dynamic ballistic movement activities, resulting in, for example, improved techniques for optimal performance of the squat jump, while quasi-static inverse dynamics optimisation and EMG-driven modelling have helped to provide an understanding of low-speed exercises. Conclusion. The present review introduces the different computational techniques and outlines their advantages and disadvantages for the informed usage by nonexperts. With sufficient validation and widespread application, muscle force calculations during strength exercises in vivo are expected to provide biomechanically based evidence for clinicians and therapists to evaluate and improve training guidelines. PMID:26417378

  20. Review of Modelling Techniques for In Vivo Muscle Force Estimation in the Lower Extremities during Strength Training

    Directory of Open Access Journals (Sweden)

    Florian Schellenberg

    2015-01-01

    Full Text Available Background. Knowledge of the musculoskeletal loading conditions during strength training is essential for performance monitoring, injury prevention, rehabilitation, and training design. However, measuring muscle forces during exercise performance as a primary determinant of training efficacy and safety has remained challenging. Methods. In this paper we review existing computational techniques to determine muscle forces in the lower limbs during strength exercises in vivo and discuss their potential for uptake into sports training and rehabilitation. Results. Muscle forces during exercise performance have almost exclusively been analysed using so-called forward dynamics simulations, inverse dynamics techniques, or alternative methods. Musculoskeletal models based on forward dynamics analyses have led to considerable new insights into muscular coordination, strength, and power during dynamic ballistic movement activities, resulting in, for example, improved techniques for optimal performance of the squat jump, while quasi-static inverse dynamics optimisation and EMG-driven modelling have helped to provide an understanding of low-speed exercises. Conclusion. The present review introduces the different computational techniques and outlines their advantages and disadvantages for the informed usage by nonexperts. With sufficient validation and widespread application, muscle force calculations during strength exercises in vivo are expected to provide biomechanically based evidence for clinicians and therapists to evaluate and improve training guidelines.

  1. Titanium Implant Impairment and Surrounding Muscle Cell Death Following High-Salt Diet: An In Vivo Study

    Science.gov (United States)

    Lecocq, Mathieu; Felix, Marie-Solenne; Linares, Jean-Marc; Chaves-Jacob, Julien; Decherchi, Patrick; Dousset, Erick

    2016-01-01

    Aim of the study High-salt consumption has been widely described as a risk factor for cardiovascular, renal and bone functions. In the present study, the extent to which high-salt diet could influence Ti6Al4V implant surface characteristic, its adhesion to rat tibial crest, and could modify muscle cell viability of two surrounding muscles, was investigated in vivo. These parameters have also been assessed following a NMES (neuro-myoelectrostimulation) program similar to that currently used in human care following arthroplasty. Results After a three-week diet, a harmful effect on titanium implant surface and muscle cell viability was noted. This is probably due to salt corrosive effect on metal and then release of toxic substance around biologic tissue. Moreover, if the use of NMES with high-salt diet induced muscles damages, the latter were higher when implant was added. Unexpectedly, higher implant-to-bone adhesion was found for implanted animals receiving salt supplementation. Conclusion Our in vivo study highlights the potential dangerous effect of high-salt diet in arthroplasty based on titanium prosthesis. This effect appears to be more important when high-salt diet is combined with NMES. PMID:26761710

  2. Models to study airway smooth muscle contraction in vivo, ex vivo and in vitro : Implications in understanding asthma

    NARCIS (Netherlands)

    Wright, David; Sharma, Pawan; Ryu, Min-Hyung; Risse, Paul-Andre; Ngo, Melanie; Maarsingh, Harm; Koziol-White, Cynthia; Jha, Aruni; Halayko, Andrew J.; West, Adrian R.

    Asthma is a chronic obstructive airway disease characterised by airway hyperresponsiveness (AHR) and airway wall remodelling. The effector of airway narrowing is the contraction of airway smooth muscle (ASM), yet the question of whether an inherent or acquired dysfunction in ASM contractile function

  3. The association of muscle and tendon elasticity with passive joint stiffness: In vivo measurements using ultrasound shear wave elastography.

    Science.gov (United States)

    Chino, Kentaro; Takahashi, Hideyuki

    2015-12-01

    Passive joint stiffness is associated with various tissues, including muscles, tendons, ligaments, and joint capsules. The specific elasticity of muscles or tendons can be measured using ultrasound shear wave elastography. To examine the association of muscle and tendon elasticity with passive joint stiffness, in vivo measurements of muscle and tendon elasticity were performed using ultrasound shear wave elastography. In 25 subjects, passive ankle joint stiffness was determined using the joint angle-passive torque relationship. The stiffness index of the muscle belly of the medial gastrocnemius (MG)--influenced by the muscle fascicles, its aponeuroses, and the proximal tendon--was quantified by the displacement of the muscle-tendon junction, which was visualized using B-mode ultrasonography during passive dorsiflexion. The stiffness index of the Achilles tendon--influenced by the tendon and the ligaments and joint capsule of the ankle--was similarly determined. The MG and Achilles tendon elasticity was measured using ultrasound shear wave elastography. Simple regression indicated a significant correlation between passive joint stiffness and stiffness index of the MG muscle belly (r=0.80) and Achilles tendon (r=0.60), but no correlation with elasticity of the MG (r=-0.37) or Achilles tendon (r=-0.39). Individual variations in the elasticity of either the MG or Achilles tendon are not associated with variations in passive ankle joint stiffness; however, variations in the elasticity of other tissues, including MG aponeuroses or the ligaments and joint capsule of the ankle, would be associated with the variations in joint stiffness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation

    NARCIS (Netherlands)

    Hooijman, P.E.; Paul, M.A.; Stienen, G.J.M.; Beishuizen, A.; van Hees, H.W.H.; Singhal, S.; Bashir, M.; Budak, M.T.; Morgen, J.; Barsotti, R.J.; Levine, S.; Ottenheijm, C.A.C.

    2014-01-01

    Several studies have indicated that diaphragm dysfunction develops in patients on mechanical ventilation (MV). Here, we tested the hypothesis that the contractility of sarcomeres, i.e., the smallest contractile unit in muscle, is affected in humans on MV. To this end, we compared diaphragm muscle

  5. Mechanical ventilation and sepsis induce skeletal muscle catabolism in neonatal pigs

    Science.gov (United States)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  6. Mechanical ventilation induces myokine expression and catabolism in peripheral skeletal muscle in pigs

    Science.gov (United States)

    Endotoxin (LPS)-induced sepsis increases circulating cytokines which have been associated with skeletal muscle catabolism. During critical illness, it has been postulated that muscle wasting associated with mechanical ventilation (MV) occurs due to inactivity. We hypothesize that MV and sepsis promo...

  7. Mechanical ventilation alone, and in the presence sepsis, induces peripheral skeletal muscle catabolism in neonatal pigs

    Science.gov (United States)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  8. Mechanical load induces sarcoplasmic wounding and FGF release in differentiated human skeletal muscle cultures

    Science.gov (United States)

    Clarke, M. S.; Feeback, D. L.

    1996-01-01

    The transduction mechanism (or mechanisms) responsible for converting a mechanical load into a skeletal muscle growth response are unclear. In this study we have used a mechanically active tissue culture model of differentiated human skeletal muscle cells to investigate the relationship between mechanical load, sarcolemma wounding, fibroblast growth factor release, and skeletal muscle cell growth. Using the Flexcell Strain Unit we demonstrate that as mechanical load increases, so too does the amount of sarcolemma wounding. A similar relationship was also observed between the level of mechanical load inflicted on the cells and the amount of bFGF (FGF2) released into the surrounding medium. In addition, we demonstrate that the muscle cell growth response induced by chronic mechanical loading in culture can be inhibited by the presence of an antibody capable of neutralizing the biological activity of FGF. This study provides direct evidence that mechanically induced, sarcolemma wound-mediated FGF release is an important autocrine mechanism for transducing the stimulus of mechanical load into a skeletal muscle growth response.

  9. Regulation of mTOR by mechanically induced signaling events in skeletal muscle.

    Science.gov (United States)

    Hornberger, Troy Alan; Sukhija, Kunal Balu; Chien, Shu

    2006-07-01

    Mechanical stimuli play a major role in the regulation of skeletal muscle mass, and the maintenance of muscle mass contributes significantly to disease prevention and the quality of life. Although a link between mechanical stimuli and the regulation of muscle mass has been recognized for decades, the mechanisms involved in converting mechanical information into the molecular events that control this process have not been defined. Nevertheless, significant advancements are being made in this field, and it has recently been established that signaling through a rapamycin-sensitive pathway is necessary for mechanically induced growth of skeletal muscle. Since rapamycin is a highly specific inhibitor of a protein kinase called the mammalian target of rapamycin (mTOR), many investigators have concluded that mTOR signaling is necessary for the mechanically induced growth of skeletal muscle. In this review, we have summarized the current knowledge regarding how mechanical stimuli activate mTOR signaling, discussed the newly discovered role of phospholipase D (PLD) and phosphatidic acid (PA) in this pathway, and considered the potential roles of PLD and PA in the mechanical regulation of skeletal muscle mass.

  10. Narrative review of the in vivo mechanics of the cervical spine after anterior arthrodesis as revealed by dynamic biplane radiography.

    Science.gov (United States)

    Anderst, William

    2016-01-01

    Arthrodesis is the standard of care for numerous pathologic conditions of the cervical spine and is performed over 150,000 times annually in the United States. The primary long-term concern after this surgery is adjacent segment disease (ASD), defined as new clinical symptoms adjacent to a previous fusion. The incidence of adjacent segment disease is approximately 3% per year, meaning that within 10 years of the initial surgery, approximately 25% of cervical arthrodesis patients require a second procedure to address symptomatic adjacent segment degeneration. Despite the high incidence of ASD, until recently, there was little data available to characterize in vivo adjacent segment mechanics during dynamic motion. This manuscript reviews recent advances in our knowledge of adjacent segment mechanics after cervical arthrodesis that have been facilitated by the use of dynamic biplane radiography. The primary observations from these studies are that current in vitro test paradigms often fail to replicate in vivo spine mechanics before and after arthrodesis, that intervertebral mechanics vary among cervical motion segments, and that joint arthrokinematics (i.e., the interactions between adjacent vertebrae) are superior to traditional kinematics measurements for identifying altered adjacent segment mechanics after arthrodesis. Future research challenges are identified, including improving the biofidelity of in vitro tests, determining the natural history of in vivo spine mechanics, conducting prospective longitudinal studies on adjacent segment kinematics and arthrokinematics after single and multiple-level arthrodesis, and creating subject-specific computational models to accurately estimate muscle forces and tissue loading in the spine during dynamic activities. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. [Objective assessment of the reactive effectiveness of middle frequency electromyostimulation using mechanical muscle diagnosis (myomechanography)].

    Science.gov (United States)

    Ullmann, P; Viol, M; Schleicher, W

    1989-03-01

    Using a new method of measuring passive-mechanical tonus-parameters of muscle tissue in situ ("Myomechanographie, MMG") we evaluated in 12 healthy men reactive changes of the muscle tonus immediate after one middle-frequent Electromyostimulations (EMS)-period (duration: 15 min). With the MMG was proved, that the applied EMS cause an organic effectiveness; the muscle in situ is more "elastic". This showes especially the increase of the single parameters 'elastic retraction' and 'total compressibility'. In the comparison group (n = 12) we obtained contrary after relaxly steady position (duration: 15 min.) clear reduced single parameters. The muscle is reactive less "elastic".

  12. Bone and skeletal muscle: Key players in mechanotransduction and potential overlapping mechanisms.

    Science.gov (United States)

    Goodman, Craig A; Hornberger, Troy A; Robling, Alexander G

    2015-11-01

    The development and maintenance of skeletal muscle and bone mass is critical for movement, health and issues associated with the quality of life. Skeletal muscle and bone mass are regulated by a variety of factors that include changes in mechanical loading. Moreover, bone mass is, in large part, regulated by muscle-derived mechanical forces and thus by changes in muscle mass/strength. A thorough understanding of the cellular mechanism(s) responsible for mechanotransduction in bone and skeletal muscle is essential for the development of effective exercise and pharmaceutical strategies aimed at increasing, and/or preventing the loss of, mass in these tissues. Thus, in this review we will attempt to summarize the current evidence for the major molecular mechanisms involved in mechanotransduction in skeletal muscle and bone. By examining the differences and similarities in mechanotransduction between these two tissues, it is hoped that this review will stimulate new insights and ideas for future research and promote collaboration between bone and muscle biologists.(1). Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Mechanisms regulating muscle mass during disuse atrophy and rehabilitation in humans.

    Science.gov (United States)

    Marimuthu, Kanagaraj; Murton, Andrew J; Greenhaff, Paul L

    2011-02-01

    Muscle mass loss accompanies periods of bedrest and limb immobilization in humans and requires rehabilitation exercise to effectively restore mass and function. Although recent evidence points to an early and transient rise in muscle protein breakdown contributing to this decline in muscle mass, the driving factor seems to be a reduction in muscle protein synthesis, not least in part due to the development of anabolic resistance to amino acid provision. Although the AKT signaling pathway has been identified in small animals as central to the regulation of muscle protein synthesis, several studies in humans have now demonstrated a disassociation between AKT signaling and muscle protein synthesis during feeding, exercise, and immobilization, suggesting that the mechanisms regulating protein synthesis in human skeletal muscle are more complex than initially thought (at least in non-inflammatory states). During rehabilitation, exercise-induced myogenesis may in part be responsible for the recovery of muscle mass. Rapid and sustained exercise-induced suppression of myostatin mRNA expression, that precedes any gain in muscle mass, points to this, along with other myogenic proteins, as being potential regulators of muscle regeneration during exercise rehabilitation in humans.

  14. Disturbance of smooth muscle regulatory function by Eisenia foetida toxin lysenin: insight into the mechanism of smooth muscle contraction.

    Science.gov (United States)

    Czuryło, Edward A; Kulikova, Natalia; Sobota, Andrzej

    2008-05-01

    Lysenin, a toxin present in the coelomic fluid of the earthworm Eisenia foetida, is known to cause a long-lasting contraction of rat aorta smooth muscle strips. We addressed the mechanisms underlying its action on smooth muscle cells and present the first report demonstrating a completely new property of lysenin unrelated to its basic sphingomyelin-binding ability. Here we report lysenin enhancement effect on smooth muscle actomyosin ATPase activity and the ability of networking the actin filaments. The maximum enhancement of the ATPase activity of actomyosin at 120 mM KCl was observed at a molar ratio of lysenin to actin of about 1:10(5), while at 70 mM KCl at the ratio of about 1:10(6). The effect of lysenin became most pronounced only when both smooth muscle regulatory proteins, tropomyosin and caldesmon, were present. Co-sedimentation experiments indicated that lysenin did not displace neither tropomyosin nor caldesmon from the thin filament. Thus, the lysenin-dependent abolishment of the inhibitory effect of caldesmon on the ATPase activity was related rather to the modification of the filament structure. The ability of the toxin to exert its stimulatory effect at extremely low concentrations (as low as one molecule of lysenin per 10(6) actin molecules) may result from the long-range cooperative transitions in the entire thin filament with an involvement of smooth muscle tropomyosin, while the role of caldesmon may be limited exclusively to the inhibition of ATPase activity.

  15. Muscle Regeneration with Intermuscular Adipose Tissue (IMAT Accumulation Is Modulated by Mechanical Constraints.

    Directory of Open Access Journals (Sweden)

    Allan F Pagano

    Full Text Available Sports trauma are able to induce muscle injury with fibrosis and accumulation of intermuscular adipose tissue (IMAT, which affect muscle function. This study was designed to investigate whether hypoactivity would influence IMAT accumulation in regenerating mouse skeletal muscle using the glycerol model of muscle regeneration. The animals were immediately hindlimb unloaded for 21 days after glycerol injection into the tibialis anterior (TA muscle. Muscle fiber and adipocyte cross-sectional area (CSA and IMAT accumulation were determined by histomorphometric analysis. Adipogenesis during regenerative processes was examined using RT-qPCR and Western blot quantification. Twenty-one days of hindlimb unloading resulted in decreases of 38% and 50.6% in the muscle weight/body weight ratio and CSA, respectively, in soleus muscle. Glycerol injection into TA induced IMAT accumulation, reaching 3% of control normal-loading muscle area. This IMAT accumulation was largely inhibited in unloading conditions (0.09% and concomitant with a marked reduction in perilipin and FABP4 protein content, two key markers of mature adipocytes. Induction of PPARγ and C/EBPα mRNA, two markers of adipogenesis, was also decreased. Furthermore, the protein expression of PDGFRα, a cell surface marker of fibro/adipogenic progenitors, was much lower in regenerating TA from the unloaded group. Exposure of regenerating muscle to hypoactivity severely reduces IMAT development and accumulation. These results provide new insight into the mechanisms regulating IMAT development in skeletal muscle and highlight the importance of taking into account the level of mechanical constraint imposed on skeletal muscle during the regeneration processes.

  16. The mechanisms of muscle hypertrophy and their application to resistance training.

    Science.gov (United States)

    Schoenfeld, Brad J

    2010-10-01

    The quest to increase lean body mass is widely pursued by those who lift weights. Research is lacking, however, as to the best approach for maximizing exercise-induced muscle growth. Bodybuilders generally train with moderate loads and fairly short rest intervals that induce high amounts of metabolic stress. Powerlifters, on the other hand, routinely train with high-intensity loads and lengthy rest periods between sets. Although both groups are known to display impressive muscularity, it is not clear which method is superior for hypertrophic gains. It has been shown that many factors mediate the hypertrophic process and that mechanical tension, muscle damage, and metabolic stress all can play a role in exercise-induced muscle growth. Therefore, the purpose of this paper is twofold: (a) to extensively review the literature as to the mechanisms of muscle hypertrophy and their application to exercise training and (b) to draw conclusions from the research as to the optimal protocol for maximizing muscle growth.

  17. Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle

    Science.gov (United States)

    St Pierre, B. A.; Kasper, C. E.; Lindsey, A. M.

    1992-01-01

    Fatigue is a common adverse effect of cancer and its therapy. However, the specific mechanisms underlying cancer fatigue are unclear. One physiologic mechanism may involve changes in skeletal muscle protein stores or metabolite concentration. A reduction in skeletal muscle protein stores may result from endogenous tumor necrosis factor (TNF) or from TNF administered as antineoplastic therapy. This muscle wasting would require patients to exert an unusually high amount of effort to generate adequate contractile force during exercise performance or during extended periods of sitting or standing. This additional effort could result in the onset of fatigue. Additionally, cancer fatigue may develop or become exacerbated during exercise as a consequence of changes in the concentration of skeletal muscle metabolites. These biochemical alterations may interfere with force that is produced by the muscle contractile proteins. These physiologic changes may play a role in the decision to include exercise in the rehabilitation plans of patients with cancer. They also may affect ideas about fatigue.

  18. A new anti-tumor strategy based on in vivo tumstatin overexpression after plasmid electrotransfer in muscle

    Energy Technology Data Exchange (ETDEWEB)

    Thevenard, Jessica, E-mail: jessica.thevenard@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); Ramont, Laurent, E-mail: lramont@chu-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Mir, Lluis M., E-mail: luis.mir@igr.fr [CNRS, UMR 8203, Institut Gustave Roussy, 114, Rue Edouard Vaillant, F-94805 Villejuif Cedex (France); Université Paris-Sud, UMR 8203, Institut Gustave Roussy, 114, Rue Edouard Vaillant, F-94405 Orsay Cedex (France); Dupont-Deshorgue, Aurélie, E-mail: aurelie.dupont@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); Maquart, François-Xavier, E-mail: fmaquart@chu-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Monboisse, Jean-Claude, E-mail: jc.monboisse@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Brassart-Pasco, Sylvie, E-mail: sylvie.brassart-pasco@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France)

    2013-03-22

    Highlights: ► A new therapeutic strategy based on tumstatin in vivo overexpression is proposed. ► pVAX1©–tumstatin electrotransfer in muscle mediates protein expression in muscle. ► A substantial expression of tumstatin is detected in the serum of electrotransfected mice. ► Tumstatin overexpression decreases tumor growth and increases mouse survival. -- Abstract: The NC1 domains from the different α(IV) collagen chains were found to exert anti-tumorigenic and/or anti-angiogenic activities. A limitation to the therapeutic use of these matrikines is the large amount of purified recombinant proteins, in the milligram range in mice that should be administered daily throughout the experimental procedures. In the current study, we developed a new therapeutic approach based on tumstatin (NC1α3(IV)) overexpression in vivo in a mouse melanoma model. Gene electrotransfer of naked plasmid DNA (pDNA) is particularly attractive because of its simplicity, its lack of immune responsiveness and its safety. The pDNA electrotransfer in muscle mediates a substantial gene expression that lasts several months. A pVAX1© vector containing the tumstatin cDNA was injected into the legs of C57BL/6 mice and submitted to electrotranfer. Sera were collected at different times and tumstatin was quantified by ELISA. Tumstatin secretion reached a plateau at day 21 with an expression level of 12 μg/mL. For testing the effects of tumstatin expression on tumor growth in vivo, B16F1 melanoma cells were subcutaneously injected in mice 7 days after empty pVAX1© (Mock) or pVAX1©–tumstatin electrotransfer. Tumstatin expression triggered a large decrease in tumor growth and an increase in mouse survival. This new therapeutic approach seems promising to inhibit tumor progression in vivo.

  19. Mechanical output from individual muscles during explosive leg extensions : The role of biarticular muscles

    NARCIS (Netherlands)

    Jacobs, Ron; Bobbert, Maarten F.; Van Ingen Schenau, Gerrit Jan

    The main result of this study is that biarticular leg muscles contribute significantly to the work done at joints, due to transfer of power during explosive leg extensions. In particular, a net power transfer was shown from hip to knee joint during jumping and sprinting. Seven elite athletes

  20. Transcriptional adaptations following exercise in Thoroughbred horse skeletal muscle highlights molecular mechanisms that lead to muscle hypertrophy

    Directory of Open Access Journals (Sweden)

    Park Stephen DE

    2009-12-01

    . These findings suggest that protein synthesis, mechanosensation and muscle remodeling contribute to skeletal muscle adaptation towards improved integrity and hypertrophy. Conclusions This is the first study to characterize global mRNA expression profiles in equine skeletal muscle using an equine-specific microarray platform. Here we reveal novel genes and mechanisms that are temporally expressed following exercise providing new knowledge about the early and late molecular responses to exercise in the equine skeletal muscle transcriptome.

  1. Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, S A; Hansen, B F

    1988-01-01

    increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased (mean +/- SE) from 34.9 +/- 1.2 mumol.g-1.h-1 at 0 h to 7.5 +/- 0.7 after 7 h of perfusion. During...... the perfusion muscle glycogen synthase activity decreased and free intracellular glucose and glucose 6-phosphate increased indicating that glucose disposal was impaired. However, glucose transport as measured by the uptake of 3-O-[14C]methyl-D-glucose was also markedly decreased after 5 and 7 h of perfusion...

  2. An integrated muscle mechanic-fluid dynamic model of lamprey swimming

    Science.gov (United States)

    Hsu, Chia-Yu; Tytell, Eric; Fauci, Lisa

    2009-11-01

    In an effort towards a detailed understanding of the generation and control of vertebrate locomotion, including the role of the CPG and its interactions with reflexive feedback, muscle mechanics, and external fluid dynamics, we study a simple vertebrate, the lamprey. Lamprey body undulations are a result of a wave of neural activation that passes from head to tail, causing a wave of muscle activation. These active forces are mediated by passive structural forces. We present recent results from a model that fully couples a viscous, incompressible fluid with nonlinear muscle mechanics. We measure the dependence of the phase lag between activation wave and mechanical wave as a function of model parameters, such as body stiffness and muscle strength. Simulation results are compared to experiments utilizing both real and synthetic lamprey.

  3. A Novel Approach to Measuring Muscle Mechanics in Vehicle Collision Conditions.

    Science.gov (United States)

    Krašna, Simon; Đorđević, Srđan; Hribernik, Marija; Trajkovski, Ana

    2017-06-14

    The aim of the study was to evaluate a novel approach to measuring neck muscle load and activity in vehicle collision conditions. A series of sled tests were performed on 10 healthy volunteers at three severity levels to simulate low-severity frontal impacts. Electrical activity-electromyography (EMG)-and muscle mechanical tension was measured bilaterally on the upper trapezius. A novel mechanical contraction (MC) sensor was used to measure the tension on the muscle surface. The neck extensor loads were estimated based on the inverse dynamics approach. The results showed strong linear correlation (Pearson's coefficient = 0.821) between the estimated neck muscle load and the muscle tension measured with the MC sensor. The peak of the estimated neck muscle force delayed 0.2 ± 30.6 ms on average vs. the peak MC sensor signal compared to the average delay of 61.8 ± 37.4 ms vs. the peak EMG signal. The observed differences in EMG and MC sensor collected signals indicate that the MC sensor offers an additional insight into the analysis of the neck muscle load and activity in impact conditions. This approach enables a more detailed assessment of the muscle-tendon complex load of a vehicle occupant in pre-impact and impact conditions.

  4. Interleukin-10 limits intense acute swimming-induced muscle mechanical hyperalgesia in mice.

    Science.gov (United States)

    Borghi, Sergio M; Pinho-Ribeiro, Felipe A; Zarpelon, Ana C; Cunha, Thiago M; Alves-Filho, Jose C; Ferreira, Sergio H; Cunha, Fernando Q; Casagrande, Rubia; Verri, Waldiceu A

    2015-04-20

    What is the central question of this study? This study investigated the role of the endogenous anti-inflammatory cytokine interleukin-10 in intense acute swimming-induced muscle mechanical hyperalgesia in mice. What is the main finding and its importance? Endogenous interleukin-10 has a key role in limiting exercise-induced muscle pain in a model presenting similarities to delayed-onset muscle soreness in mice. Interleukin-10 reduced muscle pain by diminishing leucocyte recruitment, hyperalgesic cytokine production, oxidative stress and myocyte damage. Interleukin-10 (IL-10) is an antihyperalgesic cytokine. In this study, IL-10-deficient (IL-10(-/-) ) mice were used to investigate the role of endogenous IL-10 in intense acute swimming-induced muscle mechanical hyperalgesia, which presents similarities with delayed-onset muscle soreness. An intense acute swimming session of 1 or 2 h induced significant muscle mechanical hyperalgesia in a time-dependent manner in wild-type mice compared with the sham group 24 h after the session, which was further increased in IL-10(-/-) mice (P ˂ 0.05). Intraperitoneal treatment of wild-type mice with IL-10 (1-10 ng) reduced muscle mechanical hyperalgesia in a dose-dependent manner and reversed the enhanced muscle hyperalgesia in IL-10(-/-) mice (P ˂ 0.05). The 2 h swimming session induced increases in tumour necrosis factor-α, interleukin-1β and IL-10 production in the soleus muscle. However, tumour necrosis factor-α and interleukin-1β production in the soleus muscle were even higher in IL-10(-/-) mice between 2 and 6 h after the stimulus (P ˂ 0.05). There was no statistical difference in the levels of the antihyperalgesic cytokines interleukin-4, interleukin-5, interleukin-13 and transforming growth factor-β between wild-type and IL-10(-/-) mice (P ˃ 0.05). Interleukin-10 deficiency also resulted in increased myeloperoxidase activity, greater depletion of reduced glutathione levels, increased superoxide anion

  5. A mini-overview of single muscle fibre mechanics: the effects of age, inactivity and exercise in animals and humans.

    Science.gov (United States)

    Jee, Hyunseok; Kim, Jong-Hee

    2017-09-05

    Many basic movements of living organisms are dependent on muscle function. Muscle function allows for the coordination and harmonious integrity of movement that is necessary for various biological processes. Gross and fine motor skills are both regulated at the micro-level (single muscle fibre level), controlled by neuronal regulation, and it is therefore important to understand muscle function at both micro- and macro-levels to understand the overall movement of living organisms. Single muscle mechanics and the cellular environment of muscles fundamentally allow for the harmonious movement of our bodies. Indeed, a clear understanding of the functionality of muscle at the micro-level is indispensable for explaining muscular function at the macro-(whole gross muscle) level. By investigating single muscle fibre mechanics, we can also learn how other factors such Ca2+ kinetics, enzyme activity and contractile proteins can contribute to muscle mechanics at the micro- and macro-levels. Further, we can also describe how aging affects the capacity of skeletal muscle cells, as well as how exercise can prevent aging-based sarcopenia and frailty. The purpose of this review is to introduce and summarise the current knowledge of single muscle fibre mechanics in light of aging and inactivity. We then describe how exercise mitigates negative muscle adaptations that occur under those circumstances. In addition, single muscle fibre mechanics in both animal and human models are discussed.

  6. Mechanical and histological characterization of the abdominal muscle. A previous step to modelling hernia surgery.

    Science.gov (United States)

    Hernández, B; Peña, E; Pascual, G; Rodríguez, M; Calvo, B; Doblaré, M; Bellón, J M

    2011-04-01

    The aims of this study are to experimentally characterize the passive elastic behaviour of the rabbit abdominal wall and to develop a mechanical constitutive law which accurately reproduces the obtained experimental results. For this purpose, tissue samples from New Zealand White rabbits 2150±50 (g) were mechanically tested in vitro. Mechanical tests, consisting of uniaxial loading on tissue samples oriented along the craneo-caudal and the perpendicular directions, respectively, revealed the anisotropic non-linear mechanical behaviour of the abdominal tissues. Experiments were performed considering the composite muscle (including external oblique-EO, internal oblique-IO and transverse abdominis-TA muscle layers), as well as separated muscle layers (i.e., external oblique, and the bilayer formed by internal oblique and transverse abdominis). Both the EO muscle layer and the IO-TA bilayer demonstrated a stiffer behaviour along the transversal direction to muscle fibres than along the longitudinal one. The fibre arrangement was measured by means of a histological study which confirmed that collagen fibres are mainly responsible for the passive mechanical strength and stiffness. Furthermore, the degree of anisotropy of the abdominal composite muscle turned out to be less pronounced than those obtained while studying the EO and IO-TA separately. Moreover, a phenomenological constitutive law was used to capture the measured experimental curves. A Levenberg-Marquardt optimization algorithm was used to fit the model constants to reproduce the experimental curves. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Amphiphilic block copolymers promote gene delivery in vivo to pathological skeletal muscles.

    Science.gov (United States)

    Richard, Peggy; Bossard, Florian; Desigaux, Lea; Lanctin, Caroline; Bello-Roufai, Mahajoub; Pitard, Bruno

    2005-11-01

    We reported that amphiphilic block copolymers hold promise as nonviral vectors for the delivery of plasmid DNA, ranging from 4.7 to 6.2 kb, to healthy muscle for the production of local or secreted proteins. To evaluate the efficiency of these vectors to deliver large plasmid DNA molecules to pathological muscles, plasmid DNAs of various lengths were complexed with Lutrol or poloxamine 304 and injected intramuscularly into dystrophic muscles. Lutrol-DNA and poloxamine 304-DNA complexes promoted gene transfer into muscles of the naturally occurring mouse model for DMD (mdx) in a dose- and plasmid DNA size-dependent manner. For small plasmid DNAs encoding reporter genes, this improvement over naked DNA was smaller in mdx than in the wild-type control strain. By contrast, Lutrol enabled us to deliver the large plasmid (16.1 kb) encoding the rod-deleted dystrophin in mdx mouse muscle, whereas the same amount of naked DNA did not lead to dystrophin expression, under the same experimental conditions. Lutrol-treated mdx mice showed the production of dystrophin in large numbers of muscle fibers. More importantly, we also found that expressing dystrophin with Lutrol led to restoration of the dystrophin-associated protein complex. Thus, we conclude that block copolymers constitute a novel class of vectors for the delivery of large plasmid DNA not only to healthy muscles but also to pathological muscle tissues.

  8. Clones of ectopic stem cells in the regeneration of muscle defects in vivo.

    Directory of Open Access Journals (Sweden)

    Rujing Yang

    2010-10-01

    Full Text Available Little is known about whether clones of ectopic, non-muscle stem cells contribute to muscle regeneration. Stem/progenitor cells that are isolated for experimental research or therapeutics are typically heterogeneous. Non-myogenic lineages in a heterogeneous population conceptually may compromise tissue repair. In this study, we discovered that clones of mononucleated stem cells of human tooth pulp fused into multinucleated myotubes that robustly expressed myosin heavy chain in vitro with or without co-culture with mouse skeletal myoblasts (C2C12 cells. Cloned cells were sustainably Oct4+, Nanog+ and Stro1+. The fusion indices of myogenic clones were approximately 16-17 folds greater than their parent, heterogeneous stem cells. Upon infusion into cardio-toxin induced tibialis anterior muscle defects, undifferentiated clonal progenies not only engrafted and colonized host muscle, but also expressed human dystrophin and myosin heavy chain more efficaciously than their parent heterogeneous stem cell populations. Strikingly, clonal progenies yielded ∼9 times more human myosin heavy chain mRNA in regenerating muscles than those infused with their parent, heterogeneous stem cells. The number of human dystrophin positive cells in regenerating muscles infused with clonal progenies was more than ∼3 times greater than muscles infused with heterogeneous stem cells from which clonal progenies were derived. These findings suggest the therapeutic potential of ectopic myogenic clones in muscle regeneration.

  9. Passive mechanical features of single fibers from human muscle biopsies – effects of storage

    Directory of Open Access Journals (Sweden)

    Runesson Eva

    2008-06-01

    Full Text Available Abstract Background The purpose of this study was to investigate the effect of storage of human muscle biopsies on passive mechanical properties. Methods Stress-strain analysis accompanied by laser diffraction assisted sarcomere length measurement was performed on single muscle fibres from fresh samples and compared with single fibres from stored samples (-20°C, 4 weeks with the same origin as the corresponding fresh sample. Basic morphological analysis, including cross sectional area (CSA measurement, fibre diameter measurement, fibre occupancy calculation and overall morphology evaluation was done. Results Statistical analysis of tangent values in stress-strain curves, corresponding to the elastic modulus of single muscle fibres, did not differ when comparing fresh and stored samples from the same type of muscle. Regardless of the preparation procedure, no significant differences were found, neither in fibre diameter nor the relation between muscle fibres and extra-cellular matrix measured under light microscopy. Conclusion We conclude that muscle fibre structure and mechanics are relatively insensitive to the storage procedures used and that the different preparations are interchangeable without affecting passive mechanical properties. This provides a mobility of the method when harvesting muscle biopsies away from the laboratory.

  10. In vivo quantification of spatially-varying mechanical properties in developing tissues

    Science.gov (United States)

    Serwane, Friedhelm; Mongera, Alessandro; Rowghanian, Payam; Kealhofer, David A.; Lucio, Adam A.; Hockenbery, Zachary M.; Campàs, Otger

    2017-01-01

    It is generally believed that the mechanical properties of the cellular microenvironment and their spatiotemporal variations play a central role in sculpting embryonic tissues, maintaining organ architecture and controlling cell behavior, including cell differentiation. However, no direct in vivo and in situ measurement of mechanical properties within developing 3D tissues and organs has been performed yet. Here we introduce a technique that employs biocompatible ferrofluid microdroplets as local mechanical actuators and allows quantitative spatiotemporal measurements of mechanical properties in vivo. Using this technique, we show that vertebrate body elongation entails spatially-varying tissue mechanics along the anteroposterior axis. Specifically, we find that the zebrafish tailbud is viscoelastic (elastic below a few seconds and fluid after just one minute) and displays decreasing stiffness and increasing fluidity towards its posterior elongating region. This method opens new avenues to study mechanobiology in vivo, both in embryogenesis and in disease processes, including cancer. PMID:27918540

  11. Gestational Undernourishment Modifies the Composition of Skeletal Muscle Transverse Tubule Membranes and the Mechanical Properties of Muscles in Newborn Rats

    Directory of Open Access Journals (Sweden)

    Ricardo Tonathiu Ramírez-Oseguera

    2013-10-01

    Full Text Available Backgroud/Aims: Skeletal muscle (SM constitutes more than 40% of the body weight in adulthood. Transports dietary glucose mainly through the insulin-dependent glucose transporter (Glut-4 located in the Transverse tubule membrane system (TT. The TT development ends shortly after birth. The TT membrane hosts the proteins involved in excitation-contraction coupling and glucose uptake. Glycaemic regulation through movement is a key function of fully developed skeletal muscle. In this study, we aimed to characterize the effect of gestational undernourishment (GUN in rats GLUT-4 expression and on the protein/lipid content of the TT membranes. We also examined the effect of GUN on the mechanical properties of muscles as an indication of the metabolic condition of the SM at birth. Methods: Isolated TT membrane from SM of GUN rats were used to study lipid/protein content and protein stability by differential scanning calorimetry. The effect of GUN on the SM mechanical properties was determined in isolated Extensor Digitorum Longus (EDL muscle. Results: We demonstrate that compared to control, GUN in the new-born produces; i decreases body weight; ii diminution in SM mass; iii decreases the formation of TT membranes; iv expresses TT membrane proteins with higher thermal stability. The TT membrane expression of GLUT-4 in GUN offspring was twice that of controls. The isolated EDL of GUN offspring was 20% stronger as measured by contractile force and more resistant to fatigue relative to controls. Conclusion; These results provide the first evidence of adaptive changes of the SM in new-borns exposed to severe gestational food restriction. The effects of GUN on muscle at birth are the first step toward detrimental SM metabolic function, contributing to the physiopathology of metabolic diseases in adulthood.

  12. Evidence supporting extraocular muscle pulleys: refuting the platygean view of extraocular muscle mechanics.

    Science.gov (United States)

    Demer, Joseph L

    2006-01-01

    Late in the 20th century, it was recognized that connective tissue structures in the orbit influence the paths of the extraocular muscles and constitute their functional origins. Targeted investigations of these connective tissue "pulleys" led to the formulation of the active pulley hypothesis, which proposes that pulling directions of the rectus extraocular muscles are actively controlled via connective tissues. This review rebuts a series of criticisms of the active pulley hypothesis published by Jampel, and Jampel and Shi, in which these authors have disputed the existence and function of the pulleys. This article reviews published evidence for the existence of orbital pulleys, the active pulley hypothesis, and physiological tests of the active pulley hypothesis. Magnetic resonance imaging in a living subject and histological examination of a human cadaver directly illustrate the relationship of pulleys to extraocular muscles. Strong scientific evidence is cited that supports the existence of orbital pulleys and their role in ocular motility. The criticisms of the hypothesis have ignored mathematical truisms and strong scientific evidence. Actively control led orbital pulleys play a fundamental role in ocular motility. Pulleys profoundly influence the neural commands required to control eye movements and binocular alignment. Familiarity with the anatomy and physiology of the pulleys is requisite for a rational approach to diagnosing and treating strabismus using emerging methods. Conversely, approaches that deny or ignore the pulleys risk the sorts of errors that arise in geography and navigation from incorrect assumptions such as those of a flat ("platygean") earth.

  13. Three-dimensional appearance of the lips muscles with three-dimensional isotropic MRI: in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Raphael; Reychler, H. [Universite Catholique de Louvain, Department of Oral and Maxillofacial Surgery, Cliniques Universitaires Saint Luc, Brussels (Belgium); Liu, Y.; Xu, T.M. [Peking University School and Hospital of Stomatology, Department of Orthodontics, Beijing (China); Duprez, T. [Universite Catholique de Louvain, Department of Radiology, Cliniques Universitaires Saint Luc, Brussels (Belgium)

    2009-06-15

    Our knowledge of facial muscles is based primarily on atlases and cadaveric studies. This study describes a non-invasive in vivo method (3D MRI) for segmenting and reconstructing facial muscles in a three-dimensional fashion. Three-dimensional (3D), T1-weighted, 3 Tesla, isotropic MRI was applied to a subject. One observer performed semi-automatic segmentation using the Editor module from the 3D Slicer software (Harvard Medical School, Boston, MA, USA), version 3.2. We were able to successfully outline and three-dimensionally reconstruct the following facial muscles: pars labialis orbicularis oris, m. levatro labii superioris alaeque nasi, m. levator labii superioris, m. zygomaticus major and minor, m. depressor anguli oris, m. depressor labii inferioris, m. mentalis, m. buccinator, and m. orbicularis oculi. 3D reconstruction of the lip muscles should be taken into consideration in order to improve the accuracy and individualization of existing 3D facial soft tissue models. More studies are needed to further develop efficient methods for segmentation in this field. (orig.)

  14. Gene gun bombardment-mediated expression and translocation of EGFP-tagged GLUT4 in skeletal muscle fibres in vivo

    DEFF Research Database (Denmark)

    Lauritzen, Hans P M M; Reynet, Christine; Schjerling, Peter

    2002-01-01

    Cellular protein trafficking has been studied to date only in vitro or with techniques that are invasive and have a low time resolution. To establish a gentle method for analysis of glucose transporter-4 (GLUT4) trafficking in vivo in fully differentiated rat skeletal muscle fibres we combined......-old rats and peaked around 1 week after transfection. The gene gun was used subsequently with a plasmid coding for EGFP linked to the C-terminus of GLUT4 (GLUT4-EGFP). Rats were anaesthetised 5 days after transfection and insulin given i.v. with or without accompanying electrical hindleg muscle stimulation....... After stimulation, the hindlegs were fixed by perfusion. GLUT4-EGFP-positive FDB fibres were isolated and analysed by confocal microscopy. The intracellular distribution of GLUT4-EGFP under basal conditions as well as after translocation to the plasma membrane in response to insulin, contractions...

