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...

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.

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

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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

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)

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

Superoxide activates a GDP-sensitive proton conductance in skeletal muscle mitochondria from king penguin (Aptenodytes patagonicus).

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Talbot, Darren A; Hanuise, Nicolas; Rey, Benjamin; Rouanet, Jean-Louis; Duchamp, Claude; Brand, Martin D

2003-12-26

We present the partial nucleotide sequence of the avian uncoupling protein (avUCP) gene from king penguin (Aptenodytes patagonicus), showing that the protein is 88-92% identical to chicken (Gallus gallus), turkey (Meleagris gallopavo), and hummingbird (Eupetomena macroura). We show that superoxide activates the proton conductance of mitochondria isolated from king penguin skeletal muscle. GDP abolishes the superoxide-activated proton conductance, indicating that it is mediated via avUCP. In the absence of superoxide there is no GDP-sensitive component of the proton conductance from penguin muscle mitochondria demonstrating that avUCP plays no role in the basal proton leak.

Mechanical stimulation improves tissue-engineered human skeletal muscle

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

2002-01-01

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

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.

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

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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.

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

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

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.

Duchenne muscular dystrophy carriers. Proton spin-lattice relaxation times of skeletal muscles on magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Matsumura, K.; Nakano, I. (Shimoshizu National Hospital, Chiba (Japan). Dept. of Neurology); Fukuda, N.; Ikehira, H.; Tateno, Y. (National Inst. of Radiological Sciences, Chiba (Japan). Div. of Clinical Research); Aoki, Y. (National Inst. of Radiological Sciences, Chiba (Japan))

1989-11-01

By means of magnetic resonance imaging (MRI), the proton spin-lattice relaxation times (T1 values) of the skeletal muscles were measured in Duchenne muscular dystrophy (DMD) carriers and normal controls. The bound water fraction (BWF) was calculated from the T1 values obtained, according to the fast proton diffusion model. In the DMD carriers, T1 values of the gluteus maximus and quadriceps femoris muscles were significantly higher, and BWFs of these muscles were significantly lower than in normal control. Degenerative muscular changes accompanied by interstitial edema were presumed responsible for this abnormality. No correlation was observed between the muscle T1 and serum creatine kinase values. The present study showed that MRI could be a useful method for studying the dynamic state of water in both normal and pathological skeletal muscles. Its possible utility for DMD carrier detection was discussed briefly. (orig.).

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...

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

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.

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.

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)

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...

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.

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.

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

Contribution of proton leak to oxygen consumption in skeletal muscle during intense exercise is very low despite large contribution at rest.

Directory of Open Access Journals (Sweden)

Bernard Korzeniewski

Full Text Available A computer model was used to simulate the dependence of protonmotive force (Δp, proton leak and phenomenological (involving proton leak ATP/O2 ratio on work intensity in skeletal muscle. Δp, NADH and proton leak decreased with work intensity. The contribution of proton leak to oxygen consumption ([Formula: see text] decreased from about 60% at rest to about 3 and 1% at moderate and heavy/severe exercise, respectively, while the ATP/O2 ratio increased from 2.1 to 5.5 and 5.7. A two-fold increase in proton leak activity or its decrease to zero decreased/increased the ATP/O2 ratio by only about 3 and 1% during moderate and heavy/severe exercise, respectively. The low contribution of proton leak to [Formula: see text] in intensively working skeletal muscle was mostly caused by a huge increase in ATP usage intensity during rest-to-work transition, while OXPHOS, and thus oxidative ATP supply and [Formula: see text] related to it, was mostly stimulated by high each-step activation (ESA of OXPHOS complexes. The contribution of proton leak to [Formula: see text] and ATP/O2 ratio in isolated mitochondria should not be directly extrapolated to working muscle, as mitochondria lack ESA, at least in the absence of Ca2+, and therefore [Formula: see text] cannot be elevated as much as in intact muscle.

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

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

Adaptive plasticity of skeletal muscle energetics in hibernating frogs: mitochondrial proton leak during metabolic depression.

Science.gov (United States)

Boutilier, Robert G; St-Pierre, Julie

2002-08-01

The common frog (Rana temporaria) spends the coldest months of each year overwintering in ice-covered ponds where temperatures can vary from 0.5 to 4.0 degrees C. Over the course of a winter season, the animals enter progressively into a state of metabolic depression that relies almost exclusively on aerobic production of ATP. However, if aerobic metabolism is threatened, for example by increasingly hypoxic conditions, decreases in the animal's metabolic rate can reach upwards of 75% compared with the 50% decrease seen during normoxia. Under these conditions, the major proportion of the overall reduction in whole-animal metabolic rate can be accounted for by metabolic suppression of the skeletal muscle (which makes up approximately 40% of body mass). Little is known about the properties of mitochondria during prolonged periods of metabolic depression, so we have examined several aspects of mitochondrial metabolism in the skeletal muscle of frogs over periods of hibernation of up to 4 months. Mitochondria isolated from the skeletal muscle of frogs hibernating in hypoxic water show a considerable reorganisation of function compared with those isolated from normoxic submerged animals at the same temperature (3 degrees C). Both the active (state 3) and resting (state 4) respiration rates of mitochondria decrease during hypoxic, but not normoxic, hibernation. In addition, the affinity of mitochondria for oxygen increases during periods of acute hypoxic stress during normoxic hibernation as well as during long-term hibernation in hypoxic water. The decrease in mitochondrial state 4 respiration rates during hypoxic hibernation evidently occurs through a reduction in electron-transport chain activity, not through a lowered proton conductance of the mitochondrial inner membrane. The reduced aerobic capacity of frog skeletal muscle during hypoxic hibernation is accompanied by lowered activities of key enzymes of mitochondrial metabolism caused by changes in the intrinsic

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)

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...

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.

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...

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.

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

Nuclear magnetic resonance studies on maturation of skeletal muscle

International Nuclear Information System (INIS)

Yuasa, Tatsuhiko; Kuwahara, Takeo; Ohno, Takao; Miyatake, Tadashi.

1982-01-01

The water proton relaxation time ( 1 H-T 1 ) of the maturing chick pectoral muscle and the 23 Na concentration in the muscular tissue were determined by NMR spectrometry. 1 H-T 1 was determined on 12-day-old chick embryos, 19- and 20-day-old embryos and chicks aged 8, 15 and 22 days. 23 Na concentration was determined on 12-14 day-old chick embryos, 19-day-old embryos and 4-6 day-old and 20-day-old chicks. 1 H-T 1 gradually decreased with maturation; 2.082 +- 0.091 sec, 1.605 +- 0.106 sec, 1.321 +- 0.107 sec, 1.108 +- 0.038 sec and 1.087 +- 0.053 sec. The 23 Na level showed similar decreases; 59.5 +- 3.51 μEq/gm, 49.0 +- 4.95 μEq/gm, 47.5 +- 3.87 μEq/gm and 10.3 +- 2.13 μEq/gm. The water content in the skeletal muscle decreased with maturation, and 1 H-T 1 and the water content showed an exponential relationship. Comparison between the 23 Na concentration of muscle tissues determined by NMR and the Na + concentration by flame photometry revealed a decrease of the detection rate of 23 Na by NMR from 81.9 % to 54.7 % with maturation. It was conjectured that as well as the mode of existence of water proton, that of 23 Na in the tissue was subject to changes occurring with maturation of the skeletal muscle. (Chiba, N.)

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.

SU-D-BRC-04: Development of Proton Tissue Equivalent Materials for Calibration and Dosimetry Studies

Energy Technology Data Exchange (ETDEWEB)

Olguin, E [Gainesville, FL (United States); Flampouri, S [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Lipnharski, I [University of Florida, Gainesville, FL (United States); Bolch, W [University Florida, Gainesville, FL (United States)

2016-06-15

Purpose: To develop new proton tissue equivalent materials (PTEM), urethane and fiberglass based, for proton therapy calibration and dosimetry studies. Existing tissue equivalent plastics are applicable only for x-rays because they focus on matching mass attenuation coefficients. This study aims to create new plastics that match mass stopping powers for proton therapy applications instead. Methods: New PTEMs were constructed using urethane and fiberglass resin materials for soft, fat, bone, and lung tissue. The stoichiometric analysis method was first used to determine the elemental composition of each unknown constituent. New initial formulae were then developed for each of the 4 PTEMs using the new elemental compositions and various additives. Samples of each plastic were then created and exposed to a well defined proton beam at the UF Health Proton Therapy Institute (UFHPTI) to validate its mass stopping power. Results: The stoichiometric analysis method revealed the elemental composition of the 3 components used in creating the PTEMs. These urethane and fiberglass based resins were combined with additives such as calcium carbonate, aluminum hydroxide, and phenolic micro spheres to achieve the desired mass stopping powers and densities. Validation at the UFHPTI revealed adjustments had to be made to the formulae, but the plastics eventually had the desired properties after a few iterations. The mass stopping power, density, and Hounsfield Unit of each of the 4 PTEMs were within acceptable tolerances. Conclusion: Four proton tissue equivalent plastics were developed: soft, fat, bone, and lung tissue. These plastics match each of the corresponding tissue’s mass stopping power, density, and Hounsfield Unit, meaning they are truly tissue equivalent for proton therapy applications. They can now be used to calibrate proton therapy treatment planning systems, improve range uncertainties, validate proton therapy Monte Carlo simulations, and assess in-field and out

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.

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.

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.

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.

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.

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

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.

Proton energy determinations in water and in tissue-like material

Energy Technology Data Exchange (ETDEWEB)

Laitano, R F [Ist. Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA, Roma (Italy); Rosetti, M [Div. di Fisica Applicata, ENEA, Bologna (Italy)

1997-09-01

The mean energy of proton beams in water and in a tissue substitute, respectively, were determined as a function of SOBP width, beam size and initial energy spread. Then an analytical expression to obtain the proton mean energy as a function of phantom depth and initial energy was established. This expression differs from the analogous ones reported in some current dosimetry protocols in that it accounts for the nuclear interaction effects in determining the mean energy. The preliminary results of the calculations referred to above are reported together with some comments on the specification of the proton beam quality for clinical dosimetry. (orig.)

Uncoupling protein and ATP/ADP carrier increase mitochondrial proton conductance after cold adaptation of king penguins.

Science.gov (United States)

Talbot, Darren A; Duchamp, Claude; Rey, Benjamin; Hanuise, Nicolas; Rouanet, Jean Louis; Sibille, Brigitte; Brand, Martin D

2004-07-01

Juvenile king penguins develop adaptive thermogenesis after repeated immersion in cold water. However, the mechanisms of such metabolic adaptation in birds are unknown, as they lack brown adipose tissue and uncoupling protein-1 (UCP1), which mediate adaptive non-shivering thermogenesis in mammals. We used three different groups of juvenile king penguins to investigate the mitochondrial basis of avian adaptive thermogenesis in vitro. Skeletal muscle mitochondria isolated from penguins that had never been immersed in cold water showed no superoxide-stimulated proton conductance, indicating no functional avian UCP. Skeletal muscle mitochondria from penguins that had been either experimentally immersed or naturally adapted to cold water did possess functional avian UCP, demonstrated by a superoxide-stimulated, GDP-inhibitable proton conductance across their inner membrane. This was associated with a markedly greater abundance of avian UCP mRNA. In the presence (but not the absence) of fatty acids, these mitochondria also showed a greater adenine nucleotide translocase-catalysed proton conductance than those from never-immersed penguins. This was due to an increase in the amount of adenine nucleotide translocase. Therefore, adaptive thermogenesis in juvenile king penguins is linked to two separate mechanisms of uncoupling of oxidative phosphorylation in skeletal muscle mitochondria: increased proton transport activity of avian UCP (dependent on superoxide and inhibited by GDP) and increased proton transport activity of the adenine nucleotide translocase (dependent on fatty acids and inhibited by carboxyatractylate).

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

Determination of elemental tissue composition following proton treatment using positron emission tomography

International Nuclear Information System (INIS)

Cho, Jongmin; Ibbott, Geoffrey; Gillin, Michael; Gonzalez-Lepera, Carlos; Min, Chul Hee; Zhu, Xuping; El Fakhri, Georges; Paganetti, Harald; Mawlawi, Osama

2013-01-01

Positron emission tomography (PET) has been suggested as an imaging technique for in vivo proton dose and range verification after proton induced-tissue activation. During proton treatment, irradiated tissue is activated and decays while emitting positrons. In this paper, we assessed the feasibility of using PET imaging after proton treatment to determine tissue elemental composition by evaluating the resultant composite decay curve of activated tissue. A phantom consisting of sections composed of different combinations of 1 H, 12 C, 14 N, and 16 O was irradiated using a pristine Bragg peak and a 6 cm spread-out Bragg-peak (SOBP) proton beam. The beam ranges defined at 90% distal dose were 10 cm; the delivered dose was 1.6 Gy for the near monoenergetic beam and 2 Gy for the SOBP beam. After irradiation, activated phantom decay was measured using an in-room PET scanner for 30 min in list mode. Decay curves from the activated 12 C and 16 O sections were first decomposed into multiple simple exponential decay curves, each curve corresponding to a constituent radioisotope, using a least-squares method. The relative radioisotope fractions from each section were determined. These fractions were used to guide the decay curve decomposition from the section consisting mainly of 12 C + 16 O and calculate the relative elemental composition of 12 C and 16 O. A Monte Carlo simulation was also used to determine the elemental composition of the 12 C + 16 O section. The calculated compositions of the 12 C + 16 O section using both approaches (PET and Monte Carlo) were compared with the true known phantom composition. Finally, two patients were imaged using an in-room PET scanner after proton therapy of the head. Their PET data and the technique described above were used to construct elemental composition ( 12 C and 16 O) maps that corresponded to the proton-activated regions. We compared the 12 C and 16 O compositions of seven ROIs that corresponded to the vitreous humor, adipose

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...

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.

An end-to-end assessment of range uncertainty in proton therapy using animal tissues

Science.gov (United States)

Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

2016-11-01

Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams’ superior dose advantage over conventional photon-based radiation therapy.

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.

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.

The Proton-Activated Receptor GPR4 Modulates Glucose Homeostasis by Increasing Insulin Sensitivity

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Luca Giudici

2013-11-01

Full Text Available Background: The proton-activated G protein-coupled receptor GPR4 is expressed in many tissues including white adipose tissue. GPR4 is activated by extracellular protons in the physiological pH range (i.e. pH 7.7 - 6.8 and is coupled to the production of cAMP. Methods: We examined mice lacking GPR4 and examined glucose tolerance and insulin sensitivity in young and aged mice as well as in mice fed with a high fat diet. Expression profiles of pro- and anti-inflammatory cytokines in white adipose tissue, liver and skeletal muscle was assessed. Results: Here we show that mice lacking GPR4 have an improved intraperitoneal glucose tolerance test and increased insulin sensitivity. Insulin levels were comparable but leptin levels were increased in GPR4 KO mice. Gpr4-/- showed altered expression of PPARα, IL-6, IL-10, TNFα, and TGF-1β in skeletal muscle, white adipose tissue, and liver. High fat diet abolished the differences in glucose tolerance and insulin sensitivity between Gpr4+/+ and Gpr4-/- mice. In contrast, in aged mice (12 months old, the positive effect of GPR4 deficiency on glucose tolerance and insulin sensitivity was maintained. Liver and adipose tissue showed no major differences in the mRNA expression of pro- and anti-inflammatory factors between aged mice of both genotypes. Conclusion: Thus, GPR4 deficiency improves glucose tolerance and insulin sensitivity. The effect may involve an altered balance between pro- and anti-inflammatory factors in insulin target tissues.

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...

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.

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.

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)

Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue

International Nuclear Information System (INIS)

Wage, Justin; Ma, Lili; Peluso, Michael; Lamont, Clare; Hahnfeldt, Philip; Hlatky, Lynn; Beheshti, Afshin; Evens, Andrew M.

2015-01-01

Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age. (author)

Physical measurements with a high-energy proton beam using liquid and solid tissue substitutes

International Nuclear Information System (INIS)

Constantinou, C.; Kember, N.F.; Huxtable, G.; Whitehead, C.

1980-01-01

The measurement of the physical parameters of a high-energy proton beam, using a range of liquid and solid tissue substitutes, is described. The system, the detectors used and the experimental verification of the tissue equivalence of the new tissue substitutes is presented. The measurements with the scattered but uncollimated proton beam in muscle-and brain-equivalent liquids and in water are compared to similar data obtained from the scattered but collimated beam. The effect of lung, fat and bone on the dose distributions in composite phantoms is also investigated and the necessary corrections established. A simulated patient treatment indicated that the Bragg peak can be positioned with an error not exceeding +-0.5 mm. (author)

Non-invasive measurement and imaging of tissue iron oxide nanoparticle concentrations in vivo using proton relaxometry

International Nuclear Information System (INIS)

St Pierre, T G; Clark, P R; Chua-anusorn, W; Fleming, A; Pardoe, H; Jeffrey, G P; Olynyk, J K; Pootrakul, P; Jones, S; Moroz, P

2005-01-01

Magnetic nanoparticles and microparticles can be found in biological tissues for a variety of reasons including pathological deposition of biogenic particles, administration of synthetic particles for scientific or clinical reasons, and the inclusion of biogenic magnetic particles for the sensing of the geomagnetic field. In applied magnetic fields, the magnetisation of tissue protons can be manipulated with radiofrequency radiation such that the macroscopic magnetisation of the protons precesses freely in the plane perpendicular to the applied static field. The presence of magnetic particles within tissue enhances the rate of dephasing of proton precession with higher concentrations of particles resulting in higher dephasing rates. Magnetic resonance imaging instruments can be used to measure and image the rate of decay of spin echo recoverable proton transverse magnetisation (R 2 ) within tissues enabling the measurement and imaging of magnetic particle concentrations with the aid of suitable calibration curves. Applications include the non-invasive measurement of liver iron concentrations in iron-overload disorders and measurement and imaging of magnetic particle concentrations used in magnetic hyperthermia therapy. Future applications may include the tracking of magnetically labelled drugs or biomolecules and the measurement of fibrotic liver damage

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

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.

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.

SU-E-T-470: Importance of HU-Mass Density Calibration Technique in Proton Pencil Beam Dose Calculation

Energy Technology Data Exchange (ETDEWEB)

Penfold, S; Miller, A [University of Adelaide, Adelaide, SA (Australia)

2015-06-15

Purpose: Stoichiometric calibration of Hounsfield Units (HUs) for conversion to proton relative stopping powers (RStPs) is vital for accurate dose calculation in proton therapy. However proton dose distributions are not only dependent on RStP, but also on relative scattering power (RScP) of patient tissues. RScP is approximated from material density but a stoichiometric calibration of HU-density tables is commonly neglected. The purpose of this work was to quantify the difference in calculated dose of a commercial TPS when using HU-density tables based on tissue substitute materials and stoichiometric calibrated ICRU tissues. Methods: Two HU-density calibration tables were generated based on scans of the CIRS electron density phantom. The first table was based directly on measured HU and manufacturer quoted density of tissue substitute materials. The second was based on the same CT scan of the CIRS phantom followed by a stoichiometric calibration of ICRU44 tissue materials. The research version of Pinnacle{sup 3} proton therapy was used to compute dose in a patient CT data set utilizing both HU-density tables. Results: The two HU-density tables showed significant differences for bone tissues; the difference increasing with increasing HU. Differences in density calibration table translated to a difference in calculated RScP of −2.5% for ICRU skeletal muscle and 9.2% for ICRU femur. Dose-volume histogram analysis of a parallel opposed proton therapy prostate plan showed that the difference in calculated dose was negligible when using the two different HU-density calibration tables. Conclusion: The impact of HU-density calibration technique on proton therapy dose calculation was assessed. While differences were found in the calculated RScP of bony tissues, the difference in dose distribution for realistic treatment scenarios was found to be insignificant.

Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

Energy Technology Data Exchange (ETDEWEB)

Nichols, Romaine C., E-mail: rnichols@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Huh, Soon N. [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States); Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

2012-05-01

Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

A prospective study of proton reirradiation for recurrent and secondary soft tissue sarcoma.

Science.gov (United States)

Guttmann, David M; Frick, Melissa A; Carmona, Ruben; Deville, Curtiland; Levin, William P; Berman, Abigail T; Chinniah, Chidambaram; Hahn, Stephen M; Plastaras, John P; Simone, Charles B

2017-08-01

Proton reirradiation for sarcoma has not been previously described. We hypothesized that this strategy would provide favorable toxicity and survival outcomes. Patients with soft tissue sarcoma in a previously-irradiated field were enrolled on a prospective trial of proton reirradiation. The primary endpoint was provider-reported acute toxicity. Secondary endpoints included late toxicities, local control, and overall survival. 23 patients underwent proton reirradiation. Median time between radiation courses was 40.7months (range 10-272). No grade 4-5 toxicities were observed. One patient (4%) experienced acute grade 3 dysphagia. Common grade 2 acute toxicities were fatigue (26%), anorexia (17%), and urinary incontinence (13%). There were two grade 3 late wound infections (10%) and one grade 3 late wound complication (5%). Grade 2 late complications included lymphedema (10%), fracture (5%), and fibrosis (5%). At a median follow-up of 36months, the 3-year cumulative incidence of local failure was 41% (95% CI [20-63%]). Median overall survival and progression-free survival were 44 and 29months, respectively. In extremity patients, amputation was spared in 7/10 (70%). Proton reirradiation of recurrent/secondary soft tissue sarcomas is well tolerated. While longer follow-up is needed, early survival outcomes in this high-risk population are encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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...

* 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

Proton activation analysis at the Harvard Cyclotron Laboratory

International Nuclear Information System (INIS)

Sisterson, J.M.; Koehler, A.M.

1984-01-01

High-energy proton activation analysis (PAA), a simple non-destructive technique, has been developed for use as an adjunct to neutron activation analysis. Potential advantages of protons include the ability to achieve very precise localization of the activation volume over a pre-determined depth in the target. To demonstrate the versatility of PAA, results are reported on the measurement of the whole body calcium content in animals and on the determination of the Ca/P molar ratio in small quantities (<50 mg) of chemical and biological samples. The animal experiments demonstrate the ability to achieve a uniform irradiation over a large volume and utilizes large NaI crystals with a special chamber for uniform combined detection efficiency, where the Ca/P molar ratio determination requires a Ge/Li detector and analysis of the resulting gamma ray spectrum. The feasibility is being assessed of using proton beam activation of the eye to measure blood flow in the rabbit choroid, based on earlier work where it was used to measure blood in mouse skeletal tissue. 6 references, 7 figures, 4 tables

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.

On proton CT reconstruction using MVCT-converted virtual proton projections

Energy Technology Data Exchange (ETDEWEB)

Wang Dongxu; Mackie, T. Rockwell; Tome, Wolfgang A. [Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242 (United States); Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Morgridge Institute of Research, University of Wisconsin, Madison, Wisconsin 53715 (United States); Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Oncophysics Institute, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461 (United States)

2012-06-15

Purpose: To describe a novel methodology of converting megavoltage x-ray projections into virtual proton projections that are otherwise missing due to the proton range limit. These converted virtual proton projections can be used in the reconstruction of proton computed tomography (pCT). Methods: Relations exist between proton projections and multispectral megavoltage x-ray projections for human tissue. Based on these relations, these tissues can be categorized into: (a) adipose tissue; (b) nonadipose soft tissues; and (c) bone. These three tissue categories can be visibly identified on a regular megavoltage x-ray computed tomography (MVCT) image. With an MVCT image and its projection data available, the x-ray projections through heterogeneous anatomy can be converted to the corresponding proton projections using predetermined calibration curves for individual materials, aided by a coarse segmentation on the x-ray CT image. To show the feasibility of this approach, mathematical simulations were carried out. The converted proton projections, plotted on a proton sinogram, were compared to the simulated ground truth. Proton stopping power images were reconstructed using either the virtual proton projections only or a blend of physically available proton projections and virtual proton projections that make up for those missing due to the range limit. These images were compared to a reference image reconstructed from theoretically calculated proton projections. Results: The converted virtual projections had an uncertainty of {+-}0.8% compared to the calculated ground truth. Proton stopping power images reconstructed using a blend of converted virtual projections (48%) and physically available projections (52%) had an uncertainty of {+-}0.86% compared with that reconstructed from theoretically calculated projections. Reconstruction solely from converted virtual proton projections had an uncertainty of {+-}1.1% compared with that reconstructed from theoretical projections

On proton CT reconstruction using MVCT-converted virtual proton projections

International Nuclear Information System (INIS)

Wang Dongxu; Mackie, T. Rockwell; Tomé, Wolfgang A.

2012-01-01

Purpose: To describe a novel methodology of converting megavoltage x-ray projections into virtual proton projections that are otherwise missing due to the proton range limit. These converted virtual proton projections can be used in the reconstruction of proton computed tomography (pCT). Methods: Relations exist between proton projections and multispectral megavoltage x-ray projections for human tissue. Based on these relations, these tissues can be categorized into: (a) adipose tissue; (b) nonadipose soft tissues; and (c) bone. These three tissue categories can be visibly identified on a regular megavoltage x-ray computed tomography (MVCT) image. With an MVCT image and its projection data available, the x-ray projections through heterogeneous anatomy can be converted to the corresponding proton projections using predetermined calibration curves for individual materials, aided by a coarse segmentation on the x-ray CT image. To show the feasibility of this approach, mathematical simulations were carried out. The converted proton projections, plotted on a proton sinogram, were compared to the simulated ground truth. Proton stopping power images were reconstructed using either the virtual proton projections only or a blend of physically available proton projections and virtual proton projections that make up for those missing due to the range limit. These images were compared to a reference image reconstructed from theoretically calculated proton projections. Results: The converted virtual projections had an uncertainty of ±0.8% compared to the calculated ground truth. Proton stopping power images reconstructed using a blend of converted virtual projections (48%) and physically available projections (52%) had an uncertainty of ±0.86% compared with that reconstructed from theoretically calculated projections. Reconstruction solely from converted virtual proton projections had an uncertainty of ±1.1% compared with that reconstructed from theoretical projections. If

Proton radiography to improve proton therapy treatment

NARCIS (Netherlands)

Takatsu, J.; van der Graaf, E. R.; van Goethem, Marc-Jan; van Beuzekom, M.; Klaver, T.; Visser, Jan; Brandenburg, S.; Biegun, A. K.

The quality of cancer treatment with protons critically depends on an accurate prediction of the proton stopping powers for the tissues traversed by the protons. Today, treatment planning in proton radiotherapy is based on stopping power calculations from densities of X-ray Computed Tomography (CT)

Measurement of characteristic prompt gamma rays emitted from oxygen and carbon in tissue-equivalent samples during proton beam irradiation.

Science.gov (United States)

Polf, Jerimy C; Panthi, Rajesh; Mackin, Dennis S; McCleskey, Matt; Saastamoinen, Antti; Roeder, Brian T; Beddar, Sam

2013-09-07

The purpose of this work was to characterize how prompt gamma (PG) emission from tissue changes as a function of carbon and oxygen concentration, and to assess the feasibility of determining elemental concentration in tissues irradiated with proton beams. For this study, four tissue-equivalent water-sucrose samples with differing densities and concentrations of carbon, hydrogen, and oxygen were irradiated with a 48 MeV proton pencil beam. The PG spectrum emitted from each sample was measured using a high-purity germanium detector, and the absolute detection efficiency of the detector, average beam current, and delivered dose distribution were also measured. Changes to the total PG emission from (12)C (4.44 MeV) and (16)O (6.13 MeV) per incident proton and per Gray of absorbed dose were characterized as a function of carbon and oxygen concentration in the sample. The intensity of the 4.44 MeV PG emission per incident proton was found to be nearly constant for all samples regardless of their carbon concentration. However, we found that the 6.13 MeV PG emission increased linearly with the total amount (in grams) of oxygen irradiated in the sample. From the measured PG data, we determined that 1.64 × 10(7) oxygen PGs were emitted per gram of oxygen irradiated per Gray of absorbed dose delivered with a 48 MeV proton beam. These results indicate that the 6.13 MeV PG emission from (16)O is proportional to the concentration of oxygen in tissue irradiated with proton beams, showing that it is possible to determine the concentration of oxygen within tissues irradiated with proton beams by measuring (16)O PG emission.

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...

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

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.

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.

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

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

Amide proton transfer imaging of high intensity focused ultrasound-treated tumor tissue

NARCIS (Netherlands)

Hectors, S.J.C.G.; Jacobs, I.; Strijkers, G.J.; Nicolay, K.

2014-01-01

Purpose: In this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. Methods: APT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

Amide Proton Transfer Imaging of High Intensity Focused Ultrasound-Treated Tumor Tissue

NARCIS (Netherlands)

Hectors, Stefanie J. C. G.; Jacobs, Igor; Strijkers, Gustav J.; Nicolay, Klaas

2014-01-01

PurposeIn this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. MethodsAPT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

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.

