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Sample records for skeletal tissue model

  1. Model of electrical conductivity of skeletal muscle based on tissue structure

    NARCIS (Netherlands)

    Gielen, F.L.H.; Cruts, H.E.P.; Alberts, B.A.; Boon, K.L.; Wallinga, W.; Boom, H.B.K.

    1986-01-01

    Recent experiments carried out in our laboratory with the four-electrode method showed that the electrical conductivity of skeletal muscle tissue depends on the frequency of the injected current and the distance between the current electrodes. A model is proposed in order to study these effects. The

  2. Three-Dimensional Culture Model of Skeletal Muscle Tissue with Atrophy Induced by Dexamethasone.

    Science.gov (United States)

    Shimizu, Kazunori; Genma, Riho; Gotou, Yuuki; Nagasaka, Sumire; Honda, Hiroyuki

    2017-06-15

    Drug screening systems for muscle atrophy based on the contractile force of cultured skeletal muscle tissues are required for the development of preventive or therapeutic drugs for atrophy. This study aims to develop a muscle atrophy model by inducing atrophy in normal muscle tissues constructed on microdevices capable of measuring the contractile force and to verify if this model is suitable for drug screening using the contractile force as an index. Tissue engineered skeletal muscles containing striated myotubes were prepared on the microdevices for the study. The addition of 100 µM dexamethasone (Dex), which is used as a muscle atrophy inducer, for 24 h reduced the contractile force significantly. An increase in the expression of Atrogin-1 and MuRF-1 in the tissues treated with Dex was established. A decrease in the number of striated myotubes was also observed in the tissues treated with Dex. Treatment with 8 ng/mL Insulin-like Growth Factor (IGF-I) for 24 h significantly increased the contractile force of the Dex-induced atrophic tissues. The same treatment, though, had no impact on the force of the normal tissues. Thus, it is envisaged that the atrophic skeletal muscle tissues induced by Dex can be used for drug screening against atrophy.

  3. An image-based skeletal tissue model for the ICRP reference newborn

    Energy Technology Data Exchange (ETDEWEB)

    Pafundi, Deanna; Lee, Choonsik; Bolch, Wesley [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL (United States); Watchman, Christopher; Bourke, Vincent [Department of Radiation Oncology, University of Arizona, Tucson, AZ (United States); Aris, John [Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (United States); Shagina, Natalia [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation); Harrison, John; Fell, Tim [Radiation Protection Division, Health Protection Agency, Chilton (United Kingdom)], E-mail: wbolch@ufl.edu

    2009-07-21

    Hybrid phantoms represent a third generation of computational models of human anatomy needed for dose assessment in both external and internal radiation exposures. Recently, we presented the first whole-body hybrid phantom of the ICRP reference newborn with a skeleton constructed from both non-uniform rational B-spline and polygon-mesh surfaces (Lee et al 2007 Phys. Med. Biol. 52 3309-33). The skeleton in that model included regions of cartilage and fibrous connective tissue, with the remainder given as a homogenous mixture of cortical and trabecular bone, active marrow and miscellaneous skeletal tissues. In the present study, we present a comprehensive skeletal tissue model of the ICRP reference newborn to permit a heterogeneous representation of the skeleton in that hybrid phantom set-both male and female-that explicitly includes a delineation of cortical bone so that marrow shielding effects are correctly modeled for low-energy photons incident upon the newborn skeleton. Data sources for the tissue model were threefold. First, skeletal site-dependent volumes of homogeneous bone were obtained from whole-cadaver CT image analyses. Second, selected newborn bone specimens were acquired at autopsy and subjected to micro-CT image analysis to derive model parameters of the marrow cavity and bone trabecular 3D microarchitecture. Third, data given in ICRP Publications 70 and 89 were selected to match reference values on total skeletal tissue mass. Active marrow distributions were found to be in reasonable agreement with those given previously by the ICRP. However, significant differences were seen in total skeletal and site-specific masses of trabecular and cortical bone between the current and ICRP newborn skeletal tissue models. The latter utilizes an age-independent ratio of 80%/20% cortical and trabecular bone for the reference newborn. In the current study, a ratio closer to 40%/60% is used based upon newborn CT and micro-CT skeletal image analyses. These changes in

  4. Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Sara Martina Maffioletti

    2018-04-01

    Full Text Available Summary: Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. : Maffioletti et al. generate human 3D artificial skeletal muscles from healthy donors and patient-specific pluripotent stem cells. These human artificial muscles accurately model severe genetic muscle diseases. They can be engineered to include other cell types present in skeletal muscle, such as vascular cells and motor neurons. Keywords: skeletal muscle, pluripotent stem cells, iPS cells, myogenic differentiation, tissue engineering, disease modeling, muscular dystrophy, organoids

  5. Loss of mass and performance in skeletal muscle tissue: a continuum model

    Directory of Open Access Journals (Sweden)

    Giantesio Giulia

    2018-02-01

    Full Text Available We present a continuum hyperelastic model which describes the mechanical response of a skeletal muscle tissue when its strength and mass are reduced by aging. Such a reduction is typical of a geriatric syndrome called sarcopenia. The passive behavior of the material is described by a hyperelastic, polyconvex, transversely isotropic strain energy function, and the activation of the muscle is modeled by the so called active strain approach. The loss of ability of activating of an elder muscle is then obtained by lowering of some percentage the active part of the stress, while the loss of mass is modeled through a multiplicative decomposition of the deformation gradient. The obtained stress-strain relations are graphically represented and discussed in order to study some of the effects of sarcopenia.

  6. Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering.

    Science.gov (United States)

    Maffioletti, Sara Martina; Sarcar, Shilpita; Henderson, Alexander B H; Mannhardt, Ingra; Pinton, Luca; Moyle, Louise Anne; Steele-Stallard, Heather; Cappellari, Ornella; Wells, Kim E; Ferrari, Giulia; Mitchell, Jamie S; Tyzack, Giulia E; Kotiadis, Vassilios N; Khedr, Moustafa; Ragazzi, Martina; Wang, Weixin; Duchen, Michael R; Patani, Rickie; Zammit, Peter S; Wells, Dominic J; Eschenhagen, Thomas; Tedesco, Francesco Saverio

    2018-04-17

    Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

    in the structure of fibrous collagen and myofibers at high-resolution. The results demonstrate that the collagen composition in the extra cellular matrix of Gadus morhua fish muscle is much more complex than previously anticipated, as it contains type III, IV, V  and VI collagen in addition to type I. The vascular....... Consequently, functional structures, ensuring "tissue maintenance" must form a major role of connective tissue, in addition that is to the force transmitting structures one typically finds in muscle. Vascular structures have also been shown to change their mechanical properties with age and it has been shown...

  8. Strain-time cell death threshold for skeletal muscle in a tissue-engineered model system for deep tissue injury

    NARCIS (Netherlands)

    Gefen, A.; Nierop, van B.J.; Bader, D.L.; Oomens, C.W.J.

    2008-01-01

    Deep tissue injury (DTI) is a severe pressure ulcer that results from sustained deformation of muscle tissue overlying bony prominences. In order to understand the etiology of DTI, it is essential to determine the tolerance of muscle cells to large mechanical strains. In this study, a new

  9. The essence of biophysical cues in skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Langelaan, M.L.P.

    2010-01-01

    Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications. Evidently, tissue engineered skeletal muscle can be used in the field of regenerative medicine to repair muscular defects or dystrophies. Engineered skeletal muscle constructs can also be used as a

  10. Stem Cells for Skeletal Muscle Tissue Engineering.

    Science.gov (United States)

    Pantelic, Molly N; Larkin, Lisa M

    2018-04-19

    Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML. Satellite cells are the native precursors to skeletal muscle tissue, and are thus the most commonly studied starting source for SMTE. However, satellite cells are difficult to isolate and purify, and it is presently unknown whether they would be a practical source in clinical SMTE applications. Alternative myogenic stem cells, including adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells, umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells, each have myogenic potential and have been identified as possible starting sources for SMTE, although they have yet to be studied in detail for this purpose. These alternative stem cell varieties offer unique advantages and disadvantages that are worth exploring further to advance the SMTE field toward highly functional, safe, and practical VML treatments. The following review summarizes the current state of satellite cell-based SMTE, details the properties and practical advantages of alternative myogenic stem cells, and offers guidance to tissue engineers on how alternative myogenic stem cells can be incorporated into SMTE research.

  11. A system model of the effects of exercise on plasma Interleukin-6 dynamics in healthy individuals: Role of skeletal muscle and adipose tissue.

    Science.gov (United States)

    Morettini, Micaela; Palumbo, Maria Concetta; Sacchetti, Massimo; Castiglione, Filippo; Mazzà, Claudia

    2017-01-01

    Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution. This study aimed at developing and validating a system model of exercise's effects on plasma IL-6 dynamics in healthy humans, combining the contributions of both adipose tissue and skeletal muscle. A two-compartment description was adopted to model plasma IL-6 changes in response to oxygen uptake's variation during an exercise bout. The free parameters of the model were estimated by means of a cross-validation procedure performed on four different datasets. A low coefficient of variation (dynamics during exercise and post-exercise were consistent with literature data from exercise protocols differing in intensity, duration and modality. The model successfully emulated the physiological effects of exercise on plasma IL-6 levels and provided a reliable description of the role of skeletal muscle and adipose tissue on the dynamics of plasma IL-6. The system model here proposed is suitable to simulate IL-6 response to different exercise modalities. Its future integration with existing models of GLP-1-induced insulin secretion might provide a more reliable description of exercise's effects on glucose homeostasis and hence support the definition of more tailored interventions for the treatment of type 2 diabetes.

  12. Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury.

    Science.gov (United States)

    Dearth, Christopher L; Slivka, Peter F; Stewart, Scott A; Keane, Timothy J; Tay, Justin K; Londono, Ricardo; Goh, Qingnian; Pizza, Francis X; Badylak, Stephen F

    2016-02-01

    Extracellular matrix (ECM) has been used as a biologic scaffold material to both reinforce the surgical repair of soft tissue and serve as an inductive template to promote a constructive tissue remodeling response. Success of such an approach is dependent on macrophage-mediated degradation and remodeling of the biologic scaffold. Macrophage phenotype during these processes is a predictive factor of the eventual remodeling outcome. ECM scaffolds have been shown to promote an anti-inflammatory or M2-like macrophage phenotype in vitro that includes secretion of downstream products of cycolooxygenases 1 and 2 (COX1/2). The present study investigated the effect of a common COX1/2 inhibitor (Aspirin) on macrophage phenotype and tissue remodeling in a rodent model of ECM scaffold treated skeletal muscle injury. Inhibition of COX1/2 reduced the constructive remodeling response by hindering myogenesis and collagen deposition in the defect area. The inhibited response was correlated with a reduction in M2-like macrophages in the defect area. The effects of Aspirin on macrophage phenotype were corroborated using an established in vitro macrophage model which showed a reduction in both ECM induced prostaglandin secretion and expression of a marker of M2-like macrophages (CD206). These results raise questions regarding the common peri-surgical administration of COX1/2 inhibitors when biologic scaffold materials are used to facilitate muscle repair/regeneration. COX1/2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely administered post-surgically for analgesic purposes. While COX1/2 inhibitors are important in pain management, they have also been shown to delay or diminish the healing process, which calls to question their clinical use for treating musculotendinous injuries. The present study aimed to investigate the influence of a common NSAID, Aspirin, on the constructive remodeling response mediated by an ECM scaffold (UBM) in a rat skeletal

  13. Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications.

    Science.gov (United States)

    Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu; Khademhosseini, Ali

    2014-10-01

    Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.

  14. Tracing the evolutionary origin of vertebrate skeletal tissues: insights from cephalochordate amphioxus.

    Science.gov (United States)

    Yong, Luok Wen; Yu, Jr-Kai

    2016-08-01

    Vertebrate mineralized skeletal tissues are widely considered as an evolutionary novelty. Despite the importance of these tissues to the adaptation and radiation of vertebrate animals, the evolutionary origin of vertebrate skeletal tissues remains largely unclear. Cephalochordates (Amphioxus) occupy a key phylogenetic position and can serve as a valuable model for studying the evolution of vertebrate skeletal tissues. Here we summarize recent advances in amphioxus developmental biology and comparative genomics that can help to elucidate the evolutionary origins of the vertebrate skeletal tissues and their underlying developmental gene regulatory networks (GRN). By making comparisons to the developmental studies in vertebrate models and recent discoveries in paleontology and genomics, it becomes evident that the collagen matrix-based connective tissues secreted by the somite-derived cells in amphioxus likely represent the rudimentary skeletal tissues in chordates. We propose that upon the foundation of this collagenous precursor, novel tissue mineralization genes that arose from gene duplications were incorporated into an ancestral mesodermal GRN that makes connective and supporting tissues, leading to the emergence of highly-mineralized skeletal tissues in early vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Selection, processing and clinical application of muscle-skeletal tissue

    International Nuclear Information System (INIS)

    Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G.

    2007-01-01

    Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

  16. Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model.

    Directory of Open Access Journals (Sweden)

    Darren Paul Burke

    Full Text Available Extrinsic mechanical signals have been implicated as key regulators of mesenchymal stem cell (MSC differentiation. It has been possible to test different hypotheses for mechano-regulated MSC differentiation by attempting to simulate regenerative events such as bone fracture repair, where repeatable spatial and temporal patterns of tissue differentiation occur. More recently, in vitro studies have identified other environmental cues such as substrate stiffness and oxygen tension as key regulators of MSC differentiation; however it remains unclear if and how such cues determine stem cell fate in vivo. As part of this study, a computational model was developed to test the hypothesis that substrate stiffness and oxygen tension regulate stem cell differentiation during fracture healing. Rather than assuming mechanical signals act directly on stem cells to determine their differentiation pathway, it is postulated that they act indirectly to regulate angiogenesis and hence partially determine the local oxygen environment within a regenerating tissue. Chondrogenesis of MSCs was hypothesized to occur in low oxygen regions, while in well vascularised regions of the regenerating tissue a soft local substrate was hypothesised to facilitate adipogenesis while a stiff substrate facilitated osteogenesis. Predictions from the model were compared to both experimental data and to predictions of a well established computational mechanobiological model where tissue differentiation is assumed to be regulated directly by the local mechanical environment. The model predicted all the major events of fracture repair, including cartilaginous bridging, endosteal and periosteal bony bridging and bone remodelling. It therefore provides support for the hypothesis that substrate stiffness and oxygen play a key role in regulating MSC fate during regenerative events such as fracture healing.

  17. Current opportunities and challenges in skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Koning, Merel; Harmsen, Martin C; van Luyn, Marja J A; Werker, Paul M N

    The purpose of this article is to give a concise review of the current state of the art in tissue engineering (TE) of skeletal muscle and the opportunities and challenges for future clinical applicability. The endogenous progenitor cells of skeletal muscle, i.e. satellite cells, show a high

  18. Radiology of skeletal and soft tissue changes

    International Nuclear Information System (INIS)

    Walker, H.C. Jr.; Coleman, C.C.; Hunter, D.W.

    1986-01-01

    Skeletal complications are very common in renal transplant patients. Loss of bone mass in the posttransplant period places the skeletal system in jeopardy. Osteonecrosis, while not life threatening, often prevents rehabilitation. Spontaneous fractures are frequent but are usually not a major problem except in the diabetic transplant recipient. Septic arthritis and osteomyelitis are usually successfully managed by conservative measures, except when accompanied by severe occlusive vascular disease. Juvenile onset diabetic patients still may develop disabling neuropathic joint disease or occlusive vascular disease after renal transplantation. The authors hope that successful pancreas transplantation will avert these problems in the future

  19. Adipose tissue and skeletal muscle blood flow during mental stress

    Energy Technology Data Exchange (ETDEWEB)

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

    1989-01-01

    Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

  20. Adipose tissue and skeletal muscle blood flow during mental stress

    International Nuclear Information System (INIS)

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

    1989-01-01

    Mental stress [a modified Stroop color word conflict test (CWT)] increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation

  1. 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

  2. A Novel bioreactor with mechanical stimulation for skeletal tissue engineering

    Directory of Open Access Journals (Sweden)

    M. Petrović

    2009-01-01

    Full Text Available The provision of mechanical stimulation is believed to be necessary for the functional assembly of skeletal tissues, which are normally exposed to a variety of biomechanical signals in vivo. In this paper, we present a development and validation of a novel bioreactor aimed for skeletal tissue engineering that provides dynamic compression and perfusion of cultivated tissues. Dynamic compression can be applied at frequencies up to 67.5 Hz and displacements down to 5 m thus suitable for the simulation of physiological conditions in a native cartilage tissue (0.1-1 Hz, 5-10 % strain. The bioreactor also includes a load sensor that was calibrated so to measure average loads imposed on tissue samples. Regimes of the mechanical stimulation and acquisition of load sensor outputs are directed by an automatic control system using applications developed within the LabView platform. In addition, perfusion of tissue samples at physiological velocities (10–100 m/s provides efficient mass transfer, as well as the possibilities to expose the cells to hydrodynamic shear and simulate the conditions in a native bone tissue. Thus, the novel bioreactor is suited for studies of the effects of different biomechanical signals on in vitro regeneration of skeletal tissues, as well as for the studies of newly formulated biomaterials and cell biomaterial interactions under in vivo-like settings.

  3. Tissue Engineered Strategies for Skeletal Muscle Injury

    Directory of Open Access Journals (Sweden)

    Umile Giuseppe Longo

    2012-01-01

    Full Text Available Skeletal muscle injuries are common in athletes, occurring with direct and indirect mechanisms and marked residual effects, such as severe long-term pain and physical disability. Current therapy consists of conservative management including RICE protocol (rest, ice, compression, and elevation, nonsteroidal anti-inflammatory drugs, and intramuscular corticosteroids. However, current management of muscle injuries often does not provide optimal restoration to preinjury status. New biological therapies, such as injection of platelet-rich plasma and stem-cell-based therapy, are appealing. Although some studies support PRP application in muscle-injury management, reasons for concern persist, and further research is required for a standardized and safe use of PRP in clinical practice. The role of stem cells needs to be confirmed, as studies are still limited and inconsistent. Further research is needed to identify mechanisms involved in muscle regeneration and in survival, proliferation, and differentiation of stem cells.

  4. Characterisation of connective tissue from the hypertrophic skeletal muscle of myostatin null mice.

    Science.gov (United States)

    Elashry, Mohamed I; Collins-Hooper, Henry; Vaiyapuri, Sakthivel; Patel, Ketan

    2012-06-01

    Myostatin is a potent inhibitor of muscle development. Genetic deletion of myostatin in mice results in muscle mass increase, with muscles often weighing three times their normal values. Contracting muscle transfers tension to skeletal elements through an elaborate connective tissue network. Therefore, the connective tissue of skeletal muscle is an integral component of the contractile apparatus. Here we examine the connective tissue architecture in myostatin null muscle. We show that the hypertrophic muscle has decreased connective tissue content compared with wild-type muscle. Secondly, we show that the hypertrophic muscle fails to show the normal increase in muscle connective tissue content during ageing. Therefore, genetic deletion of myostatin results in an increase in contractile elements but a decrease in connective tissue content. We propose a model based on the contractile profile of muscle fibres that reconciles this apparent incompatible tissue composition phenotype. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

  5. Meet the new meat: tissue engineered skeletal muscle

    NARCIS (Netherlands)

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

    2010-01-01

    Contemporary large-scale farming and transportation of livestock brings along a high risk of infectious animal diseases and environmental burden through greenhouse gas emission. A new approach to produce meat and thereby reducing these risks is found in tissue engineering of skeletal muscle. This

  6. Tissue Engineered Skeletal Myofibers can Directly "Sense" Gravitational Force Changes

    Science.gov (United States)

    Vandenburgh, Herman H.; Shansky, J.; DelTatto, M.; Lee, Peter; Meir, J.

    1999-01-01

    Long-term manned space flight requires a better understanding of skeletal muscle atrophy resulting from microgravity. Atrophy most likely results from changes at both the systemic level (e.g. decreased circulating growth hormone, increased circulating glucocorticoids) and locally (e.g. decreased myofiber resting tension). Differentiated skeletal myofibers in tissue culture have provided a model system over the last decade for gaining a better understanding of the interactions of exogenous growth factors, endogenous growth factors, and muscle fiber tension in regulating protein turnover rates and muscle cell growth. Tissue engineering these cells into three dimensional bioartificial muscle (BAM) constructs has allowed us to extend their use to Space flight studies for the potential future development of countermeasures. Embryonic avian muscle cells were isolated and BAMs tissue engineered as described previously. The myoblasts proliferate and fuse into aligned postmitotic myofibers after ten to fourteen days in vitro. A cylindrical muscle-like structure containing several thousand myofibers is formed which is approximately 30 mm in length, 2-3 mm in diameter, and attached at each end. For the Space Shuttle experiments, the BAMs were transferred to 55 mL bioreactor cartridges (6 BAMs/cartridge). At Kennedy Space Center, the cartridges were mounted in two Space Tissue Loss (STL) Modules (three to four cartridges per Module) and either maintained as ground controls or loaded in a Mid-Deck locker of the Space Shuttle. The BAM cartridges were continuously perfused during the experiment at 1.5 mL/ min with tissue culture medium. Eighteen BAMs were flown for nine days on Mission STS66 while eighteen BAMs served as ground controls. The complete experiment was repeated on Mission STS77 with twenty four BAMs in each group. BAMs could be maintained in a healthy state for at least 30 days in the perfusion bioreactor cartridges. The BAM muscle fibers directly detected both the

  7. Skeletal muscle atrophy in bioengineered skeletal muscle: a new model system.

    Science.gov (United States)

    Lee, Peter H U; Vandenburgh, Herman H

    2013-10-01

    Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ∼3 weeks to 2587±502 μN/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy.

  8. Responsiveness to Thyroid Hormone and to Ambient Temperature Underlies Differences Between Brown Adipose Tissue and Skeletal Muscle Thermogenesis in a Mouse Model of Diet-Induced Obesity

    Science.gov (United States)

    Ueta, Cintia B.; Olivares, Emerson L.

    2011-01-01

    Thyroid hormone accelerates energy expenditure (EE) and is critical for cold-induced thermogenesis. To define the metabolic role played by thyroid hormone in the dissipation of calories from diet, hypothyroid mice were studied for 60 d in a comprehensive lab animal monitoring system. Hypothyroidism decreased caloric intake and body fat while down-regulating genes in the skeletal muscle but not brown adipose tissue thermogenic programs, without affecting daily EE. Only at thermoneutrality (30 C) did hypothyroid mice exhibit slower rate of EE, indicating a metabolic response to hypothyroidism that depends on ambient temperature. A byproduct of this mechanism is that at room temperature (22 C), hypothyroid mice are protected against diet-induced obesity, i.e. only at thermoneutrality did hypothyroid mice become obese when placed on a high-fat diet (HFD). This is in contrast to euthyroid controls, which on a HFD gained more body weight and fat at any temperature while activating the brown adipose tissue and accelerating daily EE but not the skeletal muscle thermogenic program. In the liver of euthyroid controls, HFD caused an approximately 5-fold increase in triglyceride content and expression of key metabolic genes, whereas acclimatization to 30 C cut triglyceride content by half and normalized gene expression. However, in hypothyroid mice, HFD-induced changes in liver persisted at 30 C, resulting in marked liver steatosis. Acclimatization to thermoneutrality dramatically improves glucose homeostasis, but this was not affected by hypothyroidism. In conclusion, hypothyroid mice are metabolically sensitive to environmental temperature, constituting a mechanism that defines resistance to diet-induced obesity and hepatic lipid metabolism. PMID:21771890

  9. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    Science.gov (United States)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  10. Chord-based versus voxel-based methods of electron transport in the skeletal tissues

    International Nuclear Information System (INIS)

    Shah, Amish P.; Jokisch, Derek W.; Rajon, Didier A.; Watchman, Christopher J.; Patton, Phillip W.; Bolch, Wesley E.

    2005-01-01

    Anatomic models needed for internal dose assessment have traditionally been developed using mathematical surface equations to define organ boundaries, shapes, and their positions within the body. Many researchers, however, are now advocating the use of tomographic models created from segmented patient computed tomography (CT) or magnetic resonance (MR) scans. In the skeleton, however, the tissue structures of the bone trabeculae, marrow cavities, and endosteal layer are exceedingly small and of complex shape, and thus do not lend themselves easily to either stylistic representations or in-vivo CT imaging. Historically, the problem of modeling the skeletal tissues has been addressed through the development of chord-based methods of radiation particle transport, as given by studies at the University of Leeds (Leeds, UK) using a 44-year male subject. We have proposed an alternative approach to skeletal dosimetry in which excised sections of marrow-intact cadaver spongiosa are imaged directly via microCT scanning. The cadaver selected for initial investigation of this technique was a 66-year male subject of nominal body mass index (22.7 kg m -2 ). The objectives of the present study were to compare chord-based versus voxel-based methods of skeletal dosimetry using data from the UF 66-year male subject. Good agreement between chord-based and voxel-based transport was noted for marrow irradiation by either bone surface or bone volume sources up to 500-1000 keV (depending upon the skeletal site). In contrast, chord-based models of electron transport yielded consistently lower values of the self-absorbed fraction to marrow tissues than seen under voxel-based transport at energies above 100 keV, a feature directly attributed to the inability of chord-based models to account for nonlinear electron trajectories. Significant differences were also noted in the dosimetry of the endosteal layer (for all source tissues), with chord-based transport predicting a higher fraction of

  11. Improved Cell Culture Method for Growing Contracting Skeletal Muscle Models

    Science.gov (United States)

    Marquette, Michele L.; Sognier, Marguerite A.

    2013-01-01

    An improved method for culturing immature muscle cells (myoblasts) into a mature skeletal muscle overcomes some of the notable limitations of prior culture methods. The development of the method is a major advance in tissue engineering in that, for the first time, a cell-based model spontaneously fuses and differentiates into masses of highly aligned, contracting myotubes. This method enables (1) the construction of improved two-dimensional (monolayer) skeletal muscle test beds; (2) development of contracting three-dimensional tissue models; and (3) improved transplantable tissues for biomedical and regenerative medicine applications. With adaptation, this method also offers potential application for production of other tissue types (i.e., bone and cardiac) from corresponding precursor cells.

  12. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

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

    2002-01-01

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

  13. Proton microprobe analysis of zinc in skeletal tissues

    International Nuclear Information System (INIS)

    Doty, S.B.; Jones, K.W.; Kraner, H.W.; Shroy, R.E.; Hanson, A.L.

    1981-01-01

    A proton microprobe with windowless exit port has been used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton micorprobe is uniquely suited to this work since it combines high sensitivity for zinc determinations in thick samples with good spatial resolution. Our measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage. (orig.)

  14. Proton microprobe analysis of zinc in skeletal tissues

    Science.gov (United States)

    Doty, S. B.; Jones, K. W.; Kraner, H. W.; Shroy, R. E.; Hanson, A. L.

    1981-03-01

    A proton microprobe with windowless exit port has been used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton microprobe is uniquely suited to this work since it combines high sensitivity for zinc determination in thick samples with good spatial resolution. Our measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage.

  15. Proton microprobe analysis of zinc in skeletal tissues

    International Nuclear Information System (INIS)

    Doty, S.B.; Jones, K.W.; Kraner, H.W.; Shroy, R.E.; Hanson, A.L.

    1980-06-01

    A proton microprobe with windowless exit port was used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton microprobe is uniquely suited to this work since it combines high sensitivity for zinc determinations in thick samples with good spatial resolution. Measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage

  16. How does tissue preparation affect skeletal muscle transverse isotropy?

    Science.gov (United States)

    Wheatley, Benjamin B.; Odegard, Gregory M.; Kaufman, Kenton R.; Haut Donahue, Tammy L.

    2016-01-01

    The passive tensile properties of skeletal muscle play a key role in its physiological function. Previous research has identified conflicting reports of muscle transverse isotropy, with some data suggesting the longitudinal direction is stiffest, while others show the transverse direction is stiffest. Accurate constitutive models of skeletal muscle must be employed to provide correct recommendations for and observations of clinical methods. The goal of this work was to identify transversely isotropic tensile muscle properties as a function of post mortem handling. Six pairs of tibialis anterior muscles were harvested from Giant Flemish rabbits and split into two groups: fresh testing (within four hours post mortem), and non-fresh testing (subject to delayed testing and a freeze/thaw cycle). Longitudinal and transverse samples were removed from each muscle and tested to identify tensile modulus and relaxation behavior. Longitudinal non-fresh samples exhibited a higher initial modulus value and faster relaxation than longitudinal fresh, transverse fresh, and transverse rigor samples (p<0.05), while longitudinal fresh samples were less stiff at lower strain levels than longitudinal non-fresh, transverse fresh, and transverse non-fresh samples (p<0.05), but exhibited more nonlinear behavior. While fresh skeletal muscle exhibits a higher transverse modulus than longitudinal modulus, discrepancies in previously published data may be the result of a number of differences in experimental protocol. Constitutive modeling of fresh muscle should reflect these data by identifying the material as truly transversely isotropic and not as an isotropic matrix reinforced with fibers. PMID:27425557

  17. Calcium model for mammalian skeletal muscle

    NARCIS (Netherlands)

    Wallinga, W.; Boom, H.B.K.; Heijink, R.J.; van der Vliet, G.H.

    1981-01-01

    A model is presented describing quantitatively the events between excitation and force development in skeletal muscle. It consists of a calcium mediated activation model (c.m.a.m.) in series with a force generator model (f.g.m.). The c.m.a.m. was based on intracellular processes such as cisternal

  18. Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends.

    Science.gov (United States)

    Qazi, Taimoor H; Mooney, David J; Pumberger, Matthias; Geissler, Sven; Duda, Georg N

    2015-01-01

    Skeletal muscles have a robust capacity to regenerate, but under compromised conditions, such as severe trauma, the loss of muscle functionality is inevitable. Research carried out in the field of skeletal muscle tissue engineering has elucidated multiple intrinsic mechanisms of skeletal muscle repair, and has thus sought to identify various types of cells and bioactive factors which play an important role during regeneration. In order to maximize the potential therapeutic effects of cells and growth factors, several biomaterial based strategies have been developed and successfully implemented in animal muscle injury models. A suitable biomaterial can be utilized as a template to guide tissue reorganization, as a matrix that provides optimum micro-environmental conditions to cells, as a delivery vehicle to carry bioactive factors which can be released in a controlled manner, and as local niches to orchestrate in situ tissue regeneration. A myriad of biomaterials, varying in geometrical structure, physical form, chemical properties, and biofunctionality have been investigated for skeletal muscle tissue engineering applications. In the current review, we present a detailed summary of studies where the use of biomaterials favorably influenced muscle repair. Biomaterials in the form of porous three-dimensional scaffolds, hydrogels, fibrous meshes, and patterned substrates with defined topographies, have each displayed unique benefits, and are discussed herein. Additionally, several biomaterial based approaches aimed specifically at stimulating vascularization, innervation, and inducing contractility in regenerating muscle tissues are also discussed. Finally, we outline promising future trends in the field of muscle regeneration involving a deeper understanding of the endogenous healing cascades and utilization of this knowledge for the development of multifunctional, hybrid, biomaterials which support and enable muscle regeneration under compromised conditions

  19. Magnetic resonance tomography in skeletal and soft tissue traumas

    International Nuclear Information System (INIS)

    Stiris, Morten G.

    2000-01-01

    MRI has revolutionised the diagnostic yield in musculo-skeletal trauma. Studies have documented that MRI can be an accurate, cost-effective means of assessing injuries in the knee, the foot and the ankle and it may also be cost-effective in other anatomic locations. MRTI may have a significant impact on decision-making in relation to these patients and on the follow-up. The patient does not need to be moved for evaluation in all the anatomical planes. Each study can also be post-processes if necessary. MRI may be used in patients with fractures for evaluation of complications. The fracture lines as well as accompanying soft tissue damage are well documented

  20. Enhancement of contractile force generation of artificial skeletal muscle tissues by mild and transient heat treatment.

    Science.gov (United States)

    Sato, Masanori; Ikeda, Kazushi; Kanno, Shota; Ito, Akira; Kawabe, Yoshinori; Kamihira, Masamichi

    2014-01-01

    Artificial skeletal muscle tissues composed of cells are expected to be used for applications of regenerative medicine and drug screening. Generally, however, the physical forces generated by tissue-engineered skeletal muscle are lower than those of skeletal muscle tissues found in the body. Local hyperthermia is used for many diseases including muscle injuries. It was recently reported that mild heat treatment improved skeletal muscle functions. In this study, we investigated the effects of mild heat treatment on the tissue-engineered skeletal muscle tissues in vitro. We used magnetite cationic liposomes to label C2C12 myoblast cells magnetically, and constructed densely packed artificial skeletal muscle tissues by using magnetic force. Cell culture at 39°C promoted the differentiation of myoblast cells into myotubes. Moreover, the mild and transient heat treatment improved the contractile properties of artificial skeletal muscle tissue constructs. These findings indicate that the culture method using heat treatment is a useful approach to enhance functions of artificial skeletal muscle tissue.

  1. Functional evaluation of artificial skeletal muscle tissue constructs fabricated by a magnetic force-based tissue engineering technique.

    Science.gov (United States)

    Yamamoto, Yasunori; Ito, Akira; Fujita, Hideaki; Nagamori, Eiji; Kawabe, Yoshinori; Kamihira, Masamichi

    2011-01-01

    Skeletal muscle tissue engineering is currently applied in a variety of research fields, including regenerative medicine, drug screening, and bioactuator development, all of which require the fabrication of biomimic and functional skeletal muscle tissues. In the present study, magnetite cationic liposomes were used to magnetically label C2C12 myoblast cells for the construction of three-dimensional artificial skeletal muscle tissues by an applied magnetic force. Skeletal muscle functions, such as biochemical and contractile properties, were evaluated for the artificial tissue constructs. Histological studies revealed that elongated and multinucleated myotubes were observed within the tissue. Expression of muscle-specific markers, such as myogenin, myosin heavy chain and tropomyosin, were detected in the tissue constructs by western blot analysis. Further, creatine kinase activity increased during differentiation. In response to electric pulses, the artificial tissue constructs contracted to generate a physical force (the maximum twitch force, 33.2 μN [1.06 mN/mm2]). Rheobase and chronaxie of the tissue were determined as 4.45 V and 0.72 ms, respectively. These results indicate that the artificial skeletal muscle tissue constructs fabricated in this study were physiologically functional and the data obtained for the evaluation of their functional properties may provide useful information for future skeletal muscle tissue engineering studies.

  2. Effect of heat stress on contractility of tissue-engineered artificial skeletal muscle.

    Science.gov (United States)

    Takagi, Shunya; Nakamura, Tomohiro; Fujisato, Toshia

    2018-01-23

    The effects of heat stress on tissue like skeletal muscle have been widely studied. However, the mechanism responsible for the effect of heat stress is still unclear. A useful experimental tissue model is necessary because muscle function in cell culture may differ from native muscle and measuring its contractility is difficult. We previously reported three-dimensional tissue-engineered artificial skeletal muscle (TEM) that can be easily set in a measurement apparatus for quantitative evaluation of contractility. We have now applied TEM to the investigation of heat stress. We analyzed contractility immediately after thermal exposure at 39 °C for 24 or 48 h to evaluate the acute effects and after thermal exposure followed by normal culture to evaluate the aftereffects. Peak twitch contractile force and time-to-peak twitch were used as contractile parameters. Heat stress increased the TCF in the early stage (1 week) after normal culture; the TCF decreased temporarily in the middle to late stages (2-3 weeks). These results suggest that heat stress may affect both myoblast fusion and myotube differentiation in the early stage of TEM culture, but not myotube maturation in the late stage. The TCF increase rate with thermal exposure was significantly higher than that without thermal exposure. Although detailed analysis at the molecular level is necessary for further investigation, our artificial skeletal muscle may be a promising tool for heat stress investigation.

  3. New Skeletal-Space-Filling Models

    Science.gov (United States)

    Clarke, Frank H.

    1977-01-01

    Describes plastic, skeletal molecular models that are color-coded and can illustrate both the conformation and overall shape of small molecules. They can also be converted to space-filling counterparts by the additions of color-coded polystyrene spheres. (MLH)

  4. A DIC Based Technique to Measure the Contraction of a Skeletal Muscle Engineered Tissue

    Directory of Open Access Journals (Sweden)

    Emanuele Rizzuto

    2016-01-01

    Full Text Available Tissue engineering is a multidisciplinary science based on the application of engineering approaches to biologic tissue formation. Engineered tissue internal organization represents a key aspect to increase biofunctionality before transplant and, as regarding skeletal muscles, the potential of generating contractile forces is dependent on the internal fiber organization and is reflected by some macroscopic parameters, such as the spontaneous contraction. Here we propose the application of digital image correlation (DIC as an independent tool for an accurate and noninvasive measurement of engineered muscle tissue spontaneous contraction. To validate the proposed technique we referred to the X-MET, a promising 3-dimensional model of skeletal muscle. The images acquired through a high speed camera were correlated with a custom-made algorithm and the longitudinal strain predictions were employed for measuring the spontaneous contraction. The spontaneous contraction reference values were obtained by studying the force response. The relative error between the spontaneous contraction frequencies computed in both ways was always lower than 0.15%. In conclusion, the use of a DIC based system allows for an accurate and noninvasive measurement of biological tissues’ spontaneous contraction, in addition to the measurement of tissue strain field on any desired region of interest during electrical stimulation.

  5. Three-dimensional optical coherence micro-elastography of skeletal muscle tissue

    OpenAIRE

    Chin, Lixin; Kennedy, Brendan F.; Kennedy, Kelsey M.; Wijesinghe, Philip; Pinniger, Gavin J.; Terrill, Jessica R.; McLaughlin, Robert A.; Sampson, David D.

    2014-01-01

    In many muscle pathologies, impairment of skeletal muscle function is closely linked to changes in the mechanical properties of the muscle constituents. Optical coherence micro-elastography (OCME) uses optical coherence tomography (OCT) imaging of tissue under a quasi-static, compressive mechanical load to map variations in tissue mechanical properties on the micro-scale. We present the first study of OCME on skeletal muscle tissue. We show that this technique can resolve features of muscle t...

  6. Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

    Science.gov (United States)

    Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

    1998-01-01

    Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

  7. Creating Interactions between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System.

    Science.gov (United States)

    Smith, Alec S T; Passey, Samantha L; Martin, Neil R W; Player, Darren J; Mudera, Vivek; Greensmith, Linda; Lewis, Mark P

    2016-01-01

    Effective models of mammalian tissues must allow and encourage physiologically (mimetic) correct interactions between co-cultured cell types in order to produce culture microenvironments as similar as possible to those that would normally occur in vivo. In the case of skeletal muscle, the development of such a culture model, integrating multiple relevant cell types within a biomimetic scaffold, would be of significant benefit for investigations into the development, functional performance, and pathophysiology of skeletal muscle tissue. Although some work has been published regarding the behaviour of in vitro muscle models co-cultured with organotypic slices of CNS tissue or with stem cell-derived neurospheres, little investigation has so far been made regarding the potential to maintain isolated motor neurons within a 3D biomimetic skeletal muscle culture platform. Here, we review the current state of the art for engineering neuromuscular contacts in vitro and provide original data detailing the development of a 3D collagen-based model for the co-culture of primary muscle cells and motor neurons. The devised culture system promotes increased myoblast differentiation, forming arrays of parallel, aligned myotubes on which areas of nerve-muscle contact can be detected by immunostaining for pre- and post-synaptic proteins. Quantitative RT-PCR results indicate that motor neuron presence has a positive effect on myotube maturation, suggesting neural incorporation influences muscle development and maturation in vitro. The importance of this work is discussed in relation to other published neuromuscular co-culture platforms along with possible future directions for the field. © 2016 S. Karger AG, Basel.

  8. 3D scanning and printing skeletal tissues for anatomy education.

    Science.gov (United States)

    Thomas, Daniel B; Hiscox, Jessica D; Dixon, Blair J; Potgieter, Johan

    2016-09-01

    Detailed anatomical models can be produced with consumer-level 3D scanning and printing systems. 3D replication techniques are significant advances for anatomical education as they allow practitioners to more easily introduce diverse or numerous specimens into classrooms. Here we present a methodology for producing anatomical models in-house, with the chondrocranium cartilage from a spiny dogfish (Squalus acanthias) and the skeleton of a cane toad (Rhinella marina) as case studies. 3D digital replicas were produced using two consumer-level scanners and specimens were 3D-printed with selective laser sintering. The fidelity of the two case study models was determined with respect to key anatomical features. Larger-scale features of the dogfish chondrocranium and frog skeleton were all well-resolved and distinct in the 3D digital models, and many finer-scale features were also well-resolved, but some more subtle features were absent from the digital models (e.g. endolymphatic foramina in chondrocranium). All characters identified in the digital chondrocranium could be identified in the subsequent 3D print; however, three characters in the 3D-printed frog skeleton could not be clearly delimited (palatines, parasphenoid and pubis). Characters that were absent in the digital models or 3D prints had low-relief in the original scanned specimen and represent a minor loss of fidelity. Our method description and case studies show that minimal equipment and training is needed to produce durable skeletal specimens. These technologies support the tailored production of models for specific classes or research aims. © 2016 Anatomical Society.

  9. Calprotectin is released from human skeletal muscle tissue during exercise

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Andersen, Kasper; Fischer, Christian

    2008-01-01

    Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained...... in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at approximately 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known...... as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of approximately 50...

  10. Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.

    Science.gov (United States)

    Grant, R W; Vester Boler, B M; Ridge, T K; Graves, T K; Swanson, K S

    2013-08-01

    Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation

  11. Impact of Perturbed Pancreatic β-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism

    Science.gov (United States)

    Cochran, Blake J.; Hou, Liming; Manavalan, Anil Paul Chirackal; Moore, Benjamin M.; Tabet, Fatiha; Sultana, Afroza; Cuesta Torres, Luisa; Tang, Shudi; Shrestha, Sudichhya; Senanayake, Praween; Patel, Mili; Ryder, William J.; Bongers, Andre; Maraninchi, Marie; Wasinger, Valerie C.; Westerterp, Marit; Tall, Alan R.; Barter, Philip J.

    2016-01-01

    Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The β-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of β-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify β-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes. PMID:27702832

  12. Bioactive scaffolds for the controlled formation of complex skeletal tissues

    NARCIS (Netherlands)

    Hofmann, S.; Garcia-Fuentes, M.; Eberli, D.

    2011-01-01

    Tissue Engineering may offer new treatment alternatives for organ replacement or repair deteriorated organs. Among the clinical applications of Tissue Engineering are the production of artificial skin for burn patients, tissue engineered trachea, cartilage for knee-replacement procedures, urinary

  13. Skeletal Muscle Derived IL-6 in Liver and Adipose Tissue Metabolism

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

    Summary Physical activity can lead to metabolic disease and treatment of several metabolic diseases include exercise training. Skeletal muscle has, due to its central role in glucose and fat metabolism at rest and during exercise been studied in detail with regard to exercise training. The role...... of both liver and adipose tissue regulation in whole body metabolism has come in to focus and it has been shown that both tissues are subject to exercise training-induced adaptations. However, the contribution of endocrine factors to the regulation of exercise training-induced adaptations in liver...... and adipose tissue metabolism is unknown. It has been suggested that myokines, such as IL-6, released from skeletal muscle affects liver and adipose tissue and are involved in the regulation of exercise training adaptations. Thus, the aim of this thesis was to investigate the role of skeletal muscle derived...

  14. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard

    2013-01-01

    -specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...... of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including...

  15. Animal Cancer Models of Skeletal Metastasis

    Directory of Open Access Journals (Sweden)

    Catherine Hibberd

    2013-01-01

    Full Text Available The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. This review summarizes the current in vivo animal models used in the study of cancer metastases of the skeleton.

  16. Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges.

    Science.gov (United States)

    Duffy, Rebecca M; Feinberg, Adam W

    2014-01-01

    Skeletal muscle is a scalable actuator system used throughout nature from the millimeter to meter length scales and over a wide range of frequencies and force regimes. This adaptability has spurred interest in using engineered skeletal muscle to power soft robotics devices and in biotechnology and medical applications. However, the challenges to doing this are similar to those facing the tissue engineering and regenerative medicine fields; specifically, how do we translate our understanding of myogenesis in vivo to the engineering of muscle constructs in vitro to achieve functional integration with devices. To do this researchers are developing a number of ways to engineer the cellular microenvironment to guide skeletal muscle tissue formation. This includes understanding the role of substrate stiffness and the mechanical environment, engineering the spatial organization of biochemical and physical cues to guide muscle alignment, and developing bioreactors for mechanical and electrical conditioning. Examples of engineered skeletal muscle that can potentially be used in soft robotics include 2D cantilever-based skeletal muscle actuators and 3D skeletal muscle tissues engineered using scaffolds or directed self-organization. Integration into devices has led to basic muscle-powered devices such as grippers and pumps as well as more sophisticated muscle-powered soft robots that walk and swim. Looking forward, current, and future challenges include identifying the best source of muscle precursor cells to expand and differentiate into myotubes, replacing cardiomyocytes with skeletal muscle tissue as the bio-actuator of choice for soft robots, and vascularization and innervation to enable control and nourishment of larger muscle tissue constructs. © 2013 Wiley Periodicals, Inc.

  17. The skeletal vascular system - Breathing life into bone tissue.

    Science.gov (United States)

    Stegen, Steve; Carmeliet, Geert

    2017-08-26

    During bone development, homeostasis and repair, a dense vascular system provides oxygen and nutrients to highly anabolic skeletal cells. Characteristic for the vascular system in bone is the serial organization of two capillary systems, each typified by specific morphological and physiological features. Especially the arterial capillaries mediate the growth of the bone vascular system, serve as a niche for skeletal and hematopoietic progenitors and couple angiogenesis to osteogenesis. Endothelial cells and osteoprogenitor cells interact not only physically, but also communicate to each other by secretion of growth factors. A vital angiogenic growth factor is vascular endothelial growth factor and its expression in skeletal cells is controlled by osteogenic transcription factors and hypoxia signaling, whereas the secretion of angiocrine factors by endothelial cells is regulated by Notch signaling, blood flow and possibly hypoxia. Bone loss and impaired fracture repair are often associated with reduced and disorganized blood vessel network and therapeutic targeting of the angiogenic response may contribute to enhanced bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. State of Skeletal Muscle Tissue in Women in the Ukrainian Population

    Directory of Open Access Journals (Sweden)

    V.V. Povoroznyuk

    2015-10-01

    Full Text Available Today among geriatric syndromes, world scientists pay much attention to the study of sarcopenia. It was found that the evaluation of skeletal muscle strength has a significant correlation with the risk of falls, disability, deterioration in the quality of life, duration of hospitalization. It is proved that measurements of skeletal muscle strength, but not the determination of skeletal muscles mass, are strong and independent predictors of mortality in the elderly. Further researches are needed to study the characteristics of weight loss, strength and function of skeletal muscle with age in individuals of different sex and age. The objective of this study was to explore the features of strength and functionality of skeletal muscle tissue in women of all ages. The study involved 248 women, who were divided into groups by decades depending on age: 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, 80–89 years. Skeletal muscle strength was evaluated using spring carpal dynamometer. Functions of skeletal muscles and the risk of falls were assessed using special tests. Fat-free mass of the whole body, upper and lower extremities was evaluated by means of dual-energy X-ray absorptiometry (Prodigy, GEHC Lunar, Madison, WI, USA. The study found that maximal values of strength and functional capacity of skeletal muscles were observed in women in the age group of 20–29 years. The significant loss of skeletal muscle strength is being detected in individuals from the age group of 60–69 years and older. When determining the functional capacity of skeletal muscles and risk of falls, significantly worse performance was established in women older than 50 years compared to those in women in the age group of 20–29 years.

  19. Considerations of anthropometric, tissue volume, and tissue mass scaling for improved patient specificity of skeletal S values

    International Nuclear Information System (INIS)

    Bolch, W.E.; Patton, P.W.; Shah, A.P.; Rajon, D.A.; Jokisch, D.W.

    2002-01-01

    It is generally acknowledged that reference man (70 kg in mass and 170 cm in height) does not adequately represent the stature and physical dimensions of many patients undergoing radionuclide therapy, and thus scaling of radionuclide S values is required for patient specificity. For electron and beta sources uniformly distributed within internal organs, the mean dose from self-irradiation is noted to scale inversely with organ mass, provided no escape of electron energy occurs at the organ boundaries. In the skeleton, this same scaling approach is further assumed to be correct for marrow dosimetry; nevertheless, difficulties in quantitative assessments of marrow mass in specific skeletal regions of the patient make this approach difficult to implement clinically. Instead, scaling of marrow dose is achieved using various anthropometric parameters that presumably scale in the same proportion. In this study, recently developed three-dimensional macrostructural transport models of the femoral head and humeral epiphysis in three individuals (51-year male, 82-year female, and 86-year female) are used to test the abilities of different anthropometric parameters (total body mass, body surface area, etc.) to properly scale radionuclide S values from reference man models. The radionuclides considered are 33 P, 177 Lu, 153 Sm, 186 Re, 89 Sr, 166 Ho, 32 P, 188 Re, and 90 Y localized in either the active marrow or endosteal tissues of the bone trabeculae. S value scaling is additionally conducted in which the 51-year male subject is assigned as the reference individual; scaling parameters are then expanded to include tissue volumes and masses for both active marrow and skeletal spongiosa. The study concludes that, while no single anthropometric parameter emerges as a consistent scaler of reference man S values, lean body mass is indicated as an optimal scaler when the reference S values are based on 3D transport techniques. Furthermore, very exact patient-specific scaling of

  20. Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury

    DEFF Research Database (Denmark)

    Mackey, Abigail Louise; Kjaer, Michael

    2017-01-01

    Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibres as they undergo necrosis, followed closely by satellite cell mediated myogenesis, have been mapped in detail. Much less is known about...... the adaptation throughout this process of both the connective tissue structures surrounding the myofibres, and the fibroblasts, the cells responsible for synthesising this connective tissue. However, the few studies investigating muscle connective tissue remodelling demonstrate a strong response that appears...

  1. Monitoring temporal microstructural variations of skeletal muscle tissues by multispectral Mueller matrix polarimetry

    Science.gov (United States)

    Dong, Yang; He, Honghui; He, Chao; Ma, Hui

    2017-02-01

    Mueller matrix polarimetry is a powerful tool for detecting microscopic structures, therefore can be used to monitor physiological changes of tissue samples. Meanwhile, spectral features of scattered light can also provide abundant microstructural information of tissues. In this paper, we take the 2D multispectral backscattering Mueller matrix images of bovine skeletal muscle tissues, and analyze their temporal variation behavior using multispectral Mueller matrix parameters. The 2D images of the Mueller matrix elements are reduced to the multispectral frequency distribution histograms (mFDHs) to reveal the dominant structural features of the muscle samples more clearly. For quantitative analysis, the multispectral Mueller matrix transformation (MMT) parameters are calculated to characterize the microstructural variations during the rigor mortis and proteolysis processes of the skeletal muscle tissue samples. The experimental results indicate that the multispectral MMT parameters can be used to judge different physiological stages for bovine skeletal muscle tissues in 24 hours, and combining with the multispectral technique, the Mueller matrix polarimetry and FDH analysis can monitor the microstructural variation features of skeletal muscle samples. The techniques may be used for quick assessment and quantitative monitoring of meat qualities in food industry.

  2. 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

  3. Reliability of various skeletal indicators in assessing vertical facial soft tissue pattern

    International Nuclear Information System (INIS)

    Ahmed, M.; Shaikh, A.; Fida, M.

    2016-01-01

    Background: Angle paradigm has ruled the orthodontic diagnosis and treatment planning for past several decades, but the recent introduction of the soft tissue paradigm has significantly changed the dynamics of orthodontic practice. This study was designed to identify skeletal analyses that best correlates with the parameters use to assess facial soft tissue profile that may lead to an accurate diagnosis and efficient treatment plan. Methods: A total of 192 subjects (96 males and 96 females; mean age 22.95±4.75 years) were included in the study. The total sample was distributed into three equal groups (i.e., long, normal and short face) on the basis of soft tissue vertical pattern. Pre-treatment lateral cephalograms were used to assess various vertical linear and angular parameters. Various skeletal analyses and soft tissue parameters were correlated using the Pearson correlation in different vertical groups, separately for males and females. Results: In males, a weak positive correlation (r=0.485) was found between skeletal anterior facial height ratio (Sk. LAFH/TAFH) and soft tissue anterior facial height ratio (LAFH/TAFH), whereas in females maxillary-mandibular plane angle (MMA) showed a weak positive correlation (r=0.300). In the long face group, a positive but a weak correlation (r=0.349) was present between cranial base angle (SN-GoGn) and LAFH/TAFH. Conclusions: Skeletal analyses (MMA, Sk. LAFH/TAFH) significantly correlated to soft tissue parameters. Males and long faced individuals showed a higher correlation between skeletal and soft tissue parameters as compared to that of the females. (author)

  4. Soft tissue thickness of face profile conditioning by dento-skeletal anomalies

    Directory of Open Access Journals (Sweden)

    Tanić Tatjana

    2011-01-01

    Full Text Available Introduction. Orthodontic treatment of dento-skeletal anomalies is generally based on the correction of teeth and jaws relationship, while it is expected that soft facial tissue spontaneously adapts to therapeutically achieved relationship and to accompany hard tissue changes. Objective. To establish facial soft tissue thickness conditioning by the presence of dento-skeletal anomalies. Methods. The study was performed at the Dental Clinic of Niš, and involved the analysis of cephalometric rendgenograms in 121 patients, aged 12-18 years, with no previous orthodontical treatment. According to dento-skeletal relationship between teeth and jaws the patients were divided into four groups; class I (control group, class II of division 1, class II of division 2 and class III. The standard analysis of dento-skeletal profile was done according to Steiner and soft tissue profile according to Burstone was done in all. Results. The patients of class II/1 had a significantly thinner upper lip (t=2.650; p<0.05 and thinner upper lip sulcus (t=1.999; p<0.05. The patients of class II/2 had a significantly thicker upper lip (t=2.912; p<0.01, while those of class III had a significantly thinner lower lip (t=3.900; p<0.001. Conclusion. The thickness of facial soft tissue considerably influences facial profile appearance in persons with a dento-skeletal anomaly. Not only do soft tissues adapt to the existing jaws relationship, but can also camouflage present anomalies.

  5. A Simplified Method for Tissue Engineering Skeletal Muscle Organoids in Vitro

    Science.gov (United States)

    Shansky, Janet; DelTatto, Michael; Chromiak, Joseph; Vandenburgh, Herman

    1996-01-01

    Tissue-engineered three dimensional skeletal muscle organ-like structures have been formed in vitro from primary myoblasts by several different techniques. This report describes a simplified method for generating large numbers of muscle organoids from either primary embryonic avian or neonatal rodent myoblasts, which avoids the requirements for stretching and other mechanical stimulation.

  6. Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

    DEFF Research Database (Denmark)

    Mulla, N A; Simonsen, L; Bülow, J

    2000-01-01

    , a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease......One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid...... metabolism during a 3 h post-exercise period. Six subjects were studied twice. In one experiment, they exercised for 90 min at 40% of maximal O2 consumption (VO2,max) and in the other experiment they exercised at 60% VO2,max for 60 min. For both experiments, catheters were inserted in an artery...