  15. Human brain activity associated with painful mechanical stimulation to muscle and bone.

    Science.gov (United States)

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-08-01

    The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

  16. In vivo and in vitro evidence that in oldest-old humans intrinsic upper- and lower-limb skeletal muscle function is unaffected by ageing and disuse

    Science.gov (United States)

    Venturelli, M.; Saggin, P.; Muti, E.; Naro, F.; Cancellara, L.; Toniolo, L.; Tarperi, C.; Calabria, E.; Richardson, R.S.; Reggiani, C.; Schena, F.

    2015-01-01

    Aim To parse out the impact of advanced ageing and disuse on skeletal muscle function, we utilized both in vivo and in vitro techniques to comprehensively assess upper- and lower-limb muscle contractile properties in 8 young (YG; 25±6yrs) and 8 oldest-old mobile (OM; 87±5yrs) and 8 immobile (OI; 88±4yrs) women. Methods In vivo, maximal voluntary contraction (MVC), electrically evoked resting twitch force (RT), and physiological cross sectional area (PCSA) of the quadriceps and elbow flexors was assessed. Muscle biopsies of the vastus lateralis and biceps brachii facilitated the in vitro assessment of single fibre specific tension (Po). Results In vivo, compared to the young, both the OM and OI exhibited a more pronounced loss of MVC in the lower-limb (OM (−60%) and OI (−75%)) than the upper-limb (OM=−51%; OI=−47%). Taking into account the reduction in muscle PCSA (OM=−10%; OI=−18%), only evident in the lower-limb, by calculating voluntary muscle specific force, the lower-limb of the OI (−40%) was more compromised than the OM (−13%). However, in vivo, RT in both upper- and lower-limbs (~9.8 N·m·cm−2) and Po (~123 mN·mm−2), assessed in vitro, implies preserved intrinsic contractile function in all muscles of the oldest-old and were well correlated (r=0.81). Conclusion These findings suggest that in the oldest-old neither advanced ageing nor disuse, per se, impact intrinsic skeletal muscle function, as assessed in vitro. However, in vivo, muscle function is attenuated by age and exacerbated by disuse, implicating factors other than skeletal muscle, such as neuromuscular control, in this diminution of function. PMID:25965867

  17. In vivo and in vitro evidence that intrinsic upper- and lower-limb skeletal muscle function is unaffected by ageing and disuse in oldest-old humans.

    Science.gov (United States)

    Venturelli, M; Saggin, P; Muti, E; Naro, F; Cancellara, L; Toniolo, L; Tarperi, C; Calabria, E; Richardson, R S; Reggiani, C; Schena, F

    2015-09-01

    To parse out the impact of advanced ageing and disuse on skeletal muscle function, we utilized both in vivo and in vitro techniques to comprehensively assess upper- and lower-limb muscle contractile properties in 8 young (YG; 25 ± 6 years) and 8 oldest-old mobile (OM; 87 ± 5 years) and 8 immobile (OI; 88 ± 4 years) women. In vivo, maximal voluntary contraction (MVC), electrically evoked resting twitch force (RT), and physiological cross-sectional area (PCSA) of the quadriceps and elbow flexors were assessed. Muscle biopsies of the vastus lateralis and biceps brachii facilitated the in vitro assessment of single fibre-specific tension (Po). In vivo, compared to the young, both the OM and OI exhibited a more pronounced loss of MVC in the lower limb [OM (-60%) and OI (-75%)] than the upper limb (OM = -51%; OI = -47%). Taking into account the reduction in muscle PCSA (OM = -10%; OI = -18%), only evident in the lower limb, by calculating voluntary muscle-specific force, the lower limb of the OI (-40%) was more compromised than the OM (-13%). However, in vivo, RT in both upper and lower limbs (approx. 9.8 N m cm(-2) ) and Po (approx. 123 mN mm(-2) ), assessed in vitro, implies preserved intrinsic contractile function in all muscles of the oldest-old and were well correlated (r = 0.81). These findings suggest that in the oldest-old, neither advanced ageing nor disuse, per se, impacts intrinsic skeletal muscle function, as assessed in vitro. However, in vivo, muscle function is attenuated by age and exacerbated by disuse, implicating factors other than skeletal muscle, such as neuromuscular control, in this diminution of function. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  18. Disuse of rat muscle in vivo reduces protein kinase C activity controlling the sarcolemma chloride conductance

    Science.gov (United States)

    Pierno, Sabata; Desaphy, Jean-François; Liantonio, Antonella; De Luca, Annamaria; Zarrilli, Antonia; Mastrofrancesco, Lisa; Procino, Giuseppe; Valenti, Giovanna; Conte Camerino, Diana

    2007-01-01

    Muscle disuse produced by hindlimb unloading (HU) induces severe atrophy and slow-to-fast fibre type transition of the slow-twitch soleus muscle (Sol). After 2 weeks HU, the resting ClC-1 chloride conductance (gCl) of sarcolemma, which controls muscle excitability, increases in Sol toward a value typical of the fast-twitch EDL muscle. After 3 days of HU, the gCl increases as well before initiation of fibre type transition. Since ClC-1 channels are acutely silenced by PKC-dependent phosphorylation, we studied the modulation of gCl by PKC and serine–threonine phosphatase in Sol during HU, using a number of pharmacological tools. We show that a fraction of ClC-1 channels of control Sol are maintained in an inactive state by PKC basal activity, which contributes to the lower gCl in control Sol compared to EDL. After 14 days of HU, PKC/phosphatase manipulation produces effects on Sol gCl that corroborate the partial slow-to-fast transition. After 3 days of HU, the early increase of gCl in Sol is entirely attributable to a reduction of PKC activity and/or activation of phosphatase, maintaining ClC-1 channels in a fully active state. Accordingly, we found that HU reduces expression of PKCα, ɛ, and θ isoenzymes in Sol and EDL muscles and reduces total PKC activity. Moreover, we show that the rheobase current is increased in Sol muscle fibres as soon as after 3 days of HU, most probably in relation to the increased gCl. In conclusion, Sol muscle disuse is characterized by a rapid reduction of PKC activity, which reduces muscle excitability and is likely to contribute to disuse-induced muscle impairment. PMID:17855757

  19. Time-lapse analysis and mathematical characterization elucidate novel mechanisms underlying muscle morphogenesis.

    Directory of Open Access Journals (Sweden)

    Chelsi J Snow

    2008-10-01

    Full Text Available Skeletal muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction (MTJ. In vertebrates, a great deal is known about muscle specification as well as how somitic cells, as a cohort, generate the early myotome. However, the cellular mechanisms that generate long muscle fibers from short cells and the molecular factors that limit elongation are unknown. We show that zebrafish fast muscle fiber morphogenesis consists of three discrete phases: short precursor cells, intercalation/elongation, and boundary capture/myotube formation. In the first phase, cells exhibit randomly directed protrusive activity. The second phase, intercalation/elongation, proceeds via a two-step process: protrusion extension and filling. This repetition of protrusion extension and filling continues until both the anterior and posterior ends of the muscle fiber reach the MTJ. Finally, both ends of the muscle fiber anchor to the MTJ (boundary capture and undergo further morphogenetic changes as they adopt the stereotypical, cylindrical shape of myotubes. We find that the basement membrane protein laminin is required for efficient elongation, proper fiber orientation, and boundary capture. These early muscle defects in the absence of either lamininbeta1 or laminingamma1 contrast with later dystrophic phenotypes in lamininalpha2 mutant embryos, indicating discrete roles for different laminin chains during early muscle development. Surprisingly, genetic mosaic analysis suggests that boundary capture is a cell-autonomous phenomenon. Taken together, our results define three phases of muscle fiber morphogenesis and show that the critical second phase of elongation proceeds by a repetitive process of protrusion extension and protrusion filling. Furthermore, we show that laminin is a novel and critical molecular cue mediating fiber orientation and limiting muscle cell length.

  20. A mechanical actuator driven electrochemically by artificial molecular muscles.

    Science.gov (United States)

    Juluri, Bala Krishna; Kumar, Ajeet S; Liu, Yi; Ye, Tao; Yang, Ying-Wei; Flood, Amar H; Fang, Lei; Stoddart, J Fraser; Weiss, Paul S; Huang, Tony Jun

    2009-02-24

    A microcantilever, coated with a monolayer of redox-controllable, bistable [3]rotaxane molecules (artificial molecular muscles), undergoes reversible deflections when subjected to alternating oxidizing and reducing electrochemical potentials. The microcantilever devices were prepared by precoating one surface with a gold film and allowing the palindromic [3]rotaxane molecules to adsorb selectively onto one side of the microcantilevers, utilizing thiol-gold chemistry. An electrochemical cell was employed in the experiments, and deflections were monitored both as a function of (i) the scan rate (+0.4 V) and reducing (cycles. The microcantilevers deflect in one direction following oxidation and in the opposite direction upon reduction. The approximately 550 nm deflections were calculated to be commensurate with forces per molecule of approximately 650 pN. The thermal relaxation that characterizes the device's deflection is consistent with the double bistability associated with the palindromic [3]rotaxane and reflects a metastable contracted state. The use of the cooperative forces generated by these self-assembled, nanometer-scale artificial molecular muscles that are electrically wired to an external power supply constitutes a seminal step toward molecular-machine-based nanoelectromechanical systems (NEMS).

  1. Muscle coordination is key to the power output and mechanical efficiency of limb movements.

    Science.gov (United States)

    Wakeling, J M; Blake, O M; Chan, H K

    2010-02-01

    The purpose of this study was to determine which features of muscle mechanics and muscle coordination affect the power output from a limb during locomotion. Eight subjects were tested while cycling at maximum exertion for 25 min on a stationary dynamometer. Cadence and load were varied to span a range of power outputs and myoelectric activity was measured from 10 muscles in the leg. Cycle-by-cycle variations in muscle coordination, cadence and power output were observed and the EMG intensity across all muscles was used as an estimate of the metabolic cost for each cycle. Data for the cycles at greatest power output were separated into three groups: maximum power, 80% power but lower EMG intensity and 80% power and higher EMG intensity. Torque-angular velocity relations were determined for the ankle and knee joints. During cycling at maximum power output the ankle joint was not extending at the velocity necessary for maximum power output; thus, maximum limb power occurs when some of the individual muscles cannot be generating maximum power output. Increases in EMG intensity occurred with no increase in power output from the limb: these corresponded to decreases in the efficiency and changes in coordination. Increases in power were achieved that were not matched by equivalent increases in EMG intensity, but did occur with changes in coordination. It is proposed that the power output from the limb is limited by the coordination pattern of the muscles rather than the maximum power output from any one muscle itself.

  2. The relationship between two different mechanical cost functions and muscle oxygen consumption.

    Science.gov (United States)

    Praagman, M; Chadwick, E K J; van der Helm, F C T; Veeger, H E J

    2006-01-01

    Inverse-dynamic models often use cost functions to solve the load-sharing problem. Although it is often assumed that energy is minimised, most cost functions are based on mechanically related measures like muscle force or stress. The aim of this study was to analyse the relationships of two cost functions with experimentally determined data on muscle energy consumption. Four subjects performed isometric contractions generating combinations of elbow flexion/extension and pro/supination moments. Muscle oxygen consumption (VO2) of the m. biceps breve, m. biceps longum, m. brachioradialis and m. triceps laterale was measured with near infrared spectroscopy. Both cost functions were implemented into an existing inverse-dynamic shoulder and elbow model and the individual cost values per muscle were calculated, normalised and subsequently compared to experimental VO2 values. The minimum stress cost function led to a good correspondence between VO2 and cost for the m. triceps laterale but for the flexor muscles cost was significantly lower. A newly proposed energy-related cost function showed, however, a far better correspondence. The inclusion of a linear term and muscle mass in the new criterion led model results to correspond better to experimental results. The energy-related cost function appeared to be a better measure for muscle energy consumption than the stress cost function and led to more realistic predictions of muscle activation.

  3. Aging impairs the recovery in mechanical muscle function following 4 days of disuse

    DEFF Research Database (Denmark)

    Hvid, Lars Grøndahl; Suetta, C; Nielsen, Jacob

    2014-01-01

    As aged individuals are frequently exposed to short-term disuse caused by disease or musculoskeletal injury, it is important to understand how short-term disuse and subsequent retraining affect lower limb mechanical muscle function. The purpose of the present study was, therefore, to investigate...... dynamometry (60 and 180° s(-1), respectively) along with isometric muscle strength and rapid muscle force capacity examined as contractile rate of force development (RFD), Impulse, and relative RFD (rRFD) during the initial phase of contraction (100 ms time interval relative to onset of contraction). Prior...... to disuse, marked age-related differences (p

  4. Role of the bulbocavernosus muscles on the mechanism of human erection.

    Science.gov (United States)

    Wespes, E; Nogueira, M C; Herbaut, A G; Caufriez, M; Schulman, C C

    1990-01-01

    The role of the human bulbocavernosus muscles on the intracavernous pressure and on the venous return were investigated during artificial erection. Contractions of these muscles were voluntary or produced by dorsal nerve stimulation. During such contractions, elevations in intracavernous pressure and a decrease in the erectile flow rates to produce and to maintain the erection were observed. These results demonstrate involvement of the bulbocavernosus muscles in the process of penile rigidity and suggest that they could participate in the mechanism of rigidity during intercourse.

  5. Vascular endothelial growth factor overexpression in ischemic skeletal muscle enhances myoglobin expression in vivo

    NARCIS (Netherlands)

    van Weel, Vincent; Deckers, Martine M. L.; Grimbergen, Jos M.; van Leuven, Kees J. M.; Lardenoye, JanWillem H. P.; Schlingemann, Reinier O.; van Nieuw Amerongen, Geerten P.; van Bockel, J. Hajo; van Hinsbergh, Victor W. M.; Quax, Paul H. A.

    2004-01-01

    Therapeutic angiogenesis using vascular endothelial growth factor ( VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for

  6. In vivo antinociceptive and muscle relaxant activity of leaf and bark of Buddleja asiatica L.

    Science.gov (United States)

    Barkatullah, -; Ibrar, Muhammad; Ikram, Nazia; Rauf, Abdur; Hadda, Taibi Ben; Bawazeer, Saud; Khan, Haroon; Pervez, Samreen

    2016-09-01

    The current study was designed to assess the antinociceptive and skeleton muscle relaxant effect of leaves and barks of Buddleja asiatica in animal models. In acetic acid induced writhing test, pretreatment of ethanolic extract of leaves and barks evoked marked dose dependent antinociceptive effect with maximum of 70% and 67% pain relief at 300mg/kg i.p. respectively. In chimney test, the ethanolic extract of leaves and barks evoked maximum of 66.66% and 53.33% muscle relaxant effect after 90min of treatment at 300mg/kg i.p respectively. In traction test, the ethanolic extract of leaves and barks caused maximum of 60% and 73.33% muscle relaxant effect after 90min of treatment at 300mg/kg i.p respectively. In short, both leaves and barks demonstrated profound antinociceptive and skeleton muscle relaxant effects and thus the study provided natural healing agents for the treatment of said disorders.

  7. Mechanical muscle properties and intermuscular coordination in maximal and submaximal cycling: theoretical and practical implications

    OpenAIRE

    Barratt, Paul

    2014-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University The ability of an individual to perform a functional movement is determined by a range of mechanical properties including the force and power producing capabilities of muscle, and the interplay of force and power outputs between different muscle groups (intermuscular coordination). Cycling presents an ideal experimental model to investigate these factors as it is an ecologically valid multi-jo...

  8. Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

    Science.gov (United States)

    Wong, Sing Wan; Yao, Yifei; Hong, Ye; Ma, Zhiyao; Kok, Stanton H L; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T

    2017-04-01

    High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H2O2). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H2O2. These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

  9. Membrane Currents in Airway Smooth Muscle: Mechanisms and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Luke J Janssen

    1997-01-01

    Full Text Available Electrophysiological and pharmacological techniques were used to characterize the membrane conductance changes underlying spasmogen-evoked depolarization in airway smooth muscle (ASM. Changes included a transient activation of chloride ion channels and prolonged suppression of potassium ion channels; both changes are triggered by release of internally sequestered calcium ion and in turn cause opening of voltage-dependent calcium channels. The resultant influx of calcium ions contributes to contraction as well as to refilling of the internal calcium ion pool. Bronchodilators, on the other hand, act in part through activation of potassium channels, with consequent closure of calcium channels. The tools used to study ion channels in ASM are described, and the investigations of the roles of ion channels in ASM physiology (autacoid-evoked depolarization and hyperpolarization and pathophysiology (airway hyperresponsiveness are summarized. Finally, how the relationship between ion channels and ASM function/dysfunction may relate to the treatment of asthma and related breathing disorders is discussed.

  10. Muscle coordination limits efficiency and power output of human limb movement under a wide range of mechanical demands

    Science.gov (United States)

    Wakeling, James M.

    2015-01-01

    This study investigated the influence of cycle frequency and workload on muscle coordination and the ensuing relationship with mechanical efficiency and power output of human limb movement. Eleven trained cyclists completed an array of cycle frequency (cadence)-power output conditions while excitation from 10 leg muscles and power output were recorded. Mechanical efficiency was maximized at increasing cadences for increasing power outputs and corresponded to muscle coordination and muscle fiber type recruitment that minimized both the total muscle excitation across all muscles and the ineffective pedal forces. Also, maximum efficiency was characterized by muscle coordination at the top and bottom of the pedal cycle and progressive excitation through the uniarticulate knee, hip, and ankle muscles. Inefficiencies were characterized by excessive excitation of biarticulate muscles and larger duty cycles. Power output and efficiency were limited by the duration of muscle excitation beyond a critical cadence (120–140 rpm), with larger duty cycles and disproportionate increases in muscle excitation suggesting deteriorating muscle coordination and limitations of the activation-deactivation capabilities. Most muscles displayed systematic phase shifts of the muscle excitation relative to the pedal cycle that were dependent on cadence and, to a lesser extent, power output. Phase shifts were different for each muscle, thereby altering their mechanical contribution to the pedaling action. This study shows that muscle coordination is a key determinant of mechanical efficiency and power output of limb movement across a wide range of mechanical demands and that the excitation and coordination of the muscles is limited at very high cycle frequencies. PMID:26445873

  11. Muscle coordination limits efficiency and power output of human limb movement under a wide range of mechanical demands.

    Science.gov (United States)

    Blake, Ollie M; Wakeling, James M

    2015-12-01

    This study investigated the influence of cycle frequency and workload on muscle coordination and the ensuing relationship with mechanical efficiency and power output of human limb movement. Eleven trained cyclists completed an array of cycle frequency (cadence)-power output conditions while excitation from 10 leg muscles and power output were recorded. Mechanical efficiency was maximized at increasing cadences for increasing power outputs and corresponded to muscle coordination and muscle fiber type recruitment that minimized both the total muscle excitation across all muscles and the ineffective pedal forces. Also, maximum efficiency was characterized by muscle coordination at the top and bottom of the pedal cycle and progressive excitation through the uniarticulate knee, hip, and ankle muscles. Inefficiencies were characterized by excessive excitation of biarticulate muscles and larger duty cycles. Power output and efficiency were limited by the duration of muscle excitation beyond a critical cadence (120-140 rpm), with larger duty cycles and disproportionate increases in muscle excitation suggesting deteriorating muscle coordination and limitations of the activation-deactivation capabilities. Most muscles displayed systematic phase shifts of the muscle excitation relative to the pedal cycle that were dependent on cadence and, to a lesser extent, power output. Phase shifts were different for each muscle, thereby altering their mechanical contribution to the pedaling action. This study shows that muscle coordination is a key determinant of mechanical efficiency and power output of limb movement across a wide range of mechanical demands and that the excitation and coordination of the muscles is limited at very high cycle frequencies. Copyright © 2015 the American Physiological Society.

  12. Hindlimb muscle anatomical mechanical advantage differs among joints and stride phases in basilisk lizards.

    Science.gov (United States)

    Bergmann, Philip J; Hare-Drubka, Meredith

    2015-08-01

    The vertebrate musculoskeletal system is composed of skeletal levers powered by muscles. Effective mechanical advantage (EMA) and muscle properties influence organismal performance at various tasks. Anatomical mechanical advantage (AMA) is a proxy for EMA that facilitates the study of preserved specimens when many muscles or many species are of interest. AMA is the quotient of in-lever to out-lever length, and quantifies the force-velocity trade-off of a lever, where high AMAs translate into high force, low velocity levers. We studied AMAs, physiological cross-sectional areas (PCSAs), fiber lengths, and fiber widths for 20 hindlimb muscles of the lizard Basiliscus vittatus, moving the hip, knee, and ankle during both the stance and swing phases of the stride. We tested the hypotheses that muscles moving proximal limb joints, and those active during stance, would have characteristics that maximize force. We also tested whether adults had more force-optimized levers than juveniles to compensate for higher body mass. We found no differences between adults and juveniles, but found differences among joints and between stride phases. AMAs were lowest and PCSAs highest for the knee, and PCSA was higher for stance than swing muscles. Fiber width decreased distally, but did not differ between stride phases. Fiber length of stance muscles decreased distally and was highest for swing muscles of the knee. Our findings show that different muscle and lever characteristics allow the knee to be both force- and velocity-optimized, indicating its important role in locomotion. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. Effects of a combined mechanical stimulation protocol: Value for skeletal muscle tissue engineering.

    Science.gov (United States)

    Boonen, Kristel J M; Langelaan, Marloes L P; Polak, Roderick B; van der Schaft, Daisy W J; Baaijens, Frank P T; Post, Mark J

    2010-05-28

    Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications for regenerative medicine, in vitro physiological model systems, and in vitro meat production. Besides conventional biochemical cues to promote muscle tissue maturation in vitro, biophysical stimuli are necessary to reach the desired functionality and texture of the engineered tissue. Stretch, caused by active movements of the body, is an important factor present in the niche of muscle progenitor cells in vivo. We therefore investigated the effects of uniaxial ramp stretch (2%) followed by uniaxial intermittent dynamic stretch (4%) on C2C12 and murine muscle progenitor cells in a 2D and 3D environment and found that stretch negatively influenced maturation in all cases, demonstrated by decreased expression of MRFs and sarcomere proteins at the RNA level and a delay in the formation of cross striations. We therefore conclude that the current protocol is not recommended for skeletal muscle tissue engineering purposes. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Effect of protons on the mechanical response of rat muscle nociceptive fibers and neurons in vitro.

    Science.gov (United States)

    Hotta, Norio; Kubo, Asako; Mizumura, Kazue

    2015-03-01

    Strong exercise makes muscle acidic, and painful. The stimulus that activates muscle nociceptors in such instance may be protons. Reportedly, however, not many afferents are excited by protons alone. We, therefore, posited that protons sensitize muscular nociceptors to mechanical stimuli. We examined effects of protons on mechanical sensitivity of muscle nociceptors by single-fiber recording from rat muscle-nerve preparations in vitro and by whole cell patch-clamp recording of mechanically activated (MA) currents from cultured rat dorsal root ganglion neurons. We recorded 38 Aδ- and C-fibers. Their response magnitude was increased by both pH 6.2 and pH 6.8; in addition the mechanical threshold was lowered by pH 6.2. Decrease in the threshold by pH6.2 was also observed in MA currents. Presently observed sensitization by protons could be involved in several types of ischemic muscle pain, and may also be involved in cardiovascular and respiratory controls during exercise. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  15. Respiratory muscle dysfunction: a multicausal entity in the critically ill patient undergoing mechanical ventilation.

    Science.gov (United States)

    Díaz, Magda C; Ospina-Tascón, Gustavo A; Salazar C, Blanca C

    2014-02-01

    Respiratory muscle dysfunction, particularly of the diaphragm, may play a key role in the pathophysiological mechanisms that lead to difficulty in weaning patients from mechanical ventilation. The limited mobility of critically ill patients, and of the diaphragm in particular when prolonged mechanical ventilation support is required, promotes the early onset of respiratory muscle dysfunction, but this can also be caused or exacerbated by other factors that are common in these patients, such as sepsis, malnutrition, advanced age, duration and type of ventilation, and use of certain medications, such as steroids and neuromuscular blocking agents. In this review we will study in depth this multicausal origin, in which a common mechanism is altered protein metabolism, according to the findings reported in various models. The understanding of this multicausality produced by the same pathophysiological mechanism could facilitate the management and monitoring of patients undergoing mechanical ventilation. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

  16. In vivo gene transfer into the ocular ciliary muscle mediated by ultrasound and microbubbles.

    Science.gov (United States)

    Kowalczuk, Laura; Boudinet, Michèle; El Sanharawi, Mohamed; Touchard, Elodie; Naud, Marie-Christine; Saïed, Amena; Jeanny, Jean-Claude; Behar-Cohen, Francine; Laugier, Pascal

    2011-11-01

    This study aimed to assess application of ultrasound (US) combined with microbubbles (MB) to transfect the ciliary muscle of rat eyes. Reporter DNA plasmids encoding for Gaussia luciferase, β-galactosidase or the green fluorescent protein (GFP), alone or mixed with 50% Artison MB, were injected into the ciliary muscle, with or without US exposure (US set at 1 MHz, 2 W/cm(2), 50% duty cycle for 2 min). Luciferase activity was measured in ocular fluids at 7 and 30 days after sonoporation. At 1 week, the US+MB treatment showed a significant increase in luminescence compared with control eyes, injected with plasmid only, with or without MB (×2.6), and, reporter proteins were localized in the ciliary muscle by histochemical analysis. At 1 month, a significant decrease in luciferase activity was observed in all groups. A rise in lens and ciliary muscle temperature was measured during the procedure but did not result in any observable or microscopic damages at 1 and 8 days. The feasibility to transfer gene into the ciliary muscle by US and MB suggests that sonoporation may allow intraocular production of proteins for the treatment of inflammatory, angiogenic and/or degenerative retinal diseases. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  17. Mechanisms of Hyperhomocysteinemia Induced Skeletal Muscle Myopathy after Ischemia in the CBS−/+ Mouse Model

    Directory of Open Access Journals (Sweden)

    Sudhakar Veeranki

    2015-01-01

    Full Text Available Although hyperhomocysteinemia (HHcy elicits lower than normal body weights and skeletal muscle weakness, the mechanisms remain unclear. Despite the fact that HHcy-mediated enhancement in ROS and consequent damage to regulators of different cellular processes is relatively well established in other organs, the nature of such events is unknown in skeletal muscles. Previously, we reported that HHcy attenuation of PGC-1α and HIF-1α levels enhanced the likelihood of muscle atrophy and declined function after ischemia. In the current study, we examined muscle levels of homocysteine (Hcy metabolizing enzymes, anti-oxidant capacity and focused on protein modifications that might compromise PGC-1α function during ischemic angiogenesis. Although skeletal muscles express the key enzyme (MTHFR that participates in re-methylation of Hcy into methionine, lack of trans-sulfuration enzymes (CBS and CSE make skeletal muscles more susceptible to the HHcy-induced myopathy. Our study indicates that elevated Hcy levels in the CBS−/+ mouse skeletal muscles caused diminished anti-oxidant capacity and contributed to enhanced total protein as well as PGC-1α specific nitrotyrosylation after ischemia. Furthermore, in the presence of NO donor SNP, either homocysteine (Hcy or its cyclized version, Hcy thiolactone, not only increased PGC-1α specific protein nitrotyrosylation but also reduced its association with PPARγ in C2C12 cells. Altogether these results suggest that HHcy exerts its myopathic effects via reduction of the PGC-1/PPARγ axis after ischemia.

  18. Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation

    Science.gov (United States)

    Hooijman, Pleuni E.; Paul, Marinus A.; Stienen, Ger J. M.; Beishuizen, Albertus; Van Hees, Hieronymus W. H.; Singhal, Sunil; Bashir, Muhammad; Budak, Murat T.; Morgen, Jacqueline; Barsotti, Robert J.; Levine, Sanford

    2014-01-01

    Several studies have indicated that diaphragm dysfunction develops in patients on mechanical ventilation (MV). Here, we tested the hypothesis that the contractility of sarcomeres, i.e., the smallest contractile unit in muscle, is affected in humans on MV. To this end, we compared diaphragm muscle fibers of nine brain-dead organ donors (cases) that had been on MV for 26 ± 5 h with diaphragm muscle fibers from nine patients (controls) undergoing surgery for lung cancer that had been on MV for less than 2 h. In each diaphragm specimen we determined 1) muscle fiber cross-sectional area in cryosections by immunohistochemical methods and 2) the contractile performance of permeabilized single muscle fibers by means of maximum specific force, kinetics of cross-bridge cycling by rate of tension redevelopment, myosin heavy chain content and concentration, and calcium sensitivity of force of slow-twitch and fast-twitch muscle fibers. In case subjects, we noted no statistically significant decrease in outcomes compared with controls in slow-twitch or fast-twitch muscle fibers. These observations indicate that 26 h of MV of humans is not invariably associated with changes in the contractile performance of sarcomeres in the diaphragm. PMID:25038190

  19. Milk-derived ribonuclease 5 preparations induce myogenic differentiation in vitro and muscle growth in vivo.

    Science.gov (United States)

    Knight, Matthew I; Tester, Angus M; McDonagh, Matthew B; Brown, Andrew; Cottrell, Jeremy; Wang, Jianghui; Hobman, Peter; Cocks, Benjamin G

    2014-12-01

    Ribonuclease 5, also known as angiogenin, is a stable and abundant ribonuclease in milk whey protein, which is able to regulate several cellular functions, including capillary formation, neuron survival, and epithelial cell growth. Ribonuclease 5 is important for protein synthesis directly stimulating rRNA synthesis in the nucleolus. Here, we show that biologically active RNase5 can be purified from bovine milk. Furthermore, we show that milk-derived RNase5 directly stimulates muscle cell differentiation in vitro, inducing C2C12 cell differentiation and myogenesis. When supplemented into the diet of healthy adult mice, milk-derived RNase5 preparations promoted muscle weight gain and grip strength. Collectively, these data indicate that milk-derived RNase5 preparations exhibit a novel role in skeletal muscle cell function. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Comparative Statistical Mechanics of Muscle and Non-Muscle Contractile Systems: Stationary States of Near-Equilibrium Systems in A Linear Regime

    Directory of Open Access Journals (Sweden)

    Yves Lecarpentier

    2017-10-01

    Full Text Available A. Huxley’s equations were used to determine the mechanical properties of muscle myosin II (MII at the molecular level, as well as the probability of the occurrence of the different stages in the actin–myosin cycle. It was then possible to use the formalism of statistical mechanics with the grand canonical ensemble to calculate numerous thermodynamic parameters such as entropy, internal energy, affinity, thermodynamic flow, thermodynamic force, and entropy production rate. This allows us to compare the thermodynamic parameters of a non-muscle contractile system, such as the normal human placenta, with those of different striated skeletal muscles (soleus and extensor digitalis longus as well as the heart muscle and smooth muscles (trachea and uterus in the rat. In the human placental tissues, it was observed that the kinetics of the actin–myosin crossbridges were considerably slow compared with those of smooth and striated muscular systems. The entropy production rate was also particularly low in the human placental tissues, as compared with that observed in smooth and striated muscular systems. This is partly due to the low thermodynamic flow found in the human placental tissues. However, the unitary force of non-muscle myosin (NMII generated by each crossbridge cycle in the myofibroblasts of the human placental tissues was similar in magnitude to that of MII in the myocytes of both smooth and striated muscle cells. Statistical mechanics represents a powerful tool for studying the thermodynamics of all contractile muscle and non-muscle systems.

  1. Uncoupling of in vivo torque production from EMG in mouse muscles injured by eccentric contractions

    Science.gov (United States)

    Warren, Gordon L; Ingalls, Christopher P; Shah, Shree J; Armstrong, R B

    1999-01-01

    The main objective of this study was to determine whether eccentric contraction-induced muscle injury causes impaired plasmalemmal action potential conduction, which could explain the injury-induced excitation-contraction coupling failure. Mice were chronically implanted with stimulating electrodes on the left common peroneal nerve and with electromyographic (EMG) electrodes on the left tibialis anterior (TA) muscle. The left anterior crural muscles of anaesthetized mice were stimulated to perform 150 eccentric (ECC) (n = 12 mice) or 150 concentric (CON) (n = 11 mice) contractions. Isometric torque, EMG root mean square (RMS) and M-wave mean and median frequencies were measured before, immediately after, and at 1, 3, 5 and 14 days after the protocols. In parallel experiments, nicotinic acetylcholine receptor (AChR) concentration was measured in TA muscles to determine whether the excitation failure elicited a denervation-like response.Immediately after the ECC protocol, torque was reduced by 47–89%, while RMS was reduced by 9–21%; the RMS decrement was not different from that observed for the CON protocol, which did not elicit large torque deficits. One day later, both ECC and CON RMS had returned to baseline values and did not change over the next 2 weeks. However, torque production by the ECC group showed a slow recovery over that time and was still depressed by 12–30% after 2 weeks. M-wave mean and median frequencies were not affected by performance of either protocol.AChR concentration was elevated by 79 and 368% at 3 and 5 days, respectively, after the ECC protocol; AChR concentration had returned to control levels 2 weeks after the protocol. At the time of peak AChR concentration in the ECC protocol muscles (i.e. 5 days), AChR concentration in CON protocol muscles was not different from the control level.In conclusion, these data demonstrate no major role for impaired plasmalemmal action potential conduction in the excitation-contraction coupling

  2. Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise

    Directory of Open Access Journals (Sweden)

    Rodrigo Martins Pereira

    2017-05-01

    Full Text Available Abstract Glucose uptake is an important phenomenon for cell homeostasis and for organism health. Under resting conditions, skeletal muscle is dependent on insulin to promote glucose uptake.Insulin, after binding to its membrane receptor, triggers a cascade of intracellular reactions culminating in activation of the glucose transporter 4, GLUT4, among other outcomes.This transporter migrates to the plasma membrane and assists in glucose internalization.However, under special conditions such as physical exercise, alterations in the levels of intracellular molecules such as ATP and calcium actto regulate GLUT4 translocation and glucose uptake in skeletal muscle, regardless of insulinlevels.Regular physical exercise, due to stimulating pathways related to glucose uptake, is an important non-pharmacological intervention for improving glycemic control in obese and diabetic patients. In this mini-review the main mechanisms involved in glucose uptake in skeletal muscle in response to muscle contraction will be investigated.

  3. The mechanisms of massage and effects on performance, muscle recovery and injury prevention.

    Science.gov (United States)

    Weerapong, Pornratshanee; Hume, Patria A; Kolt, Gregory S

    2005-01-01

    Many coaches, athletes and sports medicine personnel hold the belief, based on observations and experiences, that massage can provide several benefits to the body such as increased blood flow, reduced muscle tension and neurological excitability, and an increased sense of well-being. Massage can produce mechanical pressure, which is expected to increase muscle compliance resulting in increased range of joint motion, decreased passive stiffness and decreased active stiffness (biomechanical mechanisms). Mechanical pressure might help to increase blood flow by increasing the arteriolar pressure, as well as increasing muscle temperature from rubbing. Depending on the massage technique, mechanical pressure on the muscle is expected to increase or decrease neural excitability as measured by the Hoffman reflex (neurological mechanisms). Changes in parasympathetic activity (as measured by heart rate, blood pressure and heart rate variability) and hormonal levels (as measured by cortisol levels) following massage result in a relaxation response (physiological mechanisms). A reduction in anxiety and an improvement in mood state also cause relaxation (psychological mechanisms) after massage. Therefore, these benefits of massage are expected to help athletes by enhancing performance and reducing injury risk. However, limited research has investigated the effects of pre-exercise massage on performance and injury prevention. Massage between events is widely investigated because it is believed that massage might help to enhance recovery and prepare athletes for the next event. Unfortunately, very little scientific data has supported this claim. The majority of research on psychological effects of massage has concluded that massage produces positive effects on recovery (psychological mechanisms). Post-exercise massage has been shown to reduce the severity of muscle soreness but massage has no effects on muscle functional loss. Notwithstanding the belief that massage has benefits

  4. Cervical-scapular muscles strength and severity of temporomandibular disorder in women with mechanical neck pain

    Directory of Open Access Journals (Sweden)

    Fernanda Pasinato

    Full Text Available Abstract Introduction: Changes in cervical muscle function have been observed in patients with neck pain (NP and TMD. However, the relationship between TMD severity and neck muscle strength in the presence/absence of NP is unknown. Objective: To determine the prevalence of TMD in women with and without mechanical NP and assess the cervical-scapular muscle strength and its association with TMD severity. Methods: Fifteen volunteers without neck pain (CG and 14 women with mechanical neck pain (NPG took part and were selected by the Neck Disability Index. The diagnosis and severity of TMD were determined by the Research Diagnostic Criteria for TMD and Temporomandibular Index (TI, respectively. The strength of the upper trapezius muscle, and cervical flexor and extensor muscles was measured by digital hand dynamometer. Results: 64.5% of women with NP and 33.3% without NP were diagnosed with TMD (p = 0.095. The NPG showed lower strength of the cervical flexor (p = 0.044 and extensor (p=0.006 muscles, and higher TI (p = 0.038 than in the CG. It was also verified moderate negative correlation between TI and the strength of dominant (p = 0.046, r = -0.547 and non-dominant (p = 0.007, r = -0.695 upper trapezius, and cervical flexors (p = 0.023, r = -0.606 in the NPG. Conclusion: There was no difference in the prevalence of TMD in women with and without NP. However, women with NP have lower cervical muscle strength - compared to those without NP - which was associated with greater severity of TMD. Thus, in women with NP associated with TMD, it is advisable to assess and address the severity of this dysfunction and identify the cervical-scapular muscles compromise.

  5. Muscle and prosthesis contributions to amputee walking mechanics: a modeling study.

    Science.gov (United States)

    Silverman, Anne K; Neptune, Richard R

    2012-08-31

    Unilateral, below-knee amputees have altered gait mechanics, which can significantly affect their mobility. Below-knee amputees lose the functional use of the ankle muscles, which are critical during walking to provide body support, forward propulsion, leg-swing initiation and mediolateral balance. Thus, either muscles must compensate or the prosthesis must provide the functional tasks normally provided by the ankle muscles. Three-dimensional (3D) forward dynamics simulations of amputee and non-amputee walking were generated to identify muscle and prosthesis contributions to amputee walking mechanics, including the subtasks of body support, forward propulsion, leg-swing initiation and mediolateral balance. Results showed that the prosthesis provided body support in the absence of the ankle muscles. The prosthesis contributed to braking from early to mid-stance and propulsion in late stance. The prosthesis also functioned like the uniarticular soleus muscle by transferring energy from the residual leg to the trunk to provide trunk propulsion. The residual-leg vasti and rectus femoris reduced their contributions to braking in early stance, which mitigated braking from the prosthesis during this period. The prosthesis did not replace the function of the gastrocnemius, which normally generates energy to the leg to initiate swing. As a result, lower overall energy was delivered to the residual leg. The prosthesis also acted to accelerate the body laterally in the absence of the ankle muscles. These results provide further insight into muscle and prosthesis function in below-knee amputee walking and can help guide rehabilitation methods and device designs to improve amputee mobility. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

    Directory of Open Access Journals (Sweden)

    Antônio Carlos Cicogna

    1999-04-01

    Full Text Available OBJECTIVE: To assess the effect of food restriction (FR on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR. METHODS: Isolated papillary muscle preparations of the left ventricle (LV of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1 reduction in the body weight and LV weight of SHR and WKY rats; 2 increase in the time to peak shortening and the time to peak developed tension (DT in the hypertrophied myocardium of the SHR; 3 diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

  7. Robotic hand with locking mechanism using TCP muscles for applications in prosthetic hand and humanoids

    Science.gov (United States)

    Saharan, Lokesh; Tadesse, Yonas

    2016-04-01

    This paper presents a biomimetic, lightweight, 3D printed and customizable robotic hand with locking mechanism consisting of Twisted and Coiled Polymer (TCP) muscles based on nylon precursor fibers as artificial muscles. Previously, we have presented a small-sized biomimetic hand using nylon based artificial muscles and fishing line muscles as actuators. The current study focuses on an adult-sized prosthetic hand with improved design and a position/force locking system. Energy efficiency is always a matter of concern to make compact, lightweight, durable and cost effective devices. In natural human hand, if we keep holding objects for long time, we get tired because of continuous use of energy for keeping the fingers in certain positions. Similarly, in prosthetic hands we also need to provide energy continuously to artificial muscles to hold the object for a certain period of time, which is certainly not energy efficient. In this work we, describe the design of the robotic hand and locking mechanism along with the experimental results on the performance of the locking mechanism.

  8. Changes in muscle force-length properties affect the early rise of force in vivo

    DEFF Research Database (Denmark)

    Blazevich, Anthony J; Cannavan, Dale; Horne, Sara

    2009-01-01

    . A significant proportion of the variance in RFD measured only in the initial contraction phase (0-30 ms) could be explained by shifts in the moment-angle relation (r=-0.66-0.71; R2=0.44-0.50). Training-induced increases in muscle fascicle length may lead to a reduced or complete lack of adaptive gains...

  9. Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria

    DEFF Research Database (Denmark)

    Rasmussen, Ulla Fugmann; Rasmussen, Hans N.; Krustrup, Peter

    2001-01-01

    -18 mmol O2 · min 1 · kg 1 at work rates of 22-32 W/kg). Mitochondria were isolated from the same muscle at rest. Strong correlations were obtained between O2 max and a number of mitochondrial parameters (mitochondrial protein, cytochrome aa3, citrate synthase, and respiratory activities). The activities...