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.

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.

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...

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

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

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...

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...

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.

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.

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...

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.

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.

Chiral Orientation of Skeletal Muscle Cells Requires Rigid Substrate

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Ninghao Zhu

2017-06-01

Full Text Available Reconstitution of tissue morphology with inherent left–right (LR asymmetry is essential for tissue/organ functions. For skeletal muscle, the largest tissue in mammalian organisms, successful myogenesis requires the regulation of the LR asymmetry to form the appropriate muscle alignment. However, the key factor for reproducing the LR asymmetry of skeletal tissues in a controllable, engineering context remains largely unknown. Recent reports indicate that cell chirality may underlie the LR development in tissue morphogenesis. Here, we report that a rigid substrate is required for the chirality of skeletal muscle cells. By using alternating micropatterned cell-adherent and cell-repellent stripes on a rigid substrate, we found that C2C12 skeletal muscle myoblasts exhibited a unidirectional tilted orientation with respect to the stripe boundary. Importantly, such chiral orientation was reduced when soft substrates were used instead. In addition, we demonstrated the key role of actin stress fibers in the formation of the chiral orientation. This study reveals that a rigid substrate is required for the chiral pattern of myoblasts, paving the way for reconstructing damaged muscle tissue with inherent LR asymmetry in the future.

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.

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

NARCIS (Netherlands)

Pettersen, H. E. S.; Alme, J.; Biegun, A.; van den Brink, A.; Chaar, M.; Fehlker, D.; Meric, I.; Odland, O. H.; Peitzmann, T.; Rocco, E.; Ullaland, K.; Wang, H.; Yang, S.; Zhang, C.; Rohrich, D.

2017-01-01

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the

TU-FG-BRB-01: Dual Energy CT Proton Stopping Power Ratio Calibration and Validation with Animal Tissues

Energy Technology Data Exchange (ETDEWEB)

Xie, Y; Yin, L; Ainsley, C; McDonough, J; Solberg, T; Lin, A; Teo, B [University of Pennsylvania, Philadelphia, PA (United States)

2016-06-15

Purpose: The conversion of Hounsfield Unit (HU) to proton stopping power ratio (SPR) is a main source of uncertainty in proton therapy. In this study, the SPRs of animal tissues were measured and compared with prediction from dual energy CT (DECT) and single energy CT (SECT) calibrations. Methods: A stoichiometric calibration method for DECT was applied to predict the SPR using CT images acquired at 80 kVp and 140 kVp. The dual energy index was derived based on the HUs of the paired spectral images and used to calculate the SPRs of the materials. Tissue surrogates with known chemical compositions were used for calibration, and animal tissues (pig brain, liver, kidney; veal shank, muscle) were used for validation. The materials were irradiated with proton pencil beams, and SPRs were deduced from the residual proton range measured using a multi-layer ion chamber device. In addition, Gafchromic EBT3 films were used to measure the distal dose profiles after irradiation through the tissue samples and compared with those calculated by the treatment planning system using both DECT and SECT predicted SPRs. Results: The differences in SPR between DECT prediction and measurement were −0.31±0.36% for bone, 0.47±0.42% for brain, 0.67±0.15% for liver, 0.51±0.52% for kidney, and −0.96±0.15% for muscle. The corresponding results using SECT were 3.1±0.12%, 1.90±0.45%, −0.66±0.11%, 2.33±0.21%, and −1.70±0.17%. In the film measurements, average distances between film and calculated distal dose profiles were 0.35±0.12 mm for DECT calibration and −1.22±0.12 mm for SECT calibration for a beam with a range of 15.79 cm. Conclusion: Our study indicates that DECT is superior to SECT for proton SPR prediction and has the potential to reduce the range uncertainty to less than 2%. DECT may permit the use of tighter distal and proximal range uncertainty margins for treatment, thereby increasing the precision of proton therapy.

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.

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

NARCIS (Netherlands)

Pettersen, H. E.S.; Alme, J.; Biegun, A.; van den Brink, A.; Chaar, M.; Fehlker, D.; Meric, I.; Odland, O. H.; Peitzmann, T.; Rocco, E.; Ullaland, K.; Wang, H.; Yang, S.; Zhang, C.; Röhrich, D.

2017-01-01

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2–3% of the

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.

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.

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.

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.

Dose equivalent near the bone-soft tissue interface from nuclear fragments produced by high-energy protons

Science.gov (United States)

Shavers, M. R.; Poston, J. W.; Cucinotta, F. A.; Wilson, J. W.

1996-01-01

During manned space missions, high-energy nucleons of cosmic and solar origin collide with atomic nuclei of the human body and produce a broad linear energy transfer spectrum of secondary particles, called target fragments. These nuclear fragments are often more biologically harmful than the direct ionization of the incident nucleon. That these secondary particles increase tissue absorbed dose in regions adjacent to the bone-soft tissue interface was demonstrated in a previous publication. To assess radiological risks to tissue near the bone-soft tissue interface, a computer transport model for nuclear fragments produced by high energy nucleons was used in this study to calculate integral linear energy transfer spectra and dose equivalents resulting from nuclear collisions of 1-GeV protons transversing bone and red bone marrow. In terms of dose equivalent averaged over trabecular bone marrow, target fragments emitted from interactions in both tissues are predicted to be at least as important as the direct ionization of the primary protons-twice as important, if recently recommended radiation weighting factors and "worst-case" geometry are used. The use of conventional dosimetry (absorbed dose weighted by aa linear energy transfer-dependent quality factor) as an appropriate framework for predicting risk from low fluences of high-linear energy transfer target fragments is discussed.

Orthodontics-surgical combination therapy for Class III skeletal malocclusion

Directory of Open Access Journals (Sweden)

M S Ravi

2012-01-01

Full Text Available The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical-orthodontic combination therapy has resulted in near-normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level.

Skeletal muscle inflammation and insulin resistance in obesity

Science.gov (United States)

Wu, Huaizhu; Ballantyne, Christie M.

2017-01-01

Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance. PMID:28045398

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...

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...

Normal liver tissue sparing by intensity-modulated proton stereotactic body radiotherapy for solitary liver tumours

International Nuclear Information System (INIS)

Petersen, Joergen B. B.; Hansen, Anders T.; Lassen, Yasmin; Grau, Cai; Hoeyer, Morten; Muren, Ludvig P.

2011-01-01

Background. Stereotactic body radiotherapy (SBRT) is often the preferred treatment for the advanced liver tumours which owing to tumour distribution, size and multi-focality are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients with liver tumours may be candidates for conventional SBRT because of the limited radiation tolerance of normal liver, intestine and other normal tissues. Due to the favourable depth-dose characteristics of protons, intensity-modulated proton therapy (IMPT) may be a superior alternative to photon-based SBRT. The purpose of this treatment planning study was therefore to investigate the potential sparing of normal liver by IMPT compared to photon-based intensity-modulated radiotherapy (IMRT) for solitary liver tumours. Material and methods. Ten patients with solitary liver metastasis treated at our institution with multi-field SBRT were retrospectively re-planned with IMRT and proton pencil beam scanning techniques. For the proton plans, two to three coplanar fields were used in contrast to five to six coplanar and non-coplanar photon fields. The same planning objectives were used for both techniques. A risk adapted dose prescription to the PTV surface of 12.5-16.75 Gy x 3 was used. Results. The spared liver volume for IMPT was higher compared to IMRT in all 10 patients. At the highest prescription dose level, the median liver volume receiving less than 15 Gy was 1411 cm 3 for IMPT and 955 cm 3 for IMRT (p D 15 Gy > 700 cm 3 constraint. For the D mean = 15 Gy constraint, nine of 10 cases could be treated at the highest dose level using IMPT whereas with IMRT, only two cases met this constraint at the highest dose level and six at the lowest dose level. Conclusion. A considerable sparing of normal liver tissue can be obtained using proton-based SBRT for solitary liver tumours

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...

Photothermal imaging of skeletal muscle mitochondria.

Science.gov (United States)

Tomimatsu, Toru; Miyazaki, Jun; Kano, Yutaka; Kobayashi, Takayoshi

2017-06-01

The morphology and topology of mitochondria provide useful information about the physiological function of skeletal muscle. Previous studies of skeletal muscle mitochondria are based on observation with transmission, scanning electron microscopy or fluorescence microscopy. In contrast, photothermal (PT) microscopy has advantages over the above commonly used microscopic techniques because of no requirement for complex sample preparation by fixation or fluorescent-dye staining. Here, we employed the PT technique using a simple diode laser to visualize skeletal muscle mitochondria in unstained and stained tissues. The fine mitochondrial network structures in muscle fibers could be imaged with the PT imaging system, even in unstained tissues. PT imaging of tissues stained with toluidine blue revealed the structures of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria and the swelling behavior of mitochondria in damaged muscle fibers with sufficient image quality. PT image analyses based on fast Fourier transform (FFT) and Grey-level co-occurrence matrix (GLCM) were performed to derive the characteristic size of mitochondria and to discriminate the image patterns of normal and damaged fibers.

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.

Magnetization transfer from macromolecules to water protons in murine dental tissues as revealed by 500 MHz 1H-NMR

International Nuclear Information System (INIS)

Nakamura, Koji; Era, Seiichi; Nagai, Naoki; Sogami, Masaru; Takasaki, Akihiko; Kato, Kazuo.

1997-01-01

Although much is known about magnetization transfer phenomena in biological soft tissues, little is known about those in hard tissues. Using a 500 MHz 1 H-NMR spectrometer, we studied the spin-lattice relaxation time (T 1 (H 2 O)) and the intermolecular cross-relaxation times (T IS (H 2 O)) from irradiated macromolecular protons to observed water protons in murine lower incisors (hard tissue) and compared with those in murine lens tissue (soft tissue). Mean values for the water content (%) of murine lower incisors and lens tissue were 16.02±2.39 (n=14) and 67.20±4.60 (n=15), respectively. These findings were consistent with the large different in water content between soft tissues and hard tissues. T IS (H 2 O) values obtained by f 2 -irradiation at 7.13 or -4.00 ppm showed no significant difference between lower incisors and lens tissue. Plots of 1/T IS (H 2 O) values vs. tissue dry weight (W(%)) for lower incisor tissue approximated a straight line with slope approximately equal for that obtained for lens tissue. These results suggest that the state of water in hard tissue may be similar to that in soft tissues, in spite of the significant difference in water content. Thus, saturation transfer NMR techniques such as measurement of T IS (H 2 O) values may be applicable to the study of water-macromolecule interactions in both biological soft and hard tissues. (author)

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.

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.

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...

SU-F-T-181: Proton Therapy Tissue-Equivalence of 3D Printed Materials

International Nuclear Information System (INIS)

Taylor, P; Craft, D; Followill, D; Howell, R

2016-01-01

Purpose: This work investigated the proton tissue-equivalence of various 3D printed materials. Methods: Three 3D printers were used to create 5 cm cubic phantoms made of different plastics with varying percentages of infill. White resin, polylactic acid (PLA), and NinjaFlex plastics were used. The infills ranged from 15% to 100%. Each phantom was scanned with a CT scanner to obtain the HU value. The relative linear stopping power (RLSP) was then determined using a multi-layer ion chamber in a 200 MeV proton beam. The RLSP was measured both parallel and perpendicular to the print direction for each material. Results: The HU values of the materials ranged from lung-equivalent (−820 HU σ160) when using a low infill, to soft-tissue-equivalent 159 (σ12). The RLSP of the materials depended on the orientation of the beam relative to the print direction. When the proton beam was parallel to the print direction, the RLSP was generally higher than the RLSP in the perpendicular orientation, by up to 45%. This difference was smaller (less than 6%) for the materials with 100% infill. For low infill cubes irradiated parallel to the print direction, the SOBP curve showed extreme degradation of the beam in the distal region. The materials with 15–25% infill had wide-ranging agreement with a clinical HU-RLSP conversion curve, with some measurements falling within 1% of the curve and others deviating up to 45%. The materials with 100% infill all fell within 7% of the curve. Conclusion: While some materials tested fall within 1% of a clinical HU-RLSP curve, caution should be taken when using 3D printed materials with proton therapy, as the orientation of the beam relative to the print direction can result in a large change in RLSP. Further investigation is needed to measure how the infill pattern affects the material RLSP. This work was supported by PHS grant CA180803.

SU-F-T-181: Proton Therapy Tissue-Equivalence of 3D Printed Materials

Energy Technology Data Exchange (ETDEWEB)

Taylor, P; Craft, D; Followill, D; Howell, R [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: This work investigated the proton tissue-equivalence of various 3D printed materials. Methods: Three 3D printers were used to create 5 cm cubic phantoms made of different plastics with varying percentages of infill. White resin, polylactic acid (PLA), and NinjaFlex plastics were used. The infills ranged from 15% to 100%. Each phantom was scanned with a CT scanner to obtain the HU value. The relative linear stopping power (RLSP) was then determined using a multi-layer ion chamber in a 200 MeV proton beam. The RLSP was measured both parallel and perpendicular to the print direction for each material. Results: The HU values of the materials ranged from lung-equivalent (−820 HU σ160) when using a low infill, to soft-tissue-equivalent 159 (σ12). The RLSP of the materials depended on the orientation of the beam relative to the print direction. When the proton beam was parallel to the print direction, the RLSP was generally higher than the RLSP in the perpendicular orientation, by up to 45%. This difference was smaller (less than 6%) for the materials with 100% infill. For low infill cubes irradiated parallel to the print direction, the SOBP curve showed extreme degradation of the beam in the distal region. The materials with 15–25% infill had wide-ranging agreement with a clinical HU-RLSP conversion curve, with some measurements falling within 1% of the curve and others deviating up to 45%. The materials with 100% infill all fell within 7% of the curve. Conclusion: While some materials tested fall within 1% of a clinical HU-RLSP curve, caution should be taken when using 3D printed materials with proton therapy, as the orientation of the beam relative to the print direction can result in a large change in RLSP. Further investigation is needed to measure how the infill pattern affects the material RLSP. This work was supported by PHS grant CA180803.

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.

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

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.

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.

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

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.

Circulating Docosahexaenoic Acid Associates with Insulin-Dependent Skeletal Muscle and Whole Body Glucose Uptake in Older Women Born from Normal Weight Mothers

Directory of Open Access Journals (Sweden)

Robert M. Badeau

2017-02-01

Full Text Available Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM or offspring of lean mothers (OLM. Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17 and elderly offspring from lean/normal weight mothers (OLM; n = 20 groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA was significantly lower in OOM (p = 0.015. DHA/FA associated significantly with skeletal muscle glucose uptake (GU (p = 0.031 and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value in the OLM group only (p = 0.050. Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.

A Comparison of Molecular and Histopathological Changes in Mouse Intestinal Tissue Following Whole-Body Proton- or Gamma-Irradiation

Science.gov (United States)

Purgason, Ashley; Mangala, Lingegowda; Zhang, Ye; Hamilton, Stanley; Wu, Honglu

2010-01-01

There are many consequences following exposure to the space radiation environment which can adversely affect the health of a crew member. Acute radiation syndrome (ARS) involving nausea and vomiting, damage to radio-sensitive tissue such as the blood forming organs and gastrointestinal tract, and cancer are some of these negative effects. The space radiation environment is ample with protons and contains gamma rays as well. Little knowledge exists to this point, however, regarding the effects of protons on mammalian systems; conversely several studies have been performed observing the effects of gamma rays on different animal models. For the research presented here, we wish to compare our previous work looking at whole-body exposure to protons using a mouse model to our studies of mice experiencing whole-body exposure to gamma rays as part of the radio-adaptive response. Radio-adaptation is a well-documented phenomenon in which cells exposed to a priming low dose of radiation prior to a higher dose display a reduction in endpoints like chromosomal aberrations, cell death, micronucleus formation, and more when compared to their counterparts receiving high dose-irradiation only. Our group has recently completed a radio-adaptive experiment with C57BL/6 mice. For both this study and the preceding proton research, the gastrointestinal tract of each animal was dissected four hours post-irradiation and the isolated small intestinal tissue was fixed in formalin for histopathological examination or snap-frozen in liquid nitrogen for RNA isolation. Histopathologic observation of the tissue using standard H&E staining methods to screen for morphologic changes showed an increase in apoptotic lesions for even the lowest doses of 0.1 Gy of protons and 0.05 Gy of gamma rays, and the percentage of apoptotic cells increased with increasing dose. A smaller percentage of crypts showed 3 or more apoptotic lesions in animals that received 6 Gy of gamma-irradiation compared to mice

Proton beam therapy how protons are revolutionizing cancer treatment

CERN Document Server

Yajnik, Santosh

2013-01-01

Proton beam therapy is an emerging technology with promise of revolutionizing the treatment of cancer. While nearly half of all patients diagnosed with cancer in the US receive radiation therapy, the majority is delivered via electron accelerators, where photons are used to irradiate cancerous tissue. Because of the physical properties of photon beams, photons may deposit energy along their entire path length through the body. On the other hand, a proton beam directed at a tumor travels in a straight trajectory towards its target, gives off most of its energy at a defined depth called the Bragg peak, and then stops. While photons often deposit more energy within the healthy tissues of the body than within the cancer itself, protons can deposit most of their cancer-killing energy within the area of the tumor. As a result, in the properly selected patients, proton beam therapy has the ability to improve cure rates by increasing the dose delivered to the tumor and simultaneously reduce side-effects by decreasing...

Cell potentials, cell resistance, and proton fluxes in corn root tissue. Effects of dithioerythritol

Energy Technology Data Exchange (ETDEWEB)

Lin, W.; Hanson, J.B.

1976-09-01

Studies were made of the effect of dithioerythritol on net proton flux, potassium influx and efflux, cell potential, and cell resistance in fresh and washed corn (Zea mays L. WF9XM14) root tissue. Dithioerythritol induces equal proton influx and potassium efflux rates, decreases membrane resistance, and hyperpolarizes the cell potential. Greater effects on H/sup +/ and K/sup +/ fluxes are secured at pH 7 than at pH 5. Other sulfhydryl-protecting reagents produced the same responses. No evidence could be found that dithioerythritol affected energy metabolism or membrane ATPase, and proton influx was induced in the presence of uncoupling agents. We deduce that dithioerythritol activates a passive H/sup +//K/sup +/ antiport, driven in these experiments by the outwardly directed electrochemical gradient of K/sup +/. The net effect on H/sup +/ and K/sup +/ fluxes is believed to reside with the combined activity of a polarized H/sup +//K/sup +/ exchanging ATPase and the passive H/sup +//K/sup +/ antiport. A model is presented to show how the combined system might produce stable potential differences and K/sup +/ content.

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.

Criteria for personal dosimetry in mixed radiation fields in space. [analyzing trapped protons, tissue disintegration stars, and neutrons

Science.gov (United States)

Schaefer, H. J.

1974-01-01

The complexity of direct reading and passive dosimeters for monitoring radiation is studied to strike the right balance of compromise to simplify the monitoring procedure. Trapped protons, tissue disintegration stars, and neutrons are analyzed.

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.

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.

Oncological outcomes of patients with Ewing's sarcoma: is there a difference between skeletal and extra-skeletal Ewing's sarcoma?

Science.gov (United States)

Pradhan, A; Grimer, R J; Spooner, D; Peake, D; Carter, S R; Tillman, R M; Abudu, A; Jeys, L

2011-04-01

The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing's sarcoma. We identified 300 patients with new primary Ewing's sarcoma diagnosed between 1980 and 2005 from the centres' local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing's sarcomas. Although patients with skeletal Ewing's were younger (mean age 16.8 years) than those with extra-skeletal Ewing's sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing's sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing's sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.

Importance of pH Homeostasis in Metabolic Health and Diseases: Crucial Role of Membrane Proton Transport

Directory of Open Access Journals (Sweden)

Wataru Aoi

2014-01-01

Full Text Available Protons dissociated from organic acids in cells are partly buffered. If not, they are transported to the extracellular fluid through the plasma membrane and buffered in circulation or excreted in urine and expiration gas. Several transporters including monocarboxylate transporters and Na+/H+ exchanger play an important role in uptake and output of protons across plasma membranes in cells of metabolic tissues including skeletal muscle and the liver. They also contribute to maintenance of the physiological pH of body fluid. Therefore, impairment of these transporters causes dysfunction of cells, diseases, and a decrease in physical performance associated with abnormal pH. Additionally, it is known that fluid pH in the interstitial space of metabolic tissues is easily changed due to little pH buffering capacitance in interstitial fluids and a reduction in the interstitial fluid pH may mediate the onset of insulin resistance unlike blood containing pH buffers such as Hb (hemoglobin and albumin. In contrast, habitual exercise and dietary intervention regulate expression/activity of transporters and maintain body fluid pH, which could partly explain the positive effect of healthy lifestyle on disease prognosis.

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

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...

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...

Role of histidine-related compounds to intracellular buffering in fish skeletal muscle.

Science.gov (United States)

Abe, H; Dobson, G P; Hoeger, U; Parkhouse, W S

1985-10-01

Histidine-related compounds (HRC) were analyzed in fish skeletal muscle as a means of identifying their precise role in intracellular buffering. Fish muscle was used because it contains two functionally and spatially distinct fiber types, red and white. Two fish species, rainbow trout (Salmo gairdneri) and the Pacific blue marlin (Makaira nigricans), were studied because these species demonstrate widely different activity patterns. Marlin red and white muscle buffer capacity was two times higher than trout with white muscle, buffering being two times greater than red in both species. Buffer capacity was highest in the 6.5-7.5 pH range for all tissues, which corresponded to their high anserine levels. The titrated HRC buffering was greater than the observed HRC buffering, which suggested that not all HRC were available to absorb protons. The HRC contribution to total cellular buffering varied from a high of 62% for marlin white to a low of 7% for trout red. The other principal buffers were found to be phosphate and protein with taurine contributing within red muscle in the 7.0-8.0 pH range. HRC were found to be dominant in skeletal muscle buffering by principally accounting for the buffering capacity differences found between the species and fiber types.

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

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.

Feasibility of proton-activated implantable markers for proton range verification using PET

Science.gov (United States)

Cho, Jongmin; Ibbott, Geoffrey; Gillin, Michael; Gonzalez-Lepera, Carlos; Titt, Uwe; Paganetti, Harald; Kerr, Matthew; Mawlawi, Osama

2013-11-01

Proton beam range verification using positron emission tomography (PET) currently relies on proton activation of tissue, the products of which decay with a short half-life and necessitate an on-site PET scanner. Tissue activation is, however, negligible near the distal dose fall-off region of the proton beam range due to their high interaction energy thresholds. Therefore Monte Carlo simulation is often supplemented for comparison with measurement; however, this also may be associated with systematic and statistical uncertainties. Therefore, we sought to test the feasibility of using long-lived proton-activated external materials that are inserted or infused into the target volume for more accurate proton beam range verification that could be performed at an off-site PET scanner. We irradiated samples of ≥98% 18O-enriched water, natural Cu foils, and >97% 68Zn-enriched foils as candidate materials, along with samples of tissue-equivalent materials including 16O water, heptane (C7H16), and polycarbonate (C16H14O3)n, at four depths (ranging from 100% to 3% of center of modulation (COM) dose) along the distal fall-off of a modulated 160 MeV proton beam. Samples were irradiated either directly or after being embedded in Plastic Water® or balsa wood. We then measured the activity of the samples using PET imaging for 20 or 30 min after various delay times. Measured activities of candidate materials were up to 100 times greater than those of the tissue-equivalent materials at the four distal dose fall-off depths. The differences between candidate materials and tissue-equivalent materials became more apparent after longer delays between irradiation and PET imaging, due to the longer half-lives of the candidate materials. Furthermore, the activation of the candidate materials closely mimicked the distal dose fall-off with offsets of 1 to 2 mm. Also, signals from the foils were clearly visible compared to the background from the activated Plastic Water® and balsa wood

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.

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.

Skeletal-muscle CT, with special reference to polymyositis and myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Higashi, Yasuto; Ono, Shimato; Yasuda, Takeshi; Morimoto, Kenji; Terao, Akira; Shirabe, Teruo; Yokobayashi, Tsuneo (Kawasaki Medical School, Kurashiki, Okayama (Japan))

1984-10-01

We here report on skeletal-muscle CT at the thigh level as studied using a whole-body CT scanner, with special reference to polymyositis (PM) and myasthenia gravis (MG). Early diseased muscles appeared homogenous and were likely to be almost normal. The first sign of muscular atrophy was the appearance of small, patchy or linear, low-density tissues in several muscles. These low-density tissues gradually increased in number until finally the diseased muscles were totally replaced by low-density tissue. These pathological findings were more severe in PM than in MG. There was a maldistribution of low-density tissue in several cases of PM. According to these findings, skeletal-muscle CT was thought to be of great help for the recognition of the general condition of muscles and for the follow-up on the patients. We think skeletal-muscle CT has a very practical application for the better selection of suitable muscular biopsy and EMG sites and for the better clinical interpretation of these findings.

Skeletal-muscle CT, with special reference to polymyositis and myasthenia gravis

International Nuclear Information System (INIS)

Higashi, Yasuto; Ono, Shimato; Yasuda, Takeshi; Morimoto, Kenji; Terao, Akira; Shirabe, Teruo; Yokobayashi, Tsuneo

1984-01-01

We here report on skeletal-muscle CT at the thigh level as studied using a whole-body CT scanner, with special reference to polymyositis (PM) and myasthenia gravis (MG). Early diseased muscles appeared homogenous and were likely to be almost normal. The first sign of muscular atrophy was the apperance of small, patchy or linear, low-density tissues in several muscles. These low-density tissues gradually increased in number until finally the diseased muscles were totally replaced by low-density tissue. These pathological findings were more severe in PM than in MG. There was a maldistribution of low-density tissue in several cases of PM. According to these findings, skeletal-muscle CT was thought to be of great help for the recognition of the general condition of muscles and for the follow-up on the patients. We think skeletal-muscle CT has a very practical application for the better selection of suitable muscular biopsy and EMG sites and for the better clinical interpretation of these findings. (author)

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.

Generation of a vascularized organoid using skeletal muscle as the inductive source.

LENUS (Irish Health Repository)

Messina, Aurora

2005-09-01

The technology required for creating an in vivo microenvironment and a neovasculature that can grow with and service new tissue is lacking, precluding the possibility of engineering complex three-dimensional organs. We have shown that when an arterio-venous (AV) loop is constructed in vivo in the rat groin, and placed inside a semisealed chamber, an extensive functional vasculature is generated. To test whether this unusually angiogenic environment supports the survival and growth of implanted tissue or cells, we inserted various preparations of rat and human skeletal muscle. We show that after 6 weeks incubation of muscle tissue, the chamber filled with predominantly well-vascularized recipient-derived adipose tissue, but some new donor-derived skeletal muscle and connective tissue were also evident. When primary cultured myoblasts were inserted into the chamber with the AV loop, they converted to mature striated muscle fibers. Furthermore, we identify novel adipogenesis-inducing properties of skeletal muscle. This represents the first report of a specific three-dimensional tissue grown on its own vascular supply.

Mesenchymal stem cells (MSCs) as skeletal therapeutics-an update

DEFF Research Database (Denmark)

Saeed, H.; Ahsan, M.; Saleem, Z.

2016-01-01

Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair....../regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range...

Nanoreinforced Hydrogels for Tissue Engineering: Biomaterials that are Compatible with Load-Bearing and Electroactive Tissues

DEFF Research Database (Denmark)

Mehrali, Mehdi; Thakur, Ashish; Pennisi, Christian Pablo

2017-01-01

, mechanical, and electrical properties. Here, recent advances in the fabrication and application of nanocomposite hydrogels in tissue engineering applications are described, with specific attention toward skeletal and electroactive tissues, such as cardiac, nerve, bone, cartilage, and skeletal muscle......Given their highly porous nature and excellent water retention, hydrogel-based biomaterials can mimic critical properties of the native cellular environment. However, their potential to emulate the electromechanical milieu of native tissues or conform well with the curved topology of human organs...

Performance tests and comparison of microdosimetric measurements with four tissue-equivalent proportional counters in scanning proton therapy

Czech Academy of Sciences Publication Activity Database

Farah, J.; De Saint-Hubert, M.; Mojzeszek, N.; Chiriotti, S.; Gryzinski, M.; Ploc, Ondřej; Trompier, F.; Turek, Karel; Vanhavere, F.; Olko, P.

2017-01-01

Roč. 96, JAN (2017), s. 42-52 ISSN 1350-4487 EU Projects: European Commission(XE) 662287 - CONCERT Institutional support: RVO:61389005 Keywords : tissue-equivalent proportional counters * microdosimetry * proton therapy * stray neutrons and prothons Subject RIV: JF - Nuclear Energetics OBOR OECD: Nuclear related engineering Impact factor: 1.442, year: 2016

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.)