  7. Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues.

    Directory of Open Access Journals (Sweden)

    Erica P Homan

    2014-01-01

    Full Text Available Mutations in the genes encoding cartilage associated protein (CRTAP and prolyl 3-hydroxylase 1 (P3H1 encoded by LEPRE1 were the first identified causes of recessive Osteogenesis Imperfecta (OI. These proteins, together with cyclophilin B (encoded by PPIB, form a complex that 3-hydroxylates a single proline residue on the α1(I chain (Pro986 and has cis/trans isomerase (PPIase activity essential for proper collagen folding. Recent data suggest that prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen; however, the absence of this post-translational modification may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other. Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. The relative contribution of losing this complex's 3-hydroxylation versus PPIase and collagen chaperone activities to the phenotype of recessive OI is unknown. To distinguish between these functions, we generated knock-in mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1(H662A . This substitution abolished P3h1 activity but retained ability to form a complex with Crtap and thus the collagen chaperone function. Knock-in mice showed absence of prolyl 3-hydroxylation at Pro986 of the α1(I and α1(II collagen chains but no significant over-modification at other collagen residues. They were normal in appearance, had no growth defects and normal cartilage growth plate histology but showed decreased trabecular bone mass. This new mouse model recapitulates elements of the bone phenotype of OI but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Our observations suggest differential tissue consequences due to selective inactivation of P3H1 hydroxylase

  8. Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

    International Nuclear Information System (INIS)

    Canuto, K S; Sergio, L P S; Mencalha, A L; Fonseca, A S; Paoli, F

    2016-01-01

    Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases. (paper)

  9. Multidisciplinary ''limb salvage'' treatment of soft tissue and skeletal sarcomas

    International Nuclear Information System (INIS)

    Weisenburger, T.H.; Eilber, F.R.; Grant, T.T.; Morton, D.L.; Mirra, J.J.; Steinberg, M.; Rickles, D.

    1984-01-01

    The goal of treating primary bone and soft tissue tumors, as with most other malignancies, is to control the disease locally and systematically while preserving as much function as possible. For soft tissue sarcomas the results following radical excision and post-operative radiation therapy with preservation of the limb have equaled the control rates of amputation. However, local recurrence rates of approximately 25-30% are reported for high-grade lesions of the proximal lower extremity. Amputations provides excellent local control for osteosarcoma but the functional results may be less than optimal. In an attempt to achieve limb salvage for these tumors, a multidisciplinary protocol was developed using intra-arterial doxorubicin, pre-operative radiation therapy and limb-sparing radical wide excision followed by post-operative chemotherapy for presumed micro-metastatic disease

  10. Skeletal muscle aging: stem cell function and tissue homeostasis

    OpenAIRE

    Victor, Pedro Sousa

    2012-01-01

    Muscle aging, in particular, is characterized by the reduction of tissue mass and function, which are particularly prominent in geriatric individuals undergoing sarcopenia. The age-associated muscle wasting is also associated with a decline in regenerative ability and a reduction in resident muscle stem cell (satellite cell) number and function. Although sarcopenia is one of the major contributors to the general loss of physiological function, the mechanisms involved in age-related loss of mu...

  11. Selection, processing and clinical application of muscle-skeletal tissue; Seleccion, Procesamiento y Aplicacion Clinica de Tejido Musculo-Esqueletico

    Energy Technology Data Exchange (ETDEWEB)

    Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G. [ININ, Carretera Mexico-Toluca s/n, 52750 La Marquesa, Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: dlz@nuclear.inin. mx

    2007-07-01

    Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

  12. Response functions for computing absorbed dose to skeletal tissues from neutron irradiation

    Science.gov (United States)

    Bahadori, Amir A.; Johnson, Perry; Jokisch, Derek W.; Eckerman, Keith F.; Bolch, Wesley E.

    2011-11-01

    Spongiosa in the adult human skeleton consists of three tissues—active marrow (AM), inactive marrow (IM) and trabecularized mineral bone (TB). AM is considered to be the target tissue for assessment of both long-term leukemia risk and acute marrow toxicity following radiation exposure. The total shallow marrow (TM50), defined as all tissues lying within the first 50 µm of the bone surfaces, is considered to be the radiation target tissue of relevance for radiogenic bone cancer induction. For irradiation by sources external to the body, kerma to homogeneous spongiosa has been used as a surrogate for absorbed dose to both of these tissues, as direct dose calculations are not possible using computational phantoms with homogenized spongiosa. Recent micro-CT imaging of a 40 year old male cadaver has allowed for the accurate modeling of the fine microscopic structure of spongiosa in many regions of the adult skeleton (Hough et al 2011 Phys. Med. Biol. 56 2309-46). This microstructure, along with associated masses and tissue compositions, was used to compute specific absorbed fraction (SAF) values for protons originating in axial and appendicular bone sites (Jokisch et al 2011 Phys. Med. Biol. 56 6857-72). These proton SAFs, bone masses, tissue compositions and proton production cross sections, were subsequently used to construct neutron dose-response functions (DRFs) for both AM and TM50 targets in each bone of the reference adult male. Kerma conditions were assumed for other resultant charged particles. For comparison, AM, TM50 and spongiosa kerma coefficients were also calculated. At low incident neutron energies, AM kerma coefficients for neutrons correlate well with values of the AM DRF, while total marrow (TM) kerma coefficients correlate well with values of the TM50 DRF. At high incident neutron energies, all kerma coefficients and DRFs tend to converge as charged-particle equilibrium is established across the bone site. In the range of 10 eV to 100 Me

  13. Histological Evaluation of Decellularized Skeletal Muscle Tissue Using Two Different Decellularization Agents

    Directory of Open Access Journals (Sweden)

    Hana Hrebíková

    2017-02-01

    Full Text Available The aim of the present study was to determine effect of two decellularized agents, sodium dodecyl sulphate (SDS and Triton X-100, to the skeletal muscle tissue. Final scaffold was evaluated by several histological techniques to analyse preservation of essential structures including collagen and elastic fibres, basement membranes, glycosaminoglycans and also to confirm elimination of nuclear and cytoplasmic components which are redundant in effectively prepared decellularized scaffolds. Comparison of tissue scaffolds processed with different detergents proved that SDS is superior to Triton X-100 as it can effectively decellularize muscle tissue.

  14. Bone/soft-tissue enrichment ratio in skeletal scintiscanning

    International Nuclear Information System (INIS)

    Reuschel, W.

    1982-01-01

    The thesis aimed at establishing normal values for the enrichment intensity of sup(99m)Tc-MDP above the sacrum (S) as reference point for spongy bones in relation to soft-tissue (ST) enrichment (S/St ratio). A normal range for S/ST was determined for five age groups which was given separately for males and females. In addition, the question was examined what causes there could be for S/ST exceeding, the norm or an increased F/ST ratio (F=femur centre) between bone and soft tissue. The question was studied whether or not beniguity or malignancy of a base disease has an important influence on F/ST values. Dependence of F/ST values from primary tumour localization and the tendency of metastatic spread in bones were investigated in malignoma patients. In addition, an assessment was made of what correlation existed, between the laboratory parameters measured, particularly alkaline phosphatase, and the F/ST values. The questions were examined what correlation existed between the F/ST values established and scintiscan findings; whether or not solitary radionuclide enrichments or multiple foci were found in the scintiscan; and what influence the number of foci had on the F/ST values. In tumour patients, the question examined what correlation existed between a tumour-specific treatment and the F/ST values. (orig./MG) [de

  15. Quantitatively differentiating microstructural variations of skeletal muscle tissues by multispectral Mueller matrix imaging

    Science.gov (United States)

    Dong, Yang; He, Honghui; He, Chao; Ma, Hui

    2016-10-01

    Polarized light is sensitive to the microstructures of biological tissues and can be used to detect physiological changes. Meanwhile, spectral features of the scattered light can also provide abundant microstructural information of tissues. In this paper, we take the backscattering polarization Mueller matrix images of bovine skeletal muscle tissues during the 24-hour experimental time, and analyze their multispectral behavior using quantitative Mueller matrix parameters. In the processes of rigor mortis and proteolysis of muscle samples, multispectral frequency distribution histograms (FDHs) of the Mueller matrix elements can reveal rich qualitative structural information. In addition, we analyze the temporal variations of the sample using the multispectral Mueller matrix transformation (MMT) parameters. The experimental results indicate that the different stages of rigor mortis and proteolysis for bovine skeletal muscle samples can be judged by these MMT parameters. The results presented in this work show that combining with the multispectral technique, the FDHs and MMT parameters can characterize the microstructural variation features of skeletal muscle tissues. The techniques have the potential to be used as tools for quantitative assessment of meat qualities in food industry.

  16. Basic models modeling resistance training: an update for basic scientists interested in study skeletal muscle hypertrophy.

    Science.gov (United States)

    Cholewa, Jason; Guimarães-Ferreira, Lucas; da Silva Teixeira, Tamiris; Naimo, Marshall Alan; Zhi, Xia; de Sá, Rafaele Bis Dal Ponte; Lodetti, Alice; Cardozo, Mayara Quadros; Zanchi, Nelo Eidy

    2014-09-01

    Human muscle hypertrophy brought about by voluntary exercise in laboratorial conditions is the most common way to study resistance exercise training, especially because of its reliability, stimulus control and easy application to resistance training exercise sessions at fitness centers. However, because of the complexity of blood factors and organs involved, invasive data is difficult to obtain in human exercise training studies due to the integration of several organs, including adipose tissue, liver, brain and skeletal muscle. In contrast, studying skeletal muscle remodeling in animal models are easier to perform as the organs can be easily obtained after euthanasia; however, not all models of resistance training in animals displays a robust capacity to hypertrophy the desired muscle. Moreover, some models of resistance training rely on voluntary effort, which complicates the results observed when animal models are employed since voluntary capacity is something theoretically impossible to measure in rodents. With this information in mind, we will review the modalities used to simulate resistance training in animals in order to present to investigators the benefits and risks of different animal models capable to provoke skeletal muscle hypertrophy. Our second objective is to help investigators analyze and select the experimental resistance training model that best promotes the research question and desired endpoints. © 2013 Wiley Periodicals, Inc.

  17. Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

    Science.gov (United States)

    Barruet, Emilie; Hsiao, Edward C

    2016-01-01

    Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

  18. Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury.

    Science.gov (United States)

    Mackey, Abigail L; Kjaer, Michael

    2017-03-01

    Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibers as they undergo necrosis, followed closely by satellite cell-mediated myogenesis, have been mapped in detail. Much less is known about the adaptation throughout this process of both the connective tissue structures surrounding the myofibers and the fibroblasts, the cells responsible for synthesizing this connective tissue. However, the few studies investigating muscle connective tissue remodeling demonstrate a strong response that appears to be sustained for a long time after the major myofiber responses have subsided. While the use of electrical stimulation to induce eccentric contractions vs. voluntary eccentric contractions appears to lead to a greater extent of myofiber necrosis and regenerative response, this difference is not apparent when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning against this, however, is the association between muscle matrix protein remodeling and protection against reinjury, which suggests that a (so far undefined) period of vulnerability to reinjury may exist during the remodeling phases. The role of individual muscle matrix components and their spatial interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury. Copyright © 2017 the American Physiological Society.

  19. Tissue clearing for confocal imaging of native and bio-artificial skeletal muscle.

    Science.gov (United States)

    Decroix, L; Van Muylder, V; Desender, L; Sampaolesi, M; Thorrez, L

    2015-01-01

    Novel clearing techniques have revolutionized three-dimensional confocal imaging of the brain without the need for physical tissue sectioning. We evaluated three clearing methods, ScaleA2, Clear(T2), and 3DISCO for visualizing native and tissue engineered muscle by confocal microscopy. We found that Clear(T2) treatment improved the depth of visualization of immunohistochemical staining slightly, but did not improve depth of visualization of endogenous green fluorescent protein (GFP). ScaleA2 preserved endogenous GFP signal better and permitted significantly deeper GFP imaging, but it was incompatible with tropomyosin immunohistochemical staining. 3DISCO treatment preserved both endogenous GFP and immunohistochemical staining, and permitted significantly deeper imaging. Clearing time for the 3DISCO procedure is short compared to ScaleA2 and Clear(T2). We suggest that 3DISCO is the preferable clearing method for native and tissue engineered skeletal muscle tissue.

  20. Assessing reproductive status in elasmobranch fishes using steroid hormones extracted from skeletal muscle tissue

    Science.gov (United States)

    Prohaska, Bianca K.; Tsang, Paul C. W.; Driggers, William B.; Hoffmayer, Eric R.; Wheeler, Carolyn R.; Brown, A. Christine; Sulikowski, James A.

    2013-01-01

    Elasmobranch fishes (sharks, skates, and rays) are particularly susceptible to anthropogenic threats, making a thorough understanding of their life history characteristics essential for proper management. Historically, elasmobranch reproductive data have been collected by lethal sampling, an approach that is problematic for threatened and endangered species. However, recent studies have demonstrated that non-lethal approaches can be as effective as lethal ones for assessment of the reproductive status of an animal. For example, plasma has been used to examine concentrations of steroid hormones. Additionally, skeletal muscle tissue, which can be obtained non-lethally and with minimal stress, can also be used to quantify concentrations of steroid hormones. Skeletal muscle progesterone, testosterone, and estradiol concentrations were determined to be statistically significant indicators of reproductive status in the oviparous Leucoraja erinacea, the yolk-dependent viviparous Squalus acanthias, and the yolk-sac placental viviparous Rhizoprionodon terraenovae. The results of the present study demonstrate that steroid hormones present in non-lethally harvested skeletal muscle tissue can be used as reliable indicators of reproductive status in elasmobranchs. PMID:27293612

  1. Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.

    Science.gov (United States)

    Martin, Neil R W; Turner, Mark C; Farrington, Robert; Player, Darren J; Lewis, Mark P

    2017-10-01

    The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

  2. A physiological skeletal model for radionuclide and stable element biokinetics in children and adults

    International Nuclear Information System (INIS)

    Richardson, R.B.

    2010-01-01

    A physiological skeletal model (PSM) is described that represents the skeletal uptake, retention and clearance of both bone-surface-seeking and bone-volume-seeking radionuclides and stable elements. A key objective of the PSM is to model the higher skeletal growth and bone turnover in infants and children (compared to adults) in order to to account for their greater uptake and cancer risk from bone-seeking contaminants such as lead and plutonium. The PSM is a compartmental model that allows for the incorporation of organic and inorganic material in the bone volume via quiescent bone surfaces, forming bone surfaces and the lacuno-canaliculi system. The model uniquely incorporates a tertiary phase of mineralization via bone fluids. The PSM's structural concepts and biokinetic parameters - such as realistic mass transfers, organ and tissue masses, and bone remodelling half times - are selected mainly on the basis of physiological and anatomical criteria. For brevity, model parameter values or evaluated for adults only. The PSM is an improvement on existing skeletal models that are based more on compartment structures and pathways that rendered good fits to biokinetic data rather than on being anatomically and physiologically accurate. (author)

  3. Tissue engineered tumor models.

    Science.gov (United States)

    Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

    2010-08-01

    Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

  4. Human skeletal muscles replaced to a high degree by white adipose tissue.

    Science.gov (United States)

    Ina, Keisuke; Kitamura, Hirokazu; Masaki, Takayuki; Tatsukawa, Shuji; Yoshimatsu, Hironobu; Fujikura, Yoshihisa

    2011-02-01

    Extreme replacement of skeletal muscles by adipose tissue was found in an 86-year old Japanese male cadaver during dissection practice for medical students at Oita University School of Medicine. Especially, the bilateral sartorius muscles looked overall like adipose tissue. The man had suffered from diabetes mellitus, renal failure, hypertension and hypothyroidism before his death. He was also an alcohol drinker. He had been bedridden late in life. The cause of death was renal failure. In microscopy, the adipose tissue-like sartorius muscle was shown to consist of leptin-positive adipocytes with a small number of degenerated muscle fibers. Fatty replacement, or fatty degeneration, appears to result from endocrine and metabolic disorders, and being bedridden leads to muscle atrophy and damage, although the origin of the adipocytes which emerged in the degenerated muscles is unknown.

  5. An image-based skeletal dosimetry model for the ICRP reference newborn-internal electron sources

    International Nuclear Information System (INIS)

    Pafundi, Deanna; Lee, Choonsik; Bolch, Wesley; Rajon, Didier; Jokisch, Derek

    2010-01-01

    In this study, a comprehensive electron dosimetry model of newborn skeletal tissues is presented. The model is constructed using the University of Florida newborn hybrid phantom of Lee et al (2007 Phys. Med. Biol. 52 3309-33), the newborn skeletal tissue model of Pafundi et al (2009 Phys. Med. Biol. 54 4497-531) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med. 46 344-53). Target tissues include the active bone marrow (surrogate tissue for hematopoietic stem cells), shallow marrow (surrogate tissue for osteoprogenitor cells) and unossified cartilage (surrogate tissue for chondrocytes). Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following source tissues: active marrow, trabecular bone (surfaces and volumes), cortical bone (surfaces and volumes) and cartilage. Transport results are reported as specific absorbed fractions according to the MIRD schema and are given as skeletal-averaged values in the paper with bone-specific values reported in both tabular and graphic format as electronic annexes (supplementary data). The method utilized in this work uniquely includes (1) explicit accounting for the finite size and shape of newborn ossification centers (spongiosa regions), (2) explicit accounting for active and shallow marrow dose from electron emissions in cortical bone as well as sites of unossified cartilage, (3) proper accounting of the distribution of trabecular and cortical volumes and surfaces in the newborn skeleton when considering mineral bone sources and (4) explicit consideration of the marrow cellularity changes for active marrow self-irradiation as applicable to radionuclide therapy of diseased marrow in the newborn child.

  6. An image-based skeletal dosimetry model for the ICRP reference newborn-internal electron sources

    Energy Technology Data Exchange (ETDEWEB)

    Pafundi, Deanna; Lee, Choonsik; Bolch, Wesley [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL (United States); Rajon, Didier [Department of Neurosurgery, University of Florida, Gainesville, FL (United States); Jokisch, Derek [Department of Physics and Astronomy, Francis Marion University, Florence, SC (United States)], E-mail: wbolch@ufl.edu

    2010-04-07

    In this study, a comprehensive electron dosimetry model of newborn skeletal tissues is presented. The model is constructed using the University of Florida newborn hybrid phantom of Lee et al (2007 Phys. Med. Biol. 52 3309-33), the newborn skeletal tissue model of Pafundi et al (2009 Phys. Med. Biol. 54 4497-531) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med. 46 344-53). Target tissues include the active bone marrow (surrogate tissue for hematopoietic stem cells), shallow marrow (surrogate tissue for osteoprogenitor cells) and unossified cartilage (surrogate tissue for chondrocytes). Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following source tissues: active marrow, trabecular bone (surfaces and volumes), cortical bone (surfaces and volumes) and cartilage. Transport results are reported as specific absorbed fractions according to the MIRD schema and are given as skeletal-averaged values in the paper with bone-specific values reported in both tabular and graphic format as electronic annexes (supplementary data). The method utilized in this work uniquely includes (1) explicit accounting for the finite size and shape of newborn ossification centers (spongiosa regions), (2) explicit accounting for active and shallow marrow dose from electron emissions in cortical bone as well as sites of unossified cartilage, (3) proper accounting of the distribution of trabecular and cortical volumes and surfaces in the newborn skeleton when considering mineral bone sources and (4) explicit consideration of the marrow cellularity changes for active marrow self-irradiation as applicable to radionuclide therapy of diseased marrow in the newborn child.

  7. MicroCT-Based Skeletal Models for Use in Tomographic Voxel Phantoms for Radiological Protection

    International Nuclear Information System (INIS)

    Bolch, Wesley

    2010-01-01

    The University of Florida (UF) proposes to develop two high-resolution image-based skeletal dosimetry models for direct use by ICRP Committee 2's Task Group on Dose Calculation in their forthcoming Reference Voxel Male (RVM) and Reference Voxel Female (RVF) whole-body dosimetry phantoms. These two phantoms are CT-based, and thus do not have the image resolution to delineate and perform radiation transport modeling of the individual marrow cavities and bone trabeculae throughout their skeletal structures. Furthermore, new and innovative 3D microimaging techniques will now be required for the skeletal tissues following Committee 2's revision of the target tissues of relevance for radiogenic bone cancer induction. This target tissue had been defined in ICRP Publication 30 as a 10-(micro)m cell layer on all bone surfaces of trabecular and cortical bone. The revised target tissue is now a 50-(micro)m layer within the marrow cavities of trabecular bone only and is exclusive of the marrow adipocytes. Clearly, this new definition requires the use of 3D microimages of the trabecular architecture not available from past 2D optical studies of the adult skeleton. With our recent acquisition of two relatively young cadavers (males of age 18-years and 40-years), we will develop a series of reference skeletal models that can be directly applied to (1) the new ICRP reference voxel man and female phantoms developed for the ICRP, and (2) pediatric phantoms developed to target the ICRP reference children. Dosimetry data to be developed will include absorbed fractions for internal beta and alpha-particle sources, as well as photon and neutron fluence-to-dose response functions for direct use in external dosimetry studies of the ICRP reference workers and members of the general public

  8. MicroCT-Based Skeletal Models for Use in Tomographic Voxel Phantoms for Radiological Protection

    Energy Technology Data Exchange (ETDEWEB)

    Bolch, Wesley [Univ. of Florida, Gainesville, FL (United States)

    2010-03-30

    The University of Florida (UF) proposes to develop two high-resolution image-based skeletal dosimetry models for direct use by ICRP Committee 2’s Task Group on Dose Calculation in their forthcoming Reference Voxel Male (RVM) and Reference Voxel Female (RVF) whole-body dosimetry phantoms. These two phantoms are CT-based, and thus do not have the image resolution to delineate and perform radiation transport modeling of the individual marrow cavities and bone trabeculae throughout their skeletal structures. Furthermore, new and innovative 3D microimaging techniques will now be required for the skeletal tissues following Committee 2’s revision of the target tissues of relevance for radiogenic bone cancer induction. This target tissue had been defined in ICRP Publication 30 as a 10-μm cell layer on all bone surfaces of trabecular and cortical bone. The revised target tissue is now a 50-μm layer within the marrow cavities of trabecular bone only and is exclusive of the marrow adipocytes. Clearly, this new definition requires the use of 3D microimages of the trabecular architecture not available from past 2D optical studies of the adult skeleton. With our recent acquisition of two relatively young cadavers (males of age 18-years and 40-years), we will develop a series of reference skeletal models that can be directly applied to (1) the new ICRP reference voxel man and female phantoms developed for the ICRP, and (2) pediatric phantoms developed to target the ICRP reference children. Dosimetry data to be developed will include absorbed fractions for internal beta and alpha-particle sources, as well as photon and neutron fluence-to-dose response functions for direct use in external dosimetry studies of the ICRP reference workers and members of the general public

  9. Metabolic Disturbance in PCOS: Clinical and Molecular Effects on Skeletal Muscle Tissue

    Directory of Open Access Journals (Sweden)

    Wagner Silva Dantas

    2013-01-01

    Full Text Available Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

  10. Metabolic disturbance in PCOS: clinical and molecular effects on skeletal muscle tissue.

    Science.gov (United States)

    Dantas, Wagner Silva; Gualano, Bruno; Rocha, Michele Patrocínio; Barcellos, Cristiano Roberto Grimaldi; dos Reis Vieira Yance, Viviane; Marcondes, José Antonio Miguel

    2013-01-01

    Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

  11. Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations

    Directory of Open Access Journals (Sweden)

    Timothy J. Bauler

    2011-03-01

    SHP-2 (encoded by PTPN11 is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF and receptor activator of nuclear factor kappa B ligand (RANKL was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations.

  12. Proton microprobe analysis of zinc in skeletal tissues. [Proton induced x-ray emission analysis

    Energy Technology Data Exchange (ETDEWEB)

    Doty, S B; Jones, K W; Kraner, H W; Shroy, R E; Hanson, A L

    1980-06-01

    A proton microprobe with windowless exit port was used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton microprobe is uniquely suited to this work since it combines high sensitivity for zinc determinations in thick samples with good spatial resolution. Measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage.

  13. Spatial interaction between tissue pressure and skeletal muscle perfusion during contraction.

    Science.gov (United States)

    van Donkelaar, C C; Huyghe, J M; Vankan, W J; Drost, M R

    2001-05-01

    The vascular waterfall theory attributes decreased muscle perfusion during contraction to increased intramuscular pressure (P(IM)) and concomitant increase in venous resistance. Although P(IM) is distributed during contractions, this theory does not account for heterogeneity. This study hypothesises that pressure heterogeneity could affect the interaction between P(IM) rise and perfusion. Regional tissue perfusion during submaximum (100kPa) tetanic contraction is studied, using a finite element model of perfused contracting skeletal muscle. Capillary flow in muscles with one proximal artery and vein (SIM(1)) and with an additional distal artery and vein (SIM(2)) is compared. Blood flow and pressures at rest and P(IM) during contraction ( approximately 25kPa maximally) are similar between simulations, but capillary flow and venous pressure differ. In SIM(2), venous pressure and capillary flow correspond to P(IM) distribution, whereas capillary flow in SIM(1) is less than 10% of flow in SIM(2), in the muscle half without draining vein. This difference is caused by a high central P(IM), followed by central venous pressure rise, in agreement with the waterfall theory. The high central pressure (SIM(1)), obstructs outflow from the distal veins. Distal venous pressure rises until central blood pressure is reached, although local P(IM) is low. Adding a distal vein (SIM(2)) restores the perfusion. It is concluded that regional effects contribute to the interaction between P(IM) and perfusion during contraction. Unlike stated by the vascular waterfall theory, venous pressure may locally exceed P(IM). Although this can be explained by the principles of this theory, the theory does not include this phenomenon as such.

  14. Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks.

    NARCIS (Netherlands)

    De Goede, P.; Sen, Satish; Oosterman, Johanneke E; Kalsbeek, A.

    2018-01-01

    The effects of feeding behavior and diet composition,as well as their possible interactions,on daily (clock) gene expression rhythms have mainly been studied in the liver, and to a lesser degree in white adipose tissue(WAT), but hardly in other metabolic tissues such as skeletal muscle (SM) and

  15. Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

    Directory of Open Access Journals (Sweden)

    JA DeQuach

    2012-06-01

    Full Text Available Peripheral artery disease (PAD currently affects approximately 27 million patients in Europe and North America, and if untreated, may progress to the stage of critical limb ischemia (CLI, which has implications for amputation and potential mortality. Unfortunately, few therapies exist for treating the ischemic skeletal muscle in these conditions. Biomaterials have been used to increase cell transplant survival as well as deliver growth factors to treat limb ischemia; however, existing materials do not mimic the native skeletal muscle microenvironment they are intended to treat. Furthermore, no therapies involving biomaterials alone have been examined. The goal of this study was to develop a clinically relevant injectable hydrogel derived from decellularized skeletal muscle extracellular matrix and examine its potential for treating PAD as a stand-alone therapy by studying the material in a rat hindlimb ischemia model. We tested the mitogenic activity of the scaffold’s degradation products using an in vitro assay and measured increased proliferation rates of smooth muscle cells and skeletal myoblasts compared to collagen. In a rat hindlimb ischemia model, the femoral artery was ligated and resected, followed by injection of 150 µL of skeletal muscle matrix or collagen 1 week post-injury. We demonstrate that the skeletal muscle matrix increased arteriole and capillary density, as well as recruited more desmin-positive and MyoD-positive cells compared to collagen. Our results indicate that this tissue-specific injectable hydrogel may be a potential therapy for treating ischemia related to PAD, as well as have potential beneficial effects on restoring muscle mass that is typically lost in CLI.

  16. Changes in soft tissue profile using functional appliances in the treatment of skeletal class II malocclusion

    Directory of Open Access Journals (Sweden)

    Stamenković Zorana

    2015-01-01

    Full Text Available Introduction. The effects of orthodontic treatment are considered to be successful if the facial harmony is achieved, while the structures of soft tissue profile are in harmony with skeletal structures of neurocranium and viscerocranium. In patients with skeletal distal bite caused by mandibular retrognathism, facial esthetics is disturbed often, in terms of pronounced convexity of the profile and change in the position and relationship of the lips. Objective. The aim of this study was to determine the extent of soft tissue profile changes in patients with skeletal Class II malocclusion treated with three different orthodontic appliances: Fränkel functional regulator type I (FR-I, Balters’ Bionator type I and Hotz appliance. Methods. The study included 60 patients diagnosed with skeletal Class II malocclusion caused by mandibular retrognathism, in the period of early mixed dentition. Each subgroup of 20 patients was treated with a variety of orthodontic appliances. On the lateral cephalogram, before and after treatment, the following parameters were analyzed: T angle, H angle, the height of the upper lip, the position of the upper and lower lip in relation to the esthetic line. Within the statistical analysis the mean, maximum, minimum, standard deviation, coefficient of variation, two-factor analysis of variance with repeated measures and the factor analysis of variance were calculated using ANOVA, Bonferroni test and Student’s t-test. Results. A significant decrease of angles T and H was noticed in the application of FR-I, from 21.60° to 17.15°, and from 16.45° to 13.40° (p<0.001. FR-I decreased the height of the upper lip from 26.15 mm to 25.85 mm, while Hotz appliance and Balters’ Bionator type I increased the height of the upper lip, thereby deteriorating esthetics of the patient. Conclusion. All used orthodontic appliances lead to changes in soft tissue profile in terms of improving facial esthetics, with the most distinctive

  17. Staining plastic blocks with triiodide to image cells and soft tissues in backscattered electron SEM of skeletal and dental tissues

    Directory of Open Access Journals (Sweden)

    A Boyde

    2012-07-01

    Full Text Available Backscattered electron scanning electron microscopy (BSE SEM is an invaluable method for studying the histology of the hard, mineralised components of poly-methyl methacrylate (PMMA or other resin embedded skeletal and dental tissues. Intact tissues are studied in micro-milled or polished block faces with an electron-optical section thickness of the order of a half to one micron and with the area of the section as big as a whole – large or small – bone organ. However, BSE SEM does not give information concerning the distribution of uncalcified, ‘soft’, cellular and extracellular matrix components. This can be obtained by confocal microscopy of the same block and the two sorts of images merged but the blocks have to be studied in two microscope systems. The present work shows a new, simple and economic approach to visualising both components by using the triiodide ion in Lugol's iodine solution to stain the block surface prior to the application of any conductive coating – and the latter can be omitted if charging is suppressed by use of poor vacuum conditions in the SEM sample chamber. The method permits the use of archival tissue, and it will be valuable in studies of both normal growth and development and pathological changes in bones and joints, including osteoporosis and osteoarthritis, and tissue adaptation to implants.

  18. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth; Bojsen-Moller, Kirstine N; Dirksen, Carsten

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose...... tolerant and type 2 diabetic subjects at fasting and during a hyperinsulinemic-euglycemic clamp before as well as 1 week, 3 and 12 months after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 months post-surgery...... and glycogen synthase activity were enhanced 12 months post-surgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4 and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC as well as insulin-induced changes in phosphorylation of Akt and TBC1D4 were enhanced...

  19. Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men

    DEFF Research Database (Denmark)

    Asmar, Ali; Asmar, Meena; Simonsen, Lene

    2017-01-01

    In healthy subjects, we recently demonstrated that during acute administration of GLP-1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP-1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and....../or splanchnic tissues. Nine healthy men were examined twice in random order during a 2-hour infusion of either GLP-1 (1.5 pmol kg(-1) min(-1)) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra-arterial blood pressure. Subcutaneous, abdominal adipose...... and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP-1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP-1 increases cardiac...

  20. Skeletal dosimetry models for alpha-particles for use in molecular radiotherapy

    Science.gov (United States)

    Watchman, Christopher J.

    Molecular radiotherapy is a cancer treatment methodology whereby a radionuclide is combined with a biologically active molecule to preferentially target cancer cells. Alpha-particle emitting radionuclides show significant potential for use in molecular radiotherapy due to the short range of the alpha-particles in tissue and their high rates of energy deposition. Current radiation dosimetry models used to assess alpha emitter dose in the skeleton were developed originally for occupational applications. In medical dosimetry, individual variability in uptake, translocation and other biological factors can result in poor correlation of clinical outcome with marrow dose estimates determined using existing skeletal models. Methods presented in this work were developed in response to the need for dosimetry models which account for these biological and patient-specific factors. Dosimetry models are presented for trabecular bone alpha particle dosimetry as well as a model for cortical bone dosimetry. These radiation transport models are the 3D chord-based infinite spongiosa transport model (3D-CBIST) and the chord-based infinite cortical transport model (CBICT), respectively. Absorbed fraction data for several skeletal tissues for several subjects are presented. Each modeling strategy accounts for biological parameters, such as bone marrow cellularity, not previously incorporated into alpha-particle skeletal dosimetry models used in radiation protection. Using these data a study investigating the variability in alpha-particle absorbed fractions in the human skeleton is also presented. Data is also offered relating skeletal tissue masses in individual bone sites for a range of ages. These data are necessary for dose calculations and have previously only been available as whole body tissue masses. A revised 3D-CBIST model is also presented which allows for changes in endosteum thickness to account for revised target cell location of tissues involved in the radiological

  1. Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice.

    Directory of Open Access Journals (Sweden)

    Takashi Ito

    Full Text Available Taurine (2-aminoethanesulfonic acid is found in milimolar concentrations in mammalian tissues. One of its main functions is osmoregulation; however, it also exhibits cytoprotective activity by diminishing injury caused by stress and disease. Taurine depletion is associated with several defects, many of which are found in the aging animal, suggesting that taurine might exert anti-aging actions. Therefore, in the present study, we examined the hypothesis that taurine depletion accelerates aging by reducing longevity and accelerating aging-associated tissue damage. Tissue taurine depletion in taurine transporter knockout (TauTKO mouse was found to shorten lifespan and accelerate skeletal muscle histological and functional defects, including an increase in central nuclei containing myotubes, a reduction in mitochondrial complex 1 activity and an induction in an aging biomarker, Cyclin-dependent kinase 4 inhibitor A (p16INK4a. Tissue taurine depletion also enhances unfolded protein response (UPR, which may be associated with an improvement in protein folding by taurine. Our data reveal that tissue taurine depletion affects longevity and cellular senescence; an effect possibly linked to a disturbance in protein folding.

  2. Pixel-based meshfree modelling of skeletal muscles

    OpenAIRE

    Chen, Jiun-Shyan; Basava, Ramya Rao; Zhang, Yantao; Csapo, Robert; Malis, Vadim; Sinha, Usha; Hodgson, John; Sinha, Shantanu

    2015-01-01

    This paper introduces the meshfree Reproducing Kernel Particle Method (RKPM) for 3D image-based modeling of skeletal muscles. This approach allows for construction of simulation model based on pixel data obtained from medical images. The material properties and muscle fiber direction obtained from Diffusion Tensor Imaging (DTI) are input at each pixel point. The reproducing kernel (RK) approximation allows a representation of material heterogeneity with smooth transition. A ...

  3. 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

  4. Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle.

    Science.gov (United States)

    Tran, Ha T; Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

    2017-01-01

    Gestational diabetes mellitus (GDM), which complicates up to 20% of all pregnancies, is associated with low-grade maternal inflammation and peripheral insulin resistance. Sterile inflammation and infection are key mediators of this inflammation and peripheral insulin resistance. Resveratrol, a stilbene-type phytophenol, has been implicated to exert beneficial properties including potent anti-inflammatory and antidiabetic effects in non-pregnant humans and experimental animal models of GDM. However, studies showing the effects of resveratrol on inflammation and insulin resistance associated with GDM in human tissues have been limited. In this study, human placenta, adipose (omental and subcutaneous) tissue and skeletal muscle were stimulated with pro-inflammatory cytokines TNF-α and IL-1β, the bacterial product lipopolysaccharide (LPS) and the synthetic viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) to induce a GDM-like model. Treatment with resveratrol significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, IL-1α, IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in human placenta and omental and subcutaneous adipose tissue. Resveratrol also significantly restored the defects in the insulin signalling pathway and glucose uptake induced by TNF-α, LPS and poly(I:C). Collectively, these findings suggest that resveratrol reduces inflammation and insulin resistance induced by chemical and microbial products. Resveratrol may be a useful preventative therapeutic for pregnancies complicated by inflammation and insulin resistance, like GDM.

  5. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    Science.gov (United States)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  6. Magnetic resonance tomography in skeletal and soft tissue traumas; Magnetisk resonanstomografi ved skjelett- og bloetdelstraumer

    Energy Technology Data Exchange (ETDEWEB)

    Stiris, Morten G

    2000-07-01

    MRI has revolutionised the diagnostic yield in musculo-skeletal trauma. Studies have documented that MRI can be an accurate, cost-effective means of assessing injuries in the knee, the foot and the ankle and it may also be cost-effective in other anatomic locations. MRTI may have a significant impact on decision-making in relation to these patients and on the follow-up. The patient does not need to be moved for evaluation in all the anatomical planes. Each study can also be post-processes if necessary. MRI may be used in patients with fractures for evaluation of complications. The fracture lines as well as accompanying soft tissue damage are well documented.

  7. Response functions for computing absorbed dose to skeletal tissues from photon irradiation-an update

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Perry B; Bahadori, Amir A [Nuclear and Radiological Engineering, University of Florida, Gainesville, FL 32611 (United States); Eckerman, Keith F [Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Lee, Choonsik [Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892 (United States); Bolch, Wesley E, E-mail: wbolch@ufl.edu [Nuclear and Radiological/Biomedical Engineering, University of Florida, Gainesville, FL 32611 (United States)

    2011-04-21

    A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues-active and total shallow marrow-within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R{sup 2} = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.

  8. Biocompatible, Biodegradable, and Electroactive Polyurethane-Urea Elastomers with Tunable Hydrophilicity for Skeletal Muscle Tissue Engineering.

    Science.gov (United States)

    Chen, Jing; Dong, Ruonan; Ge, Juan; Guo, Baolin; Ma, Peter X

    2015-12-30

    It remains a challenge to develop electroactive and elastic biomaterials to mimic the elasticity of soft tissue and to regulate the cell behavior during tissue regeneration. We designed and synthesized a series of novel electroactive and biodegradable polyurethane-urea (PUU) copolymers with elastomeric property by combining the properties of polyurethanes and conducting polymers. The electroactive PUU copolymers were synthesized from amine capped aniline trimer (ACAT), dimethylol propionic acid (DMPA), polylactide, and hexamethylene diisocyanate. The electroactivity of the PUU copolymers were studied by UV-vis spectroscopy and cyclic voltammetry. Elasticity and Young's modulus were tailored by the polylactide segment length and ACAT content. Hydrophilicity of the copolymer films was tuned by changing DMPA content and doping of the copolymer. Cytotoxicity of the PUU copolymers was evaluated by mouse C2C12 myoblast cells. The myogenic differentiation of C2C12 myoblasts on copolymer films was also studied by analyzing the morphology of myotubes and relative gene expression during myogenic differentiation. The chemical structure, thermal properties, surface morphology, and processability of the PUU copolymers were characterized by NMR, FT-IR, gel permeation chromatography (GPC), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and solubility testing, respectively. Those biodegradable electroactive elastic PUU copolymers are promising materials for repair of soft tissues such as skeletal muscle, cardiac muscle, and nerve.

  9. Evolution of the new vertebrate head by co-option of an ancient chordate skeletal tissue.

    Science.gov (United States)

    Jandzik, David; Garnett, Aaron T; Square, Tyler A; Cattell, Maria V; Yu, Jr-Kai; Medeiros, Daniel M

    2015-02-26

    A defining feature of vertebrates (craniates) is a pronounced head that is supported and protected by a robust cellular endoskeleton. In the first vertebrates, this skeleton probably consisted of collagenous cellular cartilage, which forms the embryonic skeleton of all vertebrates and the adult skeleton of modern jawless and cartilaginous fish. In the head, most cellular cartilage is derived from a migratory cell population called the neural crest, which arises from the edges of the central nervous system. Because collagenous cellular cartilage and neural crest cells have not been described in invertebrates, the appearance of cellular cartilage derived from neural crest cells is considered a turning point in vertebrate evolution. Here we show that a tissue with many of the defining features of vertebrate cellular cartilage transiently forms in the larvae of the invertebrate chordate Branchiostoma floridae (Florida amphioxus). We also present evidence that during evolution, a key regulator of vertebrate cartilage development, SoxE, gained new cis-regulatory sequences that subsequently directed its novel expression in neural crest cells. Together, these results suggest that the origin of the vertebrate head skeleton did not depend on the evolution of a new skeletal tissue, as is commonly thought, but on the spread of this tissue throughout the head. We further propose that the evolution of cis-regulatory elements near an ancient regulator of cartilage differentiation was a major factor in the evolution of the vertebrate head skeleton.

  10. Role of pore size and morphology in musculo-skeletal tissue regeneration

    International Nuclear Information System (INIS)

    Perez, Roman A.; Mestres, Gemma

    2016-01-01

    Biomaterials in the form of scaffolds hold great promise in the regeneration of diseased tissues. The scaffolds stimulate cellular adhesion, proliferation and differentiation. While the scaffold composition will dictate their biocompatibility, their porosity plays a key role in allowing proper cell penetration, nutrient diffusion as well as bone ingrowth. Porous scaffolds are processed with the help of a wide variety of techniques. Designing scaffolds with the appropriate porosity is a complex issue since this may jeopardize other physico-chemical properties. From a macroscopic point of view, parameters such as the overall architecture, pore morphology, interconnectivity and pore size distribution, have unique roles in allowing bone ingrowth to take place. From a microscopic perspective, the adsorption and retention of proteins in the microporosities of the material will dictate the subsequent cell adhesion. Therefore, the microstructure of the substrate can determine cell proliferation as well as the expression of specific osteogenic genes. This review aims at discussing the effect of micro- and macroporosity on the physico-chemical and biological properties of scaffolds for musculo-skeletal tissue regeneration. - Highlights: • Osteoconduction and osteoinduction of a biomaterial relies on its pattern of micro/macroporosity. • Size, morphology, distribution and interconnection of the pores influence both mechanical and biological properties. • Macroporosity (pores > 50 μm) determines cell colonization and therefore growth of vascular and bone tissue. • Micropores (< 50 μm) are crucial for proteins adsorption, which in turn can determine cell fate.

  11. Role of pore size and morphology in musculo-skeletal tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Roman A., E-mail: romanp@dankook.ac.kr [Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714 (Korea, Republic of); Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714 (Korea, Republic of); Mestres, Gemma [Department of Engineering Sciences, Uppsala University, Box 534, 751 21 Uppsala (Sweden)

    2016-04-01

    Biomaterials in the form of scaffolds hold great promise in the regeneration of diseased tissues. The scaffolds stimulate cellular adhesion, proliferation and differentiation. While the scaffold composition will dictate their biocompatibility, their porosity plays a key role in allowing proper cell penetration, nutrient diffusion as well as bone ingrowth. Porous scaffolds are processed with the help of a wide variety of techniques. Designing scaffolds with the appropriate porosity is a complex issue since this may jeopardize other physico-chemical properties. From a macroscopic point of view, parameters such as the overall architecture, pore morphology, interconnectivity and pore size distribution, have unique roles in allowing bone ingrowth to take place. From a microscopic perspective, the adsorption and retention of proteins in the microporosities of the material will dictate the subsequent cell adhesion. Therefore, the microstructure of the substrate can determine cell proliferation as well as the expression of specific osteogenic genes. This review aims at discussing the effect of micro- and macroporosity on the physico-chemical and biological properties of scaffolds for musculo-skeletal tissue regeneration. - Highlights: • Osteoconduction and osteoinduction of a biomaterial relies on its pattern of micro/macroporosity. • Size, morphology, distribution and interconnection of the pores influence both mechanical and biological properties. • Macroporosity (pores > 50 μm) determines cell colonization and therefore growth of vascular and bone tissue. • Micropores (< 50 μm) are crucial for proteins adsorption, which in turn can determine cell fate.

  12. Pixel-based meshfree modelling of skeletal muscles.

    Science.gov (United States)

    Chen, Jiun-Shyan; Basava, Ramya Rao; Zhang, Yantao; Csapo, Robert; Malis, Vadim; Sinha, Usha; Hodgson, John; Sinha, Shantanu

    2016-01-01

    This paper introduces the meshfree Reproducing Kernel Particle Method (RKPM) for 3D image-based modeling of skeletal muscles. This approach allows for construction of simulation model based on pixel data obtained from medical images. The material properties and muscle fiber direction obtained from Diffusion Tensor Imaging (DTI) are input at each pixel point. The reproducing kernel (RK) approximation allows a representation of material heterogeneity with smooth transition. A multiphase multichannel level set based segmentation framework is adopted for individual muscle segmentation using Magnetic Resonance Images (MRI) and DTI. The application of the proposed methods for modeling the human lower leg is demonstrated.

  13. Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Grunnet, Louise G; Nilsson, Emma; Ling, Charlotte

    2009-01-01

    Objective. Common variants in FTO (the fat-mass and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and non-genetic regulation of FTO mRNA in skeletal muscle...... and adipose tissue, and their influence on in vivo glucose and fat metabolism. Research Design and Methods. The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years......) and elderly (58-66 years) non-diabetic twins examined by a hyperinsulinemic euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n=226) and skeletal muscle biopsies (n=158). Results. Heritability of FTO expression in both tissues was low, and FTO...

  14. Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion

    DEFF Research Database (Denmark)

    Carey, A.; Wolsk, Emil; Bruce, C.

    2006-01-01

    Aims/hypothesis  We compared metabolic gene expression in adipose tissue and skeletal muscle from patients with type 2 diabetes and from well-matched healthy control subjects. We hypothesised that gene expression would be discordantly regulated when comparing the two groups. Our secondary aim...... was to determine the effect of Interleukin-6 (IL6) infusion on circulating adipokines and on gene expression in human adipose tissue. To do this we used real-time RT-PCR. Methods  Both diabetic and control subjects underwent basal skeletal muscle and subcutaneous adipose tissue biopsies. A subset...... necrosis factor alpha, adiponectin and resistin were all unaffected by IL6 infusion, but plasma resistin was lower in the diabetic subjects than in control subjects. Conclusions/interpretation  The observation that PPARGC1A and the PPARs were upregulated in the adipose tissue of type 2 diabetic patients...

  15. Unlocking the coral calcification process: Insights from boron isotope measurements and a skeletal growth model

    Science.gov (United States)

    Mollica, N. R.; Guo, W.; Cohen, A. L.; Huang, K. F.; Foster, G. L.; Donald, H.; Solow, A.

    2017-12-01

    Carbonate skeletons of scleractinian corals are important archives of ocean climate and environmental change. However, corals don't accrete their skeletons directly from ambient seawater, but from a calcifying fluid whose composition is strongly regulated. There is mounting evidence that the carbonate chemistry of this calcifying fluid significantly impacts the amount of carbonate the coral can precipitate, which in turn affects the geochemical composition of the skeleton produced. However the mechanistic link between calcifying fluid (cf) chemistry, particularly the up-regulation of pHcf and thereby aragonite saturation state (Ωcf), and coral calcification is not well understood. We explored this link by combining boron isotope measurements with in situ measurements of seawater temperature, salinity, and DIC to estimate Ωcf of nine Porites corals from four Pacific reefs. Associated calcification rates were quantified for each core via CT scanning. We do not observe a relationship between calcification rates and Ωcf or Ωsw. Instead, when we deconvolve calcification into linear extension and skeletal density, a significant correlation is observed between density and Ωcf, and also Ωsw while extension does not correlate with either. These observations are consistent with the two-step model of coral calcification, in which skeleton is secreted in two distinct phases: vertical extension creating new skeletal elements, followed by lateral thickening of existing elements that are covered by living tissue. We developed a numerical model of Porites skeletal growth that builds on this two-step model and links skeletal density with the external seawater environment via its influence on the chemistry of coral calcifying fluid. We validated the model using existing coral skeletal datasets from six Porites species collected across five reef sites, and quantified the effects of each seawater parameter (e.g. temperature, pH, DIC) on skeletal density. Our findings illustrate

  16. Computational Modeling in Tissue Engineering

    CERN Document Server

    2013-01-01

    One of the major challenges in tissue engineering is the translation of biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of tissue engineering. This volume discusses computational modeling tools that allow studying the biological complexity in a more quantitative way. More specifically, computational tools can help in:  (i) quantifying and optimizing the tissue engineering product, e.g. by adapting scaffold design to optimize micro-environmental signals or by adapting selection criteria to improve homogeneity of the selected cell population; (ii) quantifying and optimizing the tissue engineering process, e.g. by adapting bioreactor design to improve quality and quantity of the final product; and (iii) assessing the influence of the in vivo environment on the behavior of the tissue engineering product, e.g. by investigating vascular ingrowth. The book presents examples of each...

  17. A new approach for the validation of skeletal muscle modelling using MRI data

    Science.gov (United States)

    Böl, Markus; Sturmat, Maike; Weichert, Christine; Kober, Cornelia

    2011-05-01

    Active and passive experiments on skeletal muscles are in general arranged on isolated muscles or by consideration of the whole muscle packages, such as the arm or the leg. Both methods exhibit advantages and disadvantages. By applying experiments on isolated muscles it turns out that no information about the surrounding tissues are considered what leads to insufficient specifications of the isolated muscle. Especially, the muscle shape and the fibre directions of an embedded muscle are completely different to that of the same isolated muscle. An explicit advantage, in contrast, is the possibility to study the mechanical characteristics in an unique, isolated way. On the other hand, by applying experiments on muscle packages the aforementioned pros and cons reverse. In such situation, the whole surrounding tissue is considered in the mechanical characteristics of the muscle which are much more difficult to identify. However, an embedded muscle reflects a much more realistic situation as in isolated condition. Thus, in the proposed work to our knowledge, we, for the first time, suggest a technique that allows to study characteristics of single skeletal muscles inside a muscle package without any computation of the tissue around the muscle of interest. In doing so, we use magnetic resonance imaging data of an upper arm during contraction. By applying a three-dimensional continuum constitutive muscle model we are able to study the biceps brachii inside the upper arm and validate the modelling approach by optical experiments.

  18. Engineering skeletal muscle tissues from murine myoblast progenitor cells and application of electrical stimulation

    NARCIS (Netherlands)

    Schaft, van der D.W.J.; Spreeuwel, van A.C.C.; Boonen, K.J.M.; Langelaan, M.L.P.; Bouten, C.V.C.; Baaijens, F.P.T.

    2013-01-01

    Engineered muscle tissues can be used for several different purposes, which include the production of tissues for use as a disease model in vitro, e.g. to study pressure ulcers, for regenerative medicine and as a meat alternative 1. The first reported 3D muscle constructs have been made many years

  19. Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue

    Science.gov (United States)

    Boengler, Kerstin; Kosiol, Maik; Mayr, Manuel; Schulz, Rainer

    2017-01-01

    Abstract Age is the most important risk factor for most diseases. Mitochondria play a central role in bioenergetics and metabolism. In addition, several lines of evidence indicate the impact of mitochondria in lifespan determination and ageing. The best‐known hypothesis to explain ageing is the free radical theory, which proposes that cells, organs, and organisms age because they accumulate reactive oxygen species (ROS) damage over time. Mitochondria play a central role as the principle source of intracellular ROS, which are mainly formed at the level of complex I and III of the respiratory chain. Dysfunctional mitochondria generating less ATP have been observed in various aged organs. Mitochondrial dysfunction comprises different features including reduced mitochondrial content, altered mitochondrial morphology, reduced activity of the complexes of the electron transport chain, opening of the mitochondrial permeability transition pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial quality control or defects in mitochondrial dynamics have also been linked to senescence. Among the tissues affected by mitochondrial dysfunction are those with a high‐energy demand and thus high mitochondrial content. Therefore, the present review focuses on the impact of mitochondria in the ageing process of heart and skeletal muscle. In this article, we review different aspects of mitochondrial dysfunction and discuss potential therapeutic strategies to improve mitochondrial function. Finally, novel aspects of adipose tissue biology and their involvement in the ageing process are discussed. PMID:28432755

  20. 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

  1. The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Larsen, Steen; Danielsen, J H; Søndergård, Stine Dam

    2015-01-01

    High-intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurance training [60-90% of maximal oxygen uptake (VO2peak )]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT...... of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximal fat oxidation in either skeletal muscle or adipose tissue. Km (app) for octanoyl carnitine or palmitoyl carnitine were similar after training in skeletal...... muscle and adipose tissue. Maximal OXPHOS capacity with complex I- and II-linked substrates was increased after training in skeletal muscle but not in adipose tissue. In conclusion, 6 weeks of HIT increased VO2peak . Mitochondrial content and mitochondrial OXPHOS capacity were increased in skeletal...

  2. Effects of heat stimulation and l-ascorbic acid 2-phosphate supplementation on myogenic differentiation of artificial skeletal muscle tissue constructs.

    Science.gov (United States)

    Ikeda, Kazushi; Ito, Akira; Sato, Masanori; Kanno, Shota; Kawabe, Yoshinori; Kamihira, Masamichi

    2017-05-01

    Although skeletal muscle tissue engineering has been extensively studied, the physical forces produced by tissue-engineered skeletal muscles remain to be improved for potential clinical utility. In this study, we examined the effects of mild heat stimulation and supplementation of a l-ascorbic acid derivative, l-ascorbic acid 2-phosphate (AscP), on myoblast differentiation and physical force generation of tissue-engineered skeletal muscles. Compared with control cultures at 37°C, mouse C2C12 myoblast cells cultured at 39°C enhanced myotube diameter (skeletal muscle hypertrophy), whereas mild heat stimulation did not promote myotube formation (differentiation rate). Conversely, AscP supplementation resulted in an increased differentiation rate but did not induce skeletal muscle hypertrophy. Following combined treatment with mild heat stimulation and AscP supplementation, both skeletal muscle hypertrophy and differentiation rate were enhanced. Moreover, the active tension produced by the tissue-engineered skeletal muscles was improved following combined treatment. These findings indicate that tissue culture using mild heat stimulation and AscP supplementation is a promising approach to enhance the function of tissue-engineered skeletal muscles. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Enhanced contractile force generation by artificial skeletal muscle tissues using IGF-I gene-engineered myoblast cells.