  10. Expression of muscle anabolic and metabolic factors in mechanically loaded MLO-Y4 osteocytes.

    Science.gov (United States)

    Juffer, Petra; Jaspers, Richard T; Lips, Paul; Bakker, Astrid D; Klein-Nulend, Jenneke

    2012-02-15

    Lack of physical activity results in muscle atrophy and bone loss, which can be counteracted by mechanical loading. Similar molecular signaling pathways are involved in the adaptation of muscle and bone mass to mechanical loading. Whether anabolic and metabolic factors regulating muscle mass, i.e., insulin-like growth factor-I isoforms (IGF-I Ea), mechano growth factor (MGF), myostatin, vascular endothelial growth factor (VEGF), or hepatocyte growth factor (HGF), are also produced by osteocytes in bone in response to mechanical loading is largely unknown. Therefore, we investigated whether mechanical loading by pulsating fluid flow (PFF) modulates the mRNA and/or protein levels of muscle anabolic and metabolic factors in MLO-Y4 osteocytes. Unloaded MLO-Y4 osteocytes expressed mRNA of VEGF, HGF, IGF-I Ea, and MGF, but not myostatin. PFF increased mRNA levels of IGF-I Ea (2.1-fold) and MGF (2.0-fold) at a peak shear stress rate of 44Pa/s, but not at 22Pa/s. PFF at 22 Pa/s increased VEGF mRNA levels (1.8- to 2.5-fold) and VEGF protein release (2.0- to 2.9-fold). Inhibition of nitric oxide production decreased (2.0-fold) PFF-induced VEGF protein release. PFF at 22 Pa/s decreased HGF mRNA levels (1.5-fold) but increased HGF protein release (2.3-fold). PFF-induced HGF protein release was nitric oxide dependent. Our data show that mechanically loaded MLO-Y4 osteocytes differentially express anabolic and metabolic factors involved in the adaptive response of muscle to mechanical loading (i.e., IGF-I Ea, MGF, VEGF, and HGF). Similarly to muscle fibers, mechanical loading enhanced expression levels of these growth factors in MLO-Y4 osteocytes. Although in MLO-Y4 osteocytes expression levels of IGF-I Ea and MGF of myostatin were very low or absent, it is known that the activity of osteoblasts and osteoclasts is strongly affected by them. The abundant expression levels of these factors in muscle cells, in combination with low expression in MLO-Y4 osteocytes, provide a

  11. Topographical mapping and mechanical pain sensitivity of myofascial trigger points in the infraspinatus muscle.

    Science.gov (United States)

    Ge, Hong-You; Fernández-de-Las-Peñas, César; Madeleine, Pascal; Arendt-Nielsen, Lars

    2008-10-01

    To screen for the presence of latent and active myofascial trigger points (MTrPs) in patients with unilateral shoulder and arm pain and perform topographical mapping of mechanical pain sensitivity bilaterally in the infraspinatus muscles. Nineteen patients with unilateral musculoskeletal shoulder pain participated in the study. The area overlying the infraspinatus on each side was divided into 10 adjacent sub-areas of 1cm(2), corresponding to the area of a pressure algometer probe. Pressure pain threshold (PPT) was measured in each sub-area bilaterally in the infraspinatus muscles. Following PPT measurement, an acupuncture needle was inserted into each sub-area five times in different directions in order to induce local twitch response and/or referred pain. A significantly lower PPT level in the infraspinatus muscle was detected on the painful side compared with the non-painful side (P=0.001). PPT at midfiber region of the infraspinatus muscles was lower than that at other muscle parts (Pactive MTrPs were found in the infraspinatus muscle on the painful side and there were also multiple latent MTrPs bilaterally in the infraspinatus muscles. PPT at active MTrPs was much lower than the latent MTrPs and again lower than the non-MTrPs. There exists bilateral mechanical hyperalgesia in patients with unilateral shoulder pain. Further, the association of multiple active MTrPs with unilateral shoulder pain and the heterogeneity of mechanical pain sensitivity distribution suggest a crucial role of peripheral sensitization in chronic myofascial pain conditions. Additionally, the locations of MTrPs identified with dry needling correspond well to PPT topographical mapping, suggesting that dry needling and PPT topographical mapping are sensitive techniques in the identification of MTrPs.

  12. Posterior fixation sutures: a revised mechanical explanation for the fadenoperation based on rectus extraocular muscle pulleys.

    Science.gov (United States)

    Clark, R A; Isenberg, S J; Rosenbaum, A L; Demer, J L

    1999-12-01

    To determine the effect of the rectus extraocular muscle pulleys on the fadenoperation, an operation designed to fixate the posterior muscle belly to the underlying retroequatorial sclera. First, duction into the field of action of the operated-on muscle was quantified retrospectively after fadenoperation. Magnetic resonance imaging was then performed prospectively after surgery to verify anatomic changes. Forced duction testing was performed prospectively during surgery before and after faden placement. Finally, computed tomography in a cadaver containing radiographic markers was performed prospectively to determine the effect of fadenoperation on the position of the medial rectus insertion relative to its pulley. Mean maximum adduction after medial rectus fadenoperation was 18 degrees (range, 10 to 25 degrees; 13 eyes). Fadenoperations combined with large medial rectus recessions restricted adduction more than fadenoperations combined with smaller recessions (P = .019), but even fadenoperations without recessions substantially restricted adduction. Mean maximum abduction after lateral rectus fadenoperation was 40 degrees (range, 25 to 45 degrees; four eyes). Axial magnetic resonance imaging in two eyes demonstrated a smaller loss of muscle tangency to the globe during contraction than predicted by geometric models. Forced ductions in nine patients performed immediately after faden placement demonstrated a new mechanical restriction to duction toward the operated-on muscle. Cadaveric computed tomographic scans demonstrated posterior displacement of the medial rectus pulley during adduction after fadenoperation. Posterior fixation sutures do not significantly decrease muscle torque during contraction. Because posterior fixation sutures posteriorly displace the pulley sleeve during duction toward the operated-on muscle, the mechanical restriction after surgery probably represents the force deforming the pulley. This mechanical restriction may account for the

  13. In vivo tracing uptake and elimination of organic pesticides in fish muscle.

    Science.gov (United States)

    Xu, Jianqiao; Luo, Junpeng; Ruan, Jingwen; Zhu, Fang; Luan, Tiangang; Liu, Hong; Jiang, Ruifen; Ouyang, Gangfeng

    2014-07-15

    Bioconcentration factors (BCFs) measured in the laboratory are important for characterizing the bioaccumulative properties of chemicals entering the environment, especially the potential persistent organic pollutants (POPs), which can pose serious adverse effects on ecosystem and human health. Traditional lethal analysis methods are time-consuming and sacrifice too many experimental animals. In the present study, in vivo solid-phase microextraction (SPME) was introduced to trace the uptake and elimination processes of pesticides in living fish. BCFs and elimination kinetic coefficients of the pesticides were recorded therein. Moreover, the metabolism of fenthion was also traced with in vivo SPME. The method was time-efficient and laborsaving. Much fewer experimental animals were sacrificed during the tracing. In general, this study opened up an opportunity to measure BCFs cheaply in laboratories for the registering of emerging POPs and inspecting of suspected POPs, as well as demonstrated the potential application of in vivo SPME in the study of toxicokinetics of pollutants.

  14. In vivo measurement of mechanical properties of human long bone by using sonic sound

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, M. Jayed, E-mail: zed.hossain06@gmail.com; Rahman, M. Moshiur, E-mail: razib-121@yahoo.com; Alam, Morshed [Department of Mechanical Engineering, Bangladesh University of Engineering and Technology, Dhaka 1000 (Bangladesh)

    2016-07-12

    Vibration analysis has evaluated as non-invasive techniques for the in vivo assessment of bone mechanical properties. The relation between the resonant frequencies, long bone geometry and mechanical properties can be obtained by vibration analysis. In vivo measurements were performed on human ulna as a simple beam model with an experimental technique and associated apparatus. The resonant frequency of the ulna was obtained by Fast Fourier Transformation (FFT) analysis of the vibration response of piezoelectric accelerometer. Both elastic modulus and speed of the sound were inferred from the resonant frequency. Measurement error in the improved experimental setup was comparable with the previous work. The in vivo determination of bone elastic response has potential value in screening programs for metabolic bone disease, early detection of osteoporosis and evaluation of skeletal effects of various therapeutic modalities.

  15. The effect of neoadjuvant chemoradiotherapy on whole-body physical fitness and skeletal muscle mitochondrial oxidative phosphorylation in vivo in locally advanced rectal cancer patients--an observational pilot study.

    Directory of Open Access Journals (Sweden)

    Malcolm A West

    Full Text Available In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness.We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg-1.min-1, and the post-exercise phosphocreatine recovery rate constant (min-1, a measure of muscle mitochondrial capacity in vivo.Median age was 67 years (IQR 64-75. Differences (95%CI in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold -2.4 ml.kg-1.min-1 (-3.8, -0.9, p = 0.004; Oxygen uptake at Peak -4.0 ml.kg-1.min-1 (-6.8, -1.1, p = 0.011; and post-exercise phosphocreatine recovery rate constant -0.34 min-1 (-0.51, -0.17, p<0.001.The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery.Clinicaltrials.gov registration NCT01859442.

  16. Smooth muscle relaxant activity of Crocus sativus (saffron) and its constituents: possible mechanisms

    Science.gov (United States)

    Mokhtari-Zaer, Amin; Khazdair, Mohammad Reza; Boskabady, Mohammad Hossein

    2015-01-01

    Saffron, Crocus sativus L. (C. sativus) is rich in carotenoids and used in traditional medicine for treatment of various conditions such as coughs, stomach disorders, amenorrhea, asthma and cardiovascular disorders. These therapeutic effects of the plant are suggested to be due to its relaxant effect on smooth muscles. The effect of C. sativus and its constituents on different smooth muscles and the underlying mechanisms have been studied. Several studies have shown the relaxant effects of C. sativus and its constituents including safranal, crocin, crocetin and kaempferol on blood vessels. In addition, it was reported that saffron stigma lowers systolic blood pressure. The present review highlights the relaxant effects of C. sativus and its constituents on various smooth muscles. The possible mechanisms of this relaxing effect including activation of ß2-adrenoceptors, inhibition of histamine H1 and muscarinic receptors and calcium channels and modulation of nitric oxide (NO) are also reviewed. PMID:26468456

  17. Microstructural and mechanical properties of camel longissimus dorsi muscle during roasting, braising and microwave heating.

    Science.gov (United States)

    Yarmand, M S; Nikmaram, P; Djomeh, Z Emam; Homayouni, A

    2013-10-01

    This study was conducted to investigate the effects of various heating methods, including roasting, braising and microwave heating, on mechanical properties and microstructure of longissimus dorsi (LD) muscle of the camel. Shear value and compression force increased during microwave heating more than roasting and braising. Results obtained from scanning electron microscopy (SEM) showed more damage from roasting than in either braising or microwave heating. Granulation and fragmentation were clear in muscle fibers after roasting. The perimysium membrane of connective tissue was damaged during braising, while roasting left the perimysium membrane largely intact. The mechanical properties and microstructure of muscle can be affected by changes in water content during cooking. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); De Souza, David P. [Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Burch, Micah L. [Brigham and Women' s Hospital, Department of Medicine, Boston, MA (United States); Hamley, Steven [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Kloehn, Joachim [Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Selathurai, Ahrathy [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Tull, Dedreia; O' Callaghan, Sean; McConville, Malcolm J. [Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Bruce, Clinton R. [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia)

    2015-06-19

    Rationale: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on the use of high fat-fed rodent models and typically involve the determination of muscle glucose uptake under insulin-stimulated conditions. While insightful, they do not necessarily reflect the physiology of the postprandial state. In addition, most studies do not examine aspects of glucose metabolism beyond the uptake process. Here we present an approach to study rodent muscle glucose and intermediary metabolism under the dynamic and physiologically relevant setting of the oral glucose tolerance test (OGTT). Methods and results: In vivo muscle glucose and intermediary metabolism was investigated following oral administration of [U-{sup 13}C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates via gas chromatography–mass spectrometry. While no dietary effects were noted in the glycolytic pathway, muscle from mice fed a high fat diet (HFD) exhibited a reduction in labelling in TCA intermediates. Interestingly, this appeared to be independent of alterations in flux through pyruvate dehydrogenase. In addition, our findings suggest that TCA cycle anaplerosis is negligible in muscle during an OGTT. Conclusions: Under the dynamic physiologically relevant conditions of the OGTT, skeletal muscle from HFD fed mice exhibits alterations in glucose metabolism at the level of the TCA cycle. - Highlights: • Dynamic metabolomics was used to investigate muscle glucose metabolism in vivo. • Mitochondrial TCA cycle metabolism is altered in muscle of HFD mice. • This defect was not pyruvate dehydrogenase mediated, as has been previously thought. • Mitochondrial TCA cycle anaplerosis in muscle is virtually absent during the OGTT.

  19. In vivo monitoring of structural and mechanical changes of tissue scaffolds by multi-modality imaging.

    Science.gov (United States)

    Park, Dae Woo; Ye, Sang-Ho; Jiang, Hong Bin; Dutta, Debaditya; Nonaka, Kazuhiro; Wagner, William R; Kim, Kang

    2014-09-01

    Degradable tissue scaffolds are implanted to serve a mechanical role while healing processes occur and putatively assume the physiological load as the scaffold degrades. Mechanical failure during this period can be unpredictable as monitoring of structural degradation and mechanical strength changes at the implant site is not readily achieved in vivo, and non-invasively. To address this need, a multi-modality approach using ultrasound shear wave imaging (USWI) and photoacoustic imaging (PAI) for both mechanical and structural assessment in vivo was demonstrated with degradable poly(ester urethane)urea (PEUU) and polydioxanone (PDO) scaffolds. The fibrous scaffolds were fabricated with wet electrospinning, dyed with indocyanine green (ICG) for optical contrast in PAI, and implanted in the abdominal wall of 36 rats. The scaffolds were monitored monthly using USWI and PAI and were extracted at 0, 4, 8 and 12 wk for mechanical and histological assessment. The change in shear modulus of the constructs in vivo obtained by USWI correlated with the change in average Young's modulus of the constructs ex vivo obtained by compression measurements. The PEUU and PDO scaffolds exhibited distinctly different degradation rates and average PAI signal intensity. The distribution of PAI signal intensity also corresponded well to the remaining scaffolds as seen in explant histology. This evidence using a small animal abdominal wall repair model demonstrates that multi-modality imaging of USWI and PAI may allow tissue engineers to noninvasively evaluate concurrent mechanical stiffness and structural changes of tissue constructs in vivo for a variety of applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. In vivo photoacoustics and high frequency ultrasound imaging of mechanical high intensity focused ultrasound (HIFU) ablation

    NARCIS (Netherlands)

    Daoudi, K.; Hoogenboom, M.; Brok, M.H. den; Eikelenboom, D.C.; Adema, G.J.; Futterer, J.J.; Korte, C.L. de

    2017-01-01

    The thermal effect of high intensity focused ultrasound (HIFU) has been clinically exploited over a decade, while the mechanical HIFU is still largely confined to laboratory investigations. This is in part due to the lack of adequate imaging techniques to better understand the in-vivo pathological

  1. In vivo assessment of muscle fascicle length by extended field-of-view ultrasonography

    DEFF Research Database (Denmark)

    Noorkoiv, M; Stavnsbo, A; Aagaard, Per

    2010-01-01

    The present study examined the reliability and validity of in vivo vastus lateralis (VL) fascicle length (L(f)) assessment by extended field-of-view ultrasonography (EFOV US). Intraexperimenter and intersession reliability of EFOV US were tested. Further, L(f) measured from EFOV US images were co...

  2. Glenohumeral translation in ABER position during muscle activity in patients treated with Latarjet procedure: an in vivo MRI study.

    Science.gov (United States)

    Di Giacomo, Giovanni; Scarso, Paolo; De Vita, Andrea; Rojas Beccaglia, Mario A; Pouliart, Nicole; de Gasperis, Nicola

    2016-02-01

    The Latarjet procedure is frequently performed when treating traumatic anteroinferior shoulder instability. This procedure is supposed to have a triple effect: osseous, muscular and ligamentous. The main stabilizing mechanism in cadaver studies on fresh-frozen shoulders seems to be the sling effect produced by the subscapularis and the conjoint tendon. It has been hypothesized that muscle contraction in ABER position (abduction-external rotation) is able to translate the humeral head posteriorly and superiorly due to the sling effect. The aim of this study was to analyse the humeral head translation relative to the glenoid with the arm in ABER position with and without muscle contraction. Twenty-one subjects divided into two groups (Group A: after Latarjet; Group B: healthy subjects) were examined with an open MRI system with the shoulder in abduction-external rotation (ABER) position to analyse humeral head translation during muscle activity. In normal shoulders, there was no significant difference in anteroposterior or superoinferior translation between the rest position and the muscle-activated state. In subjects after the Latarjet procedure, the difference was significant and was also significant between both groups of subjects for posterior translation, but not for superior translation. In patients treated with Latarjet procedure, there are significant changes in glenohumeral translation during muscular activity when in ABER position, with the humeral head going more posteriorly, in comparison with normal shoulders. This study confirms the stabilizing sling effect of the transposed conjoint tendon in the ABER position. Retrospective case-control study, Level III.

  3. Causes of excitation-induced muscle cell damage in isometric contractions: mechanical stress or calcium overload?

    DEFF Research Database (Denmark)

    Fredsted, Anne; Gissel, Hanne; Madsen, Klavs

    2007-01-01

    Prolonged or unaccustomed exercise leads to muscle cell membrane damage, detectable as release of the intracellular enzyme lactic acid dehydrogenase (LDH). This is correlated to excitation-induced influx of Ca2+, but it cannot be excluded that mechanical stress contributes to the damage. We here ...

  4. Temporal effects of mechanical loading on deformation-induced damage in skeletal muscle tissue

    NARCIS (Netherlands)

    Loerakker, S.; Stekelenburg, A.; Strijkers, G. J.; Rijpkema, J. J. M.; Baaijens, F. P. T.; Bader, D. L.; Nicolay, K.; Oomens, C. W. J.

    2010-01-01

    Mechanical loading of soft tissues covering bony prominences can cause skeletal muscle damage, ultimately resulting in a severe pressure ulcer termed deep tissue injury. Recently, by means of an experimental-numerical approach, it was shown that local tissue deformations cause tissue damage once a

  5. [Action of cobamamide and leukovorin on skeletal muscle reinnervation in mechanical injury to the motor nerves].

    Science.gov (United States)

    Mikhaĭlov, V V; Mikhaĭlov, V V; Onishchenko, V V; Avakumov, V M

    1987-01-01

    The experiments on rats showed that cobamamide (0.5 mg/kg) and leukovorin (5 mg/kg) administered daily exerted a pronounced activating effect on the process of regeneration of mechanically injured nerve trunks. The combined administration of the drugs fails to potentiate the effect of each drug on the process of the skeletal muscle reinnervation.

  6. Glucose transporters and in vivo glucose uptake in skeletal and cardiac muscle: fasting, insulin stimulation and immunoisolation studies of GLUT1 and GLUT4.

    OpenAIRE

    Kraegen, E. W.; Sowden, J A; Halstead, M B; Clark, P W; Rodnick, K J; Chisholm, D. J.; James, D E

    1993-01-01

    Our aim was to study glucose transporters GLUT1 and GLUT4 in relation to in vivo glucose uptake in rat cardiac and skeletal muscle. The levels of both transporters were of a similar order of magnitude in whole muscle tissue (GLUT1/GLUT4 ratio varied from 0.1 to 0.6), suggesting that both may have an important physiological role in regulating muscle glucose metabolism. GLUT4 correlated very strongly (r2 = 0.97) with maximal insulin-stimulated glucose uptake (Rg' max., estimated using the gluco...

  7. In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis.

    Science.gov (United States)

    Jacobs, D O; Maris, J; Fried, R; Settle, R G; Rolandelli, R R; Koruda, M J; Chance, B; Rombeau, J L

    1988-11-01

    High-energy phosphate metabolism in skeletal muscle is altered during sepsis, although the chronology of events is uncertain. Phosphorus 31 magnetic resonance spectroscopy was used to measure changes in muscle energy stores of the left hind limb musculature of adult male rats during sepsis. Following control scans, cecal ligation and puncture were performed and scanning was repeated 6, 24, and 48 hours after surgery. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), a measure of energy stores, and adenosine triphosphate (ATP) to Pi ratio, a measure of the energy available for immediate use, were determined from peak heights. Intracellular pH was calculated using the distance between Pi and PCr peaks. In surviving animals, a 40% decrease in PCr/Pi ratio (+/- SEM) was observed by 24 hours (22.3 +/- 3.0 at time 0 vs 13.3 +/- 2.8 at 24 hours), whereas energy availability (beta-ATP/Pi) was statistically unchanged (18.2 +/- 2.2 at time 0 vs 15.2 +/- 1.2 at 48 hours). Intracellular pH did not change. Both PCr/Pi and ATP/Pi ratios were inversely correlated with time. In this model of documented peritonitis, skeletal muscle energy metabolism is rapidly altered following severe infection, and these changes can be detected using 31P magnetic resonance spectroscopy.

  8. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Nelson, Christopher E; Hakim, Chady H; Ousterout, David G; Thakore, Pratiksha I; Moreb, Eirik A; Castellanos Rivera, Ruth M; Madhavan, Sarina; Pan, Xiufang; Ran, F Ann; Yan, Winston X; Asokan, Aravind; Zhang, Feng; Duan, Dongsheng; Gersbach, Charles A

    2016-01-22

    Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this study, adeno-associated virus was used to deliver the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to the mdx mouse model of DMD to remove the mutated exon 23 from the dystrophin gene. This includes local and systemic delivery to adult mice and systemic delivery to neonatal mice. Exon 23 deletion by CRISPR-Cas9 resulted in expression of the modified dystrophin gene, partial recovery of functional dystrophin protein in skeletal myofibers and cardiac muscle, improvement of muscle biochemistry, and significant enhancement of muscle force. This work establishes CRISPR-Cas9-based genome editing as a potential therapy to treat DMD. Copyright © 2016, American Association for the Advancement of Science.

  9. Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG).

    Science.gov (United States)

    Shimada, Akiko; Cairns, Brian E; Vad, Nynne; Ulriksen, Kathrine; Pedersen, Anne Marie Lynge; Svensson, Peter; Baad-Hansen, Lene

    2013-01-24

    A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure. Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations. Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040). In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake.

  10. Inducing myoblast re-entry into the cell cycle: a potential mechanism for laser-enhanced skeletal muscle regeneration

    Science.gov (United States)

    Liu, T.; Fang, Y.; Zhang, C. P.; Chen, P.; Wang, C. Z.; Kang, H. X.; Shen, B. J.; Liang, J.; Fu, X. B.

    2014-09-01

    This study investigated the effect of low-level laser irradiation (LLLI) on the cell cycle and proliferative activity of cultured myoblasts, and sought to elucidate the possible cellular mechanism by which LLLI promotes the regeneration of skeletal muscle in vivo. Primary myoblasts isolated from rat hindlegs were irradiated with helium-neon laser light at different energy densities. Distributions of cell-cycle subpopulations and the expression of cell-cycle regulatory proteins in myoblasts were assessed using flow cytometric analysis and western blot assay. It was found that laser irradiation stimulated cell-cycle entry; induced the expression of cyclin A and cyclin D; and increased cell proliferation index and bromodeoxyuridine incorporation as compared to the unirradiated control cells, indicating LLLI augmented the number of proliferative myoblasts in the S phase and G2/M phase of the cell cycle. These results suggest that LLLI at certain fluxes and wavelengths could activate quiescent myoblasts, leading to cell division and facilitating new myofiber formation. This could contribute to the improvement of skeletal muscle regeneration following trauma and myopathic diseases.

  11. The in vivo mechanism of action of CD20 monoclonal antibodies depends on local tumor burden

    Science.gov (United States)

    Boross, Peter; Jansen, J.H. Marco; de Haij, Simone; Beurskens, Frank J.; van der Poel, Cees E.; Bevaart, Lisette; Nederend, Maaike; Golay, Josée; van de Winkel, Jan G.J.; Parren, Paul W.H.I.; Leusen, Jeanette H.W.

    2011-01-01

    Background CD20 monoclonal antibodies are widely used in clinical practice. Antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and direct cell death have been suggested to be important effector functions for CD20 antibodies. However, their specific contributions to the in vivo mechanism of action of CD20 immunotherapy have not been well defined. Design and Methods Here we studied the in vivo mechanism of action of type I (rituximab and ofatumumab) and type II (HuMab-11B8) CD20 antibodies in a peritoneal, syngeneic, mouse model with EL4-CD20 cells using low and high tumor burden. Results Interestingly, we observed striking differences in the in vivo mechanism of action of CD20 antibodies dependent on tumor load. In conditions of low tumor burden, complement was sufficient for tumor killing both for type I and type II CD20 antibodies. In contrast, in conditions of high tumor burden, activating FcγR (specifically FcγRIII), active complement and complement receptor 3 were all essential for tumor killing. Our data suggest that complement-enhanced antibody-dependent cellular cytotoxicity may critically affect tumor killing by CD20 antibodies in vivo. The type II CD20 antibody 11B8, which is a poor inducer of complement activation, was ineffective against high tumor burden. Conclusions Tumor burden affects the in vivo mechanism of action of CD20 antibodies. Low tumor load can be eliminated by complement alone, whereas elimination of high tumor load requires multiple effector mechanisms. PMID:21880632

  12. Regeneration of the skin and muscle tissue in rainbow trout (Oncorhynchus mykiss) following mechanical injury

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Nielsen, Michael Engelbrecht

    Mechanical injury induced by needles penetrating the skin and underlying muscle tissue in rainbow trout (Oncorhynchus mykiss) was used as a model to study the initial phase(s) of tissue regeneration. Tissue regeneration in humans is characterised by four phases; hemostatis, inflammation......, proliferation and remodelling. We investigated the expression of genes traditionally being important in these processes untill 7 days after the tissue damage in order to find inducible genetic markers following mechanical injury....

  13. Alterations in Leg Extensor Muscle-Tendon Unit Biomechanical Properties With Ageing and Mechanical Loading

    Directory of Open Access Journals (Sweden)

    Christopher McCrum

    2018-02-01

    Full Text Available Tendons transfer forces produced by muscle to the skeletal system and can therefore have a large influence on movement effectiveness and safety. Tendons are mechanosensitive, meaning that they adapt their material, morphological and hence their mechanical properties in response to mechanical loading. Therefore, unloading due to immobilization or inactivity could lead to changes in tendon mechanical properties. Additionally, ageing may influence tendon biomechanical properties directly, as a result of biological changes in the tendon, and indirectly, due to reduced muscle strength and physical activity. This review aimed to examine age-related differences in human leg extensor (triceps surae and quadriceps femoris muscle-tendon unit biomechanical properties. Additionally, this review aimed to assess if, and to what extent mechanical loading interventions could counteract these changes in older adults. There appear to be consistent reductions in human triceps surae and quadriceps femoris muscle strength, accompanied by similar reductions in tendon stiffness and elastic modulus with ageing, whereas the effect on tendon cross sectional area is unclear. Therefore, the observed age-related changes in tendon stiffness are predominantly due to changes in tendon material rather than size with age. However, human tendons appear to retain their mechanosensitivity with age, as intervention studies report alterations in tendon biomechanical properties in older adults of similar magnitudes to younger adults over 12–14 weeks of training. Interventions should implement tendon strains corresponding to high mechanical loads (i.e., 80–90% MVC with repetitive loading for up to 3–4 months to successfully counteract age-related changes in leg extensor muscle-tendon unit biomechanical properties.

  14. In vivo effects of metal ions on conformation and mechanical performance of silkworm silks.

    Science.gov (United States)

    Wang, Xin; Li, Yi; Liu, Qingsong; Chen, Quanmei; Xia, Qingyou; Zhao, Ping

    2017-03-01

    The mechanism of silk fiber formation is of particular interest. Although in vitro evidence has shown that metal ions affect conformational transitions of silks, the in vivo effects of metal ions on silk conformations and mechanical performance are still unclear. This study explored the effects of metal ions on silk conformations and mechanical properties of silk fibers by adding K+ and Cu2+ into the silk fibroin solutions or injecting them into the silkworms. Aimed by CD analysis, FTIR analysis, and mechanical testing, the conformational and mechanical changes of the silks were estimated. By using BION Web Server, the interactions of K+ and N-terminal of silk fibroin were also simulated. We presented that K+ and Cu2+ induced the conformational transitions of silk fibroin by forming β-sheet structures. Moreover, the mechanical parameters of silk fibers, such as strength, toughness and Young's modulus, were also improved after K+ or Cu2+ injection. Using BION Web Server, we found that potassium ions may have strong electrostatic interactions with the negatively charged residues. We suggest that K+ and Cu2+ play crucial roles in the conformation and mechanical performances of silks and they are involved in the silk fiber formation in vivo. Our results are helpful for clarifying the mechanism of silk fiber formation, and provide insights for modifying the mechanical properties of silk fibers. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Mechanisms of in vivo release of triamcinolone acetonide from PLGA microspheres.

    Science.gov (United States)

    Doty, Amy C; Weinstein, David G; Hirota, Keiji; Olsen, Karl F; Ackermann, Rose; Wang, Yan; Choi, Stephanie; Schwendeman, Steven P

    2017-06-28

    Little is known about the underlying effects controlling in vitro-in vivo correlations (IVIVCs) for biodegradable controlled release microspheres. Most reports of IVIVCs that exist are empirical in nature, typically based on a mathematical relationship between in vitro and in vivo drug release, with the latter often estimated by deconvolution of pharmacokinetic data. In order to improve the ability of in vitro release tests to predict microsphere behavior in vivo and develop more meaningful IVIVCs, the in vivo release mechanisms need to be characterized. Here, two poly(lactic-co-glycolic acid) (PLGA) microsphere formulations encapsulating the model steroid triamcinolone acetonide (Tr-A) were implanted subcutaneously in rats by using a validated cage model, allowing for free fluid and cellular exchange and microsphere retrieval during release. Release kinetics, as well as mechanistic indicators of release such as hydrolysis and mass loss, was measured by direct analysis of the recovered microspheres. Release of Tr-A from both formulations was greatly accelerated in vivo compared to in vitro using agitated phosphate buffered saline +0.02% Tween 80 pH7.4, including rate of PLGA hydrolysis, mass loss and water uptake. Both microsphere formulations exhibited erosion-controlled release in vitro, indicated by similar polymer mass loss kinetics, but only one of the formulations (low molecular weight, free acid terminated) exhibited the same mechanism in vivo. The in vivo release of Tr-A from microspheres made of a higher molecular weight, ester end-capped PLGA displayed an osmotically induced/pore diffusion mechanism based on confocal micrographs of percolating pores in the polymer, not previously observed in vitro. This research indicates the need to fully understand the in vivo environment and how it causes drug release from biodegradable microspheres. This understanding can then be applied to develop in vitro release tests which better mimic this environment and cause

  16. Substantial effects of epimuscular myofascial force transmission on muscular mechanics have major implications on spastic muscle and remedial surgery

    NARCIS (Netherlands)

    Yucesoy, C.A.; Huijing, P.A.J.B.M.

    2007-01-01

    The specific aim of this paper is to review the effects of epimuscular myofascial force transmission on muscular mechanics and present some new results on finite element modeling of non-isolated aponeurotomized muscle in order to discuss the dependency of mechanics of spastic muscle, as well as

  17. In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy.

    Science.gov (United States)

    Choudhury, Sourav R; Fitzpatrick, Zachary; Harris, Anne F; Maitland, Stacy A; Ferreira, Jennifer S; Zhang, Yuanfan; Ma, Shan; Sharma, Rohit B; Gray-Edwards, Heather L; Johnson, Jacob A; Johnson, Aime K; Alonso, Laura C; Punzo, Claudio; Wagner, Kathryn R; Maguire, Casey A; Kotin, Robert M; Martin, Douglas R; Sena-Esteves, Miguel

    2016-08-01

    Adeno-associated viral (AAV) vectors have shown promise as a platform for gene therapy of neurological disorders. Achieving global gene delivery to the central nervous system (CNS) is key for development of effective therapies for many of these diseases. Here we report the isolation of a novel CNS tropic AAV capsid, AAV-B1, after a single round of in vivo selection from an AAV capsid library. Systemic injection of AAV-B1 vector in adult mice and cat resulted in widespread gene transfer throughout the CNS with transduction of multiple neuronal subpopulations. In addition, AAV-B1 transduces muscle, β-cells, pulmonary alveoli, and retinal vasculature at high efficiency. This vector is more efficient than AAV9 for gene delivery to mouse brain, spinal cord, muscle, pancreas, and lung. Together with reduced sensitivity to neutralization by antibodies in pooled human sera, the broad transduction profile of AAV-B1 represents an important improvement over AAV9 for CNS gene therapy.

  18. In vivo monitoring of mRNA movement in Drosophila body wall muscle cells reveals the presence of myofiber domains.

    Directory of Open Access Journals (Sweden)

    Alice M C van Gemert

    Full Text Available BACKGROUND: In skeletal muscle each muscle cell, commonly called myofiber, is actually a large syncytium containing numerous nuclei. Experiments in fixed myofibers show that mRNAs remain localized around the nuclei in which they are produced. METHODOLOGY/PRINCIPAL FINDINGS: In this study we generated transgenic flies that allowed us to investigate the movement of mRNAs in body wall myofibers of living Drosophila embryos. We determined the dynamic properties of GFP-tagged mRNAs using in vivo confocal imaging and photobleaching techniques and found that the GFP-tagged mRNAs are not free to move throughout myofibers. The restricted movement indicated that body wall myofibers consist of three domains. The exchange of mRNAs between the domains is relatively slow, but the GFP-tagged mRNAs move rapidly within these domains. One domain is located at the centre of the cell and is surrounded by nuclei while the other two domains are located at either end of the fiber. To move between these domains mRNAs have to travel past centrally located nuclei. CONCLUSIONS/SIGNIFICANCE: These data suggest that the domains made visible in our experiments result from prolonged interactions with as yet undefined structures close to the nuclei that prevent GFP-tagged mRNAs from rapidly moving between the domains. This could be of significant importance for the treatment of myopathies using regenerative cell-based therapies.

  19. In vivo monitoring of mRNA movement in Drosophila body wall muscle cells reveals the presence of myofiber domains.

    Science.gov (United States)

    van Gemert, Alice M C; van der Laan, Annelies M A; Pilgram, Gonneke S K; Fradkin, Lee G; Noordermeer, Jasprina N; Tanke, Hans J; Jost, Carolina R

    2009-08-17

    In skeletal muscle each muscle cell, commonly called myofiber, is actually a large syncytium containing numerous nuclei. Experiments in fixed myofibers show that mRNAs remain localized around the nuclei in which they are produced. In this study we generated transgenic flies that allowed us to investigate the movement of mRNAs in body wall myofibers of living Drosophila embryos. We determined the dynamic properties of GFP-tagged mRNAs using in vivo confocal imaging and photobleaching techniques and found that the GFP-tagged mRNAs are not free to move throughout myofibers. The restricted movement indicated that body wall myofibers consist of three domains. The exchange of mRNAs between the domains is relatively slow, but the GFP-tagged mRNAs move rapidly within these domains. One domain is located at the centre of the cell and is surrounded by nuclei while the other two domains are located at either end of the fiber. To move between these domains mRNAs have to travel past centrally located nuclei. These data suggest that the domains made visible in our experiments result from prolonged interactions with as yet undefined structures close to the nuclei that prevent GFP-tagged mRNAs from rapidly moving between the domains. This could be of significant importance for the treatment of myopathies using regenerative cell-based therapies.

  20. Interactions between connected half-sarcomeres produce emergent mechanical behavior in a mathematical model of muscle.

    Science.gov (United States)

    Campbell, Kenneth S

    2009-11-01

    Most reductionist theories of muscle attribute a fiber's mechanical properties to the scaled behavior of a single half-sarcomere. Mathematical models of this type can explain many of the known mechanical properties of muscle but have to incorporate a passive mechanical component that becomes approximately 300% stiffer in activating conditions to reproduce the force response elicited by stretching a fast mammalian muscle fiber. The available experimental data suggests that titin filaments, which are the mostly likely source of the passive component, become at most approximately 30% stiffer in saturating Ca2+ solutions. The work described in this manuscript used computer modeling to test an alternative systems theory that attributes the stretch response of a mammalian fiber to the composite behavior of a collection of half-sarcomeres. The principal finding was that the stretch response of a chemically permeabilized rabbit psoas fiber could be reproduced with a framework consisting of 300 half-sarcomeres arranged in 6 parallel myofibrils without requiring titin filaments to stiffen in activating solutions. Ablation of inter-myofibrillar links in the computer simulations lowered isometric force values and lowered energy absorption during a stretch. This computed behavior mimics effects previously observed in experiments using muscles from desmin-deficient mice in which the connections between Z-disks in adjacent myofibrils are presumably compromised. The current simulations suggest that muscle fibers exhibit emergent properties that reflect interactions between half-sarcomeres and are not properties of a single half-sarcomere in isolation. It is therefore likely that full quantitative understanding of a fiber's mechanical properties requires detailed analysis of a complete fiber system and cannot be achieved by focusing solely on the properties of a single half-sarcomere.

  1. Interactions between connected half-sarcomeres produce emergent mechanical behavior in a mathematical model of muscle.

    Directory of Open Access Journals (Sweden)

    Kenneth S Campbell

    2009-11-01

    Full Text Available Most reductionist theories of muscle attribute a fiber's mechanical properties to the scaled behavior of a single half-sarcomere. Mathematical models of this type can explain many of the known mechanical properties of muscle but have to incorporate a passive mechanical component that becomes approximately 300% stiffer in activating conditions to reproduce the force response elicited by stretching a fast mammalian muscle fiber. The available experimental data suggests that titin filaments, which are the mostly likely source of the passive component, become at most approximately 30% stiffer in saturating Ca2+ solutions. The work described in this manuscript used computer modeling to test an alternative systems theory that attributes the stretch response of a mammalian fiber to the composite behavior of a collection of half-sarcomeres. The principal finding was that the stretch response of a chemically permeabilized rabbit psoas fiber could be reproduced with a framework consisting of 300 half-sarcomeres arranged in 6 parallel myofibrils without requiring titin filaments to stiffen in activating solutions. Ablation of inter-myofibrillar links in the computer simulations lowered isometric force values and lowered energy absorption during a stretch. This computed behavior mimics effects previously observed in experiments using muscles from desmin-deficient mice in which the connections between Z-disks in adjacent myofibrils are presumably compromised. The current simulations suggest that muscle fibers exhibit emergent properties that reflect interactions between half-sarcomeres and are not properties of a single half-sarcomere in isolation. It is therefore likely that full quantitative understanding of a fiber's mechanical properties requires detailed analysis of a complete fiber system and cannot be achieved by focusing solely on the properties of a single half-sarcomere.

  2. A Neuro-Mechanical Model of a Single Leg Joint Highlighting the Basic Physiological Role of Fast and Slow Muscle Fibres of an Insect Muscle System

    Science.gov (United States)

    Toth, Tibor Istvan; Schmidt, Joachim; Büschges, Ansgar; Daun-Gruhn, Silvia

    2013-01-01

    In legged animals, the muscle system has a dual function: to produce forces and torques necessary to move the limbs in a systematic way, and to maintain the body in a static position. These two functions are performed by the contribution of specialized motor units, i.e. motoneurons driving sets of specialized muscle fibres. With reference to their overall contraction and metabolic properties they are called fast and slow muscle fibres and can be found ubiquitously in skeletal muscles. Both fibre types are active during stepping, but only the slow ones maintain the posture of the body. From these findings, the general hypothesis on a functional segregation between both fibre types and their neuronal control has arisen. Earlier muscle models did not fully take this aspect into account. They either focused on certain aspects of muscular function or were developed to describe specific behaviours only. By contrast, our neuro-mechanical model is more general as it allows functionally to differentiate between static and dynamic aspects of movement control. It does so by including both muscle fibre types and separate motoneuron drives. Our model helps to gain a deeper insight into how the nervous system might combine neuronal control of locomotion and posture. It predicts that (1) positioning the leg at a specific retraction angle in steady state is most likely due to the extent of recruitment of slow muscle fibres and not to the force developed in the individual fibres of the antagonistic muscles; (2) the fast muscle fibres of antagonistic muscles contract alternately during stepping, while co-contraction of the slow muscle fibres takes place during steady state; (3) there are several possible ways of transition between movement and steady state of the leg achieved by varying the time course of recruitment of the fibres in the participating muscles. PMID:24244298

  3. A neuro-mechanical model of a single leg joint highlighting the basic physiological role of fast and slow muscle fibres of an insect muscle system.