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.)

Proton energy and scattering angle radiographs to improve proton treatment planning : a Monte Carlo study

NARCIS (Netherlands)

Biegun, Aleksandra; Takatsu, Jun; Nakaji, Taku; van Goethem, Marc-Jan; van der Graaf, Emiel; Koffeman, E.; Visser, Jan; Brandenburg, Sijtze

2016-01-01

The novel proton radiography imaging technique has a large potential to be used in direct measurement of the proton energy loss (proton stopping power, PSP) in various tissues in the patient. The uncertainty of PSPs, currently obtained from translation of X-ray Computed Tomography (xCT) images,

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

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.

Proton relaxation relationships of human and animal tissues in vitro. Changes due to autolysis and fixing

International Nuclear Information System (INIS)

Grodd, W.; Schmitt, W.G.H.

1983-01-01

The results of measurements of proton relaxation times of various tissues from rats, pigs and humans are reported; these were obtained by a resonance spectroscope at 20 MHz and 40 0 C. There were specific differences in both relaxation times (T 1 and T 2 ) of the liver and spleen. There was a difference of more than 150 ms in the longitudinal relaxation time between grey and white cerebral tissue. Autolytic changes show an increase in both relaxation times. Fixation produced a reduction in T 1 only. The significance of these findings for NMR tomography is discussed. (orig.) [de

Signalling and the control of skeletal muscle size

International Nuclear Information System (INIS)

Otto, Anthony; Patel, Ketan

2010-01-01

Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

Signalling and the control of skeletal muscle size

Energy Technology Data Exchange (ETDEWEB)

Otto, Anthony [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom); Patel, Ketan, E-mail: ketan.patel@reading.ac.uk [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom)

2010-11-01

Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

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

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

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...

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.

Proton therapy physics

CERN Document Server

2012-01-01

Proton Therapy Physics goes beyond current books on proton therapy to provide an in-depth overview of the physics aspects of this radiation therapy modality, eliminating the need to dig through information scattered in the medical physics literature. After tracing the history of proton therapy, the book summarizes the atomic and nuclear physics background necessary for understanding proton interactions with tissue. It describes the physics of proton accelerators, the parameters of clinical proton beams, and the mechanisms to generate a conformal dose distribution in a patient. The text then covers detector systems and measuring techniques for reference dosimetry, outlines basic quality assurance and commissioning guidelines, and gives examples of Monte Carlo simulations in proton therapy. The book moves on to discussions of treatment planning for single- and multiple-field uniform doses, dose calculation concepts and algorithms, and precision and uncertainties for nonmoving and moving targets. It also exami...

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.

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.

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

The precision of proton range calculations in proton radiotherapy treatment planning: experimental verification of the relation between CT-HU and proton stopping power

International Nuclear Information System (INIS)

Schaffner, B.; Pedroni, E.

1998-01-01

The precision in proton radiotherapy treatment planning depends on the accuracy of the information used to calculate the stopping power properties of the tissues in the patient's body. This information is obtained from computed tomography (CT) images using a calibration curve to convert CT Hounsfield units into relative proton stopping power values. The validity of a stoichiometric method to create the calibration curve has been verified by measuring pairs of Hounsfield units and stopping power values for animal tissue samples. It was found that the agreement between measurement and calibration curve is better than 1% if beam hardening effects in the acquisition of the CT images can be neglected. The influence of beam hardening effects on the quantitative reading of the CT measurements is discussed and an estimation for the overall range precision of proton beams is given. It is expected that the range of protons in the human body can be controlled to better than ±1.1% of the water equivalent range in soft tissue and ±1.8% in bone, which translates into a range precision of about 1-3 mm in typical treatment situations. (author)

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.

Purinergic receptors expressed in human skeletal muscle fibres

DEFF Research Database (Denmark)

Bornø, A; Ploug, Thorkil; Bune, L T

2012-01-01

distribution of purinergic receptors in skeletal muscle fibres. We speculate that the intracellular localization of purinergic receptors may reflect a role in regulation of muscle metabolism; further studies are nevertheless needed to determine the function of the purinergic system in skeletal muscle cells.......Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content...... of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age-matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy...

Decellularized Tissue and Cell-Derived Extracellular Matrices as Scaffolds for Orthopaedic Tissue Engineering

Science.gov (United States)

Cheng, Christina W.; Solorio, Loran D.; Alsberg, Eben

2014-01-01

The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic. PMID:24417915

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

Dynamics of the Skeletal Muscle Secretome during Myoblast Differentiation

DEFF Research Database (Denmark)

Henningsen, Jeanette; Rigbolt, Kristoffer T G; Blagoev, Blagoy

2010-01-01

During recent years, increased efforts have focused on elucidating the secretory function of skeletal muscle. Through secreted molecules, skeletal muscle affects local muscle biology in an auto/paracrine manner as well as having systemic effects on other tissues. Here we used a quantitative...... proteomics platform to investigate the factors secreted during the differentiation of murine C2C12 skeletal muscle cells. Using triple encoding stable isotope labeling by amino acids in cell culture, we compared the secretomes at three different time points of muscle differentiation and followed the dynamics...... of the skeletal muscle as a prominent secretory organ. In addition to previously reported molecules, we identified many secreted proteins that have not previously been shown to be released from skeletal muscle cells nor shown to be differentially released during the process of myogenesis. We found 188...

Gene Expression Changes in Mouse Intestinal Tissue Following Whole-Body Proton or Gamma-Irradiation

Science.gov (United States)

Purgason, Ashley; Zhang, Ye; Mangala, Lingegowda; Nie, Ying; Gridley, Daila; Hamilton, Stanley R.; Seidel, Derek V.; Wu, Honglu

2014-01-01

Crew members face potential consequences following exposure to the space radiation environment including acute radiation syndrome and cancer. The space radiation environment is ample with protons, and numerous studies have been devoted to the understanding of the health consequences of proton exposures. In this project, C57BL/6 mice underwent whole-body exposure to 250 MeV of protons at doses of 0, 0.1, 0.5, 2 and 6 Gy and the gastrointestinal (GI) tract of each animal was dissected four hours post-irradiation. Standard H&E staining methods to screen for morphologic changes in the tissue showed an increase in apoptotic lesions for even the lowest dose of 0.1 Gy, and the percentage of apoptotic cells increased with increasing dose. Results of gene expression changes showed consistent up- or down- regulation, up to 10 fold, of a number of genes across exposure doses that may play a role in proton-induced oxidative stress including Gpx2. A separate study in C57BL/6 mice using the same four hour time point but whole-body gamma-irradiation showed damage to the small intestine with lesions appearing at the smallest dose of 0.05 Gy and increasing with increasing absorbed dose. Expressions of genes associated with oxidative stress processes were analyzed at four hours and twenty-four hours after exposure to gamma rays. We saw a much greater number of genes with significant up- or down-regulation twenty-four hours post-exposure as compared to the four hour time point. At both four hours and twenty-four hours post-exposure, Duox1 and Mpo underwent up-regulation for the highest dose of 6 Gy. Both protons and gamma rays lead to significant variation in gene expressions and these changes may provide insight into the mechanism of injury seen in the GI tract following radiation exposure. We have also completed experiments using a BALB/c mouse model undergoing whole-body exposure to protons. Doses of 0, 0.1, 1 and 2 Gy were used and results will be compared to the work mentioned

Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1.

Science.gov (United States)

Light, Alan R; Hughen, Ronald W; Zhang, Jie; Rainier, Jon; Liu, Zhuqing; Lee, Jeewoo

2008-09-01

The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate.

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

SU-F-T-150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

Energy Technology Data Exchange (ETDEWEB)

Liu, A; Mohan, R; Liao, Z [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial. Methods: Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion-incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter-compared as were the selected dose-volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched-paired signed-rank test to determine the dose regions where the statistically significant differences existed. Results: As expected, the average 5, 20 and 50% IRVNT’s for PSPT was found to be significantly smaller than for IMRT (p < 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224). Conclusion: PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

Increased skeletal muscle capillarization enhances insulin sensitivity

DEFF Research Database (Denmark)

Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

2014-01-01

Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured...... that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole...

Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

DEFF Research Database (Denmark)

Christensen, Britt; Lundby, Carsten; Jessen, Niels

2012-01-01

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

Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

DEFF Research Database (Denmark)

Christensen, Britt; Lundby, Carsten; Jessen, Niels

2012-01-01

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

[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.

Effects of botulinum toxin type A on healing of injured skeletal muscles

Directory of Open Access Journals (Sweden)

Shokravi Ramin

2007-01-01

Full Text Available Objectives: (1 Evaluation of microscopic healing of skeletal muscle fibers after injuries, especially the arrangement of new muscle fibers and scar tissue diameter in the injury region. (2 Evaluation of alterations in microscopy of the healing procedure within skeletal muscles after injury following botulinum toxin type A (BTX -A induced muscle immobilization. Materials and Methods: The study was done on 12 white lab rabbits of either sex in a 6-month period. Results: The immobilization of skeletal muscle fibers as a result of the use of BTX-A after injury caused a qualitative increase in fibrous tissue formation in the area of injury, and the BTX-A-induced immobilization for a period of 6 months led to muscle atrophy.

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.

Upon the triple phase skeletal scintigraphy in traumatology

International Nuclear Information System (INIS)

Spitz, W.

1988-01-01

A broadly established indication catalogue for skeletal scintigraphy in traumatology is resulting from about 1500 skeletal scans. Aside from the exclusion of any osseous lesion, from the differentiation of uncertain X-ray findings, from the determination of the extent of osseous lesions in polytraumatic conditions and from the assessment of the relative fracture age, the follow-up after trauma and therapeutical intervention, the demonstration of battered child syndromes and of soft tissue lesions are of special importance with regard to these topics. For all that, the high sensitivity of the 3-phase skeletal scintigraphy for every enhancement of osseous turnover represents the elementary prerequisite for the employment of this non-invasive technique as an ideal screening method in traumatological diagnostics. The experiences from the past years have resulted in an increased frequency of skeletal scintigraphic studies to a similarly high level, as it is already established in the majority of institutions with respect to oncological problems, In the development of efficient and cost favourable diagnostic strategies with only little burden to the patient, skeletal scintigraphy will in future play an important role within the palette of modern skeletal diagnostics in traumatology. (orig.) [de

Diagnosis by proton bombardment

International Nuclear Information System (INIS)

Steward, V.W.; Koehler, A.M.

1976-01-01

Beams of monoenergetic protons or other charged ions are passed through the living human body to detect abnormalities and obstructions in body tissue, which abnormalities and obstructions are visualized as density variations in the particle image emerging from the body part under investigation. The particles used are preferably protons having an energy of 100 to 300 MeV, more especially 200 to 300 MeV. The method is of use in detecting inter alia tumors, blood clots, infarcts, soft tissue lesions and multiple sclerosis in patients without exposure to high radiation dosages. 6 claims, 2 drawing figures

A unified anatomy ontology of the vertebrate skeletal system.

Directory of Open Access Journals (Sweden)

Wasila M Dahdul

Full Text Available The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO, to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish and multispecies (teleost, amphibian vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages, and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO, Gene Ontology (GO, Uberon, and Cell Ontology (CL, and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A unified anatomy ontology of the vertebrate skeletal system.

Science.gov (United States)

Dahdul, Wasila M; Balhoff, James P; Blackburn, David C; Diehl, Alexander D; Haendel, Melissa A; Hall, Brian K; Lapp, Hilmar; Lundberg, John G; Mungall, Christopher J; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E; Vickaryous, Matthew K; Westerfield, Monte; Mabee, Paula M

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A Unified Anatomy Ontology of the Vertebrate Skeletal System

Science.gov (United States)

Dahdul, Wasila M.; Balhoff, James P.; Blackburn, David C.; Diehl, Alexander D.; Haendel, Melissa A.; Hall, Brian K.; Lapp, Hilmar; Lundberg, John G.; Mungall, Christopher J.; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E.; Vickaryous, Matthew K.; Westerfield, Monte; Mabee, Paula M.

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity. PMID:23251424

WE-EF-303-10: Single- Detector Proton Radiography as a Portal Imaging Equivalent for Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Doolan, P [University College London Hospital, London (United Kingdom); Bentefour, E [Ion Beam Applications, Louvain-la-Neuve (Belgium); Testa, M; Cascio, E; Lu, H [Massachussetts General Hospital, Boston, MA (United States); Royle, G [University College London, London (United Kingdom); Gottschalk, B [Harvard University, Cambridge, MA (United States)

2015-06-15

Purpose: In proton therapy, patient alignment is of critical importance due to the sensitivity of the proton range to tissue heterogeneities. Traditionally proton radiography is used for verification of the water-equivalent path length (WEPL), which dictates the depth protons reach. In this work we propose its use for alignment. Additionally, many new proton centers have cone-beam computed tomography in place of beamline X-ray imaging and so proton radiography offers a unique patient alignment verification similar to portal imaging in photon therapy. Method: Proton radiographs of a CIRS head phantom were acquired using the Beam Imaging System (BIS) (IBA, Louvain-la-Neuve) in a horizontal beamline. A scattered beam was produced using a small, dedicated, range modulator (RM) wheel fabricated out of aluminum. The RM wheel was rotated slowly (20 sec/rev) using a stepper motor to compensate for the frame rate of the BIS (120 ms). Dose rate functions (DRFs) over two RM wheel rotations were acquired. Calibration was made with known thicknesses of homogeneous solid water. For each pixel the time width, skewness and kurtosis of the DRFs were computed. The time width was used to compute the object WEPL. In the heterogeneous phantom, the excess skewness and excess kurtosis (i.e. difference from homogeneous cases) were computed and assessed for suitability for patient set up. Results: The technique allowed for the simultaneous production of images that can be used for WEPL verification, showing few internal details, and excess skewness and kurtosis images that can be used for soft tissue alignment. These latter images highlight areas where range mixing has occurred, correlating with phantom heterogeneities. Conclusion: The excess skewness and kurtosis images contain details that are not visible in the WET images. These images, unique to the time-resolved proton radiographic method, could be used for patient set up according to soft tissues.

Biological effects of proton radiation: an update

International Nuclear Information System (INIS)

Girdhani, S.; Hlatky, L.; Sachs, R.

2015-01-01

Proton radiation provides significant dosimetric advantages when compared with gamma radiation due to its superior energy deposition characteristics. Although the physical aspects of proton radiobiology are well understood, biological and clinical endpoints are understudied. The current practice to assume the relative biological effectiveness of low linear energy transfer (LET) protons to be a generic value of about 1.1 relative to photons likely obscures important unrecognised differentials in biological response between these radiation qualities. A deeper understanding of the biological properties induced by proton radiation would have both radiobiological and clinical impact. This article briefly points to some of the literature pertinent to the effects of protons on tissue-level processes that modify disease progression, such as angiogenesis, cell invasion and cancer metastasis. Recent findings hint that proton radiation may, in addition to offering improved radio-therapeutic targeting, be a means to provide a new dimension for increasing therapeutic benefits for patients by manipulating these tissue-level processes. (authors)

Generalized skeletal pathology: Results of radionuclide studies

International Nuclear Information System (INIS)

Fueger, G.F.; Aigner, R.

1987-01-01

Generalized pathological changes may involve the skeleton systematically (bone tissue, bone marrow) or at multiple sites involving destruction or infiltration. Appropriate radionuclide studies include total-body bone or bone marrow scintigraphy, absorptiometry (osteodensitometry) and the 24 h whole-body retention measurement. Established radioindicators are 99m-Tc-(hydroxy)methylendiphosphonate (HMDP or MDP) and 99m-Tc-human serumalbumin-nanocolloid. Absorptiometry of the forearm, extended by computer-assisted transaxial tomography, may be expected to prove as the most efficient method of bone density measurement. The 24 h whole-body retention measurement is useful for the diagnosis and follow-up of metabolic and endocrine osteopathies, if the very same osteotropic 99m-Tc-chelate is used. Whole-body bone scintigraphy today is one of the most important radionuclide studies for diagnosis and follow-up of skeletal metastases. Scintigraphy provides evidence of skeletal metastases several months earlier than radiological examinations. In about 40 percent of patients with cancer of the prostate, scintigraphy provided positive findings of skeletal metastases in the absence of both pain and increased levels of phosphatase. In patients with a history of malignancy, 60 percent of solitary findings on skeletal scintigraphy are metastases. The frequency of false negative findings obtained by whole-body skeletal scintigraphy are metastases. The frequency of false negative findings obtained by whole-body skeletal scintigraphy ranges from 2 to 4%. Compared to skeletal scintigraphy, bone marrow scintigraphy frequently yields significant additional findings in cases of plasmocytoma, histiocytoma, lymphoma and haemoblastoses. (orig.) [de

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.

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...

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

The muscle contraction mode determines lymphangiogenesis differentially in rat skeletal and cardiac muscles by modifying local lymphatic extracellular matrix microenvironments.

Science.gov (United States)

Greiwe, L; Vinck, M; Suhr, F

2016-05-01

Lymphatic vessels are of special importance for tissue homeostasis, and increases of their density may foster tissue regeneration. Exercise could be a relevant tool to increase lymphatic vessel density (LVD); however, a significant lack of knowledge remains to understand lymphangiogenesis in skeletal muscles upon training. Interestingly, training-induced lymphangiogenesis has never been studied in the heart. We studied lymphangiogenesis and LVD upon chronic concentric and chronic eccentric muscle contractions in both rat skeletal (Mm. Edl and Sol) and cardiac muscles. We found that LVD decreased in both skeletal muscles specifically upon eccentric training, while this contraction increased LVD in cardiac tissue. These observations were supported by opposing local remodelling of lymphatic vessel-specific extracellular matrix components in skeletal and cardiac muscles and protein levels of lymphatic markers (Lyve-1, Pdpn, Vegf-C/D). Confocal microscopy further revealed transformations of lymphatic vessels into vessels expressing both blood (Cav-1) and lymphatic (Vegfr-3) markers upon eccentric training specifically in skeletal muscles. In addition and phenotype supportive, we found increased inflammation (NF-κB/p65, Il-1β, Ifn-γ, Tnf-α and MPO(+) cells) in eccentrically stressed skeletal, but decreased levels in cardiac muscles. Our data provide novel mechanistic insights into lymphangiogenic processes in skeletal and cardiac muscles upon chronic muscle contraction modes and demonstrate that both tissues adapt in opposing manners specifically to eccentric training. These data are highly relevant for clinical applications, because eccentric training serves as a sufficient strategy to increase LVD and to decrease inflammation in cardiac tissue, for example in order to reduce tissue abortion in transplantation settings. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

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.)

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.)

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

Science.gov (United States)

Pettersen, H. E. S.; Alme, J.; Biegun, A.; van den Brink, A.; Chaar, M.; Fehlker, D.; Meric, I.; Odland, O. H.; Peitzmann, T.; Rocco, E.; Ullaland, K.; Wang, H.; Yang, S.; Zhang, C.; Röhrich, D.

2017-07-01

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeter was originally designed for the reconstruction of high-energy electromagnetic showers for the ALICE-FoCal project. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter concept. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. High energy protons traversing the detector leave a track through the sensor layers. These tracks are spread out through charge diffusion processes. A charge diffusion model is applied for acquisition of estimates of the deposited energy of the protons in each sensor layer by using the size of the charge diffused area. A model fit of the Bragg Curve is applied to each reconstructed track and through this, estimating the residual range of each proton. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

Energy Technology Data Exchange (ETDEWEB)

Pettersen, H.E.S., E-mail: helge.pettersen@helse-bergen.no [Department of Oncology and Medical Physics, Haukeland University Hospital, Postbox 1400, 5021 Bergen (Norway); Department of Physics and Technology, University of Bergen, Postbox 7803, 5020 Bergen (Norway); Alme, J. [Department of Physics and Technology, University of Bergen, Postbox 7803, 5020 Bergen (Norway); Biegun, A. [Kernfysisch Versneller Instituut, University of Groningen, NL-9747 AA Groningen (Netherlands); Brink, A. van den [Nikhef, Utrecht University, Postbox 41882, 1009 DB Amsterdam (Netherlands); Chaar, M.; Fehlker, D. [Department of Physics and Technology, University of Bergen, Postbox 7803, 5020 Bergen (Norway); Meric, I. [Department of Electrical Engineering, Bergen University College, Postbox 7030, 5020 Bergen (Norway); Odland, O.H. [Department of Oncology and Medical Physics, Haukeland University Hospital, Postbox 1400, 5021 Bergen (Norway); Peitzmann, T.; Rocco, E. [Nikhef, Utrecht University, Postbox 41882, 1009 DB Amsterdam (Netherlands); Ullaland, K. [Department of Physics and Technology, University of Bergen, Postbox 7803, 5020 Bergen (Norway); Wang, H. [Nikhef, Utrecht University, Postbox 41882, 1009 DB Amsterdam (Netherlands); Yang, S. [Department of Physics and Technology, University of Bergen, Postbox 7803, 5020 Bergen (Norway); Zhang, C. [Nikhef, Utrecht University, Postbox 41882, 1009 DB Amsterdam (Netherlands); Röhrich, D. [Department of Physics and Technology, University of Bergen, Postbox 7803, 5020 Bergen (Norway)

2017-07-11

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2–3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeter was originally designed for the reconstruction of high-energy electromagnetic showers for the ALICE-FoCal project. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter concept. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. High energy protons traversing the detector leave a track through the sensor layers. These tracks are spread out through charge diffusion processes. A charge diffusion model is applied for acquisition of estimates of the deposited energy of the protons in each sensor layer by using the size of the charge diffused area. A model fit of the Bragg Curve is applied to each reconstructed track and through this, estimating the residual range of each proton. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to

Expected proton signal sizes in the PRaVDA Range Telescope for proton Computed Tomography

International Nuclear Information System (INIS)

Price, T.; Parker, D.J.; Green, S.; Esposito, M.; Waltham, C.; Allinson, N.M.; Poludniowski, G.; Evans, P.; Taylor, J.; Manolopoulos, S.; Anaxagoras, T.; Nieto-Camero, J.

2015-01-01

Proton radiotherapy has demonstrated benefits in the treatment of certain cancers. Accurate measurements of the proton stopping powers in body tissues are required in order to fully optimise the delivery of such treaments. The PRaVDA Consortium is developing a novel, fully solid state device to measure these stopping powers. The PRaVDA Range Telescope (RT), uses a stack of 24 CMOS Active Pixel Sensors (APS) to measure the residual proton energy after the patient. We present here the ability of the CMOS sensors to detect changes in the signal sizes as the proton traverses the RT, compare the results with theory, and discuss the implications of these results on the reconstruction of proton tracks

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.

Proton therapy analysis using the Monte Carlo method

Energy Technology Data Exchange (ETDEWEB)

Noshad, Houshyar [Center for Theoretical Physics and Mathematics, AEOI, P.O. Box 14155-1339, Tehran (Iran, Islamic Republic of)]. E-mail: hnoshad@aeoi.org.ir; Givechi, Nasim [Islamic Azad University, Science and Research Branch, Tehran (Iran, Islamic Republic of)

2005-10-01

The range and straggling data obtained from the transport of ions in matter (TRIM) computer program were used to determine the trajectories of monoenergetic 60 MeV protons in muscle tissue by using the Monte Carlo technique. The appropriate profile for the shape of a proton pencil beam in proton therapy as well as the dose deposited in the tissue were computed. The good agreements between our results as compared with the corresponding experimental values are presented here to show the reliability of our Monte Carlo method.

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

DEFF Research Database (Denmark)

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

1993-01-01

and MRS, the in vivo field dispersion of T1 and T2 has been measured in order to evaluate whether ex vivo data are representative for the in vivo situation. Brain, skeletal muscle, and liver of healthy human volunteers were studied. Fifteen MR units with a field strength ranging from 0.08 T to 1.5 T took......T1 and T2 relaxation times are fundamental parameters for signal contrast behaviour in MRI. A number of ex vivo relaxometry studies have dealt with the magnetic field dispersion of T1. By means of multicenter study within the frame of the COMAC BME Concerted Action on Tissue Characterization by MRI......, whereas no significant variations were seen for T2. Our in vivo data were generally in reasonable agreement with proposed models based on ex vivo measurements....

The diagnosis of skeletal dysplasias: a multidisciplinary approach

International Nuclear Information System (INIS)

Mortier, Geert R.

2001-01-01

Skeletal dysplasias are heritable connective tissue disorders affecting skeletal morphogenesis and development. They represent a heterogeneous group of genetic disorders with more than 200 different entities being delineated to date. Because of this diversity, the diagnosis of a skeletal dysplasia is usually based on a combination of clinical, radiographic, morphologic, and, in some instances, biochemical and molecular studies. Tremendous advances have been made in the elucidation of the genetic defect of several of these conditions over the past 10 years. This progress has provided us with more insights into the genes controlling normal skeletal development. It also has opened new diagnostic perspectives. For several disorders, identification of the causal gene allows us now to confirm with a molecular test the diagnosis postulated on the basis of clinical, radiographic and/or morphologic studies. It also enables us to establish the diagnosis early in pregnancy. An accurate diagnosis is not only important for proper management of the affected individual but also the cornerstone for adequate genetic counseling

The diagnosis of skeletal dysplasias: a multidisciplinary approach

Energy Technology Data Exchange (ETDEWEB)

Mortier, Geert R. E-mail: geert.mortier@rug.ac.be

2001-12-01

Skeletal dysplasias are heritable connective tissue disorders affecting skeletal morphogenesis and development. They represent a heterogeneous group of genetic disorders with more than 200 different entities being delineated to date. Because of this diversity, the diagnosis of a skeletal dysplasia is usually based on a combination of clinical, radiographic, morphologic, and, in some instances, biochemical and molecular studies. Tremendous advances have been made in the elucidation of the genetic defect of several of these conditions over the past 10 years. This progress has provided us with more insights into the genes controlling normal skeletal development. It also has opened new diagnostic perspectives. For several disorders, identification of the causal gene allows us now to confirm with a molecular test the diagnosis postulated on the basis of clinical, radiographic and/or morphologic studies. It also enables us to establish the diagnosis early in pregnancy. An accurate diagnosis is not only important for proper management of the affected individual but also the cornerstone for adequate genetic counseling.

Functional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells.

Science.gov (United States)

García-Prat, Laura; Sousa-Victor, Pedro; Muñoz-Cánoves, Pura

2013-09-01

Aging of an organism is associated with the functional decline of tissues and organs, as well as a sharp decline in the regenerative capacity of stem cells. A prevailing view holds that the aging rate of an individual depends on the ratio of tissue attrition to tissue regeneration. Therefore, manipulations that favor the balance towards regeneration may prevent or delay aging. Skeletal muscle is a specialized tissue composed of postmitotic myofibers that contract to generate force. Satellite cells are the adult stem cells responsible for skeletal muscle regeneration. Recent studies on the biology of skeletal muscle and satellite cells in aging have uncovered the critical impact of systemic and niche factors on stem cell functionality and demonstrated the capacity of aged satellite cells to rejuvenate and increase their regenerative potential when exposed to a youthful environment. Here we review the current literature on the coordinated relationship between cell extrinsic and intrinsic factors that regulate the function of satellite cells, and ultimately determine tissue homeostasis and repair during aging, and which encourage the search for new anti-aging strategies. © 2013 The Authors Journal compilation © 2013 FEBS.

Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

Directory of Open Access Journals (Sweden)

João A Paredes

Full Text Available Loss of thymidine kinase 2 (TK2 causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA depletion syndrome (MDS in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

Science.gov (United States)

Paredes, João A; Zhou, Xiaoshan; Höglund, Stefan; Karlsson, Anna

2013-01-01

Loss of thymidine kinase 2 (TK2) causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA) depletion syndrome (MDS) in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy

Science.gov (United States)

Berndt, Bianca; Landry, Guillaume; Schwarz, Florian; Tessonnier, Thomas; Kamp, Florian; Dedes, George; Thieke, Christian; Würl, Matthias; Kurz, Christopher; Ganswindt, Ute; Verhaegen, Frank; Debus, Jürgen; Belka, Claus; Sommer, Wieland; Reiser, Maximilian; Bauer, Julia; Parodi, Katia

2017-03-01

The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced β + activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The elemental composition of reference tissues was assigned to closest CT numbers in DECT space (DECTdist). The method was also applied to SECT data (SECTdist). In a validation experiment, the proton irradiation induced PET activity of three brain equivalent solutions (BES) was compared to simulations based on different tissue segmentations. Five patients scanned with a dual source DECT scanner were analyzed to compare the different segmentation methods. A single magnetic resonance (MR) scan was used for comparison with an established segmentation toolkit. Additionally, one patient with SECT and post-treatment PET scans was investigated. For BES, DECTdist and SECTdist reduced differences to the reference simulation by up to 62% when compared to the conventional stoichiometric segmentation (SECTSchneider). In comparison to MR brain segmentation, Dice similarity coefficients for WM, GM and CSF were 0.61, 0.67 and 0.66 for DECTdist and 0.54, 0.41 and 0.66 for SECTdist. MC simulations of PET treatment verification in patients showed important differences between DECTdist/SECTdist and SECTSchneider for patients with large CSF areas within the treatment field but not in WM and GM. Differences could be misinterpreted as PET derived range shifts of up to 4 mm. DECTdist and SECTdist yielded comparable activity distributions, and comparison of SECTdist to a measured patient PET scan showed improved agreement when compared to SECTSchneider. The agreement between predicted and measured PET

Radiation injury to skeletal muscle

International Nuclear Information System (INIS)

Persons, C.C.M.; Wondergem, J.; Leer, J.W.H.