    Science.gov (United States)

    Sato, Masanori; Ito, Akira; Kawabe, Yoshinori; Nagamori, Eiji; Kamihira, Masamichi

    2011-09-01

    The aim of this study was to investigate whether insulin-like growth factor (IGF)-I gene delivery to myoblast cells promotes the contractile force generated by hydrogel-based tissue-engineered skeletal muscles in vitro. Two retroviral vectors allowing doxycycline (Dox)-inducible expression of the IGF-I gene were transduced into mouse myoblast C2C12 cells to evaluate the effects of IGF-I gene expression on these cells. IGF-I gene expression stimulated the proliferation of C2C12 cells, and a significant increase in the growth rate was observed for IGF-I-transduced C2C12 cells with Dox addition, designated C2C12/IGF (Dox+) cells. Quantitative morphometric analyses showed that the myotubes induced from C2C12/IGF (Dox+) cells had a larger area and a greater width than control myotubes induced from normal C2C12 cells. Artificial skeletal muscle tissues were prepared from the respective cells using hydrogels composed of type I collagen and Matrigel. Western blot analyses revealed that the C2C12/IGF (Dox+) tissue constructs showed activation of a skeletal muscle hypertrophy marker (Akt) and enhanced expression of muscle-specific markers (myogenin, myosin heavy chain and tropomyosin). Moreover, the creatine kinase activity was increased in the C2C12/IGF (Dox+) tissue constructs. The C2C12/IGF (Dox+) tissue constructs contracted in response to electrical pulses, and generated a significantly higher physical force than the control C2C12 tissue constructs. These findings indicate that IGF-I gene transfer has the potential to yield functional skeletal muscle substitutes that are capable of in vivo restoration of the load-bearing function of injured muscle or acting as in vitro electrically-controlled bio-actuators. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. Morphometric relations of fractal-skeletal based channel network model

    Directory of Open Access Journals (Sweden)

    B. S. Daya Sagar

    1998-01-01

    Full Text Available A fractal-skeletal based channel network (F-SCN model is proposed. Four regular sided initiator-basins are transformed as second order fractal basins by following a specific generating mechanism with non-random rule. The morphological skeletons, hereafter referred to as channel networks, are extracted from these fractal basins. The morphometric and fractal relationships of these F-SCNs are shown. The fractal dimensions of these fractal basins, channel networks, and main channel lengths (computed through box counting method are compared with those of estimated length–area measures. Certain morphometric order ratios to show fractal relations are also highlighted.

  5. A theoretical model for oxygen transport in skeletal muscle under conditions of high oxygen demand.

    Science.gov (United States)

    McGuire, B J; Secomb, T W

    2001-11-01

    Oxygen transport from capillaries to exercising skeletal muscle is studied by use of a Krogh-type cylinder model. The goal is to predict oxygen consumption under conditions of high demand, on the basis of a consideration of transport processes occurring at the microvascular level. Effects of the decline in oxygen content of blood flowing along capillaries, intravascular resistance to oxygen diffusion, and myoglobin-facilitated diffusion are included. Parameter values are based on human skeletal muscle. The dependence of oxygen consumption on oxygen demand, perfusion, and capillary density are examined. When demand is moderate, the tissue is well oxygenated and consumption is slightly less than demand. When demand is high, capillary oxygen content declines rapidly with axial distance and radial oxygen transport is limited by diffusion resistance within the capillary and the tissue. Under these conditions, much of the tissue is hypoxic, consumption is substantially less than demand, and consumption is strongly dependent on capillary density. Predicted consumption rates are comparable with experimentally observed maximal rates of oxygen consumption.

  6. Heat transfer modelling of pulsed laser-tissue interaction

    Science.gov (United States)

    Urzova, J.; Jelinek, M.

    2018-03-01

    Due to their attributes, the application of medical lasers is on the rise in numerous medical fields. From a biomedical point of view, the most interesting applications are the thermal interactions and the photoablative interactions, which effectively remove tissue without excessive heat damage to the remaining tissue. The objective of this work is to create a theoretical model for heat transfer in the tissue following its interaction with the laser beam to predict heat transfer during medical laser surgery procedures. The dimensions of the ablated crater (shape and ablation depth) were determined by computed tomography imaging. COMSOL Multiphysics software was used for temperature modelling. The parameters of tissue and blood, such as density, specific heat capacity, thermal conductivity and diffusivity, were calculated from the chemical ratio. The parameters of laser-tissue interaction, such as absorption and reflection coefficients, were experimentally determined. The parameters of the laser beam were power density, repetition frequency, pulse length and spot dimensions. Heat spreading after laser interaction with tissue was captured using a Fluke thermal camera. The model was verified for adipose tissue, skeletal muscle tissue and heart muscle tissue.

  7. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  8. Oesteosarcomagenic doses of radium (224Ra) and infectious endogenous retroviruses enhance proliferation and osteogenic differentiation of skeletal tissue dofferentiating in vitro

    International Nuclear Information System (INIS)

    Schmidt, J.; Heermeier, K.; Linzner, U.; Luz, A.; Silbermann, M.; Livne, E.; Erfle, V.

    1994-01-01

    Cartilage tissue from embryonic mice which undergoes osteogenic differentiation during in vitro cultivation was used to study the effect of osteosarcomagenic doses of α-irradiation and bone-tumor-inducing retroviruses on proliferation and phenotypic differentiation of skeletal cells in a defined tissue culture model. Irradiated mandibular condyles showed dose-dependent enhancement of cell proliferation at day 7 of the culture and increased osteogenic differentiation at day 14. Maximal effects were found with 7.4 Bq/ml of 224 Ra-labeled medium. Doses of 740 and 7400 Bq/ml of 224 Ra-labeled medium induced increasing cell death. Retrovirus infection enhanced osteogenic differentiation and extended the viability of irradiated cells. After transplantation none of the treated tissues developed tumors in syngeneic mice. (orig.)

  9. Effect of Peroral Administration of Chromium on Insulin Signaling Pathway in Skeletal Muscle Tissue of Holstein Calves.

    Science.gov (United States)

    Jovanović, Ljubomir; Pantelić, Marija; Prodanović, Radiša; Vujanac, Ivan; Đurić, Miloje; Tepavčević, Snežana; Vranješ-Đurić, Sanja; Korićanac, Goran; Kirovski, Danijela

    2017-12-01

    The objective of this study was to investigate the effects of peroral administration of chromium-enriched yeast on glucose tolerance in Holstein calves, assessed by insulin signaling pathway molecule determination and intravenous glucose tolerance test (IVGTT). Twenty-four Holstein calves, aged 1 month, were chosen for the study and divided into two groups: the PoCr group (n = 12) that perorally received 0.04 mg of Cr/kg of body mass daily, for 70 days, and the NCr group (n = 12) that received no chromium supplementation. Skeletal tissue samples from each calf were obtained on day 0 and day 70 of the experiment. Chromium supplementation increased protein content of the insulin β-subunit receptor, phosphorylation of insulin receptor substrate 1 at Tyrosine 632, phosphorylation of Akt at Serine 473, glucose transporter-4, and AMP-activated protein kinase in skeletal muscle tissue, while phosphorylation of insulin receptor substrate 1 at Serine 307 was not affected by chromium treatment. Results obtained during IVGTT, which was conducted on days 0, 30, 50, and 70, suggested an increased insulin sensitivity and, consequently, a better utilization of glucose in the PoCr group. Lower basal concentrations of glucose and insulin in the PoCr group on days 30 and 70 were also obtained. Our results indicate that chromium supplementation improves glucose utilization in calves by enhancing insulin intracellular signaling in the skeletal muscle tissue.

  10. Impact of Skeletal Muscle Mass Index, Intramuscular Adipose Tissue Content, and Visceral to Subcutaneous Adipose Tissue Area Ratio on Early Mortality of Living Donor Liver Transplantation.

    Science.gov (United States)

    Hamaguchi, Yuhei; Kaido, Toshimi; Okumura, Shinya; Kobayashi, Atsushi; Shirai, Hisaya; Yagi, Shintaro; Kamo, Naoko; Okajima, Hideaki; Uemoto, Shinji

    2017-03-01

    Skeletal muscle depletion has been shown to be an independent risk factor for poor survival in various diseases. However, in surgery, the significance of other body components including visceral and subcutaneous adipose tissue remains unclear. This retrospective study included 250 adult patients undergoing living donor liver transplantation (LDLT) between January 2008 and April 2015. Using preoperative plain computed tomography imaging at the third lumbar vertebra level, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by the skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral to subcutaneous adipose tissue area ratio (VSR), respectively. The cutoff values of these parameters were determined for men and women separately using the data of 657 healthy donors for LDLT between 2005 and 2016. Impact of these parameters on outcomes after LDLT was analyzed. VSR was significantly correlated with patient age (P = 0.041), neutrophil-lymphocyte ratio (P mass index (P normal group. On multivariate analysis, low SMI (hazard ratio [HR], 2.367, P = 0.002), high IMAC (HR, 2.096, P = 0.004), and high VSR (HR, 2.213, P = 0.003) were identified as independent risk factors for death after LDLT. Preoperative visceral adiposity, as well as low muscularity, was closely involved with posttransplant mortality.

  11. Effects of Vitamin D Treatment on Skeletal Muscle Histology and Ultrastructural Changes in a Rodent Model

    Directory of Open Access Journals (Sweden)

    Sobhy M. Yakout

    2012-07-01

    Full Text Available Vitamin D is well known for its role in maintaining calcium and phosphorus homeostasis and in promoting bone mineralization; however, more of its pleiotropic effects have been described recently. The aim of the present investigation was to study the effect of vitamin D treatment on skeletal muscles changes under different dietary conditions using an animal model. Four groups of C57BL/6J mice (n = 11 each were maintained on either low fat diet (LFD or high fat diet ‎‎(HFD with and without 1α,25–dihydroxyvitamin D3 (calcitriol for 16 weeks. Animal weigh was recorded at baseline and then regular intervals, and at the end of the study, skeletal muscle tissues were harvested for the evaluation of the histopathological and ultrastructural changes. When control C57BL/6J mice were fed high-fat diet for 12 weeks, body weight gain was significantly increased compared with mice fed a LFD. (30.2% vs. 8.4%, p < 0.01. There was a significant gradual decrease in the weight of HFD fed mice that were treated with vitamin D as compared with a steady increase in the weights of controls (6.8% vs. 28.7%, p < 0.01. While the LFD group showed some ultrastructural changes, HDF fed on mice showed great muscle structural abnormalities. The whole sarcosome along with its membrane and cristae were severely damaged with scattered myocytes in HFD group. Furthermore, the mitochondria appeared weak and were on the verge of degenerations. The bands were diminished with loss of connections among myofibrils. These changes were attenuated in the HFD group treated with vitamin D with tissues have regained their normal structural appearance. The current findings indicate an important effect of vitamin D on skeletal muscle histology under HFD conditions.

  12. * Tissue-Specific Extracellular Matrix Enhances Skeletal Muscle Precursor Cell Expansion and Differentiation for Potential Application in Cell Therapy.

    Science.gov (United States)

    Zhang, Deying; Zhang, Yong; Zhang, Yuanyuan; Yi, Hualin; Wang, Zhan; Wu, Rongpei; He, Dawei; Wei, Guanghui; Wei, Shicheng; Hu, Yun; Deng, Junhong; Criswell, Tracy; Yoo, James; Zhou, Yu; Atala, Anthony

    2017-08-01

    Skeletal muscle precursor cells (MPCs) are considered a key candidate for cell therapy in the treatment of skeletal muscle dysfunction due to injury, disease, or age. However, expansion of a sufficient number of functional skeletal muscle cells in vitro from a small tissue biopsy has been challenging due to changes in phenotypic expression of these cells under traditional culture conditions. Thus, the aim of the study was to develop a better culture system for the expansion and myo-differentiation of MPCs that could further be used for therapy. For this purpose, we developed an ideal method of tissue decellularization and compared the ability of different matrices to support MPC growth and differentiation. Porcine-derived skeletal muscle and liver and kidney extracellular matrix (ECM) were generated by decellularization methods consisting of distilled water, 0.2 mg/mL DNase, or 5% fetal bovine serum. Acellular matrices were further homogenized, dissolved, and combined with a hyaluronic acid-based hydrogel decorated with heparin (ECM-HA-HP). The cell proliferation and myogenic differentiation capacity of human MPCs were assessed when grown on gel alone, ECM, or each ECM-HA-HP substrate. Human MPC proliferation was significantly enhanced when cultured on the ECM-HA-HP substrates compared to the other substrates tested, with the greatest proliferation on the muscle ECM-HA-HP (mECM-HA-HP) substrate. The number of differentiated myotubes was significantly increased on the mECM-HA-HP substrate compared to the other gel-ECM substrates, as well as the numbers of MPCs expressing specific myogenic cell markers (i.e., myosin, desmin, myoD, and myf5). In conclusion, skeletal mECM-HA-HP as a culture substrate provided an optimal culture microenvironment potentially due to its similarity to the in vivo environment. These data suggest a potential use of skeletal muscle-derived ECM gel for the expansion and differentiation of human MPCs for cell-based therapy for skeletal muscle

  13. Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

    DEFF Research Database (Denmark)

    Langberg, H; Bjørn, C; Boushel, Robert Christopher

    2002-01-01

    been established. Microdialysis (molecular mass cut-off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years...... increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P increases the interstitial concentrations......Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet...

  14. Proteomic analysis indicates that mitochondrial energy metabolism in skeletal muscle tissue is negatively correlated with feed efficiency in pigs

    Science.gov (United States)

    Fu, Liangliang; Xu, Yueyuan; Hou, Ye; Qi, Xiaolong; Zhou, Lian; Liu, Huiying; Luan, Yu; Jing, Lu; Miao, Yuanxin; Zhao, Shuhong; Liu, Huazhen; Li, Xinyun

    2017-03-01

    Feed efficiency (FE) is a highly important economic trait in pig production. Investigating the molecular mechanisms of FE is essential for trait improvement. In this study, the skeletal muscle proteome of high-FE and low-FE pigs were investigated by the iTRAQ approach. A total of 1780 proteins were identified, among which 124 proteins were differentially expressed between the high- and low-FE pigs, with 74 up-regulated and 50 down-regulated in the high-FE pigs. Ten randomly selected differentially expressed proteins (DEPs) were validated by Western blotting and quantitative PCR (qPCR). Gene ontology (GO) analysis showed that all the 25 DEPs located in mitochondria were down-regulated in the high-FE pigs. Furthermore, the glucose-pyruvate-tricarboxylic acid (TCA)-oxidative phosphorylation energy metabolism signaling pathway was found to differ between high- and low-FE pigs. The key enzymes involved in the conversion of glucose to pyruvate were up-regulated in the high-FE pigs. Thus, our results suggested mitochondrial energy metabolism in the skeletal muscle tissue was negatively correlated with FE in pigs, and glucose utilization to generate ATP was more efficient in the skeletal muscle tissue of high-FE pigs. This study offered new targets and pathways for improvement of FE in pigs.

  15. Activation of AMPK improves inflammation and insulin resistance in adipose tissue and skeletal muscle from pregnant women.

    Science.gov (United States)

    Liong, Stella; Lappas, Martha

    2015-12-01

    Gestational diabetes mellitus (GDM) is characterised by maternal peripheral insulin resistance and inflammation. Sterile inflammation and bacterial infection are key mediators of this enhanced inflammatory response. Adenosine monophosphate (AMP)-activated kinase (AMPK), which is decreased in insulin resistant states, possesses potent pro-inflammatory actions. There are, however, no studies on the role of AMPK in pregnancies complicated by GDM. Thus, the aims of this study were (i) to compare the expression of AMPK in adipose tissue and skeletal muscle from women with GDM and normal glucose-tolerant (NGT) pregnant women; and (ii) to investigate the effect of AMPK activation on inflammation and insulin resistance induced by the bacterial endotoxin lipopolysaccharide (LPS) and the pro-inflammatory cytokine IL-1β. When compared to NGT pregnant women, AMPKα activity was significantly lower in women with GDM as evidenced by a decrease in threonine phosphorylation of AMPKα. Activation of AMPK, using two pharmacologically distinct compounds, AICAR or phenformin, significantly suppressed LPS- or IL-1β-induced gene expression and secretion of pro-inflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, and COX-2 and subsequent prostaglandin release from adipose tissue and skeletal muscle. In addition, activators of AMPK decreased skeletal muscle insulin resistance induced by LPS or IL-1β as evidenced by increased insulin-stimulated phosphorylation of IRS-1, GLUT-4 expression and glucose uptake. These findings suggest that AMPK may play an important role in inflammation and insulin resistance.

  16. Model for the age-dependent skeletal retention of plutonium

    International Nuclear Information System (INIS)

    Leggett, R.W.; Eckerman, K.F.

    1984-01-01

    A mathematical model of the metabolic and physiologic processes involved in the retention and translocation of plutonium in the body. The implications of the model concerning the dose as a function of age to radiosensitive tissues of the skeleton are examined. 16 references, 1 figure

  17. A critical evaluation of body composition modalities used to assess adipose and skeletal muscle tissue in cancer.

    Science.gov (United States)

    Di Sebastiano, Katie M; Mourtzakis, Marina

    2012-10-01

    The majority of cancer patients experience some form of body composition change during the disease trajectory. For example, breast cancer patients undergoing chemotherapy and prostate cancer patients undergoing androgen deprivation therapy gain fat and lose skeletal muscle, which are associated with increased risk of cancer recurrence and clinical comorbidities. In contrast, advanced cancer patients, such as lung and colorectal cancer patients, experience symptoms of cancer cachexia (accelerated loss of skeletal muscle with or without adipose tissue loss), which are associated with decreased treatment response and poorer survival rates in advanced cancers. The heterogeneity of body composition features and their diverse implications across different cancer populations supports the need for accurate quantification of muscle and adipose tissue. Use of appropriate body composition modalities will facilitate an understanding of the complex relationship between body composition characteristics and clinical outcomes. This will ultimately support the development and evaluation of future therapeutic interventions that aim to counter muscle loss and fat gain in cancer populations. Despite the various metabolic complications that may confound the accurate body composition measurement in cancer patients (i.e., dehydration may confound lean tissue measurement), there are no guidelines for selecting the most appropriate modalities to make these measurements. In this review we outline specific considerations for choosing the most optimal approaches of lean and adipose tissue measurements among different cancer populations. Anthropometric measures, bioelectrical impedance analysis, air displacement plethysmography, dual-energy X-ray absorptiometry, computed tomography, and magnetic resonance imaging will be discussed.

  18. A Mathematical Model of Oxygen Transport in Skeletal Muscle During Hindlimb Unloading

    Science.gov (United States)

    Causey, Laura; Lewandowski, Beth E.; Weinbaum, Sheldon

    2014-01-01

    During hindlimb unloading (HU) dramatic fluid shifts occur within minutes of the suspension, leading to a less precise matching of blood flow to O2 demands of skeletal muscle. Vascular resistance directs blood away from certain muscles, such as the soleus (SOL). The muscle volume gradually reduces in these muscles so that eventually the relative blood flow returns to normal. It is generally believed that muscle volume change is not due to O2 depletion, but a consequence of disuse. However, the volume of the unloaded rat muscle declines over the course of weeks, whereas the redistribution of blood flow occurs immediately. Using a Krogh Cylinder Model, the distribution of O2 was predicted in two skeletal muscles: SOL and gastrocnemius (GAS). Effects of the muscle blood flow, volume, capillary density, and O2 uptake, are included to calculate the pO2 at rest and after 10 min and 15 days of unloading. The model predicts that 32 percent of the SOL muscle tissue has a pO2 1.25 mm Hg within 10 min, whereas the GAS maintains normal O2 levels, and that equilibrium is reached only as the SOL muscle cells degenerate. The results provide evidence that there is an inadequate O2 supply to the mitochondria in the SOL muscle after 10 min HU.

  19. The role of glucose, insulin and NEFA in regulating tissue triglyceride accumulation: Substrate cooperation in adipose tissue versus substrate competition in skeletal muscle.

    Science.gov (United States)

    Guzzardi, M A; Hodson, L; Guiducci, L; La Rosa, F; Salvadori, P A; Burchielli, S; Iozzo, P

    2017-11-01

    Metabolic factors initiating adipose tissue expansion and ectopic triglyceride accumulation are not completely understood. We aimed to investigate the independent role of circulating glucose, NEFA and insulin on glucose and NEFA uptake, and lipogenesis in skeletal muscle and subcutaneous adipose tissue (SCAT). Twenty-two pigs were stratified according to four protocols: 1) and 2) low NEFA + high insulin ± high glucose (hyperinsulinaemia-hyperglycaemia or hyperinsulinaemia-euglycaemia), 3) high NEFA + low insulin (fasting), 4) low NEFA + low insulin (nicotinic acid). Positron emission tomography with [ 18 F]fluoro-2-deoxyglucose and [ 11 C]acetate, was combined with [ 14 C]acetate and [U- 13 C]palmitate enrichment techniques to assess glucose and lipid metabolism. Hyperinsulinaemia increased glucose extraction, whilst hyperglycaemia enhanced glucose uptake in skeletal muscle and SCAT. In SCAT, during hyperglycaemia, elevated glucose uptake was accompanied by greater [U- 13 C]palmitate-TG enrichment compared to the other groups, and by a 39% increase in de novo lipogenesis (DNL) compared to baseline, consistent with a 70% increment in plasma lipogenic index. Conversely, in skeletal muscle, [U- 13 C]palmitate-TG enrichment was higher after prolonged fasting. Our data show the necessary role of hyperglycaemia-hyperinsulinaemia vs euglycaemia-hyperinsulinaemia in promoting expansion of TG stores in SCAT, by the consensual elevation in plasma NEFA and glucose uptake and DNL. In contrast, skeletal muscle NEFA uptake for TG synthesis is primarily driven by circulating NEFA levels. These results suggest that a) prolonged fasting or dietary regimens enhancing lipolysis might promote muscle steatosis, and b) the control of glucose levels, in association with adequate energy balance, might contribute to weight loss. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and

  20. Soft tissue modelling with conical springs.

    Science.gov (United States)

    Omar, Nadzeri; Zhong, Yongmin; Jazar, Reza N; Subic, Aleksandar; Smith, Julian; Shirinzadeh, Bijan

    2015-01-01

    This paper presents a new method for real-time modelling soft tissue deformation. It improves the traditional mass-spring model with conical springs to deal with nonlinear mechanical behaviours of soft tissues. A conical spring model is developed to predict soft tissue deformation with reference to deformation patterns. The model parameters are formulated according to tissue deformation patterns and the nonlinear behaviours of soft tissues are modelled with the stiffness variation of conical spring. Experimental results show that the proposed method can describe different tissue deformation patterns using one single equation and also exhibit the typical mechanical behaviours of soft tissues.

  1. Tissue-specific stem cells: Lessons from the skeletal muscle satellite cell

    Science.gov (United States)

    Brack, Andrew S.; Rando, Thomas A.

    2012-01-01

    In 1961, the satellite cell was first identified when electron microscopic examination of skeletal muscle demonstrated a cell wedged between the plasma membrane of the muscle fiber and the basement membrane. In recent years it has been conclusively demonstrated that the satellite cell is the primary cellular source for muscle regeneration and is equipped with the potential to self renew, thus functioning as a bone fide skeletal muscle stem cell (MuSC). As we move past the 50th anniversary of the satellite cell, we take this opportunity to discuss the current state of the art and dissect the unknowns in the MuSC field. PMID:22560074

  2. Effect of Papaya Seed Extract (Carica papaya Linn. on Glucose Transporter 4 (GLUT 4 Expression of Skeletal Muscle Tissue in Diabetic Mice Induced by High Fructose Diet

    Directory of Open Access Journals (Sweden)

    Devyani Diah Wulansari

    2017-08-01

    Full Text Available Ethnobotany surveys show that papaya seeds are widely used as herbs for the management of some diseases such as abdominal discomfort, pain, malaria, diabetes, obesity, and infection. This research was conducted to analyze the effect of papaya seed extract on GLUT4 expression on skeletal muscle tissue of DM type II model induced by high fructose diet. This study used 24 animals, divided into 4 groups of negative control group, treated with papaya seed extract 100 mg / kgBB, 200 mg / kgBW and 300 mg / kgBW, was adapted for 14 days then induced by fructose solution 20% Orally with a dose of 1.86 grams / kgBB for 56 days. The treatment group was given papaya seed extract in accordance with the dose of each group for 14 days. GDP levels was measured using a spectrophotometer. Skeletal muscle tissue is used on the gastrocnemius part. GLUT4 expression was measured through a Immunoreactive Score (IRS method with immunohistochemical staining using GLUT4 polyclonal antibodies. Comparative test results showed that there were significant differences between groups (p <0.05 in final GDP variables and GLUT4 expression. Pearson correlation test results show that the value p = 0.001, meaning there is a significant relationship between GLUT4 expression with final GDP levels. The result of simple linear regression analysis showed that p = 0,000 (<0,05, meaning that dose of papaya seed extract had a significant influence on GLUT4 expression.

  3. Strategies for cell manipulation and skeletal tissue engineering using high-throughput polymer blend formulation and microarray techniques.

    Science.gov (United States)

    Khan, Ferdous; Tare, Rahul S; Kanczler, Janos M; Oreffo, Richard O C; Bradley, Mark

    2010-03-01

    A combination of high-throughput material formulation and microarray techniques were synergistically applied for the efficient analysis of the biological functionality of 135 binary polymer blends. This allowed the identification of cell-compatible biopolymers permissive for human skeletal stem cell growth in both in vitro and in vivo applications. The blended polymeric materials were developed from commercially available, inexpensive and well characterised biodegradable polymers, which on their own lacked both the structural requirements of a scaffold material and, critically, the ability to facilitate cell growth. Blends identified here proved excellent templates for cell attachment, and in addition, a number of blends displayed remarkable bone-like architecture and facilitated bone regeneration by providing 3D biomimetic scaffolds for skeletal cell growth and osteogenic differentiation. This study demonstrates a unique strategy to generate and identify innovative materials with widespread application in cell biology as well as offering a new reparative platform strategy applicable to skeletal tissues. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  5. BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction.

    Science.gov (United States)

    Friedman, C D; Costantino, P D; Takagi, S; Chow, L C

    1998-01-01

    BoneSource-hydroxyapatite cement is a new self-setting calcium phosphate cement biomaterial. Its unique and innovative physical chemistry coupled with enhanced biocompatibility make it useful for craniofacial skeletal reconstruction. The general properties and clinical use guidelines are reviewed. The biomaterial and surgical applications offer insight into improved outcomes and potential new uses for hydroxyapatite cement systems.

  6. Contribution of skeletal muscle and adipose tissue to adrenaline-induced thermogenesis in man

    DEFF Research Database (Denmark)

    Simonsen, L; Stallknecht, B; Bülow, J

    1993-01-01

    Elevated plasma adrenaline is known to increase whole body energy expenditure. We studied the thermogenic effect and the effects on substrate utilization in man during infusion of adrenaline. Two series were performed: in one series skeletal muscle metabolism was investigated and in another series......% of the whole body adrenaline-induced thermogenesis....

  7. Tissue-specific Role of the Na,K-ATPase α2 Isozyme in Skeletal Muscle*

    Science.gov (United States)

    Radzyukevich, Tatiana L.; Neumann, Jonathon C.; Rindler, Tara N.; Oshiro, Naomi; Goldhamer, David J.; Lingrel, Jerry B.; Heiny, Judith A.

    2013-01-01

    The Na,K-ATPase α2 isozyme is the major Na,K-ATPase of mammalian skeletal muscle. This distribution is unique compared with most other cells, which express mainly the Na,K-ATPase α1 isoform, but its functional significance is not known. We developed a gene-targeted mouse (skα2−/−) in which the α2 gene (Atp1a2) is knocked out in the skeletal muscles, and examined the consequences for exercise performance, membrane potentials, contractility, and muscle fatigue. Targeted knockout was confirmed by genotyping, Western blot, and immunohistochemistry. Skeletal muscle cells of skα2−/− mice completely lack α2 protein and have no α2 in the transverse tubules, where its expression is normally enhanced. The α1 isoform, which is normally enhanced on the outer sarcolemma, is up-regulated 2.5-fold without change in subcellular targeting. skα2−/− mice are apparently normal under basal conditions but show significantly reduced exercise capacity when challenged to run. Their skeletal muscles produce less force, are unable to increase force to match demand, and show significantly increased susceptibility to fatigue. The impairments affect both fast and slow muscle types. The subcellular targeting of α2 to the transverse tubules is important for this role. Increasing Na,K-ATPase α1 content cannot fully compensate for the loss of α2. The increased fatigability of skα2−/− muscles is reproduced in control extensor digitorum longus muscles by selectively inhibiting α2 enzyme activity with ouabain. These results demonstrate that the Na,K-ATPase α2 isoform performs an acute, isoform-specific role in skeletal muscle. Its activity is regulated by muscle use and enables working muscles to maintain contraction and resist fatigue. PMID:23192345

  8. Skeletal muscle repair in a mouse model of nemaline myopathy.

    Science.gov (United States)

    Sanoudou, Despina; Corbett, Mark A; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T; Vlahovich, Nicole; Hardeman, Edna C; Beggs, Alan H

    2006-09-01

    Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five different skeletal muscles from affected mice, which are representative of muscles with differing fiber-type compositions, different physiological specializations and variable degrees of pathology. Although these same muscles in non-affected mice showed marked variation in patterns of gene expression, with diaphragm being the most dissimilar, the presence of the mutant protein in nemaline muscles resulted in a more similar pattern of gene expression among the muscles. This result suggests a common process or mechanism operating in nemaline muscles independent of the variable degrees of pathology. Transcriptional and protein expression data indicate the presence of a repair process and possibly delayed maturation in nemaline muscles. Markers indicative of satellite cell number, activated satellite cells and immature fibers including M-Cadherin, MyoD, desmin, Pax7 and Myf6 were elevated by western-blot analysis or immunohistochemistry. Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles.

  9. The role of adipose tissue and excess of fatty acids in the induction of insulin resistance in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Agnieszka Błachnio-Zabielska

    2016-11-01

    Full Text Available Skeletal muscle is the main tissue responsible for insulin-stimulated glucose uptake. Consumption of a high-fat diet rich in saturated fats (HFD and obesity are associated with accumulation of intramuscular lipids that leads to several disorders, e.g. insulin resistance (IRes and type 2 diabetes (T2D. The mechanism underlying the induction of IRes is still unknown. It was speculated that accumulation of intramuscular triacylglycerols (TAG is linked to induction of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA, diacylglycerols (DAG and ceramides (Cer. It has been demonstrated that accumulation of each of the above-mentioned lipid classes negatively affects the insulin signaling pathway. It is not clear which of those lipids play the most important role in HFD-induced skeletal muscle IRes. The aim of the present work is to present the current knowledge of the role of adipose tissue and excess of fatty acids in the induction of insulin resistance.

  10. 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.

  11. Treating fructose-induced metabolic changes in mice with high-intensity interval training: insights in the liver, white adipose tissue, and skeletal muscle.

    Science.gov (United States)

    Motta, Victor F; Bargut, Thereza L; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A

    2017-10-01

    Fructose-rich caloric sweeteners induce adverse changes in the metabolism of humans. The study evaluated the effects of high-intensity interval training (HIIT) on a fructose feeding model, focusing on the liver, white adipose tissue (WAT), skeletal muscle, and their interplay. Male C57BL/6 mice were fed for 18 wk one of the following diets: control (C; 5% of total energy from fructose) or fructose (F; 55% of total energy from fructose). In the 10th week, for an additional 8-wk period, the groups were divided into nontrained (NT) or HIIT groups, totaling four groups: C-NT, C-HIIT, F-NT, and F-HIIT. At the end of the experiment, fructose consumption in the F-NT group led to a high systolic blood pressure, high plasma triglycerides, insulin resistance with glucose intolerance, and lower insulin sensitivity. We also observed liver steatosis, adipocyte hypertrophy, and diminished gene expressions of peroxisome proliferator-activated receptor-γ coactivator 1-α and fibronectin type III domain containing 5 (FNDC5; irisin) in this F-NT group. These results were accompanied by decreased gene expressions of nuclear respiratory factor 1 and mitochondrial transcription factor A (markers of mitochondrial biogenesis), and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1 (markers of β-oxidation). HIIT improved all of these data in the C-HIIT and F-HIIT groups. In conclusion, in mice fed a fructose diet, HIIT improved body mass, blood pressure, glucose metabolism, and plasma triglycerides. Liver, WAT, and skeletal muscle were positively modulated by HIIT, indicating HIIT as a coadjutant treatment for diseases affecting these tissues. NEW & NOTEWORTHY We investigated the effects of high-intensity interval training (HIIT) in mice fed a fructose-rich diet and the resulting severe negative effect on the liver, white adipose tissue (WAT), and skeletal muscle, which reduced the expression of fibronectin type III domain containing 5 (FNDC5, irisin) and

  12. The suprachiasmatic nucleus drives day-night variations in postprandial triglyceride uptake into skeletal muscle and brown adipose tissue.

    Science.gov (United States)

    Moran-Ramos, Sofía; Guerrero-Vargas, Natali N; Mendez-Hernandez, Rebeca; Basualdo, Maria Del Carmen; Escobar, Carolina; Buijs, Ruud M

    2017-12-01

    What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression

  13. An image-based skeletal dosimetry model for the ICRP reference adult male-internal electron sources

    International Nuclear Information System (INIS)

    Hough, Matthew; Johnson, Perry; Bolch, Wesley; Rajon, Didier; Jokisch, Derek; Lee, Choonsik

    2011-01-01

    In this study, a comprehensive electron dosimetry model of the adult male skeletal tissues is presented. The model is constructed using the University of Florida adult male hybrid phantom of Lee et al (2010 Phys. Med. Biol. 55 339-63) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med. 46 344-53). Target tissues include the active bone marrow, associated with radiogenic leukemia, and total shallow marrow, associated with radiogenic bone cancer. Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following sources: bone marrow (active and inactive), trabecular bone (surfaces and volumes), and cortical bone (surfaces and volumes). Specific absorbed fractions are computed according to the MIRD schema, and are given as skeletal-averaged values in the paper with site-specific values reported in both tabular and graphical format in an electronic annex available from http://stacks.iop.org/0031-9155/56/2309/mmedia. The distribution of cortical bone and spongiosa at the macroscopic dimensions of the phantom, as well as the distribution of trabecular bone and marrow tissues at the microscopic dimensions of the phantom, is imposed through detailed analyses of whole-body ex vivo CT images (1 mm resolution) and spongiosa-specific ex vivo microCT images (30 μm resolution), respectively, taken from a 40 year male cadaver. The method utilized in this work includes: (1) explicit accounting for changes in marrow self-dose with variations in marrow cellularity, (2) explicit accounting for electron escape from spongiosa, (3) explicit consideration of spongiosa cross-fire from cortical bone, and (4) explicit consideration of the ICRP's change in the surrogate tissue region defining the location of the osteoprogenitor cells (from a 10 μm endosteal layer covering the trabecular and cortical surfaces to a 50 μm shallow marrow layer covering trabecular and medullary cavity surfaces). Skeletal

  14. An image-based skeletal dosimetry model for the ICRP reference adult male-internal electron sources

    Energy Technology Data Exchange (ETDEWEB)

    Hough, Matthew; Johnson, Perry; Bolch, Wesley [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL (United States); Rajon, Didier [Department of Neurosurgery, University of Florida, Gainesville, FL (United States); Jokisch, Derek [Department of Physics and Astronomy, Francis Marion University, Florence, SC (United States); Lee, Choonsik, E-mail: wbolch@ufl.edu [Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD (United States)

    2011-04-21

    In this study, a comprehensive electron dosimetry model of the adult male skeletal tissues is presented. The model is constructed using the University of Florida adult male hybrid phantom of Lee et al (2010 Phys. Med. Biol. 55 339-63) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med. 46 344-53). Target tissues include the active bone marrow, associated with radiogenic leukemia, and total shallow marrow, associated with radiogenic bone cancer. Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following sources: bone marrow (active and inactive), trabecular bone (surfaces and volumes), and cortical bone (surfaces and volumes). Specific absorbed fractions are computed according to the MIRD schema, and are given as skeletal-averaged values in the paper with site-specific values reported in both tabular and graphical format in an electronic annex available from http://stacks.iop.org/0031-9155/56/2309/mmedia. The distribution of cortical bone and spongiosa at the macroscopic dimensions of the phantom, as well as the distribution of trabecular bone and marrow tissues at the microscopic dimensions of the phantom, is imposed through detailed analyses of whole-body ex vivo CT images (1 mm resolution) and spongiosa-specific ex vivo microCT images (30 {mu}m resolution), respectively, taken from a 40 year male cadaver. The method utilized in this work includes: (1) explicit accounting for changes in marrow self-dose with variations in marrow cellularity, (2) explicit accounting for electron escape from spongiosa, (3) explicit consideration of spongiosa cross-fire from cortical bone, and (4) explicit consideration of the ICRP's change in the surrogate tissue region defining the location of the osteoprogenitor cells (from a 10 {mu}m endosteal layer covering the trabecular and cortical surfaces to a 50 {mu}m shallow marrow layer covering trabecular and medullary cavity surfaces). Skeletal

  15. 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.

  16. Synchronous changes in coral chromatophore tissue density and skeletal banding as an adaptive response to environmental change

    Science.gov (United States)

    Ardisana, R. N.; Miller, C. A.; Sivaguru, M.; Fouke, B. W.

    2013-12-01

    Corals are a key reservoir of biodiversity in coastal, shallow water tropical marine environments, and density banding in their aragonite skeletons is used as a sensitive record of paleoclimate. Therefore, the cellular response of corals to environmental change and its expression in skeletal structure is of significant importance. Chromatophores, pigment-bearing cells within the ectoderm of hermatypic corals, serve to both enhance the photosynthetic activity of zooxanthellae symbionts, as well as protect the coral animal from harmful UV radiation. Yet connections have not previously been drawn between chromatophore tissue density and the development of skeletal density bands. A histological analysis of the coral Montastrea faveolata has therefore been conducted across a bathymetric gradient of 1-20 m on the southern Caribbean island of Curaçao. A combination of field and laboratory photography, serial block face imaging (SBFI), two-photon laser scanning microscopy (TPLSM), and 3D image analysis has been applied to test whether M. faveolata adapts to increasing water depth and decreasing photosynthetically active radiation by shifting toward a more heterotrophic lifestyle (decreasing zooxanthellae tissue density, increasing mucocyte tissue density, and decreasing chromatophores density). This study is among the first to collect and evaluate histological data in the spatial context of an entire unprocessed coral polyp. TPLSM was used to optically thin section unprocessed tissue biopsies with quantitative image analysis to yield a nanometer-scale three-dimensional map of the quantity and distribution of the symbionts (zooxanthellae) and a host fluorescent pigments (chromatophores), which is thought to have photoprotective properties, within the context of an entire coral polyp. Preliminary results have offered new insight regarding the three-dimensional distribution and abundance of chromatophores and have identified: (1) M. faveolata tissue collected from 8M SWD do

  17. A theoretical analysis of damage evolution in skeletal muscle tissue with reference to pressure ulcer development

    NARCIS (Netherlands)

    Breuls, R.G.M.; Bouten, C.V.C.; Oomens, C.W.J.; Bader, D.L.; Baaijens, F.P.T.

    2003-01-01

    Soft tissues are sensitive to prolonged compressive loading, eventually leading to tissue necrosis in the form of pressure ulcers [1]. Pressure ulcers can occur in situations where people are subjected to sustained mechanical loads, such as when bedridden, sitting in a wheelchair or from wearing

  18. An improved glucose transport assay system for isolated mouse skeletal muscle tissues.

    Science.gov (United States)

    Inagaki, Akiko; Maruo, Kanoko; Furuichi, Yasuro; Miyatake, Shouta; Tamura, Kotaro; Fujii, Nobuharu L; Manabe, Yasuko

    2016-07-18

    There is a growing demand for a system in the field of sarcopenia and diabetes research that could be used to evaluate the effects of functional food ingredients that enhance muscle mass/contractile force or muscle glucose uptake. In this study, we developed a new type of in vitro muscle incubation system that systemizes an apparatus for muscle incubation, using an electrode, a transducer, an incubator, and a pulse generator in a compact design. The new system enables us to analyze the muscle force stimulated by the electric pulses and glucose uptake during contraction and it may thus be a useful tool for analyzing the metabolic changes that occur during muscle contraction. The system may also contribute to the assessments of new food ingredients that act directly on skeletal muscle in the treatment of sarcopenia and diabetes.

  19. MR imaging of skeletal soft tissue infection: utility of diffusion-weighted imaging in detecting abscess formation

    International Nuclear Information System (INIS)

    Harish, Srinivasan; Rebello, Ryan; Chiavaras, Mary M.; Kotnis, Nikhil

    2011-01-01

    Our objectives were to assess if diffusion-weighted imaging (DWI) can help identify abscess formation in the setting of soft tissue infection and to assess whether abscess formation can be diagnosed confidently with a combination of DWI and other unenhanced sequences. Eight cases of soft tissue infection imaged with MRI including DWI were retrospectively reviewed. Two male and six female patients were studied (age range 23-50 years). Unenhanced MRI including DWI was performed in all patients. Post-contrast images were obtained in seven patients. All patients had clinically or surgically confirmed abscesses. Abscesses demonstrated restricted diffusion. DWI in conjunction with other unenhanced imaging showed similar confidence levels as post-contrast images in diagnosing abscess formation in four cases. In two cases, although the combined use of DWI and other unenhanced imaging yielded the same confidence levels as post-contrast imaging, DWI was more definitive for demonstrating abscess formation. In one case, post-contrast images had a better confidence for suggesting abscess. In one case, DWI helped detected the abscess, where gadolinium could not be administered because of a contraindication. This preliminary study suggests that DWI is a useful adjunct in the diagnosis of skeletal soft tissue abscesses. (orig.)

  20. Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks

    Directory of Open Access Journals (Sweden)

    Paul de Goede

    2018-01-01

    Full Text Available The effects of feeding behavior and diet composition, as well as their possible interactions, on daily (clock gene expression rhythms have mainly been studied in the liver, and to a lesser degree in white adipose tissue (WAT, but hardly in other metabolic tissues such as skeletal muscle (SM and brown adipose tissues (BAT. We therefore subjected male Wistar rats to a regular chow or free choice high-fat-high sugar (fcHFHS diet in combination with time restricted feeding (TRF to either the light or dark phase. In SM, all tested clock genes lost their rhythmic expression in the chow light fed group. In the fcHFHS light fed group rhythmic expression for some, but not all, clock genes was maintained, but shifted by several hours. In BAT the daily rhythmicity of clock genes was maintained for the light fed groups, but expression patterns were shifted as compared with ad libitum and dark fed groups, whilst the fcHFHS diet made the rhythmicity of clock genes become more pronounced. Most of the metabolic genes in BAT tissue tested did not show any rhythmic expression in either the chow or fcHFHS groups. In SM Pdk4 and Ucp3 were phase-shifted, but remained rhythmically expressed in the chow light fed groups. Rhythmic expression was lost for Ucp3 whilst on the fcHFHS diet during the light phase. In summary, both feeding at the wrong time of day and diet composition disturb the peripheral clocks in SM and BAT, but to different degrees and thereby result in a further desynchronization between metabolically active tissues such as SM, BAT, WAT and liver.

  1. 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.

  2. 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.

  3. A Physiologically Based, Multi-Scale Model of Skeletal Muscle Structure and Function

    Science.gov (United States)

    Röhrle, O.; Davidson, J. B.; Pullan, A. J.

    2012-01-01

    Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle’s response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modeling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle’s response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modeling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibers and their grouping. Together with a well-established model of motor-unit recruitment, the electro-physiological behavior of single muscle fibers within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenization. The effect of homogenization has been investigated by varying the number of embedded skeletal muscle fibers and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the tibialis anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modeling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behavior ranging from motor-unit recruitment to force generation and fatigue. PMID:22993509

  4. A physiologically based, multi-scale model of skeletal muscle structure and function

    Directory of Open Access Journals (Sweden)

    Oliver eRöhrle

    2012-09-01

    Full Text Available Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle's response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modelling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle's response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modelling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibres and their grouping. Together with a well-established model of motor unit recruitment, the electro-physiological behaviour of single muscle fibres within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenisation. The effect of homogenisation has been investigated by varying the number of embedded skeletal muscle fibres and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the Tibialis Anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modelling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behaviour ranging from motor unit recruitment to force generation and fatigue.

  5. 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

  6. Production of Accurate Skeletal Models of Domestic Animals Using Three-Dimensional Scanning and Printing Technology

    Science.gov (United States)

    Li, Fangzheng; Liu, Chunying; Song, Xuexiong; Huan, Yanjun; Gao, Shansong; Jiang, Zhongling

    2018-01-01

    Access to adequate anatomical specimens can be an important aspect in learning the anatomy of domestic animals. In this study, the authors utilized a structured light scanner and fused deposition modeling (FDM) printer to produce highly accurate animal skeletal models. First, various components of the bovine skeleton, including the femur, the…

  7. Skeletal, dental and soft tissue changes in Class III patients treated with fixed appliances and lower premolar extractions.

    Science.gov (United States)

    Abu Alhaija, Elham S J; Al-Khateeb, Susan N

    2011-05-01

    Mild Class III malocciusions can be treated by upper incisor proclination and lower incisor retroclination following extraction of the lower first premolars. To compare the skeletal, dental and soft tissue changes in Class III patients treated with fixed appliances, Class III traction and lower first premolar extractions with the changes in a group of untreated Class III patients. The Treatment group consisted of 30 Class III patients (Mean age 13.69 +/- 1.48 years) who were treated by upper and lower fixed appliances, Class III intermaxillary traction and lower first premolar extractions for 2.88 +/- 1.12 years. The Control group consisted of 20 untreated Class III patients (Mean age 13.51 +/- 0.95) matched for age and gender. The T1 to T2 changes in the treated and untreated groups were compared using a paired t-test while differences between the two groups were compared with an independent t-test. During treatment, the upper incisors were proclined about 1 degree and the lower incisors were retroclined 8 degrees. Small, but statistically significant changes in SNB, Wits and the overlying soft tissues accompanied the changes in incisor inclination. At the end of treatment a positive overbite and overjet were achieved. The increase in lower facial height in the Treatment group was comparable with the change in the Control group. A range of mild to moderate Class III malocclusions can be treated by dentoalveolar compensation.

  8. Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice.

    Science.gov (United States)

    Bal, Naresh C; Singh, Sushant; Reis, Felipe C G; Maurya, Santosh K; Pani, Sunil; Rowland, Leslie A; Periasamy, Muthu

    2017-10-06

    Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) ( i.e. uncoupling protein 1 (UCP1)-based) and skeletal muscle ( i.e. sarcolipin (SLN)-based) thermogenesis processes play important roles in temperature homeostasis, but their relative contributions differ from small to large mammals. In this study, we investigated the functional interplay between skeletal muscle- and BAT-based thermogenesis under mild versus severe cold adaptation by employing UCP1 -/- and SLN -/- mice. Interestingly, adaptation of SLN -/- mice to mild cold conditions (16 °C) significantly increased UCP1 expression, suggesting increased reliance on BAT-based thermogenesis. This was also evident from structural alterations in BAT morphology, including mitochondrial architecture, increased expression of electron transport chain proteins, and depletion of fat droplets. Similarly, UCP1 -/- mice adapted to mild cold up-regulated muscle-based thermogenesis, indicated by increases in muscle succinate dehydrogenase activity, SLN expression, mitochondrial content, and neovascularization, compared with WT mice. These results further confirm that SLN-based thermogenesis is a key player in muscle non-shivering thermogenesis (NST) and can compensate for loss of BAT activity. We also present evidence that the increased reliance on BAT-based NST depends on increased autonomic input, as indicated by abundant levels of tyrosine hydroxylase and neuropeptide Y. Our findings demonstrate that both BAT and muscle-based NST are equally recruited during mild and severe cold adaptation and that loss of heat production from one thermogenic pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic processes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Calculation of absorbed fractions to human skeletal tissues due to alpha particles using the Monte Carlo and 3-d chord-based transport techniques

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, J.G. [Institute of Radiation Protection and Dosimetry, Av. Salvador Allende s/n, Recreio, Rio de Janeiro, CEP 22780-160 (Brazil); Watchman, C.J. [Department of Radiation Oncology, University of Arizona, Tucson, AZ, 85721 (United States); Bolch, W.E. [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL, 32611 (United States); Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611 (United States)

    2007-07-01

    Absorbed fraction (AF) calculations to the human skeletal tissues due to alpha particles are of interest to the internal dosimetry of occupationally exposed workers and members of the public. The transport of alpha particles through the skeletal tissue is complicated by the detailed and complex microscopic histology of the skeleton. In this study, both Monte Carlo and chord-based techniques were applied to the transport of alpha particles through 3-D micro-CT images of the skeletal microstructure of trabecular spongiosa. The Monte Carlo program used was 'Visual Monte Carlo-VMC'. VMC simulates the emission of the alpha particles and their subsequent energy deposition track. The second method applied to alpha transport is the chord-based technique, which randomly generates chord lengths across bone trabeculae and the marrow cavities via alternate and uniform sampling of their cumulative density functions. This paper compares the AF of energy to two radiosensitive skeletal tissues, active marrow and shallow active marrow, obtained with these two techniques. (authors)

  10. Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle.

    Science.gov (United States)

    Nugent, William H; Song, Bjorn K; Pittman, Roland N; Golub, Aleksander S

    2016-05-01

    Under physiologic conditions, microvascular oxygen delivery appears to be well matched to oxygen consumption in respiring tissues. We present a technique to measure interstitial oxygen tension (PISFO2) and oxygen consumption (VO2) under steady-state conditions, as well as during the transitions from rest to activity and back. Phosphorescence Quenching Microscopy (PQM) was employed with pneumatic compression cycling to achieve 1 to 10 Hz sampling rates of interstitial PO2 and simultaneous recurrent sampling of VO2 (3/min) in the exteriorized rat spinotrapezius muscle. The compression pressure was optimized to 120-130 mmHg without adverse effect on the tissue preparation. A cycle of 5s compression followed by 15s recovery yielded a resting VO2 of 0.98 ± 0.03 ml O2/100 cm(3)min while preserving microvascular oxygen delivery. The measurement system was then used to assess VO2 dependence on PISFO2 at rest and further tested under conditions of isometric muscle contraction to demonstrate a robust ability to monitor the on-kinetics of tissue respiration and the compensatory changes in PISFO2 during contraction and recovery. The temporal and spatial resolution of this approach is well suited to studies seeking to characterize microvascular oxygen supply and demand in thin tissues. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response.

    Directory of Open Access Journals (Sweden)

    Martha Lappas

    Full Text Available Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3 plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM. Thus, the aims of this study were (i to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. In conclusion, GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators.

  12. Assessment of three types of spaceflight hardware for tissue culture studies: Comparison of skeletal tissue growth and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Klement, B.J. [Space Medicine and Life Sciences Research Center Department of Anatomy Morehouse School of Medicine 720 Westview Dr. SW Atlanta, Georgia30310-1495 (United States); Spooner, B.S. [NASA Specialized Center of Research and Training Division of Biology Ackert Hall Kansas State University Manhattan, Kansas66506 (United States)

    1997-01-01

    Three different types of spaceflight hardware, the BioProcessing Module (BPM), the Materials Dispersion Apparatus (MDA), and the Fluid Processing Apparatus (FPA), were assessed for their ability to support pre-metatarsal growth and differentiation in experiments conducted on five space shuttle flights. BPM-cultured pre-metatarsal tissue showed no difference in flight and ground control lengths. Flight and ground controls cultured in the MDA grew 135 {mu}m and 141 {mu}m, respectively, in an 11 day experiment. Only five control rods and three flight rods mineralized. In another MDA experiment, pre-metatarsals were cultured at 4{degree}C (277K) or 20{degree}C (293K) for the 16 day mission, then cultured an additional 16 days in laboratory dishes at 37{degree}C (310K). The 20{degree}C (293K) cultures died post-flight. The 4{degree}C (277K) flight pre-metatarsals grew 417 {mu}m more than the 4{degree}C (277K) ground controls post-flight. In 5 and 6 day experiments done in FPAs, flight rods grew longer than ground control rods. In a 14 day experiment, ground control and flight rods also expanded in length, but there was no difference between them. The pre-metatarsals cultured in the FPAs did not mineralize, or terminally differentiate. These experiments demonstrate, that while supporting pre-metatarsal growth in length, the three types of hardware are not suitable to support routine differentiation. {copyright} {ital 1997 American Institute of Physics.}

  13. Selumetinib Attenuates Skeletal Muscle Wasting in Murine Cachexia Model through ERK Inhibition and AKT Activation.

    Science.gov (United States)

    Quan-Jun, Yang; Yan, Huo; Yong-Long, Han; Li-Li, Wan; Jie, Li; Jin-Lu, Huang; Jin, Lu; Peng-Guo, Chen; Run, Gan; Cheng, Guo

    2017-02-01

    Cancer cachexia is a multifactorial syndrome affecting the skeletal muscle. Previous clinical trials showed that treatment with MEK inhibitor selumetinib resulted in skeletal muscle anabolism. However, it is conflicting that MAPK/ERK pathway controls the mass of the skeletal muscle. The current study investigated the therapeutic effect and mechanisms of selumetinib in amelioration of cancer cachexia. The classical cancer cachexia model was established via transplantation of CT26 colon adenocarcinoma cells into BALB/c mice. The effect of selumetinib on body weight, tumor growth, skeletal muscle, food intake, serum proinflammatory cytokines, E3 ligases, and MEK/ERK-related pathways was analyzed. Two independent experiments showed that 30 mg/kg/d selumetinib prevented the loss of body weight in murine cachexia mice. Muscle wasting was attenuated and the expression of E3 ligases, MuRF1 and Fbx32, was inhibited following selumetinib treatment of the gastrocnemius muscle. Furthermore, selumetinib efficiently reduced tumor burden without influencing the cancer cell proliferation, cumulative food intake, and serum cytokines. These results indicated that the role of selumetinib in attenuating muscle wasting was independent of cancer burden. Detailed analysis of the mechanism revealed AKT and mTOR were activated, while ERK, FoxO3a, and GSK3β were inhibited in the selumetinib -treated cachexia group. These indicated that selumetinib effectively prevented skeletal muscle wasting in cancer cachexia model through ERK inhibition and AKT activation in gastrocnemius muscle via cross-inhibition. The study not only elucidated the mechanism of MEK/ERK inhibition in skeletal muscle anabolism, but also validated selumetinib therapy as an effective intervention against cancer cachexia. Mol Cancer Ther; 16(2); 334-43. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. Sensitivity of subject-specific models to errors in musculo-skeletal geometry

    NARCIS (Netherlands)

    Carbone, V.; van der Krogt, M.M.; Koopman, H.F.J.M.; Verdonschot, N.

    2012-01-01

    Subject-specific musculo-skeletal models of the lower extremity are an important tool for investigating various biomechanical problems, for instance the results of surgery such as joint replacements and tendon transfers. The aim of this study was to assess the potential effects of errors in

  15. Production of accurate skeletal models of domestic animals using three-dimensional scanning and printing technology.

    Science.gov (United States)

    Li, Fangzheng; Liu, Chunying; Song, Xuexiong; Huan, Yanjun; Gao, Shansong; Jiang, Zhongling

    2018-01-01

    Access to adequate anatomical specimens can be an important aspect in learning the anatomy of domestic animals. In this study, the authors utilized a structured light scanner and fused deposition modeling (FDM) printer to produce highly accurate animal skeletal models. First, various components of the bovine skeleton, including the femur, the fifth rib, and the sixth cervical (C6) vertebra were used to produce digital models. These were then used to produce 1:1 scale physical models with the FDM printer. The anatomical features of the digital models and three-dimensional (3D) printed models were then compared with those of the original skeletal specimens. The results of this study demonstrated that both digital and physical scale models of animal skeletal components could be rapidly produced using 3D printing technology. In terms of accuracy between models and original specimens, the standard deviations of the femur and the fifth rib measurements were 0.0351 and 0.0572, respectively. All of the features except the nutrient foramina on the original bone specimens could be identified in the digital and 3D printed models. Moreover, the 3D printed models could serve as a viable alternative to original bone specimens when used in anatomy education, as determined from student surveys. This study demonstrated an important example of reproducing bone models to be used in anatomy education and veterinary clinical training. Anat Sci Educ 11: 73-80. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

  16. Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle.

