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Sample records for vivo mechanical muscle

  1. S1P-induced airway smooth muscle hyperresponsiveness and lung inflammation in vivo: molecular and cellular mechanisms.

    Science.gov (United States)

    Roviezzo, F; Sorrentino, R; Bertolino, A; De Gruttola, L; Terlizzi, M; Pinto, A; Napolitano, M; Castello, G; D'Agostino, B; Ianaro, A; Sorrentino, R; Cirino, G

    2015-04-01

    Sphingosine-1-phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung. BALB/c, mast cell-deficient and Nude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed. S1P administration to BALB/c mice increased airway smooth muscle reactivity, mucus production, PGD2 , IgE, IL-4 and IL-13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell-deficient Kit (W) (-sh/) (W) (-sh) mice injected with S1P did not display airway smooth muscle hyper-reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti-CD23 antibody B3B4, which blocks IgE production, inhibited both S1P-induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to Nude mice did not elicit airway smooth muscle hyper-reactivity and lung inflammation. Naïve (untreated) mice subjected to the adoptive transfer of CD4+ T-cells harvested from S1P-treated mice presented all the features elicited by S1P in the lung. S1P triggers a cascade of events that sequentially involves T-cells, IgE and mast cells reproducing several asthma-like features. This model may represent a useful tool for defining the role of S1P in the mechanism of action of currently-used drugs as well as in the development of new therapeutic approaches for asthma-like diseases. © 2014 The British Pharmacological Society.

  2. 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

    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 str...

  3. 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.

  4. Muscle and Limb Mechanics.

    Science.gov (United States)

    Tsianos, George A; Loeb, Gerald E

    2017-03-16

    Understanding of the musculoskeletal system has evolved from the collection of individual phenomena in highly selected experimental preparations under highly controlled and often unphysiological conditions. At the systems level, it is now possible to construct complete and reasonably accurate models of the kinetics and energetics of realistic muscles and to combine them to understand the dynamics of complete musculoskeletal systems performing natural behaviors. At the reductionist level, it is possible to relate most of the individual phenomena to the anatomical structures and biochemical processes that account for them. Two large challenges remain. At a systems level, neuroscience must now account for how the nervous system learns to exploit the many complex features that evolution has incorporated into muscle and limb mechanics. At a reductionist level, medicine must now account for the many forms of pathology and disability that arise from the many diseases and injuries to which this highly evolved system is inevitably prone. © 2017 American Physiological Society. Compr Physiol 7:429-462, 2017. Copyright © 2017 John Wiley & Sons, Inc.

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

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    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.

  6. Muscle mechanics and neuromuscular control

    NARCIS (Netherlands)

    Hof, AL

    The purpose of this paper is to demonstrate that the properties of the mechanical system, especially muscle elasticity and limb mass, to a large degree determine force output and movement. This makes the control demands of the central nervous system simpler and more robust. In human triceps surae, a

  7. Passive in vivo elastography from skeletal muscle noise

    International Nuclear Information System (INIS)

    Sabra, Karim G.; Conti, Stephane; Roux, Philippe; Kuperman, W. A.

    2007-01-01

    Measuring the in vivo elastic properties of muscles (e.g., stiffness) provides a means for diagnosing and monitoring muscular activity. The authors demonstrated a passive in vivo elastography technique without an active external radiation source. This technique instead uses cross correlations of contracting skeletal muscle noise recorded with skin-mounted sensors. Each passive sensor becomes a virtual in vivo shear wave source. The results point to a low-cost, noninvasive technique for monitoring biomechanical in vivo muscle properties. The efficacy of the passive elastography technique originates from the high density of cross paths between all sensor pairs, potentially achieving the same sensitivity obtained from active elastography methods

  8. Intermuscular force transmission between human plantarflexor muscles in vivo

    DEFF Research Database (Denmark)

    Bojsen-Møller, Jens; Schwartz, Sidse; Kalliokoski, Kari K

    2010-01-01

    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...... surae muscles was seen during passive hallux extension. Large interindividual differences with respect to deep plantarflexor activation during voluntary contractions were observed. The present results suggest that force may be transmitted between the triceps surae muscles in vivo, while only limited...

  9. In vivo myograph measurement of muscle contraction at optimal length

    Directory of Open Access Journals (Sweden)

    Ahmed Aminul

    2007-01-01

    Full Text Available Abstract Background Current devices for measuring muscle contraction in vivo have limited accuracy in establishing and re-establishing the optimum muscle length. They are variable in the reproducibility to determine the muscle contraction at this length, and often do not maintain precise conditions during the examination. Consequently, for clinical testing only semi-quantitative methods have been used. Methods We present a newly developed myograph, an accurate measuring device for muscle contraction, consisting of three elements. Firstly, an element for adjusting the axle of the device and the physiological axis of muscle contraction; secondly, an element to accurately position and reposition the extremity of the muscle; and thirdly, an element for the progressive pre-stretching and isometric locking of the target muscle. Thus it is possible to examine individual in vivo muscles in every pre-stretched, specified position, to maintain constant muscle-length conditions, and to accurately re-establish the conditions of the measurement process at later sessions. Results In a sequence of experiments the force of contraction of the muscle at differing stretching lengths were recorded and the forces determined. The optimum muscle length for maximal force of contraction was established. In a following sequence of experiments with smaller graduations around this optimal stretching length an increasingly accurate optimum muscle length for maximal force of contraction was determined. This optimum length was also accurately re-established at later sessions. Conclusion We have introduced a new technical solution for valid, reproducible in vivo force measurements on every possible point of the stretching curve. Thus it should be possible to study the muscle contraction in vivo to the same level of accuracy as is achieved in tests with in vitro organ preparations.

  10. 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...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

  11. 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

    immediately surrounding regenerating muscle fibres. These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell-cell cross......-talk during physiological and pathological muscle remodelling. ABSTRACT: 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 on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle...

  12. 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

  13. 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.

  14. Mechanisms of mechanical strain memory in airway smooth muscle.

    Science.gov (United States)

    Kim, Hak Rim; Hai, Chi-Ming

    2005-10-01

    We evaluated the hypothesis that mechanical deformation of airway smooth muscle induces structural remodeling of airway smooth muscle cells, thereby modulating mechanical performance in subsequent contractions. This hypothesis implied that past experience of mechanical deformation was retained (or "memorized") as structural changes in airway smooth muscle cells, which modulated the cell's subsequent contractile responses. We termed this phenomenon mechanical strain memory. Preshortening has been found to induce attenuation of both force and isotonic shortening velocity in cholinergic receptor-activated airway smooth muscle. Rapid stretching of cholinergic receptor-activated airway smooth muscle from an initial length to a final length resulted in post-stretch force and myosin light chain phosphorylation that correlated significantly with initial length. Thus post-stretch muscle strips appeared to retain memory of the initial length prior to rapid stretch (mechanical strain memory). Cytoskeletal recruitment of actin- and integrin-binding proteins and Erk 1/2 MAPK appeared to be important mechanisms of mechanical strain memory. Sinusoidal length oscillation led to force attenuation during oscillation and in subsequent contractions in intact airway smooth muscle, and p38 MAPK appeared to be an important mechanism. In contrast, application of local mechanical strain to cultured airway smooth muscle cells induced local actin polymerization and cytoskeletal stiffening. It is conceivable that deep inspiration-induced bronchoprotection may be a manifestation of mechanical strain memory such that mechanical deformation from past breathing cycles modulated the mechanical performance of airway smooth muscle in subsequent cycles in a continuous and dynamic manner.

  15. Muscle-Driven In Vivo Nanogenerator

    KAUST Repository

    Li, Zhou; Zhu, Guang; Yang, Rusen; Wang, Aurelia C.; Wang, Zhong Lin

    2010-01-01

    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.

  16. 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.

  17. [Molecular mechanisms of skeletal muscle hypertrophy].

    Science.gov (United States)

    Astratenkova, I V; Rogozkin, V A

    2014-06-01

    Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

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

    Science.gov (United States)

    Mackey, Abigail L; Magnan, Mélanie; Chazaud, Bénédicte; Kjaer, Michael

    2017-08-01

    Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. The extent of cross-talk between fibroblasts, as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell-culture studies. We observed a strong stimulation of myogenesis by human fibroblasts in cell culture. In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres. These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell-cell cross-talk during physiological and pathological muscle remodelling. 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 on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle injury protocol in young healthy men (n = 7), the number of fibroblasts (TCF7L2+), satellite cells (Pax7+), differentiating myogenic cells (myogenin+) and regenerating fibres (neonatal/embryonic myosin+) was determined from biopsy cross-sections. Fibroblasts and myogenic precursor cells (MPCs) were also isolated from human skeletal muscle (n = 4) and co-cultured using different cell ratios, with the two cell populations either in direct contact with each other or separated by a permeable

  19. Quantitative sonoelastography for the in vivo assessment of skeletal muscle viscoelasticity

    International Nuclear Information System (INIS)

    Hoyt, Kenneth; Kneezel, Timothy; Castaneda, Benjamin; Parker, Kevin J

    2008-01-01

    A novel quantitative sonoelastography technique for assessing the viscoelastic properties of skeletal muscle tissue was developed. Slowly propagating shear wave interference patterns (termed crawling waves) were generated using a two-source configuration vibrating normal to the surface. Theoretical models predict crawling wave displacement fields, which were validated through phantom studies. In experiments, a viscoelastic model was fit to dispersive shear wave speed sonoelastographic data using nonlinear least-squares techniques to determine frequency-independent shear modulus and viscosity estimates. Shear modulus estimates derived using the viscoelastic model were in agreement with that obtained by mechanical testing on phantom samples. Preliminary sonoelastographic data acquired in healthy human skeletal muscles confirm that high-quality quantitative elasticity data can be acquired in vivo. Studies on relaxed muscle indicate discernible differences in both shear modulus and viscosity estimates between different skeletal muscle groups. Investigations into the dynamic viscoelastic properties of (healthy) human skeletal muscles revealed that voluntarily contracted muscles exhibit considerable increases in both shear modulus and viscosity estimates as compared to the relaxed state. Overall, preliminary results are encouraging and quantitative sonoelastography may prove clinically feasible for in vivo characterization of the dynamic viscoelastic properties of human skeletal muscle

  20. Mechanical stimulation improves tissue-engineered human skeletal muscle

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    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.

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

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    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.

  2. Contraction and AICAR stimulate IL-6 vesicle depletion from skeletal muscle fibers in vivo.

    Science.gov (United States)

    Lauritzen, Hans P M M; Brandauer, Josef; Schjerling, Peter; Koh, Ho-Jin; Treebak, Jonas T; Hirshman, Michael F; Galbo, Henrik; Goodyear, Laurie J

    2013-09-01

    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 muscle fibers and in live animals in vivo. Using confocal imaging to visualize endogenous IL-6 protein in fixed muscle fibers, we found IL-6 in small vesicle structures distributed throughout the fibers under basal (resting) conditions. To determine the kinetics of IL-6 secretion, intact quadriceps muscles were transfected with enhanced green fluorescent protein (EGFP)-tagged IL-6 (IL-6-EGFP), and 5 days later anesthetized mice were imaged before and after muscle contractions in situ. Contractions decreased IL-6-EGFP-containing vesicles and protein by 62% (P contraction. However, contraction-mediated IL-6-EGFP reduction was normal in muscle-specific AMP-activated protein kinase (AMPK) α2-inactive transgenic mice. In contrast, the AMPK activator AICAR decreased IL-6-EGFP vesicles, an effect that was inhibited in the transgenic mice. In conclusion, resting skeletal muscles contain IL-6-positive vesicles that are expressed throughout myofibers. Contractions stimulate the rapid reduction of IL-6 in myofibers, occurring through an AMPKα2-independent mechanism. This novel imaging methodology clearly establishes IL-6 as a contraction-stimulated myokine and can be used to characterize the secretion kinetics of other putative myokines.

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

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    Mirvakili, Seyed M; Hunter, Ian W

    2018-02-01

    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.

  4. 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

  5. Evaluation of human muscle in vivo by potassium radiometric measuring

    International Nuclear Information System (INIS)

    Sousa, Wanderson de P.

    2000-01-01

    Potassium is an essential element to the human metabolism and is present in all living cells, mainly in the striated muscular fibers. K-40 is one of the natural potassium isotopes with mass percentage of 0,0118% . This isotope emits beta particle and gamma rays with 1460 keV. The energy of K-40 photon and its uniform distribution within the human body allows its in vivo measurement. The objective of this study is to optimize this technique and evaluate the possibility of its medical application in order to quantify muscle increase during recovering procedures. Subjects of both sexes measured until this moment were divided into two groups. Subjects of Group 1 do not exercise routinely and subjects of Group 2 does. In Group 1 the average potassium mass, muscle mass and potassium concentration were (101±16)g of K, (20±3)kg of muscle and (1,3±0,3)g of K/kg of body mass, respectively, while in Group 2 average values were (125±38)g of K, (25±8)kg of muscle and (1,7±0,2)g of K/kg of body mass. The comparison between average values shows a clear difference, which allows to correlate a higher K mass with routine body activity. The technique has shown enough sensitivity for this application. (author)

  6. Influence of temperature on muscle recruitment and muscle function in vivo.

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    Rome, L C

    1990-08-01

    Temperature has a large influence on the maximum velocity of shortening (Vmax) and maximum power output of muscle (Q10 = 1.5-3). In some animals, maximum performance and maximum sustainable performance show large temperature sensitivities, because these parameters are dependent solely on mechanical power output of the muscles. The mechanics of locomotion (sarcomere length excursions and muscle-shortening velocities, V) at a given speed, however, are precisely the same at all temperatures. Animals compensate for the diminished power output of their muscles at low temperatures by compressing their recruitment order into a narrower range of locomotor speeds, that is, recruiting more muscle fibers and faster fiber types at a given speed. By examining V/Vmax, I calculate that fish at 10 degrees C must recruit 1.53-fold greater fiber cross section than at 20 degrees C. V/Vmax also appears to be an important design constraint in muscle. It sets the lowest V and the highest V over which a muscle can be used effectively. Because the Vmax of carp slow red muscle has a Q10 of 1.6 between 10 and 20 degrees C, the slow aerobic fibers can be used over a 1.6-fold greater range of swim speeds at the warmer temperature. In some species of fish, Vmax can be increased during thermal acclimation, enabling animals to swim at higher speeds.

  7. Mechanisms of cisplatin-induced muscle atrophy

    International Nuclear Information System (INIS)

    Sakai, Hiroyasu; Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara; Sato, Ken; Chiba, Yoshihiko; Yamazaki, Mitsuaki; Matoba, Motohiro; Narita, Minoru

    2014-01-01

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

  8. 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.

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

    Science.gov (United States)

    Yashiro, Kazuya; Tonson, Anne; Pecchi, Émilie; Vilmen, Christophe; Le Fur, Yann; Bernard, Monique; Bendahan, David; Giannesini, Benoît

    2015-01-01

    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.

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

    International Nuclear Information System (INIS)

    Ishido, Minenori; Kasuga, Norikatsu

    2012-01-01

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

  11. The expression of the skeletal muscle force-length relationship in vivo: a simulation study.

    Science.gov (United States)

    Winter, Samantha L; Challis, John H

    2010-02-21

    The force-length relationship is one of the most important mechanical characteristics of skeletal muscle in humans and animals. For a physiologically realistic joint range of motion and therefore range of muscle fibre lengths only part of the force-length curve may be used in vivo, i.e. only a section of the force-length curve is expressed. A generalised model of a mono-articular muscle-tendon complex was used to examine the effect of various muscle architecture parameters on the expressed section of the force-length relationship for a 90 degrees joint range of motion. The parameters investigated were: the ratio of tendon resting length to muscle fibre optimum length (L(TR):L(F.OPT)) (varied from 0.5 to 11.5), the ratio of muscle fibre optimum length to average moment arm (L(F.OPT):r) (varied from 0.5 to 5), the normalised tendon strain at maximum isometric force (c) (varied from 0 to 0.08), the muscle fibre pennation angle (theta) (varied from 0 degrees to 45 degrees) and the joint angle at which the optimum muscle fibre length occurred (phi). The range of values chosen for each parameter was based on values reported in the literature for five human mono-articular muscles with different functional roles. The ratios L(TR):L(F.OPT) and L(F.OPT):r were important in determining the amount of variability in the expressed section of the force-length relationship. The modelled muscle operated over only one limb at intermediate values of these two ratios (L(TR):L(F.OPT)=5; L(F.OPT):r=3), whether this was the ascending or descending limb was determined by the precise values of the other parameters. It was concluded that inter-individual variability in the expressed section of the force-length relationship is possible, particularly for muscles with intermediate values of L(TR):L(F.OPT) and L(F.OPT):r such as the brachialis and vastus lateralis. Understanding the potential for inter-individual variability in the expressed section is important when using muscle models to

  12. Downstream mechanisms of nitric oxide-mediated skeletal muscle glucose uptake during contraction.

    Science.gov (United States)

    Merry, Troy L; Lynch, Gordon S; McConell, Glenn K

    2010-12-01

    There is evidence that nitric oxide (NO) is required for the normal increases in skeletal muscle glucose uptake during contraction, but the mechanisms involved have not been elucidated. We examined whether NO regulates glucose uptake during skeletal muscle contractions via cGMP-dependent or cGMP-independent pathways. Isolated extensor digitorum longus (EDL) muscles from mice were stimulated to contract ex vivo, and potential NO signaling pathways were blocked by the addition of inhibitors to the incubation medium. Contraction increased (P contraction by ∼50% (P contraction; however, DTT attenuated (P contraction-stimulated glucose uptake (by 70%). NOS inhibition and antioxidant treatment reduced contraction-stimulated increases in protein S-glutathionylation and tyrosine nitration (P skeletal muscle glucose uptake during ex vivo contractions via a cGMP/PKG-, AMPK-, and p38 MAPK-independent pathway. In addition, it appears that NO and ROS may regulate skeletal muscle glucose uptake during contraction through a similar pathway.

  13. 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...

  14. Mechanical Coupling between Muscle-Tendon Units Reduces Peak Stresses

    NARCIS (Netherlands)

    Maas, Huub; Finni, Taija

    2018-01-01

    The presence of mechanical linkages between synergistic muscles and their common tendons may distribute forces among the involved structures. We review studies, using humans and other animals, examining muscle and tendon interactions and discuss the hypothesis that connections between muscle bellies

  15. Spatial heterogeneity of metabolism in skeletal muscle in vivo studied by 31P-NMR spectroscopy

    International Nuclear Information System (INIS)

    Challiss, R.A.J.; Blackledge, M.J.; Radda, G.K.

    1988-01-01

    Phase modulated rotating-frame imaging, a localization technique for phosphorus nuclear magnetic resonance spectroscopy, has been applied to obtain information on heterogeneity of phosphorus-containing metabolites in skeletal muscle of the rat in vivo. The distal muscles of the rat hindlimb have been studied at rest and during steady-state isometric twitch contraction; the use of a transmitter surface coil and an electrically isolated, orthogonal receiver Helmholtz coil ensure accurate spatial assignment (1 mm resolution). At rest, intracellular pH was higher and PCr/(PCr + P i ) was lower in deeper muscle compared with superficial muscle of the distal hindlimb. Upon steady-state stimulation, the relatively more alkaline pH of deep muscle was maintained, whereas greater changes in PCr/(PCr + P i ) and P i /ATP occurred in the superficial muscle layer. This method allows rapid (75 min for each spectral image) acquisition of quantitative information on metabolic heterogeneity in vivo

  16. In vivo measurements of the triceps surae complex architecture in man: implications for muscle function

    NARCIS (Netherlands)

    Maganaris, C.N.; Baltzopoulos, V.; Sargeant, A.J.

    1998-01-01

    1. The objectives of this study were to (1) quantify experimentally in vivo changes in pennation angle, fibre length and muscle thickness in the triceps surae complex in man in response to changes in ankle position and isometric plantarflexion moment and (2) compare changes in the above muscle

  17. Mechanisms of exertional fatigue in muscle glycogenoses

    DEFF Research Database (Denmark)

    Vissing, John; Haller, Ronald G

    2012-01-01

    , which may be important for maintaining muscle membrane excitability by decreasing chloride permeability, (2) loss of the osmotic effect related to lactate accumulation, which may account for absence of the normal increase in water content of exercised muscle, and thus promote higher than normal...... concentrations of extracellular potassium in exercising muscle and (3) exaggerated accumulation of ADP during exercise that may inhibit sodium-potassium and calcium-ATPases. Disorders of muscle glycogenolysis and glycolysis reveal the crucial role of these metabolic processes for supplying both anaerobic...

  18. 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.

  19. 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

    muscle fibers and in live animals in vivo. Using confocal imaging to visualize endogenous IL-6 protein in fixed muscle fibers, we found IL-6 in small vesicle structures distributed throughout the fibers under basal (resting) conditions. To determine the kinetics of IL-6 secretion, intact quadriceps...... muscles were transfected with enhanced green fluorescent protein (EGFP)-tagged IL-6 (IL-6-EGFP), and 5 days later anesthetized mice were imaged before and after muscle contractions in situ. Contractions decreased IL-6-EGFP-containing vesicles and protein by 62% (P

  20. Creatine Loading, Resistance Exercise Performance, and Muscle Mechanics.

    Science.gov (United States)

    Stevenson, Scott W.; Dudley, Gary A.

    2001-01-01

    Examined whether creatine (CR) monohydrate loading would alter resistance exercise performance, isometric strength, or in vivo contractile properties of the quadriceps femoris muscle compared with placebo loading in resistance-trained athletes. Overall, CR loading did not provide an ergogenic benefit for the unilateral dynamic knee extension…

  1. Local myogenic pulp-derived cell injection enhances craniofacial muscle regeneration in vivo.

    Science.gov (United States)

    Jung, J E; Song, M J; Shin, S; Choi, Y J; Kim, K H; Chung, C J

    2017-02-01

    To enhance myogenic differentiation in pulp cells isolated from extracted premolars by epigenetic modification using a DNA demethylation agent, 5-aza-2'-deoxycytidine (5-Aza), and to evaluate the potent stimulatory effect of 5-Aza-treated pulp cell injection for craniofacial muscle regeneration in vivo. Pulp cells were isolated from premolars extracted for orthodontic purposes from four adults (age range, 18-22.1 years). Levels of myogenic differentiation and functional contraction response in vitro were compared between pulp cells with or without pre-treatment of 5-Aza. Changes in muscle regeneration in response to green fluorescent protein (GFP)-labelled myogenic pulp cell injection in vivo were evaluated using a cardiotoxin (CTX)-induced muscle injury model of the gastrocnemius as well as the masseter muscle in mice. Pre-treatment of 5-Aza in pulp cells stimulated myotube formation, myogenic differentiation in terms of desmin and myogenin expression, and the level of collagen gel contraction. The local injection of 5-Aza pre-treated myogenic pulp cells was engrafted into the host tissue and indicated signs of enhanced muscle regeneration in both the gastrocnemius and the masseter muscles. The epigenetic modification of pulp cells from extracted premolars and the local injection of myogenic pulp cells may stimulate craniofacial muscles regeneration in vivo. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    DEFF Research Database (Denmark)

    Christensen, Britt; Lundby, Carsten; Jessen, Niels

    2012-01-01

    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...... 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...

  3. 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...

  4. Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

    Science.gov (United States)

    Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

    2018-03-01

    The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Lower limb asymmetry in mechanical muscle function

    DEFF Research Database (Denmark)

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

    2015-01-01

    .05), and the final phase of the SJ (P AI in the CMJ concentric phase (r = 0.57, P Future research is required to assess the role of the CMJ and SJ phase-specific kinetic impulse AI......-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......) for kinetic impulse (CMJ and SJ phase-specific kinetic impulse AI). Dual x-ray absorptiometry scanning was used to assess asymmetry in lower body muscle mass. Compared with controls, ACL-R skiers had increased AI in muscle mass (P AI in the CMJ concentric phase (P 

  6. Cholinergic mechanisms in spinal cord and muscle

    International Nuclear Information System (INIS)

    Aquilonius, S.M.; Askmark, H.; Gilberg, P.G.

    1986-01-01

    Current knowledge regarding the distribution of acetylcholinesterase (ACHE) cholineacetyltranferase (ChAT) and cholinergic receptors in the spinal cord is presented as well as changes in these markers coupled to the degenerations in amyotrophic lateral sclerosis (ALS). The principal changes in ChAT and nicotonic receptors in rat hindleg muscles during denervation and reinnervation is discussed as a background for quantitative studies in human muscle biopsies. It is noted that thefirst published autoradiograph on spinal cord muscarinic receptors was from the rat, depicting an intense binding of radiolabeled quinuclikiny benzilate (tritium-QNB) in the ventral horn, and expecially in an apical part of the dorsal horn claimed to correspond to correspond to sustantia gelatinosa

  7. Effects of in vivo-like activation frequency on the length-dependent force generation of skeletal muscle fibre bundles

    NARCIS (Netherlands)

    Zuurbier, C. J.; Lee-de Groot, M. B.; van der Laarse, W. J.; Huijing, P. A.

    1998-01-01

    It is known that a range of firing frequencies can be observed during in vivo muscle activity, yet information is lacking as to how different in vivo-like frequencies may affect force generation of skeletal muscle. This study examined the effects of constant (CSF, constant within one contraction)

  8. In vivo postprandial lipid partitioning in liver and muscle of diabetic rats is disturbed

    NARCIS (Netherlands)

    Prompers, J.J.; Jonkers, R.A.M.; Loon, van L.J.C.; Nicolay, K.

    2012-01-01

    Objective: To study in vivo lipid partitioning in insulin-resistant liver and muscle of diabetic rats using magnetic resonance spectroscopy (MRS). Methods: Four groups of n=6 male Zucker diabetic fatty rats were used for this study: obese, pre-diabetic fa/fa rats and lean, non-diabetic fa/+

  9. In vivo generation of a mature and functional artificial skeletal muscle.

    Science.gov (United States)

    Fuoco, Claudia; Rizzi, Roberto; Biondo, Antonella; Longa, Emanuela; Mascaro, Anna; Shapira-Schweitzer, Keren; Kossovar, Olga; Benedetti, Sara; Salvatori, Maria L; Santoleri, Sabrina; Testa, Stefano; Bernardini, Sergio; Bottinelli, Roberto; Bearzi, Claudia; Cannata, Stefano M; Seliktar, Dror; Cossu, Giulio; Gargioli, Cesare

    2015-04-01

    Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for a large number of pathological conditions involving muscle tissue wasting. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  10. 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...... compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal....

  11. Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKα2 in the regulation of exercise capacity in vivo.

    Science.gov (United States)

    Lee-Young, R S; Ayala, J E; Fueger, P T; Mayes, W H; Kang, L; Wasserman, D H

    2011-07-01

    Skeletal muscle AMP-activated protein kinase (AMPK)α2 activity is impaired in obese, insulin-resistant individuals during exercise. We determined whether this defect contributes to the metabolic dysregulation and reduced exercise capacity observed in the obese state. C57BL/6J wild-type (WT) mice and/or mice expressing a kinase dead AMPKα2 subunit in skeletal muscle (α2-KD) were fed chow or high-fat (HF) diets from 3 to 16 weeks of age. At 15 weeks, mice performed an exercise stress test to determine exercise capacity. In WT mice, muscle glucose uptake and skeletal muscle AMPKα2 activity was assessed in chronically catheterized mice (carotid artery/jugular vein) at 16 weeks. In a separate study, HF-fed WT and α2-KD mice performed 5 weeks of exercise training (from 15 to 20 weeks of age) to test whether AMPKα2 is necessary to restore work tolerance. HF-fed WT mice had reduced exercise tolerance during an exercise stress test, and an attenuation in muscle glucose uptake and AMPKα2 activity during a single bout of exercise (Pfeeding further reduced running time ∼25% (Pexercise training, HF-fed WT and α2-KD mice increased maximum running speed ∼35% (PExercise training restored running speed to levels seen in healthy, chow-fed mice. HF feeding impairs AMPKα2 activity in skeletal muscle during exercise in vivo. Although this defect directly contributes to reduced exercise capacity, findings in HF-fed α2-KD mice show that AMPKα2-independent mechanisms are also involved. Importantly, α2-KD mice on a HF-fed diet adapt to regular exercise by increasing exercise tolerance, demonstrating that this adaptation is independent of skeletal muscle AMPKα2 activity.

  12. 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.

  13. The effect of fast and slow motor unit activation on whole-muscle mechanical performance: the size principle may not pose a mechanical paradox.

    Science.gov (United States)

    Holt, N C; Wakeling, J M; Biewener, A A

    2014-05-22

    The output of skeletal muscle can be varied by selectively recruiting different motor units. However, our knowledge of muscle function is largely derived from muscle in which all motor units are activated. This discrepancy may limit our understanding of in vivo muscle function. Hence, this study aimed to characterize the mechanical properties of muscle with different motor unit activation. We determined the isometric properties and isotonic force-velocity relationship of rat plantaris muscles in situ with all of the muscle active, 30% of the muscle containing predominately slower motor units active or 20% of the muscle containing predominately faster motor units active. There was a significant effect of active motor unit type on isometric force rise time (p motor units were active than when either fast or slow motor units were selectively activated. We propose this is due to the greater relative effects of factors such as series compliance and muscle resistance to shortening during sub-maximal contractions. The findings presented here suggest that recruitment according to the size principle, where slow motor units are activated first and faster ones recruited as demand increases, may not pose a mechanical paradox, as has been previously suggested.

  14. A mechanism for trauma induced muscle wasting and immune dysfunction

    Science.gov (United States)

    Madihally, S.; Toner, M.; Yarmush, M.; Mitchell, R.

    A diverse physiological conditions lead to a hypercatabolic state marked by the loss of proteins, primarily derived from skeletal muscle. The sustained loss of proteins results in loss of muscle mass and strength, poor healing, and long-term hospitalization. These problems are further compounded by the deterioration of immunity to infection which is a leading cause of morbidity and mortality of traumatic patients. In an attempt to understand the signal propagation mechanism(s), we tested the role of Interferon-? (IFN-? ) in an animal burn injury model; IFN-? is best conceptualized as a macrophage activating protein and known to modulate a variety of intracellular processes potentially relevant to muscle wasting and immune dysfunction. Mice congenitally -deficient in IFN-? , and IFN-? -Receptor, and wild type (WT) animals treated with IFN-? neutralizing antibody received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 following treatment, skeletal muscle, peripheral blood, and spleen were harvested from both groups. Overall body weight, protein turnovers, changes in the lymphocyte subpopulations and alterations in the major histocompatibility complex I expression (MHC I) and proliferation capacity of lymphocytes was measured using mixed lymphocyte reaction (MLR). These results indicate that we can prevent both muscle wasting and immune dysfunction. Based on these observations and our previous other animal model results (using insulin therapy), a novel mechanism of interactions leading to muscle wasting and immune dysfunction will be discussed. Further, implications of these findings on future research and clinical therapies will be discussed in detail.

  15. A bio-robotic platform for integrating internal and external mechanics during muscle-powered swimming.

    Science.gov (United States)

    Richards, Christopher T; Clemente, Christofer J

    2012-03-01

    To explore the interplay between muscle function and propulsor shape in swimming animals, we built a robotic foot to mimic the morphology and hind limb kinematics of Xenopus laevis frogs. Four foot shapes ranging from low aspect ratio (AR = 0.74) to high (AR = 5) were compared to test whether low-AR feet produce higher propulsive drag force resulting in faster swimming. Using feedback loops, two complementary control modes were used to rotate the foot: force was transmitted to the foot either from (1) a living plantaris longus (PL) muscle stimulated in vitro or (2) an in silico mathematical model of the PL. To mimic forward swimming, foot translation was calculated in real time from fluid force measured at the foot. Therefore, bio-robot swimming emerged from muscle-fluid interactions via the feedback loop. Among in vitro-robotic trials, muscle impulse ranged from 0.12 ± 0.002 to 0.18 ± 0.007 N s and swimming velocities from 0.41 ± 0.01 to 0.43 ± 0.00 m s(-1), similar to in vivo values from prior studies. Trends in in silico-robotic data mirrored in vitro-robotic observations. Increasing AR caused a small (∼10%) increase in peak bio-robot swimming velocity. In contrast, muscle force-velocity effects were strongly dependent on foot shape. Between low- and high-AR feet, muscle impulse increased ∼50%, while peak shortening velocity decreased ∼50% resulting in a ∼20% increase in net work. However, muscle-propulsion efficiency (body center of mass work/muscle work) remained independent of AR. Thus, we demonstrate how our experimental technique is useful for quantifying the complex interplay among limb morphology, muscle mechanics and hydrodynamics.

  16. Engraftment potential of dermal fibroblasts following in vivo myogenic conversion in immunocompetent dystrophic skeletal muscle

    Directory of Open Access Journals (Sweden)

    Lindsey A Muir

    2014-01-01

    Full Text Available Autologous dermal fibroblasts (dFbs are promising candidates for enhancing muscle regeneration in Duchenne muscular dystrophy (DMD due to their ease of isolation, immunological compatibility, and greater proliferative potential than DMD satellite cells. We previously showed that mouse fibroblasts, after MyoD-mediated myogenic reprogramming in vivo, engraft in skeletal muscle and supply dystrophin. Assessing the therapeutic utility of this system requires optimization of conversion and transplantation conditions and quantitation of engraftment so that these parameters can be correlated with possible functional improvements. Here, we derived dFbs from transgenic mice carrying mini-dystrophin, transduced them by lentivirus carrying tamoxifen-inducible MyoD, and characterized their myogenic and engraftment potential. After cell transplantation into the muscles of immunocompetent dystrophic mdx4cv mice, tamoxifen treatment drove myogenic conversion and fusion into myofibers that expressed high levels of mini-dystrophin. Injecting 50,000 cells/µl (1 × 106 total cells resulted in a peak of ∼600 mini-dystrophin positive myofibers in tibialis anterior muscle single cross-sections. However, extensor digitorum longus muscles with up to 30% regional engraftment showed no functional improvements; similar limitations were obtained with whole muscle mononuclear cells. Despite the current lack of physiological improvement, this study suggests a viable initial strategy for using a patient-accessible dermal cell population to enhance skeletal muscle regeneration in DMD.

  17. 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.

  18. Vasodilatory mechanisms in contracting skeletal muscle

    DEFF Research Database (Denmark)

    Clifford, Philip S.; Hellsten, Ylva

    2004-01-01

    to the sustained elevation during steady-state exercise. Exercise hyperemia is therefore thought to be the result of an integrated response of more than one vasodilator mechanism. To date, the identity of vasoactive substances involved in the regulation of exercise hyperemia remains uncertain. Numerous...

  19. 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

    2018-02-01

    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

  20. A bio-robotic platform for integrating internal and external mechanics during muscle-powered swimming

    International Nuclear Information System (INIS)

    Richards, Christopher T; Clemente, Christofer J

    2012-01-01

    To explore the interplay between muscle function and propulsor shape in swimming animals, we built a robotic foot to mimic the morphology and hind limb kinematics of Xenopus laevis frogs. Four foot shapes ranging from low aspect ratio (AR = 0.74) to high (AR = 5) were compared to test whether low-AR feet produce higher propulsive drag force resulting in faster swimming. Using feedback loops, two complementary control modes were used to rotate the foot: force was transmitted to the foot either from (1) a living plantaris longus (PL) muscle stimulated in vitro or (2) an in silico mathematical model of the PL. To mimic forward swimming, foot translation was calculated in real time from fluid force measured at the foot. Therefore, bio-robot swimming emerged from muscle–fluid interactions via the feedback loop. Among in vitro-robotic trials, muscle impulse ranged from 0.12 ± 0.002 to 0.18 ± 0.007 N s and swimming velocities from 0.41 ± 0.01 to 0.43 ± 0.00 m s −1 , similar to in vivo values from prior studies. Trends in in silico-robotic data mirrored in vitro-robotic observations. Increasing AR caused a small (∼10%) increase in peak bio-robot swimming velocity. In contrast, muscle force–velocity effects were strongly dependent on foot shape. Between low- and high-AR feet, muscle impulse increased ∼50%, while peak shortening velocity decreased ∼50% resulting in a ∼20% increase in net work. However, muscle-propulsion efficiency (body center of mass work/muscle work) remained independent of AR. Thus, we demonstrate how our experimental technique is useful for quantifying the complex interplay among limb morphology, muscle mechanics and hydrodynamics. (paper)

  1. Polypyrrole for Artificial Muscles: Ionic Mechanisms

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2006-01-01

    the matrix of a polymer electrode – thereby causing volume expansion which can be converted into work. Solvent molecules are able to penetrate the polymer too. A precise description of the nature of these ionic and solvent movements is therefore important for understanding and improving the performance....... This work examines the influence of solvent, ionic species and electrolyte concentration on the fundamental question about the ionic mechanism involved: Is the actuation process driven by anion motion, cation motion, or a mixture of the two? In addition: What is the extent of solvent motion? The discussion...... is centered on polypyrrole (PPy), which is the material most used and studied. The tetraethyl ammonium cation (TEA) is shown to be able to move in and out of PPy(DBS) polymer films, in contrast to expectations. There is a switching between ionic mechanisms during cycling in TEACl electrolyte....

  2. 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; Kleinert, Maximilian

    2017-01-01

    , 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...... uptake in vivo was only partially reduced by Rac1 mKO with no additive effect of a2KD. 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 a2 AMPK, regulates muscle glucose uptake during submaximal...

  3. 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...... 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....... efficient transgenic expression was observed after DNA electrotransfer with 100-fold increase in fluorescent intensity. The fluorescent signal peaked 1 week after transfection and returned to background level within 4 weeks. Katushka expression was not as stable as GFP expression, which was detectable for 8...

  4. Immunohistochemical and Morphofunctional Studies of Skeletal Muscle Tissues with Electric Nerve Stimulation by In Vivo Cryotechnique

    International Nuclear Information System (INIS)

    Fukasawa, Yuki; Ohno, Nobuhiko; Saitoh, Yurika; Saigusa, Takeshi; Arita, Jun; Ohno, Shinichi

    2015-01-01

    In this study, morphological and immunohistochemical alterations of skeletal muscle tissues during persistent contraction were examined by in vivo cryotechnique (IVCT). Contraction of gastrocnemius muscles was induced by sciatic nerve stimulation. The IVCT was performed immediately, 3 min or 10 min after the stimulation start. Prominent ripples of muscle fibers or wavy deformation of sarcolemma were detected immediately after the stimulation, but they gradually diminished to normal levels during the stimulation. The relative ratio of sarcomere and A band lengths was the highest in the control group, but it immediately decreased to the lowest level and then gradually recovered at 3 min or 10 min. Although histochemical intensity of PAS reaction was almost homogeneous in muscle tissues of the control group or immediately after the stimulation, it decreased at 3 min or 10 min. Serum albumin was immunolocalized as dot-like patterns within some muscle fibers at 3 min stimulation. These patterns became more prominent at 10 min, and the dots got larger and saccular in some sarcoplasmic regions. However, IgG1 and IgM were immunolocalized in blood vessels under nerve stimulation conditions. Therefore, IVCT was useful to capture the morphofunctional and metabolic changes of heterogeneous muscle fibers during the persistent contraction

  5. Differences in in vivo muscle fascicle and tendinous tissue behavior between the ankle plantarflexors during running.

    Science.gov (United States)

    Lai, A K M; Lichtwark, G A; Schache, A G; Pandy, M G

    2018-03-30

    The primary human ankle plantarflexors, soleus (SO), medial gastrocnemius (MG), and lateral gastrocnemius (LG) are typically regarded as synergists and play a critical role in running. However, due to differences in muscle-tendon architecture and joint articulation, the muscle fascicles and tendinous tissue of the plantarflexors may exhibit differences in their behavior and interactions during running. We combined in vivo dynamic ultrasound measurements with inverse dynamics analyses to identify and explain differences in muscle fascicle, muscle-tendon unit, and tendinous tissue behavior of the primary ankle plantarflexors across a range of steady-state running speeds. Consistent with their role as a force generator, the muscle fascicles of the uniarticular SO shortened less rapidly than the fascicles of the MG during early stance. Furthermore, the MG and LG exhibited delays in tendon recoil during the stance phase, reflecting their ability to transfer power and work between the knee and ankle via tendon stretch and storage of elastic strain energy. Our findings add to the growing body of evidence surrounding the distinct mechanistic functions of uni- and biarticular muscles during dynamic movements. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Robinson's computerized model of eye muscle mechanics revised.

    NARCIS (Netherlands)

    H.J. Simonsz (Huib)

    1994-01-01

    textabstractThe computerized model of static eye-muscle mechanics developed by Robinson was revised extensively and improved. An extensive literature study yielded additional information on the average diameter of the eye as related to age, on the average location of the insertions and origins of

  7. Integrative Genomic Analysis of In Vivo Muscle Regeneration After Severe Trauma

    Science.gov (United States)

    2015-11-30

    muscular dystrophy and aging. The cis-regulatory networks that orchestrate in-vivo muscle repair and regeneration after traumatic injury have only been...modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy. EMBO Rep. 12, 136-141 (2011). 46. Cachiarelli, D., Martone...I. MicroRNAs involved in molecular circuitries relevant for the Duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS

  8. 2D NMR studies on muscle and cerebral metabolism in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Gillet, B.; Doan, B.T.; Verre-Sebrie, C.; Fedeli, O.; Beloeil, J.C. (Centre National de la Recherche Scientifique (CNRS), 91 - Gif-sur-Yvette (France). Inst. de Chimie des Substances Naturelles); Peres, M. (CERMA-CEV, 91 - Bretigny-sur-Orge (France)); Barrere, B.; Seylaz, J. (Paris-7 Univ., 75 (France)); Morin, S.; Koenig, J. (Bordeaux-1 Univ., 33 - Talence (France)); Sebille, A. (Faculte de Medecine Saint-Antoine, 75 - Paris (France))

    1994-06-01

    New developments in in vivo 2D[sup 1]H NMR spectroscopy now allow several metabolites, which are not resolved by 1D NMR to be assigned. This report describes the use of this technique to follow the time courses of changes in the concentration of metabolites in the rat brain during physiological and pathophysiological processes (hyperglycemia and hypoxia) and to compare the fatty acid components of normal and dystrophic mouse gastrocnemius muscle. (authors). 15 refs., 5 figs.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

    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

  10. Plasticity of human skeletal muscle: gene expression to in vivo function.

    Science.gov (United States)

    Harridge, Stephen D R

    2007-09-01

    Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (V(max)), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing V(max) and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level.

  11. 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 (EMG dia ) and parasternal muscles (EMG para ) 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). EMG para and EMG dia did not change under mechanical ventilation (both P>.05). EMG dia 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 EMG para 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.