1997-01-01

Radiotherapy of neoplasia has increased the mean life expectancy of cancer patients. On the other hand, more reports are published on morbidity of the treatment with regard to normal tissue. Studies on skeletal muscle injury specifically are scarce, but many clinical long term follow-up studies make note of side effects as muscle atrophy, fibrosis and limited function. Furthermore it is suggested that skeletal muscles of children are more prone to radiation injury than those of adult subjects. Effects of radiation on skeletal muscle were studied in rats. On hind limb of young (100 g) and adult (350 g) rats was irradiated with single doses (15-30 Gy), while the other served as control. Follow-up was up to 12 months post treatment. Muscular function in young rats was decreased significantly at 6 months post irradiation, but did not further decrease in the following 6 months. The amount of collagen, on the other hand, was not increased at 6 months, but became highly elevated at 12 months past treatment. This suggests that at 6 months, impaired muscular function may not be explained by increased fibrotic tissues. This is an agreement with results obtained in adult rats, where function was also impaired, without concomitant increase in collagen. In an earlier study, mitochondrial oxygen consumption was dose dependently decreased after irradiation, at 12 months, but not at 6 months post treatment. Furthermore, myosin-actin interaction was measured in skinned fibers. The first results of this study indicate changes in the interaction of contraction proteins, as early as 6 months post treatment. (authors)

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

Response of a biological model to a proton beam in vivo

International Nuclear Information System (INIS)

Schuff, Juan A.; Burlon, Alejandro A.; Debray, Mario E.; Kesque, Jose M.; Kreiner, Andres J.; Stoliar, Pablo A.; Naab, Fabian; Ozafran, Mabel J.; Vazquez, Monica E.

2000-01-01

Wistar rats were locally irradiated with proton beams. By means of a plastic wedge used as an energy degradator of variable thickness, dorsal portions of skin were irradiated at several tissue depths. This model was used to perform proton irradiations with different doses in both the plateau and the Bragg portions of the Bragg curve. The particular geometry of the wedge, in which the maximum thickness is greater than the proton range, yields a portion of unaffected tissue included in the irradiated area. Thus, it was possible to obtain a reference zone contiguous to the affected area in the same animal. SSNTD were used to establish the spatial configuration and the dose of the proton beams. This methodology allows isodose curve calculations along the different tissue depths which are in agreement with the biologic effects observed. Additionally, the scattering of protons on the shielding material, that affects specific areas of the tissue, is detected by the SSNTD. (author)

Skeletal metastases from hepatoma: frequency, distribution, and radiographic features

International Nuclear Information System (INIS)

Kuhlman, J.E.; Fishman, E.K.; Leichner, P.K.; Magid, D.; Order, S.E.; Siegelman, S.S.

1986-01-01

Over the past 6 years, the authors evaluated 300 patients with hepatoma as part of phase 1 and 2 treatment protocol trials. Analysis of the available clinical data and radiographic studies revealed 22 patients (7.3%) with skeletal metastases demonstrated by radiography, computed tomography (CT), and/or nuclear scintigraphy. The plain film appearance of skeletal metastases from hepatoma was osteolytic in all cases. CT scanning best demonstrated the expansile, destructive nature of these metastases, which were often associated with large, bulky soft-tissue masses. Skeletal metastases from hepatomas demonstrated increased radiotracer uptake on standard bone scans and were gallium avid, similar to the hepatoma itself. In addition, they could be targeted therapeutically with I-131 antiferritin immunoglobulin. The most frequent sites of skeletal metastases were the ribs, spine, femur, pelvis, and humerus. An initial symptom in ten patients was skeletal pain corresponding to the osseous metastases. In five patients, pathologic fractures of the proximal femur or humerus developed and required total hip replacement or open-reduction internal fixation. Patients with long-standing cirrhosis or known hepatocellular carcinoma who also have skeletal symptoms should be evaluated for possible osseous metastases

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.

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

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.

Extra-osseous uterine pathophysiology demonstrated on skeletal scintigraphy

International Nuclear Information System (INIS)

Mansberg, R.; Lewis, G.

1999-01-01

Full text: Skeletal scintigraphy is a sensitive procedure for evaluating disease and trauma involving the skeleton. Extra-skeletal pathophysiology is also often demonstrated. This may include uptake by tumours, soft tissue calcification and infection as well as renal pathology. Skeletal scintigraphy is often performed to evaluate hip and back pain and extra-osseous uterine pathophysiology can be demonstrated in both the early and late phases of the study as in the following cases. Three women underwent skeletal scintigraphy for the investigation of low back pain in two patients and post-partum hip pain in one. A large vascular uterus with deviation of the bladder was demonstrated in the post-partum patient. Increased pelvic vascularity and bladder deviation in the second patient was shown by ultrasound to correspond to a left-sided fibroid with associated adenomyosis. In the third case, right-sided pelvic vascularity and left bladder deviation were shown on ultrasound to be due to an anteverted, anteflexed uterus tilted to the right. These cases illustrate the importance of documenting extra-osseous findings on skeletal scintigraphy and the benefits of correlation with anatomical imaging

The optimal balance between quality and efficiency in proton radiography imaging technique at various proton beam energies : A Monte Carlo study

NARCIS (Netherlands)

Biegun, A K; van Goethem, M-J; van der Graaf, E R; van Beuzekom, M; Koffeman, E N; Nakaji, T; Takatsu, J; Visser, J; Brandenburg, S

Proton radiography is a novel imaging modality that allows direct measurement of the proton energy loss in various tissues. Currently, due to the conversion of so-called Hounsfield units from X-ray Computed Tomography (CT) into relative proton stopping powers (RPSP), the uncertainties of RPSP are

Skeletal muscle as a gene regulatory endocrine organ

DEFF Research Database (Denmark)

Karstoft, Kristian; Pedersen, Bente K.

2016-01-01

Purpose of review Skeletal muscle is gaining increased attention as an endocrine organ. Recently, novel myokines and new effects of already established myokines have been identified. The objective of this review is to give an update on the recent advances in the field. Recent findings Several...... hundred putative myokines have been described, some of which are induced by contraction and differentially regulated between healthy and metabolically diseased individuals. Interleukin-6 (IL-6) is the prototype myokine, which was identified as a muscle-derived cytokine 15 years ago. Recently, IL-6 has...... on training status. IL-15 has been established as a cytokine mediating cross-talk between skeletal muscle and skin tissue, and decorin has been characterized as a contraction-induced myokine which apparently is differentially regulated between healthy and dysglycemic individuals. Summary Skeletal muscle...

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.

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 biomimetic constructs offer the possibility to replace, in part or entirely, wasted muscle by means of straight reconstruction and/or by enhancing endogenous regeneration. Reports of tissue engineering approaches for artificial muscle building appeared in large numbers in the specialized press lately, advocating the suitability of this technology for human application upon scaling up and a near future applicability for medical care of muscle wasting. http://links.lww.com/COCN/A9

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.

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.

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.

Spot-scanning proton therapy for malignant soft tissue tumors in childhood: First experiences at the Paul Scherrer Institute

International Nuclear Information System (INIS)

Timmermann, Beate; Schuck, Andreas; Niggli, Felix; Weiss, Markus; Lomax, Antony Jonathan; Pedroni, Eros; Coray, Adolf; Jermann, Martin; Rutz, Hans Peter; Goitein, Gudrun

2007-01-01

Purpose: Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. Methods and Materials: Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III in 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). Results: After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. Conclusions: Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed

Skeletal coccidioidomycosis: imaging findings in 19 patients

International Nuclear Information System (INIS)

Zeppa, M.A.; Greenspan, A.; McGahan, J.P.; Laorr, A.; Steinbach, L.S.

1996-01-01

The objective of this study was to describe the distribution and radiologic appearance of skeletal coccidioidomycosis in 19 documented cases. Medical records of 19 patients with clinically confirmed skeletal occidioidomycosis were retrospectively reviewed. The patients were studied with plain radiography, skeletal scintigraphy and MRI. Multiple lesions were seen in 11 of 19 patients (58%). Of a total of 46 lesions, 27 (59%) were described as punched-out lytic, 10 (22%) as permeative/destructive, and 9 (17%) as involving a joint and/or disk space. Lesions were identified in almost every bone (with the exception of the facial bones, ulna, carpus, and fibula) and were most commonly found in the axial skeleton (20 of 46; 43%). Plain radiographs are effective in the initial evaluation of bones and joints, scintigraphic studies can identify disseminated disease, and CT and MRI are effective in determining soft tissue involvement and spinal abnormalities. (orig./MG)

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...

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

Sparse-view proton computed tomography using modulated proton beams

Energy Technology Data Exchange (ETDEWEB)

Lee, Jiseoc; Kim, Changhwan; Cho, Seungryong, E-mail: scho@kaist.ac.kr [Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejon 305-701 (Korea, Republic of); Min, Byungjun [Department of Radiation Oncology, Kangbuk Samsung Hospital, 110–746 (Korea, Republic of); Kwak, Jungwon [Department of Radiation Oncology, Asan Medical Center, 138–736 (Korea, Republic of); Park, Seyjoon; Lee, Se Byeong [Proton Therapy Center, National Cancer Center, 410–769 (Korea, Republic of); Park, Sungyong [Proton Therapy Center, McLaren Cancer Institute, Flint, Michigan 48532 (United States)

2015-02-15

Purpose: Proton imaging that uses a modulated proton beam and an intensity detector allows a relatively fast image acquisition compared to the imaging approach based on a trajectory tracking detector. In addition, it requires a relatively simple implementation in a conventional proton therapy equipment. The model of geometric straight ray assumed in conventional computed tomography (CT) image reconstruction is however challenged by multiple-Coulomb scattering and energy straggling in the proton imaging. Radiation dose to the patient is another important issue that has to be taken care of for practical applications. In this work, the authors have investigated iterative image reconstructions after a deconvolution of the sparsely view-sampled data to address these issues in proton CT. Methods: Proton projection images were acquired using the modulated proton beams and the EBT2 film as an intensity detector. Four electron-density cylinders representing normal soft tissues and bone were used as imaged object and scanned at 40 views that are equally separated over 360°. Digitized film images were converted to water-equivalent thickness by use of an empirically derived conversion curve. For improving the image quality, a deconvolution-based image deblurring with an empirically acquired point spread function was employed. They have implemented iterative image reconstruction algorithms such as adaptive steepest descent-projection onto convex sets (ASD-POCS), superiorization method–projection onto convex sets (SM-POCS), superiorization method–expectation maximization (SM-EM), and expectation maximization-total variation minimization (EM-TV). Performance of the four image reconstruction algorithms was analyzed and compared quantitatively via contrast-to-noise ratio (CNR) and root-mean-square-error (RMSE). Results: Objects of higher electron density have been reconstructed more accurately than those of lower density objects. The bone, for example, has been reconstructed

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

Directory of Open Access Journals (Sweden)

Sulin Cheng

Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

Influence of rapid changes in cytosolic pH on oxidative phosphorylation in skeletal muscle: theoretical studies.

Science.gov (United States)

Korzeniewski, Bernard; Zoladz, Jerzy A

2002-07-01

Cytosolic pH in skeletal muscle may vary significantly because of proton production/consumption by creatine kinase and/or proton production by anaerobic glycolysis. A computer model of oxidative phosphorylation in intact skeletal muscle developed previously was used to study the kinetic effect of these variations on the oxidative phosphorylation system. Two kinds of influence were analysed: (i) via the change in pH across the inner mitochondrial membrane and (ii) via the shift in the equilibrium of the creatine kinase-catalysed reaction. Our simulations suggest that cytosolic pH has essentially no impact on the steady-state fluxes and most metabolite concentrations. On the other hand, rapid acidification/alkalization of cytosol causes a transient decrease/increase in the respiration rate. Furthermore, changes in pH seem to affect significantly the kinetic properties of transition between resting state and active state. An increase in pH brought about by proton consumption by creatine kinase at the onset of exercise lengthens the transition time. At intensive exercise levels this pH increase could lead to loss of the stability of the system, if not compensated by glycolytic H+ production. Thus our theoretical results stress the importance of processes/mechanisms that buffer/compensate for changes in cytosolic proton concentration. In particular, we suggest that the second main role of anaerobic glycolysis, apart from additional ATP supply, may be maintaining the stability of the system at intensive exercise.

Tissue Engineered Strategies for Skeletal Muscle Injury

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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.

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

Altered cross-bridge properties in skeletal muscle dystrophies

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Aziz eGuellich

2014-10-01

Full Text Available Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca2+ through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal muscle dystrophies and discuss their ultimate impacts on striated muscle function.

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)

Nonshivering thermogenesis in king penguin chicks. I. Role of skeletal muscle.

Science.gov (United States)

Duchamp, C; Barré, H; Rouanet, J L; Lanni, A; Cohen-Adad, F; Berne, G; Brebion, P

1991-12-01

In cold-acclimatized (CA) king penguin chicks exhibiting nonshivering thermogenesis (NST), protein content and cytochrome oxidase (CO) activity of tissue homogenates were measured together with protein content, CO, and respiration rates of isolated mitochondria from skeletal muscle (gastrocnemius and pectoralis) and liver. The comparison was made with chicks reared at thermoneutrality (TN) for at least 3 wk. In CA chicks showing a NST despite the lack of brown adipose tissue, an increase in thermogenic capacity was observed in skeletal muscle in which the oxidative capacity rose (+28% and +50% in gastrocnemius and pectoralis muscles, respectively), whereas no change occurred in the liver. Oxidative capacity of skeletal muscle increased together with the development of mitochondrial inner membrane plus cristae in muscles of CA chicks contrary to their TN littermates (+30 to +50%). Subsarcolemmal mitochondria of CA chicks had a higher protein content (+65% in gastrocnemius muscle) and higher oxidative capacities than in controls. The lower respiratory control ratio of these mitochondria might result from a low ADP phosphorylation rate. No change occurred in the intermyofibrillar fraction nor in liver mitochondria. These findings together with earlier results obtained in cold-acclimated ducklings indicate the marked and suited adaptation of skeletal muscle and in particular of subsarcolemmal mitochondria allowing them to play a role in NST.

Proton minibeam radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Girst, Stefanie

2016-03-08

The risk of developing adverse side effects in the normal tissue after radiotherapy is often limiting for the dose that can be applied to the tumor. Proton minibeam radiotherapy, a spatially fractionated radiotherapy method using sub-millimeter proton beams, similar to grid therapy or microbeam radiation radiotherapy (MRT) using X-rays, has recently been invented at the ion microprobe SNAKE in Munich. The aim of this new concept is to minimize normal tissue injuries in the entrance channel and especially in the skin by irradiating only a small percentage of the cells in the total irradiation field, while maintaining tumor control via a homogeneous dose in the tumor, just like in conventional broad beam radiotherapy. This can be achieved by optimizing minibeam sizes and distances according to the prevailing tumor size and depth such that after widening of the minibeams due to proton interactions in the tissue, the overlapping minibeams produce a homogeneous dose distribution throughout the tumor. The aim of this work was to elucidate the prospects of minibeam radiation therapy compared to conventional homogeneous broad beam radiotherapy in theory and in experimental studies at the ion microprobe SNAKE. Treatment plans for model tumors of different sizes and depths were created using the planning software LAPCERR, to elaborate suitable minibeam sizes and distances for the individual tumors. Radiotherapy-relevant inter-beam distances required to obtain a homogeneous dose in the target volume were found to be in the millimeter range. First experiments using proton minibeams of only 10 μm and 50 μm size (termed microchannels in the corresponding publication Zlobinskaya et al. 2013) and therapy-conform larger dimensions of 100 μm and 180 μm were performed in the artificial human in-vitro skin model EpiDermFT trademark (MatTek). The corresponding inter-beam distances were 500 μm, 1mm and 1.8 mm, respectively, leading to irradiation of only a few percent of the cells

Skeletal metastases from primary hepatocellular carcinoma

International Nuclear Information System (INIS)

Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk; Chang, Hee Kyung; Huh, Man Ha

1988-01-01

In order to detect and to evaluate the frequency, the distribution, and the radiological findings of skeletal metastases from hepatocellular carcinoma, the authors retrospectively analyzed radiographic, scintigraphic, and CT findings of 257 patients with hepatocellular carcinoma. The results were as follows: 1. Skeletal metastases were demonstrated in 21 patients (8.2%). 2. Frequent symptoms were pain, limitation of motion, paralysis, and mass. In nine of them the initial symptoms were due to skeletal metastases. 3. The common sites of metastases were spine (13 cases), ribs (8 cases), pelvis (8 cases) and femur (6 cases). Humerus, skull and sternum were also frequently involved. 4. Plain film findings were purely osteolytic in all cases and pathologic fractures were noted in 5 cases. 5. The lesions appear expansible in 7 cases, and 4 of them showed associated soft tissue masses on CT scans. 6. Bone scans were performed in 13 cases of them and showed increased radiotracer uptake in all. 7. Angiographic studies of 3 cases showed hypervascularity of the metastatic lesions as well as the primary hepatic tumor.

CT findings in skeletal cystic echinococcosis

Energy Technology Data Exchange (ETDEWEB)

Tuezuen, M.; Hekimoglu, B. [Social Security Hospital, Ankara (Turkey). Dept. of Radiology

2002-09-01

Purpose: To evaluate the CT findings of skeletal cystic echinococcosis. Material and Methods: CT findings of 7 patients with pathologically confirmed skeletal cystic echinococcosis were evaluated. Results: There were 4 men and 3 women, aged 36-75 years. Hydatid cysts were located in the spine (n=2), a rib (n=3), the pelvis and a vertebra (n=1), the pelvis and the left femur (n=1). The size of the lesions varied from 1 cm to 15 cm. CT showed well defined, single or multiple cystic lesions with no contrast enhancement, no calcification, no daughter cysts, and no germinal membrane detachment. The cystic lesion had a honeycomb appearance in 2 cases, there was pathologic fracture in 2 cases, bone expansion in 5 cases, cortical thinning in 6 cases, cortical destruction in 6 cases, bone sclerosis in 1 case, and soft tissue extension in 6 cases. Conclusion: Preoperative differential diagnosis of skeletal cystic lesions should include cystic echinococcosis, especially in endemic areas, since this diagnosis may easily be missed unless kept in mind.

Gas phase reactions of protonated 1,3-diphenylpropyne and some isomeric [C15H13]+ ions

OpenAIRE

Bäther, Wolfgang; Kuck, Dietmar; Grützmacher, Hans-Friedrich

1985-01-01

Metastable (3-phenyl-2-propynyl)benzenium ions, generated by electron impact induced fragmentation from the appropriately substituted 1,4-dihydrobenzoic acid, react by loss of ·CH3 and C6H6. The study of deuterated derivatives reveals that hydrogen/deuterium exchanges involving all hydrogen and deuterium atoms precede the fragmentations. The results suggest a skeletal rearrangement by electrophilic ring-closure reactions giving rise to protonated phenylindene and protonated 9,10-methano-9,10-...

Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans

International Nuclear Information System (INIS)

Baron, A.D.; Brechtel, G.; Wallace, P.; Edelman, S.V.

1988-01-01

In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively

The accumulation of 134Cs in heart and skeletal muscle of healthy and dystrophic hamsters

International Nuclear Information System (INIS)

Szentkuti, L.; Breitrueck, H.; Giese, W.

1976-01-01

he accumulation of cesium-134 in heart and skeletal muscle of healthy and dystrophic hamsters was compared. It was lower in dystrophic hamsters than in normal ones after only a single dose of cesium-134. The 134 Cs-concentrations of heart and 'red' skeletal muscle were different between normal and dystrophic hamsters. When the isotope had equilibrated in the animals differences in 134 Cs-accumulation in muscle tissue between normal and dystrophic hamsters were even more obvious. The faster elimination of cesium-134 from the body as affected by muscular dystrophy was due to a reduction of 134 Cs-accumulation in muscle tissue. The reduced ability of damaged muscles to accumulate Cs-ions offers the possibility to use Cs-isotopes in diagnosis of skeletal muscle dystrophy. (author)

Comparison of dose distribution for proton beams and electrons: advantages and disadvantages; Comparacao de distribuicao de dose para feixes de protons e eletrons: vantagens e desvantagens

Energy Technology Data Exchange (ETDEWEB)

Neto, Joao T.M.; Ferreira, Maira B.; Braga, Victor B. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

2016-07-01

This study consists of a simulation of cancer therapy using a beam of protons and electrons. By comparing dose distribution curves for both beams we have showed the advantages and disadvantages of both therapies. The study was performed with Monte Carlo simulations using Geant4 code for a brain tumor, and it was found that the presence of the Bragg peak in proton beam allows a higher dose deposition in tumor and protection of adjacent tissues, while the electron beam has an entry dose in the tissue higher than the proton, yielding to the tissue neighbors of the tumor, unnecessary radiation. Moreover, it was also found significant production of neutrons from the proton beam, showing its main disadvantage. The continuation of this work will add the comparison with clinical beams of photons. (author)

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

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

Directory of Open Access Journals (Sweden)

Sunil K Valaparla

2014-03-01

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

A Filtration-based Method of Preparing High-quality Nuclei from Cross-linked Skeletal Muscle for Chromatin Immunoprecipitation.

Science.gov (United States)

Nohara, Kazunari; Chen, Zheng; Yoo, Seung-Hee

2017-07-06

Chromatin immunoprecipitation (ChIP) is a powerful method to determine protein binding to chromatin DNA. Fiber-rich skeletal muscle, however, has been a challenge for ChIP due to technical difficulty in isolation of high-quality nuclei with minimal contamination of myofibrils. Previous protocols have attempted to purify nuclei before cross-linking, which incurs the risk of altered DNA-protein interaction during the prolonged nuclei preparation process. In the current protocol, we first cross-linked the skeletal muscle tissue collected from mice, and the tissues were minced and sonicated. Since we found that ultracentrifugation was not able to separate nuclei from myofibrils using cross-linked muscle tissue, we devised a sequential filtration procedure to obtain high-quality nuclei devoid of significant myofibril contamination. We subsequently prepared chromatin by using an ultrasonicator, and ChIP assays with anti-BMAL1 antibody revealed robust circadian binding pattern of BMAL1 to target gene promoters. This filtration protocol constitutes an easily applicable method to isolate high-quality nuclei from cross-linked skeletal muscle tissue, allowing consistent sample processing for circadian and other time-sensitive studies. In combination with next-generation sequencing (NGS), our method can be deployed for various mechanistic and genomic studies focusing on skeletal muscle function.

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.

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

Science.gov (United States)

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

2018-01-01

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

Knowledge Enrichment Analysis for Human Tissue- Specific Genes Uncover New Biological Insights

Directory of Open Access Journals (Sweden)

Gong Xiu-Jun

2012-06-01

Full Text Available The expression and regulation of genes in different tissues are fundamental questions to be answered in biology. Knowledge enrichment analysis for tissue specific (TS and housekeeping (HK genes may help identify their roles in biological process or diseases and gain new biological insights.In this paper, we performed the knowledge enrichment analysis for 17,343 genes in 84 human tissues using Gene Set Enrichment Analysis (GSEA and Hypergeometric Analysis (HA against three biological ontologies: Gene Ontology (GO, KEGG pathways and Disease Ontology (DO respectively.The analyses results demonstrated that the functions of most gene groups are consistent with their tissue origins. Meanwhile three interesting new associations for HK genes and the skeletal muscle tissuegenes are found. Firstly, Hypergeometric analysis against KEGG database for HK genes disclosed that three disease terms (Parkinson’s disease, Huntington’s disease, Alzheimer’s disease are intensively enriched.Secondly, Hypergeometric analysis against the KEGG database for Skeletal Muscle tissue genes shows that two cardiac diseases of “Hypertrophic cardiomyopathy (HCM” and “Arrhythmogenic right ventricular cardiomyopathy (ARVC” are heavily enriched, which are also considered as no relationship with skeletal functions.Thirdly, “Prostate cancer” is intensively enriched in Hypergeometric analysis against the disease ontology (DO for the Skeletal Muscle tissue genes, which is a much unexpected phenomenon.

Studi Distribusi Glukosa Transporter 4 pada Otot Skelet Ayam Kedu Cemani

OpenAIRE

Budipitojo, Teguh; -, Ariana; Pangestiningsih, Tri Wahyu; Wijayanto, Hery; Kusindarta, Dwi Liliek; Musana, Dewi Kania

2017-01-01

Glucose transporter (GLUT 4) is glucose transporter protein regulated by insulin, found in adipose tissue and striated muscle (skeletal and cardiac muscle). Kedu cemani chicken is one of Indonesia endemic animal, found in Kedu, Temanggung regency, Central Java. This study was required to complete microscopic documentation of  Indonesia’s native biodiversity. The objective of this study was to clarify GLUT 4 distribution in skeletal muscle fibers of kedu cemani chicken by using avidin-biotin-p...

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.

Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

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Atul S. Deshmukh

2016-02-01

Full Text Available 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, 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 proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC, MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets.

Adipocyte-myocyte crosstalk in skeletal muscle insulin resistance; is there a role for thyroid hormone?

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Havekes, Bas; Sauerwein, Hans P

2010-11-01

To review original research studies and reviews that present data on adipocyte-myocyte crosstalk in the development of skeletal muscle insulin resistance with a specific focus on thyroid hormone. Adipose tissue communicates with skeletal muscle not only through free fatty acids but also through secretion of various products called adipokines. Adipokines came out as governors of insulin sensitivity and are deregulated in obesity. In addition to well known leptin, adiponectin, interleukin-6 and tumor necrosis factor-alpha, newer adipokines like retinol-binding protein 4 have been associated with insulin resistance. There is mounting evidence that not only adipose tissue but also skeletal muscle produces and secretes biologically active proteins or 'myokines' that facilitate metabolic crosstalk between organ systems. In recent years, increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Both hypothyroidism and hyperthyroidism affect insulin sensitivity in multiple ways that might overlap adipocyte-myocyte crosstalk. Recent studies have provided new insights in effects of processing of the parent hormone T4 to the active T3 at the level of the skeletal muscle. Adipocyte-myocyte crosstalk is an important modulator in the development of skeletal muscle insulin resistance. Thyroid disorders are very common and may have detrimental effects on skeletal muscle insulin resistance, potentially by interacting with adipocyte-myocyte crosstalk.

Tissue Biopsies in Diabetes Research

DEFF Research Database (Denmark)

Højlund, Kurt; Gaster, Michael; Beck-Nielsen, Henning

2007-01-01

resistance of glucose disposal and glycogen synthesis in this tissue are hallmark features of type 2 diabetes in humans (2,3). During the past two decades, we have carried out more than 1200 needle biopsies of skeletal muscle to study the cellular mechanisms underlying insulin resistance in type 2 diabetes....... Together with morphological studies, measurement of energy stores and metabolites, enzyme activity and phosphorylation, gene and protein expression in skeletal muscle biopsies have revealed a variety of cellular abnormalities in patients with type 2 diabetes and prediabetes. The possibility to establish...... and gene expression profiling on skeletal muscle biopsies have pointed to abnormalities in mitochondrial oxidative phosphorylation in type 2 diabetes. These novel insights will inevitably cause a renewed interest in studying skeletal muscle. This chapter reviews our experience to date and gives a thorough...