    Directory of Open Access Journals (Sweden)

    Tibor Istvan Toth

    Full Text Available In legged animals, the muscle system has a dual function: to produce forces and torques necessary to move the limbs in a systematic way, and to maintain the body in a static position. These two functions are performed by the contribution of specialized motor units, i.e. motoneurons driving sets of specialized muscle fibres. With reference to their overall contraction and metabolic properties they are called fast and slow muscle fibres and can be found ubiquitously in skeletal muscles. Both fibre types are active during stepping, but only the slow ones maintain the posture of the body. From these findings, the general hypothesis on a functional segregation between both fibre types and their neuronal control has arisen. Earlier muscle models did not fully take this aspect into account. They either focused on certain aspects of muscular function or were developed to describe specific behaviours only. By contrast, our neuro-mechanical model is more general as it allows functionally to differentiate between static and dynamic aspects of movement control. It does so by including both muscle fibre types and separate motoneuron drives. Our model helps to gain a deeper insight into how the nervous system might combine neuronal control of locomotion and posture. It predicts that (1 positioning the leg at a specific retraction angle in steady state is most likely due to the extent of recruitment of slow muscle fibres and not to the force developed in the individual fibres of the antagonistic muscles; (2 the fast muscle fibres of antagonistic muscles contract alternately during stepping, while co-contraction of the slow muscle fibres takes place during steady state; (3 there are several possible ways of transition between movement and steady state of the leg achieved by varying the time course of recruitment of the fibres in the participating muscles.

  4. In-vivo degradation mechanism of Ti-6Al-4V hip joints

    DEFF Research Database (Denmark)

    Lomholt, Trine Colding; Pantleon, Karen; Somers, Marcel A. J.

    2011-01-01

    In-vivo exposed Ti-6Al-4V implants were investigated to determine the degradation mechanism occurring during the articulating movements of the hip joint in the human body. Failed implants were compared to Ti-6Al-4V samples, which were tested in the laboratory for their tribocorrosion performance....... The results strongly indicate that degradation of Ti-6Al-4V has occurred with the same mechanism for both the implants and the laboratory tested samples and, hence, block-on-ring tribocorrosion testing was found to be a useful tool for mimicking the degradation occurring in the body.The degradation mechanism...

  5. [Evolution in muscle strength in critical patients with invasive mechanical ventilation].

    Science.gov (United States)

    Via Clavero, G; Sanjuán Naváis, M; Menéndez Albuixech, M; Corral Ansa, L; Martínez Estalella, G; Díaz-Prieto-Huidobro, A

    2013-01-01

    To assess the evolution of muscle strength in critically ill patients with mechanical ventilation (MV) from withdrawal of sedatives to hospital discharge. A cohort study was conducted in two intensive care units in the Hospital Universitari de Bellvitge from November 2011 to March 2012. Consecutive patients with MV > 72h. Dependent outcome: Muscle strength measured with the Medical Research Council (MRC) scale beginning on the first day the patient was able to answer 3 out of 5 simple orders (day 1), every week, at ICU discharge and at hospital discharge or at day 60 Independent outcomes: factors associated with muscle strength loss, ventilator-free days, ICU length of stay and hospital length of stay. The patients were distributed into two groups (MRC2 (P 2 and costicosteroids. Patients with a MRC < 48 required more days with MV and a longer ICU stay. Copyright © 2013 Elsevier España, S.L. y SEEIUC. All rights reserved.

  6. Can chronic stretching change the muscle-tendon mechanical properties? A review.

    Science.gov (United States)

    Freitas, S R; Mendes, B; Le Sant, G; Andrade, R J; Nordez, A; Milanovic, Z

    2017-08-12

    It is recognized that stretching is an effective method to chronically increase the joint range of motion. However, the effects of stretching training on the muscle-tendon structural properties remain unclear. This systematic review with meta-analysis aimed to determine whether chronic stretching alter the muscle-tendon structural properties. Published papers regarding longitudinal stretching (static, dynamic and/or PNF) intervention (either randomized or not) in humans of any age and health status, with more than 2 weeks in duration and at least 2 sessions per week, were searched in PubMed, PEDro, ScienceDirect and ResearchGate databases. Structural or mechanical variables from joint (maximal tolerated passive torque or resistance to stretch) or muscle-tendon unit (muscle architecture, stiffness, extensibility, shear modulus, volume, thickness, cross-sectional area, and slack length) were extracted from those papers. A total of 26 studies were selected, with a duration ranging from 3 to 8 weeks, and an average total time under stretching of 1165 seconds per week. Small effects were seen for maximal tolerated passive torque, but trivial effects were seen for joint resistance to stretch, muscle architecture, muscle stiffness, and tendon stiffness. A large heterogeneity was seen for most of the variables. Stretching interventions with 3- to 8-week duration do not seem to change either the muscle or the tendon properties, although it increases the extensibility and tolerance to a greater tensile force. Adaptations to chronic stretching protocols shorter than 8 weeks seem to mostly occur at a sensory level. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Intramuscular connective tissue differences in spastic and control muscle: a mechanical and histological study.

    Directory of Open Access Journals (Sweden)

    Marije de Bruin

    Full Text Available Cerebral palsy (CP of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU from CP patients (n = 29 and healthy controls (n = 10. The sarcomere slack length (mean 2.5 µm, SEM 0.05 and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190 in spastic muscle than in controls (2572 µm2, SEM 322. However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold, i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23 did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients.

  8. Reference data on muscle volumes of healthy human pelvis and lower extremity muscles: an in vivo magnetic resonance imaging feasibility study.

    Science.gov (United States)

    Lube, Juliane; Cotofana, Sebastian; Bechmann, Ingo; Milani, Thomas L; Özkurtul, Orkun; Sakai, Tatsuo; Steinke, Hanno; Hammer, Niels

    2016-01-01

    Muscle volumes are of crucial interest when attempting to analyze individual physical performance and disease- or age-related alterations in muscle morphology. However, very little reference data are available in the literature on pelvis and lower extremity muscle volumes originating from healthy and young individuals. Furthermore, it is of interest if representative muscle volumes, covering large anatomical regions, can be obtained using magnetic resonance imaging (MRI) in a setting similar to the clinical routine. Our objective was therefore to provide encompassing, bilateral, 3-T MRI-based datasets on muscle volumes of the pelvis and the lower limb muscles. T1-weighted 3-T MRI records were obtained bilaterally from six young and healthy participants. Three-dimensional volumes were compiled from 28 muscles and muscle groups of each participant before the muscle volumes were computed. Muscle volumes were obtained from 28 muscles and muscle groups of the pelvis and lower extremity. Volumes were larger in male than in female participants. Volumes of the dominant and non-dominant sides were similar in both genders. The obtained results were in line with volumetric data obtained from smaller anatomical areas, thus extending the available datasets. This study provides an encompassing and feasible approach to obtain data on the muscle volumes of pelvic and limb muscles of healthy, young, and physically active individuals. The respective data form a basis to determine effects of therapeutic approaches, progression of diseases, or technical applications like automated segmentation algorithms applied to different populations.

  9. Chronic massive rotator cuff tear in rats: in vivo evaluation of muscle force and three-dimensional histologic analysis.

    Science.gov (United States)

    Ditsios, Konstantinos; Boutsiadis, Achilleas; Kapoukranidou, Dorothea; Chatzisotiriou, Athanasios; Kalpidis, Ioannis; Albani, Maria; Christodoulou, Anastasios

    2014-12-01

    Massive rotator cuff tear repair is frequently complicated by unsatisfactory clinical results due to possible tendon retraction, muscle atrophy, and fatty degeneration. The objective of this study was the development of a chronic massive tear in a rat model and the evaluation of the muscle force in vivo and of the histologic changes in a 3- dimensional manner. To simulate massive rotator cuff tears, both the supraspinatus (SS) and the infraspinatus (IS) tendons were surgically detached from the right humerus of 15 male adult Sprague-Dawley rats. Twelve weeks postoperatively, all animals underwent isometric tension recordings of both the SS and IS muscles. Histologic analysis and image deconvolution processing were performed to estimate the presence and the distribution of atrophy in 3 dimensions. An overall 30% and 35% reduction in muscle force of the SS and IS muscles, respectively, was observed compared with the left uninjured shoulder (P muscle groups. These results show that functional impairment of SS and IS muscles after chronic massive tendon tears could be attributed to the decrease in muscle force production during their repair on the greater tuberosity and, second, to the comparatively greater degeneration of their dorsal part. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  10. Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training.

    Science.gov (United States)

    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

  11. Myofascial trigger points in the masticatory muscles in patients with and without chronic mechanical neck pain.

    Science.gov (United States)

    De-la-Llave-Rincon, Ana I; Alonso-Blanco, Cristina; Gil-Crujera, Antonio; Ambite-Quesada, Silvia; Svensson, Peter; Fernández-de-Las-Peñas, César

    2012-01-01

    The purpose of this study is to describe differences in the presence of masseter and temporalis muscle trigger points (TrPs) and jaw opening between individuals with mechanical neck pain and healthy controls. Twenty patients with mechanical neck pain (60% women) without symptoms in the orofacial region, aged 20 to 37 years old, and 20 matched controls participated. Temporalis and masseter muscles were examined for the presence of TrPs in a blinded design. Trigger points were considered active if the subject recognized the pain as a familiar symptom, whereas the TrPs was considered latent if the pain was not recognized as a symptom. Jaw opening was assessed with a ruler. A greater number (P latent rather than active TrPs were found. The distribution of TrPs between groups was different for the masseter (left odds ratio [OR], 3.4; right OR, 8.1; P active jaw opening and the number of TrPs within the masticatory muscles (r(s) = -0.6; P latent TrPs in the masticatory muscles and reduced jaw opening compared to healthy controls. These findings may suggest the spread of sensitization from the cervical segment to the trigeminal brain stem sensory nuclear complex. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  12. Neural Mechanisms of Temporomandibular Joint and Masticatory Muscle Pain: A Possible Role for Peripheral Glutamate Receptor Mechanisms

    Directory of Open Access Journals (Sweden)

    David K Lam

    2005-01-01

    Full Text Available The purpose of the present review is to correlate recent knowledge of the role of peripheral ionotropic glutamate receptors in the temporomandibular joint and muscle pain from animal and human experimental pain models with findings in patients. Chronic pain is common, and many people suffer from chronic pain conditions involving deep craniofacial tissues such as temporomandibular disorders or fibromyalgia. Animal and human studies have indicated that the activation of peripheral ionotropic glutamate receptors in deep craniofacial tissues may contribute to muscle and temporomandibular joint pain and that sex differences in the activation of glutamate receptors may be involved in the female predominance in temporomandibular disorders and fibromyalgia. A peripheral mechanism involving autocrine and/or paracrine regulation of nociceptive neuronal excitability via injury or inflammation-induced release of glutamate into peripheral tissues that may contribute to the development of craniofacial pain is proposed.

  13. Design and analysis of a novel mechanical loading machine for dynamic in vivo axial loading.

    Science.gov (United States)

    Macione, James; Nesbitt, Sterling; Pandit, Vaibhav; Kotha, Shiva

    2012-02-01

    This paper describes the construction of a loading machine for performing in vivo, dynamic mechanical loading of the rodent forearm. The loading machine utilizes a unique type of electromagnetic actuator with no mechanically resistive components (servotube), allowing highly accurate loads to be created. A regression analysis of the force created by the actuator with respect to the input voltage demonstrates high linear correlation (R(2) = 1). When the linear correlation is used to create dynamic loading waveforms in the frequency (0.5-10 Hz) and load (1-50 N) range used for in vivo loading, less than 1% normalized root mean square error (NRMSE) is computed. Larger NRMSE is found at increased frequencies, with 5%-8% occurring at 40 Hz, and reasons are discussed. Amplifiers (strain gauge, linear voltage displacement transducer (LVDT), and load cell) are constructed, calibrated, and integrated, to allow well-resolved dynamic measurements to be recorded at each program cycle. Each of the amplifiers uses an active filter with cutoff frequency at the maximum in vivo loading frequencies (50 Hz) so that electronic noise generated by the servo drive and actuator are reduced. The LVDT and load cell amplifiers allow evaluation of stress-strain relationships to determine if in vivo bone damage is occurring. The strain gauge amplifier allows dynamic force to strain calibrations to occur for animals of different sex, age, and strain. Unique features are integrated into the loading system, including a weightless mode, which allows the limbs of anesthetized animals to be quickly positioned and removed. Although the device is constructed for in vivo axial bone loading, it can be used within constraints, as a general measurement instrument in a laboratory setting.

  14. Influence of mechanical ventilation and sepsis on redox balance in diaphragm, myocardium, limb muscles, and lungs.

    Science.gov (United States)

    Chacon-Cabrera, Alba; Rojas, Yeny; Martínez-Caro, Leticia; Vila-Ubach, Monica; Nin, Nicolas; Ferruelo, Antonio; Esteban, Andrés; Lorente, José A; Barreiro, Esther

    2014-12-01

    Mechanical ventilation (MV), using high tidal volumes (V(T)), causes lung (ventilator-induced lung injury [VILI]) and distant organ injury. Additionally, sepsis is characterized by increased oxidative stress. We tested whether MV is associated with enhanced oxidative stress in sepsis, the commonest underlying condition in clinical acute lung injury. Protein carbonylation and nitration, antioxidants, and inflammation (immunoblotting) were evaluated in diaphragm, gastrocnemius, soleus, myocardium, and lungs of nonseptic and septic (cecal ligation and puncture 24 hours before MV) rats undergoing MV (n = 7 per group) for 150 minutes using 3 different strategies (low V(T) [V(T) = 9 mL/kg], moderate V(T) [V(T) = 15 mL/kg], and high V(T) [V(T) = 25 mL/kg]) and in nonventilated control animals. Compared with nonventilated control animals, in septic and nonseptic rodents (1) diaphragms, limb muscles, and myocardium of high-V(T) rats exhibited a decrease in protein oxidation and nitration levels, (2) antioxidant levels followed a specific fiber-type distribution in slow- and fast-twitch muscles, (3) tumor necrosis factor α (TNF-α) levels were higher in respiratory and limb muscles, whereas no differences were observed in myocardium, and (4) in lungs, protein oxidation was increased, antioxidants were rather decreased, and TNF-α remained unmodified. In this model of VILI, oxidative stress does not occur in distant organs or skeletal muscles of rodents after several hours of MV with moderate-to-high V(T), whereas protein oxidation levels were increased in the lungs of the animals. Inflammatory events were moderately expressed in skeletal muscles and lungs of the MV rats. Concomitant sepsis did not strongly affect the MV-induced effects on muscles, myocardium, or lungs in the rodents. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients

    Directory of Open Access Journals (Sweden)

    Ákos Tényi

    2018-02-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD patients often show skeletal muscle dysfunction that has a prominent negative impact on prognosis. The study aims to further explore underlying mechanisms of skeletal muscle dysfunction as a characteristic systemic effect of COPD, potentially modifiable with preventive interventions (i.e. muscle training. The research analyzes network module associated pathways and evaluates the findings using independent measurements. Methods We characterized the transcriptionally active network modules of interacting proteins in the vastus lateralis of COPD patients (n = 15, FEV1 46 ± 12% pred, age 68 ± 7 years and healthy sedentary controls (n = 12, age 65 ± 9  years, at rest and after an 8-week endurance training program. Network modules were functionally evaluated using experimental data derived from the same study groups. Results At baseline, we identified four COPD specific network modules indicating abnormalities in creatinine metabolism, calcium homeostasis, oxidative stress and inflammatory responses, showing statistically significant associations with exercise capacity (VO2 peak, Watts peak, BODE index and blood lactate levels (P < 0.05 each, but not with lung function (FEV1. Training-induced network modules displayed marked differences between COPD and controls. Healthy subjects specific training adaptations were significantly associated with cell bioenergetics (P < 0.05 which, in turn, showed strong relationships with training-induced plasma metabolomic changes; whereas, effects of training in COPD were constrained to muscle remodeling. Conclusion In summary, altered muscle bioenergetics appears as the most striking finding, potentially driving other abnormal skeletal muscle responses. Trial registration The study was based on a retrospectively registered trial (May 2017, ClinicalTrials.gov identifier: NCT03169270

  16. Temperature elevation by HIFU in ex vivo porcine muscle: MRI measurement and simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Solovchuk, Maxim A., E-mail: solovchuk@gmail.com [Center for Advanced Study in Theoretical Sciences (CASTS), National Taiwan University, Taipei 10617, Taiwan (China); Hwang, San Chao; Chang, Hsu [Medical Engineering Research Division, National Health Research Institute, Miaoli 35053, Taiwan (China); Thiriet, Marc [Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); Sheu, Tony W. H., E-mail: twhsheu@ntu.edu.tw [Department of Engineering Science and Ocean Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan, Republic of China and Center for Advanced Study in Theoretical Sciences (CASTS), National Taiwan University, Taipei 10617, Taiwan (China)

    2014-05-15

    Purpose: High-intensity focused ultrasound is a rapidly developing medical technology with a large number of potential clinical applications. Computational model can play a pivotal role in the planning and optimization of the treatment based on the patient's image. Nonlinear propagation effects can significantly affect the temperature elevation and should be taken into account. In order to investigate the importance of nonlinear propagation effects, nonlinear Westervelt equation was solved. Weak nonlinear propagation effects were studied. The purpose of this study was to investigate the correlation between the predicted and measured temperature elevations and lesion in a porcine muscle. Methods: The investigated single-element transducer has a focal length of 12 cm, an aperture of 8 cm, and frequency of 1.08 MHz. Porcine muscle was heated for 30 s by focused ultrasound transducer with an acoustic power in the range of 24–56 W. The theoretical model consists of nonlinear Westervelt equation with relaxation effects being taken into account and Pennes bioheat equation. Results: Excellent agreement between the measured and simulated temperature rises was found. For peak temperatures above 85–90 °C “preboiling” or cavitation activity appears and lesion distortion starts, causing small discrepancy between the measured and simulated temperature rises. From the measurements and simulations, it was shown that distortion of the lesion was caused by the “preboiling” activity. Conclusions: The present study demonstrated that for peak temperatures below 85–90 °C numerical simulation results are in excellent agreement with the experimental data in three dimensions. Both temperature rise and lesion size can be well predicted. Due to nonlinear effect the temperature in the focal region can be increased compared with the linear case. The current magnetic resonance imaging (MRI) resolution is not sufficient. Due to the inevitable averaging the measured

  17. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury.

    Science.gov (United States)

    Sen, Chandan K; Khanna, Savita; Harris, Hallie; Stewart, Richard; Balch, Maria; Heigel, Mallory; Teplitsky, Seth; Gnyawali, Surya; Rink, Cameron

    2017-03-01

    The efficacy and optimization of poststroke physical therapy paradigms is challenged in part by a lack of objective tools available to researchers for systematic preclinical testing. This work represents a maiden effort to develop a robot-assisted mechanical therapy (RAMT) device to objectively address the significance of mechanical physiotherapy on poststroke outcomes. Wistar rats were subjected to right hemisphere middle-cerebral artery occlusion and reperfusion. After 24 h, rats were split into control (RAMT-) or RAMT+ groups (30 min daily RAMT over the stroke-affected gastrocnemius) and were followed up to poststroke d 14. RAMT+ increased perfusion 1.5-fold in stroke-affected gastrocnemius as compared to RAMT- controls. Furthermore, RAMT+ rats demonstrated improved poststroke track width (11% wider), stride length (21% longer), and travel distance (61% greater), as objectively measured using software-automated testing platforms. Stroke injury acutely increased myostatin (3-fold) and lowered brain-derived neurotrophic factor (BDNF) expression (0.6-fold) in the stroke-affected gastrocnemius, as compared to the contralateral one. RAMT attenuated the stroke-induced increase in myostatin and increased BDNF expression in skeletal muscle. Additional RAMT-sensitive myokine targets in skeletal muscle (IL-1ra and IP-10/CXCL10) were identified from a cytokine array. Taken together, outcomes suggest stroke acutely influences signal transduction in hindlimb skeletal muscle. Regimens based on mechanical therapy have the clear potential to protect hindlimb function from such adverse influence.-Sen, C. K., Khanna, S., Harris, H., Stewart, R., Balch, M., Heigel, M., Teplitsky, S., Gnyawali, S., Rink, C. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury. © FASEB.

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

    Directory of Open Access Journals (Sweden)

    Leão, Henrique Zaquia

    2010-03-01

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

  19. Muscle-Specific Effective Mechanical Advantage and Joint Impulse in Weightlifting.

    Science.gov (United States)

    Kipp, Kristof; Harris, Chad

    2017-07-01

    Kipp, K, and Harris, C. Muscle-specific effective mechanical advantage and joint impulse in weightlifting. J Strength Cond Res 31(7): 1905-1910, 2017-Lifting greater loads during weightlifting exercises may theoretically be achieved through increasing the magnitudes of net joint impulses or manipulating the joints' effective mechanical advantage (EMA). The purpose of this study was to investigate muscle-specific EMA and joint impulse as well as impulse-momentum characteristics of the lifter-barbell system across a range of external loads during the execution of the clean. Collegiate-level weightlifters performed submaximal cleans at 65, 75, and 85% of their 1-repetition maximum (1-RM), whereas data from a motion analysis system and a force plate were used to calculate lifter-barbell system impulse and velocity, as well as net extensor impulse generated at the hip, knee, and ankle joints and the EMA of the gluteus maximus, hamstrings, quadriceps, and triceps surae muscles. The results indicated that the lifter-barbell system impulse did not change as load increased, whereas the velocity of the lifter-barbell system decreased with greater load. In addition, the net extensor impulse at all joints increased as load increased. The EMA of all muscles did not, however, change as load increased. The load-dependent effects on the impulse-velocity characteristics of the lifter-barbell system may reflect musculoskeletal force-velocity behaviors, and may further indicate that the weightlifting performance is limited by the magnitude of ground reaction force impulse. In turn, the load-dependent effects observed at the joint level indicated that lifting greater loads were due to greater net extensor impulses generated at the joints of the lower extremity and not greater EMAs of the respective extensor muscles. In combination, these results suggest that lifting greater external loads during the clean is due to the ability to generate large extensor joint impulses, rather than

  20. Intermittent vibration protects aged muscle from mechanical and oxidative damage under prolonged compression.

    Science.gov (United States)

    Wong, Sing Wan; Cheung, Brian Chun Ho; Pang, Bruce Tak Keung; Kwong, Ateline; Chung, Anna; Lee, Kenneth Ka Ho; Mak, Arthur Fut Tak

    2017-04-11

    Deep tissue pressure ulcers, a serious clinical challenge originating in the muscle layer, are hardly detectable at the beginning. The challenge apparently occurs in aged subjects more frequently. As the ulcer propagates to the skin surface, it becomes very difficult to manage and can lead to fatal complications. Preventive measures are thus highly desirable. Although the complex pathological mechanisms have not been fully understood, prolonged and excessive physical challenges and oxidative stress are believed to be involved in the ulcer development. Previous reports have demonstrated that oxidative stress could compromise the mechanical properties of muscle cells, making them easier to be damaged when physical challenges are introduced. In this study, we used senescence accelerated (SAMP8) mice and its control breed (SAMR1) to examine the protective effects of intermittent vibration on aged and control muscle tissues during prolonged epidermal compression under 100mmHg for 6h. Results showed that an application of 35Hz, 0.25g intermittent vibration during compression decreased the compression-induced muscle breakdown in SAMP8 mice, as indicated histologically in terms of number of interstitial nuclei. The fact that no significant difference in muscle damage could be established in the corresponding groups in SAMR1 mice suggests that SAMR1 mice could better accommodate the compression insult than SAMP8 mice. Compression-induced oxidative damage was successfully curbed using intermittent vibration in SAMP8 mice, as indicated by 8-OHdG. A possible explanation is that the anti-oxidative defense could be maintained with intermittent vibration during compression. This was supported by the expression level of PGC-1-alpha, catalase, Gpx-1 and SOD1. Our data suggested intermittent vibration could serve as a preventive measure for deep tissue ulcer, particularly in aged subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Storage of Gold Nanoclusters in Muscle Leads to their Biphasic in Vivo Clearance

    CERN Document Server

    Zhang, Xiao-Dong; Chen, Jie; Wang, Hao; Song, Sha Sha; Shen, Xiu; Long, Wei; Sun, Yuan-Ming; Fan, Saijun; Zheng, Kaiyuan; Leong, David Tai; Xie, Jianping

    2014-01-01

    Ultrasmall gold nanoclusters show great potential in biomedical applications. Long term biodistribution, retention, toxicity, and pharmacokinetics profiles are prerequisites in their potential clinical applications. Here we systematically investigated the biodistribution, clearance, and toxicity of one widely used Au NC species glutathione protected Au NCs or GSH Au NCs, over a relatively long period of 90 days in mice. We observed that most of the Au NCs were cleared at 30 days post injection with a major accumulation in liver and kidney. However, it is surprising that an abnormal increase of Au amount in the heart, liver, spleen, lung, and testis was observed at 60 and 90 days, indicating that the injected Au NCs formed a V shaped time dependent distribution profile in various organs. Further investigations revealed that Au NCs were steadily accumulating in the muscle in the first 30 days p.i., and the as stored Au NCs gradually released into blood in 30 to 90 days, which induced a redistribution and reaccu...

  2. Effects of an Uphill Marathon on Running Mechanics and Lower-Limb Muscle Fatigue.

    Science.gov (United States)

    Giovanelli, Nicola; Taboga, Paolo; Rejc, Enrico; Simunic, Bostjan; Antonutto, Guglielmo; Lazzer, Stefano

    2016-05-01

    To investigate the effects of an uphill marathon (43 km, 3063-m elevation gain) on running mechanics and neuromuscular fatigue in lower-limb muscles. Maximal mechanical power of lower limbs (MMP), temporal tensiomyographic (TMG) parameters, and muscle-belly displacement (Dm) were determined in the vastus lateralis muscle before and after the competition in 18 runners (age 42.8 ± 9.9 y, body mass 70.1 ± 7.3 kg, maximal oxygen uptake 55.5 ± 7.5 mL · kg-1 · min-1). Contact (tc) and aerial (ta) times, step frequency (f), and running velocity (v) were measured at 3, 14, and 30 km and after the finish line (POST). Peak vertical ground-reaction force (Fmax), vertical displacement of the center of mass (Δz), leg-length change (ΔL), and vertical (kvert) and leg (kleg) stiffness were calculated. MMP was inversely related with race time (r = -.56, P = .016), tc (r = -.61, P = .008), and Δz (r = -.57, P = .012) and directly related with Fmax (r = .59, P = .010), ta (r = .48, P = .040), and kvert (r = .51, P = .027). In the fastest subgroup (n = 9) the following parameters were lower in POST (P running mechanics induced by fatigue. Thus, lower-limb power training could improve running performance in uphill marathons.

  3. In vivo corrosion, tumor outcome, and microarray gene expression for two types of muscle-implanted tungsten alloys.

    Science.gov (United States)

    Schuster, B E; Roszell, L E; Murr, L E; Ramirez, D A; Demaree, J D; Klotz, B R; Rosencrance, A B; Dennis, W E; Bao, W; Perkins, E J; Dillman, J F; Bannon, D I

    2012-11-15

    Tungsten alloys are composed of tungsten microparticles embedded in a solid matrix of transition metals such as nickel, cobalt, or iron. To understand the toxicology of these alloys, male F344 rats were intramuscularly implanted with pellets of tungsten/nickel/cobalt, tungsten/nickel/iron, or pure tungsten, with tantalum pellets as a negative control. Between 6 and 12 months, aggressive rhabdomyosarcomas formed around tungsten/nickel/cobalt pellets, while those of tungsten/nickel/iron or pure tungsten did not cause cancers. Electron microscopy showed a progressive corrosion of the matrix phase of tungsten/nickel/cobalt pellets over 6 months, accompanied by high urinary concentrations of nickel and cobalt. In contrast, non-carcinogenic tungsten/nickel/iron pellets were minimally corroded and urinary metals were low; these pellets having developed a surface oxide layer in vivo that may have restricted the mobilization of carcinogenic nickel. Microarray analysis of tumors revealed large changes in gene expression compared with normal muscle, with biological processes involving the cell cycle significantly up-regulated and those involved with muscle development and differentiation significantly down-regulated. Top KEGG pathways disrupted were adherens junction, p53 signaling, and the cell cycle. Chromosomal enrichment analysis of genes showed a highly significant impact at cytoband 7q22 (chromosome 7) which included mouse double minute (MDM2) and cyclin-dependant kinase (CDK4) as well as other genes associated with human sarcomas. In conclusion, the tumorigenic potential of implanted tungsten alloys is related to mobilization of carcinogenic metals nickel and cobalt from corroding pellets, while gene expression changes in the consequent tumors are similar to radiation induced animal sarcomas as well as sporadic human sarcomas. Published by Elsevier Inc.

  4. In vivo assessment of regional mechanics post-myocardial infarction: A focus on the road ahead.

    Science.gov (United States)

    Romito, Eva; Shazly, Tarek; Spinale, Francis G

    2017-10-01

    Cardiovascular disease, particularly the occurrence of myocardial infarction (MI), remains a leading cause of morbidity and mortality (Go et al., Circulation 127: e6-e245, 2013; Go et al. Circulation 129: e28-e292, 2014). There is growing recognition that a key factor for post-MI outcomes is adverse remodeling and changes in the regional structure, composition, and mechanical properties of the MI region itself. However, in vivo assessment of regional mechanics post-MI can be confounded by the species, temporal aspects of MI healing, as well as size, location, and extent of infarction across myocardial wall. Moreover, MI regional mechanics have been assessed over varying phases of the cardiac cycle, and thus, uniform conclusions regarding the material properties of the MI region can be difficult. This review assesses past studies that have performed in vivo measures of MI mechanics and attempts to provide coalescence on key points from these studies, as well as offer potential recommendations for unifying approaches in terms of regional post-MI mechanics. A uniform approach to biophysical measures of import will allow comparisons across studies, as well as provide a basis for potential therapeutic markers.

  5. Assessing the translatability of in vivo cardiotoxicity mechanisms to in vitro models using causal reasoning.

    Science.gov (United States)

    Enayetallah, Ahmed E; Puppala, Dinesh; Ziemek, Daniel; Fischer, James E; Kantesaria, Sheila; Pletcher, Mathew T

    2013-09-06

    Drug-induced cardiac toxicity has been implicated in 31% of drug withdrawals in the USA. The fact that the risk for cardiac-related adverse events goes undetected in preclinical studies for so many drugs underscores the need for better, more predictive in vitro safety screens to be deployed early in the drug discovery process. Unfortunately, many questions remain about the ability to accurately translate findings from simple cellular systems to the mechanisms that drive toxicity in the complex in vivo environment. In this study, we analyzed translatability of cardiotoxic effects for a diverse set of drugs from rodents to two different cell systems (rat heart tissue-derived cells (H9C2) and primary rat cardiomyocytes (RCM)) based on their transcriptional response. To unravel the altered pathway, we applied a novel computational systems biology approach, the Causal Reasoning Engine (CRE), to infer upstream molecular events causing the observed gene expression changes. By cross-referencing the cardiotoxicity annotations with the pathway analysis, we found evidence of mechanistic convergence towards common molecular mechanisms regardless of the cardiotoxic phenotype. We also experimentally verified two specific molecular hypotheses that translated well from in vivo to in vitro (Kruppel-like factor 4, KLF4 and Transforming growth factor beta 1, TGFB1) supporting the validity of the predictions of the computational pathway analysis. In conclusion, this work demonstrates the use of a novel systems biology approach to predict mechanisms of toxicity such as KLF4 and TGFB1 that translate from in vivo to in vitro. We also show that more complex in vitro models such as primary rat cardiomyocytes may not offer any advantage over simpler models such as immortalized H9C2 cells in terms of translatability to in vivo effects if we consider the right endpoints for the model. Further assessment and validation of the generated molecular hypotheses would greatly enhance our ability to

  6. In vivo comparison of hip mechanics for minimally invasive versus traditional total hip arthroplasty.

    Science.gov (United States)

    Glaser, Diana; Dennis, Douglas A; Komistek, Richard D; Miner, Todd M

    2008-02-01

    Minimally invasive surgery has been developed to reduce incision length, muscle damage, and rehabilitation time. However, reduced exposure of anatomical landmarks may result in technical errors and inferior implant survivorship. The objective of this study was to compare in vivo motions and hip joint contact forces during gait in total hip arthroplasty subjects, performed with either minimally invasive surgery or standard surgical approaches. Fifteen subjects implanted using either minimally invasive surgery anterolateral, minimally invasive surgery posterolateral, or traditional posterolateral total hip arthroplasty were evaluated using fluoroscopy while performing gait on a treadmill. Kinematics, obtained using 3D-to-2D image registration technique, were input as temporal functions in a 3D inverse dynamic mathematical model that determines in vivo soft tissue and hip contact forces. The subjects implanted with posterolateral and anterolateral minimally invasive surgery demonstrated significantly less separation than those implanted with the traditional approach (P<0.01). The minimally invasive surgery subjects also experienced lower average maximum peak forces, with 3.2 body weight for the anterolateral minimally invasive surgery and 2.9 body weight for the posterolateral minimally invasive surgery subjects, compared to 3.5 body weight for the traditional subjects (P=0.02 and P=0.03, respectively). This is the first study to compare in vivo weight-bearing kinematics, separation and kinetics for traditional, anterolateral minimally invasive surgery and posterolateral minimally invasive surgery total hip arthroplasty subject groups. Our data indicated in all analyzed parameters differences between the minimally invasive surgery and the traditional groups, with favorable results for the minimally invasive surgery subjects. This may be related, to a reduction in stabilizing soft tissues after a minimally invasive surgery procedure, leading to lower bearing surface

  7. Imatinib inhibits vascular smooth muscle proteoglycan synthesis and reduces LDL binding in vitro and aortic lipid deposition in vivo

    Science.gov (United States)

    Ballinger, Mandy L; Osman, Narin; Hashimura, Kazuhiko; de Haan, Judy B; Jandeleit-Dahm, Karin; Allen, Terri; Tannock, Lisa R; Rutledge, John C; Little, Peter J

    2010-01-01

    Abstract The ‘response to retention’ hypothesis of atherogenesis proposes that proteoglycans bind and retain low-density lipoproteins (LDL) in the vessel wall. Platelet-derived growth factor (PDGF) is strongly implicated in atherosclerosis and stimulates proteoglycan synthesis. Here we investigated the action of the PDGF receptor inhibitor imatinib on PDGF-mediated proteoglycan biosynthesis in vitro, lipid deposition in the aortic wall in vivo and the carotid artery ex vivo. In human vSMCs, imatinib inhibited PDGF mediated 35S-SO4 incorporation into proteoglycans by 31% (P proteoglycans from PDGF stimulated cells in the presence of imatinib was approximately 2.5-fold higher than for PDGF treatment alone. In high fat fed ApoE−/– mice, imatinib reduced total lipid staining area by ∼31% (P proteoglycans and reduces LDL binding in vitro and in vivo and this effect is mediated via the PDGF receptor. These findings validate a novel mechanism to prevent cardiac disease. PMID:19754668

  8. Experimental Study on Oscillating Wing for Propulsor with Bending Mechanism Modeled on Caudal Muscle-Skeletal Structure of Tuna

    Science.gov (United States)

    Morikawa, Hirohisa; Nakao, Seitaroh; Kobayashi, Shun-Ichi

    The purpose of our study is to investigate the effect of the caudal fin behavior resulting from the caudal muscle-skeletal structure of tuna on the propulsive force. A propulsion system by tuna-like fin stroke using two air rubber artificial muscles and a multi-joint bending mechanism (a tuna-like bending mechanism) modeled on the antagonism muscles and the caudal skeletal structure of tuna was developed. In order to realize instructed oscillation of a wing, a method of continuous path follow-up control of a wing in water was discussed in regard to the control of the internal pressure of the artificial muscles. It was found that the optimum control method for the tuna-like bending mechanism was the pressure control of the artificial muscles with both feedforward and pressure feedback compensations. The propulsion performance on a deformable wing using the propulsion system was discussed.

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

    Directory of Open Access Journals (Sweden)

    Bipradas Roy

    2016-09-01

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

  10. Ultrasound investigation of vastus medialis oblique muscle architecture: an in vivo study.

    Science.gov (United States)

    Engelina, S; Antonios, T; Robertson, C J; Killingback, A; Adds, P J

    2014-10-01

    There is thought to be a link between vastus medialis oblique (VMO) architecture and patellofemoral pain syndrome (PFPS). Historical data are largely derived from older populations, whereas PFPS commonly affects younger populations. The aim of this study was to gather data on VMO architecture in young asymptomatic adults, to provide baseline values for comparison with symptomatic sufferers. VMO maximum fiber angle and insertion ratio were measured with ultrasound. The insertion ratio represents the proportion (%) of the patella which has the muscle fibers attaching to its medial border. Eighty knees from 40 healthy young subjects (18 males, 22 females, and age 20-30) were assessed. Individual Tegner scores were recorded to assess participants' level of physical activity. Results were compared with data in the literature for PFPS sufferers and normal older individuals. Mean fiber angle and insertion ratio were 56.6° and 57.8%, respectively. There was no significant difference between age groups. The insertion ratio was higher among females (61.2% F:53.6% M). There was some evidence of increased fiber angle and decreased insertion ratio with increased Tegner score. There was some overlap in fiber angle between healthy knees in this study and values reported elsewhere for pathological knees. VMO fiber angle and insertion ratio are not age-related. The overlap in fiber angle values between healthy and pathological knees suggests that the cause of PFPS is multifactorial. An individual's VMO architecture may be affected by their physical activity level, which could have important implications for PFPS. © 2014 Wiley Periodicals, Inc.

  11. Effects of real and sham whole-body mechanical vibration on spinal excitability at rest and during muscle contraction

    NARCIS (Netherlands)

    Hortobagyi, T.; Rider, P.; DeVita, P.

    2014-01-01

    We examined the effects of whole-body mechanical vibration (WBV) on indices of motoneuronal excitability at rest and during muscle contraction in healthy humans. Real and sham WBV at 30Hz had no effect on reflexes measured during muscle contraction. Real WBV at 30 and 50Hz depressed the H-reflex

  12. Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome.

    Directory of Open Access Journals (Sweden)

    Xianming Zhang

    Full Text Available It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS, but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS.Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB and abdominal muscle paralysis group (BIPAPAP. All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35-60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment.For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml and oxygenation index (293±36 vs. 226±31 mmHg, lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7 and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9 in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1.Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.

  13. Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome

    Science.gov (United States)

    Zhang, Xianming; Wu, Weiliang; Zhu, Yongcheng; Jiang, Ying; Du, Juan; Chen, Rongchang

    2016-01-01

    Objective It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. Methods Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB) and abdominal muscle paralysis group (BIPAPAP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. Results For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1). Conclusion Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury. PMID:26745868

  14. The mechanics of the in vivo infant and toddler trunk during respiratory physiotherapy.

    Science.gov (United States)

    Sandoz, Baptiste; Vajda, Emmanuel; Alonzo, François; Bruyère, Karine; Bermond, François

    2011-07-01

    The purpose of this study is to quantify the in vivo mechanical response of the child trunk under loading during physiotherapy treatments. Twenty-six children aged 45 days to 7 years (14 girls and 12 boys) took part in this study. The forces applied by the physiotherapist were recorded using a force-plate embedded in the manipulation table supporting the child. Two synchronized cameras filmed the scene in a calibrated environment. The displacement of reflective targets glued on the physiotherapist's hands was calculated using an automatic tracking procedure and the 3D reconstruction "Direct Linear Transformation" algorithm. The progression of physical parameters was evaluated according to the age of the child. They included force, displacement, normalized displacement, loading speed, displacement and normalized displacement at the maximum force, force at the maximum displacement, viscous criterion and effective stiffness. For all patients, the mean maximum displacement and load were 22 mm (SD 9 mm) and 240 N (SD 46 N) respectively. The force-displacement curves had shown the complexity of the in vivo behavior: four phases have been distinguished with cycles in respect with the respiratory phases. The increase in force always occurred before the increase in displacement. This study helps to understand the in vivo behavior of the child trunk subjected to repetitive non-injurious mechanical loading. Further analysis in other populations and with different therapeutic maneuvers would refine the results. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. [Regulation of vasomotor tone of small skeletal muscle veins by intrinsic mechanisms].

    Science.gov (United States)

    Szénási, Annamária; Dörnyei, Gabriella; Rácz, Anita; Debreczeni, Béla; Koller, Ákos

    2016-05-22

    In many developed countries the prevalence of venous disorders and its consequences are higher than that of arterial diseases. Thus it is very important to understand the exact physiological and pathophysiological function of small veins and their control mechanisms. Small veins and venules have an important role in the regulation of capillary fluid exchange, as well as return of the venous blood into the heart. However, there is only limited knowledge available regarding the role of local mechanisms controlling the vasomotor tone and diameter of small veins. In the last decade the authors focused on the elucidation of these mechanisms in isolated skeletal muscle venules of rats. Their results suggest that the tone of small veins is controlled by the integration of several mechanisms, activated by the intraluminal pressure and flow/wall shear stress, in addition to numerous local mediators synthesized and released from the smooth muscle and endothelium. These mechanisms are involved - in a complex manner - in the control of postcapillary resistance, thus regulation of tissue blood supply, venous return and consequently in the modulation of the cardiac output, as well.

  16. Mechanisms Explaining Muscle Fatigue and Muscle Pain in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a Review of Recent Findings.