  12. Multivariable Dynamic Ankle Mechanical Impedance With Active Muscles

    Science.gov (United States)

    Lee, Hyunglae; Krebs, Hermano Igo; Hogan, Neville

    2015-01-01

    Multivariable dynamic ankle mechanical impedance in two coupled degrees-of-freedom (DOFs) was quantified when muscles were active. Measurements were performed at five different target activation levels of tibialis anterior and soleus, from 10% to 30% of maximum voluntary contraction (MVC) with increments of 5% MVC. Interestingly, several ankle behaviors characterized in our previous study of the relaxed ankle were observed with muscles active: ankle mechanical impedance in joint coordinates showed responses largely consistent with a second-order system consisting of inertia, viscosity, and stiffness; stiffness was greater in the sagittal plane than in the frontal plane at all activation conditions for all subjects; and the coupling between dorsiflexion–plantarflexion and inversion–eversion was small—the two DOF measurements were well explained by a strictly diagonal impedance matrix. In general, ankle stiffness increased linearly with muscle activation in all directions in the 2-D space formed by the sagittal and frontal planes, but more in the sagittal than in the frontal plane, resulting in an accentuated “peanut shape.” This characterization of young healthy subjects’ ankle mechanical impedance with active muscles will serve as a baseline to investigate pathophysiological ankle behaviors of biomechanically and/or neurologically impaired patients. PMID:25203497

  13. Optical imaging of luminescence for in vivo quantification of gene electrotransfer in mouse muscle and knee

    Directory of Open Access Journals (Sweden)

    Scherman D

    2006-03-01

    Full Text Available Abstract Background Optical imaging is an attractive non-invasive way to evaluate the expression of a transferred DNA, mainly thanks to its lower cost and ease of realization. In this study optical imaging was evaluated for monitoring and quantification of the mouse knee joint and tibial cranial muscle electrotransfer of a luciferase encoding plasmid. Optical imaging was applied to study the kinetics of luciferase expression in both tissues. Results The substrate of luciferase (luciferin was injected either intraperitonealy (i.p. or in situ into the muscle or the knee joint. Luminescence resulting from the luciferase-luciferin reaction was measured in vivo with a cooled CCD camera and/or in vitro on tissue lysate. Maximal luminescence of the knee joint and muscle after i.p. (2.5 mg or local injection of luciferin (50 μg in the knee joint, 100 μg in the muscle were highly correlated. With the local injection procedure adopted, in vivo and in vitro luminescences measured on the same muscles significantly correlated. Luminescence measurements were reproducible and the signal level was proportional to the amount of plasmid injected. In vivo luciferase activity in the electrotransfered knee joint was detected for two weeks. Intramuscular electrotransfer of 0.3 or 3 μg of plasmid led to stable luciferase expression for 62 days, whereas injecting 30 μg of plasmid resulted in a drop of luminescence three weeks after electrotransfer. These decreases were partially associated with the development of an immune response. Conclusion A particular advantage of the i.p. injection of substrate is a widespread distribution at luciferase production sites. We have also highlighted advantages of local injection as a more sensitive detection method with reduced substrate consumption. Besides, this route of injection is relatively free of uncontrolled parameters, such as diffusion to the target organ, crossing of biological barriers and evidencing variations in

  14. 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...

  15. THE RENIN-ANGIOTENSIN SYSTEM AND THE BIOLOGY OF SKELETAL MUSCLE: MECHANISMS OF MUSCLE WASTING IN CHRONIC DISEASE STATES.

    Science.gov (United States)

    Delafontaine, Patrice; Yoshida, Tadashi

    2016-01-01

    Sarcopenia and cachexia are muscle-wasting syndromes associated with aging and with many chronic diseases such as congestive heart failure, diabetes, cancer, chronic obstructive pulmonary disease, and renal failure. While mechanisms are complex, these conditions are often accompanied by elevated angiotensin II (Ang II). We found that Ang II infusion in rodents leads to skeletal muscle wasting via alterations in insulin-like growth factor-1 signaling, increased apoptosis, enhanced muscle protein breakdown via the ubiquitin-proteasome system, and decreased appetite resulting from downregulation of hypothalamic orexigenic neuropeptides orexin and neuropeptide Y. Furthermore, Ang II inhibits skeletal muscle stem cell proliferation, leading to lowered muscle regenerative capacity. Distinct stem cell Ang II receptor subtypes are critical for regulation of muscle regeneration. In ischemic mouse congestive heart failure model skeletal muscle wasting and attenuated muscle regeneration are Ang II dependent. These data suggest that the renin-angiotensin system plays a critical role in mechanisms underlying cachexia in chronic disease states.

  16. 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

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

    International Nuclear Information System (INIS)

    Richter, E.A.; Hansen, S.A.; Hansen, B.F.

    1988-01-01

    The extent to which muscle glycogen concentrations can be increased during exposure to maximal insulin concentrations and abundant glucose was investigated in the isolated perfused rat hindquarter preparation. Perfusion for 7 h in the presence of 20,000 μU/ml insulin and 11-13 mM glucose 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 from 34.9 μmol·g -1 ·h -1 at 0 h to 7.5 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-[ 14 C]methyl-D-glucose was also markedly decreased after 5 and 7 h of perfusion compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal

  18. In vivo functional and morphological characterization of bone and striated muscle microcirculation in NSG mice.

    Directory of Open Access Journals (Sweden)

    Haider Mussawy

    Full Text Available Organ-specific microcirculation plays a central role in tumor growth, tumor cell homing, tissue engineering, and wound healing. Mouse models are widely used to study these processes; however, these mouse strains often possess unique microhemodynamic parameters, making it difficult to directly compare experiments. The full functional characterization of bone and striated muscle microcirculatory parameters in non-obese diabetic-severe combined immunodeficiency/y-chain; NOD-Prkds IL2rg (NSG mice has not yet been reported. Here, we established either a dorsal skinfold chamber or femur window in NSG mice (n = 23, allowing direct analysis of microcirculatory parameters in vivo by intravital fluorescence microscopy at 7, 14, 21, and 28 days after chamber preparation. Organ-specific differences were observed. Bone had a significantly lower vessel density but a higher vessel diameter than striated muscle. Bone also showed higher effective vascular permeability than striated muscle. The centerline velocity values were similar in the femur window and dorsal skinfold chamber, with a higher volumetric blood flow in bone. Interestingly, bone and striated muscle showed similar tissue perfusion rates. Knowledge of physiological microhemodynamic values of bone and striated muscle in NSG mice makes it possible to analyze pathophysiological processes at these anatomic sites, such as tumor growth, tumor metastasis, and tumor microcirculation, as well as the response to therapeutic agents.

  19. Protein synthesis in vivo during the development of various muscles in the lamb

    International Nuclear Information System (INIS)

    Arnal, M.; Ferrara, M.; Fauconneau, G.

    1976-01-01

    Protein synthesis is measured in vivo after the injection of 14 C(U) L lysine. The radioactivity incorporated in the proteins is studied as a function of the specific radioactivity of the precursor. Catabolism is estimated from the difference between real and apparent anabolism. The amount of proteins synthesized per unit weight in the tensor facialatae (TFL, the anconeus externus (AE), and the diaphragm (D) decreases rapidly until the age of 10 weeks (approximately puberty). It then levels out or increases after that age, depending on the muscle in question. The real anabolism of the white muscle (TFL) is higher than that of the red (AE and D) in one-week-old lambs. At 16 weeks, protein synthesis is higher in red muscle (D) than in white. The apparent anabolism of the muscles studied is constant during the period considered. The decrease in real anabolism per unit weight is compensated by the increased volume of the muscles, and they synthesize similar quantities of protein as long as the animal is preruminant (1-5 weeks). The protein fixation efficiency (R=ratio between apparent and real anabolism) is constant and in the neighbourhood of 20% during this period. When the animal is older, the quantity of proteins synthesized by the muscles decreases. R is variable in the ruminant animal, and increases at the age of 10 weeks, especially in white muscle, after which it decreases at the age of 16 weeks. The effect of sex hormones around puberty and the particular energy foods of the ruminant (volatile fatty acids) may explain this better efficiency. The renewal time of muscular proteins increases with age. These results facilitate understanding of the differences found in the literature in the energy cost of protein production during growth. (author)

  20. Ischaemia and insulin, but not ischaemia and contraction, act synergistically in stimulating muscle glucose uptake in vivo in humans.

    NARCIS (Netherlands)

    Bosselaar, M.; Smits, P.; Tack, C.J.J.

    2009-01-01

    Ischaemia, like muscle contraction, has been reported to induce skeletal muscle glucose uptake in in vitro models. This stimulating effect appears independent of insulin and is probably mediated by activation of AMPK (AMP-activated protein kinase). In the present study, we hypothesized that in vivo

  1. On the relationship between tibia torsional deformation and regional muscle contractions in habitual human exercises in vivo.

    Science.gov (United States)

    Yang, Peng-Fei; Kriechbaumer, Andreas; Albracht, Kirsten; Sanno, Maximilian; Ganse, Bergita; Koy, Timmo; Shang, Peng; Brüggemann, Gert-Peter; Müller, Lars Peter; Rittweger, Jörn

    2015-02-05

    The mechanical relationship between bone and muscle has been long recognized. However, it still remains unclear how muscles exactly load on bone. In this study, utilizing an optical segment tracking technique, the in vivo tibia loading regimes in terms of tibia segment deformation in humans were investigated during walking, forefoot and rear foot stair ascent and running and isometric plantar flexion. Results suggested that the proximal tibia primarily bends to the posterior aspect and twists to the external aspect with respect to the distal tibia. During walking, peak posterior bending and peak torsion occurred in the first half (22%) and second half (76%) of the stance phase, respectively. During stair ascent, two noticeable peaks of torsion were found with forefoot strike (38% and 82% of stance phase), but only one peak of torsion was found with rear foot strike (78% of stance phase). The torsional deformation angle during both stair ascent and running was larger with forefoot strike than rear foot strike. During isometric plantar flexion, the tibia deformation regimes were characterized more by torsion (maximum 1.35°) than bending (maximum 0.52°). To conclude, bending and torsion predominated the tibia loading regimes during the investigated activities. Tibia torsional deformation is closely related to calf muscle contractions, which further confirm the notion of the muscle-bone mechanical link and shift the focus from loading magnitude to loading regimes in bone mechanobiology. It thus is speculated that torsion is another, yet under-rated factor, besides the compression and tension, to drive long bone mechano-adaptation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2018-01-01

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

  3. A study of fatigue in rabbit skeletal muscle by in vivo 31P MRS

    International Nuclear Information System (INIS)

    Koga, Keiko; Miura, Iwao

    1989-01-01

    Energy metabolism during exercise and recovery process of rabbit skeletal muscle was obserbed by in vivo 31 P MRS. The small value of the ratio of the intensities between inorganic phosphate and phosphocreatine at rest indicated that the observed moiety of muscle had high fast-twitch fiber content. More than half of ATP and almost all of phosphocreatine were depleted by electric stimulation at 4Hz. The extreme intracellular pH was 5.9. The recovery from this metabolic state was very slow, and only a small amount of ATP was resynthesized after 40 minutes of recovery. These phenomena show the characteristic features of the energy metabolism in the fatigue of fast-twitch muscle. The metabolic state as indicated by the intensity of phosphocreatine and intracellular pH during exercise was not always parallel to contraction power measured by straingauge. Two inorganic phosphate peaks were observed, which are regarded as the signals from fast-twitch fiber and slow-twitch fiber from their pH values. The ratios of these two peaks were different between 1Hz, 2Hz, and 4Hz electric stimulation. We conclude that we are observing the different recruitment of fiber types at different exercise level in vivo. (author)

  4. Muscle forces analysis in the shoulder mechanism during wheelchair propulsion.

    Science.gov (United States)

    Lin, Hwai-Ting; Su, Fong-Chin; Wu, Hong-Wen; An, Kai-Nan

    2004-01-01

    This study combines an ergometric wheelchair, a six-camera video motion capture system and a prototype computer graphics based musculoskeletal model (CGMM) to predict shoulder joint loading, muscle contraction force per muscle and the sequence of muscular actions during wheelchair propulsion, and also to provide an animated computer graphics model of the relative interactions. Five healthy male subjects with no history of upper extremity injury participated. A conventional manual wheelchair was equipped with a six-component load cell to collect three-dimensional forces and moments experienced by the wheel, allowing real-time measurement of hand/rim force applied by subjects during normal wheelchair operation. An ExpertVision six-camera video motion capture system collected trajectory data of markers attached on anatomical positions. The CGMM was used to simulate and animate muscle action by using an optimization technique combining observed muscular motions with physiological constraints to estimate muscle contraction forces during wheelchair propulsion. The CGMM provides results that satisfactorily match the predictions of previous work, disregarding minor differences which presumably result from differing experimental conditions, measurement technologies and subjects. Specifically, the CGMM shows that the supraspinatus, infraspinatus, anterior deltoid, pectoralis major and biceps long head are the prime movers during the propulsion phase. The middle and posterior deltoid and supraspinatus muscles are responsible for arm return during the recovery phase. CGMM modelling shows that the rotator cuff and pectoralis major play an important role during wheelchair propulsion, confirming the known risk of injury for these muscles during wheelchair propulsion. The CGMM successfully transforms six-camera video motion capture data into a technically useful and visually interesting animated video model of the shoulder musculoskeletal system. The CGMM further yields accurate

  5. 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

    the enhanced green fluorescent protein (EGFP) labelling technique with physical transfection methods in vivo: intramuscular plasmid injection or gene gun bombardment. During optimisation experiments with plasmid coding for the EGFP reporter alone EGFP-positive muscle fibres were counted after collagenase...... treatment of in vivo transfected flexor digitorum brevis (FDB) muscles. In contrast to gene gun bombardment, intramuscular injection produced EGFP expression in only a few fibres. Regardless of the transfection technique, EGFP expression was higher in muscles from 2-week-old rats than in those from 6-week......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...

  6. Neck Muscle Moment Arms Obtained In-Vivo from MRI: Effect of Curved and Straight Modeled Paths.

    Science.gov (United States)

    Suderman, Bethany L; Vasavada, Anita N

    2017-08-01

    Musculoskeletal models of the cervical spine commonly represent neck muscles with straight paths. However, straight lines do not best represent the natural curvature of muscle paths in the neck, because the paths are constrained by bone and soft tissue. The purpose of this study was to estimate moment arms of curved and straight neck muscle paths using different moment arm calculation methods: tendon excursion, geometric, and effective torque. Curved and straight muscle paths were defined for two subject-specific cervical spine models derived from in vivo magnetic resonance images (MRI). Modeling neck muscle paths with curvature provides significantly different moment arm estimates than straight paths for 10 of 15 neck muscles (p straight lines to model muscle paths can lead to overestimating neck extension moment. However, moment arm methods for curved paths should be investigated further, as different methods of calculating moment arm can provide different estimates.

  7. 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

    , 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...... of different mitochondrial phosphopeptides (87 ± 7 vs 40 ± 7, p = 0.015) and phosphoproteins (46 ± 2 vs 26 ± 3, p = 0.005) identified in each mitochondrial preparation. Almost half of the mitochondrial phosphorylation sites (n = 94) were exclusively identified in the insulin-stimulated state and included...

  8. 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

    Very little attention has been given to the combined effects of aging and disuse as separate factors causing deterioration in muscle mechanical function. Thus the purpose of this study was to investigate the effects of 2 wk of immobilization followed by 4 wk of retraining on knee extensor muscle...... to the deleterious effects of short-term muscle disuse on muscle fiber size and rapid force capacity than YM. Furthermore, OM seems to require longer time to recover and regain rapid muscle force capacity, which may lead to a larger risk of falling in aged individuals after periods of short-term disuse....

  9. 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...... compared to L(f) measured from static US images (6-cm FOV) where out-of-field fascicle portions were trigonometrically estimated (linear extrapolation). Finally, spatial accuracy of the EFOV technique was assessed by comparing L(f) measured on swine VL by EFOV US to actual measurements from digital...... and by dissective assessment (digital photographs) in isolated swine VL was 0.84% ± 2.6% with an ICC of 0.99 (CI = 0.94-1.00). These results show that EFOV US is a reliable and valid method for the measurement of long muscle fascicle in vivo. Thus EFOV US analysis was proven more accurate for the assessment...

  10. COMPARISSON OF DIFFERENT IN VIVO ESTIMATORS OF BODY FAT AND MUSCLE CONTENT IN ADULT CREOLE GOATS

    Directory of Open Access Journals (Sweden)

    Hania Vilar-Martinez

    2009-06-01

    Full Text Available The objective of the present study was to compare the effectiveness of ultrasound measurements (ULT, body condition score (BCS and body mass index (BMI to predict body fat and muscle in goats. Twenty-four adult, ovariectomized, creole goats were fed individually to achieve dissimilar stable body weights (26 to 66 kg. After a six-week period of stabilization BCS was evaluated (average of 4 separate evaluations and BMI calculated (BW/(length x heightx10; average of 2 independent length and height measurements. Fat and muscle coverage over the dorsal (12-13th, lumbar (1st and coxal (1st vertebrae were measured by ultrasound imaging. Animals were slaughtered and visceral fat dissected and weighed. Left half carcass weights were obtained and muscle and fat were dissected and weighed. Left half carcass data were adjusted to whole carcass data. Simple  regression analyses were performed with ULT, BCS and BMI as predictors and visceral (VF, carcass (CF and total fat (TF, and muscle (MU as response variables. Coefficients of variation (CV were calculated for BCS and BMI estimations. ULT measurement of total tissue (fat + muscle coverage over dorsal vertebrae presented the highest predictive value for ULT measurements; thus this measurement is the only reported. Coefficients of determination (R2 for VF, CF and TF were .55, .76 and .68; .78, .82 and .87; .81, .81 and .88 for ULT, BCS and BMI as predictors. R2 for MU were .67, .84 and .76 using ULT, BCS and BMI as predictors. R2 for proportions of VF/BW, CF/BW and TF/BW were .47, .73 and .65; .75, .78 and .88; .74, .71 and .85; when ULT, BCS and BMI were used as predictors. R2 for MS/BW were ≤ .10 using ULT, BCS and BMI as predictors. CV was greater in BCS estimation as compared to BMI estimation (9.7 vs. 3.1 %. BCS and BMI were more accurate in vivo predictors than ULT for body fat content, fat as proportion of BW and body muscle content. ULT, BCS and BMI were completely worthless for predicting

  11. Excited hydrogen bonds in the molecular mechanism of muscle contraction.

    Science.gov (United States)

    Bespalova, S V; Tolpygo, K B

    1991-11-21

    The mechanism of muscle contraction is considered. The hydrolysis of an ATP molecule is assumed to produce the excitation of hydrogen bonds A--H...B between electronegative atoms A and B, which are contained in the myosin head and actin filament. This excitation energy epsilon f depends on the interatomic distance AB = R and generates the tractive force f = -delta epsilon f/delta R, that makes atoms AB approach each other. The swing of the myosin head results in macroscopic mutual displacement of actin and myosin polymers. The motion of the actin filament under the action of this force is studied. The conditions under which a considerable portion of the excitation energy converts into the potential tension energy of the actin filament are analysed, and the probability of higher muscle efficiency existence is discussed.

  12. Ecdysteroids affect in vivo protein metabolism of the flight muscle of the tobacco hornworm (Manduca sexta)

    Science.gov (United States)

    Tischler, M. E.; Wu, M.; Cook, P.; Hodsden, S.

    1990-01-01

    Ecdysteroid growth promotion of the dorsolongitudinal flight muscle of Manduca sexta was studied by measuring in vivo protein metabolism using both "flooding-dose" and "non-carrier" techniques. These procedures differ in that the former method includes injection of non-labelled phenylalanine (30 micromoles/insect) together with the [3H]amino acid. Injected radioactivity plateaued in the haemolymph within 7 min. With the flooding-dose method, haemolymph and intramuscular specific radioactivities were similar between 15 min and 2 h. Incorporation of [3H]phenylalanine into muscle protein was linear with either method between 30 and 120 min. Fractional rates (%/12 h) of synthesis with the flooding-dose technique were best measured after 1 h because of the initial delay in radioactivity equilibration. Estimation of body phenylalanine turnover with the non-carrier method showed 24-53%/h which was negligible with the flooding-dose method. Since the two methods yielded similar rates of protein synthesis, the large injection of non-labelled amino acid did not alter the rate of synthesis. Because the flooding-dose technique requires only a single time point measurement, it is the preferred method. The decline and eventual cessation of flight-muscle growth was mostly a consequence of declining protein synthesis though degradation increased between 76-86 h before eclosion and was relatively rapid. This decline in muscle growth could be prevented by treating pupae with 20-hydroxyecdysone (10 micrograms/insect). Protein accretion was promoted by a decline of up to 80% in protein breakdown, which was offset in part by a concurrent though much smaller decrease in protein synthesis. Therefore, ecdysteroids may increase flight-muscle growth by inhibiting proteolysis.

  13. In vivo fascicle behavior of the flexor hallucis longus muscle at different walking speeds.

    Science.gov (United States)

    Péter, A; Hegyi, A; Finni, T; Cronin, N J

    2017-12-01

    Ankle plantar flexor muscles support and propel the body in the stance phase of locomotion. Besides the triceps surae, flexor hallucis longus muscle (FHL) may also contribute to this role, but very few in vivo studies have examined FHL function during walking. Here, we investigated FHL fascicle behavior at different walking speeds. Ten healthy males walked overground at three different speeds while FHL fascicle length changes were recorded with ultrasound and muscle activity was recorded with surface electromyography (EMG). Fascicle length at heel strike at toe off and at peak EMG activity did not change with speed. Range of FHL fascicle length change (3.5-4.5 and 1.9-2.9 mm on average in stance and push-off phase, respectively), as well as minimum (53.5-54.9 and 53.8-55.7 mm) and maximum (58-58.4 and 56.8-57.7 mm) fascicle length did not change with speed in the stance or push-off phase. Mean fascicle velocity did not change in the stance phase, but increased significantly in the push-off phase between slow and fast walking speeds (P=.021). EMG activity increased significantly in both phases from slow to preferred and preferred to fast speed (P<.02 in all cases). FHL muscle fascicles worked near-isometrically during the whole stance phase (at least during slow walking) and operated at approximately the same length at different walking speeds. FHL and medial gastrocnemius (MG) have similar fiber length to muscle belly length ratios and, according to our results, also exhibit similar fascicle behavior at different walking speeds. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Protection from Muscle Damage in the Absence of Changes in Muscle Mechanical Behavior.

    Science.gov (United States)

    Hoffman, Ben W; Cresswell, Andrew G; Carroll, Timothy J; Lichtwark, Glen A

    2016-08-01

    The repeated bout effect characterizes the protective adaptation after a single bout of unaccustomed eccentric exercise that induces muscle damage. Sarcomerogenesis and increased tendon compliance have been suggested as potential mechanisms for the repeated bout effect by preventing muscle fascicles from being stretched onto the descending limb of the length-tension curve (the region where sarcomere damage is thought to occur). In this study, evidence was sought for three possible mechanical changes that would support either the sarcomerogenesis or the increased tendon compliance hypotheses: a sustained rightward shift in the fascicle length-tension relationship, reduced fascicle strain amplitude, and reduced starting fascicle length. Subjects (n = 10) walked backward downhill (5 km·h, 20% incline) on a treadmill for 30 min on two occasions separated by 7 d. Kinematic data and medial gastrocnemius fascicle lengths (ultrasonography) were recorded at 10-min intervals to compare fascicle strains between bouts. Fascicle length-torque curves from supramaximal tibial nerve stimulation were constructed before, 2 h after, and 2 d after each exercise bout. Maximum torque decrement and elevated muscle soreness were present after the first, but not the second, backward downhill walking bout signifying a protective repeated bout effect. There was no sustained rightward shift in the length-torque relationship between exercise bouts, nor decreases in fascicle strain amplitude or shortening of the starting fascicle length. Protection from a repeated bout of eccentric exercise was conferred without changes in muscle fascicle strain behavior, indicating that sarcomerogenesis and increased tendon compliance were unlikely to be responsible. As fascicle strains are relatively small in humans, we suggest that changes to connective tissue structures, such as extracellular matrix remodeling, are better able to explain the repeated bout effect observed here.

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

    International Nuclear Information System (INIS)

    Eisele, Petra Sabine; Furrer, Regula; Beer, Markus; Handschin, Christoph

    2015-01-01

    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

  16. 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.

  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. 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

    to the deleterious effects of short-term muscle disuse on muscle fiber size and rapid force capacity than YM. Furthermore, OM seems to require longer time to recover and regain rapid muscle force capacity, which may lead to a larger risk of falling in aged individuals after periods of short-term disuse.......Very little attention has been given to the combined effects of aging and disuse as separate factors causing deterioration in muscle mechanical function. Thus the purpose of this study was to investigate the effects of 2 wk of immobilization followed by 4 wk of retraining on knee extensor muscle...... 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...

  19. 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.

  20. 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.

  1. Muscle Co-activation: Definitions, Mechanisms, and Functions.

    Science.gov (United States)

    Latash, Mark L

    2018-03-28

    The phenomenon of agonist-antagonist muscle co-activation is discussed with respect to its consequences for movement mechanics (such as increasing joint apparent stiffness, facilitating faster movements, and effects on action stability), implication for movement optimization, and involvement of different neurophysiological structures. Effects of co-activation on movement stability are ambiguous and depend on the effector representing a kinematic chain with a fixed origin or free origin. Further, co-activation is discussed within the framework of the equilibrium-point hypothesis and the idea of hierarchical control with spatial referent coordinates. Relations of muscle co-activation to changes in one of the basic commands, the c-command, are discussed and illustrated. A hypothesis is suggested that agonist-antagonist co-activation reflects a deliberate neural control strategy to preserve effector-level control and avoid making it degenerate and facing the necessity to control at the level of signals to individual muscles. This strategy, in particular, allows stabilizing motor actions by co-varied adjustments in spaces of control variables. This hypothesis is able to account for higher levels of co-activation in young healthy persons performing challenging tasks and across various populations with movement impairments.

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

    DEFF Research Database (Denmark)

    Rasmussen, U.F.; Rasmussen, H.N.; Krustrup, Peter

    2001-01-01

    The aim of the present study was to examine whether parameters of isolated mitochondria could account for the in vivo maximum oxygen uptake ( O2 max) of human skeletal muscle. O2 max and work performance of the quadriceps muscle of six volunteers were measured in the knee extensor model (range 10......-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...... of citrate synthase, succinate dehydrogenase, and pyruvate dehydrogenase, measured in isolated mitochondria, corresponded to, respectively, 15, 3, and 1.1 times the rates calculated from O2 max. The respiratory chain activity also appeared sufficient. Fully coupled in vitro respiration, which is limited...

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

    NARCIS (Netherlands)

    Juffer, P.; Jaspers, R.T.; Lips, P.; Bakker, A.D.; Klein-Nulend, J.

    2012-01-01

    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.,

  4. 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......, whereas no significant variations were seen for T2. Our in vivo data were generally in reasonable agreement with proposed models based on ex vivo measurements....

  5. Citrulline directly modulates muscle protein synthesis via the PI3K/MAPK/4E-BP1 pathway in a malnourished state: evidence from in vivo, ex vivo, and in vitro studies.

    Science.gov (United States)

    Le Plénier, Servane; Goron, Arthur; Sotiropoulos, Athanassia; Archambault, Eliane; Guihenneuc, Chantal; Walrand, Stéphane; Salles, Jérome; Jourdan, Marion; Neveux, Nathalie; Cynober, Luc; Moinard, Christophe

    2017-01-01

    Citrulline (CIT) is an endogenous amino acid produced by the intestine. Recent literature has consistently shown CIT to be an activator of muscle protein synthesis (MPS). However, the underlying mechanism is still unknown. Our working hypothesis was that CIT might regulate muscle homeostasis directly through the mTORC1/PI3K/MAPK pathways. Because CIT undergoes both interorgan and intraorgan trafficking and metabolism, we combined three approaches: in vivo, ex vivo, and in vitro. Using a model of malnourished aged rats, CIT supplementation activated the phosphorylation of S6K1 and 4E-BP1 in muscle. Interestingly, the increase in S6K1 phosphorylation was positively correlated (P < 0.05) with plasma CIT concentration. In a model of isolated incubated skeletal muscle from malnourished rats, CIT enhanced MPS (from 30 to 80% CIT vs. Ctrl, P < 0.05), and the CIT effect was abolished in the presence of wortmannin, rapamycin, and PD-98059. In vitro, on myotubes in culture, CIT led to a 2.5-fold increase in S6K1 phosphorylation and a 1.5-fold increase in 4E-BP1 phosphorylation. Both rapamycin and PD-98059 inhibited the CIT effect on S6K1, whereas only LY-294002 inhibited the CIT effect on both S6K1 and 4E-BP1. These findings show that CIT is a signaling agent for muscle homeostasis, suggesting a new role of the intestine in muscle mass control. Copyright © 2017 the American Physiological Society.

  6. Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action.

    Science.gov (United States)

    Farshidfar, Farnaz; Pinder, Mark A; Myrie, Semone B

    2017-01-01

    Creatine, a very popular supplement among athletic populations, is of growing interest for clinical applications. Since over 90% of creatine is stored in skeletal muscle, the effect of creatine supplementation on muscle metabolism is a widely studied area. While numerous studies over the past few decades have shown that creatine supplementation has many favorable effects on skeletal muscle physiology and metabolism, including enhancing muscle mass (growth/hypertrophy); the underlying mechanisms are poorly understood. This report reviews studies addressing the mechanisms of action of creatine supplementation on skeletal muscle growth/hypertrophy. Early research proposed that the osmotic effect of creatine supplementation serves as a cellular stressor (osmosensing) that acts as an anabolic stimulus for protein synthesis signal pathways. Other reports indicated that creatine directly affects muscle protein synthesis via modulations of components in the mammalian target of rapamycin (mTOR) pathway. Creatine may also directly affect the myogenic process (formation of muscle tissue), by altering secretions of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors, resulting in enhanced satellite cells mitotic activities and differentiation into myofiber. Overall, there is still no clear understanding of the mechanisms of action regarding how creatine affects muscle mass/growth, but current evidence suggests it may exert its effects through multiple approaches, with converging impacts on protein synthesis and myogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. 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 (IC 50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU 50 = 3.5% ± 1.6%) or without insulin (GU 50 = 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.

  8. The low-frequency dielectric properties of octopus arm muscle measured in vivo

    International Nuclear Information System (INIS)

    Hart, F.X.; Toll, R.B.; Berner, N.J.; Bennett, N.H.

    1996-01-01

    The conductance and capacitance of octopus arm are measured in vivo over the frequency range 5 Hz to 1 MHz. Measurement of these parameters for a number of electrode separations permits the determination of the variations in tissue conductivity and dielectric constant with frequency. In the range 1-100 kHz the conductivity is independent of the frequency f and the dielectric constant varies as f -1 . These results, in conjunction with those reported previously for frog skeletal muscle, are consistent with the fractal model for the dielectric properties of animal tissue proposed by Dissado. Transformation of the results to complex impedance spectra indicates the presence of a dispersion above 100 kHz. (author)

  9. Mechanics of the human hamstring muscles during sprinting.

    Science.gov (United States)

    Schache, Anthony G; Dorn, Tim W; Blanch, Peter D; Brown, Nicholas A T; Pandy, Marcus G

    2012-04-01

    An understanding of hamstring mechanics during sprinting is important for elucidating why these muscles are so vulnerable to acute strain-type injury. The purpose of this study was twofold: first, to quantify the biomechanical load (specifically, musculotendon strain, velocity, force, power, and work) experienced by the hamstrings across a full stride cycle; and second, to determine how these parameters differ for each hamstring muscle (i.e., semimembranosus (SM), semitendinosus (ST), biceps femoris long head (BF), biceps femoris short head (BF)). Full-body kinematics and ground reaction force data were recorded simultaneously from seven subjects while sprinting on an indoor running track. Experimental data were integrated with a three-dimensional musculoskeletal computer model comprised of 12 body segments and 92 musculotendon structures. The model was used in conjunction with an optimization algorithm to calculate musculotendon strain, velocity, force, power, and work for the hamstrings. SM, ST, and BF all reached peak strain, produced peak force, and formed much negative work (energy absorption) during terminal swing. The biomechanical load differed for each hamstring muscle: BF exhibited the largest peak strain, ST displayed the greatest lengthening velocity, and SM produced the highest peak force, absorbed and generated the most power, and performed the largest amount of positive and negative work. As peak musculotendon force and strain for BF, ST, and SM occurred around the same time during terminal swing, it is suggested that this period in the stride cycle may be when the biarticular hamstrings are at greatest injury risk. On this basis, hamstring injury prevention or rehabilitation programs should preferentially target strengthening exercises that involve eccentric contractions performed with high loads at longer musculotendon lengths.

  10. Theory of muscle contraction mechanism with cooperative interaction among crossbridges.

    Science.gov (United States)

    Mitsui, Toshio; Ohshima, Hiroyuki

    2012-01-01

    The power stroke model was criticized and a model was proposed for muscle contraction mechanism (Mitsui, 1999). The proposed model was further developed and calculations based on the model well reproduced major experimental data on the steady filament sliding (Mitsui and Ohshima, 2008) and on the transient phenomena (Mitsui, Takai and Ohshima, 2011). In this review more weight is put on explanation of the basic ideas of the model, especially logical necessity of the model, leaving mathematical details to the above-mentioned papers. A thermodynamic relationship that any models based upon the sliding filament theory should fulfill is derived. The model which fulfills the thermodynamic relationship is constructed on the assumption that a myosin head bound to an actin filament forms a complex with three actin molecules. In shortening muscles, the complex moves along the actin filament changing the partner actin molecules with steps of about 5.5 nm. This process is made possible through cooperative interaction among cross-bridges. The ATP hydrolysis energy is liberated by fraction at each step through chemical reactions between myosin and actin molecules. The cooperativity among crossbridges disappears in length-clamped muscles, in agreement with experimental observations that the cross-bridge produces force independently in the isometric tetanus state. The distance of the head movement per ATP hydrolysis cycle is expected to be about 5.5 nm or a few times of it under the condition of the in vitro single head experiments. Calculation results are surveyed illustrating that they are in good agreement with major experimental observations.

  11. 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%, pcontrol trials (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.

  12. In vivo determination of steric and electrostatic exclusion of albumin in rat skin and skeletal muscle.

    Science.gov (United States)

    Gyenge, Christina C; Tenstad, Olav; Wiig, Helge

    2003-11-01

    In order to estimate the magnitude of electrostatic exclusion provided by the fixed negative charges of the skin and muscle interstitia of rat in vivo we measured the distribution volumes of two differently charged albumin probes within these tissues. An implanted osmotic pump was used to reach and maintain a steady-state extracellular concentration of a mixture containing two iodine-labelled probes: a charged-modified human serum albumin, cHSA (i.e. a positive probe, isoelectirc point (pI) = 7.6) and a native human serum albumin, HSA (i.e. a normally charged, negative probe, pI = 5.0). Steady-state tissue concentrations were achieved after intravenous infusion of probes for 5-7 days. At the end of this period the animals were nephrectomized and a bolus of 51Cr-EDTA was administered for estimating the extracellular volume. Plasma volumes were measured as 5-min distribution volume of 125I-HSA in separate experiments. The steady-state interstitial fluid concentrations of all probes were determined using nylon wicks implanted postmortem. Calculations of labelled probes were made for interstitial fluid volumes (Vi), extravascular albumin distribution volumes (Vav,a) and relative interstitial excluded volume fractions (Vex,a/Vi). We found that the positive probe is excluded from a significantly smaller fraction of the interstitium. Specifically, the average relative albumin exclusion fractions obtained were: 16% and 26% in skeletal muscle and 30% and 40% in skin, for cHSA and HSA, respectively. On average, the fixed negative charges of the interstitium are responsible for about 40% of the total albumin exclusion in skeletal muscle and 25% in the whole skin tissue and thus, contribute significantly to volume exclusion in these tissues.

  13. Psoas muscle architectural design, in vivo sarcomere length range, and passive tensile properties support its role as a lumbar spine stabilizer.

    Science.gov (United States)

    Regev, Gilad J; Kim, Choll W; Tomiya, Akihito; Lee, Yu Po; Ghofrani, Hossein; Garfin, Steven R; Lieber, Richard L; Ward, Samuel R

    2011-12-15

    Controlled laboratory and cross-sectional study designs. To determine psoas major (PM) muscle architectural properties, in vivo sarcomere-length operating range, and passive mechanical properties. PM is an important hip flexor but its role in lumbar spine function is not fully understood. Several investigators have detailed the gross anatomy of PM, but comprehensive architectural data and in vivo length-tension and passive mechanical behaviors have not been documented. PM was isolated in 13 cadaver specimens, permitting architectural measurements of physiological cross-sectional area (PCSA), normalized fiber length (Lf), and Lf:muscle length (Lm) ratio. Sarcomere lengths were measured in vivo from intraoperative biopsies taken with the hip joint in flexed and extended positions. Single-fiber and fiber bundle tensile properties and titin molecular weight were then measured from separate biopsies. Architecturally, average PCSA was 18.45 ± 1.32 cm2, average Lf was 12.70 ± 2 cm, and average Lf: Lm was 0.48 ± 0.06. Intraoperative sarcomere length measurements revealed that the muscle operates from 3.18 ± 0.20 μm with hip flexed at 10.7° ± 13.9° to 3.03 ± 0.22 μm with hip flexed at 55.9° ± 21.4°. Passive mechanical data demonstrated that the elastic modulus of the PM muscle fibers was 37.44 ± 9.11 kPa and of fiber bundles was 55.3 ± 11.8 kPa. Analysis of PM architecture demonstrates that its average Lf and passive biomechanical properties resemble those of the lumbar erector spinae muscles. In addition, PM sarcomere lengths were confined to the descending portion of the length-tension curve allowing the muscle to become stronger as the hip is flexed and the spine assumes a forward leaning posture. These findings suggest that the human PM has architectural and physiologic features that support its role as both a flexor of the hip and a dynamic stabilizer of the lumbar spine.

  14. Comparison of in vivo postexercise phosphocreatine recovery and resting ATP synthesis flux for the assessment of skeletal muscle mitochondrial function

    NARCIS (Netherlands)

    Broek, van den N.M.A.; Ciapaite, J.; Nicolay, K.; Prompers, J.J.

    2010-01-01

    31P magnetic resonance spectroscopy (MRS) has been used to assess skeletal muscle mitochondrial function in vivo by measuring 1) phosphocreatine (PCr) recovery after exercise or 2) resting ATP synthesis flux with saturation transfer (ST). In this study, we compared both parameters in a rat model of

  15. 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

    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...

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

    OpenAIRE

    Kenneth S Campbell

    2009-01-01

    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, whi...

  17. Mechanism of phosphaturia elicited by administration of phosphonoformate in vivo

    International Nuclear Information System (INIS)

    VanScoy, M.; Loghman-Adham, M.; Onsgard, M.; Szczepanska-Konkel, M.; Homma, Sumiko; Knox, F.G.; Dousa, T.P.

    1988-01-01

    The authors examined whether phosphonoformate (PFA) can cause phosphaturia through its direct action on brush-border membrane (BBM) in vivo. Infusion of PFA or of parathyroid hormone (PTH) to thyroparathyroidectomized rats caused a marked increase in fractional excretion of phosphate without changes in excretion of Na + or of GFR. The PFA-induced phosphaturia was not accompanied by an increase in urinary adenosine-3',5'-cyclic monophosphate (cAMP); moreover, PFA added in vitro did not influence the PTH-sensitive adenylate cyclase and cAMP-phosphodiesterase in proximal convoluted tubules. In BBM vesicles (BBMV) from rats with PFA-elicited phosphaturia, neither the rate of Na + -P i symport nor Na + -dependent binding of [ 14 C]PFA on BBMV was changed, whereas in BBMV from PTH-infused rats the V max of Na + -P i symport decreased. PFA is almost completely ultrafiltrable; no metabolic transformation of PFA was detected after [ 14 C]PFA exposure to rat renal cortical slices, homogenate, or to blood. They conclude that PFA causes phosphaturia by direct inhibition of Na + -P i symport across BBM in proximal tubules, acting from the luminal side. Thus PFA (foscarnet) has a unique direct mechanism of phosphaturic effect, via its action on P i reabsorption in proximal tubules in vivo

  18. GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies

    Science.gov (United States)

    de Jonge, Jeroen C.; Vinkers, Christiaan H.; Hulshoff Pol, Hilleke E.; Marsman, Anouk

    2017-01-01

    Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and impairments in cognitive functioning. Evidence from postmortem studies suggests that alterations in cortical γ-aminobutyric acid (GABAergic) neurons contribute to the clinical features of schizophrenia. In vivo measurement of brain GABA levels using magnetic resonance spectroscopy (MRS) offers the possibility to provide more insight into the relationship between problems in GABAergic neurotransmission and clinical symptoms of schizophrenia patients. This study reviews and links alterations in the GABA system in postmortem studies, animal models, and human studies in schizophrenia. Converging evidence implicates alterations in both presynaptic and postsynaptic components of GABAergic neurotransmission in schizophrenia, and GABA may thus play an important role in the pathophysiology of schizophrenia. MRS studies can provide direct insight into the GABAergic mechanisms underlying the development of schizophrenia as well as changes during its course. PMID:28848455

  19. GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Jeroen C. de Jonge

    2017-08-01

    Full Text Available Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and impairments in cognitive functioning. Evidence from postmortem studies suggests that alterations in cortical γ-aminobutyric acid (GABAergic neurons contribute to the clinical features of schizophrenia. In vivo measurement of brain GABA levels using magnetic resonance spectroscopy (MRS offers the possibility to provide more insight into the relationship between problems in GABAergic neurotransmission and clinical symptoms of schizophrenia patients. This study reviews and links alterations in the GABA system in postmortem studies, animal models, and human studies in schizophrenia. Converging evidence implicates alterations in both presynaptic and postsynaptic components of GABAergic neurotransmission in schizophrenia, and GABA may thus play an important role in the pathophysiology of schizophrenia. MRS studies can provide direct insight into the GABAergic mechanisms underlying the development of schizophrenia as well as changes during its course.

  20. Mechanism of action in VIVO of some pet radiotracers

    International Nuclear Information System (INIS)

    Sachinidis, J.J.; Egan, G.F.; Berlangieri, S.U.; Scott, A.M.

    1998-01-01

    Full text: Position Emission Tomography (PET) is a technique that utilises position-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. PET studies range from standard image displays that provide indices of physiological function to complex kinetic analysis methods for absolute quantification. This paper will review some of the important PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre, Melbourne and discuss their mechanism of action in vivo. Depending on their mechanism of action, PET radiopharmaceuticals may be divided into two categories. The first category is non-specific radiotracers which follow a biochemical pathway. The second category is specific radioligands which are involved in an interaction with a receptor transporter or a receptor site. Radiopharmaceuticals from the first category may be assessed using a single or two compartmental plasma-tissue model and allow a measurement of tissue extraction or metabolism.[ 15 O] water is a freely diffusable inert which is used for cerebral blood flow measurement; [ 18 F] FDG which follows the initial phases of glucose metabolism but does not enter the Krebs cycle after phosphorylation and therefore is effectively trapped in the cells, can be used for tissue glucose metabolism measurement in oncology, cardiology and neurology; and [ 18 F]fluoromisonidazole which is a bio-reductive drug that in vivo follows an intracellular reduction pathway, can be used for hypoxic tissue measurement in stroke and tumour evaluation. Radiopharmaceuticals from the second category may be assessed using a three-compartment model: - unmetabolised free ligand in plasma, - free ligand in tissue, - and specially bound ligand in tissue. These radiotracers such as [ 11 C] flumazenil, which is an antagonist with high affinity and selectivity for a central benzodiazepine receptors, are used to study the changes in density or affinity of these receptors

  1. A Robust Method to Generate Mechanically Anisotropic Vascular Smooth Muscle Cell Sheets for Vascular Tissue Engineering.