    Science.gov (United States)

    Moore, Stephanie N; Hawley, Gregory D; Smith, Emily N; Mignemi, Nicholas A; Ihejirika, Rivka C; Yuasa, Masato; Cates, Justin M M; Liu, Xulei; Schoenecker, Jonathan G

    2016-01-01

    Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary to discriminate

  17. Ionizing Radiation Stimulates Expression of Pro-Osteoclastogenic Genes in Marrow and Skeletal Tissue

    Science.gov (United States)

    Alwood, J. S.; Shahnazari, M.; Chicana, B.; Schreurs, A. S.; Kumar, A.; Bartolini, A.; Shirazi-Fard, Y.; Globus, R. K.

    2015-01-01

    Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically-active, cancellous-bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total-body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16wk), male C57BL/6J mice were exposed to either 2Gy gamma rays (137Cs, 0.8Gy/min) or heavy ions (56Fe, 600MeV, 0.50-1.1Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is =10Gy) or accumulates over long-duration, interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4hrs-7d later. Gamma irradiation caused a prompt (2.6-fold within 4hrs) and persistent (peaking at 4.1-fold within 1d) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappaB-ligand (Rankl) within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3d of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (e.g., monocyte chemotactic protein-1 increased 11.9-fold, tumor necrosis factor-alpha increased 1.7- fold over controls). Marrow expression of the RANKL decoy receptor, osteoprotegerin (Opg), also rose after irradiation (11.3-fold). The ratio Rankl/Opg in marrow was increased 1.8-fold, a net pro-resorption balance. As expected, radiation increased a serum marker of resorption (tartrate resistant acid phosphatase) and led to cancellous bone loss (16% decrease in bone volume/total volume) through reduced trabecular struts. We conclude that total-body irradiation (gamma or heavy-ion) caused temporal, concerted regulation of gene expression within marrow and mineralized tissue for

  18. Short-term immobilization and recovery affect skeletal muscle but not collagen tissue turnover in humans

    DEFF Research Database (Denmark)

    Christensen, Britt; Dyrberg, Eva; Aagaard, Per

    2008-01-01

    Not much is known about the effects of immobilization and subsequent recovery on tendon connective tissue. In the present study, healthy young men had their nondominant leg immobilized for a 2-wk period, followed by a recovery period of the same length. Immobilization resulted in a mean decrease...... of 6% (5,413 to 5,077 mm(2)) in cross-sectional area (CSA) of the triceps surae muscles and a mean decrease of 9% (261 to 238 N.m) in strength of the immobilized calf muscles. Two weeks of recovery resulted in a 6% increased in CSA (to 5,367 mm(2)), whereas strength remained suppressed (240 N...... muscle size and strength, while tendon size and collagen turnover were unchanged. While recovery resulted in an increase in muscle size, strength was unchanged. No significant difference in tendon size could be detected between the two legs after 2 wk of recovery, although collagen synthesis...

  19. Function of skeletal muscle tissue formed after myoblast transplantation into irradiated mouse muscles.

    Science.gov (United States)

    Wernig, A; Zweyer, M; Irintchev, A

    2000-01-15

    1. Pretreatment of muscles with ionising radiation enhances tissue formation by transplanted myoblasts but little is known about the effects on muscle function. We implanted myoblasts from an expanded, male-donor-derived, culture (i28) into X-ray irradiated (16 Gy) or irradiated and damaged soleus muscles of female syngeneic mice (Balb/c). Three to 6 months later the isometric contractile properties of the muscles were studied in vitro, and donor nuclei were visualised in muscle sections with a Y chromosome-specific DNA probe. 2. Irradiated sham-injected muscles had smaller masses than untreated solei and produced less twitch and tetanic force (all by about 18 %). Injection of 106 myoblasts abolished these deficiencies and innervation appeared normal. 3. Cryodamage of irradiated solei produced muscle remnants with few (1-50) or no fibres. Additional myoblast implantation led to formation of large muscles (25 % above normal) containing numerous small-diameter fibres. Upon direct electrical stimulation, these muscles produced considerable twitch (53 % of normal) and tetanic forces (35 % of normal) but innervation was insufficient as indicated by weak nerve-evoked contractions and elevated ACh sensitivity. 4. In control experiments on irradiated muscles, reinnervation was found to be less complete after botulinum toxin paralysis than after nerve crush indicating that proliferative arrest of irradiated Schwann cells may account for the observed innervation deficits. 5. Irradiation appears to be an effective pretreatment for improving myoblast transplantation. The injected cells can even produce organised contractile tissue replacing whole muscle. However, impaired nerve regeneration limits the functional performance of the new muscle.

  20. A model for determining baseline morphometrics of skeletal myofibres

    Directory of Open Access Journals (Sweden)

    Maurice Mars

    2014-11-01

    Full Text Available The minimum diameter method of morphometry (MDM is used to measure and detect changes in myofibre diameters (FD. The MDM is used to identify pathology in skeletal muscle. In such studies, an assumption is made that the mean FD in a particular muscle in both limbs is essentially the same. This study explored this premise to determine the accuracy of MDM as a means of morphometric analysis. Muscle biopsies were obtained from the left (G1 and right (G2 tibialis anterior of four vervet monkeys and from the massaged left (G3 and untreated right (G4 tibialis anterior of four animals. Wax sections were prepared for MDM and FD was measured. Three specimens were re-measured on four occasions. The mean FD of each biopsy from G1 and G2 limbs were compared and the number of measurements necessary to produce a meaningful result determined. Repeated measurement showed a difference of 175 FD were measured, the difference from the final mean was less than 2.0%. These data show that, (1 FD data derived from a muscle in an untreated limb can be used as a control for experiment mediated changes of FD in the other, (2 MDM is a reliable means of measuring FD and (3 150–175 FD are needed to provide a dependable result.

  1. Damage Models for Soft Tissues: A Survey.

    Science.gov (United States)

    Li, Wenguang

    Damage to soft tissues in the human body has been investigated for applications in healthcare, sports, and biomedical engineering. This paper reviews and classifies damage models for soft tissues to summarize achievements, identify new directions, and facilitate finite element analysis. The main ideas of damage modeling methods are illustrated and interpreted. A few key issues related to damage models, such as experimental data curve-fitting, computational effort, connection between damage and fractures/cracks, damage model applications, and fracture/crack extension simulation, are discussed. Several new challenges in the field are identified and outlined. This review can be useful for developing more advanced damage models and extending damage modeling methods to a variety of soft tissues.

  2. Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients

    DEFF Research Database (Denmark)

    Dela, Flemming; Stallknecht, Bente Merete

    2010-01-01

    in CON but not in FDR, whereas glucose-mediated GU increased (P groups. Adipose tissue GU was not affected by training, but it was higher (abdominal, P Training increased skeletal muscle lipolysis (P ...- to sevenfold. We conclude that insulin-secretory capacity is lower in FDR than in CON and that there is dissociation between training-induced changes in insulin secretion and insulin-mediated GU. Maximal GU rates are similar between groups and increases with physical training.......Physical training affects insulin secretion and action, but there is a paucity of data on the direct effects in skeletal muscle and adipose tissue and on the effect of training in first-degree relatives (FDR) of patients with type 2 diabetes. We studied insulin action at the whole body level...

  3. Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system

    Science.gov (United States)

    Xin, Frances; Smith, Lauren M; Susiarjo, Martha; Jepsen, Karl J

    2018-01-01

    Abstract Early life exposures to endocrine-disrupting chemicals (EDCs) have been associated with physiological changes of endocrine-sensitive tissues throughout postnatal life. Although hormones play a critical role in skeletal growth and maintenance, the effects of prenatal EDC exposure on adult bone health are not well understood. Moreover, studies assessing skeletal changes across multiple generations are limited. In this article, we present previously unpublished data demonstrating dose-, sex-, and generation-specific changes in bone morphology and function in adult mice developmentally exposed to the model estrogenic EDC bisphenol A (BPA) at doses of 10 μg (lower dose) or 10 mg per kg bw/d (upper dose) throughout gestation and lactation. We show that F1 generation adult males, but not females, developmentally exposed to bisphenol A exhibit dose-dependent reductions in outer bone size resulting in compromised bone stiffness and strength. These structural alterations and weaker bone phenotypes in the F1 generation did not persist in the F2 generation. Instead, F2 generation males exhibited greater bone strength. The underlying mechanisms driving the EDC-induced physiological changes remain to be determined. We discuss potential molecular changes that could contribute to the EDC-induced skeletal effects, with an emphasis on epigenetic dysregulation. Furthermore, we assess the necessity of intact sex steroid receptors to mediate these effects. Expanding future assessments of EDC-induced effects to the skeleton may provide much needed insight into one of the many health effects of these chemicals and aid in regulatory decision making regarding exposure of vulnerable populations to these chemicals. PMID:29732168

  4. Protein profiles of Taenia solium cysts obtained from skeletal muscles and the central nervous system of pigs: Search for tissue-specific proteins.

    Science.gov (United States)

    Navarrete-Perea, José; Moguel, Bárbara; Bobes, Raúl José; Villalobos, Nelly; Carrero, Julio César; Sciutto, Edda; Soberón, Xavier; Laclette, Juan Pedro

    2017-01-01

    Taeniasis/cysticercosis caused by the tapeworm Taenia solium is a parasite disease transmitted among humans and pigs, the main intermediate host. The larvae/cysts can lodge in several tissues of the pig, i.e. skeletal muscles and different locations of the central nervous system. The molecular mechanisms associated to tissue preferences of the cysts remain poorly understood. The major public health concern about this zoonosis is due to the human infections by the larval form in the central nervous system, causing a highly pleomorphic and debilitating disease known as neurocysticercosis. This study was aimed to explore the 2DE protein maps of T. solium cysts obtained from skeletal muscles and central nervous system of naturally infected pigs. The gel images were analyzed through a combination of PDQuest™ and multivariate analysis. Results showed that differences in the protein patterns of cysts obtained from both tissues were remarkably discrete. Only 7 protein spots were found specifically associated to the skeletal muscle localization of the cysts; none was found significantly associated to the central nervous system. The use of distinct protein fractions of cysts allowed preliminary identification of several tissue-specific antigenic bands. The implications of these findings are discussed, as well as several strategies directed to achieve the complete characterization of this parasite's proteome, in order to extend our understanding of the molecular mechanisms underlying tissue localization of the cysts and to open avenues for the development of immunological tissue-specific diagnosis of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Autologous Minced Muscle Grafts: A Tissue Engineering Therapy for the Volumetric Loss of Skeletal Muscle

    Science.gov (United States)

    2013-07-24

    in nonrepaired muscles was restored). Additionally, voluntary wheel running was shown to reduce the heightened accu- mulation of extracellular matrix...is apparent in a variety of animal injury models, such as toxin (44), freeze (67), eccentric contraction (34), laceration (31), and ischemia-rep...were given access to running wheels in their cages beginning at 1 wk postinjury and until 2 or 8 wk postinjury, at which time muscle mechanical

  6. Model analysis of the relationship between intracellular Po2 and energy demand in skeletal muscle

    OpenAIRE

    Spires, Jessica; Gladden, L. Bruce; Grassi, Bruno; Saidel, Gerald M.; Lai, Nicola

    2012-01-01

    On the basis of experimental studies, the intracellular O2 (iPo2)-work rate (WR) relationship in skeletal muscle is not unique. One study found that iPo2 reached a plateau at 60% of maximal WR, while another found that iPo2 decreased linearly at higher WR, inferring capillary permeability-surface area (PS) and blood-tissue O2 gradient, respectively, as alternative dominant factors for determining O2 diffusion changes during exercise. This relationship is affected by several factors, including...

  7. Impaired autoregulation of blood flow in skeletal muscle and subcutaneous tissue in long-term Type 1 (insulin-dependent) diabetic patients with microangiopathy

    DEFF Research Database (Denmark)

    Faris, I; Vagn Nielsen, H; Henriksen, O

    1983-01-01

    Autoregulation of blood flow was studied in skeletal muscle and subcutaneous tissue in seven Type 1 (insulin-dependent) diabetic patients (median age: 36 years) with nephropathy and retinopathy and in eight normal subjects of the same age. Blood flow was measured by the local 133Xe washout...... technique. Reduction in arterial perfusion pressure was produced by elevating the limb 20 and 40 cm above heart level. Blood flow remained within 10% of control values when the limb was elevated in normal subjects. In five of the seven diabetic subjects blood flow fell significantly in both tissues when...

  8. A novel three-filament model of force generation in eccentric contraction of skeletal muscles.

    Directory of Open Access Journals (Sweden)

    Gudrun Schappacher-Tilp

    Full Text Available We propose and examine a three filament model of skeletal muscle force generation, thereby extending classical cross-bridge models by involving titin-actin interaction upon active force production. In regions with optimal actin-myosin overlap, the model does not alter energy and force predictions of cross-bridge models for isometric contractions. However, in contrast to cross-bridge models, the three filament model accurately predicts history-dependent force generation in half sarcomeres for eccentric and concentric contractions, and predicts the activation-dependent forces for stretches beyond actin-myosin filament overlap.

  9. Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography.

    Science.gov (United States)

    Altman, Allison R; Tseng, Wei-Ju; de Bakker, Chantal M J; Chandra, Abhishek; Lan, Shenghui; Huh, Beom Kang; Luo, Shiming; Leonard, Mary B; Qin, Ling; Liu, X Sherry

    2015-12-01

    In this study we established an image analysis scheme for the investigation of cortical and trabecular bone development during skeletal growth and tested this concept on in vivo μCT images of rats. To evaluate its efficacy, we applied the technique to young (1-month-old) and adult (3-month-old) rat tibiae with vehicle (Veh) or intermittent parathyroid hormone (PTH) treatment. By overlaying 2 sequential scans based on their distinct trabecular microarchitecture, we calculated the linear growth rate of young rats to be 0.31 mm/day at the proximal tibia. Due to rapid growth (3.7 mm in 12 days), the scanned bone region at day 12 had no overlap with the bone tissue scanned at day 0. Instead, the imaged bone region at day 12 represented newly generated bone tissue from the growth plate. The new bone of the PTH-treated rats had significantly greater trabecular bone volume fraction, number, and thickness than those of the Veh-treated rats, indicating PTH's anabolic effect on bone modeling. In contrast, the effect of PTH on adult rat trabecular bone was found to be caused by PTH's anabolic effect on bone remodeling. The cortical bone at the proximal tibia of young rats also thickened more in the PTH group (23%) than the Veh group (14%). This was primarily driven by endosteal bone formation and coalescence of trabecular bone into the cortex. This process can be visualized by aligning the local bone structural changes using image registration. As a result, the cortex after PTH treatment was 31% less porous, and had a 22% greater polar moment of inertia compared to the Veh group. Lastly, we monitored the longitudinal bone growth in adult rats by measuring the distance of bone flow away from the proximal tibial growth plate from 3 months to 19 months of age and discovered a total of 3.5mm growth in 16 months. It was demonstrated that this image analysis scheme can efficiently evaluate bone growth, bone modeling, and bone remodeling, and is ready to be translated into a

  10. Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: preliminary study.

    Science.gov (United States)

    Bar-El Dadon, Shimrit; Shahar, Ron; Katalan, Vered; Monsonego-Ornan, Efrat; Reifen, Ram

    2011-09-01

    Skeletal abnormalities are one of the hallmarks of growth delay during gestation. The aim of this study was to determine changes induced by leptin in skeletal growth and development in a rat model of intrauterine growth retardation (IUGR) and to elucidate the possible underlying mechanisms. Intrauterine growth retardation was induced prepartum and the effects of leptin to mothers prenatally or to offspring postnatally were studied. Radii were harvested and tested mechanically and structurally. Tibias were evaluated for growth-plate morphometry. On day 40 postpartum, total bone length and mineral density and tibial growth-plate width and numbers of cells within its zones of offspring treated with leptin were significantly greater than in the control group. Postnatal leptin administration in an IUGR model improves the structural properties and elongation rate of bone. These findings could pave the way to preventing some phenotypic presentations of IUGR. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

    2003-01-01

    OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment......, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics. Bone-related biochemistry was measured in serum and urine. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were used to determine bone...... no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P

  12. Extracellular Matrix Hydrogel Promotes Tissue Remodeling, Arteriogenesis, and Perfusion in a Rat Hindlimb Ischemia Model

    Directory of Open Access Journals (Sweden)

    Jessica L. Ungerleider, BS

    2016-01-01

    Full Text Available Although surgical and endovascular revascularization can be performed in peripheral arterial disease (PAD, 40% of patients with critical limb ischemia do not have a revascularization option. This study examines the efficacy and mechanisms of action of acellular extracellular matrix-based hydrogels as a potential novel therapy for treating PAD. We tested the efficacy of using a tissue-specific injectable hydrogel derived from decellularized porcine skeletal muscle (SKM and compared this to a new human umbilical cord-derived matrix (hUC hydrogel, which could have greater potential for tissue regeneration because of the younger age of the tissue source. In a rodent hindlimb ischemia model, both hydrogels were injected 1-week post-surgery and perfusion was regularly monitored with laser speckle contrast analysis to 35 days post-injection. There were significant improvements in hindlimb tissue perfusion and perfusion kinetics with both biomaterials. Histologic analysis indicated that the injected hydrogels were biocompatible, and resulted in arteriogenesis, rather than angiogenesis, as well as improved recruitment of skeletal muscle progenitors. Skeletal muscle fiber morphology analysis indicated that the muscle treated with the tissue-specific SKM hydrogel more closely matched healthy tissue morphology. Whole transcriptome analysis indicated that the SKM hydrogel caused a shift in the inflammatory response, decreased cell death, and increased blood vessel and muscle development. These results show the efficacy of an injectable ECM hydrogel alone as a potential therapy for treating patients with PAD. Our results indicate that the SKM hydrogel improved functional outcomes through stimulation of arteriogenesis and muscle progenitor cell recruitment.

  13. Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test.

    Science.gov (United States)

    Yu, Fang Fang; Lin, Xia Lu; Yang, Lei; Liu, Huan; Wang, Xi; Fang, Hua; Lammi, ZMikko J; Guo, Xiong

    2017-11-01

    Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  14. Twente spine model : A complete and coherent dataset for musculo-skeletal modeling of the thoracic and cervical regions of the human spine

    NARCIS (Netherlands)

    Bayoglu, Riza; Geeraedts, Leo; Groenen, Karlijn H.J.; Verdonschot, Nico; Koopman, Bart; Homminga, Jasper

    2017-01-01

    Musculo-skeletal modeling could play a key role in advancing our understanding of the healthy and pathological spine, but the credibility of such models are strictly dependent on the accuracy of the anatomical data incorporated. In this study, we present a complete and coherent musculo-skeletal

  15. Mutations in B3GALT6, which encodes a glycosaminoglycan linker region enzyme, cause a spectrum of skeletal and connective tissue disorders.

    Science.gov (United States)

    Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie; Chitayat, David; Howard, Andrew; Leal, Gabriela F; Cavalcanti, Denise; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Watanabe, Shigehiko; Lausch, Ekkehart; Unger, Sheila; Bonafé, Luisa; Ohashi, Hirofumi; Superti-Furga, Andrea; Matsumoto, Naomichi; Sugahara, Kazuyuki; Nishimura, Gen; Ikegawa, Shiro

    2013-06-06

    Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Parameter interdependence and succes of skeletal muscle modelling

    NARCIS (Netherlands)

    Huijing, P.A.J.B.M.

    1995-01-01

    In muscle and movement modelling it is almost invariably assumed that force actually exerted is determined by several independent factors. This review considers the fact that length force characteristics are not a relatively fixed property of muscle but should be considered the product of a

  17. Bone marrow mesenchymal cells improve muscle function in a skeletal muscle re-injury model.

    Directory of Open Access Journals (Sweden)

    Bruno M Andrade

    Full Text Available Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively. Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model.

  18. Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis

    Directory of Open Access Journals (Sweden)

    Tracy A. Brennan

    2014-05-01

    Full Text Available A major medical challenge in the elderly is osteoporosis and the high risk of fracture. Telomere dysfunction is a cause of cellular senescence and telomere shortening, which occurs with age in cells from most human tissues, including bone. Telomere defects contribute to the pathogenesis of two progeroid disorders characterized by premature osteoporosis, Werner syndrome and dyskeratosis congenital. It is hypothesized that telomere shortening contributes to bone aging. We evaluated the skeletal phenotypes of mice with disrupted telomere maintenance mechanisms as models for human bone aging, including mutants in Werner helicase (Wrn−/−, telomerase (Terc−/− and Wrn−/−Terc−/− double mutants. Compared with young wild-type (WT mice, micro-computerized tomography analysis revealed that young Terc−/− and Wrn−/−Terc−/− mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing. In cortical bone, young Terc−/− and Wrn−/−Terc−/− mice have increased cortical thinning, and increased porosity relative to age-matched WT mice. These trabecular and cortical changes were accelerated with age in Terc−/− and Wrn−/−Terc−/− mice compared with older WT mice. Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc−/− and Wrn−/−Terc−/− bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice. Except in the Wrn−/− single mutant, osteoclast number did not increase in any genotype. Significant alterations in mechanical parameters (structure model index, degree of anistrophy and moment of inertia of the Terc−/− and Wrn−/−Terc−/− femurs compared with WT mice were also observed. Young Wrn

  19. Modeling collagen remodeling in tissue engineered cardiovascular tissues

    NARCIS (Netherlands)

    Soares, A.L.F.

    2012-01-01

    Commonly, heart valve replacements consist of non-living materials lacking the ability to grow, repair and remodel. Tissue engineering (TE) offers a promising alternative to these replacement strategies since it can overcome its disadvantages. The technique aims to create an autologous living tissue

  20. Skeletal muscle repair in a mouse model of nemaline myopathy

    OpenAIRE

    Sanoudou, Despina; Corbett, Mark A.; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T.; Vlahovich, Nicole; Hardeman, Edna C.; Beggs, Alan H.

    2006-01-01

    Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five d...

  1. Rabbit tissue model (RTM) harvesting technique.

    Science.gov (United States)

    Medina, Marelyn

    2002-01-01

    A method for creating a tissue model using a female rabbit for laparoscopic simulation exercises is described. The specimen is called a Rabbit Tissue Model (RTM). Dissection techniques are described for transforming the rabbit carcass into a small, compact unit that can be used for multiple training sessions. Preservation is accomplished by using saline and refrigeration. Only the animal trunk is used, with the rest of the animal carcass being discarded. Practice exercises are provided for using the preserved organs. Basic surgical skills, such as dissection, suturing, and knot tying, can be practiced on this model. In addition, the RTM can be used with any pelvic trainer that permits placement of larger practice specimens within its confines.

  2. Tissue Sampling Guides for Porcine Biomedical Models.

    Science.gov (United States)

    Albl, Barbara; Haesner, Serena; Braun-Reichhart, Christina; Streckel, Elisabeth; Renner, Simone; Seeliger, Frank; Wolf, Eckhard; Wanke, Rüdiger; Blutke, Andreas

    2016-04-01

    This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ∼50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitative analyses, including cryohistology, paraffin, and plastic histology; immunohistochemistry;in situhybridization; electron microscopy; and quantitative stereology as well as molecular analyses of DNA, RNA, proteins, metabolites, and electrolytes. With regard to the planned extent of sampling efforts, time, and personnel expenses, and dependent upon the scheduled analyses, different protocols are provided. These protocols are adjusted for (I) routine screenings, as used in general toxicity studies or in analyses of gene expression patterns or histopathological organ alterations, (II) advanced analyses of single organs/tissues, and (III) large-scale sampling procedures to be applied in biobank projects. Providing a robust reference for studies of porcine models, the described protocols will ensure the efficiency of sampling, the systematic recovery of high-quality samples representing the entire organ or tissue as well as the intra-/interstudy comparability and reproducibility of results. © The Author(s) 2016.

  3. Cloning and tissue distribution of rat hear fatty acid binding protein mRNA: identical forms in heart and skeletal muscle

    International Nuclear Information System (INIS)

    Claffey, K.P.; Herrera, V.L.; Brecher, P.; Ruiz-Opazo, N.

    1987-01-01

    A fatty acid binding protein (FABP) as been identified and characterized in rat heart, but the function and regulation of this protein are unclear. In this study the cDNA for rat heart FABP was cloned from a λ gt11 library. Sequencing of the cDNA showed an open reading frame coding for a protein with 133 amino acids and a calculated size of 14,776 daltons. Several differences were found between the sequence determined from the cDNA and that reported previously by protein sequencing techniques. Northern blot analysis using rat heart FABP cDNA as a probe established the presence of an abundant mRNA in rat heart about 0.85 kilobases in length. This mRNA was detected, but was not abundant, in fetal heart tissue. Tissue distribution studies showed a similar mRNA species in red, but not white, skeletal muscle. In general, the mRNA tissue distribution was similar to that of the protein detected by Western immunoblot analysis, suggesting that heart FABP expression may be regulated at the transcriptional level. S1 nuclease mapping studies confirmed that the mRNA hybridized to rat heart FABP cDNA was identical in heart and red skeletal muscle throughout the entire open reading frame. The structural differences between heart FABP and other members of this multigene family may be related to the functional requirements of oxidative muscle for fatty acids as a fuel source

  4. Cloning and tissue distribution of rat hear fatty acid binding protein mRNA: identical forms in heart and skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Claffey, K.P.; Herrera, V.L.; Brecher, P.; Ruiz-Opazo, N.

    1987-12-01

    A fatty acid binding protein (FABP) as been identified and characterized in rat heart, but the function and regulation of this protein are unclear. In this study the cDNA for rat heart FABP was cloned from a lambda gt11 library. Sequencing of the cDNA showed an open reading frame coding for a protein with 133 amino acids and a calculated size of 14,776 daltons. Several differences were found between the sequence determined from the cDNA and that reported previously by protein sequencing techniques. Northern blot analysis using rat heart FABP cDNA as a probe established the presence of an abundant mRNA in rat heart about 0.85 kilobases in length. This mRNA was detected, but was not abundant, in fetal heart tissue. Tissue distribution studies showed a similar mRNA species in red, but not white, skeletal muscle. In general, the mRNA tissue distribution was similar to that of the protein detected by Western immunoblot analysis, suggesting that heart FABP expression may be regulated at the transcriptional level. S1 nuclease mapping studies confirmed that the mRNA hybridized to rat heart FABP cDNA was identical in heart and red skeletal muscle throughout the entire open reading frame. The structural differences between heart FABP and other members of this multigene family may be related to the functional requirements of oxidative muscle for fatty acids as a fuel source.

  5. MR imaging of overuse injuries in the skeletally immature gymnast: spectrum of soft-tissue and osseous lesions in the hand and wrist

    International Nuclear Information System (INIS)

    Dwek, Jerry R.; Cardoso, Fabiano; Chung, Christine B.

    2009-01-01

    In the pediatric gymnast, stress-related physeal injuries have been well described with characteristic imaging findings. However, a spectrum of overuse injuries, some rarely reported in the literature, can be encountered in the gymnast's hand and wrist. To demonstrate the MR appearance of a spectrum of overuse injuries in the skeletally immature wrist and hand of pediatric gymnasts. A total of 125 MR exams of the hand and wrist in skeletally immature children were performed at our institution during a 2-year period. Clinical histories were reviewed for gymnastics participation. MR studies of that subpopulation were reviewed and abnormalities tabulated. Of the MR studies reviewed, ten gymnasts were identified, all girls age 12-16 years (mean age 14.2 years) who presented with wrist or hand pain. Three of these children had bilateral MR exams. Abnormalities included chronic physeal injuries in three children. Two girls exhibited focal lunate osteochondral defects. Triangular fibrocartilage tears were present in three girls, one of whom had a scapholunate ligament tear. Two girls manifested metacarpal head flattening and necrosis. A variety of soft-tissue and osseous lesions can be encountered in the skeletally immature gymnast. Familiarity with these stress-related injuries is important for accurate diagnosis. (orig.)

  6. MR imaging of overuse injuries in the skeletally immature gymnast: spectrum of soft-tissue and osseous lesions in the hand and wrist

    Energy Technology Data Exchange (ETDEWEB)

    Dwek, Jerry R. [Department of Radiology, Rady Children' s Hospital and Health Center, San Diego, CA (United States); Cardoso, Fabiano; Chung, Christine B. [University of California at San Diego, Department of Radiology, San Diego, CA (United States)

    2009-12-15

    In the pediatric gymnast, stress-related physeal injuries have been well described with characteristic imaging findings. However, a spectrum of overuse injuries, some rarely reported in the literature, can be encountered in the gymnast's hand and wrist. To demonstrate the MR appearance of a spectrum of overuse injuries in the skeletally immature wrist and hand of pediatric gymnasts. A total of 125 MR exams of the hand and wrist in skeletally immature children were performed at our institution during a 2-year period. Clinical histories were reviewed for gymnastics participation. MR studies of that subpopulation were reviewed and abnormalities tabulated. Of the MR studies reviewed, ten gymnasts were identified, all girls age 12-16 years (mean age 14.2 years) who presented with wrist or hand pain. Three of these children had bilateral MR exams. Abnormalities included chronic physeal injuries in three children. Two girls exhibited focal lunate osteochondral defects. Triangular fibrocartilage tears were present in three girls, one of whom had a scapholunate ligament tear. Two girls manifested metacarpal head flattening and necrosis. A variety of soft-tissue and osseous lesions can be encountered in the skeletally immature gymnast. Familiarity with these stress-related injuries is important for accurate diagnosis. (orig.)

  7. Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

    DEFF Research Database (Denmark)

    Plomgaard, P; Nielsen, A R; Fischer, C P

    2007-01-01

    AIMS/HYPOTHESIS: Clear evidence exists that TNF-alpha inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-alpha in type 2 diabetes. METHODS: We obtained blood and biopsy samples from skeletal muscle...... and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103). RESULTS: Patients with type 2 diabetes had higher plasma levels of fasting insulin (p ...) uptake (VO2/kg) in the diabetes group (p type 2 diabetic patients. Immunohistochemistry revealed more TNF-alpha protein...

  8. Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects

    DEFF Research Database (Denmark)

    Bruun, Jens M; Helge, Jørn W; Richelsen, Bjørn

    2006-01-01

    Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle...... (SM) in 27 severely obese subjects (mean body mass index: 45.8 kg/m2). Plasma samples, subcutaneous abdominal AT biopsies, and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR. The intervention reduced body weight (P

  9. Pseudofracture: an acute peripheral tissue trauma model.

    Science.gov (United States)

    Darwiche, Sophie S; Kobbe, Philipp; Pfeifer, Roman; Kohut, Lauryn; Pape, Hans-Christoph; Billiar, Timothy

    2011-04-18

    Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; this response is often accompanied by a delayed immunosuppression that adds the clinical complications of infection and can also increase mortality. Many studies have begun to assess these changes in the reactivity of the immune system following trauma. Immunologic studies are greatly supported through the wide variety of transgenic and knockout mice available for in vivo modeling; these strains aid in detailed investigations to assess the molecular pathways involved in the immunologic responses. The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible. This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone. The pseudofracture model consists of two parts: a bilateral muscle crush injury to the hindlimbs, followed by injection of a bone solution into these injured muscles. The bone solution is prepared by harvesting the long bones from both hindlimbs of an age- and weight-matched syngeneic donor. These bones are then crushed and resuspended in phosphate buffered saline to create the bone solution. Bilateral femur fracture is a commonly used and well-established model of extremity trauma, and was the comparative model during the development of the pseudofracture model. Among the variety of available fracture models, we chose to use a closed method of fracture with soft tissue injury as our comparison to the

  10. Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis.

    Science.gov (United States)

    Kalinkovich, Alexander; Livshits, Gregory

    2017-05-01

    Sarcopenia, an age-associated decline in skeletal muscle mass coupled with functional deterioration, may be exacerbated by obesity leading to higher disability, frailty, morbidity and mortality rates. In the combination of sarcopenia and obesity, the state called sarcopenic obesity (SOB), some key age- and obesity-mediated factors and pathways may aggravate sarcopenia. This review will analyze the mechanisms underlying the pathogenesis of SOB. In obese adipose tissue (AT), adipocytes undergo hypertrophy, hyperplasia and activation resulted in accumulation of pro-inflammatory macrophages and other immune cells as well as dysregulated production of various adipokines that together with senescent cells and the immune cell-released cytokines and chemokines create a local pro-inflammatory status. In addition, obese AT is characterized by excessive production and disturbed capacity to store lipids, which accumulate ectopically in skeletal muscle. These intramuscular lipids and their derivatives induce mitochondrial dysfunction characterized by impaired β-oxidation capacity and increased reactive oxygen species formation providing lipotoxic environment and insulin resistance as well as enhanced secretion of some pro-inflammatory myokines capable of inducing muscle dysfunction by auto/paracrine manner. In turn, by endocrine manner, these myokines may exacerbate AT inflammation and also support chronic low grade systemic inflammation (inflammaging), overall establishing a detrimental vicious circle maintaining AT and skeletal muscle inflammation, thus triggering and supporting SOB development. Under these circumstances, we believe that AT inflammation dominates over skeletal muscle inflammation. Thus, in essence, it redirects the vector of processes from "sarcopenia→obesity" to "obesity→sarcopenia". We therefore propose that this condition be defined as "obese sarcopenia", to reflect the direction of the pathological pathway. Copyright © 2016 Elsevier B.V. All rights

  11. Skeletal, cardiac, and respiratory muscle function and histopathology in the P448Lneo- mouse model of FKRP-deficient muscular dystrophy.

    Science.gov (United States)

    Yu, Qing; Morales, Melissa; Li, Ning; Fritz, Alexander G; Ruobing, Ren; Blaeser, Anthony; Francois, Ershia; Lu, Qi-Long; Nagaraju, Kanneboyina; Spurney, Christopher F

    2018-04-06

    Fukutin-related protein (FKRP) mutations are the most common cause of dystroglycanopathies known to cause both limb girdle and congenital muscular dystrophy. The P448Lneo- mouse model has a knock-in mutation in the FKRP gene and develops skeletal, respiratory, and cardiac muscle disease. We studied the natural history of the P448Lneo- mouse model over 9 months and the effects of twice weekly treadmill running. Forelimb and hindlimb grip strength (Columbus Instruments) and overall activity (Omnitech Electronics) assessed skeletal muscle function. Echocardiography was performed using VisualSonics Vevo 770 (FujiFilm VisualSonics). Plethysmography was performed using whole body system (ADInstruments). Histological evaluations included quantification of inflammation, fibrosis, central nucleation, and fiber size variation. P448Lneo- mice had significantly increased normalized tissue weights compared to controls at 9 months of age for the heart, gastrocnemius, soleus, tibialis anterior, quadriceps, and triceps. There were no significant differences seen in forelimb or hindlimb grip strength or activity monitoring in P448Lneo- mice with or without exercise compared to controls. Skeletal muscles demonstrated increased inflammation, fibrosis, central nucleation, and variation in fiber size compared to controls (p muscular dystrophies.

  12. Seasonal changes in the expression of energy metabolism-related genes in white adipose tissue and skeletal muscle in female Japanese black bears.

    Science.gov (United States)

    Shimozuru, Michito; Nagashima, Akiko; Tanaka, Jun; Tsubota, Toshio

    2016-01-01

    Bears undergo annual cycles in body mass: rapid fattening in autumn (i.e., hyperphagia), and mass loss in winter (i.e., hibernation). To investigate how Japanese black bears (Ursus thibetanus japonicus) adapt to such extreme physiological conditions, we analyzed changes in the mRNA expression of energy metabolism-related genes in white adipose tissues and skeletal muscle throughout three physiological stages: normal activity (June), hyperphagia (November), and hibernation (March). During hyperphagia, quantitative real-time polymerase chain reaction analysis revealed the upregulation of de novo lipogenesis-related genes (e.g., fatty acid synthase and diacylglycerol O-acyltransferase 2) in white adipose tissue, although the bears had been maintained with a constant amount of food. In contrast, during the hibernation period, we observed a downregulation of genes involved in glycolysis (e.g., glucose transporter 4) and lipogenesis (e.g., acetyl-CoA carboxylase 1) and an upregulation of genes in fatty acid catabolism (e.g., carnitine palmitoyltransferase 1A) in both tissue types. In white adipose tissues, we observed upregulation of genes involved in glyceroneogenesis, including pyruvate carboxylase and phosphoenolpyruvate carboxykinase 1, suggesting that white adipose tissue plays a role in the recycling of circulating free fatty acids via re-esterification. In addition, the downregulation of genes involved in amino acid catabolism (e.g., alanine aminotransferase) and the TCA cycle (e.g., pyruvate carboxylase) indicated a role of skeletal muscle in muscle protein sparing and pyruvate recycling via the Cori cycle. These examples of coordinated transcriptional regulation would contribute to rapid mass gain during the pre-hibernation period and to energy preservation and efficient energy production during the hibernation period. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Sensitivity of subject-specific models to errors in musculo-skeletal geometry.

    Science.gov (United States)

    Carbone, V; van der Krogt, M M; Koopman, H F J M; Verdonschot, N

    2012-09-21

    Subject-specific musculo-skeletal models of the lower extremity are an important tool for investigating various biomechanical problems, for instance the results of surgery such as joint replacements and tendon transfers. The aim of this study was to assess the potential effects of errors in musculo-skeletal geometry on subject-specific model results. We performed an extensive sensitivity analysis to quantify the effect of the perturbation of origin, insertion and via points of each of the 56 musculo-tendon parts contained in the model. We used two metrics, namely a Local Sensitivity Index (LSI) and an Overall Sensitivity Index (OSI), to distinguish the effect of the perturbation on the predicted force produced by only the perturbed musculo-tendon parts and by all the remaining musculo-tendon parts, respectively, during a simulated gait cycle. Results indicated that, for each musculo-tendon part, only two points show a significant sensitivity: its origin, or pseudo-origin, point and its insertion, or pseudo-insertion, point. The most sensitive points belong to those musculo-tendon parts that act as prime movers in the walking movement (insertion point of the Achilles Tendon: LSI=15.56%, OSI=7.17%; origin points of the Rectus Femoris: LSI=13.89%, OSI=2.44%) and as hip stabilizers (insertion points of the Gluteus Medius Anterior: LSI=17.92%, OSI=2.79%; insertion point of the Gluteus Minimus: LSI=21.71%, OSI=2.41%). The proposed priority list provides quantitative information to improve the predictive accuracy of subject-specific musculo-skeletal models. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Mild myopathy is associated with COMP but not MATN3 mutations in mouse models of genetic skeletal diseases.

    Directory of Open Access Journals (Sweden)

    Katarzyna A Piróg

    Full Text Available Pseudoachondroplasia (PSACH and multiple epiphyseal dysplasia (MED are skeletal disorders resulting from mutations in COMP, matrilin-3 or collagen IX and are characterised by short-limbed dwarfism and premature osteoarthritis. Interestingly, recent reports suggest patients can also manifest with muscle weakness. Here we present a detailed analysis of two mouse models of the PSACH/MED disease spectrum; ΔD469 T3-COMP (PSACH and V194D matrilin-3 (MED. In grip test experiments T3-COMP mice were weaker than wild-type littermates, whereas V194D mice behaved as controls, confirming that short-limbed dwarfism alone does not contribute to PSACH/MED-related muscle weakness. Muscles from T3-COMP mice showed an increase in centronuclear fibers at the myotendinous junction. T3-COMP tendons became more lax in cyclic testing and showed thicker collagen fibers when compared with wild-type tissue; matrilin-3 mutant tissues were indistinguishable from controls. This comprehensive study of the myopathy associated with PSACH/MED mutations enables a better understanding of the disease progression, confirms that it is genotype specific and that the limb weakness originates from muscle and tendon pathology rather than short-limbed dwarfism itself. Since some patients are primarily diagnosed with neuromuscular symptoms, this study will facilitate better awareness of the differential diagnoses that might be associated with the PSACH/MED spectrum and subsequent care of PSACH/MED patients.

  15. A new conceptual model of coral biomineralisation: hypoxia as the physiological driver of skeletal extension

    Science.gov (United States)

    Wooldridge, S.

    2013-05-01

    That corals skeletons are built of aragonite crystals with taxonomy-linked ultrastructure has been well understood since the 19th century. Yet, the way by which corals control this crystallization process remains an unsolved question. Here, I outline a new conceptual model of coral biomineralisation that endeavours to relate known skeletal features with homeostatic functions beyond traditional growth (structural) determinants. In particular, I propose that the dominant physiological driver of skeletal extension is night-time hypoxia, which is exacerbated by the respiratory oxygen demands of the coral's algal symbionts (= zooxanthellae). The model thus provides a new narrative to explain the high growth rate of symbiotic corals, by equating skeletal deposition with the "work-rate" of the coral host needed to maintain a stable and beneficial symbiosis. In this way, coral skeletons are interpreted as a continuous (long-run) recording unit of the stability and functioning of the coral-algae endosymbiosis. After providing supportive evidence for the model across multiple scales of observation, I use coral core data from the Great Barrier Reef (Australia) to highlight the disturbed nature of the symbiosis in recent decades, but suggest that its onset is consistent with a trajectory that has been followed since at least the start of the 1900s. In concluding, I outline how the proposed capacity of cnidarians (which includes modern reef corals) to overcome the metabolic limitation of hypoxia via skeletogenesis also provides a new hypothesis to explain the sudden appearance in the fossil record of calcified skeletons at the Precambrian-Cambrian transition - and the ensuing rapid appearance of most major animal phyla.

  16. A new conceptual model of coral biomineralisation: hypoxia as the physiological driver of skeletal extension

    Directory of Open Access Journals (Sweden)

    S. Wooldridge

    2013-05-01

    Full Text Available That corals skeletons are built of aragonite crystals with taxonomy-linked ultrastructure has been well understood since the 19th century. Yet, the way by which corals control this crystallization process remains an unsolved question. Here, I outline a new conceptual model of coral biomineralisation that endeavours to relate known skeletal features with homeostatic functions beyond traditional growth (structural determinants. In particular, I propose that the dominant physiological driver of skeletal extension is night-time hypoxia, which is exacerbated by the respiratory oxygen demands of the coral's algal symbionts (= zooxanthellae. The model thus provides a new narrative to explain the high growth rate of symbiotic corals, by equating skeletal deposition with the "work-rate" of the coral host needed to maintain a stable and beneficial symbiosis. In this way, coral skeletons are interpreted as a continuous (long-run recording unit of the stability and functioning of the coral–algae endosymbiosis. After providing supportive evidence for the model across multiple scales of observation, I use coral core data from the Great Barrier Reef (Australia to highlight the disturbed nature of the symbiosis in recent decades, but suggest that its onset is consistent with a trajectory that has been followed since at least the start of the 1900s. In concluding, I outline how the proposed capacity of cnidarians (which includes modern reef corals to overcome the metabolic limitation of hypoxia via skeletogenesis also provides a new hypothesis to explain the sudden appearance in the fossil record of calcified skeletons at the Precambrian–Cambrian transition – and the ensuing rapid appearance of most major animal phyla.

  17. A Human Pluripotent Stem Cell Model of Facioscapulohumeral Muscular Dystrophy-Affected Skeletal Muscles.

    Science.gov (United States)

    Caron, Leslie; Kher, Devaki; Lee, Kian Leong; McKernan, Robert; Dumevska, Biljana; Hidalgo, Alejandro; Li, Jia; Yang, Henry; Main, Heather; Ferri, Giulia; Petek, Lisa M; Poellinger, Lorenz; Miller, Daniel G; Gabellini, Davide; Schmidt, Uli

    2016-09-01

    : Facioscapulohumeral muscular dystrophy (FSHD) represents a major unmet clinical need arising from the progressive weakness and atrophy of skeletal muscles. The dearth of adequate experimental models has severely hampered our understanding of the disease. To date, no treatment is available for FSHD. Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies. We developed a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation. Here we show that SkMCs derived from FSHD1-affected hESC lines exclusively express the FSHD pathogenic marker double homeobox 4 and exhibit some of the defects reported in FSHD. FSHD1 myotubes are thinner when compared with unaffected and Becker muscular dystrophy myotubes, and differentially regulate genes involved in cell cycle control, oxidative stress response, and cell adhesion. This cellular model will be a powerful tool for studying FSHD and will ultimately assist in the development of effective treatments for muscular dystrophies. This work describes an efficient and highly scalable monolayer system to differentiate human pluripotent stem cells (hPSCs) into skeletal muscle cells (SkMCs) and demonstrates disease-specific phenotypes in SkMCs derived from both embryonic and induced hPSCs affected with facioscapulohumeral muscular dystrophy. This study represents the first human stem cell-based cellular model for a muscular dystrophy that is suitable for high-throughput screening and drug development. ©AlphaMed Press.

  18. FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration

    Science.gov (United States)

    Castiglioni, Alessandra; Basso, Veronica; Vezzoli, Michela; Monno, Antonella; Almada, Albert E.; Mondino, Anna; Wagers, Amy J.; Manfredi, Angelo A.; Rovere-Querini, Patrizia

    2015-01-01

    Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue. PMID:26039259

  19. Nonlinear Rheology in a Model Biological Tissue

    Science.gov (United States)

    Matoz-Fernandez, D. A.; Agoritsas, Elisabeth; Barrat, Jean-Louis; Bertin, Eric; Martens, Kirsten

    2017-04-01

    The rheological response of dense active matter is a topic of fundamental importance for many processes in nature such as the mechanics of biological tissues. One prominent way to probe mechanical properties of tissues is to study their response to externally applied forces. Using a particle-based model featuring random apoptosis and environment-dependent division rates, we evidence a crossover from linear flow to a shear-thinning regime with an increasing shear rate. To rationalize this nonlinear flow we derive a theoretical mean-field scenario that accounts for the interplay of mechanical and active noise in local stresses. These noises are, respectively, generated by the elastic response of the cell matrix to cell rearrangements and by the internal activity.

  20. Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia

    Science.gov (United States)

    Kim, Kyoung Min; Jang, Hak Chul; Lim, Soo

    2016-01-01

    Aging processes are inevitably accompanied by structural and functional changes in vital organs. Skeletal muscle, which accounts for 40% of total body weight, deteriorates quantitatively and qualitatively with aging. Skeletal muscle is known to play diverse crucial physical and metabolic roles in humans. Sarcopenia is a condition characterized by significant loss of muscle mass and strength. It is related to subsequent frailty and instability in the elderly population. Because muscle tissue is involved in multiple functions, sarcopenia is closely related to various adverse health outcomes. Along with increasing recognition of the clinical importance of sarcopenia, several international study groups have recently released their consensus on the definition and diagnosis of sarcopenia. In practical terms, various skeletal muscle mass indices have been suggested for assessing sarcopenia: appendicular skeletal muscle mass adjusted for height squared, weight, or body mass index. A different prevalence and different clinical implications of sarcopenia are highlighted by each definition. The discordances among these indices have emerged as an issue in defining sarcopenia, and a unifying definition for sarcopenia has not yet been attained. This review aims to compare these three operational definitions and to introduce an optimal skeletal muscle mass index that reflects the clinical implications of sarcopenia from a metabolic perspective. PMID:27334763

  1. Absorption and scattering coefficient dependence of laser-Doppler flowmetry models for large tissue volumes

    International Nuclear Information System (INIS)

    Binzoni, T; Leung, T S; Ruefenacht, D; Delpy, D T

    2006-01-01

    Based on quasi-elastic scattering theory (and random walk on a lattice approach), a model of laser-Doppler flowmetry (LDF) has been derived which can be applied to measurements in large tissue volumes (e.g. when the interoptode distance is >30 mm). The model holds for a semi-infinite medium and takes into account the transport-corrected scattering coefficient and the absorption coefficient of the tissue, and the scattering coefficient of the red blood cells. The model holds for anisotropic scattering and for multiple scattering of the photons by the moving scatterers of finite size. In particular, it has also been possible to take into account the simultaneous presence of both Brownian and pure translational movements. An analytical and simplified version of the model has also been derived and its validity investigated, for the case of measurements in human skeletal muscle tissue. It is shown that at large optode spacing it is possible to use the simplified model, taking into account only a 'mean' light pathlength, to predict the blood flow related parameters. It is also demonstrated that the 'classical' blood volume parameter, derived from LDF instruments, may not represent the actual blood volume variations when the investigated tissue volume is large. The simplified model does not need knowledge of the tissue optical parameters and thus should allow the development of very simple and cost-effective LDF hardware

  2. Effects of Human Mesenchymal Stem Cells Isolated from Wharton's Jelly of the Umbilical Cord and Conditioned Media on Skeletal Muscle Regeneration Using a Myectomy Model.

    Science.gov (United States)

    Pereira, T; Armada-da Silva, P A S; Amorim, I; Rêma, A; Caseiro, A R; Gärtner, A; Rodrigues, M; Lopes, M A; Bártolo, P J; Santos, J D; Luís, A L; Maurício, A C

    2014-01-01

    Skeletal muscle has good regenerative capacity, but the extent of muscle injury and the developed fibrosis might prevent complete regeneration. The in vivo application of human mesenchymal stem cells (HMSCs) of the umbilical cord and the conditioned media (CM) where the HMSCs were cultured and expanded, associated with different vehicles to induce muscle regeneration, was evaluated in a rat myectomy model. Two commercially available vehicles and a spherical hydrogel developed by our research group were used. The treated groups obtained interesting results in terms of muscle regeneration, both in the histological and in the functional assessments. A less evident scar tissue, demonstrated by collagen type I quantification, was present in the muscles treated with HMSCs or their CM. In terms of the histological evaluation performed by ISO 10993-6 scoring, it was observed that HMSCs apparently have a long-term negative effect, since the groups treated with CM presented better scores. CM could be considered an alternative to the in vivo transplantation of these cells, as it can benefit from the local tissue response to secreted molecules with similar results in terms of muscular regeneration. Searching for an optimal vehicle might be the key point in the future of skeletal muscle tissue engineering.

  3. Archform comparisons between skeletal class II and III malocclusions.

    Directory of Open Access Journals (Sweden)

    Wei Zou

    Full Text Available The purpose of this cross-sectional research was to explore the relationship of the mandibular dental and basal bone archforms between severe Skeletal Class II (SC2 and Skeletal Class III (SC3 malocclusions. We also compared intercanine and intermolar widths in these two malocclusion types. Thirty-three virtual pretreatment mandibular models (Skeletal Class III group and Thirty-five Skeletal Class II group pretreatment models were created with a laser scanning system. FA (the midpoint of the facial axis of the clinical crownand WALA points (the most prominent point on the soft-tissue ridgewere employed to produce dental and basal bone archforms, respectively. Gained scatter diagrams of the samples were processed by nonlinear regression analysis via SPSS 17.0. The mandibular dental and basal bone intercanine and intermolar widths were significantly greater in the Skeletal Class III group compared to the Skeletal Class II group. In both groups, a moderate correlation existed between dental and basal bone arch widths in the canine region, and a high correlation existed between dental and basal bone arch widths in the molar region. The coefficient of correlation of the Skeletal Class III group was greater than the Skeletal Class II group. Fourth degree, even order power functions were used as best-fit functions to fit the scatter plots. The radius of curvature was larger in Skeletal Class III malocclusions compared to Skeletal Class II malocclusions (rWALA3>rWALA2>rFA3>rFA2. In conclusion, mandibular dental and basal intercanine and intermolar widths were significantly different between the two groups. Compared with Skeletal Class II subjects, the mandibular archform was more flat for Skeletal Class III subjects.

  4. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

    , of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle......Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence...

  5. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

    2003-01-01

    OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment...... mass ex vivo.RESULTS: Most (90%) of the rats survived the study period (8 months); six rats died from bowel obstruction at the level of the entero-anastomosis and four had to be killed because of persistent severe diarrhoea. Vital intestinal mucosa was found in all augmented bladders. There were...... no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P

  6. Tools for assessing mitochondrial dynamics in mouse tissues and neurodegenerative models

    Science.gov (United States)

    Pham, Anh H.

    Mitochondria are dynamic organelles that undergo membrane fusion and fission and transport. The dynamic properties of mitochondria are important for regulating mitochondrial function. Defects in mitochondrial dynamics are linked neurodegenerative diseases and affect the development of many tissues. To investigate the role of mitochondrial dynamics in diseases, versatile tools are needed to explore the physiology of these dynamic organelles in multiple tissues. Current tools for monitoring mitochondrial dynamics have been limited to studies in cell culture, which may be inadequate model systems for exploring the network of tissues. Here, we have generated mouse models for monitoring mitochondrial dynamics in a broad spectrum of tissues and cell types. The Photo-Activatable Mitochondrial (PhAM floxed) line enables Cre-inducible expression of a mitochondrial targeted photoconvertible protein, Dendra2 (mito-Dendra2). In the PhAMexcised line, mito-Dendra2 is ubiquitously expressed to facilitate broad analysis of mitochondria at various developmental processes. We have utilized these models to study mitochondrial dynamics in the nigrostriatal circuit of Parkinson's disease (PD) and in the development of skeletal muscles. Increasing evidences implicate aberrant regulation of mitochondrial fusion and fission in models of PD. To assess the function of mitochondrial dynamics in the nigrostriatal circuit, we utilized transgenic techniques to abrogate mitochondrial fusion. We show that deletion of the Mfn2 leads to the degeneration of dopaminergic neurons and Parkinson's-like features in mice. To elucidate the dynamic properties of mitochondria during muscle development, we established a platform for examining mitochondrial compartmentalization in skeletal muscles. This model system may yield clues to the role of mitochondrial dynamics in mitochondrial myopathies.

  7. Systemic Administration of Carbon Monoxide-Releasing Molecule-3 Protects the Skeletal Muscle in Porcine Model of Compartment Syndrome.

    Science.gov (United States)

    Bihari, Aurelia; Cepinskas, Gediminas; Sanders, David; Lawendy, Abdel-Rahman

    2018-05-01

    Acute limb compartment syndrome, a complication of musculoskeletal trauma, results in muscle necrosis and cell death. Carbon monoxide, liberated from the carbon monoxide-releasing molecule-3, has been shown protective in a rat model of compartment syndrome. The purpose of this study was to test the effect of carbon monoxide-releasing molecule-3 in a preclinical large animal model of compartment syndrome, with the ultimate goal of developing a pharmacologic adjunct treatment for compartment syndrome. Animal research study. Basic research laboratory in a hospital setting. Male Yorkshire-Landrace pigs (50-60 kg). Pigs underwent 6 hours of intracompartmental pressure elevation by infusing fluid into the anterior compartment of the right hind limb. Carbon monoxide-releasing molecule-3 was administered systemically (2 mg/kg, IV) at fasciotomy, followed by 3-hour reperfusion. Muscle perfusion, inflammation, injury, and apoptosis were assessed in the skeletal muscle. Systemic leukocyte activation was assessed during compartment syndrome and reperfusion. Elevation of hind limb intracompartmental pressure resulted in significant microvascular perfusion deficits (44% ± 1% continuously perfused capillaries in compartment syndrome vs 76% ± 4% in sham; p molecule-3 at fasciotomy increased the number of continuously perfused capillaries (68% ± 3%; p molecule-3 at fasciotomy offered protection against compartment syndrome-induced microvascular perfusion deficit, tissue injury, and systemic leukocyte activation. The data suggest the potential therapeutic application of carbon monoxide-releasing molecule-3 to patients at risk of developing compartment syndrome.