    Science.gov (United States)

    Gerwyn, Morris; Maes, Michael

    2017-01-01

    Here, we review potential causes of muscle dysfunction seen in many patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) such as the effects of oxidative and nitrosative stress (O&NS) and mitochondrial impairments together with reduced heat shock protein production and a range of metabolic abnormalities. Several studies published in the last few years have highlighted the existence of chronic O&NS, inflammation, impaired mitochondrial function and reduced heat shock protein production in many patients with ME/CFS. These studies have also highlighted the detrimental effects of chronically elevated O&NS on muscle functions such as reducing the time to muscle fatigue during exercise and impairing muscle contractility. Mechanisms have also been revealed by which chronic O&NS and or impaired heat shock production may impair muscle repair following exercise and indeed the adaptive responses in the striated muscle to acute and chronic increases in physical activity. The presence of chronic O&NS, low-grade inflammation and impaired heat shock protein production may well explain the objective findings of increased muscle fatigue, impaired contractility and multiple dimensions of exercise intolerance in many patients with ME/CFS.

  17. Investigating in vivo airway wall mechanics during tidal breathing with optical coherence tomography

    Science.gov (United States)

    Robertson, Claire; Lee, Sang-Won; Ahn, Yeh-Chan; Mahon, Sari; Chen, Zhongping; Brenner, Matthew; George, Steven C.

    2011-10-01

    Optical coherence tomography (OCT) is a nondestructive imaging technique offering high temporal and spatial resolution, which makes it a natural choice for assessing tissue mechanical properties. We have developed methods to mechanically analyze the compliance of the rabbit trachea in vivo using tissue deformations induced by tidal breathing, offering a unique tool to assess the behavior of the airways during their normal function. Four-hundred images were acquired during tidal breathing with a custom-built endoscopic OCT system. The surface of the tissue was extracted from a set of these images via image processing algorithms, filtered with a bandpass filter set at respiration frequency to remove cardiac and probe motion, and compared to ventilatory pressure to calculate wall compliance. These algorithms were tested on elastic phantoms to establish reliability and reproducibility. The mean tracheal wall compliance (in five animals) was 1.3+/-0.3×10-5 (mm Pa)-1. Unlike previous work evaluating airway mechanics, this new method is applicable in vivo, noncontact, and loads the trachea in a physiological manner. The technique may have applications in assessing airway mechanics in diseases such as asthma that are characterized by significant airway remodeling.

  18. Striated Muscle Function, Regeneration, and Repair

    Science.gov (United States)

    Shadrin, I.Y.; Khodabukus, A.; Bursac, N.

    2016-01-01

    As the only striated muscle tissues in the body, skeletal and cardiac muscle share numerous structural and functional characteristics, while exhibiting vastly different size and regenerative potential. Healthy skeletal muscle harbors a robust regenerative response that becomes inadequate after large muscle loss or in degenerative pathologies and aging. In contrast, the mammalian heart loses its regenerative capacity shortly after birth, leaving it susceptible to permanent damage by acute injury or chronic disease. In this review, we compare and contrast the physiology and regenerative potential of native skeletal and cardiac muscles, mechanisms underlying striated muscle dysfunction, and bioengineering strategies to treat muscle disorders. We focus on different sources for cellular therapy, biomaterials to augment the endogenous regenerative response, and progress in engineering and application of mature striated muscle tissues in vitro and in vivo. Finally, we discuss the challenges and perspectives in translating muscle bioengineering strategies to clinical practice. PMID:27271751

  19. A comparative study of embedded and anesthetized zebrafish in vivo on myocardiac calcium oscillation and heart muscle contraction

    Directory of Open Access Journals (Sweden)

    Brian eMuntean

    2010-12-01

    Full Text Available The zebrafish (Danio rerio has been used as a model for studying vertebrate development in the cardiovascular system. In order to monitor heart contraction and cytosolic calcium oscillations, fish were either embedded in methylcellulose or anesthetized with tricaine. Using high-resolution differential interference contrast (DIC and calcium imaging microscopy, we here show that dopamine and verapamil alter calcium signaling and muscle contraction in anesthetized zebrafish, but not in embedded zebrafish. In anesthetized fish, dopamine increases the amplitude of cytosolic calcium oscillation with a subsequent increase in heart contraction, whereas verapamil decreases the frequency of calcium oscillation and heart rate. Interestingly, verapamil also increases myocardial contraction. Our data further indicate that verapamil can increase myocardial calcium sensitivity in anesthetized fish. Taken together, our data reinforce in vivo cardiac responses to dopamine and verapamil. Furthermore, effects of dopamine and verapamil on myocardial calcium and contraction are greater in anesthetized than embedded fish. We suggest that while the zebrafish is an excellent model for a cardiovascular imaging study, the cardio-pharmacological profiles are very different between anesthetized and embedded fish.

  20. A Comparative Study of Embedded and Anesthetized Zebrafish in vivo on Myocardiac Calcium Oscillation and Heart Muscle Contraction.

    Science.gov (United States)

    Muntean, Brian S; Horvat, Christine M; Behler, James H; Aboualaiwi, Wissam A; Nauli, Andromeda M; Williams, Frederick E; Nauli, Surya M

    2010-01-01

    The zebrafish (Danio rerio) has been used as a model for studying vertebrate development in the cardiovascular system. In order to monitor heart contraction and cytosolic calcium oscillations, fish were either embedded in methylcellulose or anesthetized with tricaine. Using high-resolution differential interference contrast and calcium imaging microscopy, we here show that dopamine and verapamil alter calcium signaling and muscle contraction in anesthetized zebrafish, but not in embedded zebrafish. In anesthetized fish, dopamine increases the amplitude of cytosolic calcium oscillation with a subsequent increase in heart contraction, whereas verapamil decreases the frequency of calcium oscillation and heart rate. Interestingly, verapamil also increases myocardial contraction. Our data further indicate that verapamil can increase myocardial calcium sensitivity in anesthetized fish. Taken together, our data reinforce in vivo cardiac responses to dopamine and verapamil. Furthermore, effects of dopamine and verapamil on myocardial calcium and contraction are greater in anesthetized than embedded fish. We suggest that while the zebrafish is an excellent model for a cardiovascular imaging study, the cardio-pharmacological profiles are very different between anesthetized and embedded fish.

  1. Balboa binds to pickpocket in vivo and is required for mechanical nociception in Drosophila larvae.

    Science.gov (United States)

    Mauthner, Stephanie E; Hwang, Richard Y; Lewis, Amanda H; Xiao, Qi; Tsubouchi, Asako; Wang, Yu; Honjo, Ken; Skene, J H Pate; Grandl, Jörg; Tracey, W Daniel

    2014-12-15

    The Drosophila gene pickpocket (ppk) encodes an ion channel subunit of the degenerin/epithelial sodium channel (DEG/ENaC) family. PPK is specifically expressed in nociceptive, class IV multidendritic (md) neurons and is functionally required for mechanical nociception responses. In this study, in a genome-wide genetic screen for other ion channel subunits required for mechanical nociception, we identify a gene that we name balboa (also known as CG8546, ppk26). Interestingly, the balboa locus encodes a DEG/ENaC ion channel subunit highly similar in amino acid sequence to PPK. Moreover, laser-capture isolation of RNA from larval neurons and microarray analyses reveal that balboa is also highly enriched in nociceptive neurons. The requirement for Balboa and PPK in mechanical nociception behaviors and their specific expression in larval nociceptors led us to hypothesize that these DEG/ENaC subunits form an ion channel complex in vivo. In nociceptive neurons, Balboa::GFP proteins distribute uniformly throughout dendrites but remarkably localize to discrete foci when ectopically expressed in other neuron subtypes (where PPK is not expressed). Indeed, ectopically coexpressing ppk transforms this punctate Balboa::GFP expression pattern to the uniform distribution observed in its native cell type. Furthermore, ppk-RNAi in class IV neurons alters the broad Balboa::GFP pattern to a punctate distribution. Interestingly, this interaction is mutually codependent as balboa-RNAi eliminates Venus::PPK from the sensory dendrites of nociceptors. Finally, using a GFP-reconstitution approach in transgenic larvae, we directly detect in vivo physical interactions among PPK and Balboa subunits. Combined, our results indicate a critical mechanical nociception function for heteromeric PPK and Balboa channels in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.

    Science.gov (United States)

    Kang, Changkeun; Lee, Hyunkyoung; Jung, Eun-Sun; Seyedian, Ramin; Jo, MiNa; Kim, Jehein; Kim, Jong-Shu; Kim, Euikyung

    2012-12-15

    Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Tumor response to radiotherapy is dependent on genotype-associated mechanisms in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Williams Jerry R

    2010-08-01

    Full Text Available Abstract Background We have previously shown that in vitro radiosensitivity of human tumor cells segregate non-randomly into a limited number of groups. Each group associates with a specific genotype. However we have also shown that abrogation of a single gene (p21 in a human tumor cell unexpectedly sensitized xenograft tumors comprised of these cells to radiotherapy while not affecting in vitro cellular radiosensitivity. Therefore in vitro assays alone cannot predict tumor response to radiotherapy. In the current work, we measure in vitro radiosensitivity and in vivo response of their xenograft tumors in a series of human tumor lines that represent the range of radiosensitivity observed in human tumor cells. We also measure response of their xenograft tumors to different radiotherapy protocols. We reduce these data into a simple analytical structure that defines the relationship between tumor response and total dose based on two coefficients that are specific to tumor cell genotype, fraction size and total dose. Methods We assayed in vitro survival patterns in eight tumor cell lines that vary in cellular radiosensitivity and genotype. We also measured response of their xenograft tumors to four radiotherapy protocols: 8 × 2 Gy; 2 × 5Gy, 1 × 7.5 Gy and 1 × 15 Gy. We analyze these data to derive coefficients that describe both in vitro and in vivo responses. Results Response of xenografts comprised of human tumor cells to different radiotherapy protocols can be reduced to only two coefficients that represent 1 total cells killed as measured in vitro 2 additional response in vivo not predicted by cell killing. These coefficients segregate with specific genotypes including those most frequently observed in human tumors in the clinic. Coefficients that describe in vitro and in vivo mechanisms can predict tumor response to any radiation protocol based on tumor cell genotype, fraction-size and total dose. Conclusions We establish an analytical

  4. Large-scale Models Reveal the Two-component Mechanics of Striated Muscle

    Directory of Open Access Journals (Sweden)

    Robert Jarosch

    2008-12-01

    Full Text Available This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and α-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical “two-component model” of active muscle differentiated a “contractile component” which stretches the “series elastic component” during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit. Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation. Since each thin filament is anchored by four elastic α-actinin Z-filaments (provided with forceregulating sites for Ca2+ binding, the thin filament rotations change the torsional twist of the four Z-filaments as the “series elastic components”. Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments.

  5. Mechanism of action of honey bee (Apis mellifera L.) venom on different types of muscles.

    Science.gov (United States)

    Nabil, Z I; Hussein, A A; Zalat, S M; Rakha, M Kh

    1998-03-01

    1. The effect of crude honeybee (Apis mellifera) venom on the skeletal, smooth as well as cardiac muscles were studied in this investigation. 2. Perfusion of gastrocnemius-sciatic nerve preparation of frogs with 1 microgram/ml venom solution has weakened the mechanical contraction of the muscle without recovery. Blocking of nicotinic receptors with 3 micrograms/ml flaxedil before bee venom application sustained normal contraction of gastrocnemius muscle. 3. The electrical activity of duodenum rabbits was recorded before and after the application of 1 microgram/ml venom solution. The venom has depressed the amplitude of the muscle contraction after 15 min pretreatment with atropine nearly abolished the depressor effect of the venom on smooth muscle. 4. In concentrations from 0.5-2 micrograms/ml, bee venom caused decrease of heart rate of isolated perfused toad heart. This bradycardia was accompanied by elongation in the P-R interval. A gradual and progressive increase in the R-wave amplitude reflected a positive inotropism of the venom. Application of 5 micrograms/ml verapamil, a calcium channels blocking agent, abolished the noticed effect of the venom. 5. Marked electrocardiographic changes were produced within minutes of the venom application on the isolated perfused hearts, like marked injury current (elevation or depression of the S-T segment), atrioventricular conduction disturbances and sinus arrhythmias. Atropine and nicotine could decrease the toxic effect of the venom on the myocardium. 6. Results of the present work lead to the suggestion that bee venom is mediated through the peripheral cholinergic neurotransmitter system. General neurotoxicity of an inhibitory nature involving the autonomic as well as neuromuscular system are established as a result of the venom, meanwhile a direct effect on the myocardium membrane stabilization has been suggested.

  6. Mechanisms causing effects of muscle position on proximo-distal muscle force differences in extra-muscular myofascial force transmission.

    NARCIS (Netherlands)

    Yucesoy, C.A.; Maas, J.H.; Maas, Huub; Koopman, Hubertus F.J.M.; Grootenboer, H.J.; Huijing, P.A.J.B.M.

    2006-01-01

    Certain recent studies showed that extra-muscular myofascial force transmission affects the length–force characteristics of rat extensor digitorium longus (EDL) muscle significantly after distal or proximal lengthening. This suggested that the relative position of a muscle with respect to its

  7. Mechanically relevant consequences of the composite laminate-like design of the abdominal wall muscles and connective tissues.

    Science.gov (United States)

    Brown, Stephen H M

    2012-05-01

    Together, three abdominal wall muscles (external oblique, internal oblique and transversus abdominis) form a tightly bound muscular sheet that has been likened to a composite-laminate structure. Previous work has demonstrated the ability of force generated by these three muscles to be passed between one another through connective tissue linkages. Muscle fibres in each muscle are obliquely oriented with respect to its neighbouring muscles. It is proposed here is that this unique morphology of the abdominal wall muscles functions, through the application of constraining forces amongst the muscles, to increase force- and stiffness-generating capabilities. This paper presents a mathematical formulation of the stress-strain relationship for a transversely isotropic fibrous composite, and establishes a strengthening and stiffening effect when stress can be transferred between the fibrous layers. Application of empirical mechanical properties to this formulation demonstrates this effect for the abdominal wall muscles and, in greater proportion, for the anterior aponeurosis of the abdominal wall. This has implications for increasing the stiffness and passive load bearing ability of the abdominal wall muscles, and has the potential to modulate the whole muscle force-length and force-velocity relationships during contraction. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

  8. Mechanical characterization of the mouse diaphragm with optical coherence elastography reveals fibrosis-related change of direction-dependent muscle tissue stiffness

    Science.gov (United States)

    Wang, Shang; Loehr, James A.; Larina, Irina V.; Rodney, George G.; Larin, Kirill V.

    2016-03-01

    The diaphragm, composed of skeletal muscle, plays an important role in respiration through its dynamic contraction. Genetic and molecular studies of the biomechanics of mouse diaphragm can provide great insights into an improved understanding and potential treatment of the disorders that lead to diaphragm dysfunction (i.e. muscular dystrophy). However, due to the small tissue size, mechanical assessment of mouse diaphragm tissue under its proper physiological conditions has been challenging. Here, we present the application of noncontact optical coherence elastography (OCE) for quantitative elastic characterization of ex vivo mouse diaphragm. Phase-sensitive optical coherence tomography was combined with a focused air-puff system to capture and measure the elastic wave propagation from tissue surface. Experiments were performed on wildtype and dystrophic mouse diaphragm tissues containing different levels of fibrosis. The OCE measurements of elastic wave propagation were conducted along both the longitudinal and transverse axis of the muscle fibers. Cross-correlation of the temporal displacement profiles from different spatial locations was utilized to obtain the propagation time delay, which was used to calculate the wave group velocity and to further quantify the tissue Young's modulus. Prior to and after OCE assessment, peak tetanic force was measured to monitor viability of the tissue during the elasticity measurements. Our experimental results indicate a positive correlation between fibrosis level and tissue stiffness, suggesting this elastic-wave-based OCE method could be a useful tool to monitor mechanical properties of skeletal muscle under physiological and pathological conditions.

  9. Mecanismos de perda muscular da sarcopenia Mechanisms of muscle wasting in sarcopenia

    Directory of Open Access Journals (Sweden)

    Vivian de Oliveira Nunes Teixeira

    2012-04-01

    Full Text Available Cerca de 66% dos pacientes com artrite reumatoide (AR apresentam significativa perda de massa celular, denominada caquexia reumatoide, predominantemente de músculo esquelético (sarcopenia reumatoide. A sarcopenia é caracterizada por perda de massa muscular associada a prejuízos de função. Pacientes com AR apresentam uma redução significativa na força muscular, causada pela perda de proteínas musculares, alterando sua funcionalidade. As diversas condições que levam à perda de massa muscular envolvem distintas cascatas de sinalização intracelular, que podem levar: (i à morte celular programada (apoptose; (ii ao aumento da degradação proteica, por meio de autofagia, de proteases dependentes de cálcio (calpaínas e caspases e do sistema proteossomo; e (iii à diminuição da ativação das células-satélite responsáveis pela regeneração muscular. Este artigo tem como objetivo revisar esses mecanismos gerais de sarcopenia e seu envolvimento na AR. O melhor conhecimento desses mecanismos pode levar ao desenvolvimento de terapias inovadoras para essa debilitante complicação.Approximately 66% of the patients with rheumatoid arthritis (RA have significant loss of cell mass (rheumatoid cachexia, mainly of skeletal muscle (rheumatoid sarcopenia. Sarcopenia is defined as muscle wasting associated with functional impairment. Patients with RA possess significant reduction in muscle strength, caused by muscle protein wasting, and loss of functionality. Various conditions leading to muscle wasting involve different pathways of intracellular signaling that trigger: (i programmed cell death (apoptosis; (ii increased protein degradation through autophagy, calcium-dependent proteases (calpains and caspases, and proteasome system; (iii decreased satellite cell activation, responsible for muscle regeneration. This article aimed at reviewing these general mechanisms of sarcopenia and their involvement in RA. Greater knowledge of these

  10. Noninvasive In-Vivo Quantification of Mechanical Heterogeneity of Invasive Breast Carcinomas.

    Directory of Open Access Journals (Sweden)

    Tengxiao Liu

    Full Text Available Heterogeneity is a hallmark of cancer whether one considers the genotype of cancerous cells, the composition of their microenvironment, the distribution of blood and lymphatic microvasculature, or the spatial distribution of the desmoplastic reaction. It is logical to expect that this heterogeneity in tumor microenvironment will lead to spatial heterogeneity in its mechanical properties. In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging. By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors. Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous.

  11. Noninvasive In-Vivo Quantification of Mechanical Heterogeneity of Invasive Breast Carcinomas.

    Science.gov (United States)

    Liu, Tengxiao; Babaniyi, Olalekan A; Hall, Timothy J; Barbone, Paul E; Oberai, Assad A

    2015-01-01

    Heterogeneity is a hallmark of cancer whether one considers the genotype of cancerous cells, the composition of their microenvironment, the distribution of blood and lymphatic microvasculature, or the spatial distribution of the desmoplastic reaction. It is logical to expect that this heterogeneity in tumor microenvironment will lead to spatial heterogeneity in its mechanical properties. In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging. By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors. Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous.

  12. Entropy as a new measure of mechanical pain sensitivity in the masseter muscle

    DEFF Research Database (Denmark)

    Castrillon, Eduardo; Sato, Hitoshi; Tanosoto, Tomohiro

    be utilized to assess the homogeneity of mechanical sensitivity in a given muscle adding more information to simply the magnitude of sensitivity. AIM: To test whether experimental manipulation of mechanical pain sensitivity in the masseter muscle pain would influence measures of spatial characteristics (i.......e., entropy). Methods: Twenty healthy and pain-free subjects (10 women 25.2±4.0 and 10 men 26.5±3.2 years old) volunteered for this study. Pain levels were assessed on a 0-10 electronic visual analog scale (VAS) and the sensitivity to mechanical palpation was assessed at 15 sites (3 x 5) marked and equally...... included 3 time points of mechanical sensitivity assessments: baseline, 5 min after injection and 30 min after injection. ANOVAs were used to test for differences between sites, time, force, session and sex. 3 Results: VAS peak pain intensity was 8.2±1.5 for the glutamate and 2.5±3.1 for isotonic saline...

  13. Regulation of high mobility group box protein 1 expression following mechanical loading by orthodontic forces in vitro and in vivo

    National Research Council Canada - National Science Library

    Wolf, Michael; Lossdörfer, Stefan; Küpper, Katharina; Jäger, Andreas

    2014-01-01

    ...) cells challenged by mechanical loading similar to force levels being applied in orthodontic treatment in vitro and to transfer these findings to an in vivo microenvironment in an animal model of tooth movement in rats...

  14. Protective effects and mechanisms of curcumin on podophyllotoxin toxicity in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Li, Juan; Dai, Cai-Xia; Sun, Hua [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China); Jin, Lu [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China); State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203 (China); Guo, Chong-Yi; Cao, Wei; Wu, Jie; Tian, Hai-Yan [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China); Luo, Cheng [State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203 (China); Ye, Wen-Cai [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China); Jiang, Ren-Wang, E-mail: trwjiang@jnu.edu.cn [Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632 (China)

    2012-12-01

    Podophyllotoxin (POD) is a naturally occurring lignan with pronounced antineoplastic and antiviral properties. POD binds to tubulin and prevents the formation of mitotic spindle. Although cases of overdose or accidental ingestion are quite often, no specific therapy is currently available to treat the POD intoxication. In the current investigation, the protective effects and mechanisms of curcumin (CUR) on podophyllotoxin toxicity were evaluated in vitro and in vivo. The results showed that CUR could protect POD-induced cytotoxicity by recovering the G2/M arrest and decrease the changes of membrane potential and microtubule structure in Vero cells. A significant decrease of mortality rates was observed in Swiss mice treated by intragastrical administration of POD + CUR as compared with POD alone. The POD + CUR group also exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde level but elevated superoxide dismutase and glutathione levels as compared to the POD group. Histological examination of the liver and kidney demonstrated less morphological changes in the treatment of POD + CUR as compared with POD alone. The mechanism of the protective effects might be due to the competitive binding of CUR with POD in the same colchicines binding site as revealed by the tubulin polymerization assay and the molecular docking analysis, and the antioxidant activity against the oxidative stress induced by POD. In summary, both in vitro and in vivo data indicated the promising role of CUR as a protective agent against the POD poisoning. Highlights: ► A potential antidote to treat the podophyllotoxin (POD) intoxication is found. ► Curcumin showed promising effects against POD poisoning in vitro and in vivo. ► The mechanisms lie in the antioxidant activity and competitive binding with tubulin.

  15. Cancer cachexia causes skeletal muscle damage via transient receptor potential vanilloid 2-independent mechanisms, unlike muscular dystrophy.

    Science.gov (United States)

    Iwata, Yuko; Suzuki, Nobuyuki; Ohtake, Hitomi; Kamauchi, Shinya; Hashimoto, Naohiro; Kiyono, Tohru; Wakabayashi, Shigeo

    2016-06-01

    Muscle wasting during cancer cachexia contributes to patient morbidity. Cachexia-induced muscle damage may be understood by comparing its symptoms with those of other skeletal muscle diseases, but currently available data are limited. We modelled cancer cachexia in mice bearing Lewis lung carcinoma/colon adenocarcinoma and compared the associated muscle damage with that in a murine muscular dystrophy model (mdx mice). We measured biochemical and immunochemical parameters: amounts/localization of cytoskeletal proteins and/or Ca(2+) signalling proteins related to muscle function and abnormality. We analysed intracellular Ca(2+) mobilization and compared results between the two models. Involvement of Ca(2+)-permeable channel transient receptor potential vanilloid 2 (TRPV2) was examined by inoculating Lewis lung carcinoma cells into transgenic mice expressing dominant-negative TRPV2. Tumourigenesis caused loss of body and skeletal muscle weight and reduced muscle force and locomotor activity. Similar to mdx mice, cachexia muscles exhibited myolysis, reduced sarcolemmal sialic acid content, and enhanced lysosomal exocytosis and sarcolemmal localization of phosphorylated Ca(2+)/CaMKII. Abnormal autophagy and degradation of dystrophin also occurred. Unlike mdx muscles, cachexia muscles did not exhibit regeneration markers (centrally nucleated fibres), and levels of autophagic proteolytic pathway markers increased. While a slight accumulation of TRPV2 was observed in cachexia muscles, Ca(2+) influx via TRPV2 was not elevated in cachexia-associated myotubes, and the course of cachexia pathology was not ameliorated by dominant-negative inhibition of TRPV2. Thus, cancer cachexia may induce muscle damage through TRPV2-independent mechanisms distinct from those in muscular dystrophy; this may help treat patients with tumour-induced muscle wasting.

  16. Suppressive activities and mechanisms of ugonin J on vascular smooth muscle cells and balloon angioplasty-induced neointimal hyperplasia.

    Science.gov (United States)

    Pan, Chun-Hsu; Li, Pei-Chuan; Chien, Yi-Chung; Yeh, Wan-Ting; Liaw, Chih-Chuang; Sheu, Ming-Jyh; Wu, Chieh-Hsi

    2017-12-18

    Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell-cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry. Cell migration was examined using a wound-healing analysis and a transwell assay. Protein expressions and gelatinase activities were, respectively, measured using Western blot and gelatin zymography. Balloon angioplasty-induced neointimal formation was induced in a rat carotid artery model and then examined using immunohistochemical staining. Ugonin J induced cell-cycle arrest at the G0 /G1 phase and apoptosis to inhibit VSMC growth. Ugonin J also exhibited marked suppressive activity on VSMC migration. Ugonin J significantly reduced activations of focal adhesion kinase, phosphoinositide 3-kinase, v-akt murine thymoma viral oncogene homolog 1, and extracellular signal-regulated kinase 1/2 proteins. Moreover, ugonin J obviously reduced expressions and activity levels of matrix metalloproteinase-2 and matrix metalloproteinase-9. In vivo data indicated that ugonin J prevented balloon angioplasty-induced neointimal hyperplasia. Our study suggested that ugonin J has the potential for application in the prevention of balloon injury-induced neointimal formation. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Muscle lengthening surgery causes differential acute mechanical effects in both targeted and non-targeted synergistic muscles.

    Science.gov (United States)

    Ateş, Filiz; Özdeşlik, Rana N; Huijing, Peter A; Yucesoy, Can A

    2013-10-01

    Epimuscular myofascial force transmission (EMFT) is a major determinant of muscle force exerted, as well as length range of force exertion. Therefore, EMFT is of importance in remedial surgery performed, e.g., in spastic paresis. We aimed to test the following hypotheses: (1) muscle lengthening surgery (involving preparatory dissection (PD) and subsequent proximal aponeurotomy (AT)) affects the target muscle force exerted at its distal and proximal tendons differentially, (2) forces of non-operated synergistic muscles are affected as well, (3) PD causes some of these effects. In three conditions (control, post-PD, and post-AT exclusively on m. extensor digitorum longus (EDL)), forces exerted by rat anterior crural muscles were measured simultaneously. Our results confirm hypotheses (1-2), and hypothesis (3) in part: Reduction of EDL maximal force differed by location (i.e. 26.3% when tested distally and 44.5% when tested proximally). EDL length range of active force exertion increased only distally. Force reductions were shown also for non-operated tibialis anterior (by 11.9%), as well as for extensor hallucis longus (by 8.4%) muscles. In tibialis anterior only, part of the force reduction (4.9%) is attributable to PD. Due to EMFT, remedial surgery should be considered to have differential effects for targeted and non-targeted synergistic muscles. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice

    DEFF Research Database (Denmark)

    Fentz, Joachim; Kjøbsted, Rasmus; Birk, Jesper Bratz

    2015-01-01

    The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα mdK...

  19. Separating in vivo mechanical stimuli for postpneumonectomy compensation: imaging and ultrastructural assessment

    Science.gov (United States)

    Ravikumar, Priya; Yilmaz, Cuneyt; Bellotto, Dennis. J.; Dane, D. Merrill; Estrera, Aaron S.

    2013-01-01

    Following right pneumonectomy (PNX), the remaining lung expands and its perfusion more than doubles. Tissue and microvascular mechanical stresses are putative stimuli for compensatory lung growth and remodeling, but their relative contribution remains uncertain. To temporally separate expansion- and perfusion-related stimuli, we replaced the right lung of adult dogs with a customized inflated prosthesis. Four months later, the prosthesis was either acutely deflated (DEF) or kept inflated (INF). Thoracic high-resolution computed tomography (HRCT) was performed pre- and post-PNX before and after prosthesis deflation. Lungs were fixed for morphometric analysis ∼12 mo post-PNX. The INF prosthesis prevented mediastinal shift and lateral lung expansion while allowing the remaining lung to expand 27–38% via caudal elongation, associated with reversible capillary congestion in dependent regions at low inflation and 40–60% increases in the volumes of alveolar sepal cells, matrix, and fibers. Delayed prosthesis deflation led to further significant increases in lung volume, alveolar tissue volumes, and alveolar-capillary surface areas. At postmortem, alveolar tissue volumes were 33% higher in the DEF than the INF group. Lateral expansion explains ∼65% of the total post-PNX increase in left lung volume assessed in vivo or ex vivo, ∼36% of the increase in HRCT-derived (tissue + microvascular blood) volume, ∼45% of the increase in ex vivo septal extravascular tissue volume, and 60% of the increase in gas exchange surface areas. This partition agrees with independent physiological measurements obtained in these animals. We conclude that in vivo signals related to lung expansion and perfusion contribute separately and nearly equally to post-PNX growth and remodeling. PMID:23329819

  20. Effects of menthol on circular smooth muscle of human colon: analysis of the mechanism of action.

    Science.gov (United States)

    Amato, Antonella; Liotta, Rosa; Mulè, Flavia

    2014-10-05

    Menthol is the major constituent of peppermint oil, an herbal preparation commonly used to treat nausea, spasms during colonoscopy and irritable bowel disease. The mechanism responsible for its spasmolytic action remains unclear. The aims of this study were to investigate the effects induced by menthol on the human distal colon mechanical activity in vitro and to analyze the mechanism of action. The spontaneous or evoked-contractions of the circular smooth muscle were recorded using vertical organ bath. Menthol (0.1 mM-30 mM) reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. The inhibitory effect was not affected by 5-benzyloxytryptamine (1 μM), a transient receptor potential-melastatin8 channel antagonist, or tetrodotoxin (1 μM), a neural blocker, or 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (10 µM), inhibitor of nitric oxide (NO)-sensitive soluble guanylyl cyclase, or tetraethylammonium (10 mM), a blocker of potassium (K+)-channels. On the contrary, nifedipine (3 nM), a voltage-activated L-type Ca2+ channel blocker, significantly reduced the inhibitory menthol actions. Menthol also reduced in a concentration-dependent manner the contractile responses caused by exogenous application of Ca2+ (75-375 μM) in a Ca2+-free solution, or induced by potassium chloride (KCl; 40 mM). Moreover menthol (1-3 mM) strongly reduced the electrical field stimulation (EFS)-evoked atropine-sensitive contractions and the carbachol-contractile responses. The present results suggest that menthol induces spasmolytic effects in human colon circular muscle inhibiting directly the gastrointestinal smooth muscle contractility, through the block of Ca2+ influx through sarcolemma L-type Ca2+ channels. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Mechanism of soman-induced contractions in canine tracheal smooth muscle. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Adler, M.; Moore, D.H.; Filbert, M.G.

    1992-12-31

    The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine trachea smooth muscle in vitro. Concentrations of soman > or - 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman > or - 3 nM led to the appearance of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction. Tracheal smooth muscle, Cholinesterase inhibitors, Muscarinic receptor, Soman, Organophosphate.

  2. Alpha-smooth muscle actin in pathological human disc nucleus pulposus cells in vivo and in vitro.

    Science.gov (United States)

    Hastreiter, Dawn; Chao, Jeannie; Wang, Qi; Ozuna, Richard M; Spector, Myron

    2004-01-01

    That a contractile actin isoform has been found in cells of other cartilage tissues in healing and disease states prompted this investigation of the presence of alpha-smooth muscle actin (alpha-SMA) in pathological human intervertebral disc tissue. The presence of this isoform has been reported in human intervertebral disc specimens obtained at autopsy from subjects for whom there were no reported symptoms. An objective of this study was to evaluate the cell density and percentage of alpha-SMA-containing cells in pathological nucleus pulposus tissue obtained from lumbar disc surgery from 17 patients. Additionally, explants of nucleus pulposus material were cultured to determine how alpha-SMA expression changed with time in vitro. Seventy-six 5-mm diameter explants (approximately 2 mm thick) pooled from six lumbar surgeries were cultured for 1, 2, 4, or 6 weeks. Microtomed sections of paraffin-embedded specimens were stained with hematoxylin and eosin or a monoclonal antibody to alpha-SMA. Histologically, cells were categorized as to alpha-SMA phenotype (positive or negative), and the areal cell density was determined. The evaluation of the cultured nucleus pulposus explants also included documentation of the percentage of cells that were round or elongated and the percentage of the cells that were part of a group (group: >/= 2 cells). Every nucleus pulposus section exhibited the presence of alpha-SMA-containing cells, which accounted for approximately 24 percent of the cells in vivo. In vivo, the cell density was significantly higher in older individuals (p = 0.02). The average time for cell outgrowth from the explants was 8.6 days. Approximately 10-15 percent of the cells in the explants stained positive for alpha-SMA. The time in culture had no significant effect on any of the outcome measures except the percentage of alpha-SMA-containing cells that were round (p = 0.008), with values decreasing through 4 weeks and then slightly rising at 6 weeks. The role of

  3. Device for Investigation of Mechanical Tension of Isolated Smooth Muscle Vessels and Airway Segments of Animals

    Science.gov (United States)

    Aleinik, A.; Karpovich, N.; Turgunova, N.; Nosarev, A.

    2016-11-01

    For the purpose of testing and the search for new drug compounds, designed to heal many human diseases, it is necessary to investigate the deformation of experimental tissue samples under influence of these drugs. For this task a precision force sensor for measuring the mechanical tension, produced by isolated ring segments of blood vessels and airways was created. The hardware and software systems for the study of changes in contractile responses of the airway smooth muscles and blood vessels of experimental animals was developed.

  4. Mechanism to induce scoliosis in Duchenne muscular dystrophy; A study of paraspinal muscle by X-ray computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Noriaki; Fujimoto, Yasuyo (National Nishinara Hosital, Nara (Japan)); Takayanagi, Tetsuya; Mano, Yukio

    1992-09-01

    We studied the mechanism to induce scoliosis in Duchenne muscular dystrophy (DMD) by use of X-ray computed tomography (CT) of paraspinal muscles. CT examination of paraspinal muscles was performed on 15 DMD patients at the following six levels: (1) Th3 vertebrae (upper thoracic spine level); (2) Th6 vertebrae (middle thoracic spine level); (3) Th10 vertebrae (lower thoracic spine level); (4) L1 vertebrae (upper lumbar spine level); (5) L3 vertebrae (middle lumbar spine level); (6) L5 vertebrae (lower lumbar spine level). We evaluated the degeneration of paraspinal muscle by a decrese in ratio-density of the muscle which indicates infiltration of fatty tissue. The degeneration of the lateral portion of paraspinal muscle was more marked than that of the medial portion. The muscle was most severely affected at the middle lumbar spine level, showing a tendency to increase degeneration at the lower level of the spine. In cases showing laterality of the degeneration of paraspinal muscle, the less affected muscle on CT was located at the convex site of scoliosis. We speculate that the scoliosis occurs when DMD patients have asymmetrical paraspinal muscle degeneration, leading them to take compensatory posture. (author).

  5. Mechanisms of the nitroglycerine-induced vasodilation in vascular smooth muscles of the rabbit and pig.

    Science.gov (United States)

    Itoh, T; Kuriyama, H; Ueno, H

    1983-01-01

    The effects of nitroglycerine (NG) on the mechanical responses of small pieces of intact and skinned smooth muscles of the mesenteric artery, were investigated, as were the Ca fluxes of isolated smooth muscle cells of the coronary artery. NG (10(-6)-10(-5) M) inhibited both phasic and tonic components of the K-induced contraction; however, the tonic component was more sensitive to NG. The minimum concentration of NG required to decrease significantly the tonic response evoked by 39 mM-external K was 10(-8) M. NG (10(-5) M) reduced the number of oscillatory contractions evoked by 10(-5) M-noradrenaline (NAd). After complete removal of stored Ca, the addition of Ca did not produce contraction in polarized muscle (5.9 mM-external K), yet depolarized muscles (128 mM-external K) did contract. Addition of NG (10(-5) M) with Ca produced no change in the resting tone in polarized muscles but inhibited the contraction in depolarized muscles. After application of NG (10(-5) M), caffeine or NAd consistently produced smaller contraction in both polarized and depolarized muscles in Ca-free solution. NG (10(-5) M) inhibited the Na-free contraction evoked by prolonged treatment with Na-free solution. Contractions evoked by repetitive applications of 10(-5) M-NAd or 10 mM-caffeine persisted longer in Na-free, Ca-free (EGTA) solution than those observed in Ca-free Krebs solution, but when NG was added to the Na-free, Ca-free (EGTA) solution, the contractions ceased more rapidly than in the absence of NG. In chemically skinned muscles, 10(-5) M-NG had no effect on the pCa-tension relationship. The absolute amplitude of Ca-induced contraction was also not affected by 10(-5) M-NG. In these muscles, when the amount of stored Ca was estimated from the amplitude of the caffeine-induced contraction, Ca accumulation into and release from store sites were unaffected by 10(-5) M-NG. The effects of 10(-5) M-NG on the accumulation and efflux of 45Ca in isolated cell suspensions prepared from

  6. An experimental study on the impacts of inspiratory and expiratory muscles activities during mechanical ventilation in ARDS animal model

    Science.gov (United States)

    Zhang, Xianming; Du, Juan; Wu, Weiliang; Zhu, Yongcheng; Jiang, Ying; Chen, Rongchang

    2017-01-01

    In spite of intensive investigations, the role of spontaneous breathing (SB) activity in ARDS has not been well defined yet and little has been known about the different contribution of inspiratory or expiratory muscles activities during mechanical ventilation in patients with ARDS. In present study, oleic acid-induced beagle dogs’ ARDS models were employed and ventilated with the same level of mean airway pressure. Respiratory mechanics, lung volume, gas exchange and inflammatory cytokines were measured during mechanical ventilation, and lung injury was determined histologically. As a result, for the comparable ventilator setting, preserved inspiratory muscles activity groups resulted in higher end-expiratory lung volume (EELV) and oxygenation index. In addition, less lung damage scores and lower levels of system inflammatory cytokines were revealed after 8 h of ventilation. In comparison, preserved expiratory muscles activity groups resulted in lower EELV and oxygenation index. Moreover, higher lung injury scores and inflammatory cytokines levels were observed after 8 h of ventilation. Our findings suggest that the activity of inspiratory muscles has beneficial effects, whereas that of expiratory muscles exerts adverse effects during mechanical ventilation in ARDS animal model. Therefore, for mechanically ventilated patients with ARDS, the demands for deep sedation or paralysis might be replaced by the strategy of expiratory muscles paralysis through epidural anesthesia. PMID:28230150

  7. Relaxant effect of Curcuma longa on rat tracheal smooth muscle and its possible mechanisms.

    Science.gov (United States)

    Emami, Bahman; Shakeri, Farzaneh; Ghorani, Vahideh; Boskabady, Mohammad Hossein

    2017-12-01

    Turmeric is a spice obtained from the root of Curcuma longa L. (Zingiberaceae) with anti-aging, anticancer, anti-Alzheimer's disease, antioxidant and other medicinal properties. The relaxant effect of C. longa on rat tracheal smooth muscle and its possible mechanisms were investigated in this study. The relaxant effects of four cumulative concentrations of hydro-ethanol extract of C. longa (6.25, 12.5, 25, 50 mg/mL) were studied on tracheal smooth muscle precontracted by methacholine or KCl in non-incubated or incubated with different substances including propranolol, diltiazem, L-NAME, glibenclamide, atropine, chlorpheniramine, indomethacin and papaverine. The duration of the study was 84 days. In non-incubated tracheal smooth muscle, the extract of C. longa showed significant concentration-dependent relaxant effects (p longa and theophylline in both methacholine and KCl-induced contraction conditions. In tissues incubated with propranolol, diltiazem, L-NAME and glibenclamide on methacholine-induced contraction and in tissues incubated with atropine, chlorpheniramine, indomethacin and papaverine on KCl-induced contraction, the extract also showed significant concentration-dependent relaxant effects (p longa between non-incubated (16.22 ± 0.62) and incubated tissues (atropine: 13.03 ± 0.55, chlorpheniramine: 12.94 ± 0.68, indomethacin: 14.80 ± 0.57 and papaverine: 16.16 ± 1.42) were not significantly different. Tracheal smooth muscle relaxant effects of C. longa, were comparable to those of theophylline, which could be due to the presence of methylxanthines or its possible interaction with non-adrenergic non-cholinergic nervous system.

  8. Association of manual muscle tests and mechanical neck pain: results from a prospective pilot study.

    Science.gov (United States)

    Cuthbert, Scott C; Rosner, Anthony L; McDowall, Donald

    2011-04-01

    To determine whether there was a statistical difference for manual muscle test (MMT) findings for cervical muscles in subjects with and without mechanical neck pain (MNP), and to use confidence intervals to evaluate the sensitivity and specificity of the MMT in this group of subjects. Manual muscle strength tests were conducted on two groups of patients who reported to two outpatient chiropractic clinics. In group 1, 148 patients were evaluated for MMT data (50 males and 98 females, average age 37), 127 with "whiplash"-type injuries (average duration 16 weeks) and 21 with non-traumatic chronic neck pain (average duration 36 weeks). In group 2, 100 patients were evaluated for comparative MMT data (39 males and 61 females, average age 38) with no current MNP or remarkable history of MNP. Standardized MMT assessments of the strength of the sternocleidomastoid, anterior scalene, upper trapezius, and cervical extensor muscles bilaterally were performed on all subjects in groups 1 and 2. In group 1, 139 of 148 patients reporting neck pain also showed positive results in at least one of four MMT tests (sternocleidomastoid, anterior scalene, upper trapezius, and cervical extensors). In group 2, 30 of the 100 patients without MNP showed positive results in one or more of the four MMT tests. Confidence intervals were calculated and showed that, in terms of MMT findings, there was a significant difference between the two groups of patients. A symptomatic group of patients with MNP demonstrated significantly increased MMT findings in the form of reduced strength levels compared to a control group. This evidence suggests that the MMT is potentially a sensitive and specific test for evaluating cervical spine muscular impairments in patients with MNP. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. The Effect of Lateral Ankle Ligament Repair in Muscle Reaction Time in Patients with Mechanical Ankle Instability.