    Science.gov (United States)

    Backman, Daniel E; LeSavage, Bauer L; Shah, Shivem B; Wong, Joyce Y

    2017-06-01

    In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure and further disease. With bottom-up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve the necessary macroscale properties in the final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle cell (VSMC) sheets by photografting N-isopropylacrylamide (NIPAAm) onto micropatterned poly(dimethysiloxane) (PDMS). The grafting process is experimentally and computationally optimized to produce PNIPAAm-PDMS substrates optimal for VSMC attachment. To allow long-term VSMC sheet culture and increase the rate of VSMC sheet formation, PNIPAAm-PDMS surfaces were further modified with 3-aminopropyltriethoxysilane yielding a robust, thermoresponsive cell culture platform for culturing VSMC sheets. VSMC cell sheets cultured on patterned thermoresponsive substrates exhibit cellular and collagen alignment in the direction of the micropattern. Mechanical characterization of patterned, single-layer VSMC sheets reveals increased stiffness in the aligned direction compared to the perpendicular direction whereas nonpatterned cell sheets exhibit no directional dependence. Structural and mechanical anisotropy of aligned, single-layer VSMC sheets makes this platform an attractive microstructural building block for engineering a vascular graft to match the in vivo mechanical properties of native arterial tissue. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  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. Evaluation of intra-cellular lipid of skeletal muscle by 1H-MR spectroscopy: in vivo and phantom study

    International Nuclear Information System (INIS)

    Ma Ling; Gao Zhenhua; Meng Quanfei; Lin Erjian; Zhang Xiaoling; Deng Demao

    2009-01-01

    Objective: To elucidate the spectrum of lipid peaks in 1 H-MRS of skeletal muscle and it's interpretation, to investigate the utility of 1 H-MRS in evaluating intramyocellular lipid (IMCL). Methods: 1 H-MRS was acquired in vivo on tibialis anterior muscle (TA) and soleus muscle (S) on 5 healthy volunteers. The spectrum of the lipid peak between 0.80 and 1.80 ppm was observed with different angle between the long axis of the calf and B 0 . Ex vivo phantom was an cluster of capillary tubers filled with soybean oil and fat emulsion, simulating the extramyocellular lipid (EMCL) and IMCL, respectively. The spectra of the lipid peaks were compared using different angles between the phantom and Bo field. Results: The lipid spectrum split to 3 to 4 peaks between 0.80 and 1.80 ppm on calf muscles, with 0.20 to 0.30 ppm interval between each neighbouring peak. The methylene peak of EMCL shifted to the right when the angle between long axis of the calf and B 0 increased. The phantom could simulate the spectrum of 1 H-MRS of the muscle, presenting two peaks with 0.20 to 0.30 ppm chemical shift difference between 0.80 and 1.80 ppm. They are methyl triglyceride and methylene, representing IMCL and EMCL, respectively. The peak splitting could be attributed to the high ordered muscle fibers and their chemical shift difference between inta-and extra-cellular distribution. The interval of IMCL and EMCL peaks attenuated when the angle between the muscle fiber and B 0 increased from 0 to the magic angle (54.7 degree). Conclusion: On 1 H- MRS spectrum, the peak of the EMCL and IMCL splits. This indicated that 1 H-MRS is an applicable method to detect IMCL noninvasively. TA is an optimizing muscle for 1 H-MRS study. (authors)

  4. 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

    2014-01-01

    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

  5. Insulin Resistance Is Not Associated with an Impaired Mitochondrial Function in Contracting Gastrocnemius Muscle of Goto-Kakizaki Diabetic Rats In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Macia

    Full Text Available Insulin resistance, altered lipid metabolism and mitochondrial dysfunction in skeletal muscle would play a major role in type 2 diabetes mellitus (T2DM development, but the causal relationships between these events remain conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in Goto-Kakizaki (GK rats, a non-obese T2DM model developing peripheral insulin resistant without abnormal level of plasma non-esterified fatty acids (NEFA. Wistar rats were used as controls. Mechanical performance and energy metabolism were assessed strictly non-invasively using magnetic resonance (MR imaging and 31-phosphorus MR spectroscopy (31P-MRS. Compared with control group, plasma insulin and glucose were respectively lower and higher in GK rats, but plasma NEFA level was normal. In resting GK muscle, phosphocreatine content was reduced whereas glucose content and intracellular pH were both higher. However, there were not differences between both groups for basal oxidative ATP synthesis rate, citrate synthase activity, and intramyocellular contents for lipids, glycogen, ATP and ADP (an important in vivo mitochondrial regulator. During a standardized fatiguing protocol (6 min of maximal repeated isometric contractions electrically induced at a frequency of 1.7 Hz, mechanical performance and glycolytic ATP production rate were reduced in diabetic animals whereas oxidative ATP production rate, maximal mitochondrial capacity and ATP cost of contraction were not changed. These findings provide in vivo evidence that insulin resistance is not caused by an impairment of mitochondrial function in this diabetic model.

  6. 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.

  7. Effects of intra-arterial epinephrine on energy metabolism in exercising rabbit gastrocnemius muscle, studied by in vivo phosphorus nuclear magnetic resonance.

    Science.gov (United States)

    Argov, Z; Nioka, S; Eleff, S; Chance, B

    1991-10-01

    Epinephrine has an inotropic effect on skeletal muscle, especially on glycolytic type 2 fibers. The mechanism of this effect is not completely clear and its association with a change in oxidative metabolism or glycolytic activation was not fully investigated. Epinephrine's effects on muscle bioenergetics were studied by in vivo 31P nuclear magnetic resonance to find if mitochondrial metabolism is changed during the inotropic action and if the known glycolytic activation by epinephrine is operative during muscle twitch. The study was also used as a model for the application of in vivo 31P nuclear magnetic resonance in the evaluation of short-term acting drugs. When injected intra-arterially, epinephrine (1 micrograms/kg) augmented the twitch tension of indirectly stimulated, continuously working rabbit gastrocnemius muscle by 15.4 + 6.5%. This increase in work was associated with reduction of phosphocreatine to inorganic phosphate ratio (PCr/Pi) from 3.4 to 2.1 without change in ATP levels. Intracellular pH was reduced from 6.9 to 6.75, but no accumulation of glycolytic intermediates could be observed. The increase in work was not associated with a rise in ADP. All these changes occurred for a few minutes only. The findings suggest that epinephrine's inotropic action is not mediated by a change in mitochondrial metabolism. Glycolytic activation by epinephrine occurs even during twitch and contributes partly to the energy demands of the augmented force. Epinephrine's inotropic effect is, however, not primarily due to changes in bioenergetic kinetics, but to effects on force generating mechanisms, with secondary reduction in energy state.

  8. 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.

  9. Molecular mechanisms of muscle atrophy in myotonic dystrophies

    OpenAIRE

    Timchenko, Lubov

    2013-01-01

    Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystemic diseases that primarily affect skeletal muscle, causing myotonia, muscle atrophy, and muscle weakness. DM1 and DM2 pathologies are caused by expansion of CTG and CCTG repeats in non-coding regions of the genes encoding myotonic dystrophy protein kinase (DMPK) and Zinc finger protein 9 (ZNF9) respectively. These expansions cause DM pathologies through accumulation of mutant RNAs that alter RNA metabolism in p...

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. 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 ( R 2 =0.9), providing confidence in our model estimates. Our simulation results suggest that different exoskeleton behaviors can alter the functioning of the muscles and tendons acting at the assisted joint. Furthermore, our results support the idea that the series tendon helps reduce positive work done by the muscle fibers by storing and returning energy elastically. We expect the results from this study to promote the use of electromyography-driven simulations to gain insight into the operation of muscle-tendon units and to guide the design and control of assistive devices. © 2017. Published by The Company of Biologists Ltd.

  17. 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

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

    Science.gov (United States)

    Gehlert, Sebastian; Bloch, Wilhelm; Suhr, Frank

    2015-01-01

    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. PMID:25569087

  19. 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...

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

    Directory of Open Access Journals (Sweden)

    Mathieu Lecocq

    Full Text Available 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.

  1. Mechanical performance of artificial pneumatic muscles to power an ankle-foot orthosis.

    Science.gov (United States)

    Gordon, Keith E; Sawicki, Gregory S; Ferris, Daniel P

    2006-01-01

    We developed a powered ankle-foot orthosis that uses artificial pneumatic muscles to produce active plantar flexor torque. The purpose of this study was to quantify the mechanical performance of the orthosis during human walking. Three subjects walked at a range of speeds wearing ankle-foot orthoses with either one or two artificial muscles working in parallel. The orthosis produced similar total peak plantar flexor torque and network across speeds independent of the number of muscles used. The orthosis generated approximately 57% of the peak ankle plantar flexor torque during stance and performed approximately 70% of the positive plantar flexor work done during normal walking. Artificial muscle bandwidth and force-length properties were the two primary factors limiting torque production. The lack of peak force and work differences between single and double muscle conditions can be explained by force-length properties. Subjects altered their ankle kinematics between conditions resulting in changes in artificial muscle length. In the double muscle condition greater plantar flexion yielded shorter artificial muscles lengths and decreased muscle forces. This finding emphasizes the importance of human testing in the design and development of robotic exoskeleton devices for assisting human movement. The results of this study outline the mechanical performance limitations of an ankle-foot orthosis powered by artificial pneumatic muscles. This orthosis could be valuable for gait rehabilitation and for studies investigating neuromechanical control of human walking.

  2. 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.

  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

    compared with U, and S also demonstrated greater type II fiber CSA than did U and E. The proportion of type I fibers was greater in E compared with U and S. CONCLUSIONS: Muscle fiber size and mechanical muscle performance, particularly RFD, were consistently elevated in aged individuals exposed to chronic...

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

    Science.gov (United States)

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

    2010-05-01

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

  5. 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

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

    Science.gov (United States)

    Walker, Simon M; Schwyn, Daniel A; Mokso, Rajmund; Wicklein, Martina; Müller, Tonya; Doube, Michael; Stampanoni, Marco; Krapp, Holger G; Taylor, Graham K

    2014-03-01

    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 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 insect flight motor.

  7. 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.

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

    International Nuclear Information System (INIS)

    Thevenard, Jessica; Ramont, Laurent; Mir, Lluis M.; Dupont-Deshorgue, Aurélie; Maquart, François-Xavier; Monboisse, Jean-Claude; Brassart-Pasco, Sylvie

    2013-01-01

    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

  9. Small diameter electrospun silk fibroin vascular grafts: Mechanical properties, in vitro biodegradability, and in vivo biocompatibility.

    Science.gov (United States)

    Catto, Valentina; Farè, Silvia; Cattaneo, Irene; Figliuzzi, Marina; Alessandrino, Antonio; Freddi, Giuliano; Remuzzi, Andrea; Tanzi, Maria Cristina

    2015-09-01

    To overcome the drawbacks of autologous grafts currently used in clinical practice, vascular tissue engineering represents an alternative approach for the replacement of small diameter blood vessels. In the present work, the production and characterization of small diameter tubular matrices (inner diameter (ID)=4.5 and 1.5 mm), obtained by electrospinning (ES) of Bombyx mori silk fibroin (SF), have been considered. ES-SF tubular scaffolds with ID=1.5 mm are original, and can be used as vascular grafts in pediatrics or in hand microsurgery. Axial and circumferential tensile tests on ES-SF tubes showed appropriate properties for the specific application. The burst pressure and the compliance of ES-SF tubes were estimated using the Laplace's law. Specifically, the estimated burst pressure was higher than the physiological pressures and the estimated compliance was similar or higher than that of native rat aorta and Goretex® prosthesis. Enzymatic in vitro degradation tests demonstrated a decrease of order and crystallinity of the SF outer surface as a consequence of the enzyme activity. The in vitro cytocompatibility of the ES-SF tubes was confirmed by the adhesion and growth of primary porcine smooth muscle cells. The in vivo subcutaneous implant into the rat dorsal tissue indicated that ES-SF matrices caused a mild host reaction. Thus, the results of this investigation, in which comprehensive morphological and mechanical aspects, in vitro degradation and in vitro and in vivo biocompatibility were considered, indicate the potential suitability of these ES-SF tubular matrices as scaffolds for the regeneration of small diameter blood vessels. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Passive mechanical properties of gastrocnemius muscles of people with ankle contracture after stroke.

    Science.gov (United States)

    Kwah, Li Khim; Herbert, Robert D; Harvey, Lisa A; Diong, Joanna; Clarke, Jillian L; Martin, Joshua H; Clarke, Elizabeth C; Hoang, Phu D; Bilston, Lynne E; Gandevia, Simon C

    2012-07-01

    To investigate the mechanisms of contracture after stroke by comparing passive mechanical properties of gastrocnemius muscle-tendon units, muscle fascicles, and tendons in people with ankle contracture after stroke with control participants. Cross-sectional study. Laboratory in a research institution. A convenience sample of people with ankle contracture after stroke (n=20) and able-bodied control subjects (n=30). Not applicable. Stiffness and lengths of gastrocnemius muscle-tendon units, lengths of muscle fascicles, and tendons at specific tensions. At a tension of 100N, the gastrocnemius muscle-tendon unit was significantly shorter in participants with stroke (mean, 436mm) than in able-bodied control participants (mean, 444mm; difference, 8mm; 95% confidence interval [CI], 0.2-15mm; P=.04). Muscle fascicles were also shorter in the stroke group (mean, 44mm) than in the control group (mean, 50mm; difference, 6mm; 95% CI, 1-12mm; P=.03). There were no significant differences between groups in the mean stiffness or length of the muscle-tendon units and fascicles at low tension, or in the mean length of the tendons at any tension. People with ankle contracture after stroke have shorter gastrocnemius muscle-tendon units and muscle fascicles than control participants at high tension. This difference is not apparent at low tension. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  11. Supersonic Shear Imaging Elastography in Skeletal Muscles: Relationship Between In Vivo and Synthetic Fiber Angles and Shear Modulus.

    Science.gov (United States)

    Lima, Kelly; Rouffaud, Remi; Pereira, Wagner; Oliveira, Liliam F

    2018-04-30

    To verify a relationship between the pennation angle of synthetic fibers and muscle fibers with the shear modulus (μ) generated by Supersonic shear imaging (SSI) elastography and to compare the anisotropy of synthetic and in vivo pennate muscle fibers in the x 2 -x 3 plane (probe perpendicular to water surface or skin). First, the probe of Aixplorer ultrasound scanner (v.9, Supersonic Imagine, Aix-en-Provence, France) was placed in 2 positions (parallel [aligned] and transverse to the fibers) to test the anisotropy in the x 2 -x 3 plane. Subsequently, it was inclined (x 1 -x 3 plane) in relation to the fibers, forming 3 angles (18.25 °, 21.55 °, 36.86 °) for synthetic fibers and one (approximately 0 °) for muscle fibers. On the x 2 -x 3 plane, μ values of the synthetic and vastus lateralis fibers were significantly lower (P < .0001) at the transverse probe position than the longitudinal one. In the x 1 -x 3 plane, the μ values were significantly reduced (P < .0001) with the probe angle increasing, only for the synthetic fibers (approximately 0.90 kPa for each degree of pennation angle). The pennation angle was not related to the μ values generated by SSI elastography for the in vivo lateral head of the gastrocnemius and vastus lateralis muscles. However, a μ reduction with an angle increase in the synthetic fibers was observed. These findings contribute to increasing the applicability of SSI in distinct muscle architecture at normal or pathologic conditions. © 2018 by the American Institute of Ultrasound in Medicine.

  12. Skeletal muscle blood flow in vivo: detection with rubidium-82 and effects of glucose, insulin, and exercise

    International Nuclear Information System (INIS)

    Mossberg, K.A.; Mullani, N.; Gould, K.L.; Taegtmeyer, H.

    1987-01-01

    In order to assess the effects of glucose, insulin, and exercise on skeletal muscle blood flow in vivo, we measured positron emission from the thigh muscle of anesthetized rabbits after simultaneous aortic bolus injection of 82 Rb and radiolabeled microspheres (15 micron diameter). Estimates of flow with 82 Rb were based on first-pass regional extraction of 82 Rb by skeletal muscle. Flow estimates were made serially as a function of variations in plasma glucose and insulin and changing the muscle contractile state by electrical stimulation. Flow ranged from 3.1 ml/min/100 g at rest to 71 ml/min/100 g during stimulation. There was good agreement between the two methods of flow measurement over the entire range of flows (r = 0.96 at a slope of 0.90). Flow measured by either method did not vary significantly from baseline over a range of plasma glucose from 5 to 30 mM and plasma insulin from 0 to 20 microU/ml. When flow was increased up to 20-fold by electrical stimulation there was a decrease in extraction of 82 Rb proportional to the increase in flow. However, at pharmacologic levels of insulin (greater than 150 microU/ml) flow was increased twofold as measured by radiolabeled microspheres, but not as measured by rubidium. There was no apparent decrease in extraction of 82 Rb with high insulin. The discrepancy between the microsphere measured flow and rubidium measured flow with high plasma insulin levels can be explained by the assumption that the expected decrease in the extraction fraction was counteracted by an increase in Na+/K+-ATPase activity. It is concluded that the first-pass flow model gives valid estimates of skeletal muscle blood flow in vivo with 82 Rb, provided that plasma insulin levels are normal

  13. Effects of plyometric and isometric training on muscle and tendon stiffness in vivo.

    Science.gov (United States)

    Kubo, Keitaro; Ishigaki, Tomonobu; Ikebukuro, Toshihiro

    2017-08-01

    The purpose of this study was to compare the effects of plyometric and isometric training on tendon properties during ramp and ballistic contractions and muscle stiffness under passive and active conditions. Eleven subjects completed 12 weeks (3 days/week) of a unilateral training program for the plantar flexors. They performed plyometric training on one side (PLY) and isometric training on the other side (ISO). Active muscle stiffness in the medial gastrocnemius muscle was calculated according to changes in estimated muscle force and fascicle length during fast stretching after submaximal isometric contractions. Passive muscle stiffness was also calculated from estimated passive muscle force and fascicle length during slow passive stretching. Stiffness and hysteresis of tendon structures were measured using ultrasonography during ramp and ballistic contractions. Passive muscle stiffness and tendon hysteresis did not change for PLY or ISO Active muscle stiffness significantly increased for PLY, but not for ISO Tendon stiffness during ramp and ballistic contractions increased significantly for ISO, but not for PLY In addition, tendon elongation values at force production levels beyond 100 N during ballistic contractions increased for PLY These results suggest that plyometric training (but not isometric training) enhances the extensibility of tendon structures during ballistic contractions and active muscle stiffness during fast stretching, and these changes may be related to improved performances during stretch-shortening cycle exercises. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  14. Terbinafine: effects on platelet-derived growth factor-stimulated smooth muscle cells in vitro and myointimal proliferation in vivo

    International Nuclear Information System (INIS)

    McCarthy, L.; Van Halen, R.G.; St Denny, I.H.; Glinka, K.G.; Handley, D.A.; Stuetz, A.; Nemecek, G.M.

    1987-01-01

    Terbinafine (T; (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic agent with antimitogenic activity in fibroblasts, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and myointimal proliferation in vivo. Exposure of smooth muscle cells to 1-25 μM T resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by [ 3 H]thymidine incorporation or cell number. The IC 50 for T was approximately 5 μM. The inhibitory effect of terbinafine persisted in the presence of 0.4-8.0 μg/ml cholesterol or 130 μg/ml mevalonate. Administration of T to rats for 2 d before and 14 d after balloon catheter carotid injury resulted in a 40% decrease in lesion area. These observations indicate that T is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated, orally active inhibitor of myointimal proliferation in vivo

  15. Terbinafine: effects on platelet-derived growth factor-stimulated smooth muscle cells in vitro and myointimal proliferation in vivo

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, L.; Van Halen, R.G.; St. Denny, I.H.; Glinka, K.G.; Handley, D.A.; Stuetz, A.; Nemecek, G.M.

    1987-05-01

    Terbinafine (T; (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic agent with antimitogenic activity in fibroblasts, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and myointimal proliferation in vivo. Exposure of smooth muscle cells to 1-25 ..mu..M T resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by (/sup 3/H)thymidine incorporation or cell number. The IC/sub 50/ for T was approximately 5 ..mu..M. The inhibitory effect of terbinafine persisted in the presence of 0.4-8.0 ..mu..g/ml cholesterol or 130 ..mu..g/ml mevalonate. Administration of T to rats for 2 d before and 14 d after balloon catheter carotid injury resulted in a 40% decrease in lesion area. These observations indicate that T is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated, orally active inhibitor of myointimal proliferation in vivo.

  16. 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 (artificial molecular muscles, were compared with (i) data from nominally bare microcantilevers precoated with gold and (ii) those coated with two types of control compounds, namely, dumbbell molecules to simulate the redox activity of the palindromic bistable [3]rotaxane molecules and inactive 1-dodecanethiol molecules. The comparisons demonstrate that the artificial molecular muscles are responsible for the deflections, which can be repeated over many 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).

  17. Characterisation of mechanical behaviour of human skin in vivo

    NARCIS (Netherlands)

    Douven, L.F.A.; Meijer, R.; Oomens, C.W.J.

    2000-01-01

    Characterization of the biomechanical properties of human skin in vivo is studied both experimentally and by numerical modeling. These properties can be important in the evaluation of skin condition (e.g. aging) as well as skin disorders. In this study the authors focus on the static behavior of the

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

    OpenAIRE

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

    2011-01-01

    Purpose 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). Methods 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 ac...

  19. The role of human ankle plantar flexor muscle-tendon interaction and architecture in maximal vertical jumping examined in vivo.

    Science.gov (United States)

    Farris, Dominic James; Lichtwark, Glen A; Brown, Nicholas A T; Cresswell, Andrew G

    2016-02-01

    Humans utilise elastic tendons of lower limb muscles to store and return energy during walking, running and jumping. Anuran and insect species use skeletal structures and/or dynamics in conjunction with similarly compliant structures to amplify muscle power output during jumping. We sought to examine whether human jumpers use similar mechanisms to aid elastic energy usage in the plantar flexor muscles during maximal vertical jumping. Ten male athletes performed maximal vertical squat jumps. Three-dimensional motion capture and a musculoskeletal model were used to determine lower limb kinematics that were combined with ground reaction force data in an inverse dynamics analysis. B-mode ultrasound imaging of the lateral gastrocnemius (GAS) and soleus (SOL) muscles was used to measure muscle fascicle lengths and pennation angles during jumping. Our results highlighted that both GAS and SOL utilised stretch and recoil of their series elastic elements (SEEs) in a catapult-like fashion, which likely serves to maximise ankle joint power. The resistance of supporting of body weight allowed initial stretch of both GAS and SOL SEEs. A proximal-to-distal sequence of joint moments and decreasing effective mechanical advantage early in the extension phase of the jumping movement were observed. This facilitated a further stretch of the SEE of the biarticular GAS and delayed recoil of the SOL SEE. However, effective mechanical advantage did not increase late in the jump to aid recoil of elastic tissues. © 2016. Published by The Company of Biologists Ltd.

  20. 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.

  1. 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.

  2. Muscle-related side-effects of statins: from mechanisms to evidence-based solutions.

    Science.gov (United States)

    Taylor, Beth A; Thompson, Paul D

    2015-06-01

    This article highlights the recent findings regarding statin-associated muscle side effects, including mechanisms and treatment as well as the need for more comprehensive clinical trials in statin myalgia. Statin myalgia is difficult to diagnose and treat, as major clinical trials have not routinely assessed muscle side-effects, there are few clinically relevant biomarkers and assessment tools for the symptoms, many apparent statin-related muscle symptoms may be nonspecific and related to other drugs or health conditions, and prevalence estimates vary widely. Data thus suggest that only 30-50% of patients with self-reported statin myalgia actually experience muscle pain on statins during blinded, placebo-controlled trials. In addition, evidence to date involving mechanisms underlying statin myalgia and its range of symptoms and presentations supports the hypothesis that there are multiple, interactive and potentially additive mechanisms underlying statin-associated muscle side-effects. There are likely multiple and interactive mechanisms underlying statin myalgia, and recent studies have produced equivocal data regarding prevalence of statin-associated muscle side-effects, contributing factors and effectiveness of common interventions. Therefore, more clinical trials on statin myalgia are critical to the field, as are systematic resources for quantifying, predicting and reporting statin-associated muscle side-effects.

  3. A novel method for determining human ex vivo submaximal skeletal muscle mitochondrial function

    DEFF Research Database (Denmark)

    Hey-Mogensen, Martin; Gram, Martin; Jensen, Martin Borch

    2015-01-01

    previously used. Muscle biopsies were taken from 64 old or young male subjects (60-70 or 20-30 years old). Aged subjects were recruited as trained or untrained. Muscle biopsies were used for isolation of mitochondria and subsequent measurements of DNA repair, antioxidant capacity and mitochondrial protein...

  4. 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.)

  5. In vivo determination of the optical properties of muscle with time-resolved reflectance using a layered model

    International Nuclear Information System (INIS)

    Kienle, A.; Glanzmann, T.

    1999-01-01

    We have investigated the possibility of determining the optical coefficients of muscle in the extremities with in vivo time-resolved reflectance measurements using a layered model. A solution of the diffusion equation for two layers was fitted to three-layered Monte Carlo calculations simulating the skin, the subcutaneous fat and the muscle. Relative time-resolved reflectance data at two distances were used to derive the optical coefficients of the layers. We found for skin and subcutaneous fat layer thicknesses (l 2 ) of up to 10 mm that the estimated absorption coefficients of the second layer of the diffusion model have differences of less than 20% compared with those of the muscle layer of the Monte Carlo simulations if the thickness of the first layer of the diffusion model is also fitted. If l 2 is known, the differences are less than 5%, whereas the use of a semi-infinite model delivers differences of up to 55%. Even if l 2 is only approximately known the absorption coefficient of the muscle can be determined accurately. Experimentally, the time-resolved reflectance was measured on the forearms of volunteers at two distances from the incident beam by means of a streak camera. The thicknesses of the tissues involved were determined by ultrasound. The optical coefficients were derived from these measurements by applying the two-layered diffusion model, and results in accordance with the theoretical studies were observed. (author)

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

    Science.gov (United States)

    Olszewski, Raphael; Liu, Y; Duprez, T; Xu, T M; Reychler, H

    2009-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Simon Krašna

    2017-06-01

    Full Text Available 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.

  8. Cycle training induces muscle hypertrophy and strength gain: strategies and mechanisms.

    Science.gov (United States)

    Ozaki, Hayao; Loenneke, J P; Thiebaud, R S; Abe, T

    2015-03-01

    Cycle training is widely performed as a major part of any exercise program seeking to improve aerobic capacity and cardiovascular health. However, the effect of cycle training on muscle size and strength gain still requires further insight, even though it is known that professional cyclists display larger muscle size compared to controls. Therefore, the purpose of this review is to discuss the effects of cycle training on muscle size and strength of the lower extremity and the possible mechanisms for increasing muscle size with cycle training. It is plausible that cycle training requires a longer period to significantly increase muscle size compared to typical resistance training due to a much slower hypertrophy rate. Cycle training induces muscle hypertrophy similarly between young and older age groups, while strength gain seems to favor older adults, which suggests that the probability for improving in muscle quality appears to be higher in older adults compared to young adults. For young adults, higher-intensity intermittent cycling may be required to achieve strength gains. It also appears that muscle hypertrophy induced by cycle training results from the positive changes in muscle protein net balance.

  9. 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.

  10. Parallel in vivo monitoring of pH in gill capillaries and muscles of fishes using microencapsulated biomarkers

    Directory of Open Access Journals (Sweden)

    Ekaterina Borvinskaya

    2017-05-01

    Full Text Available Tracking physiological parameters in different organs within the same organism simultaneously and in real time can provide an outstanding representation of the organism's physiological status. The state-of-the-art technique of using encapsulated fluorescent molecular probes (microencapsulated biomarkers is a unique tool that can serve as a platform for the development of new methods to obtain in vivo physiological measurements and is applicable to a broad range of organisms. Here, we describe a novel technique to monitor the pH of blood inside the gill capillaries and interstitial fluid of muscles by using microencapsulated biomarkers in a zebrafish model. The functionality of the proposed technique is shown by the identification of acidification under anesthesia-induced coma and after death. The pH in muscles reacts to hypoxia faster than that in the gill bloodstream, which makes both parameters applicable as markers of either local or bodily reactions.

  11. Maltitol inhibits small intestinal glucose absorption and increases insulin mediated muscle glucose uptake ex vivo but not in normal and type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2017-02-01

    This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.

  12. 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.

  13. Gestational undernourishment modifies the composition of skeletal muscle transverse tubule membranes and the mechanical properties of muscles in newborn rats.

    Science.gov (United States)

    Ramírez-Oseguera, Ricardo Tonathiu; Jiménez-Garduño, Aura Matilde; Alvarez, Rocío; Heine, Katharina; Pinzón-Estrada, Enrique; Torres-Saldaña, Ismael; Ortega, Alicia

    2013-01-01

    [corrected] 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. 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. 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. 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. © 2013 S. Karger AG, Basel

  14. Structural imprints in vivo decode RNA regulatory mechanisms.

    Science.gov (United States)

    Spitale, Robert C; Flynn, Ryan A; Zhang, Qiangfeng Cliff; Crisalli, Pete; Lee, Byron; Jung, Jong-Wha; Kuchelmeister, Hannes Y; Batista, Pedro J; Torre, Eduardo A; Kool, Eric T; Chang, Howard Y

    2015-03-26

    Visualizing the physical basis for molecular behaviour inside living cells is a great challenge for biology. RNAs are central to biological regulation, and the ability of RNA to adopt specific structures intimately controls every step of the gene expression program. However, our understanding of physiological RNA structures is limited; current in vivo RNA structure profiles include only two of the four nucleotides that make up RNA. Here we present a novel biochemical approach, in vivo click selective 2'-hydroxyl acylation and profiling experiment (icSHAPE), which enables the first global view, to our knowledge, of RNA secondary structures in living cells for all four bases. icSHAPE of the mouse embryonic stem cell transcriptome versus purified RNA folded in vitro shows that the structural dynamics of RNA in the cellular environment distinguish different classes of RNAs and regulatory elements. Structural signatures at translational start sites and ribosome pause sites are conserved from in vitro conditions, suggesting that these RNA elements are programmed by sequence. In contrast, focal structural rearrangements in vivo reveal precise interfaces of RNA with RNA-binding proteins or RNA-modification sites that are consistent with atomic-resolution structural data. Such dynamic structural footprints enable accurate prediction of RNA-protein interactions and N(6)-methyladenosine (m(6)A) modification genome wide. These results open the door for structural genomics of RNA in living cells and reveal key physiological structures controlling gene expression.

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

    DEFF Research Database (Denmark)

    Jensen, Carsten; Aagaard, Per; Overgaard, Søren

    2011-01-01

    the posterior-lateral approach. Prior to surgery no training program was initiated but the patients were encouraged to live as usual. Post surgery all patients were allowed fully weight-bearing and they were instructed to follow a conventional home-based rehabilitation, but were otherwise not engaged in any......-test for between group comparisons while ANOVA was used for repeated measures for comparisons over time (α=0.05)   RESULTS The results were calculated as deficits in percentages of the unaffected side (A-NA/NA)*100)) in order to evaluate degree of asymmetry. Our overall side-to-side deficits for peak torque ranged...... from 32.6 to 0.4% and hip flexion deficit being significantly more impacted then the other muscle groups (32.6%).  At baseline all muscle groups showed a significant torque deficit. At 8 weeks post surgery that asymmetry had increased for 4 out of 6 muscle groups. At 26 weeks the hip adduction and hip...

  16. 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.

  17. An in vivo model for studying the dynamics of intracellular free calcium changes in slow- and fast-twitch muscle fibres.

    Science.gov (United States)

    Bátkai, S; Rácz, I B; Ivanics, T; Tóth, A; Hamar, J; Slaaf, D W; Reneman, R S; Ligeti, L

    1999-10-01

    The understanding of the regulation of the free cytosolic [Ca2+] ([Ca2+]i) in skeletal muscle is hampered by the lack of techniques for quantifying free [Ca2+]i in muscle fibres in situ. We describe a model for studying the dynamics of free [Ca2+]i in the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus (SOL) muscles of the rat in vivo using caffeine superfusion to induce changes in free [Ca2+]i. We assumed that differences in sensitivity between the two muscle types for this substance reflect differences in intracellular Ca2+ handling in the fibres of which these muscles consist. The Indo-1 ratiometric method, using intravital microscopy with incident light, was adapted to measure free [Ca2+]i in vivo. Fluorescence images were collected by means of a digital camera. Caffeine superfusion at 37 degrees C for 2 min, at concentrations of 1, 2, 5, 10 or 20 mmol/l, induced a concentration-dependent increase in free [Ca2+]i and revealed differences in caffeine sensitivity between the muscle types, with the SOL being more sensitive. In a separate set of experiments the contracture threshold, as assessed by topical application of caffeine, was determined in both muscle types. EDL had a higher threshold for developing contracture than SOL. These finding are in agreement with previous in vitro studies. We may conclude that the dynamics of free [Ca2+]i can be assessed reliably in intact mammalian muscle in vivo.

  18. Smad3 induces atrogin-1, inhibits mTOR and protein synthesis, and promotes muscle atrophy in vivo.

    Science.gov (United States)

    Goodman, Craig A; McNally, Rachel M; Hoffmann, F Michael; Hornberger, Troy A

    2013-11-01

    Myostatin, a member of the TGF superfamily, is sufficient to induce skeletal muscle atrophy. Myostatin-induced atrophy is associated with increases in E3-ligase atrogin-1 expression and protein degradation and decreases in Akt/mechanistic target of rapamycin (mTOR) signaling and protein synthesis. Myostatin signaling activates the transcription factor Smad3 (Small Mothers Against Decapentaplegic), which has been shown to be necessary for myostatin-induced atrogin-1 expression and atrophy; however, it is not known whether Smad3 is sufficient to induce these events or whether Smad3 simply plays a permissive role. Thus, the aim of this study was to address these questions with an in vivo model. To accomplish this goal, in vivo transfection of plasmid DNA was used to create transient transgenic mouse skeletal muscles, and our results show for the first time that Smad3 expression is sufficient to stimulate atrogin-1 promoter activity, inhibit Akt/mTOR signaling and protein synthesis, and induce muscle fiber atrophy. Moreover, we propose that Akt/mTOR signaling is inhibited by a Smad3-induced decrease in microRNA-29 (miR-29) expression and a subsequent increase in the translation of phosphatase and tensin homolog (PTEN) mRNA. Smad3 is also sufficient to inhibit peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) promoter activity and to increase FoxO (Forkhead Box Protein, Subclass O)-mediated signaling and the promoter activity of plasminogen activator inhibitor 1 (PAI-1). Combined, this study provides the first evidence that Smad3 is sufficient to regulate many of the events associated with myostatin-induced atrophy and therefore suggests that Smad3 signaling may be a viable target for therapies aimed at preventing myostatin-induced muscle atrophy.

  19. Insulin and GH signaling in human skeletal muscle in vivo following exogenous GH exposure: impact of an oral glucose load.

    Directory of Open Access Journals (Sweden)

    Thomas Krusenstjerna-Hafstrøm

    2011-05-01

    Full Text Available GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load.Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1 after an intravenous GH bolus 2 after an intravenous GH bolus plus an oral glucose load (OGTT, and 3 after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA.GH increased AUC(glucose after an OGTT (p<0.05 without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473 and thr(308, and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1 A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2 Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3 The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH.ClinicalTrials.gov NCT00477997.

  20. Study of Statin- and Loratadine-Induced Muscle Pain Mechanisms Using Human Skeletal Muscle Cells

    OpenAIRE

    Yat Hei Leung; Jacques Turgeon; Veronique Michaud

    2017-01-01

    Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs) may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4). The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lact...

  1. Gamma-sarcoglycan is required for the response of archvillin to mechanical stimulation in skeletal muscle

    Science.gov (United States)

    Spinazzola, Janelle M.; Smith, Tara C.; Liu, Min; Luna, Elizabeth J.; Barton, Elisabeth R.

    2015-01-01

    Loss of gamma-sarcoglycan (γ-SG) induces muscle degeneration and signaling defects in response to mechanical load, and its absence is common to both Duchenne and limb girdle muscular dystrophies. Growing evidence suggests that aberrant signaling contributes to the disease pathology; however, the mechanisms of γ-SG-mediated mechanical signaling are poorly understood. To uncover γ-SG signaling pathway components, we performed yeast two-hybrid screens and identified the muscle-specific protein archvillin as a γ-SG and dystrophin interacting protein. Archvillin protein and message levels were significantly upregulated at the sarcolemma of murine γ-SG-null (gsg−/−) muscle but delocalized in dystrophin-deficient mdx muscle. Similar elevation of archvillin protein was observed in human quadriceps muscle lacking γ-SG. Reintroduction of γ-SG in gsg−/− muscle by rAAV injection restored archvillin levels to that of control C57 muscle. In situ eccentric contraction of tibialis anterior (TA) muscles from C57 mice caused ERK1/2 phosphorylation, nuclear activation of P-ERK1/2 and stimulus-dependent archvillin association with P-ERK1/2. In contrast, TA muscles from gsg−/− and mdx mice exhibited heightened P-ERK1/2 and increased nuclear P-ERK1/2 localization following eccentric contractions, but the archvillin–P-ERK1/2 association was completely ablated. These results position archvillin as a mechanically sensitive component of the dystrophin complex and demonstrate that signaling defects caused by loss of γ-SG occur both at the sarcolemma and in the nucleus. PMID:25605665

  2. 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.

  3. 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.

  4. 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.

  5. Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients.

    Science.gov (United States)

    Weijs, Peter J M; Looijaard, Wilhelmus G P M; Dekker, Ingeborg M; Stapel, Sandra N; Girbes, Armand R; Oudemans-van Straaten, H M; Beishuizen, Albertus

    2014-01-13

    Higher body mass index (BMI) is associated with lower mortality in mechanically ventilated critically ill patients. However, it is yet unclear which body component is responsible for this relationship. This retrospective analysis in 240 mechanically ventilated critically ill patients included adult patients in whom a computed tomography (CT) scan of the abdomen was made on clinical indication between 1 day before and 4 days after admission to the intensive care unit. CT scans were analyzed at the L3 level for skeletal muscle area, expressed as square centimeters. Cutoff values were defined by receiver operating characteristic (ROC) curve analysis: 110 cm2 for females and 170 cm2 for males. Backward stepwise regression analysis was used to evaluate low-muscle area in relation to hospital mortality, with low-muscle area, sex, BMI, Acute Physiologic and Chronic Health Evaluation (APACHE) II score, and diagnosis category as independent variables. This study included 240 patients, 94 female and 146 male patients. Mean age was 57 years; mean BMI, 25.6 kg/m2. Muscle area for females was significantly lower than that for males (102 ± 23 cm2 versus 158 ± 33 cm2; P muscle area was observed in 63% of patients for both females and males. Mortality was 29%, significantly higher in females than in males (37% versus 23%; P = 0.028). Low-muscle area was associated with higher mortality compared with normal-muscle area in females (47.5% versus 20%; P = 0.008) and in males (32.3% versus 7.5%; P muscle area, sex, and APACHE II score, whereas BMI and admission diagnosis were not. Odds ratio for low-muscle area was 4.3 (95% confidence interval, 2.0 to 9.0, P muscle mass appeared as primary predictor, not sex. Low skeletal muscle area, as assessed by CT scan during the early stage of critical illness, is a risk factor for mortality in mechanically ventilated critically ill patients, independent of sex and APACHE II score. Further analysis suggests muscle mass as primary predictor, not

  6. Thick filament mechano-sensing is a calcium-independent regulatory mechanism in skeletal muscle.

    Science.gov (United States)

    Fusi, L; Brunello, E; Yan, Z; Irving, M

    2016-10-31

    Recent X-ray diffraction studies on actively contracting fibres from skeletal muscle showed that the number of myosin motors available to interact with actin-containing thin filaments is controlled by the stress in the myosin-containing thick filaments. Those results suggested that thick filament mechano-sensing might constitute a novel regulatory mechanism in striated muscles that acts independently of the well-known thin filament-mediated calcium signalling pathway. Here we test that hypothesis using probes attached to the myosin regulatory light chain in demembranated muscle fibres. We show that both the extent and kinetics of thick filament activation depend on thick filament stress but are independent of intracellular calcium concentration in the physiological range. These results establish direct control of myosin motors by thick filament mechano-sensing as a general regulatory mechanism in skeletal muscle that is independent of the canonical calcium signalling pathway.

  7. An in vivo analysis of facial muscle change treated with botulinum toxin type A using digital image speckle correlation

    Science.gov (United States)

    Xu, Yan; Palmaccio, Samantha Palmaccio; Bui, Duc; Dagum, Alexander; Rafailovich, Miriam

    Been famous for clinical use from early 1980s, the neuromuscular blocking agent Botulinum toxin type A (BTX-A), has been used to reduce wrinkles for a long time. Only little research has been done to quantify the change of muscle contraction before and after injection and most research paper depend on subjective evaluation from both patients and surgeons. In our research, Digital Image Speckle Correlation (DISC) was employed to study the mechanical properties of skin, contraction mode of muscles (injected) and reaction of neighbor muscle group (un-injected).At the same time, displacement patterns (vector maps)generated by DISC can predict injection locus for surgeons who normally handle it depending only on visual observation.

  8. Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

    Directory of Open Access Journals (Sweden)

    Ferdinandus

    Full Text Available This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing. A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects.

  9. Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

    Science.gov (United States)

    Ferdinandus; Arai, Satoshi; Ishiwata, Shin'ichi; Suzuki, Madoka; Sato, Hirotaka

    2015-01-01

    This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects.

  10. Study of Statin- and Loratadine-Induced Muscle Pain Mechanisms Using Human Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Yat Hei Leung

    2017-10-01

    Full Text Available Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4. The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lactone forms, rosuvastatin, and loratadine on l-lactic acid transport using primary human skeletal muscle cells (SkMC. Loratadine (IC50 31 and 15 µM and atorvastatin (IC50 ~130 and 210 µM demonstrated the greatest potency for inhibition of l-lactic acid efflux at pH 7.0 and 7.4, respectively (~2.5-fold l-lactic acid intracellular accumulation. Simvastatin acid exhibited weak inhibitory potency on l-lactic acid efflux with an intracellular lactic acid increase of 25–35%. No l-lactic acid efflux inhibition was observed for simvastatin lactone or rosuvastatin. Pretreatment studies showed no change in inhibitory potential and did not affect lactic acid transport for all tested drugs. In conclusion, we have demonstrated that loratadine and atorvastatin can inhibit the efflux transport of l-lactic acid in SkMC. Inhibition of l-lactic acid efflux may cause an accumulation of intracellular l-lactic acid leading to the reported drug-induced myotoxicity.

  11. Noggin inactivation affects the number and differentiation potential of muscle progenitor cells in vivo

    Science.gov (United States)

    Costamagna, Domiziana; Mommaerts, Hendrik; Sampaolesi, Maurilio; Tylzanowski, Przemko

    2016-01-01

    Inactivation of Noggin, a secreted antagonist of Bone Morphogenetic Proteins (BMPs), in mice leads, among others, to severe malformations of the appendicular skeleton and defective skeletal muscle fibers. To determine the molecular basis of the phenotype, we carried out a histomorphological and molecular analysis of developing muscles Noggin−/− mice. We show that in 18.5 dpc embryos there is a marked reduction in muscle fiber size and a failure of nuclei migration towards the cell membrane. Molecularly, the absence of Noggin results in an increased BMP signaling in muscle tissue as shown by the increase in SMAD1/5/8 phosphorylation, concomitant with the induction of BMP target genes such as Id1, 2, 3 as well as Msx1. Finally, upon removal of Noggin, the number of mesenchymal Pax7+ muscle precursor cells is reduced and they are more prone to differentiate into adipocytes in vitro. Thus, our results highlight the importance of Noggin/BMP balance for myogenic commitment of early fetal progenitor cells. PMID:27573479

  12. Tissue elasticity of in vivo skeletal muscles measured in the transverse and longitudinal planes using shear wave elastography.

    Science.gov (United States)

    Chino, Kentaro; Kawakami, Yasuo; Takahashi, Hideyuki

    2017-07-01

    The aim of the present study was to measure in vivo skeletal muscle elasticity in the transverse and longitudinal planes using shear wave elastography and then to compare the image stability, measurement values and measurement repeatability between these imaging planes. Thirty-one healthy males participated in this study. Tissue elasticity (shear wave velocity) of the medial gastrocnemius, rectus femoris, biceps brachii and rectus abdominis was measured in both the transverse and longitudinal planes using shear wave elastography. Image stability was evaluated by the standard deviation of the colour distribution in the shear wave elastography image. Measurement repeatability was assessed by the coefficient of variance obtained from three measurement values. Image stability of all tested muscles was significantly higher in the longitudinal plane (Pplanes (P>0·05), except in the biceps brachii (P = 0·001). Measurement values of the medial gastrocnemius, rectus femoris and biceps brachii were significantly different between the imaging planes (Pplane, which indicates that imaging plane should be considered when measuring skeletal muscle tissue elasticity by shear wave elastography. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  13. Influence of the contractile properties of muscle on motor unit firing rates during a moderate-intensity contraction in vivo.

    Science.gov (United States)

    Trevino, Michael A; Herda, Trent J; Fry, Andrew C; Gallagher, Philip M; Vardiman, John P; Mosier, Eric M; Miller, Jonathan D

    2016-08-01

    It is suggested that firing rate characteristics of motor units (MUs) are influenced by the physical properties of the muscle. However, no study has correlated MU firing rates at recruitment, targeted force, or derecruitment with the contractile properties of the muscle in vivo. Twelve participants (age = 20.67 ± 2.35 yr) performed a 40% isometric maximal voluntary contraction of the leg extensors that included linearly increasing, steady force, and decreasing segments. Muscle biopsies were collected with myosin heavy chain (MHC) content quantified, and surface electromyography (EMG) was recorded from the vastus lateralis. The EMG signal was decomposed into the firing events of single MUs. Slopes and y-intercepts were calculated for 1) firing rates at recruitment vs. recruitment threshold, 2) mean firing rates at steady force vs. recruitment threshold, and 3) firing rates at derecruitment vs. derecruitment threshold relationships for each subject. Correlations among type I %MHC isoform content and the slopes and y-intercepts from the three relationships were examined. Type I %MHC isoform content was correlated with MU firing rates at recruitment (y-intercepts: r = -0.577; slopes: r = 0.741) and targeted force (slopes: r = 0.853) vs. recruitment threshold and MU firing rates at derecruitment (y-intercept: r = -0.597; slopes: r = 0.701) vs. derecruitment threshold relationships. However, the majority of the individual MU firing rates vs. recruitment and derecruitment relationships were not significant (P > 0.05) and, thus, revealed no systematic pattern. In contrast, MU firing rates during the steady force demonstrated a systematic pattern with higher firing rates for the lower- than higher-threshold MUs and were correlated with the physical properties of MUs in vivo. Copyright © 2016 the American Physiological Society.

  14. 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.

  15. SPARC Interacts with Actin in Skeletal Muscle in Vitro and in Vivo

    DEFF Research Database (Denmark)

    Jørgensen, Louise H; Jepsen, Pia Lørup; Boysen, Anders

    2017-01-01

    to actin. This interaction is present in regenerating myofibers of patients with Duchenne muscular dystrophy, polymyositis, and compartment syndrome. Analysis of the α-, β-, and γ-actin isoforms in SPARC knockout myoblasts reveals a changed expression pattern with dominance of γ-actin. In SPARC knockout......The cytoskeleton is an integral part of skeletal muscle structure, and reorganization of the cytoskeleton occurs during various modes of remodeling. We previously found that the extracellular matrix protein secreted protein acidic and rich in cysteine (SPARC) is up-regulated and expressed...... intracellularly in developing muscle, during regeneration and in myopathies, which together suggests that SPARC might serve a specific role within muscle cells. Using co-immunoprecipitation combined with mass spectrometry and verified by staining for direct protein-protein interaction, we find that SPARC binds...

  16. In vivo 31P-NMR studies on the energy metabolism of atrophic muscles in rate

    International Nuclear Information System (INIS)

    Yamagiwa, Tetsuo

    1988-01-01

    Using P-31 NMR spectra, energy metabolism in the rat calf muscle was examined. The body weight in the atrophy and control groups did not differ significantly. Both the wet weight and dry weight of the calf muscle were significantly lower in the atrophy group than the control group. The muscle weight relative to the body weight was significantly lower in the atrophy group as well than the control group. There was no significant difference in the P-31 NMR spectral pattern before tourniquet ischemia between the atrophy and control groups. Rapid decrease in phosphocreatine (PCr) and rapid increase in inorganic phosphate (Pi) were observed in both groups immediately after application of the tourniquet; however, the rates of these changes were slightly greater and the PCr/Pi ratio in the peak values was significantly smaller in the atrophy group than the control group. The pH value before the ischemia was 7.15 ± 0.02 for the control group and 7.16 ± 0.02 for the atrophy group, with no significant difference between the groups. During ischemia, the pH value decreased progressively in the two groups; however, it became significantly decreased in the atrophy group from 10 to 60 min after application of tourniquet. The decrease in pH became gradual 60 min later. Since the decrease in pH was more rapid in the atrophic muscle than the intact muscle, this buffering capacity seems to be reduced in the atrophic muscle. (N.K.)

  17. 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.

  18. Molecular Mechanisms for Age-Associated Mitochondrial Deficiency in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Akira Wagatsuma

    2012-01-01

    Full Text Available The abundance, morphology, and functional properties of mitochondria decay in skeletal muscle during the process of ageing. Although the precise mechanisms remain to be elucidated, these mechanisms include decreased mitochondrial DNA (mtDNA repair and mitochondrial biogenesis. Mitochondria possess their own protection system to repair mtDNA damage, which leads to defects of mtDNA-encoded gene expression and respiratory chain complex enzymes. However, mtDNA mutations have shown to be accumulated with age in skeletal muscle. When damaged mitochondria are eliminated by autophagy, mitochondrial biogenesis plays an important role in sustaining energy production and physiological homeostasis. The capacity for mitochondrial biogenesis has shown to decrease with age in skeletal muscle, contributing to progressive mitochondrial deficiency. Understanding how these endogenous systems adapt to altered physiological conditions during the process of ageing will provide a valuable insight into the underlying mechanisms that regulate cellular homeostasis. Here we will summarize the current knowledge about the molecular mechanisms responsible for age-associated mitochondrial deficiency in skeletal muscle. In particular, recent findings on the role of mtDNA repair and mitochondrial biogenesis in maintaining mitochondrial functionality in aged skeletal muscle will be highlighted.

  19. 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.

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

    DEFF Research Database (Denmark)

    Mackey, Abigail L.; Kjaer, Michael

    2017-01-01

    and highlights the importance of the basement membrane in the process of regeneration. In addition, it provides insight into parallels between the regeneration of adult skeletal muscle in mouse and man, confirming that this model may be a useful tool in investigating myofibre and matrix formation, as well...

  1. Improvement of in vivo transfer of plasmid DNA in muscle : Comparison of electroporation versus ultrasound

    NARCIS (Netherlands)

    Kusumanto, Yoka H.; Mulder, Nanno H.; Dam, Wendy A.; Losen, Mario H.; Meijer, Coby; Hospers, Geke A. P.

    Plasmid-based gene delivery to muscle is a treatment strategy for many diseases with potential advantages above viral-based gene delivery methods, however, with a relative low transfection efficiency. We compared two physical methods-electroporation and ultrasound-that facilitate DNA uptake into

  2. 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

    Changes in contractile rate of force development (RFD), measured within a short time interval from contraction initiation, were measured after a period of strength training that led to increases in muscle fascicle length but no measurable change in neuromuscular activity. The relationship between...

  3. 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.

  4. 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.

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

    International Nuclear Information System (INIS)

    Kowalski, Greg M.; De Souza, David P.; Burch, Micah L.; Hamley, Steven; Kloehn, Joachim; Selathurai, Ahrathy; Tull, Dedreia; O'Callaghan, Sean; McConville, Malcolm J.; Bruce, Clinton R.

    2015-01-01

    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- 13 C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring 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

  6. 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.

  7. 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.

  8. Mechanisms of lumen formation during sprouting angiogenesis in vivo

    OpenAIRE

    Gebala, V. M.

    2016-01-01

    During development, vascular networks expand following a process known as sprouting angiogenesis. New vascular branches arise from pre-existing vessels through the coordinated migration and proliferation of endothelial cells, and eventually connect to form new vascular loops. The functionality of these new vessel segments is dependent on the opening of a central lumen to allow perfusion. While mechanisms of lumen formation during the establishment of the primary vasculature by vasculogenesis ...

  9. 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.

  10. 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.

  11. [Influence of the occlusal interference time on masticatory muscle mechanical hyperalgesia in rats].

    Science.gov (United States)

    Liu, Cun-rui; Xu, Xiao-xiang; Cao, Ye; Xie, Qiu-fei

    2016-02-18

    To investigate the relationship between the removal time of 0.2 mm occlusal interference and the recovery of masticatory muscle mechanical hyperalgesia in rats. Forty male Sprague-Dawley rats (200-220 g) were randomly assigned to eight groups, with five rats in each group: (1) naive group: these rats were anesthetized and their mouths were forced open for about 5 min (the same duration as the other groups), but restorations were not applied; (2) sham-occlusal interference control group: bands were bonded to the right maxillary first molars which did not interfere with occlusion; (3)occlusal interference group: 0.2 mm thick crowns were bonded to the right maxillary first molars; (4) 2, 3, 4, 5, and 6 d removal of occlusal interference groups: 0.2 mm thick crowns were bonded to the right maxillary first molars and removed on days 2, 3, 4, 5, and 6. The naive group and sham-occlusal interference control group were control groups. The other groups were experimental groups. Bilateral masticatory muscle mechanical withdrawal thresholds were tested on pre-application days 1, 2, and 3, and on post-application days 1, 3, 5, 7, 10, 14, 21 and 28. The rats were weighed on pre-application day 1 and on post-application days 1, 2, 3, 4, 5, 6, and 7. Between the naive group and the sham-occlusal interference control group, there was no significant difference in the masticatory muscle mechanical withdrawal threshold of bilateral temporalis and masseters at each time point. No significant difference was detected between the contralateral side and ipsilateral side in experimental groups (P>0.05). In the 2, 3, 4, and 5 d removal of occlusal interference groups, the masticatory muscle mechanical withdrawal thresholds decreased after occlusal interference and increased after removal of the crowns and recovered to the baseline on days 7, 10, 14, and 14, respectively [the masticatory muscle mechanical withdrawal thresholds of right masseter muscle were (137.46 ± 2.08) g, (139.02 ± 2

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

    DEFF Research Database (Denmark)

    Hvid, L G; Suetta, C; Nielsen, J H

    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...... the effect of 4 days of lower limb disuse followed by 7 days of active recovery on mechanical muscle function of the knee extensors in young (24.3±0.9 years, n=11) and old (67.2±1.0 years, n=11) recreationally active healthy males. Slow and moderate dynamic muscle strength were assessed using isokinetic...... to disuse, marked age-related differences (p

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

    Directory of Open Access Journals (Sweden)

    Amin Mokhtari-Zaer

    2015-08-01

    Full Text Available 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.

  14. Possible mechanisms underlying slow component of V̇O2 on-kinetics in skeletal muscle.

    Science.gov (United States)

    Korzeniewski, Bernard; Zoladz, Jerzy A

    2015-05-15

    A computer model of a skeletal muscle bioenergetic system is used to study the background of the slow component of oxygen consumption V̇O2 on-kinetics in skeletal muscle. Two possible mechanisms are analyzed: inhibition of ATP production by anaerobic glycolysis by progressive cytosol acidification (together with a slow decrease in ATP supply by creatine kinase) and gradual increase of ATP usage during exercise of constant power output. It is demonstrated that the former novel mechanism is potent to generate the slow component. The latter mechanism further increases the size of the slow component; it also moderately decreases metabolite stability and has a small impact on muscle pH. An increase in anaerobic glycolysis intensity increases the slow component, elevates cytosol acidification during exercise, and decreases phosphocreatine and Pi stability, although slightly increases ADP stability. A decrease in the P/O ratio (ATP molecules/O2 molecules) during exercise cannot also be excluded as a relevant mechanism, although this issue requires further study. It is postulated that both the progressive inhibition of anaerobic glycolysis by accumulating protons (together with a slow decrease of the net creatine kinase reaction rate) and gradual increase of ATP usage during exercise, and perhaps a decrease in P/O, contribute to the generation of the slow component of the V̇O2 on-kinetics in skeletal muscle. Copyright © 2015 the American Physiological Society.

  15. Mechanisms of pollution-induced airway disease: in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Peden, D.B. [Univ. of North Carolina School of Medicine, Center for Environmental Medicine and Lung Biology, North Carolina (United States)

    1997-12-31

    Several studies have investigated the effects of ozone, sulphur dioxide (SO{sub 2}), and nitrogen dioxide (NO{sub 2}) on lung function in normal and asthmatic subjects. Decreased lung function has been observed with ozone levels as low as 0.15 ppm - this effect is concentration dependent and is exacerbated by exercise. A number of lines of evidence suggest that the effect on lung function is mediated, at lest in part, by neural mechanisms. In both normals and asthmatics, ozone has been shown to induce neutrophilic inflammation, with increased levels of several inflammatory mediators, including prostaglandin E{sub 2}. However, in normal subjects, none of the markers of inflammation correlate with changes in lung function. The lung function changes in asthmatics may be associated with inflammatory effects; alternatively, ozone may prime the airways for an increased response to subsequently inhaled allergen. Indeed, an influx of both polymorphonucleocytes and eosinophils has been observed in asthmatic patients after ozone exposure. It has been suggested that the effect of ozone on classic allergen-induced bronchoconstriction may be more significant than any direct effect of this pollutant in asthmatics. SO{sub 2} does not appear to affect lung function in normal subjects, but may induce bronchoconstriction in asthmatics. Nasal breathing, which is often impaired in asthmatics, reduces the pulmonary effects of SO{sub 2}, since this water-soluble gas is absorbed by the nasal mucosa. NO{sub 2} may also influence lung function in asthmatics, but further research is warranted. SO{sub 2} and NO{sub 2} alone do not seem to have a priming effect in asthmatics, but a combination of these two gases has resulted in a heightened sensitivity to subsequently inhaled allergen. (au)

  16. Mutagenic and DNA damaging activity in muscle of trout exposed in vivo to nitrite

    Energy Technology Data Exchange (ETDEWEB)

    De Flora, S; Arillo, A

    1983-09-01

    Muscle ether extracts of rainbow trout (Salmo gairdneri) exposed to lake water enriched with nitrite (450 micrograms/l) reverted plasmid-containing his- strains of Salmonella typhimurium, mainly eliciting frameshift mutations, and induced a DNA damage in Escherichia coli reparable through the recA/lexA-dependent SOS functions. The number of revertants was related to their content in nitroso-derivatives and to the physiological condition of the fish. Mutagenicity was efficiently decreased, through NADPH-requiring pathways, by liver S-9 fractions from rats or rainbow trout, while it was not affected by preliminary heating nor by pre-incubation with human gastric juice.

  17. Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study

    DEFF Research Database (Denmark)

    Kupers, Rron; Svensson, Peter; Jensen, Troels Staehlin

    2004-01-01

    Functional neuroimaging studies of the human brain have revealed a network of brain regions involved in the processing of nociceptive information. However, little is known of the cerebral processing of pain originating from muscles. The aim of this study was to investigate the cerebral activation...... pattern evoked by experimental jaw-muscle pain and its interference by simultaneous mechanical stimuli, which has been shown to evoke hyperesthesia. Ten healthy subjects participated in a PET study and jaw-muscle pain was induced by bolus injections of 5% hypertonic saline into the right masseter muscle....... Repeated von Frey hair stimulation (0.5 Hz) of the skin above the masseter muscle was used as the mechanical stimulus. Hypertonic saline injections caused strong muscle pain spreading to adjacent areas. von Frey stimulation was rated as non-painful but produced hyperesthesia during jaw-muscle pain. Jaw...

  18. 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

  19. 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.

  20. 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.

  1. Muscle and neural isoforms of agrin increase utrophin expression in cultured myotubes via a transcriptional regulatory mechanism.

    Science.gov (United States)

    Gramolini, A O; Burton, E A; Tinsley, J M; Ferns, M J; Cartaud, A; Cartaud, J; Davies, K E; Lunde, J A; Jasmin, B J

    1998-01-09

    . Furthermore, this increase in transcriptional activity in response to agrin resulted from a greater number of myonuclei expressing the 1.3-kilobase pair utrophin promoter-nlsLacZ construct. Deletion of 800 base pairs 5' from this fragment decreased the basal levels of nlsLacZ expression and abolished the sensitivity of the utrophin promoter to exogenously applied agrin. In addition, site-directed mutagenesis of an N-box motif contained within this 800-base pair fragment demonstrated its essential contribution in this regulatory mechanism. Finally, direct gene transfer studies performed in vivo further revealed the importance of this DNA element for the synapse-specific expression of the utrophin gene along multinucleated muscle fibers. These data show that both muscle and neural isoforms of agrin can regulate expression of the utrophin gene and further indicate that agrin is not only involved in the mechanisms leading to the formation of clusters containing presynthesized synaptic molecules but that it can also participate in the local regulation of genes encoding synaptic proteins. Together, these observations are therefore relevant for our basic understanding of the events involved in the assembly and maintenance of the postsynaptic membrane domain of the neuromuscular junction and for the potential use of utrophin as a therapeutic strategy to counteract the effects of Duchenne muscular dystrophy.

  2. 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.

  3. Inflammatory Mechanisms Associated with Skeletal Muscle Sequelae after Stroke: Role of Physical Exercise

    Science.gov (United States)

    Coelho Junior, Hélio José; Gambassi, Bruno Bavaresco; Diniz, Tiego Aparecido; Fernandes, Isabela Maia da Cruz; Caperuto, Érico Chagas; Uchida, Marco Carlos; Lira, Fabio Santos

    2016-01-01

    Inflammatory markers are increased systematically and locally (e.g., skeletal muscle) in stroke patients. Besides being associated with cardiovascular risk factors, proinflammatory cytokines seem to play a key role in muscle atrophy by regulating the pathways involved in this condition. As such, they may cause severe decrease in muscle strength and power, as well as impairment in cardiorespiratory fitness. On the other hand, physical exercise (PE) has been widely suggested as a powerful tool for treating stroke patients, since PE is able to regenerate, even if partially, physical and cognitive functions. However, the mechanisms underlying the beneficial effects of physical exercise in poststroke patients remain poorly understood. Thus, in this study we analyze the candidate mechanisms associated with muscle atrophy in stroke patients, as well as the modulatory effect of inflammation in this condition. Later, we suggest the two strongest anti-inflammatory candidate mechanisms, myokines and the cholinergic anti-inflammatory pathway, which may be activated by physical exercise and may contribute to a decrease in proinflammatory markers of poststroke patients. PMID:27647951

  4. Ex Vivo Gene Therapy Using Human Mesenchymal Stem Cells to Deliver Growth Factors in the Skeletal Muscle of a Familial ALS Rat Model.

    Science.gov (United States)

    Suzuki, Masatoshi; Svendsen, Clive N

    2016-01-01

    Therapeutic protein and molecule delivery to target sites by transplanted human stem cells holds great promise for ex vivo gene therapy. Our group has demonstrated the therapeutic benefits of ex vivo gene therapy targeting the skeletal muscles in a transgenic rat model of familial amyotrophic lateral sclerosis (ALS). We used human mesenchymal stem cells (hMSCs) and genetically modified them to release neuroprotective growth factors such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF). Intramuscular growth factor delivery via hMSCs can enhance neuromuscular innervation and motor neuron survival in a rat model of ALS (SOD1(G93A) transgenic rats). Here, we describe the protocol of ex vivo delivery of growth factors via lentiviral vector-mediated genetic modification of hMSCs and hMSC transplantation into the skeletal muscle of a familial ALS rat model.

  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

    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......, variably compliant joint motions can be produced without mechanically bulky and complex mechanisms or complex force/toque sensing at each joint. Moreover, through tuning the damping coefficient of the VAAM, the functions of the VAAM are comparable to biological muscles. Originality/value – The model (i.......e., VAAM) provides a way forward to emulate muscle-like functions that are comparable to those found in physiological experiments of biological muscles. Based on these muscle-like functions, the robotic joints can easily achieve variable compliance that does not require complex physical components...

  6. 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.

  7. [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.

  8. Differences in feedforward trunk muscle activity in subgroups of patients with mechanical low back pain.

    Science.gov (United States)

    Silfies, Sheri P; Mehta, Rupal; Smith, Sue S; Karduna, Andrew R

    2009-07-01

    To investigate alterations in trunk muscle timing patterns in subgroups of patients with mechanical low back pain (MLBP). Our hypothesis was that subjects with MLBP would demonstrate delayed muscle onset and have fewer muscles functioning in a feedforward manner than the control group. We further hypothesized that we would find differences between subgroups of our patients with MLBP, grouped according to diagnosis (segmental instability and noninstability). Case-control. Laboratory. Forty-three patients with chronic MLBP (25 instability, 18 noninstability) and 39 asymptomatic controls. Not applicable. Surface electromyography was used to measure onset time of 10 trunk muscles during a self-perturbation task. Trunk muscle onset latency relative to the anterior deltoid was calculated and the number of muscles functioning in feedforward determined. Activation timing patterns (Pfeedforward (P=.02; eta=.30; 1-beta=.83) were statistically different between patients with MLBP and controls. The control group activated the external oblique, lumbar multifidus, and erector spinae muscles in a feedforward manner. The heterogeneous MLBP group did not activate the trunk musculature in feedforward, but responded with significantly delayed activations. MLBP subgroups demonstrated significantly different timing patterns. The noninstability MLBP subgroup activated trunk extensors in a feedforward manner, similar to the control group, but significantly earlier than the instability subgroup. Lack of feedforward activation of selected trunk musculature in patients with MLBP may result in a period of inefficient muscular stabilization. Activation timing was more impaired in the instability than the noninstability MLBP subgroup. Training specifically for recruitment timing may be an important component of the rehabilitation program.

  9. On Using Model Populations to Determine Mechanical Properties of Skeletal Muscle. Application to Concentric Contraction Simulation.

    Science.gov (United States)

    Sierra, M; Miana-Mena, F J; Calvo, B; Muñoz, M J; Rodríguez, J F; Grasa, J

    2015-10-01

    In the field of computational biomechanics, the experimental evaluation of the material properties is crucial for the development of computational models that closely reproduce real organ systems. When simulations of muscle tissue are concerned, stress/strain relations for both passive and active behavior are required. These experimental relations usually exhibit certain variability. In this study, a set of material parameters involved in a 3D skeletal muscle model are determined by using a system biology approach in which the parameters are randomly varied leading to a population of models. Using a set of experimental results from an animal model, a subset of the entire population of models was selected. This reduced population predicted the mechanical response within the window of experimental observations. Hence, a range of model parameters, instead of a single set of them, was determined. Rat Tibialis Anterior muscle was selected for this study. Muscles ([Formula: see text]) were activated through the sciatic nerve and during contraction the tissue pulled a weight fixed to the distal tendon (concentric contraction). Three different weights 1, 2 and 3 N were used and the time course of muscle stretch was analyzed obtaining values of (mean [Formula: see text] standard deviation): [Formula: see text], [Formula: see text] and [Formula: see text] respectively. A paired two-sided sign rank test showed significant differences between the muscle response for the three weights ([Formula: see text]). This study shows that the Monte Carlo method could be used for determine muscle characteristic parameters considering the variability of the experimental population.

  10. Dynamic mechanical assessment of muscle hyperalgesia in humans: The dynamic algometer

    Science.gov (United States)

    Finocchietti, Sara; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars

    2015-01-01

    BACKGROUND: Musculoskeletal pain is often associated with a nonhomogeneous distribution of mechanical hyperalgesia. Consequently, new methods able to detect this distribution are needed. OBJECTIVE: To develop and test a new method for assessing muscle hyperalgesia with high temporal and spatial resolution that provides complementary information compared with information obtained by traditional static pressure algometry. METHODS: The dynamic pressure algometer was tested bilaterally on the tibialis anterior muscle in 15 healthy subjects and compared with static pressure algometry. The device consisted of a wheel that was rolled over the muscle tissue with a fixed velocity and different predefined forces. The pain threshold force was determined and pain intensity to a fixed-force stimulation was continuously rated on a visual analogue scale while the wheel was rolling over the muscle. The pressure pain sensitivity was evaluated before, during, and after muscle pain and hyperalgesia induced unilaterally by either injection of hypertonic saline (0.5 mL, 6%) into the tibialis anterior or eccentric exercise evoking delayed-onset muscle soreness (DOMS). RESULTS: The intraclass correlation coefficient was >0.88 for the dynamic thresholds; thus, the method was reliable. Compared with baseline, both techniques detected hyperalgesia at the saline injection site and during DOMS (Palgometer also detected the widespread, patchy distribution of sensitive loci during DOMS, which was difficult to evaluate using static pressure algometry. DISCUSSION AND CONCLUSION: The present study showed that dynamic pressure algometry is a reliable tool for evaluating muscle hyperalgesia (threshold and pain rating) with high temporal and spatial resolution. It can be applied as a simple clinical bed-side test and as a quantitative tool in pharmacological profiling studies. PMID:25664539

  11. Intramuscular Connective Tissue Differences in Spastic and Control Muscle: A Mechanical and Histological Study

    Science.gov (United States)

    de Bruin, Marije; Smeulders, Mark J.; Kreulen, Michiel; Huijing, Peter A.; Jaspers, Richard T

    2014-01-01

    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. PMID:24977410

  12. Correlation between Mechanical Properties of the Ankle Muscles and Postural Sway during the Menstrual Cycle.

    Science.gov (United States)

    Yim, JongEun; Petrofsky, Jerrold; Lee, Haneul

    2018-03-01

    Ankle and foot injuries are common among athletes and physically active individuals. The most common residual disability, ankle sprain, is characterized by instability along with postural sway. If the supporting structures around a joint become lax, posture stability and balance are also affected. Previous studies have examined muscle stiffness and elasticity and postural sway separately; however, the relationship between these factors is yet unknown. It is well known that the levels of sex hormones, especially estrogen, change in women over the phase of the menstrual cycle. Therefore, this study examined the relationship between the mechanical properties of tissue and balance activity using a non-invasive digital palpation device to determine if they undergo any changes over the menstrual cycle in young women. Sixteen young women with regular menstrual cycles completed the study. Tone, stiffness, and elasticity of the ankle muscles (lateral gastrocnemius, peroneus longus, and tibialis anterior) were measured using a non-invasive digital palpation device. Postural sway was recorded while the participants performed balance tasks during ovulation and menstruation. Significantly greater posture sway characteristics and ankle muscle elasticity were found during ovulation than during menstruation; lower tone and stiffness of the ankle muscles were observed at ovulation (p connective tissues. We therefore postulate that estrogen increases joint and muscle laxity and affects posture stability according to the phase of the menstrual cycle.

  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

    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 whet...

  14. 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

  15. MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review.

    Science.gov (United States)

    Trommelen, Jorn; Groen, Bart B L; Hamer, Henrike M; de Groot, Lisette C P G M; van Loon, Luc J C

    2015-07-01

    Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects. From the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50, 000  pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults. © 2015 European Society of Endocrinology.

  16. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

    Science.gov (United States)

    Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

    2016-10-14

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2 fl/fl ) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2 fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist, was significantly enhanced in MLC-Cre:GRK2 fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy*

    Science.gov (United States)

    Woodall, Benjamin P.; Woodall, Meryl C.; Luongo, Timothy S.; Grisanti, Laurel A.; Tilley, Douglas G.; Elrod, John W.; Koch, Walter J.

    2016-01-01

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2fl/fl) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. PMID:27566547

  18. 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

  19. Smooth muscle fatigue due to repeated urinary bladder neurostimulation: an in vivo study.

    Science.gov (United States)

    Bross, S; Schumacher, S; Scheepe, J R; Seif, C; Jünemann, K P; Alken, P

    1999-01-01

    The presented study investigates the influence of different pause lengths between two consecutive stimulations of the S3 roots on intravesical pressure during bladder neurostimulation. In eight male foxhounds (aged 7-18 months), laminectomy and placement of a modified Brindley electrode were performed. In four series with different pause lengths between two consecutive stimulations (1, 3, 5, and 15 min), the maximum intravesical pressure was measured during stimulation. The changes in intravesical pressure were registered in these four series, each series with six stimulations. A 15-min interval elapsed before the commencement of each series. In the series with a pause length of 15 min, the consecutive stimulations did not result in significant changes in maximum intravesical pressure. In the 5-min series, a significant decrease in intravesical pressure was not observed after the third stimulation. In the 3-min series, a significant decrease was seen at almost every stimulation (average decrease of 3.8% per stimulation) and in the 1-min series, a significant decrease was also observed at almost every stimulation (average decrease of 5.9% per stimulation). The results of repeated bladder neurostimulation demonstrate that the maximum intravesical pressure is dependent on the pause length between two consecutive stimulations. The detrusor muscle showed reversible and short-lived signs of fatigue. This implies the importance of a minimum 5-min interval between two subsequent stimulations. A pause length <5 min leads to a falsification of the results and thus to lower validity of the investigation.

  20. Impact of a nickel-reduced stainless steel implant on striated muscle microcirculation: a comparative in vivo study.

    Science.gov (United States)

    Kraft, C N; Burian, B; Perlick, L; Wimmer, M A; Wallny, T; Schmitt, O; Diedrich, O

    2001-12-05

    The impairment of skeletal muscle microcirculation by a biomaterial may have profound consequences. With moderately good physical and corrosion characteristics, implant-quality stainless steel is particularly popular in orthopedic surgery. However, due to the presence of a considerable amount of nickel in the alloy, concern has been voiced in respect to local tissue responses. More recently a stainless steel alloy with a significant reduction of nickel has become commercially available. We, therefore, studied in vivo nutritive perfusion and leukocytic response of striated muscle to this nickel-reduced alloy, and compared these results with those of the materials conventional stainless steel and titanium. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, we could demonstrate that reduction of the nickel quantity in a stainless steel implant has a positive effect on local microvascular parameters. Although the implantation of a conventional stainless steel sample led to a distinct and persistent activation of leukocytes combined with disruption of the microvascular endothelial integrity, marked leukocyte extravasation, and considerable venular dilation, animals with a nickel-reduced stainless steel implant showed only a moderate increase of these parameters, with a clear tendency of recuperation. Titanium implants merely caused a transient increase of leukocyte-endothelial cell interaction within the first 120 min, and no significant change in macromolecular leakage, leukocyte extravasation, or venular diameter. Pending biomechanical and corrosion testing, nickel-reduced stainless steel may be a viable alternative to conventional implant-quality stainless steel for biomedical applications. Concerning tolerance by the local vascular system, titanium currently remains unsurpassed. Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 57: 404-412, 2001

  1. 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

  2. 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

  3. MUSCLEMOTION: A Versatile Open Software Tool to Quantify Cardiomyocyte and Cardiac Muscle Contraction In Vitro and In Vivo.

    Science.gov (United States)

    Sala, Luca; van Meer, Berend J; Tertoolen, Leon G J; Bakkers, Jeroen; Bellin, Milena; Davis, Richard P; Denning, Chris; Dieben, Michel A E; Eschenhagen, Thomas; Giacomelli, Elisa; Grandela, Catarina; Hansen, Arne; Holman, Eduard R; Jongbloed, Monique R M; Kamel, Sarah M; Koopman, Charlotte D; Lachaud, Quentin; Mannhardt, Ingra; Mol, Mervyn P H; Mosqueira, Diogo; Orlova, Valeria V; Passier, Robert; Ribeiro, Marcelo C; Saleem, Umber; Smith, Godfrey L; Burton, Francis L; Mummery, Christine L

    2018-02-02

    There are several methods to measure cardiomyocyte 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 models and laboratories, analysis is time consuming, and only specialist researchers can quantify data. Here, we describe and validate an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes, and pharmacological responses. MUSCLEMOTION allowed rapid and easy measurement of movement from high-speed movies in (1) 1-dimensional in vitro models, such as isolated adult and human pluripotent stem cell-derived cardiomyocytes; (2) 2-dimensional in vitro models, such as beating cardiomyocyte monolayers or small clusters of human pluripotent stem cell-derived cardiomyocytes; (3) 3-dimensional multicellular in vitro or in vivo contractile tissues, such as cardiac "organoids," engineered heart tissues, and zebrafish and human hearts. MUSCLEMOTION was effective under different recording conditions (bright-field microscopy with simultaneous patch-clamp recording, phase contrast microscopy, and traction force microscopy). Outcomes were virtually identical to the current gold standards for contraction measurement, such as optical flow, post deflection, edge-detection systems, or manual analyses. Finally, we used the algorithm to quantify contraction in in vitro and in vivo arrhythmia models and to measure pharmacological responses. Using a single open-source method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell, animal, and human models. © 2017 The Authors.

  4. Spring or string: does tendon elastic action influence wing muscle mechanics in bat flight?

    Science.gov (United States)

    Konow, Nicolai; Cheney, Jorn A; Roberts, Thomas J; Waldman, J Rhea S; Swartz, Sharon M

    2015-10-07

    Tendon springs influence locomotor movements in many terrestrial animals, but their roles in locomotion through fluids as well as in small-bodied mammals are less clear. We measured muscle, tendon and joint mechanics in an elbow extensor of a small fruit bat during ascending flight. At the end of downstroke, the tendon was stretched by elbow flexion as the wing was folded. At the end of upstroke, elastic energy was recovered via tendon recoil and extended the elbow, contributing to unfurling the wing for downstroke. Compared with a hypothetical 'string-like' system lacking series elastic compliance, the tendon spring conferred a 22.5% decrease in muscle fascicle strain magnitude. Our findings demonstrate tendon elastic action in a small flying mammal and expand our understanding of the occurrence and action of series elastic actuator mechanisms in fluid-based locomotion. © 2015 The Author(s).

  5. 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...

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

    International Nuclear Information System (INIS)

    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.

    2012-01-01

    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. -- Highlights: ► Tungsten/nickel/cobalt, tungsten/nickel/iron, and pure tungsten were studied. ► Male Fischer rats implanted with

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

    Energy Technology Data Exchange (ETDEWEB)

    Schuster, B.E. [U.S. Army Research Laboratory, Weapons and Materials Research Directorate, B434 Mulberry Road, Aberdeen Proving Ground, MD 21005-5609 (United States); Roszell, L.E. [U.S. Army Institute of Public Health, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010‐5403 (United States); Murr, L.E.; Ramirez, D.A. [Department of Metallurgical and Materials Engineering, University of Texas, El Paso, TX 79968 (United States); Demaree, J.D. [U.S. Army Research Laboratory, Weapons and Materials Research Directorate, B434 Mulberry Road, Aberdeen Proving Ground, MD 21005-5609 (United States); Klotz, B.R. [Dynamic Science Inc., Aberdeen Proving Ground, MD 21005‐5609 (United States); Rosencrance, A.B.; Dennis, W.E. [U.S. Army Center for Environmental Health Research, Department of Chemistry, Ft. Detrick, MD 21702‐5010 (United States); Bao, W. [SAS Institute, Inc. SAS Campus Drive, Cary, NC 27513 (United States); Perkins, E.J. [U.S. Army Engineer Research and Development Center, 3909 Hall Ferry Road, Vicksburg MS 39180 (United States); Dillman, J.F. [U.S. Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010‐5400 (United States); Bannon, D.I., E-mail: desmond.bannon@us.army.mil [U.S. Army Institute of Public Health, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010‐5403 (United States)

    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. -- Highlights: ► Tungsten/nickel/cobalt, tungsten/nickel/iron, and pure tungsten were studied. ► Male Fischer rats implanted with

  8. 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.

  9. 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.

  10. Entropy as a new measure of mechanical pain sensitivity in the masseter muscle

    DEFF Research Database (Denmark)

    Castrillon, Eduardo; Sato, Hitoshi; Tanosoto, Tomohiro

    ENTROPY AS A NEW MEASURE OF MECHANICAL PAIN SENSITIVITY IN THE MASSETER MUSCLE Author Block: E. E. Castrillon1, H. Sato2,3, T. Tanosoto4, T. Arima4, L. Baad-Hansen1, P. Svensson1, 1Clinical Oral Physiology, Århus Univ., Aarhus, Denmark, 2Dept. of Dentistry & Oral Physiology, Sch. of Med., Keio Un...... injections (Pmechanical pain sensitivity that captures new aspects of spatial characteristics and could therefore complement more classical assessments of TMD pain patients.......ENTROPY AS A NEW MEASURE OF MECHANICAL PAIN SENSITIVITY IN THE MASSETER MUSCLE Author Block: E. E. Castrillon1, H. Sato2,3, T. Tanosoto4, T. Arima4, L. Baad-Hansen1, P. Svensson1, 1Clinical Oral Physiology, Århus Univ., Aarhus, Denmark, 2Dept. of Dentistry & Oral Physiology, Sch. of Med., Keio Univ......., Tokyo, Japan, 3Japan Society for the Promotion of Sci., Tokyo, Japan, 4Dept. of Oral Rehabilitation, Graduate Sch. of Dental Med., Hokkaido Univ., Sapporo, Japan : Aim of Investigation: Manual palpation is a psychophysical technique to evaluate mechanical pain sensitivity in craniofacial muscles...

  11. Mechanism and bias considerations for design of a bi-directional pneumatic artificial muscle actuator

    International Nuclear Information System (INIS)

    Vocke III, Robert D; Wereley, Norman M; Kothera, Curt S

    2014-01-01

    Pneumatic artificial muscles (PAMs), or McKibben actuators, have received considerable attention for robotic manipulators and in aerospace applications due to their similarity to natural muscles. Like natural muscles, PAMs are a purely contractile actuator, so that, in order to produce bi-directional or rotational motion, they must be arranged in an agonist/antagonist pair, which inherently limits the deflection of the system due to the high parasitic stiffness of the antagonistic PAM. This study presents two methods for increasing the performance of an antagonistic PAM system by decreasing the passive parasitic torque, rather than increasing the active torque. The first involves selection of the kinematic mechanism geometry, and the second involves the introduction of bias into the system, both in terms of PAM contraction and passive (antagonistic) PAM pressure. It was found with the proper selection of design parameters, including mechanism geometry, PAM geometry, and bias conditions, that an ideal actuator configuration can be chosen that maximizes deflection for a given arbitrary loading. When comparing a baseline design to an improved design for a simplified case, a nearly 50% increase in maximum deflection was predicted simply by optimizing mechanism geometry and bias contraction. These results were experimentally verified with quasi-static testing that showed a 300% increase in actuator deflection over the baseline design. (paper)

  12. 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.

  13. 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.

  14. 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

  15. Nuclear import mechanism for myocardin family members and their correlation with vascular smooth muscle cell phenotype.

    Science.gov (United States)

    Nakamura, Seiji; Hayashi, Ken'ichiro; Iwasaki, Kazuhiro; Fujioka, Tomoaki; Egusa, Hiroshi; Yatani, Hirofumi; Sobue, Kenji

    2010-11-26

    Myocardin (Mycd), which is essential for the differentiation of the smooth muscle cell lineage, is constitutively located in the nucleus, although its family members, myocardin-related transcription factors A and B (MRTF-A/B), mostly reside in the cytoplasm and translocate to the nucleus in response to Rho signaling. The mechanism for their nuclear import is unclear. Here we investigated the mechanism for the nuclear import of Mycd family members and demonstrated any correlation between such mechanism and the phenotype of vascular smooth muscle cells (VSMCs). In cultured VSMCs, the knockdown of importin β1 inhibited the nuclear import of Mycd and MRTF-A/B. Their NH(2)-terminal basic domain was identified as a binding site for importin α/β1 by in vitro analyses. However, Mycd had a higher affinity for importin α/β1 than did MRTF-A/B, even in the absence of G-actin, and Mycd affinity for importin α1/β1 was stronger than for any other importin α/β1 heterodimers. The binding of Mycd to importin α/β1 was insensitive to G-actin, whereas that of MRTF-A/B was differently inhibited by G-actin. In dedifferentiated VSMCs, the levels of importins α1 and β1 were reduced concomitant with down-regulation of Mycd, serum response factor, and smooth muscle cell markers. By contrast, in differentiated VSMCs, their expressions were up-regulated. Thus, the nuclear import of Mycd family members in VSMCs depends on importin α/β1, and their relative affinities for importin α/β1 heterodimers determine Mycd nuclear import. The expression of Mycd nuclear import machineries is related to the expression levels of VSMC phenotype-dependent smooth muscle cell markers.

  16. 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.

  17. 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

    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.

  18. Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling.

    Science.gov (United States)

    Verheijen, Marcha; Schrooders, Yannick; Gmuender, Hans; Nudischer, Ramona; Clayton, Olivia; Hynes, James; Niederer, Steven; Cordes, Henrik; Kuepfer, Lars; Kleinjans, Jos; Caiment, Florian

    2018-05-24

    Doxorubicin (DOX) is a chemotherapeutic agent of which the medical use is limited due to cardiotoxicity. While acute cardiotoxicity is reversible, chronic cardiotoxicity is persistent or progressive, dose-dependent and irreversible. While DOX mechanisms of action are not fully understood yet, 3 toxicity processes are known to occur in vivo: cardiomyocyte dysfunction, mitochondrial dysfunction and cell death. We present an in vitro experimental design aimed at detecting DOX-induced cardiotoxicity by obtaining a global view of the induced molecular mechanisms through RNA-sequencing. To better reflect the in vivo situation, human 3D cardiac microtissues were exposed to physiologically-based pharmacokinetic (PBPK) relevant doses of DOX for 2 weeks. We analysed a therapeutic and a toxic dosing profile. Transcriptomics analysis revealed significant gene expression changes in pathways related to "striated muscle contraction" and "respiratory electron transport", thus suggesting mitochondrial dysfunction as an underlying mechanism for cardiotoxicity. Furthermore, expression changes in mitochondrial processes differed significantly between the doses. Therapeutic dose reflects processes resembling the phenotype of delayed chronic cardiotoxicity, while toxic doses resembled acute cardiotoxicity. Overall, these results demonstrate the capability of our innovative in vitro approach to detect the three known mechanisms of DOX leading to toxicity, thus suggesting its potential relevance for reflecting the patient situation. Our study also demonstrated the importance of applying physiologically relevant doses during toxicological research, since mechanisms of acute and chronic toxicity differ. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Passive mechanical properties of rat abdominal wall muscles suggest an important role of the extracellular connective tissue matrix.