Skeletal muscle proteomics: current approaches, technical challenges and emerging techniques

LENUS (Irish Health Repository)

Ohlendieck, Kay

2011-02-01

Abstract Background Skeletal muscle fibres represent one of the most abundant cell types in mammals. Their highly specialised contractile and metabolic functions depend on a large number of membrane-associated proteins with very high molecular masses, proteins with extensive posttranslational modifications and components that exist in highly complex supramolecular structures. This makes it extremely difficult to perform conventional biochemical studies of potential changes in protein clusters during physiological adaptations or pathological processes. Results Skeletal muscle proteomics attempts to establish the global identification and biochemical characterisation of all members of the muscle-associated protein complement. A considerable number of proteomic studies have employed large-scale separation techniques, such as high-resolution two-dimensional gel electrophoresis or liquid chromatography, and combined them with mass spectrometry as the method of choice for high-throughput protein identification. Muscle proteomics has been applied to the comprehensive biochemical profiling of developing, maturing and aging muscle, as well as the analysis of contractile tissues undergoing physiological adaptations seen in disuse atrophy, physical exercise and chronic muscle transformation. Biomedical investigations into proteome-wide alterations in skeletal muscle tissues were also used to establish novel biomarker signatures of neuromuscular disorders. Importantly, mass spectrometric studies have confirmed the enormous complexity of posttranslational modifications in skeletal muscle proteins. Conclusions This review critically examines the scientific impact of modern muscle proteomics and discusses its successful application for a better understanding of muscle biology, but also outlines its technical limitations and emerging techniques to establish new biomarker candidates.

In utero undernutrition programs skeletal and cardiac muscle metabolism

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Brittany eBeauchamp

2016-01-01

Full Text Available In utero undernutrition is associated with increased risk for insulin resistance, obesity, and cardiovascular disease during adult life. A common phenotype associated with low birth weight is reduced skeletal muscle mass. Given the central role of skeletal muscle in whole body metabolism, alterations in its mass as well as its metabolic characteristics may contribute to disease risk. This review highlights the metabolic alterations in cardiac and skeletal muscle associated with in utero undernutrition and low birth weight. These tissues have high metabolic demands and are known to be sites of major metabolic dysfunction in obesity, type 2 diabetes, and cardiovascular disease. Recent research demonstrates that mitochondrial energetics are decreased in skeletal and cardiac muscles of adult offspring from undernourished mothers. These effects apparently lead to the development of a thrifty phenotype, which may represent overall a compensatory mechanism programmed in utero to handle times of limited nutrient availability. However, in an environment characterized by food abundance, the effects are maladaptive and increase adulthood risks of metabolic disease.

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

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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

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...

Dosimetric Feasibility of Hypofractionated Proton Radiotherapy for Neoadjuvant Pancreatic Cancer Treatment

International Nuclear Information System (INIS)

Kozak, Kevin R.; Kachnic, Lisa A.; Adams, Judith C; Crowley, Elizabeth M.; Alexander, Brian M.; Mamon, Harvey J.; Fernandez-Del Castillo, Carlos; Ryan, David P.; DeLaney, Thomas F.; Hong, Theodore S.

2007-01-01

Purpose: To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic adenocarcinoma. Methods and Materials: The first 9 pancreatic cancer patients treated with neoadjuvant intensity-modulated radiotherapy (1.8 Gy x 28) at the Massachusetts General Hospital had treatment plans generated using a 5 CGE x 5 fraction proton regimen. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Hypofractionated proton and conventionally fractionated intensity-modulated radiotherapy plans both provided acceptable target volume coverage and dose homogeneity. Improved dose conformality provided by the hypofractionated proton regimen resulted in significant sparing of kidneys, liver, and small bowel, evidenced by significant reductions in the mean doses, expressed as percentage prescribed dose, to these structures. Kidney and liver sparing was most evident in low-dose regions (≤20% prescribed dose for both kidneys and ≤60% prescribed dose for liver). Improvements in small-bowel dosimetry were observed in high- and low-dose regions. Mean stomach and duodenum doses, expressed as percentage prescribed dose, were similar for the two techniques. Conclusions: A proton radiotherapy schedule consisting of 5 fractions of 5 CGE as part of neoadjuvant therapy for adenocarcinoma of the pancreas seems dosimetrically feasible, providing excellent target volume coverage, dose homogeneity, and normal tissue sparing. Hypofractionated proton radiotherapy in this setting merits Phase I clinical trial investigation

Developmental expression of the alpha-skeletal actin gene

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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.

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

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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

Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

International Nuclear Information System (INIS)

Ehara, Shigeru; Nishida, Jun; Shiraishi, Hideo; Yoshioka, Hiroshi; Okada, Kyoji; Sumiya, Hisashi; Takano, Hideyuki

2007-01-01

The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. The primary lesions were in the thigh (n 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion. (orig.)

Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

Energy Technology Data Exchange (ETDEWEB)

Ehara, Shigeru [Iwate Medical University School of Medicine, Department of Radiology, Morioka (Japan); Nishida, Jun; Shiraishi, Hideo [Iwate Medical University School of Medicine, Department of Orthopedic Surgery, Iwate (Japan); Yoshioka, Hiroshi [University of Tsukuba School of Medicine, Department of Radiology, Tsukuba (Japan); Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Okada, Kyoji [Akita University School of Medicine, Department of Orthopedic Surgery, Akita (Japan); Sumiya, Hisashi [Kanazawa University School of Medicine, Department of Nuclear Medicine, Kanazawa (Japan); Yawata Medical Center, Komatsu (Japan); Takano, Hideyuki [Chiba Cancer Center, Division of Diagnostic Imaging, Chiba (Japan)

2007-09-15

The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. The primary lesions were in the thigh (n = 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion. (orig.)

Skeletal Geometry and Indices of Bone Strength in Artistic Gymnasts

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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

Optically transmitted and inductively coupled electric reference to access in vivo concentrations for quantitative proton-decoupled ¹³C magnetic resonance spectroscopy.

Science.gov (United States)

Chen, Xing; Pavan, Matteo; Heinzer-Schweizer, Susanne; Boesiger, Peter; Henning, Anke

2012-01-01

This report describes our efforts on quantification of tissue metabolite concentrations in mM by nuclear Overhauser enhanced and proton decoupled (13) C magnetic resonance spectroscopy and the Electric Reference To access In vivo Concentrations (ERETIC) method. Previous work showed that a calibrated synthetic magnetic resonance spectroscopy-like signal transmitted through an optical fiber and inductively coupled into a transmit/receive coil represents a reliable reference standard for in vivo (1) H magnetic resonance spectroscopy quantification on a clinical platform. In this work, we introduce a related implementation that enables simultaneous proton decoupling and ERETIC-based metabolite quantification and hence extends the applicability of the ERETIC method to nuclear Overhauser enhanced and proton decoupled in vivo (13) C magnetic resonance spectroscopy. In addition, ERETIC signal stability under the influence of simultaneous proton decoupling is investigated. The proposed quantification method was cross-validated against internal and external reference standards on human skeletal muscle. The ERETIC signal intensity stability was 100.65 ± 4.18% over 3 months including measurements with and without proton decoupling. Glycogen and unsaturated fatty acid concentrations measured with the ERETIC method were in excellent agreement with internal creatine and external phantom reference methods, showing a difference of 1.85 ± 1.21% for glycogen and 1.84 ± 1.00% for unsaturated fatty acid between ERETIC and creatine-based quantification, whereas the deviations between external reference and creatine-based quantification are 6.95 ± 9.52% and 3.19 ± 2.60%, respectively. Copyright © 2011 Wiley Periodicals, Inc.

Endurance training increases the efficiency of rat skeletal muscle mitochondria.

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Zoladz, Jerzy A; Koziel, Agnieszka; Woyda-Ploszczyca, Andrzej; Celichowski, Jan; Jarmuszkiewicz, Wieslawa

2016-10-01

Endurance training enhances mitochondrial oxidative capacity, but its effect on mitochondria functioning is poorly understood. In the present study, the influence of an 8-week endurance training on the bioenergetic functioning of rat skeletal muscle mitochondria under different assay temperatures (25, 35, and 42 °C) was investigated. The study was performed on 24 adult 4-month-old male Wistar rats, which were randomly assigned to either a treadmill training group (n = 12) or a sedentary control group (n = 12). In skeletal muscles, endurance training stimulated mitochondrial biogenesis and oxidative capacity. In isolated mitochondria, endurance training increased the phosphorylation rate and elevated levels of coenzyme Q. Moreover, a decrease in mitochondrial uncoupling, including uncoupling protein-mediated proton leak, was observed after training, which could explain the increased reactive oxygen species production (in nonphosphorylating mitochondria) and enhanced oxidative phosphorylation efficiency. At all studied temperatures, endurance training significantly augmented H2O2 production (and coenzyme Q reduction level) in nonphosphorylating mitochondria and decreased H2O2 production (and coenzyme Q reduction level) in phosphorylating mitochondria. Endurance training magnified the hyperthermia-induced increase in oxidative capacity and attenuated the hyperthermia-induced decline in oxidative phosphorylation efficiency and reactive oxygen species formation of nonphosphorylating mitochondria via proton leak enhancement. Thus, endurance training induces both quantitative and qualitative changes in muscle mitochondria that are important for cell signaling as well as for maintaining muscle energy homeostasis, especially at high temperatures.

Human skeletal muscle fatty acid and glycerol metabolism during rest, exercise and recovery

DEFF Research Database (Denmark)

Van Hall, Gerrit; Sacchetti, M; Rådegran, G

2002-01-01

glycerol uptake was observed, which was substantially higher during exercise. Total body skeletal muscle FA and glycerol uptake/release was estimated to account for 18-25 % of whole body R(d) or R(a). In conclusion: (1) skeletal muscle FA and glycerol metabolism, using the leg arterial-venous difference......This study was conducted to investigate skeletal muscle fatty acid (FA) and glycerol kinetics and to determine the contribution of skeletal muscle to whole body FA and glycerol turnover during rest, 2 h of one-leg knee-extensor exercise at 65 % of maximal leg power output, and 3 h of recovery....... To this aim, the leg femoral arterial-venous difference technique was used in combination with a continuous infusion of [U-(13)C]palmitate and [(2)H(5)]glycerol in five post-absorptive healthy volunteers (22 +/- 3 years). The influence of contamination from non-skeletal muscle tissues, skin and subcutaneous...

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

Science.gov (United States)

Crist, Colin

2017-01-01

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

Proton therapy in Australia

International Nuclear Information System (INIS)

Jackson, M.

2000-01-01

Full text: Proton therapy has been in use since 1954 and over 25,000 patients have been treated worldwide. Until recently most patients were treated at physics research facilities but with the development of more compact and reliable accelerators it is now possible to realistically plan for proton therapy in an Australian hospital. The Australian National Proton Project has been formed to look at the feasibility of a facility which would be primarily for patient treatment but would also be suitable for research and commercial applications. A detailed report will be produced by the end of the year. The initial clinical experience was mainly with small tumours and other lesions close to critical organs. Large numbers of eye tumours have also been treated. Protons have a well-defined role in these situations and are now being used in the treatment of more common cancers. With the development of hospital-based facilities, over 2,500 patients with prostate cancer have been treated using a simple technique which gives results at least as good as radical surgery, external beam radiotherapy or brachytherapy. Importantly, the incidence of severe complications is very low. There are encouraging results in many disease sites including lung, liver, soft tissue sarcomas and oesophagus. As proton therapy becomes more widely available, randomised trials comparing it with conventional radiotherapy or Intensity Modulated Radiation Therapy (IMRT) will be possible. In most situations the use of protons will enable a higher dose to be given safely but in situations where local control rates are already satisfactory, protons are expected to produce less complications than conventional treatment. The initial costs of a proton facility are high but the recurrent costs are similar to other forms of high technology radiotherapy. . Simple treatment techniques with only a few fields are usually possible and proton therapy avoids the high integral doses associated with IMRT. This reduction in

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

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.

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.

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.

Physical and biological factors determining the effective proton range

International Nuclear Information System (INIS)

Grün, Rebecca; Friedrich, Thomas; Krämer, Michael; Scholz, Michael; Zink, Klemens; Durante, Marco; Engenhart-Cabillic, Rita

2013-01-01

Purpose: Proton radiotherapy is rapidly becoming a standard treatment option for cancer. However, even though experimental data show an increase of the relative biological effectiveness (RBE) with depth, particularly at the distal end of the treatment field, a generic RBE of 1.1 is currently used in proton radiotherapy. This discrepancy might affect the effective penetration depth of the proton beam and thus the dose to the surrounding tissue and organs at risk. The purpose of this study was thus to analyze the impact of a tissue and dose dependent RBE of protons on the effective range of the proton beam in comparison to the range based on a generic RBE of 1.1.Methods: Factors influencing the biologically effective proton range were systematically analyzed by means of treatment planning studies using the Local Effect Model (LEM IV) and the treatment planning software TRiP98. Special emphasis was put on the comparison of passive and active range modulation techniques.Results: Beam energy, tissue type, and dose level significantly affected the biological extension of the treatment field at the distal edge. Up to 4 mm increased penetration depth as compared to the depth based on a constant RBE of 1.1. The extension of the biologically effective range strongly depends on the initial proton energy used for the most distal layer of the field and correlates with the width of the distal penumbra. Thus, the range extension, in general, was more pronounced for passive as compared to active range modulation systems, whereas the maximum RBE was higher for active systems.Conclusions: The analysis showed that the physical characteristics of the proton beam in terms of the width of the distal penumbra have a great impact on the RBE gradient and thus also the biologically effective penetration depth of the beam

Proton therapy of tumours and possibilities of its implementation in the Slovak Republic

International Nuclear Information System (INIS)

Hanula, M.; Ruzicka, J.; Combor, I.; Cesakova, H.

2008-01-01

Besides other modalities irradiation of tumours with a beam of ionizing particles is applied in the treatment of cancer. Currently treatment with photon and electron beams is a standard worldwide and in Slovakia as well. These particles exhibit exponential fall off in tissues. This results in the irradiation of large volume of healthy tissues, which are located in the beam's path. Radiotoxicity of normal tissues is the limiting factor in radiotherapy. Protons are characterized by loosing the most of their energy at the end of their path. The range of protons can be controlled by the proper selection of their initial energy. These properties of protons make it possible to achieve lower doses to the healthy tissues thereby allowing escalation of dose to the tumour. Higher doses to the tumour result in higher efficiency of the treatment. Proton therapy represents a modern and highly effective tool in the struggle against cancer. The present clinical outcomes have proved the benefit of the proton therapy for the improvement of the treatment success-fullness. Slovakia has created conditions allowing implementation of the depth proton therapy within the frame of the Cyclotron centre of the SR project in a relatively short period of time. (author)

Characterizing the Effects of Chronic 2G Centrifugation on the Rat Skeletal System

Science.gov (United States)

Johnson, Aimee; Scott, Ryan; Ronca, April E.; Hoban-Higgins, Tana M.; Fuller, Charles A.; Alwood, Joshua S.

2017-01-01

During weightlessness, the skeletal system of astronauts is negatively affected by decreased calcium absorption and bone mass loss. Therefore, it is necessary to counteract these changes for long-term skeletal health during space flights. Our long-term plan is to assess artificial gravity (AG) as a possible solution to mitigate these changes. In this study, we aim to determine the skeletal acclimation to chronic centrifugation. We hypothesize that a 2G hypergravity environment causes an anabolic response in growing male rats. Specifically, we predict chronic 2G to increase tissue mineral density, bone volume fraction of the cancellous tissue and to increase overall bone strength. Systemically, we predict that bone formation markers (i.e., osteocalcin) are elevated and resorption markers (i.e., tartrate resistant acid phosphatase) are decreased or unchanged from controls. The experiment has three groups, each with an n8: chronic 2g, cage control (housed on the centrifuge, but not spun), and a vivarium control (normal rat caging). Pre-pubescent, male Long-Evans rats were used to assess our hypothesis. This group was subject to 90 days of 2G via centrifugation performed at the Chronic Acceleration Research Unit (CARU) at University of California Davis. After 90 days, animals were euthanized and tissues collected. Blood was drawn via cardiac puncture and the right leg collected for structural (via microcomputed tomography) and strength quantification. Understanding how counteract these skeletal changes will have major impacts for both the space-faring astronauts and the people living on Earth.

The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine

Energy Technology Data Exchange (ETDEWEB)

Widder, Joachim, E-mail: j.widder@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Lambin, Philippe [Department of Radiation Oncology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht (Netherlands); Marijnen, Corrie A.M. [Department of Radiation Oncology, Leiden University Medical Center, Leiden (Netherlands); Pignol, Jean-Philippe [Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Rasch, Coen R. [Department of Radiation Oncology, Academic Medical Center, Amsterdam (Netherlands); Slotman, Ben J. [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands); Verheij, Marcel [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

2016-05-01

Purpose: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Methods and Materials: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. Results: By analogy with biologically targeted therapies, the technology needs to be tested in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Conclusions: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.

Molecular Signals and Skeletal Muscle Adaptation to Exercise

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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

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

Clinical Features and Outcomes Differ between Skeletal and Extraskeletal Osteosarcoma

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Sheila Thampi

2014-01-01

Full Text Available Background. Extraskeletal osteosarcoma (ESOS is a rare subtype of osteosarcoma. We investigated patient characteristics, overall survival, and prognostic factors in ESOS. Methods. We identified cases of high-grade osteosarcoma with known tissue of origin in the Surveillance, Epidemiology, and End Results database from 1973 to 2009. Demographics were compared using univariate tests. Overall survival was compared with log-rank tests and multivariate analysis using Cox proportional hazards methods. Results. 256/4,173 (6% patients with high-grade osteosarcoma had ESOS. Patients with ESOS were older, were more likely to have an axial tumor and regional lymph node involvement, and were female. Multivariate analysis showed ESOS to be favorable after controlling for stage, age, tumor site, gender, and year of diagnosis [hazard ratio 0.75 (95% CI 0.62 to 0.90; p=0.002]. There was an interaction between age and tissue of origin such that older patients with ESOS had superior outcomes compared to older patients with skeletal osteosarcoma. Adverse prognostic factors in ESOS included metastatic disease, larger tumor size, older age, and axial tumor site. Conclusion. Patients with ESOS have distinct clinical features but similar prognostic factors compared to skeletal osteosarcoma. Older patients with ESOS have superior outcomes compared to older patients with skeletal osteosarcoma.

Establishment and cryopreservation of a giant panda skeletal muscle-derived cell line.

Science.gov (United States)

Yu, Fang-Jian; Zeng, Chang-Jun; Zhang, Yan; Wang, Cheng-Dong; Xiong, Tie-Yi; Fang, Sheng-Guo; Zhang, He-Min

2015-06-01

The giant panda Ailuropoda melanoleuca is an endangered species and is a symbol for wildlife conservation. Although efforts have been made to protect this rare and endangered species through breeding and conservative biology, the long-term preservation of giant panda genome resources (gametes, tissues, organs, genomic libraries, etc.) is still a practical option. In this study, the giant panda skeletal muscle-derived cell line was successfully established via primary explants culture and cryopreservation techniques. The population doubling time of giant panda skeletal cells was approximately 33.8 h, and this population maintained a high cell viability before and after cryopreservation (95.6% and 90.7%, respectively). The two skeletal muscle-specific genes SMYD1 and MYF6 were expressed and detected by RT-PCR in the giant panda skeletal muscle-derived cell line. Karyotyping analysis revealed that the frequencies of giant panda skeletal muscle cells showing a chromosome number of 2n=42 ranged from 90.6∼94.2%. Thus, the giant panda skeletal muscle-derived cell line provides a vital resource and material platform for further studies and is likely to be useful for the protection of this rare and endangered species.

Skeletal Dysplasias Associated with Mild Myopathy—A Clinical and Molecular Review

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Katarzyna A. Piróg

2010-01-01

Full Text Available Musculoskeletal system is a complex assembly of tissues which acts as scaffold for the body and enables locomotion. It is often overlooked that different components of this system may biomechanically interact and affect each other. Skeletal dysplasias are diseases predominantly affecting the development of the osseous skeleton. However, in some cases skeletal dysplasia patients are referred to neuromuscular clinics prior to the correct skeletal diagnosis. The muscular complications seen in these cases are usually mild and may stem directly from the muscle defect and/or from the altered interactions between the individual components of the musculoskeletal system. A correct early diagnosis may enable better management of the patients and a better quality of life. This paper attempts to summarise the different components of the musculoskeletal system which are affected in skeletal dysplasias and lists several interesting examples of such diseases in order to enable better understanding of the complexity of human musculoskeletal system.

Gender-related differences in the apparent timing of skeletal density bands in the reef-building coral Siderastrea siderea

Science.gov (United States)

Carricart-Ganivet, J. P.; Vásquez-Bedoya, L. F.; Cabanillas-Terán, N.; Blanchon, P.

2013-09-01

Density banding in skeletons of reef-building corals is a valuable source of proxy environmental data. However, skeletal growth strategy has a significant impact on the apparent timing of density-band formation. Some corals employ a strategy where the tissue occupies previously formed skeleton during as the new band forms, which leads to differences between the actual and apparent band timing. To investigate this effect, we collected cores from female and male colonies of Siderastrea siderea and report tissue thicknesses and density-related growth parameters over a 17-yr interval. Correlating these results with monthly sea surface temperature (SST) shows that maximum skeletal density in the female coincides with low winter SSTs, whereas in the male, it coincides with high summer SSTs. Furthermore, maximum skeletal densities in the female coincide with peak Sr/Ca values, whereas in the male, they coincide with low Sr/Ca values. Both results indicate a 6-month difference in the apparent timing of density-band formation between genders. Examination of skeletal extension rates also show that the male has thicker tissue and extends faster, whereas the female has thinner tissue and a denser skeleton—but both calcify at the same rate. The correlation between extension and calcification, combined with the fact that density banding arises from thickening of the skeleton throughout the depth reached by the tissue layer, implies that S. siderea has the same growth strategy as massive Porites, investing its calcification resources into linear extension. In addition, differences in tissue thicknesses suggest that females offset the greater energy requirements of gamete production by generating less tissue, resulting in differences in the apparent timing of density-band formation. Such gender-related offsets may be common in other corals and require that environmental reconstructions be made from sexed colonies and that, in fossil corals where sex cannot be determined

Myo/Nog cells: targets for preventing the accumulation of skeletal muscle-like cells in the human lens.

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Jacquelyn Gerhart

Full Text Available Posterior capsule opacification (PCO is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human lens tissue. Myo/Nog cells were present in anterior, equatorial and bow regions of the human lens, cornea and ciliary processes. In anterior lens tissue removed by capsulorhexis, Myo/Nog cells had synthesized myofibroblast and skeletal muscle proteins, including vimentin, MyoD and sarcomeric myosin. Alpha smooth muscle actin (α-SMA was detected in a subpopulation of Myo/Nog cells. Areas of the capsule denuded of epithelial cells were surrounded by Myo/Nog cells. Some of these cell free areas contained a wrinkle in the capsule. Depletion of Myo/Nog cells eliminated cells expressing skeletal muscle proteins in 5-day cultures but did not affect cells immunoreactive for beaded filament proteins that accumulate in differentiating lens epithelial cells. Transforming growth factor-betas 1 and 2 that mediate an epithelial-mesenchymal transition, did not induce the expression of skeletal muscle proteins in lens cells following Myo/Nog cell depletion. This study demonstrates that Myo/Nog cells in anterior lens tissue removed from cataract patients have undergone a partial differentiation to skeletal muscle. Myo/Nog cells appear to be the source of skeletal muscle-like cells in explants of human lens tissue. Targeting Myo/Nog cells with the G8 antibody during cataract surgery may reduce the incidence of PCO.

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

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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

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

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

Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle

Science.gov (United States)

Koh, Ho-Jin; Toyoda, Taro; Didesch, Michelle M.; Lee, Min-Young; Sleeman, Mark W.; Kulkarni, Rohit N.; Musi, Nicolas; Hirshman, Michael F.; Goodyear, Laurie J.

2013-01-01

Endoplasmic Reticulum (ER) stress has been linked to insulin resistance in multiple tissues but the role of ER stress in skeletal muscle has not been explored. ER stress has also been reported to increase tribbles 3 (TRB3) expression in multiple cell lines. Here, we report that high fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases TRB3 and ER stress markers in skeletal muscle. Overexpression of TRB3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signaling. Incubation of C2C12 cells and mouse skeletal muscle with ER stressors thapsigargin and tunicamycin increases TRB3 and impairs insulin signaling and glucose uptake, effects reversed in cells overexpressing RNAi for TRB3 and in muscles from TRB3 knockout mice. Furthermore, TRB3 knockout mice are protected from high fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that TRB3 mediates ER stress-induced insulin resistance in skeletal muscle. PMID:23695665

Radium-223 in treatment of castration-resistant prostate cancer with skeletal metastases

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V. B. Matveev

2017-01-01

Full Text Available More than 90 % of patients with metastatic castration-resistant prostate cancer (CRPC have radiologically confirmed skeletal metastases. Traditional treatment methods such as administration of painkillers, external beam therapy, bisphosphonates or denosumab, as well as injections of strontium-89 or samarium-153 radionuclides, have only palliative effect and in some cases can postpone development of skeletal complications. Alpha-emitter radium-223 dichloride (Ra-223; alpharadin previously is currently one of the known drugs with proven effectiveness in relation to increasing overall survival of patients with CRPC. Ra-223 was developed specifically for patients with CRPC and symptomatic skeletal metastases. The drug targets the areas of skeletal tissue remodeling. Ra-223 is the therapy of choice in patients with CRPC and skeletal metastases and without confirmed visceral metastases before and after docetaxel chemotherapy. Chemotherapy after treatment with Ra-223 is a possible and satisfactory tolerable treatment option. Combination of Ra-223 with abiraterone, enzalutamide, or denosumab is, apparently, effective and safe, but further studies are necessary.

The relationship between heat shock protein 72 expression in skeletal muscle and insulin sensitivity is dependent on adiposity

DEFF Research Database (Denmark)

Henstridge, Darren C; Forbes, Josephine M; Penfold, Sally A

2010-01-01

Decreased gene expression of heat shock protein 72 (HSP72) in skeletal muscle is associated with insulin resistance in humans. We aimed to determine whether HSP72 protein expression in insulin-sensitive tissues is related to criterion standard measures of adiposity and insulin resistance in a young...... healthy human population free of hyperglycemia. Healthy participants (N = 17; age, 30 ± 3 years) underwent measurement of body composition (dual-energy x-ray absorptiometry), a maximum aerobic capacity test (VO(2max)), an oral glucose tolerance test, and a hyperinsulinemic-euglycemic clamp (M) to access...... insulin sensitivity. Skeletal muscle and subcutaneous adipose tissue biopsies were obtained by percutaneous needle biopsy. HSP72 protein expression in skeletal muscle was inversely related to percentage body fat (r = -0.54, P

In vivo characterisation of soft tissue tumours by 1.5-T proton MR spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Russo, F.; Mazzetti, S.; Grignani, G.; Rosa, G.De; Aglietta, M.; Anselmetti, G.C.; Stasi, M.; Regge, D. [Institute for Cancer Research and Treatment (IRCC), Candiolo, Torino (Italy)

2012-05-15

To determine whether proton magnetic resonance spectroscopy (1H-MRS) can help differentiate between benign and malignant soft tissue lesions, and to assess if there is a correlation between 1H-MRS data and the mitotic index. MR measurements were performed in 43 patients with soft tissue tumours >15 mm in diameter. Six cases were excluded for technical failure. Examinations were performed at 1.5 T using a single-voxel point resolved spectroscopy sequence (PRESS) with TR/TE = 2000/150 ms. The volume of interest was positioned within the lesion avoiding inclusion of necrotic regions. In all patients, a histological diagnosis was obtained and the corresponding mitotic index was also computed. 1H-MRS results and histopathological findings were compared using the chi-squared test and correlation coefficient. Choline was detected in 18/19 patients with malignant tumours and in 3/18 patients with benign lesions. The three benign lesions included one desmoid tumour, one ossificans myositis and one eccrine spiradenoma. Choline was not detected in 15 patients with benign lesions or in one patient with dermatofibrosarcoma protuberans. Resulting 1H-MRS sensitivity and specificity were 95% and 83% respectively. Absence of choline peak is highly predictive of benign tumours suggesting that 1H-MRS can help to differentiate malignant from benign tumours. (orig.)

In vivo characterisation of soft tissue tumours by 1.5-T proton MR spectroscopy

International Nuclear Information System (INIS)

Russo, F.; Mazzetti, S.; Grignani, G.; Rosa, G.De; Aglietta, M.; Anselmetti, G.C.; Stasi, M.; Regge, D.

2012-01-01

To determine whether proton magnetic resonance spectroscopy (1H-MRS) can help differentiate between benign and malignant soft tissue lesions, and to assess if there is a correlation between 1H-MRS data and the mitotic index. MR measurements were performed in 43 patients with soft tissue tumours >15 mm in diameter. Six cases were excluded for technical failure. Examinations were performed at 1.5 T using a single-voxel point resolved spectroscopy sequence (PRESS) with TR/TE = 2000/150 ms. The volume of interest was positioned within the lesion avoiding inclusion of necrotic regions. In all patients, a histological diagnosis was obtained and the corresponding mitotic index was also computed. 1H-MRS results and histopathological findings were compared using the chi-squared test and correlation coefficient. Choline was detected in 18/19 patients with malignant tumours and in 3/18 patients with benign lesions. The three benign lesions included one desmoid tumour, one ossificans myositis and one eccrine spiradenoma. Choline was not detected in 15 patients with benign lesions or in one patient with dermatofibrosarcoma protuberans. Resulting 1H-MRS sensitivity and specificity were 95% and 83% respectively. Absence of choline peak is highly predictive of benign tumours suggesting that 1H-MRS can help to differentiate malignant from benign tumours. (orig.)

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

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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.

MALDI imaging mass spectrometry: discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures.

Science.gov (United States)

Klein, Oliver; Strohschein, Kristin; Nebrich, Grit; Oetjen, Janina; Trede, Dennis; Thiele, Herbert; Alexandrov, Theodore; Giavalisco, Patrick; Duda, Georg N; von Roth, Philipp; Geissler, Sven; Klose, Joachim; Winkler, Tobias

2014-10-01

Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological regions in injured skeletal muscle is inadequate, underlying mechanisms of the beneficial effects of mesenchymal stromal cell transplantation on primary trauma and trauma adjacent muscle area remain elusive. For discrimination of these pathophysiological regions, formalin-fixed injured skeletal muscle tissue was analyzed by MALDI imaging MS. By using two computational evaluation strategies, a supervised approach (ClinProTools) and unsupervised segmentation (SCiLS Lab), characteristic m/z species could be assigned to primary trauma and trauma adjacent muscle regions. Using "bottom-up" MS for protein identification and validation of results by immunohistochemistry, we could identify two proteins, skeletal muscle alpha actin and carbonic anhydrase III, which discriminate between the secondary damage on adjacent tissue and the primary traumatized muscle area. Our results underscore the high potential of MALDI imaging MS to describe the spatial characteristics of pathophysiological changes in muscle. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

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

Applications of Mesenchymal Stem Cells and Neural Crest Cells in Craniofacial Skeletal Research

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Satoru Morikawa

2016-01-01

Full Text Available Craniofacial skeletal tissues are composed of tooth and bone, together with nerves and blood vessels. This composite material is mainly derived from neural crest cells (NCCs. The neural crest is transient embryonic tissue present during neural tube formation whose cells have high potential for migration and differentiation. Thus, NCCs are promising candidates for craniofacial tissue regeneration; however, the clinical application of NCCs is hindered by their limited accessibility. In contrast, mesenchymal stem cells (MSCs are easily accessible in adults, have similar potential for self-renewal, and can differentiate into skeletal tissues, including bones and cartilage. Therefore, MSCs may represent good sources of stem cells for clinical use. MSCs are classically identified under adherent culture conditions, leading to contamination with other cell lineages. Previous studies have identified mouse- and human-specific MSC subsets using cell surface markers. Additionally, some studies have shown that a subset of MSCs is closely related to neural crest derivatives and endothelial cells. These MSCs may be promising candidates for regeneration of craniofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology of MSCs in craniofacial research.

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...

FXIIIA and TGF-beta over-expression produces normal musculo-skeletal phenotype in TG2-/- mice.

Science.gov (United States)

Tarantino, U; Oliva, F; Taurisano, G; Orlandi, A; Pietroni, V; Candi, E; Melino, G; Maffulli, N

2009-04-01

Transglutaminase (TGs) enzymes and proteins crosslinking have for long time been implicated in the formation of hard tissue development, matrix maturation and mineralization. Among the TGs family members, in the context of connective tissue formation, TG2 and Factor XIII are expressed in cartilage by hypertrophic chondrocytes. Here, we analyse the morphological consequences of TG2 deficiency, during the development of skeletal elements. When TG2 is absent, there are not gross abnormalities in the development of the skeletal system, probably from compensatory mechanisms resulting in increased expression of FXIIIA and TGF-beta 1. In vivo other TGs may be involved in promoting chondrocytes and osteoblast differentiation and matrix mineralisation.

Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

DEFF Research Database (Denmark)

Frydelund-Larsen, Lone; Åkerström, Thorbjörn; Nielsen, Søren

2006-01-01

in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4......Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression.......5, and 6 h in response to exercise (n = 8) compared with preexercise samples and compared with the resting control group (n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied...

Progressive damage to rat skin induced by protons

International Nuclear Information System (INIS)

Molinari, Beatriz L.; Saint-Martin, Maria L.G.; Bernaola, Omar A.; Duran, Hebe; Policastro, Lucia L.; O'Connor, Silvia E.; Palmieri, Monica; Davidson, Miguel; Davidson, Jorge

2003-01-01

Wistar rats were locally irradiated with proton beams. Dorsal portions of the skin were irradiated to a dose of 20 Gy employing a plastic wedge as a variable thickness energy degrader. The animals were sacrificed 2,5,6,7,and 9 days post-irradiation. The doses were monitored with a transmission camera. Solid track detectors (Makrofold E) were placed on the area to be irradiated to determine spatial correlation with the dose. Tissue reactions were clearly observed and were quantitatively assessed as a function of dose. Track detectors proved to be valuable to determine the correlation between the dose and tissue damage . This biological experimental model proved useful to analyze the response of tissues to a gradient of doses yielded by a proton beam. (author)

Extrarenal potassium adaptation: role of skeletal muscle

International Nuclear Information System (INIS)

Blachley, J.D.; Crider, B.P.; Johnson, J.H.

1986-01-01

Following the ingestion of a high-potassium-content diet for only a few days, the plasma potassium of rats rises only modestly in response to a previously lethal dose of potassium salts. This acquired tolerance, termed potassium adaptation, is principally the result of increased capacity to excrete potassium into the urine. However, a substantial portion of the acute potassium dose is not immediately excreted and is apparently translocated into cells. Previous studies have failed to show an increase in the content of potassium of a variety of tissues from such animals. Using 86 Rb as a potassium analogue, we have shown that the skeletal muscle of potassium-adapted rats takes up significantly greater amounts of potassium in vivo in response to an acute challenge than does that of control animals. Furthermore, the same animals exhibit greater efflux of 86 Rb following the termination of the acute infusion. We have also shown that the Na+-K+-ATPase activity and ouabain-binding capacity of skeletal muscle microsomes are increased by the process of potassium adaptation. We conclude that skeletal muscle is an important participant in potassium adaptation and acts to temporarily buffer acute increases in the extracellular concentration of potassium

SU-E-J-63: Feasibility Study of Proton Digital Tomosynthesis in Proton Beam Therapy.

Science.gov (United States)

Min, B; Kwak, J; Lee, J; Cho, S; Park, S; Yoo, S; Chung, K; Cho, S; Lim, Y; Shin, D; Lee, S; Kim, J

2012-06-01

We investigated the feasibility of proton tomosynthesis as daily positioning of patients and compared the results with photon tomosynthesis as an alternative to conventional portal imaging or on-board cone-beam computed tomography. Dedicated photon-like proton beam using the passively scattered proton beams by the cyclotron was generated for proton imaging. The eleven projections were acquired over 30 degree with 3 degree increment in order to investigate the performance of proton tomosynthesis. The cylinder blocks and resolution phantom were used to evaluate imaging performance. Resolution phantom of a cylinder of diameter 12 cm was used to investigate the reconstructed imaging characteristics. Electron density cylinder blocks with diameter of 28 mm and height of 70 mm were employed to assess the imaging quality. The solid water, breast, bone, adipose, lung, muscle, and liver, which were tissue equivalent inserts, were positioned around the resolution phantom. The images were reconstructed by projection onto convex sets (POCS) algorithm and total variation minimization (TVM) methods. The Gafchromic EBT films were utilized for measuring the photon-like proton beams as a proton detector. In addition, the photon tomosynthesis images were obtained for a comparison with proton tomosynthesis images. The same angular sampling data were acquired for both proton and photon tomosynthesis. In the resolution phantom image obtained proton tomosynthesis, down to 1.6 mm diameter rods were resolved visually, although the separation between adjacent rods was less distinct. In contrast, down to 1.2 mm diameter rods were resolved visually in the reconstructed image obtained photon tomosynthesis. Both proton and photon tomosynthesis images were similar in intensities of different density blocks. Our results demonstrated that proton tomosynthesis could make it possible to provide comparable tomography imaging to photon tomosynthesis for positioning as determined by manual registration

IL-6 selectively stimulates fat metabolism in human skeletal muscle

DEFF Research Database (Denmark)

Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

2010-01-01

and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed......Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... before, during, and 2 h after cessation of the infusion. Glucose metabolism was unaffected by rhIL-6. In contrast, rhIL-6 increased systemic fatty acid oxidation approximately twofold after 60 min, and it remained elevated even 2 h after the infusion. The increase in oxidation was followed by an increase...

IL-6 selectively stimulates fat metabolism in human skeletal muscle

DEFF Research Database (Denmark)

Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

2010-01-01

and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed......Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... before, during, and 2 h after cessation of the infusion. Glucose metabolism was unaffected by rhIL-6. In contrast, rhIL-6 increased systemic fatty acid oxidation approximately twofold after 60 min, and it remained elevated even 2 h after the infusion. The increase in oxidation was followed by an increase...

The effect of purinergic P2 receptor blockade on skeletal muscle exercise hyperemia in miniature swine

DEFF Research Database (Denmark)

Mortensen, Stefan Peter; McAllister, R M; Yang, H T

2014-01-01

PURPOSE: ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via purinergic P2 receptors. This study investigated the role of P2 receptors in exercise hyperemia in miniature swine. METHODS: We measured regional blood flow with radiolabeled......-microsphere technique and systemic hemodynamics before and after arterial infusion of the P2 receptor antagonist reactive blue 2 during treadmill exercise (5.2 km/h, ~60 % VO2max) and arterial ATP infusion in female Yucatan miniature swine (~29 kg). RESULTS: Mean blood flow during exercise from the 16 sampled skeletal...... muscle tissues was 138 ± 18 mL/min/100 g (mean ± SEM), and it was reduced in 11 (~25 %) of the 16 sampled skeletal muscles after RB2 was infused. RB2 also lowered diaphragm blood flow and kidney blood flow, whereas lung tissue blood flow was increased (all P

Mitigating HZE Radiation-Induced Deficits in Marrow-Derived Mesenchymal Progenitor Cells and Skeletal Structure

Science.gov (United States)

Globus, Ruth K.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Terada, Masahiro; Alwood, Joshua; Halloran, Bernard; Tahimic, Candice

2016-01-01

Future long-duration space exploration beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure causes progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility.

Macrophage Plasticity and the Role of Inflammation in Skeletal Muscle Repair

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Yacine Kharraz

2013-01-01

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

Competitive cation binding computations of proton balance for reactions of the phosphagen and glycolytic energy systems within skeletal muscle

Science.gov (United States)

2017-01-01

Limited research and data has been published for the H+ coefficients for the metabolites and reactions involved in non-mitochondrial energy metabolism. The purpose of this investigation was to compute the fractional binding of H+, K+, Na+ and Mg2+ to 21 metabolites of skeletal muscle non-mitochondrial energy metabolism, resulting in 104 different metabolite-cation complexes. Fractional binding of H+ to these metabolite-cation complexes were applied to 17 reactions of skeletal muscle non-mitochondrial energy metabolism, and 8 conditions of the glycolytic pathway based on the source of substrate (glycogen vs. glucose), completeness of glycolytic flux, and the end-point of pyruvate vs. lactate. For pH conditions of 6.0 and 7.0, respectively, H+ coefficients (-‘ve values = H+ release) for the creatine kinase, adenylate kinase, AMP deaminase and ATPase reactions were 0.8 and 0.97, -0.13 and -0.02, 1.2 and 1.09, and -0.01 and -0.66, respectively. The glycolytic pathway is net H+ releasing, regardless of lactate production, which consumes 1 H+. For glycolysis fueled by glycogen and ending in either pyruvate or lactate, H+ coefficients for pH 6.0 and 7.0 were -3.97 and -2.01 (pyruvate), and -1.96 and -0.01 (lactate), respectively. When starting with glucose, the same conditions result in H+ coefficients of -3.98 and -2.67, and -1.97 and –0.67, respectively. The most H+ releasing reaction of glycolysis is the glyceraldehyde-3-phosphate dehydrogenase reaction, with H+ coefficients for pH 6.0 and 7.0 of -1.58 and -0.76, respectively. Incomplete flux of substrate through glycolysis would increase net H+ release due to the absence of the pyruvate kinase and lactate dehydrogenase reactions, which collectively result in H+ coefficients for pH 6.0 and 7.0 of 1.35 and 1.88, respectively. The data presented provide an extensive reference source for academics and researchers to accurately profile the balance of protons for all metabolites and reactions of non-mitochondrial energy

Competitive cation binding computations of proton balance for reactions of the phosphagen and glycolytic energy systems within skeletal muscle.

Science.gov (United States)

Robergs, Robert Andrew

2017-01-01

Limited research and data has been published for the H+ coefficients for the metabolites and reactions involved in non-mitochondrial energy metabolism. The purpose of this investigation was to compute the fractional binding of H+, K+, Na+ and Mg2+ to 21 metabolites of skeletal muscle non-mitochondrial energy metabolism, resulting in 104 different metabolite-cation complexes. Fractional binding of H+ to these metabolite-cation complexes were applied to 17 reactions of skeletal muscle non-mitochondrial energy metabolism, and 8 conditions of the glycolytic pathway based on the source of substrate (glycogen vs. glucose), completeness of glycolytic flux, and the end-point of pyruvate vs. lactate. For pH conditions of 6.0 and 7.0, respectively, H+ coefficients (-'ve values = H+ release) for the creatine kinase, adenylate kinase, AMP deaminase and ATPase reactions were 0.8 and 0.97, -0.13 and -0.02, 1.2 and 1.09, and -0.01 and -0.66, respectively. The glycolytic pathway is net H+ releasing, regardless of lactate production, which consumes 1 H+. For glycolysis fueled by glycogen and ending in either pyruvate or lactate, H+ coefficients for pH 6.0 and 7.0 were -3.97 and -2.01 (pyruvate), and -1.96 and -0.01 (lactate), respectively. When starting with glucose, the same conditions result in H+ coefficients of -3.98 and -2.67, and -1.97 and -0.67, respectively. The most H+ releasing reaction of glycolysis is the glyceraldehyde-3-phosphate dehydrogenase reaction, with H+ coefficients for pH 6.0 and 7.0 of -1.58 and -0.76, respectively. Incomplete flux of substrate through glycolysis would increase net H+ release due to the absence of the pyruvate kinase and lactate dehydrogenase reactions, which collectively result in H+ coefficients for pH 6.0 and 7.0 of 1.35 and 1.88, respectively. The data presented provide an extensive reference source for academics and researchers to accurately profile the balance of protons for all metabolites and reactions of non-mitochondrial energy

Competitive cation binding computations of proton balance for reactions of the phosphagen and glycolytic energy systems within skeletal muscle.

Directory of Open Access Journals (Sweden)

Robert Andrew Robergs

Full Text Available Limited research and data has been published for the H+ coefficients for the metabolites and reactions involved in non-mitochondrial energy metabolism. The purpose of this investigation was to compute the fractional binding of H+, K+, Na+ and Mg2+ to 21 metabolites of skeletal muscle non-mitochondrial energy metabolism, resulting in 104 different metabolite-cation complexes. Fractional binding of H+ to these metabolite-cation complexes were applied to 17 reactions of skeletal muscle non-mitochondrial energy metabolism, and 8 conditions of the glycolytic pathway based on the source of substrate (glycogen vs. glucose, completeness of glycolytic flux, and the end-point of pyruvate vs. lactate. For pH conditions of 6.0 and 7.0, respectively, H+ coefficients (-'ve values = H+ release for the creatine kinase, adenylate kinase, AMP deaminase and ATPase reactions were 0.8 and 0.97, -0.13 and -0.02, 1.2 and 1.09, and -0.01 and -0.66, respectively. The glycolytic pathway is net H+ releasing, regardless of lactate production, which consumes 1 H+. For glycolysis fueled by glycogen and ending in either pyruvate or lactate, H+ coefficients for pH 6.0 and 7.0 were -3.97 and -2.01 (pyruvate, and -1.96 and -0.01 (lactate, respectively. When starting with glucose, the same conditions result in H+ coefficients of -3.98 and -2.67, and -1.97 and -0.67, respectively. The most H+ releasing reaction of glycolysis is the glyceraldehyde-3-phosphate dehydrogenase reaction, with H+ coefficients for pH 6.0 and 7.0 of -1.58 and -0.76, respectively. Incomplete flux of substrate through glycolysis would increase net H+ release due to the absence of the pyruvate kinase and lactate dehydrogenase reactions, which collectively result in H+ coefficients for pH 6.0 and 7.0 of 1.35 and 1.88, respectively. The data presented provide an extensive reference source for academics and researchers to accurately profile the balance of protons for all metabolites and reactions of non

Synthetic Secoisolariciresinol Diglucoside (LGM2605 Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

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Anastasia Velalopoulou

2017-11-01

Full Text Available Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS, pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.

Clypeotheca, a new skeletal structure in scleractinian corals: a potential stress indicator

Science.gov (United States)

Nothdurft, L. D.; Webb, G. E.

2009-03-01

Physiological responses to environmental stress are increasingly well studied in scleractinian corals. This work reports a new stress-related skeletal structure we term clypeotheca. Clypeotheca was observed in several live-collected common reef-building coral genera and a two to three kya subfossil specimen from Heron Reef, Great Barrier Reef and consists of an epitheca-like skeletal wall that seals over the surface of parts of the corallum in areas of stress or damage. It appears to form from a coordinated process wherein neighboring polyps and adjoining coenosarc seal themselves off from the surrounding environment as they contract and die. Clypeotheca forms from inward skeletal centripetal growth at the edges of corallites and by the merging of flange-like outgrowths that surround individual spines over the surface of the coenosteum. Microstructurally, the merged flanges are similar to upside-down dissepiments and true epitheca. Clypeotheca is interpreted primarily as a response to stress that may help protect the colony from invasion of unhealthy tissues by parasites or disease by retracting tissues in areas that have become unhealthy for the polyps. Identification of skeletal responses of corals to environmental stress may enable the frequency of certain types of environmental stress to be documented in past environments. Such data may be important for understanding the nature of reef dynamics through intervals of climate change and for monitoring the effects of possible anthropogenic stress in modern coral reef habitats.

Tissue Engineering Organs for Space Biology Research

Science.gov (United States)

Vandenburgh, H. H.; Shansky, J.; DelTatto, M.; Lee, P.; 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.

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

Science.gov (United States)

Gehlert, Sebastian; Bloch, Wilhelm; Suhr, Frank

2015-01-01

Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca2+ is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca2+ regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca2+-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca2+ ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca2+ ions in adult muscle but also highlight recent findings of critical Ca2+-dependent mechanisms essential for skeletal muscle-regulation and maintenance. PMID:25569087

Deep bite malocclusion: exploration of the skeletal and dental factors

International Nuclear Information System (INIS)

Bhateja, N.K.; Fida, M.; Shaikh, A.

2016-01-01

Correction of deep bite is crucial for maintenance of dental hard and soft tissue structures and for prevention of temporomandibular joint disorders. Exploration of underlying skeletal and dental factors is essential for efficient and individualized treatment planning. To date etiological factors of dental and skeletal deep bite have not been explored in Pakistani orthodontic patients. The objectives of this study were to explore frequencies of dental and skeletal etiological factors in deep bite patients and to determine correlations amongst dental and skeletal etiological factors of deep bite. Methods: The study included a total of 113 subjects (males=35; females=78) with no craniofacial syndromes or prior orthodontic treatment. Pre-treatment orthodontic records were used to evaluate various dental and skeletal parameters. Descriptive statistics of each parameter were calculated. The various study parameters were correlated using Pearson's Correlation. Results: Deep curve of Spee was most frequently seen factor of dental deep bite (72.6%), followed by increased coronal length of upper incisors (28.3%), retroclined upper incisors (17.7%), retroclined lower incisors (8%) and increased coronal length of lower incisors (5.3%). Decreased gonial angle was most commonly found factor of skeletal deep bite (43.4%), followed by decreased mandibular plane angle (27.4%) and maxillary plane's clockwise rotation (26.5%). Frankfort mandibular plane angle and gonial angle showed a strong positive correlation (r=0.66, p=0.000). Conclusions: Reduced gonial angle is most frequently seen skeletal factor, signifying the importance of angulation and growth of ramus in development of deep bite. Deep curve of Spee is most frequently seen dental etiological component in deep bite subjects, hence signifying the importance of intruding the lower anterior teeth. (author)

Mild cold induced thermogenesis: are BAT and skeletal muscle synergistic partners?

Science.gov (United States)

Bal, Naresh C; Maurya, Santosh K; Pani, Sunil; Sethy, Chinmayee; Banerjee, Ananya; Das, Sarita; Patnaik, Srinivas; Kundu, Chanakya N

2017-10-31

There are two well-described thermogenic sites; brown adipose tissue (BAT) and skeletal muscle, which utilize distinct mechanisms of heat production. In BAT, mitochondrial metabolism is the molecular basis of heat generation, while it serves only a secondary role in supplying energy for thermogenesis in muscle. Here, we wanted to document changes in mitochondrial ultrastructure in these two tissue types based upon adaptation to mild (16°C) and severe (4°C) cold in mice. When reared at thermoneutrality (29°C), mitochondria in both tissues were loosely packed with irregular cristae. Interestingly, adaptation to even mild cold initiated ultrastructural remodeling of mitochondria including acquisition of more elaborate cristae structure in both thermogenic sites. The shape of mitochondria in the BAT remained mostly circular, whereas the intermyofibrilar mitochondria in the skeletal muscle became more elongated and tubular. The most dramatic remodeling of mitochondrial architecture was observed upon adaptation to severe cold. In addition, we report cold-induced alteration in levels of humoral factors: fibroblast growth factor 21 (FGF21), IL1α, peptide YY (PYY), tumor necrosis factor α (TNFα), and interleukin 6 (IL6) were all induced whereas both insulin and leptin were down-regulated. In summary, adaptation to cold leads to enhanced cristae formation in mitochondria in skeletal muscle as well as the BAT. Further, the present study indicates that circulating cytokines might play an important role in the synergistic recruitment of the thermogenic program including cross-talk between muscle and BAT. © 2017 The Author(s).

High energy protons application for radiotherapy of the esophagus affected with cancer

International Nuclear Information System (INIS)

Ruderman, A.I.; Astrakhan, B.V.; Kulakov, G.A.; Makarova, G.V.; Zhuravleva, N.T.

1975-01-01

As in radiation therapy of tumours located elsewhere, local radiation treatment of an esophagus tumour is often aggravated by the development, after some time, of a trophic ulcer as a result of decreased regenerative ability of the irradiated sound tissues and also of newly formed hystostructures which have replaced the destroyed tumorous tissue. It has been established that the number of complications increases with the total focal dose, but at the same time (up to a certain point) the number of local curings increases as well. Some promise was shown by high-energy protons with their physical advantages unique for radiation therapy, such as the strictly controlled free path length of particles in the tissues, the presence of the Bragg peak, the absence of lateral scattering, i.e. features which permit of a high dose in the target with a minimum injury to the sound tissues surrounding the tumour. Proton therapy of esophagus cancer was carried out by two techniques, static and shuttle-rotary. The results of proton therapy of esophagus cancer indicate that the use of high-energy protons for treating esophagus cancer holds promise

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

Science.gov (United States)

Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

1998-01-01

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

Aging and Spaceflight: Catalase Targeted to Mitochondria Alters Skeletal Structure and Responses to Musculoskeletal Disuse

Science.gov (United States)

Globus, Ruth K.; Tahimic, Candice; Schreurs, Ann-Sofie

2018-01-01

Microgravity and ionizing radiation in the spaceflight environment pose multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration which resembles aging. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment. To accomplish this, we will use both wildtype (WT) mice and a well-established, genetically-engineered animal model (mCAT mice) which displays extended lifespan (Schriner et al. 2005). The animal model selected to test these ideas is engineered to quench ROS in mitochondria by targeted over-expression of the human catalase gene to the mitochondrial matrix. We showed previously that mCAT mice express the catalase transgene in skeletal tissues, bone forming osteoblasts, and bone resorbing osteoclasts. In addition, mCAT mice also display increased catalase activity in bone. Our findings revealed that exposure of adult, male, C57Bl/6J mice to simulated spaceflight (hindlimb unloading and gamma radiation) led to an increase in markers of oxidative damage (malondialdehyde, 4-hydroxynonenol) in skeletal tissue of WT mice but not mCAT mice. To extend our hypothesis to other, spaceflight-relevant tissues, we are performing a ground-based study simulating 30 days of spaceflight by hindlimb unloading to determine potential protective effects of mitochondrial catalase activity on aging of multiple tissues (cardiovascular, nervous and skeletal).

Morphologic and hemodynamic analysis of dental pulp in dogs after molar intrusion with the skeletal anchorage system.

Science.gov (United States)

Konno, Yuichi; Daimaruya, Takayoshi; Iikubo, Masahiro; Kanzaki, Reiko; Takahashi, Ichiro; Sugawara, Junji; Sasano, Takashi

2007-08-01

We have successfully treated skeletal open bite by intruding posterior teeth with the skeletal anchorage system. Our aim in this study was to morphologically and hemodynamically evaluate the changes in pulp tissues when molars are radically intruded. The mandibular fourth premolars of 9 adult beagle dogs were divided into 3 groups: a sham operated group (n = 6, 3 dogs), 4-month intrusion group (n = 6, 3 dogs), and a further 4-month retention group (n = 6, 3 dogs). We evaluated the morphological changes of the pulp and dentin-the amount of vacuolar degeneration in the odontoblast layer, the predentin width and nervous continuity in the pulp tissue, and the pulpal blood-flow response evoked by electrical stimulation in the dental pulp. Extreme molar intrusion with the skeletal anchorage system caused slight degenerative changes in the pulp tissue, followed by recovery after the orthodontic force was released. Circulatory system and nervous functions were basically maintained during the intrusion, although a certain level of downregulation was observed. These morphologic and functional regressive changes in the pulp tissue after molar intrusion improved during the retention period. Histologic changes and changes in pulpal blood flow and function are reversible, even during radical intrusion of molars.

TP53 and ATM mRNA expression in skin and skeletal muscle after low-level laser exposure.

Science.gov (United States)

Guedes de Almeida, Luciana; Sergio, Luiz Philippe da Silva; de Paoli, Flavia; Mencalha, Andre Luiz; da Fonseca, Adenilson de Souza

2017-08-01

Low-level lasers are widespread in regenerative medicine, but the molecular mechanisms involved in their biological effects are not fully understood, particularly those on DNA stability. Therefore, this study aimed to investigate mRNA expression of genes related to DNA genomic stability in skin and skeletal muscle tissue from Wistar rats exposed to low-level red and infrared lasers. For this, TP53 (Tumor Protein 53) and ATM (Ataxia Telangiectasia Mutated gene) mRNA expressions were evaluated by real-time quantitative PCR (RT-qPCR) technique 24 hours after low-level red and infrared laser exposure. Our data showed that relative TP53 mRNA expression was not significantly altered in both tissues exposed to lasers. For ATM, relative mRNA expression in skin tissue was not significantly altered, but in muscle tissue, laser exposure increased relative ATM mRNA expression. Low-level red and infrared laser radiations alter ATM mRNA expression related to DNA stability in skeletal muscle tissue.

Vasodilator interactions in skeletal muscle blood flow regulation

DEFF Research Database (Denmark)

Hellsten, Ylva; Nyberg, Michael Permin; Jensen, Lasse Gliemann

2012-01-01

During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or the extraluminal side of the blood vessels. A number...... vasodilators are both stimulated by several compounds, eg. adenosine, ATP, acetylcholine, bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other...... is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important vasodilators and interactions have been identified, a large part of the exercise hyperemic response remains unexplained. It is plausible...

Effect of ionizing radiations on connective tissue

International Nuclear Information System (INIS)

Altman, K.I.; Gerber, G.B.

1980-01-01

The effects of ionizing radiations on connective tissue in lung, heart, vasculature, kidney, skin, and skeletal tissues are reviewed. Special emphasis is given to the effect of ionizing radiations on vasculo-connective tissue and fibrotic changes following radiation-induced injury to organs and tissues. In order to put the subject matter in proper prospective, the general biochemistry, physiology, and pathology of connective tissue is reviewed briefly together with the participation of connective tissue in disease. The review closes with an assessment of future problems and an enumeration and discussion of important, as yet unanswered questions

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....

The Biological Effect of Fast Neutrons and High-Energy Protons

International Nuclear Information System (INIS)

Moskalev, Ju.I.; Petrovich, I.K.; Strel'cova, V.N.