    Science.gov (United States)

    Li, H-Y; Zheng, J-J; Zhang, J; Hua, Y-H; Chen, S-Y

    2015-11-01

    Studies have shown that functional ankle instability can result in prolonged muscle reaction time. However, the deficit in muscle reaction time in patients with mechanical ankle instability (MAI) and the effect of lateral ankle ligament repair on muscle reaction time are unclear. The purpose of this study was to identify the deficit in muscle reaction time, and to evaluate the role of lateral ligament repair in improving muscle reaction time in MAI patients. Sixteen MAI patients diagnosed with lateral ankle ligament tears by ultrasonography and magnetic resonance imaging underwent arthroscopic debridement and open lateral ankle ligament repair with a modified Broström procedure. One day before the operation, reaction times of the tibialis anterior and peroneus longus muscles were recorded following sudden inversion perturbation while walking on a custom walkway, and anterior drawer test (ADT) and American Orthopaedic Foot and Ankle Society (AOFAS) scale score were evaluated. Six months postoperatively, muscle reaction time, ADT and AOFAS scale score were reevaluated, and muscle reaction times in 15 healthy controls were also recorded. Preoperatively, the affected ankles in the MAI group had significantly delayed tibialis anterior and peroneus longus muscles reaction times compared with controls. Six months after the operation, median AOFAS scale scores were significantly greater than preoperatively, and ADT was negative in the MAI group. However, the affected ankles in the MAI group showed no difference in muscle reaction time compared with preoperative values. MAI patients had prolonged muscle reaction time. The modified Broström procedure produced satisfactory clinical outcomes in MAI patients, but did not shorten reaction times of the tibialis anterior and peroneus longus muscles. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Divergent impact of Toll-like receptor 2 deficiency on repair mechanisms in healthy muscle versus Duchenne muscular dystrophy.

    Science.gov (United States)

    Mojumdar, Kamalika; Giordano, Christian; Lemaire, Christian; Liang, Feng; Divangahi, Maziar; Qureshi, Salman T; Petrof, Basil J

    2016-05-01

    Injury to skeletal muscle, whether acute or chronic, triggers macrophage-mediated innate immunity in a manner which can be either beneficial or harmful for subsequent repair. Endogenous ligands for Toll-like receptor 2 (TLR2) are released by damaged tissues and might play an important role in activating the innate immune system following muscle injury. To test this hypothesis, we compared macrophage behaviour and muscle repair mechanisms in mice lacking TLR2 under conditions of either acute (cardiotoxin-induced) or chronic (mdx mouse genetic model of Duchenne muscular dystrophy; DMD) muscle damage. In previously healthy muscle subjected to acute damage, TLR2 deficiency reduced macrophage numbers in the muscle post-injury but did not alter the expression pattern of the prototypical macrophage polarization markers iNOS and CD206. In addition, there was abnormal persistence of necrotic fibres and impaired regeneration in TLR2-/- muscles after acute injury. In contrast, TLR2 ablation in chronically diseased muscles of mdx mice not only resulted in significantly reduced macrophage numbers but additionally modified their phenotype by shifting from inflammatory (iNOS(pos) CD206(neg) ) to more anti-inflammatory (iNOS(neg) CD206(pos) ) characteristics. This decrease in macrophage-mediated inflammation was associated with ameliorated muscle histopathology and improved force-generating capacity of the dystrophic muscle. Our results suggest that the role of TLR2 in macrophage function and skeletal muscle repair depends greatly upon the muscle injury context, and raise the possibility that inhibition of TLR2 could serve as a useful therapeutic measure in DMD. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. Optical palpation in vivo: imaging human skin lesions using mechanical contrast

    Science.gov (United States)

    Es'haghian, Shaghayegh; Kennedy, Kelsey M.; Gong, Peijun; Sampson, David D.; McLaughlin, Robert A.; Kennedy, Brendan F.

    2015-01-01

    We demonstrate the first application of the recently proposed method of optical palpation to in vivo imaging of human skin. Optical palpation is a tactile imaging technique that probes the spatial variation of a sample's mechanical properties by producing an en face map of stress measured at the sample surface. This map is determined from the thickness of a translucent, compliant stress sensor placed between a loading element and the sample and is measured using optical coherence tomography. We assess the performance of optical palpation using a handheld imaging probe on skin-mimicking phantoms, and demonstrate its use on human skin lesions. Our results demonstrate the capacity of optical palpation to delineate the boundaries of lesions and to map the mechanical contrast between lesions and the surrounding normal skin.

  12. From single muscle fiber to whole muscle mechanics: a finite element model of a muscle bundle with fast and slow fibers.

    Science.gov (United States)

    Marcucci, Lorenzo; Reggiani, Carlo; Natali, Arturo N; Pavan, Piero G

    2017-12-01

    Muscles exhibit highly complex, multi-scale architecture with thousands of muscle fibers, each with different properties, interacting with each other and surrounding connective structures. Consequently, the results of single-fiber experiments are scarcely linked to the macroscopic or whole muscle behavior. This is especially true for human muscles where it would be important to understand of how skeletal muscles disorders affect patients' life. In this work, we developed a mathematical model to study how fast and slow muscle fibers, well characterized in single-fiber experiments, work and generate together force and displacement in muscle bundles. We characterized the parameters of a Hill-type model, using experimental data on fast and slow single human muscle fibers, and comparing experimental data with numerical simulations obtained from finite element (FE) models of single fibers. Then, we developed a FE model of a bundle of 19 fibers, based on an immunohistochemically stained cross section of human diaphragm and including the corresponding properties of each slow or fast fiber. Simulations of isotonic contractions of the bundle model allowed the generation of its apparent force-velocity relationship. Although close to the average of the force-velocity curves of fast and slow fibers, the bundle curve deviates substantially toward the fast fibers at low loads. We believe that the present model and the characterization of the force-velocity curve of a fiber bundle represents the starting point to link the single-fiber properties to those of whole muscle with FE application in phenomenological models of human muscles.

  13. Advancing In Vitro-In Vivo Extrapolations of Mechanism-Specific Toxicity Data Through Toxicokinetic Modeling.

    Science.gov (United States)

    Brinkmann, Markus; Preuss, Thomas G; Hollert, Henner

    International legislation, such as the European REACH regulation (registration, evaluation, authorization, and restriction of chemicals), mandates the assessment of potential risks of an ever-growing number of chemicals to the environment and human health. Although this legislation is considered one of the most important investments in consumer safety ever, the downside is that the current testing strategies within REACH rely on extensive animal testing. To address the ethical conflicts arising from these increased testing requirements, decision-makers, such as the European Chemicals Agency (ECHA), are committed to Russel and Burch's 3R principle (i.e., reduction, replacement, refinement) by demanding that animal experiments should be substituted with appropriate alternatives whenever possible. A potential solution of this dilemma might be the application of in vitro bioassays to estimate toxic effects using cells or cellular components instead of whole organisms. Although such assays are particularly useful to assess potential mechanisms of toxic action, scientists require appropriate methods to extrapolate results from the in vitro level to the situation in vivo. Toxicokinetic models are a straightforward means of bridging this gap. The present chapter describes different available options for in vitro-in vivo extrapolation (IVIVE) of mechanism-specific effects focused on fish species and also reviews the implications of confounding factors during the conduction of in vitro bioassays and their influence on the optimal choice of different dose metrics.

  14. Scapholunate ligament injury adversely alters in vivo wrist joint mechanics: an MRI-based modeling study.

    Science.gov (United States)

    Johnson, Joshua E; Lee, Phil; McIff, Terence E; Toby, E Bruce; Fischer, Kenneth J

    2013-09-01

    We investigated the effects of scapholunate ligament injury on in vivo radiocarpal joint mechanics using image-based surface contact modeling. Magnetic resonance images of 10 injured and contralateral normal wrists were acquired at high resolution (hand relaxed) and during functional grasp. Three-dimensional surface models of the radioscaphoid and radiolunate articulations were constructed from the relaxed images, and image registration between the relaxed and grasp images provided kinematics. The displacement driven models were implemented in contact modeling software. Contact parameters were determined from interpenetration of interacting bodies and a linear contact rule. Peak and mean contact pressures, contact forces and contact areas were compared between the normal and injured wrists. Also measured were effective (direct) contact areas and intercentroid distances from the grasp images. Means of the model contact areas were within 10 mm(2) of the direct contact areas for both articulations. With injury, all contact parameters significantly increased in the radioscaphoid articulation, while only peak contact pressure and contact force significantly increased in the radiolunate articulation. Intercentroid distances also increased significantly with injury. This study provides novel in vivo contact mechanics data from scapholunate ligament injury and confirms detrimental alterations as a result of injury. Copyright © 2013 Orthopaedic Research Society.

  15. Regional differences of energetics, mechanics, and kinetics of myosin cross-bridge in human ureter smooth muscle.

    Science.gov (United States)

    Vargiu, Romina; Perinu, Anna; Tintrup, Frank; Broccia, Francesca; Lisa, Antonello De

    2015-01-01

    This study provides information about baseline mechanical properties of the entire muscle and the molecular contractile mechanism in human ureter smooth muscle and proposed to investigate if changes in mechanical motor performance in different regions of isolated human ureter are attributable to differences in myosin crossbridge interactions. Classic mechanical, contraction and energetic parameters derived from the tension-velocity relationship were studied in ureteral smooth muscle strips oriented longitudinally and circularly from abdominal and pelvic human ureter parts. By applying of Huxley's mathematical model we calculated the total working crossbridge number per mm(2) (Ψ), elementary force per single crossbridge (Π0), duration of maximum rate constant of crossbridge attachment 1/f1 and detachment 1/g2 and peak mechanical efficiency (Eff.max). Abdominal longitudinal smooth muscle strips exhibited significantly higher maximum isometric tension and faster maximum unloaded shortening velocity compared to pelvic ones. Contractile differences were associated with significantly higher crossbridge number per mm(2). Abdominal longitudinal muscle strips showed a lower duration of maximum rate constant of crossbridge attachment and detachment and higher peak mechanical efficiency than pelvic ones. Such data suggest that the abdominal human ureter showed better mechanical motor performance mainly related to a higher crossbridge number and crossbridge kinetics differences. Such results were more evident in the longitudinal rather than in the circular layer.

  16. New methodology for mechanical characterization of human superficial facial tissue anisotropic behaviour in vivo.

    Science.gov (United States)

    Then, C; Stassen, B; Depta, K; Silber, G

    2017-07-01

    Mechanical characterization of human superficial facial tissue has important applications in biomedical science, computer assisted forensics, graphics, and consumer goods development. Specifically, the latter may include facial hair removal devices. Predictive accuracy of numerical models and their ability to elucidate biomechanically relevant questions depends on the acquisition of experimental data and mechanical tissue behavior representation. Anisotropic viscoelastic behavioral characterization of human facial tissue, deformed in vivo with finite strain, however, is sparse. Employing an experimental-numerical approach, a procedure is presented to evaluate multidirectional tensile properties of superficial tissue layers of the face in vivo. Specifically, in addition to stress relaxation, displacement-controlled multi-step ramp-and-hold protocols were performed to separate elastic from inelastic properties. For numerical representation, an anisotropic hyperelastic material model in conjunction with a time domain linear viscoelasticity formulation with Prony series was employed. Model parameters were inversely derived, employing finite element models, using multi-criteria optimization. The methodology provides insight into mechanical superficial facial tissue properties. Experimental data shows pronounced anisotropy, especially with large strain. The stress relaxation rate does not depend on the loading direction, but is strain-dependent. Preconditioning eliminates equilibrium hysteresis effects and leads to stress-strain repeatability. In the preconditioned state tissue stiffness and hysteresis insensitivity to strain rate in the applied range is evident. The employed material model fits the nonlinear anisotropic elastic results and the viscoelasticity model reasonably reproduces time-dependent results. Inversely deduced maximum anisotropic long-term shear modulus of linear elasticity is G∞,max(aniso)=2.43kPa and instantaneous initial shear modulus at an

  17. Ex vivo flexural mechanical properties of bovine bone plates after tibiae osteosynthesis in rabbits

    Directory of Open Access Journals (Sweden)

    Manuela Aleluia Drago

    2015-10-01

    Full Text Available ABSTRACT. Drago M.A., Drago M., Cerqueira H.D.B., Tiburcio M.F., Souza G.B., Barbosa D.H., Santos C.M.L., Silva R.V. & Freitas P.M.C. [Ex vivo flexural mechanical properties of bovine bone plates after tibiae osteosynthesis in rabbits.] Avaliação ex vivo das propriedades mecânicas em flexão de placas ósseas bovina na osteossíntese de tíbias de coelhos. Revista Brasileira de Medicina Veterinária, 37(3:245-249, 2015. Programa de Pós-Graduação em Ciências Veterinárias, Universidade Federal do Espírito Santo (UFES, Alto Universitário, s/nº, Bairro Guararema, Alegre, ES 29500-000, Brasil. E-mail: manudrago@hotmail.com The use of materials produced from bovine bone has been proposed in the manufacture of implants such as pins, plates and screws, due to their osteoinductive and osteoconductive properties or functions of bone graft. However, structural and mechanical aspects must be evaluated prior to the use, in vivo of bone implants. The aim of this study was to evaluate mechanical strength, through a mechanical bending test, of plates produced from bovine cortical bone, used to repair fractures of the tíbia of rabbits ex vivo. Twenty six plates were manufactured from bovine cortical bone and stored in saturated salt solution. Three study groups were used: group GP (n = 10, made up of the bone plates; GTP group (n = 16, rabbit tibia osteotomized and stabilized with bone plates and four screws and Group GT (n = 10, intact tibia. A three-point bending biomechanical test was used to determine the maximum tension, maximum deflection, and stiffness. The results were submitted to Kruskal-Wallis test (p <0.05 and the Dunn test. Comparing GT with the GTP, an 80% reduction was observed in maximum tension. Also noted was a reduction of 87% in maximum tension when comparing GP with GTP. Therefore, the bovine bone plate had a higher maximum tension then the intact rabbit tibia. There was a reduction of 52% in the rigidity of GTP to GT. No

  18. The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK Pathway and Increased Muscle Glut4 Content

    Directory of Open Access Journals (Sweden)

    Ali Benhaddou-Andaloussi

    2011-01-01

    Full Text Available The antidiabetic effect of N. sativa seed ethanol extract (NSE was assessed in Meriones shawi after development of diabetes. Meriones shawi were divided randomly into four groups: normal control, diabetic control, diabetic treated with NSE (2 g eq plant/kg or with metformin (300 mg/kg positive control, both administered by daily intragastric gavage for 4 weeks. Glycaemia and body weight were evaluated weekly. At study's end, an Oral Glucose Tolerance Test (OGTT was performed to estimate insulin sensitivity. Upon sacrifice, plasma lipid profile, insulin, leptin, and adiponectin levels were assessed. ACC phosphorylation and Glut4 protein content were determined in liver and skeletal muscle. NSE animals showed a progressive normalization of glycaemia, albeit slower than that of metformin controls. Moreover, NSE increased insulinemia and HDL-cholesterol, compared to diabetic controls. Leptin and adiponectin were unchanged. NSE treatment decreased OGTT and tended to decrease liver and muscle triglyceride content. NSE stimulated muscle and liver ACC phosphorylation and increased muscle Glut4. These results confirm NSE's previously reported hypoglycaemic and hypolipidemic activity. More significantly, our data demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation, a major component of the insulin-independent AMPK signaling pathway, and by enhancing muscle Glut4 expression.

  19. Strain rate effects on the mechanical properties and fracture mode of skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Shapiro, Michael; Tovar, Nick; Yoo, Daniel [Biomaterials and Biomimetics, New York University College of Dentistry (United States); Sobieraj, Micheal [Orthopedic Surgery, Hospital for Joint Diseases (United States); Gupta, Nikhil [Mechanical and Aerospace Engineering, NYU-Poly (United States); Branski, Ryan C. [Dept of Otolaryngology, New York University School of Medicine (United States); Coelho, Paulo G., E-mail: pc92@nyu.edu [Biomaterials and Biomimetics, New York University College of Dentistry (United States)

    2014-06-01

    The present study aimed to characterize the mechanical response of beagle sartorius muscle fibers under strain rates that increase logarithmically (0.1 mm/min, 1 mm/min and 10 mm/min), and provide an analysis of the fracture patterns of these tissues via scanning electron microscopy (SEM). Muscle tissue from dogs' sartorius was excised and test specimens were sectioned with a lancet into sections with nominal length, width, and thickness of 7, 2.5 and 0.6 mm, respectively. Trimming of the tissue was done so that the loading would be parallel to the direction of the muscle fiber. Samples were immediately tested following excision and failures were observed under the SEM. No statistically significant difference was observed in strength between the 0.1 mm/min (2.560 ± 0.37 MPa) and the 1 mm/min (2.702 ± 0.55 MPa) groups. However, the 10 mm/min group (1.545 ± 0.50 MPa) had a statistically significant lower strength than both the 1 mm/min group and the 0.1 mm/min group with p < 0.01 in both cases. At the 0.1 mm/min rate the primary fracture mechanism was that of a shear mode failure of the endomysium with a significant relative motion between fibers. At 1 mm/min this continues to be the predominant failure mode. At the 10 mm/min strain rate there is a significant change in the fracture pattern relative to other strain rates, where little to no evidence of endomysial shear failure nor of significant motion between fibers was detected.

  20. Effects of Contract-Relax, Static Stretching, and Isometric Contractions on Muscle-Tendon Mechanics.

    Science.gov (United States)

    Kay, Anthony D; Husbands-Beasley, Jade; Blazevich, Anthony J

    2015-10-01

    Loading characteristics of stretching techniques likely influence the specific mechanisms responsible for acute increases in range of motion (ROM). Therefore, the effects of a version of contract-relax (CR) proprioceptive neuromuscular facilitation stretching, static stretching (SS), and maximal isometric contraction (Iso) interventions were studied in 17 healthy human volunteers. Passive ankle moment was recorded on an isokinetic dynamometer, with EMG recording from the triceps surae, simultaneous real-time motion analysis, and ultrasound-imaging-recorded gastrocnemius medialis muscle and Achilles tendon elongation. Subjects then performed each intervention randomly on separate days before reassessment. Significant increases in dorsiflexion ROM (2.5°-5.3°; P stretching (P stretching and Iso (17.7%-22.1%; P 0.05), whereas significant reductions in muscle stiffness occurred after CR stretching and SS (16.0%-20.5%; P 0.05). Increases in peak passive moment (stretch tolerance) occurred after Iso (6.8%; P stretching (10.6%; P = 0.08), and SS (5.2%; P = 0.08); no difference in changes between conditions was found (P > 0.05). Significant correlations (rs = 0.69-0.82; P stretching suggest a broader adaptive response that likely explains its superior efficacy in acutely increasing ROM. Although mechanical changes appear tissue-specific between interventions, similar increases in stretch tolerance after all interventions are strongly correlated with changes in ROM.

  1. Exploratory factor analysis for differentiating sensory and mechanical variables related to muscle-tendon unit elongation

    Directory of Open Access Journals (Sweden)

    Mauro H. Chagas

    2016-01-01

    Full Text Available ABSTRACT Background Stretching exercises are able to promote adaptations in the muscle-tendon unit (MTU, which can be tested through physiological and biomechanical variables. Identifying the key variables in MTU adaptations is crucial to improvements in training. Objective To perform an exploratory factor analysis (EFA involving the variables often used to evaluate the response of the MTU to stretching exercises. Method Maximum joint range of motion (ROMMAX, ROM at first sensation of stretching (FSTROM, peak torque (torqueMAX, passive stiffness, normalized stiffness, passive energy, and normalized energy were investigated in 36 participants during passive knee extension on an isokinetic dynamometer. Stiffness and energy values were normalized by the muscle cross-sectional area and their passive mode assured by monitoring the EMG activity. Results EFA revealed two major factors that explained 89.68% of the total variance: 53.13% was explained by the variables torqueMAX, passive stiffness, normalized stiffness, passive energy, and normalized energy, whereas the remaining 36.55% was explained by the variables ROMMAX and FSTROM. Conclusion This result supports the literature wherein two main hypotheses (mechanical and sensory theories have been suggested to describe the adaptations of the MTU to stretching exercises. Contrary to some studies, in the present investigation torqueMAX was significantly correlated with the variables of the mechanical theory rather than those of the sensory theory. Therefore, a new approach was proposed to explain the behavior of the torqueMAX during stretching exercises.

  2. Oxidative Stress-Mediated Skeletal Muscle Degeneration: Molecules, Mechanisms, and Therapies

    Directory of Open Access Journals (Sweden)

    Min Hee Choi

    2016-01-01

    Full Text Available Oxidative stress is a loss of balance between the production of reactive oxygen species during cellular metabolism and the mechanisms that clear these species to maintain cellular redox homeostasis. Increased oxidative stress has been associated with muscular dystrophy, and many studies have proposed mechanisms that bridge these two pathological conditions at the molecular level. In this review, the evidence indicating a causal role of oxidative stress in the pathogenesis of various muscular dystrophies is revisited. In particular, the mediation of cellular redox status in dystrophic muscle by NF-κB pathway, autophagy, telomere shortening, and epigenetic regulation are discussed. Lastly, the current stance of targeting these pathways using antioxidant therapies in preclinical and clinical trials is examined.

  3. Quantified Mechanical Properties of the Deltoid Muscle Using the Shear Wave Elastography: Potential Implications for Reverse Shoulder Arthroplasty.

    Directory of Open Access Journals (Sweden)

    Taku Hatta

    Full Text Available The deltoid muscle plays a critical role in the biomechanics of shoulders undergoing reverse shoulder arthroplasty (RSA. However, both pre- and postoperative assessment of the deltoid muscle quality still remains challenging. The purposes of this study were to establish a novel methodology of shear wave elastography (SWE to quantify the mechanical properties of the deltoid muscle, and to investigate the reliability of this technique using cadaveric shoulders for the purpose of RSA. Eight fresh-frozen cadaveric shoulders were obtained. The deltoid muscles were divided into 5 segments (A1, A2, M, P1 and P2 according to the muscle fiber orientation and SWE values were measured for each segment. Intra- and inter-observer reliability was evaluated using intraclass correlation coefficient (ICC. To measure the response of muscle tension during RSA, the humeral shaft was osteotomized and subsequently elongated by an external fixator (intact to 15 mm elongation. SWE of the deltoid muscle was measured under each stretch condition. Intra- and inter-observer reliability of SWE measurements for all regions showed 0.761-0.963 and 0.718-0.947 for ICC(2,1. Especially, SWE measurements for segments A2 and M presented satisfactory repeatability. Elongated deltoid muscles by the external fixator showed a progressive increase in passive stiffness for all muscular segments. Especially, SWE outcomes of segments A2 and M reliably showed an exponential growth upon stretching (R2 = 0.558 and 0.593. Segmental measurements using SWE could be reliably and feasibly used to quantitatively assess the mechanical properties of the deltoid muscle, especially in the anterior and middle portions. This novel technique based on the anatomical features may provide helpful information of the deltoid muscle properties during treatment of RSA.

  4. A review of the relaxant effect of various medicinal plants on tracheal smooth muscle, their possible mechanism(s) and potency.

    Science.gov (United States)

    Shakeri, Farzaneh; Boskabady, Mohammad Hossein

    2015-12-04

    The therapeutic effects of the medicinal plants described in the current review on obstructive pulmonary diseases have found mention in ancient Iranian medical texts and in traditional folk medicine. These effects are attributed to their bronchodilatory activity, which relaxes the smooth muscles of the airway. Therefore, in the present review, the relaxant effects of various extracts, fractions and constituents of medicinal plants on tracheal smooth muscle are reviewed in light of their therapeutic effects on obstructive pulmonary diseases. The online literature was searched using Medline, PubMed, ScienceDirect, Scopus, Google Scholar, Web of Science and SID (for articles written in Persian). Moreover, local books on ethnopharmacology from 1918 to 2014 were searched with keywords such as tracheal smooth muscle, airway smooth muscle, relaxant effect, bronchodilatory effect and related mechanisms to identify studies on the relaxant effects of medicinal plants on tracheal smooth muscle and the possible mechanism(s) of these effects. All studied plants showed significant relaxant effects on tracheal smooth muscle, which were similar or superior to the effect of theophylline at the used concentrations. According to the results, most of these plants also showed an inhibitory effect on muscarinic and histamine (H1) receptors, whereas some plants showed more pronounced stimulatory effects on the beta-adrenergic receptor. Some of the studied plants also showed inhibitory effects on calcium and potassium channels. The present article reviewed the relaxant effects of several medicinal plants on tracheal smooth muscle, which were comparable or superior to the effect of theophylline at the studied concentration. The possible mechanisms of the relaxant effects of the studied medicinal plants and a comparison of these effects were also reviewed. This review presents the fractions and constituents of plants with potent relaxant effects on tracheal smooth muscle, which can be used

  5. Virtual Agonist-antagonist Mechanisms Produce Biological Muscle-like Functions: An Application for Robot Joint Control

    DEFF Research Database (Denmark)

    Xiong, Xiaofeng; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    or torque sensing systems; thereby capable of implementing the model on small legged robots driven by, e.g., standard servo motors. Thus, the VAAM minimizes hardware and reduces system complexity. From this point of view, the model opens up another way of simulating muscle behaviors on artificial machines......Purpose – Biological muscles of animals have a surprising variety of functions, i.e., struts, springs, and brakes. According to this, the purpose of this paper is to apply virtual agonist-antagonist mechanisms to robot joint control allowing for muscle-like functions and variably compliant joint...... motions. Design/methodology/approach – Each joint is driven by a pair of virtual agonist-antagonist mechanism (VAAM, i.e., passive components). The muscle-like functions as well as the variable joint compliance are simply achieved by tuning the damping coefficient of the VAAM. Findings – With the VAAM...

  6. Effects and Mechanisms of Metformin on the Proliferation of Esophageal Cancer Cells In Vitro and In Vivo.

    Science.gov (United States)

    Tang, Jian-Cai; An, Rui; Jiang, Yi-Qing; Yang, Jian

    2017-07-01

    The purpose of this study was to observe the effects of metformin on human esophageal cancer cell and to investigate its possible mechanisms. Cell viability was detected by using a Cell Counting Kit-8, while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo. Immunohistochemistry was determined based on the expression of PKM2 and Bim in tumor tissues. Tunnel was used to assess tumor cell apoptosis. Esophageal cancer cells viability was reduced after metformin treatment. The cell cycle was arrested in the G0/G1 phase, apoptosis was induced, caspase 3 was activated, caspase 9 was downregulated, and the pro-apoptotic protein Bim increased. Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2. Insulin-like growth factor 1 partly reversed metfromin-induced apoptosis and attenuated the repression effect of metfomin to PI3K, pAKT, and PKM2. Knockout PKM2 resulted in the activation of caspase 3, down-regulation of caspase 9, and increased expression of Bim. In the Eca109 xenograft model, metformin significantly reduced tumor growth. Furthermore, we found that metformin treatment increased the rate of apoptosis, down-regulation of PKM2, and up-regulation of Bim in tumor tissues. Metformin restrained esophageal cancer cell proliferation partly by suppressing the PI3K/AKT/mTOR pathway.

  7. Mechanics of the knee. A study of joint and muscle load with clinical applications.

    Science.gov (United States)

    Nisell, R

    1985-01-01

    The load moment of force about the knee joint during machine milking and when lifting a 12.8 kg box was quantified using a computerized static sagittal plane body model. Surface electromyography of quadriceps and hamstrings muscles was normalized and expressed as a percentage of an isometric maximum voluntary test contraction. Working with straight knees and the trunk flexed forwards induced extending knee load moments of maximum 55 Nm. Lifting the box with flexed knees gave flexing moments of 50 Nm at the beginning of the lift, irrespective of whether the burden was between or in front of the feet. During machine milking, a level difference between operator and cow of 0.70 m - 1.0 m significantly lowered the knee extending moments. To quantify the force magnitudes acting in the tibio-femoral and patello-femoral joints, a local biomechanical model of the knee was developed using a combination of cadaver knee dissections and lateral knee radiographs of healthy subjects. The moment arm of the knee extensor was significantly shorter for women than for men, which resulted in higher knee joint forces in women if the same moment was produced. A diagram for quantifying patellar forces was worked out. The force magnitudes given by the knee joint biomechanical model correlated well with experimentally forces measured by others. During the parallel squat in powerlifting, the maximum flexing knee load moment was estimated to 335-550 Nm when carrying a 382.5 kg burden and the in vivo force of a complete quadriceps tendon-muscle rupture to between 10,900 and 18,300 N. During isokinetic knee extension, the tibio-femoral compressive force reached peak magnitudes of 9 times body weight and the anteroposterior shear force was close to 1 body weight at knee angles straighter than 60 degrees, indicating that high forces stress the anterior cruciate ligament. A proximal resistance pad position decreased the shear force considerably, and this position is recommended in early

  8. Elite swimmers with and without unilateral shoulder pain: mechanical hyperalgesia and active/latent muscle trigger points in neck-shoulder muscles.

    Science.gov (United States)

    Hidalgo-Lozano, A; Fernández-de-las-Peñas, C; Calderón-Soto, C; Domingo-Camara, A; Madeleine, P; Arroyo-Morales, M

    2013-02-01

    Our aim was to investigate the presence of mechanical hypersensitivity and active trigger points (TrPs) in the neck-shoulder muscles in elite swimmers with/without unilateral shoulder pain. Seventeen elite swimmers with shoulder pain; 18 swimmers without shoulder pain; and 15 elite athletes matched controls were recruited. Pressure pain thresholds (PPT) were assessed over the levator scapulae, sternocleidomastoid, upper trapezius, infraspinatus, scalene, subscapularis and tibialis anterior muscles. TrPs in the levator scapulae, upper trapezius, infraspinatus, scalene, sternocleidomastoid and subscapularis muscles were also explored. Swimmers with shoulder pain showed significant lower PPT in all muscles compared with controls (Pactive; 2.6 ± 1.4 latent) and 4.7 ± 1.3 (1.3 ± 1.3 active; 3.4 ± 1.5 latent), whereas healthy athletes only showed latent TrPs (2.4 ± 1.2). Elite swimmers with shoulder pain showed higher number of active TrPs than swimmers without pain, whereas it was the opposite for the number of latent muscle TrP (Pactive TrPs play a role in the development of shoulder pain in elite swimmers. © 2011 John Wiley & Sons A/S.

  9. Significance of KATP channels, L-type Ca2+ channels and CYP450-4A enzymes in oxygen sensing in mouse cremaster muscle arterioles In vivo

    DEFF Research Database (Denmark)

    Ngo, Thuc Anh; Riemann, Mads; von Holstein-Rathlou, Niels-Henrik

    2013-01-01

    ATP-sensitive K⁺ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca²⁺ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance of these mec......ATP-sensitive K⁺ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca²⁺ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance...

  10. Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.

    Directory of Open Access Journals (Sweden)

    Matthew S Barnabei

    Full Text Available Duchenne muscular dystrophy (DMD is a progressive and fatal disease of muscle wasting caused by loss of the cytoskeletal protein dystrophin. In the heart, DMD results in progressive cardiomyopathy and dilation of the left ventricle through mechanisms that are not fully understood. Previous reports have shown that loss of dystrophin causes sarcolemmal instability and reduced mechanical compliance of isolated cardiac myocytes. To expand upon these findings, here we have subjected the left ventricles of dystrophin-deficient mdx hearts to mechanical stretch. Unexpectedly, isolated mdx hearts showed increased left ventricular (LV compliance compared to controls during stretch as LV volume was increased above normal end diastolic volume. During LV chamber distention, sarcomere lengths increased similarly in mdx and WT hearts despite greater excursions in volume of mdx hearts. This suggests that the mechanical properties of the intact heart cannot be modeled as a simple extrapolation of findings in single cardiac myocytes. To explain these findings, a model is proposed in which disruption of the dystrophin-glycoprotein complex perturbs cell-extracellular matrix contacts and promotes the apparent slippage of myocytes past each other during LV distension. In comparison, similar increases in LV compliance were obtained in isolated hearts from β-sarcoglycan-null and laminin-α(2 mutant mice, but not in dysferlin-null mice, suggesting that increased whole-organ compliance in mdx mice is a specific effect of disrupted cell-extracellular matrix contacts and not a general consequence of cardiomyopathy via membrane defect processes. Collectively, these findings suggest a novel and cell-death independent mechanism for the progressive pathological LV dilation that occurs in DMD.

  11. Mechanism and in vivo evaluation :photodynamic antibacterial chemotherapy of lysine-porphyrin conjugate

    Directory of Open Access Journals (Sweden)

    Zengping eXu

    2016-03-01

    Full Text Available We previously reported lysine-porphyrin conjugate 4i, which had potent photosensitive antibacterial effect on clinical isolated Methicillin-resistant Staphylococcus aureus (MRSA, Escherichia coli (E. coli and Pseudomonas aeruginosa (P. aeruginosa bacterial strains. The aim of this paper is to evaluate the mechanism of photodynamic antibacterial chemotherapy of 4i (4i-PACT in vitro and the treatment effect in vivo. Atomic force microscopy (AFM revealed 4i-PACT could effectively destroy bacterial membrane and wall, making the bacterial content leakage, which was confirmed by dual fluorescent staining with acridine orange/ethidium bromide (AO/EB and absorbance at 260 nm, agarose gel electrophoresis indicated 4i-PACT could damage genomic DNA. The results combined AFM and DNA electrophoresis revealed why the bacterial strains had no resistance to 4i-PACT. Wound healing in rat model with mixed bacteria infected wounds showed the efficiency of 4i-PACT was light-dose dependent. These results showed 4i-PACT had promising bactericidal effect both in vitro and in vivo.

  12. A method to determine the mechanical properties of the retina based on an experiment in vivo.

    Science.gov (United States)

    Qian, Xiuqing; Zhang, Kunya; Liu, Zhicheng

    2015-01-01

    A method is proposed to determine the mechanical properties of retina based on in vivo experiments and numerical simulations. First, saline water was injected into the anterior chamber of the right eye of a cat to cause acute high intraocular pressure. After the eye was scanned using optical coherence tomography under different acute high intraocular pressures, the images of the retina in vivo were obtained and the thickness of the retina was calculated. Then, the three-dimensional structure of the optic nerve head including the retina and the choroid were reconstructed using image processing technology. Three different material models for the retina and the choroid were taken and the finite element models of the optic nerve head were constructed. Finally, an inverse method was proposed to determine the parameters of a constitutive model of the retina and of the choroid simultaneously. The results showed that the deformation of the retina can be properly simulated taking into consideration the nonlinear elastic properties of the retina and of the choroid.

  13. Mechanically corrected EMG for the continuous estimation of erector spinae muscle loading during repetitive lifting.

    Science.gov (United States)

    Potvin, J R; Norman, R W; McGill, S M

    1996-01-01

    Few studies have been carried out on the changes in biomechanical loading on low-back tissues during prolonged lifting. The purpose of this paper was to develop a model for continuously estimating erector spinae muscle loads during repetitive lifting and lowering tasks. The model was based on spine kinematics and bilateral lumbar and thoracic erector spinae electromyogram (EMG) signals and was developed with the data from eight male subjects. Each subject performed a series of isometric contractions to develop extensor moments about the low back. Maximum voluntary contractions (MVCs) were used to normalize all recorded EMG and moment time-histories. Ramp contractions were used to determine the non-linear relationship between extensor moments and EMG amplitudes. In addition, the most appropriate low-pass filter cut-off frequencies were calculated for matching the rectified EMG signals with the moment patterns. The mean low-pass cut-off frequency was 2.7 (0.4) Hz. The accuracy of the non-linear EMG-based estimates of isometric extensor moment were tested with data from a series of six rapid contractions by each subject. The mean error over the duration of these contractions was 9.2 (2.6)% MVC. During prolonged lifting sessions of 20 min and of 2 h, a model was used to calculate changes in muscle length based on monitored spine kinematics. EMG signals were first processed according to the parameters determined from the isometric contractions and then further processed to account for the effects of instantaneous muscle length and velocity. Simple EMG estimates were found to underestimate peak loading by 9.1 (4.0) and 25.7 (11.6)% MVC for eccentric and concentric phases of lifting respectively, when compared to load estimates based on the mechanically corrected EMG. To date, the model has been used to analyze over 5300 lifts.

  14. Hormonal and neuromuscular responses to mechanical vibration applied to upper extremity muscles.

    Directory of Open Access Journals (Sweden)

    Riccardo Di Giminiani

    Full Text Available OBJECTIVE: To investigate the acute residual hormonal and neuromuscular responses exhibited following a single session of mechanical vibration applied to the upper extremities among different acceleration loads. METHODS: Thirty male students were randomly assigned to a high vibration group (HVG, a low vibration group (LVG, or a control group (CG. A randomized double-blind, controlled-parallel study design was employed. The measurements and interventions were performed at the Laboratory of Biomechanics of the University of L'Aquila. The HVG and LVG participants were exposed to a series of 20 trials ×10 s of synchronous whole-body vibration (WBV with a 10-s pause between each trial and a 4-min pause after the first 10 trials. The CG participants assumed an isometric push-up position without WBV. The outcome measures were growth hormone (GH, testosterone, maximal voluntary isometric contraction during bench-press, maximal voluntary isometric contraction during handgrip, and electromyography root-mean-square (EMGrms muscle activity (pectoralis major [PM], triceps brachii [TB], anterior deltoid [DE], and flexor carpi radialis [FCR]. RESULTS: The GH increased significantly over time only in the HVG (P = 0.003. Additionally, the testosterone levels changed significantly over time in the LVG (P = 0.011 and the HVG (P = 0.001. MVC during bench press decreased significantly in the LVG (P = 0.001 and the HVG (P = 0.002. In the HVG, the EMGrms decreased significantly in the TB (P = 0.006 muscle. In the LVG, the EMGrms decreased significantly in the DE (P = 0.009 and FCR (P = 0.006 muscles. CONCLUSION: Synchronous WBV acutely increased GH and testosterone serum concentrations and decreased the MVC and their respective maximal EMGrms activities, which indicated a possible central fatigue effect. Interestingly, only the GH response was dependent on the acceleration with respect to the subjects' responsiveness.

  15. Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism In Vivo.

    Science.gov (United States)

    Dong, Ze-Xi; Shi, Zhi-Hao; Li, Nian-Guang; Zhang, Wei; Gu, Ting; Zhang, Peng-Xuan; Wu, Wen-Yu; Tang, Yu-Ping; Fang, Fang; Xue, Xin; Li, He-Min; Cheng, Hai-Bo; Yang, Jian-Ping; Duan, Jin-Ao

    2016-06-01

    Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2 O2 -induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment. © 2016 John Wiley & Sons A/S.

  16. Mechanical properties and in vivo study of modified-hydroxyapatite/polyetheretherketone biocomposites.

    Science.gov (United States)

    Ma, Rui; Li, Qiankuan; Wang, Lin; Zhang, Xianghua; Fang, Lin; Luo, Zhongkuan; Xue, Bai; Ma, Lei

    2017-04-01

    Polyether ether ketone (PEEK) has received much attention for its excellent mechanical properties and biocompatibility. Here, the silane coupling agent KH560 [γ-(2,3-epoxypropoxy)propyltrimethoxysilane] is used for graft modification of bioactive HA (hydroxyapatite) particles and for preparing HA/PEEK composites via a hot-press molding method. The prepared HA/PEEK composites were tested for their mechanical properties with SEM (scanning electron microscopy), infrared spectroscopy, and thermo-analysis. The results show that silane coupling KH-560 modifies HA successfully and that the tensile strengths of HA/PEEK and m-HA/PEEK composites indicate an increasing and then a decreasing tendency with increasing HA contents. The non-modified HA/PEEK composites display the same trend as the modified specimens with lower tensile strength and consist of sharp points. When the HA content is 5wt.%, the tensile strength of m-HA/PEEK composite reaches its maximum, which is 23% higher than that of pure PEEK specimens. The in vivo experiments of m-HA/PEEK used a biomechanical push-out test, SEM, optical microscopy, and an Image-Pro Express C image analysis system. The growth of the bone tissues around the m-HA/PEEK composites with an HA content of 5wt.% is better than that of specimens with different HA contents. This finding shows the nano-scale effect of the bioactive filler HA in PEEK substrates, which obviously contributes to the growth of the surrounding bone issues in vivo. This study could provide theoretical support for the further promotion and application of high-performance engineering plastics such as PEEK in biomedical fields. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Alterations in Muscle Mass and Contractile Phenotype in Response to Unloading Models: Role of Transcriptional/Pretranslational Mechanisms

    Directory of Open Access Journals (Sweden)

    Kenneth M Baldwin

    2013-10-01

    Full Text Available Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a muscle unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s. Hence, this review will examine findings from three different animal models of unloading: 1 space flight (SF, i.e., microgravity; 2 hindlimb suspension (HS, a procedure that chronically eliminates weight bearing of the lower limbs; and 3 spinal cord isolation (SI, a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: 1 all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; 2 transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and 3 signaling pathways impacting these alterations appear to be similar in each of the models

  18. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice

    KAUST Repository

    Chatel, Benjamin

    2017-03-03

    The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1(+/-) mice). Twenty-four MCT1(+/-) and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1(+/-) mice had lower MCT1 (-61%; P < 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1(+/-) mice at rest (P < 0.001), the mice showed higher acidosis during the first minute of exercise (P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1(+/-) mice had higher specific peak (P < 0.05) and maximum tetanic (P < 0.01) forces and lower fatigability (P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1(+/-) mice remain unexplained.-Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    effects against muscle fatigue and ultrastructural damages, preventing or reducing the loss in mechanical muscle function after running. Subjects were tested before and after IERT protocol for maximal isometric, concentric and eccentric isokinetic knee extensor strength (60° and 180° s(-1)). In a second...... = 8). The effects of acute running-induced fatigue and training on isokinetic and isometric peak torque, and rate of force development (RFD) were investigated. Before IERT, running-induced eccentric torque loss at 180° s(-1) was -8 %, and RFD loss was -11 %. Longitudinal IERT led to reduced or absent...... acute running-induced losses in maximal IERT torque at 180° s(-1) (+2 %), being significantly reduced compared to before IERT (p  0.05). In conclusion, IERT yields a reduced strength loss after high-intensity running workouts, which may suggest a protective effect against fatigue and/or morphological...