    Science.gov (United States)

    Brown, Stephen H M; Carr, John Austin; Ward, Samuel R; Lieber, Richard L

    2012-08-01

    Abdominal wall muscles have a unique morphology suggesting a complex role in generating and transferring force to the spinal column. Studying passive mechanical properties of these muscles may provide insights into their ability to transfer force among structures. Biopsies from rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA) were harvested from male Sprague-Dawley rats, and single muscle fibers and fiber bundles (4-8 fibers ensheathed in their connective tissue matrix) were isolated and mechanically stretched in a passive state. Slack sarcomere lengths were measured and elastic moduli were calculated from stress-strain data. Titin molecular mass was also measured from single muscle fibers. No significant differences were found among the four abdominal wall muscles in terms of slack sarcomere length or elastic modulus. Interestingly, across all four muscles, slack sarcomere lengths were quite long in individual muscle fibers (>2.4 µm), and demonstrated a significantly longer slack length in comparison to fiber bundles (p resistance to lengthening at long muscle lengths. Titin molecular mass was significantly less in TrA compared to each of the other three muscles (p < 0.0009), but this difference did not correspond to hypothesized differences in stiffness. Copyright © 2012 Orthopaedic Research Society.

  20. Integrative pathway dissection of molecular mechanisms of moxLDL-induced vascular smooth muscle phenotype transformation

    Directory of Open Access Journals (Sweden)

    Karagiannis George S

    2013-01-01

    Full Text Available Abstract Background Atherosclerosis (AT is a chronic inflammatory disease characterized by the accumulation of inflammatory cells, lipoproteins and fibrous tissue in the walls of arteries. AT is the primary cause of heart attacks and stroke and is the leading cause of death in Western countries. To date, the pathogenesis of AT is not well-defined. Studies have shown that the dedifferentiation of contractile and quiescent vascular smooth muscle cells (SMC to the proliferative, migratory and synthetic phenotype in the intima is pivotal for the onset and progression of AT. To further delineate the mechanisms underlying the pathogenesis of AT, we analyzed the early molecular pathways and networks involved in the SMC phenotype transformation. Methods Quiescent human coronary artery SMCs were treated with minimally-oxidized LDL (moxLDL, for 3 hours and 21 hours, respectively. Transcriptomic data was generated for both time-points using microarrays and was subjected to pathway analysis using Gene Set Enrichment Analysis, GeneMANIA and Ingenuity software tools. Gene expression heat maps and pathways enriched in differentially expressed genes were compared to identify functional biological themes to elucidate early and late molecular mechanisms of moxLDL-induced SMC dedifferentiation. Results Differentially expressed genes were found to be enriched in cholesterol biosynthesis, inflammatory cytokines, chemokines, growth factors, cell cycle control and myogenic contraction themes. These pathways are consistent with inflammatory responses, cell proliferation, migration and ECM production, which are characteristic of SMC dedifferentiation. Furthermore, up-regulation of cholesterol synthesis and dysregulation of cholesterol metabolism was observed in moxLDL-induced SMC. These observations are consistent with the accumulation of cholesterol and oxidized cholesterol esters, which induce proinflammatory reactions during atherogenesis. Our data implicate for the

  1. [Relationship between PMI and fourier transform infrared spectral changes in muscle of rats after death caused by mechanical asphyxial].

    Science.gov (United States)

    Li, Shi-ying; Shao, Yu; Li, Zheng-dong; Liu, Ning-guo; Zou, Dong-hua; Qin, Zhi-qiang; Chen, Yi-jiu; Huang, Ping

    2012-06-01

    To observe the postmortem degradation process in rat myocardium and skeletal muscle using Fourier transform infrared (FTIR) spectroscopy and to provide a new method for estimating postmortem interval (PMI). Left ventricle and skeletal muscles of rats dying of mechanical asphyxiated were sampled at different PMIs. The changes of different chemical functional group in the myocardium and skeletal muscle samples were measured by FTIR spectroscopy. The different absorbance (A) ratios of peaks were calculated and the curve estimation analysis between absorbance ratios (x) and PMI (y) were performed to establish six mathematical models. FTIR spectral absorption peak of rat myocardium and skeletal muscle showed three changes: increase, decrease and stable. The cubic model function showed the strongest correlation coefficient. The A1080/A1396 ratio of skeletal muscle showed the strongest correlation coefficient (r = 0.832) with more accurate determination of PMI. FYIR spectroscopy can be potentially used as an effective method for estimating PMI in forensic practice using myocardium and skeletal muscle.

  2. [Molecular mechanism for ET-1-induced insulin resistance in skeletal muscle cells].

    Science.gov (United States)

    Horinouchi, Takahiro; Mazaki, Yuichi; Terada, Koji; Miwa, Soichi

    2018-01-01

    Insulin resistance is a condition where the sensitivity to insulin of the tissues expressing insulin receptor (InsR) is decreased due to a functional disturbance of InsR-mediated intracellular signaling. Insulin promotes the entry of glucose into the tissues and skeletal muscle is the most important tissue responsible for the insulin's action of decreasing blood glucose levels. Endothelin-1 (ET-1), a potent vasoconstrictor and pro-inflammatory peptide, induces insulin resistance through a direct action on skeletal muscle. However, the signaling pathways of ET-1-induced insulin resistance in skeletal muscle remain unclear. Here we show molecular mechanism underlying the inhibitory effect of ET-1 on insulin-stimulated Akt phosphorylation and glucose uptake in myotubes of rat L6 skeletal muscle cell line. mRNA expression levels of differentiation marker genes, MyoD and myogenin, were increased during L6 myoblasts differentiation into myotubes. Some of myotubes possessed the ability to spontaneously contract. In myotubes, insulin promoted Akt phosphorylation at Thr 308 and Ser 473 , and [ 3 H]-labelled 2-deoxy-D-glucose ([ 3 H]2-DG) uptake. The insulin-facilitated Akt phosphorylation and [ 3 H]2-DG uptake were inhibited by ET-1. The inhibitory effect of ET-1 was counteracted by blockade of ET type A receptor (ET A R), inhibition of G q/11 protein, and siRNA knockdown of G protein-coupled receptor kinase 2 (GRK2). The exogenously overexpressed GRK2 directly bound to endogenous Akt and their association was facilitated by ET-1. In summary, activation of ET A R with ET-1 inhibits insulin-induced Akt phosphorylation and [ 3 H]2-DG uptake in a G q/11 protein- and GRK2-dependent manner in skeletal muscle. These findings indicate that ET A R and GRK2 are potential targets for insulin resistance.

  3. 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.

  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. Reliability and Measurement Error of Tensiomyography to Assess Mechanical Muscle Function: A Systematic Review.

    Science.gov (United States)

    Martín-Rodríguez, Saúl; Loturco, Irineu; Hunter, Angus M; Rodríguez-Ruiz, David; Munguia-Izquierdo, Diego

    2017-12-01

    Martín-Rodríguez, S, Loturco, I, Hunter, AM, Rodríguez-Ruiz, D, and Munguia-Izquierdo, D. Reliability and measurement error of tensiomyography to assess mechanical muscle function: A systematic review. J Strength Cond Res 31(12): 3524-3536, 2017-Interest in studying mechanical skeletal muscle function through tensiomyography (TMG) has increased in recent years. This systematic review aimed to (a) report the reliability and measurement error of all TMG parameters (i.e., maximum radial displacement of the muscle belly [Dm], contraction time [Tc], delay time [Td], half-relaxation time [½ Tr], and sustained contraction time [Ts]) and (b) to provide critical reflection on how to perform accurate and appropriate measurements for informing clinicians, exercise professionals, and researchers. A comprehensive literature search was performed of the Pubmed, Scopus, Science Direct, and Cochrane databases up to July 2017. Eight studies were included in this systematic review. Meta-analysis could not be performed because of the low quality of the evidence of some studies evaluated. Overall, the review of the 9 studies involving 158 participants revealed high relative reliability (intraclass correlation coefficient [ICC]) for Dm (0.91-0.99); moderate-to-high ICC for Ts (0.80-0.96), Tc (0.70-0.98), and ½ Tr (0.77-0.93); and low-to-high ICC for Td (0.60-0.98), independently of the evaluated muscles. In addition, absolute reliability (coefficient of variation [CV]) was low for all TMG parameters except for ½ Tr (CV = >20%), whereas measurement error indexes were high for this parameter. In conclusion, this study indicates that 3 of the TMG parameters (Dm, Td, and Tc) are highly reliable, whereas ½ Tr demonstrate insufficient reliability, and thus should not be used in future studies.

  6. Administration of exercise-conditioned plasma alters muscle catalase kinetics in rat: An argument for in vivo-like Km instead of in vitro-like Vmax

    Directory of Open Access Journals (Sweden)

    Aristidis S. Veskoukis

    2018-05-01

    Full Text Available Maximal velocity (Vmax is a well established biomarker for the assessment of tissue redox status. There is scarce evidence, though, that it does not probably reflect sufficiently in vivo tissue redox profile. Instead, the Michaelis constant (Km could more adequately image tissue oxidative stress and, thus, be a more physiologically relevant redox biomarker. Therefore, the aim of the present study was to side-by-side compare Vmax and Km of an antioxidant enzyme after implementing an in vivo set up that induces alterations in tissue redox status. Forty rats were divided into two groups including rats injected with blood plasma originating from rats that had previously swam until exhaustion and rats injected with blood plasma originating from sedentary rats. Tail-vein injections were performed daily for 21 days. Catalase Vmax and Km measured in gastrocnemius muscle were increased after administration of the exercise-conditioned plasma, denoting enhancement of the enzyme activity but impairment of its affinity for the substrate, respectively. These alterations are potential adaptations stimulated by the administered plasma pointing out that blood is an active fluid capable of regulating tissue homeostasis. Our findings suggest that Km adequately reflects in vivo modifications of skeletal muscle catalase and seems to surpass Vmax regarding its physiological relevance and biological interpretation. In conclusion, Km can be regarded as an in vivo-like biomarker that satisfactorily images the intracellular environment, as compared to Vmax that could be aptly parallelized with a biomarker that describes tissue oxidative stress in an in vitro manner.

  7. 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

    2018-02-01

    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 G 0 /G 1 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.

  8. MR angiography, MR imaging and proton MR spectroscopy in-vivo assessment of skeletal muscle ischemia in diabetic rats.

    Directory of Open Access Journals (Sweden)

    Stefano Delli Pizzi

    Full Text Available To prospectively evaluate the feasibility of using magnetic resonance (MR techniques for in-vivo assessing a rat diabetic model of limb ischemia. Unilateral hind limb ischemia was induced by ligation of the iliac-femoral artery in male streptozotocin-treated and non-diabetic control rats. Four weeks after ligation, rats underwent MR Angiography (MRA, T(1-weighted and Short Time Inversion Recovery (STIR sequences and muscle Proton MR Spectroscopy ((1H-MRS on both hind limbs. After MR examinations, immunoblotting and immunofluorescence analysis were performed. MRA showed a signal void due to flow discontinuation distal to the artery ligation. T(1-weighted and STIR images showed, respectively, the presence of tissue swelling (p = 0.018 for non-diabetic; p = 0.027 for diabetic rats and signal hyperintensity in tissue affected by occlusion. Mean total creatine/water for the occluded limb was significantly lower than for the non-occluded limbs in both non-diabetic (5.46×10(-4 vs 1.14×10(-3, p = 0.028 and diabetic rats (1.37×10(-4 vs 1.10×10(-3; p = 0.018. MR Imaging and (1H-MRS changes were more pronounced in diabetic than in non-diabetic occluded limbs (p = 0.032. MR findings were confirmed by using histological findings. Combined MR techniques can be used to demonstrate the presence of structural and metabolic changes produced by iliac-femoral artery occlusion in rat diabetic model of limb ischemia.

  9. Effect of cyclosporine and l-name on skeletal muscle arteriole dilation to lipopolysaccharide in vivo

    International Nuclear Information System (INIS)

    Purton, B.J.; Hill, M.A.; Potocnik, S.J.

    1999-01-01

    likely due to changes in the rate of receptor cycling between the cell surface and endosomes. Increasing the pretreatment period to 3 h, however, resulted in alterations of both [ 3 H]NMS and [ 3 H]QNB B max levels that were similar in magnitude to those observed after 24 h pretreatment, thus reflecting changes in receptor protein synthesis. The effects of carbachol and atropine on mAChR receptor expression are in agreement with previous studies and reflect the agonist and inverse agonist properties, respectively, of the two ligands. The effect of gallamine, however, is novel. It is possible that gallamine behaves as an inverse agonist via a conformational change induced at the allosteric site. Alternatively, the ability of gallamine to modify the dynamic trafficking properties of the M 2 mAChR may be a manifestation of a mechanism that is divorced from any effects the modulator may exert on ligand-receptor efficacy, and represents a potentially new therapeutic modality. Copyright (1999) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  10. Bacteriostatic Effect of Quercetin as an Antibiotic Alternative In Vivo and Its Antibacterial Mechanism In Vitro.

    Science.gov (United States)

    Wang, Shengan; Yao, Jiaying; Zhou, Bo; Yang, Jiaxin; Chaudry, Maria T; Wang, Mi; Xiao, Fenglin; Li, Yao; Yin, Wenzhe

    2018-01-01

    Quercetin, a ubiquitous flavonoid, is known to have antibacterial effects. The purpose of this study was to investigate the effect of quercetin on cecal microbiota of Arbor Acre (AA) broiler chickens in vivo and the bacteriostatic effect and antibacterial mechanism of quercetin in vitro. In vivo, 480 AA broilers (1 day old) were randomly allotted to four treatments (negative control and 0.2, 0.4, or 0.6 g of quercetin per kg of diet) for 42 days. Cecal microbial population and distribution were measured at the end of the experiment. The cecal microflora in these broilers included Proteobacteria, Fimicutes, Bacteroidetes, and Deferribacteres. Compared with the negative control, quercetin significantly decreased the copies of Pseudomonas aeruginosa ( P 0.05). These results suggest that quercetin has potential as an alternative antibiotic feed additive in animal production.

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

    Science.gov (United States)

    Daoudi, Khalid; Hoogenboom, Martijn; den Brok, Martijn; Eikelenboom, Dylan; Adema, Gosse J; Fütterer, Jürgen J; de Korte, Chris L

    2017-04-01

    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 and immunological effects caused by the mechanical treatment. In this work, we explore the use of high frequency ultrasound (US) and photoacoustics (PA) as a potential tool to evaluate the effect of mechanical ablation in-vivo , e.g. boiling histotripsy. Two mice bearing a neuroblastoma tumor in the right leg were ablated using an MRI-HIFU system conceived for small animals and monitored using MRI thermometry. High frequency US and PA imaging were performed before and after the HIFU treatment. Afterwards, the tumor was resected for further assessment and evaluation of the ablated region using histopathology. High frequency US imaging revealed the presence of liquefied regions in the treated area together with fragmentized tissue which appeared with different reflecting proprieties compared to the surrounding tissue. Photoacoustic imaging on the other hand revealed the presence of deoxygenated blood within the tumor after the ablation due to the destruction of blood vessel network while color Doppler imaging confirmed the blood vessel network destruction within the tumor. The treated area and the presence of red blood cells detected by photoacoustics were further confirmed by the histopathology. This feasibility study demonstrates the potential of high frequency US and PA approach for assessing in-vivo the effect of mechanical HIFU tumor ablation.

  12. 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).

  13. In vitro and in vivo mechanical stability of orthodontic mini-implants.

    Science.gov (United States)

    Cho, Il-Sik; Kim, Sung-Kyun; Chang, Young-Il; Baek, Seung-Hak

    2012-07-01

    To compare in vivo and in vitro mechanical stability of orthodontic mini-implants (OMIs) treated with a sandblasted, large-grit, and anodic-oxidation (SLAO) method vs those treated with a sandblasted, large-grit, and acid-etching (SLA) method. Fifty-four titanium OMIs (cylindrical shape, drill-free type; diameter  =  1.45 mm, length  =  8 mm, Biomaterials Korea Inc, Seoul, Korea) were allocated into control, SLA, and SLAO groups (N  =  12 for in vivo and N  =  6 for in vitro studies per group). In vitro study was carried out on a polyurethane foam bone block (Sawbones, Pacific Research Laboratories Inc, Vashon, Wash). In vivo study was performed in the tibias of Beagles (6 males, age  =  1 year, weight  =  10 to 13 kg; OMIs were removed at 8 weeks after installation). For insertion and removal of OMIs, the speed and maximum torque of the surgical engine were set to 30 rpm and 40 Ncm, respectively. Maximum torque (MT), total energy (TE), and near peak energy (NPE) during the insertion and removal procedures were statistically analyzed. In the in vitro study, although the control group had a higher insertion MT value than the SLA and SLAO groups (P < .01), no differences in insertion TE and NPE or in any of the removal variables were noted among the three groups. In the in vivo study, the control group exhibited higher values for all insertion variables compared with the SLA and SLAO groups (MT, P < .001; TE, P < .01; NPE, P < .001). Although no difference in removal TE and removal NPE was noted among the three groups, the SLAO group presented with a higher removal MT than the SLA and control groups (P < .001). SLAO treatment may be an effective tool in reducing insertion damage to surrounding tissue and improving the mechanical stability of OMIs.

  14. 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.

  15. Cross-bridge mechanism of residual force enhancement after stretching in a skeletal muscle.

    Science.gov (United States)

    Tamura, Youjiro

    2018-01-01

    A muscle model that uses a modified Langevin equation with actomyosin potentials was used to describe the residual force enhancement after active stretching. Considering that the new model uses cross-bridge theory to describe the residual force enhancement, it is different from other models that use passive stretching elements. Residual force enhancement was simulated using a half sarcomere comprising 100 myosin molecules. In this paper, impulse is defined as the integral of an excess force from the steady isometric force over the time interval for which a stretch is applied. The impulse was calculated from the force response due to fast and slow muscle stretches to demonstrate the viscoelastic property of the cross-bridges. A cross-bridge mechanism was proposed as a way to describe the residual force enhancement on the basis of the impulse results with reference to the compliance of the actin filament. It was assumed that the period of the actin potential increased by 0.5% and the amplitude of the potential decreased by 0.5% when the half sarcomere was stretched by 10%. The residual force enhancement after 21.0% sarcomere stretching was 6.9% of the maximum isometric force of the muscle; this value was due to the increase in the number of cross-bridges.

  16. 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.

  17. Training-induced acceleration of oxygen uptake kinetics in skeletal muscle: the underlying mechanisms.

    Science.gov (United States)

    Zoladz, J A; Korzeniewski, B; Grassi, B

    2006-11-01

    It is well known that the oxygen uptake kinetics during rest-to-work transition (V(O2) on-kinetics) in trained subjects is significantly faster than in untrained individuals. It was recently postulated that the main system variable that determines the transition time (t(1/2)) of the V(O2) on-kinetics in skeletal muscle, at a given moderate ATP usage/work intensity, and under the assumption that creatine kinase reaction works near thermodynamic equilibrium, is the absolute (in mM) decrease in [PCr] during rest-to-work transition. Therefore we postulate that the training-induced acceleration of the V(O2) on-kinetics is a marker of an improvement of absolute metabolic stability in skeletal muscles. The most frequently postulated factor responsible for enhancement of muscle metabolic stability is the training-induced increase in mitochondrial proteins. However, the mechanism proposed by Gollnick and Saltin (1982) can improve absolute metabolic stability only if training leads to a decrease in resting [ADP(free)]. This effect is not observed in many examples of training causing an acceleration of the V(O2) on-kinetics, especially in early stages of training. Additionally, this mechanism cannot account for the significant training-induced increase in the relative (expressed in % or as multiples of the resting values) metabolic stability at low work intensities, condition in which oxidative phosphorylation is not saturated with [ADP(free)]. Finally, it was reported that in the early stage of training, acceleration in the V(O2) on-kinetics and enhancement of muscle metabolic stability may precede adaptive responses in mitochondrial enzymes activities or mitochondria content. We postulate that the training-induced acceleration in the V(O2) on-kinetics and the improvement of the metabolite stability during moderate intensity exercise in the early stage of training is mostly caused by an intensification of the "parallel activation" of ATP consumption and ATP supply pathways

  18. 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.

  19. 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.

  20. Finite element model of intermuscular pressure during isometric contraction of skeletal muscle

    NARCIS (Netherlands)

    Jenkyn, T.R.; Koopman, B.; Huijing, P.A.J.B.M.; Lieber, R.L.; Kaufman, K.R.

    2002-01-01

    The measurement of in vivo intramuscular pressure (IMP) has recently become practical and IMP appears well correlated with muscle tension. A numerical model of skeletal muscle was developed to examine the mechanisms producing IMP. Unipennate muscle is modelled as a two-dimensional material continuum

  1. Determination of mouse skeletal muscle architecture using three dimensional diffusion tensor imaging

    NARCIS (Netherlands)

    Heemskerk, A.M.; Strijkers, G.J.; Vilanova, A.; Drost, M.R.; Nicolaij, K.

    2005-01-01

    Muscle architecture is the main determinant of the mechanical behavior of skeletal muscles. This study explored the feasibility of diffusion tensor imaging (DTI) and fiber tracking to noninvasively determine the in vivo three-dimensional (3D) architecture of skeletal muscle in mouse hind leg. In six

  2. Determination of mouse skeletal muscle architecture using three-dimensional diffusion tensor imaging

    NARCIS (Netherlands)

    Heemskerk, Anneriet M.; Strijkers, Gustav J.; Vilanova, Anna; Drost, Maarten R.; Nicolay, Klaas

    2005-01-01

    Muscle architecture is the main determinant of the mechanical behavior of skeletal muscles. This study explored the feasibility of diffusion tensor imaging (DTI) and fiber tracking to noninvasively determine the in vivo three-dimensional (3D) architecture of skeletal muscle in mouse hind leg. In six

  3. A Novel Ex Vivo Model to Investigate the Underlying Mechanisms in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Emanuele Brai

    2017-09-01

    Full Text Available Currently there is no widely accepted animal model reproducing the full pathological profile of Alzheimer’s disease (AD, since the basic mechanisms of neurodegeneration are still poorly understood. We have proposed that the interaction between the α7 nicotinic acetylcholine receptor (α7-nAChR and a recently discovered toxic peptide, cleaved from the acetylcholinesterase (AChE C-terminus, could account for the aberrant processes occurring in AD. In this article we describe a new application on ex vivo model procedure, which combines the advantages of both in vivo and in vitro preparations, to study the effects of the AChE-derived peptide on the rat basal forebrain (BF. Western blot analysis showed that the levels of α7-nAChR, p-Tau and Aβ are differentially expressed upon the AChE-peptide administration, in a selective site-dependent manner. In conclusion, this methodology demonstrates the action of a novel peptide in triggering an AD-like phenotype and proposes a new ex vivo approach for manipulating and monitoring neurochemical processes contributing to neurodegeneration, in a time-dependent and site-specific manner.

  4. Rotating magnetic field induced oscillation of magnetic particles for in vivo mechanical destruction of malignant glioma.

    Science.gov (United States)

    Cheng, Yu; Muroski, Megan E; Petit, Dorothée C M C; Mansell, Rhodri; Vemulkar, Tarun; Morshed, Ramin A; Han, Yu; Balyasnikova, Irina V; Horbinski, Craig M; Huang, Xinlei; Zhang, Lingjiao; Cowburn, Russell P; Lesniak, Maciej S

    2016-02-10

    Magnetic particles that can be precisely controlled under a magnetic field and transduce energy from the applied field open the way for innovative cancer treatment. Although these particles represent an area of active development for drug delivery and magnetic hyperthermia, the in vivo anti-tumor effect under a low-frequency magnetic field using magnetic particles has not yet been demonstrated. To-date, induced cancer cell death via the oscillation of nanoparticles under a low-frequency magnetic field has only been observed in vitro. In this report, we demonstrate the successful use of spin-vortex, disk-shaped permalloy magnetic particles in a low-frequency, rotating magnetic field for the in vitro and in vivo destruction of glioma cells. The internalized nanomagnets align themselves to the plane of the rotating magnetic field, creating a strong mechanical force which damages the cancer cell structure inducing programmed cell death. In vivo, the magnetic field treatment successfully reduces brain tumor size and increases the survival rate of mice bearing intracranial glioma xenografts, without adverse side effects. This study demonstrates a novel approach of controlling magnetic particles for treating malignant glioma that should be applicable to treat a wide range of cancers. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 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.

  6. Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism.

    Science.gov (United States)

    Cheah, Esther Y; Burcham, Philip C; Mann, Tracy S; Henry, Peter J

    2014-05-01

    Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE₂ was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK₁ receptor antagonist RP-67580, and the EP₂ receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE₂ release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK₁ receptor-expressing epithelial cells, and EP₂-receptor expressing airway smooth muscle cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. 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.

  8. 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.

  9. Rate equation for creatine kinase predicts the in vivo reaction velocity: 31P NMR surface coil studies in brain, heart, and skeletal muscle of the living rat

    International Nuclear Information System (INIS)

    Bittl, J.A.; DeLayre, J.; Ingwall, J.S.

    1987-01-01

    Brain, heart, and skeletal muscle contain four different creatine kinase isozymes and various concentrations of substrates for the creatine kinase reaction. To identify if the velocity of the creatine kinase reaction under cellular conditions is regulated by enzyme activity and substrate concentrations as predicted by the rate equation, the authors used 31 P NMR and spectrophotometric techniques to measure reaction velocity, enzyme content, isozyme distribution, and concentrations of substrates in brain, heart, and skeletal muscle of living rat under basal or resting conditions. The total tissue activity of creatine kinase in the direction of MgATP synthesis provided an estimate for V/sub max/ and exceeded the NMR-determined in vivo reaction velocities by an order of magnitude. The isozyme composition varied among the three tissues: >99% BB for brain; 14% MB, 61% MM, and 25% mitochondrial for heart; and 98% MM and 2% mitochondrial for skeletal muscle. The NMR-determined reaction velocities agreed with predicted values from the creatine kinase rate equation. The concentrations of free creatine and cytosolic MgADP, being less than or equal to the dissociation constants for each isozyme, were dominant terms in the creatine kinase rate equation for predicting the in vivo reaction velocity. Thus, they observed that the velocity of the creatine kinase reaction is regulated by total tissue enzyme activity and by the concentrations of creatine and MgADP in a manner that is independent of isozyme distribution

  10. Smitin, a novel smooth muscle titin-like protein, interacts with myosin filaments in vivo and in vitro.

    Science.gov (United States)

    Kim, Kyoungtae; Keller, Thomas C S

    2002-01-07

    Smooth muscle cells use an actin-myosin II-based contractile apparatus to produce force for a variety of physiological functions, including blood pressure regulation and gut peristalsis. The organization of the smooth muscle contractile apparatus resembles that of striated skeletal and cardiac muscle, but remains much more poorly understood. We have found that avian vascular and visceral smooth muscles contain a novel, megadalton protein, smitin, that is similar to striated muscle titin in molecular morphology, localization in a contractile apparatus, and ability to interact with myosin filaments. Smitin, like titin, is a long fibrous molecule with a globular domain on one end. Specific reactivities of an anti-smitin polyclonal antibody and an anti-titin monoclonal antibody suggest that smitin and titin are distinct proteins rather than differentially spliced isoforms encoded by the same gene. Smitin immunofluorescently colocalizes with myosin in chicken gizzard smooth muscle, and interacts with two configurations of smooth muscle myosin filaments in vitro. In physiological ionic strength conditions, smitin and smooth muscle myosin coassemble into irregular aggregates containing large sidepolar myosin filaments. In low ionic strength conditions, smitin and smooth muscle myosin form highly ordered structures containing linear and polygonal end-to-end and side-by-side arrays of small bipolar myosin filaments. We have used immunogold localization and sucrose density gradient cosedimentation analyses to confirm association of smitin with both the sidepolar and bipolar smooth muscle myosin filaments. These findings suggest that the titin-like protein smitin may play a central role in organizing myosin filaments in the contractile apparatus and perhaps in other structures in smooth muscle cells.

  11. The effects of mechanical loading on tendons--an in vivo and in vitro model study.

    Directory of Open Access Journals (Sweden)

    Jianying Zhang

    Full Text Available Mechanical loading constantly acts on tendons, and a better understanding of its effects on the tendons is essential to gain more insights into tendon patho-physiology. This study aims to investigate tendon mechanobiological responses through the use of mouse treadmill running as an in vivo model and mechanical stretching of tendon cells as an in vitro model. In the in vivo study, mice underwent moderate treadmill running (MTR and intensive treadmill running (ITR regimens. Treadmill running elevated the expression of mechanical growth factors (MGF and enhanced the proliferative potential of tendon stem cells (TSCs in both patellar and Achilles tendons. In both tendons, MTR upregulated tenocyte-related genes: collagen type I (Coll. I ∼10 fold and tenomodulin (∼3-4 fold, but did not affect non-tenocyte-related genes: LPL (adipocyte, Sox9 (chondrocyte, Runx2 and Osterix (both osteocyte. However, ITR upregulated both tenocyte (Coll. I ∼7-11 fold; tenomodulin ∼4-5 fold and non-tenocyte-related genes (∼3-8 fold. In the in vitro study, TSCs and tenocytes were stretched to 4% and 8% using a custom made mechanical loading system. Low mechanical stretching (4% of TSCs from both patellar and Achilles tendons increased the expression of only the tenocyte-related genes (Coll. I ∼5-6 fold; tenomodulin ∼6-13 fold, but high mechanical stretching (8% increased the expression of both tenocyte (Coll. I ∼28-50 fold; tenomodulin ∼14-48 fold and non-tenocyte-related genes (2-5-fold. However, in tenocytes, non-tenocyte related gene expression was not altered by the application of either low or high mechanical stretching. These findings indicate that appropriate mechanical loading could be beneficial to tendons because of their potential to induce anabolic changes in tendon cells. However, while excessive mechanical loading caused anabolic changes in tendons, it also induced differentiation of TSCs into non-tenocytes, which may lead to the development

  12. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice

    KAUST Repository

    Chatel, Benjamin; Bendahan, David; Hourdé , Christophe; Pellerin, Luc; Lengacher, Sylvain; Magistretti, Pierre J.; Le Fur, Yann; Vilmen, Christophe; Bernard, Monique; Messonnier, Laurent A.

    2017-01-01

    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.

  13. 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.

  14. 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

  15. Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

    Science.gov (United States)

    Ito, Reio; Shinoda, Masamichi; Honda, Kuniya; Urata, Kentaro; Lee, Jun; Maruno, Mitsuru; Soma, Kumi; Okada, Shinji; Gionhaku, Nobuhito; Iwata, Koichi

    To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

  16. Attenuation of p38α MAPK stress response signaling delays the in vivo aging of skeletal muscle myofibers and progenitor cells.

    Science.gov (United States)

    Papaconstantinou, John; Wang, Chen Z; Zhang, Min; Yang, San; Deford, James; Bulavin, Dmitry V; Ansari, Naseem H

    2015-09-01

    Functional competence and self-renewal of mammalian skeletal muscle myofibers and progenitor cells declines with age. Progression of the muscle aging phenotype involves the decline of juvenile protective factorsi.e., proteins whose beneficial functions translate directly to the quality of life, and self-renewal of progenitor cells. These characteristics occur simultaneously with the age-associated increase of p38α stress response signaling. This suggests that the maintenance of low levels of p38α activity of juvenile tissues may delay or attenuate aging. We used the dominant negative haploinsufficient p38α mouse (DN-p38α(AF/+)) to demonstrate that in vivo attenuation of p38α activity in the gastrocnemius of the aged mutant delays age-associated processes that include: a) the decline of the juvenile protective factors, BubR1, aldehyde dehydrogenase 1A (ALDH1A1), and aldehyde dehydrogenase 2 (ALDH2); b) attenuated expression of p16(Ink4a) and p19(Arf) tumor suppressor genes of the Cdkn2a locus; c) decreased levels of hydroxynonenal protein adducts, expression of COX2 and iNOS; d) decline of the senescent progenitor cell pool level and d) the loss of gastrocnemius muscle mass. We propose that elevated P-p38α activity promotes skeletal muscle aging and that the homeostasis of p38α impacts the maintenance of a beneficial healthspan.

  17. 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.

  18. Neuromuscular mechanisms and neural strategies in the control of time-varying muscle contractions.

    Science.gov (United States)

    Erimaki, Sophia; Agapaki, Orsalia M; Christakos, Constantinos N

    2013-09-01

    The organization of the neural input to motoneurons that underlies time-varying muscle force is assumed to depend on muscle transfer characteristics and neural strategies or control modes utilizing sensory signals. We jointly addressed these interlinked, but previously studied individually and partially, issues for sinusoidal (range 0.5-5.0 Hz) force-tracking contractions of a human finger muscle. Using spectral and correlation analyses of target signal, force signal, and motor unit (MU) discharges, we studied 1) patterns of such discharges, allowing inferences on the motoneuronal input; 2) transformation of MU population activity (EMG) into quasi-sinusoidal force; and 3) relation of force oscillation to target, carrying information on the input's organization. A broad view of force control mechanisms and strategies emerged. Specifically, synchronized MU and EMG modulations, reflecting a frequency-modulated motoneuronal input, accompanied the force variations. Gain and delay drops between EMG modulation and force oscillation, critical for the appropriate organization of this input, occurred with increasing target frequency. According to our analyses, gain compensation was achieved primarily through rhythmical activation/deactivation of higher-threshold MUs and secondarily through the adaptation of the input's strength expected during tracking tasks. However, the input's timing was not adapted to delay behaviors and seemed to depend on the control modes employed. Thus, for low-frequency targets, the force oscillation was highly coherent with, but led, a target, this timing error being compatible with predictive feedforward control partly based on the target's derivatives. In contrast, the force oscillation was weakly coherent, but in phase, with high-frequency targets, suggesting control mainly based on a target's rhythm.

  19. Hormonal and Neuromuscular Responses to Mechanical Vibration Applied to Upper Extremity Muscles

    Science.gov (United States)

    Di Giminiani, Riccardo; Fabiani, Leila; Baldini, Giuliano; Cardelli, Giovanni; Giovannelli, Aldo; Tihanyi, Jozsef

    2014-01-01

    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. PMID:25368995

  20. 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

  1. Direct effects of doxorubicin on skeletal muscle contribute to fatigue

    NARCIS (Netherlands)

    Norren, van K.; Helvoort, van A.; Argiles, J.M.; Tuijl, van S.; Arts, K.; Gorselink, M.; Laviano, A.; Kegler, D.; Haagsman, H.P.; Beek, E.M.

    2009-01-01

    Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation

  2. 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...... in GLUT-1 protein content was found. In contrast, GLUT-4 mRNA was unchanged, but transcripts for GLUT-1 were increased > or = 150% in all three muscles from CTX-treated rats. The findings suggest that CTX via increased cAMP impairs basal as well as insulin- and contraction-stimulated muscle glucose...

  3. Biophysical modeling of in vitro and in vivo processes underlying regulated photoprotective mechanism in cyanobacteria.

    Science.gov (United States)

    Shirshin, Evgeny A; Nikonova, Elena E; Kuzminov, Fedor I; Sluchanko, Nikolai N; Elanskaya, Irina V; Gorbunov, Maxim Y; Fadeev, Victor V; Friedrich, Thomas; Maksimov, Eugene G

    2017-09-01

    Non-photochemical quenching (NPQ) is a mechanism responsible for high light tolerance in photosynthetic organisms. In cyanobacteria, NPQ is realized by the interplay between light-harvesting complexes, phycobilisomes (PBs), a light sensor and effector of NPQ, the photoactive orange carotenoid protein (OCP), and the fluorescence recovery protein (FRP). Here, we introduced a biophysical model, which takes into account the whole spectrum of interactions between PBs, OCP, and FRP and describes the experimental PBs fluorescence kinetics, unraveling interaction rate constants between the components involved and their relative concentrations in the cell. We took benefit from the possibility to reconstruct the photoprotection mechanism and its parts in vitro, where most of the parameters could be varied, to develop the model and then applied it to describe the NPQ kinetics in the Synechocystis sp. PCC 6803 mutant lacking photosystems. Our analyses revealed  that while an excess of the OCP over PBs is required to obtain substantial PBs fluorescence quenching in vitro, in vivo the OCP/PBs ratio is less than unity, due to higher local concentration of PBs, which was estimated as ~10 -5 M, compared to in vitro experiments. The analysis of PBs fluorescence recovery on the basis of the generalized model of enzymatic catalysis resulted in determination of the FRP concentration in vivo close to 10% of the OCP concentration. Finally, the possible role of the FRP oligomeric state alteration in the kinetics of PBs fluorescence was shown. This paper provides the most comprehensive model of the OCP-induced PBs fluorescence quenching to date and the results are important for better understanding of the regulatory molecular mechanisms underlying NPQ in cyanobacteria.

  4. Structural Changes in Isometrically Contracting Insect Flight Muscle Trapped following a Mechanical Perturbation

    Science.gov (United States)

    Wu, Shenping; Liu, Jun; Perz-Edwards, Robert J.; Tregear, Richard T.; Winkler, Hanspeter; Franzini-Armstrong, Clara; Sasaki, Hiroyuki; Goldman, Yale E.; Reedy, Michael K.; Taylor, Kenneth A.

    2012-01-01

    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 model

  5. Administration of exercise-conditioned plasma alters muscle catalase kinetics in rat: An argument for in vivo-like Km instead of in vitro-like Vmax.

    Science.gov (United States)

    Veskoukis, Aristidis S; Paschalis, Vassilis; Kyparos, Antonios; Nikolaidis, Michalis G

    2018-05-01

    Maximal velocity (V max ) is a well established biomarker for the assessment of tissue redox status. There is scarce evidence, though, that it does not probably reflect sufficiently in vivo tissue redox profile. Instead, the Michaelis constant (K m ) could more adequately image tissue oxidative stress and, thus, be a more physiologically relevant redox biomarker. Therefore, the aim of the present study was to side-by-side compare V max and K m of an antioxidant enzyme after implementing an in vivo set up that induces alterations in tissue redox status. Forty rats were divided into two groups including rats injected with blood plasma originating from rats that had previously swam until exhaustion and rats injected with blood plasma originating from sedentary rats. Tail-vein injections were performed daily for 21 days. Catalase V max and K m measured in gastrocnemius muscle were increased after administration of the exercise-conditioned plasma, denoting enhancement of the enzyme activity but impairment of its affinity for the substrate, respectively. These alterations are potential adaptations stimulated by the administered plasma pointing out that blood is an active fluid capable of regulating tissue homeostasis. Our findings suggest that K m adequately reflects in vivo modifications of skeletal muscle catalase and seems to surpass V max regarding its physiological relevance and biological interpretation. In conclusion, K m can be regarded as an in vivo-like biomarker that satisfactorily images the intracellular environment, as compared to V max that could be aptly parallelized with a biomarker that describes tissue oxidative stress in an in vitro manner. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  6. 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 ... increased Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 ± 7% (P Na+,K+ pump content by 18 ± 9% (P

  7. 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.

  8. The mechanism of inhibitory effect of γ-ray irradiation on rat vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Zhuang Yongzhi; Wang Junjie; Zhang Zhanchun; Jia Tingzhen

    2001-01-01

    Objective: To investigate the inhibitory effect of γ-ray irradiation on rat vascular smooth muscle cells (VSMCs). Methods: Dose-survival curve of VSMCs was figured by colony formation. The effect of γ-ray irradiation on viability and proliferation of VSMCs was observed by 3 H incorporation. Flow cytometry and DNA Ladder were used to detect the apoptosis effect of γ-ray irradiation on VSMCs. Results: The values of D 0 , D q , D 37 and N for VSMCs were 1.95 Gy, 1.76 Gy, 3.71 Gy and 2.47, respectively. The inhibitory effect of γ-ray irradiation on VSMCs proliferation was dose-dependent, being stronger along with increase of dose. VSMCs did not undergo apoptosis within 48 hours after γ-ray irradiation. Conclusion: γ-ray irradiation could inhibit the proliferation of VSMCs, the main mechanism of which is the killing effect and inhibition of mitosis of VSMCs

  9. 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.

  10. In vivo confirmation of hydration based contrast mechanisms for terahertz medical imaging using MRI

    Science.gov (United States)

    Bajwa, Neha; Sung, Shijun; Garritano, James; Nowroozi, Bryan; Tewari, Priyamvada; Ennis, Daniel B.; Alger, Jeffery; Grundfest, Warren; Taylor, Zachary

    2014-09-01

    Terahertz (THz) detection has been proposed and applied to a variety of medical imaging applications in view of its unrivaled hydration profiling capabilities. Variations in tissue dielectric function have been demonstrated at THz frequencies to generate high contrast imagery of tissue, however, the source of image contrast remains to be verified using a modality with a comparable sensing scheme. To investigate the primary contrast mechanism, a pilot comparison study was performed in a burn wound rat model, widely known to create detectable gradients in tissue hydration through both injured and surrounding tissue. Parallel T2 weighted multi slice multi echo (T2w MSME) 7T Magnetic Resonance (MR) scans and THz surface reflectance maps were acquired of a full thickness skin burn in a rat model over a 5 hour time period. A comparison of uninjured and injured regions in the full thickness burn demonstrates a 3-fold increase in average T2 relaxation times and a 15% increase in average THz reflectivity, respectively. These results support the sensitivity and specificity of MRI for measuring in vivo burn tissue water content and the use of this modality to verify and understand the hydration sensing capabilities of THz imaging for acute assessments of the onset and evolution of diseases that affect the skin. A starting point for more sophisticated in vivo studies, this preliminary analysis may be used in the future to explore how and to what extent the release of unbound water affects imaging contrast in THz burn sensing.

  11. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Richter, Erik; Wojtaszewski, Jørgen

    2006-01-01

    The 5'-AMP-activated protein kinase (AMPK) is a potent regulator of skeletal muscle metabolism and gene expression. AMPK is activated both in response to in vivo exercise and ex vivo contraction. AMPK is therefore believed to be an important signalling molecule in regulating muscle metabolism...... during exercise as well as in adaptation of skeletal muscle to exercise training. The first part of this review is focused on different mechanisms regulating AMPK activity during muscle work such as alterations in nucleotide concentrations, availability of energy substrates and upstream AMPK kinases. We...... in relation to adaptation of skeletal muscle to exercise training....

  12. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    DEFF Research Database (Denmark)

    Lundsgaard, Annemarie; Kiens, Bente

    2014-01-01

    higher insulin sensitivity of female skeletal muscle can be related to gender-specific regulation of molecular metabolism will be topic for discussion. Gender differences in muscle fiber type distribution and substrate availability to and in skeletal muscle are highly relevant for substrate metabolism...