1964-01-01

The paper gives the results of comparative experiments on the effects of fast neutrons and high-energy protons (500 MeV) on life expectancy, peripheral blood, incidence and rate of appearance of tumours in the rat as a function of administered dose and time of observation. The neutron experiment was performed on 573 and the proton experiment on 490 white rats. The animals irradiated with fast neutrons were given doses between 8.5 and 510 rad, and those irradiated with protons received doses between 28 and 1008 rad. The effective doses for the acute, sub-acute and chronic forms of sickness were established for fast neutrons and for protons. LD 50/30 for neutrons was 408 and for protons 600 rad, and the corresponding LD 50 / 120 values were 380 and 600 rad. The conditions governing rat mortality were analysed both in the early and the later stages of the experiment. It is shown that the average life expectancy of rats irradiated with fast neutrons does not depend on sex. The shape of the dose-effect curve for the various peripheral-blood indexes is strongly dependent not only on the radiosensitivity of the blood cells in question but also on the time of observation. It may change greatly in time for one and the same index. A considerable time after irradiation with either fast neutrons or protons, benign and malignant tumours appear in different tissues of the rats, including the haemopoeitic tissues, mammary glands, pituitary, uterus, ovaries, prostate gland, testicles, liver, kidneys, lungs, gastro-intestinal tract, subcutaneous tissue, lymph nodes, urinary bladder, etc. The over-all incidence of tumours and the number of cases of multi centred neoplasms in females are two to three times higher than in males. The minimum tumour dose for the mammary glands with neutron irradiation is apparently rather less than 42.5 rad. The maximum incidence of tumours of the pituitary is found after irradiation with a dose of 42.5 rad.- At this same dose leucosis and tumour of the

Association of expression levels in skeletal muscle and a SNP in the ...

Indian Academy of Sciences (India)

dicted breeding value for rib eye area in two experiments using 100 sires (P ... In the real-time PCR-based analysis, we used skeletal muscle tissues of eight JB .... mediates recruitment of muscle-type creatine kinase (CK) to myosin. Biochem.

Selenium regulates gene expression of selenoprotein W in chicken skeletal muscle system.

Science.gov (United States)

Ruan, Hongfeng; Zhang, Ziwei; Wu, Qiong; Yao, Haidong; Li, Jinlong; Li, Shu; Xu, Shiwen

2012-01-01

Selenoprotein W (SelW) is abundantly expressed in skeletal muscles of mammals and necessary for the metabolism of skeletal muscles. However, its expression pattern in skeletal muscle system of birds is still uncovered. Herein, to investigate the distribution of SelW mRNA in chicken skeletal muscle system and its response to different selenium (Se) status, 1-day-old chickens were exposed to various concentrations of Se as sodium selenite in the feed for 35 days. In addition, myoblasts were treated with different concentrations of Se in the medium for 72 h. Then the levels of SelW mRNA in skeletal muscles (wing muscle, pectoral muscle, thigh muscle) and myoblasts were determined on days 1, 15, 25, and 35 and at 0, 24, 48, and 72 h, respectively. The results showed that SelW was detected in all these muscle components and it increased both along with the growth of organism and the differentiation process of myoblasts. The thigh muscle is more responsive to Se intake than the other two skeletal muscle tissues while the optimal Se supplementation for SelW mRNA expression in chicken myoblasts was 10(-7) M. In summary, Se plays important roles in the development of chicken skeletal muscles. To effect optimal SelW gene expression, Se must be provided in the diet and the media in adequate amounts and neither at excessive nor deficient levels.

Radiobiology of Proton Therapy - Results of an international expert workshop

DEFF Research Database (Denmark)

Lühr, Armin; von Neubeck, Cläre; Pawelke, Jörg

2018-01-01

The physical properties of proton beams offer the potential to reduce toxicity in tumor-adjacent normal tissues. Toward this end, the number of proton radiotherapy facilities has steeply increased over the last 10-15 years to currently around 70 operational centers worldwide. However, taking full...... in proton therapy combined with systemic treatments, and (4) testing biological effects of protons in clinical trials. Finally, important research avenues for improvement of proton radiotherapy based on radiobiological knowledge are identified. The clinical distribution of radiobiological effectiveness...... of protons alone or in combination with systemic chemo- or immunotherapies as well as patient stratification based on biomarker expressions are key to reach the full potential of proton beam therapy. Dedicated preclinical experiments, innovative clinical trial designs, and large high-quality data...

Skeletal muscle injury induced by a pneumatic tourniquet: an enzyme- and immunohistochemical study in rabbits.

Science.gov (United States)

Pedowitz, R A; Fridén, J; Thornell, L E

1992-03-01

The pathophysiology of skeletal muscle injury induced by compression beneath pneumatic tourniquets is poorly understood. Tourniquet hemostasis was induced in rabbit hindlimbs for 2 hr with a cuff inflation pressure of either 125 mm Hg (n = 5) or 350 mm Hg (n = 5). Skeletal muscle biopsies, taken 2 days later from tissue beneath and distal to the tourniquet, were frozen and analyzed using enzyme- and immunohistochemical techniques. In the 350 mm Hg tourniquet group, four of 10 thigh muscle samples demonstrated significant regional necrosis (mean 37.3% of the total cross-sectional area). Regional necrosis was not observed in thigh muscles of the 125 mm Hg tourniquet group or in any of the ischemic leg muscles. A topographic pattern of necrosis consistent with the arterial distribution of skeletal muscle suggested pathogenic events during the reperfusion period, such as granulocyte-mediated superoxide radical formation. Extremely large and rounded fibers (histochemically identified as Type IIB fibers) were observed in compressed thigh muscles, indicating differential fiber sensitivity to tourniquet compression and ischemia. The present study demonstrated significant skeletal muscle necrosis after a 2 hr tourniquet applied at a clinically relevant cuff inflation pressure. Recent studies of systemic changes associated with limb "ischemia" should be reassessed in consideration of the confounding effects of tissue compression induced beneath pneumatic tourniquets.

Proton therapy

International Nuclear Information System (INIS)

Jongen, Y.

1995-01-01

Ideal radiotherapy deposits a large amount of energy in the tumour volume, and none in the surrounding healthy tissues. Proton therapy comes closer to this goal because of a greater concentration of dose, well defined proton ranges and points of energy release which are precisely known - the Bragg peak1. In the past, the development of clinical proton therapy has been hampered by complexity, size, and cost. To be clinically effective, energies of several hundred MeV are required; these were previously unavailable for hospital installations, and pioneering institutions had to work with complex, inadequate equipment originally intended for nuclear physics research. Recently a number of specialist organizations and commercial companies have been working on dedicated systems for proton therapy. One, IBA of Belgium, has equipment for inhouse hospital operation which encompasses a complete therapy centre, delivered as a turnkey package and incorporating a compact, automated, higher energy cyclotron with isocentric gantries. Their system will be installed at Massachusetts General Hospital, Boston. The proton therapy system comprises: - a 235 MeV isochronous cyclotron to deliver beams of up to 1.5 microamps, but with a hardware limitation to restrict the maximum possible dose; - variable energy beam (235 to 70 MeV ) with energy spread and emittance verification; - a beam transport and switching system to connect the exit of the energy selection system to the entrances of a number of gantries and fixed beamlines. Along the beam transport system, the beam characteristics are monitored with non-interceptive multiwire ionization chambers for automatic tuning; - gantries fitted with nozzles and beamline elements for beam control; both beam scattering and beam wobbling techniques are available for shaping the beam;

Characteristics of Skeletal Musculature of Pheasants Hatched from Eggs of Different Eggshell Colour

Directory of Open Access Journals (Sweden)

Dragan Zikic

2016-05-01

Full Text Available The aim of this paper was to examine morphodinamics of development of skeletal musculature of pheasants hatched from eggs of different eggshell colour. Four groups of pheasant eggs (dark brown, light brown, brown/green and blue/green were incubated. Samples of skeletal musculature of leg and breast were taken during the embryonic and neonatal period of development. From taken samples histological preparations were made. In pheasants hatched from blue/green eggs the smaller diameter of leg and breast muscle cells and the higher volume density of connective tissue in leg and breast muscles were recorded. It was concluded that pheasants hatched from blue/green eggs had the weakest development of skeletal musculature, which can be related to structural differences of eggshell of various colour.

Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration

DEFF Research Database (Denmark)

Saclier, Marielle; Yacoub-Youssef, Houda; Mackey, Abigail

2013-01-01

, we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory...... anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates......Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here...

SU-E-J-149: Secondary Emission Detection for Improved Proton Relative Stopping Power Identification

Energy Technology Data Exchange (ETDEWEB)

Saunders, J; Musall, B; Erickson, A [Georgia Institute of Technology, Atlanta, GA (Georgia)

2015-06-15

Purpose: This research investigates application of secondary prompt gamma (PG) emission spectra, resulting from nuclear reactions induced by protons, to characterize tissue composition along the particle path. The objective of utilizing the intensity of discrete high-energy peaks of PG is to improve the accuracy of relative stopping power (RSP) values available for proton therapy treatment planning on a patient specific basis and to reduce uncertainty in dose depth calculations. Methods: In this research, MCNP6 was used to simulate PG emission spectra generated from proton induced nuclear reactions in medium of varying composition of carbon, oxygen, calcium and nitrogen, the predominant elements found in human tissue. The relative peak intensities at discrete energies predicted by MCNP6 were compared to the corresponding atomic composition of the medium. Results: The results have shown a good general agreement with experimentally measured values reported by other investigators. Unexpected divergence from experimental spectra was noted in the peak intensities for some cases depending on the source of the cross-section data when using compiled proton table libraries vs. physics models built into MCNP6. While the use of proton cross-section libraries is generally recommended when available, these libraries lack data for several less abundant isotopes. This limits the range of their applicability and forces the simulations to rely on physics models for reactions with natural atomic compositions. Conclusion: Current end-of-range proton imaging provides an average RSP for the total estimated track length. The accurate identification of tissue composition along the incident particle path using PG detection and characterization allows for improved determination of the tissue RSP on the local level. While this would allow for more accurate depth calculations resulting in tighter treatment margins, precise understanding of proton beam behavior in tissue of various

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.

Initial intramuscular perfusion pressure predicts early skeletal muscle function following isolated tibial fractures

Directory of Open Access Journals (Sweden)

Haas Norbert P

2008-04-01

Full Text Available Abstract Background The severity of associated soft tissue trauma in complex injuries of the extremities guides fracture treatment and decisively determines patient's prognosis. Trauma-induced microvascular dysfunction and increased tissue pressure is known to trigger secondary soft tissue damage and seems to adversely affect skeletal muscle function. Methods 20 patients with isolated tibial fractures were included. Blood pressure and compartment pressure (anterior and deep posterior compartment were measured continuously up to 24 hours. Corresponding perfusion pressure was calculated. After 4 and 12 weeks isokinetic muscle peak torque and mean power of the ankle joint in dorsal and plantar flexion were measured using a Biodex dynamometer. Results A significant inverse correlation between the anterior perfusion pressure at 24 hours and deficit in dorsiflexion at 4 weeks was found for both, the peak torque (R = -0.83; p Conclusion The functional relationship between the decrease in intramuscular perfusion pressures and muscle performance in the early rehabilitation period indicate a causative and prognostic role of early posttraumatic microcirculatory derangements and skeletal muscle function. Therapeutic concepts aimed at effective muscle recovery, early rehabilitation, and decreased secondary tissue damage, should consider the maintenance of an adequate intramuscular perfusion pressure.

Power of protons in the fight against cancer

International Nuclear Information System (INIS)

Hansen, W.

2011-01-01

a large percentage of patients with cancer are receiving radiotherapy as part of their treatment. At present it is possible to plan with precision these treatments, reducing the risk of side effects and increasing therapeutic efficiency. Proton therapy (also known as particle therapy) is a form external radiotherapy that uses beams of energized protons to treat cancer. The main advantage of proton therapy is its ability to accurately manage an optimal dose of radiation to the tumor, without damaging surrounding healthy tissues and significantly reducing the likelihood and/or severity of side effects. (Author)

Exercise and Regulation of Bone and Collagen Tissue Biology

DEFF Research Database (Denmark)

Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja

2015-01-01

The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensur...

Code of practice for clinical proton dosimetry

International Nuclear Information System (INIS)

Vynckier, S.

1991-01-01

The objective of this document is to make recommendations for the determination of absorbed dose to tissue for clinical proton beams and to achieve uniformity in proton dosimetry. A Code of Practice (CoP) has been chosen, providing specific guidelines for the choice of the detector and the method of determination of absorbed dose for proton beams only. This CoP is confined specifically to the determination of absorbed dose and is not concerned with the biological effects of proton beams. It is recommended that dosimeters be calibrated by comparison with a calorimeter. If this is not available, a Faraday cup, or alter-natively, an ionization chamber, with a 60 Co calibration factor should be used. Physical parameters for determining the dose from tissue-equivalent ionization chamber measurements are given together with a worksheet. It is recommended that calibrations be carried out in water at the centre of the spread-out-Bragg-peak and that dose distributions be measured in a water phantom. It is estimated that the error in the calibrations will be less than +-5 per cent (1 S.D.) in all cases. Adoption and implementation of this CoP will facilitate the exchange of clinical information. (author). 34 refs.; 5 figs.; 5 tabs

Minibeam Therapy With Protons and Light Ions: Physical Feasibility and Potential to Reduce Radiation Side Effects and to Facilitate Hypofractionation

Energy Technology Data Exchange (ETDEWEB)

Dilmanian, F. Avraham, E-mail: avraham.dilmanian@stonybrook.edu [Departments of Radiation Oncology, Neurology, and Radiology, Stony Brook University Medical Center, Stony Brook, New York (United States); Eley, John G. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Krishnan, Sunil [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-06-01

Purpose: Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Methods and Materials: Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulations were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. Results: A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Conclusions: Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage.

Microgravity cultivation of cells and tissues

Science.gov (United States)

Freed, L. E.; Pellis, N.; Searby, N.; de Luis, J.; Preda, C.; Bordonaro, J.; Vunjak-Novakovic, G.

1999-01-01

In vitro studies of cells and tissues in microgravity, either simulated by cultivation conditions on earth or actual, during spaceflight, are expected to help identify mechanisms underlying gravity sensing and transduction in biological organisms. In this paper, we review rotating bioreactor studies of engineered skeletal and cardiovascular tissues carried out in unit gravity, a four month long cartilage tissue engineering study carried out aboard the Mir Space Station, and the ongoing laboratory development and testing of a system for cell and tissue cultivation aboard the International Space Station.

MO-F-CAMPUS-T-01: IROC Houston QA Center’s Anthropomorphic Proton Phantom Program

International Nuclear Information System (INIS)

Lujano, C; Hernandez, N; Keith, T; Nguyen, T; Taylor, P; Molineu, A; Followill, D

2015-01-01

Purpose: To describe the proton phantoms that IROC Houston uses to approve and credential proton institutions to participate in NCI-sponsored clinical trials. Methods: Photon phantoms cannot necessarily be used for proton measurements because protons react differently than photons in some plastics. As such plastics that are tissue equivalent for protons were identified. Another required alteration is to ensure that the film dosimeters are housed in the phantom with no air gap to avoid proton streaming. Proton-equivalent plastics/materials used include RMI Solid Water, Techron HPV, blue water, RANDO soft tissue material, balsa wood, compressed cork and polyethylene. Institutions wishing to be approved or credentialed request a phantom and are prioritized for delivery. At the institution, the phantom is imaged, a treatment plan is developed, positioned on the treatment couch and the treatment is delivered. The phantom is returned and the measured dose distributions are compared to the institution’s electronically submitted treatment plan dosimetry data. Results: IROC Houston has developed an extensive proton phantom approval/credentialing program consisting of five different phantoms designs: head, prostate, lung, liver and spine. The phantoms are made with proton equivalent plastics that have HU and relative stopping powers similar (within 5%) of human tissues. They also have imageable targets, avoidance structures, and heterogeneities. TLD and radiochromic film are contained in the target structures. There have been 13 head, 33 prostate, 18 lung, 2 liver and 16 spine irradiations with either passive scatter, or scanned proton beams. The pass rates have been: 100%, 69.7%, 72.2%, 50%, and 81.3%, respectively. Conclusion: IROC Houston has responded to the recent surge in proton facilities by developing a family of anthropomorphic phantoms that are able to be used for remote audits of proton beams. Work supported by PHS grant CA10953 and CA081647

MO-F-CAMPUS-T-01: IROC Houston QA Center’s Anthropomorphic Proton Phantom Program

Energy Technology Data Exchange (ETDEWEB)

Lujano, C; Hernandez, N; Keith, T; Nguyen, T; Taylor, P; Molineu, A; Followill, D [UT MD Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: To describe the proton phantoms that IROC Houston uses to approve and credential proton institutions to participate in NCI-sponsored clinical trials. Methods: Photon phantoms cannot necessarily be used for proton measurements because protons react differently than photons in some plastics. As such plastics that are tissue equivalent for protons were identified. Another required alteration is to ensure that the film dosimeters are housed in the phantom with no air gap to avoid proton streaming. Proton-equivalent plastics/materials used include RMI Solid Water, Techron HPV, blue water, RANDO soft tissue material, balsa wood, compressed cork and polyethylene. Institutions wishing to be approved or credentialed request a phantom and are prioritized for delivery. At the institution, the phantom is imaged, a treatment plan is developed, positioned on the treatment couch and the treatment is delivered. The phantom is returned and the measured dose distributions are compared to the institution’s electronically submitted treatment plan dosimetry data. Results: IROC Houston has developed an extensive proton phantom approval/credentialing program consisting of five different phantoms designs: head, prostate, lung, liver and spine. The phantoms are made with proton equivalent plastics that have HU and relative stopping powers similar (within 5%) of human tissues. They also have imageable targets, avoidance structures, and heterogeneities. TLD and radiochromic film are contained in the target structures. There have been 13 head, 33 prostate, 18 lung, 2 liver and 16 spine irradiations with either passive scatter, or scanned proton beams. The pass rates have been: 100%, 69.7%, 72.2%, 50%, and 81.3%, respectively. Conclusion: IROC Houston has responded to the recent surge in proton facilities by developing a family of anthropomorphic phantoms that are able to be used for remote audits of proton beams. Work supported by PHS grant CA10953 and CA081647.

Biofilm formation on surface characterized micro-implants for skeletal anchorage in orthodontics

NARCIS (Netherlands)

Chin, Yeen; Sandham, John; de Vries, Jacob; van der Mei, Henderina; Busscher, Hendrik

Micro-implants are increasingly popular in clinical orthodontics to effect skeletal anchorage. However, biofilm formation on their surfaces and subsequent infection of peri-implant tissues can result in either exfoliation or surgical removal of these devices. The present study aimed to assess

Single molecular image of cytosolic free Ca2+ of skeletal muscle cells in rats pre- and post-exercise-induced fatigue

Science.gov (United States)

Liu, Yi; Zhang, Heming; Zhao, Yanping; Liu, Zhiming

2009-08-01

A growing body of literature indicated the cytosolic free Ca2+ concentration of skeletal muscle cells changes significantly during exercise-induced fatigue. But it is confusing whether cytosolic free Ca2+ concentration increase or decrease. Furthermore, current researches mainly adopt muscle tissue homogenate as experiment material, but the studies based on cellular and subcellular level is seldom. This study is aimed to establish rat skeletal muscle cell model of exercise-induced fatigue, and confirm the change of cytosolic free Ca2+ concentration of skeletal muscle cells in rats preand post- exercise-induced fatigue. In this research, six male Wistar rats were randomly divided into two groups: control group (n=3) and exercise-induced fatigue group (n=3). The former group were allowed to freely move and the latter were forced to loaded swimming to exhaustive. Three days later, all the rats were sacrificed, the muscle tissue from the same site of skeletal muscle were taken out and digested to cells. After primary culture of the two kinds of skeletal muscle cells from tissue, a fluorescent dye-Fluo-3 AM was used to label the cytosolic free Ca2+. The fluorescent of Ca2+ was recorded by confocal laser scanning microscopy. The results indicated that, the Ca2+ fluorescence intensity of cells from the rat of exercise-induced fatigue group was significantly higher than those in control group. In conclusion, cytosolic free Ca2+ concentration of skeletal muscle cells has a close relation with exercise-induced fatigue, and the increase of cytosolic free Ca2+ concentration may be one of the important factors of exercise-induced fatigue.

Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity

Directory of Open Access Journals (Sweden)

Hao Shi

2018-05-01

Full Text Available Objective: Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT, the enzyme that mediates O-GlcNAcylation, in skeletal muscle. Methods: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses. Results: We found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2. Conclusions: Elevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders. Keywords: O-GlcNAc signaling, Type 2 diabetes, N

Wnt Signaling in Skeletal Muscle Development and Regeneration.

Science.gov (United States)

Girardi, Francesco; Le Grand, Fabien

2018-01-01

Wnt is a family of signaling molecules involved in embryogenesis, adult tissue repair, and cancer. They activate canonical and noncanonical Wnt signaling cascades in target cells. Several studies, within the last decades, showed that several Wnt ligands are involved in myogenesis and both canonical and noncanonical Wnt pathways regulate muscle formation and the maintenance of adult tissue homeostasis. In this review, we provide a comprehensive overview of the roles of Wnt signaling during muscle development and an updated description of Wnt functions during muscle repair. Lastly, we discuss the crosstalk between Wnt and TGFβ signaling pathways in skeletal muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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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

EFFECTS OF PHYSICAL EXERCISES ON TRIACYLGLYCEROL LEVEL IN SKELETAL MUSCLES IN DIETARY-INDUCED OBESE RATS

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I. Yu. Yakimovich

2014-01-01

Full Text Available The accumulation of triacylglycerol in peripheral tissues is one of mechanisms of insulin resistance. This paper presents the investigation of the influence of aerobic and anaerobic physical exercises on triacylglycerol level in skeletal muscles and on insulin resistance in dietary-induced obese rats. It is estimated that a high-energy (HE diet causes the accumulation of triacylglycerols in skeletal muscles that leads to high resistance to insulin. Aerobic and anaerobic physical exercises reduce the level of triacylglycerols in skeletal  muscles  and  raise  sensitivity to  insulin  in  obese  rats.  Physical  exercises  raise  the  level  of triacylglycerols in skeletal muscles in standard-diet rats that probably is the adaptation to high energy expenditure, but does not lead to high insulin resistance.

Serial water changes in human skeletal muscles on exercise studied with proton magnetic resonance spectroscopy and imaging

International Nuclear Information System (INIS)

Ogino, Toru; Ikehira, Hiroo; Arimizu, Noboru

1994-01-01

In vivo 1 H-magnetic resonance imaging (MRI) enabled us to study the distribution of water in living tissues and to document changes in human skeletal muscles during physical exercise. The purpose of the present study was to determine the total muscle water changes after exercise using water in 1 H-MR spectroscopy and to compare these changes to the signal intensity change on T 2 * -weighted images and/or to the T 2 value change. Seven young male volunteers were positioned in a 1.5 T Philips MR imaging system. They were then asked to dorsiflex their ankle joint against a 2 kg weight once every 2 seconds for 2 minutes. The peak height of water declined according to the clearance curve after exercise in all seven cases with the 1 H-MRS similar to the signal intensity. The increasing rate at peak height of total muscle water exceeded both the signal intensity and the T 2 value because the water peak height on the 1 H-MRS included the extracellular water. In addition, we measured the changes in signal intensity in both calf muscles after walking race exercise. The time intensity curves were used to draw a clearance curve for each muscle group after exercise. It was possible to discern which muscle was used most from the T 2 * -weighted image that was obtained once after exercise. (author)

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

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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.

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

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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.

ALDH2 restores exhaustive exercise-induced mitochondrial dysfunction in skeletal muscle

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Zhang, Qiuping; Zheng, Jianheng; Qiu, Jun; Wu, Xiahong; Xu, Yangshuo; Shen, Weili; Sun, Mengwei

2017-01-01

Background: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is highly expressed in heart and skeletal muscles, and is the major enzyme that metabolizes acetaldehyde and toxic aldehydes. The cardioprotective effects of ALDH2 during cardiac ischemia/reperfusion injury have been recognized. However, less is known about the function of ALDH2 in skeletal muscle. This study was designed to evaluate the effect of ALDH2 on exhaustive exercise-induced skeletal muscle injury. Methods: We created transgenic mice expressing ALDH2 in skeletal muscles. Male wild-type C57/BL6 (WT) and ALDH2 transgenic mice (ALDH2-Tg), 8-weeks old, were challenged with exhaustive exercise for 1 week to induce skeletal muscle injury. Animals were sacrificed 24 h post-exercise and muscle tissue was excised. Results: ALDH2-Tg mice displayed significantly increased treadmill exercise capacity compared to WT mice. Exhaustive exercise caused an increase in mRNA levels of the muscle atrophy markers, Atrogin-1 and MuRF1, and reduced mitochondrial biogenesis and fusion in WT skeletal muscles; these effects were attenuated in ALDH2-Tg mice. Exhaustive exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of Beclin1 and Bnip3; the effects of which were mitigated by ALDH2 overexpression. In addition, ALDH2-Tg reversed the increase of an oxidative stress biomarker (4-hydroxynonenal) and decreased levels of mitochondrial antioxidant proteins, including manganese superoxide dismutase and NAD(P)H:quinone oxidoreductase 1, in skeletal muscle induced by exhaustive exercise. Conclusion: ALDH2 may reverse skeletal muscle mitochondrial dysfunction due to exhaustive exercise by regulating mitochondria dynamic remodeling and enhancing the quality of mitochondria. - Highlights: • Skeletal muscle ALDH2 expression and activity declines during exhaustive exercise. • ALDH2 overexpression enhances physical performance and restores muscle

Tissue- and Condition-Specific Isoforms of Mammalian Cytochrome c Oxidase Subunits: From Function to Human Disease

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Christopher A. Sinkler

2017-01-01

Full Text Available Cytochrome c oxidase (COX is the terminal enzyme of the electron transport chain and catalyzes the transfer of electrons from cytochrome c to oxygen. COX consists of 14 subunits, three and eleven encoded, respectively, by the mitochondrial and nuclear DNA. Tissue- and condition-specific isoforms have only been reported for COX but not for the other oxidative phosphorylation complexes, suggesting a fundamental requirement to fine-tune and regulate the essentially irreversible reaction catalyzed by COX. This article briefly discusses the assembly of COX in mammals and then reviews the functions of the six nuclear-encoded COX subunits that are expressed as isoforms in specialized tissues including those of the liver, heart and skeletal muscle, lung, and testes: COX IV-1, COX IV-2, NDUFA4, NDUFA4L2, COX VIaL, COX VIaH, COX VIb-1, COX VIb-2, COX VIIaH, COX VIIaL, COX VIIaR, COX VIIIH/L, and COX VIII-3. We propose a model in which the isoforms mediate the interconnected regulation of COX by (1 adjusting basal enzyme activity to mitochondrial capacity of a given tissue; (2 allosteric regulation to adjust energy production to need; (3 altering proton pumping efficiency under certain conditions, contributing to thermogenesis; (4 providing a platform for tissue-specific signaling; (5 stabilizing the COX dimer; and (6 modulating supercomplex formation.

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

Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells.

Science.gov (United States)

Hjorth, M; Pourteymour, S; Görgens, S W; Langleite, T M; Lee, S; Holen, T; Gulseth, H L; Birkeland, K I; Jensen, J; Drevon, C A; Norheim, F

2016-05-01

Some health benefits of exercise may be explained by an altered secretion of myokines. Because previous focus has been on upregulated myokines, we screened for downregulated myokines and identified myostatin. We studied the expression of myostatin in relation to exercise and dysglycaemia in skeletal muscle, adipose tissue and plasma. We further examined some effects of myostatin on energy metabolism in primary human muscle cells and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Sedentary men with or without dysglycaemia underwent a 45-min acute bicycle test before and after 12 weeks of combined endurance and strength training. Blood samples and biopsies from m. vastus lateralis and adipose tissue were collected. Myostatin mRNA expression was reduced in skeletal muscle after acute as well as long-term exercise and was even further downregulated by acute exercise on top of 12-week training. Furthermore, the expression of myostatin at baseline correlated negatively with insulin sensitivity. Myostatin expression in the adipose tissue increased after 12 weeks of training and correlated positively with insulin sensitivity markers. In cultured muscle cells but not in SGBS cells, myostatin promoted an insulin-independent increase in glucose uptake. Furthermore, muscle cells incubated with myostatin had an enhanced rate of glucose oxidation and lactate production. Myostatin was differentially expressed in the muscle and adipose tissue in relation to physical activity and dysglycaemia. Recombinant myostatin increased the consumption of glucose in human skeletal muscle cells, suggesting a complex regulatory role of myostatin in skeletal muscle homeostasis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Guidelines on the radiological diagnosis of the more common primary skeletal tumors

International Nuclear Information System (INIS)

Nemiro, J.; Riza, J.

2002-01-01

The rate of the skeletal tumors ia as high as 10% among skeletal disorders and the future of patients often depends on the early diagnosis of them. Radiological methods, such as X-ray examinations, conventional tomography, and computed tomography as well as magnetic resonance imaging (MRI) are very helpful in their diagnosis. Useful additional information may be obtained by using selective angiography and radionuclide diagnosis. The main objectives of the radiological diagnosis of skeletal tumors include: 1) possibly early detection of the signs of tumor itself; 2) specification of its location and of the involvement of bone and surrounding tissues; 3) evaluating of its nature (benign / malignant) and also making of the preventive prognosis and outlining of an adequate treatment for it; 4) determination of its nosologic status. Main conclusions: 1) the majority of skeletal tumors present a sufficiently well-defined radiological information to make the determination of their nature and nosologic status possible; systemic clinical signs are more of a signaling value; 2) classical X-ray examination provides a sufficiently objective basic information about skeletal tumors, which may be used as the basis for a purposeful employment of computed tomography and MRI which appear to be very promising methods in this field. (authors)

Renin-angiotensin system: an old player with novel functions in skeletal muscle.

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Cabello-Verrugio, Claudio; Morales, María Gabriela; Rivera, Juan Carlos; Cabrera, Daniel; Simon, Felipe

2015-05-01

Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle. © 2015 Wiley Periodicals, Inc.

Decellularized Human Skeletal Muscle as Biologic Scaffold for Reconstructive Surgery

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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.

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

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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.

Methodologies and tools for proton beam design for lung tumors

International Nuclear Information System (INIS)

Moyers, Michael F.; Miller, Daniel W.; Bush, David A.; Slater, Jerry D.

2001-01-01

Purpose: Proton beams can potentially increase the dose delivered to lung tumors without increasing the dose to critical normal tissues because protons can be stopped before encountering the normal tissues. This potential can only be realized if tissue motion and planning uncertainties are correctly included during planning. This study evaluated several planning strategies to determine which method best provides adequate tumor coverage, minimal normal tissue irradiation, and simplicity of use. Methods and Materials: Proton beam treatment plans were generated using one or more of three different planning strategies. These strategies included designing apertures and boluses to the PTV, apertures to the PTV and boluses to the CTV, and aperture and bolus to the CTV. Results: The planning target volume as specified in ICRU Report 50 can be used only to design the lateral margins of beams, because the distal and proximal margins resulting from CT number uncertainty, beam range uncertainty, tissue motions, and setup uncertainties, are different than the lateral margins resulting from these same factors. The best strategy for target coverage with the planning tools available overirradiated some normal tissues unnecessarily. The available tools also made the planning of lung tumors difficult. Conclusions: This study demonstrated that inclusion of target motion and setup uncertainties into a plan should be performed in the beam design step instead of creating new targets. New computerized treatment planning system tools suggested by this study will ease planning, facilitate abandonment of the PTV concept, improve conformance of the dose distribution to the target, and improve conformal avoidance of critical normal tissues

Comparative analysis of the skeletal changes in tetrapods after brief influence of microgravity.

Science.gov (United States)

Nikitin, V B; Gulimova, V I; Ilyin, E A; Asadchikov, V E; Buzmakov, A V; Okshtein, I L; Saveliev, S V

2007-07-01

Experiments involving lower tetrapods demonstrate that the degree of skeletal demineralization in spaceflights is related to the type of environmental behaviour of the animal. Probably the sensing of support reaction decreases the negative effect of spaceflight upon the bone tissue.

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.

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)

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.

Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity.

Science.gov (United States)

Shi, Hao; Munk, Alexander; Nielsen, Thomas S; Daughtry, Morgan R; Larsson, Louise; Li, Shize; Høyer, Kasper F; Geisler, Hannah W; Sulek, Karolina; Kjøbsted, Rasmus; Fisher, Taylor; Andersen, Marianne M; Shen, Zhengxing; Hansen, Ulrik K; England, Eric M; Cheng, Zhiyong; Højlund, Kurt; Wojtaszewski, Jørgen F P; Yang, Xiaoyong; Hulver, Matthew W; Helm, Richard F; Treebak, Jonas T; Gerrard, David E

2018-05-01

Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses. We found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2). Elevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Neonatal epicardial-derived progenitors aquire myogenic traits in skeletal muscle, but not cardiac muscle

DEFF Research Database (Denmark)

Andersen, Ditte C; Jensen, Charlotte H; Skovrind, Ida

2016-01-01

heart missing regenerative signals essential for directed differentiation of EPDCs. Herein, we aimed to evaluate the myogenic potential of neonatal EPDCs in adult and neonatal mouse myocardium, as well as in skeletal muscle. The two latter tissues have an intrinsic capability to develop and regenerate......, in contrast to the adult heart. METHODS: Highly purified mouse EPDCs were transplanted into damaged neonatal and adult myocardium as well as regenerating skeletal muscle. Co-cultures with skeletal myoblasts were used to distinguish fusion independent myogenic conversion. RESULTS: No donor EPDC...... that EPDCs may be more myogenic than previously anticipated. But, the heart may lack factors for induction of myogenesis of EPDCs, a scenario that should be taken into consideration when aiming for repair of damaged myocardium by stem cell transplantation....

Theoretical variance analysis of single- and dual-energy computed tomography methods for calculating proton stopping power ratios of biological tissues

International Nuclear Information System (INIS)

Yang, M; Zhu, X R; Mohan, R; Dong, L; Virshup, G; Clayton, J

2010-01-01

We discovered an empirical relationship between the logarithm of mean excitation energy (ln I m ) and the effective atomic number (EAN) of human tissues, which allows for computing patient-specific proton stopping power ratios (SPRs) using dual-energy CT (DECT) imaging. The accuracy of the DECT method was evaluated for 'standard' human tissues as well as their variance. The DECT method was compared to the existing standard clinical practice-a procedure introduced by Schneider et al at the Paul Scherrer Institute (the stoichiometric calibration method). In this simulation study, SPRs were derived from calculated CT numbers of known material compositions, rather than from measurement. For standard human tissues, both methods achieved good accuracy with the root-mean-square (RMS) error well below 1%. For human tissues with small perturbations from standard human tissue compositions, the DECT method was shown to be less sensitive than the stoichiometric calibration method. The RMS error remained below 1% for most cases using the DECT method, which implies that the DECT method might be more suitable for measuring patient-specific tissue compositions to improve the accuracy of treatment planning for charged particle therapy. In this study, the effects of CT imaging artifacts due to the beam hardening effect, scatter, noise, patient movement, etc were not analyzed. The true potential of the DECT method achieved in theoretical conditions may not be fully achievable in clinical settings. Further research and development may be needed to take advantage of the DECT method to characterize individual human tissues.

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

Primary extra-skeletal Ewing's sarcoma mimicking a disc protrusion.

Science.gov (United States)

Ruelle, A; Boccardo, M

1987-07-01

One of the rarest cases of primary epidural neoplasm is a soft tissue sarcoma histologically similar to Ewing's sarcoma of the bone. In the literature only eleven cases of such an extra-skeletal Ewing's sarcoma have been described. The authors report an additional case presenting as a disc protrusion in a young male. The authors include some diagnostic, prognostic and nosologic remarks about this condition.

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.

Lactate kinetics in human tissues at rest and during exercise

DEFF Research Database (Denmark)

van Hall, Gerrit

2010-01-01

lactate metabolism at rest and during exercise and suggestions are put forward to explain the simultaneous lactate uptake and release; and (2) lactate metabolism in the heart, liver, kidneys, brain, adipose tissue and lungs will be discussed and its potential importance in these tissues.......Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during exercise is much debated. In the early days skeletal muscle was mainly seen as the site of lactate production during contraction and lactate production...... associated with a lack of muscle oxygenation and fatigue. Later it was recognized that skeletal muscle not only played an important role in lactate production but also in lactate clearance and this led to a renewed interest, not the least from the Copenhagen School in the 1930s, in the metabolic role...

Australian national proton facility

International Nuclear Information System (INIS)

Jackson, M.

2000-01-01

Full text: Proton therapy has been in use since 1954 and over 25,000 patients have been treated worldwide. Until recently most patients were treated at physics research facilities and apart from the Harvard Cyclotron Laboratory and some low energy machines for eye treatment, only small numbers of patients were treated in each centre and conditions were less than optimal. Limited beam time and lack of support facilities restricted the type of patient treated and conventional fractionation could not be used. The initial clinical experience was mainly with small tumours and other lesions close to critical organs. Large numbers of eye tumours have also been treated. Protons have a well-defined role in these situations and are now being used in the treatment of more common cancers. Since the development of hospital-based facilities, such as the one in Loma Linda in California, over 2,500 patients with prostate cancer have been treated using a simple technique which gives results at least as good as radical surgery, external beam radiotherapy or brachytherapy. Importantly, the incidence of severe complications is very low. There are encouraging results in many disease sites including lung, liver, soft tissue sarcomas and oesophagus. As proton therapy becomes more widely available, randomised trials comparing it with conventional radiotherapy or intensity modulated radiotherapy (IMRT) will be possible. In most situations the use of protons will enable a higher dose to be given safely but in situations where local control rates are already satisfactory, protons are expected to produce less complications than conventional treatment. The initial costs of a proton facility are high but the recurrent costs are similar to other forms of high technology radiotherapy. Simple treatment techniques with only a few fields are usually possible and proton therapy avoids the high integral doses associated with IMRT. This reduction in the low dose volume is likely to be particularly

MicroRNA Dysregulation in Aging and Pathologies of the Skeletal Muscle.

Science.gov (United States)

McCormick, Rachel; Goljanek-Whysall, Katarzyna

2017-01-01

Skeletal muscle is one of the biggest organs of the body with important mechanistic and metabolic functions. Muscle homeostasis is controlled by environmental, genetic, and epigenetic factors. Indeed, MiRNAs, small noncoding RNAs robust regulators of gene expression, have and have been shown to regulate muscle homeostasis on several levels: through controlling myogenesis, muscle growth (hypertrophy) and atrophy, as well as interactions of muscle with other tissues. Given the large number of MiRNA target genes and the important role of MiRNAs in most physiological processes and various diseases, MiRNAs may have an enormous potential as therapeutic targets against numerous disorders, including pathologies of muscle. The purpose of this review is to present the current knowledge of the role of MiRNAs in skeletal muscle homeostasis and pathologies and the potential of MiRNAs as therapeutics for skeletal muscle wasting, with particular focus on the age- and disease-related loss of muscle mass and function. © 2017 Elsevier Inc. All rights reserved.

Adipose Tissue Redistribution and Ectopic Lipid Deposition in Active Acromegaly and Effects of Surgical Treatment

Science.gov (United States)

Reyes-Vidal, Carlos M.; Mojahed, Hamed; Shen, Wei; Jin, Zhezhen; Arias-Mendoza, Fernando; Fernandez, Jean Carlos; Gallagher, Dympna; Bruce, Jeffrey N.; Post, Kalmon D.

2015-01-01

Context: GH and IGF-I have important roles in the maintenance of substrate metabolism and body composition. However, when in excess in acromegaly, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) deposition. Objectives: The purpose of this study was to examine the effect of surgery for acromegaly on AT distribution and ectopic lipid deposition in liver and muscle. Design: This was a prospective study before and up to 2 years after pituitary surgery. Setting: The setting was an academic pituitary center. Patients: Participants were 23 patients with newly diagnosed, untreated acromegaly. Main Outcome Measures: We determined visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue (IMAT), and skeletal muscle compartments by total-body magnetic resonance imaging, intrahepatic and intramyocellular lipid by proton magnetic resonance spectroscopy, and serum endocrine, metabolic, and cardiovascular risk markers. Results: VAT and SAT masses were lower than predicted in active acromegaly, but increased after surgery in male and female subjects along with lowering of GH, IGF-I, and insulin resistance. VAT and SAT increased to a greater extent in men than in women. Skeletal muscle mass decreased in men. IMAT was higher in active acromegaly and decreased in women after surgery. Intrahepatic lipid increased, but intramyocellular lipid did not change after surgery. Conclusions: Acromegaly may present a unique type of lipodystrophy characterized by reduced storage of AT in central depots and a shift of excess lipid to IMAT. After surgery, this pattern partially reverses, but differentially in men and women. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use. PMID:26037515

Antiobesity effects of resveratrol: which tissues are involved?

Science.gov (United States)

Fernández-Quintela, Alfredo; Milton-Laskibar, Iñaki; González, Marcela; Portillo, Maria P

2017-09-01

The prevalence of obesity has been increasing in recent decades and is reaching epidemic proportions. The current options for overweight and obesity management are energy restriction and physical activity. However, compliance with these treatments is frequently poor and less successful than expected. Therefore, the scientific community is interested in active biomolecules, which may be useful in body weight management. Among them, resveratrol (3,5,4'-trihydroxy-trans-stilbene) has generated great interest as an antiobesity agent. The focus of this report is the mechanisms of action of resveratrol on several tissues (i.e., white and brown adipose tissues, liver, and skeletal muscle). Resveratrol blunts fat accumulation through decreasing adipogenesis and/or de novo lipogenesis in white adipose tissue. The effects on lipolysis are controversial. Regarding brown adipose tissue, resveratrol increases the capacity for adaptive thermogenesis. As far as liver and skeletal muscle is concerned, resveratrol increases lipid oxidation in both tissues. Therefore, in rodents, there is a general consensus concerning the effect of resveratrol on reducing body fat accumulation. By contrast, in humans, the studies are scarce, and no clear antiobesity action has been revealed so far. © 2017 New York Academy of Sciences.

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D [M.D. Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

International Nuclear Information System (INIS)

Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

2015-01-01

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted

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

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

Proton-minibeam radiation therapy: A proof of concept

Energy Technology Data Exchange (ETDEWEB)

Prezado, Y. [IMNC-UMR 8165, CNRS, Paris 7 and Paris 11 Universities, 15 rue Georges Clemenceau, 91406 Orsay Cedex (France); Fois, G. R. [Dipartimento di Fisica, Universita degli Studi di Cagliari, Strada provinciale Monserrato Sestu km 0.700, Monserrato, Cagliari 09042 (Italy)

2013-03-15

Purpose: This Monte Carlo simulation work aims at studying a new radiotherapy approach called proton-minibeam radiation therapy (pMBRT). The main objective of this proof of concept was the evaluation of the possible gain in tissue sparing, thanks to the spatial fractionation of the dose, which could be used to deposit higher and potentially curative doses in clinical cases where tissue tolerances are a limit for conventional methods. Methods: Monte Carlo simulations (GATE v.6) have been used as a method to calculate the ratio of the peak-to-valley doses (PVDR) for arrays of proton minibeams of 0.7 mm width and several center-to-center distances, at different depths in a water phantom. The beam penumbras were also evaluated as an important parameter for tissue sparing, for example, in the treatment of non-cancer diseases like epilepsy. Two proton energies were considered in this study: a clinically relevant energy (105 MeV) and a very high energy (1 GeV), to benefit from a reduced lateral scattering. For the latter case, an interlaced geometry was also evaluated. Results: Higher or similar PVDR than the ones obtained in x-rays minibeam radiation therapy were achieved in several pMBRT configurations. In addition, for the two energies studied, the beam penumbras are smaller than in the case of Gamma Knife radiosurgery. Conclusions: The high PVDR obtained for some configurations and the small penumbras in comparison with existing radiosurgery techniques, suggest a potential gain in healthy tissue sparing in this new technique. Biological studies are warranted to assess the effects of pMBRT on both normal and tumoral tissues.

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

Directory of Open Access Journals (Sweden)

Stefano Delli Pizzi

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

Skeletal muscle weakness in osteogenesis imperfecta mice.

Science.gov (United States)

Gentry, Bettina A; Ferreira, J Andries; McCambridge, Amanda J; Brown, Marybeth; Phillips, Charlotte L

2010-09-01

Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (P(o), P(o)/mg and P(o)/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased P(o) and an inability to sustain P(o) for the 300-ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology. Copyright © 2010 Elsevier B.V. All rights reserved.

A simple irradiation facility for radiobiological experiments with low energy protons from a cyclotron

International Nuclear Information System (INIS)

Mukherjee, B.

1982-01-01

An experimental facility for irradiation of small biological targets with low-energy protons has been developed. The depth-dose distribution in soft-tissue is calculated from the proton energy spectrum. (orig.)

Proton therapy with spot scanning: the Rinecker Proton Therapy Center in Munich. Part 2: Technical and physical aspects

International Nuclear Information System (INIS)

Borchert, H. J.; Mayr, M.; Schneider, R. A.; Arnold, M. R.; Geismar, D. E.; Wilms, M.; Wisser, L.; Herbst, M.

2008-01-01

The Rinecker Proton Therapy Center (RPTC) in Munich is about to introduce into clinical radiation therapy, a 2D scanning technique (spot scanning) of a single proton pencil beam. It will be available at four gantries and a fifth treatment room allocates a fixed beam unit for a scattering technique. A superconducting cyclotron extracts protons with a constant energy of 250 MeV. Far upstream of the patient follows modulation of the energy with a degrader according to the prescription of the patients treatment planning. A 10 mm pencil beam at full width of half maximum (FWHM) will enable scanning of individual tumour volumes at any depth i.e. 1 minute for a target volume of 1 litre and a dose of 2 Gy. Innovative solutions will be established for other important issues such as dosimetric monitoring, safety concepts and positioning of the patient. The physical characteristics of proton beam spot scanning offer exceptional possibilities in conformal radiation therapy. Together with intensity modulated proton therapy (IMPT) it significantly improves the sparing of organs at risk and of healthy tissues. (author)

Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy

Energy Technology Data Exchange (ETDEWEB)

Yohannes, Indra; Vasiliniuc, Stefan [Radiation Oncology, University Hospital Erlangen, Erlangen 91054 (Germany); Hild, Sebastian [Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054, Germany and Department of Biophysics, GSI - Helmholtz Centre for Heavy Ion Research, Darmstadt 64291 (Germany); Langner, Oliver [QRM - Quality Assurance in Radiology and Medicine GmbH, Möhrendorf 91096 (Germany); Graeff, Christian [Department of Biophysics, GSI - Helmholtz Centre for Heavy Ion Research, Darmstadt 64291 (Germany); Bert, Christoph, E-mail: christoph.bert@uk-erlangen.de [Radiation Oncology, University Hospital Erlangen, Erlangen 91054 (Germany); Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054 (Germany); Department of Biophysics, GSI - Helmholtz Centre for Heavy Ion Research, Darmstadt 64291 (Germany)

2016-01-15

Purpose: Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated. Methods: Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93 MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated. Results: Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively. Conclusions: The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy.

Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy

International Nuclear Information System (INIS)

Yohannes, Indra; Vasiliniuc, Stefan; Hild, Sebastian; Langner, Oliver; Graeff, Christian; Bert, Christoph

2016-01-01

Purpose: Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated. Methods: Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93 MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated. Results: Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively. Conclusions: The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy

Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy.

Science.gov (United States)

Yohannes, Indra; Hild, Sebastian; Vasiliniuc, Stefan; Langner, Oliver; Graeff, Christian; Bert, Christoph

2016-01-01

Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated. Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93 MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated. Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively. The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy.

Overweight in elderly people induces impaired autophagy in skeletal muscle.

Science.gov (United States)

Potes, Yaiza; de Luxán-Delgado, Beatriz; Rodriguez-González, Susana; Guimarães, Marcela Rodrigues Moreira; Solano, Juan J; Fernández-Fernández, María; Bermúdez, Manuel; Boga, Jose A; Vega-Naredo, Ignacio; Coto-Montes, Ana

2017-09-01

Sarcopenia is the gradual loss of skeletal muscle mass, strength and quality associated with aging. Changes in body composition, especially in skeletal muscle and fat mass are crucial steps in the development of chronic diseases. We studied the effect of overweight on skeletal muscle tissue in elderly people without reaching obesity to prevent this extreme situation. Overweight induces a progressive protein breakdown reflected as a progressive withdrawal of anabolism against the promoted catabolic state leading to muscle wasting. Protein turnover is regulated by a network of signaling pathways. Muscle damage derived from overweight displayed by oxidative and endoplasmic reticulum (ER) stress induces inflammation and insulin resistance and forces the muscle to increase requirements from autophagy mechanisms. Our findings showed that failure of autophagy in the elderly deprives it to deal with the cell damage caused by overweight. This insufficiently efficient autophagy leads to an accumulation of p62 and NBR1, which are robust markers of protein aggregations. This impaired autophagy affects myogenesis activity. Depletion of myogenic regulatory factors (MRFs) without links to variations in myostatin levels in overweight patients suggest a possible reduction of satellite cells in muscle tissue, which contributes to declined muscle quality. This discovery has important implications that improve the understanding of aged-related atrophy caused by overweight and demonstrates how impaired autophagy is one of the main responsible mechanisms that aggravate muscle wasting. Therefore, autophagy could be an interesting target for therapeutic interventions in humans against muscle impairment diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Biochemical background of the VO2 on-kinetics in skeletal muscles.

Science.gov (United States)

Korzeniewski, Bernard; Zoladz, Jerzy A

2006-02-01

This review discusses the present knowledge on the oxygen uptake kinetics at the onset of exercise in skeletal muscle and the contribution of a previously developed computer model of oxidative phosphorylation in intact skeletal muscle to the understanding of the factors determining this kinetics on the biochemical level. It has been demonstrated recently that an increase in the total creatine pool [PCr + Cr] and in glycolytic ATP supply lengthen the half-transition time of the VO2 on-kinetics, while an increase in mitochondria content, in parallel activation of ATP supply and ATP usage, in muscle oxygen concentration, in proton leak, in resting energy demand, in resting cytosolic pH, and in initial alkalization diminish this parameter. It has also been shown that the half-transition time is near-linearly proportional to the absolute difference between the phosphocreatine concentration during work and at rest (deltaPCr). The present review discusses whether the V/O2 on-kinetics on the muscle level is strictly or only approximately exponential. Finally, it is postulated that a short transition time of the VO2 on-kinetics in itself does not need be profitable for the skeletal muscle functioning during exercise, but usually a short transition time is correlated with factors that improve exercise capacity. The transition time is a phenomenological parameter resulting from the biochemical properties of the system and not a physical factor that can cause anything in the system.

Exercise and Regulation of Bone and Collagen Tissue Biology.

Science.gov (United States)

Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja; Magnusson, S Peter

2015-01-01

The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity. For several of the mechanically loaded connective tissues, only limited information regarding molecular and cellular signaling pathways and their adaptation to exercise is available. In contrast to tissue responses with exercise, lack of mechanical tissue loading through inactivity or immobilization of the human body will result in a dramatic loss of connective tissue content, structure, and tolerable load within weeks, to a degree (30-40%) that mimics that of contractile skeletal musculature. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity and exercise. © 2015 Elsevier Inc. All rights reserved.

Human skeletal muscle contains no detectable guanidinoacetic acid

DEFF Research Database (Denmark)

Ostojic, Sergej M; Ostojic, Jelena

2018-01-01

We analyzed data from previously completed trials to determine the effects of supplemental guanidinoacetic acid (GAA) on markers of muscle bioenergetics in healthy men using 1.5 T magnetic resonance spectroscopy. No detectable GAA (<0.1 μmol/L) was found in the vastus medialis muscle at baseline ...... nor at follow-up. This implies deficient GAA availability in the human skeletal muscle, suggesting absent or negligible potential for creatine synthesis from GAA inside this tissue, even after GAA loading....

Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.

Directory of Open Access Journals (Sweden)

Tingqing Guo

Full Text Available Myostatin (Mstn is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn(-/- mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/- mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn(-/- mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn(-/- mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn(-/- mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/- mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes.

Elevated Cardiac Troponin T in Patients With Skeletal Myopathies.

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Schmid, Johannes; Liesinger, Laura; Birner-Gruenberger, Ruth; Stojakovic, Tatjana; Scharnagl, Hubert; Dieplinger, Benjamin; Asslaber, Martin; Radl, Roman; Beer, Meinrad; Polacin, Malgorzata; Mair, Johannes; Szolar, Dieter; Berghold, Andrea; Quasthoff, Stefan; Binder, Josepha S; Rainer, Peter P

2018-04-10

Cardiac troponins are often elevated in patients with skeletal muscle disease who have no evidence of cardiac disease. The goal of this study was to characterize cardiac troponin concentrations in patients with myopathies and derive insights regarding the source of elevated troponin T measurements. Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) concentrations were determined by using high sensitivity assays in 74 patients with hereditary and acquired skeletal myopathies. Patients underwent comprehensive cardiac evaluation, including 12-lead electrocardiogram, 24-h electrocardiogram, cardiac magnetic resonance imaging, and coronary artery computed tomography. cTnT and cTnI protein expression was determined in skeletal muscle samples of 9 patients and in control tissues derived from autopsy using antibodies that are used in commercial assays. Relevant Western blot bands were subjected to liquid chromatography tandem mass spectrometry for protein identification. Levels of cTnT (median: 24 ng/l; interquartile range: 11 to 54 ng/l) were elevated (>14 ng/l) in 68.9% of patients; cTnI was elevated (>26 ng/l) in 4.1% of patients. Serum cTnT levels significantly correlated with creatine kinase and myoglobin (r = 0.679 and 0.786, respectively; both p < 0.001). Based on cTnT serial testing, 30.1% would have fulfilled current rule-in criteria for myocardial infarction. Noncoronary cardiac disease was present in 23%. Using cTnT antibodies, positive bands were found in both diseased and healthy skeletal muscle at molecular weights approximately 5 kDa below cTnT. Liquid chromatography tandem mass spectrometry identified the presence of skeletal troponin T isoforms in these bands. Measured cTnT concentrations were chronically elevated in the majority of patients with skeletal myopathies, whereas cTnI elevation was rare. Our data indicate that cross-reaction of the cTnT immunoassay with skeletal muscle troponin isoforms was the likely cause. Copyright © 2018 The

Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

Science.gov (United States)

Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

2014-08-01

The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

Type 2 Iodothyronine Deiodinase in Skeletal Muscle: Effects of Hypothyroidism and Fasting

NARCIS (Netherlands)

Heemstra, Karen A.; Soeters, Maarten R.; Fliers, Eric; Serlie, Mireille J.; Burggraaf, Jacobus; van Doorn, Martijn B.; van der Klaauw, Agatha A.; Romijn, Johannes A.; Smit, Johannes W.; Corssmit, Eleonora P.; Visser, Theo J.

2009-01-01

Context: The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific adaptation of thyroid hormone levels in response to various conditions, such as hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle is intriguing because this enzyme could play a role in

Ethnicity and skeletal Class III morphology: a pubertal growth analysis using thin-plate spline analysis.

Science.gov (United States)

Alkhamrah, B; Terada, K; Yamaki, M; Ali, I M; Hanada, K

2001-01-01

A longitudinal retrospective study using thin-plate spline analysis was used to investigate skeletal Class III etiology in Japanese female adolescents. Headfilms of 40 subjects were chosen from the archives of the Orthodontic department at Niigata University Dental Hospital, and were traced at IIIB and IVA Hellman dental ages. Twenty-eight homologous landmarks, representing hard and soft tissue, were digitized. These were used to reproduce a consensus for the profilogram, craniomaxillary complex, mandible, and soft tissue for each age and skeletal group. Generalized least-square analysis revealed a significant shape difference between age-matched groups (P spline and partial warps (PW)3 and 2 showed a maxillary retrusion at stage IIIB opposite an acute cranial base at stage IVA. Mandibular total spline and PW4, 5 showed changes affecting most landmarks and their spatial interrelationship, especially a stretch along the articulare-pogonion axis. In soft tissue analysis, PW8 showed large and local changes which paralleled the underlying hard tissue components. Allometry of the mandible and anisotropy of the cranial base, the maxilla, and the mandible asserted the complexity of craniofacial growth and the difficulty of predicting its outcome.

Predicted high-performing piglets exhibit more and larger skeletal muscle fibers

NARCIS (Netherlands)

Paredes Escobar, S.P.; Kalbe, C.; Jansman, A.J.M.; Verstegen, M.W.A.; Hees, van H.M.J.; Lösel, D.; Gerrits, W.J.J.; Rehfeldt, C.

2013-01-01

Postnatal (muscle) growth potential in pigs depends on the total number and hypertrophy of myofibers in skeletal muscle tissue. In a previous study an algorithm was developed to predict piglet BW at the end of the nursery period (10 wk of age) on the basis of BW at birth, at weaning, and at 6 wk of