  20. Mahanine enhances the glucose-lowering mechanisms in skeletal muscle and adipocyte cells.

    Science.gov (United States)

    Nooron, Nattakarn; Athipornchai, Anan; Suksamrarn, Apichart; Chiabchalard, Anchalee

    2017-12-09

    Insulin resistance is a major defect underlying type 2 diabetes development. Skeletal muscle tissue and adipocyte tissue are the major sites of postprandial glucose disposal, and enhancing glucose uptake into this tissue may decrease insulin resistance in type 2 diabetes patients. Mahanine (3,11-dihydro-3,5-dimethyl-3-(4-methyl-3-pentenyl)pyrano[3,2-a]carbazol-9-ol) has been reported to be a major bioactive carbazole alkaloid that has many biological activities including antitumor, anti-inflammatory, antioxidant and anti-diabetic activities. However, the molecular mechanism and signaling pathways mediating the anti-diabetic effects of mahanine require further investigation. Therefore, the aim of this study was to investigate the effects of mahanine, a carbazole alkaloid from Murraya koenigii, on glucose uptake and glucose transporter 4 (GLUT4) translocation in skeletal muscle and adipocyte cells. Mahanine treatment promoted a dose dependent increased in glucose uptake in L6 myotubes and adipocyte cells via activation of the Akt signaling pathway. Mahanine induced Akt-activation was reversed by co-treatment with wortmannin, an Akt inhibitor. Moreover, it was found that mahanine significantly enhanced GLUT4 translocation to the plasma membrane in L6 myotubes. These results suggest that increased activation of the Akt signaling pathway lead to increased plasma membrane GLUT4 content and increased glucose uptake. These data strongly suggest that mahanine has anti-diabetic potential for treating diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Mechanisms Underlying the Onset of Oral Lipid–Induced Skeletal Muscle Insulin Resistance in Humans

    Science.gov (United States)

    Nowotny, Bettina; Zahiragic, Lejla; Krog, Dorothea; Nowotny, Peter J.; Herder, Christian; Carstensen, Maren; Yoshimura, Toru; Szendroedi, Julia; Phielix, Esther; Schadewaldt, Peter; Schloot, Nanette C.; Shulman, Gerald I.; Roden, Michael

    2013-01-01

    Several mechanisms, such as innate immune responses via Toll-like receptor-4, accumulation of diacylglycerols (DAG)/ceramides, and activation of protein kinase C (PKC), are considered to underlie skeletal muscle insulin resistance. In this study, we examined initial events occurring during the onset of insulin resistance upon oral high-fat loading compared with lipid and low-dose endotoxin infusion. Sixteen lean insulin-sensitive volunteers received intravenous fat (iv fat), oral fat (po fat), intravenous endotoxin (lipopolysaccharide [LPS]), and intravenous glycerol as control. After 6 h, whole-body insulin sensitivity was reduced by iv fat, po fat, and LPS to 60, 67, and 48%, respectively (all P insulin sensitivity was unaffected. Muscle PKCθ activation increased by 50% after iv and po fat, membrane Di-C18:2 DAG species doubled after iv fat and correlated with PKCθ activation after po fat, whereas ceramides were unchanged. Only after LPS, circulating inflammatory markers (tumor necrosis factor-α, interleukin-6, and interleukin-1 receptor antagonist), their mRNA expression in subcutaneous adipose tissue, and circulating cortisol were elevated. Po fat ingestion rapidly induces insulin resistance by reducing nonoxidative glucose disposal, which associates with PKCθ activation and a rise in distinct myocellular membrane DAG, while endotoxin-induced insulin resistance is exclusively associated with stimulation of inflammatory pathways. PMID:23454694

  2. Effects of mechanical properties of muscle and tendon on performance in long distance runners.

    Science.gov (United States)

    Kubo, Keitaro; Tabata, Tomonori; Ikebukuro, Toshihiro; Igarashi, Katsumi; Yata, Hideaki; Tsunoda, Naoya

    2010-10-01

    The purpose of this study was to investigate the mechanical properties of muscle and tendon in long distance runners and their relations to running performance. Fifteen long distance runners (LDR) and 21 untrained subjects (CON) participated in this study. Muscle strength and activation level of knee extensors and plantar flexors were measured. Tendon elongation was determined using ultrasonography, while subjects performed ramp isometric knee extension and plantar flexion up to the voluntary maximum. Relative MVC (to body mass) of LDR was significantly lower than that of CON for knee extensors, but not for plantar flexors. No significant difference in the neural activation levels was found between LDR and CON for both sites. Maximal tendon elongation of LDR was significantly lower than that of CON for knee extensors, but not for plantar flexors. Furthermore, faster running time in a 5,000 m race (best official record of LDR) was associated with lower tendon stiffness for both sites. In conclusion, the tendon of long distance runners is less extensible than those of untrained subjects for knee extensors, but not for plantar flexors. For both sites, however, the lower tendon stiffness may be in favor of the running performance in long distance runners.

  3. Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity.

    Science.gov (United States)

    Frechette, Danielle M; Krishnamoorthy, Divya; Pamon, Tee; Chan, M Ete; Patel, Vihitaben; Rubin, Clinton T

    2017-09-11

    The incidence of obesity is rapidly rising, increasing morbidity and mortality rates worldwide. Associated comorbidities include type 2 diabetes, heart disease, fatty liver disease, and cancer. The impact of excess fat on musculoskeletal health is still unclear, although it is associated with increased fracture risk and a decline in muscular function. The complexity of obesity makes understanding the etiology of bone and muscle abnormalities difficult. Exercise is an effective and commonly prescribed nonpharmacological treatment option, but it can be difficult or unsafe for the frail, elderly, and morbidly obese. Exercise alternatives, such as low-intensity vibration (LIV), have potential for improving musculoskeletal health, particularly in conditions with excess fat. LIV has been shown to influence bone marrow mesenchymal stem cell differentiation toward higher-order tissues (i.e., bone) and away from fat. While the exact mechanisms are not fully understood, recent studies utilizing LIV both at the bench and in the clinic have demonstrated some efficacy. Here, we discuss the current literature investigating the effects of obesity on bone, muscle, and bone marrow and how exercise and LIV can be used as effective treatments for combating the negative effects in the presence of excess fat. © 2017 New York Academy of Sciences.

  4. Structural changes in isometrically contracting insect flight muscle trapped following a mechanical perturbation.

    Directory of Open Access Journals (Sweden)

    Shenping Wu

    Full Text Available The application of rapidly applied length steps to actively contracting muscle is a classic method for synchronizing the response of myosin cross-bridges so that the average response of the ensemble can be measured. Alternatively, electron tomography (ET is a technique that can report the structure of the individual members of the ensemble. We probed the structure of active myosin motors (cross-bridges by applying 0.5% changes in length (either a stretch or a release within 2 ms to isometrically contracting insect flight muscle (IFM fibers followed after 5-6 ms by rapid freezing against a liquid helium cooled copper mirror. ET of freeze-substituted fibers, embedded and thin-sectioned, provides 3-D cross-bridge images, sorted by multivariate data analysis into ~40 classes, distinct in average structure, population size and lattice distribution. Individual actin subunits are resolved facilitating quasi-atomic modeling of each class average to determine its binding strength (weak or strong to actin. ~98% of strong-binding acto-myosin attachments present after a length perturbation are confined to "target zones" of only two actin subunits located exactly midway between successive troponin complexes along each long-pitch helical repeat of actin. Significant changes in the types, distribution and structure of actin-myosin attachments occurred in a manner consistent with the mechanical transients. Most dramatic is near disappearance, after either length perturbation, of a class of weak-binding cross-bridges, attached within the target zone, that are highly likely to be precursors of strong-binding cross-bridges. These weak-binding cross-bridges were originally observed in isometrically contracting IFM. Their disappearance following a quick stretch or release can be explained by a recent kinetic model for muscle contraction, as behaviour consistent with their identification as precursors of strong-binding cross-bridges. The results provide a detailed

  5. Further Development of a Tissue Engineered Muscle Repair Construct In Vitro for Enhanced Functional Recovery Following Implantation In Vivo in a Murine Model of Volumetric Muscle Loss Injury

    Science.gov (United States)

    2012-01-01

    cultured cell population.12 Briefly, skeletal muscles were digested in 0.2% collagenase (Worthington biochemicals) solution prepared in low glucose...against desmin (Santa Cruz, 7955), MyoD (Hybridoma Bank), and Pax7 (Hybridoma Bank) or phalloidin-Alexa Fluor 488 or 594 conjugated (1:50, Invitro - gen

  6. Mechanical stimuli of skeletal muscle: implications on mTOR/p70s6k and protein synthesis.

    Science.gov (United States)

    Zanchi, Nelo Eidy; Lancha, Antonio Herbert

    2008-02-01

    The skeletal muscle is a tissue with adaptive properties which are essential to the survival of many species. When mechanically stimulated it is liable to undergo remodeling, namely, changes in its mass/volume resulting mainly from myofibrillar protein accumulation. The mTOR pathway (mammalian target of rapamycin) via its effector p70s6k (ribosomal protein kinase S6) has been reported to be of importance to the control of skeletal muscle mass, particularly under mechanical stimulation. However, not all mechanical stimuli are capable of activating this pathway, and among those who are, there are differences in the activation magnitude. Likewise, not all skeletal muscle fibers respond to the same extent to mechanical stimulation. Such evidences suggest specific mechanical stimuli through appropriate cellular signaling to be responsible for the final physiological response, namely, the accumulation of myofibrillar protein. Lately, after the mTOR signaling pathway has been acknowledged as of importance for remodeling, the interest for the mechanical/chemical mediators capable of activating it has increased. Apart from the already known MGF (mechano growth factor), some other mediators such as phosphatidic acid (PA) have been identified. This review article comprises and discusses relevant information on the mechano-chemical transduction of the pathway mTOR, with special emphasis on the muscle protein synthesis.

  7. Dexamethasone up-regulates skeletal muscle maximal Na+,K+ pump activity by muscle group specific mechanisms in humans

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Goodmann, Craig; McKenna, Michael J.

    2005-01-01

    Dexamethasone, a widely clinically used glucocorticoid, increases human skeletal muscle Na+,K+ pump content, but the effects on maximal Na+,K+ pump activity and subunit specific mRNA are unknown. Ten healthy male subjects ingested dexamethasone for 5 days and the effects on Na+,K+ pump content......, maximal activity and subunit specific mRNA level (a1, a2, ß1, ß2, ß3) in deltoid and vastus lateralis muscle were investigated. Before treatment, maximal Na+,K+ pump activity, as well as a1, a2, ß1 and ß2 mRNA levels were higher (P Dexamethasone treatment...... increased Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 ± 7% (P dexamethasone resulted in a higher a1, a2, ß1 and ß2 mRNA expression in the deltoid...

  8. Mechanical Characterization and Shape Optimization of Fascicle-Like 3D Skeletal Muscle Tissues Contracted with Electrical and Optical Stimuli.

    Science.gov (United States)

    Neal, Devin; Sakar, Mahmut Selman; Bashir, Rashid; Chan, Vincent; Asada, Haruhiko Harry

    2015-06-01

    In this study, we present a quantitative approach to construct effective 3D muscle tissues through shape optimization and load impedance matching with electrical and optical stimulation. We have constructed long, thin, fascicle-like skeletal muscle tissue and optimized its form factor through mechanical characterization. A new apparatus was designed and built, which allowed us to measure force-displacement characteristics with diverse load stiffnesses. We have found that (1) there is an optimal form factor that maximizes the muscle stress, (2) the energy transmitted to the load can be maximized with matched load stiffness, and (3) optical stimulation using channelrhodopsin2 in the muscle tissue can generate a twitch force as large as its electrical counterpart for well-developed muscle tissue. Using our tissue construct method, we found that an optimal initial diameter of 500 μm outperformed tissues using 250 μm by more than 60% and tissues using 760 μm by 105%. Using optimal load stiffness, our tissues have generated 12 pJ of energy per twitch at a peak generated stress of 1.28 kPa. Additionally, the difference in optically stimulated twitch performance versus electrically stimulated is a function of how well the overall tissue performs, with average or better performing strips having less than 10% difference. The unique mechanical characterization method used is generalizable to diverse load conditions and will be used to match load impedance to muscle tissue impedance for a wide variety of applications.

  9. Mechanical Ventilation Weaning in Inclusion Body Myositis: Feasibility of Isokinetic Inspiratory Muscle Training as an Adjunct Therapy

    Directory of Open Access Journals (Sweden)

    Leonardo Cordeiro de Souza

    2014-01-01

    Full Text Available Inclusion body myositis is a rare myopathy associated with a high rate of respiratory complications. This condition usually requires prolonged mechanical ventilation and prolonged intensive care stay. The unsuccessful weaning is mainly related to respiratory muscle weakness that does not promptly respond to immunosuppressive therapy. We are reporting a case of a patient in whom the use of an inspiratory muscle-training program which started after a two-week period of mechanical ventilation was associated with a successful weaning in one week and hospital discharge after 2 subsequent weeks.

  10. A new device combining mechanical stimulation of plantar sole and Achilles' tendon to alleviate the consequences of muscle deconditioning.

    Science.gov (United States)

    Canu, Marie-Hélène; Fryziel, Fabrice; Noel, Jean-Pierre; Tiffreau, Vincent; Digumber, Marc; Bastide, Bruno

    2016-05-01

    Limb immobilization or confinement to bed results in a severe atrophy and weakness of lower leg muscles. Full recovery of muscle strength and physical function is rare and may impact the patient's outcome. Studies performed on rodents have demonstrated that the deleterious structural and functional adaptations which occur during muscle deconditioning can be counteracted through adequate physiological stimuli. Thus, based on this fundamental work, we developed a device that combines mechanical stimulation of proprioceptors located in the plantar sole and Achilles' tendon. The device is adapted to patients immobilized and confined to bed. Stimulations can be applied on muscle in passive state. The protocol is non-invasive and is well accepted by patients. This paper presents the technical features of the device, as well as preliminary results of the first clinical study. This device might allow considering new therapeutic strategies for prevention of atrophy in many pathologies.

  11. Distinct effects of subcellular glycogen localization on tetanic relaxation time and endurance in mechanically skinned rat skeletal muscle fibres

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Schrøder, H D; Rix, C G

    2009-01-01

    In vitro experiments indicate a non-metabolic role of muscle glycogen in contracting skeletal muscles. Since the sequence of events in excitation\\#8211;contraction (E\\#8211;C) coupling is known to be located close to glycogen granules, at specific sites on the fibre, we hypothesized...... that the distinct compartments of glycogen have specific effects on muscle fibre contractility and fatigability. Single skeletal muscle fibres (n = 19) from fed and fasted rats were mechanically skinned and divided into two segments. In one segment glycogen localization and volume fraction were estimated......, range 22-252 contractions). Initially the total myofibrillar glycogen volume percentage was 0.46 +/- 0.07%, with 72 +/- 3% in the intermyofibrillar space and 28 +/- 3% in the intramyofibrillar space. The intramyofibrillar glycogen content was positively correlated with the fatigue resistance capacity (r...

  12. Interactive effects of corticosteroid and mechanical ventilation on diaphragm muscle function.

    Science.gov (United States)

    Sassoon, Catherine S H; Zhu, Ercheng; Fang, Liwei; Ramar, Kannan; Jiao, Guang-Yu; Caiozzo, Vincent J

    2011-01-01

    Information on the interactive effects of methylprednisolone, controlled mechanical ventilation (CMV), and assisted mechanical ventilation (AMV) on diaphragm function is sparse. Sedated rabbits received 2 days of CMV, AMV, and spontaneous breathing (SB), with either methylprednisolone (MP; 60 mg/kg/day intravenously) or saline. There was also a control group. In vitro diaphragm force, myofibril ultrastructure, αII-spectrin proteins, insulin-like growth factor-1 (IGF-1), and muscle atrophy F-box (MAF-box) mRNA were measured. Maximal tetanic tension (P(o)) decreased significantly with CMV. Combined MP plus CMV did not decrease P(o) further. With AMV, P(o) was similar to SB and controls. Combined MP plus AMV or MP plus SB decreased P(o) substantially. Combined MP plus CMV, MP plus AMV, or MP plus SB induced myofibrillar disruption that correlated with the reduced P(o). αII-spectrin increased, IGF-1 decreased, and MAF-box mRNA increased in both the CMV group and MP plus CMV group. Short-term, high-dose MP had no additive effects on CMV-induced diaphragm dysfunction. Combined MP plus AMV impaired diaphragm function, but AMV alone did not. We found that acute, high-dose MP produces diaphragm dysfunction depending on the mode of mechanical ventilation. Copyright © 2010 Wiley Periodicals, Inc.

  13. Cellular mechanism of eccentric-induced muscle injury and its relationship with sarcomere heterogeneity

    OpenAIRE

    Choi, Seung Jun

    2014-01-01

    Activity-induced muscle injury and dysfunction have been identified as key components of musculoskeletal injuries. These injuries often occur following eccentric contractions, when the muscle is under tension and stretched by a force that is greater than the force generated by the muscle. Many daily activities require muscles to perform eccentric contractions, including walking (or running) downhill or down stairs, lowering heavy objects, and landing from a jump. Injuries often occur when the...

  14. In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment.

    Science.gov (United States)

    Courtoy, Guillaume E; Donnez, Jacques; Marbaix, Etienne; Dolmans, Marie-Madeleine

    2015-08-01

    To study the in vivo mechanisms of action of ulipristal acetate (UPA) on uterine myomas. Retrospective histologic and immunohistochemical (IHC) study of myomas. Academic research unit. Among 59 women with symptomatic myomas who underwent myomectomy, 42 were treated preoperatively with UPA, while 17 were not. Histology and IHC were analyzed on tissue microarrays obtained from surgical specimens. Proliferation, apoptosis, extracellular matrix (ECM) remodeling, and matrix metalloproteinase 2 (MMP-2) expression. Proliferation was low in all conditions, with no statistical difference between groups. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay showed an increase in cell death in UPA-treated myomas compared with untreated myomas, but only after short-term treatment; this was not associated with elevated levels of cleaved caspase-3. After long-term treatment, cell density was higher and the ECM volume fraction lower in UPA-treated myomas than in untreated myomas. MMP-2 expression was found to be increased after treatment, showing the highest level after long-term treatment, compared with untreated myomas. Regarding sustained clinical volume reduction of myomas, this study strongly points to multifactorial mechanisms of action of UPA, involving: 1) a persistently low cell proliferation rate; 2) a limited period of cell death; and 3) ECM remodeling concomitant with stimulation of MMP-2 expression. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Antimicrobial photodynamic therapy with fulleropyrrolidine: photoinactivation mechanism of Staphylococcus aureus, in vitro and in vivo studies.

    Science.gov (United States)

    Grinholc, Mariusz; Nakonieczna, Joanna; Fila, Grzegorz; Taraszkiewicz, Aleksandra; Kawiak, Anna; Szewczyk, Grzegorz; Sarna, Tadeusz; Lilge, Lothar; Bielawski, Krzysztof P

    2015-05-01

    A family of N-methylpyrrolidinium fullerene iodide salts has been intensively studied to determine their applicability in antimicrobial photodynamic therapy (APDT). This study examined in vitro the efficacy of a C60 fullerene functionalized with one methylpyrrolidinium group to kill upon irradiation with white light gram-negative and gram-positive bacteria, as well as fungal cells, and the corresponding mechanism of the fullerene bactericidal action. The in vitro studies revealed that the high antistaphylococcal efficacy of functionalized fullerene could be linked to their ability to photogenerate singlet oxygen and superoxide anion. Following Staphylococcus aureus photoinactivation, no modifications of its genomic DNA were detected. In contrast, photodamage of the cell envelope seemed to be a dominant mechanism of bactericidal action. In in vivo studies, a 2 log10 reduction in the average bioluminescent radiance between treated and non-treated mice was reached. One day post APDT treatment, moist and abundant growth of bacteria could be observed on wounds of non-fulleropyrrolidine and dark control mice. APDT-treated wounds stayed visibly clear up to the third day. Moreover, cytotoxicity test on human dermal keratinocytes revealed great safety of using the sensitizer toward eukaryotic cells. These data indicate potential application of functionalized fullerene as antistaphylococcal sensitizer for superficial infections.

  16. Exercise and CaMK activation both increase the binding of MEF2A to the Glut4 promoter in skeletal muscle in vivo.

    Science.gov (United States)

    Smith, James A H; Collins, Malcolm; Grobler, Liesl A; Magee, Carrie J; Ojuka, Edward O

    2007-02-01

    In vitro binding assays have indicated that the exercise-induced increase in muscle GLUT4 is preceded by increased binding of myocyte enhancer factor 2A (MEF2A) to its cis-element on the Glut4 promoter. Because in vivo binding conditions are often not adequately recreated in vitro, we measured the amount of MEF2A that was bound to the Glut4 promoter in rat triceps after an acute swimming exercise in vivo, using chromatin immunoprecipitation (ChIP) assays. Bound MEF2A was undetectable in nonexercised controls or at 24 h postexercise but was significantly elevated approximately 6 h postexercise. Interestingly, the increase in bound MEF2A was preceded by an increase in autonomous activity of calcium/calmodulin-dependent protein kinase (CaMK) II in the same muscle. To determine if CaMK signaling mediates MEF2A/DNA associations in vivo, we performed ChIP assays on C(2)C(12) myotubes expressing constitutively active (CA) or dominant negative (DN) CaMK IV proteins. We found that approximately 75% more MEF2A was bound to the Glut4 promoter in CA compared with DN CaMK IV-expressing cells. GLUT4 protein increased approximately 70% 24 h after exercise but was unchanged by overexpression of CA CaMK IV in myotubes. These results confirm that exercise increases the binding of MEF2A to the Glut4 promoter in vivo and provides evidence that CaMK signaling is involved in this interaction.

  17. Rapid in vivo determination of tetrodotoxin in pufferfish (Fugu) muscle by solid-phase microextraction coupled to high-performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Chen, Le; Qiu, Junlang; Tang, Yijia; Xu, Jianqiao; Huang, Shuyao; Liu, Yuan; Ouyang, Gangfeng

    2017-08-15

    Tetrodotoxin (TTX) is one of the most toxic substances of non-protein in nature. In present study, a rapid and sensitive method based on in vivo solid-phase microextraction (SPME) coupled to liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed to detect the endogenous TTX in pufferfish (Fugu). Fiber evaluation experiments demonstrated that, compared with the commercial PDMS and PA fibers, the home-made electrospun PS@PDA-GA fibers exhibited much better extraction performance towards to TTX in water (120 times and 20 times, respectively), under the optimized conditions. Then, the home-made SPME fibers were employed to extract TTX in spiked homogeneous fish muscle samples, and a LC-MS-MS was used for the analysis. The reproducibilities (RSDs of inter and intra fiber were 12.1%, and 7.9% respectively), linear range (10-1000ngg-1, R2=0.9963) and sensitivity (the LOD was 2.3ngg-1) of the method were found to be excellent and satisfactory for further in vivo experiments. Especially the LOD of the established method is lower than the National Standard Method of China (GB/T 23217-2008, LOD 50ngg-1). Subsequently, the method was successfully applied to detect the TTX in the dorsal muscle of living pufferfish, and the accuracy was verified with traditional liquid extraction (LE) method. In general, this is the first study to detect TTX in pufferfish by in vivo sampling method, which provided a promising alternative method for the studies of TTX, and also advanced the implementation of SPME for more in vivo studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Foot muscle morphology is related to center of pressure sway and control mechanisms during single-leg standing.

    Science.gov (United States)

    Zhang, Xianyi; Schütte, Kurt Heinrich; Vanwanseele, Benedicte

    2017-09-01

    Maintaining balance is vitally important in everyday life. Investigating the effects of individual foot muscle morphology on balance may provide insights into neuromuscular balance control mechanisms. This study aimed to examine the correlation between the morphology of foot muscles and balance performance during single-leg standing. Twenty-eight recreational runners were recruited in this study. An ultrasound device was used to measure the thickness and cross-sectional area of three intrinsic foot muscles (abductor hallucis, flexor digitorum brevis and quadratus plantae) and peroneus muscles. Participants were required to perform 30s of single-leg standing for three trials on a force plate, which was used to record the center of pressure (COP). The standard deviation of the amplitude and ellipse area of the COP were calculated. In addition, stabilogram diffusion analysis (SDA) was performed on COP data. Pearson correlation coefficients were computed to examine the correlation between foot muscle morphology and traditional COP parameters as well as with SDA parameters. Our results showed that larger abductor hallucis correlated to smaller COP sway, while larger peroneus muscles correlated to larger COP sway during single-leg standing. Larger abductor hallucis also benefited open-loop dynamic stability, as well as supported a more efficient transfer from open-loop to closed loop control mechanisms. These results suggest that the morphology of foot muscles plays an important role in balance performance, and that strengthening the intrinsic foot muscles may be an effective way to improve balance. Copyright © 2017. Published by Elsevier B.V.

  19. Smooth muscle cells can express cytokeratins of "simple" epithelium. Immunocytochemical and biochemical studies in vitro and in vivo.

    Science.gov (United States)

    Gown, A M; Boyd, H C; Chang, Y; Ferguson, M; Reichler, B; Tippens, D

    1988-08-01

    Cytokeratins are a set of 19 proteins that together constitute the class of intermediate filament protein expressed by epithelial cells and tumors. Using a panel of 9 different monoclonal anti-cytokeratin antibodies, the authors have performed immunocytochemistry on methanol-fixed, frozen sections and methacarn-fixed, paraffin-embedded tissue of human myometrial specimens. Anomalous cytokeratin expression (ACE) by smooth muscle cells was found in all specimens. Immunoblots of this tissue confirmed the presence of cytokeratin 19, and possibly 8. In addition, immunocytochemical studies demonstrated ACE in human fetal tissues within the intestinal muscularis and the heart, especially in the region of the aortic outflow tract, and in 8 of 19 cases of leiomyosarcoma from adults. Indirect immunofluorescence studies were also performed on cells explanted from myometrial tissue; the overwhelming majority of cells derived from these cultures were smooth muscle cells as verified by expression of muscle actins, and a subpopulation of these cells was found to be cytokeratin-positive. ACE was confirmed in vitro by double labeling experiments demonstrating simultaneous expression of muscle actins and cytokeratins within the same cell. The significance of this smooth muscle cell ACE is unknown, but it may be a phenotypic marker of smooth muscle in a proliferative state. ACE could be a source of confusion in the immunocytochemical analysis of poorly differentiated malignancies if a complete panel of antibodies is not employed.

  20. Mechanisms of adhesion and subsequent actions of a haematopoietic stem cell line, HPC-7, in the injured murine intestinal microcirculation in vivo.

    Directory of Open Access Journals (Sweden)

    Dean P J Kavanagh

    Full Text Available Although haematopoietic stem cells (HSCs migrate to injured gut, therapeutic success clinically remains poor. This has been partially attributed to limited local HSC recruitment following systemic injection. Identifying site specific adhesive mechanisms underpinning HSC-endothelial interactions may provide important information on how to enhance their recruitment and thus potentially improve therapeutic efficacy. This study determined (i the integrins and inflammatory cyto/chemokines governing HSC adhesion to injured gut and muscle (ii whether pre-treating HSCs with these cyto/chemokines enhanced their adhesion and (iii whether the degree of HSC adhesion influenced their ability to modulate leukocyte recruitment.Adhesion of HPC-7, a murine HSC line, to ischaemia-reperfused (IR injured mouse gut or cremaster muscle was monitored intravitally. Critical adhesion molecules were identified by pre-treating HPC-7 with blocking antibodies to CD18 and CD49d. To identify cyto/chemokines capable of recruiting HPC-7, adhesion was monitored following tissue exposure to TNF-α, IL-1β or CXCL12. The effects of pre-treating HPC-7 with these cyto/chemokines on surface integrin expression/clustering, adhesion to ICAM-1/VCAM-1 and recruitment in vivo was also investigated. Endogenous leukocyte adhesion following HPC-7 injection was again determined intravitally.IR injury increased HPC-7 adhesion in vivo, with intestinal adhesion dependent upon CD18 and muscle adhesion predominantly relying on CD49d. Only CXCL12 pre-treatment enhanced HPC-7 adhesion within injured gut, likely by increasing CD18 binding to ICAM-1 and/or CD18 surface clustering on HPC-7. Leukocyte adhesion was reduced at 4 hours post-reperfusion, but only when local HPC-7 adhesion was enhanced using CXCL12.This data provides evidence that site-specific molecular mechanisms govern HPC-7 adhesion to injured tissue. Importantly, we show that HPC-7 adhesion is a modulatable event in IR injury and

  1. Refuting The Polemic Against the Extraocular Muscle Pulleys: Jampel and Shi’s Platygean View of Extraocular Muscle Mechanics

    Science.gov (United States)

    Demer, Joseph L.

    2007-01-01

    Background Late in the 20th Century, it was recognized that connective tissue structures in the orbit influence the paths of the extraocular muscles, and constitute their functional origins. Targeted investigations of these connective tissue “pulleys” led to the formulation of the active pulley hypothesis, which proposes that pulling directions of the rectus extraocular muscles are actively controlled via connective tissues. Purpose This review rebuts a series of criticisms of the active pulley hypothesis published by Jampel, and Jampel and Shi, in which these authors have disputed the existence and function of the pulleys. Methods The current paper reviews published evidence for the existence of orbital pulleys, the active pulley hypothesis, and physiologic tests of the active pulley hypothesis. Magnetic resonance imaging in a living subject, and histological examination of a human cadaver directly illustrate the relationship of pulleys to extraocular muscles. Results Strong scientific evidence is cited that supports the existence of orbital pulleys, and their role in ocular motility. The criticisms of have ignored mathematical truisms and strong scientific evidence. Conclusions Actively controlled orbital pulleys play a fundamental role in ocular motility. Pulleys profoundly influence the neural commands required to control eye movements and binocular alignment. Familiarity with the anatomy and physiology of the pulleys is requisite for a rational approach to diagnosing and treating strabismus using emerging methods. Conversely, approaches that deny or ignore the pulleys risk the sorts of errors that arise in geography and navigation from incorrect assumptions such as those of a flat (“platygean”) earth. PMID:17022164

  2. The ankle ergometer: A new tool for quantifying changes in mechanical properties of human muscle as a result of spaceflight

    Science.gov (United States)

    Mainar, A.; Vanhoutte, C.; Pérot, C.; Voronine, L.; Goubel, F.

    A mechanical device for studying changes in mechanical properties of human muscle as a result of spaceflight is presented. Its main capacities are to allow during a given experiment investigation of both contractile and visco-elastic properties of a musculo-articular complex using respectively isometric contractions, isokinetic movements, quick-release tests and sinusoidal perturbations. This device is a motor driven ergometer associated to an experimental protocol designed for pre- and post-flight experiments. As microgravity preferentially affects postural muscles, the apparatus was designed to test muscle groups crossing the ankle joint. Three subjects were tested during the Euromir '94 mission. Preliminary results obtained on the european astronaut are briefly reported. During the next two years the experiments will be performed during six missions.

  3. Mechanical muscle function, morphology, and fiber type in lifelong trained elderly

    DEFF Research Database (Denmark)

    Aagaard, Per; Magnusson, Peter S; Larsson, Benny

    2007-01-01

    ), and muscle fiber composition and size (CSA) were studied in elderly individuals (68-78 yr) chronically exposed (> 50 yr) to either endurance (E) or strength (S) training, and in age-matched, untrained (U) elderly group. RESULTS: E and S showed greater MVC than did U. Contractile RFD was elevated in S......PURPOSE: Maximal muscle contraction force and muscle mass are both reduced during the natural aging process. Long-term training may be used to attenuate this age-related loss in muscle function and muscle size. METHODS: Maximum isometric quadriceps strength (MVC), rate of force development (RFD...... (i.e., lifelong) strength training. This relative preservation in muscle morphology and function may provide an important physical reserve capacity to retain muscle mass and function above the critical threshold for independent living at old age....

  4. Efficacy of respiratory muscle training in weaning of mechanical ventilation in patients with mechanical ventilation for 48hours or more: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Sandoval Moreno, L M; Casas Quiroga, I C; Wilches Luna, E C; García, A F

    2018-02-02

    To evaluate the efficacy of respiratory muscular training in the weaning of mechanical ventilation and respiratory muscle strength in patients on mechanical ventilation of 48hours or more. Randomized controlled trial of parallel groups, double-blind. Ambit: Intensive Care Unit of a IV level clinic in the city of Cali. 126 patients in mechanical ventilation for 48hours or more. The experimental group received daily a respiratory muscle training program with treshold, adjusted to 50% of maximal inspiratory pressure, additional to standard care, conventional received standard care of respiratory physiotherapy. MAIN INTEREST VARIABLES: weaning of mechanical ventilation. Other variables evaluated: respiratory muscle strength, requirement of non-invasive mechanical ventilation and frequency of reintubation. intention-to-treat analysis was performed with all variables evaluated and analysis stratified by sepsis condition. There were no statistically significant differences in the median weaning time of the MV between the groups or in the probability of extubation between groups (HR: 0.82 95% CI: 0.55-1.20 P=.29). The maximum inspiratory pressure was increased in the experimental group on average 9.43 (17.48) cmsH20 and in the conventional 5.92 (11.90) cmsH20 (P=.48). The difference between the means of change in maximal inspiratory pressure was 0.46 (P=.83 95%CI -3.85 to -4.78). respiratory muscle training did not demonstrate efficacy in the reduction of the weaning period of mechanical ventilation nor in the increase of respiratory muscle strength in the study population. Registered study at ClinicalTrials.gov (NCT02469064). Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  5. Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Zuyderduyn Suzanne

    2010-09-01

    Full Text Available Abstract Background Acetylcholine, the primary parasympathetic neurotransmitter in the airways, plays an important role in bronchoconstriction and mucus production. Recently, it has been shown that acetylcholine, by acting on muscarinic receptors, is also involved in airway inflammation and remodelling. The mechanism(s by which muscarinic receptors regulate inflammatory responses are, however, still unknown. Methods The present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells (hASMc and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M2 and M3 receptors were stimulated with the muscarinic receptor agonist methacholine, alone, and in combination with cigarette smoke extract (CSE, TNF-α, PDGF-AB or IL-1β. Results Muscarinic receptor stimulation induced modest IL-8 secretion by itself, yet augmented IL-8 secretion in combination with CSE, TNF-α or PDGF-AB, but not with IL-1β. Pretreatment with GF109203X, a protein kinase C (PKC inhibitor, completely normalized the effect of methacholine on CSE-induced IL-8 secretion, whereas PMA, a PKC activator, mimicked the effects of methacholine, inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of IκB-kinase-2 (SC514 and MEK1/2 (U0126, both downstream effectors of PKC. Accordingly, western blot analysis revealed that methacholine augmented the degradation of IκBα and the phosphorylation of ERK1/2 in combination with CSE, but not with IL-1β in hASMc. Conclusions We conclude that muscarinic receptors facilitate CSE-induced IL-8 secretion by hASMc via PKC dependent activation of IκBα and ERK1/2. This mechanism could be of importance for COPD patients using anticholinergics.

  6. [Ex Vivo Testing of Mechanical Properties of Canine Metacarpal/Metatarsal Bones after Simulated Implant Removal].

    Science.gov (United States)

    Srnec, R; Fedorová, P; Pěnčík, J; Vojtová, L; Sedlinská, M; Nečas, A

    2016-01-01

    PURPOSE OF THE STUDY In a long-term perspective, it is better to remove implants after fracture healing. However, subsequent full or excessive loading of an extremity may result in refracture, and the bone with holes after screw removal may present a site with predilection for this. The aim of the study was to find ways of how to decrease risk factors for refracture in such a case. This involved support to the mechanical properties of a bone during its remodelling until defects following implant removal are repaired, using a material tolerated by bone tissue and easy to apply. It also included an assessment of the mechanical properties of a bone after filling the holes in it with a newly developed biodegradable polymer-composite gel ("bone paste"). The composite also has a prospect of being used to repair bony defects produced by pathological processes. MATERIAL AND METHODS Experiments were carried out on intact weight-bearing small bones in dogs. A total of 27 specimens of metacarpal/metatarsal bones were used for ex vivo testing. They were divided into three groups: K1 (n = 9) control undamaged bones; K2 (n = 9) control bones with iatrogenic damage simulating holes left after cortical screw removal; EXP (n = 9) experimental specimens in which simulated holes in bone were filled with the biodegradable self-hardening composite. The bone specimens were subjected to three-point bending in the caudocranial direction by a force acting parallel to the direction of drilling in their middiaphyses. The value of maximum load achieved (N) and the corresponding value of a vertical displacement (mm) were recorded in each specimen, then compared and statistically evaluated. RESULTS On application of a maximum load (N), all bone specimens broke in the mid-part of their diaphyses. In group K1 the average maximum force of 595.6 ± 79.5 N was needed to break the bone; in group K2 it was 347.6 ± 58.6 N; and in group EXP it was 458.3 ± 102.7 N. The groups with damaged bones, K2 and

  7. The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

    Full Text Available Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading.Jiri Heřt introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gauges to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced.Experiments combining strain gauge instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats and mice has yielded significant insight into the control of strain-related adaptive (remodeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice which is now the model of choice for many studies. Together such studies have demonstrated that; over the physiological strain range, bone’s mechanically-adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles and that these are most effective when interrupted by short periods of

  8. Evaluation of Muscle Mechanical Capacities through the Two-load Method: Optimization of the Load Selection.

    Science.gov (United States)

    Pérez-Castilla, Alejandro; Jaric, Slobodan; Feriche, Belén; Padial, Paulino; García-Ramos, Amador

    2017-04-25

    Recent research has revealed that the force-velocity relationship obtained from the 'two-load method' (i.e., functional movements tested against just 2 external loads) could be a feasible method for the selective assessment of muscle force, velocity, and power-producing capacities. The study investigated the reliability and concurrent validity of the outcomes of the two-load method observed from (1) farther vs. closer data points (20-70%1RM, 30-60%1RM, and 40-50%1RM), and (2) force-biased (50-70%1RM) vs. velocity-biased (20-40%1RM) data points. Twenty-two men were tested on a ballistic bench press throw performed against 6 incremental loads ranging from 20% to 70% of the bench press one-repetition maximum (1RM). The two-load methods were constructed based on pairs of individually selected external loads and compared with the outcome of the force-velocity regression method applied to all 6 loads. The reliability and validity of the force-velocity relationship parameters decreased with the proximity of the data points (40-50%1RM loads (i.e., lighter and heavier loads, respectively) revealed a similar, but relatively moderate reliability and validity. Overall, the farthest pair of loads (i.e., 20%1RM and 70%1RM) revealed the highest reliability (CV = 5.5%, ICC = 0.89) and validity (r = 0.98) among all the two-load methods evaluated. These results demonstrate that the 20-70%1RM two-load method could be a feasible approach for testing individual muscle mechanical capacities, while the observed outcomes could be the most reliable and valid when obtained from the farthest pairs of applied loads.

  9. No release of interstitial glutamate in experimental human model of muscle pain

    DEFF Research Database (Denmark)

    Ashina, M.; Jørgensen, M.; Stallknecht, Bente

    2005-01-01

    Glutamate may be released from muscle nociceptors and thereby contribute to mechanisms underlying acute and chronic muscle pain. In vivo concentration of glutamate during muscle pain has not previously been studied in either animals or humans. In the present study, we aimed to study the in vivo...... flow increased significantly over time in response to infusion of chemical mixture and placebo (p = 0.001). However, we found no difference in changes in muscle blood flow between chemical mixture and placebo (p > 0.05). In conclusion, the present study demonstrates no signs of increased release...... of glutamate from myofascial nociceptors during and after acute experimentally induced muscle pain and tenderness....