  8. Animal models for bone tissue engineering and modelling disease

    Science.gov (United States)

    Griffin, Michelle

    2018-01-01

    ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

  9. Transcriptome analysis of skeletal muscle tissue to identify genes involved in pre-slaughter stress response in pigs

    Directory of Open Access Journals (Sweden)

    Vincenzo Russo

    2010-01-01

    Full Text Available The knowledge of genes and molecular processes controlling stress reactions and involved in the genetic system determining resistance to stress in pigs could be important for the improvement of meat quality. This research aimed to compare the expression profiles of skeletal muscle between physically stressed and not stressed pigs of different breeds immediately before slaughter. DNA microarray analysis showed that different functional categories of genes are up-regulated in stressed compared to not stressed pigs and relevant differences among breeds were found.

  10. Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues

    Directory of Open Access Journals (Sweden)

    Jenny Chun-Yee Ng

    2015-10-01

    Full Text Available Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA or coral tumors are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch’s postulates in efforts to understand the etiology and progression of SGA.

  11. Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model

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    Dinani Matoso Fialho de Oliveira Armstrong

    2013-04-01

    Full Text Available PURPOSE: To investigate the effect of sildenafil citrate (SC on skeletal muscle ischemia-reperfusion (IR injury in rats. METHODS: Adult male Wistar rats were randomized into three groups: vehicle-treated control (CTG, sildenafil citrate-treated (SCG, and sham group (SG. CTG and SCG had femoral artery occluded for 6 hours. Saline or 1 mg/kg of SC was given 5.5 hours after occlusion. SG had a similar procedure without artery occlusion. Soleus muscle samples were acquired 4 or 24h after the reperfusion. Immunohistochemistry caspase-3 analysis was used to estimate apoptosis using the apoptotic ratio (computed as positive/negative cells. Wilcoxon rank-sum or Kruskal-Wallis tests were used to assess differences among groups. RESULTS: Eighteen animals were included in the 4h reperfusion groups and 21 animals in the 24h reperfusion groups. The mean apoptotic ratio was 0.18±0.1 for the total cohort; 0.14±0.06 for the 4h reperfusion groups and 0.19±0.08 for the 24h groups (p<0.05. The SCG had lower caspase-3 ratio compared to the control groups at the 24h reperfusion time point (p<0.05. CONCLUSION: Sildenafil citrate administration after the onset of the ischemic injury reduces IR-induced cellular damage in skeletal muscle in this rat hindlimb ischemia model.

  12. Restoring facial shape in face lifting: the role of skeletal support in facial analysis and midface soft-tissue repositioning.

    Science.gov (United States)

    Stuzin, James M

    2007-01-01

    Aesthetic analysis in facial rejuvenation has traditionally been subordinate to technical solutions. While concerns regarding correction of facial laxity, a reduction in the depth of the nasolabial fold, and improvement of both the jowl and the jawline are worthy goals in rhytidectomy, the aesthetic concept of restoring facial shape to a more youthful appearance is equally important. Restoring facial shape in face lifting requires an understanding of how the face ages and then the formulation of a treatment plan that is individualized for the patient. Re-establishment of facial contour is significantly influenced by the re-elevation of descended facial fat through superficial musculoaponeurotic system manipulation; it can be approached through a variety of technical solutions. Underlying skeletal support affects not only the appearance of the face in youth but also how the face ages and influences the operative plan in terms of the requirements for fat repositioning. Formulating a treatment plan that is patient specific and based on the artistic goals as influenced by skeletal support is the key element for consistency in restoring facial shape in face lifting.

  13. 3D Bioprinting of Tissue/Organ Models.

    Science.gov (United States)

    Pati, Falguni; Gantelius, Jesper; Svahn, Helene Andersson

    2016-04-04

    In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Terrorist attacks in the largest metropolitan city of Pakistan: Profile of soft tissue and skeletal injuries from a single trauma center.

    Science.gov (United States)

    Khan, Muhammad Shahid; Waheed, Shahan; Ali, Arif; Mumtaz, Narjis; Feroze, Asher; Noordin, Shahryar

    2015-01-01

    Pakistan has been hugely struck with massive bomb explosions (car and suicide bombs) resulting in multiple casualties in the past few years. The aim of this study is to present the patterns of skeletal and soft tissue injuries and to review the outcome of the victims who presented to our hospital. This is a retrospective chart review from January 2008 to December 2012. The medical record numbers of patients were obtained from the hospital Health Information and Management Sciences (HIMS) as per the ICD-9 coding. During the study period, more than 100 suicide and implanted bomb blast attacks took place in the public proceedings, government offices, residential areas and other places of the city. Altogether 262 patients were enrolled in the study. The mean age of the patients was 31±14 years. The shrapnel inflicted wounds were present on to the upper limb in 24 patients and the lower limb in 50. Long bone fractures were the most common skeletal injuries. The fractures were complicated by penetrating fragments and nails which result in post operative infections and prolonged hospital stay.

  15. Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity

    Directory of Open Access Journals (Sweden)

    William Dott

    2014-01-01

    Full Text Available Mitochondrial toxicity is increasingly being implicated as a contributing factor to many xenobiotic-induced organ toxicities, including skeletal muscle toxicity. This has necessitated the need for predictive in vitro models that are able to sensitively detect mitochondrial toxicity of chemical entities early in the research and development process. One such cell model involves substituting galactose for glucose in the culture media. Since cells cultured in galactose are unable to generate sufficient ATP from glycolysis they are forced to rely on mitochondrial oxidative phosphorylation for ATP generation and consequently are more sensitive to mitochondrial perturbation than cells grown in glucose. The aim of this study was to characterise cellular growth, bioenergetics and mitochondrial toxicity of the L6 rat skeletal muscle cell line cultured in either high glucose or galactose media. L6 myoblasts proliferated more slowly when cultured in galactose media, although they maintained similar levels of ATP. Galactose cultured L6 cells were significantly more sensitive to classical mitochondrial toxicants than glucose-cultured cells, confirming the cells had adapted to galactose media. Analysis of bioenergetic function with the XF Seahorse extracellular flux analyser demonstrated that oxygen consumption rate (OCR was significantly increased whereas extracellular acidification rate (ECAR, a measure of glycolysis, was decreased in cells grown in galactose. Mitochondria operated closer to state 3 respiration and had a lower mitochondrial membrane potential and basal mitochondrial O2·– level compared to cells in the glucose model. An antimycin A (AA dose response revealed that there was no difference in the sensitivity of OCR to AA inhibition between glucose and galactose cells. Importantly, cells in glucose were able to up-regulate glycolysis, while galactose cells were not. These results confirm that L6 cells are able to adapt to growth in a

  16. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...... models then use the directions of greatest diffusion as estimates of white matter fibre orientation. Several fibre tracking algorithms have emerged in the last few years that provide reproducible visualizations of three-dimensional fibre bundles. One class of these algorithms is probabilistic...... the possibility of using high-field experimental MR scanners and long scanning times, thereby significantly improving the signal-to-noise ratio (SNR) and anatomical resolution. Moreover, many of the degrading effects observed in vivo, such as physiological noise, are no longer present. However, the post mortem...

  17. Skeletal Stem Cells: Origins, Functions and Uncertainties.

    Science.gov (United States)

    Mohamed, Fatma F; Franceschi, Renny T

    2017-12-01

    The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

  18. A tissue in the tissue: models of microvascular plasticity

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Hornbech, Morten Sonne; Holstein-Rathlou, Niels-Henrik

    2009-01-01

    network. The pronounced plasticity and the inherently complex nature of vascular networks have spurred an enduring interest in mathematical modeling of the microcirculation. This has been advanced by the continuous increase in computing power over recent decades enabling simulation of increasingly...

  19. Autosomal dominant Marfan-like connective-tissue disorder with aortic dilation and skeletal anomaslies not linked to the Fibrillin genes

    Energy Technology Data Exchange (ETDEWEB)

    Boileau, C.; Coulon, M.; Alexandre, J.-A.; Junien, C. (Laboratorie Central de Biochimie et de Genetique Moleculaire (France)); Jondeau, G.; Delorme, G.; Dubourg, O.; Bourdarias, J.-P. (CHU Ambroise Pare, Boulogne (France)); Babron, M.-C.; Bonaieti-Pellie, C. (INSERM, Chateau de Longchamp, Paris (France)); Sakai, L. (Shriners' Hospital for Crippled Children, Portland, OR (United States)); Melki, J. (Hopital Necker-Enfants Malades, Paris (France))

    1993-07-01

    The authors describe a large family with a connective-tissue disorder that exhibits some of the skeletal and cardiovascular features seen in Marfan syndrome. However, none of the 19 affected individuals displayed ocular abnormalities and therefore did not comply with recognized criteria for this disease. These patients could alternatively be diagnosed as MASS (mitral valve, aorta, skeleton, and skin) phenotype patients or represent a distinct clinical entity, i.e., a new autosomal dominant connective-tissue disorder. The fibrillin genes located on chromosomes 15 and 5 are clearly involved in the classic form of Marfan syndrome and a clinically related disorder (congenital contractural arachnodactyly), respectively. To test whether one of these genes was also implicated in this French family, the authors performed genetic analyses. Blood samples were obtained for 56 family members, and four polymorphic fibrillin gene markers, located on chromosomes 15 (Fib15) and 5 (Fib5), respectively, were tested. Linkage between the disease allele and the markers of these two genes was excluded with lod scores of [minus]11.39 (for Fib15) and [minus]13.34 (for Fib5), at 0 = .001, indicating that the mutation is at a different locus. This phenotype thus represents a new connective-tissue disorder, overlapping but different from classic Marfan syndrome. 33 refs., 1 fig. 2 tabs.

  20. Virtual skeletal complex model- and landmark-guided orthognathic surgery system.

    Science.gov (United States)

    Lee, Sang-Jeong; Woo, Sang-Yoon; Huh, Kyung-Hoe; Lee, Sam-Sun; Heo, Min-Suk; Choi, Soon-Chul; Han, Jeong Joon; Yang, Hoon Joo; Hwang, Soon Jung; Yi, Won-Jin

    2016-05-01

    In this study, correction of the maxillofacial deformities was performed by repositioning bone segments to an appropriate location according to the preoperative planning in orthognathic surgery. The surgery was planned using the patient's virtual skeletal models fused with optically scanned three-dimensional dentition. The virtual maxillomandibular complex (MMC) model of the patient's final occlusal relationship was generated by fusion of the maxillary and mandibular models with scanned occlusion. The final position of the MMC was simulated preoperatively by planning and was used as a goal model for guidance. During surgery, the intraoperative registration was finished immediately using only software processing. For accurate repositioning, the intraoperative MMC model was visualized on the monitor with respect to the simulated MMC model, and the intraoperative positions of multiple landmarks were also visualized on the MMC surface model. The deviation errors between the intraoperative and the final positions of each landmark were visualized quantitatively. As a result, the surgeon could easily recognize the three-dimensional deviation of the intraoperative MMC state from the final goal model without manually applying a pointing tool, and could also quickly determine the amount and direction of further MMC movements needed to reach the goal position. The surgeon could also perform various osteotomies and remove bone interference conveniently, as the maxillary tracking tool could be separated from the MMC. The root mean square (RMS) difference between the preoperative planning and the intraoperative guidance was 1.16 ± 0.34 mm immediately after repositioning. After surgery, the RMS differences between the planning and the postoperative computed tomographic model were 1.31 ± 0.28 mm and 1.74 ± 0.73 mm for the maxillary and mandibular landmarks, respectively. Our method provides accurate and flexible guidance for bimaxillary orthognathic surgery based on

  1. 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...

  2. Bayesian models and meta analysis for multiple tissue gene expression data following corticosteroid administration

    Directory of Open Access Journals (Sweden)

    Kelemen Arpad

    2008-08-01

    Full Text Available Abstract Background This paper addresses key biological problems and statistical issues in the analysis of large gene expression data sets that describe systemic temporal response cascades to therapeutic doses in multiple tissues such as liver, skeletal muscle, and kidney from the same animals. Affymetrix time course gene expression data U34A are obtained from three different tissues including kidney, liver and muscle. Our goal is not only to find the concordance of gene in different tissues, identify the common differentially expressed genes over time and also examine the reproducibility of the findings by integrating the results through meta analysis from multiple tissues in order to gain a significant increase in the power of detecting differentially expressed genes over time and to find the differential differences of three tissues responding to the drug. Results and conclusion Bayesian categorical model for estimating the proportion of the 'call' are used for pre-screening genes. Hierarchical Bayesian Mixture Model is further developed for the identifications of differentially expressed genes across time and dynamic clusters. Deviance information criterion is applied to determine the number of components for model comparisons and selections. Bayesian mixture model produces the gene-specific posterior probability of differential/non-differential expression and the 95% credible interval, which is the basis for our further Bayesian meta-inference. Meta-analysis is performed in order to identify commonly expressed genes from multiple tissues that may serve as ideal targets for novel treatment strategies and to integrate the results across separate studies. We have found the common expressed genes in the three tissues. However, the up/down/no regulations of these common genes are different at different time points. Moreover, the most differentially expressed genes were found in the liver, then in kidney, and then in muscle.

  3. An electromechanical based deformable model for soft tissue simulation.

    Science.gov (United States)

    Zhong, Yongmin; Shirinzadeh, Bijan; Smith, Julian; Gu, Chengfan

    2009-11-01

    Soft tissue deformation is of great importance to surgery simulation. Although a significant amount of research efforts have been dedicated to simulating the behaviours of soft tissues, modelling of soft tissue deformation is still a challenging problem. This paper presents a new deformable model for simulation of soft tissue deformation from the electromechanical viewpoint of soft tissues. Soft tissue deformation is formulated as a reaction-diffusion process coupled with a mechanical load. The mechanical load applied to a soft tissue to cause a deformation is incorporated into the reaction-diffusion system, and consequently distributed among mass points of the soft tissue. Reaction-diffusion of mechanical load and non-rigid mechanics of motion are combined to govern the simulation dynamics of soft tissue deformation. An improved reaction-diffusion model is developed to describe the distribution of the mechanical load in soft tissues. A three-layer artificial cellular neural network is constructed to solve the reaction-diffusion model for real-time simulation of soft tissue deformation. A gradient based method is established to derive internal forces from the distribution of the mechanical load. Integration with a haptic device has also been achieved to simulate soft tissue deformation with haptic feedback. The proposed methodology does not only predict the typical behaviours of living tissues, but it also accepts both local and large-range deformations. It also accommodates isotropic, anisotropic and inhomogeneous deformations by simple modification of diffusion coefficients.

  4. The role of tissue oxygen tension in the control of local blood flow in the microcirculation of skeletal muscles

    DEFF Research Database (Denmark)

    Ngo, Thuc Anh

    2010-01-01

    In the microcirculation blood flow is highly regulated dependent on the metabolic activity of the tissues. Among several mechanisms, mechanisms involved in the coupling of changes in tissue oxygen tension due to changes in the metabolic activity of the tissue play an important role. In the systemic...... (inhibitor of KATP channels) in the superfusate abolished both vasodilatation and constriction to low and high oxygen superfusate, indicating that KATP channels are involved in both hypoxic vasodilatation and hyperoxic vasoconstriction. Red blood cells (RBCs) have been proposed to release ATP and...... as in the intact blood-perfused arteriole. This indicates that RBCs are not essential for hypoxic vasodilatation. In addition several potential pathways were evaluated. Application of DPCPX (inhibitor of adenosine A1 and A2 receptors) and L-NAME (inhibitor of NO-synthase) did not affect vasomotor responses to low...

  5. Insulin Sensitivity in Adipose and Skeletal Muscle Tissue of Dairy Cows in Response to Dietary Energy Level and 2,4-Thiazolidinedione (TZD.

    Directory of Open Access Journals (Sweden)

    Afshin Hosseini

    Full Text Available The effects of dietary energy level and 2,4-thiazolidinedione (TZD injection on feed intake, body fatness, blood biomarkers and TZD concentrations, genes related to insulin sensitivity in adipose tissue (AT and skeletal muscle, and peroxisome proliferator-activated receptor gamma (PPARG protein in subcutaneous AT (SAT were evaluated in Holstein cows. Fourteen nonpregnant nonlactating cows were fed a control low-energy (CON, 1.30 Mcal/kg diet to meet 100% of estimated nutrient requirements for 3 weeks, after which half of the cows were assigned to a higher-energy diet (OVE, 1.60 Mcal/kg and half of the cows continued on CON for 6 weeks. All cows received an intravenous injection of TZD starting 2 weeks after initiation of dietary treatments and for an additional 2 weeks, which served as the washout period. Cows fed OVE had greater energy intake and body mass than CON, and TZD had no effect during the administration period. The OVE cows had greater TZD clearance rate than CON cows. The lower concentration of nonesterified fatty acids (NEFA and greater concentration of insulin in blood of OVE cows before TZD injection indicated positive energy balance and higher insulin sensitivity. Administration of TZD increased blood concentrations of glucose, insulin, and beta-hydroxybutyrate (BHBA at 2 to 4 weeks after diet initiation, while the concentration of NEFA and adiponectin (ADIPOQ remained unchanged during TZD. The TZD upregulated the mRNA expression of PPARG and its targets FASN and SREBF1 in SAT, but also SUMO1 and UBC9 which encode sumoylation proteins known to down-regulate PPARG expression and curtail adipogenesis. Therefore, a post-translational response to control PPARG gene expression in SAT could be a counteregulatory mechanism to restrain adipogenesis. The OVE cows had greater expression of the insulin sensitivity-related genes IRS1, SLC2A4, INSR, SCD, INSIG1, DGAT2, and ADIPOQ in SAT. In skeletal muscle, where PPARA and its targets

  6. Insulin Sensitivity in Adipose and Skeletal Muscle Tissue of Dairy Cows in Response to Dietary Energy Level and 2,4-Thiazolidinedione (TZD).

    Science.gov (United States)

    Hosseini, Afshin; Tariq, Muhammad Rizwan; Trindade da Rosa, Fernanda; Kesser, Julia; Iqbal, Zeeshan; Mora, Ofelia; Sauerwein, Helga; Drackley, James K; Trevisi, Erminio; Loor, Juan J

    2015-01-01

    The effects of dietary energy level and 2,4-thiazolidinedione (TZD) injection on feed intake, body fatness, blood biomarkers and TZD concentrations, genes related to insulin sensitivity in adipose tissue (AT) and skeletal muscle, and peroxisome proliferator-activated receptor gamma (PPARG) protein in subcutaneous AT (SAT) were evaluated in Holstein cows. Fourteen nonpregnant nonlactating cows were fed a control low-energy (CON, 1.30 Mcal/kg) diet to meet 100% of estimated nutrient requirements for 3 weeks, after which half of the cows were assigned to a higher-energy diet (OVE, 1.60 Mcal/kg) and half of the cows continued on CON for 6 weeks. All cows received an intravenous injection of TZD starting 2 weeks after initiation of dietary treatments and for an additional 2 weeks, which served as the washout period. Cows fed OVE had greater energy intake and body mass than CON, and TZD had no effect during the administration period. The OVE cows had greater TZD clearance rate than CON cows. The lower concentration of nonesterified fatty acids (NEFA) and greater concentration of insulin in blood of OVE cows before TZD injection indicated positive energy balance and higher insulin sensitivity. Administration of TZD increased blood concentrations of glucose, insulin, and beta-hydroxybutyrate (BHBA) at 2 to 4 weeks after diet initiation, while the concentration of NEFA and adiponectin (ADIPOQ) remained unchanged during TZD. The TZD upregulated the mRNA expression of PPARG and its targets FASN and SREBF1 in SAT, but also SUMO1 and UBC9 which encode sumoylation proteins known to down-regulate PPARG expression and curtail adipogenesis. Therefore, a post-translational response to control PPARG gene expression in SAT could be a counteregulatory mechanism to restrain adipogenesis. The OVE cows had greater expression of the insulin sensitivity-related genes IRS1, SLC2A4, INSR, SCD, INSIG1, DGAT2, and ADIPOQ in SAT. In skeletal muscle, where PPARA and its targets orchestrate

  7. Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: Lessons from mouse models.

    Science.gov (United States)

    Yakar, Shoshana; Isaksson, Olle

    2016-06-01

    The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone acquisition, while during aging their levels decline and associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous biological systems including rodent models and cell cultures. Both hormones act in an endocrine and autocrine/paracrine fashion and understanding their distinct and overlapping contributions to skeletal acquisition is still a matter of debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their cognate receptor, leading to activation of an array of genes that mediate cellular differentiation and function. Both hormones interact with other skeletal regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to facilitate skeletal growth and metabolism. In this review we summarized several rodent models of the GH/IGF-1 axis and described key experiments that shed new light on the regulation of skeletal growth by the GH/IGF-1 axis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Microarray analysis of gene expression by skeletal muscle of three mouse models of Kennedy disease/spinal bulbar muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Kaiguo Mo

    2010-09-01

    Full Text Available Emerging evidence implicates altered gene expression within skeletal muscle in the pathogenesis of Kennedy disease/spinal bulbar muscular atrophy (KD/SBMA. We therefore broadly characterized gene expression in skeletal muscle of three independently generated mouse models of this disease. The mouse models included a polyglutamine expanded (polyQ AR knock-in model (AR113Q, a polyQ AR transgenic model (AR97Q, and a transgenic mouse that overexpresses wild type AR solely in skeletal muscle (HSA-AR. HSA-AR mice were included because they substantially reproduce the KD/SBMA phenotype despite the absence of polyQ AR.We performed microarray analysis of lower hindlimb muscles taken from these three models relative to wild type controls using high density oligonucleotide arrays. All microarray comparisons were made with at least 3 animals in each condition, and only those genes having at least 2-fold difference and whose coefficient of variance was less than 100% were considered to be differentially expressed. When considered globally, there was a similar overlap in gene changes between the 3 models: 19% between HSA-AR and AR97Q, 21% between AR97Q and AR113Q, and 17% between HSA-AR and AR113Q, with 8% shared by all models. Several patterns of gene expression relevant to the disease process were observed. Notably, patterns of gene expression typical of loss of AR function were observed in all three models, as were alterations in genes involved in cell adhesion, energy balance, muscle atrophy and myogenesis. We additionally measured changes similar to those observed in skeletal muscle of a mouse model of Huntington's Disease, and to those common to muscle atrophy from diverse causes.By comparing patterns of gene expression in three independent models of KD/SBMA, we have been able to identify candidate genes that might mediate the core myogenic features of KD/SBMA.

  9. Computational Intelligence Based Data Fusion Algorithm for Dynamic sEMG and Skeletal Muscle Force Modelling

    Energy Technology Data Exchange (ETDEWEB)

    Chandrasekhar Potluri,; Madhavi Anugolu; Marco P. Schoen; D. Subbaram Naidu

    2013-08-01

    In this work, an array of three surface Electrography (sEMG) sensors are used to acquired muscle extension and contraction signals for 18 healthy test subjects. The skeletal muscle force is estimated using the acquired sEMG signals and a Non-linear Wiener Hammerstein model, relating the two signals in a dynamic fashion. The model is obtained from using System Identification (SI) algorithm. The obtained force models for each sensor are fused using a proposed fuzzy logic concept with the intent to improve the force estimation accuracy and resilience to sensor failure or misalignment. For the fuzzy logic inference system, the sEMG entropy, the relative error, and the correlation of the force signals are considered for defining the membership functions. The proposed fusion algorithm yields an average of 92.49% correlation between the actual force and the overall estimated force output. In addition, the proposed fusionbased approach is implemented on a test platform. Experiments indicate an improvement in finger/hand force estimation.

  10. A Convenient In Vivo Model Using Small Interfering RNA Silencing to Rapidly Assess Skeletal Gene Function.

    Directory of Open Access Journals (Sweden)

    Wen Zhang

    Full Text Available It is difficult to study bone in vitro because it contains various cell types that engage in cross-talk. Bone biologically links various organs, and it has thus become increasingly evident that skeletal physiology must be studied in an integrative manner in an intact animal. We developed a model using local intraosseous small interfering RNA (siRNA injection to rapidly assess the effects of a target gene on the local skeletal environment. In this model, 160-g male Sprague-Dawley rats were treated for 1-2 weeks. The left tibia received intraosseous injection of a parathyroid hormone 1 receptor (Pth1r or insulin-like growth factor 1 receptor (Igf-1r siRNA transfection complex loaded in poloxamer 407 hydrogel, and the right tibia received the same volume of control siRNA. All the tibias received an intraosseous injection of recombinant human parathyroid hormone (1-34 (rhPTH (1-34 or insulin-like growth factor-1 (IGF-1. Calcein green and alizarin red were injected 6 and 2 days before euthanasia, respectively. IGF-1R and PTH1R expression levels were detected via RT-PCR assays and immunohistochemistry. Bone mineral density (BMD, microstructure, mineral apposition rates (MARs, and strength were determined by dual-energy X-ray absorptiometry, micro-CT, histology and biomechanical tests. The RT-PCR and immunohistochemistry results revealed that IGF-1R and PTH1R expression levels were dramatically diminished in the siRNA-treated left tibias compared to the right tibias (both p<0.05. Using poloxamer 407 hydrogel as a controlled-release system prolonged the silencing effect of a single dose of siRNA; the mRNA expression levels of IGF-1R were lower at two weeks than at one week (p<0.01. The BMD, bone microstructure parameters, MAR and bone strength were significantly decreased in the left tibias compared to the right tibias (all p<0.05. This simple and convenient local intraosseous siRNA injection model achieved gene silencing with very small quantities of

  11. High-fat diet decreases energy expenditure and expression of genes controlling lipid metabolism, mitochondrial function and skeletal system development in the adipose tissue, along with increased expression of extracellular matrix remodelling- and inflammation-related genes.

    Science.gov (United States)

    Choi, Myung-Sook; Kim, Young-Je; Kwon, Eun-Young; Ryoo, Jae Young; Kim, Sang Ryong; Jung, Un Ju

    2015-03-28

    The aim of the present study was to identify the genes differentially expressed in the visceral adipose tissue in a well-characterised mouse model of high-fat diet (HFD)-induced obesity. Male C57BL/6J mice (n 20) were fed either HFD (189 % of energy from fat) or low-fat diet (LFD, 42 % of energy from fat) for 16 weeks. HFD-fed mice exhibited obesity, insulin resistance, dyslipidaemia and adipose collagen accumulation, along with higher levels of plasma leptin, resistin and plasminogen activator inhibitor type 1, although there were no significant differences in plasma cytokine levels. Energy intake was similar in the two diet groups owing to lower food intake in the HFD group; however, energy expenditure was also lower in the HFD group than in the LFD group. Microarray analysis revealed that genes related to lipolysis, fatty acid metabolism, mitochondrial energy transduction, oxidation-reduction, insulin sensitivity and skeletal system development were down-regulated in HFD-fed mice, and genes associated with extracellular matrix (ECM) components, ECM remodelling and inflammation were up-regulated. The top ten up- or down-regulated genes include Acsm3, mt-Nd6, Fam13a, Cyp2e1, Rgs1 and Gpnmb, whose roles in the deterioration of obesity-associated adipose tissue are poorly understood. In conclusion, the genes identified here provide new therapeutic opportunities for prevention and treatment of diet-induced obesity.

  12. Optical study of the skeletal muscle during exercise with a second-generation frequency-domain tissue oximeter

    Science.gov (United States)

    Franceschini, Maria-Angela; Wallace, Don J.; Barbieri, Beniamino B.; Fantini, Sergio; Mantulin, William W.; Pratesi, Simone; Donzelli, Gian Paolo; Gratton, Enrico

    1997-08-01

    We present a re-engineered frequency-domain tissue oximeter operating in the near-infrared spectral region. This instrument is based on the multi-distance measurement protocol, which we have implemented in our original design by multiplexing multiple light sources. The new instrument uses intensity modulated (110 MHz) laser diodes emitting at 750 and 840 nm. The laser diodes are coupled to glass optical fibers (600 micrometer core diameter). The average light intensity delivered to the tissue is about 3 mW. The multiplexing electronics are based on solid state switches that allow for acquisition times per point as short as tens of milliseconds. Our tests on phantoms and in vivo with the new oximeter have shown significant improvement in terms of stability, reliability, and reproducibility with respect to the original prototype. Furthermore, by using optical fibers we achieve a high versatility in the design of the measuring probe, permitting custom design for various tissue contours and different measurements. To verify the improved performance of the new oximeter, we have performed an in vivo test consisting of monitoring the hemoglobin saturation (Y) and concentration (THC) on the calf of 18 healthy volunteers during walking and running routines.

  13. Micromechanics and constitutive modeling of connective soft tissues.

    Science.gov (United States)

    Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

    2016-07-01

    In this paper, a micromechanical model for connective soft tissues based on the available histological evidences is developed. The proposed model constituents i.e. collagen fibers and ground matrix are considered as hyperelastic materials. The matrix material is assumed to be isotropic Neo-Hookean while the collagen fibers are considered to be transversely isotropic hyperelastic. In order to take into account the effects of tissue structure in lower scales on the macroscopic behavior of tissue, a strain energy density function (SEDF) is developed for collagen fibers based on tissue hierarchical structure. Macroscopic response and properties of tissue are obtained using the numerical homogenization method with the help of ABAQUS software. The periodic boundary conditions and the proposed constitutive models are implemented into ABAQUS using the DISP and the UMAT subroutines, respectively. The existence of the solution and stable material behavior of proposed constitutive model for collagen fibers are investigated based on the poly-convexity condition. Results of the presented micromechanics model for connective tissues are compared and validated with available experimental data. Effects of geometrical and material parameters variation at microscale on macroscopic mechanical behavior of tissues are investigated. The results show that decrease in collagen content of the connective tissues like the tendon due to diseases leads 20% more stretch than healthy tissue under the same load which can results in connective tissue malfunction and hypermobility in joints. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. New mouse model of skeletal muscle atrophy using spiral wire immobilization.

    Science.gov (United States)

    Onda, Akiko; Kono, Hajime; Jiao, Qibin; Akimoto, Takayuki; Miyamoto, Toshikazu; Sawada, Yasuhiro; Suzuki, Katsuhiko; Kusakari, Yoichiro; Minamisawa, Susumu; Fukubayashi, Toru

    2016-10-01

    Disuse-induced skeletal muscle atrophy is a serious concern; however, there is not an effective mouse model to elucidate the molecular mechanisms. We developed a noninvasive atrophy model in mice. After the ankle joints of mice were bandaged into a bilateral plantar flexed position, either bilateral or unilateral hindlimbs were immobilized by wrapping in bonsai steel wire. After 3, 5, or 10 days of immobilization of the hip, knee, and ankle, the weight of the soleus and plantaris muscles decreased significantly in both bilateral and unilateral immobilization. MAFbx/atrogin-1 and MuRF1 mRNA was found to have significantly increased in both muscles, consistent with disuse-induced atrophy. Notably, the procedure did not result in either edema or necrosis in the fixed hindlimbs. This method allows repeated, direct access to the immobilized muscle, making it a useful procedure for concurrent application and assessment of various therapeutic interventions. Muscle Nerve 54: 788-791, 2016. © 2016 Wiley Periodicals, Inc.

  15. Soft Tissue Biomechanical Modeling for Computer Assisted Surgery

    CERN Document Server

    2012-01-01

      This volume focuses on the biomechanical modeling of biological tissues in the context of Computer Assisted Surgery (CAS). More specifically, deformable soft tissues are addressed since they are the subject of the most recent developments in this field. The pioneering works on this CAS topic date from the 1980's, with applications in orthopaedics and biomechanical models of bones. More recently, however, biomechanical models of soft tissues have been proposed since most of the human body is made of soft organs that can be deformed by the surgical gesture. Such models are much more complicated to handle since the tissues can be subject to large deformations (non-linear geometrical framework) as well as complex stress/strain relationships (non-linear mechanical framework). Part 1 of the volume presents biomechanical models that have been developed in a CAS context and used during surgery. This is particularly new since most of the soft tissues models already proposed concern Computer Assisted Planning, with ...

  16. Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q10 Deficiency.

    Science.gov (United States)

    Romero-Moya, Damià; Santos-Ocaña, Carlos; Castaño, Julio; Garrabou, Gloria; Rodríguez-Gómez, José A; Ruiz-Bonilla, Vanesa; Bueno, Clara; González-Rodríguez, Patricia; Giorgetti, Alessandra; Perdiguero, Eusebio; Prieto, Cristina; Moren-Nuñez, Constanza; Fernández-Ayala, Daniel J; Victoria Cascajo, Maria; Velasco, Iván; Canals, Josep Maria; Montero, Raquel; Yubero, Delia; Jou, Cristina; López-Barneo, José; Cardellach, Francesc; Muñoz-Cánoves, Pura; Artuch, Rafael; Navas, Plácido; Menendez, Pablo

    2017-07-01

    Coenzyme Q 10 (CoQ 10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ 10 biosynthesis (COQ genes) cause primary CoQ 10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c.483G > C (E161D)) in COQ4. The patient's fibroblasts showed a decrease in [CoQ 10 ], CoQ 10 biosynthesis, MRC activity affecting complexes I/II + III, and respiration defects. Bona fide induced pluripotent stem cell (iPSCs) lines carrying the COQ4 mutation (CQ4-iPSCs) were generated, characterized and genetically edited using the CRISPR-Cas9 system (CQ4 ed -iPSCs). Extensive differentiation and metabolic assays of control-iPSCs, CQ4-iPSCs and CQ4 ed -iPSCs demonstrated a genotype association, reproducing the disease phenotype. The COQ4 mutation in iPSC was associated with CoQ 10 deficiency, metabolic dysfunction, and respiration defects. iPSC differentiation into SkM was compromised, and the resulting SkM also displayed respiration defects. Remarkably, iPSC differentiation in dopaminergic or motor neurons was unaffected. This study offers an unprecedented iPSC model recapitulating CoQ 10 deficiency-associated functional and metabolic phenotypes caused by COQ4 mutation. Stem Cells 2017;35:1687-1703. © 2017 AlphaMed Press.

  17. Modeling the development of tissue engineered cartilage

    NARCIS (Netherlands)

    Sengers, B.G.

    2005-01-01

    The limited healing capacity of articular cartilage forms a major clinical problem. In general, current treatments of cartilage damage temporarily reliefs symptoms, but fail in the long term. Tissue engineering (TE) has been proposed as a more permanent repair strategy. Cartilage TE aims at

  18. Investigating human skeletal muscle physiology with unilateral exercise models: when one limb is more powerful than two.

    Science.gov (United States)

    MacInnis, Martin J; McGlory, Chris; Gibala, Martin J; Phillips, Stuart M

    2017-06-01

    Direct sampling of human skeletal muscle using the needle biopsy technique can facilitate insight into the biochemical and histological responses resulting from changes in exercise or feeding. However, the muscle biopsy procedure is invasive, and analyses are often expensive, which places pragmatic restraints on sample sizes. The unilateral exercise model can serve to increase statistical power and reduce the time and cost of a study. With this approach, 2 limbs of a participant are randomized to 1 of 2 treatments that can be applied almost concurrently or sequentially depending on the nature of the intervention. Similar to a typical repeated measures design, comparisons are made within participants, which increases statistical power by reducing the amount of between-person variability. A washout period is often unnecessary, reducing the time needed to complete the experiment and the influence of potential confounding variables such as habitual diet, activity, and sleep. Variations of the unilateral exercise model have been employed to investigate the influence of exercise, diet, and the interaction between the 2, on a wide range of variables including mitochondrial content, capillary density, and skeletal muscle hypertrophy. Like any model, unilateral exercise has some limitations: it cannot be used to study variables that potentially transfer across limbs, and it is generally limited to exercises that can be performed in pairs of treatments. Where appropriate, however, the unilateral exercise model can yield robust, well-controlled investigations of skeletal muscle responses to a wide range of interventions and conditions including exercise, dietary manipulation, and disuse or immobilization.

  19. From cells to tissue: A continuum model of epithelial mechanics

    Science.gov (United States)

    Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

    2017-08-01

    A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

  20. Omega-3 Fatty Acids and Skeletal Muscle Health

    Directory of Open Access Journals (Sweden)

    Stewart Jeromson

    2015-11-01

    Full Text Available Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

  1. Differences in three-dimensional soft tissue changes after upper, lower, or both jaw orthognathic surgery in skeletal class III patients.

    Science.gov (United States)

    Verdenik, M; Ihan Hren, N

    2014-11-01

    The decision is not always straightforward as to which orthognathic procedure is best for a good aesthetic result; three-dimensional imaging has brought new insight into this topic. The aim of this prospective study was to verify objectively whether postoperative changes occur within those regions not directly affected by surgical movements of the underlying jaw bones. The study included 83 young adults with skeletal class III deformities. They were classified into three groups according to the type of surgery: bilateral sagittal split osteotomy set-back of the mandible (BSSO), Le Fort I advancement of the maxilla, or a combination of both. Pre- and postoperative optical scans were registered as regional best-fits on the areas of the foreheads and both orbits. The shell to shell differences were measured and the average distances between the observed regions were calculated. As expected, changes were greatest in the regions where the underlying bones had been moved, but regardless of the operation performed, changes were found over the whole face. Changes in the nose, cheek, and upper lip regions in the BSSO group and in the lower lip and chin region in the Le Fort I group confirmed the concept of the facial soft tissue mask acting as one unit. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Topologically Micropatterned Collagen and Poly(ε-caprolactone) Struts Fabricated Using the Poly(vinyl alcohol) Fibrillation/Leaching Process To Develop Efficiently Engineered Skeletal Muscle Tissue.

    Science.gov (United States)

    Kim, Minseong; Kim, WonJin; Kim, GeunHyung

    2017-12-20

    Optimally designed three-dimensional (3D) biomedical scaffolds for skeletal muscle tissue regeneration pose significant research challenges. Currently, most studies on scaffolds focus on the two-dimensional (2D) surface structures that are patterned in the micro-/nanoscales with various repeating sizes and shapes to induce the alignment of myoblasts and myotube formation. The 2D patterned surface clearly provides effective analytical results of pattern size and shape of the myoblast alignment and differentiation. However, it is inconvenient in terms of the direct application for clinical usage due to the limited thickness and 3D shapeability. Hence, the present study suggests an innovative hydrogel or synthetic structure that consists of uniaxially surface-patterned cylindrical struts for skeleton muscle regeneration. The alignment of the pattern on the hydrogel (collagen) and poly(ε-caprolactone) struts was attained with the fibrillation of poly(vinyl alcohol) and the leaching process. Various cell culture results indicate that the C2C12 cells on the micropatterned collagen structure were fully aligned, and that a significantly high level of myotube formation was achieved when compared to the collagen structures that were not treated with the micropatterning process.

  3. The Ptch1DL mouse: a new model to study lambdoid craniosynostosis and basal cell nevus syndrome associated skeletal defects

    OpenAIRE

    Feng, Weiguo; Choi, Irene; Clouthier, David E.; Niswander, Lee; Williams, Trevor

    2013-01-01

    Mouse models provide valuable opportunities for probing the underlying pathology of human birth defects. Employing an ENU-based screen for recessive mutations affecting craniofacial anatomy we isolated a mouse strain, Dogface-like (DL), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture. Further analysis revealed skeletal defects related to the pathology of basal cell nevus syndrome (BCNS) including de...

  4. DIFFERENTIAL RESPONSE OF HEAT SHOCK PROTEINS TO UPHILL AND DOWNHILL EXERCISE IN HEART, SKELETAL MUSCLE, LUNG AND KIDNEY TISSUES

    Directory of Open Access Journals (Sweden)

    Pablo C. B. Lollo

    2013-09-01

    Full Text Available Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP, but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric and downhill (predominantly eccentric muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7% and downhill (-7% of inclination. At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK and lactate dehydrogenase (LDH were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal. When the contraction was concentric (uphill and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL-1 in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively. The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus

  5. A constitutive model of soft tissue: From nanoscale collagen to tissue continuum

    KAUST Repository

    Tang, Huang

    2009-04-08

    Soft collagenous tissue features many hierarchies of structure, starting from tropocollagen molecules that form fibrils, and proceeding to a bundle of fibrils that form fibers. Here we report the development of an atomistically informed continuum model of collagenous tissue. Results from full atomistic and molecular modeling are linked with a continuum theory of a fiber-reinforced composite, handshaking the fibril scale to the fiber and continuum scale in a hierarchical multi-scale simulation approach. Our model enables us to study the continuum-level response of the tissue as a function of cross-link density, making a link between nanoscale collagen features and material properties at larger tissue scales. The results illustrate a strong dependence of the continuum response as a function of nanoscopic structural features, providing evidence for the notion that the molecular basis for protein materials is important in defining their larger-scale mechanical properties. © 2009 Biomedical Engineering Society.

  6. Spatial distribution of "tissue-specific" antigens in the developing human heart and skeletal muscle. I. An immunohistochemical analysis of creatine kinase isoenzyme expression patterns

    NARCIS (Netherlands)

    Wessels, A.; Vermeulen, J. L.; Virágh, S.; Kálmán, F.; Morris, G. E.; Man, N. T.; Lamers, W. H.; Moorman, A. F.

    1990-01-01

    Using monoclonal antibodies against the M and B subunit isoforms of creatine kinase (CK) we have investigated their distribution in developing human skeletal and cardiac muscle immunohistochemically. It is demonstrated that in skeletal muscle, a switch from CK-B to CK-M takes place around the week 8

  7. Differential response of heat shock proteins to uphill and downhill exercise in heart, skeletal muscle, lung and kidney tissues.

    Science.gov (United States)

    Lollo, Pablo C B; Moura, Carolina S; Morato, Priscila N; Amaya-Farfan, Jaime

    2013-01-01

    Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP), but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric) and downhill (predominantly eccentric) muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7%) and downhill (-7% of inclination). At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK) and lactate dehydrogenase (LDH) were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal). When the contraction was concentric (uphill) and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL(-1)) in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively). The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus. Key PointsExercise can induce increases in HSP70 in

  8. 7-Tesla Magnetic Resonance Imaging Precisely and Noninvasively Reflects Inflammation and Remodeling of the Skeletal Muscle in a Mouse Model of Antisynthetase Syndrome

    Directory of Open Access Journals (Sweden)

    Clara Sciorati

    2014-01-01

    Full Text Available Inflammatory myopathies comprise heterogeneous disorders. Their etiopathogenesis is poorly understood, because of the paucity of informative experimental models and of approaches for the noninvasive study of inflamed tissues. Magnetic resonance imaging (MRI provides information about the state of the skeletal muscle that reflects various facets of inflammation and remodeling. This technique has been scarcely used in experimental models of inflammatory myopathies. We characterized the performance of MRI in a well-established mouse model of myositis and the antisynthetase syndrome, based on the immunization of wild-type mice with the amino-terminal fragment of histidyl-tRNA synthetase (HisRS. Over an eight-week period following myositis induction, MRI enabled precise identification of pathological events taking place in muscle tissue. Areas of edema and of active inflammation identified by histopathology paralleled muscle modifications detected noninvasively by MRI. Muscles changes were chronologically associated with the establishment of autoimmunity, as reflected by the development of anti-HisRS antibodies in the blood of immunized mice. MR imaging easily appreciated muscle damage and remodeling even if actual disruption of myofiber integrity (as assessed by serum concentrations of creatinine phosphokinase was limited. Thus, MR imaging represents an informative and noninvasive analytical tool for studying in vivo immune-mediated muscle involvement.

  9. 7-Tesla Magnetic Resonance Imaging Precisely and Noninvasively Reflects Inflammation and Remodeling of the Skeletal Muscle in a Mouse Model of Antisynthetase Syndrome

    Science.gov (United States)

    Sciorati, Clara; Esposito, Antonio; Campana, Lara; Canu, Tamara; Monno, Antonella; Palmisano, Anna; De Cobelli, Francesco; Del Maschio, Alessandro; Ascheman, Dana P.; Manfredi, Angelo A.; Rovere-Querini, Patrizia

    2014-01-01

    Inflammatory myopathies comprise heterogeneous disorders. Their etiopathogenesis is poorly understood, because of the paucity of informative experimental models and of approaches for the noninvasive study of inflamed tissues. Magnetic resonance imaging (MRI) provides information about the state of the skeletal muscle that reflects various facets of inflammation and remodeling. This technique has been scarcely used in experimental models of inflammatory myopathies. We characterized the performance of MRI in a well-established mouse model of myositis and the antisynthetase syndrome, based on the immunization of wild-type mice with the amino-terminal fragment of histidyl-tRNA synthetase (HisRS). Over an eight-week period following myositis induction, MRI enabled precise identification of pathological events taking place in muscle tissue. Areas of edema and of active inflammation identified by histopathology paralleled muscle modifications detected noninvasively by MRI. Muscles changes were chronologically associated with the establishment of autoimmunity, as reflected by the development of anti-HisRS antibodies in the blood of immunized mice. MR imaging easily appreciated muscle damage and remodeling even if actual disruption of myofiber integrity (as assessed by serum concentrations of creatinine phosphokinase) was limited. Thus, MR imaging represents an informative and noninvasive analytical tool for studying in vivo immune-mediated muscle involvement. PMID:24895622

  10. 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.

  11. Microstructure based hygromechanical modelling of deformation of fruit tissue

    Science.gov (United States)

    Abera, M. K.; Wang, Z.; Verboven, P.; Nicolai, B.

    2017-10-01

    Quality parameters such as firmness and susceptibility to mechanical damage are affected by the mechanical properties of fruit tissue. Fruit tissue is composed of turgid cells that keep cell walls under tension, and intercellular gas spaces where cell walls of neighboring cells have separated. How the structure and properties of these complex microstructures are affecting tissue mechanics is difficult to unravel experimentally. In this contribution, a modelling methodology is presented to calculate the deformation of apple fruit tissue affected by differences in structure and properties of cells and cell walls. The model can be used to perform compression experiments in silico using a hygromechanical model that computes the stress development and water loss during tissue deformation, much like in an actual compression test. The advantage of the model is that properties and structure can be changed to test the influence on the mechanical deformation process. The effect of microstructure, turgor pressure, cell membrane permeability, wall thickness and damping) on the compressibility of the tissue was simulated. Increasing the turgor pressure and thickness of the cell walls results in increased compression resistance of apple tissue increases, as do decreasing cell size and porosity. Geometric variability of the microstructure of tissues plays a major role, affecting results more than other model parameters. Different fruit cultivars were compared, and it was demonstrated, that microstructure variations within a cultivar are so large that interpretation of cultivar-specific effects is difficult.

  12. Deep Proteomics of Mouse Skeletal Muscle Enables Quantitation of Protein Isoforms, Metabolic Pathways, and Transcription Factors*

    Science.gov (United States)

    Deshmukh, Atul S.; Murgia, Marta; Nagaraj, Nagarjuna; Treebak, Jonas T.; Cox, Jürgen; Mann, Matthias

    2015-01-01

    Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging because of highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art MS workflow and a strategy to map identifications from the C2C12 cell line model to tissues, we identified a total of 10,218 proteins, including skeletal muscle specific transcription factors like myod1 and myogenin and circadian clock proteins. We obtain absolute abundances for proteins expressed in a muscle cell line and skeletal muscle, which should serve as a valuable resource. Quantitation of protein isoforms of glucose uptake signaling pathways and in glucose and lipid metabolic pathways provides a detailed metabolic map of the cell line compared with tissue. This revealed unexpectedly complex regulation of AMP-activated protein kinase and insulin signaling in muscle tissue at the level of enzyme isoforms. PMID:25616865

  13. Reference Models for Multi-Layer Tissue Structures

    Science.gov (United States)

    2016-09-01

    function of multi-layer tissues (etiology and management of pressure ulcers ). What was the impact on other disciplines? As part of the project, a data...simplification to develop cost -effective models of surface manipulation of multi-layer tissues. Deliverables. Specimen- (or subject) and region-specific...simplification to develop cost -effective models of surgical manipulation. Deliverables. Specimen-specific surrogate models of upper legs confirmed against data

  14. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    International Nuclear Information System (INIS)

    Juneja, Prabhjot; Harris, Emma J.; Kirby, Anna M.; Evans, Philip M.

    2012-01-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue segmentation

  15. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    Energy Technology Data Exchange (ETDEWEB)

    Juneja, Prabhjot, E-mail: Prabhjot.Juneja@icr.ac.uk [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom); Harris, Emma J. [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom); Kirby, Anna M. [Department of Academic Radiotherapy, Royal Marsden National Health Service Foundation Trust, Sutton (United Kingdom); Evans, Philip M. [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom)

    2012-11-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue

  16. Mechanical characterization of bioprinted in vitro soft tissue models

    International Nuclear Information System (INIS)

    Zhang, Ting; Ouyang, Liliang; Sun, Wei; Yan, Karen Chang

    2013-01-01

    Recent development in bioprinting technology enables the fabrication of complex, precisely controlled cell-encapsulated tissue constructs. Bioprinted tissue constructs have potential in both therapeutic applications and nontherapeutic applications such as drug discovery and screening, disease modelling and basic biological studies such as in vitro tissue modelling. The mechanical properties of bioprinted in vitro tissue models play an important role in mimicking in vivo the mechanochemical microenvironment. In this study, we have constructed three-dimensional in vitro soft tissue models with varying structure and porosity based on the 3D cell-assembly technique. Gelatin/alginate hybrid materials were used as the matrix material and cells were embedded. The mechanical properties of these models were assessed via compression tests at various culture times, and applicability of three material constitutive models was examined for fitting the experimental data. An assessment of cell bioactivity in these models was also carried out. The results show that the mechanical properties can be improved through structure design, and the compression modulus and strength decrease with respect to time during the first week of culture. In addition, the experimental data fit well with the Ogden model and experiential function. These results provide a foundation to further study the mechanical properties, structural and combined effects in the design and the fabrication of in vitro soft tissue models. (paper)

  17. Geometry Modeling Program Implementation of Human Hip Tissue

    Directory of Open Access Journals (Sweden)

    WANG Mo-nan

    2017-10-01

    Full Text Available Abstract:Aiming to design a simulate software of human tissue modeling and analysis,Visual Studio 2010 is selected as a development tool to develop a 3 D reconstruction software of human tissue with language C++.It can be used alone. It also can be a module of the virtual surgery systems. The system includes medical image segmentation modules and 3 D reconstruction modules,and can realize the model visualization. This software system has been used to reconstruct hip muscles,femur and hip bone accurately. The results show these geometry models can simulate the structure of hip tissues.

  18. Geometry Modeling Program Implementation of Human Hip Tissue

    Directory of Open Access Journals (Sweden)

    WANG Monan

    2017-04-01

    Full Text Available Aiming to design a simulate software of human tissue modeling and analysis,Visual Studio 2010 is selected as a development tool to develop a 3 D reconstruction software of human tissue with language C++.It can be used alone. It also can be a module of the virtual surgery systems. The system includes medical image segmentation modules and 3 D reconstruction modules,and can realize the model visualization. This software system has been used to reconstruct hip muscles,femur and hip bone accurately. The results show these geometry models can simulate the structure of hip tissues.

  19. A simple tissue model for practicing ultrasound guided vascular ...

    African Journals Online (AJOL)

    Introduction: The use of ultrasound in anaesthetic practice continues to be more established and the use of ultrasound guidance in establishing vascular access is recommended by various groups. We have developed a tissue model for the practice and skills development in ultrasound vascular access. Method: The tissue ...

  20. Modeling light–tissue interaction in optical coherence tomography systems

    DEFF Research Database (Denmark)

    Andersen, Peter E.; Jørgensen, Thomas Martini; Thrane, Lars

    2015-01-01

    Optical coherence tomography (OCT) performs high-resolution, cross-sectional tomographic imaging of the internal tissue microstructure by measuring backscattered or backreflected light. The scope of this chapter is to present analytical and numerical models that are able to describe light-tissue ...

  1. Modelling the electrical properties of tissue as a porous medium

    International Nuclear Information System (INIS)

    Smye, S W; Evans, C J; Robinson, M P; Sleeman, B D

    2007-01-01

    Models of the electrical properties of biological tissue have been the subject of many studies. These models have sought to explain aspects of the dielectric dispersion of tissue. This paper develops a mathematical model of the complex permittivity of tissue as a function of frequency f, in the range 10 4 7 Hz, which is derived from a formulation used to describe the complex permittivity of porous media. The model introduces two parameters, porosity and percolation probability, to the description of the electrical properties of any tissue which comprises a random arrangement of cells. The complex permittivity for a plausible porosity and percolation probability distribution is calculated and compared with the published measured electrical properties of liver tissue. Broad agreement with the experimental data is noted. It is suggested that future detailed experimental measurements should be undertaken to validate the model. The model may be a more convenient method of parameterizing the electrical properties of biological tissue and subsequent measurement of these parameters in a range of tissues may yield information of biological and clinical significance

  2. Micromechanical modeling of rate-dependent behavior of Connective tissues.

    Science.gov (United States)

    Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

    2017-03-07

    In this paper, a constitutive and micromechanical model for prediction of rate-dependent behavior of connective tissues (CTs) is presented. Connective tissues are considered as nonlinear viscoelastic material. The rate-dependent behavior of CTs is incorporated into model using the well-known quasi-linear viscoelasticity (QLV) theory. A planar wavy representative volume element (RVE) is considered based on the tissue microstructure histological evidences. The presented model parameters are identified based on the available experiments in the literature. The presented constitutive model introduced to ABAQUS by means of UMAT subroutine. Results show that, monotonic uniaxial test predictions of the presented model at different strain rates for rat tail tendon (RTT) and human patellar tendon (HPT) are in good agreement with experimental data. Results of incremental stress-relaxation test are also presented to investigate both instantaneous and viscoelastic behavior of connective tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Role of skeletal muscle in lung development.

    Science.gov (United States)

    Baguma-Nibasheka, Mark; Gugic, Dijana; Saraga-Babic, Mirna; Kablar, Boris

    2012-07-01

    Skeletal (striated) muscle is one of the four basic tissue types, together with the epithelium, connective and nervous tissues. Lungs, on the other hand, develop from the foregut and among various cell types contain smooth, but not skeletal muscle. Therefore, during earlier stages of development, it is unlikely that skeletal muscle and lung depend on each other. However, during the later stages of development, respiratory muscle, primarily the diaphragm and the intercostal muscles, execute so called fetal breathing-like movements (FBMs), that are essential for lung growth and cell differentiation. In fact, the absence of FBMs results in pulmonary hypoplasia, the most common cause of death in the first week of human neonatal life. Most knowledge on this topic arises from in vivo experiments on larger animals and from various in vitro experiments. In the current era of mouse mutagenesis and functional genomics, it was our goal to develop a mouse model for pulmonary hypoplasia. We employed various genetically engineered mice lacking different groups of respiratory muscles or lacking all the skeletal muscle and established the criteria for pulmonary hypoplasia in mice, and therefore established a mouse model for this disease. We followed up this discovery with systematic subtractive microarray analysis approach and revealed novel functions in lung development and disease for several molecules. We believe that our approach combines elements of both in vivo and in vitro approaches and allows us to study the function of a series of molecules in the context of lung development and disease and, simultaneously, in the context of lung's dependence on skeletal muscle-executed FBMs.

  4. The dielectric properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues

    International Nuclear Information System (INIS)

    Gabriel, S.; Lau, R.W.; Gabriel, C.

    1996-01-01

    A parametric model was developed to describe the variation of dielectric properties of tissues as a function of frequency. The experimental spectrum from 10 Hz to 100 GHz was modelled with four dispersion regions. The development of the model was based on recently acquired data, complemented by data surveyed from the literature. The purpose is to enable the prediction of dielectric data that are in line with those contained in the vast body of literature on the subject. The analysis was carried out on a Microsoft Excel spreadsheet. Parameters are given for 17 tissue types. (author)

  5. Human tissue models in cancer research: looking beyond the mouse.

    Science.gov (United States)

    Jackson, Samuel J; Thomas, Gareth J

    2017-08-01

    Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

  6. Statistical validation of normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; van t Veld, Aart; Langendijk, Johannes A.; Schilstra, Cornelis

    2012-01-01

    PURPOSE: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: A penalized regression method, LASSO (least absolute shrinkage

  7. Bioprinting towards Physiologically Relevant Tissue Models for Pharmaceutics.

    Science.gov (United States)

    Peng, Weijie; Unutmaz, Derya; Ozbolat, Ibrahim T

    2016-09-01

    Improving the ability to predict the efficacy and toxicity of drug candidates earlier in the drug discovery process will speed up the introduction of new drugs into clinics. 3D in vitro systems have significantly advanced the drug screening process as 3D tissue models can closely mimic native tissues and, in some cases, the physiological response to drugs. Among various in vitro systems, bioprinting is a highly promising technology possessing several advantages such as tailored microarchitecture, high-throughput capability, coculture ability, and low risk of cross-contamination. In this opinion article, we discuss the currently available tissue models in pharmaceutics along with their limitations and highlight the possibilities of bioprinting physiologically relevant tissue models, which hold great potential in drug testing, high-throughput screening, and disease modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. [Effects of lycopene on the skeletal system].

    Science.gov (United States)

    Sołtysiak, Patrycja; Folwarczna, Joanna

    2015-02-21

    Antioxidant substances of plant origin, such as lycopene, may favorably affect the skeletal system. Lycopene is a carotenoid pigment, responsible for characteristic red color of tomatoes. It is believed that lycopene may play a role in the prevention of various diseases; despite theoretical premises and results of experimental studies, the effectiveness of lycopene has not yet been clearly demonstrated in studies carried out in humans. The aim of the study was to present the current state of knowledge on the effects of lycopene on the osseous tissue in in vitro and in vivo experimental models and on the skeletal system in humans. Results of the studies indicate that lycopene may inhibit bone resorption. Favorable effects of high doses of lycopene on the rat skeletal system in experimental conditions, including the model of osteoporosis induced by estrogen deficiency, have been demonstrated. The few epidemiological and clinical studies, although not fully conclusive, suggest a possible beneficial effect of lycopene present in the diet on the skeletal system.

  9. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  10. Presentation : Development of an age-specific genome-scale model of skeletal muscle metabolism

    NARCIS (Netherlands)

    Cabbia, A.; van Riel, N.A.W.

    2017-01-01

    Skeletal myocytes are among the most metabolically active cell types, implicated in nutrient balance, contributing to the insulin-stimulated clearance of glucose from the blood, and secreting myokines that contribute in regulating inflammation and the ageing process. The loss of muscle mass and

  11. A Standardized Rat Model of Volumetric Muscle Loss Injury for the Development of Tissue Engineering Therapies

    Science.gov (United States)

    2012-12-01

    appropriate sample size and dura- tion required to adequately characterize a treatment. Further compounding the need for a standard preclinical VML...al. In vivo tissue engineer- ing of functional skeletal muscle by freshly isolated satellite cells embedded in a photopolymerizable hydrogel. FASEB J

  12. Analysis of dextromethorphan and dextrorphan in decomposed skeletal tissues by microwave assisted extraction, microplate solid-phase extraction and gas chromatography- mass spectrometry (MAE-MPSPE-GCMS).

    Science.gov (United States)

    Fraser, Candice D; Cornthwaite, Heather M; Watterson, James H

    2015-08-01

    Analysis of decomposed skeletal tissues for dextromethorphan (DXM) and dextrorphan (DXT) using microwave assisted extraction (MAE), microplate solid-phase extraction (MPSPE) and gas chromatography-mass spectrometry (GC-MS) is described. Rats (n = 3) received 100 mg/kg DXM (i.p.) and were euthanized by CO2 asphyxiation roughly 20 min post-dose. Remains decomposed to skeleton outdoors and vertebral bones were recovered, cleaned, and pulverized. Pulverized bone underwent MAE using methanol as an extraction solvent in a closed microwave system, followed by MPSPE and GC-MS. Analyte stability under MAE conditions was assessed and found to be stable for at least 60 min irradiation time. The majority (>90%) of each analyte was recovered after 15 min. The MPSPE-GCMS method was fit to a quadratic response (R(2)  > 0.99), over the concentration range 10-10 000 ng⋅mL(-1) , with coefficients of variation <20% in triplicate analysis. The MPSPE-GCMS method displayed a limit of detection of 10 ng⋅mL(-1) for both analytes. Following MAE for 60 min (80 °C, 1200 W), MPSPE-GCMS analysis of vertebral bone of DXM-exposed rats detected both analytes in all samples (DXM: 0.9-1.5 µg⋅g(-1) ; DXT: 0.5-1.8 µg⋅g(-1) ). Copyright © 2014 John Wiley & Sons, Ltd.

  13. A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

    Directory of Open Access Journals (Sweden)

    Matthew E. Brown

    2018-04-01

    Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

  14. Mathematical modeling in wound healing, bone regeneration and tissue engineering.

    Science.gov (United States)

    Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

    2010-12-01

    The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

  15. POLARIZATION IMAGING AND SCATTERING MODEL OF CANCEROUS LIVER TISSUES

    Directory of Open Access Journals (Sweden)

    DONGZHI LI

    2013-07-01

    Full Text Available We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI, degree of polarization imaging (DOPI and rotating linear polarization imaging (RLPI. Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.

  16. Dynamic skin deformation simulation using musculoskeletal model and soft tissue dynamics

    Institute of Scientific and Technical Information of China (English)

    Akihiko Murai; Q. Youn Hong; Katsu Yamane; Jessica K. Hodgins

    2017-01-01

    Deformation of skin and muscle is essential for bringing an animated character to life. This deformation is difficult to animate in a realistic fashion using traditional techniques because of the subtlety of the skin deformations that must move appropriately for the character design. In this paper, we present an algorithm that generates natural, dynamic, and detailed skin deformation (movement and jiggle) from joint angle data sequences. The algorithm has two steps: identification of parameters for a quasi-static muscle deformation model, and simulation of skin deformation. In the identification step, we identify the model parameters using a musculoskeletal model and a short sequence of skin deformation data captured via a dense marker set. The simulation step first uses the quasi-static muscle deformation model to obtain the quasi-static muscle shape at each frame of the given motion sequence (slow jump). Dynamic skin deformation is then computed by simulating the passive muscle and soft tissue dynamics modeled as a mass–spring–damper system. Having obtained the model parameters, we can simulate dynamic skin deformations for subjects with similar body types from new motion data. We demonstrate our method by creating skin deformations for muscle co-contraction and external impacts from four different behaviors captured as skeletal motion capture data. Experimental results show that the simulated skin deformations are quantitatively and qualitatively similar to measured actual skin deformations.

  17. Dynamic skin deformation simulation using musculoskeletal model and soft tissue dynamics

    Institute of Scientific and Technical Information of China (English)

    Akihiko Murai; Q.Youn Hong; Katsu Yamane; Jessica K.Hodgins

    2017-01-01

    Deformation of skin and muscle is essential for bringing an animated character to life. This deformation is difficult to animate in a realistic fashion using traditional techniques because of the subtlety of the skin deformations that must move appropriately for the character design. In this paper, we present an algorithm that generates natural, dynamic, and detailed skin deformation(movement and jiggle) from joint angle data sequences. The algorithm has two steps: identification of parameters for a quasi-static muscle deformation model, and simulation of skin deformation. In the identification step, we identify the model parameters using a musculoskeletal model and a short sequence of skin deformation data captured via a dense marker set. The simulation step first uses the quasi-static muscle deformation model to obtain the quasi-static muscle shape at each frame of the given motion sequence(slow jump). Dynamic skin deformation is then computed by simulating the passive muscle and soft tissue dynamics modeled as a mass–spring–damper system. Having obtained the model parameters, we can simulate dynamic skin deformations for subjects with similar body types from new motion data. We demonstrate our method by creating skin deformations for muscle co-contraction and external impacts from four different behaviors captured as skeletal motion capture data. Experimental results show that the simulated skin deformations are quantitatively and qualitatively similar to measured actual skin deformations.

  18. Human tissue models in cancer research: looking beyond the mouse

    Directory of Open Access Journals (Sweden)

    Samuel J. Jackson

    2017-08-01

    Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

  19. Finite-element modeling of soft tissue rolling indentation.

    Science.gov (United States)

    Sangpradit, Kiattisak; Liu, Hongbin; Dasgupta, Prokar; Althoefer, Kaspar; Seneviratne, Lakmal D

    2011-12-01

    We describe a finite-element (FE) model for simulating wheel-rolling tissue deformations using a rolling FE model (RFEM). A wheeled probe performing rolling tissue indentation has proven to be a promising approach for compensating for the loss of haptic and tactile feedback experienced during robotic-assisted minimally invasive surgery (H. Liu, D. P. Noonan, B. J. Challacombe, P. Dasgupta, L. D. Seneviratne, and K. Althoefer, "Rolling mechanical imaging for tissue abnormality localization during minimally invasive surgery, " IEEE Trans. Biomed. Eng., vol. 57, no. 2, pp. 404-414, Feb. 2010; K. Sangpradit, H. Liu, L. Seneviratne, and K. Althoefer, "Tissue identification using inverse finite element analysis of rolling indentation," in Proc. IEEE Int. Conf. Robot. Autom. , Kobe, Japan, 2009, pp. 1250-1255; H. Liu, D. Noonan, K. Althoefer, and L. Seneviratne, "The rolling approach for soft tissue modeling and mechanical imaging during robot-assisted minimally invasive surgery," in Proc. IEEE Int. Conf. Robot. Autom., May 2008, pp. 845-850; H. Liu, P. Puangmali, D. Zbyszewski, O. Elhage, P. Dasgupta, J. S. Dai, L. Seneviratne, and K. Althoefer, "An indentation depth-force sensing wheeled probe for abnormality identification during minimally invasive surgery," Proc. Inst. Mech. Eng., H, vol. 224, no. 6, pp. 751-63, 2010; D. Noonan, H. Liu, Y. Zweiri, K. Althoefer, and L. Seneviratne, "A dual-function wheeled probe for tissue viscoelastic property identification during minimally invasive surgery," in Proc. IEEE Int. Conf. Robot. Autom. , 2008, pp. 2629-2634; H. Liu, J. Li, Q. I. Poon, L. D. Seneviratne, and K. Althoefer, "Miniaturized force indentation-depth sensor for tissue abnormality identification," IEEE Int. Conf. Robot. Autom., May 2010, pp. 3654-3659). A sound understanding of wheel-tissue rolling interaction dynamics will facilitate the evaluation of signals from rolling indentation. In this paper, we model the dynamic interactions between a wheeled probe and a

  20. Molecular Signals and Skeletal Muscle Adaptation to Exercise

    Directory of Open Access Journals (Sweden)

    Mark Wilson

    2013-09-01

    Full Text Available The phenotypic plasticity of skeletal muscle affords a considerable degree of adaptability not seen in other bodily tissues. The mechanical properties of skeletal muscle are highly dependent on loading conditions. The extent of skeletal muscle plasticity is distinctly highlighted by a loss of muscle mass, or atrophy, after a period of reduced weight-bearing activity, for example during periods of extended bed rest, space flight and in spinal cord injury. On the other hand, increased mechanical loading, or resistance training, induces muscle growth, or hypertrophy. Endurance exercise performance is also dependent on the adaptability of skeletal muscle, especially muscles that contribute to posture, locomotion and the mechanics of breathing.  However, the molecular pathways governing skeletal muscle adaptations are yet to be satisfactorily delineated and require further investigation. Researchers in the areas of exercise physiology, physiotherapy and sports medicine are endeavoring to translate experimental knowledge into effective, innovative treatments and regimens in order to improve physical performance and health in both elite athletes and the general community. The efficacy of the translation of molecular biological paradigms in experimental exercise physiology has long been underappreciated. Indeed, molecular biology tools can now be used to answer questions regarding skeletal muscle adaptation in response to exercise and provide new frameworks to improve physical performance. Furthermore, transgenic animal models, knockout animal models and in vivo studies provide tools to test questions concerned with how exercise initiates adaptive changes in gene expression. In light of these perceived deficiencies, an attempt is made here to elucidate the molecular mechanisms of skeletal muscle adaptation to exercise. An examination will be made of the functional capacity of skeletal muscle to respond to a variety of exercise conditions, namely

  1. Molecular Signals and Skeletal Muscle Adaptation to Exercise

    Directory of Open Access Journals (Sweden)

    Mark Wilson

    2013-08-01

    Full Text Available The phenotypic plasticity of skeletal muscle affords a considerable degree of adaptability not seen in other bodily tissues. The mechanical properties of skeletal muscle are highly dependent on loading conditions. The extent of skeletal muscle plasticity is distinctly highlighted by a loss of muscle mass, or atrophy, after a period of reduced weight-bearing activity, for example during periods of extended bed rest, space flight and in spinal cord injury. On the other hand, increased mechanical loading, or resistance training, induces muscle growth, or hypertrophy. Endurance exercise performance is also dependent on the adaptability of skeletal muscle, especially muscles that contribute to posture, locomotion and the mechanics of breathing. However, the molecular pathways governing skeletal muscle adaptations are yet to be satisfactorily delineated and require further investigation. Researchers in the areas of exercise physiology, physiotherapy and sports medicine are endeavoring to translate experimental knowledge into effective, innovative treatments and regimens in order to improve physical performance and health in both elite athletes and the general community. The efficacy of the translation of molecular biological paradigms in experimental exercise physiology has long been underappreciated. Indeed, molecular biology tools can now be used to answer questions regarding skeletal muscle adaptation in response to exercise and provide new frameworks to improve physical performance. Furthermore, transgenic animal models, knockout animal models and in vivo studies provide tools to test questions concerned with how exercise initiates adaptive changes in gene expression. In light of these perceived deficiencies, an attempt is made here to elucidate the molecular mechanisms of skeletal muscle adaptation to exercise. An examination will be made of the functional capacity of skeletal muscle to respond to a variety of exercise conditions, namely

  2. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation. Final Technical Report

    International Nuclear Information System (INIS)

    John R. Ford

    2005-01-01

    Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols

  3. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation

    Energy Technology Data Exchange (ETDEWEB)

    John R. Ford

    2005-11-01

    Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.

  4. Development of a 3D bone marrow adipose tissue model.

    Science.gov (United States)

    Fairfield, Heather; Falank, Carolyne; Farrell, Mariah; Vary, Calvin; Boucher, Joshua M; Driscoll, Heather; Liaw, Lucy; Rosen, Clifford J; Reagan, Michaela R

    2018-01-26

    Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications. In adipose biology and cancer research, these models serve as physiologically relevant 3D platforms to bridge the divide between 2D cultures and in vivo models, bringing about more reliable and translationally useful data to accelerate benchtop to bedside research. Currently, no model has been developed for bone marrow adipose tissue (BMAT), a novel adipose depot that has previously been overlooked as "filler tissue" but has more recently been recognized as endocrine-signaling and systemically relevant. Herein we describe the development of the first 3D, BMAT model derived from either human or mouse bone marrow (BM) mesenchymal stromal cells (MSCs). We found that BMAT models can be stably cultured for at least 3 months in vitro, and that myeloma cells (5TGM1, OPM2 and MM1S cells) can be cultured on these for at least 2 weeks. Upon tumor cell co-culture, delipidation occurred in BMAT adipocytes, suggesting a bidirectional relationship between these two important cell types in the malignant BM niche. Overall, our studies suggest that 3D BMAT represents a "healthier," more realistic tissue model that may be useful for elucidating the effects of MAT on tumor cells, and tumor cells on MAT, to identify novel therapeutic

  5. Peripheral endocannabinoids regulate skeletal muscle development and maintenance

    Directory of Open Access Journals (Sweden)

    Dongjiao Zhao

    2010-12-01

    Full Text Available As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interest, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of C2C12 cells, primary satellite cells and mouse skeletal muscle single fibers were used as model systems for our studies. We found an increase in cannabinoid receptor type 1 (CB1 mRNA and endocannabinoid synthetic enzyme mRNA skeletal muscle cells during differentiation. We also found that activation of CB1 inhibited myoblast differentiation, expanded the number of satellite cells, and stimulated the fast-muscle oxidative phenotype. Our findings contribute to understanding of the role of the endocannabinoid system in skeletal muscle metabolism and muscle oxygen consumption, and also help to explain the effects of the peripheral endocannabinoid system on whole-body energy balance.

  6. Ferulic Acid Promotes Hypertrophic Growth of Fast Skeletal Muscle in Zebrafish Model.

    Science.gov (United States)

    Wen, Ya; Ushio, Hideki

    2017-09-26

    As a widely distributed and natural existing antioxidant, ferulic acid and its functions have been extensively studied in recent decades. In the present study, hypertrophic growth of fast skeletal myofibers was observed in adult zebrafish after ferulic acid administration for 30 days, being reflected in increased body weight, body mass index (BMI), and muscle mass, along with an enlarged cross-sectional area of myofibers. qRT-PCR analyses demonstrated the up-regulation of relative mRNA expression levels of myogenic transcriptional factors (MyoD, myogenin and serum response factor (SRF)) and their target genes encoding sarcomeric unit proteins involved in muscular hypertrophy (skeletal alpha-actin, myosin heavy chain, tropomyosin, and troponin I). Western blot analyses detected a higher phosphorylated level of zTOR (zebrafish target of rapamycin), p70S6K, and 4E-BP1, which suggests an enhanced translation efficiency and protein synthesis capacity of fast skeletal muscle myofibers. These changes in transcription and translation finally converge and lead to higher protein contents in myofibers, as confirmed by elevated levels of myosin heavy chain (MyHC), and an increased muscle mass. To the best of our knowledge, these findings have been reported for the first time in vivo and suggest potential applications of ferulic acid as functional food additives and dietary supplements owing to its ability to promote muscle growth.

  7. Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

    Science.gov (United States)

    Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

    2016-10-01

    In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Expression of Gla proteins during fish skeletal development

    OpenAIRE

    Gavaia, Paulo J.

    2006-01-01

    Senegal sole skeletal development; Skeletal malformations; Skeletal malformation in mediterranean species; Senegal sole skeletal deformities; Zebra fish as model system: skeletal development; Identification of bone cells / skeletal development; Spatial - temporal pattern of bgp expression; Single cell resolution: localization of bgp mRNA; Single cell resolution: Immunolocalization of Bgp; Single cell resolution: localization of mgp mRNA; Single cell resolution: Immunolocalization of Mgp; An i...

  9. Multiphase poroelastic finite element models for soft tissue structures

    International Nuclear Information System (INIS)

    Simon, B.R.

    1992-01-01

    During the last two decades, biological structures with soft tissue components have been modeled using poroelastic or mixture-based constitutive laws, i.e., the material is viewed as a deformable (porous) solid matrix that is saturated by mobile tissue fluid. These structures exhibit a highly nonlinear, history-dependent material behavior; undergo finite strains; and may swell or shrink when tissue ionic concentrations are altered. Give the geometric and material complexity of soft tissue structures and that they are subjected to complicated initial and boundary conditions, finite element models (FEMs) have been very useful for quantitative structural analyses. This paper surveys recent applications of poroelastic and mixture-based theories and the associated FEMs for the study of the biomechanics of soft tissues, and indicates future directions for research in this area. Equivalent finite-strain poroelastic and mixture continuum biomechanical models are presented. Special attention is given to the identification of material properties using a porohyperelastic constitutive law ans a total Lagrangian view for the formulation. The associated FEMs are then formulated to include this porohyperelastic material response and finite strains. Extensions of the theory are suggested in order to include inherent viscoelasticity, transport phenomena, and swelling in soft tissue structures. A number of biomechanical research areas are identified, and possible applications of the porohyperelastic and mixture-based FEMs are suggested. 62 refs., 11 figs., 3 tabs

  10. Normal tissue dose-effect models in biological dose optimisation

    International Nuclear Information System (INIS)

    Alber, M.

    2008-01-01

    Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

  11. Mathematical modelling of tissue formation in chondrocyte filter cultures.

    Science.gov (United States)

    Catt, C J; Schuurman, W; Sengers, B G; van Weeren, P R; Dhert, W J A; Please, C P; Malda, J

    2011-12-17

    In the field of cartilage tissue engineering, filter cultures are a frequently used three-dimensional differentiation model. However, understanding of the governing processes of in vitro growth and development of tissue in these models is limited. Therefore, this study aimed to further characterise these processes by means of an approach combining both experimental and applied mathematical methods. A mathematical model was constructed, consisting of partial differential equations predicting the distribution of cells and glycosaminoglycans (GAGs), as well as the overall thickness of the tissue. Experimental data was collected to allow comparison with the predictions of the simulation and refinement of the initial models. Healthy mature equine chondrocytes were expanded and subsequently seeded on collagen-coated filters and cultured for up to 7 weeks. Resulting samples were characterised biochemically, as well as histologically. The simulations showed a good representation of the experimentally obtained cell and matrix distribution within the cultures. The mathematical results indicate that the experimental GAG and cell distribution is critically dependent on the rate at which the cell differentiation process takes place, which has important implications for interpreting experimental results. This study demonstrates that large regions of the tissue are inactive in terms of proliferation and growth of the layer. In particular, this would imply that higher seeding densities will not significantly affect the growth rate. A simple mathematical model was developed to predict the observed experimental data and enable interpretation of the principal underlying mechanisms controlling growth-related changes in tissue composition.

  12. Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

    Directory of Open Access Journals (Sweden)

    Maide Ö. Raeker

    2011-01-01

    Full Text Available During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues.

  13. Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

    Science.gov (United States)

    Raeker, Maide Ö.; Russell, Mark W.

    2011-01-01

    During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues. PMID:22190853

  14. A Dirichlet process mixture model for brain MRI tissue classification.

    Science.gov (United States)

    Ferreira da Silva, Adelino R

    2007-04-01

    Accurate classification of magnetic resonance images according to tissue type or region of interest has become a critical requirement in diagnosis, treatment planning, and cognitive neuroscience. Several authors have shown that finite mixture models give excellent results in the automated segmentation of MR images of the human normal brain. However, performance and robustness of finite mixture models deteriorate when the models have to deal with a variety of anatomical structures. In this paper, we propose a nonparametric Bayesian model for tissue classification of MR images of the brain. The model, known as Dirichlet process mixture model, uses Dirichlet process priors to overcome the limitations of current parametric finite mixture models. To validate the accuracy and robustness of our method we present the results of experiments carried out on simulated MR brain scans, as well as on real MR image data. The results are compared with similar results from other well-known MRI segmentation methods.

  15. Metabolic dynamics in skeletal muscle during acute reduction in blood flow and oxygen supply to mitochondria: in-silico studies using a multi-scale, top-down integrated model.

    Science.gov (United States)

    Dash, Ranjan K; Li, Yanjun; Kim, Jaeyeon; Beard, Daniel A; Saidel, Gerald M; Cabrera, Marco E

    2008-09-09

    Control mechanisms of cellular metabolism and energetics in skeletal muscle that may become evident in response to physiological stresses such as reduction in blood flow and oxygen supply to mitochondria can be quantitatively understood using a multi-scale computational model. The analysis of dynamic responses from such a model can provide insights into mechanisms of metabolic regulation that may not be evident from experimental studies. For the purpose, a physiologically-based, multi-scale computational model of skeletal muscle cellular metabolism and energetics was developed to describe dynamic responses of key chemical species and reaction fluxes to muscle ischemia. The model, which incorporates key transport and metabolic processes and subcellular compartmentalization, is based on dynamic mass balances of 30 chemical species in both capillary blood and tissue cells (cytosol and mitochondria) domains. The reaction fluxes in cytosol and mitochondria are expressed in terms of a general phenomenological Michaelis-Menten equation involving the compartmentalized energy controller ratios ATP/ADP and NADH/NAD(+). The unknown transport and reaction parameters in the model are estimated simultaneously by minimizing the differences between available in vivo experimental data on muscle ischemia and corresponding model outputs in coupled with the resting linear flux balance constraints using a robust, nonlinear, constrained-based, reduced gradient optimization algorithm. With the optimal parameter values, the model is able to simulate dynamic responses to reduced blood flow and oxygen supply to mitochondria associated with muscle ischemia of several key metabolite concentrations and metabolic fluxes in the subcellular cytosolic and mitochondrial compartments, some that can be measured and others that can not be measured with the current experimental techniques. The model can be applied to test complex hypotheses involving dynamic regulation of cellular metabolism and

  16. AMPK in skeletal muscle function and metabolism

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Hingst, Janne Rasmuss; Fentz, Joachim

    2018-01-01

    Skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions. AMPK is a sensor of intracellular energy status that maintains energy stores by fine-tuning anabolic and catabolic pathways. AMPK's role as an energy sensor is particularly critical in tissues displaying...... highly changeable energy turnover. Due to the drastic changes in energy demand that occur between the resting and exercising state, skeletal muscle is one such tissue. Here, we review the complex regulation of AMPK in skeletal muscle and its consequences on metabolism (e.g., substrate uptake, oxidation......, and storage as well as mitochondrial function of skeletal muscle fibers). We focus on the role of AMPK in skeletal muscle during exercise and in exercise recovery. We also address adaptations to exercise training, including skeletal muscle plasticity, highlighting novel concepts and future perspectives...

  17. The exercised skeletal muscle: a review

    Directory of Open Access Journals (Sweden)

    Marina Marini

    2010-09-01

    Full Text Available The skeletal muscle is the second more plastic tissue of the body - second to the nervous tissue only. In fact, both physical activity and inactivity contribute to modify the skeletal muscle, by continuous signaling through nerve impulses, mechanical stimuli and humoral clues. In turn, the skeletal muscle sends signals to the body, thus contributing to its homeostasis. We'll review here the contribute of physical exercise to the shaping of skeletal muscle, to the adaptation of its mass and function to the different needs imposed by different physical activities and to the attainment of the health benefits associated with active skeletal muscles. Focus will primarily be on the molecular pathways and on gene regulation that result in skeletal muscle adaptation to exercise.

  18. A Framework for Modelling Connective Tissue Changes in VIIP Syndrome

    Science.gov (United States)

    Ethier, C. R.; Best, L.; Gleason, R.; Mulugeta, L.; Myers, J. G.; Nelson, E. S.; Samuels, B. C.

    2014-01-01

    Insertion of astronauts into microgravity induces a cascade of physiological adaptations, notably including a cephalad fluid shift. Longer-duration flights carry an increased risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. The slow onset of changes in VIIP, their chronic nature, and the similarity of certain clinical features of VIIP to ophthalmic findings in patients with raised intracranial pressure strongly suggest that: (i) biomechanical factors play a role in VIIP, and (ii) connective tissue remodeling must be accounted for if we wish to understand the pathology of VIIP. Our goal is to elucidate the pathophysiology of VIIP and suggest countermeasures based on biomechanical modeling of ocular tissues, suitably informed by experimental data, and followed by validation and verification. We specifically seek to understand the quasi-homeostatic state that evolves over weeks to months in space, during which ocular tissue remodeling occurs. This effort is informed by three bodies of work: (i) modeling of cephalad fluid shifts; (ii) modeling of ophthalmic tissue biomechanics in glaucoma; and (iii) modeling of connective tissue changes in response to biomechanical loading.

  19. Artery Soft-Tissue Modelling for Stent Implant Training System

    Directory of Open Access Journals (Sweden)

    Giovanni Aloisio

    2004-08-01

    Full Text Available Virtual reality technology can be utilised to provide new systematic training methods for surgical procedures. Our aim is to build a simulator that allows medical students to practice the coronary stent implant procedure and avoids exposing patients to risks. The designed simulation system consists of a virtual environment and a haptic interface, in order to provide both the visualization of the coronary arteries and the tactile and force feedback generated during the interactions of the surgical instruments in the virtual environment. Since the arteries are soft tissues, their shape may change during an operation; for this reason physical modelling of the organs is necessary to render their behaviour under the influence of surgeon's instruments. The idea is to define a model that computes the displacement of the tissue versus time; from the displacement it is possible to calculate the response of the tissue to the surgical tool external stimuli. Information about tools displacements and tissue responses are also used to graphically model the artery wall and virtual surgical instrument deformations generated as a consequence of their coming into contact. In order to obtain a realistic simulation, the Finite Element Method has been used to model the soft tissues of the artery, using linear elasticity to reduce computational time and speed up interaction rates.

  20. Computational model of soft tissues in the human upper airway.

    Science.gov (United States)

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  1. Computer modeling the boron compound factor in normal brain tissue

    International Nuclear Information System (INIS)

    Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

    1993-01-01

    The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

  2. High-intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension.

    Science.gov (United States)

    Holloway, Tanya M; Bloemberg, Darin; da Silva, Mayne L; Quadrilatero, Joe; Spriet, Lawrence L

    2015-06-01

    Skeletal muscle is extremely adaptable to a variety of metabolic challenges, as both traditional moderate-intensity endurance (ET) and high-intensity interval training (HIIT) increases oxidative potential in a coordinated manner. Although these responses have been clearly demonstrated in healthy individuals, it remains to be determined whether both produce similar responses in the context of hypertension, one of the most prevalent and costly diseases worldwide. Therefore, in the current study, we used the Dahl sodium-sensitive rat, a model of hypertension, to determine the molecular responses to 4 wk of either ET or HIIT in the red (RG) and white gastrocnemius (WG) muscles. In the RG, both ET and HIIT increased the content of electron transport chain proteins and increased succinate dehydrogenase (SDH) content in type I fibers. Although both intensities of exercise shifted fiber type in RG (increased IIA, decreased IIX), only HIIT was associated with a reduction in endothelial nitric oxide synthase and an increase in HIF-1α proteins. In the WG, both ET and HIIT increased markers of the electron transport chain; however, HIIT decreased SDH content in a fiber-specific manner. ET increased type IIA, decreased IIB fibers, and increased capillarization, while, in contrast, HIIT increased the percentage of IIB fibers, decreased capillary-to-fiber ratios, decreased endothelial nitric oxide synthase, and increased hypoxia inducible factor-1α (HIF-1α) protein. Altogether, these data show that unlike in healthy animals, ET and HIIT have divergent effects in the skeletal muscle of hypertensive rats. This suggests ET may be optimal at improving the oxidative capacity of skeletal muscle in animals with hypertension. Copyright © 2015 the American Physiological Society.

  3. A biphasic model for bleeding in soft tissue

    Science.gov (United States)

    Chang, Yi-Jui; Chong, Kwitae; Eldredge, Jeff D.; Teran, Joseph; Benharash, Peyman; Dutson, Erik

    2017-11-01

    The modeling of blood passing through soft tissues in the body is important for medical applications. The current study aims to capture the effect of tissue swelling and the transport of blood under bleeding or hemorrhaging conditions. The soft tissue is considered as a non-static poro-hyperelastic material with liquid-filled voids. A biphasic formulation effectively, a generalization of Darcy's law-is utilized, treating the phases as occupying fractions of the same volume. The interaction between phases is captured through a Stokes-like friction force on their relative velocities and a pressure that penalizes deviations from volume fractions summing to unity. The soft tissue is modeled as a hyperelastic material with a typical J-shaped stress-strain curve, while blood is considered as a Newtonian fluid. The method of Smoothed Particle Hydrodynamics is used to discretize the conservation equations based on the ease of treating free surfaces in the liquid. Simulations of swelling under acute hemorrhage and of draining under gravity and compression will be demonstrated. Ongoing progress in modeling of organ tissues under injuries and surgical conditions will be discussed.

  4. Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor

    Science.gov (United States)

    Wu, Yingjie; Sun, Hui; Basta-Pljakic, Jelena; Cardoso, Luis; Kennedy, Oran D; Jasper, Hector; Domené, Horacio; Karabatas, Liliana; Guida, Clara; Schaffler, Mitchell B; Rosen, Clifford J; Yakar, Shoshana

    2013-01-01

    States of growth hormone (GH) resistance, such those observed in Laron’s dwarf patients, are characterized by mutations in the GH receptor (GHR), decreased serum and tissue IGF-1 levels, impaired glucose tolerance, and impaired skeletal acquisition. IGF-1 replacement therapy in such patients increases growth velocity but does not normalize growth. Herein we combined the GH-resistant (GHR knockout, GHRKO) mouse model with mice expressing the hepatic Igf-1 transgene (HIT) to generate the GHRKO-HIT mouse model. In GHRKOHIT mice, serum IGF-1 levels were restored via transgenic expression of Igf-1 allowing us to study how endocrine IGF-1 affects growth, metabolic homeostasis, and skeletal integrity. We show that in a GH-resistant state, normalization of serum IGF-1 improved body adiposity and restored glucose tolerance but was insufficient to support normal skeletal growth, resulting in an osteopenic skeletal phenotype. The inability of serum IGF-1 to restore skeletal integrity in the total absence of GHR likely resulted from reduced skeletal Igf-1 gene expression, blunted GH-mediated effects on the skeleton that are independent of serum or tissue IGF-1, and from poor delivery of IGF-1 to the tissues. These findings are consistent with clinical data showing that IGF-I replacement therapy in patients with Laron’s syndrome does not achieve full skeletal growth. PMID:23456957

  5. A dynamic cellular vertex model of growing epithelial tissues

    Science.gov (United States)

    Lin, Shao-Zhen; Li, Bo; Feng, Xi-Qiao

    2017-04-01

    Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

  6. High-Density Spot Seeding for Tissue Model Formation

    Science.gov (United States)

    Marquette, Michele L. (Inventor); Sognier, Marguerite A. (Inventor)

    2016-01-01

    A model of tissue is produced by steps comprising seeding cells at a selected concentration on a support to form a cell spot, incubating the cells to allow the cells to partially attach, rinsing the cells to remove any cells that have not partially attached, adding culture medium to enable the cells to proliferate at a periphery of the cell spot and to differentiate toward a center of the cell spot, and further incubating the cells to form the tissue. The cells may be C2C12 cells or other subclones of the C2 cell line, H9c2(2-1) cells, L6 cells, L8 cells, QM7 cells, Sol8 cells, G-7 cells, G-8 cells, other myoblast cells, cells from other tissues, or stem cells. The selected concentration is in a range from about 1 x 10(exp 5) cells/ml to about 1 x 10(exp 6) cells/ml. The tissue formed may be a muscle tissue or other tissue depending on the cells seeded.

  7. Effects of Whey, Soy or Leucine Supplementation with 12 Weeks of Resistance Training on Strength, Body Composition, and Skeletal Muscle and Adipose Tissue Histological Attributes in College-Aged Males

    Directory of Open Access Journals (Sweden)

    C. Brooks Mobley

    2017-09-01

    Full Text Available We sought to determine the effects of L-leucine (LEU or different protein supplements standardized to LEU (~3.0 g/serving on changes in body composition, strength, and histological attributes in skeletal muscle and adipose tissue. Seventy-five untrained, college-aged males (mean ± standard error of the mean (SE; age = 21 ± 1 years, body mass = 79.2 ± 0.3 kg were randomly assigned to an isocaloric, lipid-, and organoleptically-matched maltodextrin placebo (PLA, n = 15, LEU (n = 14, whey protein concentrate (WPC, n = 17, whey protein hydrolysate (WPH, n = 14, or soy protein concentrate (SPC, n = 15 group. Participants performed whole-body resistance training three days per week for 12 weeks while consuming supplements twice daily. Skeletal muscle and subcutaneous (SQ fat biopsies were obtained at baseline (T1 and ~72 h following the last day of training (T39. Tissue samples were analyzed for changes in type I and II fiber cross sectional area (CSA, non-fiber specific satellite cell count, and SQ adipocyte CSA. On average, all supplement groups including PLA exhibited similar training volumes and experienced statistically similar increases in total body skeletal muscle mass determined by dual X-ray absorptiometry (+2.2 kg; time p = 0.024 and type I and II fiber CSA increases (+394 μm2 and +927 μm2; time p < 0.001 and 0.024, respectively. Notably, all groups reported increasing Calorie intakes ~600–800 kcal/day from T1 to T39 (time p < 0.001, and all groups consumed at least 1.1 g/kg/day of protein at T1 and 1.3 g/kg/day at T39. There was a training, but no supplementation, effect regarding the reduction in SQ adipocyte CSA (−210 μm2; time p = 0.001. Interestingly, satellite cell counts within the WPC (p < 0.05 and WPH (p < 0.05 groups were greater at T39 relative to T1. In summary, LEU or protein supplementation (standardized to LEU content does not provide added benefit in increasing whole-body skeletal muscle mass or strength above PLA

  8. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models

    Directory of Open Access Journals (Sweden)

    Schiaffino Stefano

    2011-01-01

    Full Text Available Abstract A highly conserved signaling pathway involving insulin-like growth factor 1 (IGF1, and a cascade of intracellular components that mediate its effects, plays a major role in the regulation of skeletal muscle growth. A central component in this cascade is the kinase Akt, also called protein kinase B (PKB, which controls both protein synthesis, via the kinases mammalian target of rapamycin (mTOR and glycogen synthase kinase 3β (GSK3β, and protein degradation, via the transcription factors of the FoxO family. In this paper, we review the composition and function of this pathway in skeletal muscle fibers, focusing on evidence obtained in vivo by transgenic and knockout models and by muscle transient transfection experiments. Although this pathway is essential for muscle growth during development and regeneration, its role in adult muscle response to mechanical load is less clear. A full understanding of the operation of this pathway could help to design molecularly targeted therapeutics aimed at preventing muscle wasting, which occurs in a variety of pathologic contexts and in the course of aging.

  9. Skeletal stem cells in space and time

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Bianco, Paolo

    2015-01-01

    The nature, biological characteristics, and contribution to organ physiology of skeletal stem cells are not completely determined. Chan et al. and Worthley et al. demonstrate that a stem cell for skeletal tissues, and a system of more restricted, downstream progenitors, can be identified in mice...

  10. Robust generation and expansion of skeletal muscle progenitors and myocytes from human pluripotent stem cells.

    Science.gov (United States)

    Shelton, Michael; Kocharyan, Avetik; Liu, Jun; Skerjanc, Ilona S; Stanford, William L

    2016-05-15

    Human pluripotent stem cells provide a developmental model to study early embryonic and tissue development, tease apart human disease processes, perform drug screens to identify potential molecular effectors of in situ regeneration, and provide a source for cell and tissue based transplantation. Highly efficient differentiation protocols have been established for many cell types and tissues; however, until very recently robust differentiation into skeletal muscle cells had not been possible unless driven by transgenic expression of master regulators of myogenesis. Nevertheless, several breakthrough protocols have been published in the past two years that efficiently generate cells of the skeletal muscle lineage from pluripotent stem cells. Here, we present an updated version of our recently described 50-day protocol in detail, whereby chemically defined media are used to drive and support muscle lineage development from initial CHIR99021-induced mesoderm through to PAX7-expressing skeletal muscle progenitors and mature skeletal myocytes. Furthermore, we report an optional method to passage and expand differentiating skeletal muscle progenitors approximately 3-fold every 2weeks using Collagenase IV and continued FGF2 supplementation. Both protocols have been optimized using a variety of human pluripotent stem cell lines including patient-derived induced pluripotent stem cells. Taken together, our differentiation and expansion protocols provide sufficient quantities of skeletal muscle progenitors and myocytes that could be used for a variety of studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Bayesian state space models for dynamic genetic network construction across multiple tissues.

    Science.gov (United States)

    Liang, Yulan; Kelemen, Arpad

    2016-08-01

    Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

  12. Skeletal muscle proteins: a new approach to delimitate the time since death.

    Science.gov (United States)

    Foditsch, Elena Esra; Saenger, Alexandra Maria; Monticelli, Fabio Carlo

    2016-03-01

    Skeletal muscle tissue is proposed as a forensic model tissue with strong potential, as it is easily accessible and its true-to-life state structure and function is well known. Despite this strong potential, skeletal muscle degradation studies are rare. The aim of this study was to test if a skeletal muscle-based protein analysis is applicable to delimitate the time since death. Under standard conditions, two pigs were stored either at 22 °C for 5 days or 4 °C for 21 days. Their Mm. biceps femori were sampled periodically for analyses of ten skeletal muscle proteins postmortem. All analyzed proteins can serve as markers for a delimitation of the time since death. Desmin, nebulin, titin, and SERCA 1 displayed distinct protein patterns at certain points of time. The other five proteins, α-actinin, calsequestrin-1, laminin, troponin T-C, and SERCA 2, showed no degradation patterns within the analyzed postmortem time frame. Referring to specific skeletal muscle proteins, results showed short-term stabilities for just a minority of analyzed proteins, while the majority of investigated proteins displayed characteristics as long-term markers. Due to specific patterns and the possibility to determine definite constraints of the presence, absence, or pattern alterations of single proteins, the feasibility of porcine skeletal muscle as forensic model tissue is outlined and the potential of skeletal muscle as forensic model tissue is underlined, especially with respect to later postmortem phases, which so far lack feasible methods to delimitate the time since death.

  13. Bioprinted three dimensional human tissues for toxicology and disease modeling.

    Science.gov (United States)

    Nguyen, Deborah G; Pentoney, Stephen L

    2017-03-01

    The high rate of attrition among clinical-stage therapies, due largely to an inability to predict human toxicity and/or efficacy, underscores the need for in vitro models that better recapitulate in vivo human biology. In much the same way that additive manufacturing has revolutionized the production of solid objects, three-dimensional (3D) bioprinting is enabling the automated production of more architecturally and functionally accurate in vitro tissue culture models. Here, we provide an overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Lagrangian speckle model and tissue-motion estimation--theory.

    Science.gov (United States)

    Maurice, R L; Bertrand, M

    1999-07-01

    It is known that when a tissue is subjected to movements such as rotation, shearing, scaling, etc., changes in speckle patterns that result act as a noise source, often responsible for most of the displacement-estimate variance. From a modeling point of view, these changes can be thought of as resulting from two mechanisms: one is the motion of the speckles and the other, the alterations of their morphology. In this paper, we propose a new tissue-motion estimator to counteract these speckle decorrelation effects. The estimator is based on a Lagrangian description of the speckle motion. This description allows us to follow local characteristics of the speckle field as if they were a material property. This method leads to an analytical description of the decorrelation in a way which enables the derivation of an appropriate inverse filter for speckle restoration. The filter is appropriate for linear geometrical transformation of the scattering function (LT), i.e., a constant-strain region of interest (ROI). As the LT itself is a parameter of the filter, a tissue-motion estimator can be formulated as a nonlinear minimization problem, seeking the best match between the pre-tissue-motion image and a restored-speckle post-motion image. The method is tested, using simulated radio-frequency (RF) images of tissue undergoing axial shear.

  15. Dietary phosphate restriction normalizes biochemical and skeletal abnormalities in a murine model of tumoral calcinosis.

    Science.gov (United States)

    Ichikawa, Shoji; Austin, Anthony M; Gray, Amie K; Allen, Matthew R; Econs, Michael J

    2011-12-01

    Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis.

  16. Tissue Acoustoelectric Effect Modeling From Solid Mechanics Theory.

    Science.gov (United States)

    Song, Xizi; Qin, Yexian; Xu, Yanbin; Ingram, Pier; Witte, Russell S; Dong, Feng

    2017-10-01

    The acoustoelectric (AE) effect is a basic physical phenomenon, which underlies the changes made in the conductivity of a medium by the application of focused ultrasound. Recently, based on the AE effect, several biomedical imaging techniques have been widely studied, such as ultrasound-modulated electrical impedance tomography and ultrasound current source density imaging. To further investigate the mechanism of the AE effect in tissue and to provide guidance for such techniques, we have modeled the tissue AE effect using the theory of solid mechanics. Both bulk compression and thermal expansion of tissue are considered and discussed. Computation simulation shows that the muscle AE effect result, conductivity change rate, is 3.26×10 -3 with 4.3-MPa peak pressure, satisfying the theoretical value. Bulk compression plays the main role for muscle AE effect, while thermal expansion makes almost no contribution to it. In addition, the AE signals of porcine muscle are measured at different focal positions. With the same magnitude order and the same change trend, the experiment result confirms that the simulation result is effective. Both simulation and experimental results validate that tissue AE effect modeling using solid mechanics theory is feasible, which is of significance for the further development of related biomedical imaging techniques.

  17. Skeletal muscle, but not cardiovascular function, is altered in a mouse model of autosomal recessive hypophosphatemic rickets

    Directory of Open Access Journals (Sweden)

    Michael J. Wacker

    2016-05-01

    Full Text Available Autosomal recessive hypophosphatemic rickets (ARHR is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL- fast-twitch muscle, soleus (SOL- slow-twitch muscle, heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2a or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In

  18. Structure-function relationship of skeletal muscle provides inspiration for design of new artificial muscle

    Science.gov (United States)

    Gao, Yingxin; Zhang, Chi

    2015-03-01

    A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure-function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure-function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure-function relationship of skeletal muscle into the design of artificial muscle.

  19. Structure–function relationship of skeletal muscle provides inspiration for design of new artificial muscle

    International Nuclear Information System (INIS)

    Gao, Yingxin; Zhang, Chi

    2015-01-01

    A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure–function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure–function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure–function relationship of skeletal muscle into the design of artificial muscle. (topical review)

  20. Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model.

    Science.gov (United States)

    Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Kawaguchi, Naomasa; Nakatani, Satoshi; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

    2016-02-01

    Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P dilated cardiomyopathy heart.

  1. Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

    Directory of Open Access Journals (Sweden)

    Peter A. Bell

    2013-06-01

    Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.

  2. Skeletal Geometry and Indices of Bone Strength in Artistic Gymnasts

    Science.gov (United States)

    Dowthwaite, Jodi N.; Scerpella, Tamara A.

    2010-01-01

    This review addresses bone geometry and indices of skeletal strength associated with exposure to gymnastic loading during growth. A brief background characterizes artistic gymnastics as a mechanical loading model and outlines densitometric techniques, skeletal outcomes and challenges in assessment of skeletal adaptation. The literature on bone geometric adaptation to gymnastic loading is sparse and consists of results for disparate skeletal sites, maturity phases, gender compositions and assessment methods, complicating synthesis of an overriding view. Furthermore, most studies assess only females, with little information on males and adults. Nonetheless, gymnastic loading during growth appears to yield significant enlargement of total and cortical bone geometry (+10 to 30%) and elevation of trabecular density (+20%) in the forearm, yielding elevated indices of skeletal strength (+20 to +50%). Other sites exhibit more moderate geometric and densitometric adaptations (5 to 15%). Mode of adaptation appears to be site-specific; some sites demonstrate marked periosteal and endosteal expansion, whereas other sites exhibit negligible or moderate periosteal expansion coupled with endocortical contraction. Further research is necessary to address sex-, maturity- and bone tissue-specific adaptation, as well as maintenance of benefits beyond loading cessation. PMID:19949278

  3. Statistical Validation of Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Veld, Aart A. van' t; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Radiotherapy Institute Friesland, Leeuwarden (Netherlands)

    2012-09-01

    Purpose: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. Methods and Materials: A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Results: Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Conclusion: Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.

  4. Statistical validation of normal tissue complication probability models.

    Science.gov (United States)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Van't Veld, Aart A; Langendijk, Johannes A; Schilstra, Cornelis

    2012-09-01

    To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Theoretical model of intravascular paramagnetic tracers effect on tissue relaxation

    DEFF Research Database (Denmark)

    Kjølby, Birgitte Fuglsang; Østergaard, Leif; Kiselev, Valerij G

    2006-01-01

    The concentration of MRI tracers cannot be measured directly by MRI and is commonly evaluated indirectly using their relaxation effect. This study develops a comprehensive theoretical model to describe the transverse relaxation in perfused tissue caused by intravascular tracers. The model takes...... into account a number of individual compartments. The signal dephasing is simulated in a semianalytical way by embedding Monte Carlo simulations in the framework of analytical theory. This approach yields a tool for fast, realistic simulation of the change in the transverse relaxation. The results indicate...... with bulk blood. The enhancement of relaxation in tissue is due to the contrast in magnetic susceptibility between blood vessels and parenchyma induced by the presence of paramagnetic tracer. Beyond the perfusion measurements, the results can be applied to quantitation of functional MRI and to vessel size...

  6. Local stem cell depletion model for normal tissue damage

    International Nuclear Information System (INIS)

    Yaes, R.J.; Keland, A.

    1987-01-01

    The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

  7. A model of engineering materials inspired by biological tissues

    Directory of Open Access Journals (Sweden)

    Holeček M.

    2009-12-01

    Full Text Available The perfect ability of living tissues to control and adapt their mechanical properties to varying external conditions may be an inspiration for designing engineering materials. An interesting example is the smooth muscle tissue since this "material" is able to change its global mechanical properties considerably by a subtle mechanism within individual muscle cells. Multi-scale continuum models may be useful in designing essentially simpler engineering materials having similar properties. As an illustration we present the model of an incompressible material whose microscopic structure is formed by flexible, soft but incompressible balls connected mutually by linear springs. This simple model, however, shows a nontrivial nonlinear behavior caused by the incompressibility of balls and is very sensitive on some microscopic parameters. It may elucidate the way by which "small" changes in biopolymer networks within individual muscular cells may control the stiffness of the biological tissue, which outlines a way of designing similar engineering materials. The 'balls and springs' material presents also prestress-induced stiffening and allows elucidating a contribution of extracellular fluids into the tissue’s viscous properties.

  8. Performance of a Deep-Learning Neural Network Model in Assessing Skeletal Maturity on Pediatric Hand Radiographs.

    Science.gov (United States)

    Larson, David B; Chen, Matthew C; Lungren, Matthew P; Halabi, Safwan S; Stence, Nicholas V; Langlotz, Curtis P

    2018-04-01

    Purpose To compare the performance of a deep-learning bone age assessment model based on hand radiographs with that of expert radiologists and that of existing automated models. Materials and Methods The institutional review board approved the study. A total of 14 036 clinical hand radiographs and corresponding reports were obtained from two children's hospitals to train and validate the model. For the first test set, composed of 200 examinations, the mean of bone age estimates from the clinical report and three additional human reviewers was used as the reference standard. Overall model performance was assessed by comparing the root mean square (RMS) and mean absolute difference (MAD) between the model estimates and the reference standard bone ages. Ninety-five percent limits of agreement were calculated in a pairwise fashion for all reviewers and the model. The RMS of a second test set composed of 913 examinations from the publicly available Digital Hand Atlas was compared with published reports of an existing automated model. Results The mean difference between bone age estimates of the model and of the reviewers was 0 years, with a mean RMS and MAD of 0.63 and 0.50 years, respectively. The estimates of the model, the clinical report, and the three reviewers were within the 95% limits of agreement. RMS for the Digital Hand Atlas data set was 0.73 years, compared with 0.61 years of a previously reported model. Conclusion A deep-learning convolutional neural network model can estimate skeletal maturity with accuracy similar to that of an expert radiologist and to that of existing automated models. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on January 19, 2018.

  9. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Steven D Kunkel

    Full Text Available Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II, blood vessel recruitment (Vegfa and autocrine/paracrine IGF-I signaling (Igf1. As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  10. Cyclic Loading of Growing Tissue in a Bioreactor: Mathematical Model and Asymptotic Analysis

    KAUST Repository

    Pohlmeyer, J. V.; Cummings, L. J.

    2013-01-01

    A simplified 2D mathematical model for tissue growth within a cyclically-loaded tissue engineering scaffold is presented and analyzed. Such cyclic loading has the potential to improve yield and functionality of tissue such as bone and cartilage when

  11. Increments in cytokines and matrix metalloproteinases in skeletal muscle after injection of tissue-damaging toxins from the venom of the snake Bothrops asper

    Directory of Open Access Journals (Sweden)

    Alexandra Rucavado

    2002-01-01

    Full Text Available Envenomations by the snake Bothrops asper are characterized by prominent local tissue damage (i.e. myonecrosis, blistering, hemorrhage and edema. Various phospholipases A2 and metalloproteinases that induce local pathological alterations have been purified from this venom. Since these toxins induce a conspicuous inflammatory response, it has been hypothesized that inflammatory mediators may contribute to the local pathological alterations described. This study evaluated the local production of cytokines and matrix metalloproteinases (MMPs as a consequence of intramuscular injections of an Asp-49 myotoxic phospholipase A2 (myotoxin III (MT-III and a P-I type hemorrhagic metalloproteinase (BaP1 isolated from B. asper venom. Both enzymes induced prominent tissue alterations and conspicuous increments in interleukin (IL-1β, IL-6 and a number of MMPs, especially gelatinase MMP-9, rapidly after injection. In contrast, no increments in tumor necrosis factor-α (TNF-α and interferon-γ were detected. In agreement, MT-III and BaP1 did not induce the synthesis of TNF-α by resident peritoneal macrophages in vitro. Despite the conspicuous expression of latent forms of MMPs in muscle, evidenced by zymography, there were no increments in activated MMP-2 and only a small increase in activated MMP-9, as detected by a functional enzymatic assay. This suggests that MMP activity was regulated by a highly controlled activation of latent forms and, probably, by a concomitant synthesis of MMP inhibitors. Since no hemorrhage nor dermonecrosis were observed after injection of MT-III, despite a prominent increase in MMP expression, and since inflammatory exudate did not enhance hemorrhage induced by BaP1, it is suggested that endogenous MMPs released in the tissue are not responsible for the dermonecrosis and hemorrhage characteristic of B. asper envenomation. Moreover, pretreatment of mice with the peptidomimetic MMP inhibitor batimastat did not reduce myotoxic nor

  12. Modeling biological tissue growth: discrete to continuum representations.

    Science.gov (United States)

    Hywood, Jack D; Hackett-Jones, Emily J; Landman, Kerry A

    2013-09-01

    There is much interest in building deterministic continuum models from discrete agent-based models governed by local stochastic rules where an agent represents a biological cell. In developmental biology, cells are able to move and undergo cell division on and within growing tissues. A growing tissue is itself made up of cells which undergo cell division, thereby providing a significant transport mechanism for other cells within it. We develop a discrete agent-based model where domain agents represent tissue cells. Each agent has the ability to undergo a proliferation event whereby an additional domain agent is incorporated into the lattice. If a probability distribution describes the waiting times between proliferation events for an individual agent, then the total length of the domain is a random variable. The average behavior of these stochastically proliferating agents defining the growing lattice is determined in terms of a Fokker-Planck equation, with an advection and diffusion term. The diffusion term differs from the one obtained Landman and Binder [J. Theor. Biol. 259, 541 (2009)] when the rate of growth of the domain is specified, but the choice of agents is random. This discrepancy is reconciled by determining a discrete-time master equation for this process and an associated asymmetric nonexclusion random walk, together with consideration of synchronous and asynchronous updating schemes. All theoretical results are confirmed with numerical simulations. This study furthers our understanding of the relationship between agent-based rules, their implementation, and their associated partial differential equations. Since tissue growth is a significant cellular transport mechanism during embryonic growth, it is important to use the correct partial differential equation description when combining with other cellular functions.

  13. Mathematical models of tumour and normal tissue response

    International Nuclear Information System (INIS)

    Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

    1999-01-01

    The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

  14. Modeling the behavior of human body tissues on penetration

    Science.gov (United States)

    Conci, A.; Brazil, A. L.; Popovici, D.; Jiga, G.; Lebon, F.

    2018-02-01

    Several procedures in medicine (such as anesthesia, injections, biopsies and percutaneous treatments) involve a needle insertion. Such procedures operate without vision of the internal involved areas. Physicians and anesthetists rely on manual (force and tactile) feedback to guide their movements, so a number of medical practice is strongly based on manual skill. In order to be expert in the execution of such procedures the medical students must practice a number of times, but before practice in a real patient they must be trained in some place and a virtual environment, using Virtual Reality (VR) or Augmented Reality (AR) is the best possible solution for such training. In a virtual environment the success of user practices is improved by the addition of force output using haptic device to improve the manual sensations in the interactions between user and computer. Haptic devices enable simulate the physical restriction of the diverse tissues and force reactions to movements of operator hands. The trainees can effectively "feel" the reactions to theirs movements and receive immediate feedback from the actions executed by them in the implemented environment. However, in order to implement such systems, the tissue reaction to penetration and cutting must be modeled. A proper model must emulate the physical sensations of the needle action in the skin, fat, muscle, and so one, as if it really done in a patient that is as they are holding a real needle and feeling each tissue resistance when inserting it through the body. For example an average force value for human skin puncture is 6.0 N, it is 2.0 N for subcutaneous fat tissue and 4.4 N for muscles: this difference of sensations to penetration of each layers trespassed by the needle makes possible to suppose the correct position inside the body. This work presents a model for tissues before and after the cutting that with proper assumptions of proprieties can model any part of human body. It was based on experiments

  15. Biomechanics of cells and tissues experiments, models and simulations

    CERN Document Server

    2013-01-01

    The application of methodological approaches and mathematical formalisms proper to Physics and Engineering to investigate and describe biological processes and design biological structures has led to the development of many disciplines in the context of computational biology and biotechnology. The best known applicative domain is tissue engineering and its branches. Recent domains of interest are in the field of biophysics, e.g.: multiscale mechanics of biological membranes and films and filaments; multiscale mechanics of adhesion; biomolecular motors and force generation.   Modern hypotheses, models, and tools are currently emerging and resulting from the convergence of the methods and philosophical approaches of the different research areas and disciplines. All these emerging approaches share the purpose of disentangling the complexity of organisms, tissues, and cells and mimicking the function of living systems. The contributions presented in this book are current research highlights of six challenging an...

  16. Mathematical model of normal tissue injury in telegammatherapy

    International Nuclear Information System (INIS)

    Belov, S.A.; Lyass, F.M.; Mamin, R.G.; Minakova, E.I.; Raevskaya, S.A.

    1983-01-01

    A model of normal tissue injury as a result of exposure to ionizing radiation is based on an assumption that the degree of tissue injury is determined by the degree of destruction by certain critical cells. The dependence of the number of lethal injuriies on a single dose is expressed by a trinomial - linear and quadratic parts and a constant, obtained as a result of the processing of experimental data. Quantitative correlations have been obtained for the skin and brain. They have been tested using clinical and experimental material. The results of the testing point out to the absence of time dependence on a single up to 6-week irradiation cources. Correlation with an irradiation field has been obtained for the skin. A conclusion has been made that the concept of isoefficacy of irradiation cources is conditional. Spatial-time fractionation is a promising direction in the development of radiation therapy

  17. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

    Energy Technology Data Exchange (ETDEWEB)

    Benny Klimek, Margaret E.; Aydogdu, Tufan [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Link, Majik J.; Pons, Marianne [Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Koniaris, Leonidas G. [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States); Zimmers, Teresa A., E-mail: tzimmers@med.miami.edu [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States)

    2010-01-15

    Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is a devastating complication of cancer associated with poor quality of life and increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We tested how myostatin inhibition might influence cancer cachexia using genetic and pharmacological approaches. First, hypermuscular myostatin null mice were injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice were more sensitive to tumor-induced cachexia, losing more absolute mass and proportionately more muscle mass than wild-type mice. Because myostatin null mice lack expression from development, however, we also sought to manipulate myostatin acutely. The histone deacetylase inhibitor Trichostatin A has been shown to increase muscle mass in normal and dystrophic mice by inducing the myostatin inhibitor, follistatin. Although Trichostatin A administration induced muscle growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia. Finally we sought to inhibit myostatin and related ligands by administration of the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic administration of ACVR2B-Fc potently inhibited muscle wasting and protected adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that host-derived myostatin is not the sole mediator of muscle wasting in cancer. More importantly, skeletal muscle preservation with ACVR2B-Fc establishes that targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an important and potent therapeutic avenue in cancer cachexia.

  18. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

    International Nuclear Information System (INIS)

    Benny Klimek, Margaret E.; Aydogdu, Tufan; Link, Majik J.; Pons, Marianne; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2010-01-01

    Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is a devastating complication of cancer associated with poor quality of life and increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We tested how myostatin inhibition might influence cancer cachexia using genetic and pharmacological approaches. First, hypermuscular myostatin null mice were injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice were more sensitive to tumor-induced cachexia, losing more absolute mass and proportionately more muscle mass than wild-type mice. Because myostatin null mice lack expression from development, however, we also sought to manipulate myostatin acutely. The histone deacetylase inhibitor Trichostatin A has been shown to increase muscle mass in normal and dystrophic mice by inducing the myostatin inhibitor, follistatin. Although Trichostatin A administration induced muscle growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia. Finally we sought to inhibit myostatin and related ligands by administration of the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic administration of ACVR2B-Fc potently inhibited muscle wasting and protected adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that host-derived myostatin is not the sole mediator of muscle wasting in cancer. More importantly, skeletal muscle preservation with ACVR2B-Fc establishes that targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an important and potent therapeutic avenue in cancer cachexia.

  19. Engineered Muscle Actuators: Cells and Tissues

    National Research Council Canada - National Science Library

    Dennis, Robert G; Herr, Hugh; Parker, Kevin K; Larkin, Lisa; Arruda, Ellen; Baar, Keith

    2007-01-01

    .... Our primary objectives were to engineer living skeletal muscle actuators in culture using integrated bioreactors to guide tissue development and to maintain tissue contractility, to achieve 50...

  20. Impact of anesthesia and euthanasia on metabolomics of mammalian tissues: studies in a C57BL/6J mouse model.

    Science.gov (United States)

    Overmyer, Katherine A; Thonusin, Chanisa; Qi, Nathan R; Burant, Charles F; Evans, Charles R

    2015-01-01

    A critical application of metabolomics is the evaluation of tissues, which are often the primary sites of metabolic dysregulation in disease. Laboratory rodents have been widely used for metabolomics studies involving tissues due to their facile handing, genetic manipulability and similarity to most aspects of human metabolism. However, the necessary step of administration of anesthesia in preparation for tissue sampling is not often given careful consideration, in spite of its potential for causing alterations in the metabolome. We examined, for the first time using untargeted and targeted metabolomics, the effect of several commonly used methods of anesthesia and euthanasia for collection of skeletal muscle, liver, heart, adipose and serum of C57BL/6J mice. The data revealed dramatic, tissue-specific impacts of tissue collection strategy. Among many differences observed, post-euthanasia samples showed elevated levels of glucose 6-phosphate and other glycolytic intermediates in skeletal muscle. In heart and liver, multiple nucleotide and purine degradation metabolites accumulated in tissues of euthanized compared to anesthetized animals. Adipose tissue was comparatively less affected by collection strategy, although accumulation of lactate and succinate in euthanized animals was observed in all tissues. Among methods of tissue collection performed pre-euthanasia, ketamine showed more variability compared to isoflurane and pentobarbital. Isoflurane induced elevated liver aspartate but allowed more rapid initiation of tissue collection. Based on these findings, we present a more optimal collection strategy mammalian tissues and recommend that rodent tissues intended for metabolomics studies be collected under anesthesia rather than post-euthanasia.

  1. Impact of Anesthesia and Euthanasia on Metabolomics of Mammalian Tissues: Studies in a C57BL/6J Mouse Model

    Science.gov (United States)

    Overmyer, Katherine A.; Thonusin, Chanisa; Qi, Nathan R.; Burant, Charles F.; Evans, Charles R.

    2015-01-01

    A critical application of metabolomics is the evaluation of tissues, which are often the primary sites of metabolic dysregulation in disease. Laboratory rodents have been widely used for metabolomics studies involving tissues due to their facile handing, genetic manipulability and similarity to most aspects of human metabolism. However, the necessary step of administration of anesthesia in preparation for tissue sampling is not often given careful consideration, in spite of its potential for causing alterations in the metabolome. We examined, for the first time using untargeted and targeted metabolomics, the effect of several commonly used methods of anesthesia and euthanasia for collection of skeletal muscle, liver, heart, adipose and serum of C57BL/6J mice. The data revealed dramatic, tissue-specific impacts of tissue collection strategy. Among many differences observed, post-euthanasia samples showed elevated levels of glucose 6-phosphate and other glycolytic intermediates in skeletal muscle. In heart and liver, multiple nucleotide and purine degradation metabolites accumulated in tissues of euthanized compared to anesthetized animals. Adipose tissue was comparatively less affected by collection strategy, although accumulation of lactate and succinate in euthanized animals was observed in all tissues. Among methods of tissue collection performed pre-euthanasia, ketamine showed more variability compared to isoflurane and pentobarbital. Isoflurane induced elevated liver aspartate but allowed more rapid initiation of tissue collection. Based on these findings, we present a more optimal collection strategy mammalian tissues and recommend that rodent tissues intended for metabolomics studies be collected under anesthesia rather than post-euthanasia. PMID:25658945

  2. Faster and stronger manifestation of mitochondrial diseases in skeletal muscle than in heart related to cytosolic inorganic phosphate (Pi) accumulation.

    Science.gov (United States)

    Korzeniewski, Bernard

    2016-08-01

    A model of the cell bioenergetic system was used to compare the effect of oxidative phosphorylation (OXPHOS) deficiencies in a broad range of moderate ATP demand in skeletal muscle and heart. Computer simulations revealed that kinetic properties of the system are similar in both cases despite the much higher mitochondria content and "basic" OXPHOS activity in heart than in skeletal muscle, because of a much higher each-step activation (ESA) of OXPHOS in skeletal muscle than in heart. Large OXPHOS deficiencies lead in both tissues to a significant decrease in oxygen consumption (V̇o2) and phosphocreatine (PCr) and increase in cytosolic ADP, Pi, and H(+) The main difference between skeletal muscle and heart is a much higher cytosolic Pi concentration in healthy tissue and much higher cytosolic Pi accumulation (level) at low OXPHOS activities in the former, caused by a higher PCr level in healthy tissue (and higher total phosphate pool) and smaller Pi redistribution between cytosol and mitochondria at OXPHOS deficiency. This difference does not depend on ATP demand in a broad range. A much greater Pi increase and PCr decrease during rest-to-moderate work transition in skeletal muscle at OXPHOS deficiencies than at normal OXPHOS activity significantly slows down the V̇o2 on-kinetics. Because high cytosolic Pi concentrations cause fatigue in skeletal muscle and can compromise force generation in skeletal muscle and heart, this system property can contribute to the faster and stronger manifestation of mitochondrial diseases in skeletal muscle than in heart. Shortly, skeletal muscle with large OXPHOS deficiencies becomes fatigued already during low/moderate exercise. Copyright © 2016 the American Physiological Society.

  3. Developmental expression of the alpha-skeletal actin gene

    Directory of Open Access Journals (Sweden)

    Vonk Freek J

    2008-06-01

    Full Text Available Abstract Background Actin is a cytoskeletal protein which exerts a broad range of functions in almost all eukaryotic cells. In higher vertebrates, six primary actin isoforms can be distinguished: alpha-skeletal, alpha-cardiac, alpha-smooth muscle, gamma-smooth muscle, beta-cytoplasmic and gamma-cytoplasmic isoactin. Expression of these actin isoforms during vertebrate development is highly regulated in a temporal and tissue-specific manner, but the mechanisms and the specific differences are currently not well understood. All members of the actin multigene family are highly conserved, suggesting that there is a high selective pressure on these proteins. Results We present here a model for the evolution of the genomic organization of alpha-skeletal actin and by molecular modeling, illustrate the structural differences of actin proteins of different phyla. We further describe and compare alpha-skeletal actin expression in two developmental stages of five vertebrate species (mouse, chicken, snake, salamander and fish. Our findings confirm that alpha-skeletal actin is expressed in skeletal muscle and in the heart of all five species. In addition, we identify many novel non-muscular expression domains including several in the central nervous system. Conclusion Our results show that the high sequence homology of alpha-skeletal actins is reflected by similarities of their 3 dimensional protein structures, as well as by conserved gene expression patterns during vertebrate development. Nonetheless, we find here important differences in 3D structures, in gene architectures and identify novel expression domains for this structural and functional important gene.

  4. Electrode-tissues interface: modeling and experimental validation

    International Nuclear Information System (INIS)

    Sawan, M; Laaziri, Y; Mounaim, F; Elzayat, E; Corcos, J; Elhilali, M M

    2007-01-01

    The electrode-tissues interface (ETI) is one of the key issues in implantable devices such as stimulators and sensors. Once the stimulator is implanted, safety and reliability become more and more critical. In this case, modeling and monitoring of the ETI are required. We propose an empirical model for the ETI and a dedicated integrated circuit to measure its corresponding complex impedance. These measurements in the frequency range of 1 Hz to 100 kHz were achieved in acute dog experiments. The model demonstrates a closer fitting with experimental measurements. In addition, a custom monitoring device based on a stimuli current generator has been completed to evaluate the phase shift and voltage across the electrodes and to transmit wirelessly the values to an external controller. This integrated circuit has been fabricated in a CMOS 0.18 μm process, which consumes 4 mW only during measurements and occupies an area of 1 mm 2 . (review article)

  5. A Pharmacokinetic Model of a Tissue Implantable Cortisol Sensor.

    Science.gov (United States)

    Lee, Michael A; Bakh, Naveed; Bisker, Gili; Brown, Emery N; Strano, Michael S

    2016-12-01

    Cortisol is an important glucocorticoid hormone whose biochemistry influences numerous physiological and pathological processes. Moreover, it is a biomarker of interest for a number of conditions, including posttraumatic stress disorder, Cushing's syndrome, Addison's disease, and others. An implantable biosensor capable of real time monitoring of cortisol concentrations in adipose tissue may revolutionize the diagnosis and treatment of these disorders, as well as provide an invaluable research tool. Toward this end, a mathematical model, informed by the physiological literature, is developed to predict dynamic cortisol concentrations in adipose, muscle, and brain tissues, where a significant number of important processes with cortisol occur. The pharmacokinetic model is applied to both a prototypical, healthy male patient and a previously studied Cushing's disease patient. The model can also be used to inform the design of an implantable sensor by optimizing the sensor dissociation constant, apparent delay time, and magnitude of the sensor output versus system dynamics. Measurements from such a sensor would help to determine systemic cortisol levels, providing much needed insight for proper medical treatment for various cortisol-related conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Ethical tissue: a not-for-profit model for human tissue supply.

    Science.gov (United States)

    Adams, Kevin; Martin, Sandie

    2011-02-01

    Following legislative changes in 2004 and the establishment of the Human Tissue Authority, access to human tissues for biomedical research became a more onerous and tightly regulated process. Ethical Tissue was established to meet the growing demand for human tissues, using a process that provided ease of access by researchers whilst maintaining the highest ethical and regulatory standards. The establishment of a licensed research tissue bank entailed several key criteria covering ethical, legal, financial and logistical issues being met. A wide range of stakeholders, including the HTA, University of Bradford, flagged LREC, hospital trusts and clinical groups were also integral to the process.

  7. Temperature Change When Drilling Near the Distal Femoral Physis in a Skeletally Immature Ovine Model.

    Science.gov (United States)

    Tenfelde, Allison M; Esquivel, Amanda O; Cracchiolo, Allison M; Lemos, Stephen E

    2016-01-01

    The possibility of physeal injury during anterior cruciate ligament reconstruction in the pediatric population is a concern. The purpose of this study was to determine whether drilling at or near the physis could cause a temperature increase that could trigger chondrolysis. Skeletally immature cadaveric lamb distal femurs were used for this study and randomly placed in 1 of 6 groups (n=10 in each group). We examined the 8 and 10 mm Flipcutter at a distance of 0.5 mm from the physis and an 8 and 10 mm acorn-tipped reamer at a distance of 0.5 and 3.0 mm from the physis. During drilling, temperature change at the distal femoral physis was continuously measured until the temperature decreased to the original value. An interreamer comparison yielded a significant difference when drilling 0.5 mm from the physis (P=0.001). Pair-wise Mann-Whitney post hoc tests were performed to further evaluate the differences among the groups. The 8 mm FlipCutter had a significantly higher maximum temperature (39.8±1.4°C) compared with the 10 mm FlipCutter (38.0±0.6°C, P=0.001), 8 mm acorn-tipped reamer (38.1±0.9°C, P=0.007), and 10 mm acorn-tipped reamer (37.5±0.3°C, Pdrilling technique, when a traditional acorn-tipped reamer over a guidepin is utilized, even if the drilling occurs very close to the physis. In addition, the risk of drilling with a FlipCutter is low, but may be greater than a traditional reamer. Thermal-induced necrosis is a realistic concern, due to the characteristics of the distal femoral physis, and the propensity for this physis to respond poorly to injury. Our study supports that drilling near the physis can be done safely, although smaller reamers and nontraditional designs may generate higher heat. Level I-basic science.

  8. Genetic engineering for skeletal regenerative medicine.

    Science.gov (United States)

    Gersbach, Charles A; Phillips, Jennifer E; García, Andrés J

    2007-01-01

    The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.

  9. Diet-induced weight loss and exercise alone and in combination enhance the expression of adiponectin receptors in adipose tissue and skeletal muscle, but only diet-induced weight loss enhanced circulating adiponectin

    DEFF Research Database (Denmark)

    Christiansen, Tore; Paulsen, Søren K; Bruun, Jens M

    2009-01-01

    and adiponectin receptors (AdipoR) in adipose tissue (AT) and skeletal muscle (SM). Design and Methods: Seventy-nine obese males and females were randomized into the following: 1) exercise only (12 wk of exercise without diet restriction); 2) hypocaloric diet [8 wk of very low energy diet (600 kcal/d) followed...... by 4 wk with a weight maintenance diet]; and 3) hypocaloric diet and exercise (DEX; 8 wk very low energy diet 800 kcal/d followed by 4 wk weight maintenance diet combined with exercise throughout the 12 wk). Blood samples and biopsies from sc abdominal AT and SM were collected at baseline and after 12...... in all three groups (all P hypocaloric diet groups (both P

  10. 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.

  11. Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

    Science.gov (United States)

    Osaki, Yoshinori; Nakagawa, Yoshimi; Miyahara, Shoko; Iwasaki, Hitoshi; Ishii, Akiko; Matsuzaka, Takashi; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Sone, Hirohito; Ohashi, Ken; Ishibashi, Shun; Yamada, Nobuhiro; Shimano, Hitoshi

    2015-10-23

    HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Options and pitfalls of normal tissues complication probability models

    International Nuclear Information System (INIS)

    Dorr, Wolfgang

    2011-01-01

    Full text: Technological improvements in the physical administration of radiotherapy have led to increasing conformation of the treatment volume (TV) with the planning target volume (PTV) and of the irradiated volume (IV) with the TV. In this process of improvement of the physical quality of radiotherapy, the total volumes of organs at risk exposed to significant doses have significantly decreased, resulting in increased inhomogeneities in the dose distributions within these organs. This has resulted in a need to identify and quantify volume effects in different normal tissues. Today, irradiated volume today must be considered a 6t h 'R' of radiotherapy, in addition to the 5 'Rs' defined by Withers and Steel in the mid/end 1980 s. The current status of knowledge of these volume effects has recently been summarized for many organs and tissues by the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) initiative [Int. J. Radiat. Oncol. BioI. Phys. 76 (3) Suppl., 2010]. However, the concept of using dose-volume histogram parameters as a basis for dose constraints, even without applying any models for normal tissue complication probabilities (NTCP), is based on (some) assumptions that are not met in clinical routine treatment planning. First, and most important, dose-volume histogram (DVH) parameters are usually derived from a single, 'snap-shot' CT-scan, without considering physiological (urinary bladder, intestine) or radiation induced (edema, patient weight loss) changes during radiotherapy. Also, individual variations, or different institutional strategies of delineating organs at risk are rarely considered. Moreover, the reduction of the 3-dimentional dose distribution into a '2dimensl' DVH parameter implies that the localization of the dose within an organ is irrelevant-there are ample examples that this assumption is not justified. Routinely used dose constraints also do not take into account that the residual function of an organ may be

  13. Model of Ca(2+) Concentration Controlled by Sarcoplasmic Reticulum of Skeletal Muscle, Using the State Transition

    National Research Council Canada - National Science Library

    Yokota, M

    2001-01-01

    ...). This report proposed a model that represents Ca(2+) in a muscle cell controlled by the SR using a state transition probability model in which one state means that protein in the SR is binding ligands, and the other...

  14. Modeling of light absorption in tissue during infrared neural stimulation

    Science.gov (United States)

    Thompson, Alexander C.; Wade, Scott A.; Brown, William G. A.; Stoddart, Paul R.

    2012-07-01

    A Monte Carlo model has been developed to simulate light transport and absorption in neural tissue during infrared neural stimulation (INS). A range of fiber core sizes and numerical apertures are compared illustrating the advantages of using simulations when designing a light delivery system. A range of wavelengths, commonly used for INS, are also compared for stimulation of nerves in the cochlea, in terms of both the energy absorbed and the change in temperature due to a laser pulse. Modeling suggests that a fiber with core diameter of 200 μm and NA=0.22 is optimal for optical stimulation in the geometry used and that temperature rises in the spiral ganglion neurons are as low as 0.1°C. The results show a need for more careful experimentation to allow different proposed mechanisms of INS to be distinguished.

  15. The assessment of cold atmospheric plasma treatment of DNA in synthetic models of tissue fluid, tissue and cells

    Science.gov (United States)

    Szili, Endre J.; Gaur, Nishtha; Hong, Sung-Ha; Kurita, Hirofumi; Oh, Jun-Seok; Ito, Masafumi; Mizuno, Akira; Hatta, Akimitsu; Cowin, Allison J.; Graves, David B.; Short, Robert D.

    2017-07-01

    There is a growing literature database that demonstrates the therapeutic potential of cold atmospheric plasma (herein referred to as plasma). Given the breadth of proposed applications (e.g. from teeth whitening to cancer therapy) and vast gamut of plasma devices being researched, it is timely to consider plasma interactions with specific components of the cell in more detail. Plasma can produce highly reactive oxygen and nitrogen species (RONS) such as the hydroxyl radical (OH•), peroxynitrite (ONOO-) and superoxide (\\text{O}2- ) that would readily modify essential biomolecules such as DNA. These modifications could in principle drive a wide range of biological processes. Against this possibility, the reported therapeutic action of plasmas are not underpinned by a particularly deep knowledge of the potential plasma-tissue, -cell or -biomolecule interactions. In this study, we aim to partly address this issue by developing simple models to study plasma interactions with DNA, in the form of DNA-strand breaks. This is carried out using synthetic models of tissue fluid, tissue and cells. We argue that this approach makes experimentation simpler, more cost-effective and faster than compared to working with real biological materials and cells. Herein, a helium plasma jet source was utilised for these experiments. We show that the plasma jet readily induced DNA-strand breaks in the tissue fluid model and in the cell model, surprisingly without any significant poration or rupture of the phospholipid membrane. In the plasma jet treatment of the tissue model, DNA-strand breaks were detected in the tissue mass after pro-longed treatment (on the time-scale of minutes) with no DNA-strand breaks being detected in the tissue fluid model underneath the tissue model. These data are discussed in the context of the therapeutic potential of plasma.

  16. Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia.

    Science.gov (United States)

    Conte, Elena; Camerino, Giulia Maria; Mele, Antonietta; De Bellis, Michela; Pierno, Sabata; Rana, Francesco; Fonzino, Adriano; Caloiero, Roberta; Rizzi, Laura; Bresciani, Elena; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Martinez, Jean; Giustino, Arcangela; Mariggiò, Maria Addolorata; Coluccia, Mauro; Tricarico, Domenico; Lograno, Marcello Diego; De Luca, Annamaria; Torsello, Antonio; Conte, Diana; Liantonio, Antonella

    2017-06-01

    Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose-limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium-dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS-R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood. By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast-twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin-induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention. Cisplatin-treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up-regulation of atrogin1/Murf-1 genes and a down-regulation of Pgc1-a gene, all indexes of muscle atrophy, and by a two-fold increase in resting intracellular calcium, [Ca 2+ ] i , compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store-operated calcium entry were ~50% significantly reduced in cisplatin-treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in

  17. Experimental Human Cell and Tissue Models of Pemphigus

    Science.gov (United States)

    van der Wier, Gerda; Pas, Hendri H.; Jonkman, Marcel F.

    2010-01-01

    Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model. PMID:20585596

  18. Training for laparoscopic Nissen fundoplication with a newly designed model: a replacement for animal tissue models?

    Science.gov (United States)

    Christie, Lorna; Goossens, Richard; Jakimowicz, Jack J.

    2010-01-01

    Background To bridge the early learning curve for laparoscopic Nissen fundoplication from the clinical setting to a safe environment, training models can be used. This study aimed to develop a reusable, low-cost model to be used for training in laparoscopic Nissen fundoplication procedure as an alternative to the use of animal tissue models. Methods From artificial organs and tissue, an anatomic model of the human upper abdomen was developed for training in performing laparoscopic Nissen fundoplication. The 20 participants and tutors in the European Association for Endoscopic Surgery (EAES) upper gastrointestinal surgery course completed four complementary tasks of laparoscopic Nissen fundoplication with the artificial model, then compared the realism, haptic feedback, and training properties of the model with those of animal tissue models. Results The main difference between the two training models was seen in the properties of the stomach. The wrapping of the stomach in the artificial model was rated significantly lower than that in the animal tissue model (mean, 3.6 vs. 4.2; p = 0.010). The main criticism of the stomach of the artificial model was that it was too rigid for making a proper wrap. The suturing of the stomach wall, however, was regarded as fairly realistic (mean, 3.6). The crura on the artificial model were rated better (mean, 4.3) than those on the animal tissue (mean, 4.0), although the difference was not significant. The participants regarded the model as a good to excellent (mean, 4.3) training tool. Conclusion The newly developed model is regarded as a good tool for training in laparoscopic Nissen fundoplication procedure. It is cheaper, more durable, and more readily available for training and can therefore be used in every training center. The stomach of this model, however, still needs improvement because it is too rigid for making the wrap. PMID:20526629

  19. L-carnitine pretreatment protects slow-twitch skeletal muscles in a rat model of ischemia-reperfusion injury.

    Science.gov (United States)

    Demirel, Mert; Kaya, Burak; Cerkez, Cem; Ertunc, Mert; Sara, Yildirim

    2013-10-01

    Ischemia-reperfusion (I/R) injury negatively affects the outcome of surgical interventions for amputated or severely traumatized extremities. This study aimed to evaluate the protective role of l-carnitine on the contractile properties of fast-twitch (extensor digitorum longus [EDL]) and slow-twitch (soleus [SOL]) skeletal muscles following I/R-induced injury in a rat model. Rats were divided into 4 groups (1) saline pretreatment, (2) l-carnitine pretreatment, (3) saline pretreatment and I/R, and (4) l-carnitine pretreatment and I/R. Twitch and tetanic contractions in the EDL and SOL muscles in each group were recorded. Additionally, a fatigue protocol was performed in these muscles. Twitch and tetanic contraction amplitudes were lower in the EDL and SOL muscles in which I/R was induced (P contraction amplitude in the SOL muscles following I/R (P muscles. l-Carnitine pretreatment did not alter the fatigue response in any of the muscles.

  20. A structural model of the pore-forming region of the skeletal muscle ryanodine receptor (RyR1.

    Directory of Open Access Journals (Sweden)

    Srinivas Ramachandran

    2009-04-01

    Full Text Available Ryanodine receptors (RyRs are ion channels that regulate muscle contraction by releasing calcium ions from intracellular stores into the cytoplasm. Mutations in skeletal muscle RyR (RyR1 give rise to congenital diseases such as central core disease. The absence of high-resolution structures of RyR1 has limited our understanding of channel function and disease mechanisms at the molecular level. Here, we report a structural model of the pore-forming region of RyR1. Molecular dynamics simulations show high ion binding to putative pore residues D4899, E4900, D4938, and D4945, which are experimentally known to be critical for channel conductance and selectivity. We also observe preferential localization of Ca(2+ over K(+ in the selectivity filter of RyR1. Simulations of RyR1-D4899Q mutant show a loss of preference to Ca(2+ in the selectivity filter as seen experimentally. Electrophysiological experiments on a central core disease mutant, RyR1-G4898R, show constitutively open channels that conduct K(+ but not Ca(2+. Our simulations with G4898R likewise show a decrease in the preference of Ca(2+ over K(+ in the selectivity filter. Together, the computational and experimental results shed light on ion conductance and selectivity of RyR1 at an atomistic level.

  1. Validation of transport measurements in skeletal muscle with N-13 amino acids using a rabbit isolated hindlimb model

    International Nuclear Information System (INIS)

    Conlon, K.C.; Bading, J.R.; DiResta, G.R.; Corbally, M.T.; Gelbard, A.S.; Brennan, M.F.

    1989-01-01

    The authors are studying the transport of C-11 and N-13 labeled amino acids in tumor-bearing rabbits to determine the role of amino acid transport in the pathogenesis of muscle wasting in cancer. To validate a new, in vivo, method for measuring transport in skeletal muscle with these compounds, an isolated hindlimb model was developed in rabbits. The limb was perfused with a non-recirculating, normothermic, constant pressure system and a cell-free perfusate. Hemodynamic and metabolic parameters were measured during the first 75 min. of perfusion and found to remain normal and stable. Flow varied directly with perfusion pressure over the normal range of resting flows in the intact rabbit hindlimb. Time-activity curves (TAC's) were recorded from the medial thigh following bolus co-injection of L-[amide N-13] glutamine or N-13 L-glutamate with Tc-99m human serum albumin (HSA) into the femoral artery. Regional plasma flow was determined from the Tc-99m data

  2. A Tissue Engineered Model of Aging: Interdependence and Cooperative Effects in Failing Tissues.

    Science.gov (United States)

    Acun, A; Vural, D C; Zorlutuna, P

    2017-07-11

    Aging remains a fundamental open problem in modern biology. Although there exist a number of theories on aging on the cellular scale, nearly nothing is known about how microscopic failures cascade to macroscopic failures of tissues, organs and ultimately the organism. The goal of this work is to bridge microscopic cell failure to macroscopic manifestations of aging. We use tissue engineered constructs to control the cellular-level damage and cell-cell distance in individual tissues to establish the role of complex interdependence and interactions between cells in aging tissues. We found that while microscopic mechanisms drive aging, the interdependency between cells plays a major role in tissue death, providing evidence on how cellular aging is connected to its higher systemic consequences.

  3. Analytical model of diffuse reflectance spectrum of skin tissue

    Energy Technology Data Exchange (ETDEWEB)

    Lisenko, S A; Kugeiko, M M; Firago, V A [Belarusian State University, Minsk (Belarus); Sobchuk, A N [B.I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk (Belarus)

    2014-01-31

    We have derived simple analytical expressions that enable highly accurate calculation of diffusely reflected light signals of skin in the spectral range from 450 to 800 nm at a distance from the region of delivery of exciting radiation. The expressions, taking into account the dependence of the detected signals on the refractive index, transport scattering coefficient, absorption coefficient and anisotropy factor of the medium, have been obtained in the approximation of a two-layer medium model (epidermis and dermis) for the same parameters of light scattering but different absorption coefficients of layers. Numerical experiments on the retrieval of the skin biophysical parameters from the diffuse reflectance spectra simulated by the Monte Carlo method show that commercially available fibre-optic spectrophotometers with a fixed distance between the radiation source and detector can reliably determine the concentration of bilirubin, oxy- and deoxyhaemoglobin in the dermis tissues and the tissue structure parameter characterising the size of its effective scatterers. We present the examples of quantitative analysis of the experimental data, confirming the correctness of estimates of biophysical parameters of skin using the obtained analytical expressions. (biophotonics)

  4. Luminol testing in detecting modern human skeletal remains: a test on different types of bone tissue and a caveat for PMI interpretation.

    Science.gov (United States)

    Caudullo, Giorgio; Caruso, Valentina; Cappella, Annalisa; Sguazza, Emanuela; Mazzarelli, Debora; Amadasi, Alberto; Cattaneo, Cristina

    2017-01-01

    When forensic pathologists and anthropologists have to deal with the evaluation of the post-mortem interval (PMI) in skeletal remains, luminol testing is frequently performed as a preliminary screening method. However, the repeatability of this test on the same bone, as well as comparative studies on different bones of the same individual, has never been performed. Therefore, with the aim of investigating the influence that different types of bones may exert on the response to the luminol test, the present study analysed three different skeletal elements (femoral diaphysis, vertebra and cranial vault), gathered from ten recent exhumed skeletons (all with a 20-year PMI). The analysis was performed twice on the same bone after 2 months: the analysis at time 0 concerned the whole bone, whereas the second concerned only a part of the same bone taken during the first test (which already had been broken). The overall results showed different responses, depending on the type of bone and on the integrity of the samples. Negative results at the first analysis (6.6% out of the total of samples) are consistent with what is reported in the literature, whilst at the second analysis, the increase of about 20% of false-negative results highlights that the luminol test ought to be performed with caution in case of broken bones or elements which are taphonomically altered. Results have thus proven that the exposition to environmental agents might result in haemoglobin (Hb) loss, as detected even after only 2 months. The study also focused on the crucial issue of the type of bone subjected to testing, remarking the suitability of the femoral diaphysis (100% of positive responses at the first analysis vs only 18% of false-negative results at the second test, corresponding to 5% of total false-negative results) as opposed to other bone elements that showed a low yield. In particular, the cranial vault gave poor results, with 40% of discrepancy between results from the two analyses

  5. Muscle-skeletal model of the thigh: a tool for understanding the biomechanics of gait in patients with cerebral palsy

    Science.gov (United States)

    Ravera, Emiliano Pablo; Catalfamo Formento, Paola Andrea; José Crespo, Marcos; Andrés Braidot, Ariel

    2011-12-01

    Cerebral Palsy represents the most common cause of physical disability in modern world and within the pediatrics orthopedics units. The gait analysis provides great contributions to the understanding of gait disorders in CP. Giving a more comprehensive treatment plan, including or excluding surgical procedures that can potentially decrease the number of surgical interventions in the life of these patients. Recommendations for orthopedic surgery may be based on a quantitative description of how to alter the properties probably muscle force generation, and how this affects the action of the muscle to determine how these muscles, impaired by disease or surgery, contributing to the movement of the segments of the limb during crouch gait. So the causes and appropriate treatment of gait abnormalities are difficult to determine because the movements generated by the muscular forces of these patients are not clearly understood. A correct determination of the etiology of abnormal patterns of the knee is the key to select the appropriate therapy, presenting a major challenge at present since there is no theoretical basis to determine the biomechanical causes of abnormal gait of these patients. The potential and necessity of using correct biomechanical models that consistently study the abnormalities becomes clear. Reinforcing and correcting a simple gait analysis and eliminating the unknowns when selecting the appropriate treatment is crucial in clinical settings. In this paper a computer muscle-skeletal model is proposed. The model represents a person's thigh simulating the six most representative muscles and joints of the hip and knee. In this way you can have a better understanding of gait abnormalities present in these patients. So the quality of these estimates of individual muscle dynamics facilitate better understanding of the biomechanics of gait pathologies helping to reach better diagnosis prior to surgery and rehabilitation treatments.

  6. Muscle-skeletal model of the thigh: a tool for understanding the biomechanics of gait in patients with cerebral palsy

    International Nuclear Information System (INIS)

    Ravera, Emiliano Pablo; Catalfamo Formento, Paola Andrea; Crespo, Marcos José; Braidot, Ariel Andrés

    2011-01-01

    Cerebral Palsy represents the most common cause of physical disability in modern world and within the pediatrics orthopedics units. The gait analysis provides great contributions to the understanding of gait disorders in CP. Giving a more comprehensive treatment plan, including or excluding surgical procedures that can potentially decrease the number of surgical interventions in the life of these patients. Recommendations for orthopedic surgery may be based on a quantitative description of how to alter the properties probably muscle force generation, and how this affects the action of the muscle to determine how these muscles, impaired by disease or surgery, contributing to the movement of the segments of the limb during crouch gait. So the causes and appropriate treatment of gait abnormalities are difficult to determine because the movements generated by the muscular forces of these patients are not clearly understood. A correct determination of the etiology of abnormal patterns of the knee is the key to select the appropriate therapy, presenting a major challenge at present since there is no theoretical basis to determine the biomechanical causes of abnormal gait of these patients. The potential and necessity of using correct biomechanical models that consistently study the abnormalities becomes clear. Reinforcing and correcting a simple gait analysis and eliminating the unknowns when selecting the appropriate treatment is crucial in clinical settings. In this paper a computer muscle-skeletal model is proposed. The model represents a person's thigh simulating the six most representative muscles and joints of the hip and knee. In this way you can have a better understanding of gait abnormalities present in these patients. So the quality of these estimates of individual muscle dynamics facilitate better understanding of the biomechanics of gait pathologies helping to reach better diagnosis prior to surgery and rehabilitation treatments.

  7. Simulating the activation, contraction and movement of skeletal muscles using the bidomain model.

    Science.gov (United States)

    Lopez Rincon, A; Cantu, C; Soto, R; Shimoda, S

    2016-08-01

    A simulation of the muscle activation, contraction and movement is here presented. This system was developed based on the Bidomain mathematical model of the electrical propagation in muscles. This study shows an electrical stimuli input to a muscle and how this behave. The comparison between healthy subject and patient with muscle activation impairment is depicted, depending on whether the signal reaches a threshold. A 3D model of a bicep muscle and a forearm bone connected was constructed using OpenGL. This platform could be used for development of controllers for biomechatronic systems in future works. This kind of bioinspired model could be used for a better understanding of the neuromotor system.

  8. A Mathematical Model of Skeletal Muscle Disease and Immune Response in the mdx Mouse

    Directory of Open Access Journals (Sweden)

    Abdul Salam Jarrah

    2014-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is a genetic disease that results in the death of affected boys by early adulthood. The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a significant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared.

  9. Role of Akirin in Skeletal Myogenesis

    Directory of Open Access Journals (Sweden)

    Dingbiao Long

    2013-02-01

    Full Text Available Akirin is a recently discovered nuclear factor that plays an important role in innate immune responses. Beyond its role in innate immune responses, Akirin has recently been shown to play an important role in skeletal myogenesis. In this article, we will briefly review the structure and tissue distribution of Akirin and discuss recent advances in our understanding of its role and signal pathway in skeletal myogenesis.

  10. A functional model for adult stem cells in epithelial tissues.

    NARCIS (Netherlands)

    Verstappen, J.; Katsaros, C.; Torensma, R.; Hoff, J.W. Von den

    2009-01-01

    Tissue turnover, regeneration, and repair take place throughout life. Stem cells are key players in these processes. The characteristics and niches of the stem cell populations in different tissues, and even in related tissues, vary extensively. In this review, stem cell differentiation and stem

  11. Blood flow in skin, subcutaneous adipose tissue and skeletal muscle in the forearm of normal man during an oral glucose load

    DEFF Research Database (Denmark)

    Bülow, J; Astrup, A; Christensen, N J

    1987-01-01

    Blood flow to the forearm, and the subcutaneous tissue and skin in the forearm were measured by strain gauge plethysmography, 133Xe-elimination and Laser Doppler flowmetry during an oral glucose load (I g glucose kg-1 lean body mass) and during control conditions. The forearm blood flow remained...... constant during both experiments. Glucose induced a two-fold vasodilatation in subcutaneous tissue. In skin, glucose induced a relative vasodilatation and later a relative vasoconstriction compared with control experiments. When estimated from forearm blood flow and subcutaneous and skin blood flows......, muscle blood flow decreased about 20-30% during both experiments. Proximal nervous blockade did not abolish the glucose-induced vasodilatation in subcutaneous tissue. In the glucose experiment, arterial glucose concentration increased to 7.8 +/- 1.17 mmol l-1 30 min after the load was given...

  12. Decellularized Human Skeletal Muscle as Biologic Scaffold for Reconstructive Surgery

    Directory of Open Access Journals (Sweden)

    Andrea Porzionato

    2015-07-01

    Full Text Available Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin-EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation.

  13. Elastic properties of synthetic materials for soft tissue modeling

    International Nuclear Information System (INIS)

    Mansy, H A; Grahe, J R; Sandler, R H

    2008-01-01

    Mechanical models of soft tissue are useful for studying vibro-acoustic phenomena. They may be used for validating mathematical models and for testing new equipment and techniques. The objective of this study was to measure density and visco-elastic properties of synthetic materials that can be used to build such models. Samples of nine different materials were tested under dynamic (0.5 Hz) compressive loading conditions. The modulus of elasticity of the materials was varied, whenever possible, by adding a softener during manufacturing. The modulus was measured over a nine month period to quantify the effect of ageing and softener loss on material properties. Results showed that a wide range of the compression elasticity modulus (10 to 1400 kPa) and phase (3.5 0 -16.7 0 ) between stress and strain were possible. Some materials tended to exude softener over time, resulting in a weight loss and elastic properties change. While the weight loss under normal conditions was minimal in all materials (<3% over nine months), loss under accelerated weight-loss conditions can reach 59%. In the latter case an elasticity modulus increase of up to 500% was measured. Key advantages and limitations of candidate materials were identified and discussed

  14. Satellite cell proliferation in adult skeletal muscle

    Science.gov (United States)

    Booth, Frank W. (Inventor); Thomason, Donald B. (Inventor); Morrison, Paul R. (Inventor); Stancel, George M. (Inventor)

    1995-01-01

    Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

  15. Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

    Directory of Open Access Journals (Sweden)

    Teruyo Oishi

    Full Text Available Heterotopic ossification (HO is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+ and PDGFRα(+ cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+ cells and PDGFRα(+ cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+ cells formed bone-like tissue and showed successful engraftment, while CD56(+ cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+ cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+ cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+ cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+ cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+ cells. Our results suggest that PDGFRα(+ cells may be the major source of HO and that the newly identified mi

  16. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1994-01-01

    have performed experiments to determine whether mechanical stimulation of cultured avian muscle cells alters their response to anabolic steroids or glucocorticoids. In static cultures, testosterone had no effect on muscle cell growth, but 5alpha-dihydrotestosterone and the synthetic steroid stanozolol increased cell growth by up to 18% and 30%, respectively, after a three day exposure. We completed development of a new IBM-based mechanical cell stimulator system to provide greater flexibility in operating and monitoring our experiments. Our previous long term studies on myofiber growth were designed around a perfusion system of our own design. We have recently changed to performing these studies using a modified CELLCO cartridge bioreactor system Z since it has been certified as the ground-based model for the Shuttle's Space Tissue Loss (STL) F= Cell Culture Module. The current goals of this aspect of the project are three fold: 1) to design a Z cell culture system for studying avian skeletal myofiber atrophy on the Shuttle and Space Station; 0 2) to expand the use of bioreactors to cells which do not grow in either suspension or attached to the hollow fibers; and 3) to combine the bioreactor system with our computerized mechanical cell stimulator to have a better in vitro model to study tension/gravity/stretch regulation of skeletal muscle size. Preliminary studies also reported on involved : (1) how release of tension can induce rapid atrophy of tissues cultured avian skeletal muscle cells, and (2) a mechanism to transfer and maintain avian skeletal muscle organoids in modified cartridges in the Space Tissue Loss Module.

  17. Phytanic acid stimulates glucose uptake in a model of skeletal muscles, the primary porcine myotubes

    DEFF Research Database (Denmark)

    Che, Brita Ngum; Oksbjerg, Niels; Hellgren, Lars

    2013-01-01

    and tritiated 2-deoxyglucose (2-DOG) was used to measure glucose uptake, in relation to PA and 2-DOG exposure times and also in relation to PA and insulin concentrations. The MIXED procedure model of SAS was used for statistical analysis of data. RESULTS: PA increased glucose uptake by approximately 35...

  18. Models for radiation-induced tissue degeneration and conceptualization of rehabilitation of irradiated tissue by cell therapy

    International Nuclear Information System (INIS)

    Phulpin, Berengere

    2011-01-01

    Radiation therapy induced acute and late sequelae within healthy tissue included in the irradiated area. In general, lesions are characterized by ischemia, cell apoptosis and fibrosis. In this context, cell therapy using bone marrow mesenchymal stem cells (BMSC) might represent an attractive new therapeutic approach, based partly on their angiogenic ability and their involvement in the natural processes of tissue repair. The first part of this work consisted in the development of experimental mouse model of radio-induced tissue degeneration similar to that occurring after radiotherapy. The aim was to better understand the physiopathological mechanisms of radiation-induced tissue damage and to determine the best treatment strategy. The second part of this work investigated the feasibility of autologous BMSC therapy on the murine model of radiation previously established with emphasis on two pre-requisites: the retention of the injected cells within the target tissue and the evaluation of the graft on bone metabolism. This preclinical investigation in a mouse model constitutes an essential step allowing an evaluation of the benefit of cell therapy for the treatment of radiation-induced tissue injury. Data from these studies could allow the proposal of clinical studies [fr

  19. Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging

    DEFF Research Database (Denmark)

    Reichkendler, M. H.; Auerbach, P.; Rosenkilde, M.

    2013-01-01

    abdominal SAT compared with CON but not in either intra- or retroperitoneal VAT. Total adipose tissue mass decreased in both exercise groups, and the decrease was distributed equally among subcutaneous and intra-abdominal depots. In conclusion, aerobic exercise training increases insulin-stimulated glucose...

  20. Toxoplasmosis in sentinel chickens (Gallus domesticus) in New England farms: seroconversion, distribution of tissue cysts in brain, heart, and skeletal muscle by bioassay in mice and cats

    Science.gov (United States)

    Free-range chickens are a good indicator of soil contamination with oocysts because they feed from the ground and they are also an important source of infection for cats that in turn shed oocysts after eating tissues of intermediate hosts. Little is known of the epidemiology of toxoplasmosis in chic...

  1. Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

    Directory of Open Access Journals (Sweden)

    Bruno dos Santos

    2013-01-01

    Full Text Available This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet; soybean oil (S; lard (L; and hydrogenated vegetable fat (H. We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver.

  2. Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts' Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.

    Science.gov (United States)

    Serena, Elena; Zatti, Susi; Zoso, Alice; Lo Verso, Francesca; Tedesco, F Saverio; Cossu, Giulio; Elvassore, Nicola

    2016-12-01

    : Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model. We designed an ad hoc experimental strategy to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. It is based on the coculture, at different ratios, of human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts in a substrate with muscle-like physiological stiffness and cell micropatterns. Results showed that both healthy myoblasts and mesoangioblasts restored dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected efficiency with respect to myoblasts in dystrophin production in terms of the amount of protein produced (40% vs. 15%) and length of the dystrophin membrane domain (210-240 µm vs. 40-70 µm). These results show that our microscaled in vitro model of human DMD skeletal muscle validated previous in vivo preclinical work and may be used to predict efficacy of new methods aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo, reducing time, costs, and variability of clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of human mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from

  3. Evaluation of 3-dimensional superimposition techniques on various skeletal structures of the head using surface models.

    Directory of Open Access Journals (Sweden)

    Nikolaos Gkantidis

    Full Text Available To test the applicability, accuracy, precision, and reproducibility of various 3D superimposition techniques for radiographic data, transformed to triangulated surface data.Five superimposition techniques (3P: three-point registration; AC: anterior cranial base; AC + F: anterior cranial base + foramen magnum; BZ: both zygomatic arches; 1Z: one zygomatic arch were tested using eight pairs of pre-existing CT data (pre- and post-treatment. These were obtained from non-growing orthodontic patients treated with rapid maxillary expansion. All datasets were superimposed by three operators independently, who repeated the whole procedure one month later. Accuracy was assessed by the distance (D between superimposed datasets on three form-stable anatomical areas, located on the anterior cranial base and the foramen magnum. Precision and reproducibility were assessed using the distances between models at four specific landmarks. Non parametric multivariate models and Bland-Altman difference plots were used for analyses.There was no difference among operators or between time points on the accuracy of each superimposition technique (p>0.05. The AC + F technique was the most accurate (D0.05, the detected structural changes differed significantly between different techniques (p<0.05. Bland-Altman difference plots showed that BZ superimposition was comparable to AC, though it presented slightly higher random error.Superimposition of 3D datasets using surface models created from voxel data can provide accurate, precise, and reproducible results, offering also high efficiency and increased post-processing capabilities. In the present study population, the BZ superimposition was comparable to AC, with the added advantage of being applicable to scans with a smaller field of view.

  4. Evaluation of 3-dimensional superimposition techniques on various skeletal structures of the head using surface models.

    Science.gov (United States)

    Gkantidis, Nikolaos; Schauseil, Michael; Pazera, Pawel; Zorkun, Berna; Katsaros, Christos; Ludwig, Björn

    2015-01-01

    To test the applicability, accuracy, precision, and reproducibility of various 3D superimposition techniques for radiographic data, transformed to triangulated surface data. Five superimposition techniques (3P: three-point registration; AC: anterior cranial base; AC + F: anterior cranial base + foramen magnum; BZ: both zygomatic arches; 1Z: one zygomatic arch) were tested using eight pairs of pre-existing CT data (pre- and post-treatment). These were obtained from non-growing orthodontic patients treated with rapid maxillary expansion. All datasets were superimposed by three operators independently, who repeated the whole procedure one month later. Accuracy was assessed by the distance (D) between superimposed datasets on three form-stable anatomical areas, located on the anterior cranial base and the foramen magnum. Precision and reproducibility were assessed using the distances between models at four specific landmarks. Non parametric multivariate models and Bland-Altman difference plots were used for analyses. There was no difference among operators or between time points on the accuracy of each superimposition technique (p>0.05). The AC + F technique was the most accurate (D0.05), the detected structural changes differed significantly between different techniques (p<0.05). Bland-Altman difference plots showed that BZ superimposition was comparable to AC, though it presented slightly higher random error. Superimposition of 3D datasets using surface models created from voxel data can provide accurate, precise, and reproducible results, offering also high efficiency and increased post-processing capabilities. In the present study population, the BZ superimposition was comparable to AC, with the added advantage of being applicable to scans with a smaller field of view.

  5. Model of adipose tissue cellularity dynamics during food restriction.

    Science.gov (United States)

    Soula, H A; Géloën, A; Soulage, C O

    2015-01-07

    Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Biomechanical implications of skeletal muscle hypertrophy and atrophy: a musculoskeletal model

    Directory of Open Access Journals (Sweden)

    Andrew D. Vigotsky

    2015-11-01

    Full Text Available Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-sectional area (ACSA of a muscle and its MA length. In the model, the ACSAs of the biceps brachii and brachialis were altered to hypertrophy up to twice their original size and to atrophy to one-half of their original size. The change in MA length was found to be proportional to the arcsine of the square root of the change in ACSA. This change in MA length may be a small but important contributor to strength, especially in sports that require large joint moments at slow joint angular velocities, such as powerlifting. The paradoxical implications of the increase in MA are discussed, as physiological factors influencing muscle contraction velocity appear to favor a smaller MA length for high velocity movements but a larger muscle MA length for low velocity, high force movements.

  7. Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle.

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    Haruka Amitani

    Full Text Available Hydrogen (H(2 acts as a therapeutic antioxidant. However, there are few reports on H(2 function in other capacities in diabetes mellitus (DM. Therefore, in this study, we investigated the role of H(2 in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2 promoted 2-[(14C]-deoxy-d-glucose (2-DG uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K, protein kinase C (PKC, and AMP-activated protein kinase (AMPK, although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2 significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p. and oral (p.o. administration. However, long-term p.o. administration of H(2 had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2 exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

  8. Thoracic and lumbar vertebral bone mineral density changes in a natural occurring dog model of diffuse idiopathic skeletal hyperostosis.

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    Steven De Decker

    Full Text Available Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD. There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH. DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30 or without (n=29 DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p <0.001, lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01, and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03 were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001 and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001 were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding.

  9. High-Fat Diet-Induced Obesity Promotes Expansion of Bone Marrow Adipose Tissue and Impairs Skeletal Stem Cell Functions in Mice

    DEFF Research Database (Denmark)

    Tencerova, Michaela; Figeac, Florence; Ditzel, Nicholas

    2018-01-01

    that link obesity, BM adiposity, and bone fragility. Thus, in an obesity intervention study in C57BL/6J mice fed with a high-fat diet (HFD) for 12 weeks, we investigated the molecular and cellular phenotype of bone marrow adipose tissue (BMAT), BM progenitor cells, and BM microenvironment in comparison...... to peripheral adipose tissue (AT). HFD decreased trabecular bone mass by 29%, cortical thickness by 5%, and increased BM adiposity by 184%. In contrast to peripheral AT, BMAT did not exhibit pro-inflammatory phenotype. BM progenitor cells isolated from HFD mice exhibited decreased mRNA levels of inflammatory...... demonstrate that BMAT expansion in response to HFD exerts a deleterious effect on the skeleton. Continuous recruitment of progenitor cells to adipogenesis leads to progenitor cell exhaustion, decreased recruitment to osteoblastic cells, and decreased bone formation. In addition, the absence of insulin...

  10. Mutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue Disorders

    OpenAIRE

    Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie

    2013-01-01

    Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a sever...

  11. Skeletal and soft tissue changes and stability in cleft lip and palate patients after distraction osteogenesis using a new intraoral maxillary device.

    Science.gov (United States)

    Ansari, Edward; Tomat, Catherine; Kadlub, Natacha; Diner, Patrick A; Bellocq, Thomas; Vazquez, Marie-Paule; Picard, Arnaud

    2015-04-01

    The authors have recently reported on the use of an internal maxillary distraction device. In this study, we report on the hard and soft tissue movements achieved with this intraoral distraction device, and the stability changes after distraction osteogenesis for maxillary hypoplasia in patients with cleft lip and palate. Ten male patients with severe hypoplasia of the maxilla, with complete uni- or bilateral cleft lip and palate were included. The mean age of the patients at the time of operation was 11.91 years (±3.41). To evaluate the distraction process and stability, superimpositions on the preoperative lateral cephalograms were performed. The mean follow-up (FU) was 15.42 months (±3.94). Cephalometric measurements at all of the maxillary hard and soft tissue points improved significantly. Maxillary point A was advanced by 8.25 mm (±3.17; P distraction soft tissue point A' had advanced 7.10 mm (±2.69; P distraction. Maxillary horizontal relapse at point A was 14.1% at FU. Vertical relapse was not significant. This rigid intraoral distraction device can be successfully used in the correction of severe maxillary hypoplasia. The marked aesthetic improvement and low psychological encumbrance make this device viable for the treatment of cleft-related hypoplasia of the maxilla. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. Intraurethral Injection of Autologous Minced Skeletal Muscle

    DEFF Research Database (Denmark)

    Gräs, Søren; Klarskov, Niels; Lose, Gunnar

    2014-01-01

    noted. CONCLUSIONS: Intraurethral injection of minced autologous muscle tissue is a simple surgical procedure that appears safe and moderately effective in women with uncomplicated stress urinary incontinence. It compares well to a more complicated regenerative strategy using in vitro expanded muscle......PURPOSE: Intraurethral injection of in vitro expanded autologous skeletal muscle derived cells is a new regenerative therapy for stress urinary incontinence. We examined the efficacy and safety of a simpler alternative strategy using freshly harvested, minced autologous skeletal muscle tissue...... with its inherent content of regenerative cells. MATERIALS AND METHODS: A total of 20 and 15 women with uncomplicated and complicated stress urinary incontinence, respectively, received intraurethral injections of minced autologous skeletal muscle tissue and were followed for 1 year. Efficacy was assessed...

  13. Insights into skeletal muscle development and applications in regenerative medicine.

    Science.gov (United States)

    Tran, T; Andersen, R; Sherman, S P; Pyle, A D

    2013-01-01

    Embryonic and postnatal development of skeletal muscle entails highly regulated processes whose complexity continues to be deconstructed. One key stage of development is the satellite cell, whose niche is composed of multiple cell types that eventually contribute to terminally differentiated myotubes. Understanding these developmental processes will ultimately facilitate treatments of myopathies such as Duchenne muscular dystrophy (DMD), a disease characterized by compromised cell membrane structure, resulting in severe muscle wasting. One theoretical approach is to use pluripotent stem cells in a therapeutic setting to help replace degenerated muscle tissue. This chapter discusses key myogenic developmental stages and their regulatory pathways; artificial myogenic induction in pluripotent stem cells; advantages and disadvantages of DMD animal models; and therapeutic approaches targeting DMD. Furthermore, skeletal muscle serves as an excellent paradigm for understanding general cell fate decisions throughout development. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Exercise training reverses skeletal muscle atrophy in an experimental model of VCP disease.

    Directory of Open Access Journals (Sweden)

    Angèle Nalbandian

    Full Text Available The therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weakness, which negatively impact independence and quality of life levels. Mutations in the valosin containing protein (VCP gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD and more recently affect 2% of amyotrophic lateral sclerosis (ALS-diagnosed cases.The present investigation was undertaken to examine the effects of uphill and downhill exercise training on muscle histopathology and the autophagy cascade in an experimental VCP mouse model carrying the R155H mutation. Progressive uphill exercise in VCP(R155H/+ mice revealed significant improvement in muscle strength and performance by grip strength and Rotarod analyses when compared to the sedentary mice. In contrast, mice exercised to run downhill did not show any significant improvement. Histologically, the uphill exercised VCP(R155H/+ mice displayed an improvement in muscle atrophy, and decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43 autophagy markers, suggesting an alleviation of disease-induced myopathy phenotypes. There was also an improvement in the Paget-like phenotype.Collectively, our data highlights that uphill exercise training in VCP(R155H/+ mice did not have any detrimental value to the function of muscle, and may offer effective therapeutic options for patients with VCP-associated diseases.

  15. A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD.

    Science.gov (United States)

    Davidsen, Peter K; Herbert, John M; Antczak, Philipp; Clarke, Kim; Ferrer, Elisabet; Peinado, Victor I; Gonzalez, Constancio; Roca, Josep; Egginton, Stuart; Barberá, Joan A; Falciani, Francesco

    2014-01-01

    A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting. We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting. We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle. We conclude that

  16. Immunology Guides Skeletal Muscle Regeneration

    Directory of Open Access Journals (Sweden)

    F. Andrea Sass

    2018-03-01

    Full Text Available Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

  17. Discrete vessel heat transfer in perfused tissue - model comparison

    NARCIS (Netherlands)

    Stanczyk, M.; Leeuwen, van G.M.J.; Steenhoven, van A.A.

    2007-01-01

    The aim of this paper is to compare two methods of calculating heat transfer in perfused biological tissue using a discrete vessel description. The methods differ in two important aspects: the representation of the vascular system and the algorithm for calculating the heat flux between tissue and

  18. 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

  19. Viscoelastic properties of bovine orbital connective tissue and fat: constitutive models.

    Science.gov (United States)

    Yoo, Lawrence; Gupta, Vijay; Lee, Choongyeop; Kavehpore, Pirouz; Demer, Joseph L

    2011-12-01

    Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain-stress relationships underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were taken from rectus pulley regions and 30 samples of fatty tissues from the posterior orbit. Additional samples were defatted to determine connective tissue weight proportion, which was verified histologically. Mechanical testing in shear employed a triborheometer to perform: strain sweeps at 0.5-2.0 Hz; shear stress relaxation with 1% strain; viscometry at 0.01-0.5 s(-1) strain rate; and shear oscillation at 1% strain. Average connective tissue weight proportion was 98% for predominantly connective tissue and 76% for fatty tissue. Connective tissue specimens reached a long-term relaxation modulus of 668 Pa after 1,500 s, while corresponding values for fatty tissue specimens were 290 Pa and 1,100 s. Shear stress magnitude for connective tissue exceeded that of fatty tissue by five-fold. Based on these data, we developed a multi-mode UCM model with variable viscosities and time constants, and a damped hyperelastic response that accurately described measured properties of both connective and fatty tissues. Model parameters differed significantly between the two tissues. Viscoelastic properties of predominantly connective orbital tissues under shear loading differ markedly from properties of orbital fat, but both are accurately reflected using UCM models. These viscoelastic models will facilitate realistic global modeling of EOM behavior in binocular alignment and strabismus.

  20. Impact of anesthesia and euthanasia on metabolomics of mammalian tissues: studies in a C57BL/6J mouse model.

    Directory of Open Access Journals (Sweden)

    Katherine A Overmyer

    Full Text Available A critical application of metabolomics is the evaluation of tissues, which are often the primary sites of metabolic dysregulation in disease. Laboratory rodents have been widely used for metabolomics studies involving tissues due to their facile handing, genetic manipulability and similarity to most aspects of human metabolism. However, the necessary step of administration of anesthesia in preparation for tissue sampling is not often given careful consideration, in spite of its potential for causing alterations in the metabolome. We examined, for the first time using untargeted and targeted metabolomics, the effect of several commonly used methods of anesthesia and euthanasia for collection of skeletal muscle, liver, heart, adipose and serum of C57BL/6J mice. The data revealed dramatic, tissue-specific impacts of tissue collection strategy. Among many differences observed, post-euthanasia samples showed elevated levels of glucose 6-phosphate and other glycolytic intermediates in skeletal muscle. In heart and liver, multiple nucleotide and purine degradation metabolites accumulated in tissues of euthanized compared to anesthetized animals. Adipose tissue was comparatively less affected by collection strategy, although accumulation of lactate and succinate in euthanized animals was observed in all tissues. Among methods of tissue collection performed pre-euthanasia, ketamine showed more variability compared to isoflurane and pentobarbital. Isoflurane induced elevated liver aspartate but allowed more rapid initiation of tissue collection. Based on these findings, we present a more optimal collection strategy mammalian tissues and recommend that rodent tissues intended for metabolomics studies be collected under anesthesia rather than post-euthanasia.

  1. Krogh’s principle or a multiple fish model approach to phosphate balance: is there a centrally regulated intestinal-skeletal-renal axis?

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Guerreiro

    2015-10-01

    Full Text Available Inorganic phosphate (Pi is a crucial ion for vertebrate life. In addition to many physiological roles it is, together with calcium, the major element forming the internal skeleton and Pi balance has been considered a secondary consequence of calciotropic endocrine factors. However, contrary to calcium which can be readily obtained from even Ca-poor environments, Pi is not available in water, and fish can only obtain it via the food. Intestinal absorption drives Pi into the blood stream, but a central part of Pi balance is renal excretion and conservation. Recently, several Pi specific regulatory factors have been brought to light, and we use fish models to investigate their role and the hypothesis of a centrally controlled intestinal-skeletal-renal Pi axis. Using tissues mounted in Ussing chambers under symmetrical and asymmetrical short-circuited conditions we measure unidirectional 33Pi fluxes and test PTHrP, but also STC and FGF23 as regulatory factors, as well as specific drugs to unveil the functional transporting mechanisms. Pi absorption is modified in starved and fed sea bass, an effect dependent on Pi availability in diet, which modifies gene expression of uptake mechanisms. Phosphate secretion across flounder primary renal cell cultures is increased by PTHrP, which reduces the expression of reabsorption mechanisms such as NaPiII and evokes an increase in GFR in cannulated fish, thus resulting in net Pi excretion. A similar effect occurs in the toadfish urinary bladder, which displays moderate Pi transport that is abolished by the drug ouabain and modified by endocrines. Finally we used the shark choroid plexus (CP to show active CSF-to-blood transport with biochemical properties consistent with PiT Na+-dependent transporters. RT-PCR revealed the PiT1/2, but no NaPiII gene expression and we localized PiT2 in CP apical membranes while PiT1 occurred in vascular endothelial cells. Shark CP expresses both PTHrP and its receptor. Could

  2. Induced skeletal mutations

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

  3. Biophotonics in diagnosis and modeling of tissue pathologies

    Science.gov (United States)

    Serafetinides, A. A.; Makropoulou, M.; Drakaki, E.

    2008-12-01

    Biophotonics techniques are applied to several fields in medicine and biology. The laser based techniques, such as the laser induced fluorescence (LIF) spectroscopy and the optical coherence tomography (OCT), are of particular importance in dermatology, where the laser radiation could be directly applied to the tissue target (e.g. skin). In addition, OCT resolves architectural tissue properties that might be useful as tumour discrimination parameters for skin as well as for ocular non-invasive visualization. Skin and ocular tissues are complex multilayered and inhomogeneous organs with spatially varying optical properties. This fact complicates the quantitative analysis of the fluorescence and/or light scattering spectra, even from the same tissue sample. To overcome this problem, mathematical simulation is applied for the investigation of the human tissue optical properties, in the visible/infrared range of the spectrum, resulting in a better discrimination of several tissue pathologies. In this work, we present i) a general view on biophotonics applications in diagnosis of human diseases, ii) some specific results on laser spectroscopy techniques, as LIF measurements, applied in arterial and skin pathologies and iii) some experimental and theoretical results on ocular OCT measurements. Regarding the LIF spectroscopy, we examined the autofluorescence properties of several human skin samples, excised from humans undergoing biopsy examination. A nitrogen laser was used as an excitation source, emitting at 337 nm (ultraviolet excitation). Histopathology examination of the samples was also performed, after the laser spectroscopy measurements and the results from the spectroscopic and medical analysis were compared, to differentiate malignancies, e.g. basal cell carcinoma tissue (BCC), from normal skin tissue. Regarding the OCT technique, we correlated human data, obtained from patients undergoing OCT examination, with Monte Carlo simulated cornea and retina tissues

  4. Multiaxial mechanical response and constitutive modeling of esophageal tissues: Impact on esophageal tissue engineering.

    Science.gov (United States)

    Sommer, Gerhard; Schriefl, Andreas; Zeindlinger, Georg; Katzensteiner, Andreas; Ainödhofer, Herwig; Saxena, Amulya; Holzapfel, Gerhard A

    2013-12-01

    Congenital defects of the esophagus are relatively frequent, with 1 out of 2500 babies suffering from such a defect. A new method of treatment by implanting tissue engineered esophagi into newborns is currently being developed and tested using ovine esophagi. For the reconstruction of the biological function of native tissues with engineered esophagi, their cellular structure as well as their mechanical properties must be considered. Since very limited mechanical and structural data for the esophagus are available, the aim of this study was to investigate the multiaxial mechanical behavior of the ovine esophagus and the underlying microstructure. Therefore, uniaxial tensile, biaxial tensile and extension-inflation tests on esophagi were performed. The underlying microstructure was examined in stained histological sections through standard optical microscopy techniques. Moreover, the uniaxial ultimate tensile strength and residual deformations of the tissue were determined. Both the mucosa-submucosa and the muscle layers showed nonlinear and anisotropic mechanical behavior during uniaxial, biaxial and inflation testing. Cyclical inflation of the intact esophageal tube caused marked softening of the passive esophagi in the circumferential direction. The rupture strength of the mucosa-submucosa layer was much higher than that of the muscle layer. Overall, the ovine esophagus showed a heterogeneous and anisotropic behavior with different mechanical properties for the individual layers. The intact and layer-specific multiaxial properties were characterized using a well-known three-dimensional microstructurally based strain-energy function. This novel and complete set of data serves the basis for a better understanding of tissue remodeling in diseased esophagi and can be used to perform computer simulations of surgical interventions or medical-device applications. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. Receptor model for the molecular basis of tissue selectivity of 1,4-dihydropyridine calcium channel drugs

    Science.gov (United States)

    Langs, David A.; Strong, Phyllis D.; Triggle, David J.

    1990-09-01

    Our analysis of the solid state conformations of nifedipine [dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylate] and its 1,4-dihydropyridine (1,4-DHP) analogues produced a cartoon description of the important interactions between these drugs and their voltage-dependent calcium channel receptor. In the present study a molecular-level detailed model of the 1,4-DHP receptor binding site has been built from the published amino acid sequence of the 215-1 subunit of the voltage-dependent calcium channel isolated from rabbit skeletal muscle transverse tubule membranes. The voltage-sensing component of the channel described in this work differs from others reported for the homologous sodium channel in that it incorporates a water structure and a staggered, rather than eclipsed, hydrogen bonded S4 helix conformation. The major recognition surfaces of the receptor lie in helical grooves on the S4 or voltagesensing α-helix that is positioned in the center of the bundle of transmembrane helices that define each of the four calcium channel domains. Multiple binding clefts defined by Arg-X-X-Arg-P-X-X-S `reading frames' exist on the S4 strand. The tissue selectivity of nifedipine and its analogues may arise, in part, from conservative changes in the amino acid residues at the P and S positions of the reading frame that define the ester-binding regions of receptors from different tissues. The crystal structures of two tissue-selective nifedipine analogues, nimodipine [isopropyl (2-methoxyethyl) 1,4-dihydro-2,6- dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] and nitrendipine [ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] are reported. Nimodipine was observed to have an unusual ester side chain conformation that enhances the fit to the proposed ester-sensing region of the receptor.

  6. Quantitative skeletal scintiscanning

    International Nuclear Information System (INIS)

    Haushofer, R.

    1982-01-01

    330 patients were examined by skeletal scintiscanning with sup(99m)Tc pyrophosphate and sup(99m)methylene diphosphonate in the years between 1977 and 1979. Course control examinations were carried out in 12 patients. The collective of patients presented with primary skeletal tumours, metastases, inflammatory and degenerative skeletal diseases. Bone scintiscanning combined with the ''region of interest'' technique was found to be an objective and reproducible technique for quantitative measurement of skeletal radioactivity concentrations. The validity of nuclear skeletal examinations can thus be enhanced as far as diagnosis, course control, and differential diagnosis are concerned. Quantitative skeletal scintiscanning by means of the ''region of interest'' technique has opened up a new era in skeletal diagnosis by nuclear methods. (orig./MG) [de

  7. High-Fat Diet-Induced Obesity Promotes Expansion of Bone Marrow Adipose Tissue and Impairs Skeletal Stem Cell Functions in Mice.

    Science.gov (United States)

    Tencerova, Michaela; Figeac, Florence; Ditzel, Nicholas; Taipaleenmäki, Hanna; Nielsen, Tina Kamilla; Kassem, Moustapha

    2018-06-01

    Obesity represents a risk factor for development of insulin resistance and type 2 diabetes. In addition, it has been associated with increased adipocyte formation in the bone marrow (BM) along with increased risk for bone fragility fractures. However, little is known on the cellular mechanisms that link obesity, BM adiposity, and bone fragility. Thus, in an obesity intervention study in C57BL/6J mice fed with a high-fat diet (HFD) for 12 weeks, we investigated the molecular and cellular phenotype of bone marrow adipose tissue (BMAT), BM progenitor cells, and BM microenvironment in comparison to peripheral adipose tissue (AT). HFD decreased trabecular bone mass by 29%, cortical thickness by 5%, and increased BM adiposity by 184%. In contrast to peripheral AT, BMAT did not exhibit pro-inflammatory phenotype. BM progenitor cells isolated from HFD mice exhibited decreased mRNA levels of inflammatory genes (Tnfα, IL1β, Lcn2) and did not manifest an insulin resistant phenotype evidenced by normal levels of pAKT after insulin stimulation as well as normal levels of insulin signaling genes. In addition, BM progenitor cells manifested enhanced adipocyte differentiation in HFD condition. Thus, our data demonstrate that BMAT expansion in response to HFD exerts a deleterious effect on the skeleton. Continuous recruitment of progenitor cells to adipogenesis leads to progenitor cell exhaustion, decreased recruitment to osteoblastic cells, and decreased bone formation. In addition, the absence of insulin resistance and inflammation in the BM suggest that BMAT buffers extra energy in the form of triglycerides and thus plays a role in whole-body energy homeostasis. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

  8. Deep proteomics of mouse skeletal muscle enables quantitation of protein isoforms, metabolic pathways, and transcription factors.

    Science.gov (United States)

    Deshmukh, Atul S; Murgia, Marta; Nagaraj, Nagarjuna; Treebak, Jonas T; Cox, Jürgen; Mann, Matthias

    2015-04-01

    Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging because of highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art MS workflow and a strategy to map identifications from the C2C12 cell line model to tissues, we identified a total of 10,218 proteins, including skeletal muscle specific transcription factors like myod1 and myogenin and circadian clock proteins. We obtain absolute abundances for proteins expressed in a muscle cell line and skeletal muscle, which should serve as a valuable resource. Quantitation of protein isoforms of glucose uptake signaling pathways and in glucose and lipid metabolic pathways provides a detailed metabolic map of the cell line compared with tissue. This revealed unexpectedly complex regulation of AMP-activated protein kinase and insulin signaling in muscle tissue at the level of enzyme isoforms. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Generalized Beer-Lambert model for near-infrared light propagation in thick biological tissues

    Science.gov (United States)

    Bhatt, Manish; Ayyalasomayajula, Kalyan R.; Yalavarthy, Phaneendra K.

    2016-07-01

    The attenuation of near-infrared (NIR) light intensity as it propagates in a turbid medium like biological tissue is described by modified the Beer-Lambert law (MBLL). The MBLL is generally used to quantify the changes in tissue chromophore concentrations for NIR spectroscopic data analysis. Even though MBLL is effective in terms of providing qualitative comparison, it suffers from its applicability across tissue types and tissue dimensions. In this work, we introduce Lambert-W function-based modeling for light propagation in biological tissues, which is a generalized version of the Beer-Lambert model. The proposed modeling provides parametrization of tissue properties, which includes two attenuation coefficients μ0 and η. We validated our model against the Monte Carlo simulation, which is the gold standard for modeling NIR light propagation in biological tissue. We included numerous human and animal tissues to validate the proposed empirical model, including an inhomogeneous adult human head model. The proposed model, which has a closed form (analytical), is first of its kind in providing accurate modeling of NIR light propagation in biological tissues.

  10. Human tissue optical properties measurements and light propagation modelling

    CSIR Research Space (South Africa)

    Dam, JS

    2006-07-01

    Full Text Available Biomedical Optics is the study of the optical properties of living biological material, especially its scattering and absorption characteristics, and their significance to light propagation within the material. Determination of tissue optical...

  11. Skeletal muscle stem cells from animals I. Basic cell biology

    Science.gov (United States)

    Skeletal muscle stem cells from food-producing animals have been of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding...

  12. A new take on an old story: chick limb organ culture for skeletal niche development and regenerative medicine evaluation

    Directory of Open Access Journals (Sweden)

    EL Smith

    2013-09-01

    Full Text Available Scientific research and progress, particularly in the drug discovery and regenerative medicine fields, is typically dependent on suitable animal models to develop new and improved clinical therapies for injuries and diseases. In vivo model systems are frequently utilised, but these models are expensive, highly complex and pose a number of ethical considerations leading to the development and use of a number of alternative ex vivo model systems. The ex vivo embryonic chick long bone and limb bud models have been utilised in the scientific research field as a model to understand skeletal development for over eighty years. The rapid development of avian skeletal tissues, coupled with the ease of experimental manipulation, availability of genome sequence and the presence of multiple cell and tissue types has seen such model systems gain significant research interest in the last few years in the tissue engineering field. The models have been explored both as systems for understanding the developmental bone niche and as potential testing tools for tissue engineering strategies for bone repair and regeneration. This review details the evolution of the chick limb organ culture system and presents recent innovative developments and emerging techniques and technologies applied to these models that are aiding our understanding of skeletal developmental and regenerative medicine research and application.

  13. Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models.

    Science.gov (United States)

    Deddens, Janine C; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W; Buijsrogge, Marc; Doevendans, Pieter A; Khademhosseini, Ali; Sluijter, Joost P G

    2017-02-01

    Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart. With recent advances in both disease biology and cardiac tissue engineering, the translation of fundamental laboratory research toward the treatment of chronic heart failure patients becomes a more realistic option. Here, the current understanding of cardiac fibrosis and the great potential of tissue engineering are presented. Approaches using hydrogel-based tissue engineered heart constructs are discussed to contemplate key challenges for modeling tissue engineered cardiac fibrosis and to provide a future outlook for preclinical and clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. The influence of serum-free culture conditions on skeletal muscle differentiation in a tissue-engineered model

    NARCIS (Netherlands)

    Gawlitta, D.; Boonen, K.J.M.; Oomens, C.W.J.; Baaijens, F.P.T.; Bouten, C.V.C.

    2008-01-01

    The influence of differentiation medium (DM) components on C2C12 murine myoblast differentiation has only been studied in monolayer cultures. Serum-free formulations have been applied that omit the use of sera with unknown composition. The goal of the present study was to compare the influence of

  15. An extract of Artemisia dracunculus L. inhibits ubiquitin-proteasome activity and preserves skeletal muscle mass in a murine model of diabetes.

    Directory of Open Access Journals (Sweden)

    Heather Kirk-Ballard

    Full Text Available Impaired insulin signaling is a key feature of type 2 diabetes and is associated with increased ubiquitin-proteasome-dependent protein degradation in skeletal muscle. An extract of Artemisia dracunculus L. (termed PMI5011 improves insulin action by increasing insulin signaling in skeletal muscle. We sought to determine if the effect of PMI5011 on insulin signaling extends to regulation of the ubiquitin-proteasome system. C2C12 myotubes and the KK-A(y murine model of type 2 diabetes were used to evaluate the effect of PMI5011 on steady-state levels of ubiquitylation, proteasome activity and expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are upregulated with impaired insulin signaling. Our results show that PMI5011 inhibits proteasome activity and steady-state ubiquitylation levels in vitro and in vivo. The effect of PMI5011 is mediated by PI3K/Akt signaling and correlates with decreased expression of Atrogin-1 and MuRF-1. Under in vitro conditions of hormonal or fatty acid-induced insulin resistance, PMI5011 improves insulin signaling and reduces Atrogin-1 and MuRF-1 protein levels. In the KK-A(y murine model of type 2 diabetes, skeletal muscle ubiquitylation and proteasome activity is inhibited and Atrogin-1 and MuRF-1 expression is decreased by PMI5011. PMI5011-mediated changes in the ubiquitin-proteasome system in vivo correlate with increased phosphorylation of Akt and FoxO3a and increased myofiber size. The changes in Atrogin-1 and MuRF-1 expression, ubiquitin-proteasome activity and myofiber size modulated by PMI5011 in the presence of insulin resistance indicate the botanical extract PMI5011 may have therapeutic potential in the preservation of muscle mass in type 2 diabetes.

  16. Soft tissue deformation modelling through neural dynamics-based reaction-diffusion mechanics.

    Science.gov (United States)

    Zhang, Jinao; Zhong, Yongmin; Gu, Chengfan

    2018-05-30

    Soft tissue deformation modelling forms the basis of development of surgical simulation, surgical planning and robotic-assisted minimally invasive surgery. This paper presents a new methodology for modelling of soft tissue deformation based on reaction-diffusion mechanics via neural dynamics. The potential energy stored in soft tissues due to a mechanical load to deform tissues away from their rest state is treated as the equivalent transmembrane potential energy, and it is distributed in the tissue masses in the manner of reaction-diffusion propagation of nonlinear electrical waves. The reaction-diffusion propagation of mechanical potential energy and nonrigid mechanics of motion are combined to model soft tissue deformation and its dynamics, both of which are further formulated as the dynamics of cellular neural networks to achieve real-time computational performance. The proposed methodology is implemented with a haptic device for interactive soft tissue deformation with force feedback. Experimental results demonstrate that the proposed methodology exhibits nonlinear force-displacement relationship for nonlinear soft tissue deformation. Homogeneous, anisotropic and heterogeneous soft tissue material properties can be modelled through the inherent physical properties of mass points. Graphical abstract Soft tissue deformation modelling with haptic feedback via neural dynamics-based reaction-diffusion mechanics.

  17. Molecular Alterations in a Mouse Cardiac Model of Friedreich Ataxia

    DEFF Research Database (Denmark)

    Anzovino, Amy; Chiang, Shannon; Brown, Bronwyn E

    2017-01-01

    mechanisms. Using a mouse conditional frataxin knockout (KO) model in the heart and skeletal muscle, we examined the Nrf2 pathway in these tissues. Frataxin KO results in fatal cardiomyopathy, whereas skeletal muscle was asymptomatic. In the KO heart, protein oxidation and a decreased glutathione...

  18. Modelling of Combustion and Pollutant Formation in a Large, Two-Stroke Marine Diesel Engine using Integrated CFD-Skeletal Chemical Mechanism

    DEFF Research Database (Denmark)

    Pang, Kar Mun; Karvounis, Nikolas; Schramm, Jesper

    In this reported work, simulation studies of in-cylinder diesel combustion and pollutant formation processesin a two-stroke, low-speed uniflow-scavenged marine diesel engine are presented. Numerical computation is performed by integrating chemical kinetics into CFD computations. In order...... to minimize the computational runtime, an in-house skeletal n-heptane chemical mechanism is coupled with the CFD model. This surrogate fuel model comprises 89 reactions with 32 species essential to diesel ignition/combustion processes as well as the formation of soot precursors and nitrogen monoxide (NO......). Prior to the marine engine simulation,coupling of the newly developed surrogate fuel model and a revised multi-step soot model [1] is validated on the basis of optical diagnostics measurement obtained at varying ambient pressure levels [2]. It is demonstrated that the variation of ignition delay times...

  19. Differential expression among tissues in morbidly obese individuals using a finite mixture model under BLUP approach

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Trabzuni, Daniah; Bonder, Marc Jan

    effects of the interactions between tissues and probes using BLUP (Best Linear Unbiased Prediction) linear models correcting for gender, which were subsequently used in a finite mixture model to detect DE genes in each tissue. This approach evades the multiple-testing problem and is able to detect...

  20. Topographic modelling of haptic properties of tissue products

    International Nuclear Information System (INIS)

    Rosen, B-G; Fall, A; Farbrot, A; Bergström, P; Rosen, S

    2014-01-01

    The way a product or material feels when touched, haptics, has been shown to be a property that plays an important role when consumers determine the quality of products For tissue products in constant touch with the skin, ''softness'' becomes a primary quality parameter. In the present work, the relationship between topography and the feeling of the surface has been investigated for commercial tissues with varying degree of texture from the low textured crepe tissue to the highly textured embossed- and air-dried tissue products. A trained sensory panel at was used to grade perceived haptic ''roughness''. The technique used to characterize the topography was Digital light projection (DLP) technique, By the use of multivariate statistics, strong correlations between perceived roughness and topography were found with predictability of above 90 percent even though highly textured products were included. Characterization was made using areal ISO 25178-2 topography parameters in combination with non-contacting topography measurement. The best prediction ability was obtained when combining haptic properties with the topography parameters auto-correlation length (Sal), peak material volume (Vmp), core roughness depth (Sk) and the maximum height of the surface (Sz)

  1. Modeling and remodeling of the collagen architecture in cardiovascular tissues

    NARCIS (Netherlands)

    Driessen, N.J.B.

    2006-01-01

    Heart valve replacement by a mechanical or biological prosthesis represents a common surgical therapy for end-stage valvular heart diseases. A critical drawback of these prostheses is the inability to grow, repair and remodel in response to changes in the tissue’s environment. Tissue engineering

  2. Cartilage and bone cells do not participate in skeletal regeneration in Ambystoma mexicanum limbs.

    Science.gov (United States)

    McCusker, Catherine D; Diaz-Castillo, Carlos; Sosnik, Julian; Q Phan, Anne; Gardiner, David M

    2016-08-01

    The Mexican Axolotl is one of the few tetrapod species that is capable of regenerating complete skeletal elements in injured adult limbs. Whether the skeleton (bone and cartilage) plays a role in the patterning and contribution to the skeletal regenerate is currently unresolved. We tested the induction of pattern formation, the effect on cell proliferation, and contributions of skeletal tissues (cartilage, bone, and periosteum) to the regenerating axolotl limb. We found that bone tissue grafts from transgenic donors expressing GFP fail to induce pattern formation and do not contribute to the newly regenerated skeleton. Periosteum tissue grafts, on the other hand, have both of these activities. These observations reveal that skeletal tissue does not contribute to the regeneration of skeletal elements; rather, these structures are patterned by and derived from cells of non-skeletal connective tissue origin. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Heterogeneous Deformable Modeling of Bio-Tissues and Haptic Force Rendering for Bio-Object Modeling

    Science.gov (United States)

    Lin, Shiyong; Lee, Yuan-Shin; Narayan, Roger J.

    This paper presents a novel technique for modeling soft biological tissues as well as the development of an innovative interface for bio-manufacturing and medical applications. Heterogeneous deformable models may be used to represent the actual internal structures of deformable biological objects, which possess multiple components and nonuniform material properties. Both heterogeneous deformable object modeling and accurate haptic rendering can greatly enhance the realism and fidelity of virtual reality environments. In this paper, a tri-ray node snapping algorithm is proposed to generate a volumetric heterogeneous deformable model from a set of object interface surfaces between different materials. A constrained local static integration method is presented for simulating deformation and accurate force feedback based on the material properties of a heterogeneous structure. Biological soft tissue modeling is used as an example to demonstrate the proposed techniques. By integrating the heterogeneous deformable model into a virtual environment, users can both observe different materials inside a deformable object as well as interact with it by touching the deformable object using a haptic device. The presented techniques can be used for surgical simulation, bio-product design, bio-manufacturing, and medical applications.

  4. High-Resolution X-Ray Tomography: A 3D Exploration Into the Skeletal Architecture in Mouse Models Submitted to Microgravity Constraints

    Directory of Open Access Journals (Sweden)

    Alessandra Giuliani

    2018-03-01

    Full Text Available Bone remodeling process consists in a slow building phase and in faster resorption with the objective to maintain a functional skeleton locomotion to counteract the Earth gravity. Thus, during spaceflights, the skeleton does not act against gravity, with a rapid decrease of bone mass and density, favoring bone fracture. Several studies approached the problem by imaging the bone architecture and density of cosmonauts returned by the different spaceflights. However, the weaknesses of the previously reported studies was two-fold: on the one hand the research suffered the small statistical sample size of almost all human spaceflight studies, on the other the results were not fully reliable, mainly due to the fact that the observed bone structures were small compared with the spatial resolution of the available imaging devices. The recent advances in high-resolution X-ray tomography have stimulated the study of weight-bearing skeletal sites by novel approaches, mainly based on the use of the mouse and its various strains as an animal model, and sometimes taking advantage of the synchrotron radiation support to approach studies of 3D bone architecture and mineralization degree mapping at different hierarchical levels. Here we report the first, to our knowledge, systematic review of the recent advances in studying the skeletal bone architecture by high-resolution X-ray tomography after submission of mice models to microgravity constrains.

  5. A 3D intestinal tissue model supports Clostridioides difficile germination, colonization, toxin production and epithelial damage.

    Science.gov (United States)

    Shaban, Lamyaa; Chen, Ying; Fasciano, Alyssa C; Lin, Yinan; Kaplan, David L; Kumamoto, Carol A; Mecsas, Joan

    2018-04-01

    Endospore-forming Clostridioides difficile is a causative agent of antibiotic-induced diarrhea, a major nosocomial infection. Studies of its interactions with mammalian tissues have been hampered by the fact that C. difficile requires anaerobic conditions to survive after spore germination. We recently developed a bioengineered 3D human intestinal tissue model and found that low O 2 conditions are produced in the lumen of these tissues. Here, we compared the ability of C. difficile spores to germinate, produce toxin and cause tissue damage in our bioengineered 3D tissue model versus in a 2D transwell model in which human cells form a polarized monolayer. 3D tissue models or 2D polarized monolayers on transwell filters were challenged with the non-toxin producing C. difficile CCUG 37787 serotype X (ATCC 43603) and the toxin producing UK1 C. difficile spores in the presence of the germinant, taurocholate. Spores germinated in both the 3D tissue model as well as the 2D transwell system, however toxin activity was significantly higher in the 3D tissue models compared to the 2D transwells. Moreover, the epithelium damage in the 3D tissue model was significantly more severe than in 2D transwells and damage correlated significantly with the level of toxin activity detected but not with the amount of germinated spores. Combined, these results show that the bioengineered 3D tissue model provides a powerful system with which to study early events leading to toxin production and tissue damage of C. difficile with mammalian cells under anaerobic conditions. Furthermore, these systems may be useful for examining the effects of microbiota, novel drugs and other potential therapeutics directed towards C. difficile infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Uniaxial cyclic strain enhances adipose-derived stem cell fusion with skeletal myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Jens Isak; Juhl, Morten; Nielsen, Thøger; Emmersen, Jeppe; Fink, Trine; Zachar, Vladimir; Pennisi, Cristian Pablo, E-mail: cpennisi@hst.aau.dk

    2014-07-25

    Highlights: • Uniaxial cyclic tensile strain (CTS) applied to ASCs alone or in coculture with myogenic precursors. • CTS promoted the formation of a highly ordered array of parallel ASCs. • Without biochemical supplements, CTS did not support advanced myogenic differentiation of ASCs. • Mechanical stimulation of cocultures boosted fusion of ASCs with skeletal myoblasts. - Abstract: Although adult muscle tissue possesses an exceptional capacity for regeneration, in the case of large defects, the restoration to original state is not possible. A well-known source for the de novo regeneration is the adipose-derived stem cells (ASCs), which can be readily isolated and have been shown to have a broad differentiation and regenerative potential. In this work, we employed uniaxial cyclic tensile strain (CTS), to mechanically stimulate human ASCs to participate in the formation skeletal myotubes in an in vitro model of myogenesis. The application of CTS for 48 h resulted in the formation of a highly ordered array of parallel ASCs, but failed to support skeletal muscle terminal differentiation. When the same stimulation paradigm was applied to cocultures with mouse skeletal muscle myoblasts, the percentage of ASCs contributing to the formation of myotubes significantly exceeded the levels reported in the literature hitherto. In perspective, the mechanical strain may be used to increase the efficiency of incorporation of ASCs in the skeletal muscles, which could be found useful in diverse traumatic or pathologic scenarios.

  7. Average intensity and spreading of partially coherent model beams propagating in a turbulent biological tissue

    International Nuclear Information System (INIS)

    Wu, Yuqian; Zhang, Yixin; Wang, Qiu; Hu, Zhengda

    2016-01-01

    For Gaussian beams with three different partially coherent models, including Gaussian-Schell model (GSM), Laguerre-Gaussian Schell-model (LGSM) and Bessel-Gaussian Schell-model (BGSM) beams propagating through a biological turbulent tissue, the expression of the spatial coherence radius of a spherical wave propagating in a turbulent biological tissue, and the average intensity and beam spreading for GSM, LGSM and BGSM beams are derived based on the fractal model of power spectrum of refractive-index variations in biological tissue. Effects of partially coherent model and parameters of biological turbulence on such beams are studied in numerical simulations. Our results reveal that the spreading of GSM beams is smaller than LGSM and BGSM beams on the same conditions, and the beam with larger source coherence width has smaller beam spreading than that with smaller coherence width. The results are useful for any applications involved light beam propagation through tissues, especially the cases where the average intensity and spreading properties of the light should be taken into account to evaluate the system performance and investigations in the structures of biological tissue. - Highlights: • Spatial coherence radius of a spherical wave propagating in a turbulent biological tissue is developed. • Expressions of average intensity and beam spreading for GSM, LGSM and BGSM beams in a turbulent biological tissue are derived. • The contrast for the three partially coherent model beams is shown in numerical simulations. • The results are useful for any applications involved light beam propagation through tissues.

  8. Interleukin-6 myokine signaling in skeletal muscle

    DEFF Research Database (Denmark)

    Muñoz-Cánoves, Pura; Scheele, Camilla; Pedersen, Bente K

    2013-01-01

    Interleukin (IL)-6 is a cytokine with pleiotropic functions in different tissues and organs. Skeletal muscle produces and releases significant levels of IL-6 after prolonged exercise and is therefore considered as a myokine. Muscle is also an important target of the cytokine. IL-6 signaling has b...

  9. Lyophilized skeletal imaging composition

    International Nuclear Information System (INIS)

    Vanduzee, B.F.

    1983-01-01

    This invention encompasses a process for producing a dry-powder skeletal imaging kit. An aqueous solution of a diphosphonate, a stannous reductant, and, optionally, a stabilizer is prepared. The solution is adjusted to a pH within the range 4.2 to 4.8 and the pH-adjusted solution is then lyophilized. The adjustment of pH, within a particular range, during the process of manufacturing lyophilized diphosphonate containing skeletal imaging kits yields a kit which produces a technetium skeletal imaging agent with superior imaging properties. This improved performance is manifested through faster blood clearance and higher skeletal uptake of the technetium imaging agent

  10. Tissue characterization using magnetic resonance elastography: preliminary results

    International Nuclear Information System (INIS)

    Kruse, S.A.; Smith, J.A.; Lawrence, A.J.; Dresner, M.A.; Manduca, A.; Greenleaf, J.F.; Ehman, R.L.

    2000-01-01

    The well-documented effectiveness of palpation as a diagnostic technique for detecting cancer and other diseases has provided motivation for developing imaging techniques for non-invasively evaluating the mechanical properties of tissue. A recently described approach for elasticity imaging, using propagating acoustic shear waves and phase-contrast MRI, has been called magnetic resonance elastography (MRE). The purpose of this work was to conduct preliminary studies to define methods for using MRE as a tool for addressing the paucity of quantitative tissue mechanical property data in the literature. Fresh animal liver and kidney tissue specimens were evaluated with MRE at multiple shear wave frequencies. The influence of specimen temperature and orientation on measurements of stiffness was studied in skeletal muscle. The results demonstrated that all of the materials tested (liver, kidney, muscle and tissue-simulating gel) exhibit systematic dependence of shear stiffness on shear rate. These data are consistent with a viscoelastic model of tissue mechanical properties, allowing calculation of two independent tissue properties from multiple-frequency MRE data: shear modulus and shear viscosity. The shear stiffness of tissue can be substantially affected by specimen temperature. The results also demonstrated evidence of shear anisotropy in skeletal muscle but not liver tissue. The measured shear stiffness in skeletal muscle was found to depend on both the direction of propagation and polarization of the shear waves. (author)

  11. Ossified skeletal muscle hemangioma: Radiologic and pathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Engelstad, B L; Gilula, L A [Mallinckrodt Inst. of Radiology, St. Louis, MO (USA); Kynakos, M [Washington Univ., St. Louis, MO (USA). Dept. of Surgical Pathology

    1980-01-01

    Skeletal muscle hemangiomas are relatively uncommon tumors in children and young adults. Although the operative management of these lesions may be affected by their vascularity, the correct preoperative diagnosis is often not made. Ossification of these lesions is rare. Two patients are described whose skeletal muscle hemangiomas contained abundant osseous tissue. This was radiologically reflected by the 'swiss cheese' appearance of the tumors. Such an appearance in an ossified soft tissue mass may allow the correct preoperative diagnosis of this condition.

  12. Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology.

    Science.gov (United States)

    Sopko, Nikolai A; Matsui, Hotaka; Lough, Denver M; Miller, Devin; Harris, Kelly; Kates, Max; Liu, Xiaopu; Billups, Kevin; Redett, Richard; Burnett, Arthur L; Brandacher, Gerald; Bivalacqua, Trinity J

    2017-04-01

    Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited

  13. Experimental study and constitutive modeling of the viscoelastic mechanical properties of the human prolapsed vaginal tissue.

    Science.gov (United States)

    Peña, Estefania; Calvo, B; Martínez, M A; Martins, P; Mascarenhas, T; Jorge, R M N; Ferreira, A; Doblaré, M

    2010-02-01

    In this paper, the viscoelastic mechanical properties of vaginal tissue are investigated. Using previous results of the authors on the mechanical properties of biological soft tissues and newly experimental data from uniaxial tension tests, a new model for the viscoelastic mechanical properties of the human vaginal tissue is proposed. The structural model seems to be sufficiently accurate to guarantee its application to prediction of reliable stress distributions, and is suitable for finite element computations. The obtained results may be helpful in the design of surgical procedures with autologous tissue or prostheses.

  14. Curcumin attenuates skeletal muscle mitochondrial impairment in COPD rats: PGC-1α/SIRT3 pathway involved.

    Science.gov (United States)

    Zhang, Ming; Tang, Jingjing; Li, Yali; Xie, Yingying; Shan, Hu; Chen, Mingxia; Zhang, Jie; Yang, Xia; Zhang, Qiuhong; Yang, Xudong

    2017-11-01

    Curcumin has been widely used to treat numerous diseases due to its antioxidant property. The aim of the present study is to investigate the effect of curcumin on skeletal muscle mitochondria in chronic obstructive pulmonary disease (COPD) and its underlying mechanism. The rat model of COPD was established by cigarette smoke exposure combined with intratracheal administration of lipopolysaccharide. Airway inflammation and emphysema were notably ameliorated by the treatment with curcumin. Oral administration of curcumin significantly improved muscle fiber atrophy, myofibril disorganization, interstitial fibrosis and mitochondrial structure damage in the skeletal muscle of COPD rats. Mitochondrial enzyme activities of cytochrome c oxidase, succinate dehydrogenase, Na + /K + -ATPase and Ca 2+ -ATPase in skeletal muscle mitochondria from COPD rats were significantly increased after treatment with curcumin. Moreover, curcumin significantly decreased oxidative stress and inflammation by determining the levels of malondialdehyde, manganese superoxide dismutase, glutathione peroxidase, catalase, IL-6 and TNF-α in skeletal muscle of COPD rats. Furthermore, curcumin significantly increased the mRNA and protein expression of PGC-1α and SIRT3 in the skeletal muscle tissues of COPD rats. These results suggested that curcumin can attenuate skeletal muscle mitochondrial impairment in COPD rats possibly by the up-regulation of PGC-1α/SIRT3 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Cauli: a mouse strain with an Ift140 mutation that results in a skeletal ciliopathy modelling Jeune syndrome.

    Directory of Open Access Journals (Sweden)

    Kerry A Miller

    2013-08-01

    Full Text Available Cilia are architecturally complex organelles that protrude from the cell membrane and have signalling, sensory and motility functions that are central to normal tissue development and homeostasis. There are two broad categories of cilia; motile and non-motile, or primary, cilia. The central role of primary cilia in health and disease has become prominent in the past decade with the recognition of a number of human syndromes that result from defects in the formation or function of primary cilia. This rapidly growing class of conditions, now known as ciliopathies, impact the development of a diverse range of tissues including the neural axis, craniofacial structures, skeleton, kidneys, eyes and lungs. The broad impact of cilia dysfunction on development reflects the pivotal position of the primary cilia within a signalling nexus involving a growing number of growth factor systems including Hedgehog, Pdgf, Fgf, Hippo, Notch and both canonical Wnt and planar cell polarity. We have identified a novel ENU mutant allele of Ift140, which causes a mid-gestation embryonic lethal phenotype in homozygous mutant mice. Mutant embryos exhibit a range of phenotypes including exencephaly and spina bifida, craniofacial dysmorphism, digit anomalies, cardiac anomalies and somite patterning defects. A number of these phenotypes can be attributed to alterations in Hedgehog signalling, although additional signalling systems are also likely to be involved. We also report the identification of a homozygous recessive mutation in IFT140 in a Jeune syndrome patient. This ENU-induced Jeune syndrome model will be useful in delineating the origins of dysmorphology in human ciliopathies.

  16. A minimal spatial cell lineage model of epithelium: tissue stratification and multi-stability

    Science.gov (United States)

    Yeh, Wei-Ting; Chen, Hsuan-Yi

    2018-05-01

    A minimal model which includes spatial and cell lineage dynamics for stratified epithelia is presented. The dependence of tissue steady state on cell differentiation models, cell proliferation rate, cell differentiation rate, and other parameters are studied numerically and analytically. Our minimal model shows some important features. First, we find that morphogen or mechanical stress mediated interaction is necessary to maintain a healthy stratified epithelium. Furthermore, comparing with tissues in which cell differentiation can take place only during cell division, tissues in which cell division and cell differentiation are decoupled can achieve relatively higher degree of stratification. Finally, our model also shows that in the presence of short-range interactions, it is possible for a tissue to have multiple steady states. The relation between our results and tissue morphogenesis or lesion is discussed.

  17. Proteomic Analyses of the Acute Tissue Response for Explant Rabbit Corneas and Engineered Corneal Tissue Models Following In Vitro Exposure to 1540 nm Laser Light

    National Research Council Canada - National Science Library

    Eurell, T. E; Johnson, T. E; Roach, W. P

    2005-01-01

    Two-dimensional electrophoresis and histomorphometry were used to determine if equivalent protein changes occurred within native rabbit corneas and engineered corneal tissue models following in vitro...

  18. A mechano-biological model of multi-tissue evolution in bone

    Science.gov (United States)

    Frame, Jamie; Rohan, Pierre-Yves; Corté, Laurent; Allena, Rachele

    2017-12-01

    Successfully simulating tissue evolution in bone is of significant importance in predicting various biological processes such as bone remodeling, fracture healing and osseointegration of implants. Each of these processes involves in different ways the permanent or transient formation of different tissue types, namely bone, cartilage and fibrous tissues. The tissue evolution in specific circumstances such as bone remodeling and fracturing healing is currently able to be modeled. Nevertheless, it remains challenging to predict which tissue types and organization can develop without any a priori assumptions. In particular, the role of mechano-biological coupling in this selective tissue evolution has not been clearly elucidated. In this work, a multi-tissue model has been created which simultaneously describes the evolution of bone, cartilage and fibrous tissues. The coupling of the biological and mechanical factors involved in tissue formation has been modeled by defining two different tissue states: an immature state corresponding to the early stages of tissue growth and representing cell clusters in a weakly neo-formed Extra Cellular Matrix (ECM), and a mature state corresponding to well-formed connective tissues. This has allowed for the cellular processes of migration, proliferation and apoptosis to be described simultaneously with the changing ECM properties through strain driven diffusion, growth, maturation and resorption terms. A series of finite element simulations were carried out on idealized cantilever bending geometries. Starting from a tissue composition replicating a mid-diaphysis section of a long bone, a steady-state tissue formation was reached over a statically loaded period of 10,000 h (60 weeks). The results demonstrated that bone formation occurred in regions which are optimally physiologically strained. In two additional 1000 h bending simulations both cartilaginous and fibrous tissues were shown to form under specific geometrical and loading

  19. A model of a code of ethics for tissue banks operating in developing countries.

    Science.gov (United States)

    Morales Pedraza, Jorge

    2012-12-01

    Ethical practice in the field of tissue banking requires the setting of principles, the identification of possible deviations and the establishment of mechanisms that will detect and hinder abuses that may occur during the procurement, processing and distribution of tissues for transplantation. This model of a Code of Ethics has been prepared with the purpose of being used for the elaboration of a Code of Ethics for tissue banks operating in the Latin American and the Caribbean, Asia and the Pacific and the African regions in order to guide the day-to-day operation of these banks. The purpose of this model of Code of Ethics is to assist interested tissue banks in the preparation of their own Code of Ethics towards ensuring that the tissue bank staff support with their actions the mission and values associated with tissue banking.

  20. Mitochondrial Function in an In Vitro Model of Skeletal Muscle of Patients With Protracted Critical Illness and Intensive Care Unit-Acquired Weakness.

    Science.gov (United States)

    Jiroutková, Kateřina; Krajčová, Adéla; Žiak, Jakub; Fric, Michal; Gojda, Jan; Džupa, Valér; Kalous, Martin; Tůmová, Jana; Trnka, Jan; Duška, František

    2017-09-01

    Functional mitochondria in skeletal muscle of patients with protracted critical illness and intensive care unit-acquired weakness are depleted, but remaining mitochondria have increased functional capacities of respiratory complexes II and III. This can be an adaptation to relative abundancy of fatty acid over glucose caused by insulin resistance. We hypothesized that the capacity of muscle mitochondria to oxidize fatty acid is increased in protracted critical illness. We assessed fatty acid oxidation (FAO) and mitochondrial functional indices in vitro by using extracellular flux analysis in cultured myotubes obtained by isolating and culturing satellite cells from vastus lateralis muscle biopsy samples from patients with ICU-acquired weakness (n = 6) and age-matched healthy controls (n = 7). Bioenergetic measurements were performed at baseline and after 6 days of exposure to free fatty acids (FFAs). Mitochondrial density in myotubes from ICU patients was 69% of healthy controls ( P = .051). After adjustment to mitochondrial content, there were no differences in adenosine triphosphate (ATP) synthesis or the capacity and coupling of the respiratory chain. FAO capacity in ICU patients was 157% of FAO capacity in controls ( P = .015). In myotubes of ICU patients, unlike healthy controls, the exposure to FFA significantly ( P = .009) increased maximum respiratory chain capacity. In an in vitro model of skeletal muscle of patients with protracted critical illness, we have shown signs of adaptation to increased FAO. Even in the presence of glucose and insulin, elevation of FFAs in the extracellular environment increased maximal capacity of the respiratory chain.

  1. Lasting consequences of traumatic events on behavioral and skeletal parameters in a mouse model for post-traumatic stress disorder (PTSD).

    Science.gov (United States)

    Yu, Hongrun; Watt, Heather; Kesavan, Chandrasekhar; Johnson, Patrick J; Wergedal, Jon E; Mohan, Subburaman

    2012-01-01

    Post-traumatic stress disorder (PTSD) is an anxiety disorder that not only affects mental health, but may also affect bone health. However, there have been no studies to examine the direct relationship between PTSD and bone. We employed electric shocks in mice to simulate traumatic events that cause PTSD. We also injected the anxiogenic drug FG-7142 prior to electric shocks. Electric shocks created lasting conditioned fear memory in all mice. In young mice, electric shocks elicited not only behavioral response but also skeletal response, and injection of FG-7142 appeared to increase both types of response. For example in behavioral response within the first week, mice shocked alone froze an average of 6.2 sec in 10 sec tests, and mice injected with FG-7142 froze 7.6 sec, both significantly different (PPTSD-like behavior was associated with reduced bone mass acquisition. This is the first study to document evidence that traumatic events induce lasting consequences on both behavior and skeletal growth, and electric shocks coupled with injection of anxiogenic FG-7142 in young mice can be used as a model to study the effect of PTSD-like symptoms on bone development.

  2. Morphological and functional analyses of skeletal muscles from an immunodeficient animal model of limb-girdle muscular dystrophy type 2E.

    Science.gov (United States)

    Giovannelli, Gaia; Giacomazzi, Giorgia; Grosemans, Hanne; Sampaolesi, Maurilio

    2018-02-24

    Limb-girdle muscular dystrophy type 2E (LGMD2E) is caused by mutations in the β-sarcoglycan gene, which is expressed in skeletal, cardiac, and smooth muscles. β-Sarcoglycan-deficient (Sgcb-null) mice develop severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. In this study we performed morphological (histological and cellular characterization) and functional (isometric tetanic force and fatigue) analyses in dystrophic mice. Comparison studies were carried out in 1-month-old (clinical onset of the disease) and 7-month-old control mice (C57Bl/6J, Rag2/γc-null) and immunocompetent and immunodeficient dystrophic mice (Sgcb-null and Sgcb/Rag2/γc-null, respectively). We found that the lack of an immunological system resulted in an increase of calcification in striated muscles without impairing extensor digitorum longus muscle performance. Sgcb/Rag2/γc-null muscles showed a significant reduction of alkaline phosphate-positive mesoangioblasts. The immunological system counteracts skeletal muscle degeneration in the murine model of LGMD2E. Muscle Nerve, 2018. © 2018 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.

  3. Lipid profiling of in vitro cell models of adipogenic differentiation: relationships with mouse adipose tissues

    OpenAIRE

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A.; Anunciado-Koza, Rea V.; Siviski, Matthew E.; Lindner, Volkhard; Friesel, Robert E.; Rosen, Clifford J.; Baker, Paul R.S.; Simons, Brigitte; Vary, Calvin P.H.

    2016-01-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MSALL. Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-...

  4. Could a functional artificial skeletal muscle be useful in muscle wasting?

    Science.gov (United States)

    Fuoco, Claudia; Cannata, Stefano; Gargioli, Cesare

    2016-05-01

    Regardless of the underlying cause, skeletal muscle wasting is detrimental for a person's life quality, leading to impaired strength, locomotion, and physiological activity. Here, we propose a series of studies presenting tissue engineering-based approaches to reconstruct artificial muscle in vitro and in vivo. Skeletal muscle tissue engineering is attracting more and more attention from scientists, clinicians, patients, and media, thanks to the promising results obtained in the last decade with animal models of muscle wasting. The use of novel and refined biomimetic scaffolds mimicking three-dimensional muscle environment, thus supporting cell survival and differentiation, in combination with well characterized myogenic stem/progenitor cells, revealed the noteworthy potential of these technologies for creating artificial skeletal muscle tissue. In vitro, the production of three-dimensional muscle structures offer the possibility to generate a drug-screening platform for patient-specific pharmacological treatment, opening new frontiers in the development of new compounds with specific therapeutic actions. In vivo, three-dimensional artificial muscle biomimet