  13. Biocompatibility of calcium phosphate bone cement with optimised mechanical properties: an in vivo study.

    Science.gov (United States)

    Palmer, Iwan; Nelson, John; Schatton, Wolfgang; Dunne, Nicholas J; Buchanan, Fraser; Clarke, Susan A

    2016-12-01

    This work establishes the in vivo performance of modified calcium phosphate bone cements for vertebroplasty of spinal fractures using a lapine model. A non-modified calcium phosphate bone cement and collagen-calcium phosphate bone cements composites with enhanced mechanical properties, utilising either bovine collagen or collagen from a marine sponge, were compared to a commercial poly(methyl methacrylate) cement. Conical cement samples (8 mm height × 4 mm base diameter) were press-fit into distal femoral condyle defects in New Zealand White rabbits and assessed after 5 and 10 weeks. Bone apposition and tartrate-resistant acid phosphatase activity around cements were assessed. All implants were well tolerated, but bone apposition was higher on calcium phosphate bone cements than on poly(methyl methacrylate) cement. Incorporation of collagen showed no evidence of inflammatory or immune reactions. Presence of positive tartrate-resistant acid phosphatase staining within cracks formed in calcium phosphate bone cements suggested active osteoclasts were present within the implants and were actively remodelling within the cements. Bone growth was also observed within these cracks. These findings confirm the biological advantages of calcium phosphate bone cements over poly(methyl methacrylate) and, coupled with previous work on enhancement of mechanical properties through collagen incorporation, suggest collagen-calcium phosphate bone cement composite may offer an alternative to calcium phosphate bone cements in applications where low setting times and higher mechanical stability are important.

  14. Stimulation of chondrocyte proliferation following photothermal, thermal, and mechanical injury in ex-vivo cartilage grafts

    Science.gov (United States)

    Pandoh, Nidhi S.; Truong, Mai T.; Diaz-Valdes, Sergio H.; Gardiner, David M.; Wong, Brian J.

    2002-06-01

    Laser irradiation may stimulate chondrocytes proliferation in the peripheral region surrounding a photothermally-heated area in rabbit nasal septal cartilage. In this study, ex- vivo rabbit nasal septal cartilages maintained in culture were irradiated with an Nd:YAG laser ((lambda) equals1.32 micrometers , 4-16 sec, 10-45 W/cm2) to examine the relationship between the diameter of replicating cells and irradiation time. Also, this study investigated whether proliferation occurs following heating (by immersion in hot saline baths, with a heated metal rod, and a soldering iron) and mechanical modification (crushing with a metal stamp and scoring with a scalpel). Replicating chondrocytes were identified using a Bromodeoxyuridine (BrdU) double antibody detection system in whole mount tissue. Light microscopy was used to confirm the presence of BrdU stained chondrocytes. The mechanical and thermal stressors used failed to produce a proliferative response in chondrocytes as previously seen with laser irradiation. We suspect that chondrocyte proliferation may be induced as a response to alteration in matrix structure produced by photothermal, thermal, or mechanical modification of the matrix. Heat generated by a laser to stimulate chondrocyte proliferation may lead to new treatment options for degenerative articular diseases and disorders. Laser technology can be adapted for use with minimally invasive surgical instrumentation to deliver light into otherwise inaccessible regions of the body.

  15. In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

    Science.gov (United States)

    Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

    2015-01-01

    The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

  16. Ingestion of Wheat Protein Increases In Vivo Muscle Protein Synthesis Rates in Healthy Older Men in a Randomized Trial.

    Science.gov (United States)

    Gorissen, Stefan Hm; Horstman, Astrid Mh; Franssen, Rinske; Crombag, Julie Jr; Langer, Henning; Bierau, Jörgen; Respondek, Frederique; van Loon, Luc Jc

    2016-09-01

    Muscle mass maintenance is largely regulated by basal muscle protein synthesis and the capacity to stimulate muscle protein synthesis after food intake. The postprandial muscle protein synthetic response is modulated by the amount, source, and type of protein consumed. It has been suggested that plant-based proteins are less potent in stimulating postprandial muscle protein synthesis than animal-derived proteins. However, few data support this contention. We aimed to assess postprandial plasma amino acid concentrations and muscle protein synthesis rates after the ingestion of a substantial 35-g bolus of wheat protein hydrolysate compared with casein and whey protein. Sixty healthy older men [mean ± SEM age: 71 ± 1 y; body mass index (in kg/m(2)): 25.3 ± 0.3] received a primed continuous infusion of l-[ring-(13)C6]-phenylalanine and ingested 35 g wheat protein (n = 12), 35 g wheat protein hydrolysate (WPH-35; n = 12), 35 g micellar casein (MCas-35; n = 12), 35 g whey protein (Whey-35; n = 12), or 60 g wheat protein hydrolysate (WPH-60; n = 12). Plasma and muscle samples were collected at regular intervals. The postprandial increase in plasma essential amino acid concentrations was greater after ingesting Whey-35 (2.23 ± 0.07 mM) than after MCas-35 (1.53 ± 0.08 mM) and WPH-35 (1.50 ± 0.04 mM) (P protein synthesis rates increased after ingesting MCas-35 (P protein synthesis rates above basal rates (0.049% ± 0.007%/h; P = 0.02). The myofibrillar protein synthetic response to the ingestion of 35 g casein is greater than after an equal amount of wheat protein. Ingesting a larger amount of wheat protein (i.e., 60 g) substantially increases myofibrillar protein synthesis rates in healthy older men. This trial was registered at clinicaltrials.gov as NCT01952639. © 2016 American Society for Nutrition.

  17. 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...... regions and between the contractile elements within the muscle fibers; and in pericytes situated on the skeletal muscle capillaries. Quantitation of the subsarcolemmal density of VEGF vesicles, calculated on top of myonuclei, in the muscle fibers revealed a ∼50% increase (P...

  18. A primary reduced TCA flux governs substrate oxidation in T2D skeletal muscle

    DEFF Research Database (Denmark)

    Gaster, Michael

    2012-01-01

    Our current knowledge on substrate oxidation in skeletal muscle in relation to insulin resistance and type 2 diabetes (T2D) originate mainly from in vivo studies. The oxidative capacity of skeletal muscle is highly influenced by physical activity, ageing, hormonal status, and fiber type composition...... further regulatory mechanism to our understanding of substrate oxidation in human skeletal muscle during normo- an pathophysiological conditions, focusing especially on the governing influence of a primary reduced TCA flux for the diabetic phenotype in skeletal muscle....

  19. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

    Science.gov (United States)

    Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  20. 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.

  1. Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPK?2 in the regulation of exercise capacity in vivo

    OpenAIRE

    Lee-Young, Robert S.; Ayala, Julio E.; Fueger, Patrick T.; Mayes, Wesley H.; Kang, Li; Wasserman, David H.

    2010-01-01

    Objective Skeletal muscle AMP-activated protein kinase (AMPK)?2 activity is impaired in obese, insulin resistant individuals during exercise. We determined whether this defect contributes to the metabolic dysregulation and reduced exercise capacity observed in the obese state. Design C57BL/6J wild-type (WT) mice and/or mice expressing a kinase dead AMPK?2 subunit in skeletal muscle (?2-KD) were fed chow or high fat (HF) diets from 3?16 weeks (wks) of age. At 15wks mice performed an exercise s...

  2. Acute fatigue-induced changes in muscle mechanical properties and neuromuscular activity in elite handball players following a handball match

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Michalsik, L B; Madsen, Klavs

    2008-01-01

    The purpose of the present study was to determine the acute fatigue development in muscle mechanical properties and neuromuscular activity in response to handball match play. Male elite handball players (n = 10) were tested before and after a simulated handball match for maximal isometric strength...... work (6.8%, P handball match play, which...

  3. 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

  4. In vivo control mechanisms of motor-cargo movement on microtubules

    Science.gov (United States)

    Gunawardena, Shermali

    2014-03-01

    Within axons, molecular motors transport essential components required for neuronal growth and viability. Although many levels of regulation must exist for proper anterograde and retrograde transport of vital proteins, little is known about these mechanisms. Previous work suggested that the amyloid precursor protein (APP) functions as a kinesin-1 receptor during transport. However, how APP vesicle motility is regulated is unclear. Using genetics and in vivo imaging in Drosophila we showed that reduction of presenilin (PS) substantially increased anterograde and retrograde APP vesicle velocities. Strikingly, PS deficiency had no effect on an unrelated cargo vesicle containing synaptotagmin, which is powered by a different kinesin motor. Increased PS-mediated velocities required functional kinesin-1 and dynein motors. We also found that these PS-mediated effects on motor protein function were mediated via a pathway that involves glycogen synthase kinase-3 β (GSK-3 β) . PS genetically interacted with GSK-3 β in an activity dependent manner. Excess of active GSK-3 β perturbed transport by causing axonal blockages, which were enhanced by reduction of kinesin-1 or dynein, while excess of non-functional GSK-3 β had no effect. Strikingly, GSK-3 β-activity dependent transport defects were enhanced by reduction of PS. Collectively, our findings suggest that PS and GSK-3 β are required for normal motor protein function, and we propose a model in which PS likely regulates GSK-3 β activity during transport. These findings have important implications for our understanding of the complex regulatory machinery that must exist in vivo and how this system is coordinated during vesicle motility on microtubules.

  5. Functional coupling of glycolysis and phosphocreatine utilization in anoxic fish muscle. : An in vivo 31P NMR study

    NARCIS (Netherlands)

    Van Waarde, A; Van den Thillart, G; Erkelens, Cees; Addink, A; Lugtenburg, J

    1990-01-01

    Three fish species with different strategies for anoxic survival (goldfish, tilapia, and common carp) were exposed to environmental anoxia (4, 3, and 1 h, respectively). The concentrations of high energy phosphate compounds and inorganic phosphate, besides the intracellular pH in the epaxial muscle

  6. 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

  7. 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

  8. 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

  9. 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...

  10. 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.

  11. 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

  12. 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

  13. [Cellular mechanism of the generation of spontaneous activity in gastric muscle].

    Science.gov (United States)

    Nakamura, Eri; Kito, Yoshihiko; Fukuta, Hiroyasu; Yanai, Yoshimasa; Hashitani, Hikaru; Yamamoto, Yoshimichi; Suzuki, Hikaru

    2004-03-01

    In gastric smooth muscles, interstitial cells of Cajal (ICC) might be the pacemaker cells of spontaneous activities since ICC are rich in mitochondria and are connected with smooth muscle cells via gap junctions. Several types of ICC are distributed widely in the stomach wall. A group of ICC distributed in the myenteric layer (ICC-MY) were the pacemaker cells of gastrointestinal smooth muscles. Pacemaker potentials were generated in ICC-MY, and the potentials were conducted to circular smooth muscles to trigger slow waves and also conducted to longitudinal muscles to form follower potentials. In circular muscle preparations, interstitial cells distributed within muscle bundles (ICC-IM) produced unitary potentials, which were conducted to circular muscles to form slow potentials by summation. In mutant mice lacking inositol trisphosphate (IP(3)) receptor, slow waves were absent in gastric smooth muscles. The generation of spontaneous activity was impaired by the inhibition of Ca(2+)-release from internal stores through IP(3) receptors, inhibition of mitochondrial Ca(2+)-handling with proton pump inhibitors, and inhibition of ATP-sensitive K(+)-channels at the mitochondrial inner membrane. These results suggested that mitochondrial Ca(2+)-handling causes the generation of spontaneous activity in pacemaker cells. Possible involvement of protein kinase C (PKC) in the Ca(2+) signaling system was also suggested.

  14. Mechanical properties and in vivo study of modified-hydroxyapatite/polyetheretherketone biocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Rui [College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China, (China); Li, Qiankuan [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen 518060 (China); Wang, Lin, E-mail: wanglinhitsz@163.com [Shenzhen Institute of Geriatrics, Shenzhen 518020 (China); Zhang, Xianghua [College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China, (China); Laboratory of Glasses and Ceramics, Institute of Chemical Science, University of Rennes 1, Rennes 35042 (France); Fang, Lin; Luo, Zhongkuan; Xue, Bai [College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China, (China); Ma, Lei, E-mail: leima@szu.edu.cn [College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China, (China)

    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 5 wt.%, 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 5 wt.% 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. - Highlight: • The modification of hydroxyapatite with KH-560 can increase the efficient dispersion of hydroxyapatite in PEEK substrates. • When the HA content is 5 wt. %, the tensile strength of modified-HA/PEEK composite reaches its maximum. • The nano-scale effect of HA fillers in PEEK substrates contributes to the growth of the

  15. Mechanical properties and in vivo study of modified-hydroxyapatite/polyetheretherketone biocomposites

    International Nuclear Information System (INIS)

    Ma, Rui; Li, Qiankuan; Wang, Lin; Zhang, Xianghua; Fang, Lin; Luo, Zhongkuan; Xue, Bai; Ma, Lei

    2017-01-01

    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 5 wt.%, 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 5 wt.% 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. - Highlight: • The modification of hydroxyapatite with KH-560 can increase the efficient dispersion of hydroxyapatite in PEEK substrates. • When the HA content is 5 wt. %, the tensile strength of modified-HA/PEEK composite reaches its maximum. • The nano-scale effect of HA fillers in PEEK substrates contributes to the growth of the

  16. [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

  17. 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

  18. The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

    Science.gov (United States)

    Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

    2014-01-01

    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 Hert 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 gages 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 gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. 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 rest between them

  19. A simple model to estimate plantarflexor muscle-tendon mechanics and energetics during walking with elastic ankle exoskeletons

    Science.gov (United States)

    Sawicki, Gregory S.; Khan, Nabil S.

    2016-01-01

    Goal A recent experiment demonstrated that when humans wear unpowered elastic ankle exoskeletons with intermediate spring stiffness they can reduce their metabolic energy cost to walk by ~7%. Springs that are too compliant or too stiff have little benefit. The purpose of this study was to use modeling and simulation to explore the muscle-level mechanisms for the ‘sweet-spot’ in stiffness during exoskeleton assisted walking. Methods We developed a simple lumped, uniarticular musculoskeletal model of the plantarflexors operating in parallel with an elastic ‘exo-tendon’. Using an inverse approach with constrained kinematics and kinetics, we rapidly simulated human walking over a range of exoskeleton stiffness values and examined the underlying neuromechanics and energetics of the biological plantarflexors. Results Stiffer ankle exoskeleton springs resulted in larger decreases in plantarflexor muscle forces, activations and metabolic energy consumption. However, in the process of unloading the compliant biological muscle-tendon unit (MTU), the muscle fascicles (CE) experienced larger excursions that negatively impacted series elastic element (SEE) recoil that is characteristic of a tuned ‘catapult mechanism’. Conclusion The combination of disrupted muscle-tendon dynamics and the need to produce compensatory forces/moments to maintain overall net ankle moment invariance could explain the ‘sweet spot’ in metabolic performance at intermediate ankle exoskeleton stiffness. Future work will aim to provide experimental evidence to support the model predictions presented here using ultrasound imaging of muscle-level dynamics during walking with elastic ankle exoskeletons. Significance Engineers must account for the muscle-level effects of exoskeleton designs in order to achieve maximal performance objectives. PMID:26485350

  20. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    Science.gov (United States)

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  1. Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

    DEFF Research Database (Denmark)

    Hansen, M; Miller, B F; Holm, L

    2009-01-01

    concentrations of estradiol and progesterone (control, n = 12). Subjects performed 1 h of one-legged kicking exercise. The next day collagen fractional synthesis rates (FSR) in tendon and muscle connective tissue were measured after a flooding dose of [(13)C]proline followed by biopsies from the patellar tendon......, body composition, and exercise-training status were included. The two groups were either habitual users of oral contraceptives exposed to a high concentration of synthetic estradiol and progestogens (OC, n = 11), or non-OC-users tested in the follicular phase of the menstrual cycle characterized by low...... bioavailability of IGF-I in OC. In conclusion, synthetic female sex hormones administered as OC had an inhibiting effect on collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I....

  2. Dynamic adaptation of tendon and muscle connective tissue to mechanical loading

    DEFF Research Database (Denmark)

    Mackey, Abigail; Heinemeier, Katja Maria; Koskinen, Satu Osmi Anneli

    2008-01-01

    The connective tissue of tendon and skeletal muscle is a crucial structure for force transmission. A dynamic adaptive capacity of these tissues in healthy individuals is evident from reports of altered gene expression and protein levels of the fibrillar and network-forming collagens, when subjected...... in this article provide strong evidence for the highly adaptable nature of connective tissue in muscle and tendon....

  3. 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…

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

    NARCIS (Netherlands)

    Boonen, K.J.M.; Langelaan, M.L.P.; Polak, R.B.; Schaft, van der D.W.J.; Baaijens, F.P.T.; Post, M.J.

    2010-01-01

    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

  5. Retraction: Myostatin Induces Degradation of Sarcomeric Proteins through a Smad3 Signaling Mechanism During Skeletal Muscle Wasting

    Science.gov (United States)

    Lokireddy, Sudarsanareddy; McFarlane, Craig; Ge, Xiaojia; Zhang, Huoming; Sze, Siu Kwan; Sharma, Mridula

    2011-01-01

    Ubiquitination-mediated proteolysis is a hallmark of skeletal muscle wasting manifested in response to negative growth factors, including myostatin. Thus, the characterization of signaling mechanisms that induce the ubiquitination of intracellular and sarcomeric proteins during skeletal muscle wasting is of great importance. We have recently characterized myostatin as a potent negative regulator of myogenesis and further demonstrated that elevated levels of myostatin in circulation results in the up-regulation of the muscle-specific E3 ligases, Atrogin-1 and muscle ring finger protein 1 (MuRF1). However, the exact signaling mechanisms by which myostatin regulates the expression of Atrogin-1 and MuRF1, as well as the proteins targeted for degradation in response to excess myostatin, remain to be elucidated. In this report, we have demonstrated that myostatin signals through Smad3 (mothers against decapentaplegic homolog 3) to activate forkhead box O1 and Atrogin-1 expression, which further promotes the ubiquitination and subsequent proteasome-mediated degradation of critical sarcomeric proteins. Smad3 signaling was dispensable for myostatin-dependent overexpression of MuRF1. Although down-regulation of Atrogin-1 expression rescued approximately 80% of sarcomeric protein loss induced by myostatin, only about 20% rescue was seen when MuRF1 was silenced, implicating that Atrogin-1 is the predominant E3 ligase through which myostatin manifests skeletal muscle wasting. Furthermore, we have highlighted that Atrogin-1 not only associates with myosin heavy and light chain, but it also ubiquitinates these sarcomeric proteins. Based on presented data we propose a model whereby myostatin induces skeletal muscle wasting through targeting sarcomeric proteins via Smad3-mediated up-regulation of Atrogin-1 and forkhead box O1. PMID:21964591

  6. In Vivo and In Silico Investigation Into Mechanisms of Frequency Dependence of Repolarization Alternans in Human Ventricular Cardiomyocytes.

    Science.gov (United States)

    Zhou, Xin; Bueno-Orovio, Alfonso; Orini, Michele; Hanson, Ben; Hayward, Martin; Taggart, Peter; Lambiase, Pier D; Burrage, Kevin; Rodriguez, Blanca

    2016-01-22

    Repolarization alternans (RA) are associated with arrhythmogenesis. Animal studies have revealed potential mechanisms, but human-focused studies are needed. RA generation and frequency dependence may be determined by cell-to-cell variability in protein expression, which is regulated by genetic and external factors. To characterize in vivo RA in human and to investigate in silico using human models, the ionic mechanisms underlying the frequency-dependent differences in RA behavior identified in vivo. In vivo electrograms were acquired at 240 sites covering the epicardium of 41 patients at 6 cycle lengths (600-350 ms). In silico investigations were conducted using a population of biophysically detailed human models incorporating variability in protein expression and calibrated using in vivo recordings. Both in silico and in vivo, 2 types of RA were identified, with Fork- and Eye-type restitution curves, based on RA persistence or disappearance, respectively, at fast pacing rates. In silico simulations show that RA are strongly correlated with fluctuations in sarcoplasmic reticulum calcium, because of strong release and weak reuptake. Large L-type calcium current conductance is responsible for RA disappearance at fast frequencies in Eye-type (30% larger in Eye-type versus Fork-type; Psilico, 2 types of RA are identified, with RA persistence/disappearance as frequency increases. In silico, L-type calcium current and Na(+)/Ca(2+) exchanger current determine RA human cell-to-cell differences through intracellular and sarcoplasmic reticulum calcium regulation. © 2015 The Authors.

  7. 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.

  8. 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.

  9. 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.

  10. Impaired thromboxane receptor dimerization reduces signaling efficiency: A potential mechanism for reduced platelet function in vivo.

    Science.gov (United States)

    Capra, Valérie; Mauri, Mario; Guzzi, Francesca; Busnelli, Marta; Accomazzo, Maria Rosa; Gaussem, Pascale; Nisar, Shaista P; Mundell, Stuart J; Parenti, Marco; Rovati, G Enrico

    2017-01-15

    Thromboxane A 2 is a potent mediator of inflammation and platelet aggregation exerting its effects through the activation of a G protein-coupled receptor (GPCR), termed TP. Although the existence of dimers/oligomers in Class A GPCRs is widely accepted, their functional significance still remains controversial. Recently, we have shown that TPα and TPβ homo-/hetero-dimers interact through an interface of residues in transmembrane domain 1 (TM1) whose disruption impairs dimer formation. Here, biochemical and pharmacological characterization of this dimer deficient mutant (DDM) in living cells indicates a significant impairment in its response to agonists. Interestingly, two single loss-of-function TPα variants, namely W29C and N42S recently identified in two heterozygous patients affected by bleeding disorders, match some of the residues mutated in our DDM. These two naturally occurring variants display a reduced potency to TP agonists and are characterized by impaired dimer formation in transfected HEK-293T cells. These findings provide proofs that lack of homo-dimer formation is a crucial process for reduced TPα function in vivo, and might represent one molecular mechanism through which platelet TPα receptor dysfunction affects the patient(s) carrying these mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Mechanisms underlying enhancements in muscle force and power output during maximal cycle ergometer exercise induced by chronic β2-adrenergic stimulation in men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Onslev, Johan

    2015-01-01

    The study was a randomized placebo-controlled trial investigating mechanisms by which chronic β2-adrenergic stimulation enhances muscle force and power output during maximal cycle ergometer exercise in young men. Eighteen trained men were assigned to an experimental group (oral terbutaline 5 mg∙30...... of muscle proteins involved in growth, ion handling, lactate production and clearance increased (P≤0.05) with the intervention in TER compared to PLA, with no change in oxidative enzymes. Our observations suggest that muscle hypertrophy is the primary mechanism underlying enhancements in muscle force...... and peak power during maximal cycling induced by chronic β2-adrenergic stimulation in humans....

  12. In Vivo Study on Analgesic, Muscle-Relaxant, Sedative Activity of Extracts of Hypochaeris radicata and In Silico Evaluation of Hypochaeris Glucoside and Guaiane-Type Sesquiterpene

    Directory of Open Access Journals (Sweden)

    Tareq Abu-Izneid

    2018-01-01

    Full Text Available Background. Hypochaeris radicata (flatweed from the family Asteraceae is a medicinal plant found in Europe, Middle East, and India. In folkloric medication, it is used to heal jaundice, dyspepsia, constipation, rheumatism, and hypoglycemia as well as renal problems. Leaves and roots of the plant have antioxidant and antibacterial properties. The plant is a rich source of pharmacologically active phytochemicals; however, it is explored scantily. The objective of the current study was to identify the chemical composition and investigate the in vivo biological potency of crude extracts of this plant. Methods. The crude extract and the fractions were screened for various phytochemical groups of constituents following standard procedures. The acute toxicity was assayed for safe range of dose determination. The analgesic potential of the extract and fractions was assessed by acetic acid-induced writhing test. The muscle-relaxant activity was examined by standard inclined-plane test and traction test. Sedative potential of extract/fractions was assessed by using standard white wood procedures. Furthermore, docking analysis of two compounds isolated from the ethyl acetate fraction of the plant was assessed against 3D cyclooxygenase-1 and -2 (COX-1 and COX-2. Results. The extract/fractions of H. radicata showed significant analgesic effect in in vivo model of peripheral algesia. The docking analysis of previously isolated molecules from the plant also exhibited promising interaction with COX-1 and COX-2. Also, the plant has a mild sedative and muscle-relaxant potential. Thus, our study provided pharmacological rationale for the traditional uses of the plant as analgesic and anti-inflammatory remedy. Conclusion. The crude extracts and fractions exhibited excellent activity due to active phytochemicals. These active phytochemicals also exhibited promising interaction with COX-1 and COX-2. This finding directed researcher to isolate active compounds from H

  13. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

    Directory of Open Access Journals (Sweden)

    Fabio Demontis

    2013-11-01

    Full Text Available A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.

  14. In vivo 31P NMR spectroscopic assessment of the endurance and recovery capacity of skeletal muscle: Comparison between the sedentaries and canoe athletes

    International Nuclear Information System (INIS)

    Lim, Tae Hawn; Lee, Tae Keun; Seong, Ki Hong; Mun, Chi Woong; Kim, Sang Tae; Shin, Myung Jin

    1992-01-01

    In vivo 3P NMR spectroscopic study of forearm wrist flexor muscles was performed in two groups of volunteers composed respectively of 6 sedentaries and 6 canoe athletes. A continuous isometric contraction of endurance exercise was adopted in order to assess the endurance capacity and recovery potential of skeletal muscles. Differences in high energy phosphorus metabolism between the sedentaries and athletes were evaluated with and emphasis on the intracellular pH and Pi/PCr ratio as indicators of high energy phosphorus metabolism, There were no differences of baseline pH and Pi/ PCr ratio between the two groups. The athletes sustained the exercise at a more acidic intracellular pH and at a higher Pi/ PCr radio of intracellular conditions for an all out than did the sedentaries. The recovery rate of pH showed no difference between the two groups. There was a tendency of faster recovery of Pi/ PCr in athletes showing half recovery time (T 1/2 ) of 39.0 ± 3.0 seconds as compared to that of sedentaries (55.7 ± 7.5 seconds). The recovery rate of Pi/ PCr as a function of Pi/ PCr rate at a given period of time was significantly faster in athletes than in sedentaries (P<0.001). The correlation coefficient of the recovery rate of Pi/ PCr against the Pi/ PCr ratio was 0.985 and 0.914 respectively for the athletes and sedentaries. The pH and the Pi/ PCr ratio at an all-out state can be used as indicators of endurance capacity and the recovery rate of Pi/ PCr, as a recovery potential of skeletal muscles

  15. Design and simulative experiment of an innovative trailing edge morphing mechanism driven by artificial muscles embedded in skin

    Science.gov (United States)

    Li, Hongda; Liu, Long; Xiao, Tianhang; Ang, Haisong

    2016-09-01

    In this paper, conceptual design of a tailing edge morphing mechanism developed based on a new kind of artificial muscle embedded in skin, named Driving Skin, is proposed. To demonstrate the feasibility of this conceptual design, an experiment using ordinary fishing lines to simulate the function of artificial muscles was designed and carried out. Some measures were designed to ensure measurement accuracy. The experiment result shows that the contraction ratio and force required by the morphing mechanism can be satisfied by the new artificial muscles, and a relationship between contraction ratios and morphing angles can be found. To demonstrate the practical application feasibility of this conceptual design, a wing section using ordinary ropes to simulate the function of the Driving Skin mechanism was designed and fabricated. The demonstration wing section, extremely light in weight and capable of changing thickness, performs well, with a -30^\\circ /+30^\\circ morphing angle achieved. The trailing edge morphing mechanism is efficient in re-contouring the wing profile.

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

    Science.gov (United States)

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

    1980-01-01

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

  17. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle

    DEFF Research Database (Denmark)

    Hunter, Roger W; Treebak, Jonas Thue; Wojtaszewski, Jørgen

    2011-01-01

    AND METHODS We recently generated knock-in mice in which wild-type muscle GS was replaced by a mutant (Arg582Ala) that could not be activated by glucose-6-phosphate (G6P), but possessed full catalytic activity and could still be activated normally by dephosphorylation. Muscles from GS knock-in or transgenic......-insensitive GS knock-in mice, although AICAR-stimulated AMPK activation, glucose transport, and total glucose utilization were normal. CONCLUSIONS We provide genetic evidence that AMPK activation promotes muscle glycogen accumulation by allosteric activation of GS through an increase in glucose uptake...

  18. Muscle Contraction.

    Science.gov (United States)

    Sweeney, H Lee; Hammers, David W

    2018-02-01

    SUMMARYMuscle cells are designed to generate force and movement. There are three types of mammalian muscles-skeletal, cardiac, and smooth. Skeletal muscles are attached to bones and move them relative to each other. Cardiac muscle comprises the heart, which pumps blood through the vasculature. Skeletal and cardiac muscles are known as striated muscles, because the filaments of actin and myosin that power their contraction are organized into repeating arrays, called sarcomeres, that have a striated microscopic appearance. Smooth muscle does not contain sarcomeres but uses the contraction of filaments of actin and myosin to constrict blood vessels and move the contents of hollow organs in the body. Here, we review the principal molecular organization of the three types of muscle and their contractile regulation through signaling mechanisms and discuss their major structural and functional similarities that hint at the possible evolutionary relationships between the cell types. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  19. In vivo evaluation of adipose- and muscle-derived stem cells as a treatment for nonhealing diabetic wounds using multimodal microscopy

    Science.gov (United States)

    Li, Joanne; Pincu, Yair; Marjanovic, Marina; Bower, Andrew J.; Chaney, Eric J.; Jensen, Tor; Boppart, Marni D.; Boppart, Stephen A.

    2016-08-01

    Impaired skin wound healing is a significant comorbid condition of diabetes, which often results in nonhealing diabetic ulcers due to poor peripheral microcirculation, among other factors. The effectiveness of the regeneration of adipose-derived stem cells (ADSCs) and muscle-derived stem cells (MDSCs) was assessed using an integrated multimodal microscopy system equipped with two-photon fluorescence and second-harmonic generation imaging. These imaging modalities, integrated in a single platform for spatial and temporal coregistration, allowed us to monitor in vivo changes in the collagen network and cell dynamics in a skin wound. Fluorescently labeled ADSCs and MDSCs were applied topically to the wound bed of wild-type and diabetic (db/db) mice following punch biopsy. Longitudinal imaging demonstrated that ADSCs and MDSCs provided remarkable capacity for improved diabetic wound healing, and integrated microscopy revealed a more organized collagen remodeling in the wound bed of treated mice. The results from this study verify the regenerative capacity of stem cells toward healing and, with multimodal microscopy, provide insight regarding their impact on the skin microenvironment. The optical method outlined in this study, which has the potential for in vivo human use, may optimize the care and treatment of diabetic nonhealing wounds.

  20. Early decrease in dietary protein:energy ratio by fat addition and ontogenetic changes in muscle growth mechanisms of rainbow trout: short- and long-term effects.

    Science.gov (United States)

    Alami-Durante, Hélène; Cluzeaud, Marianne; Duval, Carine; Maunas, Patrick; Girod-David, Virginia; Médale, Françoise

    2014-09-14

    As the understanding of the nutritional regulation of muscle growth mechanisms in fish is fragmentary, the present study aimed to (1) characterise ontogenetic changes in muscle growth-related genes in parallel to changes in muscle cellularity; (2) determine whether an early decrease in dietary protein:energy ratio by fat addition affects the muscle growth mechanisms of rainbow trout (Oncorhynchus mykiss) alevins; and (3) determine whether this early feeding of a high-fat (HF) diet to alevins had a long-term effect on muscle growth processes in juveniles fed a commercial diet. Developmental regulation of hyperplasia and hypertrophy was evidenced at the molecular (expression of myogenic regulatory factors, proliferating cell nuclear antigen and myosin heavy chains (MHC)) and cellular (number and diameter of white muscle fibres) levels. An early decrease in dietary protein:energy ratio by fat addition stimulated the body growth of alevins but led to a fatty phenotype, with accumulation of lipids in the anterior part, and less caudal muscle when compared at similar body weights, due to a decrease in both the white muscle hyperplasia and maximum hypertrophy of white muscle fibres. These HF diet-induced cellular changes were preceded by a very rapid down-regulation of the expression of fast-MHC. The present study also demonstrated that early dietary composition had a long-term effect on the subsequent muscle growth processes of juveniles fed a commercial diet for 3 months. When compared at similar body weights, initially HF diet-fed juveniles indeed had a lower mean diameter of white muscle fibres, a smaller number of large white muscle fibres, and lower expression levels of MyoD1 and myogenin. These findings demonstrated the strong effect of early feed composition on the muscle growth mechanisms of trout alevins and juveniles.

  1. 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

    onto a custom designed seeding chamber made of silicon ( McMaster Carr, Cleveland, OH). Scaffolds and silicon seeding chambers were then individually...TRAUMATIZED SKELETAL MUSCLE 707 observations in an effort to reduce the variability within this group. Ultimately, the coefficient of variation (CV

  2. Experimental tooth clenching. A model for studying mechanisms of muscle pain.

    Science.gov (United States)

    Dawson, Andreas

    2013-01-01

    ) participated in two sessions at a minimum interval of 1 wk. Microdialysis was done to collect 5-HT, glutamate, pyruvate, and lactate and to measure masseter 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 time point were observed between groups. Time and group had significant main effects on pain intensity. Qu-ATEBS, the 7-item evidence-based quality assessment tool, is reliable, exhibits face-validity, and has excellent discriminative validity. Tooth clenching was associated with pain, fatigue, and short-lasting mechanical hyperalgesia, but not with proprioceptive allodynia. It seems that tooth clenching is not directly related to delayed onset muscle soreness. In healthy subjects and in patients with M-TMD, levels of 5-HT, glutamate, pyruvate, and lactate were unaltered after tooth clenching. But 5-HT levels were significantly higher and blood flows significantly lower in M-TMD patients than in healthy controls at all time points. These two factors may facilitate the release, and enhance the effects, of other algesic substances that may cause pain.

  3. Differences in muscle mechanical properties between elite power and endurance athletes: a comparative study.

    Science.gov (United States)

    Loturco, Irineu; Gil, Saulo; Laurino, Cristiano Frota de Souza; Roschel, Hamilton; Kobal, Ronaldo; Cal Abad, Cesar C; Nakamura, Fabio Y

    2015-06-01

    The aim of this study was to compare muscle mechanical properties (using tensiomyography-TMG) and jumping performance of endurance and power athletes and to quantify the associations between TMG parameters and jumping performance indices. Forty-one high-level track and field athletes from power (n = 22; mean ± SD age, height, and weight were 27.2 ± 3.6 years; 180.2 ± 5.4 cm; and 79.4 ± 8.6 kg, respectively) and endurance (endurance runners and triathletes; n = 19; mean ± SD age, height, and weight were 27.1 ± 6.9 years; 169.6 ± 9.8 cm; 62.2 ± 13.1 kg, respectively) specialties had the mechanical properties of their rectus femoris (RF) and biceps femoris (BF) assessed by TMG. Muscle displacement (Dm), contraction time (Tc), and delay time (Td) were retained for analyses. Furthermore, they performed squat jumps (SJs), countermovement jumps (CMJs), and drop jumps to assess reactive strength index (RSI), using a contact platform. Comparisons between groups were performed using differences based on magnitudes, and associations were quantified by the Spearman's ρ correlation. Power athletes showed almost certain higher performance in all jumping performance indices when compared with endurance athletes (SJ = 44.9 ± 4.1 vs. 30.7 ± 6.8 cm; CMJ = 48.9 ± 4.5 vs. 33.6 ± 7.2 cm; RSI = 2.19 ± 0.58 vs. 0.84 ± 0.39, for power and endurance athletes, mean ± SD, respectively; 00/00/100, almost certain, p ≤ 0.05), along with better contractile indices reflected by lower Dm, Tc, and Td (Tc BF = 14.3 ± 2.3 vs. 19.4 ± 3.3 milliseconds; Dm BF = 1.67 ± 1.05 vs. 4.23 ± 1.75 mm; Td BF = 16.8 ± 1.6 vs. 19.6 ± 1.3 milliseconds; Tc RF = 18.3 ± 2.8 vs. 22.9 ± 4.0 milliseconds; Dm RF = 4.98 ± 3.71 vs. 8.88 ± 3.45 mm; Td RF = 17.5 ± 1.0 vs. 20.9 ± 1.6 milliseconds, for power and endurance athletes, mean ± SD, respectively; 00/00/100, almost certain, p ≤ 0.05). Moderate correlations (Spearman's ρ between -0.61 and -0.72) were found between TMG and jumping

  4. Expression of androgen receptor target genes in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Kesha Rana

    2014-10-01

    Full Text Available We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (ARΔZF2 versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR∆ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7 , p57 Kip2, Igf2 and calcineurin Aa, was increased in AR∆ZF2 muscle, and the expression of all but p57 Kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.

  5. Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.

    Science.gov (United States)

    Carnagarin, Revathy; Dharmarajan, Arun M; Dass, Crispin R

    2015-12-05

    Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. α-Actinin/titin interaction: A dynamic and mechanically stable cluster of bonds in the muscle Z-disk.

    Science.gov (United States)

    Grison, Marco; Merkel, Ulrich; Kostan, Julius; Djinović-Carugo, Kristina; Rief, Matthias

    2017-01-31

    Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important interaction are still unknown. Here, we use a dual-beam optical tweezers assay to study the mechanics of this interaction at the single-molecule level. A single interaction of α-actinin and titin turns out to be surprisingly weak if force is applied. Depending on the direction of force application, the unbinding forces can more than triple. Our results suggest a model where multiple α-actinin/Z-repeat interactions cooperate to ensure long-term stable titin anchoring while allowing the individual components to exchange dynamically.

  7. Dietary energy source affecting fat deposition mechanism, muscle fiber metabolic and overall meat quality

    Directory of Open Access Journals (Sweden)

    M. Al-Hijazeen

    2017-03-01

    Full Text Available A study was conducted to investigate the effect of two dietary energy sources, soy bean oil, and sucrose on regulatory mechanisms of meat preservation. Twenty one day-old Hubbard commercial broilers were randomly allocated into two dietary treatment groups with six replicates per treatment, and four broilers per replicate. All birds were coded for the influence of energy source: fat based diet (FD, and sugar based diet (SD. Formulated grower diets were isonitrogenous and isocaloric. The chickens were slaughtered and then boneless, skinless ground chicken tight meat was prepared. Both raw and cooked meats were analyzed for lipid and protein oxidation, and sensory panel evaluation. In addition, meat from the small muscles of the raw thigh was used to evaluate other meat quality characteristics. Proximate analyses showed no significant differences between both dietary treatments on protein, ash and moisture percentage values. Meat samples of the group that was fed FD showed higher significant values of both TBARS and total carbonyl at day 7 of storage time. However, samples of the second group (Fed SD showed lower values of both ultimate pH and water separation % using raw thigh meat. The effect of FD treatment on the meat composition appeared clearly especially on fat percentage content. In addition, meat samples obtained from chickens fed SD showed better significant values of the overall acceptability attribute. According to the current findings, sucrose could be an excellent alternative to oil in dietary broilers which improved the meat preservation bio-system, and post-mortem storage stability.

  8. Insights into the In Vivo Regulation of Glutamate Dehydrogenase from the Foot Muscle of an Estivating Land Snail

    Directory of Open Access Journals (Sweden)

    Ryan A. V. Bell

    2012-01-01

    Full Text Available Land snails, Otala lactea, survive in seasonally hot and dry environments by entering a state of aerobic torpor called estivation. During estivation, snails must prevent excessive dehydration and reorganize metabolic fuel use so as to endure prolonged periods without food. Glutamate dehydrogenase (GDH was hypothesized to play a key role during estivation as it shuttles amino acid carbon skeletons into the Krebs cycle for energy production and is very important to urea biosynthesis (a key molecule used for water retention. Analysis of purified foot muscle GDH from control and estivating conditions revealed that estivated GDH was approximately 3-fold more active in catalyzing glutamate deamination as compared to control. This kinetic difference appears to be regulated by reversible protein phosphorylation, as indicated by ProQ Diamond phosphoprotein staining and incubations that stimulate endogenous protein kinases and phosphatases. The increased activity of the high-phosphate form of GDH seen in the estivating land snail foot muscle correlates well with the increased use of amino acids for energy and increased synthesis of urea for water retention during prolonged estivation.

  9. Microvascular response of striated muscle to metal debris. A comparative in vivo study with titanium and stainless steel.

    Science.gov (United States)

    Kraft, C N; Diedrich, O; Burian, B; Schmitt, O; Wimmer, M A

    2003-01-01

    Wear products of metal implants are known to induce biological events which may have profound consequences for the microcirculation of skeletal muscle. Using the skinfold chamber model and intravital microscopy we assessed microcirculatory parameters in skeletal muscle after confrontation with titanium and stainless-steel wear debris, comparing the results with those of bulk materials. Implantation of stainless-steel bulk and debris led to a distinct activation of leukocytes combined with a disruption of the microvascular endothelial integrity and massive leukocyte extravasation. While animals with bulk stainless steel showed a tendency to recuperation, stainless-steel wear debris induced such severe inflammation and massive oedema that the microcirculation broke down within 24 hours after implantation. Titanium bulk caused only a transient increase in leukocyte-endothelial cell interaction within the first 120 minutes and no significant change in macromolecular leakage, leukocyte extravasation or venular diameter. Titanium wear debris produced a markedly lower inflammatory reaction than stainless-steel bulk, indicating that a general benefit of bulk versus debris could not be claimed. Depending on its constituents, wear debris is capable of eliciting acute inflammation which may result in endothelial damage and subsequent failure of microperfusion. Our results indicate that not only the bulk properties of orthopaedic implants but also the microcirculatory implications of inevitable wear debris play a pivotal role in determining the biocompatibility of an implant.

  10. Real time monitoring in-vivo micro-environment through the wound heal mechanism

    Science.gov (United States)

    Yan, Jack

    2013-02-01

    One of the In-vivo system's challenge is real time display the sensing information. Usually Ultrasound, CT, MRI, PET are used to get the internal information, this thesis proposed another approach to address the display challenge. Special nano-particles are in-taken or injected to living subject (usually into blood circulation) to sense and collect psychological information when the active particles pass through the tissues of interest. Using the wound healing mechanism, these activated particles (Information collected) can be drifted out to the wound area and adhibited close to the skin, then skin can show different color if the activated particles are concentrated enough in the specific area to create a skin screen. The skin screen can display the blood status, internal organ's temperature, pressure depending the nano-particles' function and their pathway. This approach can also be used to display in-body video if the particles are sensitive and selective enough. In the future, the skin screen can be bio-computer's monitor. The wound healing in an animal model normally divides in four phase: Hemostasis, Inflammation, Proliferation and Maturation. Hemostasis phase is to form a stable clot sealing the damaged vessel. Inflammation phase causes the blood vessels to become leaky releasing plasma and PMN's (polymorphonucleocytes) into the surrounding tissue and provide the first line of defense against infection. Proliferation phase involves replacement of dermal tissues and sometimes subdermal tissues in deeper wounds as well as contraction of the wound. Maturation phase remodels the dermal tissues mainly by fibroblast to produce greater tensile strength. The skin screen wound will be carefully controlled to be triggered at dermis layer.

  11. G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

    Science.gov (United States)

    White, James P; Wrann, Christiane D; Rao, Rajesh R; Nair, Sreekumaran K; Jedrychowski, Mark P; You, Jae-Sung; Martínez-Redondo, Vicente; Gygi, Steven P; Ruas, Jorge L; Hornberger, Troy A; Wu, Zhidan; Glass, David J; Piao, Xianhua; Spiegelman, Bruce M

    2014-11-04

    Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

  12. MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms.

    Directory of Open Access Journals (Sweden)

    Valentina Conti

    Full Text Available Rett syndrome (RTT is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.

  13. Animal model for angiotensin II effects in the internal anal sphincter smooth muscle: mechanism of action.

    Science.gov (United States)

    Fan, Ya-Ping; Puri, Rajinder N; Rattan, Satish

    2002-03-01

    Effect of ANG II was investigated in in vitro smooth muscle strips and in isolated smooth muscle cells (SMC). Among different species, rat internal and sphincter (IAS) smooth muscle showed significant and reproducible contraction that remained unmodified by different neurohumoral inhibitors. The AT(1) antagonist losartan but not AT(2) antagonist PD-123319 antagonized ANG II-induced contraction of the IAS smooth muscle and SMC. ANG II-induced contraction of rat IAS smooth muscle and SMC was attenuated by tyrosine kinase inhibitors genistein and tyrphostin, protein kinase C (PKC) inhibitor H-7, Ca(2+) channel blocker nicardipine, Rho kinase inhibitor Y-27632 or p(44/42) mitogen-activating protein kinase (MAPK(44/42)) inhibitor PD-98059. Combinations of nicardipine and H-7, Y-27632, and PD-98059 caused further attenuation of the ANG II effects. Western blot analyses revealed the presence of both AT(1) and AT(2) receptors. We conclude that ANG II causes contraction of rat IAS smooth muscle by the activation of AT(1) receptors at the SMC and involves multiple intracellular pathways, influx of Ca(2+), and activation of PKC, Rho kinase, and MAPK(44/42).

  14. Development of an in vivo visual robot system with a magnetic anchoring mechanism and a lens cleaning mechanism for laparoendoscopic single-site surgery (LESS).

    Science.gov (United States)

    Feng, Haibo; Dong, Dinghui; Ma, Tengfei; Zhuang, Jinlei; Fu, Yili; Lv, Yi; Li, Liyi

    2017-12-01

    Surgical robot systems which can significantly improve surgical procedures have been widely used in laparoendoscopic single-site surgery (LESS). For a relative complex surgical procedure, the development of an in vivo visual robot system for LESS can effectively improve the visualization for surgical robot systems. In this work, an in vivo visual robot system with a new mechanism for LESS was investigated. A finite element method (FEM) analysis was carried out to ensure the safety of the in vivo visual robot during the movement, which was the most important concern for surgical purposes. A master-slave control strategy was adopted, in which the control model was established by off-line experiments. The in vivo visual robot system was verified by using a phantom box. The experiment results show that the robot system can successfully realize the expected functionalities and meet the demands of LESS. The experiment results indicate that the in vivo visual robot with high manipulability has great potential in clinical application. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Nuclear fusion-independent smooth muscle differentiation of human adipose-derived stem cells induced by a smooth muscle environment.

    Science.gov (United States)

    Zhang, Rong; Jack, Gregory S; Rao, Nagesh; Zuk, Patricia; Ignarro, Louis J; Wu, Benjamin; Rodríguez, Larissa V

    2012-03-01

    Human adipose-derived stem cells hASC have been isolated and were shown to have multilineage differentiation capacity. Although both plasticity and cell fusion have been suggested as mechanisms for cell differentiation in vivo, the effect of the local in vivo environment on the differentiation of adipose-derived stem cells has not been evaluated. We previously reported the in vitro capacity of smooth muscle differentiation of these cells. In this study, we evaluate the effect of an in vivo smooth muscle environment in the differentiation of hASC. We studied this by two experimental designs: (a) in vivo evaluation of smooth muscle differentiation of hASC injected into a smooth muscle environment and (b) in vitro evaluation of smooth muscle differentiation capacity of hASC exposed to bladder smooth muscle cells. Our results indicate a time-dependent differentiation of hASC into mature smooth muscle cells when these cells are injected into the smooth musculature of the urinary bladder. Similar findings were seen when the cells were cocultured in vitro with primary bladder smooth muscle cells. Chromosomal analysis demonstrated that microenvironment cues rather than nuclear fusion are responsible for this differentiation. We conclude that cell plasticity is present in hASCs, and their differentiation is accomplished in the absence of nuclear fusion. Copyright © 2011 AlphaMed Press.

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

    Science.gov (United States)

    Grassi, Bruno; Quaresima, Valentina

    2016-09-01

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

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

    Science.gov (United States)

    Grassi, Bruno; Quaresima, Valentina

    2016-09-01

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

  18. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Somik [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yin, Hongshan [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Cardiovascular Medicine, Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei (China); Nam, Deokhwa [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Li, Yong [Department of Pediatric Surgery, Center for Stem Cell Research and Regenerative Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Ma, Ke, E-mail: kma@houstonmethodist.org [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States)

    2015-02-01

    Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1{sup −/−} mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation.

  19. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

    International Nuclear Information System (INIS)

    Chatterjee, Somik; Yin, Hongshan; Nam, Deokhwa; Li, Yong; Ma, Ke

    2015-01-01

    Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1 −/− mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation

  20. Application of the principles of systems biology and Wiener's cybernetics for analysis of regulation of energy fluxes in muscle cells in vivo.

    Science.gov (United States)

    Guzun, Rita; Saks, Valdur

    2010-03-08

    The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener's cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener's cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures - intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations of

  1. Application of the Principles of Systems Biology and Wiener’s Cybernetics for Analysis of Regulation of Energy Fluxes in Muscle Cells in Vivo

    Science.gov (United States)

    Guzun, Rita; Saks, Valdur

    2010-01-01

    The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener’s cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener’s cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures – intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations

  2. Quantum-mechanical simulations for in vivo MR spectroscopy: Principles and possibilities demonstrated with the program NMRScopeB

    Czech Academy of Sciences Publication Activity Database

    Starčuk jr., Zenon; Starčuková, Jana

    2017-01-01

    Roč. 529, JULY (2017), s. 79-97 ISSN 0003-2697 R&D Projects: GA MŠk(CZ) LO1212; GA MŠk ED0017/01/01; GA ČR(CZ) GA15-12607S Institutional support: RVO:68081731 Keywords : magnetic resonance spectroscopy * quantum mechanical simulation * metabolite concentration quantitation * in vivo spectroscopy Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Biophysics Impact factor: 2.334, year: 2016

  3. Correction to: Direct effects of doxorubicin on skeletal muscle contribute to fatigue

    NARCIS (Netherlands)

    Norren, van K.; Helvoort, van A.; Agriles, J.M.; Tuijl, van S.; Arts, K.; Gorselink, M.; Laviano, A.; Kegler, D.; Haagsman, H.P.; Beek, van der E.M.

    2009-01-01

    Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation

  4. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Albers, Peter Hjorth; Rose, Adam John

    2011-01-01

    The aim of this study was to investigate the molecular mechanisms regulating FAT/CD36 translocation and fatty acid uptake in skeletal muscle during contractions. In one model, WT and AMPK KD mice were exercised or EDL and SOL muscles were contracted, ex vivo. In separate studies, FAT/CD36 translo...

  5. Artificial muscle: facts and fiction.

    Science.gov (United States)

    Schaub, Marcus C

    2011-12-19

    Mechanical devices are sought to support insufficient or paralysed striated muscles including the failing heart. Nickel-titanium alloys (nitinol) present the following two properties: (i) super-elasticity, and (ii) the potential to assume different crystal structures depending on temperature and/or stress. Starting from the martensite state nitinol is able to resume the austenite form (state of low potential energy and high entropy) even against an external resistance. This one-way shape change is deployed in self-expanding vascular stents. Heating induces the force generating transformation from martensite to the austenite state while cooling induces relaxation back to the martensite state. This two-way shape change oscillating between the two states may be used in cyclically contracting support devices of silicon-coated nitinol wires. Such a contractile device sutured to the right atrium has been tested in vitro in a bench model and in vivo in sheep. The contraction properties of natural muscles, specifically of the myocardium, and the tight correlation with ATP production by oxidative phosphorylation in the mitochondria is briefly outlined. Force development by the nitinol device cannot be smoothly regulated as in natural muscle. Its mechanical impact is forced onto the natural muscle regardless of the actual condition with regard to metabolism and Ca2+-homeostasis. The development of artificial muscle on the basis of nitinol wires is still in its infancy. The nitinol artificial muscle will have to prove its viability in the various clinical settings.

  6. The Teratogenicity and the Action Mechanism of Gallic Acid Relating with Brain and Cervical Muscles

    Science.gov (United States)

    Hsieh, Chiu Lan; Lin, Chien-Hong; Chen, Kuan Chou; Peng, Chiung-Chi; Peng, Robert Y.

    2015-01-01

    Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) and other flavanoids are extensively used in nutraceuticals because of their antioxidant and antiinflammatory properties. While examining whether GA is effective in alleviating valproic-acid-induced teratogenesis in a chicken embryo model (CEM), we observed embryo hemorrhage and liposis in the musculi longissimus cervicis. We conducted this study to determine whether GA is inherently teratogenic and the extent to which the risk can be transferred to fetuses. A CEM was used to administer GA at 2, 6, 10, and 14 μM. GA at 2 μM did not exhibit cytotoxicity. At 6, 10, and 14 μM, GA caused severe decreases in body and liver weights, causing -5.6%, -21.3%, and -27.5% body weights and 4.0, 3.8, and 3.2-g, liver weights, respectively, in day-1 chicks. The optimal alive birth rate (or damaging rate) reached 33.3%, 39.4%, and 29.2% at 6, 10, and 14 μM GA, respectively. The damaged tissue was primarily cervical muscle (musculi longissimus cervicis), as evidenced by liposis, Zenker’s necrosis, and hemolysis. The erythrocyte, hemoglobin, eosinophil, lymphocyte, and monocyte counts were severely reduced and PPAR-α was downregulated, whereas the Ras/Raf/JAK/STAT pathway was upregulated. The GA dose required to induce teratogenesis was ≥ 6 μM (1.02 mg/kg), which can be easily consumed by pregnant women in typical teas such as Chinese Pu-’Er and Chinese black teas, indicating a potential risk to human fetuses. GA at doses ≥ 1.02 mg/kg of body weight potentially causes characteristic cerebral hemolysis and liposis in the musculi longissimus cervicis. The mechanism of action of GA is multidisciplinary: The liposis can be ascribed to downregulation of PPAR-α; the erythrocyte hemolysis can be attributed to its unique autooxidative and prooxidant behavior and the inhibition of carbonic anhydrase; and the proliferation and differentiation deficits can be attributed to the upregulation of the Ras/Raf/JAK/STAT pathway. PMID

  7. Limitations of rotational manoeuvrability in insects and hummingbirds: evaluating the effects of neuro-biomechanical delays and muscle mechanical power.

    Science.gov (United States)

    Liu, Pan; Cheng, Bo

    2017-07-01

    Flying animals ranging in size from fruit flies to hummingbirds are nimble fliers with remarkable rotational manoeuvrability. The degrees of manoeuvrability among these animals, however, are noticeably diverse and do not simply follow scaling rules of flight dynamics or muscle power capacity. As all manoeuvres emerge from the complex interactions of neural, physiological and biomechanical processes of an animal's flight control system, these processes give rise to multiple limiting factors that dictate the maximal manoeuvrability attainable by an animal. Here using functional models of an animal's flight control system, we investigate the effects of three such limiting factors, including neural and biomechanical (from limited flapping frequency) delays and muscle mechanical power, for two insect species and two hummingbird species, undergoing roll, pitch and yaw rotations. The results show that for animals with similar degree of manoeuvrability, for example, fruit flies and hummingbirds, the underlying limiting factors are different, as the manoeuvrability of fruit flies is only limited by neural delays and that of hummingbirds could be limited by all three factors. In addition, the manoeuvrability also appears to be the highest about the roll axis as it requires the least muscle mechanical power and can tolerate the largest neural delays. © 2017 The Author(s).

  8. Exploring the vascular smooth muscle receptor landscape in vivo: ultrasound Doppler versus near-infrared spectroscopy assessments.

    Science.gov (United States)

    Ives, Stephen J; Fadel, Paul J; Brothers, R Matthew; Sander, Mikael; Wray, D Walter

    2014-03-01

    Ultrasound Doppler and near-infrared spectroscopy (NIRS) are routinely used for noninvasive monitoring of peripheral hemodynamics in both clinical and experimental settings. However, the comparative ability of these methodologies to detect changes in microvascular and whole limb hemodynamics during pharmacological manipulation of vascular smooth muscle receptors located at varied locations within the arterial tree is unknown. Thus, in 10 healthy subjects (25 ± 2 yr), changes in resting leg blood flow (ultrasound Doppler; femoral artery) and muscle oxygenation (oxyhemoglobin + oxymyoglobin; vastus lateralis) were simultaneously evaluated in response to intra-arterial infusions of phenylephrine (PE, 0.025-0.8 μg·kg(-1)·min(-1)), BHT-933 (2.5-40 μg·kg(-1)·min(-1)), and angiotensin II (ANG II, 0.5-8 ng·kg(-1)·min(-1)). All drugs elicited significant dose-dependent reductions in leg blood flow and oxyhemoglobin + oxymyoglobin. Significant relationships were found between ultrasound Doppler and NIRS changes across doses of PE (r(2) = 0.37 ± 0.08), BHT-933 (r(2) = 0.74 ± 0.06), and ANG II (r(2) = 0.68 ± 0.13), with the strongest relationships evident with agonists for receptors located preferentially "downstream" in the leg microcirculation (BHT-933 and ANG II). Analyses of drug potency revealed similar EC50 between ultrasound Doppler and NIRS measurements for PE (0.06 ± 0.02 vs. 0.10 ± 0.01), BHT-933 (5.0 ± 0.9 vs. 4.5 ± 1.3), and ANG II (1.4 ± 0.8 vs. 1.3 ± 0.3). These data provide evidence that both ultrasound Doppler and NIRS track pharmacologically induced changes in peripheral hemodynamics and are equally capable of determining drug potency. However, considerable disparity was observed between agonist infusions targeting different levels of the arterial tree, suggesting that receptor landscape is an important consideration for proper interpretation of hemodynamic monitoring with these methodologies.

  9. Mechanosensing of matrix by stem cells: From matrix heterogeneity, contractility, and the nucleus in pore-migration to cardiogenesis and muscle stem cells in vivo.

    Science.gov (United States)

    Smith, Lucas; Cho, Sangkyun; Discher, Dennis E

    2017-11-01

    Stem cells are particularly 'plastic' cell types that are induced by various cues to become specialized, tissue-functional lineages by switching on the expression of specific gene programs. Matrix stiffness is among the cues that multiple stem cell types can sense and respond to. This seminar-style review focuses on mechanosensing of matrix elasticity in the differentiation or early maturation of a few illustrative stem cell types, with an intended audience of biologists and physical scientists. Contractile forces applied by a cell's acto-myosin cytoskeleton are often resisted by the extracellular matrix and transduced through adhesions and the cytoskeleton ultimately into the nucleus to modulate gene expression. Complexity is added by matrix heterogeneity, and careful scrutiny of the evident stiffness heterogeneity in some model systems resolves some controversies concerning matrix mechanosensing. Importantly, local stiffness tends to dominate, and 'durotaxis' of stem cells toward stiff matrix reveals a dependence of persistent migration on myosin-II force generation and also rigid microtubules that confer directionality. Stem and progenitor cell migration in 3D can be further affected by matrix porosity as well as stiffness, with nuclear size and rigidity influencing niche retention and fate choices. Cell squeezing through rigid pores can even cause DNA damage and genomic changes that contribute to de-differentiation toward stem cell-like states. Contraction of acto-myosin is the essential function of striated muscle, which also exhibit mechanosensitive differentiation and maturation as illustrated in vivo by beating heart cells and by the regenerative mobilization of skeletal muscle stem cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release

    Directory of Open Access Journals (Sweden)

    Thomas E. Jensen

    2014-10-01

    Full Text Available Understanding how muscle contraction orchestrates insulin-independent muscle glucose transport may enable development of hyperglycemia-treating drugs. The prevailing concept implicates Ca2+ as a key feed forward regulator of glucose transport with secondary fine-tuning by metabolic feedback signals through proteins such as AMPK. Here, we demonstrate in incubated mouse muscle that Ca2+ release is neither sufficient nor strictly necessary to increase glucose transport. Rather, the glucose transport response is associated with metabolic feedback signals through AMPK, and mechanical stress-activated signals. Furthermore, artificial stimulation of AMPK combined with passive stretch of muscle is additive and sufficient to elicit the full contraction glucose transport response. These results suggest that ATP-turnover and mechanical stress feedback are sufficient to fully increase glucose transport during muscle contraction, and call for a major reconsideration of the established Ca2+ centric paradigm.

  11. Mechanical properties of mammalian single smooth muscle cells. I. A low cost large range microforce transducer.

    NARCIS (Netherlands)

    J.J. Glerum (Jacobus); R. van Mastrigt (Ron)

    1990-01-01

    textabstractA transducer has been developed for measuring the minute forces generated during isometric contractions (1.0-10.0 microN) of single smooth muscle cells from the pig urinary bladder and the human uterus. In addition to its high sensitivity, resolution and stability (100 mV microN-1, and

  12. Mechanical and neural stretch responses of the human soleus muscle at different walking speeds

    DEFF Research Database (Denmark)

    Cronin, Neil J; Ishikawa, Masaki; Grey, Michael J

    2009-01-01

    responses. Twelve healthy subjects walked on a treadmill with the left leg attached to an actuator capable of rapidly dorsiflexing the ankle joint. Ultrasound was used to measure fascicle lengths in SOL during walking, and surface electromyography (EMG) was used to record muscle activation. Dorsiflexion...

  13. Rectus extraocular muscle paths and decompression surgery for Graves orbitopathy: mechanism of motility disturbances

    NARCIS (Netherlands)

    Abràmoff, Michael D.; Kalmann, Rachel; de Graaf, Mieke E. L.; Stilma, Jan S.; Mourits, Maarten P.

    2002-01-01

    PURPOSE: To study possible causes of motility disturbances that may result from orbital decompression surgery in patients with Graves orbitopathy and especially the role of rectus extraocular muscle paths. METHODS: Sixteen patients with Graves orbitopathy were studied before and 3 to 6 months after

  14. Quasi-static analysis of muscle forces in the shoulder mechanism during wheelchair propulsion

    NARCIS (Netherlands)

    van der Helm, Frans C T; Veeger, H. E J

    During wheelchair propulsion the largest net joint moments and net joint powers are generated around the shoulder. The analysis of the contribution of arm- and shoulder muscles to the joint moments could explain the low efficiency of wheelchair propulsion. Basically, it is assumed that a large

  15. Sepsis and development impede muscle protein synthesis in neonatal pigs by different ribosomal mechanisms

    Science.gov (United States)

    In muscle, sepsis reduces protein synthesis (MPS) by restraining translation in neonates and adults. Even though protein accretion decreases with development as neonatal MPS rapidly declines by maturation, the changes imposed by development on the sepsis-associated decrease in MPS have not been desc...

  16. Rac1- a novel regulator of contraction-stimulated glucose uptake in skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian

    2014-01-01

    -stimulated glucose uptake in skeletal muscle, since muscle-specific Rac1 knockout mice display reduced ex vivo contraction- and in vivo exercise-stimulated glucose uptake in skeletal muscle. The molecular mechanisms by which Rac1 regulate glucose uptake is presently unknown. However, recent studies link Rac1......Muscle contraction stimulates muscle glucose uptake by facilitating translocation of the glucose transporter 4 from intracellular locations to the cell surface, which allows for diffusion of glucose into the myofibers. However, the intracellular mechanisms regulating this process are not well...... understood. The GTPase, Rac1 has, until recently, only been investigated with regards to its involvement in insulin-stimulated glucose uptake. However, we recently found that Rac1 is activated during muscle contraction and exercise in mice and humans. Remarkably, Rac1 seems to be necessary for exercise/contraction...

  17. Mechanical muscle function and lean body mass during supervised strength training and testosterone therapy in aging men with low-normal testosterone levels

    DEFF Research Database (Denmark)

    Kvorning, Thue; Christensen, Louise L; Madsen, Klavs

    2013-01-01

    To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study.......To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low-normal testosterone levels in a randomized, double-blind, placebo-controlled 24-week study....

  18. Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo

    Directory of Open Access Journals (Sweden)

    Brian C. Jensen

    2017-06-01

    Full Text Available Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR, whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR and platelet-derived growth factor receptor (PDGFR.TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities. Cardiotoxicity is very rare in patients treated with erlotinib, but considerably more common after sunitinib treatment. We hypothesized that the deleterious effects of TKIs on the heart were related to their impact on cardiac metabolism. Methods: Female FVB/N mice (10/group were treated with therapeutic doses of sunitinib (40 mg/kg, erlotinib (50 mg/kg, or vehicle daily for two weeks. Echocardiographic assessment of the heart in vivo was performed at baseline and on Day 14. Heart, skeletal muscle, liver and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Results: Compared to vehicle-treated controls, sunitinib-treated mice had significant decreases in systolic function, whereas erlotinib-treated mice did not. Non-targeted metabolomics analysis of heart identified significant decreases in docosahexaenoic acid (DHA, arachidonic acid (AA/ eicosapentaenoic acid (EPA, O-phosphocolamine, and 6-hydroxynicotinic acid after sunitinib treatment. DHA was significantly decreased in skeletal muscle (quadriceps femoris, while elevated cholesterol was identified in liver and elevated ethanolamine identified in serum. In contrast, erlotinib affected only one metabolite (spermidine significantly increased. Conclusions: Mice treated with sunitinib exhibited systolic dysfunction within two weeks, with significantly lower heart and skeletal muscle

  19. Striated muscle microvascular response to silver implants: A comparative in vivo study with titanium and stainless steel.

    Science.gov (United States)

    Kraft, C N; Hansis, M; Arens, S; Menger, M D; Vollmar, B

    2000-02-01

    Local microvascular perfusion is the primary line of defense of tissue against microorganisms and plays a considerable role in reparative processes. The impairment of the microcirculation by a biomaterial may therefore have profound consequences. Silver is known to have excellent antimicrobial activity and, although regional and systemic toxic effects have been described, silver is regularly discussed as an implant material in bone surgery. Because little is known about the influence of silver implants on the adjacent host tissue microvasculature, we studied in vivo nutritive perfusion and leukocytic response, and compared these results with those of the conventionally used materials titanium and stainless steel. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, the implantation of a commercially pure silver sample led to a distinct and persistent activation of leukocytes combined with a marked disruption of the microvascular endothelial integrity, massive leukocyte extravasation, and considerable venular dilation. Whereas animals with stainless-steel implants showed a moderate increase in these parameters with a tendency to recuperate, titanium implants caused only a transient increase of leukocyte-endothelial cell interaction within the first 120 min and no significant change in macromolecular leakage, leukocyte extravasation and venular diameter. After 3 days, five of six preparations with silver samples showed severe inflammation and massive edema. Thus, the use of silver as an implant material should be critically judged despite its bactericidal properties. The implant material titanium seems to be well tolerated by the local vascular system and currently represents the golden standard. Copyright 2000 John Wiley & Sons, Inc.

  20. Stretching skeletal muscle: chronic muscle lengthening through sarcomerogenesis.

    Directory of Open Access Journals (Sweden)

    Alexander M Zöllner

    Full Text Available Skeletal muscle responds to passive overstretch through sarcomerogenesis, the creation and serial deposition of new sarcomere units. Sarcomerogenesis is critical to muscle function: It gradually re-positions the muscle back into its optimal operating regime. Animal models of immobilization, limb lengthening, and tendon transfer have provided significant insight into muscle adaptation in vivo. Yet, to date, there is no mathematical model that allows us to predict how skeletal muscle adapts to mechanical stretch in silico. Here we propose a novel mechanistic model for chronic longitudinal muscle growth in response to passive mechanical stretch. We characterize growth through a single scalar-valued internal variable, the serial sarcomere number. Sarcomerogenesis, the evolution of this variable, is driven by the elastic mechanical stretch. To analyze realistic three-dimensional muscle geometries, we embed our model into a nonlinear finite element framework. In a chronic limb lengthening study with a muscle stretch of 1.14, the model predicts an acute sarcomere lengthening from 3.09[Formula: see text]m to 3.51[Formula: see text]m, and a chronic gradual return to the initial sarcomere length within two weeks. Compared to the experiment, the acute model error was 0.00% by design of the model; the chronic model error was 2.13%, which lies within the rage of the experimental standard deviation. Our model explains, from a mechanistic point of view, why gradual multi-step muscle lengthening is less invasive than single-step lengthening. It also explains regional variations in sarcomere length, shorter close to and longer away from the muscle-tendon interface. Once calibrated with a richer data set, our model may help surgeons to prevent muscle overstretch and make informed decisions about optimal stretch increments, stretch timing, and stretch amplitudes. We anticipate our study to open new avenues in orthopedic and reconstructive surgery and enhance

  1. Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome.

    Science.gov (United States)

    García-Herrera, Claudio M; Celentano, Diego J; Herrera, Emilio A

    2017-03-01

    Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention.

  2. Mechanical stress-induced apoptosis of nucleus pulposus cells: an in vitro and in vivo rat model.

    Science.gov (United States)

    Kuo, Yi-Jie; Wu, Lien-Chen; Sun, Jui-Sheng; Chen, Ming-Hong; Sun, Man-Ger; Tsuang, Yang-Hwei

    2014-03-01

    Un-physiological loads play an important role in the degenerative process of inter-vertebral discs (IVD). In this study, we used an in vitro and in vivo rat model to investigate the mechanism of nucleus pulposus (NP) cells apoptosis induced by mechanical stress. Static compressive load to IVDs of rat tails was used as the in vivo model. For the in vitro model, NP cells were tested under the physiological and un-physiological loading. For histological examination, apoptotic index study, and apoptotic gene expression, we also selected cytokines [bone morphogenetic protein (BMP)-2/7, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)] to be analyzed. Under mechanical loading, cellular density was significantly decreased, but there was an increase of TUNEL positive cells and apoptosis index. In a dose-dependent manner; the necrosis became apparent in the un-physiologic strain. The selected cytokines (BMP-2/7, IGF-1, PDGF) can significantly reduce the percentage of apoptotic and necrotic cells. We conclude that the intrinsic (mitochondrial) apoptotic pathway plays an important role in the compressive load-induced apoptosis of NP cells. Combination therapy reducing the mechanical load and selected cytokines (BMP-2/7, IGF-1 and PDGF) may have considerable promise in the treatment of spine disc degeneration.

  3. A Novel Regulatory Mechanism of Smooth Muscle α-Actin Expression by NRG-1/circACTA2/miR-548f-5p Axis.

    Science.gov (United States)

    Sun, Yan; Yang, Zhan; Zheng, Bin; Zhang, Xin-Hua; Zhang, Man-Li; Zhao, Xue-Shan; Zhao, Hong-Ye; Suzuki, Toru; Wen, Jin-Kun

    2017-09-01

    Neuregulin-1 (NRG-1) includes an extracellular epidermal growth factor-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor-β1, its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB (erythroblastic leukemia viral oncogene homolog) receptor. However, NRG-1-ICD function in VSMCs remains unknown. Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs. Immunofluorescence staining, Western blotting, and quantitative real-time polymerase chain reaction showed that NRG-1 was expressed in rat, mouse, and human VSMCs and was upregulated and cleaved in response to transforming growth factor-β1. In the cytoplasm of HASMCs (human aortic smooth muscle cells), the NRG-1-ICD participated in filamentous actin formation by interacting with α-SMA (smooth muscle α-actin). In the nucleus, the Nrg-1-ICD induced circular ACTA2 (alpha-actin-2; circACTA2) formation by recruitment of the zinc-finger transcription factor IKZF1 (IKAROS family zinc finger 1) to the first intron of α-SMA gene. We further confirmed that circACTA2, acting as a sponge binding microRNA (miR)-548f-5p, interacted with miR-548f-5p targeting 3' untranslated region of α-SMA mRNA, which in turn relieves miR-548f-5p repression of the α-SMA expression and thus upregulates α-SMA expression, thereby facilitating stress fiber formation and cell contraction in HASMCs. Accordingly, in vivo studies demonstrated that the localization of the interaction of circACTA2 with miR-548f-5p is significantly decreased in human intimal hyperplastic arteries compared with normal arteries, implicating that dysregulation of circACTA2 and miR-548f-5p expression is involved in intimal hyperplasia. These results suggest that circACTA2 mediates NRG-1-ICD regulation of α-SMA expression in HASMCs via the NRG-1-ICD/circACTA2/miR-548f-5p axis. Our data provide a molecular

  4. The Physiological Mechanisms of Effect of Vitamins and Amino Acids on Tendon and Muscle Healing: A Systematic Review.

    Science.gov (United States)

    Tack, Christopher; Shorthouse, Faye; Kass, Lindsy

    2018-05-01

    To evaluate the current literature via systematic review to ascertain whether amino acids/vitamins provide any influence on musculotendinous healing and if so, by which physiological mechanisms. EBSCO, PubMed, ScienceDirect, Embase Classic/Embase, and MEDLINE were searched using terms including "vitamins," "amino acids," "healing," "muscle," and "tendon." The primary search had 479 citations, of which 466 were excluded predominantly due to nonrandomized design. Randomized human and animal studies investigating all supplement types/forms of administration were included. Critical appraisal of internal validity was assessed using the Cochrane risk of Bias Tool or the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias Tool for human and animal studies, respectively. Two reviewers performed duel data extraction. Twelve studies met criteria for inclusion: eight examined tendon healing and four examined muscle healing. All studies used animal models, except two human trials using a combined integrator. Narrative synthesis was performed via content analysis of demonstrated statistically significant effects and thematic analysis of proposed physiological mechanisms of intervention. Vitamin C/taurine demonstrated indirect effects on tendon healing through antioxidant activity. Vitamin A/glycine showed direct effects on extracellular matrix tissue synthesis. Vitamin E shows an antiproliferative influence on collagen deposition. Leucine directly influences signaling pathways to promote muscle protein synthesis. Preliminary evidence exists, demonstrating that vitamins and amino acids may facilitate multilevel changes in musculotendinous healing; however, recommendations on clinical utility should be made with caution. All animal studies and one human study showed high risk of bias with moderate interobserver agreement (k = 0.46). Currently, there is limited evidence to support the use of vitamins and amino acids for musculotendinous injury. Both

  5. The role of tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in mediating autophagy in myositis skeletal muscle: A potential non-immune mechanism of muscle damage

    Science.gov (United States)

    Alger, Heather M.; Raben, Nina; Pistilli, Emidio; Francia, Dwight; Rawat, Rashmi; Getnet, Derese; Ghimbovschi, Svetlana; Chen, Yi-Wen; Lundberg, Ingrid E.; Nagaraju, Kanneboyina

    2011-01-01

    Objective Multinucleated cells are relatively resistant to classical apoptosis, and the factors initiating cell-death and damage in myositis are not well defined. We hypothesized that non-immune autophagic cell death may play a role in muscle fiber damage. Recent literature indicates that tumor necrosis factor-alpha-related apoptosis inducing ligand (TRAIL) may induce both NFκB (nuclear factor kappa-light chain enhancer of activated B cells) activation and autophagic cell death in other systems. Here, we have investigated its role in cell death and pathogenesis in vitro and in vivo using myositis (human and mouse) muscle tissues. Methods Gene expression profiling indicated that expression of TRAIL and several autophagy markers was specifically upregulated in myositis muscle tissue; these results were confirmed by immunohistochemistry and immunoblotting. We also analyzed TRAIL-induced cell death (apoptosis and autophagy) and NFκB activation in vitro in cultured cells. Results TRAIL was expressed predominantly in muscle fibers of myositis, but not in biopsies from normal or other dystrophic-diseased muscle. Autophagy markers were upregulated in human and mouse models of myositis. TRAIL expression was restricted to regenerating/atrophic areas of muscle fascicles, blood vessels, and infiltrating lymphocytes. TRAIL induced NFκB activation and IκB degradation in cultured cells that are resistant to TRAIL-induced apoptosis but undergo autophagic cell death. Conclusion Our data demonstrate that TRAIL is expressed in myositis muscle and may mediate both activation of NFκB and autophagic cell death in myositis. Thus, this non-immune pathway may be an attractive target for therapeutic intervention in myositis. PMID:21769834

  6. On the mechanism by which dietary nitrate improves human skeletal muscle function

    Directory of Open Access Journals (Sweden)

    Charles eAffourtit

    2015-07-01

    Full Text Available Inorganic nitrate is present at high levels in beetroot and celery, and in green leafy vegetables such as spinach and lettuce. Though long believed inert, nitrate can be reduced to nitrite in the human mouth and, further, under hypoxia and/or low pH, to nitric oxide. Dietary nitrate has thus been associated favourably with nitric-oxide-regulated processes including blood flow and energy metabolism. Indeed, the therapeutic potential of dietary nitrate in cardiovascular disease and metabolic syndrome – both ageing-related medical disorders – has attracted considerable recent research interest. We and others have shown that dietary nitrate supplementation lowers the oxygen cost of human exercise, as less respiratory activity appears to be required for a set rate of skeletal muscle work. This striking observation predicts that nitrate benefits the energy metabolism of human muscle, increasing the efficiency of either mitochondrial ATP synthesis and/or of cellular ATP-consuming processes. In this mini-review, we evaluate experimental support for the dietary nitrate effects on muscle bioenergetics and we critically discuss the likelihood of nitric oxide as the molecular mediator of such effects.

  7. MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

    Science.gov (United States)

    Brøns, Charlotte; Grunnet, Louise Groth

    2017-02-01

    Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver. © 2017 European Society of Endocrinology.

  8. Nanoparticulate-induced toxicity and related mechanism in vitro and in vivo

    International Nuclear Information System (INIS)

    Kim, Hye Won; Ahn, Eun-Kyung; Jee, Bo Keun; Yoon, Hyoung-Kyu; Lee, Kweon Haeng; Lim, Young

    2009-01-01

    In urban areas, the quantity of exhaust particles from vehicle emissions is tremendous and has been regarded as the main contributor to particulate matter (PM) pollution. Recently, the nano-sized PM on public health has begun to raise the attention. The increased toxicity of nanoparticulate can be largely explained by their small size, high airborne concentration, extensive surface area and high content of organic carbon and transition metals. We have attempted to address the toxicity of nano sized-particlulate matter by comparing various particulates including micro-SiO 2 (mSiO 2 ), nano-SiO 2 (nSiO 2 ), micro-TiO 2 (mTiO 2 ), and nano-TiO 2 (nTiO 2 ) in RAW264.7 cells and in vivo. The cell viability of all particulates decreased dose dependently. 24-h incubation with nSiO2 demonstrated apoptosis in RAW264.7 using Annexin-V binding immunofluorescent microscopy, but not in any other particulates. In vivo, cytotoxicity of nanosized was higher than micro-sized particulates. As higher the concentration of particulates, the more pulmonary injury and neutrophilic infiltration were observed in nano-sized than micro-sized particulates, respectively. Particularly, 5.0 mg/kg of mTiO 2 never shows any increase of neutrophile even with high cellularity of total cells and macrophages. From these results, we suggested that particulate-induced respiratory toxicity be influenced by component, size, and dose of particulates including the characteristic nature of the target cells in vitro and in vivo.

  9. Mechanical Defects of Muscle Fibers with Myosin Light Chain Mutants that Cause Cardiomyopathy

    OpenAIRE

    Roopnarine, Osha

    2003-01-01

    Familial hypertrophic cardiomyopathy is a disease caused by single mutations in several sarcomeric proteins, including the human myosin ventricular regulatory light chain (vRLC). The effects of four of these mutations (A13T, F18L, E22K, and P95A) in vRLC on force generation were determined as a function of Ca2+ concentration. The endogenous RLC was removed from skinned rabbit psoas muscle fibers, and replaced with either rat wildtype vRLC or recombinant rat vRLC (G13T, F18L, E22K, and P95A). ...

  10. TU-C-12A-01: Measurement of Skeletal Muscle Lipids in Type 2 Diabetes Using in Vivo Proton MR Spectroscopy

    International Nuclear Information System (INIS)

    Valaparla, S; Boone, G; Ripley, E; Abdul-Ghani, M; Duong, T; Clarke, G

    2014-01-01

    Purpose: To quantify and compare the intramyocellular (IMCL), extramyocellular (EMCL) lipids and total fat fraction in human vastus lateralis (VL) muscle between lean controls and type 2 diabetic (T2DM) subjects using long echo time in vivo proton MR spectroscopy ( 1 H-MRS) Methods: 1 H-MRS single voxel (15 × 15 × 15 mm 3 ) stimulated acquisition mode (STEAM) was performed in right vastus lateralis m. on 10 lean controls (age: 28.3±3.94 yrs, BMI: 24.25±3.20 kg/m 2 ) and 7 type 2 diabetic (age: 54.28±6.42 yrs, BMI: 31.34±3.13 kg/m 2 ) subjects with Siemens 3T MRI and four-channel flex coil. Unsuppressed water spectra (NSA = 16) with TR/TE = 3000/30 msec, TM = 10 msec, BW = 2000 Hz, and water-suppressed spectra (NSA = 128) with TR/TE = 3000/270 msec, TM = 10 msec, and fixed water suppression BW = 50 Hz were acquired. Spectral intensity ratios of IMCL-CH 2 , EMCL-CH 2 and total lipid (IMCL + EMCL) with unsuppressed water signal (W) were converted into absolute concentrations expressed in mmol/kg. Fat fraction (100 × F/(W+F)) was calculated, where F includes the signal intensities of IMCL and EMCL methylene (CH 2 )n, peaks only. Results: Comparison of IMCL (controls: 11.70 ± 6.7, T2DM: 21.74 ± 10.2, p ≤ 0.01), EMCL (controls: 22.89 ± 18.42, T2DM: 77.21 ± 33.4, p ≤ 0.001) and total lipid (64.35 mmol/kg less in controls, p ≤ 0.001) showed statistical significance using two-tailed student t-test. Fat fraction (%) exhibited considerable inter-individual variability for controls (3.14 ± 2.09; range: 1.34 - 7.04) and T2DM (9.34 ± 2.88; range: 4.15 - 13.67) and deemed significant (p ≤ 0.05 Conclusion: Single voxel STEAM 1 H-MRS at long TE provides a robust non-invasive method for characterizing lipids within localized muscle regions, with well-resolved IMCL/EMCL peak separation. Regional lipid estimate and fat fraction in VL m. was significantly different in T2DM compared to lean controls. American Heart Association Southwest Affiliate Pre

  11. TU-C-12A-01: Measurement of Skeletal Muscle Lipids in Type 2 Diabetes Using in Vivo Proton MR Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Valaparla, S; Boone, G; Ripley, E; Abdul-Ghani, M; Duong, T; Clarke, G [UT Health Science Center, San Antonio, TX (United States)

    2014-06-15

    Purpose: To quantify and compare the intramyocellular (IMCL), extramyocellular (EMCL) lipids and total fat fraction in human vastus lateralis (VL) muscle between lean controls and type 2 diabetic (T2DM) subjects using long echo time in vivo proton MR spectroscopy ({sup 1}H-MRS) Methods: {sup 1}H-MRS single voxel (15 × 15 × 15 mm{sup 3}) stimulated acquisition mode (STEAM) was performed in right vastus lateralis m. on 10 lean controls (age: 28.3±3.94 yrs, BMI: 24.25±3.20 kg/m{sup 2}) and 7 type 2 diabetic (age: 54.28±6.42 yrs, BMI: 31.34±3.13 kg/m{sup 2}) subjects with Siemens 3T MRI and four-channel flex coil. Unsuppressed water spectra (NSA = 16) with TR/TE = 3000/30 msec, TM = 10 msec, BW = 2000 Hz, and water-suppressed spectra (NSA = 128) with TR/TE = 3000/270 msec, TM = 10 msec, and fixed water suppression BW = 50 Hz were acquired. Spectral intensity ratios of IMCL-CH{sub 2}, EMCL-CH{sub 2} and total lipid (IMCL {sub +} EMCL) with unsuppressed water signal (W) were converted into absolute concentrations expressed in mmol/kg. Fat fraction (100 × F/(W+F)) was calculated, where F includes the signal intensities of IMCL and EMCL methylene (CH{sub 2})n, peaks only. Results: Comparison of IMCL (controls: 11.70 ± 6.7, T2DM: 21.74 ± 10.2, p ≤ 0.01), EMCL (controls: 22.89 ± 18.42, T2DM: 77.21 ± 33.4, p ≤ 0.001) and total lipid (64.35 mmol/kg less in controls, p ≤ 0.001) showed statistical significance using two-tailed student t-test. Fat fraction (%) exhibited considerable inter-individual variability for controls (3.14 ± 2.09; range: 1.34 - 7.04) and T2DM (9.34 ± 2.88; range: 4.15 - 13.67) and deemed significant (p ≤ 0.05 Conclusion: Single voxel STEAM {sup 1}H-MRS at long TE provides a robust non-invasive method for characterizing lipids within localized muscle regions, with well-resolved IMCL/EMCL peak separation. Regional lipid estimate and fat fraction in VL m. was significantly different in T2DM compared to lean controls. American Heart

  12. An artificial tendon with durable muscle interface.

    Science.gov (United States)

    Melvin, Alan; Litsky, Alan; Mayerson, Joel; Witte, David; Melvin, David; Juncosa-Melvin, Natalia

    2010-02-01

    A coupling mechanism that can permanently fix a forcefully contracting muscle to a bone anchor or any totally inert prosthesis would meet a serious need in orthopaedics. Our group developed the OrthoCoupler device to satisfy these demands. The objective of this study was to test OrthoCoupler's performance in vitro and in vivo in the goat semitendinosus tendon model. For in vitro evaluation, 40 samples were fatigue-tested, cycling at 10 load levels, n = 4 each. For in vivo evaluation, the semitendinosus tendon was removed bilaterally in eight goats. Left sides were reattached with an OrthoCoupler, and right sides were reattached using the Krackow stitch with #5 braided polyester sutures. Specimens were harvested 60 days postsurgery and assigned for biomechanics and histology. Fatigue strength of the devices in vitro was several times the contractile force of the semitendinosus muscle. The in vivo devices were built equivalent to two of the in vitro devices, providing an additional safety factor. In strength testing at necropsy, suture controls pulled out at 120.5 +/- 68.3 N, whereas each OrthoCoupler was still holding after the muscle tore, remotely, at 298 +/- 111.3 N (mean +/- SD) (p < 0.0003). Muscle tear strength was reached with the fiber-muscle composite produced in healing still soundly intact. This technology may be of value for orthopaedic challenges in oncology, revision arthroplasty, tendon transfer, and sports-injury reconstruction. (c) 2009 Orthopaedic Research Society.

  13. A Preliminary Study on the Pattern, the Physiological Bases and the Molecular Mechanism of the Adductor Muscle Scar Pigmentation in Pacific Oyster Crassostrea gigas

    Directory of Open Access Journals (Sweden)

    Wenchao Yu

    2017-09-01

    Full Text Available The melanin pigmentation of the adductor muscle scar and the outer surface of the shell are among attractive features and their pigmentation patterns and mechanism still remains unknown in the Pacific oyster Crassostrea gigas. To study these pigmentation patterns, the colors of the adductor muscle scar vs. the outer surface of the shell on the same side were compared. No relevance was found between the colors of the adductor muscle scars and the corresponding outer surface of the shells, suggesting that their pigmentation processes were independent. Interestingly, a relationship between the color of the adductor muscle scars and the dried soft-body weight of Pacific oysters was found, which could be explained by the high hydroxyl free radical scavenging capacity of the muscle attached to the black adductor muscle scar. After the transcriptomes of pigmented and unpigmented adductor muscles and mantles were studied by RNAseq and compared, it was found that the retinol metabolism pathway were likely to be involved in melanin deposition on the adductor muscle scar and the outer surface of the shell, and that the different members of the tyrosinase or Cytochrome P450 gene families could play a role in the independent pigmentation of different organs.

  14. TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome.

    Directory of Open Access Journals (Sweden)

    Pavan Kumar P

    2014-03-01

    Full Text Available TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing.

  15. TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome.

    Science.gov (United States)

    Kumar P, Pavan; Franklin, Sarah; Emechebe, Uchenna; Hu, Hao; Moore, Barry; Lehman, Chris; Yandell, Mark; Moon, Anne M

    2014-03-01

    TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing.

  16. Relaxation-compensated CEST-MRI at 7 T for mapping of creatine content and pH--preliminary application in human muscle tissue in vivo.

    Science.gov (United States)

    Rerich, Eugenia; Zaiss, Moritz; Korzowski, Andreas; Ladd, Mark E; Bachert, Peter

    2015-11-01

    The small biomolecule creatine is involved in energy metabolism. Mapping of the total creatine (mostly PCr and Cr) in vivo has been done with chemical shift imaging. Chemical exchange saturation transfer (CEST) allows an alternative detection of creatine via water MRI. Living tissue exhibits CEST effects from different small metabolites, including creatine, with four exchanging protons of its guanidinium group resonating about 2 ppm from the water peak and hence contributing to the amine proton CEST peak. The intermediate exchange rate (≈ 1000 Hz) of the guanidinium protons requires high RF saturation amplitude B1. However, strong B1 fields also label semi-solid magnetization transfer (MT) effects originating from immobile protons with broad linewidths (~kHz) in the tissue. Recently, it was shown that endogenous CEST contrasts are strongly affected by the MT background as well as by T1 relaxation of the water protons. We show that this influence can be corrected in the acquired CEST data by an inverse metric that yields the apparent exchange-dependent relaxation (AREX). AREX has some useful linearity features that enable preparation of both concentration, and--by using the AREX-ratio of two RF irradiation amplitudes B1--purely exchange-rate-weighted CEST contrasts. These two methods could be verified in phantom experiments with different concentration and pH values, but also varying water relaxation properties. Finally, results from a preliminary application to in vivo CEST imaging data of the human calf muscle before and after exercise are presented. The creatine concentration increases during exercise as expected and as confirmed by (31)P NMR spectroscopic imaging. However, the estimated concentrations obtained by our method were higher than the literature values: cCr,rest=24.5±3.74mM to cCr,ex=38.32±13.05mM. The CEST-based pH method shows a pH decrease during exercise, whereas a slight increase was observed by (31)P NMR spectroscopy. Copyright © 2015

  17. Resolving shifting patterns of muscle energy use in swimming fish.

    Directory of Open Access Journals (Sweden)

    Shannon P Gerry

    Full Text Available Muscle metabolism dominates the energy costs of locomotion. Although in vivo measures of muscle strain, activity and force can indicate mechanical function, similar muscle-level measures of energy use are challenging to obtain. Without this information locomotor systems are essentially a black box in terms of the distribution of metabolic energy. Although in situ measurements of muscle metabolism are not practical in multiple muscles, the rate of blood flow to skeletal muscle tissue can be used as a proxy for aerobic metabolism, allowing the cost of particular muscle functions to be estimated. Axial, undulatory swimming is one of the most common modes of vertebrate locomotion. In fish, segmented myotomal muscles are the primary power source, driving undulations of the body axis that transfer momentum to the water. Multiple fins and the associated fin muscles also contribute to thrust production, and stabilization and control of the swimming trajectory. We have used blood flow tracers in swimming rainbow trout (Oncorhynchus mykiss to estimate the regional distribution of energy use across the myotomal and fin muscle groups to reveal the functional distribution of metabolic energy use within a swimming animal for the first time. Energy use by the myotomal muscle increased with speed to meet thrust requirements, particularly in posterior myotomes where muscle power outputs are greatest. At low speeds, there was high fin muscle energy use, consistent with active stability control. As speed increased, and fins were adducted, overall fin muscle energy use declined, except in the caudal fin muscles where active fin stiffening is required to maintain power transfer to the wake. The present data were obtained under steady-state conditions which rarely apply in natural, physical environments. This approach also has potential to reveal the mechanical factors that underlie changes in locomotor cost associated with movement through unsteady flow regimes.

  18. Resolving Shifting Patterns of Muscle Energy Use in Swimming Fish

    Science.gov (United States)

    Gerry, Shannon P.; Ellerby, David J.

    2014-01-01

    Muscle metabolism dominates the energy costs of locomotion. Although in vivo measures of muscle strain, activity and force can indicate mechanical function, similar muscle-level measures of energy use are challenging to obtain. Without this information locomotor systems are essentially a black box in terms of the distribution of metabolic energy. Although in situ measurements of muscle metabolism are not practical in multiple muscles, the rate of blood flow to skeletal muscle tissue can be used as a proxy for aerobic metabolism, allowing the cost of particular muscle functions to be estimated. Axial, undulatory swimming is one of the most common modes of vertebrate locomotion. In fish, segmented myotomal muscles are the primary power source, driving undulations of the body axis that transfer momentum to the water. Multiple fins and the associated fin muscles also contribute to thrust production, and stabilization and control of the swimming trajectory. We have used blood flow tracers in swimming rainbow trout (Oncorhynchus mykiss) to estimate the regional distribution of energy use across the myotomal and fin muscle groups to reveal the functional distribution of metabolic energy use within a swimming animal for the first time. Energy use by the myotomal muscle increased with speed to meet thrust requirements, particularly in posterior myotomes where muscle power outputs are greatest. At low speeds, there was high fin muscle energy use, consistent with active stability control. As speed increased, and fins were adducted, overall fin muscle energy use declined, except in the caudal fin muscles where active fin stiffening is required to maintain power transfer to the wake. The present data were obtained under steady-state conditions which rarely apply in natural, physical environments. This approach also has potential to reveal the mechanical factors that underlie changes in locomotor cost associated with movement through unsteady flow regimes. PMID:25165858

  19. Technologies and mechanisms for safety control of ready-to-eat muscle foods: an updated review.

    Science.gov (United States)

    Jiang, Jiang; Xiong, Youling L

    2015-01-01

    Ready-to-eat (RTE) muscle foods refer to a general category of meat and poultry products that are fully cooked and consumable without reheating. These products, including whole and sliced pork, beef, turkey, chicken, and variety of meats, in the forms of ham, roast, rolls, sausage, and frankfurter, are widely available in the delicatessen section of retail stores or various food service outlets. However, difficulties in avoidance of contamination by foodborne pathogens, notably Listeria monocytogenes, during product postlethality repackaging render RTE meats labile to outbreaks. Accordingly, the USDA-FSIS has established processing guidelines and regulations, which are constantly updated, to minimize foodborne pathogens in RTE products. Technologies that complement good manufacturing practice have been developed to control RTE meat safety. Among them, various antimicrobial product formulations, postpackaging pasteurization (thermal and nonthermal), and antimicrobial packaging are being used. Through these efforts, outbreaks linked to RTE meat consumption have substantially reduced in recent years. However, the pervasive and virulent nature of L. monocytogenes and the possible presence of other cold-tolerant pathogens entail continuing developments of new intervention technologies. This review updates existing and emerging physical and chemical methods and their mode of action to inactivate or inhibit threatening microorganisms in RTE muscle foods.

  20. The effects of work surface hardness on mechanical stress, muscle activity, and wrist postures.

    Science.gov (United States)

    Kim, Jeong Ho; Aulck, Lovenoor; Trippany, David; Johnson, Peter W

    2015-01-01

    Contact pressure is a risk factor which can contribute to musculoskeletal disorders. The objective of the present study was to determine whether a work surface with a soft, pliable front edge could reduce contact pressure, muscle activity, and subjective musculoskeletal comfort, and improve wrist posture relative to a conventional, hard work surface. In a repeated-measures blinded experiment with eighteen subjects (8 females and 10 males), contact pressure, wrist posture, typing productivity, perceived fatigue, wrist and shoulder muscle activity, and subjective comfort were compared between the two different work surfaces during keyboard use, mouse use and mixed mouse and keyboard use. The results showed that across the three modes of computer work, the contact pressure was lower on the soft-edge work surface compared to the conventional work surface (p's work surfaces. Given the significant reduction in contact pressure and corresponding lower ratings in perceived fatigue, the soft-edge work surface subjectively and objectively improved measures of contact stress which may reduce physical exposures associated with the onset and development of musculoskeletal disorders.

  1. Mechanical response of knee muscles in high level bodyboarders during performance

    Directory of Open Access Journals (Sweden)

    Dario Rodríguez-Matoso

    2015-04-01

    Full Text Available INTRODUCTION: bodyboarding is a kind of surfing that has been growing very rapidly over the last decade and has now developed into one of the fastest growing water sports in the world. OBJECTIVES: evaluate the effects of fatigue on rectus femoris RF, vastus lateralis VL and vastus medialis VM and biceps femoris BF and semitendinosus ST during a high-level bodyboard competition using tensiomyography TMG. METHODS: subjects were 11 highly experienced years of practice: 15, SD=4.65 male bodyboarders age: 28.17, SD=2.89, body weight: 74.83, SD=6.13kg; height: 179.25, SD=3.93cm; BMI: 23.29, SD=1.81 participating in the final of the 2010 Spanish championship. RESULTS: the fatigue is especially evident due to a decrease in the values of relaxation time Tr and sustain time Ts caused by the specific characteristics of waves, how the waves evolve and the type of manoeuvre executed in competition due to the wave characteristics. The maximum radial displacement Dm value increased slightly in all muscles analysed and normalised response speed Vrn was stable, with a tendency to improve as athletes adapted to the type of physical effort and the environmental conditions of the competition. CONCLUSIONS: the study shows that the fatigue in the extensor and flexor muscles of the knee occurs in response to the demands of competition.

  2. Recovery in mechanical muscle strength following resurfacing vs standard total hip arthroplasty - a randomised clinical trial

    DEFF Research Database (Denmark)

    Jensen, Carsten; Aagaard, Per; Overgaard, S

    2011-01-01

    rather than implant design per se. Thus, the present data failed to support the hypothesis that R-THA would result in an enhanced strength rehabilitation compared to S-THA. Further, between-limb asymmetry remained present for hip flexors and adductors after 52 wks. Trial registration: NCT01229293....... randomised into (A) standard total hip arthroplasty (S-THA) and (B) resurfacing total hip arthroplasty (R-THA). Pre-surgery assessment and follow-up were conducted (8, 26 and 52 wks). Maximal isometric muscle strength (Nm) and between-limb asymmetry for the knee extensors/flexors, hip adductors....../abductors, hip extensors/flexors were analysed. RESULTS: Maximal knee extensor and hip abductor strength were higher in S-THA than R-THA at 52 wks post-surgery (P ≤ 0.05) and hip extensors tended to be higher in S-THA at 52 wks (P = 0.06). All muscle groups showed substantial between-limb strength asymmetry (7...

  3. Metabolic Adaptation to Muscle Ischemia

    Science.gov (United States)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  4. EFFECTIVENESS OF MUSCLE STRETCHING IN OCCUPATION RELATED CHRONIC MECHANICAL LOW BACK PAIN IN COMMUNITY NURSES –A SINGLE BLIND STUDY

    OpenAIRE

    Khwairakpam Zhimina Devi; Sai Kumar. N; Vinod Babu. K; V.R. Ayyappan

    2014-01-01

    Background and Objective: Stretching of Lower Back Muscle, Hamstring and Tensor Fasciae Latae have an immediate effect on Chronic Lower Back Pain. Hence the purpose is to find the short term effect of stretching of Lower Back Muscle, Hamstring and Tensor Fasciae Latae on intensity of low back pain, flexibility and functional disability in occupation related Chronic Mechanical Low Back Pain in Community Nurses. Method: Single blind experimental study design, 40 subjects with Chronic mechani...

  5. Different mechanisms of modulation of gap junction communication by non-genotoxic carcinogens in rat liver in vivo

    International Nuclear Information System (INIS)

    Cowles, C.; Mally, A.; Chipman, J.K.

    2007-01-01

    This is a comparative study of the mechanisms by which three different rodent non-genotoxic carcinogens modulate connexin-mediated gap junction intercellular communication in male rat liver in vivo. In the case of the peroxisome proliferating agent Wy-14,643, a non-hepatotoxic dose of 50 mg/kg led to a marked loss of inter-hepatocyte dye transfer associated with a loss of both Cx32 and Cx26 protein expression. In contrast, p,p'-dichlorodiphenyltrichloroethane (DDT) at a non-hepatotoxic dose (25 mg/kg) was not found to alter Cx32 or Cx26 expression or to produce a measurable Cx32 serine phosphorylation but did give a small, significant reduction of cell communication. Carbon tetrachloride (CCl 4 ) did not affect cell communication (despite a small significant reduction of Cx32 content) at a non-hepatotoxic dose. Both loss of communication and Cx32 expression was observed only at a dose that caused hepatocyte toxicity as evidenced by increased serum alanine aminotransferase activity. Overall, the findings emphasise that loss of gap junctional communication in vivo can contribute to carcinogenesis by non-genotoxic carcinogens through different primary mechanism. In contrast to Wy-14,643 and DDT, the results with CCl 4 are consistent with a requirement for hepatotoxicity in its carcinogenic action

  6. In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives

    Science.gov (United States)

    Rocha e Silva, Luiz Francisco; Nogueira, Karla Lagos; Pinto, Ana Cristina da Silva; Katzin, Alejandro Miguel; Sussmann, Rodrigo A. C.; Muniz, Magno Perêa; Neto, Valter Ferreira de Andrade; Chaves, Francisco Célio Maia; Coutinho, Julia Penna; Lima, Emerson Silva; Krettli, Antoniana Ursine; Tadei, Wanderli Pedro

    2015-01-01

    4-Nerolidylcatechol (1) is an abundant antiplasmodial metabolite that is isolated from Piper peltatum roots. O-Acylation or O-alkylation of compound 1 provides derivatives exhibiting improved stability and significant in vitro antiplasmodial activity. The aim of this work was to study the in vitro inhibition of hemozoin formation, inhibition of isoprenoid biosynthesis in Plasmodium falciparum cultures, and in vivo antimalarial activity of several 4-nerolidylcatechol derivatives. 1,2-O,O-Diacetyl-4-nerolidylcatechol (2) inhibited in vitro hemozoin formation by up to 50%. In metabolic labeling studies using [1-(n)-3H]geranylgeranyl pyrophosphate, diester 2 significantly inhibited the biosynthesis of isoprenoid metabolites ubiquinone 8, menaquinone 4, and dolichol 12 in cultures of P. falciparum 3D7. Similarly, 2-O-benzyl-4-nerolidylcatechol (3) significantly inhibited the biosynthesis of dolichol 12. P. falciparum in vitro protein synthesis was not affected by compounds 2 or 3. At oral doses of 50 mg per kg of body weight per day, compound 2 suppressed Plasmodium berghei NK65 in infected BALB/c mice by 44%. This in vivo result for derivative 2 represents marked improvement over that obtained previously for natural product 1. Compound 2 was not detected in mouse blood 1 h after oral ingestion or in mixtures with mouse blood/blood plasma in vitro. However, it was detected after in vitro contact with human blood or blood plasma. Derivatives of 4-nerolidylcatechol exhibit parasite-specific modes of action, such as inhibition of isoprenoid biosynthesis and inhibition of hemozoin formation, and they therefore merit further investigation for their antimalarial potential. PMID:25801563

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  8. Rapid increases in training load affects markers of skeletal muscle damage and mechanical performance

    DEFF Research Database (Denmark)

    Kamandulis, Sigitas; Snieckus, Audrius; Venckunas, Tomas

    2012-01-01

    The aim of the present study was to monitor the changes in indirect markers of muscle damage during 3 weeks (nine training sessions) of stretch-shortening (drop jump) exercise with constant load alternated with steep increases in load. Physically active men (n = 9, mean age 19.1 years) performed....... Maximal jump height increased by 7.8% ± 6.3% (P training session, respectively. Gains in isometric knee extension MVC (7.9% ± 8.2%) and 100-Hz-evoked torque (9.9% ± 9.6%) (both P ... within 17 days after the end of training. The magnitude of improvement was greater after this protocol than that induced by a continuous constant progression loading pattern with small gradual load increments in each training session. These findings suggest that plyometric training using infrequent...

  9. Mechanical behaviour of hamstring muscles in low-back pain patients and control subjects.

    Science.gov (United States)

    Tafazzoli, F; Lamontagne, M

    1996-01-01

    The purpose of this study was to measure and compare the passive elastic moment, the stiffness and the damping coefficient of the hip joint, as functions of the hip and knee joint angles in men with and without low-back pain. Two conventional tests, the straight-leg-raising test and the trunk forward flexion, were also performed and compared between these subjects. The passive elastic moment was measured using an isokinetic device in the passive mode. This device raised the lower limb from the horizontal position to the straight-leg-raising angle at a slow and constant angular velocity. A custom-made splint connected with the lever arm of the isokinetic device maintained the knee in extension and the ankle in the neutral position. The damping coefficient of the hip joint was measured for 0, 15, 45, 60, 75 and 90% of straight leg raising angle of each subject, using the suspension method based on small oscillation theory. To ensure that muscles were inactive during the passive hip moment tests, muscle activity was monitored with surface EMG. The stiffness was computed as the ratio of the change in passive elastic moment to the change in the hip angle. The passive elastic moment, the stiffness and the normalized trunk flexion were significantly different between the two groups respectively. There was, however, no difference between the two groups in the results of straight-leg-raise and damping coefficient of the hip. The passive elastic moment was a nonlinear function of the hip flexion angle and showed large intersubject differences, especially as the joint limit was approached. The damping coefficient was a polynomial function of the hip flexion angle. The measured variables were analysed using a discriminant function and it was shown that the two groups were clearly discriminable in a meaningful manner.

  10. Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Shunzhen Zheng

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm and zeta potential (∼-11 mV, and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo. CONCLUSIONS/SIGNIFICANCE: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

  11. Modeling the Mechanical Response of In Vivo Human Skin Under a Rich Set of Deformations

    KAUST Repository

    Flynn, Cormac; Taberner, Andrew; Nielsen, Poul

    2011-01-01

    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

  12. Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

    2018-02-21

    Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

  13. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  14. Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Cao, Jian; Chiarelli, Christian; Panettieri, Reynold A; Foda, Hussein D

    2005-09-01

    Airway smooth muscle (ASM) proliferation and migration are major components of airway remodeling in asthma. Asthmatic airways are exposed to mechanical strain, which contributes to their remodeling. Matrix metalloproteinase (MMP) plays an important role in remodeling. In the present study, we examined if the mechanical strain of human ASM (HASM) cells contributes to their proliferation and migration and the role of MMPs in this process. HASM were exposed to mechanical strain using the FlexCell system. HASM cell proliferation, migration and MMP release, activation, and expression were assessed. Our results show that cyclic strain increased the proliferation and migration of HASM; cyclic strain increased release and activation of MMP-1, -2, and -3 and membrane type 1-MMP; MMP release was preceded by an increase in extracellular MMP inducer; Prinomastat [a MMP inhibitor (MMPI)] significantly decreased cyclic strain-induced proliferation and migration of HASM; and the strain-induced increase in the release of MMPs was accompanied by an increase in tenascin-C release. In conclusion, cyclic mechanical strain plays an important role in HASM cell proliferation and migration. This increase in proliferation and migration is through an increase in MMP release and activation. Pharmacological MMPIs should be considered in the pursuit of therapeutic options for airway remodeling in asthma.

  15. The associations between quadriceps muscle strength, power, and knee joint mechanics in knee osteoarthritis: A cross-sectional study.

    Science.gov (United States)

    Murray, Amanda M; Thomas, Abbey C; Armstrong, Charles W; Pietrosimone, Brian G; Tevald, Michael A

    2015-12-01

    Abnormal knee joint mechanics have been implicated in the pathogenesis and progression of knee osteoarthritis. Deficits in muscle function (i.e., strength and power) may contribute to abnormal knee joint loading. The associations between quadriceps strength, power and knee joint mechanics remain unclear in knee osteoarthritis. Three-dimensional motion analysis was used to collect peak knee joint angles and moments during the first 50% of stance phase of gait in 33 participants with knee osteoarthritis. Quadriceps strength and power were assessed using a knee extension machine. Strength was quantified as the one repetition maximum. Power was quantified as the peak power produced at 40-90% of the one repetition maximum. Quadriceps strength accounted for 15% of the variance in peak knee flexion angle (P=0.016). Quadriceps power accounted for 20-29% of the variance in peak knee flexion angle (Pknee adduction moment (P=0.05). These data suggest that quadriceps power explains more variance in knee flexion angle and knee adduction moment during gait in knee osteoarthritis than quadriceps strength. Additionally, quadriceps power at multiple loads is associated with knee joint mechanics and therefore should be assessed at a variety of loads. Taken together, these results indicate that quadriceps power may be a potential target for interventions aimed at changing knee joint mechanics in knee osteoarthritis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice.

    Science.gov (United States)

    Almind, Katrine; Manieri, Monia; Sivitz, William I; Cinti, Saverio; Kahn, C Ronald

    2007-02-13

    C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a beta3-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice.

  17. Hydrogen peroxide increases depolarization-induced contraction of mechanically skinned slow twitch fibres from rat skeletal muscles.

    Science.gov (United States)

    Plant, David R; Lynch, Gordon S; Williams, David A

    2002-03-15

    The effect of exogenous hydrogen peroxide (H(2)O(2)) on excitation-contraction (E-C) coupling and sarcoplasmic reticulum (SR) function was compared in mechanically skinned slow twitch fibres (prepared from the soleus muscles) and fast twitch fibres (prepared from the extensor digitorum longus; EDL muscles) of adult rats. Equilibration (5 min) with 1 mM H(2)O(2) diminished the ability of the Ca(2+)-depleted SR to reload Ca(2+) in both slow (P fast twitch fibres (P fast twitch fibres by 24 +/- 5 % (P slow twitch fibres. Treatment with 1 mM H(2)O(2) also increased the peak force of low [caffeine] contracture by approximately 45% in both fibre types compared to control (P slow twitch fibres, compared to control (no H(2)O(2); P fast twitch fibres was not altered by 1 mM H(2)O(2) treatment. Equilibration with 5 mM H(2)O(2) induced a spontaneous force response in both slow and fast twitch fibres, which could be partly reversed by 2 min treatment with 10 mM DTT. Peak DICR was also increased approximately 40% by 5 mM H(2)O(2) in slow twitch fibres compared to control (no H(2)O(2); P slow but not fast twitch fibres. The increase in depolarization-induced contraction in slow twitch fibres might be mediated by an increased SR Ca(2+) release during contraction and/or an increase in Ca(2+) sensitivity.

  18. Potential mechanisms of carbon monoxide and high oxygen packaging in maintaining color stability of different bovine muscles.

    Science.gov (United States)

    Liu, Chenglong; Zhang, Yimin; Yang, Xiaoyin; Liang, Rongrong; Mao, Yanwei; Hou, Xu; Lu, Xiao; Luo, Xin

    2014-06-01

    The objectives were to compare the effects of packaging methods on color stability, metmyoglobin-reducing-activity (MRA), total-reducing-activity and NADH concentration of different bovine muscles and to explore potential mechanisms in the enhanced color stability by carbon monoxide modified atmosphere packaging (CO-MAP, 0.4% CO/30% CO2/69.6% N2). Steaks from longissimus lumborum (LL), psoas major (PM) and longissimus thoracis (LT) packaged in CO-MAP, high-oxygen modified atmosphere packaging (HiOx-MAP, 80% O2/20% CO2) or vacuum packaging were stored for 0day, 4days, 9days, and 14days or stored for 9days then displayed in air for 0day, 1day, or 3days. The CO-MAP significantly increased red color stability of all muscles, and especially for PM. The PM and LT were more red than LL in CO-MAP, whereas PM had lowest redness in HiOx-MAP. The content of MetMb in CO-MAP was lower than in HiOx-MAP. Steaks in CO-MAP maintained a higher MRA compared with those in HiOx-MAP during storage. After opening packages, the red color of steaks in CO-MAP deteriorated more slowly compared with that of steaks in HiOx-MAP. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Influence of a 12.8-km military load carriage activity on lower limb gait mechanics and muscle activity.

    Science.gov (United States)

    Rice, Hannah; Fallowfield, Joanne; Allsopp, Adrian; Dixon, Sharon

    2017-05-01

    The high stress fracture occurrence in military populations has been associated with frequent load carriage activities. This study aimed to assess the influence of load carriage and of completing a load carriage training activity on gait characteristics. Thirty-two Royal Marine recruits completed a 12.8-km load carriage activity as part of their military training. Data were collected during walking in military boots, pre and post-activity, with and without the additional load (35.5 kg). Ground contact time, lower limb sagittal plane kinematics and kinetics, and electromyographic variables were obtained for each condition. When carrying load, there was increased ground contact time, increased joint flexion and joint moments, and increased plantar flexor and knee extensor muscle activity. Post-activity, there were no changes to kinematic variables, knee extensor moments were reduced, and there was evidence of plantar flexor muscle fatigue. The observed gait changes may be associated with stress fracture development. Practitioner Summary: This study identified gait changes due to load carriage and after a military load carriage training activity. Such activities are associated with lower limb stress fractures. A pre-post study design was used. Gait mechanics changed to a greater extent when carrying load, than after completion of the activity when assessed without load.

  20. Mechanical and morphological properties of different muscle-tendon units in the lower extremity and running mechanics: effect of aging and physical activity.

    Science.gov (United States)

    Karamanidis, Kiros; Arampatzis, Adamantios

    2005-10-01

    The objectives of this work were (i) to investigate whether chronic endurance running is a sufficient stimulus to counteract the age-related changes in the mechanical and morphological properties of human triceps surae (TS) and quadriceps femoris (QF) muscle-tendon units (MTUs) by comparing runners and non-active subjects at different ages (young and old), (ii) to identify adaptational phenomena in running mechanics due to age-related changes in the mechanical and morphological properties of the TS and QF MTUs, and finally (iii) to examine whether chronic endurance-running exercise is associated with adaptational effects on running characteristics in old and young adults. The investigation was conducted on 30 old and 19 young adult males divided into two subgroups according to their running activity: endurance-runners vs non-active. To analyse the properties of the MTUs, all subjects performed isometric maximal voluntary (MVC) ankle plantarflexion and knee extension contractions at 11 different MTU lengths on a dynamometer. The activation of the TS and QF during MVC was estimated by surface electromyography. The gastrocnemius medialis and the vastus lateralis and their distal aponeuroses were visualized by ultrasonography at rest and during MVC, respectively. Ground reaction forces and kinematic data were recorded during running trials at 2.7 m s(-1). The TS and QF MTU capacities were reduced with aging (lower muscle strength and lower tendon stiffness). Runners and non-active subjects had similar MTU properties, suggesting that chronic endurance-running exercise does not counteract the age-related degeneration of the MTUs. Runners showed a higher mechanical advantage for the QF MTU while running (lower gear ratio) compared to non-active subjects, indicating a task-specific adaptation even at old age. Older adults reacted to the reduced capacities of their MTUs by increasing running safety (higher duty factor, lower flight time) and benefitting from a mechanical

  1. Mechanical ventilation and volutrauma: study in vivo of a healthy pig model

    Directory of Open Access Journals (Sweden)

    Camilla V Pastore

    2011-01-01

    Full Text Available Mechanical ventilation is essential in intensive care units. However, it may itself induce lung injury. Current studies are based on rodents, using exceptionally large tidal volumes for very short periods, often after a "priming" pulmonary insult. Our study deepens a clinically relevant large animal model, closely resembling human physiology and the ventilator setting used in clinic settings. Our aim was to evaluate the pathophysiological mechanisms involved in alveolo/capillary barrier damage due to mechanical stress in healthy subjects. We randomly divided 18 pigs (sedated with medetomidine/tiletamine-zolazepam and anesthetised with thiopental sodium into three groups (n=6: two were mechanically ventilated (tidal volume of 8 or 20 ml/kg, the third breathed spontaneously for 4 hours, then animals were sacrificed (thiopental overdose. We analyzed every 30' hemogasanalysis and the main circulatory and respiratory parameters. Matrix gelatinase expression was evaluated on bronchoalveolar lavage fluid after surgery and before euthanasia. On autoptic samples we performed zymographic analysis of lung, kidney and liver tissues and histological examination of lung. Results evidenced that high Vt evoked profound alterations of lung mechanics and structure, although low Vt strategy was not devoid of side effects, too. Unexpectedly, also animals that were spontaneously breathing showed a worsening of the respiratory functions.

  2. Biceps femoris and semitendinosus—teammates or competitors? New insights into hamstring injury mechanisms in male football players: a muscle functional MRI study

    Science.gov (United States)

    Schuermans, Joke; Van Tiggelen, Damien; Danneels, Lieven; Witvrouw, Erik

    2014-01-01

    Background The hamstring injury mechanism was assessed by investigating the exercise-related metabolic activity characteristics of the hamstring muscles using a muscle functional MRI (mfMRI) protocol. Methods 27 healthy male football players and 27 football players with a history of hamstring injuries (recovered and playing fully) underwent standardised mfMR Imaging. The mfMRI protocol consisted of a resting scan, a strenuous bilateral eccentric hamstring exercise and a postexercise scan. The exercise-related T2 increase or the signal intensity shift between both scans was used to detect differences in metabolic activation characteristics (1) between the different hamstring muscle bellies and (2) between the injury group and the control group. Results A more symmetrical muscle recruitment pattern corresponding to a less economic hamstring muscle activation was demonstrated in the formerly injured group (phamstring exercise. Conclusions These findings suggest that the vulnerability of the hamstring muscles to football-related injury is related to the complexity and close coherence in the synergistic muscle recruitment of the biceps femoris and the semitendinosus. Discrete differences in neuromuscular coordination and activity distribution, with the biceps femoris partly having to compensate for the lack of endurance capacity of the semitendinosus, probably increase the hamstring injury risk. PMID:25388959

  3. Biceps femoris and semitendinosus--teammates or competitors? New insights into hamstring injury mechanisms in male football players: a muscle functional MRI study.

    Science.gov (United States)

    Schuermans, Joke; Van Tiggelen, Damien; Danneels, Lieven; Witvrouw, Erik

    2014-12-01

    The hamstring injury mechanism was assessed by investigating the exercise-related metabolic activity characteristics of the hamstring muscles using a muscle functional MRI (mfMRI) protocol. 27 healthy male football players and 27 football players with a history of hamstring injuries (recovered and playing fully) underwent standardised mfMR Imaging. The mfMRI protocol consisted of a resting scan, a strenuous bilateral eccentric hamstring exercise and a postexercise scan. The exercise-related T2 increase or the signal intensity shift between both scans was used to detect differences in metabolic activation characteristics (1) between the different hamstring muscle bellies and (2) between the injury group and the control group. A more symmetrical muscle recruitment pattern corresponding to a less economic hamstring muscle activation was demonstrated in the formerly injured group (phamstring exercise. These findings suggest that the vulnerability of the hamstring muscles to football-related injury is related to the complexity and close coherence in the synergistic muscle recruitment of the biceps femoris and the semitendinosus. Discrete differences in neuromuscular coordination and activity distribution, with the biceps femoris partly having to compensate for the lack of endurance capacity of the semitendinosus, probably increase the hamstring injury risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle.

    Science.gov (United States)

    Umeki, Daisuke; Ohnuki, Yoshiki; Mototani, Yasumasa; Shiozawa, Kouichi; Fujita, Takayuki; Nakamura, Yoshiki; Saeki, Yasutake; Okumura, Satoshi

    2013-01-01

    To examine the effects of the Akt/mammalian target of rapamycin (mTOR) pathway on masseter muscle hypertrophy and myosin heavy chain (MHC) transition in response to mechanical overload, we analyzed the effects of bite-opening (BO) on the hypertrophy and MHC composition of masseter muscle of BO-rats treated or not treated with rapamycin (RAPA), a selective mTOR inhibitor. The masseter muscle weight in BO-rats was significantly greater than that in controls, and this increase was attenuated by RAPA treatment. Expression of slow-twitch MHC isoforms was significantly increased in BO-rats with/without RAPA treatment, compared with controls, but the magnitude of the increase was much smaller in RAPA-treated BO-rats. Phosphorylation of p44/42 MAPK (ERK1/2), which preserves fast-twitch MHC isoforms in skeletal muscle, was significantly decreased in BO-rats, but the decrease was abrogated by RAPA treatment. Calcineurin signaling is known to be important for masseter muscle hypertrophy and fast-to-slow MHC isoform transition, but expression of known calcineurin activity modulators was unaffected by RAPA treatment. Taken together, these results indicate that the Akt/mTOR pathway is involved in both development of masseter muscle hypertrophy and fast-to-slow MHC isoform transition in response to mechanical overload with inhibition of the ERK1/2 pathway and operates independently of the calcineurin pathway.

  5. Mechanism of the 2,3-diphosphoglycerate-dependent phosphoglycerate mutase from rabbit muscle

    Science.gov (United States)

    Britton, H. G.; Clarke, J. B.

    1972-01-01

    1. The properties and kinetics of the 2,3-diphosphoglycerate-dependent phosphoglycerate mutases are discussed. There are at least three possible mechanisms for the reaction: (i) a phosphoenzyme (Ping Pong) mechanism; (ii) an intermolecular transfer of phosphate from 2,3-diphosphoglycerate to the substrates (sequential mechanism); (iii) an intramolecular transfer of phosphate. It is concluded that these mechanisms cannot be distinguished by conventional kinetic measurements. 2. The fluxes for the different mechanisms are calculated and it is shown that it should be possible to distinguish between the mechanisms by appropriate induced-transport tests and by comparing the fluxes of 32P- and 14C-labelled substrates at chemical equilibrium. 3. With 14C-labelled substrates no induced transport was found over a wide concentration range, and with 32P-labelled substrates co-transport occurred that was independent of concentration over a twofold range. 14C-labelled substrates exchange at twice the rate of 32P-labelled substrates at chemical equilibrium. The results were completely in accord with a phosphoenzyme mechanism and indicated a rate constant for the isomerization of the phosphoenzyme of not less than 4×106s−1. The intramolecular transfer of phosphate (and intermolecular transfer between two or more molecules of substrate) were completely excluded. The intermolecular transfer of phosphate from 2,3-diphosphoglycerate would have been compatible with the results only if the Km for 2-phosphoglycerate had been over 7.5-fold smaller than the observed value and if an isomerization of the enzyme-2,3-diphosphoglycerate complex had been the major rate-limiting step in the reaction. 4. The very rapid isomerization of the phosphoenzyme that the experiments demonstrate suggests a mechanism that does not involve a formal isomerization. According to this new scheme the enzyme is closely related mechanistically and perhaps evolutionarily to a 2,3-diphosphoglycerate diphosphatase

  6. Mechanism of the 2,3-diphosphoglycerate-dependent phosphoglycerate mutase from rabbit muscle.

    Science.gov (United States)

    Britton, H G; Clarke, J B

    1972-11-01

    1. The properties and kinetics of the 2,3-diphosphoglycerate-dependent phosphoglycerate mutases are discussed. There are at least three possible mechanisms for the reaction: (i) a phosphoenzyme (Ping Pong) mechanism; (ii) an intermolecular transfer of phosphate from 2,3-diphosphoglycerate to the substrates (sequential mechanism); (iii) an intramolecular transfer of phosphate. It is concluded that these mechanisms cannot be distinguished by conventional kinetic measurements. 2. The fluxes for the different mechanisms are calculated and it is shown that it should be possible to distinguish between the mechanisms by appropriate induced-transport tests and by comparing the fluxes of (32)P- and (14)C-labelled substrates at chemical equilibrium. 3. With (14)C-labelled substrates no induced transport was found over a wide concentration range, and with (32)P-labelled substrates co-transport occurred that was independent of concentration over a twofold range. (14)C-labelled substrates exchange at twice the rate of (32)P-labelled substrates at chemical equilibrium. The results were completely in accord with a phosphoenzyme mechanism and indicated a rate constant for the isomerization of the phosphoenzyme of not less than 4x10(6)s(-1). The intramolecular transfer of phosphate (and intermolecular transfer between two or more molecules of substrate) were completely excluded. The intermolecular transfer of phosphate from 2,3-diphosphoglycerate would have been compatible with the results only if the K(m) for 2-phosphoglycerate had been over 7.5-fold smaller than the observed value and if an isomerization of the enzyme-2,3-diphosphoglycerate complex had been the major rate-limiting step in the reaction. 4. The very rapid isomerization of the phosphoenzyme that the experiments demonstrate suggests a mechanism that does not involve a formal isomerization. According to this new scheme the enzyme is closely related mechanistically and perhaps evolutionarily to a 2,3-diphosphoglycerate

  7. Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients

    OpenAIRE

    Weijs, Peter JM; Looijaard, Wilhelmus GPM; Dekker, Ingeborg M; Stapel, Sandra N; Girbes, Armand R; Straaten, Heleen M Oudemans-van; Beishuizen, Albertus

    2014-01-01

    Introduction Higher body mass index (BMI) is associated with lower mortality in mechanically ventilated critically ill patients. However, it is yet unclear which body component is responsible for this relationship. Methods This retrospective analysis in 240 mechanically ventilated critically ill patients included adult patients in whom a computed tomography (CT) scan of the abdomen was made on clinical indication between 1 day before and 4 days after admission to the intensive care unit. CT s...

  8. Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.

    Directory of Open Access Journals (Sweden)

    Jason A Bleedorn

    Full Text Available Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK, phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt, and mammalian target of rapamycin (mTOR. However, anabolic signaling responses to bone loading using a whole animal in vivo model have not been studied in detail. Therefore, we examined mechanically-induced signaling events at five time points from 0 to 24 hours after loading using the rat in vivo ulna end-loading model. Western blot analysis of bone for MAPK's, PI3K/Akt, and mTOR signaling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR to estimate gene expression of calcitonin gene-related protein alpha (CGRP-α, brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, c-jun, and c-fos in dorsal root ganglion (DRG of the brachial intumescence were performed. There was a significant increase in signaling through MAPK's including extracellular signal-related kinase (ERK and c-Jun N-terminal kinase (JNK in loaded limbs at 15 minutes after mechanical loading. Ulna loading did not significantly influence expression of the genes of interest in DRG neurons. Bone signaling and DRG gene expression from the loaded and contralateral limbs was correlated (SR>0.40, P<0.05. However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the

  9. Efficacy of kinesiology tape versus postural correction exercises on neck disability and axioscapular muscles fatigue in mechanical neck dysfunction: A randomized blinded clinical trial.

    Science.gov (United States)

    El-Abd, Aliaa M; Ibrahim, Abeer R; El-Hafez, Haytham M

    2017-04-01

    Mechanical neck dysfunction (MND), with axioscapular muscles fatigue, is highly prevalent worldwide. While postural correction is commonly used for its treatment, efficacy of kinesiology tape (KT) has received considerable attention. To determine the effectiveness of KT versus correction exercises on neck disability, and axioscapular muscles fatigue in MND patients. 46 MND patients were randomly assigned into 1 of 2 groups receiving 4 weeks treatment of either KT or correction exercises. Neck disability and axioscapular muscles fatigue as median frequency of electromyography (EMG-MF) were measured pre and post treatment. Group-by-time interaction was not significant in the multivariable test. Post hoc tests revealed that KT produced more disability reduction than the postural exercises. However, there was no significant interaction for EMG-MF. KT has been found to be more effective than postural exercises to reduce neck disability. However, both modalities have similar effects to reduce axioscapular muscles fatigue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Non-muscle myosin II in disease: mechanisms and therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Karen A. Newell-Litwa

    2015-12-01

    Full Text Available The actin motor protein non-muscle myosin II (NMII acts as a master regulator of cell morphology, with a role in several essential cellular processes, including cell migration and post-synaptic dendritic spine plasticity in neurons. NMII also generates forces that alter biochemical signaling, by driving changes in interactions between actin-associated proteins that can ultimately regulate gene transcription. In addition to its roles in normal cellular physiology, NMII has recently emerged as a critical regulator of diverse, genetically complex diseases, including neuronal disorders, cancers and vascular disease. In the context of these disorders, NMII regulatory pathways can be directly mutated or indirectly altered by disease-causing mutations. NMII regulatory pathway genes are also increasingly found in disease-associated copy-number variants, particularly in neuronal disorders such as autism and schizophrenia. Furthermore, manipulation of NMII-mediated contractility regulates stem cell pluripotency and differentiation, thus highlighting the key role of NMII-based pharmaceuticals in the clinical success of stem cell therapies. In this Review, we discuss the emerging role of NMII activity and its regulation by kinases and microRNAs in the pathogenesis and prognosis of a diverse range of diseases, including neuronal disorders, cancer and vascular disease. We also address promising clinical applications and limitations of NMII-based inhibitors in the treatment of these diseases and the development of stem-cell-based therapies.

  11. Cellular Force Microscopy for in Vivo Measurements of Plant Tissue Mechanics1[W][OA

    Science.gov (United States)

    Routier-Kierzkowska, Anne-Lise; Weber, Alain; Kochova, Petra; Felekis, Dimitris; Nelson, Bradley J.; Kuhlemeier, Cris; Smith, Richard S.

    2012-01-01

    Although growth and morphogenesis are controlled by genetics, physical shape change in plant tissue results from a balance between cell wall loosening and intracellular pressure. Despite recent work demonstrating a role for mechanical signals in morphogenesis, precise measurement of mechanical properties at the individual cell level remains a technical challenge. To address this challenge, we have developed cellular force microscopy (CFM), which combines the versatility of classical microindentation techniques with the high automation and resolution approaching that of atomic force microscopy. CFM’s large range of forces provides the possibility to map the apparent stiffness of both plasmolyzed and turgid tissue as well as to perform micropuncture of cells using very high stresses. CFM experiments reveal that, within a tissue, local stiffness measurements can vary with the level of turgor pressure in an unexpected way. Altogether, our results highlight the importance of detailed physically based simulations for the interpretation of microindentation results. CFM’s ability to be used both to assess and manipulate tissue mechanics makes it a method of choice to unravel the feedbacks between mechanics, genetics, and morphogenesis. PMID:22353572

  12. A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

    Science.gov (United States)

    Randolph, Matthew E.; Pavlath, Grace K.

    2015-01-01

    The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The