  10. Spinal loads and trunk muscles forces during level walking - A combined in vivo and in silico study on six subjects.

    Science.gov (United States)

    Arshad, Rizwan; Angelini, Lorenza; Zander, Thomas; Di Puccio, Francesca; El-Rich, Marwan; Schmidt, Hendrik

    2017-08-26

    During level walking, lumbar spine is subjected to cyclic movements and intricate loading of the spinal discs and trunk musculature. This study aimed to estimate the spinal loads (T12-S1) and trunk muscles forces during a complete gait cycle. Six men, 24-33years walk barefoot at self-selected speed (4-5km/h). 3D kinematics and ground reaction forces were recorded using a motion capturing system and two force plates, implemented in an inverse dynamic musculoskeletal model to predict the spinal loads and trunk muscles forces. Additionally, the sensitivity of the intra-abdominal pressure and lumbar segment rotational stiffness was investigated. Peak spinal loads and trunk muscle forces were between the gait instances of heel strike and toe off. In L4-L5 segment, sensitivity analysis showed that average peak compressive, antero-posterior and medio-lateral shear forces were 130-179%, 2-15% and 1-6%, with max standard deviation (±STD) of 40%, 6% and 3% of the body weight. Average peak global muscles forces were 24-55% (longissimus thoracis), 11-23% (iliocostalis thoracis), 12-16% (external oblique), 17-25% (internal oblique) and 0-8% (rectus abdominus) of body weight whereas, the average peak local muscles forces were 11-19% (longissimus lumborum), 14-31% (iliocostalis lumborum) and 12-17% (multifidus). Maximum±STD of the global and local muscles forces were 13% and 8% of the body weight. Large inter-individual differences were found in peak compressive and trunk muscles forces whereas the sensitivity analysis also showed a substantial variation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. [Determination of lifetime and remoteness of mechanical injury using electron-paramagnetic resonance spectra of the skeletal muscles].

    Science.gov (United States)

    Shakar'iants, Zh E

    2009-01-01

    This study was designed to evaluate the possibility to use electron-paramagnetic resonance (EPMR) spectra of skeletal muscles for the post-mortem diagnosis of intravital character and prescription of mechanical injury. Objective criteria were developed for the determination of the prescription (intravital character) of the injury.

  12. The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain

    NARCIS (Netherlands)

    Wal, S.E.I. van der; Heuvel, S.A.S. van den; Radema, S.A.; Berkum, B.F. van; Vaneker, M.; Steegers, M.A.H.; Scheffer, G.J.; Vissers, K.C.P.

    2016-01-01

    INTRODUCTION: The neuroinflammatory response plays a key role in several pain syndromes. Intravenous (iv) lidocaine is beneficial in acute and chronic pain. This review delineates the current literature concerning in vitro mechanisms and in vivo efficacy of iv lidocaine on the neuroinflammatory

  13. In Vivo Corrosion of Two Novel Magnesium Alloys ZEK100 and AX30 and Their Mechanical Suitability as Biodegradable Implants

    Directory of Open Access Journals (Sweden)

    Andrea Meyer-Lindenberg

    2011-06-01

    Full Text Available In magnesium alloys, the components used modify the alloy properties. For magnesium implants in contact with bone, rare earths alloys are commonly examined. These were shown to have a higher corrosion resistance than other alloys and a high mechanical strength, but their exact composition is hard to predict. Therefore a reduction of their content could be favorable. The alloys ZEK100 and AX30 have a reduced content or contain no rare earths at all. The aim of the study was to investigate their in vivo degradation and to assess the suitability of the in vivo µCT for the examination of their corrosion. Implants were inserted in rabbit tibiae. Clinical examinations, X-rays and in vivo µCT scans were done regularly. Afterwards implants were analyzed with REM, electron dispersive X-ray (EDX, weighing and mechanical testing. The in vivo µCT is of great advantage, because it allows a quantification of the corrosion rate and qualitative 3D assessment of the corrosion morphology. The location of the implant has a remarkable effect on the corrosion rate. Due to its mechanical characteristics and its corrosion behavior, ZEK100 was judged to be suitable, while AX30, which displays favorable degradation behavior, has too little mechanical strength for applications in weight bearing bones.

  14. In vivo evidence of significant levator ani muscle stretch on MR images of a live childbirth.

    Science.gov (United States)

    Sindhwani, Nikhil; Bamberg, Christian; Famaey, Nele; Callewaert, Geertje; Dudenhausen, Joachim W; Teichgräber, Ulf; Deprest, Jan

    2017-08-01

    Vaginal childbirth is believed to be a significant risk factor for the development of pelvic floor dysfunction later in life. Previous studies have explored the use of medical imaging and simulations of childbirth to determine the stretch in the levator ani muscle. A report in 2012 has recorded magnetic resonance images of a live childbirth of a 24 year old woman giving birth vaginally for the second time, using a 1.0 Tesla open, high-field scanner. Our objective was to determine the stretch ratios in the levator muscle using these magnetic resonance images of live childbirth. Three-dimensional magnetic resonance image sequences were obtained to visualize coronal and axial planes before and after the childbirth. These images were obtained before the expulsion phase without pushing and were used to reconstruct the levator muscle and the fetal head in 3 dimensions. The fetal head was approximated to be an ellipsoid, and it is assumed that its middle section is visible in dynamic magnetic resonance images. Assuming incompressibility, the full deformation field of the fetal head is then calculated. Real-time cine magnetic resonance images were acquired for the during the expulsion phase, occurring over 2 contractions in the midsagittal plane. The levator muscle stretch is estimated using a custom program. The program calculates points of contact between the fetal head ellipsoid and the levator ani muscle model as the head descends down the birth canal and moves them orthogonal to its surface. Circumferential stretch was calculated to represent the extension needed to allow the passage of the fetal head. Starting from a position in the preexpulsion phase, the levator muscle experiences a maximum circumferential stretch of 248% on the posterior-medial portion of the levator ani muscle, as shown in previously published finite element simulations. However, the maximal stretch was notably less than that predicted by finite element models. This is because our baseline 3

  15. Study on osteogenesis promoted by low sound pressure level infrasound in vivo and some underlying mechanisms.

    Science.gov (United States)

    Long, Hua; Zheng, Liheng; Gomes, Fernando Cardoso; Zhang, Jinhui; Mou, Xiang; Yuan, Hua

    2013-09-01

    To clarify the effects of low sound pressure level (LSPL) infrasound on local bone turnover and explore its underlying mechanisms, femoral defected rats were stabilized with a single-side external fixator. After exposure to LSPL infrasound for 30min twice everyday for 6 weeks, the pertinent features of bone healing were assessed by radiography, peripheral quantitative computerized tomography (pQCT), histology and immunofluorescence assay. Infrasound group showed a more consecutive and smoother process of fracture healing and modeling in radiographs and histomorphology. It also showed significantly higher average bone mineral content (BMC) and bone mineral density (BMD). Immunofluorescence showed increased expression of calcitonin gene related peptide (CGRP) and decreased Neuropeptide Y (NPY) innervation in microenvironment. The results suggested the osteogenesis promotion effects of LSPL infrasound in vivo. Neuro-osteogenic network in local microenvironment was probably one target mediating infrasonic osteogenesis, which might provide new strategy to accelerate bone healing and remodeling. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Modeling the Mechanical Response of In Vivo Human Skin Under a Rich Set of Deformations

    KAUST Repository

    Flynn, Cormac

    2011-03-11

    Determining the mechanical properties of an individual\\'s skin is important in the fields of pathology, biomedical device design, and plastic surgery. To address this need, we present a finite element model that simulates the skin of the anterior forearm and posterior upper arm under a rich set of three-dimensional deformations. We investigated the suitability of the Ogden and Tong and Fung strain energy functions along with a quasi-linear viscoelastic law. Using non-linear optimization techniques, we found material parameters and in vivo pre-stresses for different volunteers. The model simulated the experiments with errors-of-fit ranging from 13.7 to 21.5%. Pre-stresses ranging from 28 to 92 kPa were estimated. We show that using only in-plane experimental data in the parameter optimization results in a poor prediction of the out-of-plane response. The identifiability of the model parameters, which are evaluated using different determinability criteria, improves by increasing the number of deformation orientations in the experiments. © 2011 Biomedical Engineering Society.

  17. An In Vivo Zebrafish Screen Identifies Organophosphate Antidotes with Diverse Mechanisms of Action

    Science.gov (United States)

    Jin, Shan; Sarkar, Kumar S.; Jin, Youngnam N.; Liu, Yan; Kokel, David; Van Ham, Tjakko J.; Roberts, Lee D.; Gerszten, Robert E.; MacRae, Calum A.; Peterson, Randall T.

    2014-01-01

    Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a high priority. Early life stage zebrafish exposed to organophosphates exhibit several phenotypes that parallel the human response to organophosphates, including behavioral deficits, paralysis, and eventual death. Here, we have developed a high-throughput zebrafish screen in a 96-well plate format to find new antidotes that counteract organophosphate-induced lethality. In a pilot screen of 1200 known drugs, we identified 16 compounds that suppress organophosphate toxicity in zebrafish. Several in vitro assays coupled with liquid chromatography/tandem mass spectrometry–based metabolite profiling enabled determination of mechanisms of action for several of the antidotes, including reversible acetylcholinesterase inhibition, cholinergic receptor antagonism, and inhibition of bioactivation. Therefore, the in vivo screen is capable of discovering organophosphate antidotes that intervene in distinct pathways. These findings suggest that zebrafish screens might be a broadly applicable approach for discovering compounds that counteract the toxic effects of accidental or malicious poisonous exposures. PMID:22960781

  18. RIVETS: a mechanical system for in vivo and in vitro electrophysiology and imaging.

    Directory of Open Access Journals (Sweden)

    Jason E Osborne

    Full Text Available A number of recent studies have provided compelling demonstrations that both mice and rats can be trained to perform a variety of behavioral tasks while restrained by mechanical elements mounted to the skull. The independent development of this technique by a number of laboratories has led to diverse solutions. We found that these solutions often used expensive materials and impeded future development and modification in the absence of engineering support. In order to address these issues, here we report on the development of a flexible single hardware design for electrophysiology and imaging both in brain tissue in vitro. Our hardware facilitates the rapid conversion of a single preparation between physiology and imaging system and the conversion of a given system between preparations. In addition, our use of rapid prototyping machines ("3D printers" allows for the deployment of new designs within a day. Here, we present specifications for design and manufacturing as well as some data from our lab demonstrating the suitability of the design for physiology in behaving animals and imaging in vitro and in vivo.

  19. Do Mechanical and Physicochemical Properties of Orthodontic NiTi Wires Remain Stable In Vivo?

    Directory of Open Access Journals (Sweden)

    Michał Sarul

    2016-01-01

    Full Text Available Introduction and Aim. Exceptional properties of the NiTi archwires may be jeopardized by the oral cavity; thus its long-term effect on the mechanical and physiochemical properties of NiTi archwires was the aim of work. Material and Methods. Study group comprised sixty 0.016 × 0.022 NiTi archwires from the same manufacturer evaluated (group A after the first 12 weeks of orthodontic treatment. 30 mm long pieces cut off from each wire prior to insertion formed the control group B. Obeying the strict rules of randomization, all samples were subjected to microscopic evaluation and nanoindentation test. Results. Both groups displayed substantial presence of nonmetallic inclusions. Heterogeneity of the structure and its alteration after usage were found in groups B and A, respectively. Conclusions. Long-term, reliable prediction of biomechanics of NiTi wires in vivo is impossible, especially new archwires from the same vendor display different physiochemical properties. Moreover, manufacturers have to decrease contamination in the production process in order to minimize risk of mutual negative influence of nickel-titanium archwires and oral environment.

  20. A semi-quantitative RT-PCR method to measure the in vivo effect of dietary conjugated linoleic acid on porcine muscle PPAR gene expression

    Directory of Open Access Journals (Sweden)

    Meadus W.J.

    2003-01-01

    Full Text Available Conjugated linoleic acid (CLA can activate (in vitro the nuclear transcription factors known as the peroxisome proliferators activated receptors (PPAR. CLA was fed at 11 g CLA/kg of feed for 45d to castrated male pigs (barrows to better understand long term effects of PPAR activation in vivo. The barrows fed CLA had lean muscle increased by 3.5% and overall fat reduced by 9.2% but intramuscular fat (IMF % was increased by 14% (P < 0.05. To measure the effect of long term feeding of CLA on porcine muscle gene expression, a semi-quantitative RT-PCR method was developed using cDNA normalized against the housekeeping genes cyclophilin and &bgr;-actin. This method does not require radioactivity or expensive PCR instruments with real-time fluorescent detection. PPAR&ggr; and the PPAR responsive gene AFABP but not PPAR&agr; were significantly increased (P < 0.05 in the CLA fed pig’s muscle. PPAR&agr; and PPAR&ggr; were also quantitatively tested for large differences in gene expression by western blot analysis but no significant difference was detected at this level. Although large differences in gene expression of the PPAR transcriptional factors could not be confirmed by western blotting techniques. The increased expression of AFABP gene, which is responsive to PPAR transcriptional factors, confirmed that dietary CLA can induce a detectable increase in basal PPAR transcriptional activity in the live animal.

  1. Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

    Science.gov (United States)

    Chitano, P; Rado, V; Di Stefano, A; Papi, A; Boniotti, A; Zancuoghi, G; Boschetto, P; Romano, M; Salmona, M; Ciaccia, A; Fabbri, L M; Mapp, C E

    1996-06-01

    In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats.

  2. Exercise-induced translocation of protein kinase C and production of diacylglycerol and phosphatidic acid in rat skeletal muscle in vivo. Relationship to changes in glucose transport.

    Science.gov (United States)

    Cleland, P J; Appleby, G J; Rattigan, S; Clark, M G

    1989-10-25

    Contraction-induced translocation of protein kinase C (Richter E.A., Cleland, P.J.F., Rattigan, S., and Clark, M.G. (1987) FEBS Lett. 217, 232-236) implies a role for this enzyme in muscle contraction or the associated metabolic adjustments. In the present study, this role is further examined particularly in relation to changes in glucose transport. Electrical stimulation of the sciatic nerve of the anesthetized rat in vivo led to a time-dependent translocation of protein kinase C and a 2-fold increase in the concentrations of both diacylglycerol and phosphatidic acid. Maximum values for the latter were reached at 2 min and preceded the maximum translocation of protein kinase C (10 min). Stimulation of muscles in vitro increased the rate of glucose transport, but this required 20 min to reach maximum. There was no reversal of translocation or decrease in the concentrations of diacylglycerol and phosphatidic acid even after 30 min of rest following a 5-min period of stimulation in vivo. Translocation was not influenced by variations in applied load at maximal fiber recruitment but was dependent on the frequency of nontetanic stimuli, reaching a maximum at 4 Hz. The relationship between protein kinase C and glucose transport was also explored by varying the number of tetanic stimuli. Whereas only one train of stimuli (200 ms, 100 Hz) was required for maximal effects on protein kinase C, diacylglycerol, and phosphatidic acid, more than 35 trains of stimuli were required to activate glucose transport. It is concluded that the production of diacylglycerol and the translocation of protein kinase C may be causally related. However, if the translocated protein kinase C is involved in the activation of glucose transport during muscle contractions, an accumulated exposure to Ca2+, resulting from multiple contractions, would appear to be necessary.

  3. Second harmonic generation analysis of early Achilles tendinosis in response to in vivo mechanical loading

    Science.gov (United States)

    2011-01-01

    Background Tenocytes have been implicated in the development of tendinosis, a chronic condition commonly seen in musculoskeletal overuse syndromes. However, the relation between abnormal tenocyte morphology and early changes in the fibrillar collagen matrix has not been closely examined in vivo. Second harmonic generation (SHG) microscopy is a recently developed technique which allows examination of fibrillar collagen structures with a high degree of specificity and resolution. The goal of this study was to examine the potential utility of SHG and multiphoton excitation fluorescence (MPEF) microscopy in understanding the relation between tenocytes and their surrounding collagenous matrix in early tendon overuse lesions. Methods Histological preparations of tendon were prepared from adult male Sprague-Dawley rats subjected to an Achilles tendon loading protocol for 12 weeks (Rat-A-PED), or from sedentary age-matched cage controls. Second harmonic generation and multiphoton excitation fluorescence were performed simultaneously on these tissue sections in at least three different areas. Results SHG microscopy revealed an association between abnormal tenocyte morphology and morphological changes in the fibrillar collagen matrix of mechanically loaded Achilles tendons. Collagen density and organization was significantly reduced in focal micro-regions of mechanically loaded tendons. These pathological changes occurred specifically in association with altered tenocyte morphology. Normal tendons displayed a regular distribution of fibre bundles, and the average size of these bundles as determined by Gaussian analysis was 0.47 μm ± 0.02. In comparison, fibre bundle measures from tendon regions in the vicinity of abnormal tenocytes could not be quantified due to a reduction in their regularity of distribution and orientation. Conclusions SHG microscopy allowed high resolution detection of focal tendon abnormalities affecting the fibrillar collagen matrix. With ongoing

  4. Second harmonic generation analysis of early Achilles tendinosis in response to in vivo mechanical loading

    Directory of Open Access Journals (Sweden)

    Fong Gloria

    2011-01-01

    Full Text Available Abstract Background Tenocytes have been implicated in the development of tendinosis, a chronic condition commonly seen in musculoskeletal overuse syndromes. However, the relation between abnormal tenocyte morphology and early changes in the fibrillar collagen matrix has not been closely examined in vivo. Second harmonic generation (SHG microscopy is a recently developed technique which allows examination of fibrillar collagen structures with a high degree of specificity and resolution. The goal of this study was to examine the potential utility of SHG and multiphoton excitation fluorescence (MPEF microscopy in understanding the relation between tenocytes and their surrounding collagenous matrix in early tendon overuse lesions. Methods Histological preparations of tendon were prepared from adult male Sprague-Dawley rats subjected to an Achilles tendon loading protocol for 12 weeks (Rat-A-PED, or from sedentary age-matched cage controls. Second harmonic generation and multiphoton excitation fluorescence were performed simultaneously on these tissue sections in at least three different areas. Results SHG microscopy revealed an association between abnormal tenocyte morphology and morphological changes in the fibrillar collagen matrix of mechanically loaded Achilles tendons. Collagen density and organization was significantly reduced in focal micro-regions of mechanically loaded tendons. These pathological changes occurred specifically in association with altered tenocyte morphology. Normal tendons displayed a regular distribution of fibre bundles, and the average size of these bundles as determined by Gaussian analysis was 0.47 μm ± 0.02. In comparison, fibre bundle measures from tendon regions in the vicinity of abnormal tenocytes could not be quantified due to a reduction in their regularity of distribution and orientation. Conclusions SHG microscopy allowed high resolution detection of focal tendon abnormalities affecting the fibrillar collagen

  5. True Gold or Pyrite: A Review of Reference Point Indentation for Assessing Bone Mechanical Properties In Vivo.

    Science.gov (United States)

    Allen, Matthew R; McNerny, Erin Mb; Organ, Jason M; Wallace, Joseph M

    2015-09-01

    Although the gold standard for determining bones' mechanical integrity is the direct measure of mechanical properties, clinical evaluation has long relied on surrogates of mechanical properties for assessment of fracture risk. Nearly a decade ago, reference point indentation (RPI) emerged as an innovative way to potentially assess mechanical properties of bone in vivo. Beginning with the BioDent device, and then followed by the newer generation OsteoProbe, this RPI technology has been utilized in several publications. In this review we present an overview of the technology and some important details about the two devices. We also highlight select key studies, focused specifically on the in vivo application of these devices, as a way of synthesizing where the technology stands in 2015. The BioDent machine has been shown, in two clinical reports, to be able to differentiate fracture versus nonfracture patient populations and in preclinical studies to detect treatment effects that are consistent with those quantified using traditional mechanical tests. The OsteoProbe appears able to separate clinical cohorts yet there exists a lack of clarity regarding details of testing, which suggests more rigorous work needs to be undertaken with this machine. Taken together, RPI technology has shown promising results, yet much more work is needed to determine if its theoretical potential to assess mechanical properties in vivo can be realized. © 2015 American Society for Bone and Mineral Research.

  6. Mechanical isolation, and measurement of force and myoplasmic free [Ca(2+)] in fully intact single skeletal muscle fibers.

    Science.gov (United States)

    Cheng, Arthur J; Westerblad, Håkan

    2017-09-01

    Mechanical dissection of single intact mammalian skeletal muscle fibers permits real-time measurement of intracellular properties and contractile function of living fibers. A major advantage of mechanical over enzymatic fiber dissociation is that single fibers can be isolated with their tendons remaining attached, which allows contractile forces (in the normal expected range of 300-450 kN/m(2)) to be measured during electrical stimulation. Furthermore, the sarcolemma of single fibers remains fully intact after mechanical dissection, and hence the living fibers can be studied with intact intracellular milieu and normal function and metabolic properties, as well as ionic control. Given that Ca(2+) is the principal regulator of the contractile force, measurements of myoplasmic free [Ca(2+)] ([Ca(2+)]i) can be used to further delineate the intrinsic mechanisms underlying changes in skeletal muscle function. [Ca(2+)]i measurements are most commonly performed in intact single fibers using ratiometric fluorescent indicators such as indo-1 or fura-2. These Ca(2+) indicators are introduced into the fiber by pressure injection or by using the membrane-permeable indo-1 AM, and [Ca(2+)]i is measured by calculating a ratio of the fluorescence at specific wavelengths emitted for the Ca(2+)-free and Ca(2+)-bound forms of the dye. We describe here the procedures for mechanical dissection, and for force and [Ca(2+)]i measurement in intact single fibers from mouse flexor digitorum brevis (FDB) muscle, which is the most commonly used muscle in studies using intact single fibers. This technique can also be used to isolate intact single fibers from various muscles and from various species. As an alternative to Ca(2+) indicators, single fibers can also be loaded with fluorescent indicators to measure, for instance, reactive oxygen species, pH, and [Mg(2+)], or they can be injected with proteins to change functional properties. The entire protocol, from dissection to the start of an

  7. Constitutive expression of pregnancy-associated plasma protein-A in arterial smooth muscle reduces the vascular response to injury in vivo

    Science.gov (United States)

    Bale, Laurie K.; Resch, Zachary T.; Harstad, Sara L.; Overgaard, Michael T.

    2013-01-01

    Pregnancy-associated plasma protein-A (PAPP-A) functions to increase local IGF-I bioactivity. In this study, we used transgenic mice that constitutively express human PAPP-A in arterial smooth muscle to test the hypothesis that overexpression of PAPP-A enhances vascular smooth muscle cell (SMC) response to IGF-I in vivo. PAPP-A transgenic (Tg) and wild-type (WT) mice underwent unilateral carotid ligation, a model of injury-induced SMC hyperplasia and neointimal formation. In both WT and PAPP-A Tg mice, endogenous PAPP-A mRNA expression showed peak elevation 5 days after carotid ligation. However, PAPP-A Tg mice had 70–75% less neointima than WT at 5 and 10 days postligation, with a significant reduction in occlusion of the ligated artery. WT and PAPP-A Tg mice had equivalent increases in medial area and vessel remodeling postligation. There was little change in medial area and no evidence of neointima in the contralateral carotid of WT or PAPP-A Tg mice. Both WT and PAPP-A Tg carotids exhibited signs of dedifferentiation of SMC, which precedes the increase in proliferation and migration that results in neointimal formation. However, the number of proliferating cells in the media and neointima of the ligated PAPP-A Tg artery was reduced by 90% on day 5 postsurgery compared with WT. This decrease was associated with a significant decrease in an in vivo marker of IGF-I bioactivity and reduced IGF-I-stimulated receptor phosphorylation ex vivo. These data suggest differential effects of chronic (transgenic) and transient (endogenous) PAPP-A expression on neointimal formation following vascular injury that may be due in part to the differential impact on IGF-I signaling. PMID:23169786

  8. Rapid in vivo determination of fluoroquinolones in cultured puffer fish (Takifugu obscurus) muscle by solid-phase microextraction coupled with liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Tang, Yijia; Xu, Jianqiao; Chen, Le; Qiu, Junlang; Liu, Yuan; Ouyang, Gangfeng

    2017-12-01

    Fluoroquinolones (FQs) are a group of antimicrobial agents that have been widely used for therapeutic purposes in clinical medicine for human and veterinary diseases, as well as in aquaculture production. Their residues, however, may survive in foods of animal origin, thus causing health risks for human. In this study, a rapid and sensitive method based on in vivo solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to detect the residues of five FQs in cultured puffer fish (Takifugu obscurus). In vitro fiber evaluation experiment demonstrated that, compared with the thicker polydimethylsiloxane (PDMS) coating (165µm), the custom-made biocompatible C18-PAN fibers (45µm) exhibited much higher extraction efficiencies towards FQs (approximately 9-31 times). The custom-made C18-PAN coating also possessed excellent reproducibility in fish muscle with the intra-fiber relative standard deviations (RSDs) ranging from 11.2% to 14.3% (n = 6) and inter-fiber RSDs ranging from 13.1% to 16.1% (n = 6), which was suitable for in vivo sampling. The custom-made SPME fibers were subsequently applied to determine fluoroquinolones in dorsal-epaxial muscle of living puffer fish. The accuracies were verified through the comparison with traditional liquid extraction (LE) method, and the sensitivities were demonstrated to be satisfying with the limits of detection (LODs) ranging from 0.3ngg -1 to 1.5ngg -1 . In general, this study presented a convenient and high-efficient method to determine fluoroquinolones in puffer fish by in vivo sampling. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Experimental tooth clenching. A model for studying mechanisms of muscle pain.

    Science.gov (United States)

    Dawson, Andreas

    2013-01-01

    The overall goal of this thesis was to broaden knowledge of pain mechanisms in myofascial temporomandibular disorders (M-TMD). The specific aims were to: Develop a quality assessment tool for experimental bruxism studies (study I). Investigate proprioceptive allodynia after experimental tooth clenching exercises (study II). Evaluate the release of serotonin (5-HT), glutamate, pyruvate, and lactate in healthy subjects (study III) and in patients with M-TMD (study IV), after experimental tooth clenching exercises. In (I), tool development comprised 5 steps: (i) preliminary decisions, (ii) item generation, (iii) face-validity assessment, (iv) reliability and discriminative validity testing, and (v) instrument refinement. After preliminary decisions and a literature review, a list of 52 items to be considered for inclusion in the tool was generated. Eleven experts were invited to participate on the Delphi panel, of which 10 agreed. After four Delphi rounds, 8 items remained and were included in the Quality Assessment Tool for Experimental Bruxism Studies (Qu-ATEBS). Inter-observer reliability was acceptable (k = 0.77), and discriminative validity high (phi coefficient 0.79; P muscle blood flow. Two hours after the start of microdialysis, participants were randomized to a 20-min repetitive experimental tooth clenching task (50% of MVCF) or a control session (no clenching). Pain intensity was measured throughout the experiment. Substance levels and blood flow were unaltered at all time points between sessions, and between genders in each session. Pain intensity was significantly higher after clenching in the clenching session compared to the same time point in the control session. In (IV), 15 patients with M-TMD and 15 healthy controls participated in one session and the methodology described above was used. M-TMD patients had significantly higher levels of 5-HT and significantly lower blood flows than healthy controls. No significant differences for any substance at any

  10. Muscle tissue oxygenation, pressure, electrical, and mechanical responses during dynamic and static voluntary contractions

    DEFF Research Database (Denmark)

    Vedsted, Pernille; Blangsted, Anne Katrine; Søgaard, Karen

    2006-01-01

    Dynamic muscle contractions have been shown to cause greater energy turnover and fatigue than static contractions performed at a corresponding force level. Therefore, we hypothesized that: (1) electro- (EMG) and mechanomyography (MMG), intramuscular pressure (IMP), and reduction in muscle oxygen...... similar in spite of major differences in the MMG and EMG responses of the muscle during contraction periods. This may relate to the surprisingly lower IMP in DYN than IST....

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

    Science.gov (United States)

    Yu, Zhi-Bin

    2013-11-01

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

  12. Mechanical muscle and tendon properties of the plantar flexors are altered even in highly functional children with spastic cerebral palsy.

    Science.gov (United States)

    Kruse, Annika; Schranz, Christian; Svehlik, Martin; Tilp, Markus

    2017-12-01

    Recent ultrasound studies found increased passive muscle stiffness and no difference in tendon stiffness in highly impaired children and young adults with cerebral palsy. However, it is not known if muscle and tendon mechanical properties are already altered in highly functional children with cerebral palsy. Therefore, the purpose of this study was to compare the mechanical and material properties of the plantar flexors in highly functional children with cerebral palsy and typically developing children. Besides strength measurements, ultrasonography was used to assess gastrocnemius medialis and Achilles tendon elongation and stiffness, Achilles tendon stress, strain, and Young's modulus in twelve children with cerebral palsy (GMFCS levels I and II) and twelve typically developing peers during passive dorsiflexion rotations as well as maximum voluntary contractions. Despite no difference in ankle joint stiffness (P>0.05) between groups, passive but not active Achilles tendon stiffness was significantly decreased (-39%) and a tendency of increased passive muscle stiffness was observed even in highly functional children with cerebral palsy. However, material properties of the tendon were not altered. Maximum voluntary contraction showed reduced plantar flexor strength (-48%) in the cerebral palsy group. Even in children with mild spastic cerebral palsy, muscle and tendon mechanical properties are altered. However, it appears that the Achilles tendon stiffness is different only when low forces act on the tendon during passive movements. Although maximum voluntary force is already decreased, forces acting on the Achilles tendon during activity appear to be sufficient to maintain typical material properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Task failure during exercise to exhaustion in normoxia and hypoxia is due to reduced muscle activation caused by central mechanisms while muscle metaboreflex does not limit performance

    Directory of Open Access Journals (Sweden)

    Rafael eTorres-Peralta

    2016-01-01

    Full Text Available To determine whether task failure during incremental exercise to exhaustion (IE is principally due to reduced neural drive and increased metaboreflex activation eleven men (22±2 years performed a 10s control isokinetic sprint (IS; 80 rpm after a short warm-up. This was immediately followed by an IE in normoxia (Nx, PIO2:143 mmHg and hypoxia (Hyp, PIO2:73 mmHg in random order, separated by a 120 min resting period. At exhaustion, the circulation of both legs was occluded instantaneously (300 mmHg during 10 or 60s to impede recovery and increase metaboreflex activation. This was immediately followed by an IS with open circulation. Electromyographic recordings were obtained from the vastus medialis and lateralis. Muscle biopsies and blood gases were obtained in separate experiments. During the last 10s of the IE, pulmonary ventilation, VO2, power output and muscle activation were lower in hypoxia than in normoxia, while pedaling rate was similar. Compared to the control sprint, performance (IS-Wpeak was reduced to a greater extent after the IE-Nx (11% lower P<0.05 than IE-Hyp. The root mean square (EMGRMS was reduced by 38 and 27% during IS performed after IE-Nx and IE-Hyp, respectively (Nx vs. Hyp: P<0.05. Post-ischemia IS-EMGRMS values were higher than during the last 10s of IE. Sprint exercise mean (IS-MPF and median (IS-MdPF power frequencies, and burst duration, were more reduced after IE-Nx than IE-Hyp (P<0.05. Despite increased muscle lactate accumulation, acidification, and metaboreflex activation from 10 to 60s of ischemia, IS-Wmean (+23% and burst duration (+10% increased, while IS-EMGRMS decreased (-24%, P<0.05, with IS-MPF and IS-MdPF remaining unchanged. In conclusion, close to task failure, muscle activation is lower in hypoxia than in normoxia. Task failure is predominantly caused by central mechanisms, which recover to great extent within one minute even when the legs remain ischemic. There is dissociation between the recovery of

  14. The Role of Endothelial Cells in Myofiber Differentiation and the Vascularization and Innervation of Bioengineered Muscle Tissue in vivo

    Science.gov (United States)

    2012-10-08

    muscle in vitro. MPCs, ECs and PCs were co-cultured together on either Matrigel-coated dishes (A, B) or on the BAM scaffold (C, D) and live cell imaging was...differentiated in DM (D) were visualized using live cell imaging . Arrows (C) indicate branched vessel-like structures. Scale bars: 65 mm (E) EC content on the BAM

  15. In vivo measurements of T1 relaxation times of 31P-metabolites in human skeletal muscle

    DEFF Research Database (Denmark)

    Thomsen, C; Jensen, K E; Henriksen, O

    1989-01-01

    The T1 relaxation times were estimated for 31P-metabolites in human skeletal muscle. Five healthy volunteers were examined in a 1.5 Tesla wholebody imaging system using an inversion recovery pulse sequence. The calculated T1 relaxation times ranged from 5.517 sec for phosphocreatine to 3.603 sec...

  16. Effect of in vivo injection of cholera and pertussis toxin on glucose transport in rat skeletal muscle

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Han, X; Petersen, L N

    1997-01-01

    Cholera toxin (CTX) and pertussis toxin (PTX) were examined for their ability to inhibit glucose transport in perfused skeletal muscle. Twenty-five hours after an intravenous injection of CTX, basal transport was decreased approximately 30%, and insulin- and contraction-stimulated transport...

  17. MUSCLEMOTION : A Versatile Open Software Tool to Quantify Cardiomyocyte and Cardiac Muscle Contraction In Vitro and In Vivo

    NARCIS (Netherlands)

    Sala, Luca; van Meer, Berend J; Tertoolen, Leon T; Bakkers, Jeroen; Bellin, Milena; Davis, Richard P; Denning, Chris N; Dieben, Michel A; Eschenhagen, Thomas; Giacomelli, Elisa; Grandela, Catarina; Hansen, Arne; Holman, Eduard; Jongbloed, Monique R; Kamel, Sarah M; Koopman, Charlotte D; Lachaud, Quentin; Mannhardt, Ingra; Mol, Mervyn P; Mosqueira, Diogo; Orlova, Valeria V; Passier, Robert; Ribeiro, Marcelo C; Saleem, Umber; Smith, Godfrey; Burton, Francis L L; Mummery, Christine L

    2017-01-01

    Rationale: There are several methods to measure cardiomyocyte (CM) and muscle contraction but these require customized hardware, expensive apparatus and advanced informatics or can only be used in single experimental models. Consequently, data and techniques have been difficult to reproduce across

  18. Therapeutic metabolic inhibition: hydrogen sulfide significantly mitigates skeletal muscle ischemia reperfusion injury in vitro and in vivo

    NARCIS (Netherlands)

    Henderson, Peter W.; Singh, Sunil P.; Weinstein, Andrew L.; Nagineni, Vijay; Rafii, Daniel C.; Kadouch, Daniel; Krijgh, David D.; Spector, Jason A.

    2010-01-01

    BACKGROUND:: Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree of cellular damage associated with ischemia-reperfusion injury. The purpose of this study was to determine whether it is protective in skeletal muscle. METHODS:: This study used both in vitro (cultured

  19. Impaired Bronchoprotection Is Not Induced by Increased Smooth Muscle Mass in Chronic Treatment In Vivo with Formoterol in Asthmatic Mouse Model

    Directory of Open Access Journals (Sweden)

    W Luo

    2014-09-01

    Full Text Available Objective: Inhaling β2-adrenoceptor agonist is first-line asthma treatment, which is used for both acute relief and prevention of bronchoconstriction. However, chronic use of β-agonists results in impaired bronchoprotection and increasing occurrences of severe asthma exacerbation, even death in clinical practice. The mechanism of β-adrenoceptor hyposensitivity has not been thoroughly elucidated thus far. Bronchial smooth muscle contraction induces airway narrowing and also mediates airway inflammation. Moreover, bronchial smooth muscle mass significantly increases in asthmatics. We aimed to establish an asthmatic model that demonstrated that formoterol induced impaired bronchoprotection and to see whether increased smooth muscle mass played a role in it. Methods: We combined routine allergen challenging (seven weeks with repeated application of formoterol, formoterol plus budesonide or physiological saline in allergen-sensitized BALB/c mouse. The bronchoprotection mediated by β-agonist was measured in five consecutive weeks. Smooth muscle mass was shown by morphometric analysis, and α-actin expression was detected by western blot. Results: The trend of bronchoprotection was wavy in drug interventional groups, which initially increased and then decreased. Chronic treatment with formoterol significantly impaired bronchoprotection. According to the morphometric analysis and α-actin expression, no significant difference was detected in smooth muscle mass in all groups. Conclusion: This experiment successfully established that a chronic asthmatic mouse model, which manifested typical features of asthmatic patients, with chronic use of formoterol, results in a loss of bronchoprotection. No significant difference was detected in smooth muscle mass in all groups, which implied some subcellular signalling changes may be the key points.

  20. Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

    Science.gov (United States)

    2014-01-01

    functional analysis Torque production of the left anterior crural muscles (primarily due to the contraction of the TA and EDL mus- cles) was measured in...responders based on the following criteria. A TA muscle transplanted with a TEMR construct that recovered a peak torque value greater than 1 standard deviation...Functionally, removal of the EDL and EHL muscles resulted in a - 29.4% – 7.4% loss of peak torque from 4 to 12 weeks postablation when normalized to preinjury

  1. IGF-Loaded Silicon and Zinc Doped Brushite Cement: Physico-Mechanical Characterization and In Vivo Osteogenesis Evaluation

    Science.gov (United States)

    Vahabzadeh, Sahar; Bandyopadhyay, Amit; Bose, Susmita; Mandal, Rakesh; Nandi, Samit Kumar

    2015-01-01

    Dopants play critical roles in controlling the physical, mechanical, degradation kinetics, and in vivo properties of calcium phosphates. The aim of the present study was to evaluate the effects of Silicon (Si) and Zinc (Zn) dopants on physico-mechanical, and in vivo osteogenesis properties of brushite cements (BrCs) alone and in combination with insulin like growth factor 1(IGF-1). Although addition of 0.5 wt.% Si did not alter the setting time, β-TCP content, and compressive strength of BrCs significantly, 0.25 wt. % Zn incorporation was accompanied by a significant decrease in mechanical strength from 4.78±0.21 MPa for pure BrC to 3.78±0.59 MPa and 3.28±0.22 MPa for Zn-BrC and Si/Zn-BrC, respectively. The in vivo bone regeneration properties of doped BrCs alone and in combination with IGF-1 were assessed and compared using chronological radiography, histology, scanning electron microscopy and fluorochrome labeling after 2 and 4 months post implantation in rabbit femoral defect model. Based on different in vivo characterization, better osteogenesis and vasculogenesis was observed for Si-BrC and Si/Zn-BrC, whereas moderate bone regeneration was found in Zn-BrC as compared to pure BrCs. Excellent bone regeneration was observed when doped BrCs were combined with IGF-1. Our findings signify that addition of Si and/or Zn alters the physico-mechanical properties of BrCs and promotes the early stage in vivo osseointegration and bone remodeling properties. Moreover, addition of IGF-1 further improved the performance of BrCs in terms of bone regeneration in animal model. PMID:26530147

  2. The mechanism of MAP kinase activation under acidic condition in feline esophageal smooth muscle cells.

    Science.gov (United States)

    Park, Sun Young; Lee, Young Ju; Min, Youngsil; Kim, Hak Rim; Jeong, Ji Hoon; Sohn, Uy Dong

    2011-10-01

    Reflux esophagitis results from repeated exposure of the esophagus to acidic gastric juice or bile-containing duodenal contents. In Barrett's adenocarcinoma, acid increases proliferation via ERK and p38 MAPK activation. This study was focused on determination of the mechanism(s) underlying MAPKs (ERK 1/2, p38 MAPK, and JNK) activation induced by acidic medium at pH 4 in normal feline primary cultured esophageal smooth muscle cells (FESMCs). We detected ERK 1/2 and p38 MAPK phosphorylation after exposure to pH 4 or neutral media in the presence or absence of several inhibitors and quantified the MAPK levels using western blotting analysis and densitometry. Acidic medium markedly increased the phosphorylation of ERK 1/2 and p38 MAPK within 10 min. Acid-induced ERK 1/2 and p38 MAPK activation was inhibited by pertussis toxin (PTX-sensitive G(i/o) protein inhibitor), DEDA (phospholipase (PL) A(2) inhibitor), ρCMB (PLD inhibitor), GF109203X (protein kinase C (PKC) inhibitor) and D609 (phosphatidylcholine-specific PLC inhibitor). But, genistein (tyrosine kinase inhibitor), forskolin (adenylate cyclase activator) and U73122 (phosphatidylinositol-specific PLC inhibitor) had no effect on acid-induced ERK1/2 and p38 MAPK activation. These findings indicate that the activation of ERK 1/2 and p38 MAPK pathways by acidic conditions, at least in part, may be mediated by activation of the G(i/o) protein coupled receptors, PC-PLC, PLD, PLA(2), and PKC in FESMCs.

  3. Subcellular localization and mechanism of secretion of vascular endothelial growth factor in human skeletal muscle

    DEFF Research Database (Denmark)

    Høier, Birgitte; Prats Gavalda, Clara; Qvortrup, Klaus

    2013-01-01

    The subcellular distribution and secretion of vascular endothelial growth factor (VEGF) was examined in skeletal muscle of healthy humans. Skeletal muscle biopsies were obtained from m.v. lateralis before and after a 2 h bout of cycling exercise. VEGF localization was conducted on preparations...

  4. Exercise and Type 2 Diabetes: Molecular Mechanisms Regulating Glucose Uptake in Skeletal Muscle

    Science.gov (United States)

    Stanford, Kristin I.; Goodyear, Laurie J.

    2014-01-01

    Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial…