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Sample records for human bioartificial muscles

  1. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

    Science.gov (United States)

    Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

    1999-01-01

    Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

  2. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

    Science.gov (United States)

    Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

    1999-01-01

    Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

  3. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( muscle-wasting disorders.

  4. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( muscle-wasting disorders.

  5. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.

  6. Recombinant human growth hormone secreted from tissue-engineered bioartificial muscle improves left ventricular function in rat with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    RONG Shu-ling; WANG Yong-jin; WANG Xiao-lin; LU Yong-xin; CHANG Chao; WANG Feng-zhi; LIU Qi-yun; LIU Xiang-yang; GAO Yan-zhang; MI Shao-hua

    2009-01-01

    Background Experimental studies and preliminary clinical studies have suggested that growth hormone (GH) treatment may improve cardiovascular parameters in chronic heart failure (CHF). Recombinant human GH (rhGH) has been delivered by a recombinant protein, by plasmid DNA, and by genetically engineered cells with different pharmacokinetic and physiological properties. The present study aimed to examine a new method for delivery of rhGH using genetically modified bioartificial muscles (BAMs), and investigate whether the rhGH delivered by this technique improves left ventricular (LV) function in rats with CHF.Methods Primary skeletal myoblasts were isolated from several Sprague-Dawley (SD) rats, cultured, purified, and retrovirally transduced to synthesize and secrete human rhGH, and tissue-engineered into implantable BAMs. Ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 2 groups: CHF control group (n=6) and CHF treatment group (n=6). The CHF control group received non-rhGH-secreting BAM (GFP-BAMs) transplantation, and the CHF treatment group received rhGH-secreting BAM (GH-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: sham control group (n=6) and sham treatment group (n=6). The sham control group underwent GFP-BAM transplantation, and the sham treatment group underwent GH-BAM transplantation. GH-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats with ligaUon of the left coronary artery or sham operation was performed. Eight weeks after the treatment,echocardiography was performed, hGH, insulin-like growth factor-1 (IGF-1) and TNF-a levels in rat serum were measured by radioimmunoassay and ELISA, and then the rats were killed and ventricular samples were subjected to immunohistochemistry. Results Primary rat myoblasts were retrovirally transduced to secrete rhGH and tissue-engineered into

  7. Experimental study of bioartificial liver with cultured human liver cells

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To establish an extracorporeal bioartificial liver support system (EBLSS) using cultured human liver cells and to study its support effect for fulminant hepatic failure (FHF).METHODS The liver support experiment of EBLSS consisting of aggregates cultured human liver cells, hollow fiber bioreactor, and circulation unit was carried out in dizhepatic dogs.RESULTS The viability of isolated hepatocytes and nonparenchymal liver cells reached 96%. These cells were successfully cultured as multicellular spheroids with synthetic technique. The typical morphological appearance was retained up to the end of the artificial liver experiment. Compared with the control dogs treated with EBLSS without liver cells, the survival time of artificial liver support dogs was significantly prolonged. The changes of blood pressure, heart rate and ECG were slow. Both serum ammonia and lactate levels were significantly lowered at the 3rd h and 5th h. In addition, a good viability of human liver cells was noted after 5 h experiment.CONCLUSION EBLSS playing a metabolic role of cultured human hepatocytes, is capable of compensating the function of the liver, and could provide effective artificial liver support and therapy for patients with FHF.

  8. Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

    Directory of Open Access Journals (Sweden)

    Ruchi Sharma

    2010-01-01

    Full Text Available The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

  9. Bioartificial heart: a human-sized porcine model--the way ahead.

    Directory of Open Access Journals (Sweden)

    Alexander Weymann

    Full Text Available BACKGROUND: A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop a tissue-engineered whole-heart neoscaffold in human-sized porcine hearts. METHODS: We decellularized porcine hearts (n = 10 by coronary perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy, quantified residual DNA by spectrophotometry, and evaluated biomechanical stability with ex-vivo left-ventricular pressure/volume studies, all compared to controls. We then mounted the decellularized porcine hearts in a bioreactor and reseeded them with murine neonatal cardiac cells and human umbilical cord derived endothelial cells (HUVEC under simulated physiological conditions. RESULTS: Decellularized hearts lacked intracellular components but retained specific collagen fibers, proteoglycan, elastin and mechanical integrity; quantitative DNA analysis demonstrated a significant reduction of DNA compared to controls (82.6±3.2 ng DNA/mg tissue vs. 473.2±13.4 ng DNA/mg tissue, p<0.05. Recellularized porcine whole-heart neoscaffolds demonstrated re-endothelialization of coronary vasculature and measurable intrinsic myocardial electrical activity at 10 days, with perfused organ culture maintained for up to 3 weeks. CONCLUSIONS: Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.

  10. The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas.

    Science.gov (United States)

    Peloso, Andrea; Urbani, Luca; Cravedi, Paolo; Katari, Ravi; Maghsoudlou, Panagiotis; Fallas, Mario Enrique Alvarez; Sordi, Valeria; Citro, Antonio; Purroy, Carolina; Niu, Guoguang; McQuilling, John P; Sittadjody, Sivanandane; Farney, Alan C; Iskandar, Samy S; Zambon, Joao P; Rogers, Jeffrey; Stratta, Robert J; Opara, Emmanuel C; Piemonti, Lorenzo; Furdui, Cristina M; Soker, Shay; De Coppi, Paolo; Orlando, Giuseppe

    2016-07-01

    Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.

  11. Establishing the framework to support bioartificial heart fabrication using fibrin-based three-dimensional artificial heart muscle.

    Science.gov (United States)

    Hogan, Matthew; Mohamed, Mohamed; Tao, Ze-Wei; Gutierrez, Laura; Birla, Ravi

    2015-02-01

    Only 3000 heart transplants are performed in the USA every year, leaving some 30 000-70 000 Americans without proper care. Current treatment modalities for heart failure have saved many lives yet still do not correct the underlying problems of congestive heart failure. Tissue engineering represents a potential field of study wherein a combination of cells, scaffolds, and/or bioreactors can be utilized to create constructs to mimic, replace, and/or repair defective tissue. The focus of this study was to generate a bioartificial heart (BAH) model using artificial heart muscle (AHM), composed of fibrin gel and neonatal rat cardiac myocytes, and a decellularized scaffold, formed by subjecting an adult rat heart to a series of decellularization solutions. By suturing the AHM around the outside of the decellularized heart and culturing while suspended in media, we were able to retain functional cardiac cells on the scaffold as evinced by visible contractility. Observed contractility rate was correlated with biopotential measurements to confirm essential functionality of cardiac constructs. Cross-sections of the BAH show successful decellularization of the scaffold and contiguous cell-rich AHM around the perimeter of the heart.

  12. Bioartificial Liver Support

    Directory of Open Access Journals (Sweden)

    Vincent G Bain

    2001-01-01

    Full Text Available Bioartificial liver support has been increasingly the focus of both basic and clinical research in an attempt to replicate the multiplicity of normal liver function. The concept is attractive because, if it is effective, patients with acute liver failure may be supported until native liver regeneration occurs or, by optimizing their condition, until liver transplantation is possible. Current bioartificial liver support systems utilize primary porcine hepatocytes or transformed human hepatocytes, which are housed within a bioreactor, through which the patient's blood or plasma is pumped in an extracorporeal circuit. The optimal source for the hepatocytes is an area of debate; however, a genetically engineered cell line may provide optimal function. Novel three-dimensional matrices that anchor the hepatocytes are being designed to mimic architectural features of the normal liver. Large multicentre, randomized, controlled trials are ongoing following several pilot studies. Serious side effects such as hemodynamic instability and immune reactions have been infrequent. Much controversy, however, surrounds the issue of possible transmission of pig endogenous retrovirus to humans, and current trials are being carefully monitored. Bioartificial liver support is a promising technology, and the results of current and planned studies are awaited with great interest.

  13. Recombinant proteins secreted from tissue-engineered bioartificial muscle improve cardiac dysfunction and suppress cardiomyocyte apoptosis in rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    RONG Shu-ling; WANG Yong-jin; WANG Xiao-lin; LU Yong-xin; WU Yin; LIU Qi-yun; MI Shao-hua; XU Yu-lan

    2010-01-01

    Background Tissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 (IGF-1) protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction (MI) and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles (BAMs) following coronary artery ligation in Sprague-Dawley rats.Methods Ligation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 (rhIGF-1), and green fluorescent protein (GFP), and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups: MI-IGF group (n=6) and MI-GFP group (n=6). The MI-IGF group received rhIGF-secreting BAM (IGF-BAMs) transplantation, and the MI-GFP group received GFP-secreting BAM (GFP-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: S-IGF group (n=6)and S-GFP group (n=6). The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting.Results Primary rat myoblasts were retrovirally transduced to

  14. Design and development of a hybrid bioartificial water-induced shape memory polymeric material as an integral component for the anastomosis of human hollow organs.

    Science.gov (United States)

    Paonessa, Siriana; Barbani, Niccoletta; Rocchietti, Elisa Cibrario; Giachino, Claudia; Cristallini, Caterina

    2017-06-01

    A large number of pathologies require the resection of the bowel and anastomoses to rejoin the two remaining stumps to regain lumen patency. Various materials have been used to rejoin one bowel end to the other such as catgut, stainless steel, and absorbable sutures. The present method for anastomosis surgery uses an entero-entero anastomosis (EEA) circular stapler with only a staple line. This method can have some drawbacks, such as intracellular fluid leakage and local inflammations. The aim of this study is to design and develop a novel bioartificial polymer with a ring shape made of polyvinyl alcohol (PVA) and gelatin (80/20 ratio (w/w)) loaded both directly with acetylsalicylic acid and with nanoparticles incorporating the same drug to reduce local inflammation even for a prolonged period of time. A physical method (8cycles freezing/thawing) was used to obtain a crosslinked bioartificial shape memory ring. Mechanical analysis showed a storage modulus having a comparable value with that of the human colon. HPLC analysis pointed out a sustained and prolonged release of the anti-inflammatory drug both immediately after anastomosis surgery and during healing period. Cell culture tests indicated the cytocompatibility of the bioartificial device. A shape memory of the hydrogel prepared in ring form was observed at 37°C after immersion in water. These bioartificial devices can represent a new approach to serve as a multifunctional anastomotic ring. Copyright © 2017. Published by Elsevier B.V.

  15. Bioartificial liver: current status.

    Science.gov (United States)

    Pless, G; Sauer, I M

    2005-11-01

    Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

  16. BioArtificial polymers

    Science.gov (United States)

    Szałata, Kamila; Gumi, Tania

    2017-07-01

    Nowadays, the polymer science has impact in practically all life areas. Countless benefits coming from the usage of materials with high mechanical and chemical resistance, variety of functionalities and potentiality of modification drive to the development of new application fields. Novel approaches of combining these synthetic substances with biomolecules lead to obtain multifunctional hybrid conjugates which merge the bioactivity of natural component with outstanding properties of artificial polymer. Over the decades, an immense progress in bioartificial composites domain allowed to reach a high level of knowledge in terms of natural-like systems engineering, leading to diverse strategies of biomolecule immobilization. Together with different available options, including covalent and noncovalent attachment, come various challenges, related mainly with maintaining the biological activity of fixed molecules. Even though the amount of applications that achieve commercial status is still not substantial, and is expanding continuously in the disciplines like "smart materials," biosensors, delivery systems, nanoreactors and many others. A huge number of remarkable developments reported in the literature present a potential of bioartificial conjugates as a fabrics with highly controllable structure and multiple functionalities, serving as a powerful nanotechnological tool. This novel approach brings closer biologists, chemists and engineers, who sharing their effort and complementing the knowledge can revolutionize the field of bioartificial polymer science.

  17. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

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

    2002-01-01

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

  18. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

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

    2002-01-01

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

  19. The Use of Fibrous, Supramolecular Membranes and Human Tubular Cells for Renal Epithelial Tissue Engineering : Towards a Suitable Membrane for a Bioartificial Kidney

    NARCIS (Netherlands)

    Dankers, Patricia Y. W.; Boomker, Jasper M.; Huizinga-van der Vlag, Ali; Smedts, Frank M. M.; Harmsen, Martin C.; van Luyn, Marja J. A.

    2010-01-01

    A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypoth

  20. New Phase of Growth for Xenogeneic-Based Bioartificial Organs

    Directory of Open Access Journals (Sweden)

    Zorina Pitkin

    2016-09-01

    Full Text Available In this article, we examine the advanced clinical development of bioartificial organs and describe the challenges to implementing such systems into patient care. The case for bioartificial organs is evident: they are meant to reduce patient morbidity and mortality caused by the persistent shortage of organs available for allotransplantation. The widespread introduction and adoption of bioengineered organs, incorporating cells and tissues derived from either human or animal sources, would help address this shortage. Despite the decades of development, the variety of organs studied and bioengineered, and continuous progress in the field, only two bioengineered systems are currently commercially available: Apligraf® and Dermagraft® are both approved by the FDA to treat diabetic foot ulcers, and Apligraf® is approved to treat venous leg ulcers. Currently, no products based on xenotransplantation have been approved by the FDA. Risk factors include immunological barriers and the potential infectivity of porcine endogenous retrovirus (PERV, which is unique to xenotransplantation. Recent breakthroughs in gene editing may, however, mitigate risks related to PERV. Because of its primary role in interrupting progress in xenotransplantation, we present a risk assessment for PERV infection, and conclude that the formerly high risk has been reduced to a moderate level. Advances in gene editing, and more broadly in the field, may make it more likely than ever before that bioartificial organs will alleviate the suffering of patients with organ failure.

  1. New Phase of Growth for Xenogeneic-Based Bioartificial Organs.

    Science.gov (United States)

    Pitkin, Zorina

    2016-09-21

    In this article, we examine the advanced clinical development of bioartificial organs and describe the challenges to implementing such systems into patient care. The case for bioartificial organs is evident: they are meant to reduce patient morbidity and mortality caused by the persistent shortage of organs available for allotransplantation. The widespread introduction and adoption of bioengineered organs, incorporating cells and tissues derived from either human or animal sources, would help address this shortage. Despite the decades of development, the variety of organs studied and bioengineered, and continuous progress in the field, only two bioengineered systems are currently commercially available: Apligraf(®) and Dermagraft(®) are both approved by the FDA to treat diabetic foot ulcers, and Apligraf(®) is approved to treat venous leg ulcers. Currently, no products based on xenotransplantation have been approved by the FDA. Risk factors include immunological barriers and the potential infectivity of porcine endogenous retrovirus (PERV), which is unique to xenotransplantation. Recent breakthroughs in gene editing may, however, mitigate risks related to PERV. Because of its primary role in interrupting progress in xenotransplantation, we present a risk assessment for PERV infection, and conclude that the formerly high risk has been reduced to a moderate level. Advances in gene editing, and more broadly in the field, may make it more likely than ever before that bioartificial organs will alleviate the suffering of patients with organ failure.

  2. New Phase of Growth for Xenogeneic-Based Bioartificial Organs

    Science.gov (United States)

    Pitkin, Zorina

    2016-01-01

    In this article, we examine the advanced clinical development of bioartificial organs and describe the challenges to implementing such systems into patient care. The case for bioartificial organs is evident: they are meant to reduce patient morbidity and mortality caused by the persistent shortage of organs available for allotransplantation. The widespread introduction and adoption of bioengineered organs, incorporating cells and tissues derived from either human or animal sources, would help address this shortage. Despite the decades of development, the variety of organs studied and bioengineered, and continuous progress in the field, only two bioengineered systems are currently commercially available: Apligraf® and Dermagraft® are both approved by the FDA to treat diabetic foot ulcers, and Apligraf® is approved to treat venous leg ulcers. Currently, no products based on xenotransplantation have been approved by the FDA. Risk factors include immunological barriers and the potential infectivity of porcine endogenous retrovirus (PERV), which is unique to xenotransplantation. Recent breakthroughs in gene editing may, however, mitigate risks related to PERV. Because of its primary role in interrupting progress in xenotransplantation, we present a risk assessment for PERV infection, and conclude that the formerly high risk has been reduced to a moderate level. Advances in gene editing, and more broadly in the field, may make it more likely than ever before that bioartificial organs will alleviate the suffering of patients with organ failure. PMID:27657057

  3. Progress and challenges of the bioartificial pancreas

    Science.gov (United States)

    Hwang, Patrick T. J.; Shah, Dishant K.; Garcia, Jacob A.; Bae, Chae Yun; Lim, Dong-Jin; Huiszoon, Ryan C.; Alexander, Grant C.; Jun, Ho-Wook

    2016-11-01

    Pancreatic islet transplantation has been validated as a treatment for type 1 diabetes since it maintains consistent and sustained type 1 diabetes reversal. However, one of the major challenges in pancreatic islet transplantation is the body's natural immune response to the implanted islets. Immunosuppressive drug treatment is the most popular immunomodulatory approach for islet graft survival. However, administration of immunosuppressive drugs gives rise to negative side effects, and long-term effects are not clearly understood. A bioartificial pancreas is a therapeutic approach to enable pancreatic islet transplantation without or with minimal immune suppression. The bioartificial pancreas encapsulates the pancreatic islets in a semi-permeable environment which protects islets from the body's immune responses, while allowing the permeation of insulin, oxygen, nutrients, and waste. Many groups have developed various types of the bioartificial pancreas and tested their efficacy in animal models. However, the clinical application of the bioartificial pancreas still requires further investigation. In this review, we discuss several types of bioartificial pancreases and address their advantages and limitations. We also discuss recent advances in bioartificial pancreas applications with microfluidic or micropatterning technology.

  4. Viabilidade do fígado bioartificial utilizando hepatócitos humanos imunoprotegidos por macroencapsulação Assessment of bioartificial liver using human hepatocytes immunoprotected by macroencapsulation

    Directory of Open Access Journals (Sweden)

    João Eduardo Leal Nicoluzzi

    2004-10-01

    Full Text Available OBJETIVO: O transplante de hepatócitos xenogênicos encapsulados pode ser utilizado no futuro em situações como a insuficiência hepática fulminante. Porém, observa-se perda precoce da expressão de genes hepatocitários específicos em hepatócitos humanos. O objetivo deste estudo é avaliar a influência da resposta imunológica na perda da expressão genética hepatocitária de hepatócitos humanos encapsulados e transplantados em ratos. MÉTODO: Hepatócitos humanos foram isolados de fragmentos hepáticos, encapsulados em fibras e transplantados em ratos. Nos dias 3, 7 e 14 após o transplante as fibras foram coletadas e avaliadas a morfologia por microscopia óptica e eletrônica, e a expressão dos genes por biologia molecular. O ARNm da albumina humana foi quantificado por RT-PCR e Northern blot. A resposta imunológica contra os hepatócitos foi avaliada através do ADN hepatocitário na busca de apoptose do núcleo celular e pelo aumento da expressão do CMH de classe I. RESULTADOS: Os aspectos morfológicos dos hepatócitos mantiveram-se normais até o sétimo dia após o transplante. Não se observaram células envolvidas com resposta imunológica do receptor nas fibras. Os transcritos da albumina foram detectados até D-14. Entre os dias 3 e 7 estavam em 30% em relação ao dia 0. A análise do ADN mostrou bandas preservadas sem a presença de fenômenos de apoptose nos diferentes dias. Não ocorreu aumento da expressão do CMH de classe I. CONCLUSÕES: Hepatócitos humanos encapsulados e transplantados em ratos permanecem viáveis apesar da diminuição da expressão de determinados genes. Este fenômeno, não se deve à resposta imunológica do receptor, mas ao próprio processo de isolamento celular.BACKGROUND: Xenogeneic hepatocytes encapsulated in semipermeable membranes could be used in the future; however, encapsulated human hepatocytes presented an early decrease of hepatocyte gene expression. The objective of this study

  5. Trichinella spiralis in human muscle (image)

    Science.gov (United States)

    This is the parasite Trichinella spiralis in human muscle tissue. The parasite is transmitted by eating undercooked ... produce large numbers of larvae that migrate into muscle tissue. The cysts may cause muscle pain and ...

  6. Microencapsulation of pancreatic islets for use in a bioartificial pancreas.

    Science.gov (United States)

    Opara, Emmanuel C; McQuilling, John P; Farney, Alan C

    2013-01-01

    Islet transplantation is the most exciting treatment option for individuals afflicted with Type 1 diabetes. However, the severe shortage of human pancreas and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles for the routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets with biopolymers for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this chapter, we provide a detailed description of the microencapsulation process.

  7. Esterase profile of human masseter muscle

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D; Vilmann, H

    1988-01-01

    The esterase profile of fresh human masseter muscle was investigated by use of histochemistry and electrophoresis. The histochemical methods included reactions for alpha-naphthyl esterase, myofibrillar ATPase, reverse myofibrillar ATPase and succinic dehydrogenase. In frozen sections of the muscl...

  8. Muscle spindles in the human bulbospongiosus and ischiocavernosus muscles.

    Science.gov (United States)

    Peikert, Kevin; May, Christian Albrecht

    2015-07-01

    Muscle spindles are crucial for neuronal regulation of striated muscles, but their presence and involvement in the superficial perineal muscles is not known. Bulbospongiosus and ischiocavernosus muscle specimens were obtained from 31 human cadavers. Serial sections were stained with hematoxylin and eosin, Sirius red, antibodies against Podocalyxin, myosin heavy chain isoforms (MyHC-slow tonic, S46; MyHC-2a/2x, A4.74), and neurofilament for the purpose of muscle spindle screening, counting, and characterization. A low but consistent number of spindles were detected in both muscles. The muscles contained few intrafusal fibers, but otherwise showed normal spindle morphology. The extrafusal fibers of both muscles were small in diameter. The presence of muscle spindles in bulbospongiosus and ischiocavernosus muscles supports physiological models of pelvic floor regulation and may provide a basis for further clinical observations regarding sexual function and micturition. The small number of muscle spindles points to a minor level of proprioceptive regulation. © 2014 Wiley Periodicals, Inc.

  9. Synthetic and Bio-Artificial Tactile Sensing: A Review

    Directory of Open Access Journals (Sweden)

    Maria Chiara Carrozza

    2013-01-01

    Full Text Available This paper reviews the state of the art of artificial tactile sensing, with a particular focus on bio-hybrid and fully-biological approaches. To this aim, the study of physiology of the human sense of touch and of the coding mechanisms of tactile information is a significant starting point, which is briefly explored in this review. Then, the progress towards the development of an artificial sense of touch are investigated. Artificial tactile sensing is analysed with respect to the possible approaches to fabricate the outer interface layer: synthetic skin versus bio-artificial skin. With particular respect to the synthetic skin approach, a brief overview is provided on various technologies and transduction principles that can be integrated beneath the skin layer. Then, the main focus moves to approaches characterized by the use of bio-artificial skin as an outer layer of the artificial sensory system. Within this design solution for the skin, bio-hybrid and fully-biological tactile sensing systems are thoroughly presented: while significant results have been reported for the development of tissue engineered skins, the development of mechanotransduction units and their integration is a recent trend that is still lagging behind, therefore requiring research efforts and investments. In the last part of the paper, application domains and perspectives of the reviewed tactile sensing technologies are discussed.

  10. Satellite cells in human skeletal muscle plasticity.

    Science.gov (United States)

    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  11. Effect of extracorporeal bioartificial liver support system on fulminant hepatic failure rabbits

    Institute of Scientific and Technical Information of China (English)

    Ying Jie Wang; Meng Dong Li; Yu Ming Wang; Guo Zheng Chen; Guo Dong Lu; Zao Xia Tan

    2000-01-01

    AIM To evaluate the possibility of using cultured human hepatocytes as a bridge between bioartificial liver and liver transplantation. METHODS In this experiment, the efficacy of extracorporeal bioartificial liver support system (EBLSS) consisting of spheriodal human liver cells and cultured hepatocytes supernatant was assessed in vivo using galactosamine induced rabbit model of fulminant hepatic failure. RiESULTS There was no difference of survival between the two groups of rabbits, but in the supported rabbits serum alanine aminotransferase, total bilirubin and creatinine were significantly lower and hepatocyte necrosis was markedly milder than those in control animals. In addition, a good viability of human liver cells was noted after the experiment. CONCLUSION EBLSS plays a biologic role in maintaining and compensating the function of the liver.

  12. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

    Liu, J P; Gluud, L L; Als-Nielsen, B;

    2004-01-01

    Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery.......Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery....

  13. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

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

    2012-01-01

    and adipose tissue leptin release in vivo. We recruited 16 healthy male human participants. Catheters were inserted into the femoral artery and vein draining skeletal muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose tissue. By combining the veno-arterial differences in plasma......Leptin 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...... leptin with measurements of blood flow, leptin release from both tissues was quantified. To induce changes in leptin, the participants were infused with either saline or adrenaline in normo-physiological concentrations. The presence of leptin in skeletal muscle was confirmed by western blotting. Leptin...

  14. Lactate oxidation in human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Meinild, Anne-Kristine; Nordsborg, Nikolai B

    2013-01-01

    Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver, and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we...... analyze the ability of skeletal muscle to respire lactate by using an in situ mitochondrial preparation that leaves the native tubular reticulum and subcellular interactions of the organelle unaltered. Skeletal muscle biopsies were obtained from vastus lateralis muscle in 16 human subjects. Samples were...... of exogenous LDH failed to increase lactate-stimulated respiration (P = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within...

  15. Human Muscle Fatigue Model in Dynamic Motions

    CERN Document Server

    Ma, Ruina; Bennis, Fouad; Ma, Liang

    2012-01-01

    Human muscle fatigue is considered to be one of the main reasons for Musculoskeletal Disorder (MSD). Recent models have been introduced to define muscle fatigue for static postures. However, the main drawbacks of these models are that the dynamic effect of the human and the external load are not taken into account. In this paper, each human joint is assumed to be controlled by two muscle groups to generate motions such as push/pull. The joint torques are computed using Lagrange's formulation to evaluate the dynamic factors of the muscle fatigue model. An experiment is defined to validate this assumption and the result for one person confirms its feasibility. The evaluation of this model can predict the fatigue and MSD risk in industry production quickly.

  16. Recent advances in "bioartificial polymeric materials" based nanovectors

    Science.gov (United States)

    Conte, Raffaele; De Luca, Ilenia; Valentino, Anna; Di Salle, Anna; Calarco, Anna; Riccitiello, Francesco; Peluso, Gianfranco

    2017-04-01

    This chapter analyzes the advantages of the use of bioartificial polymers as carriers and the main strategies used for their design. Despite the enormous progresses in this field, more studies are required for the fully evaluation of these nanovectors in complex organisms and for the characterization of the pharmacodynamic and pharmacokinetic of the loaded drugs. Moreover, progresses in polymer chemistry are introducing a wide range of functionalities in the bioartificial polymeric material (BPM) nanostructures leading to a second generation of bioartificial polymer therapeutics based on novel and heterogeneous architectures with higher molecular weight and predictable structures, in order to achieve greater multivalency and increased loading capacity. Therefore, research on bioartificial polymeric nanovectors is an "on-going" field capable of attracting medical interest.

  17. Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).

    Science.gov (United States)

    Johnston, Kimberly A; Westover, Angela J; Rojas-Pena, Alvaro; Buffington, Deborah A; Pino, Christopher J; Smith, Peter L; Humes, H David

    2016-11-18

    Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 × 10(8) renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. The Human Skeletal Muscle Proteome Project

    DEFF Research Database (Denmark)

    Gonzalez-Freire, Marta; Semba, Richard D.; Ubaida-Mohien, Ceereena

    2017-01-01

    Skeletal muscle is a large organ that accounts for up to half the total mass of the human body. A progressive decline in muscle mass and strength occurs with ageing and in some individuals configures the syndrome of ‘sarcopenia’, a condition that impairs mobility, challenges autonomy, and is a risk...... factor for mortality. The mechanisms leading to sarcopenia as well as myopathies are still little understood. The Human Skeletal Muscle Proteome Project was initiated with the aim to characterize muscle proteins and how they change with ageing and disease. We conducted an extensive review...... of the literature and analysed publically available protein databases. A systematic search of peer-reviewed studies was performed using PubMed. Search terms included ‘human’, ‘skeletal muscle’, ‘proteome’, ‘proteomic(s)’, and ‘mass spectrometry’, ‘liquid chromatography-mass spectrometry (LC-MS/MS)’. A catalogue...

  19. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

    Liu, Jianping; Kjaergard, Lise Lotte; Als-Nielsen, Bodil;

    2002-01-01

    Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure.......Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure....

  20. GLUT-3 expression in human skeletal muscle

    Science.gov (United States)

    Stuart, C. A.; Wen, G.; Peng, B. H.; Popov, V. L.; Hudnall, S. D.; Campbell, G. A.

    2000-01-01

    Muscle biopsy homogenates contain GLUT-3 mRNA and protein. Before these studies, it was unclear where GLUT-3 was located in muscle tissue. In situ hybridization using a midmolecule probe demonstrated GLUT-3 within all muscle fibers. Fluorescent-tagged antibody reacting with affinity-purified antibody directed at the carboxy-terminus demonstrated GLUT-3 protein in all fibers. Slow-twitch muscle fibers, identified by NADH-tetrazolium reductase staining, possessed more GLUT-3 protein than fast-twitch fibers. Electron microscopy using affinity-purified primary antibody and gold particle-tagged second antibody showed that the majority of GLUT-3 was in association with triads and transverse tubules inside the fiber. Strong GLUT-3 signals were seen in association with the few nerves that traversed muscle sections. Electron microscopic evaluation of human peripheral nerve demonstrated GLUT-3 within the axon, with many of the particles related to mitochondria. GLUT-3 protein was found in myelin but not in Schwann cells. GLUT-1 protein was not present in nerve cells, axons, myelin, or Schwann cells but was seen at the surface of the peripheral nerve in the perineurium. These studies demonstrated that GLUT-3 mRNA and protein are expressed throughout normal human skeletal muscle, but the protein is predominantly found in the triads of slow-twitch muscle fibers.

  1. Noninvasive analysis of human neck muscle function

    Science.gov (United States)

    Conley, M. S.; Meyer, R. A.; Bloomberg, J. J.; Feeback, D. L.; Dudley, G. A.

    1995-01-01

    selected muscles that have been examined in human electromyographic studies. Neck muscle function and morphology can be studied at a detailed level using exercise-induced shifts in magnetic resonance images.

  2. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Kjaergard, Lise L; Liu, Jianping; Als-Nielsen, Bodil;

    2003-01-01

    Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation.......Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation....

  3. Anisotropic photon migration in human skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Binzoni, T [Departement de Neurosciences Fondamentales, University of Geneva (Switzerland); Department of Radiology, University Hospital, Geneva (Switzerland); Courvoisier, C [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Giust, R [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Tribillon, G [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Gharbi, T [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Hebden, J C [Department of Medical Physics and Bioengineering, University College London (United Kingdom); Leung, T S [Department of Medical Physics and Bioengineering, University College London (United Kingdom); Roux, J [Hamamatsu Photonics, Grenoble (France); Delpy, D T [Department of Medical Physics and Bioengineering, University College London (United Kingdom)

    2006-03-07

    It is demonstrated in the short head of the human biceps brachii of 16 healthy subjects (12 males and 4 females) that near infrared photon migration is anisotropic. The probability for a photon to travel along the direction of the muscle fibres is higher ({approx}0.4) than that of travelling along a perpendicular axis ({approx}0.3) while in the adipose tissue the probability is the same ({approx}0.33) in all directions. Considering that the muscle fibre orientation is different depending on the type of muscle considered, and that inside a given skeletal muscle the orientation may change, the present findings in part might explain the intrasubject variability observed in the physiological parameters measured by near infrared spectroscopy techniques. In other words, the observed regional differences might not only be physiological differences but also optical artefacts. (note)

  4. Muscle pain: animal and human experimental and clinical studies.

    Science.gov (United States)

    Marchettini, P

    1993-10-01

    The search for the identification of the sensory apparatus encoding muscle pain sensation in humans is recounted. Basic neurophysiologic animal studies, leading to a description of slowly conducting afferent from muscle and definition of high threshold polymodal muscle nociceptors, and pioneer psychophysic human studies together with recent microneurographic experiments in humans are described. The phenomena of muscle pain broad localization and distant referral are discussed, and clinical implications are extrapolated to interpret muscle pain as a localizing sign of mononeuropathy or radiculopathy. The identification of human muscle nociceptors has defined the scientific standard to test emerging clinical descriptions having muscle pain as a symptom.

  5. Skeletal muscle responses to unweighting in humans

    Science.gov (United States)

    Dudley, Gary A.

    1991-01-01

    An overview of earth-based studies is presented emphasizing the data on muscular strength and size derived from experiments under simulated microgravity. The studies involve the elimination of weight-bearing responsibility of lower-limb human musculature to simulate the unweighting effects of space travel in the absence of exercise. Reference is given to bedrest and unilateral lower-limb suspension, both of which provide data that demonstrate the decreased strength of the knee extensors of 20-25 percent. The response is related to the decrease in cross-sectional area of the knee extensors which is a direct indication of muscle-fiber atrophy. Most of the effects of unweighting are associated with extensor muscles in the lower limbs and not with postural muscles. Unweighting is concluded to cause significant adaptations in the human neuromuscular system that require further investigation.

  6. Modeling human muscle disease in zebrafish

    OpenAIRE

    Guyon, Jeffrey R.; Steffen, Leta S; Howell, Melanie H.; Pusack, Timothy J; Lawrence, Chris; Kunkel, Louis M

    2007-01-01

    Modeling human muscle disease in zebrafish correspondence: Corresponding author. Children's Hospital Boston, Enders Bldg, Rm 570, 300 Longwood Ave Boston, MA 02115. Tel.: +1 617 355 7576. (Kunkel, Louis M.) (Kunkel, Louis M.) Program in Genomics and Howard Hughes Medical Institute at Children's Hospital Boston - Boston--> , MA 02115--> - UNITED STATES (Guyon, Jeffrey R.) Program in Genomics a...

  7. Regulation of Metabolic Signaling in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth

    sensitivity in type I muscle fibers possibly reflects a superior effect of insulin on metabolic signaling compared to type II muscle fibers. This was investigated in the present thesis by examining muscle biopsies from lean and obese healthy subjects as well as patients with type 2 diabetes. From these muscle...... enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance...... of human type I muscle fibers is illustrated by the finding of a positive correlation between the relative distribution of type I fibers in the muscle and whole-body insulin sensitivity. This suggests, that type I muscle fibers are more insulin sensitive than type II muscle fibers. Improved insulin...

  8. Construction of modular novel bioartificial liver support system.

    Science.gov (United States)

    Liu, Jianfeng; Song, Tao; Jiang, Wei; Zhang, Yimin; Lv, Guoliang; Zhao, Lifu; Zhang, Guanghao; Li, Lanjuan

    2009-01-01

    A modular novel bioartificial liver support system was designed and constructed in order to simplify tedious operation of artificial liver treatment and to improve the applicability in the system. The design ideas, structure composition, system function, and etc, were described in detail. In this system, the variety of the therapy modes could be conveniently connected by the interface of modular structure. Industrial control computer was used as the main control platform, and physical of control parameters such as pressure, pump speed, dissolved oxygen, temperature, and etc, were transmitted into computer, then according to the instruction, process of the treatment was accomplished by the executing units implemented by main control system. Touch screen of human-computer interface was adopted, which made the system better operational and more comfortable. The system has passed the spot function test, and all indexes can meet requirements for the clinical treatment requested. It has the character such as modular design, systematic distribution, building-block structure, and etc, which supports a great novel operation platform for artificial therapy.

  9. Tissue engineering of a bioartificial kidney: a universal donor organ.

    Science.gov (United States)

    Humes, H D

    1996-08-01

    Cell therapy and tissue engineering may well likely dominate medical therapeutics in the next century. Growing a functional glomerular filter and tubule reabsorber from a combination of cells, biomaterials, and synthetic polymers to replace renal excretory and regulatory functions is a specific example of these evolving technologies. The kidney was the first organ whose function was substituted by an artificial device. The kidney was also the first organ to be successfully transplanted. The ability to replace renal function with these revolutionary technologies in the past was due to the fact that renal excretory function is based on natural physical forces which govern solute and fluid movement from the body compartment to the external environment. The need for coordinated mechanical or electrical activities got renal substitution was not required. Accordingly, the kidney may well be the first organ to be available as a tissue-engineered implantable device as a fully functional replacement part for the human body. The prospects of a "universal donor" bioartificial kidney for the treatment of end-stage renal disease are clearly achievable as we approach the next millennium.

  10. En bloc prefabrication of vascularized bioartificial bone grafts in sheep and complete workflow for custom-made transplants.

    Science.gov (United States)

    Kokemüller, H; Jehn, P; Spalthoff, S; Essig, H; Tavassol, F; Schumann, P; Andreae, A; Nolte, I; Jagodzinski, M; Gellrich, N-C

    2014-02-01

    The aim of this pilot study was to determine, in a new experimental model, whether complex bioartificial monoblocs of relevant size and stability can be prefabricated in a defined three-dimensional design, in which the latissimus dorsi muscle serves as a natural bioreactor and the thoracodorsal vessel tree is prepared for axial construct perfusion. Eighteen sheep were included in the study, with six animals in each of three experimental groups. Vitalization of the β-tricalcium phosphate-based constructs was performed by direct application of unmodified osteogenic material from the iliac crest (group A), in vivo application of nucleated cell concentrate (NCC) from bone marrow aspirate (group B), and in vitro cultivation of bone marrow stromal cells (BMSC) in a perfusion bioreactor system (group C). The contours of the constructs were designed digitally and transferred onto the bioartificial bone grafts using a titanium cage, which was bent over a stereolithographic model of the defined subvolume intraoperatively. At the end of the prefabrication process, only the axial vascularized constructs of group A demonstrated vital bone formation with considerable stability. In groups B and C, the applied techniques were not able to induce ectopic bone formation. The presented computer-assisted workflow allows the prefabrication of custom-made bioartificial transplants.

  11. Motor endplate cholinesterase in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Fujii,Masafumi

    1982-08-01

    Full Text Available The activity and properties of cholinesterase (ChE of the motor endplate and its fractions were studied in isolated human skeletal muscle. This preparation was used since the ChE activity of the membrane preparation was localized only in the motor endplate. The endplate ChE was stable in the isolated membrane for 4 weeks at 4 degrees C. The specific activity of the extracted ChE of human muscle membrane was 29.6% higher than that of the original membrane. Studies with specific substrates and ChE inhibitors indicated that most of the ChE of human muscle membrane and its fractions was acetylcholinesterase, and that the minor component was pseudocholinesterase. A Michaelis-Menten constant of 3.82 mM was estimated in the endplate ChE, and 0.88 mM in the extracted ChE of the endplate. The extracted human endplate ChE was separated into three fractions by Sephadex G-200 chromatography, and into two fractions by acrylamide gel electrophoresis.

  12. Bioartificial liver systems: why, what, whither?

    Science.gov (United States)

    Gerlach, Jörg C; Zeilinger, Katrin; Patzer Ii, John F

    2008-07-01

    Acute liver disease is a life-threatening condition for which liver transplantation is the only recognized effective therapy. While etiology varies considerably, the clinical course of acute liver failure is common among the etiologies: encephalopathy progressing toward coma and multiple organ failure. Detoxification processes, such as molecular adsorbent recirculating system (MARS) and Prometheus, have had limited success in altering blood chemistries positively in clinical evaluations, but have not been shown to be clinically effective with regard to patient survival or other clinical outcomes in any Phase III prospective, randomized trial. Bioartificial liver systems, which use liver cells (hepatocytes) to provide metabolic support as well as detoxification, have shown promising results in early clinical evaluations, but again have not demonstrated clinical significance in any Phase III prospective, randomized trial. Cell transplantation therapy has had limited success but is not practicable for wide use owing to a lack of cells (whole-organ transplantation has priority). New approaches in regenerative medicine for treatment of liver disease need to be directed toward providing a functional cell source, expandable in large quantities, for use in various applications. To this end, a novel bioreactor design is described that closely mimics the native liver cell environment and is easily scaled from microscopic (<1 ml cells) to clinical ( approximately 600 ml cells) size, while maintaining the same local cell environment throughout the bioreactor. The bioreactor is used for study of primary liver cell isolates, liver-derived cell lines and stem/progenitor cells.

  13. Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver

    NARCIS (Netherlands)

    di Nicuolo, G.; D'Alessandro, A.; Andria, B.; Scuderi, V.; Scognamiglio, M.; Tammaro, A.; Mancini, A.; Cozzolino, S.; di Florio, E.; Bracco, A.; Calise, F.; Chamuleau, R.A.F.M.

    2010-01-01

    Background: Clinical use of porcine cell-based bioartificial liver (BAL) support in acute liver failure as bridging therapy for liver transplantation exposes the patient to the risk of transmission of porcine endogenous retroviruses (PERVs) to human. This risk may be enhanced when patients receive l

  14. Myofibre damage in human skeletal muscle

    DEFF Research Database (Denmark)

    Crameri, R M; Aagaard, P; Qvortrup, K

    2007-01-01

    Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation but not in hum......Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation...... but not in humans using voluntary exercise. Untrained males (n=8, range 22-27 years) performed 210 maximal eccentric contractions with each leg on an isokinetic dynamometer, voluntarily (VOL) with one leg and electrically induced (ES) with the other leg. Assessments from the skeletal muscle were obtained prior...... to exercise and at 5, 24, 96 and 192 h postexercise. Muscle tenderness rose in VOL and ES after 24 h, and did not differ between groups. Maximal isometric contraction strength, rate of force development and impulse declined in the VOL leg from 4 h after exercise, but not in ES (except at 24 h). In contrast...

  15. Challenges on the road to a multicellular bioartificial liver

    NARCIS (Netherlands)

    Starokozhko, Viktoriia; Groothuis, Geny M M

    2016-01-01

    Over the past years the progress in the development of a bioartificial liver (BAL) as an extracorporeal device or as a tissue engineered transplantable organ has been immense. However, many important BAL characteristics that are necessary to meet clinical demands, have not been sufficiently addresse

  16. Challenges on the road to a multicellular bioartificial liver

    NARCIS (Netherlands)

    Starokozhko, Viktoriia; Groothuis, Geny M M

    2016-01-01

    Over the past years the progress in the development of a bioartificial liver (BAL) as an extracorporeal device or as a tissue engineered transplantable organ has been immense. However, many important BAL characteristics that are necessary to meet clinical demands, have not been sufficiently

  17. Alleviating liver failure conditions using an integrated hybrid cryogel based cellular bioreactor as a bioartificial liver support

    Science.gov (United States)

    Damania, Apeksha; Hassan, Mohsin; Shirakigawa, Nana; Mizumoto, Hiroshi; Kumar, Anupam; Sarin, Shiv K.; Ijima, Hiroyuki; Kamihira, Masamichi; Kumar, Ashok

    2017-01-01

    Conventionally, some bioartificial liver devices are used with separate plasmapheresis unit to separate out plasma from whole blood and adsorbent column to detoxify plasma before it passes through a hepatocytes-laden bioreactor. We aim to develop a hybrid bioreactor that integrates the separate modules in one compact design improving the efficacy of the cryogel based bioreactor as a bioartificial liver support. A plasma separation membrane and an activated carbon cloth are placed over a HepG2-loaded cryogel scaffold in a three-chambered bioreactor design. This bioreactor is consequently connected extracorporeally to a rat model of acute liver failure for 3 h and major biochemical parameters studied. Bilirubin and aspartate transaminase showed a percentage decrease of 20–60% in the integrated bioreactor as opposed to 5–15% in the conventional setup. Urea and ammonia levels which showed negligible change in the conventional setup increase (40%) and decrease (18%), respectively in the integrated system. Also, an overall increase of 5% in human albumin in rat plasma indicated bioreactor functionality in terms of synthetic functions. These results were corroborated by offline evaluation of patient plasma. Hence, integrating the plasmapheresis and adsorbent units with the bioreactor module in one compact design improves the efficacy of the bioartificial liver device. PMID:28079174

  18. Glucose transporter expression in human skeletal muscle fibers

    DEFF Research Database (Denmark)

    Gaster, M; Handberg, A; Beck-Nielsen, H

    2000-01-01

    amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation......, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas...... after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle...

  19. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  20. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  1. Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.

    NARCIS (Netherlands)

    Serlie, M.J.; Haan, J.H.A. de; Tack, C.J.J.; Verberne, H.J.; Ackermans, M.T.; Heerschap, A.; Sauerwein, H.P.

    2005-01-01

    The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

  2. Molecular biology of human muscle disease

    Energy Technology Data Exchange (ETDEWEB)

    Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

    1991-01-01

    The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

  3. Regulation of Metabolic Signaling in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth

    Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic enz...... interval exercise). The abundance of signaling proteins and metabolic enzymes are in most cases different in type I and type II muscle fibers, indicating that their glucose metabolism is different.......Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic...... enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance...

  4. Xanthine oxidase in human skeletal muscle following eccentric exercise

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik; Orthenblad, N.

    1997-01-01

    1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one-legged eccentric exercise. Muscle biopsies from both the exercised and the ......1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one-legged eccentric exercise. Muscle biopsies from both the exercised...... the increase in xanthine oxidase in the muscle there were no detectable changes in the levels of muscle malondialdehyde or in plasma antioxidant capacity up to 4 days post-exercise. 5. It is concluded that eccentric exercise leads to an increased level of xanthine oxidase in human muscle and that the increase...

  5. The expression of HSP in human skeletal muscle. Effects of muscle fiber phenotype and training background

    DEFF Research Database (Denmark)

    Folkesson, Mattias; Mackey, Abigail L; Langberg, Henning;

    2013-01-01

    AIM: Exercise-induced adaptations of skeletal muscle are related to training mode and can be muscle fibre type specific. This study aimed to investigate heat shock protein expression in type I and type II muscle fibres in resting skeletal muscle of subjects with different training backgrounds...... HSPs in human skeletal muscle is influenced by muscle fibre phenotype. The fibre type specific expression of HSP70 is influenced by resistance and endurance training whereas those of αB-crystallin and HSP27 are influenced only by endurance training suggesting the existence of a training......-modality specific action on the adaptive processes including heat shock proteins in human skeletal muscle. This article is protected by copyright. All rights reserved....

  6. Localization of nitric oxide synthase in human skeletal muscle

    DEFF Research Database (Denmark)

    Frandsen, Ulrik; Lopez-Figueroa, M.; Hellsten, Ylva

    1996-01-01

    The present study investigated the cellular localization of the neuronal type I and endothelial type III nitric oxide synthase in human skeletal muscle. Type I NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all muscle fibres. Stronger immunoreactivity was expressed...... I NO synthase immunoreactivity and NADPH diaphorase activity. Type III NO synthase immunoreactivity was observed both in the endothelium of larger vessels and of microvessels. The results establish that human skeletal muscle expresses two different constitutive isoforms of NO synthase in different...... endothelium is consistent with a role for NO in the control of blood flow in human skeletal muscle....

  7. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

    Larsen, Steen; Wright-Paradis, C; Gnaiger, E

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain...... loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples....... functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...

  8. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

    Larsen, S; Wright-Paradis, C; Gnaiger, E

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain...... functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...... loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples....

  9. [(Bio)artificial liver support: ready for the patient?].

    Science.gov (United States)

    Chamuleau, R A F M

    2016-05-01

    In 2016, an intensive-care physician has at his disposal a number of artificial organs for the support of patients with organ failure. Examples are the artificial kidney and the heart-lung machine. Artificial livers are being developed for patients with severe liver failure whose lives can only be saved at the present time by a transplant with a donor liver. These artificial livers are based either on a device that removes toxic materials from the patient's blood with, for example, albumin dialysis, or make use of bio-reactors filled with functioning liver cells, the so-called bio-artificial liver. In theory, the bio-artificial liver has the greatest potential to increase life expectancy. The results of clinical studies are also very promising. They are not yet sufficient, however, to permit general clinical use.

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

    Science.gov (United States)

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

    2017-08-01

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

  11. Muscle fiber and motor unit behavior in the longest human skeletal muscle.

    Science.gov (United States)

    Harris, A John; Duxson, Marilyn J; Butler, Jane E; Hodges, Paul W; Taylor, Janet L; Gandevia, Simon C

    2005-09-14

    The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers.

  12. THE CAPILLARY PATTERN IN HUMAN MASSETER MUSCLE DURING AGEING

    Directory of Open Access Journals (Sweden)

    Erika Cvetko

    2013-10-01

    Full Text Available The effect of ageing on the capillary network in skeletal muscles has produced conflicting results in both, human and animals studies. Some of the inconsistencies are due to non-comparable and biased methods that were applied on thin transversal sections, especially in muscles with complicated morphological structures, such as in human masseter muscle. We present a new immunohistochemical method for staining capillaries and muscle fibres in 100 µm thick sections as well as novel approach to 3D visualization of capillaries and muscle fibres. Applying confocal microscopy and virtual 3D stereological grids, or tracing capillaries in virtual reality, length of capillaries within a muscle volume or length of capillaries adjacent to muscle fibre per fibre length, fibre surface or fibre volume were evaluated in masseter muscle of young and old subjects by an unbiased approach. Our findings show that anatomic capillarity is well maintained in masseter muscle in old subjects; however, vascular remodelling occurs with age, which could be a response to changed muscle function and age-related muscle fibre type transformations.

  13. Determination of human muscle protein fractional synthesis rate

    DEFF Research Database (Denmark)

    Bornø, Andreas; Hulston, Carl J; van Hall, Gerrit

    2014-01-01

    In the present study, different MS methods for the determination of human muscle protein fractional synthesis rate (FSR) using [ring-(13)C6 ]phenylalanine as a tracer were evaluated. Because the turnover rate of human skeletal muscle is slow, only minute quantities of the stable isotopically......-MS/MS) and GC-tandem MS (GC-MS/MS) have made these techniques an option for human muscle FSR measurements. Human muscle biopsies were freeze dried, cleaned, and hydrolyzed, and the amino acids derivatized using either N-acetyl-n-propyl, phenylisothiocyanate, or N.......89 ± 0.01, P muscle FSR, (2) LC-MS/MS comes quite close and is a good alternative when tissue quantities are too small for GC-C-IRMS, and (3) If GC-MS/MS is to be used, then the HFBA derivative should be used instead...

  14. Muscle fascicle strains in human gastrocnemius during backward downhill walking.

    Science.gov (United States)

    Hoffman, B W; Cresswell, A G; Carroll, T J; Lichtwark, G A

    2014-06-01

    Extensive muscle damage can be induced in isolated muscle preparations by performing a small number of stretches during muscle activation. While typically these fiber strains are large and occur over long lengths, the extent of exercise-induced muscle damage (EIMD) observed in humans is normally less even when multiple high-force lengthening actions are performed. This apparent discrepancy may be due to differences in muscle fiber and tendon dynamics in vivo; however, muscle and tendon strains have not been quantified during muscle-damaging exercise in humans. Ultrasound and an infrared motion analysis system were used to measure medial gastrocnemius fascicle length and lower limb kinematics while humans walked backward, downhill for 1 h (inducing muscle damage), and while they walked briefly forward on the flat (inducing no damage). Supramaximal tibial nerve stimulation, ultrasound, and an isokinetic dynamometer were used to quantify the fascicle length-torque relationship pre- and 2 h postexercise. Torque decreased ~23%, and optimal fascicle length shifted rightward ~10%, indicating that EIMD occurred during the damage protocol even though medial gastrocnemius fascicle stretch amplitude was relatively small (~18% of optimal fascicle length) and occurred predominantly within the ascending limb and plateau region of the length-torque curve. Furthermore, tendon contribution to overall muscle-tendon unit stretch was ~91%. The data suggest the compliant tendon plays a role in attenuating muscle fascicle strain during backward walking in humans, thus minimizing the extent of EIMD. As such, in situ or in vitro mechanisms of muscle damage may not be applicable to EIMD of the human gastrocnemius muscle. Copyright © 2014 the American Physiological Society.

  15. Molecular aging and rejuvenation of human muscle stem cells

    DEFF Research Database (Denmark)

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

    2009-01-01

    Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans....... Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular...

  16. Effect of flow on the detoxification function of rat hepatocytes in a bioartificial liver reactor.

    Science.gov (United States)

    Roy, P; Washizu, J; Tilles, A W; Yarmush, M L; Toner, M

    2001-01-01

    Ethoxyresorufin-o-deethylation (EROD) can be used as a sensitive measure of hepatic detoxification function. In this study, we employed a fluorescence assay based on EROD to study the effect of varying Peclet number (or flow) on hepatic function in a microchannel flat-plate bioartificial liver (BAL) reactor containing a coculture of hepatocytes and fibroblasts. Static culture and reactor flow experiments established that: 1) a pseudo-steady-state detoxification rate could be attained at each Peclet number, 2) the steady-state detoxification rate increased nonlinearly with Peclet number (ranging from 167 to 2500), 3) the uptake rate of substrate was a linear function of cell surface substrate concentration (reactor for human application.

  17. Tirasemtiv amplifies skeletal muscle response to nerve activation in humans

    OpenAIRE

    Hansen,Richard; Saikali, Khalil G; Chou, Willis; Alan J Russell; Chen, Michael M.; Vijayakumar, Vipin; Stoltz, Randall R.; Baudry, Stephane; Enoka, Roger M.; Morgans, David J; Wolff, Andrew A.; Malik, Fady I

    2014-01-01

    Introduction: In this study we tested the hypothesis that tirasemtiv, a selective fast skeletal muscle troponin activator that sensitizes the sarcomere to calcium, could amplify the response of muscle to neuromuscular input in humans. Methods: Healthy men received tirasemtiv and placebo in a randomized, double-blind, 4-period, crossover design. The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot. The force–freque...

  18. Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle

    DEFF Research Database (Denmark)

    Mounier, Rémi; Pedersen, Bente Klarlund; Plomgaard, Peter

    2010-01-01

    from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1...... a significantly higher VEGF protein content than vastus lateralis and triceps muscle. In conclusion, we have shown that there are muscle-specific differences in HIF-1alpha and VEGF expression within human skeletal muscle at rest in normoxic conditions. Recent results, when combined with the findings described...

  19. High efficiency in human muscle: an anomaly and an opportunity?

    Science.gov (United States)

    Nelson, Frank E; Ortega, Justus D; Jubrias, Sharon A; Conley, Kevin E; Kushmerick, Martin J

    2011-08-15

    Can human muscle be highly efficient in vivo? Animal muscles typically show contraction-coupling efficiencies FDI) muscle of the hand has an efficiency value in vivo of 68%. We examine two key factors that could account for this apparently high efficiency value: (1) transfer of cross-bridge work into mechanical work and (2) the use of elastic energy to do external work. Our analysis supports a high contractile efficiency reflective of nearly complete transfer of muscular to mechanical work with no contribution by recycling of elastic energy to mechanical work. Our survey of reported contraction-coupling efficiency values puts the FDI value higher than typical values found in small animals in vitro but within the range of values for human muscle in vivo. These high efficiency values support recent studies that suggest lower Ca(2+) cycling costs in working contractions and a decline in cost during repeated contractions. In the end, our analysis indicates that the FDI muscle may be exceptional in having an efficiency value on the higher end of that reported for human muscle. Thus, the FDI muscle may be an exception both in contraction-coupling efficiency and in Ca(2+) cycling costs, which makes it an ideal muscle model system offering prime conditions for studying the energetics of muscle contraction in vivo.

  20. Observational Study on the Occurrence of Muscle Spindles in Human Digastric and Mylohyoideus Muscles

    Directory of Open Access Journals (Sweden)

    Daniele Saverino

    2014-01-01

    Full Text Available Although the occurrence of muscle spindles (MS is quite high in most skeletal muscles of humans, few MS, or even absence, have been reported in digastric and mylohyoideus muscles. Even if this condition is generally accepted and quoted in many papers and books, observational studies are scarce and based on histological sections of a low number of specimens. The aim of the present study is to confirm previous data, assessing MS number in a sample of digastric and mylohyoideus muscles. We investigated 11 digastric and 6 mylohyoideus muscles from 13 donors. Muscle samples were embedded in paraffin wax, cross-sectioned in a rostrocaudal direction, and stained using haematoxylin-eosin. A mean of 5.1 ± 1.1 (range 3–7 MS was found in digastric muscles and mean of 0.5 ± 0.8 (range 0–2 in mylohyoideus muscles. A significant difference (P<0.001 was found with the control sample, confirming the correctness of the histological procedure. Our results support general belief that the absolute number of spindles is sparse in digastric and mylohyoideus muscles. External forces, such as food resistance during chewing or gravity, do not counteract jaw-opening muscles. It is conceivable that this condition gives them a limited proprioceptive importance and a reduced need for having specific receptors as MS.

  1. IMP metabolism in human skeletal muscle after exhaustive exercise

    DEFF Research Database (Denmark)

    Tullson, P. C.; Bangsbo, Jens; Hellsten, Ylva

    1995-01-01

    This study addressed whether AMP deaminase (AMPD)myosin binding occurs with deamination during intense exercise in humans and the extent of purine loss from muscle during the initial minutes of recovery. Male subjects performed cycle exercise (265 +/- 2 W for 4.39 +/- 0.04 min) to stimulate muscle...

  2. Regression of polyneural innervation in the human psoas muscle

    NARCIS (Netherlands)

    Gramsbergen, A; IjkemaPaassen, J; Nikkels, PGJ; HaddersAlgra, M

    1997-01-01

    During the early stages of mammalian ontogeny muscle fibres are innervated by more than one axon. This polyneural innervation is replaced by mononeural innervation in the course of development. The regression of polyneural innervation in the psoas muscle in the human is the topic of the present stud

  3. Reflex control of human jaw muscles.

    Science.gov (United States)

    Türker, Kemal S

    2002-01-01

    The aim of this review is to discuss what is known about the reflex control of the human masticatory system and to propose a method for standardized investigation. Literature regarding the current knowledge of activation of jaw muscles, receptors involved in the feedback control, and reflex pathways is discussed. The reflexes are discussed under the headings of the stimulation conditions. This was deliberately done to remind the reader that under each stimulation condition, several receptor systems are activated, and that it is not yet possible to stimulate only one afferent system in isolation in human mastication experiments. To achieve a method for uniform investigation, we need to set a method for stimulation of the afferent pathway under study with minimal simultaneous activation of other receptor systems. This stimulation should also be done in an efficient and reproducible way. To substantiate our conviction to standardize the stimulus type and parameters, we discuss the advantages and disadvantages of mechanical and electrical stimuli. For mechanical stimulus to be delivered in a reproducible way, the following precautions are suggested: The stimulus delivery system (often a probe attached to a vibrator) should be brought into secure contact with the area of stimulation. To minimize the slack between the probe, the area to be stimulated should be taken up by the application of pre-load, and the delivered force should be recorded in series. Electrical stimulus has advantages in that it can be delivered in a reproducible way, though its physiological relevance can be questioned. It is also necessary to standardize the method for recording and analyzing the responses of the motoneurons to the stimulation. For that, a new technique is introduced, and its advantages over the currently used methods are discussed. The new method can illustrate the synaptic potential that is induced in the motoneurons without the errors that are unavoidable in the current

  4. ATP economy of force maintenance in human tibialis anterior muscle

    DEFF Research Database (Denmark)

    Nakagawa, Yoshinao; Ratkevicius, Aivaras; Mizuno, Masao

    2005-01-01

    PURPOSE: The aim of this study was investigate ATP economy of force maintenance in the human tibialis anterior muscle during 60 s of anaerobic voluntary contraction at 50% of maximum voluntary contraction (MVC). METHODS: ATP turnover rate was evaluated using P magnetic resonance spectroscopy (P......-MRS). The total volume of ankle dorsiflexor muscles was assessed by H magnetic resonance imaging (MRI) (H-MRI), and the fiber type composition of the tibialis anterior muscle was evaluated using histochemical analysis of muscle biopsies. RESULTS: The tibialis anterior muscle occupied 59.7 +/- 0.6% (mean +/- SEM......) of the total ankle dorsiflexor muscle volume, which was 267 +/- 10 cm. Relative cross-sectional areas occupied by Type I, IIA, and IIB fibers in the tibialis anterior were 69.3 +/- 2.2, 27.4 +/- 2.76, and 3.2 +/- 1.0%, respectively. ATP economy of force maintenance did not change significantly during the 60-s...

  5. Detection of PERV by polymerase chain reaction and its safety in bioartificial liver support system

    Institute of Scientific and Technical Information of China (English)

    Hai-Hui Wang; Ying-Jie Wang; Hong-Ling Liu; Jun Liu; Yan-Ping Huang; Hai-Tao Guo; Yu-Ming Wang

    2006-01-01

    AIM: To establish a method detecting porcine endogenous retrovirus (PERV) in China experimental minipigs and to evaluate the safety of PERV in three individuals treated with bioartificial liver support systems based on porcine hepatocytes.METHODS: Porcine hepatocytes were isolated with two-stage perfusion method, then cultured in the bioreactor, which is separated by a semipermeable membrane (0.2μm) from the lumen through which the patients' blood plasma was circulated. After post-hemoperfusion, patients' blood was obtained for screening. Additionally, samples of medium collected from both intraluminal and extraluminal compartments of the laboratory bioreactor and culture supernate in vitro was analyzed. The presence of viral sequences was estimated by polymerase chain reaction (PCR) and reverse transcriptase-polymerase chain reaction (RT-PCR). Finally, the infection of virus in the supernate of common culture was ascertained by exposure to the fetal liver cells.RESULTS: PERV-specific gag sequences were found in the porcine hepatocytes using RT-PCR. and were detected in all samples from the intraluminal,extraluminal samples and culture supernate. However,culture supernatant from primary porcine hepatocytes (cleared of cellular debris) failed to infect human fetal liver cells. Finally, RT-PCR detected no PERV infection was found in the blood samples obtained from three patients at various times post-hemoperfusion.CONCLUSION: The assays used are specific and sensitive, identified by second PCR. PERVs could be released from hepatocytes cultured in bioreactor without the stimulation of mitogen and could not be prevented by the hollow fiber semipermeable membrane, indicating the existence of PERV safety in extracorporeal bioartificial liver support system (EBLSS).

  6. The intramuscular nerve supply of the human lateral cricoarytenoid muscle.

    Science.gov (United States)

    Sanders, I; Mu, L; Wu, B L; Biller, H F

    1993-09-01

    The lateral cricoarytenoid (LCA) muscle is one of the adductors of the vocal cords; however, some investigators believe that the lateral edge of the muscle may be involved in abduction. The possibility of functionally distinct compartments within the LCA was investigated by observing the pattern of the intramuscular nerve supply. This technique has previously clearly demonstrated neural compartments in the posterior cricoarytenoid, thyroarytenoid and cricothyroid muscles. Five adult human larynges were processed by the Sihler's stain which clears all soft tissue while counterstaining the nerves. The results of our study showed that the innervation pattern of the human LCA muscle is composed of a homogenous nerve plexus localized to the middle region of the muscle. This pattern correlates with the location of motor endplates described by prior investigators. The consistent neural pattern suggests that the LCA is composed of a single neuromuscular compartment.

  7. Afferent contribution to locomotor muscle activity during unconstrained overground human walking: an analysis of triceps surae muscle fascicles

    DEFF Research Database (Denmark)

    Klint, Richard af; Cronin, Neil J.; Ishikawa, Masaki

    2010-01-01

    Plantar flexor series elasticity can be used to dissociate muscle fascicle and muscle tendon behaviour and, therefore, afferent feedback during human walking. We used electromyography (EMG) and high speed ultrasonography concomitantly to monitor muscle activity and muscle fascicle behaviour in ni...

  8. Decellularized Human Skeletal Muscle as Biologic Scaffold for Reconstructive Surgery

    Directory of Open Access Journals (Sweden)

    Andrea Porzionato

    2015-07-01

    Full Text Available Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin-EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation.

  9. Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles

    Directory of Open Access Journals (Sweden)

    Xiaoti Xu

    2015-09-01

    Full Text Available Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2–4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50–70 fiber-associated, or 1,000–5,000 FACS-enriched CD56+/CD29+ human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications.

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

    Science.gov (United States)

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

    2011-11-01

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

  11. Morphology of muscle attachment sites in the modern human hand does not reflect muscle architecture.

    Science.gov (United States)

    Williams-Hatala, E M; Hatala, K G; Hiles, S; Rabey, K N

    2016-06-23

    Muscle attachment sites (entheses) on dry bones are regularly used by paleontologists to infer soft tissue anatomy and to reconstruct behaviors of extinct organisms. This method is commonly applied to fossil hominin hand bones to assess their abilities to participate in Paleolithic stone tool behaviors. Little is known, however, about how or even whether muscle anatomy and activity regimes influence the morphologies of their entheses, especially in the hand. Using the opponens muscles from a sample of modern humans, we tested the hypothesis that aspects of hand muscle architecture that are known to be influenced by behavior correlate with the size and shape of their associated entheses. Results show no consistent relationships between these behaviorally-influenced aspects of muscle architecture and entheseal morphology. Consequently, it is likely premature to infer patterns of behavior, such as stone tool making in fossil hominins, from these same entheses.

  12. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Søren; Scheele, Camilla; Yfanti, Christina;

    2010-01-01

    of all four myomiRs (P training expression levels 14 days after ceasing the training programme. Components of major pathways involved in endurance adaptation such as MAPK and TGF-ß were predicted to be targeted by the myomiRs examined. Tested......, but their role in regulating human skeletal muscle adaptation remains unknown.......Muscle specific miRNAs, myomiRs, have been shown to control muscle development in vitro and are differentially expressed at rest in diabetic skeletal muscle. Therefore, we investigated the expression of these myomiRs, including miR-1, miR-133a, miR-133b and miR-206 in muscle biopsies from vastus...

  13. Effect of exercise on insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Mikines, K J; Galbo, Henrik

    1989-01-01

    The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization was perfo...... recovery of human skeletal muscle.......The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

  14. Tissue engineering skeletal muscle for orthopaedic applications

    Science.gov (United States)

    Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

    2002-01-01

    With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

  15. Intramuscular architecture of the autochthonous back muscles in humans.

    Science.gov (United States)

    Stark, Heiko; Fröber, Rosemarie; Schilling, Nadja

    2013-02-01

    Many training concepts take muscle properties such as contraction speed or muscle topography into account to achieve an optimal training outcome. Thus far, the internal architecture of muscles has largely been neglected, although it is well known that parameters such as pennation angles or the lengths of fascicles but also the proportions of fleshy and tendinous fascicle parts have a major impact on the contraction behaviour of a muscle. Here, we present the most detailed description of the intramuscular fascicle architecture of the human perivertebral muscles available so far. For this, one adult male cadaver was studied. Our general approach was to digitize the geometry of each fascicle of the muscles of back proper (Erector spinae) - the Spinalis thoracis, Iliocostalis lumborum, Longissimus thoracis and the Multifidus thoracis et lumborum - and of the deep muscles of the abdomen - Psoas minor, Psoas major and Quadratus lumborum - during a layerwise dissection. Architectural parameters such as fascicle angles to the sagittal and the frontal planes as well as fascicle lengths were determined for each fascicle, and are discussed regarding their consequences for the function of the muscle. For example, compared with the other dorsovertebral muscles, the Longissimus thoracis can produce greater shortening distances because of its relatively long fleshy portions, and it can store more elastic energy due to both its relatively long fleshy and tendinous fascicle portions. The Quadratus lumborum was outstanding because of its many architectural subunits defined by distinct attachment sites and fascicle lengths. The presented database will improve biomechanical models of the human trunk by allowing the incorporation of anisotropic muscle properties such as the fascicle direction into finite element models. This information will help to increase our understanding of the functionality of the human back musculature, and may thereby improve future training concepts.

  16. Shared muscle synergies in human walking and cycling.

    Science.gov (United States)

    Barroso, Filipe O; Torricelli, Diego; Moreno, Juan C; Taylor, Julian; Gomez-Soriano, Julio; Bravo-Esteban, Elisabeth; Piazza, Stefano; Santos, Cristina; Pons, José L

    2014-10-15

    The motor system may rely on a modular organization (muscle synergies activated in time) to execute different tasks. We investigated the common control features of walking and cycling in healthy humans from the perspective of muscle synergies. Three hypotheses were tested: 1) muscle synergies extracted from walking trials are similar to those extracted during cycling; 2) muscle synergies extracted from one of these motor tasks can be used to mathematically reconstruct the electromyographic (EMG) patterns of the other task; 3) muscle synergies of cycling can result from merging synergies of walking. A secondary objective was to identify the speed (and cadence) at which higher similarities emerged. EMG activity from eight muscles of the dominant leg was recorded in eight healthy subjects during walking and cycling at four matched cadences. A factorization technique [nonnegative matrix factorization (NNMF)] was applied to extract individual muscle synergy vectors and the respective activation coefficients behind the global muscular activity of each condition. Results corroborated hypotheses 2 and 3, showing that 1) four synergies from walking and cycling can successfully explain most of the EMG variability of cycling and walking, respectively, and 2) two of four synergies from walking appear to merge together to reconstruct one individual synergy of cycling, with best reconstruction values found for higher speeds. Direct comparison of the muscle synergy vectors of walking and the muscle synergy vectors of cycling (hypothesis 1) produced moderated values of similarity. This study provides supporting evidence for the hypothesis that cycling and walking share common neuromuscular mechanisms.

  17. Preliminary observations on the microarchitecture of the human abdominal muscles.

    Science.gov (United States)

    Woodley, Stephanie J; Duxson, Marilyn J; Mercer, Susan R

    2007-10-01

    Precise knowledge of muscle architecture and innervation patterns is essential for the development of accurate clinical and biomechanical models. Although the gross anatomy of the human abdominal muscles has been investigated, the finer details of their microanatomy are not well described. Fascicles were systematically sampled from each of the human abdominal muscles, and small fiber bundles from selected fascicles stained with acetylcholinesterase to determine the location of motor endplate bands, myomyonal junctions, and myotendinous junctions. Statistical analysis was used to ascertain the association between fascicular length and number of endplate bands. The number of endplate bands along a fascicle was variable between different portions of each muscle, but was strongly correlated with fascicular length (r = 0.814). In fascicles less than 50 millimeters (mm) in length, only a single endplate band was generally present, while multiple endplate bands (usually two or three) were found in fascicles longer than 50 mm. The presence of myomyonal junctions throughout the longer (>50 mm) fascicles verified that they were composed of short, intrafascicularly terminating fibers, while shorter fascicles comprised fibers spanning the entire fascicular length. This preliminary study provides evidence that multiple endplate bands are contained in some regions of the abdominal muscles, an arrangement that differs from most human appendicular muscles. It is not clear whether the variations in the described fine architectural features reflect regional differences in muscle function.

  18. Expiratory muscle loading increases intercostal muscle blood flow during leg exercise in healthy humans

    Science.gov (United States)

    Athanasopoulos, Dimitris; Louvaris, Zafeiris; Cherouveim, Evgenia; Andrianopoulos, Vasilis; Roussos, Charis; Zakynthinos, Spyros

    2010-01-01

    We investigated whether expiratory muscle loading induced by the application of expiratory flow limitation (EFL) during exercise in healthy subjects causes a reduction in quadriceps muscle blood flow in favor of the blood flow to the intercostal muscles. We hypothesized that, during exercise with EFL quadriceps muscle blood flow would be reduced, whereas intercostal muscle blood flow would be increased compared with exercise without EFL. We initially performed an incremental exercise test on eight healthy male subjects with a Starling resistor in the expiratory line limiting expiratory flow to ∼ 1 l/s to determine peak EFL exercise workload. On a different day, two constant-load exercise trials were performed in a balanced ordering sequence, during which subjects exercised with or without EFL at peak EFL exercise workload for 6 min. Intercostal (probe over the 7th intercostal space) and vastus lateralis muscle blood flow index (BFI) was calculated by near-infrared spectroscopy using indocyanine green, whereas cardiac output (CO) was measured by an impedance cardiography technique. At exercise termination, CO and stroke volume were not significantly different during exercise, with or without EFL (CO: 16.5 vs. 15.2 l/min, stroke volume: 104 vs. 107 ml/beat). Quadriceps muscle BFI during exercise with EFL (5.4 nM/s) was significantly (P = 0.043) lower compared with exercise without EFL (7.6 nM/s), whereas intercostal muscle BFI during exercise with EFL (3.5 nM/s) was significantly (P = 0.021) greater compared with that recorded during control exercise (0.4 nM/s). In conclusion, increased respiratory muscle loading during exercise in healthy humans causes an increase in blood flow to the intercostal muscles and a concomitant decrease in quadriceps muscle blood flow. PMID:20507965

  19. Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

    Science.gov (United States)

    Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

    2016-07-01

    Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies

  20. Development of bioartificial myocardium using stem cells and nanobiotechnology templates.

    Science.gov (United States)

    Chachques, Juan Carlos

    2010-12-29

    Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The development of a bioartificial myocardium is a new challenge; in this approach, tissue-engineered procedures are associated with cell therapy. Organ decellularization for bioscaffolds fabrication is a new investigated concept. Nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/administration properties. Investigating the electrophysiological properties of bioartificial myocardium is the challenging objective of future research, associating a multielectrode network to provide electrical stimulation could improve the coupling of grafted cells and scaffolds with host cardiomyocytes. In summary, until now stem cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases. Supported by relevant scientific background, the development of myocardial tissue engineering may constitute a new avenue and hope for the treatment of myocardial diseases.

  1. Development of Bioartificial Myocardium Using Stem Cells and Nanobiotechnology Templates

    Directory of Open Access Journals (Sweden)

    Juan Carlos Chachques

    2011-01-01

    Full Text Available Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The development of a bioartificial myocardium is a new challenge; in this approach, tissue-engineered procedures are associated with cell therapy. Organ decellularization for bioscaffolds fabrication is a new investigated concept. Nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/administration properties. Investigating the electrophysiological properties of bioartificial myocardium is the challenging objective of future research, associating a multielectrode network to provide electrical stimulation could improve the coupling of grafted cells and scaffolds with host cardiomyocytes. In summary, until now stem cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases. Supported by relevant scientific background, the development of myocardial tissue engineering may constitute a new avenue and hope for the treatment of myocardial diseases.

  2. Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass.

    Science.gov (United States)

    Râdegran, G; Blomstrand, E; Saltin, B

    1999-12-01

    The knee extensor exercise model was specifically developed to enable in vivo estimates of peak muscle blood flow and O(2) uptake in humans. The original finding, using thermodilution measurements to measure blood flow in relation to muscle mass [P. Andersen and B. Saltin. J. Physiol. (Lond.) 366: 233-249, 1985], was questioned, however, as the measurements were two- to threefold higher than those previously obtained with the (133)Xe clearance and the plethysmography technique. As thermodilution measurements have now been confirmed by other methods and independent research groups, we aimed to address the impact of muscle mass estimates on the peak values of muscle perfusion and O(2) uptake. In the present study, knee extensor volume was determined from multiple measurements with computer tomography along the full length of the muscle. In nine healthy humans, quadriceps muscle volume was 2.36 +/- 0.17 (range 1. 31-3.27) liters, corresponding to 2.48 +/- 0.18 (range 1.37-3.43) kg. Anthropometry overestimated the muscle volume by approximately 21-46%, depending on whether quadriceps muscle length was estimated from the patella to either the pubic bone, inguinal ligament, or spina iliaca anterior superior. One-legged, dynamic knee extensor exercise up to peak effort of 67 +/- 7 (range 55-100) W rendered peak values for leg blood flow (thermodilution) of 5.99 +/- 0.66 (range 4.15-9.52) l/min and leg O(2) uptake of 856 +/- 109 (range 590-1,521) ml/min. Muscle perfusion and O(2) uptake reached peak values of 246 +/- 24 (range 149-373) and 35.2 +/- 3.7 (range 22.6-59. 6) ml. min(-1). 100 g muscle(-1), respectively. These peak values are approximately 19-33% larger than those attained by applying anthropometric muscle mass estimates. In conclusion, the present findings emphasize that peak perfusion and O(2) uptake in human skeletal muscle may be up to approximately 30% higher than previous anthropometric-based estimates that use equivalent techniques for blood flow

  3. Increased Plin2 Expression in Human Skeletal Muscle Is Associated with Sarcopenia and Muscle Weakness

    Science.gov (United States)

    Conte, Maria; Vasuri, Francesco; Trisolino, Giovanni; Bellavista, Elena; Santoro, Aurelia; Degiovanni, Alessio; Martucci, Ermanno; D’Errico-Grigioni, Antonia; Caporossi, Daniela; Capri, Miriam; Maier, Andrea B.; Seynnes, Olivier; Barberi, Laura; Musarò, Antonio; Narici, Marco V.; Franceschi, Claudio; Salvioli, Stefano

    2013-01-01

    Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL) muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength. PMID:23977392

  4. Increased Plin2 expression in human skeletal muscle is associated with sarcopenia and muscle weakness.

    Directory of Open Access Journals (Sweden)

    Maria Conte

    Full Text Available Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2. It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength.

  5. Regenerating human muscle fibres express GLUT3 protein

    DEFF Research Database (Denmark)

    Gaster, M; Beck-Nielsen, H; Schrøder, H D

    2002-01-01

    The presence of the GLUT3 glucose transporter protein in human muscle cells is a matter of debate. The present study was designed to establish whether GLUT3 is expressed in mature human skeletal muscle fibres and, if so, whether its expression changes under different conditions, such as metabolic...... stress (obesity, obese non-insulin-dependent diabetes mellitus), hypertrophy (training), de- and reinnervation (amyotrophic lateral sclerosis) or regeneration (polymyositis). We used an immunohistochemical approach to detect and localise GLUT3. GLUT3 immunoreactivity was not detectable in adult skeletal...... muscle fibres, nor did metabolic stress, training or de- and re-innervation induce GLUT3 expression, while a few GLUT3 expressing fibres were seen in some cases of polymyositis. In contrast, GLUT4 was expressed in all investigated muscle fibres. GLUT3 immunoreactivity was found in perineural...

  6. Glutamine attenuates post-traumatic glutathione depletion in human muscle.

    Science.gov (United States)

    Fläring, U B; Rooyackers, O E; Wernerman, J; Hammarqvist, F

    2003-03-01

    Glutathione is quantitatively the most important endogenous scavenger system. Glutathione depletion in skeletal muscle is pronounced following major trauma and sepsis in intensive care unit patients. Also, following elective surgery, glutathione depletion occurs in parallel with a progressive decline in muscle glutamine concentration. The present study was designed to test the hypothesis that glutamine supplementation may counteract glutathione depletion in a human trauma model. A homogeneous group of patients (n = 17) undergoing a standardized surgical procedure were prospectively randomly allocated to receive glutamine (0.56 g x day(-1) x kg(-1)) or placebo as part of isonitrogenous and isocaloric nutrition. Percutaneous muscle biopsies and blood samples were taken pre-operatively and at 24 and 72 h after surgery. The concentrations of muscle glutathione and related amino acids were determined in muscle tissue and plasma. In the control (unsupplemented) subjects, total muscle glutathione had decreased by 47+/-8% and 37+/-11% and reduced glutathione had decreased by 53+/-10% and 45+/-16% respectively at 24 and 72 h after surgery (P glutamine supplementation attenuates glutathione depletion in skeletal muscle in humans following standardized surgical trauma.

  7. Myosin Heavy Chain Composition of the Human Genioglossus Muscle

    Science.gov (United States)

    Daugherty, Megan; Luo, Qingwei; Sokoloff, Alan J.

    2012-01-01

    Background: The human tongue muscle genioglossus (GG) is active in speech, swallowing, respiration, and oral transport, behaviors encompassing a wide range of tongue shapes and movement speeds. Studies demonstrate substantial diversity in patterns of human GG motor unit activation, but whether this is accompanied by complex expression of muscle…

  8. Myosin Heavy Chain Composition of the Human Genioglossus Muscle

    Science.gov (United States)

    Daugherty, Megan; Luo, Qingwei; Sokoloff, Alan J.

    2012-01-01

    Background: The human tongue muscle genioglossus (GG) is active in speech, swallowing, respiration, and oral transport, behaviors encompassing a wide range of tongue shapes and movement speeds. Studies demonstrate substantial diversity in patterns of human GG motor unit activation, but whether this is accompanied by complex expression of muscle…

  9. Human muscle proteins: analysis by two-dimensional electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Giometti, C.S.; Danon, M.J.; Anderson, N.G.

    1983-09-01

    Proteins from single frozen sections of human muscle were separated by two-dimensional gel electrophoresis and detected by fluorography or Coomassie Blue staining. The major proteins were identical in different normal muscles obtained from either sex at different ages, and in Duchenne and myotonic dystrophy samples. Congenital myopathy denervation atrophy, polymyositis, and Becker's muscular dystrophy samples, however, showed abnormal myosin light chain compositions, some with a decrease of fast-fiber myosin light chains and others with a decrease of slow-fiber light chains. These protein alterations did not correlate with any specific disease, and may be cause by generalized muscle-fiber damage.

  10. Cyclooxygenase products sensitize muscle mechanoreceptors in humans with heart failure.

    Science.gov (United States)

    Middlekauff, Holly R; Chiu, Josephine; Hamilton, Michele A; Fonarow, Gregg C; Maclellan, W Robb; Hage, Antoine; Moriguchi, Jaime; Patel, Jignesh

    2008-04-01

    Prior work in animals and humans suggests that muscle mechanoreceptor control of sympathetic activation [muscle sympathetic nerve activity (MSNA)] during exercise in heart failure (HF) patients is heightened compared with that of healthy humans and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether cyclooxygenase products and/or endogenous adenosine, two metabolites of ischemic exercise, sensitize muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in HF patients. Indomethacin, which inhibits the production of prostaglandins, and saline control were infused in 12 HF patients. In a different protocol, aminophylline, which inhibits adenosine receptors, and saline control were infused in 12 different HF patients. MSNA was recorded (microneurography). During exercise following saline, MSNA increased in the first minute of exercise, consistent with baseline heightened mechanoreceptor sensitivity. MSNA continued to increase during 3 min of RHG, indicative that muscle mechanoreceptors are sensitized by ischemia metabolites. Indomethacin, but not aminophylline, markedly attenuated the increase in MSNA during the entire 3 min of low-level rhythmic exercise, consistent with the sensitization of muscle mechanoreceptors by cyclooxygenase products. Interestingly, even the early increase in MSNA was abolished by indomethacin infusion, indicative of the very early generation of cyclooxygenase products after the onset of exercise in HF patients. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in HF. Cyclooxygenase products, but not endogenous adenosine, play a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli, which also appears to be mediated by the early generation of cyclooxygenase products, resulting in exaggerated early increases in MSNA.

  11. Signaling pathways in failing human heart muscle cells.

    Science.gov (United States)

    Drexler, H; Hasenfuss, G; Holubarsch, C

    1997-07-01

    Experimental studies have delineated important signaling pathways in cardiomyocytes and their alterations in heart failure; however, there is now evidence that these observations are not necessarily applicable to human cardiac muscle cells. For example, angiotensin II (A II) does not exert positive inotropic effects in human ventricular muscle cells, in contrast to observation in rats. Thus, it is important to elucidate cardiac signaling pathways in humans in order to appreciate the functional role of neurohumoral or mechanical stimulation in human myocardium in health and disease. In the present article, we review signal pathways in the failing human heart based on studies in human cardiac tissues and in vivo physiological studies related to A II, nitric oxide, and β-adrenergic stimulation. (Trends Cardiovasc Med 1997; 7:151-160). © 1997, Elsevier Science Inc.

  12. 人骨髓干细胞在中空纤维滤器中诱导分化构建生物人工肝反应器的可行性研究%Construction of a novel bioreactor of bioartificial liver system with human bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    朱章华; 仇毓东; 施晓雷; 谢婷; 丁义涛

    2010-01-01

    目的 探讨以人骨髓干细胞在中空纤维滤器中直接扩增并诱导分化为类肝细胞,从而直接构建成生物人工肝反应器的可行性. 方法 取志愿者骨髓血,人骨髓间充质干细胞分离、扩增至107数量级后种植入中空纤维滤器,继续培养扩增10 d后,以含重组人肝细胞生长因子(rhHGF)、重组人碱性成纤维细胞生长因子4(rhFGF-4)、重组人制瘤素M(rhOSM)等细胞因子的培养液诱导分化,检测培养上清液中白蛋白、甲胎蛋白(AFP)水平;诱导18 d后检测氨代谢、安定代谢及尿素合成等功能.培养结束后以流式细胞仪检测消化滤器内细胞白蛋白表达率.培养全过程监测滤器内培养液葡萄糖浓度变化. 结果 ①扩增培养期人骨髓间充质干细胞在中空纤维滤器内种植后的葡萄糖摄取量呈进行性升高,在诱导分化期保持相对平稳,诱导培养结束时细胞总数达109数量级.②进行诱导培养后6 d,培养上清液中出现AFP,12 d达到峰值;9 d出现白蛋白并持续进行性升高;诱导培养18 d时,滤器内细胞总体氨清除速率为2.0~2.7 mmol/24 h,尿素产生速率为1.8~2.2 mmol/24 h,安定清除速率为3.2~3.8 mg/24 h.③21 d滤器内细胞白蛋白表达率为66.18%~76.91%. 结论 人骨髓干细胞可在中空纤维滤器内扩增,并分化为肝细胞样细胞,成为具有一定功能的生物人工肝反应器.%Objective To design a novel bioreactor of bioartificial liver system by using expanded and differentiated human bone marrow mesenchymal stem cells(hBMMSCs) as active cells. Methods hBMMSCs were isolated from bone marrow of volunteers and grown to 107 population,and then replanted into hollow fiber cartridge to expand continuously for 10 days.They were incubated in differentiation medium containing recombinant human hepatocyte growth factor(rhHGF),recombinant human fibroblast growth factor 4(rhFGF-4),recombinant human oncostatin M(rhOSM),and the cells were induced

  13. A 3-Dimensional Atlas of Human Tongue Muscles

    Science.gov (United States)

    SANDERS, IRA; MU, LIANCAI

    2013-01-01

    The human tongue is one of the most important yet least understood structures of the body. One reason for the relative lack of research on the human tongue is its complex anatomy. This is a real barrier to investigators as there are few anatomical resources in the literature that show this complex anatomy clearly. As a result, the diagnosis and treatment of tongue disorders lags behind that for other structures of the head and neck. This report intended to fill this gap by displaying the tongue’s anatomy in multiple ways. The primary material used in this study was serial axial images of the male and female human tongue from the Visible Human (VH) Project of the National Library of Medicine. In addition, thick serial coronal sections of three human tongues were rendered translucent. The VH axial images were computer reconstructed into serial coronal sections and each tongue muscle was outlined. These outlines were used to construct a 3-dimensional computer model of the tongue that allows each muscle to be seen in its in vivo anatomical position. The thick coronal sections supplement the 3-D model by showing details of the complex interweaving of tongue muscles throughout the tongue. The graphics are perhaps the clearest guide to date to aid clinical or basic science investigators in identifying each tongue muscle in any part of the human tongue. PMID:23650264

  14. A three-dimensional atlas of human tongue muscles.

    Science.gov (United States)

    Sanders, Ira; Mu, Liancai

    2013-07-01

    The human tongue is one of the most important yet least understood structures of the body. One reason for the relative lack of research on the human tongue is its complex anatomy. This is a real barrier to investigators as there are few anatomical resources in the literature that show this complex anatomy clearly. As a result, the diagnosis and treatment of tongue disorders lags behind that for other structures of the head and neck. This report intended to fill this gap by displaying the tongue's anatomy in multiple ways. The primary material used in this study was serial axial images of the male and female human tongue from the Visible Human (VH) Project of the National Library of Medicine. In addition, thick serial coronal sections of three human tongues were rendered translucent. The VH axial images were computer reconstructed into serial coronal sections and each tongue muscle was outlined. These outlines were used to construct a three-dimensional (3D) computer model of the tongue that allows each muscle to be seen in its in vivo anatomical position. The thick coronal sections supplement the 3D model by showing details of the complex interweaving of tongue muscles throughout the tongue. The graphics are perhaps the clearest guide to date to aid clinical or basic science investigators in identifying each tongue muscle in any part of the human tongue.

  15. Development of digastric muscles in human fetuses: a review and findings in the flexor digitorum superficialis muscle.

    Science.gov (United States)

    Rodríguez-Vázquez, José Francisco; Jin, Zhe Wu; Zhao, Peng; Murakami, Gen; Li, Xiang Wu; Jin, Yu

    2017-09-04

    The digastricus and omohyoideus muscles are digastric muscles with two muscle bellies. An insertion tendon of the posterior belly becomes an intermediate tendon in digastricus muscles, whereas a single band-like muscle in omohyoideus muscles may later be interrupted by an intermediate tendon, possibly due to muscle cell death caused by mechanical stress. In human fetuses, an intermediate tendon provides the temporal origins of the tensor veli palatini and tensor tympani muscles. Some reptiles, including snakes, carry multiple series of digastric-like axial muscles, in which each intersegmental septum is likely to become an intermediate tendon. These findings indicate that many pathways are involved in the development of digastric muscles. A review of these morphologies suggested that the flexor digitorum superficialis (FDS) muscle was a digastric muscle, although the intermediate tendon may not be visible in the surface view in adults. The present observations support the hypothesis that the proximal anlage at the elbow develops into a deep muscle slip to a limited finger, while the distal anlage at the wrist develops into the other slips. The findings suggest that, in the FDS muscle, the proximal and distal bellies of the embryonic digastric muscle fuse together to form a laminar structure, in which muscle slips accumulate from the palmar to the deep side of the forearm.

  16. 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...... at time points 0, 3 and 6 h in these individuals and in resting controls. Affymetrix microarray analysis of gene expression changes in skeletal muscle biopsies identified a small set of genes changed by IL-6 infusion. RT-PCR validation confirmed that S100A8 and S100A9 mRNA were up-regulated 3-fold...... 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...

  17. Robotic Powered Transfer Mechanism modeling on Human Muscle Structure

    Science.gov (United States)

    Saito, Yukio

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

  18. Duchenne Muscular Dystrophy Gene Expression in Normal and Diseased Human Muscle

    Science.gov (United States)

    Oronzi Scott, M.; Sylvester, J. E.; Heiman-Patterson, T.; Shi, Y.-J.; Fieles, W.; Stedman, H.; Burghes, A.; Ray, P.; Worton, R.; Fischbeck, K. H.

    1988-03-01

    A probe for the 5' end of the Duchenne muscular dystrophy (DMD) gene was used to study expression of the gene in normal human muscle, myogenic cell cultures, and muscle from patients with DMD. Expression was found in RNA from normal fetal muscle, adult cardiac and skeletal muscle, and cultured muscle after myoblast fusion. In DMD muscle, expression of this portion of the gene was also revealed by in situ RNA hybridization, particularly in regenerating muscle fibers.

  19. Training affects muscle phospholipid fatty acid composition in humans

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Wu, B J; Willer, Mette

    2001-01-01

    Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect...... on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk......, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 +/- 0.5% and 3.2 +/- 0.4% of total fatty acids, respectively) than the untrained leg (8.8 +/- 0.5% and 2.6 +/- 0.4%, P

  20. Relationship between Human Aging Muscle and Oxidative System Pathway

    Directory of Open Access Journals (Sweden)

    Enrico Doria

    2012-01-01

    Full Text Available Ageing is a complex process that in muscle is usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia. This inevitable biological process is characterized by a general decline in the physiological and biochemical functions of the major systems. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS generated by the addition of a single electron to the oxygen molecule. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fibre composition, muscle type, and function.

  1. Exercise-induced metallothionein expression in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Pernille; Keller, Charlotte;

    2005-01-01

    in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

  2. Adaptability of elderly human muscles and tendons to increased loading.

    Science.gov (United States)

    Narici, Marco V; Maganaris, Constantinos N

    2006-04-01

    Senile sarcopenia, the loss of muscle mass associated with aging, is one of the main causes of muscle weakness and reduced locomotor ability in old age. Although this condition is mainly driven by neuropathic processes, nutritional, hormonal and immunological factors, as well as a reduction in physical activity, contribute to this phenomenon. Sarcopenia alone, however, does not fully account for the observed muscle weakness, as the loss of force is greater than that accounted for by the decrease in muscle size. As a consequence, a reduction in the force per unit area, both at single fibre and at whole muscle level, is observed. We recently suggested that at whole muscle level, this reduction in intrinsic force is the result of the combined effect of changes in (1) muscle architecture, (2) tendon mechanical properties, (3) neural drive (reduced agonist and increased antagonist muscle activity) and (4) single fibre-specific tension. Whereas several studies support the role of the last two factors in the loss of intrinsic muscle force with aging, alterations in muscle architecture and in tendon mechanical properties have also been shown to contribute to the above phenomenon. Indeed, sarcopenia of the human plantarflexors, represented by a 25% reduction in muscle volume, was found to be associated with a 10% reduction in fibre fascicle length and 13% reduction in pennation angle. These architectural alterations were accompanied by a 10% decrease in tendon stiffness, attributable to alterations in tendon material properties, as suggested by a 14% decrease in Young's modulus. Most of these changes may be reversed by 14 weeks of resistive training; both fibre fascicle length and tendon stiffness were found to be increased by 10 and 64%, respectively. Surprisingly, however, training had no effect on the estimated relative length-tension properties of the muscle, indicating that the effects of greater tendon stiffness and increased fascicle length cancelled out each other

  3. Development of the stapedius muscle and pyramidal eminence in humans.

    Science.gov (United States)

    Rodríguez-Vázquez, J F

    2009-09-01

    The aim of the study was to systematize the key developmental phases of the stapedius muscle and the pyramidal eminence to clarify their formation, as well as to understand the variations and anomalies that can affect these structures. Sixty human embryos and fetuses between 38 days and 17 weeks of development were studied. The stapedius muscle is formed by two anlagen, one for the tendon, which derives from the internal segment of the interhyale, and another for the belly, located in the second pharyngeal arch medial to the facial nerve and near the interhyale but forming a completely independent anlage. In the interhyale, two segments were differentiated, these forming an angle; at the vertex, the belly of the stapedius muscle is attached. The internal segment is located from the attachment of the belly of the stapedius muscle to the anlage of the stapes, forming the anlage of the tendon of the stapedius muscle. The external segment completely disappears at the beginning of the fetal period. The pyramidal eminence is formed by an anlage independent of Reichert's cartilage, from the mesenchymal tissue of the tympanic cavity, which condenses around the belly of the stapedius muscle from 12 weeks of post-conception development. The length of the tendon of the stapedius muscle in adults varies, depending on the attachment site of the belly of the stapedius muscle in the interhyale, which would determine the length of the internal segment (anlage of the tendon) and consequently the tendon length. This variation depends on the greater or lesser persistence of the angulation observed during development, between the tendon and the belly of the stapedius muscle.

  4. Construction of devices in bioartificial liver support system.

    Science.gov (United States)

    Liu, Jianfeng; Li, Ming; Yang, Wei; Lou, Hanfen

    2005-01-01

    An automatic control device in Bioartificial Liver Support System is designed and implemented. Details of the hardware structure, design of the control system and the applied software in the device are described. Main controller uses the WS-843AW industrial control computer; precision electromagnetic valves are selected as implements to control the flux of three-gases (oxygen, carbon dioxide and nitrogen). The interconnected rule of controlled parameters in the system is analysed, and then matched by the mass balance equation. By a series of logic judgements of signals from sensors and direct digital calculations (DDC), a simple proportional plus integral (PI) controller can firstly manipulate the operations of electromagnetic valves, and then the on-line and off-line predictive control algorithm is used in accordance with practical experience to meet the requirements of the parameters in the culture and metabolism of hepatocytes. Software based on Visual C++ is implemented. All these serve to ensure high operational reliability, expansibility and better maneuverability of the whole system. Experiments show that this method can achieve sound performances in practice although there exist very strong coupling, dead-delay and lots of non-linear factors in the bioreactor. The controlling range is: Dissolved Oxygen 0-200±5%; pH 6-8±0.05pH; Temperature 20-45±0.1°C. The device can work in a steady state, and the control precision is high. It can meet the needs in the Bioartificial Liver Support System, and hopefully improve clinical therapeutic effect.

  5. Nutrition and muscle loss in humans during spaceflight

    Science.gov (United States)

    Stein, T. P.

    1999-01-01

    The protein loss in humans during spaceflight is partly due to a normal adaptive response to a decreased work load on the muscles involved in weight bearing. The process is mediated by changes in prostaglandin release, secondary to the decrease in tension on the affected muscles. On missions, where there is a high level of physical demands on the astronauts, there tends to be an energy deficit, which adds to the muscle protein loss and depletes the body fat reserves. While the adaptive response is a normal part of homeostasis, the additional protein loss from an energy deficit can, in the long run, have a negative effect on health and capability of humans to live and work in space and afterward return to Earth.

  6. Erythropoietin treatment enhances muscle mitochondrial capacity in humans

    DEFF Research Database (Denmark)

    Plenge, Ulla; Belhage, Bo; Guadalupe-Grau, Amelia;

    2012-01-01

    Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity...... in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis...... before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler...

  7. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...... 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...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...

  8. Ultrastructure of interstitial cells of Cajal in circular muscle of human small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Mikkelsen, H B; Qvortrup, Klaus;

    1993-01-01

    Interstitial cells of Cajal (ICC) may be important regulatory cells in gut muscle layers. This study examined ICC within the circular muscle of human small intestine.......Interstitial cells of Cajal (ICC) may be important regulatory cells in gut muscle layers. This study examined ICC within the circular muscle of human small intestine....

  9. The accommodative ciliary muscle function is preserved in older humans

    Science.gov (United States)

    Tabernero, Juan; Chirre, Emmanuel; Hervella, Lucia; Prieto, Pedro; Artal, Pablo

    2016-05-01

    Presbyopia, the loss of the eye’s accommodation capability, affects all humans aged above 45–50 years old. The two main reasons for this to happen are a hardening of the crystalline lens and a reduction of the ciliary muscle functionality with age. While there seems to be at least some partial accommodating functionality of the ciliary muscle at early presbyopic ages, it is not yet clear whether the muscle is still active at more advanced ages. Previous techniques used to visualize the accommodation mechanism of the ciliary muscle are complicated to apply in the older subjects, as they typically require fixation stability during long measurement times and/or to have an ultrasound probe directly in contact with the eye. Instead, we used our own developed method based on high-speed recording of lens wobbling to study the ciliary muscle activity in a small group of pseudophakic subjects (around 80 years old). There was a significant activity of the muscle, clearly able to contract under binocular stimulation of accommodation. This supports a purely lenticular-based theory of presbyopia and it might stimulate the search for new solutions to presbyopia by making use of the remaining contraction force still presented in the aging eye.

  10. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

    Directory of Open Access Journals (Sweden)

    Barbora de Courten

    Full Text Available Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists.Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography, % body fat (bioimpedance, abdominal subcutaneous and visceral adiposity (magnetic resonance imaging, insulin sensitivity (euglycaemic hyperinsulinemic clamp, resting energy expenditure (REE, indirect calorimetry, free-living ambulatory physical activity (accelerometers and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04 and subcutaneous (r = 0.38, p = 0.02 but not visceral fat (r = 0.17, p = 0.33. Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008, REE (r = -0.58, p<0.001 and HDL-cholesterol levels (r = -0.34, p = 0.048. Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity.Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

  11. Electromyogram premotion silent period and tension development in human muscle.

    Science.gov (United States)

    Kawahats, K; Miyashita, M

    1983-11-01

    The EMG silent period has been observed frequently just before rapid movement from a slightly sustained contraction of the muscle. Our experiments were designed to show the relation between the tension developed in an intact human muscle and the occurrence of this silent period. Tension in the knee extensor was obtained from the floor reaction force of a living subject in a squatting position on the basis of a lever ratio-joint angle diagram obtained directly from measurements on an isolated knee extensor muscle of a human cadaver. The muscle tension was calculated under the condition that the floor reaction force in the squatting position passed through the anklebone, and decreased from 8.7 to 0.8 kN with an increase in the knee joint angle from 1.13 to 2.74 rad. When the center of pressure was not assumed, the increased knee extensor muscle torque with a decrease in the knee angle was estimated biomechanically from the free body diagram. Consistently, the EMG recordings confirmed an increased muscle activity with a reduction in the joint angle. The premotion silent period for the knee extensors and their antagonist with movement from the squatting position appeared to be limited to a knee joint angle of 2.44 to 3.07 rad, where the requirement for tension in those muscles was low. This silent period could be interpreted as an electromyographic transitional phase attributable to a switching mechanism in central nervous activity. The premotion silent period was most likely to appear prior to a swift, well coordinated movement.

  12. Physiological characterization of human muscle acetylcholine receptors from ALS patients

    Science.gov (United States)

    Palma, Eleonora; Inghilleri, Maurizio; Conti, Luca; Deflorio, Cristina; Frasca, Vittorio; Manteca, Alessia; Pichiorri, Floriana; Roseti, Cristina; Torchia, Gregorio; Limatola, Cristina; Grassi, Francesca; Miledi, Ricardo

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons leading to muscle paralysis. Research in transgenic mice suggests that the muscle actively contributes to the disease onset, but such studies are difficult to pursue in humans and in vitro models would represent a good starting point. In this work we show that tiny amounts of muscle from ALS or from control denervated muscle, obtained by needle biopsy, are amenable to functional characterization by two different technical approaches: “microtransplantation” of muscle membranes into Xenopus oocytes and culture of myogenic satellite cells. Acetylcholine (ACh)-evoked currents and unitary events were characterized in oocytes and multinucleated myotubes. We found that ALS acetylcholine receptors (AChRs) retain their native physiological characteristics, being activated by ACh and nicotine and blocked by α-bungarotoxin (α-BuTX), d-tubocurarine (dTC), and galantamine. The reversal potential of ACh-evoked currents and the unitary channel behavior were also typical of normal muscle AChRs. Interestingly, in oocytes injected with muscle membranes derived from ALS patients, the AChRs showed a significant decrease in ACh affinity, compared with denervated controls. Finally, riluzole, the only drug currently used against ALS, reduced, in a dose-dependent manner, the ACh-evoked currents, indicating that its action remains to be fully characterized. The two methods described here will be important tools for elucidating the role of muscle in ALS pathogenesis and for developing drugs to counter the effects of this disease. PMID:22128328

  13. Re-evaluation of sarcolemma injury and muscle swelling in human skeletal muscles after eccentric exercise.

    Science.gov (United States)

    Yu, Ji-Guo; Liu, Jing-Xia; Carlsson, Lena; Thornell, Lars-Eric; Stål, Per S

    2013-01-01

    The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2-3 days and 7-8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7-8 days than at 2-3 days post exercise (pexercise (lower in 5 of the 6 subjects at 7-8 days than at 2-3 days; pexercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS.

  14. Pericapillary basement membrane thickening in human skeletal muscles.

    Science.gov (United States)

    Baum, Oliver; Bigler, Marius

    2016-09-01

    The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases.

  15. Enhanced Muscle Afferent Signals during Motor Learning in Humans.

    Science.gov (United States)

    Dimitriou, Michael

    2016-04-25

    Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a function of adaptation state. Specifically, spindle control was independent of concurrent muscle activity but was specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80 ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "γ" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning.

  16. Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers

    Science.gov (United States)

    Yu, Cheng-Bo; Pan, Xiao-Ping; Yu, Liang; Yu, Xiao-Peng; Du, Wei-Bo; Cao, Hong-Cui; Li, Jun; Chen, Ping; Li, Lan-Juan

    2014-01-01

    AIM: To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor (CFBB) based on microencapsulated immortalized human hepatocytes. METHODS: Encapsulated hepatocytes were placed in the constructed CFBB and circulated through Dulbecco’s Modified Eagle’s Medium (DMEM) for 12 h, and then through exchanged plasma for 6 h, and compared with encapsulated cells cultivated under static conditions in a spinner flask. Levels of alanine aminotransferase (ALT) and albumin were used to evaluate the CFBB during media circulation, whereas levels of ALT, total bilirubin (TBil), and albumin were used to evaluate it during plasma circulation. Mass transfer and hepatocyte injury were evaluated by comparing the results from the two experimental conditions. In addition, the viability and microstructure of encapsulated cells were observed in the different environments. RESULTS: The bioartificial liver model based on a CFBB was verified by in vitro experiments. The viability of encapsulated cells accounting for 84.6% ± 3.7% in CFBB plasma perfusion was higher than the 74.8% ± 3.1% in the static culture group (P circulation and static medium culture groups, respectively. Albumin secretion from cells was 234.2 ± 27.8 μg/1 × 107 cells vs 167.8 ± 29.3 μg/1 × 107 cells at 6 h (P circulation/culture groups, respectively. Furthermore, ALT and TBil levels were 172.3 ± 24.1 U/L vs 236.3 ± 21.5 U/L (P 0.05) at 6 h in the CFBB plasma perfusion and static plasma culture groups, respectively. There was no significant difference in albumin concentration between the two experimental plasma groups at any time point. The microstructure of the encapsulated hepatocytes remained healthier in the CFBB group compared with the static culture group after 6 h of plasma perfusion. CONCLUSION: The CFBB can function as a bioartificial liver based on a bioreactor. The efficacy of this novel bioreactor is promising for the study of liver failure. PMID:24944477

  17. Multi-frequency bioimpedance in human muscle assessment

    DEFF Research Database (Denmark)

    Bartels, Else Marie; Sørensen, Emma Rudbæk; Harrison, Adrian Paul

    2015-01-01

    Bioimpedance analysis (BIA) is a well-known and tested method for body mass and muscular health assessment. Multi-frequency BIA (mfBIA) equipment now makes it possible to assess a particular muscle as a whole, as well as looking at a muscle at the fiber level. The aim of this study was to test...... healthy human control subjects and three selected cases were examined to demonstrate the extent to which this method may be used clinically, and in relation to training in sport. The electrode setup is shown to affect the mfBIA parameters recorded. Our recommendation is the use of noble metal electrodes...

  18. Erythropoietin treatment enhances mitochondrial function in human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Ulla ePlenge

    2012-03-01

    Full Text Available Abstract Erythropoietin (Epo treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over eight weeks with oral iron (100 mg supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92±5 to 113±7 pmol.sec-1.mg-1 and ETS (107±4 to 143±14 pmol.sec-1.mg-1, P<0.05, demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

  19. The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity.

    Science.gov (United States)

    Love, Lorenzo K; LeBlanc, Paul J; Inglis, J Greig; Bradley, Nicolette S; Choptiany, Jon; Heigenhauser, George J F; Peters, Sandra J

    2011-08-01

    Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r(2) = 0.399, P = 0.001) and PDP1 protein expression (r(2) = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α (r(2) = 0.310, P = 0.002) and PDK2 protein (r(2) = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼ 18% of the variance in PDP activity (r(2) = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼ 38% of the variance in PDP activity (r(2) = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity).

  20. Regional Differences in Muscle Energy Metabolism in Human Muscle by 31P-Chemical Shift Imaging.

    Science.gov (United States)

    Kime, Ryotaro; Kaneko, Yasuhisa; Hongo, Yoshinori; Ohno, Yusuke; Sakamoto, Ayumi; Katsumura, Toshihito

    2016-01-01

    Previous studies have reported significant region-dependent differences in the fiber-type composition of human skeletal muscle. It is therefore hypothesized that there is a difference between the deep and superficial parts of muscle energy metabolism during exercise. We hypothesized that the inorganic phosphate (Pi)/phosphocreatine (PCr) ratio of the superficial parts would be higher, compared with the deep parts, as the work rate increases, because the muscle fiber-type composition of the fast-type may be greater in the superficial parts compared with the deep parts. This study used two-dimensional 31Phosphorus Chemical Shift Imaging (31P-CSI) to detect differences between the deep and superficial parts of the human leg muscles during dynamic knee extension exercise. Six healthy men participated in this study (age 27±1 year, height 169.4±4.1 cm, weight 65.9±8.4 kg). The experiments were carried out with a 1.5-T superconducting magnet with a 5-in. diameter circular surface coil. The subjects performed dynamic one-legged knee extension exercise in the prone position, with the transmit-receive coil placed under the right quadriceps muscles in the magnet. The subjects pulled down an elastic rubber band attached to the ankle at a frequency of 0.25, 0.5 and 1 Hz for 320 s each. The intracellular pH (pHi) was calculated from the median chemical shift of the Pi peak relative to PCr. No significant difference in Pi/PCr was observed between the deep and the superficial parts of the quadriceps muscles at rest. The Pi/PCr of the superficial parts was not significantly increased with increasing work rate. Compared with the superficial areas, the Pi/PCr of the deep parts was significantly higher (p<0.05) at 1 Hz. The pHi showed no significant difference between the two parts. These results suggest that muscle oxidative metabolism is different between deep and superficial parts of quadriceps muscles during dynamic exercise.

  1. Intermuscular force transmission between human plantarflexor muscles in vivo

    DEFF Research Database (Denmark)

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

    2010-01-01

    of the present study was to investigate if intermuscular force transmission occurs within and between human plantarflexor muscles in vivo. Seven subjects performed four types of either active contractile tasks or passive joint manipulations: passive knee extension, voluntary isometric plantarflexion, voluntary...... isometric hallux flexion, passive hallux extension, and selective percutaneous stimulation of the gastrocnemius medialis (MG). In each experiment plantar- and hallux flexion force and corresponding EMG activity were sampled. During all tasks ultrasonography was applied at proximal and distal sites to assess...... task-induced tissue displacement (which is assumed to represent loading) for the plantarflexor muscles [MG, soleus (SOL), and flexor hallucis longus (FHL)]. Selective MG stimulation and passive knee extension resulted in displacement of both the MG and SOL muscles. Minimal displacement of the triceps...

  2. MuscleBuilder:A Modeling Tool for Human Anatomy

    Institute of Scientific and Technical Information of China (English)

    Amaury Aubel; Daniel Thalmann

    2004-01-01

    A traditional multi-layered approach is adopted to human body modeling and deformation. The model is split into three general anatomical structures: the skeleton, musculature and skin. It is shown that each of these layers is modeled and deformed by using fast, procedural, ad-hoc methods that can painlessly be reimplemented. The modeling approach is generic enough to handle muscles of varying shape, size and characteristics and does not break in extreme skeleton poses. It is also described that the integrated MuscleBuilder system whose main features are: i) easy and quick creation of muscle deformation models; ii) automatic deformation of an overlying skin. It is shown that visually realistic results can be obtained at interactive frame rates with very little input from the designer.

  3. Artificial and bioartificial liver support: A review of perfusion treatment for hepatic failure patients

    Institute of Scientific and Technical Information of China (English)

    Katsutoshi Naruse; Wei Tang; Masatoshi Makuuchi

    2007-01-01

    Liver transplantation and blood purification therapy, including plasmapheresis, hemodiafiltration, and bioartificial liver support, are the available treatments for patients with severe hepatic failure. Bioartificial liver support, in which living liver tissue is used to support hepatic function, has been anticipated as an effective treatment for hepatic failure. The two mainstream systems developed for bioartificial liver support are extracorporeal whole liver perfusion (ECLP) and bioreactor systems. Comparing various types of bioartificial liver in view of function, safety, and operability, we concluded that the best efficacy can be provided by the ECLP system. Moreover, in our subsequent experiments comparing ECLP and apheresis therapy, ECLP offers more ammonia metabolism than HD and HF. In addition, ECLP can compensate amino acid imbalance and can secret bile. A controversial point with ECLP is the procedure is labor intensive, resulting in high costs. However, ECLP has the potential to reduce elevated serum ammonia levels of hepatic coma patients in a short duration. When these problems are solved, bioartificial liver support, especially ECLP, can be adopted as an option in ordinary clinical therapy to treat patients with hepatic failure.

  4. Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Gnaiger, Erich; Calbet, Jose A L

    2011-01-01

    Across a wide range of species and body mass a close matching exists between maximal conductive oxygen delivery and mitochondrial respiratory rate. In this study we investigated in humans how closely in-vivo maximal oxygen consumption (VO(2) max) is matched to state 3 muscle mitochondrial...... respiration. High resolution respirometry was used to quantify mitochondrial respiration from the biopsies of arm and leg muscles while in-vivo arm and leg VO(2) were determined by the Fick method during leg cycling and arm cranking. We hypothesized that muscle mitochondrial respiratory rate exceeds...... that of systemic oxygen delivery. The state 3 mitochondrial respiration of the deltoid muscle (4.3±0.4 mmol o(2)kg(-1) min(-1)) was similar to the in-vivo VO(2) during maximal arm cranking (4.7±0.5 mmol O(2) kg(-1) min(-1)) with 6 kg muscle. In contrast, the mitochondrial state 3 of the quadriceps was 6.9±0.5 mmol...

  5. Passive heat acclimation improves skeletal muscle contractility in humans.

    Science.gov (United States)

    Racinais, S; Wilson, M G; Périard, J D

    2017-01-01

    The aim of this study was to investigate the effect of repeated passive heat exposure (i.e., acclimation) on muscle contractility in humans. Fourteen nonheat-acclimated males completed two trials including electrically evoked twitches and voluntary contractions in thermoneutral conditions [Cool: 24°C, 40% relative humidity (RH)] and hot ambient conditions in the hyperthermic state (Hot: 44-50°C, 50% RH) on consecutive days in a counterbalanced order. Rectal temperature was ~36.5°C in Cool and was maintained at ~39°C throughout Hot. Both trials were repeated after 11 days of passive heat acclimation (1 h per day, 48-50°C, 50% RH). Heat acclimation decreased core temperature in Cool (-0.2°C, P heat acclimation improved skeletal muscle contractility as evidenced by an increase in evoked peak twitch amplitude both in Cool (20.5 ± 3.6 vs. 22.0 ± 4.0 N·m) and Hot (20.5 ± 4.7 vs. 22.0 ± 4.0 N·m) (+9%, P heat acclimation improves skeletal muscle contractile function during electrically evoked and voluntary muscle contractions of different intensities both in Cool and Hot. These results suggest that repeated heat exposure may have important implications to passively maintain or even improve muscle function in a variety of performance and clinical settings. Copyright © 2017 the American Physiological Society.

  6. Purinergic effects on Na,K-ATPase activity differ in rat and human skeletal muscle

    DEFF Research Database (Denmark)

    Juel, Carsten; Nordsborg, Nikolai Baastrup; Bangsbo, Jens

    2014-01-01

    P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle.......P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle....

  7. Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes

    Directory of Open Access Journals (Sweden)

    Kang Peter B

    2006-03-01

    Full Text Available Abstract Background Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. Methods Orthologous (whole, sub- transcriptome profiles were compared among four mouse-human transcriptome datasets: (M six muscle groups obtained from three mouse strains (wildtype, mdx, mdx5cv; (H1 biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2 four different control human muscle types obtained at autopsy; and (H3 12 different control human tissues (ten non-muscle. Results Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy. Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3, indicating this finding to be muscle specific. Conclusion This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled.

  8. Carotid baroreceptor-muscle sympathetic relation in humans.

    Science.gov (United States)

    Rea, R F; Eckberg, D L

    1987-12-01

    The purpose of this study was to define the relation between carotid distending pressure and muscle sympathetic activity in humans. Carotid baroreceptors of nine healthy subjects were compressed or stretched for 5 s with graded neck pressure or suction (+40 to -65 mmHg), and muscle sympathetic nerve activity was recorded. The results delineate several features of human baroreflex function. First, the carotid-muscle sympathetic relation is well described by an inverse sigmoid function. Second, a linear relation exists between carotid distending pressure and sympathetic outflow over a range of approximately 25 mmHg. Third, sympathetic responses to changes of carotid pressures are asymmetric; increases of sympathetic activity during carotid compression are much greater than reductions of sympathetic activity during carotid stretch. Fourth, at rest, normal subjects operate near the threshold level for sympathetic excitation. Thus the carotid-muscle sympathetic baroreflex is poised to oppose reductions more effectively than elevations of arterial pressure, and the range of pressures over which the reflex is active is wider than thought hitherto.

  9. Morphometric and Statistical Analysis of the Palmaris Longus Muscle in Human and Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Roqueline A. G. M. F. Aversi-Ferreira

    2014-01-01

    Full Text Available The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal joint flexor muscle in humans, a small vestigial forearm muscle; it is the most variable muscle in humans, showing variation in position, duplication, slips and could be reverted. It is frequently studied in papers about human anatomical variations in cadavers and in vivo, its variation has importance in medical clinic, surgery, radiological analysis, in studies about high-performance athletes, in genetics and anthropologic studies. Most studies about palmaris longus in humans are associated to frequency or case studies, but comparative anatomy in primates and comparative morphometry were not found in scientific literature. Comparative anatomy associated to morphometry of palmaris longus could explain the degeneration observed in this muscle in two of three of the great apes. Hypothetically, the comparison of the relative length of tendons and belly could indicate the pathway of the degeneration of this muscle, that is, the degeneration could be associated to increased tendon length and decreased belly from more primitive primates to those most derivate, that is, great apes to modern humans. In conclusion, in primates, the tendon of the palmaris longus increase from Lemuriformes to modern humans, that is, from arboreal to terrestrial primates and the muscle became weaker and tending to be missing.

  10. Muscle Gene Expression Patterns in Human Rotator Cuff Pathology

    Science.gov (United States)

    Choo, Alexander; McCarthy, Meagan; Pichika, Rajeswari; Sato, Eugene J.; Lieber, Richard L.; Schenk, Simon; Lane, John G.; Ward, Samuel R.

    2014-01-01

    Background: Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology. Methods: Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis. Results: Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear. Conclusions: Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of

  11. Reflex influences on muscle spindle activity in relaxed human leg muscles.

    Science.gov (United States)

    Gandevia, S C; Miller, S; Aniss, A M; Burke, D

    1986-07-01

    The study was designed to determine whether low-threshold cutaneous and muscle afferents from the foot reflexly activate gamma-motoneurons innervating relaxed muscles of the leg. In 15 experiments multiunit recordings were made from 21 nerve fascicles innervating triceps surae or tibialis anterior. In a further nine experiments the activity of 19 identified single muscle spindle afferents was recorded, 13 from triceps surae, 5 from tibialis anterior, and 1 from extensor digitorum longus. Trains of electrical stimuli (5 stimuli, 300 Hz) were delivered to the sural nerve at the ankle (intensity, twice sensory threshold) and the posterior tibial nerve at the ankle (intensity, 1.1 times motor threshold for the small muscles of the foot). In addition, a tap on the appropriate tendon at varying times after the stimuli was used to assess the dynamic responsiveness of the afferents under study. The conditioning electrical stimuli did not change the discharge of single spindle afferents. Recordings of rectified and averaged multiunit activity also revealed no change in the overall level of background neural activity following the electrical stimuli. The afferent responses to tendon taps did not differ significantly whether or not they were preceded by stimulation of the sural or posterior tibial nerves. These results suggest that low-threshold afferents from the foot do not produce significant activation of fusimotor neurons in relaxed leg muscles, at least as judged by their ability to alter the discharge of muscle spindle afferents. As there may be no effective background activity in fusimotor neurons innervating relaxed human muscles, it is possible that these inputs from the foot could influence the fusimotor system during voluntary contractions when the fusimotor neurons have been brought to firing threshold. In one subject trains of stimuli were delivered to the posterior tibial nerve at painful levels (30 times motor threshold). They produced an acceleration of the

  12. Human intersegmental reflexes from intercostal afferents to scalene muscles.

    Science.gov (United States)

    McBain, Rachel A; Taylor, Janet L; Gorman, Robert B; Gandevia, Simon C; Butler, Jane E

    2016-10-01

    What is the central question of this study? The aim was to determine whether specific reflex connections operate between intercostal afferents and the scalene muscles in humans, and whether these connections operate after a clinically complete cervical spinal cord injury. What is the main finding and its importance? This is the first description of a short-latency inhibitory reflex connection between intercostal afferents from intercostal spaces to the scalene muscles in able-bodied participants. We suggest that this reflex is mediated by large-diameter afferents. This intercostal-to-scalene inhibitory reflex is absent after cervical spinal cord injury and may provide a way to monitor the progress of the injury. Short-latency intersegmental reflexes have been described for various respiratory muscles in animals. In humans, however, only short-latency reflex responses to phrenic nerve stimulation have been described. Here, we examined the reflex connections between intercostal afferents and scalene muscles in humans. Surface EMG recordings were made from scalene muscles bilaterally, in seven able-bodied participants and seven participants with motor- and sensory-complete cervical spinal cord injury (median 32 years postinjury, range 5 months to 44 years). We recorded the reflex responses produced by stimulation of the eighth or tenth left intercostal nerve. A short-latency (∼38 ms) inhibitory reflex was evident in able-bodied participants, in ipsilateral and contralateral scalene muscles. This bilateral intersegmental inhibitory reflex occurred in 46% of recordings at low stimulus intensities (at three times motor threshold). It was more frequent (in 75-85% of recordings) at higher stimulus intensities (six and nine times motor threshold), but onset latency (38 ± 9 ms, mean ± SD) and the size of inhibition (23 ± 10%) did not change with stimulus intensity. The reflex was absent in all participants with spinal cord injury. As the intercostal

  13. Development of a bioreactor based on magnetically stabilized fluidized bed for bioartificial liver.

    Science.gov (United States)

    Deng, Fei; Chen, Li; Zhang, Ying; Zhao, Shan; Wang, Yu; Li, Na; Li, Shen; Guo, Xin; Ma, Xiaojun

    2015-12-01

    Bioartificial liver (BAL) based on microcapsules has been proposed as a potential treatment for acute liver failure. The bioreactors used in such BAL are usually expected to achieve sufficient flow rate and minimized void volume for effective application. Due to the superiorities in bed pressure drop and operation velocity, magnetically stabilized fluidized beds (MSFBs) show the potential to serve as ideal microcapsule-based bioreactors. In the present study, we attempted to develop a microcapsule-based MSFB bioreactor for bioartificial liver device. Compared to conventional-fluidized bed bioreactors, the bioreactor presented here increased perfusion velocity and decreased void volume significantly. Meanwhile, the mechanical stability as well as the immunoisolation property of magnetite microcapsules were well maintained during the fluidization. Besides, the magnetite microcapsules were found no toxicity to cell survival. Therefore, our study might provide a novel approach for the design of microcapsule-based bioartificial liver bioreactors.

  14. Analysis of glucose and insulin mass transfer in a novel 2-channel bioartificial pancreas.

    Science.gov (United States)

    Moussy, Y; Moussy, F

    1995-01-01

    This paper introduces a newly developed 2-channel bioartificial pancreas for the treatment of type I diabetes. In this device, insulin secreting cells (islets of Langerhans) are placed between 2 semi-permeable membranes that form a flat rectangular chamber. One side of the chamber is in contact with blood from an artery and the other side with blood from a vein. In addition to the diffusive transfer of glucose and insulin, the pressure difference between the artery and the vein creates an ultrafiltration flux through the islet chamber. This diffusion and ultrafiltration flux carries glucose from the artery to the islets, and insulin from the islets to the vein. The bioartificial pancreas has a compact geometry and the blood channels were designed to prevent blood clotting. The predicted insulin release in response to a square-wave and a triangular-wave glucose stimulation is given for the bioartificial pancreas of dimensions necessary for implantation in diabetic patients.

  15. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    was to investigate whether subdivisions within the human trapezius can be independently activated by voluntary command using biofeedback guidance. Bipolar electromyographical electrodes were situated on four subdivisions of the trapezius muscle. The threshold for "active" and "rest" for each subdivision was set...... to >12% and biofeedback from each of the four trapezius subdivisions, 11 of 15 subjects learned selective activation of at least one of the four anatomical subdivisions of the trapezius...

  16. Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth.

    Science.gov (United States)

    Farup, Jean; Rahbek, Stine Klejs; Riis, Simon; Vendelbo, Mikkel Holm; Paoli, Frank de; Vissing, Kristian

    2014-10-15

    Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type-specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P hypertrophy correlated with whole muscle hypertrophy exclusively following Conc training (P eccentric resistance training while type II fiber hypertrophy was accentuated when combining concentric resistance training with whey protein supplementation.

  17. The bioartificial pancreas (BAP): Biological, chemical and engineering challenges.

    Science.gov (United States)

    Iacovacci, Veronica; Ricotti, Leonardo; Menciassi, Arianna; Dario, Paolo

    2016-01-15

    The bioartificial pancreas (BAP) represents a viable solution for the treatment of type 1 diabetes (T1D). By encapsulating pancreatic cells in a semipermeable membrane to allow nutrient, insulin and glucose exchange, the side effects produced by islets and whole organ transplantation-related immunosuppressive therapy can be circumvented. Several factors, mainly related to materials properties, capsule morphology and biological environment, play a key role in optimizing BAP systems. The BAP is an extremely complex delivery system for insulin. Despite considerable efforts, in some instances meeting with limited degree of success, a BAP capable of restoring physiological pancreas functions without the need for immunosuppressive drugs and of controlling blood glucose levels especially in large animal models and a few clinical trials, does not exist. The state of the art in terms of materials, fabrication techniques and cell sources, as well as the current status of commercial devices and clinical trials, are described in this overview from an interdisciplinary viewpoint. In addition, challenges to the creation of effective BAP systems are highlighted including future perspectives in terms of component integration from both a biological and an engineering viewpoint. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Ingeniería tisular y miocardio bioartificial

    Directory of Open Access Journals (Sweden)

    Juan Carlos Chachques

    2011-07-01

    La investigación y desarrollo de un miocardio bioartificial tiene gran interés clínico. La estrategia es el uso de biomateriales para desarrollar una microatmósfera que proporcione a las células endógenas y exógenas un ambiente óptimo para la reparación de tejidos. Los conocimientos adquiridos en el desarrollo de biomateriales aportan las bases para desarrollar matrices 3D que ofrecen el ambiente idóneo para la liberación de células y genes que dirijan las células terapéuticas hacia el fenotipo funcional. La descelularización de órganos para construir nuevas matrices es un nuevo concepto de investigación, desarrollado gracias al desarrollo de nanomateriales que aseguran un nicho celular apropiado para la diferenciación celular y la terapia génica o farmacológica.

  19. Engineering analysis and development of the spheroid reservoir bioartificial liver.

    Science.gov (United States)

    McIntosh, Malcolm B; Corner, Stephen M; Amiot, Bruce P; Nyberg, Scott L

    2009-01-01

    A significant demand exists for a liver support device such as a Bioartifical Liver (BAL) to treat patients experiencing acute liver failure. This descriptive paper outlines the design and development of two of the key components of the Mayo Spheroid Reservoir Bioartificial Liver (SRBAL) system. One of the components is the multifunctional Spheroid Reservoir and the other is Multi-shelf Rocker. The Spheroid Reservoir provides an environment to support the viability and functionality of the hepatocyte spheroids at very high cell densities. The Spheroid Reservoir is the biologically active component of this extracorporeal liver support device. Since the Spheroid Reservoir is designed to support 200-400 grams of hepatocyte spheroids, a method to quickly produce large quantities of spheroids is required. The Multi-Shelf Rocker fulfills the production requirement by allowing the culturing of up to six liters of hepatocyte suspension in a conventional laboratory incubator. The SRBAL is designed to provide life sustaining liver-like function to patients in acute liver failure.

  20. Analysis of ultrafiltration and mass transfer in a bioartificial pancreas.

    Science.gov (United States)

    Jaffrin, M Y; Reach, G; Notelet, D

    1988-02-01

    A bioartificial pancreas is an implantable device which contains insulin secreting cells (Langerhans islets), separated from the circulating blood by a semi-permeable membrane to avoid rejection. This paper describes the operation of such a device and evaluates the respective contributions of diffusion and ultrafiltration to the glucose and insulin mass transfer. It is shown that the pressure drop along the blood channel produces across the first half of the channel an ultrafiltration flux toward the islet compartment followed in the second half by an equal flux in reverse direction from islets to blood. The mass transfer analysis is carried out for an optimal geometry in which a U-shaped blood channel surrounds closely a very thin islet compartment formed by a folded flat membrane. A complete model of insulin release by this device is developed and is compared with in vitro data obtained with rats islets. Satisfactory kinetics is achieved with a polyacrylonitrile membrane used in hemodialysis. But the model shows that the membrane hydraulic permeability should be increased by a factor of 10 to significantly improve the performance.

  1. Synthetic biology routes to bio-artificial intelligence.

    Science.gov (United States)

    Nesbeth, Darren N; Zaikin, Alexey; Saka, Yasushi; Romano, M Carmen; Giuraniuc, Claudiu V; Kanakov, Oleg; Laptyeva, Tetyana

    2016-11-30

    The design of synthetic gene networks (SGNs) has advanced to the extent that novel genetic circuits are now being tested for their ability to recapitulate archetypal learning behaviours first defined in the fields of machine and animal learning. Here, we discuss the biological implementation of a perceptron algorithm for linear classification of input data. An expansion of this biological design that encompasses cellular 'teachers' and 'students' is also examined. We also discuss implementation of Pavlovian associative learning using SGNs and present an example of such a scheme and in silico simulation of its performance. In addition to designed SGNs, we also consider the option to establish conditions in which a population of SGNs can evolve diversity in order to better contend with complex input data. Finally, we compare recent ethical concerns in the field of artificial intelligence (AI) and the future challenges raised by bio-artificial intelligence (BI). © 2016 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

  2. Bionic Humans Using EAP as Artificial Muscles Reality and Challenges

    Directory of Open Access Journals (Sweden)

    Yoseph Bar-Cohen

    2008-11-01

    Full Text Available For many years, the idea of a human with bionic muscles immediately conjures up science fiction images of a TV series superhuman character that was implanted with bionic muscles and portrayed with strength and speed far superior to any normal human. As fantastic as this idea may seem, recent developments in electroactive polymers (EAP may one day make such bionics possible. Polymers that exhibit large displacement in response to stimulation that is other than electrical signal were known for many years. Initially, EAP received relatively little attention due to their limited actuation capability. However, in the recent years, the view of the EAP materials has changed due to the introduction of effective new materials that significantly surpassed the capability of the widely used piezoelectric polymer, PVDF. As this technology continues to evolve, novel mechanisms that are biologically inspired are expected to emerge. EAP materials can potentially provide actuation with lifelike response and more flexible configurations. While further improvements in performance and robustness are still needed, there already have been several reported successes. In recognition of the need for cooperation in this multidisciplinary field, the author initiated and organized a series of international forums that are leading to a growing number of research and development projects and to great advances in the field. In 1999, he challenged the worldwide science and engineering community of EAP experts to develop a robotic arm that is actuated by artificial muscles to win a wrestling match against a human opponent. In this paper, the field of EAP as artificial muscles will be reviewed covering the state of the art, the challenges and the vision for the progress in future years.

  3. Localization and function of ATP-sensitive potassium channels in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Jens Jung; Kristensen, Michael; Hellsten, Ylva

    2003-01-01

    The present study investigated the localization of ATP-sensitive K+ (KATP) channels in human skeletal muscle and the functional importance of these channels for human muscle K+ distribution at rest and during muscle activity. Membrane fractionation based on the giant vesicle technique...

  4. Muscle spindle composition and distribution in human young masseter and biceps brachii muscles reveal early growth and maturation.

    Science.gov (United States)

    Osterlund, Catharina; Liu, Jing-Xia; Thornell, Lars-Eric; Eriksson, Per-Olof

    2011-04-01

    Significant changes in extrafusal fiber type composition take place in the human masseter muscle from young age, 3-7 years, to adulthood, in parallel with jaw-face skeleton growth, changes of dentitions and improvement of jaw functions. As motor and sensory control systems of muscles are interlinked, also the intrafusal fiber population, that is, muscle spindles, should undergo age-related changes in fiber type appearance. To test this hypothesis, we examined muscle spindles in the young masseter muscle and compared the result with previous data on adult masseter spindles. Also muscle spindles in the young biceps brachii muscle were examined. The result showed that muscle spindle composition and distribution were alike in young and adult masseter. As for the adult masseter, young masseter contained exceptionally large muscle spindles, and with the highest spindle density and most complex spindles found in the deep masseter portion. Hence, contrary to our hypothesis, masseter spindles do not undergo major morphological changes between young age and adulthood. Also in the biceps, young spindles were alike adult spindles. Taken together, the results showed that human masseter and biceps muscle spindles are morphologically mature already at young age. We conclude that muscle spindles in the human young masseter and biceps precede the extrafusal fiber population in growth and maturation. This in turn suggests early reflex control and proprioceptive demands in learning and maturation of jaw motor skills. Similarly, well-developed muscle spindles in young biceps reflect early need of reflex control in learning and performing arm motor behavior. Copyright © 2011 Wiley-Liss, Inc.

  5. Adenosine concentrations in the interstitium of resting and contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Maclean, D.; Rådegran, G.

    1998-01-01

    effect remain unanswered. METHODS AND RESULTS: The interstitial adenosine concentration was determined in the vastus lateralis muscle of healthy humans via dialysis probes inserted in the muscle. The probes were perfused with buffer, and the dialysate samples were collected at rest and during graded knee...... and demonstrates that adenosine and its precursors increase in the exercising muscle interstitium, at a rate associated with intensity of muscle contraction and the magnitude of muscle blood flow....

  6. Ultrastructure of striated muscle fibers in the middle third of the human esophagus

    OpenAIRE

    Faussone-Pellegrini, M.S; Cortesini, C.

    1986-01-01

    Striated muscle fibers and .their spatial relationship to smooth muscle cells have been studied in the middle third of human esophagus. Biopsies were obtained from 3 patients during surgery. In both the circular and longitudinal layers, the muscle coat of this transition zone was composed of fascicles of uniform dimensioi~ (100-200 pm of diameter); some of these bundles were made up of striated muscle fibers, others were pure bundles of smooth muscle cells and ...

  7. Human skeletal muscle fibre types and force: velocity properties.

    Science.gov (United States)

    MacIntosh, B R; Herzog, W; Suter, E; Wiley, J P; Sokolosky, J

    1993-01-01

    It has been reported that there is a relationship between power output and fibre type distribution in mixed muscle. The strength of this relationship is greater in the range of 3-8 rad.s-1 during knee extension compared to slower or faster angular knee extensor speeds. A mathematical model of the force: velocity properties of muscle with various combinations of fast- and slow-twitch fibres may provide insight into why specific velocities may give better predictions of fibre type distribution. In this paper, a mathematical model of the force:velocity relationship for mixed muscle is presented. This model demonstrates that peak power and optimal velocity should be predictive of fibre distribution and that the greatest fibre type discrimination in human knee extensor muscles should occur with measurement of power output at an angular velocity just greater than 7 rad.s-1. Measurements of torque:angular velocity relationships for knee extension on an isokinetic dynamometer and fibre type distribution in biopsies of vastus lateralis muscles were made on 31 subjects. Peak power and optimal velocity were determined in three ways: (1) direct measurement, (2) linear regression, and (3) fitting to the Hill equation. Estimation of peak power and optimal velocity using the Hill equation gave the best correlation with fibre type distribution (r < 0.5 for peak power or optimal velocity and percentage of fast-twitch fibres). The results of this study confirm that prediction of fibre type distribution is facilitated by measurement of peak power at optimal velocity and that fitting of the data to the Hill equation is a suitable method for evaluation of these parameters.

  8. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... sympathetic vasoconstriction. ATP is released into plasma from erythrocytes and endothelial cells and the plasma concentration increases in both the feeding artery and the vein draining the contracting skeletal muscle. Adenosine also stimulates the formation of NO and prostaglandins, but the plasma adenosine...... and endothelial cells. In the interstitium, both ATP and adenosine stimulate the formation of NO and prostaglandins, but ATP has also been suggested to induce vasoconstriction and stimulate afferent nerves that signal to increase sympathetic nerve activity. Adenosine has been shown to contribute to exercise...

  9. Induction of GLUT-1 protein in adult human skeletal muscle fibers

    DEFF Research Database (Denmark)

    Gaster, M; Franch, J; Staehr, P

    2000-01-01

    fibers. Metabolic stress (obesity, non-insulin-dependent diabetes mellitus), contractile activity (training), and conditions of de- and reinnervation (amyotrophic lateral sclerosis) could not induce GLUT-1 expression in human muscle fibers. However, regenerating muscle fibers in polymyositis expressed...

  10. Skeletal muscle vasodilation during systemic hypoxia in humans.

    Science.gov (United States)

    Dinenno, Frank A

    2016-01-15

    In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that 1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; 2) PGs do not normally contribute to vascular tone during hypoxia, however, they do affect vascular tone when NO is inhibited; 3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and 4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, skeletal muscle blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts augmented vasodilation and hyperemia compared with control (normoxic) conditions by ∼50%; however, in contrast to hypoxia alone, the response is not abolished, suggesting that other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release, or nitrite reduction to NO, or both likely play a role in regulating this response.

  11. Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth

    DEFF Research Database (Denmark)

    Farup, Jean; Rahbek, Stine Klejs; Riis, Simon

    2014-01-01

    -specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose......Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type......) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P

  12. Hyper-elastic properties of the human sternocleidomastoideus muscle in tension

    OpenAIRE

    Gras, Laure-Lise; MITTON, David; VIOT, Philippe; Laporte, Sébastien

    2012-01-01

    Numerical models of the human body require realistic mechanical properties of the muscles as input, but, generally, such data are available only for animals’ muscles. As a consequence, the aim of this study was to identify the hyper-elastic behavior of the human sternocleidomastoideus muscle in tension using different constitutive laws. Ten sternocleidomastoideus muscles were tested in vitro. The hyper-elastic behavior was modeled with an exponential law and a hyper-elastic constitutive...

  13. Afferent contribution to locomotor muscle activity during unconstrained overground human walking: an analysis of triceps surae muscle fascicles.

    Science.gov (United States)

    af Klint, R; Cronin, N J; Ishikawa, M; Sinkjaer, T; Grey, M J

    2010-03-01

    Plantar flexor series elasticity can be used to dissociate muscle-fascicle and muscle-tendon behavior and thus afferent feedback during human walking. We used electromyography (EMG) and high-speed ultrasonography concomitantly to monitor muscle activity and muscle fascicle behavior in 19 healthy volunteers as they walked across a platform. On random trials, the platform was dropped (8 cm, 0.9 g acceleration) or held at a small inclination (up to +/-3 degrees in the parasagittal plane) with respect to level ground. Dropping the platform in the mid and late phases of stance produced a depression in the soleus muscle activity with an onset latency of about 50 ms. The reduction in ground reaction force also unloaded the plantar flexor muscles. The soleus muscle fascicles shortened with a minimum delay of 14 ms. Small variations in platform inclination produced significant changes in triceps surae muscle activity; EMG increased when stepping on an inclined surface and decreased when stepping on a declined surface. This sensory modulation of the locomotor output was concomitant with changes in triceps surae muscle fascicle and gastrocnemius tendon length. Assuming that afferent activity correlates to these mechanical changes, our results indicate that within-step sensory feedback from the plantar flexor muscles automatically adjusts muscle activity to compensate for small ground irregularities. The delayed onset of muscle fascicle movement after dropping the platform indicates that at least the initial part of the soleus depression is more likely mediated by a decrease in force feedback than length-sensitive feedback, indicating that force feedback contributes to the locomotor activity in human walking.

  14. Severely atrophic human muscle fibers with nuclear misplacement survive many years of permanent denervation

    Directory of Open Access Journals (Sweden)

    Ugo Carraro

    2016-06-01

    Full Text Available Likewise in rodents, after complete spinal cord injury (SCI the lower motor neuron (LMN denervated human muscle fibers lose completely the myofibrillar apparatus and the coil distribution of myonuclei that are relocated in groups (nuclear clumps in the center of severely atrophic muscle fibers. Up to two years of LMN denervation the muscle fibers with nuclear clumps are very seldom, but in this cohort of patients the severely atrophic muscle fibers are frequent in muscle biopsies harvested three to six years after SCI. Indeed, the percentage increased to 27 ± 9% (p< 0.001, and then abruptly decreased from the 6th year onward, when fibrosis takes over to neurogenic muscle atrophy. Immunohistochemical analyses shown that nuclear misplacements occurred in both fast and slow muscle fibers. In conclusion, human muscle fibers survive permanent denervation much longer than generally accepted and relocation of nuclei is a general behavior in long term denervated muscle fibers.

  15. Activity of upper limb muscles during human walking.

    Science.gov (United States)

    Kuhtz-Buschbeck, Johann P; Jing, Bo

    2012-04-01

    The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Substance P stimulation of cultured human smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Mitsuhashi, M.; Payan, D.G.

    1986-03-01

    Substance P (SP) has been shown to be mitogenic for cells active in the inflammatory response, such as lymphocytes and macrophages, and demonstrates vasodilatory and bronchoconstrictor properties, implicating SP receptor-mediated responses on smooth muscle cells. The effects of SP on cultured human vascular smooth muscle cell (HSMC) proliferative responses and protein synthesis were assessed by measuring the incorporation of (/sup 3/H)thymidine into DNA and (/sup 3/H)leucine into intracellular proteins, respectively. SP at concentrations of 10/sup -6/ to 10/sup -5/M stimulated a 40-50% increase in the incorporation of (/sup 3/H)thymidine in HMSC. In addition, the uptake of (/sup 3/H)leucine into HSMC proteins was increased significantly by SP over the concentration range 10/sup -11/ to 10/sup -6/M. Moreover, an enhancement of protein synthesis in HSMC by 10/sup -9/M SP was demonstrated by an increased incorporation of (/sup 35/S)methionine into cellular proteins of MW 40-30,000 daltons as assessed by autoradiographic analysis of HSMC lysates analyzed by SDS-PAGE. Furthermore, the uptake of (/sup 3/H)inositol into HSMC membrane phospholipid was increased significantly by SP in a dose-dependent manner over the concentration range 10/sup -11/ to 10/sup -6/M. Peptides such as SP which stimulate smooth muscle contraction, also demonstrate mitogenic properties on HSMC, suggesting that these cellular response shares common pathways of activation.

  17. Experimental neck muscle pain impairs standing balance in humans

    CERN Document Server

    Vuillerme, Nicolas; 10.1007/s00221-008-1639-7

    2009-01-01

    Impaired postural control has been reported in patients with chronic neck pain of both traumatic and non-traumatic etiologies, but whether painful stimulation of neck muscle per se can affect balance control during quiet standing in humans remains unclear. The purpose of the present experiment was thus to investigate the effect of experimental neck muscle pain on standing balance in young healthy adults. To achieve this goal, 16 male university students were asked to stand upright as still as possible on a force platform with their eyes closed in two conditions of No pain and Pain of the neck muscles elicited by experimental painful electrical stimulation. Postural control and postural performance were assessed by the displacements of the center of foot pressure (CoP) and of the center of mass (CoM), respectively. The results showed increased CoP and CoM displacements variance, range, mean velocity, and mean and median frequencies in the Pain relative to the No pain condition. The present findings emphasize t...

  18. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Deshmukh, Atul; Long, Yun Chau

    2007-01-01

    suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were...... incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P ... exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure....

  19. Stretch reflex instability compared in three different human muscles.

    Science.gov (United States)

    Durbaba, R; Taylor, A; Manu, C A; Buonajuti, M

    2005-06-01

    The possibility of causing instability in the stretch reflex has been examined in three different human muscles: biceps, first dorsal interosseous (FDI) of the hand and digastric. Tremor recorded as fluctuation of isometric force was compared with that occurring during contraction against a spring load. The spring compliance was selected to make the natural frequency of the part in each case appropriate for oscillations in the short latency stretch reflex. A computer model of the whole system was used to predict the frequency at which oscillations should be expected and to estimate the reflex gain required in each case to cause sustained oscillations. Estimates were computed of the autospectra of the force records and of the rectified surface EMG signals and of the coherence functions. Normal subjects showed no evidence of a distinct spectral peak during isometric recording from any of the three muscles. However, in anisometric conditions regular oscillations in force occurred in biceps, but not in FDI or digastric. The oscillations in biceps at 8-9 Hz were accompanied by similar oscillations in the EMG which were highly coherent with the force signal. The results are consistent with the presence of a strong segmental stretch reflex effect in biceps and weak or absent reflex in FDI. Digastric is known to contain no muscle spindles and therefore to lack a stretch reflex. In two subjects who volunteered that they had more tremor than normal, but had no known neurological abnormality, there was a distinct peak in the force spectrum at 8-9 Hz in biceps and FDI in isometric conditions with coherent EMG activity. The peak increased in size in anisometric conditions in biceps but not in FDI. This component appears to be of central rather than of reflex origin. No equivalent component was found in digastric records. The results are discussed in relation to the possible role of the short latency stretch reflex in the genesis of physiological tremor in different muscles.

  20. Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

    DEFF Research Database (Denmark)

    Lundby, Carsten; Hellsten, Ylva; Jensen, Mie B. F.;

    2008-01-01

    The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study...... the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects...... (n = 11) received a single Epo injection of 15,000 IU (double blinded, cross over, placebo). A single Epo injection reduced myoglobin and increased transferrin receptor and MRF-4 mRNA content within 10 h after injection. Plasma hormones remained unaltered. Capillarization and fiber hypertrophy...

  1. Effects of lubiprostone on human uterine smooth muscle cells.

    Science.gov (United States)

    Cuppoletti, John; Malinowska, Danuta H; Chakrabarti, Jayati; Ueno, Ryuji

    2008-06-01

    Lubiprostone, a bicyclic fatty acid derivative and member of a new class of compounds called prostones, locally activates ClC-2 Cl(-) channels without activation of prostaglandin receptors. The present study was specifically designed to test and compare lubiprostone and prostaglandin effects at the cellular level using human uterine smooth muscle cells. Effects on [Ca(2+)](i), membrane potential and [cAMP](i) in human uterine smooth muscle cells were measured. 10 nM lubiprostone significantly decreased [Ca(2+)](i) from 188 to 27 nM, which was unaffected by 100 nM SC-51322, a prostaglandin EP receptor antagonist. In contrast 10nM PGE(2) and PGE(1) both increased [Ca(2+)](i) 3-5-fold which was blocked by SC-51322. Similarly, lubiprostone and prostaglandins had opposite/different effects on membrane potential and [cAMP](i). Lubiprostone caused SC-51322-insensitive membrane hyperpolarization and no effect on [cAMP](i). PGE(2) and PGE(1) both caused SC-51322-sensitive membrane depolarization and increased [cAMP](i). Lubiprostone has fundamentally different cellular effects from prostaglandins that are not mediated by EP receptors.

  2. Series elasticity of the human triceps surae muscle : Measurement by controlled-release vs. resonance methods.

    NARCIS (Netherlands)

    Hof, AL; Boom, H; Robinson, C; Rutten, W; Neuman, M; Wijkstra, H

    1997-01-01

    With a newly developed Controlled-Release Ergometer the complete characteristic of the series elastic component can be measured in human muscles. Previous estimates were based on the resonance method: muscle elasticity was assessed from the resonance frequency of the muscle elasticity connected to a

  3. Expression profiles of muscle disease-associated genes and their isoforms during differentiation of cultured human skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Abdul-Hussein Saba

    2012-12-01

    Full Text Available Abstract Background The formation of contractile myofibrils requires the stepwise onset of expression of muscle specific proteins. It is likely that elucidation of the expression patterns of muscle-specific sarcomeric proteins is important to understand muscle disorders originating from defects in contractile sarcomeric proteins. Methods We investigated the expression profile of a panel of sarcomeric components with a focus on proteins associated with a group of congenital disorders. The analyses were performed in cultured human skeletal muscle cells during myoblast proliferation and myotube development. Results Our culture technique resulted in the development of striated myotubes and the expression of adult isoforms of the sarcomeric proteins, such as fast TnI, fast TnT, adult fast and slow MyHC isoforms and predominantly skeletal muscle rather than cardiac actin. Many proteins involved in muscle diseases, such as beta tropomyosin, slow TnI, slow MyBPC and cardiac TnI were readily detected in the initial stages of muscle cell differentiation, suggesting the possibility of an early role for these proteins as constituent of the developing contractile apparatus during myofibrillogenesis. This suggests that in disease conditions the mechanisms of pathogenesis for each of the mutated sarcomeric proteins might be reflected by altered expression patterns, and disturbed assembly of cytoskeletal, myofibrillar structures and muscle development. Conclusions In conclusion, we here confirm that cell cultures of human skeletal muscle are an appropriate tool to study developmental stages of myofibrillogenesis. The expression of several disease-associated proteins indicates that they might be a useful model system for studying the pathogenesis of muscle diseases caused by defects in specific sarcomeric constituents.

  4. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    DEFF Research Database (Denmark)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees......, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy...... metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized...

  5. Load and failure behavior of human muscle samples in the context of proximal femur replacement

    OpenAIRE

    Schleifenbaum, Stefan; Schmidt, Michael; Möbius, Robert; Wolfskämpf, Thomas; Schröder, Christian; Grunert, Ronny; Hammer, Niels; Prietzel, Torsten

    2016-01-01

    Background: To ensure adequate function after orthopedic tumor reconstruction, it is important to reattach the remaining soft tissue to the implant. This study aimed at obtaining mechanical properties of textile muscle-implant and muscle-bone connections in a preliminary test. Methods: Two groups of soft-tissue attachment were mechanically tested and compared: Native bone-muscle samples obtained from human femora and muscles attached to a prosthetic implant by means of Trevira® attachment tu...

  6. Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

    OpenAIRE

    Pietrangelo, Tiziana; Puglielli, Cristina; Mancinelli, Rosa; Beccafico, Sara; Fanò, Giorgio; Fulle, Stefania

    2009-01-01

    Abstract Sarcopenia is the age-related loss of muscle mass, strength and function. Human muscle proteins are synthesized at a slower rate in the elderly than in young adults, leading to atrophy and muscle mass loss with a decline in the functional capability. Additionally, aging is accompanied by a decrease in the ability of muscle tissue to regenerate following injury or overuse due to the impairment of intervening satellite cells, in which we previously reported oxidative damage ...

  7. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

    DEFF Research Database (Denmark)

    Suetta, Charlotte; Frandsen, Ulrik; Nielsen, Line;

    2012-01-01

    Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1a and PGC-1ß (1-4 days) and a ~10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

  8. Muscle Patterning in Mouse and Human Abdominal Wall Development and Omphalocele Specimens of Humans

    OpenAIRE

    Nichol, Peter F.; Corliss, Robert F.; Yamada, Shigehito; SHIOTA, KOHEI; Saijoh, Yukio

    2012-01-01

    Human omphalocele is a congenital defect of the abdominal wall in which the secondary abdominal wall structures (muscle and connective tissue) in an area centered around the umbilicus are replaced by a translucent membranous layer of tissue. Histological examination of omphalocele development and moreover the staging of normal human abdominal wall development has never been described. We hypothesized that omphalocele is the result of an arrest in the secondary abdominal wall development and p...

  9. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration.

    Science.gov (United States)

    Choi, Ji Suk; Yoon, Hwa In; Lee, Kyoung Soo; Choi, Young Chan; Yang, Seong Hyun; Kim, In-San; Cho, Yong Woo

    2016-01-28

    Exosomes released from skeletal muscle cells play important roles in myogenesis and muscle development via the transfer of specific signal molecules. In this study, we investigated whether exosomes secreted during myotube differentiation from human skeletal myoblasts (HSkM) could induce a cellular response from human adipose-derived stem cells (HASCs) and enhance muscle regeneration in a muscle laceration mouse model. The exosomes contained various signal molecules including myogenic growth factors related to muscle development, such as insulin-like growth factors (IGFs), hepatocyte growth factor (HGF), fibroblast growth factor-2 (FGF2), and platelet-derived growth factor-AA (PDGF-AA). Interestingly, exosome-treated HASCs fused with neighboring cells at early time points and exhibited a myotube-like phenotype with increased expression of myogenic proteins (myosin heavy chain and desmin). On day 21, mRNAs of terminal myogenic genes were also up-regulated in exosome-treated HASCs. Moreover, in vivo studies demonstrated that exosomes from differentiating HSkM reduced the fibrotic area and increased the number of regenerated myofibers in the injury site, resulting in significant improvement of skeletal muscle regeneration. Our findings suggest that exosomes act as a biochemical cue directing stem cell differentiation and provide a cell-free therapeutic approach for muscle regeneration.

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

    Science.gov (United States)

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

    2012-03-01

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

  11. Molecular networks of human muscle adaptation to exercise and age.

    Directory of Open Access Journals (Sweden)

    Bethan E Phillips

    2013-03-01

    Full Text Available Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44 who then undertook 20 weeks of supervised resistance-exercise training (RET. Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%, and when applying Ingenuity Pathway Analysis (IPA up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR signaling associating with growth (P = 1.4 × 10(-30. Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6 × 10(-13 and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = -2.3; P = 3 × 10(-7 with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET, they appear to represent "generic" physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52, with a continuum of subject ages (18-78 y, the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1 × 10(-6 and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to

  12. Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

    Science.gov (United States)

    Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

    2017-01-01

    This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature (P < 0.05). This result indicated that repeated local muscle cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

  13. Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

    Science.gov (United States)

    Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

    2017-07-01

    This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature ( P muscle cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

  14. Characterization of human carbonic anhydrase III from skeletal muscle.

    Science.gov (United States)

    Carter, N; Jeffery, S; Shiels, A; Edwards, Y; Tipler, T; Hopkinson, D A

    1979-10-01

    A third form of human carbonic anhydrase (CA III), found at high concentrations in skeletal muscle, has been purified and characterized. This isozyme shows relatively poor hydratase and esterase activities compared to the red cell isozymes, CA I and CA II, but is similar to these isozymes in subunit structure (monomer) and molecular size (28,000). CA III is liable to posttranslational modification by thiol group interaction. Monomeric secondary isozymes, sensitive to beta-mercaptoethanol, are found in both crude and purified material and can be generated in vitro by the addition of thiol reagents. Active dimeric isozymes, generated apparently by the formation of intermolecular disulfide bridges, also occur but account for only a small proportion of the total protein and appear only when the concentration of CA III is particularly high.

  15. Regional neuromuscular regulation within human rectus femoris muscle during gait.

    Science.gov (United States)

    Watanabe, Kohei; Kouzaki, Motoki; Moritani, Toshio

    2014-11-01

    The spatial distribution pattern of neuromuscular activation within the human rectus femoris (RF) muscle was investigated during gait by multi-channel surface electromyography (surface EMG). Eleven healthy men walked on a treadmill with three gait speeds (4, 5, and 6 km/h) and gradients (0°, 12.5°, and 25°). The spatial distribution of surface EMG was tested by central locus activation (CLA), which is calculated from 2-D multi-channel surface EMG with 46 surface electrodes. For all conditions, CLA was around the middle regions during the swing-to-stance transition and moved in a proximal direction during the stance phase and stance-to-swing transition (pphase significantly moved to proximal site with increasing gait speed (pphases, with increasing grade, CLA significantly moved distally (pgait cycle and is non-uniformly regulated longitudinally.

  16. Human eosinophil–airway smooth muscle cell interactions

    Directory of Open Access Journals (Sweden)

    J. Margaret Hughes

    2000-01-01

    Full Text Available Eosinophils are present throughout the airway wall of asthmatics. The nature of the interaction between human airway smooth muscle cells (ASMC and eosinophils was investigated in this study. We demonstrated, using light microscopy, that freshly isolated eosinophils from healthy donors rapidly attach to ASMC in vitro. Numbers of attached eosinophils were highest at 2 h, falling to 50% of maximum by 20 h. Eosinophil attachment at 2 h was reduced to 72% of control by anti-VCAM-1, and to 74% at 20 h by anti-ICAM-1. Pre-treatment of ASMC for 24 h with TNF-α, 10 nM, significantly increased eosinophil adhesion to 149 and 157% of control after 2 and 20 h. These results provide evidence that eosinophil interactions with ASMC involve VCAM-1 and ICAM-1 and are modulated by TNF-α.

  17. Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration.

    Science.gov (United States)

    de la Garza-Rodea, Anabel S; Boersma, Hester; Dambrot, Cheryl; de Vries, Antoine Af; van Bekkum, Dirk W; Knaän-Shanzer, Shoshan

    2015-05-20

    To study regeneration of damaged human and murine muscle implants and the contribution of added xenogeneic mesenchymal stem cells (MSCs). Minced human or mouse skeletal muscle tissues were implanted together with human or mouse MSCs subcutaneously on the back of non-obese diabetic/severe combined immunodeficient mice. The muscle tissues (both human and murine) were minced with scalpels into small pieces (< 1 mm(3)) and aliquoted in portions of 200 mm(3). These portions were either cryopreserved in 10% dimethylsulfoxide or freshly implanted. Syngeneic or xenogeneic MSCs were added to the minced muscles directly before implantation. Implants were collected at 7, 14, 30 or 45 d after transplantation and processed for (immuno)histological analysis. The progression of muscle regeneration was assessed using a standard histological staining (hematoxylin-phloxin-saffron). Antibodies recognizing Pax7 and von Willebrand factor were used to detect the presence of satellite cells and blood vessels, respectively. To enable detection of the bone marrow-derived MSCs or their derivatives we used MSCs previously transduced with lentiviral vectors expressing a cytoplasmic LacZ gene. X-gal staining of the fixed tissues was used to detect β-galactosidase-positive cells and myofibers. Myoregeneration in implants of fresh murine muscle was evident as early as day 7, and progressed with time to occupy 50% to 70% of the implants. Regeneration of fresh human muscle was slower. These observations of fresh muscle implants were in contrast to the regeneration of cryopreserved murine muscle that proceeded similarly to that of fresh tissue except for day 45 (P < 0.05). Cryopreserved human muscle showed minimal regeneration, suggesting that the freezing procedure was detrimental to human satellite cells. In fresh and cryopreserved mouse muscle supplemented with LacZ-tagged mouse MSCs, β-galactosidase-positive myofibers were identified early after grafting at the well-vascularized periphery of

  18. Interstitial pH in human skeletal muscle during and after dynamic graded exercise

    DEFF Research Database (Denmark)

    Street, D; Bangsbo, Jens; Juel, Carsten

    2001-01-01

    In this study a new method has been used to measure interstitial pH continuously in human muscle during graded exercise. Human subjects performed 5 min of one-legged knee-extensor exercise at power outputs of 30, 50 and 70 W. Muscle interstitial pH was measured continuously in microdialysis...

  19. Growth factor-induced contraction of human bronchial smooth muscle is Rho-kinase-dependent

    NARCIS (Netherlands)

    Gosens, Reinout; Schaafsma, D.; Grootte Bromhaar, M.M; Vrugt, B.; Zaagsma, Hans; Meurs, Herman; Nelemans, Herman

    2004-01-01

    Growth factors have been implicated in the pathophysiology of asthma. However, the putative effects of these growth factors on human airway smooth muscle tone are still largely unknown. We performed contraction experiments using human bronchial smooth muscle ring preparations. The growth factor

  20. A microcalorimetric study of the sodium-potassium-pump and thermogenesis in human skeletal muscle.

    Science.gov (United States)

    Fagher, B; Sjögren, A; Monti, M

    1987-11-01

    Thermogenesis in human skeletal muscle was monitored by measurement of heat production using perfusion microcalorimetry. Heat production significantly correlated with relative body weight. The energy expenditure of the Na-K-pump (delta P), assessed after inhibition by ouabain in Krebs-Ringer phosphate buffer containing glucose and insulin, amounted to 6% of the total heat production in vastus lateralis muscle. Muscle potassium positively correlated with delta P (r = 0.84, P less than 0.005). For rectus abdominis muscle delta P was 8-15%; 95% confidence interval for the difference was 3-5% when comparison was made with vastus lateralis. The finding of a positive relationship between delta P and muscle magnesium (r = 0.68, P less than 0.04) is possibly explained by the dependence of ATP hydrolysis on internal magnesium. Our data on resting thermogenesis in small muscle samples agree to previous estimates of O2 consumption in human skeletal muscle in vivo.

  1. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects

    DEFF Research Database (Denmark)

    Larsen, Steen; Nielsen, Joachim; Neigaard Nielsen, Christina

    2012-01-01

    closely associated these commonly used biochemical measures are to muscle mitochondrial content and muscle oxidative capacity (OXPHOS).Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake (VO(2peak)) and muscle......Skeletal muscle mitochondrial content varies extensively between human subjects. Biochemical measures of mitochondrial proteins, enzyme activities and lipids are often used as markers of mitochondrial content and muscle oxidative capacity (OXPHOS). The purpose of this study was to determine how...... to muscle oxidative capacity followed by complex II activity.We conclude that cardiolipin content, CS and complex I activity are the biomarkers that exhibit the strongest association to mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle....

  2. Subcellular localization and mechanism of secretion of vascular endothelial growth factor in human skeletal muscle

    DEFF Research Database (Denmark)

    Høier, Birgitte; Prats Gavalda, Clara; Qvortrup, Klaus

    2013-01-01

    The subcellular distribution and secretion of vascular endothelial growth factor (VEGF) was examined in skeletal muscle of healthy humans. Skeletal muscle biopsies were obtained from m.v. lateralis before and after a 2 h bout of cycling exercise. VEGF localization was conducted on preparations...... of teased muscle fibers by transmission electron microscopy (TEM) and confocal microscopy (CM). Muscle interstitial fluid was sampled from microdialysis probes placed in the thigh muscle. TEM and CM analysis revealed two primary sites of localization of VEGF: in vesicles located in the subsarcolemmal...... regions and between the contractile elements within the muscle fibers; and in pericytes situated on the skeletal muscle capillaries. Quantitation of the subsarcolemmal density of VEGF vesicles, calculated on top of myonuclei, in the muscle fibers revealed a ∼50% increase (P...

  3. Metabolic control of muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher

    2003-01-01

    During muscle contraction, several mechanisms regulate blood flow to ensure a close coupling between muscle oxygen delivery and metabolic demand. No single factor has been identified to constitute the primary metabolic regulator, yet there are signal transduction pathways between skeletal muscle...

  4. A predictive model of muscle excitations based on muscle modularity for a large repertoire of human locomotion conditions

    Directory of Open Access Journals (Sweden)

    Jose eGonzalez-Vargas

    2015-09-01

    Full Text Available Humans can efficiently walk across a large variety of terrains and locomotion conditions with little or no mental effort. It has been hypothesized that the nervous system simplifies neuromuscular control by using muscle synergies, thus organizing multi-muscle activity into a small number of coordinative co-activation modules. In the present study we investigated how muscle modularity is structured across a large repertoire of locomotion conditions including five different speeds and five different ground elevations. For this we have used the non-negative matrix factorization technique in order to explain EMG experimental data with a low-dimensional set of four motor components. In this context each motor components is composed of a non-negative factor and the associated muscle weightings. Furthermore, we have investigated if the proposed descriptive analysis of muscle modularity could be translated into a predictive model that could: 1 Estimate how motor components modulate across locomotion speeds and ground elevations. This implies not only estimating the non-negative factors temporal characteristics, but also the associated muscle weighting variations. 2 Estimate how the resulting muscle excitations modulate across novel locomotion conditions and subjects.The results showed three major distinctive features of muscle modularity: 1 the number of motor components was preserved across all locomotion conditions, 2 the non-negative factors were consistent in shape and timing across all locomotion conditions, and 3 the muscle weightings were modulated as distinctive functions of locomotion speed and ground elevation. Results also showed that the developed predictive model was able to reproduce well the muscle modularity of un-modeled data, i.e. novel subjects and conditions. Muscle weightings were reconstructed with a cross-correlation factor greater than 70% and a root mean square error less than 0.10. Furthermore, the generated muscle excitations

  5. A predictive model of muscle excitations based on muscle modularity for a large repertoire of human locomotion conditions.

    Science.gov (United States)

    Gonzalez-Vargas, Jose; Sartori, Massimo; Dosen, Strahinja; Torricelli, Diego; Pons, Jose L; Farina, Dario

    2015-01-01

    Humans can efficiently walk across a large variety of terrains and locomotion conditions with little or no mental effort. It has been hypothesized that the nervous system simplifies neuromuscular control by using muscle synergies, thus organizing multi-muscle activity into a small number of coordinative co-activation modules. In the present study we investigated how muscle modularity is structured across a large repertoire of locomotion conditions including five different speeds and five different ground elevations. For this we have used the non-negative matrix factorization technique in order to explain EMG experimental data with a low-dimensional set of four motor components. In this context each motor components is composed of a non-negative factor and the associated muscle weightings. Furthermore, we have investigated if the proposed descriptive analysis of muscle modularity could be translated into a predictive model that could: (1) Estimate how motor components modulate across locomotion speeds and ground elevations. This implies not only estimating the non-negative factors temporal characteristics, but also the associated muscle weighting variations. (2) Estimate how the resulting muscle excitations modulate across novel locomotion conditions and subjects. The results showed three major distinctive features of muscle modularity: (1) the number of motor components was preserved across all locomotion conditions, (2) the non-negative factors were consistent in shape and timing across all locomotion conditions, and (3) the muscle weightings were modulated as distinctive functions of locomotion speed and ground elevation. Results also showed that the developed predictive model was able to reproduce well the muscle modularity of un-modeled data, i.e., novel subjects and conditions. Muscle weightings were reconstructed with a cross-correlation factor greater than 70% and a root mean square error less than 0.10. Furthermore, the generated muscle excitations matched

  6. Reduced short-interval intracortical inhibition after eccentric muscle damage in human elbow flexor muscles.

    Science.gov (United States)

    Pitman, Bradley M; Semmler, John G

    2012-09-01

    The purpose of this study was to use paired-pulse transcranial magnetic stimulation (TMS) to examine the effect of eccentric exercise on short-interval intracortical inhibition (SICI) after damage to elbow flexor muscles. Nine young (22.5 ± 0.6 yr; mean ± SD) male subjects performed maximal eccentric exercise of the elbow flexor muscles until maximal voluntary contraction (MVC) force was reduced by ∼40%. TMS was performed before, 2 h after, and 2 days after exercise under Rest and Active (5% MVC) conditions with motor-evoked potentials (MEPs) recorded from the biceps brachii (BB) muscle. Peripheral electrical stimulation of the brachial plexus was used to assess maximal M-waves, and paired-pulse TMS with a 3-ms interstimulus interval was used to assess changes in SICI at each time point. The eccentric exercise resulted in a 34% decline in strength (P muscle strength (27%, P muscle soreness (P muscle damage. When the test MEP amplitudes were matched between sessions, we found that SICI was reduced by 27% in resting and 23% in active BB muscle 2 h after exercise. SICI recovered 2 days after exercise when muscle pain and soreness were present, suggesting that delayed onset muscle soreness from eccentric exercise does not influence SICI. The change in SICI observed 2 h after exercise suggests that eccentric muscle damage has widespread effects throughout the motor system that likely includes changes in motor cortex.

  7. No release of interstitial glutamate in experimental human model of muscle pain

    DEFF Research Database (Denmark)

    Ashina, M.; Jørgensen, M.; Stallknecht, Bente;

    2005-01-01

    Glutamate may be released from muscle nociceptors and thereby contribute to mechanisms underlying acute and chronic muscle pain. In vivo concentration of glutamate during muscle pain has not previously been studied in either animals or humans. In the present study, we aimed to study the in vivo...... flow increased significantly over time in response to infusion of chemical mixture and placebo (p = 0.001). However, we found no difference in changes in muscle blood flow between chemical mixture and placebo (p > 0.05). In conclusion, the present study demonstrates no signs of increased release...... of glutamate from myofascial nociceptors during and after acute experimentally induced muscle pain and tenderness....

  8. Regenerative medicine for insulin deficiency: creation of pancreatic islets and bioartificial pancreas.

    OpenAIRE

    Sumi, Shoichiro

    2011-01-01

    Recent advances in pancreas organogenesis have greatly improved the understanding of cell lineage from inner cell mass to fully differentiated β-cells. Based upon such knowledge, insulin-producing cells similar to β-cells to a certain extent have been generated from various cell sources including embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells, although fully differentiated cells comparable to β-cells are not yet available. The bioartificial pancreas is a therapeutic appr...

  9. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition

    DEFF Research Database (Denmark)

    Nielsen, Anders Rinnov; Mounier, Remi; Plomgaard, Peter

    2007-01-01

    of recovery without any changes in muscle IL-15 protein content or plasma IL-15 at any of the investigated time points. In conclusion, IL-15 mRNA level is enhanced in skeletal muscles dominated by type 2 fibres and resistance exercise induces increased muscular IL-15 mRNA levels. IL-15 mRNA levels in skeletal......The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus...... lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers (n = 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects (n = 8) not involved...

  10. An in vitro model of the glomerular capillary wall using electrospun collagen nanofibres in a bioartificial composite basement membrane.

    Directory of Open Access Journals (Sweden)

    Sadie C Slater

    Full Text Available The filtering unit of the kidney, the glomerulus, contains capillaries whose walls function as a biological sieve, the glomerular filtration barrier. This comprises layers of two specialised cells, glomerular endothelial cells (GEnC and podocytes, separated by a basement membrane. Glomerular filtration barrier function, and dysfunction in disease, remains incompletely understood, partly due to difficulties in studying the relevant cell types in vitro. We have addressed this by generation of unique conditionally immortalised human GEnC and podocytes. However, because the glomerular filtration barrier functions as a whole, it is necessary to develop three dimensional co-culture models to maximise the benefit of the availability of these cells. Here we have developed the first two tri-layer models of the glomerular capillary wall. The first is based on tissue culture inserts and provides evidence of cell-cell interaction via soluble mediators. In the second model the synthetic support of the tissue culture insert is replaced with a novel composite bioartificial membrane. This consists of a nanofibre membrane containing collagen I, electrospun directly onto a micro-photoelectroformed fine nickel supporting mesh. GEnC and podocytes grew in monolayers on either side of the insert support or the novel membrane to form a tri-layer model recapitulating the human glomerular capillary in vitro. These models will advance the study of both the physiology of normal glomerular filtration and of its disruption in glomerular disease.

  11. Suction-modified needle biopsy technique for the human soleus muscle.

    Science.gov (United States)

    Cotter, Joshua A; Yu, Alvin; Kreitenberg, Arthur; Haddad, Fadia H; Baker, Michael J; Fox, John C; Adams, Gregory R

    2013-10-01

    The needle biopsy technique for the soleus muscle is of particular interest because of the muscle's unique fiber type distribution, contractile properties, and sensitivity to unloading. Unlike other commonly biopsied muscles, the soleus is not fully superficial and is in close proximity to neurovascular structures, resulting in a more challenging biopsy. Because of this, a standardized protocol for performing needle biopsies on the human soleus muscle that is safe, reliable, and repeatable is presented. Ultrasonography was used on an initial set of 12 subjects to determine the optimal biopsy zone, thereby guiding the location of the incision site. There were 45 subjects recruited who attended 2 separate biopsy sessions. Each biopsy session incorporated 3 passes of the biopsy needle proximal, posterior, and distal using suction from a portable vacuum source producing 3 separate muscle specimens. There were 84 soleus muscle biopsy procedures which were successfully conducted yielding 252 total samples without complication. Ultrasonography was used to confirm biopsy needle infiltration of the soleus muscle. Average sample weight obtained per pass was 61.5 +/- 15.7 mg. Histochemistry and molecular analyses demonstrated a considerably higher amount of slow type I MHC in comparison to the vastus lateralis, providing verification for the successful sampling of the soleus muscle. The procedure presented consists of a detailed protocol to accurately and consistently obtain muscle biopsy samples from the human soleus muscle. We have demonstrated that the human soleus biopsy is a safe, reliable, and repeatable procedure providing ample tissue for multiple types of analyses.

  12. Heparin inhibits human coronary artery smooth muscle cell migration.

    Science.gov (United States)

    Kohno, M; Yokokawa, K; Yasunari, K; Minami, M; Kano, H; Mandal, A K; Yoshikawa, J

    1998-09-01

    Heparin, an anticoagulant, has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies, but the clinical trials of heparin in coronary balloon angioplasty have been negative. The current study, therefore, examined the effect of heparin on basal or stimulated migration by serum and platelet-derived growth factor (PDGF)-BB in cultured human coronary artery smooth muscle cells (SMCs) by Boyden's chamber method. In addition, the reversibility of the heparin effect on human coronary artery SMC migration was examined. Fetal calf serum (FCS) and PDGF-BB stimulated SMC migration in a concentration-dependent manner. Heparin in moderate to high concentration (10 to 100 U/mL) exhibited concentration-related inhibition of FCS- and PDGF-BB-stimulated SMC migration; however, a low concentration (1 U/mL) of heparin had no inhibitory effects. Heparin also had weak inhibitory effects on nonstimulated SMC migration. The SMCs that were exposed to a high concentration (100 U/mL) of heparin for 6 hours were capable of migrating after a short lag period of removal of heparin from the culture medium. These SMCs also showed recovery of responses to FCS and PDGF-BB by migrating significantly greater than the nonstimulated level. Furthermore, heparin-containing medium did not contain detached cells. These results indicate that heparin inhibits human coronary artery SMC migration, especially when stimulated by FCS or PDGF-BB, and that this inhibitory effect of heparin is reversible and not simply a function of killing cells.

  13. Task-dependent spatial distribution of neural activation pattern in human rectus femoris muscle.

    Science.gov (United States)

    Watanabe, Kohei; Kouzaki, Motoki; Moritani, Toshio

    2012-04-01

    Compartmentalization of skeletal muscle by multiple motor nerve branches, named as neuromuscular compartment (NMC), has been demonstrated in animals as well as humans. While different functional roles among individual NMCs were reported in the animal studies, no studies have clarified the region-specific functional role within a muscle related with NMCs arrangement in human skeletal muscle. It was reported that the rectus femoris (RF) muscle is innervated by two nerve branches attached at proximal and distal parts of the muscle. The purpose of the present study is to clarify the possible region-specific functional role in the human RF muscle. Multi-channel surface electromyography (SEMG) were recorded from the RF muscle by using 128 electrodes during two different submaximal isometric contractions that the muscle contributes, i.e. isometric knee extension and hip flexion, at 20%, 40%, 60% and 80% of maximal voluntary contraction (MVC). Results indicated that the central locus activation for the amplitude map of SEMG during hip flexion located at more proximal region compared with that during knee extension. Significant higher normalized root mean square (RMS) values were observed at the proximal region during the hip flexion in comparison to those at middle and distal regions at 60% and 80% of MVC (pMVC (p<0.05). The results of the present study suggest possible region-specific functional role in the human RF muscle.

  14. Muscle triacylglycerol and hormone-sensitive lipase activity in untrained and trained human muscles

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Biba, Taus O; Galbo, Henrik

    2006-01-01

    During exercise, triacylglycerol (TG) is recruited in skeletal muscles. We hypothesized that both muscle hormone-sensitive lipase (HSL) activity and TG recruitment would be higher in trained than in untrained subjects in response to prolonged exercise. Healthy male subjects (26 +/- 1 years, body ...

  15. SUPERNORMAL MUSCLE-FIBER CONDUCTION-VELOCITY DURING INTERMITTENT ISOMETRIC-EXERCISE IN HUMAN MUSCLE

    NARCIS (Netherlands)

    VANDERHOEVEN, JH; LANGE, F

    1994-01-01

    Muscle fiber conduction velocity (MFCV) and surface electromyographic parameters were studied in the brachial biceps muscle of healthy males during voluntary intermittent isometric contractions at 50% of maximum force. Recovery in the following 15 min was then observed. The measurements were perform

  16. Provocation of delayed-onset muscle soreness in the human jaw-closing muscles

    NARCIS (Netherlands)

    Türker, K.S.; Koutris, M.; Sümer, N.C.; Atis, E.S.; Linke, I.R.; Lobbezoo, F.; Naeije, M.

    2010-01-01

    Eccentric contractions of jaw-closing muscles are difficult to perform. This may explain why fatigue-inducing experiments performed so far suggest the jaw-closing muscles to be fatigue resistant. Aim of this study was to construct an apparatus that can impose intense eccentric contractions to the ja

  17. Muscles within muscles: a tensiomyographic and histochemical analysis of the normal human vastus medialis longus and vastus medialis obliquus muscles.

    Science.gov (United States)

    Travnik, Ludvik; Djordjevič, Srdjan; Rozman, Sergej; Hribernik, Marija; Dahmane, Raja

    2013-06-01

    The aim of this study was to show the connection between structure (anatomical and histochemical) and function (muscle contraction properties) of vastus medialis obliquus (VMO) and vastus medialis longus (VML). The non-invasive tensiomyography (TMG) method was used to determine the contractile properties (contraction time; T(c)) of VML and VMO muscle, as a reflection of the ratio between the slow and fast fibers in two groups of nine young men. VML and VMO significantly (P knee, and to the VMO, which maintains the stable position of the patella in the femoral groove. Our results obtained by TMG provided additional evidence that muscle fibers within the segments of VM muscle were not homogenous with regard to their contractile properties, thereby confirming the histochemical results. T(c) can be attributed to the higher percentage of slow-twitch fibers - type 1. The statistically shorter T(c) (P ≤ 0.001) of VMO (22.8 ± 4.0 ms) compared with VML (26.7 ± 4.0 ms) in our study is consistent with previously found differences in histochemical, morphological and electrophysiological data. In conclusion, the results of this study provide evidence that the VML and VMO muscles are not only anatomically and histochemically different muscles, but also functionally different biological structures.

  18. Low muscle glycogen and elevated plasma free fatty acid modify but do not prevent exercise-induced PDH activation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian; Gudmundsson, Mikkel; Birk, Jesper Bratz;

    2010-01-01

    Objective: Test the hypothesis that FFA and muscle glycogen modify exercise-induced regulation of PDH in human skeletal muscle through regulation of PDK4 expression. Research Design and Methods: On two occasions, healthy male subjects lowered (by exercise) muscle glycogen in one leg (LOW) relativ...

  19. Effects of muscle activation on shear between human soleus and gastrocnemius muscles.

    Science.gov (United States)

    Finni, T; Cronin, N J; Mayfield, D; Lichtwark, G A; Cresswell, A G

    2017-01-01

    Lateral connections between muscles provide pathways for myofascial force transmission. To elucidate whether these pathways have functional roles in vivo, we examined whether activation could alter the shear between the soleus (SOL) and lateral gastrocnemius (LG) muscles. We hypothesized that selective activation of LG would decrease the stretch-induced shear between LG and SOL. Eleven volunteers underwent a series of knee joint manipulations where plantar flexion force, LG, and SOL muscle fascicle lengths and relative displacement of aponeuroses between the muscles were obtained. Data during a passive full range of motion were recorded, followed by 20° knee extension stretches in both passive conditions and with selective electrical stimulation of LG. During active stretch, plantar flexion force was 22% greater (P muscles, at least at flexed knee joint angles, which may serve to facilitate myofascial force transmission. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    DEFF Research Database (Denmark)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng;

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees......, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy...

  1. Functional Compartmentalization of the Human Superficial Masseter Muscle

    OpenAIRE

    Guzmán-Venegas, Rodrigo A.; Biotti Picand, Jorge L.; Francisco J Berral de la Rosa

    2015-01-01

    Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM) muscle's motor units using high-density surface e...

  2. Functional Echomyography of the human denervated muscle: first results

    Directory of Open Access Journals (Sweden)

    Riccardo Zanato

    2011-03-01

    Full Text Available In this study we followed with ultrasound three patients with permanent denervation to evaluate changes in morphology, thickness, contraction and vascularisation of muscles undergoing the home-based electrical stimulation program of the Rise2-Italy project. During a period of 1 year for the first subject, 6 months for the second subject and 3 months for the third subject we studied with ultrasound the denervated muscle comparing it (if possible to the contralateral normal muscle. We evaluated: 1. Changes in morphology and sonographic structure of the pathologic muscle; 2. Muscular thickness in response to the electrical stimulation therapy; 3. Short-term modifications in muscle perfusion and arterial flow patterns after stimulation; 4. Contraction-relaxation kinetic induced by volitional activity or electrical stimulation. Morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete muscular atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third than in the proximal and distal third of the denervated muscle, reaching in the last measurements of the first subject approximately the same thickness as the contralateral normal muscle. In all the measurements done within this study, arterial flow of the denervated muscle showed at rest a low-resistance pattern with Doppler Ultra Sound (US, and a pulsed pattern after electrical stimulation. The stimulation- induced pattern is similar to the trifasic high-resistance pattern of the normal muscle. Contraction- relaxation kinetic, measured by recording the muscular movements during electrical stimulation, showed an abnormal behaviour of the denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle (880 msec in the denervated muscle vs 240 msec in the contralateral normal one

  3. Multi-frequency bioimpedance in human muscle assessment

    DEFF Research Database (Denmark)

    Bartels, Else Marie; Sørensen, Emma Rudbæk; Harrison, Adrian Paul

    2015-01-01

    Bioimpedance analysis (BIA) is a well-known and tested method for body mass and muscular health assessment. Multi-frequency BIA (mfBIA) equipment now makes it possible to assess a particular muscle as a whole, as well as looking at a muscle at the fiber level. The aim of this study was to test......, contracted state, and cell transport/metabolic activity, which relate to muscle performance. Our findings indicate that mfBIA provides a noninvasive, easily measurable and very precise momentary assessment of skeletal muscles....

  4. Silk fibroin scaffolds with muscle-like elasticity support in vitro differentiation of human skeletal muscle cells.

    Science.gov (United States)

    Chaturvedi, Vishal; Naskar, Deboki; Kinnear, Beverley F; Grenik, Elizabeth; Dye, Danielle E; Grounds, Miranda D; Kundu, Subhas C; Coombe, Deirdre R

    2016-11-22

    Human adult skeletal muscle has a limited ability to regenerate after injury and therapeutic options for volumetric muscle loss are few. Technologies to enhance regeneration of tissues generally rely upon bioscaffolds to mimic aspects of the tissue extracellular matrix (ECM). In the present study, silk fibroins from four Lepidoptera (silkworm) species engineered into three-dimensional scaffolds were examined for their ability to support the differentiation of primary human skeletal muscle myoblasts. Human skeletal muscle myoblasts (HSMMs) adhered, spread and deposited extensive ECM on all the scaffolds, but immunofluorescence and quantitative polymerase chain reaction analysis of gene expression revealed that myotube formation occurred differently on the various scaffolds. Bombyx mori fibroin scaffolds supported formation of long, well-aligned myotubes, whereas on Antheraea mylitta fibroin scaffolds the myotubes were thicker and shorter. Myotubes were oriented in two perpendicular layers on Antheraea assamensis scaffolds, and scaffolds of Philosamia/Samia ricini (S. ricini) fibroin poorly supported myotube formation. These differences were not caused by fibroin composition per se, as HSMMs adhered to, proliferated on and formed striated myotubes on all four fibroins presented as two-dimensional fibroin films. The Young's modulus of A. mylitta and B. mori scaffolds mimicked that of normal skeletal muscle, but A. assamensis and S. ricini scaffolds were more flexible. The present study demonstrates that although myoblasts deposit matrix onto fibroin scaffolds and create a permissive environment for cell proliferation, a scaffold elasticity resembling that of normal muscle is required for optimal myotube length, alignment, and maturation. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

  5. Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Gejl, Kasper D; Hey-Mogensen, Martin;

    2016-01-01

    that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents and improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements. This article is protected by copyright. All rights reserved.......-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose...

  6. Parameter estimation of the Huxley cross-bridge muscle model in humans.

    Science.gov (United States)

    Vardy, Alistair N; de Vlugt, Erwin; van der Helm, Frans C T

    2012-01-01

    The Huxley model has the potential to provide more accurate muscle dynamics while affording a physiological interpretation at cross-bridge level. By perturbing the wrist at different velocities and initial force levels, reliable Huxley model parameters were estimated in humans in vivo using a Huxley muscle-tendon complex. We conclude that these estimates may be used to investigate and monitor changes in microscopic elements of muscle functioning from experiments at joint level.

  7. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy.

    Directory of Open Access Journals (Sweden)

    Charlotte Suetta

    Full Text Available Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2-4 days of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days and a ~10% decrease in myofiber size (4 days. Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days of immobilization. In contrast, Akt phosphorylation was unchanged in old muscle after 2 days and increased after 4 days of immobilization. Further, an age-specific down-regulation of MuRF-1 and Atrogin-1 expression levels was observed following 2 weeks of immobilization, along with a slowing atrophy response in aged skeletal muscle. Neither the immediate loss of muscle mass, nor the subsequent age-differentiated signaling responses could be explained by changes in inflammatory mediators, apoptosis markers or autophagy indicators. Collectively, these findings indicate that the time-course and regulation of human skeletal muscle atrophy is age dependent, leading to an attenuated loss in aging skeletal muscle when exposed to longer periods of immobility-induced disuse.

  8. Comparison of rotator cuff muscle architecture between humans and other selected vertebrate species

    Science.gov (United States)

    Mathewson, Margie A.; Kwan, Alan; Eng, Carolyn M.; Lieber, Richard L.; Ward, Samuel R.

    2014-01-01

    In this study, we compare rotator cuff muscle architecture of typically used animal models with that of humans and quantify the scaling relationships of these muscles across mammals. The four muscles that correspond to the human rotator cuff – supraspinatus, infraspinatus, subscapularis and teres minor – of 10 commonly studied animals were excised and subjected to a series of comparative measurements. When body mass among animals was regressed against physiological cross-sectional area, muscle mass and normalized fiber length, the confidence intervals suggested geometric scaling but did not exclude other scaling relationships. Based on the architectural difference index (ADI), a combined measure of fiber length-to-moment arm ratio, fiber length-to-muscle length ratio and the fraction of the total rotator cuff physiological cross-sectional area contributed by each muscle, chimpanzees were found to be the most similar to humans (ADI=2.15), followed closely by capuchins (ADI=2.16). Interestingly, of the eight non-primates studied, smaller mammals such as mice, rats and dogs were more similar to humans in architectural parameters compared with larger mammals such as sheep, pigs or cows. The force production versus velocity trade-off (indicated by fiber length-to-moment arm ratio) and the excursion ability (indicated by fiber length-to-muscle length ratio) of humans were also most similar to those of primates, followed by the small mammals. Overall, primates provide the best architectural representation of human muscle architecture. However, based on the muscle architectural parameters of non-primates, smaller rather than larger mammals may be better models for studying muscles related to the human rotator cuff. PMID:24072803

  9. Comparison of rotator cuff muscle architecture between humans and other selected vertebrate species.

    Science.gov (United States)

    Mathewson, Margie A; Kwan, Alan; Eng, Carolyn M; Lieber, Richard L; Ward, Samuel R

    2014-01-15

    In this study, we compare rotator cuff muscle architecture of typically used animal models with that of humans and quantify the scaling relationships of these muscles across mammals. The four muscles that correspond to the human rotator cuff - supraspinatus, infraspinatus, subscapularis and teres minor - of 10 commonly studied animals were excised and subjected to a series of comparative measurements. When body mass among animals was regressed against physiological cross-sectional area, muscle mass and normalized fiber length, the confidence intervals suggested geometric scaling but did not exclude other scaling relationships. Based on the architectural difference index (ADI), a combined measure of fiber length-to-moment arm ratio, fiber length-to-muscle length ratio and the fraction of the total rotator cuff physiological cross-sectional area contributed by each muscle, chimpanzees were found to be the most similar to humans (ADI=2.15), followed closely by capuchins (ADI=2.16). Interestingly, of the eight non-primates studied, smaller mammals such as mice, rats and dogs were more similar to humans in architectural parameters compared with larger mammals such as sheep, pigs or cows. The force production versus velocity trade-off (indicated by fiber length-to-moment arm ratio) and the excursion ability (indicated by fiber length-to-muscle length ratio) of humans were also most similar to those of primates, followed by the small mammals. Overall, primates provide the best architectural representation of human muscle architecture. However, based on the muscle architectural parameters of non-primates, smaller rather than larger mammals may be better models for studying muscles related to the human rotator cuff.

  10. Behavior of human gastrocnemius muscle fascicles during ramped submaximal isometric contractions.

    Science.gov (United States)

    Héroux, Martin E; Stubbs, Peter W; Herbert, Robert D

    2016-09-01

    Precise estimates of muscle architecture are necessary to understand and model muscle mechanics. The primary aim of this study was to estimate continuous changes in fascicle length and pennation angle in human gastrocnemius muscles during ramped plantar flexor contractions at two ankle angles. The secondary aim was to determine whether these changes differ between proximal and distal fascicles. Fifteen healthy subjects performed ramped contractions (0-25% MVC) as ultrasound images were recorded from the medial (MG, eight sites) and lateral (LG, six sites) gastrocnemius muscle with the ankle at 90° and 120° (larger angles correspond to shorter muscle lengths). In all subjects, fascicles progressively shortened with increasing torque. MG fascicles shortened 5.8 mm (11.1%) at 90° and 4.5 mm (12.1%) at 120°, whereas LG muscle fascicles shortened 5.1 mm (8.8%) at both ankle angles. MG pennation angle increased 1.4° at 90° and 4.9° at 120°, and LG pennation angle decreased 0.3° at 90° and increased 2.6° at 120°. Muscle architecture changes were similar in proximal and distal fascicles at both ankle angles. This is the first study to describe continuous changes in fascicle length and pennation angle in the human gastrocnemius muscle during ramped isometric contractions. Very similar changes occurred in proximal and distal muscle regions. These findings are relevant to studies modeling active muscle mechanics.

  11. Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise.

    Science.gov (United States)

    Penkowa, Milena; Keller, Charlotte; Keller, Pernille; Jauffred, Sune; Pedersen, Bente Klarlund

    2003-11-01

    Interleukin-6 (IL-6) is produced by many different cell types. Human skeletal muscles produce and release high amounts of IL-6 during exercise; however, the cell source of origin in the muscle is not known. Therefore, we studied the protein expression of IL-6 by immunohistochemistry in human muscle tissue from biopsies obtained at time points 0, 3, 4.5, 6, 9, and 24 h in relation to 3 h of bicycle exercise performed by healthy young males (n=12) and in resting controls (n=6). The IL-6 expression was clearly increased after exercise and remained high even by 24 h, relative to pre-exercise or resting individuals. The IL-6 immunostainings of skeletal muscle cells were homogeneous and without difference between muscle fiber types. The IL-6 mRNA peaked immediately after the exercise, and, in accordance, the IL-6 protein expression within muscle cells was most pronounced around 3 h post-exercise. However, the finding that plasma IL-6 concentration peaked in the end of exercise indicates a high turnover of muscle-derived IL-6. In conclusion, the finding of marked IL-6 protein expression exclusively within skeletal muscle fibers following exercise demonstrates that skeletal muscle fibers of all types are the dominant cell source of exercise-induced release of IL-6 from working muscle.

  12. Analysis of human muscle extracts by proton NMR

    Energy Technology Data Exchange (ETDEWEB)

    Venkatasubramanian, P.N.; Barany, M.; Arus, C.

    1986-03-01

    Perchloric acid extracts were prepared from pooled human muscle biopsies from patients diagnosed with scoliosis (SCOL) and cerebral palsy (CP). After neutralization with KOH and removal of perchlorate, the extracts were concentrated by freeze drying and dissolved in /sup 2/H/sub 2/O to contain 120 O.D. units at 280 nm per 0.5 ml. /sup 1/H NMR spectroscopy was performed with the 5 mm probe of a Varian XL300 instrument. Creatine, lactate, carnosine, and choline were the major resonances in the one-dimensional spectra of both extracts. With creatine as reference, 2.5-fold more lactate was found in SCOL than in CP, and a much smaller difference was also found in their carnosine content. Two-dimensional COSY comparison revealed several differences between the two extracts. Taurine, N-acetyl glutamate, glycerophosphoryl choline (or phosphoryl choline) and an unidentified spot were present only in the extract from SCOL but not in that from CP. On the other hand, aspartate, hydroxy-proline, carnitine and glycerophosphoryl ethanolamine were only present in CP but absent in SCOL. Alanine, cysteine, lysine and arginine appeared in both extracts without an apparent intensity difference.

  13. Common errors in textbook descriptions of muscle fiber size in nontrained humans.

    Science.gov (United States)

    Chalmers, Gordon R; Row, Brandi S

    2011-09-01

    Exercise science and human anatomy and physiology textbooks commonly report that type IIB muscle fibers have the largest cross-sectional area of the three fiber types. These descriptions of muscle fiber sizes do not match with the research literature examining muscle fibers in young adult nontrained humans. For men, most commonly type IIA fibers were significantly larger than other fiber types (six out of 10 cases across six different muscles). For women, either type I, or both I and IIA muscle fibers were usually significantly the largest (five out of six cases across four different muscles). In none of these reports were type IIB fibers significantly larger than both other fiber types. In 27 studies that did not include statistical comparisons of mean fiber sizes across fiber types, in no cases were type IIB or fast glycolytic fibers larger than both type I and IIA, or slow oxidative and fast oxidative glycolytic fibers. The likely reason for mistakes in textbook descriptions of human muscle fiber sizes is that animal data were presented without being labeled as such, and without any warning that there are interspecies differences in muscle fiber properties. Correct knowledge of muscle fiber sizes may facilitate interpreting training and aging adaptations.

  14. Cell-Surface Protein Profiling Identifies Distinctive Markers of Progenitor Cells in Human Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Akiyoshi Uezumi

    2016-08-01

    Full Text Available Skeletal muscle contains two distinct stem/progenitor populations. One is the satellite cell, which acts as a muscle stem cell, and the other is the mesenchymal progenitor, which contributes to muscle pathogeneses such as fat infiltration and fibrosis. Detailed and accurate characterization of these progenitors in humans remains elusive. Here, we performed comprehensive cell-surface protein profiling of the two progenitor populations residing in human skeletal muscle and identified three previously unrecognized markers: CD82 and CD318 for satellite cells and CD201 for mesenchymal progenitors. These markers distinguish myogenic and mesenchymal progenitors, and enable efficient isolation of the two types of progenitors. Functional study revealed that CD82 ensures expansion and preservation of myogenic progenitors by suppressing excessive differentiation, and CD201 signaling favors adipogenesis of mesenchymal progenitors. Thus, cell-surface proteins identified here are not only useful markers but also functionally important molecules, and provide valuable insight into human muscle biology and diseases.

  15. TGF-β1 inhibits connexin-43 expression in cultured smooth muscle cells of human bladder

    Institute of Scientific and Technical Information of China (English)

    Chi Qiang; Zhou Fenghai; Wang Yangmin

    2009-01-01

    Objective: In this research, we studied the TGF-β1 effects on connexin-43 expression in cultured human bladder smooth muscle cells. Methods: Human bladder smooth muscle cells primary cultures, with bladder tissue obtained from patients undergoing cystectomy, were intervened by recombinant human TGF-β1. Connexin-43 expression in human bladder smooth muscle cells was then examined by Western blotting and immunocytochemistry. Results: Stimulation with TGF-β1 led to significant reduction of cormexin-43 immunoreactivity and coupling (P<0.0001). Connexin-43 protein expression was significantly downregnlated (P<0.05). Simultaneously, low phosphorylation species of connexin-43 were particularly affected. Conclusion: Our experiments demonstrated a significant downregulation of connexin-43 by TGF-β1 in cultured human bladder smooth muscle cells. These findings support the view that TGF-β1 is involved in the pathophysiology of urinary bladder dysfunction.

  16. Oxidation of urate in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Tullson, P. C.; Richter, Erik

    1997-01-01

    The purpose of the present study was to investigate whether high metabolic stress to skeletal muscle, induced by intensive exercise, would lead to an oxidation of urate to allantoin in the exercised muscle. Seven healthy male subjects performed short term (4.39 +/- 0.04 [+/-SE] min) exhaustive cy...

  17. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.

    Directory of Open Access Journals (Sweden)

    Anthony E Civitarese

    2007-03-01

    Full Text Available Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood.The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y, overweight (body mass index, 27.8 +/- 0.7 kg/m(2 individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX, 12.5% CR + 12.5% increased energy expenditure (EE. In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008. Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05. In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005 and 21% +/- 4% in the CREX group (p < 0.004, with no change in the control group (2% +/- 2%. However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid cycle (citrate synthase, beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase, and electron transport chain (cytochrome C oxidase II was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003 and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011, but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR.The observed increase in

  18. Restoration of skeletal muscle ischemia-reperfusion injury in humanized immunodeficient mice.

    Science.gov (United States)

    Sheu, Eric G; Oakes, Sean M; Ahmadi-Yazdi, Cyrus; Afnan, Jalil; Carroll, Michael C; Moore, Francis D

    2009-08-01

    Ischemia and reperfusion (I/R) of tissue provokes an inflammatory process that is highly dependent on circulating natural immunoglobulin M (IgM) and the complement cascade. In mice, a single IgM specificity produced by peritoneal B cells can initiate reperfusion injury. It is unknown whether humans express natural IgM with a similar specificity. It is also unknown whether pathogenic IgM is produced solely from peritoneal B cells or can also be made by circulating B cells. Immunodeficient mice lacking endogenous immunoglobulin were used. Mice were reconstituted with 0.9% normal saline, human serum, or xenografted human peripheral blood lymphocytes (PBLs) and then subjected to tourniquet-induced hindlimb I/R. Serum human IgM and immunoglobulin G (IgG) were measured by enzyme-linked immunosorbent (ELISA) assay. Skeletal muscle was harvested for injury assessment by histology and for immunohistochemistry. Immunodeficient mice were protected from skeletal muscle injury after hindlimb I/R. Transfer of human serum restored skeletal muscle damage. Rag2/gammaR-/- mice that were engrafted with human PBL (huPBL-SCID) had high levels of human IgM. huPBL-SCID mice developed significantly more skeletal muscle injury than control saline-treated mice (P < or = .01) and human serum-reconstituted Rag2/gammaR-/- mice (P < or = 0.01). Sham-treated huPBL-SCID mice had no muscle injury, demonstrating that human lymphocyte engraftment did not cause injury in the absence of ischemia. Deposition of human IgM was observed on injured but not sham-injured muscle. Human serum can initiate murine skeletal muscle I/R injury. Circulating human PBL may be a source of pathogenic IgM. The huPBL-SCID mouse may be a useful model to define the specificity of pathogenic human IgM and to test therapeutics for I/R injury.

  19. Purinergic receptors expressed in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Bornø, A; Ploug, Thorkil; Bune, L T

    2012-01-01

    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...... in immunolabelled transverse sections of muscle biopsies. The receptors P2Y(4), P2Y(11) and likely P2X(1) were present intracellularly or in the plasma membrane of muscle fibres and were thus selected for further detailed morphological analysis. P2X(1) receptors were expressed in intracellular vesicles...

  20. 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...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  1. 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...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  2. Regulation of pH in human skeletal muscle: adaptations to physical activity

    DEFF Research Database (Denmark)

    Juel, C

    2008-01-01

    Regulation of pH in skeletal muscle is the sum of mechanisms involved in maintaining intracellular pH within the normal range. Aspects of pH regulation in human skeletal muscle have been studied with various techniques from analysis of membrane proteins, microdialysis, and the nuclear magnetic...

  3. Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Birk, Jesper Bratz; Wojtaszewski, Jørgen

    2006-01-01

    5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK a/ß/¿-heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between ...

  4. Synergistic Structure in the Speed Dependent Modulation of Muscle Activity in Human Walking

    NARCIS (Netherlands)

    Buurke, Tom J W; Lamoth, Claudine J C; van der Woude, Lucas H V; Otter, den A. Rob

    2016-01-01

    Recently, a modular organisation has been proposed to simplify control of the large number of muscles involved in human walking. Although previous research indicates that a single set of modular activation patterns can account for muscle activity at different speeds, these studies only provide indir

  5. Synergistic Structure in the Speed Dependent Modulation of Muscle Activity in Human Walking

    NARCIS (Netherlands)

    Buurke, Tom J. W.; Lamoth, Claudine J C; van der Woude, Lucas H V; Otter, den A. Rob

    2016-01-01

    Recently, a modular organisation has been proposed to simplify control of the large number of muscles involved in human walking. Although previous research indicates that a single set of modular activation patterns can account for muscle activity at different speeds, these studies only provide

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

    Hof, AL

    1998-01-01

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

  8. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

    NARCIS (Netherlands)

    Oliver, Brian G G; Johnston, Sebastian L; Baraket, Melissa; Burgess, Janette K; King, Nicholas J C; Roth, Michael; Lim, Sam; Black, Judith L

    2006-01-01

    BACKGROUND: Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV) are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscl

  9. Muscle patterning in mouse and human abdominal wall development and omphalocele specimens of humans.

    Science.gov (United States)

    Nichol, Peter F; Corliss, Robert F; Yamada, Shigehito; Shiota, Kohei; Saijoh, Yukio

    2012-12-01

    Human omphalocele is a congenital defect of the abdominal wall in which the secondary abdominal wall structures (muscle and connective tissue) in an area centered around the umbilicus are replaced by a translucent membranous layer of tissue. Histological examination of omphalocele development and moreover the staging of normal human abdominal wall development has never been described. We hypothesized that omphalocele is the result of an arrest in the secondary abdominal wall development and predicted that we would observe delays in myoblast maturation and an arrest in secondary abdominal wall development. To look for evidence in support of our hypothesis, we performed a histological analysis of normal human abdominal wall development and compared this to mouse. We also conducted the first histological analysis of two human specimens with omphalocele. In these two omphalocele specimens, secondary abdominal wall development appears to have undergone an arrest around Carnegie Stage 19. In both specimens disruptions in the unidirectional orientation of myofibers were observed in the external and internal obliques, and rectus abdominis but not in the transversus abdominis. These latter findings support a model of normal abdominal wall development in which positional information instructs the orientation of myoblasts as they organize into individual muscle groups.

  10. In vivo myogenic potential of human CD133+ muscle-derived stem cells: a quantitative study.

    Science.gov (United States)

    Negroni, Elisa; Riederer, Ingo; Chaouch, Soraya; Belicchi, Marzia; Razini, Paola; Di Santo, James; Torrente, Yvan; Butler-Browne, Gillian S; Mouly, Vincent

    2009-10-01

    In recent years, numerous reports have identified in mouse different sources of myogenic cells distinct from satellite cells that exhibited a variable myogenic potential in vivo. Myogenic stem cells have also been described in humans, although their regenerative potential has rarely been quantified. In this study, we have investigated the myogenic potential of human muscle-derived cells based on the expression of the stem cell marker CD133 as compared to bona fide satellite cells already used in clinical trials. The efficiency of these cells to participate in muscle regeneration and contribute to the renewal of the satellite cell pool, when injected intramuscularly, has been evaluated in the Rag2(-/-) gammaC(-/-) C5(-/-) mouse in which muscle degeneration is induced by cryoinjury. We demonstrate that human muscle-derived CD133+ cells showed a much greater regenerative capacity when compared to human myoblasts. The number of fibers expressing human proteins and the number of human cells in a satellite cell position are all dramatically increased when compared to those observed after injection of human myoblasts. In addition, CD133+/CD34+ cells exhibited a better dispersion in the host muscle when compared to human myoblasts. We propose that muscle-derived CD133+ cells could be an attractive candidate for cellular therapy.

  11. Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise

    DEFF Research Database (Denmark)

    Miller, Benjamin F; Olesen, Jens L; Hansen, Mette

    2005-01-01

    We hypothesized that an acute bout of strenuous, non-damaging exercise would increase rates of protein synthesis of collagen in tendon and skeletal muscle but these would be less than those of muscle myofibrillar and sarcoplasmic proteins. Two groups (n = 8 and 6) of healthy young men were studied...... collagen (0.077% h(-1)), muscle collagen (0.054% h(-1)), myofibrillar protein (0.121% h(-1)), and sarcoplasmic protein (0.134% h(-1))). The rates decreased toward basal values by 72 h although rates of tendon collagen and myofibrillar protein synthesis remained elevated. There was no tissue damage...... of muscle visible on histological evaluation. Neither tissue microdialysate nor serum concentrations of IGF-I and IGF binding proteins (IGFBP-3 and IGFBP-4) or procollagen type I N-terminal propeptide changed from resting values. Thus, there is a rapid increase in collagen synthesis after strenuous exercise...

  12. Cellular infiltrates in human skeletal muscle: exercise induced damage as a model for inflammatory muscle disease?

    Science.gov (United States)

    Round, J M; Jones, D A; Cambridge, G

    1987-12-01

    The type and distribution of mononuclear cell infiltrates in muscle biopsies taken from 9 subjects at differing times after exercise in which the muscle is stretched (eccentric exercise) has been characterised. The appearances are compared to those seen in muscle from patients with inflammatory muscle disease. After exercise infiltrating cells were seen in perivascular, perimysial and endomysial regions, the extent being greater in the later biopsies (9-14 days). The predominant cell type was the macrophage (46-100% of all infiltrating cells), the remainder were T lymphocytes with a predominance of the CD4 positive helper/inducer subset. Approximately one third of the T cells expressed DA2 (class 2) antigen indicating that they were activated. Very few B lymphocytes and no Leu7 positive cells were seen. There was evidence of class 1 expression on some of the damaged muscle fibres. The appearance of the experimentally damaged muscle in normal subjects was very similar to untreated polymyositis suggesting that a proportion of the infiltrating cells seen in this disease may be present as part of a natural response to damage rather than being its cause.

  13. Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans

    Science.gov (United States)

    Cui, J.; Wilson, T. E.; Shibasaki, M.; Hodges, N. A.; Crandall, C. G.

    2001-01-01

    To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

  14. Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content.

    Science.gov (United States)

    Keller, C; Steensberg, A; Pilegaard, H; Osada, T; Saltin, B; Pedersen, B K; Neufer, P D

    2001-12-01

    In humans, the plasma interleukin 6 (IL-6) concentration increases dramatically during low-intensity exercise. Measurements across the working limb indicate that skeletal muscle is the source of IL-6 production. To determine whether energy availability influences the regulation of IL-6 expression during prolonged exercise, six male subjects completed two trials consisting of 180 min of two-legged dynamic knee extensor with either normal or low (~60% of control) pre-exercise muscle glycogen levels. Increases in plasma IL-6 during exercise were significantly higher (P<0.05) in the low-glycogen (16-fold) trial verses the control (10-fold) trial. Transcriptional activation of the IL-6 gene in skeletal muscle was also higher in the low-glycogen trial; it increased by about 40-fold after 90 min of exercise and about 60-fold after 180 min of exercise. Muscle IL-6 mRNA followed a similar but delayed pattern, increasing by more than 100-fold in the low-glycogen trial and by about 30-fold in the control trial. These data demonstrate that exercise activates transcription of the IL-6 gene in working skeletal muscle, a response that is dramatically enhanced when glycogen levels are low. These findings also support the hypothesis that IL-6 may be produced by contracting myofibers when glycogen levels become critically low as a means of signaling the liver to increase glucose production.

  15. Architectural and morphological assessment of rat abdominal wall muscles: comparison for use as a human model.

    Science.gov (United States)

    Brown, Stephen H M; Banuelos, Karina; Ward, Samuel R; Lieber, Richard L

    2010-09-01

    The abdominal wall is a composite of muscles that are important for the mechanical stability of the spine and pelvis. Tremendous clinical attention is given to these muscles, yet little is known about how they function in isolation or how they interact with one another. Given the morphological, vascular, and innervation complexities associated with these muscles and their proximity to the internal organs, an appropriate animal model is important for understanding their physiological and mechanical significance during function. To determine the extent to which the rat abdominal wall resembles that of human, 10 adult male Sprague-Dawley rats were killed and formalin-fixed for architectural and morphological analyses of the four abdominal wall muscles (rectus abdominis, external oblique, internal oblique, and transversus abdominis). Physiological cross-sectional areas and optimal fascicle lengths demonstrated a pattern that was similar to human abdominal wall muscles. In addition, sarcomere lengths measured in the neutral spine posture were similar to human in their relation to optimal sarcomere length. These data indicate that the force-generating and length change capabilities of these muscles, relative to one another, are similar in rat and human. Finally, the fiber lines of action of each abdominal muscle were similar to human over most of the abdominal wall. The main exception was in the lower abdominal region (inferior to the pelvic crest), where the external oblique becomes aponeurotic in human but continues as muscle fibers into its pelvic insertion in the rat. We conclude that, based on the morphology and architecture of the abdominal wall muscles, the adult male Sprague-Dawley rat is a good candidate for a model representation of human, particularly in the middle and upper abdominal wall regions.

  16. Variation of neck muscle strength along the human cervical spine.

    Science.gov (United States)

    Oi, Nelson; Pandy, Marcus G; Myers, Barry S; Nightingale, Roger W; Chancey, Valeta Carol

    2004-11-01

    The aim of this study was to describe and explain the variation of neck muscle strength along the cervical spine. A three-dimensional model of the head-neck complex was developed to test the hypothesis that the moment-generating capacity of the neck musculature is lower in the upper cervical spine than in the lower cervical spine. The model calculations suggest that the neck muscles can protect the lower cervical spine from injury during extension and lateral bending. The maximum flexor moment developed in the lower cervical spine was 2 times higher than that developed in the upper spine. The model also predicted that the neck musculature is 30% stronger in the lower cervical spine during lateral bending. Peak compressive forces (up to 3 times body weight) were higher in the lower cervical spine. These results are consistent with the clinical finding that extension loading of the neck often leads to injuries in the upper cervical spine. Analysis of the model results showed that neck flexor strength was greater in the lower cervical spine because of the relatively large size of the sternocleidomastoid muscle. The hyoid muscles developed significant flexor moments about the joints of the upper cervical spine, as these muscles had relatively large flexor moment arms; however, this effect was offset by the action of the sternocleidomastoid, which exerted a large extensor moment in the upper spine. Lateral bending strength of the neck muscles was governed by geometry (i.e., moment arms) rather than by muscle size.

  17. NGF-evoked sensitization of muscle fascia nociceptors in humans.

    Science.gov (United States)

    Deising, Saskia; Weinkauf, Benjamin; Blunk, James; Obreja, Otilia; Schmelz, Martin; Rukwied, Roman

    2012-08-01

    Nerve growth factor (NGF) induces local hyperalgesia for a few days after intramuscular injection, but longer-lasting muscle pain upon systemic administration. As the muscle fascia is densely innervated by free nerve endings, we hypothesized a lasting sensitization of fascia nociceptors by NGF. We administered 1 μg NGF (dissolved in 100 μL saline) ultrasound-guided to the fascia of the Musculus erector spinae muscle at the lumbar level of 14 male volunteers and assessed hypersensitivity after 6 hours, and 1, 3, 7, 14, and 21 days. Pain upon mechanical stimuli (constant pressure and dynamic impact), upon exercise and electrically induced M. erector spinae contraction, and upon injection of 100 μL phosphate buffer pH4 (at day 7 and 14 only) to the fascia of both NGF- and saline-treated muscles, was investigated. Injections into the muscle fascia did not cause acute pain. Local heat pain thresholds were unchanged following NGF and saline (control) administration. NGF evoked a lasting (days 1-7) and significant reduction of pressure pain, pressure thresholds, exercise-evoked muscle pain, and hyperalgesia to impact stimuli (12 m/s). Pain upon injected protons was significantly elevated (Pfascia to mechanical and chemical stimuli lasting for up to 2 weeks. As nociceptors in the fascia appear to be particularly prone to sensitization, they may contribute to acute or chronic muscle pain. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  18. Muscle architectural changes after massive human rotator cuff tear.

    Science.gov (United States)

    Gibbons, Michael C; Sato, Eugene J; Bachasson, Damien; Cheng, Timothy; Azimi, Hassan; Schenk, Simon; Engler, Adam J; Singh, Anshuman; Ward, Samuel R

    2016-12-01

    Rotator cuff (RC) tendon tears lead to negative structural and functional changes in the associated musculature. The structural features of muscle that predict function are termed "muscle architecture." Although the architectural features of "normal" rotator cuff muscles are known, they are poorly understood in the context of cuff pathology. The purpose of this study was to investigate the effects of tear and repair on RC muscle architecture. To this end thirty cadaveric shoulders were grouped into one of four categories based on tear magnitude: Intact, Full-thickness tear (FTT), Massive tear (MT), or Intervention if sutures or hardware were present, and key parameters of muscle architecture were measured. We found that muscle mass and fiber length decreased proportionally with tear size, with significant differences between all groups. Conversely, sarcomere number was reduced in both FTT and MT with no significant difference between these two groups, in large part because sarcomere length was significantly reduced in MT but not FTT. The loss of muscle mass in FTT is due, in part, to subtraction of serial sarcomeres, which may help preserve sarcomere length. This indicates that function in FTT may be impaired, but there is some remaining mechanical loading to maintain "normal" sarcomere length-tension relationships. However, the changes resulting from MT suggest more severe limitations in force-generating capacity because sarcomere length-tension relationships are no longer normal. The architectural deficits observed in MT muscles may indicate deeper deficiencies in muscle adaptability to length change, which could negatively impact RC function despite successful anatomical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2089-2095, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. Induction and modulation of referred muscle pain in humans

    DEFF Research Database (Denmark)

    Laursen, René Johannes

    afferents. Furthermore, cutaneous anesthesia of the RP area resulted in a reduction of RP intensity of 22%, while a complete nerve block of afferents from the RP area resulted in a 40% reduction. In summary, observations from the presented experiments suggest that elicitation of referred muscle pain...... are needed. Spinal cord and higher centers are likely structures to study. The data presented in this thesis have made further contributions to understanding the mechanisms of muscle pain and RP that can be helpful in diagnosis, control, and treatment of muscle pain. Moreover, the intramuscular, electrical...

  20. Robustness of muscle synergies underlying three-dimensional force generation at the hand in healthy humans

    Science.gov (United States)

    Rymer, William Z.; Beer, Randall F.

    2012-01-01

    Previous studies using advanced matrix factorization techniques have shown that the coordination of human voluntary limb movements may be accomplished using combinations of a small number of intermuscular coordination patterns, or muscle synergies. However, the potential use of muscle synergies for isometric force generation has been evaluated mostly using correlational methods. The results of such studies suggest that fixed relationships between the activations of pairs of muscles are relatively rare. There is also emerging evidence that the nervous system uses independent strategies to control movement and force generation, which suggests that one cannot conclude a priori that isometric force generation is accomplished by combining muscle synergies, as shown in movement control. In this study, we used non-negative matrix factorization to evaluate the ability of a few muscle synergies to reconstruct the activation patterns of human arm muscles underlying the generation of three-dimensional (3-D) isometric forces at the hand. Surface electromyographic (EMG) data were recorded from eight key elbow and shoulder muscles during 3-D force target-matching protocols performed across a range of load levels and hand positions. Four synergies were sufficient to explain, on average, 95% of the variance in EMG datasets. Furthermore, we found that muscle synergy composition was conserved across biomechanical task conditions, experimental protocols, and subjects. Our findings are consistent with the view that the nervous system can generate isometric forces by assembling a combination of a small number of muscle synergies, differentially weighted according to task constraints. PMID:22279190

  1. Cortical activation associated with muscle synergies of the human male pelvic floor.

    Science.gov (United States)

    Asavasopon, Skulpan; Rana, Manku; Kirages, Daniel J; Yani, Moheb S; Fisher, Beth E; Hwang, Darryl H; Lohman, Everett B; Berk, Lee S; Kutch, Jason J

    2014-10-08

    Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm, using transcranial magnetic stimulation, that the fMRI-identified medial wall region is likely to generate pelvic floor muscle activation. Thus, muscle synergies of the human male pelvic floor appear to involve activation of motor cortical areas associated with pelvic floor control.

  2. Subcellular localization and mechanism of secretion of vascular endothelial growth factor in human skeletal muscle.

    Science.gov (United States)

    Hoier, Birgitte; Prats, Clara; Qvortrup, Klaus; Pilegaard, Henriette; Bangsbo, Jens; Hellsten, Ylva

    2013-09-01

    The subcellular distribution and secretion of vascular endothelial growth factor (VEGF) was examined in skeletal muscle of healthy humans. Skeletal muscle biopsies were obtained from m.v. lateralis before and after a 2 h bout of cycling exercise. VEGF localization was conducted on preparations of teased muscle fibers by transmission electron microscopy (TEM) and confocal microscopy (CM). Muscle interstitial fluid was sampled from microdialysis probes placed in the thigh muscle. TEM and CM analysis revealed two primary sites of localization of VEGF: in vesicles located in the subsarcolemmal regions and between the contractile elements within the muscle fibers; and in pericytes situated on the skeletal muscle capillaries. Quantitation of the subsarcolemmal density of VEGF vesicles, calculated on top of myonuclei, in the muscle fibers revealed a ∼50% increase (P<0.05) after exercise. The observation of more VEGF vesicles close to sarcolemma after exercise, combined with a 5-fold increase (P<0.05) in VEGF in the interstitial fluid, suggest that VEGF-containing vesicles redistribute to sarcolemma and that VEGF is secreted to the extracellular fluid. This study provides the first evidence in humans for a mechanism by which skeletal muscle fibers can control capillary growth by releasing VEGF from intracellular vesicles during contraction.

  3. Maximal force, voluntary activation and muscle soreness after eccentric damage to human elbow flexor muscles

    Science.gov (United States)

    Prasartwuth, O; Taylor, JL; Gandevia, SC

    2005-01-01

    Muscle damage reduces voluntary force after eccentric exercise but impaired neural drive to the muscle may also contribute. To determine whether the delayed-onset muscle soreness, which develops ∼1 day after exercise, reduces voluntary activation and to identify the possible site for any reduction, voluntary activation of elbow flexor muscles was examined with both motor cortex and motor nerve stimulation. We measured maximal voluntary isometric torque (MVC), twitch torque, muscle soreness and voluntary activation in eight subjects before, immediately after, 2 h after, 1, 2, 4 and 8 days after eccentric exercise. Motor nerve stimulation and motor cortex stimulation were used to derive twitch torques and measures of voluntary activation. Eccentric exercise immediately reduced the MVC by 38 ± 3% (mean ±s.d., n = 8). The resting twitch produced by motor nerve stimulation fell by 82 ± 6%, and the estimated resting twitch by cortical stimulation fell by 47 ± 15%. While voluntary torque recovered after 8 days, both measures of the resting twitch remained depressed. Muscle tenderness occurred 1–2 days after exercise, and pain during contractions on days 1–4, but changes in voluntary activation did not follow this time course. Voluntary activation assessed with nerve stimulation fell 19 ± 6% immediately after exercise but was not different from control values after 2 days. Voluntary activation assessed by motor cortex stimulation was unchanged by eccentric exercise. During MVCs, absolute increments in torque evoked by nerve and cortical stimulation behaved differently. Those to cortical stimulation decreased whereas those to nerve stimulation tended to increase. These findings suggest that reduced voluntary activation contributes to the early force loss after eccentric exercise, but that it is not due to muscle soreness. The impairment of voluntary activation to nerve stimulation but not motor cortical stimulation suggests that the activation deficit lies in the

  4. Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity

    Directory of Open Access Journals (Sweden)

    Dirk van Moorsel

    2016-08-01

    Conclusions: Our results suggest that the biological clock drives robust rhythms in human skeletal muscle oxidative metabolism. It is tempting to speculate that disruption of these rhythms contribute to the deterioration of metabolic health associated with circadian misalignment.

  5. Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease

    DEFF Research Database (Denmark)

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L;

    2016-01-01

    , variations in fiber size, vacuoles, and some internal nuclei associated with cytosolic glycogen accumulation and ongoing regeneration; structural damage was seen only in a minority of human patients. Neither liver nor brain isoforms of glycogen phosphorylase were upregulated in muscles, thus providing...... no substitution for the missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were invariably more damaged than the quadriceps muscles. This may relate to a 7-fold higher level of myophosphorylase in TA compared to quadriceps in wild-type mice and suggests higher glucose turnover in the TA. Thus......McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings...

  6. Secondary tensor and supinator muscles of the human proximal radio-ulnar joint.

    Science.gov (United States)

    Hast, M H; Perkins, R E

    1986-01-01

    A gross anatomical study was made of the human elbow. Three very small muscles were found that are not described in contemporary anatomical publications. A lateral tensor muscle of the annular ligament was observed in seven of every ten cadavers; its action is to tense or pull the annular ligament laterally during supination. A medial tensor muscle of the annular ligament was found in two of every ten cadavers; its action is to tense the annular ligament, pulling it medially and distally, and to assist in supination. An accessory supinator muscle was found in four of ten cadavers; its action is to assist in supination. These muscles would be synergistic to the primary supinator muscles of the radio-ulnar joint. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:3693061

  7. Mechanisms of Cigarette Smoke Effects on Human Airway Smooth Muscle.

    Directory of Open Access Journals (Sweden)

    Mark E Wylam

    Full Text Available Cigarette smoke contributes to or exacerbates airway diseases such as asthma and COPD, where airway hyperresponsiveness and airway smooth muscle (ASM proliferation are key features. While factors such as inflammation contribute to asthma in part by enhancing agonist-induced intracellular Ca(2+ ([Ca(2+]i responses of ASM, the mechanisms by which cigarette smoke affect ASM are still under investigation. In the present study, we tested the hypothesis that cigarette smoke enhances the expression and function of Ca(2+ regulatory proteins leading to increased store operated Ca(2+ entry (SOCE and cell proliferation. Using isolated human ASM (hASM cells, incubated in the presence and absence cigarette smoke extract (CSE we determined ([Ca(2+]i responses and expression of relevant proteins as well as ASM proliferation, reactive oxidant species (ROS and cytokine generation. CSE enhanced [Ca(2+]i responses to agonist and SOCE: effects mediated by increased expression of TRPC3, CD38, STIM1, and/or Orai1, evident by attenuation of CSE effects when siRNAs against these proteins were used, particularly Orai1. CSE also increased hASM ROS generation and cytokine secretion. In addition, we found in the airways of patients with long-term smoking history, TRPC3 and CD38 expression were significantly increased compared to life-long never-smokers, supporting the role of these proteins in smoking effects. Finally, CSE enhanced hASM proliferation, an effect confirmed by upregulation of PCNA and Cyclin E. These results support a critical role for Ca(2+ regulatory proteins and enhanced SOCE to alter airway structure and function in smoking-related airway disease.

  8. Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans

    Science.gov (United States)

    Szendroedi, Julia; Yoshimura, Toru; Phielix, Esther; Koliaki, Chrysi; Marcucci, Mellissa; Zhang, Dongyan; Jelenik, Tomas; Müller, Janette; Herder, Christian; Nowotny, Peter; Shulman, Gerald I.; Roden, Michael

    2014-01-01

    Muscle insulin resistance is a key feature of obesity and type 2 diabetes and is strongly associated with increased intramyocellular lipid content and inflammation. However, the cellular and molecular mechanisms responsible for causing muscle insulin resistance in humans are still unclear. To address this question, we performed serial muscle biopsies in healthy, lean subjects before and during a lipid infusion to induce acute muscle insulin resistance and assessed lipid and inflammatory parameters that have been previously implicated in causing muscle insulin resistance. We found that acute induction of muscle insulin resistance was associated with a transient increase in total and cytosolic diacylglycerol (DAG) content that was temporally associated with protein kinase (PKC)θ activation, increased insulin receptor substrate (IRS)-1 serine 1101 phosphorylation, and inhibition of insulin-stimulated IRS-1 tyrosine phosphorylation and AKT2 phosphorylation. In contrast, there were no associations between insulin resistance and alterations in muscle ceramide, acylcarnitine content, or adipocytokines (interleukin-6, adiponectin, retinol-binding protein 4) or soluble intercellular adhesion molecule-1. Similar associations between muscle DAG content, PKCθ activation, and muscle insulin resistance were observed in healthy insulin-resistant obese subjects and obese type 2 diabetic subjects. Taken together, these data support a key role for DAG activation of PKCθ in the pathogenesis of lipid-induced muscle insulin resistance in obese and type 2 diabetic individuals. PMID:24979806

  9. Eccentric exercise slows in vivo microvascular reactivity during brief contractions in human skeletal muscle.

    Science.gov (United States)

    Larsen, Ryan G; Hirata, Rogerio P; Madzak, Adnan; Frøkjær, Jens B; Graven-Nielsen, Thomas

    2015-12-01

    Unaccustomed exercise involving eccentric contractions results in muscle soreness and an overall decline in muscle function, however, little is known about the effects of eccentric exercise on microvascular reactivity in human skeletal muscle. Fourteen healthy men and women performed eccentric contractions of the dorsiflexor muscles in one leg, while the contralateral leg served as a control. At baseline, and 24 and 48 h after eccentric exercise, the following were acquired bilaterally in the tibialis anterior muscle: 1) transverse relaxation time (T2)-weighted magnetic resonance images to determine muscle cross-sectional area (mCSA) and T2; 2) blood oxygen level-dependent (BOLD) images during and following brief, maximal voluntary contractions (MVC) to monitor the hyperemic responses with participants positioned supine in a 3T magnet; 3) muscle strength; and 4) pain pressure threshold. Compared with the control leg, eccentric exercise resulted in soreness, decline in strength (∼20%), increased mCSA (∼7%), and prolonged T2 (∼7%) at 24 and 48 h (P eccentric exercise, such that time-to-peak (∼35%, P eccentric exercise may impede rapid adjustments in muscle blood flow at exercise onset and during activities involving brief bursts of muscle activation, which may impair O2 delivery and contribute to reduced muscle function after eccentric exercise. Copyright © 2015 the American Physiological Society.

  10. Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Milène Catoire

    Full Text Available Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max. Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

  11. Topography of the femoral nerve in relation to components of the iliopsoas muscle in human fetuses.

    Science.gov (United States)

    Jakubowicz, M

    1991-01-01

    Studies were performed on 60 human fetuses of both sexes of 35 to 365 mm C.-R. length (9-40 weeks). The psoas minor muscle was found in 25.8% of cases independently of sex and body side. In 6.45% of cases the muscle continued into psoas major muscle by short, weakly developed tendon. In 97.5% of studied fetuses junctions between tendons of psoas major and iliacus muscles was observed. In 2.5% of cases an independent, short tendon was found in the half of length of the iliacus muscle. In 7.5% of cases connection between the psoas major and iliacus muscles was found. In all cases femoral nerve originated from the lumbar plexus between two layers of the psoas major muscle and it ran in the groove between the psoas major and iliacus muscles towards the muscular lacuna. In 5.0% of cases the nerve divided into crura. In 2.5% of cases the crura embraced anteriorly and posteriorly bundles of the psoas major muscle as well as in 2.5% of cases bundles of the iliacus muscle.

  12. Single motor unit activity in human extraocular muscles during the vestibulo-ocular reflex.

    Science.gov (United States)

    Weber, Konrad P; Rosengren, Sally M; Michels, Rike; Sturm, Veit; Straumann, Dominik; Landau, Klara

    2012-07-01

    Motor unit activity in human eye muscles during the vestibulo-ocular reflex (VOR) is not well understood, since the associated head and eye movements normally preclude single unit recordings. Therefore we recorded single motor unit activity following bursts of skull vibration and sound, two vestibular otolith stimuli that elicit only small head and eye movements. Inferior oblique (IO) and inferior rectus (IR) muscle activity was measured in healthy humans with concentric needle electrodes. Vibration elicited highly synchronous, short-latency bursts of motor unit activity in the IO (latency: 10.5 ms) and IR (14.5 ms) muscles. The activation patterns of the two muscles were similar, but reciprocal, with delayed activation of the IR muscle. Sound produced short-latency excitation of the IO muscle (13.3 ms) in the eye contralateral to the stimulus. Simultaneous needle and surface recordings identified the IO as the muscle of origin of the vestibular evoked myogenic potential (oVEMP) thus validating the physiological basis of this recently developed clinical test of otolith function. Single extraocular motor unit recordings provide a window into neural activity in humans that can normally only be examined using animal models and help identify the pathways of the translational VOR from otoliths to individual eye muscles.

  13. GH receptor blocker administration and muscle-tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Nielsen, Rie Harboe; Doessing, Simon; Goto, Kazushige;

    2011-01-01

    The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans.......The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans....

  14. The effects of TSH on human vascular endothelial cells and smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    田利民

    2014-01-01

    Objective To study the effect of thyroid-stimulating hormone(TSH)on human vascular endothelial cells and smooth muscle cells and to explore the roles of TSH in the development of atherosclerosis.Methods Human vascular endothelial cells and smooth muscle cells were cultured in vitro.MTT method was used to assay the effect of TSH on cell viability.Real-time PCR was used

  15. Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Daniel eBoulton

    2016-05-01

    Full Text Available During voluntary contractions, muscle sympathetic nerve activity (MSNA to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-minute isometric dorsiflexion contractions (left leg separated by 2-minute rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10 % of maximum. MSNA was recorded continuously (microneurography from the left peroneal nerve and quantified from cardiac-synchronised, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34 % (P 0.05. MSNA analysed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01, remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction.

  16. Interstitial and plasma adenosine stimulate nitric oxide and prostacyclin formation in human skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Thaning, Pia;

    2010-01-01

    One major unresolved issue in muscle blood flow regulation is that of the role of circulating versus interstitial vasodilatory compounds. The present study determined adenosine-induced formation of NO and prostacyclin in the human muscle interstitium versus in femoral venous plasma to elucidate....... In young healthy humans, microdialysate was collected at rest, during arterial infusion of adenosine, and during interstitial infusion of adenosine through microdialysis probes inserted into musculus vastus lateralis. Muscle interstitial NO and prostacyclin increased with arterial and interstitial infusion...... levels. These findings provide novel insight into the role of adenosine in skeletal muscle blood flow regulation and vascular function by revealing that both interstitial and plasma adenosine have a stimulatory effect on NO and prostacyclin formation. In addition, both skeletal muscle and microvascular...

  17. Two-Dimensional Proton Chemical-Shift Imaging of Human Muscle Metabolites

    Science.gov (United States)

    Hu, Jiani; Willcott, M. Robert; Moore, Gregory J.

    1997-06-01

    Large lipid signals and strong susceptibility gradients introduced by muscle-bone interfaces represent major technical challenges forin vivoproton MRS of human muscle. Here, the demonstration of two-dimensional proton chemical-shift imaging of human muscle metabolites is presented. This technique utilizes a chemical-shift-selective method for water and lipid suppression and automatic shimming for optimal homogeneity of the magnetic field. The 2D1H CSI technique described facilitates the acquisition of high-spatial-resolution spectra, and allows one to acquire data from multiple muscle groups in a single experiment. A preliminary investigation utilizing this technique in healthy adult males (n= 4) revealed a highly significant difference in the ratio of the creatine to trimethylamine resonance between the fast and slow twitch muscle groups examined. The technique is robust, can be implemented on a commercial scanner with relative ease, and should prove to be a useful tool for both clinical and basic investigators.

  18. Human Leg Model Predicts Muscle Forces, States, and Energetics during Walking.

    Science.gov (United States)

    Markowitz, Jared; Herr, Hugh

    2016-05-01

    Humans employ a high degree of redundancy in joint actuation, with different combinations of muscle and tendon action providing the same net joint torque. Both the resolution of these redundancies and the energetics of such systems depend on the dynamic properties of muscles and tendons, particularly their force-length relations. Current walking models that use stock parameters when simulating muscle-tendon dynamics tend to significantly overestimate metabolic consumption, perhaps because they do not adequately consider the role of elasticity. As an alternative, we posit that the muscle-tendon morphology of the human leg has evolved to maximize the metabolic efficiency of walking at self-selected speed. We use a data-driven approach to evaluate this hypothesis, utilizing kinematic, kinetic, electromyographic (EMG), and metabolic data taken from five participants walking at self-selected speed. The kinematic and kinetic data are used to estimate muscle-tendon lengths, muscle moment arms, and joint moments while the EMG data are used to estimate muscle activations. For each subject we perform an optimization using prescribed skeletal kinematics, varying the parameters that govern the force-length curve of each tendon as well as the strength and optimal fiber length of each muscle while seeking to simultaneously minimize metabolic cost and maximize agreement with the estimated joint moments. We find that the metabolic cost of transport (MCOT) values of our participants may be correctly matched (on average 0.36±0.02 predicted, 0.35±0.02 measured) with acceptable joint torque fidelity through application of a single constraint to the muscle metabolic budget. The associated optimal muscle-tendon parameter sets allow us to estimate the forces and states of individual muscles, resolving redundancies in joint actuation and lending insight into the potential roles and control objectives of the muscles of the leg throughout the gait cycle.

  19. Human Leg Model Predicts Muscle Forces, States, and Energetics during Walking.

    Directory of Open Access Journals (Sweden)

    Jared Markowitz

    2016-05-01

    Full Text Available Humans employ a high degree of redundancy in joint actuation, with different combinations of muscle and tendon action providing the same net joint torque. Both the resolution of these redundancies and the energetics of such systems depend on the dynamic properties of muscles and tendons, particularly their force-length relations. Current walking models that use stock parameters when simulating muscle-tendon dynamics tend to significantly overestimate metabolic consumption, perhaps because they do not adequately consider the role of elasticity. As an alternative, we posit that the muscle-tendon morphology of the human leg has evolved to maximize the metabolic efficiency of walking at self-selected speed. We use a data-driven approach to evaluate this hypothesis, utilizing kinematic, kinetic, electromyographic (EMG, and metabolic data taken from five participants walking at self-selected speed. The kinematic and kinetic data are used to estimate muscle-tendon lengths, muscle moment arms, and joint moments while the EMG data are used to estimate muscle activations. For each subject we perform an optimization using prescribed skeletal kinematics, varying the parameters that govern the force-length curve of each tendon as well as the strength and optimal fiber length of each muscle while seeking to simultaneously minimize metabolic cost and maximize agreement with the estimated joint moments. We find that the metabolic cost of transport (MCOT values of our participants may be correctly matched (on average 0.36±0.02 predicted, 0.35±0.02 measured with acceptable joint torque fidelity through application of a single constraint to the muscle metabolic budget. The associated optimal muscle-tendon parameter sets allow us to estimate the forces and states of individual muscles, resolving redundancies in joint actuation and lending insight into the potential roles and control objectives of the muscles of the leg throughout the gait cycle.

  20. Human Leg Model Predicts Muscle Forces, States, and Energetics during Walking

    Science.gov (United States)

    Markowitz, Jared; Herr, Hugh

    2016-01-01

    Humans employ a high degree of redundancy in joint actuation, with different combinations of muscle and tendon action providing the same net joint torque. Both the resolution of these redundancies and the energetics of such systems depend on the dynamic properties of muscles and tendons, particularly their force-length relations. Current walking models that use stock parameters when simulating muscle-tendon dynamics tend to significantly overestimate metabolic consumption, perhaps because they do not adequately consider the role of elasticity. As an alternative, we posit that the muscle-tendon morphology of the human leg has evolved to maximize the metabolic efficiency of walking at self-selected speed. We use a data-driven approach to evaluate this hypothesis, utilizing kinematic, kinetic, electromyographic (EMG), and metabolic data taken from five participants walking at self-selected speed. The kinematic and kinetic data are used to estimate muscle-tendon lengths, muscle moment arms, and joint moments while the EMG data are used to estimate muscle activations. For each subject we perform an optimization using prescribed skeletal kinematics, varying the parameters that govern the force-length curve of each tendon as well as the strength and optimal fiber length of each muscle while seeking to simultaneously minimize metabolic cost and maximize agreement with the estimated joint moments. We find that the metabolic cost of transport (MCOT) values of our participants may be correctly matched (on average 0.36±0.02 predicted, 0.35±0.02 measured) with acceptable joint torque fidelity through application of a single constraint to the muscle metabolic budget. The associated optimal muscle-tendon parameter sets allow us to estimate the forces and states of individual muscles, resolving redundancies in joint actuation and lending insight into the potential roles and control objectives of the muscles of the leg throughout the gait cycle. PMID:27175486

  1. Force enhancement during and following muscle stretch of maximal voluntarily activated human quadriceps femoris.

    Science.gov (United States)

    Hahn, Daniel; Seiberl, Wolfgang; Schwirtz, Ansgar

    2007-08-01

    Force enhancement during and following muscle stretch has been observed for electrically and voluntarily activated human muscle. However, especially for voluntary contractions, the latter observation has only been made for adductor pollicis and the ankle joint muscles, but not for large muscles like quadriceps femoris. Therefore, the aim of this study was to investigate the effects of active muscle stretch on force production for maximal voluntary contractions of in vivo human quadriceps femoris (n = 15). Peak torques during and torques at the end of stretch, torques following stretch, and passive torques following muscle deactivation were compared to the isometric torques at corresponding muscle length. In addition, muscle activation of rectus femoris, vastus medialis and vastus lateralis was obtained using surface EMG. Stretches with different amplitudes (15, 25 and 35 degrees at a velocity of 60 degrees s(-1)) were performed on the plateau region and the descending limb of the force-length relation in a random order. Data analysis showed four main results: (1) peak torques did not occur at the end of the stretch, but torques at the end of the stretch exceeded the corresponding isometric torque; (2) there was no significant force enhancement following muscle stretch, but a small significant passive force enhancement persisted for all stretch conditions; (3) forces during and following stretch were independent of stretch amplitude; (4) muscle activation during and following muscle stretch was significantly reduced. In conclusion, although our results showed passive force enhancement, we could not provide direct evidence that there is active force enhancement in voluntarily activated human quadriceps femoris.

  2. "Nutraceuticals" in relation to human skeletal muscle and exercise.

    Science.gov (United States)

    Deane, Colleen S; Wilkinson, Daniel J; Phillips, Bethan E; Smith, Kenneth; Etheridge, Timothy; Atherton, Philip J

    2017-04-01

    Skeletal muscles have a fundamental role in locomotion and whole body metabolism, with muscle mass and quality being linked to improved health and even lifespan. Optimizing nutrition in combination with exercise is considered an established, effective ergogenic practice for athletic performance. Importantly, exercise and nutritional approaches also remain arguably the most effective countermeasure for muscle dysfunction associated with aging and numerous clinical conditions, e.g., cancer cachexia, COPD, and organ failure, via engendering favorable adaptations such as increased muscle mass and oxidative capacity. Therefore, it is important to consider the effects of established and novel effectors of muscle mass, function, and metabolism in relation to nutrition and exercise. To address this gap, in this review, we detail existing evidence surrounding the efficacy of a nonexhaustive list of macronutrient, micronutrient, and "nutraceutical" compounds alone and in combination with exercise in relation to skeletal muscle mass, metabolism (protein and fuel), and exercise performance (i.e., strength and endurance capacity). It has long been established that macronutrients have specific roles and impact upon protein metabolism and exercise performance, (i.e., protein positively influences muscle mass and protein metabolism), whereas carbohydrate and fat intakes can influence fuel metabolism and exercise performance. Regarding novel nutraceuticals, we show that the following ones in particular may have effects in relation to 1) muscle mass/protein metabolism: leucine, hydroxyl β-methylbutyrate, creatine, vitamin-D, ursolic acid, and phosphatidic acid; and 2) exercise performance: (i.e., strength or endurance capacity): hydroxyl β-methylbutyrate, carnitine, creatine, nitrates, and β-alanine. Copyright © 2017 the American Physiological Society.

  3. Identification of muscle synergies associated with gait transition in humans

    Directory of Open Access Journals (Sweden)

    Shota eHagio

    2015-02-01

    Full Text Available There is no theoretical or empirical evidence to suggest how the central nervous system (CNS controls a variety of muscles associated with gait transition between walking and running. Here, we examined the motor control during a gait transition based on muscle synergies, which modularly organize functionally similar muscles. To this end, the subjects walked or ran on a treadmill and performed a gait transition spontaneously as the treadmill speed increased or decreased (a changing speed condition or voluntarily following an experimenter’s instruction at constant treadmill speed (a constant speed condition. Surface electromyograms (EMGs were recorded from 11 lower limb muscles bilaterally. We then extracted the muscle weightings of synergies and their activation coefficients from the EMG data using non-negative matrix factorization. As a result, the gait transition was controlled by approximately 9 muscle synergies, which were common during a walking and running, and their activation profiles were changed before and after a gait transition. Near a gait transition, the peak activation phases of the synergies, which were composed of plantar flexor muscles, were shifted to an earlier phase at the walk-to-run transition, and vice versa. The shifts were gradual in the changing speed condition, but an abrupt change was observed in the constant speed condition. These results suggest that the CNS low-dimensionally regulate the activation profiles of the specific synergies based on afferent information (spontaneous gait transition or by changing only the descending neural input to the muscle synergies (voluntary gait transition to achieve a gait transition.

  4. Functional anatomy of the human lateral pterygoid muscle.

    Science.gov (United States)

    El Haddioui, A; Laison, F; Zouaoui, A; Bravetti, P; Gaudy, J F

    2005-11-01

    The authors studied the lateral pterygoid muscle of 179 fresh cadavers by both anatomical dissection and magnetic resonance imaging. The aim was to define the general morphology and the architectural organisation of the lateral pterygoid muscle. Dissection plane by plane, anatomical sections in different planes of space and dissections via multiple approaches on harvested blocks allowed the demonstration that the lateral pterygoid shows an architectural arrangement different from that which is usually described but similar to that, from its typically penniform structure of the masseter and the medial pterygoid. The anatomical situation of this muscle gives rise to numerous differences in opinion much to its morphology as to its functional examination. This study has shown that one part of the muscle has a typical penniform structure made up of alternating musculo-aponeurotic layers and by the absence of individual muscle bellies. In addition the particular shape of this muscle makes it useless to insert intramuscular electrodes in its only accessible portion, which makes the results of electromyographic studies debatable.

  5. Secreted Protein Acidic and Rich in Cysteine (SPARC) in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Jørgensen, Louise H; Petersson, Stine J; Sellathurai, Jeeva

    2009-01-01

    indicated a function of SPARC in skeletal muscle. We therefore found it of interest to study SPARC expression in human skeletal muscle during development and in biopsies from Duchenne and Becker muscular dystrophy and congenital muscular dystrophy, congenital myopathy, inclusion body myositis...... in the majority of analyzed muscle biopsies (23 of 24), mainly in mononuclear cells of which few were pax7 positive. Myotubes and regenerating myofibers also expressed SPARC. The expression-degree seemed to reflect the severity of the lesion. In accordance with these in vivo findings, primary human...

  6. Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Charlotte; Keller, Pernille

    2003-01-01

    Interleukin-6 (IL-6) is produced by many different cell types. Human skeletal muscles produce and release high amounts of IL-6 during exercise; however, the cell source of origin in the muscle is not known. Therefore, we studied the protein expression of IL-6 by immunohistochemistry in human muscle...... tissue from biopsies obtained at time points 0, 3, 4.5, 6, 9, and 24 h in relation to 3 h of bicycle exercise performed by healthy young males (n=12) and in resting controls (n=6). The IL-6 expression was clearly increased after exercise and remained high even by 24 h, relative to pre-exercise or resting...

  7. Influence of passive muscle tension on electromechanical delay in humans.

    Directory of Open Access Journals (Sweden)

    Lilian Lacourpaille

    Full Text Available BACKGROUND: Electromechanical delay is the time lag between onsets of muscle activation and muscle force production and reflects both electro-chemical processes and mechanical processes. The aims of the present study were two-fold: to experimentally determine the slack length of each head of the biceps brachii using elastography and to determine the influence of the length of biceps brachii on electromechanical delay and its electro-chemical/mechanical processes using very high frame rate ultrasound. METHODS/RESULTS: First, 12 participants performed two passive stretches to evaluate the change in passive tension for each head of the biceps brachii. Then, they underwent two electrically evoked contractions from 120 to 20° of elbow flexion (0°: full extension, with the echographic probe maintained over the muscle belly and the myotendinous junction of biceps brachii. The slack length was found to occur at 95.5 ± 6.3° and 95.3 ± 8.2° of the elbow joint angle for the long and short heads of the biceps brachii, respectively. The electromechanical delay was significantly longer at 120° (16.9 ± 3.1 ms; p0.95. CONCLUSION: In contrast to previous observations on gastrocnemius medialis, the onset of muscle motion and the onset of myotendinous junction motion occurred simultaneously regardless of the length of the biceps brachii. That suggests that the between-muscles differences reported in the literature cannot be explained by different muscle passive tension but instead may be attributable to muscle architectural differences.

  8. Task-dependent effects evoked by foot muscle afferents on leg muscle activity in humans.

    Science.gov (United States)

    Abbruzzese, M; Rubino, V; Schieppati, M

    1996-08-01

    The effect of low intensity electrical stimulation of the posterior tibial nerve (PTN) at the ankle on the active triceps surae (TS) muscles was studied in normal subjects, both in a prone position and while standing. PTN stimulation regularly evoked the H-reflex in the flexor digitorum brevis and, in the prone position, a short-latency facilitatory effect in the soleus muscle. During standing, the facilitatory effect was preceded by a clear-cut reduction in electromyograph (EMG) activity. The inhibition-facilitation sequence was evoked in the gastrocnemii under both conditions, on average, though individual differences were present. An EMG modulation similar to that observed under standing conditions was present also in the prone position when subjects pressed the sole of the foot against the wall. Stimulation of sural or digital nerves did not evoke similar effects. It is concluded that foot muscle afferents establish oligosynaptic connections transmitting mixed effects to the TS motoneuronal pool, and that contact with the sole of the foot plays an enabling role for the inhibitory pathway directed to the soleus muscle.

  9. Evidence of skeletal muscle damage following electrically stimulated isometric muscle contractions in humans

    DEFF Research Database (Denmark)

    Mackey, Abigail; Bojsen-Moller, Jens; Qvortrup, Klaus

    2008-01-01

    It is unknown whether muscle damage at the level of the sarcomere can be induced without lengthening contractions. To investigate this, we designed a study where seven young, healthy men underwent 30 min of repeated electrical stimulated contraction of m. gastrocnemius medialis, with the ankle an...

  10. Effect of side dominance on myoelectric manifestations of muscle fatigue in the human upper trapezius muscle

    NARCIS (Netherlands)

    Farina, Dario; Kallenberg, Laura A.C.; Merletti, Roberto; Hermens, Hermie J.

    2003-01-01

    The purpose of this study was to investigate whether differences in the peripheral and control properties of the neuromuscular system due to long-term preferential use, related to side dominance, affect postural muscles, such as the upper trapezius. Therefore, fatigability properties of the upper tr

  11. The variability of co-activation pattern of antagonist muscles in human infant crawling.

    Science.gov (United States)

    Xiong, Qi L; Wu, Xiao Y; Nong Xiao; Zeng, Si Y; Zheng, Xiao L; Di Wu; Hou, Wen S

    2016-08-01

    Infant crawling is part of normal human gross motor development, and a 4-beat gait that involves rhythmical flexion and extension of limbs and the underlying muscle co-activation of antagonist muscle around the joint. However, detection the co-activation pattern of antagonist muscle are sparse due to the general difficulty of measuring locomotion in human infants. In this paper, sEMG of antagonist muscles and the corresponding kinematics data of limbs were collected when infants were crawling on hands and knees at their self-selected speed. The infant's gross motor developmental status was assessed by the global Gross Motor Function Measure Scale (GMFM-88) as well. The method based on EMG-EMG plots was used to quantify the variability of co-activation pattern of antagonist muscle. After that, we observed that antagonist muscles of upper limb (triceps brachii and biceps brachii) showed less variability of co-activation pattern of muscles than lower limb(quadriceps femoris and hamstrings) during crawling, and this variability was also varied in different crawling phases (stance and swing). Furthermore, we found some varied behaviors in the co-activation patterns of antagonist muscles when gross motor developmental level increased. The preliminary work suggests that such adaptive changes may be related to the adjustment of neuromuscular in the early stage of gross motor development.

  12. Fiber type composition and maximum shortening velocity of muscles crossing the human shoulder.

    Science.gov (United States)

    Srinivasan, R C; Lungren, M P; Langenderfer, J E; Hughes, R E

    2007-03-01

    A study of the fiber type composition of fourteen muscles spanning the human glenohumeral joint was carried out with the purpose of determining the contribution of fiber types to overall muscle cross-sectional area (CSA) and to estimate the maximum shortening velocity (V(max)) of those muscles. Muscle biopsies were procured from 4 male cadavers (mean age 50) within 24 hr of death, snap frozen, mounted, and transversely sectioned (10 microm). Slides were stained for myofibrillar ATPase after alkaline preincubation. Photoimages were taken of defined areas (100 fibers) using the Bioquant system, and fiber type and CSA were measured from these images. Staining for mATPase produced three different fiber types: slow-oxidative (SO), fast-oxidative-glycolytic (FOG), and fast-glycolytic (FG). On average, the muscle fiber type composition ranged from 22 to 40% of FG, from 17 to 51% of FOG, and from 23 to 56% of SO. Twelve out of the 14 muscles had average SO proportions ranging from 35 to 50%. V(max) was calculated from the fiber type contribution relative to CSA and shortening velocity values taken from the literature. The maximum velocities of shortening presented here provide a physiological basis for the development of human shoulder musculoskeletal models suitable for predicting muscle forces for functionally relevant tasks encompassing conditions of muscle shortening and lengthening.

  13. Ammonia uptake in inactive muscles during exercise in humans

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Kiens, Bente; Richter, Erik

    1996-01-01

    The present study examined NH3 (ammonia and ammonium) uptake in resting leg muscle. Six male subjects performed intermittent arm exercise at various intensities in two separate 32-min periods (part I and part II) and in one subsequent 20-min period in which one-legged exercise was also performed ...... unchanged throughout the experiment. The present data suggest that resting muscles extract NH3 and contribute significantly to clearance of NH3 during exercise and in early recovery from exercise. The extracted NH3 appears to be metabolized within the resting muscles.......The present study examined NH3 (ammonia and ammonium) uptake in resting leg muscle. Six male subjects performed intermittent arm exercise at various intensities in two separate 32-min periods (part I and part II) and in one subsequent 20-min period in which one-legged exercise was also performed.......0 +/- 4.5, and 57.7 +/- 18.3 mumol/min. Throughout each exercise period a net uptake of NH3 was observed in the resting leg (P muscle NH3 concentration of 195.1 +/- 15.0 mumol/kg wet wt at rest was largely...

  14. Skeletal muscle

    Science.gov (United States)

    There are approximately 650-850 muscles in the human body these include skeletal (striated), smooth and cardiac muscle. The approximation is based on what some anatomists consider separate muscle or muscle systems. Muscles are classified based on their anatomy (striated vs. smooth) and if they are v...

  15. EMG-normalised kinase activation during exercise is higher in human gastrocnemius compared to soleus muscle.

    Directory of Open Access Journals (Sweden)

    Thomas E Jensen

    Full Text Available In mice, certain proteins show a highly confined expression in specific muscle groups. Also, resting and exercise/contraction-induced phosphorylation responses are higher in rat skeletal muscle with low mitochondrial content compared to muscles with high mitochondrial content, possibly related to differential reactive oxygen species (ROS-scavenging ability or resting glycogen content. To evaluate these parameters in humans, biopsies from soleus, gastrocnemius and vastus lateralis muscles were taken before and after a 45 min inclined (15% walking exercise bout at 69% VO2(max aimed at simultaneously activating soleus and gastrocnemius in a comparable dynamic work-pattern. Hexokinase II and GLUT4 were 46-59% and 26-38% higher (p<0.05 in soleus compared to the two other muscles. The type I muscle fiber percentage was highest in soleus and lowest in vastus lateralis. No differences were found in protein expression of signalling proteins (AMPK subunits, eEF2, ERK1/2, TBC1D1 and 4, mitochondrial markers (F1 ATPase and COX1 or ROS-handling enzymes (SOD2 and catalase. Gastrocnemius was less active than soleus measured as EMG signal and glycogen use yet gastrocnemius displayed larger increases than soleus in phosphorylation of AMPK Thr172, eEF2 Thr56 and ERK 1/2 Thr202/Tyr204 when normalised to the mean relative EMG-signal. In conclusion, proteins with muscle-group restricted expression in mice do not show this pattern in human lower extremity muscle groups. Nonetheless the phosphorylation-response is greater for a number of kinase signalling pathways in human gastrocnemius than soleus at a given activation-intensity. This may be due to the combined subtle effects of a higher type I muscle fiber content and higher training status in soleus compared to gastrocnemius muscle.

  16. Regulation of human airway smooth muscle cell migration and relevance to asthma.

    Science.gov (United States)

    Salter, Brittany; Pray, Cara; Radford, Katherine; Martin, James G; Nair, Parameswaran

    2017-08-16

    Airway remodelling is an important feature of asthma pathogenesis. A key structural change inherent in airway remodelling is increased airway smooth muscle mass. There is emerging evidence to suggest that the migration of airway smooth muscle cells may contribute to cellular hyperplasia, and thus increased airway smooth muscle mass. The precise source of these cells remains unknown. Increased airway smooth muscle mass may be collectively due to airway infiltration of myofibroblasts, neighbouring airway smooth muscle cells in the bundle, or circulating hemopoietic progenitor cells. However, the relative contribution of each cell type is not well understood. In addition, although many studies have identified pro and anti-migratory agents of airway smooth muscle cells, whether these agents can impact airway remodelling in the context of human asthma, remains to be elucidated. As such, further research is required to determine the exact mechanism behind airway smooth muscle cell migration within the airways, how much this contributes to airway smooth muscle mass in asthma, and whether attenuating this migration may provide a therapeutic avenue for asthma. In this review article, we will discuss the current evidence with respect to the regulation of airway smooth muscle cell migration in asthma.

  17. Experimental human muscle damage: morphological changes in relation to other indices of damage.

    Science.gov (United States)

    Jones, D A; Newham, D J; Round, J M; Tolfree, S E

    1986-06-01

    The effects of eccentric exercise have been examined in human calf and biceps muscles. Release of muscle creatine kinase and uptake of technetium pyrophosphate have been followed for up to 20 days after the exercise and the results are related to the morphological changes seen in needle biopsy samples. The response to exercise was variable, all subjects developing pain and tenderness in the exercised muscles after 1-2 days and this was followed, in most subjects, by a large increase in plasma creatine kinase 4-6 days after the exercise. This was paralleled by an increased uptake of technetium pyrophosphate into the exercised muscle. Biopsies of the affected muscles showed little or no change in the first 7 days after the exercise but later degenerating fibres were seen, as well as infiltration by mononuclear cells and eventually, by 20 days, signs of regeneration. Very extensive changes were seen in the calf muscle of one subject; changes in the biceps were qualitatively similar but not so severe. In the severely affected calf muscle type II fibres were preferentially damaged. Mononuclear cell infiltration both between and within degenerating fibres was maximal well after the time of peak plasma creatine kinase and it is likely that in eccentrically exercised muscle infiltrating mononuclear cells act to scavenge cellular debris rather than to cause damage to the muscle.

  18. Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy.

    Science.gov (United States)

    Sun, Guilian; Haginoya, Kazuhiro; Wu, Yanling; Chiba, Yoko; Nakanishi, Tohru; Onuma, Akira; Sato, Yuko; Takigawa, Masaharu; Iinuma, Kazuie; Tsuchiya, Shigeru

    2008-04-15

    The detailed process of how dystrophic muscles are replaced by fibrotic tissues is unknown. In the present study, the immunolocalization and mRNA expression of connective tissue growth factor (CTGF) in muscles from normal and dystrophic human muscles were examined with the goal of elucidating the pathophysiological function of CTGF in muscular dystrophy. Biopsies of frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, congenital muscular dystrophy, spinal muscular atrophy, congenital myopathy were analyzed using anti-CTGF polyclonal antibody. Reverse transcription-polymerase chain reaction (RT-PCR) was also performed to evaluate the expression of CTGF mRNA in dystrophic muscles. In normal muscle, neuromuscular junctions and vessels were CTGF-immunopositive, which suggests a physiological role for CTGF in these sites. In dystrophic muscle, CTGF immunoreactivity was localized to muscle fiber basal lamina, regenerating fibers, and the interstitium. Triple immunolabeling revealed that activated fibroblasts were immunopositive for CTGF and transforming growth factor-beta1 (TGF-beta1). RT-PCR analysis revealed increased levels of CTGF mRNA in the muscles of DMD patients. Co-localization of TGF-beta1 and CTGF in activated fibroblasts suggests that CTGF expression is regulated by TGF-beta1 through a paracrine/autocrine mechanism. In conclusion, TGF-beta1-CTGF pathway may play a role in the fibrosis that is commonly observed in muscular dystrophy.

  19. Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects

    DEFF Research Database (Denmark)

    Davegårdh, Cajsa; Broholm, Christa; Perfilyev, Alexander

    2017-01-01

    is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA......BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity...... methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals. Functional follow-up experiments were performed using siRNA mediated gene silencing in primary human myoblasts and a transgenic mouse model. RESULTS: We observed genome...

  20. Norepinephrine spillover from skeletal muscle during exercise in humans

    DEFF Research Database (Denmark)

    Savard, G K; Richter, Erik; Strange, S

    1989-01-01

    The purpose of this study was to determine the effect of increasing muscle mass involvement in dynamic exercise on both sympathetic nervous activation and local hemodynamic variables of individual active and inactive skeletal muscle groups. Six male subjects performed 15-min bouts of one...... in both legs. Arterial and venous plasma concentrations of norepinephrine (NE) and epinephrine were analyzed, and the calculated NE spillover was used as an index of sympathetic nervous activity to the limb. NE spillover increased gradually both in the resting, and to a larger extent in the exercising...... legs, with a steeper rise occurring approximately 70% VO2max. These increases were not associated with any significant changes in leg blood flow or leg vascular conductance at the exercise intensities examined. These results suggest that, as the total active muscle mass increases, the rise...

  1. Group Ia afferents contribute to short-latency interlimb reflexes in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre

    2017-01-01

    and velocity of the iKnee rotations. Methods 11 seated participants (mean age: 25 ± 5 years) performed a voluntary isometric knee extension with the ipsilateral leg and contralateral knee flexion to 10% of maximum voluntary contraction (MVC). A mechanical actuator (MTS-Systems Corporation) imposed i...... amplitudes (4 vs. 8°) at the same 150°/s velocity (p’s > 0.08). Conclusion Because fast conducting group Ia muscle spindle afferents are sensitive to changes in muscle stretch velocity, while group II spindle afferents are sensitive to changes in amplitude (Grey et al., JPhysiol., 2001; Matthews, Trends...... Neurosci., 1991), group Ia velocity sensitive muscle spindle afferents likely contribute to the short-latency crossed spinal reflexes in the cBF muscle following iKnee joint rotations. This supports the findings for the short-latency crossed responses in the human soleus muscle (Stubbs & Mrachacz...

  2. Intramuscular fatty acid metabolism in contracting and non-contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Sacchetti, M; Saltin, B; Osada, T

    2002-01-01

    The present study was undertaken to investigate the fate of blood-borne non-esterified fatty acids (NEFA) entering contracting and non-contracting knee extensor muscles of healthy young individuals. [U-(13)C]-palmitate was infused into a forearm vein during 5 h of one-legged knee extensor exercise.......05) in the contracting muscle, whereas it was unchanged in the non-contracting muscle. The uptake of plasma NEFA, as well as the proportion directed towards oxidation, was higher in the exercising compared to the non-exercising leg, whereas the rate of palmitate incorporation into mTAG was fourfold lower (0.70 +/- 0.......14 vs. 0.17 +/- 0.04 micromol (g dry wt)(-1) h(-1); P contracting and non-contracting muscle, respectively. These findings demonstrate that mTAG in human skeletal muscle is continuously synthesised...

  3. Na+,K+-ATPase concentration in rodent and human heart and skeletal muscle

    DEFF Research Database (Denmark)

    Kjeldsen, K; Bjerregaard, P; Richter, Erik

    1988-01-01

    rats, cardiomyopathic hamsters, and human subjects. These methods have earlier been shown to quantify the Na+,K+-ATPase concentration in muscle tissue with high accuracy. When rats were swim trained for six weeks the heart ventricular muscle Na+,K+-ATPase concentration was increased by 20% (p less than......To investigate whether the sodium-potassium pump or Na+,K+-ATPase concentration in muscles is related to the capacity for muscle performance, the 3H-ouabain binding site concentration or 3-O-methylflourescein phosphatase activity was determined in samples of heart ventricular muscles from trained...... was increased by up to 46% (p less than 0.001) and decreased by up to 30% (p less than 0.005) after training and immobilisation respectively. Cardiomyopathic hamsters showed a reduction of 33% (p less than 0.005) in the heart ventricular Na+,K+-ATPase concentration compared with normal hamsters. This decrease...

  4. Primary establishment of human uterine muscle proteomic profiling by two-dimensional electrophoresis and mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Lin Hai-yuan; Lang Jing-he; Liu Zhu-feng; Zhu Lan; Leng Jin-hua; Sun Da-wei; Wang Xiao-rong

    2008-01-01

    Objective:To establish the protein profiling of human uterine muscle by two-dimensional electrophoresis.Methods:Five patients who underwent trans-abdominal hysterectomy due to cervical carcinoma in situ were in-cluded in this study.Postoperative uterine muscles were normal histologically.The total protein extracts from uter-ine muscle were separated using two-dimensional electrophoresis(2DE).Protein spots were stained by silver and de-tected by image analysis software.Matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS)and peptide mass fingerprint(PMF)were used to identify the selected protein spots.Results:Well-resolved,reproducible 2DE maps of human uterine muscle were obtained.Average protein spots were 468±52 and matching rate was 82.76%.Five protein spots were successfully identified by mass spectrome-try.Conclusions:2DE coupled with MALDI-TOF-MS and PMF is a useful approach for establishing human uterine muscle proteomic profiling.This data will be useful for establishing human uterine muscle proteome database.

  5. Muscle parameters for musculoskeletal modelling of the human neck

    NARCIS (Netherlands)

    Borst, J.; Forbes, P.A.; Happee, R.; Veeger, H.E.J.

    2011-01-01

    Background: To study normal or pathological neuromuscular control, a musculoskeletal model of the neck has great potential but a complete and consistent anatomical dataset which comprises the muscle geometry parameters to construct such a model is not yet available. Methods: A dissection experiment

  6. Acute exercise remodels promoter methylation in human skeletal muscle

    DEFF Research Database (Denmark)

    Barrès, Romain; Yan, Jie; Egan, Brendan

    2012-01-01

    DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene ex...

  7. Determinants of inspiratory muscle strength in healthy humans.

    Science.gov (United States)

    Brown, Peter I; Johnson, Michael A; Sharpe, Graham R

    2014-06-01

    We investigated (1) the relationship between the baseline and inspiratory muscle training (IMT) induced increase in maximal inspiratory pressure (P(I,max)) and (2) the relative contributions of the inspiratory chest wall muscles and the diaphragm (P(oes)/P(di)) to P(I,max) prior to and following-IMT. Experiment 1: P(I,max) was assessed during a Müeller manoeuvre before and after 4-wk IMT (n=30). Experiment 2: P(I,max) and the relative contribution of the inspiratory chest wall muscles to the diaphragm (P(oes)/P(di)) were assessed during a Müeller manoeuvre before and after 4-wk IMT (n=20). Experiment 1: P(I,max) increased 19% (Pinspiratory muscles relative to the diaphragm affect, in part, baseline and IMT-induced P(I,max). Great care should be taken when designing future IMT studies to ensure parity in the between-subject baseline P(I,max).

  8. Muscle metaboreflex and autonomic regulation of heart rate in humans

    DEFF Research Database (Denmark)

    Fisher, James P; Adlan, Ahmed M; Shantsila, Alena

    2013-01-01

    We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling...

  9. Skeletal muscle glucose uptake during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Richter, Erik; Kiens, Bente; Saltin, Bengt;

    1988-01-01

    uptake was not compensated for by increased uptake of free fatty acids but was accompanied by decreases in plasma insulin and increases in plasma epinephrine and norepinephrine. During work with large muscle masses, arterial lactate increased to approximately 6 mM, and net leg lactate release reverted...

  10. Human masticatory muscle activity and jaw position under experimental stress.

    Science.gov (United States)

    Tsai, C-M; Chou, S-L; Gale, E N; McCall, W D

    2002-01-01

    The purpose of the present study was to determine whether stress induced a consistent pattern of increased electromyographic (EMG) activity in different masticatory muscles, and whether stress produced changes in jaw position. Thirty-five dental students at Taipei Medical College volunteered for this study. Mental arithmetic was used to create a stress condition and relaxation instruction was used to help relax the subjects. Subjects were asked to evaluate the stress they felt under each experimental condition with a visual analogue scale (VAS). Surface electrodes were used to monitor the EMG activities of the right masseter, right posterior temporalis and suprahyoid muscles. A kinesiograph was used to observe the jaw position. Data collected before mental arithmetic or relaxation monitored the baseline level. The VAS means were significantly increased during the stress condition and significantly decreased following relaxation, compared with the baseline. There was also a significant increase in EMG activity of all three muscles during mental arithmetic compared with baseline; different patterns of increased EMG activity were noticed in the three muscles under a continuous stress condition. Under stress, the incidence of tooth contact at intercuspal position was also increased.

  11. Muscle parameters for musculoskeletal modelling of the human neck

    NARCIS (Netherlands)

    Borst, J.; Forbes, P.A.; Happee, R.; Veeger, H.E.J.

    2011-01-01

    Background: To study normal or pathological neuromuscular control, a musculoskeletal model of the neck has great potential but a complete and consistent anatomical dataset which comprises the muscle geometry parameters to construct such a model is not yet available. Methods: A dissection experiment

  12. Intramuscular EMG from the hip flexor muscles during human locomotion.

    Science.gov (United States)

    Andersson, E A; Nilsson, J; Thorstensson, A

    1997-11-01

    The purpose was to investigate the activation pattern of five major hip flexor muscles and its adaptation to changing speed and mode of progression. A total of 11 healthy subjects performed walking and running on a motor-driven treadmill at speeds ranging from 1.0 to 6.0 m s-1. Intramuscular fine-wire electrodes were used to record myoelectric signals from the iliacus, psoas, sartorius, rectus femoris and tensor fascia latae muscles. The basic pattern, with respect to number of activation periods, remained the same irrespective of speed and mode of progression. However, differences in the relative duration and timing of onset of activation occurred between individual muscles. Over the speed range in walking, a progressively earlier onset was generally seen for the activation period related to hip flexion. Changes in EMG amplitude were measured in the iliacus and psoas muscles and showed a marked increase and difference between walking and running at speeds above 2.0 m s-1. Thus, the alternating flexion-extension movements at the hip during locomotion appear to be governed by a rather fixed 'neural program' which normally only needs minor modulations to accomplish the adjustments accompanying an increase in speed of progression as well as a change from walking to running.

  13. Factors regulating fat oxidation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiens, Bente; Alsted, Thomas Junker; Jeppesen, Jacob

    2011-01-01

    In modern societies, oversupply of calories leads to obesity and chronic metabolic stress, which may lead to development of disease. Oversupply of calories is often associated with elevated plasma lipid concentrations and accumulation of lipids in skeletal muscle leading to decreased insulin...

  14. Pyruvate carboxylase is expressed in human skeletal muscle

    DEFF Research Database (Denmark)

    Minet, Ariane D; Gaster, Michael

    2010-01-01

    Pyruvate carboxylase (PC) is a mitochondrial enzyme that catalyses the carboxylation of pyruvate to oxaloacetate thereby allowing supplementation of citric acid cycle intermediates. The presence of PC in skeletal muscle is controversial. We report here, that PC protein is easily detectable...

  15. PDB73 – The Expected Value Of Bio-Artificial Pancreas Development In View Of Endocrinologists' And Patients' Preferences

    NARCIS (Netherlands)

    Wissing, T.B.; Apeldoorn, van A.A.; IJzerman, M.J.

    2013-01-01

    Objectives Islet transplantation is an accepted transplantation method in type I Diabetes Mellitus, yet islet survival is hampered due to an insufficient transplantation site and severe immunological and inflammatory responses. The development of a bio-artificial pancreas (BAP) may contribute to tra

  16. Functional changes of human quadriceps muscle injured by eccentric exercise

    Directory of Open Access Journals (Sweden)

    F.V. Serrão

    2003-06-01

    Full Text Available The present study evaluated functional changes of quadriceps muscle after injury induced by eccentric exercise. Maximal isometric torque of quadriceps and the surface electromyography (root mean square, RMS, and median frequency, MDF of the vastus medialis oblique (VMO and vastus lateralis (VL muscles were examined before, immediately after and during the first 7 days after injury. Serum creatine kinase (CK levels and magnetic resonance imaging (MRI were used to identify muscle injury. The subject was used as her own control and percent refers to pre-injury data. Experiments were carried out with a sedentary 23-year-old female. Injury was induced by 4 bouts of 15 maximal isokinetic eccentric contractions (angular velocity of 5º/s; range of motion from 40º to 110º of knee flexion. The isometric torque of the quadriceps (knee at 90º flexion decreased 52% immediately after eccentric exercise and recovered on the 5th day. The highest reduction of RMS occurred on the 2nd day after injury in both VL (63% and VMO (66% and only VL recovered to the pre-injury level on the 7th day. Immediately after injury, the MDF decreased by 5 and 3% (VMO and VL, respectively and recovered one day later. Serum CK levels increased by 109% on the 2nd day and were still increased by 32% on the 7th day. MRI showed large areas of injury especially in the deep region of quadriceps. In conclusion, eccentric exercise decreased the isometric torque and electromyographic signals of quadriceps muscle, which were recovered in one week, despite the muscle regeneration signals.

  17. Engineering 3D bio-artificial heart muscle: the acellular ventricular extracellular matrix model.

    Science.gov (United States)

    Patel, Nikita M; Tao, Ze-Wei; Mohamed, Mohamed A; Hogan, Matt K; Gutierrez, Laura; Birla, Ravi K

    2015-01-01

    Current therapies in left ventricular systolic dysfunction and end-stage heart failure include mechanical assist devices or transplant. The development of a tissue-engineered integrative platform would present a therapeutic option that overcomes the limitations associated with current treatment modalities. This study provides a foundation for the fabrication and preliminary viability of the acellular ventricular extracellular matrix (AVEM) model. Acellular ventricular extracellular matrix was fabricated by culturing 4 million rat neonatal cardiac cells around an excised acellular ventricular segment. Acellular ventricular extracellular matrix generated a maximum spontaneous contractile force of 388.3 μN and demonstrated a Frank-Starling relationship at varying pretensions. Histologic assessment displayed cell cohesion and adhesion within the AVEM as a result of passive cell seeding.

  18. Metabolomics-on-a-chip and predictive systems toxicology in microfluidic bioartificial organs.

    Science.gov (United States)

    Shintu, Laetitia; Baudoin, Régis; Navratil, Vincent; Prot, Jean-Matthieu; Pontoizeau, Clément; Defernez, Marianne; Blaise, Benjamin J; Domange, Céline; Péry, Alexandre R; Toulhoat, Pierre; Legallais, Cécile; Brochot, Céline; Leclerc, Eric; Dumas, Marc-Emmanuel

    2012-02-21

    The world faces complex challenges for chemical hazard assessment. Microfluidic bioartificial organs enable the spatial and temporal control of cell growth and biochemistry, critical for organ-specific metabolic functions and particularly relevant to testing the metabolic dose-response signatures associated with both pharmaceutical and environmental toxicity. Here we present an approach combining a microfluidic system with (1)H NMR-based metabolomic footprinting, as a high-throughput small-molecule screening approach. We characterized the toxicity of several molecules: ammonia (NH(3)), an environmental pollutant leading to metabolic acidosis and liver and kidney toxicity; dimethylsulfoxide (DMSO), a free radical-scavenging solvent; and N-acetyl-para-aminophenol (APAP, or paracetamol), a hepatotoxic analgesic drug. We report organ-specific NH(3) dose-dependent metabolic responses in several microfluidic bioartificial organs (liver, kidney, and cocultures), as well as predictive (99% accuracy for NH(3) and 94% for APAP) compound-specific signatures. Our integration of microtechnology, cell culture in microfluidic biochips, and metabolic profiling opens the development of so-called "metabolomics-on-a-chip" assays in pharmaceutical and environmental toxicology.

  19. Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle

    DEFF Research Database (Denmark)

    Hütter, Eveline; Skovbro, Mette; Lener, Barbara;

    2007-01-01

    According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain....... However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated...... from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high-resolution respirometry, and ROS production was analyzed by in situ staining with the redox-sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional...

  20. Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate

    DEFF Research Database (Denmark)

    Green, C J; Bunprajun, T; Pedersen, B K

    2013-01-01

      The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture...... and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism...... in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance...

  1. Simultaneous 31P NMR spectroscopy and EMG in exercising and recovering human skeletal muscle: technical aspects

    DEFF Research Database (Denmark)

    Vestergaard-Poulsen, P; Thomsen, C; Sinkjaer, T

    1994-01-01

    . A nonmagnetic ergometer was used for ankle dorsiflexions that activated only the anterior tibial muscle as verified by post exercise imaging. The coil design and the adiabatic sech/tanh pulse improved sensitivity by 45% and 56% respectively, compared with standard techniques. Simultaneous electromyographic......The bioenergetics of human skeletal muscle can be studied by 31P NMR spectroscopy (31P-MRS) and by surface electromyography (SEMG). Simultaneous 31P-MRS and SEMG permit accurate and noninvasive studies of the correlation between metabolic and electrical changes in exercising and recovering human...... skeletal muscle, a relationship that is still poorly understood. This study describes the optimization of skeletal muscle 31P-MRS in a whole-body magnet, involving surface coil design, utilization of adiabatic radio frequency pulses and advanced time-domain fitting, to the technical design of SEMG...

  2. Motor unit activity after eccentric exercise and muscle damage in humans.

    Science.gov (United States)

    Semmler, J G

    2014-04-01

    It is well known that unaccustomed eccentric exercise leads to muscle damage and soreness, which can produce long-lasting effects on muscle function. How this muscle damage influences muscle activation is poorly understood. The purpose of this brief review is to highlight the effect of eccentric exercise on the activation of muscle by the nervous system, by examining the change in motor unit activity obtained from surface electromyography (EMG) and intramuscular recordings. Previous research shows that eccentric exercise produces unusual changes in the EMG–force relation that influences motor performance during isometric, shortening and lengthening muscle contractions and during fatiguing tasks. When examining the effect of eccentric exercise at the single motor unit level, there are substantial changes in recruitment thresholds, discharge rates, motor unit conduction velocities and synchronization, which can last for up to 1 week after eccentric exercise. Examining the time course of these changes suggests that the increased submaximal EMG after eccentric exercise most likely occurs through a decrease in motor unit conduction velocity and an increase in motor unit activity related to antagonist muscle coactivation and low-frequency fatigue. Furthermore, there is a commonly held view that eccentric exercise produces preferential damage to high-threshold motor units, but the evidence for this in humans is limited. Further research is needed to establish whether there is preferential damage to high-threshold motor units after eccentric exercise in humans, preferably by linking changes in motor unit activity with estimates of motor unit size using selective intramuscular recording techniques.

  3. In Vivo Myogenic Potential of Human CD133+ Muscle-derived Stem Cells: A Quantitative Study

    Science.gov (United States)

    Negroni, Elisa; Riederer, Ingo; Chaouch, Soraya; Belicchi, Marzia; Razini, Paola; Di Santo, James; Torrente, Yvan; Butler-Browne, Gillian S; Mouly, Vincent

    2009-01-01

    In recent years, numerous reports have identified in mouse different sources of myogenic cells distinct from satellite cells that exhibited a variable myogenic potential in vivo. Myogenic stem cells have also been described in humans, although their regenerative potential has rarely been quantified. In this study, we have investigated the myogenic potential of human muscle–derived cells based on the expression of the stem cell marker CD133 as compared to bona fide satellite cells already used in clinical trials. The efficiency of these cells to participate in muscle regeneration and contribute to the renewal of the satellite cell pool, when injected intramuscularly, has been evaluated in the Rag2−/− γC−/− C5−/− mouse in which muscle degeneration is induced by cryoinjury. We demonstrate that human muscle–derived CD133+ cells showed a much greater regenerative capacity when compared to human myoblasts. The number of fibers expressing human proteins and the number of human cells in a satellite cell position are all dramatically increased when compared to those observed after injection of human myoblasts. In addition, CD133+/CD34+ cells exhibited a better dispersion in the host muscle when compared to human myoblasts. We propose that muscle-derived CD133+ cells could be an attractive candidate for cellular therapy. PMID:19623164

  4. Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6

    DEFF Research Database (Denmark)

    Keller, Pernille; Penkowa, Milena; Keller, Charlotte

    2005-01-01

    . Therefore, we investigated IL-6 receptor regulation in response to exercise and IL-6 infusion in humans. Furthermore, using IL-6-deficient mice, we investigated the role of IL-6 in the IL-6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise...

  5. Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans.

    Science.gov (United States)

    Kamiya, Atsunori; Michikami, Daisaku; Shiozawa, Tomoki; Iwase, Satoshi; Hayano, Junichiro; Kawada, Toru; Sunagawa, Kenji; Mano, Tadaaki

    2004-05-01

    Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P antigravity leg muscles.

  6. Limitations of surface EMG signals of extrinsic muscles in predicting postures of human hand.

    Science.gov (United States)

    Vinjamuri, Ramana; Mao, Zhi-Hong; Sclabassi, Robert; Sun, Mingui

    2006-01-01

    This paper explores the limitations of sEMG (surface Electromyography) signals collected from the extrinsic muscles in the forearm in predicting the postures of human hand. Four subjects were asked to try ten extreme postures of hand which need high effort. Two of these four subjects were asked to try ten more normal postures which did not need effort During the experiments, muscle activity and static postures of the hand were measured. The data obtained were analyzed by principal component analysis. The results obtained revealed the limitations of sEMG signals of extrinsic muscles in reproducing the postures of the hand.

  7. Regulation of human skeletal muscle perfusion and its heterogeneity during exercise in moderate hypoxia

    DEFF Research Database (Denmark)

    Heinonen, Ilkka H; Kemppainen, Jukka; Kaskinoro, Kimmo

    2010-01-01

    Although many effects of both acute and chronic hypoxia on the circulation are well characterized, the distribution and regulation of blood flow (BF) heterogeneity in skeletal muscle during systemic hypoxia is not well understood in humans. We measured muscle BF within the thigh muscles of nine...... healthy young men using positron emission tomography during one-leg dynamic knee extension exercise in normoxia and moderate physiological systemic hypoxia (14% O(2) corresponding to approximately 3,400 m of altitude) without and with local adenosine receptor inhibition with femoral artery infusion...

  8. Mitochondrial function in human skeletal muscle following high-altitude exposure

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Boushel, Robert; Wright-Paradis, Cynthia

    2013-01-01

    Studies regarding mitochondrial modifications in human skeletal muscle following acclimatization to high altitude are conflicting, and these inconsistencies may be due to the prevalence of representing mitochondrial function through static and isolated measurements of specific mitochondrial.......059) to limit mass-specific maximal oxidative phosphorylation capacity. These data suggest that 9-11 days of exposure to high altitude do not markedly modify integrated measures of mitochondrial functional capacity in skeletal muscle despite significant decrements in the concentrations of enzymes involved...

  9. Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in human skeletal muscle

    DEFF Research Database (Denmark)

    Middelbeek, R J W; Chambers, M A; Tantiwong, P

    2013-01-01

    Individuals with obesity and type 2 diabetes (T2D) are typically insulin resistant, exhibiting impaired skeletal muscle glucose uptake. Animal and cell culture experiments have shown that site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 and TBC1D1 is critical for GLUT4 tr...... translocation facilitating glucose uptake, but their regulation in human skeletal muscle is not well understood....

  10. Arterial supply in the human pectoralis minor muscle.

    Science.gov (United States)

    Moriya, A; Takafuji, T; Sato, Y

    1993-03-01

    In the following, we report our findings obtained as a result of injecting an acrylic pigment in the arteries supplying the pectoralis minor muscle in 50 lateral chests of 26 Japanese adults (15 males and 11 females). In the pectoralis minor muscle, the muscular bundle near the terminal is supplied by A. processus coracoideris (Pc, Sato-Takafuji, '85) or A. coracobrachialis (Cb, Sato, '80) of A. axillaris (Ax), while its middle upper and lower peripherals are supplied by A. thoracoacromialis (Ta) and A. partis abdominalis (Pab, Sato, '76), respectively. Further, the upper and lower peripherals at its origin are supplied by A. thoracica suprema (Ts) and A. thoracica lateralis (Tl), respectively. Pc, Cb, Pab and Ts may occasionally be absent. Arteries supplying this muscle are classified according to their origins and routes of distribution, as follows. Type I-a: Pc or Cb, Ta, Pab, Ts and Tl are present, 32%; Type II-a: Ts is absent from Type I-a, 14%; Type III-a: Pb and Pc are absent from Type I-a, 20%; Type IV-a: Cb, Pc and Ts are absent from Type I-a, 10%. Type b is Type a without Pab. The rates of appearance of Type I-b, II-b, III-b and IV-b were all 6%. The ratios of distribution in area a were as follows, in order of decreasing ratio: 37.6% for Pab (37 cases), 32.4% for Tl (49 cases), 30.2% for Ta (49 cases), 10.8% for Ts (32 cases), 7% for Cb (9 cases), and 6.37% for Pc. In the pectoralis minor muscle, the major supplying arteries are Pab, Tl and Ta, and where Pab was absent, this was compensated for by a branch of Ta. The total number of supplying arteries in this muscle was two to five, with the majority, or 36%, having four arteries. As for sex differences in the incidence of each type, Type I-a appeared more often in males (40%) than in females (20%). The rates according to the ribs of origin were 46%, 36%, 16%, and 2% for types 2.3.4.5, 3.4.5, 2.3.4, and 2.3.4.5.6, respectively. It was interesting that all Type II and Type IV cases without Ts corresponded

  11. Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Chunlei Miao

    2017-01-01

    Full Text Available Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious.

  12. Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering

    Science.gov (United States)

    Miao, Chunlei; Zhou, Lulu; Tian, Lufeng; Zhang, Yingjie; Zhang, Wei; Yang, Fanghong; Liu, Tianyi

    2017-01-01

    Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious. PMID:28210626

  13. Human skeletal muscle glycogen utilization in exhaustive exercise

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Holmberg, Hans-Christer; Schrøder, Henrik Daa

    2011-01-01

    to be influenced by fibre type prior to exercise, as well as carbohydrate availability during the subsequent period of recovery. These findings provide insight into the significance of fibre type-specific compartmentalization of glycogen metabolism in skeletal muscle during exercise and subsequent recovery. .......Although glycogen is known to be heterogeneously distributed within skeletal muscle cells, there is presently little information available about the role of fibre types, utilization and resynthesis during and after exercise with respect to glycogen localization. Here, we tested the hypothesis...... contained more intramyofibrillar and subsarcolemmal glycogen than the latter. In highly glycogen-depleted fibres, the remaining small intermyofibrillar and subsarcolemmal glycogen particles were often found to cluster in groupings. In the recovery period, when the athletes received either a carbohydrate...

  14. Signs of muscle thixotropy during human ballistic wrist joint movements.

    Science.gov (United States)

    Axelson, H W

    2005-11-01

    A study was conducted on healthy subjects to determine whether voluntary ballistic wrist flexion movements are influenced by immediately preceding conditioning of the forearm muscles. Single rapid wrist flexion movements were made in response to an auditory "Go" signal. Rectified surface EMG was recorded from wrist flexors and extensors, and joint position was measured by a goniometer. The movements were preceded (2-3 s) by four different conditioning routines: 40-s rest (Rest), 10-s voluntary alternating wrist joint flexion and extension movements (Osc), and 10 s of 25 degrees weak isometric wrist extensor (Ext) or flexor contractions (Flex). When subjects made ballistic movements after Osc compared with Rest, peak velocity was higher (P = 0.02) and movement time shorter (P = 0.06), but there was no difference (P = 0.83) in motor reaction time (time between the onset of the first agonist burst and movement onset). If the movements were preceded by Ext compared with Flex, motor reaction time was longer (P = 0.01), indicating a longer electromechanical delay. There were no indications that postconditioning differences in agonist or antagonist muscle activity could explain the results. It was also demonstrated that, after Rest, peak velocity was lower (P < 0.01) for the first than for the second of a series of repetitive ballistic movements. The observations corresponded to results from passive experiments in which the median nerve was electrically stimulated. In conclusion, history-dependent (thixotropic) changes in skeletal muscle resistance seem to have implications for voluntary ballistic wrist movements. The study also provided evidence that muscle conditioning influences the central nervous reaction time preceding ballistic contractions.

  15. Microbiological safety of a novel bio-artificial liver support system based on porcine hepatocytes: a experimental study

    Directory of Open Access Journals (Sweden)

    Han Bing

    2012-05-01

    Full Text Available Abstract Background Our institute has developed a novel bio-artificial liver (BAL support system, based on a multi-layer radial-flow bioreactor carrying porcine hepatocytes and mesenchymal stem cells. It has been shown that porcine hepatocytes are capable of carrying infectious porcine endogenous retroviruses (PERVs into human cells, thus the microbiological safety of any such system must be confirmed before clinical trials can be performed. In this study, we focused on assessing the status of PERV infection in beagles treated with the novel BAL. Methods Five normal beagles were treated with the novel BAL for 6 hours. The study was conducted for 6 months, during which plasma was collected from the BAL and whole blood from the beagles at regular intervals. DNA and RNA in both the collected peripheral blood mononuclear cells (PBMCs and plasma samples were extracted for conventional PCR and reverse transcriptase (RT-PCR with PERV-specific primers and the porcine-specific primer Sus scrofa cytochrome B. Meanwhile, the RT activity and the in vitro infectivity of the plasma were measured. Results Positive PERV RNA and RT activity were detected only in the plasma samples taken from the third circuit of the BAL system. All other samples including PBMCs and other plasma samples were negative for PERV RNA, PERV DNA, and RT activity. In the in vitro infection experiment, no infection was found in HEK293 cells treated with plasma. Conclusions No infective PERV was detected in the experimental animals, thus the novel BAL had a reliable microbiological safety profile.

  16. A bio-artificial renal epithelial cell system conveys survival advantage in a porcine model of septic shock.

    Science.gov (United States)

    Westover, Angela J; Buffington, Deborah A; Johnston, Kimberly A; Smith, Peter L; Pino, Christopher J; Humes, H David

    2017-03-01

    Renal cell therapy using the hollow fiber based renal assist device (RAD) improved survival time in an animal model of septic shock (SS) through the amelioration of cardiac and vascular dysfunction. Safety and ability of the RAD to improve clinical outcomes was demonstrated in a Phase II clinical trial, in which patients had high prevalence of sepsis. Even with these promising results, clinical delivery of cell therapy is hampered by manufacturing hurdles, including cell sourcing, large-scale device manufacture, storage and delivery. To address these limitations, the bioartificial renal epithelial cell system (BRECS) was developed. The BRECS contains human renal tubule epithelial cells derived from adult progenitor cells using enhanced propagation techniques. Cells were seeded onto trabeculated disks of niobium-coated carbon, held within cryopreservable, perfusable, injection-moulded polycarbonate housing. The study objective was to evaluate the BRECS in a porcine model of SS to establish conservation of efficacy after necessary cell sourcing and design modifications; a pre-clinical requirement to move back into clinical trials. SS was incited by peritoneal injection of E. coli simultaneous to insertion of BRECS (n=10) or control (n=15), into the ultrafiltrate biofeedback component of an extracorporeal circuit. Comparable to RAD, prolonged survival of the BRECS cohort was conveyed through stabilization of cardiac output and vascular leak. In conclusion, the demonstration of conserved efficacy with BRECS therapy in a porcine SS model represents a crucial step toward returning renal cell therapy to the clinical setting, initially targeting ICU patients with acute kidney injury requiring continuous renal replacement therapy. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  17. An assessment of six muscle spindle models for predicting sensory information during human wrist movements.

    Directory of Open Access Journals (Sweden)

    Puja eMalik

    2016-01-01

    Full Text Available Background: The muscle spindle is an important sensory organ for proprioceptive information, yet there have been few attempts to use Shannon information theory to quantify the capacity of human muscle spindles to encode sensory input.Methods: Computer simulations linked kinematics, to biomechanics, to six muscle spindle models that generated predictions of firing rate. The predicted firing rates were compared to firing rates of human muscle spindles recorded during a step-tracking (center-out task to validate their use. The models were then used to predict firing rates during random movements with statistical properties matched to the ergonomics of human wrist movements. The data were analyzed for entropy and mutual information.Results: Three of the six models produced predictions that approximated the firing rate of human spindles during the step-tracking task. For simulated random movements these models predicted mean rates of 16.0±4.1 imp/s (mean±sd, peak firing rates <50 imp/s and zero firing rate during an average of 25% of the movement. The average entropy of the neural response was 4.1±0.3 bits and is an estimate of the maximum information that could be carried by muscles spindles during ecologically valid movements. The information about tendon displacement preserved in the neural response was 0.10±0.05 bits per symbol; whereas 1.25±0.30 bits per symbol of velocity input were preserved in the neural response of the spindle models.Conclusions: Muscle spindle models, originally based on cat experiments, have predictive value for modeling responses of human muscle spindles with minimal parameter optimization. These models predict more than 10-fold more velocity over length information encoding during ecologically valid movements. These results establish theoretical parameters for developing neuroprostheses for proprioceptive function.

  18. Light- and electron microscopical studies of interstitial cells of Cajal and muscle cells at the submucosal border of human colon

    DEFF Research Database (Denmark)

    Rumessen, J J; Peters, S; Thuneberg, L

    1993-01-01

    It has been suggested that interstitial cells of Cajal (ICC) at the submucosal border of the colonic circular muscle are pacemaker cells. We studied smooth muscle cells and ICC at the submucosal surface of the circular muscle layer of the normal human colon....

  19. The vascular anatomy of the human temporalis muscle: implications for surgical splitting techniques.

    Science.gov (United States)

    Cheung, L K

    1996-12-01

    Despite the wide application of the temporalis muscle flap and its modifications, understanding of the vascular pattern and territories within the muscle remains poor. This study aimed to evaluate the vascular architecture in the human temporalis muscle for surgical application. The material comprised 15 fresh cadavers (30 muscle specimens), which were divided into three groups for vascular infusion by either Indian ink solution, lead oxide solution, or methylmethacrylate resin. The vascular network in the temporalis muscle was analyzed by stereomicroscopy, radiography, and scanning electron microscopy. The human temporalis muscle was found to have vascular supply from three primary arteries: the anterior deep temporal artery (ADTA), the posterior deep temporal artery (PDTA), and the middle temporal artery (MTA). Each primary artery branched into the secondary arterioles and then the terminal arterioles. The venous network accompanied the arteries, and double veins pairing one artery was a common finding. The capillaries formed a dense, interlacing network with orientation along the muscle fibres. Arteriovenous anastomosis was absent. In the coronal plane, the vessels were located mainly on the lateral and medial aspects of the muscle with a significantly lower vascular density in the midline. Morphometric analysis of the arterial network showed that the PDTA was larger in size at primary and secondary branching levels than the ADTA and the MTA, whereas no differences were present at the terminal arteriolar levels. The distribution of the arterial territories was as follows: the ADTA occupied 21% anteriorly, the PDTA occupied 41% in the middle region, and the MTA occupied 38% in the posterior region. This improved understanding of the vascular architecture within the temporalis muscle complements the anatomic basis of the flap-splitting technique and increases the safety of its application.

  20. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle

    Science.gov (United States)

    Pecorella, Shelly R. H.; Potter, Jennifer V. F.; Cherry, Anne D.; Peacher, Dionne F.; Welty-Wolf, Karen E.; Moon, Richard E.; Suliman, Hagir B.

    2015-01-01

    The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity. PMID:26186946

  1. Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons

    Science.gov (United States)

    Agarwal, Andrea B.; Feng, Cheng-Yuan; Altick, Amy L.; Quilici, David R.; Wen, Dan; Johnson, L. Alan; von Bartheld, Christopher S.

    2016-01-01

    Purpose To determine whether structural protein composition and expression of key regulatory genes are altered in strabismic human extraocular muscles. Methods Samples from strabismic horizontal extraocular muscles were obtained during strabismus surgery and compared with normal muscles from organ donors. We used proteomics, standard and customized PCR arrays, and microarrays to identify changes in major structural proteins and changes in gene expression. We focused on muscle and connective tissue and its control by enzymes, growth factors, and cytokines. Results Strabismic muscles showed downregulation of myosins, tropomyosins, troponins, and titin. Expression of collagens and regulators of collagen synthesis and degradation, the collagenase matrix metalloproteinase (MMP)2 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)1 and TIMP2, was upregulated, along with tumor necrosis factor (TNF), TNF receptors, and connective tissue growth factor (CTGF), as well as proteoglycans. Growth factors controlling extracellular matrix (ECM) were also upregulated. Among 410 signaling genes examined by PCR arrays, molecules with downregulation in the strabismic phenotype included GDNF, NRG1, and PAX7; CTGF, CXCR4, NPY1R, TNF, NTRK1, and NTRK2 were upregulated. Signaling molecules known to control extraocular muscle plasticity were predominantly expressed in the tendon rather than the muscle component. The two horizontal muscles, medial and lateral rectus, displayed similar changes in protein and gene expression, and no obvious effect of age. Conclusions Quantification of proteins and gene expression showed significant differences in the composition of extraocular muscles of strabismic patients with respect to important motor proteins, elements of the ECM, and connective tissue. Therefore, our study supports the emerging view that the molecular composition of strabismic muscles is substantially altered. PMID:27768799

  2. Human leg model predicts ankle muscle-tendon morphology, state, roles and energetics in walking.

    Directory of Open Access Journals (Sweden)

    Pavitra Krishnaswamy

    2011-03-01

    Full Text Available A common feature in biological neuromuscular systems is the redundancy in joint actuation. Understanding how these redundancies are resolved in typical joint movements has been a long-standing problem in biomechanics, neuroscience and prosthetics. Many empirical studies have uncovered neural, mechanical and energetic aspects of how humans resolve these degrees of freedom to actuate leg joints for common tasks like walking. However, a unifying theoretical framework that explains the many independent empirical observations and predicts individual muscle and tendon contributions to joint actuation is yet to be established. Here we develop a computational framework to address how the ankle joint actuation problem is resolved by the neuromuscular system in walking. Our framework is founded upon the proposal that a consideration of both neural control and leg muscle-tendon morphology is critical to obtain predictive, mechanistic insight into individual muscle and tendon contributions to joint actuation. We examine kinetic, kinematic and electromyographic data from healthy walking subjects to find that human leg muscle-tendon morphology and neural activations enable a metabolically optimal realization of biological ankle mechanics in walking. This optimal realization (a corresponds to independent empirical observations of operation and performance of the soleus and gastrocnemius muscles, (b gives rise to an efficient load-sharing amongst ankle muscle-tendon units and (c causes soleus and gastrocnemius muscle fibers to take on distinct mechanical roles of force generation and power production at the end of stance phase in walking. The framework outlined here suggests that the dynamical interplay between leg structure and neural control may be key to the high walking economy of humans, and has implications as a means to obtain insight into empirically inaccessible features of individual muscle and tendons in biomechanical tasks.

  3. Human Leg Model Predicts Ankle Muscle-Tendon Morphology, State, Roles and Energetics in Walking

    Science.gov (United States)

    Krishnaswamy, Pavitra; Brown, Emery N.; Herr, Hugh M.

    2011-01-01

    A common feature in biological neuromuscular systems is the redundancy in joint actuation. Understanding how these redundancies are resolved in typical joint movements has been a long-standing problem in biomechanics, neuroscience and prosthetics. Many empirical studies have uncovered neural, mechanical and energetic aspects of how humans resolve these degrees of freedom to actuate leg joints for common tasks like walking. However, a unifying theoretical framework that explains the many independent empirical observations and predicts individual muscle and tendon contributions to joint actuation is yet to be established. Here we develop a computational framework to address how the ankle joint actuation problem is resolved by the neuromuscular system in walking. Our framework is founded upon the proposal that a consideration of both neural control and leg muscle-tendon morphology is critical to obtain predictive, mechanistic insight into individual muscle and tendon contributions to joint actuation. We examine kinetic, kinematic and electromyographic data from healthy walking subjects to find that human leg muscle-tendon morphology and neural activations enable a metabolically optimal realization of biological ankle mechanics in walking. This optimal realization (a) corresponds to independent empirical observations of operation and performance of the soleus and gastrocnemius muscles, (b) gives rise to an efficient load-sharing amongst ankle muscle-tendon units and (c) causes soleus and gastrocnemius muscle fibers to take on distinct mechanical roles of force generation and power production at the end of stance phase in walking. The framework outlined here suggests that the dynamical interplay between leg structure and neural control may be key to the high walking economy of humans, and has implications as a means to obtain insight into empirically inaccessible features of individual muscle and tendons in biomechanical tasks. PMID:21445231

  4. Immunohistochemical changes in the expression of HSP27 in exercised human vastus lateralis muscle

    DEFF Research Database (Denmark)

    Folkesson, M; Mackey, Abigail; Holm, L;

    2008-01-01

    . METHODS: Two different exercise protocols were used: (1) one-leg ergometer cycling (EC, n = 6) consisting of two 30-min bouts at 40% and 75% of peak oxygen uptake, respectively, and (2) leg extension resistance exercise (RE, n = 9) including 10 sets of eight repetitions at a load corresponding to 70......AIM: The role of HSP27 in the adaptive process of skeletal muscle to exercise, especially in humans, is not well understood. The objective of this study was to investigate immunohistochemical changes in HSP27 expression in human vastus lateralis muscle following resistance and endurance exercises......% of one maximal repetition (1RM). Immunohistochemistry using specific monoclonal antibodies was used to determine the location of HSP27 protein in muscle biopsies from human vastus lateralis. RESULTS: Our results show that RE, but not EC, induced a significant appearance of scattered accumulations of HSP...

  5. Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M. (Stanford Univ. School of Medicine, CA (USA))

    1990-10-01

    Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.

  6. Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle

    DEFF Research Database (Denmark)

    Suetta, C.; Frandsen, Ulrik; Mackey, Abigail

    2013-01-01

    expression analysis of key growth and transcription factors associated with local skeletal muscle milieu were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of re-training. OM demonstrated no detectable gains in MFA (VL muscle) and no increases in number of Pax7......Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and old human subjects subsequent to 2 weeks of immobility......-induced muscle atrophy. Re-training consisted of 4 weeks of supervised resistive exercise in 9 older (OM: 67.3yrs, range 61-74) and 11 young (YM: 24.4yrs, range 21-30) males. Measures of myofiber area (MFA), Pax7-positive satellite cells (SC) associated with type I and type II muscle fibres, as well as gene...

  7. Functional compartmentalization of the human superficial masseter muscle.

    Directory of Open Access Journals (Sweden)

    Rodrigo A Guzmán-Venegas

    Full Text Available Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM muscle's motor units using high-density surface electromyography (EMGs at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF were randomly requested. Using a two-dimensional grid (four columns, six electrodes located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001.The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001. The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001. The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20-60% MVBF.

  8. Functional compartmentalization of the human superficial masseter muscle.

    Science.gov (United States)

    Guzmán-Venegas, Rodrigo A; Biotti Picand, Jorge L; de la Rosa, Francisco J Berral

    2015-01-01

    Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM) muscle's motor units using high-density surface electromyography (EMGs) at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm) were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF) were randomly requested. Using a two-dimensional grid (four columns, six electrodes) located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001).The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001). The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001). The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20-60% MVBF).

  9. Fibroblast growth factor-23 induces cellular senescence in human mesenchymal stem cells from skeletal muscle.

    Science.gov (United States)

    Sato, Chisato; Iso, Yoshitaka; Mizukami, Takuya; Otabe, Koji; Sasai, Masahiro; Kurata, Masaaki; Sanbe, Takeyuki; Sekiya, Ichiro; Miyazaki, Akira; Suzuki, Hiroshi

    2016-02-12

    Although muscle wasting and/or degeneration are prevalent in patients with chronic kidney disease, it remains unknown whether FGF-23 influences muscle homeostasis and regeneration. Mesenchymal stem cells (MSCs) in skeletal muscle are distinct from satellite cells and have a known association with muscle degeneration. In this study we sought to investigate the effects of FGF-23 on MSCs isolated from human skeletal muscle in vitro. The MSCs expressed FGF receptors (1 through 4) and angiotensin-II type 1 receptor, but no traces of the Klotho gene were detected. MSCs and satellite cells were treated with FGF-23 and angiotensin-II for 48 h. Treatment with FGF-23 significantly decreased the number of MSCs compared to controls, while treatment with angiotensin-II did not. FGF-23 and angiotensin-II both left the cell counts of the satellite cells unchanged. The FGF-23-treated MSCs exhibited the senescent phenotype, as judged by senescence-associated β-galactosidase assay, cell morphology, and increased expression of p53 and p21 in western blot analysis. FGF-23 also significantly altered the gene expression of oxidative stress regulators in the cells. In conclusion, FGF-23 induced premature senescence in MSCs from skeletal muscle via the p53/p21/oxidative-stress pathway. The interaction between the MSCs and FGF-23 may play a key role in the impaired muscle reparative mechanisms of chronic kidney disease.

  10. Human skeletal muscle digitalis glycoside receptors (Na,K-ATPase)--importance during digitalization.

    Science.gov (United States)

    Schmidt, T A; Holm-Nielsen, P; Kjeldsen, K

    1993-02-01

    The aims of the present study were to evaluate in humans the putative importance of skeletal muscle digitalis glycoside receptors (Na,K-ATPase) in the volume of distribution of digoxin and to assess whether therapeutic digoxin exposure might cause digitalis receptor upregulation in skeletal muscle. Samples of the vastus lateralis were obtained postmortem from 11 long-term (9 months to 9 years) digitalized (125-187.5 micrograms daily) and eight undigitalized subjects. In intact samples from digitalized patients, vanadate-facilitated 3H-ouabain binding increased 15% (p 0.30) before and after washing in specific digoxin antibody fragments, respectively. Thus, the present study indicates a approximately 13% occupancy of skeletal muscle digitalis glycoside receptors with digoxin during digitalization. In light of the large skeletal muscle contribution to body mass, this indicates that the skeletal muscle Na,K-ATPase pool constitutes a major volume of distribution for digoxin during digitalization. The results gave no indication of skeletal muscle digitalis glycoside receptor upregulation in response to digoxin treatment. On the contrary, there was evidence of significantly lower (37%, p digitalized patients, which may be of importance for skeletal muscle incapacity in heart failure.

  11. Reduced blood flow to contracting skeletal muscle in ageing humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Hellsten, Ylva

    2016-01-01

    consequences of ageing and physical inactivity can be challenging; yet, observations from cross-sectional and longitudinal studies on the effects of physical activity have provided some insight. Physical activity has the potential to offset the age-related decline in blood flow to contracting skeletal muscle...... and the ability for functional sympatholysis; an attenuation of the vasoconstrictor effect of sympathetic nervous activity. These vascular adaptations with physical activity are likely to be an effect of improved nitric oxide and ATP signaling. Collectively, precise matching of blood flow and O2 delivery to meet...

  12. The Structure and Regulation of Human Muscle α-Actinin

    OpenAIRE

    Ribeiro, Euripedes de Almeida; Pinotsis, Nikos; Holt, Mark R.; Aachmann, Finn L.; Žagrović, Bojan; Bordignon, Enrica; Pirker, Katharina F.; Svergun, Dmitri; Gautel, Mathias; Djinović-Carugo, Kristina; Ghisleni, Andrea; Salmazo, Anita; Konarev, Petr; Kostan, Julius; Sjöblom, Björn

    2014-01-01

    Summary The spectrin superfamily of proteins plays key roles in assembling the actin cytoskeleton in various cell types, crosslinks actin filaments, and acts as scaffolds for the assembly of large protein complexes involved in structural integrity and mechanosensation, as well as cell signaling. α-actinins in particular are the major actin crosslinkers in muscle Z-disks, focal adhesions, and actin stress fibers. We report a complete high-resolution structure of the 200 kDa α-actinin-2 dimer f...

  13. Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans

    DEFF Research Database (Denmark)

    Xu, G; Hansen, Jakob; Zhao, X J

    2016-01-01

    BACKGROUND: Plasma acylcarnitine levels are elevated by physiological conditions such as fasting and exercise but also in states of insulin resistance and obesity. AIM: To elucidate the contribution of liver and skeletal muscle to plasma acylcarnitines in the fasting state and during exercise...... in humans. METHODS: In 2 independent studies, young healthy males were fasted overnight and performed an acute bout of exercise to investigate either acylcarnitines in skeletal muscle biopsies and arterial-to-venous plasma differences over the exercising and resting leg (n = 9) or the flux over the hepato...... in the exercising leg. In plasma and in the exercising muscle, exercise induced an increase of most acylcarnitines followed by a rapid decline to preexercise values during recovery. In contrast, free carnitine was decreased in the exercising muscle and quickly restored thereafter. C8-, C10-, C10:1-, C12-, and C12...

  14. Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Nesterov, Sergey V; Kemppainen, Jukka;

    2007-01-01

    ) muscles during exercise, measured using positron emission tomography. In six healthy young women, BF was measured at rest and then during three incremental low and moderate intermittent isometric one-legged knee-extension exercise intensities without and with theophylline-induced nonselective adenosine...... exercise intensity in the QF muscle group. Adenosine seems to play a role in muscle BF heterogeneity even in the absence of changes in bulk BF at low and moderate one-leg intermittent isometric exercise intensities.......Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF...

  15. Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

    DEFF Research Database (Denmark)

    Fritzen, Andreas Mæchel; Madsen, Agnete Louise Bjerregaard; Kleinert, Maximilian

    2016-01-01

    . The decrease in LC3-II/LC3-I ratio did not correlate with activation of AMPK trimer complexes in human muscle. Consistently, pharmacological AMPK activation with AICAR in mouse muscle did not affect the LC3-II/LC3-I ratio. Four hours after exercise, insulin further reduced (p80......%) in muscle of the exercised and non-exercised leg in man. This coincided with increased Ser-757 phosphorylation of ULK1, which is suggested as an mTORC1 target. Accordingly, inhibition of mTOR signalling in mouse muscle prevented the ability of insulin to reduce the LC3-II/LC3-I ratio. In response to 3 weeks...

  16. Interstitial and arterial-venous [K+] in human calf muscle during dynamic exercise

    DEFF Research Database (Denmark)

    Green, S; Langberg, Henning; Skovgaard, D

    2000-01-01

    little information on the response of [K+]I to exercise in human skeletal muscle. Five young healthy subjects performed plantar flexion exercise for four 5 min periods at increasing power outputs ( approximately 1-6 W) with 10 min intervening recovery periods, as well as for two 5 min periods......Changes in the concentration of interstitial K+ surrounding skeletal muscle fibres ([K+]I) probably play some role in the regulation of cardiovascular adjustments to muscular activity, as well as in the aetiology of muscle pain and fatigue during high-intensity exercise. However, there is very...... with ischaemia at approximately 1 and approximately 3 W. Microdialysis probes were inserted into the gastrocnemius medialis muscle of the right leg to measure [K+]I, and K+ release from the plantar flexors during and after incremental exercise was calculated from plasma flow and arterial-venous differences for K...

  17. T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases

    Directory of Open Access Journals (Sweden)

    Al-Qusairi Lama

    2011-07-01

    Full Text Available Abstract In skeletal muscle, the excitation-contraction (EC coupling machinery mediates the translation of the action potential transmitted by the nerve into intracellular calcium release and muscle contraction. EC coupling requires a highly specialized membranous structure, the triad, composed of a central T-tubule surrounded by two terminal cisternae from the sarcoplasmic reticulum. While several proteins located on these structures have been identified, mechanisms governing T-tubule biogenesis and triad formation remain largely unknown. Here, we provide a description of triad structure and plasticity and review the role of proteins that have been linked to T-tubule biogenesis and triad formation and/or maintenance specifically in skeletal muscle: caveolin 3, amphiphysin 2, dysferlin, mitsugumins, junctophilins, myotubularin, ryanodine receptor, and dihydhropyridine Receptor. The importance of these proteins in triad biogenesis and subsequently in muscle contraction is sustained by studies on animal models and by the direct implication of most of these proteins in human myopathies.

  18. Strain and elongation of the human semitendinosus muscle - tendon unit.

    Science.gov (United States)

    Kellis, Eleftherios; Patsika, Glykeria; Karagiannidis, Evaggelos

    2013-12-01

    The semitendinosus (ST) consists of a long distal tendon and it is divided in two parts by a tendinous inscription (TI). The purpose of this study was to quantify strain and elongation of the TI and the distal tendon of ST. Fourteen subjects performed ramp isometric contractions of the knee flexors at 0°, 45° and 90° of knee flexion. Two ultrasound probes were used to visualize the displacement of the distal tendon and selected points across the TI and aponeuroses. Three-way analysis of variance designs indicated that: (a) strain and elongation of the ST distal muscle-tendon junction were higher than that of the aponeurosis - TI junction points (p segments significantly increased from 90° to 0° of knee flexion while the inverse was observed for the TI arm length (p segments at 45° and 90° of knee flexion while the opposite was observed at 0° of knee flexion. The arrangement of TI along ST length results in differential local strains, indicating that the mechanical properties of the ST muscle are affected by tendon, aponeuroses and tendinous inscription interactions.

  19. Autonomic control of the heart during exercise in humans: role of skeletal muscle afferents.

    Science.gov (United States)

    Fisher, James P

    2014-02-01

    What is the topic of this review? The autonomic nervous system plays a key role in bringing about the cardiovascular responses to exercise necessitated by the increased metabolic requirements of the active skeletal muscle. The complex interaction of central and peripheral neural control mechanisms evokes a decrease in parasympathetic activity and an increase sympathetic activity to the heart during exercise. What advances does it highlight? This review presents some of the recent insights provided by human studies into the role of mechanically and metabolically sensitive skeletal muscle afferents in the regulation of cardiac autonomic control during exercise. The autonomic responses to exercise are orchestrated by the interactions of several central and peripheral neural mechanisms. This report focuses on the role of peripheral feedback from skeletal muscle afferents in the autonomic control of the heart during exercise in humans. Heart rate responses to passive calf stretch are abolished with cardiac parasympathetic blockade, indicating that the activation of mechanically sensitive skeletal muscle afferents (muscle mechanoreceptors) can inhibit cardiac parasympathetic activity and is likely to contribute to the increase in heart rate at the onset of exercise. Recent experiments show that the partial restriction of blood flow to the exercising skeletal muscles, to augment the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreceptors) in humans, evokes an increase in heart rate that is attenuated with β1-adrenergic blockade, thus suggesting that this response is principally mediated via an increase in cardiac sympathetic activity. Heart rate remains at resting levels during isolated activation of muscle metaboreceptors with postexercise ischaemia following hand grip, unless cardiac parasympathetic activity is inhibited, whereupon a sympathetically mediated increase in heart rate is unmasked. During postexercise ischaemia following leg

  20. Nitrosative stress in human skeletal muscle attenuated by exercise countermeasure after chronic disuse

    Directory of Open Access Journals (Sweden)

    Michele Salanova

    2013-01-01

    Full Text Available Activity-induced nitric oxide (NO imbalance and “nitrosative stress” are proposed mechanisms of disrupted Ca2+ homeostasis in atrophic skeletal muscle. We thus mapped S-nitrosylated (SNO functional muscle proteins in healthy male subjects in a long-term bed rest study (BBR2-2 Study without and with exercise as countermeasure in order to assess (i the negative effects of chronic muscle disuse by nitrosative stress, (ii to test for possible attenuation by exercise countermeasure in bed rest and (iii to identify new NO target proteins. Muscle biopsies from calf soleus and hip vastus lateralis were harvested at start (Pre and at end (End from a bed rest disuse control group (CTR, n=9 and two bed rest resistive exercise groups either without (RE, n=7 or with superimposed vibration stimuli (RVE, n=7. At subcellular compartments, strong anti-SNO-Cys immunofluorescence patterns in control muscle fibers after bed rest returned to baseline following vibration exercise. Total SNO-protein levels, Nrf-2 gene expression and nucleocytoplasmic shuttling were changed to varying degrees in all groups. Excess SNO-protein levels of specific calcium release/uptake proteins (SNO-RyR1, –SERCA1 and –PMCA and of contractile myosin heavy chains seen in biopsy samples of chronically disused skeletal muscle were largely reduced by vibration exercise. We also identified NOS1 as a novel NO target in human skeletal muscle controlled by activity driven auto-nitrosylation mechanisms. Our findings suggest that aberrant levels of functional SNO-proteins represent signatures of uncontrolled nitrosative stress management in disused human skeletal muscle that can be offset by exercise as countermeasure.

  1. Co-expression of SERCA isoforms, phospholamban and sarcolipin in human skeletal muscle fibers.

    Directory of Open Access Journals (Sweden)

    Val A Fajardo

    Full Text Available Sarcolipin (SLN and phospholamban (PLN inhibit the activity of sarco(endoplasmic reticulum Ca(2+-ATPases (SERCAs by reducing their apparent affinity for Ca(2+. A ternary complex between SLN, PLN, and SERCAs results in super-inhibition of SERCA activity. Analysis of skeletal muscle homogenate has limited our current understanding of whether SLN and PLN regulate SERCA1a, SERCA2a, or both in skeletal muscle and whether SLN and PLN are co-expressed in skeletal muscle fibers. Biopsies from human vastus lateralis were analyzed through single fiber Western blotting and immunohisto/fluorescence staining to circumvent this limitation. With a newly generated SLN antibody, we report for the first time that SLN protein is present in human skeletal muscle. Addition of the SLN antibody (50 µg to vastus lateralis homogenates increased the apparent Ca(2+ affinity of SERCA (K Ca, pCa units (-Ab, 5.85 ± 0.02 vs. +Ab, 5.95 ± 0.02 and maximal SERCA activity (μmol/g protein/min (-Ab, 122 ± 6.4 vs. +Ab, 159 ± 11 demonstrating a functional interaction between SLN and SERCAs in human vastus lateralis. Specifically, our results suggest that although SLN and PLN may preferentially regulate SERCA1a, and SERCA2a, respectively, physiologically they both may regulate either SERCA isoform. Furthermore, we show that SLN and PLN co-immunoprecipitate in human vastus lateralis homogenate and are simultaneously expressed in 81% of the fibers analyzed with Western blotting which implies that super-inhibition of SERCA may exist in human skeletal muscle. Finally, we demonstrate unequivocally that mouse soleus contains PLN protein suggesting that super-inhibition of SERCA may also be important physiologically in rodent skeletal muscle.

  2. Effects of contraction intensity on muscle fascicle and stretch reflex behavior in the human triceps surae.

    Science.gov (United States)

    Cronin, Neil J; Peltonen, Jussi; Ishikawa, Masaki; Komi, Paavo V; Avela, Janne; Sinkjaer, Thomas; Voigt, Michael

    2008-07-01

    The aims of this study were to examine changes in the distribution of a stretch to the muscle fascicles with changes in contraction intensity in the human triceps surae and to relate fascicle stretch responses to short-latency stretch reflex behavior. Thirteen healthy subjects were seated in an ankle ergometer, and dorsiflexion stretches (8 degrees ; 250 degrees /s) were applied to the triceps surae at different moment levels (0-100% of maximal voluntary contraction). Surface EMG was recorded in the medial gastrocnemius, soleus, and tibialis anterior muscles, and ultrasound was used to measure medial gastrocnemius and soleus fascicle lengths. At low forces, reflex amplitudes increased despite a lack of change or even a decrease in fascicle stretch velocities. At high forces, lower fascicle stretch velocities coincided with smaller stretch reflexes. The results revealed a decline in fascicle stretch velocity of over 50% between passive conditions and maximal force levels in the major muscles of the triceps surae. This is likely to be an important factor related to the decline in stretch reflex amplitudes at high forces. Because short-latency stretch reflexes contribute to force production and stiffness regulation of human muscle fibers, a reduction in afferent feedback from muscle spindles could decrease the efficacy of human movements involving the triceps surae, particularly where high force production is required.

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

    Science.gov (United States)

    Sasaki, Kazushige; Ishii, Naokata

    2010-09-27

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

  4. Changes in the mechanical properties of human and amphibian muscle after eccentric exercise.

    Science.gov (United States)

    Jones, C; Allen, T; Talbot, J; Morgan, D L; Proske, U

    1997-01-01

    Following a series of eccentric contractions, that is stretching of the muscle while generating active tension, the length-tension relationship of isolated amphibian muscle has been shown to shift towards longer muscle length (Katz 1939; Wood et al. 1993). Here we report observations of electrically stimulated ankle extensor muscles of nine human subjects, demonstrating a similar shift in optimum angle for torque generation [3.9 (1.5) degrees] following exercise on an inclined treadmill that involved eccentric contractions in one leg. (All values are means with the SEMs in parentheses). The shift in the unexercised, control leg was significantly less [mean 0.4 (0.7) degree P post-exercise, while torque took a week to recover. A similar shift in optimum length [12 (1.3)% of rest length] was obtained for five toad (Bufo marinus) sartorius muscles subjected to 25 eccentric contractions. Isometrically contracted control muscles showed a smaller shift [3.5 (1.6)%, n = 5]. Accompanying the shift was a drop in tension of 46 (3)% after the eccentric contractions [control isometric, 23 (6)%, P < 0.0001]. By 5 h after the eccentric contractions the shift had returned to control values, while tension had not recovered. When viewed with an electron microscope, sartorius muscles fixed immediately after the eccentric contractions exhibited many small, and a few larger, regions of myofilament disruption. In muscles fixed 5 h after the contractions, no small regions of disruption were visible, and the number of large regions was no greater than in those muscles fixed immediately after the eccentric contractions. These disruptions are interpreted as the cause of the shift in length-tension relationship.

  5. Human-robot interaction: kinematics and muscle activity inside a powered compliant knee exoskeleton.

    Science.gov (United States)

    Knaepen, Kristel; Beyl, Pieter; Duerinck, Saartje; Hagman, Friso; Lefeber, Dirk; Meeusen, Romain

    2014-11-01

    Until today it is not entirely clear how humans interact with automated gait rehabilitation devices and how we can, based on that interaction, maximize the effectiveness of these exoskeletons. The goal of this study was to gain knowledge on the human-robot interaction, in terms of kinematics and muscle activity, between a healthy human motor system and a powered knee exoskeleton (i.e., KNEXO). Therefore, temporal and spatial gait parameters, human joint kinematics, exoskeleton kinetics and muscle activity during four different walking trials in 10 healthy male subjects were studied. Healthy subjects can walk with KNEXO in patient-in-charge mode with some slight constraints in kinematics and muscle activity primarily due to inertia of the device. Yet, during robot-in-charge walking the muscular constraints are reversed by adding positive power to the leg swing, compensating in part this inertia. Next to that, KNEXO accurately records and replays the right knee kinematics meaning that subject-specific trajectories can be implemented as a target trajectory during assisted walking. No significant differences in the human response to the interaction with KNEXO in low and high compliant assistance could be pointed out. This is in contradiction with our hypothesis that muscle activity would decrease with increasing assistance. It seems that the differences between the parameter settings of low and high compliant control might not be sufficient to observe clear effects in healthy subjects. Moreover, we should take into account that KNEXO is a unilateral, 1 degree-of-freedom device.

  6. An animal model for human masseter muscle: histochemical characterization of mouse, rat, rabbit, cat, dog, pig, and cow masseter muscle

    DEFF Research Database (Denmark)

    Tuxen, A; Kirkeby, S

    1990-01-01

    .4, type IM fibers react moderately, and type II fibers react strongly. Rat and mouse masseter muscles contained type II fibers only, as did some rabbit masseter muscles, whereas other rabbit masseter muscles possessed equal amounts of type I and II fibers. Cat and dog masseter muscles possessed both type...

  7. Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle.

    Science.gov (United States)

    Mackey, Abigail L; Brandstetter, Simon; Schjerling, Peter; Bojsen-Moller, Jens; Qvortrup, Klaus; Pedersen, Mette M; Doessing, Simon; Kjaer, Michael; Magnusson, S Peter; Langberg, Henning

    2011-06-01

    The purpose of this study was to test the hypothesis that remodeling of skeletal muscle extracellular matrix (ECM) is involved in protecting human muscle against injury. Biopsies were obtained from medial gastrocnemius muscles after a single bout of electrical stimulation (B) or a repeated bout (RB) 30 d later, or 30 d after a single stimulation bout (RBc). A muscle biopsy was collected from the control leg for comparison with the stimulated leg. Satellite cell content, tenascin C, and muscle regeneration were assessed by immunohistochemistry; real-time PCR was used to measure mRNA levels of collagens, laminins, heat-shock proteins (HSPs), inflammation, and related growth factors. The large responses of HSPs, CCL2, and tenascin C detected 48 h after a single bout were attenuated in the RB trial, indicative of protection against injury. Satellite cell content and 12 target genes, including IGF-1, were elevated 30 d after a single bout. Among those displaying the greatest difference vs. control muscle, ECM laminin-β1 and collagen types I and III were elevated ∼6- to 9-fold (P<0.001). The findings indicate that the sequenced events of load-induced early deadhesion and later strengthening of skeletal muscle ECM play a role in protecting human muscle against future injury.

  8. Corticospinal contribution to arm muscle activity during human walking

    DEFF Research Database (Denmark)

    Barthélemy, Dorothy; Nielsen, Jens Bo

    2010-01-01

    potentials (MEPs) elicited in the posterior deltoid muscle (PD) by transcranial magnetic stimulation (TMS) were modulated during the gait cycle in parallel with changes in the background EMG activity. There was no significant difference in the size of the MEPs at a comparable level of background EMG during...... walking and during static PD contraction. Short latency intracortical inhibition (SICI; 2 ms interval) studied by paired-pulse TMS was diminished during bursts of PD EMG activity. This could not be explained only by changes in background EMG activity and/or control MEP size, since SICI showed...... no correlation to the level of background EMG activity during static PD contraction. Finally, TMS at intensity below the threshold for activation of corticospinal tract fibres elicited a suppression of the PD EMG activity during walking. Since TMS at this intensity is likely to only activate intracortical...

  9. Composition and adaptation of human myotendinous junction and neighboring muscle fibers to heavy resistance training

    DEFF Research Database (Denmark)

    Jakobsen, J R; Mackey, A L; Knudsen, A B

    2016-01-01

    The myotendinous junction (MTJ) is a common site of strain injury and yet understanding of its composition and ability to adapt to loading is poor. The main aims of this study were to determine the profile of selected collagens and macrophage density in human MTJ and adjoining muscle fibers...... and were sectioned and stained immunohistochemically for collagen types I, III, VI, XII, XIV, XXII, Tenascin-C and CD68. Macrophage density and distribution was evaluated and the amount of each collagen type in muscle and MTJ was graded. Collagen XXII was observed solely at the MTJ, while all other...... collagens were abundant at the MTJ and in muscle perimysium or endomysium. The endomysial content of collagen XIV, macrophages and Tenascin-C increased following 4 weeks of training. These findings illustrate the heterogeneity of collagen type composition of human MTJ. The increase in collagen XIV following...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    There is increasing evidence that multiple proteins involved in key regulatory processes in mitochondria are phosphorylated in mammalian tissues. Insulin regulates glucose metabolism by phosphorylation-dependent signaling and has been shown to stimulate ATP synthesis in human skeletal muscle. Here...... the majority of novel sites. Phosphorylation sites detected more often or exclusively in insulin-stimulated samples include multiple sites in mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle, and fatty acid metabolism, as well as several components of the newly defined......, we investigated the effect of insulin on the phosphorylation of mitochondrial proteins in human skeletal muscle in vivo. Using a combination of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC−MS/MS, we compared the phosphoproteomes of isolated mitochondria from skeletal muscle samples...

  11. Mechanical properties of tendon and aponeurosis of human gastrocnemius muscle in vivo.

    Science.gov (United States)

    Muramatsu, T; Muraoka, T; Takeshita, D; Kawakami, Y; Hirano, Y; Fukunaga, T

    2001-05-01

    Load-strain characteristics of tendinous tissues (Achilles tendon and aponeurosis) were determined in vivo for human medial gastrocnemius (MG) muscle. Seven male subjects exerted isometric plantar flexion torque while the elongation of tendinous tissues of MG was determined from the tendinous movements by using ultrasonography. The maximal strain of the Achilles tendon and aponeurosis, estimated separately from the elongation data, was 5.1 +/- 1.1 and 5.9 +/- 1.6%, respectively. There was no significant difference in strain between the Achilles tendon and aponeurosis. In addition, no significant difference in strain was observed between the proximal and distal regions of the aponeurosis. The results indicate that tendinous tissues of the MG are homogeneously stretched along their lengths by muscle contraction, which has functional implications for the operation of the human MG muscle-tendon unit in vivo.

  12. Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle

    DEFF Research Database (Denmark)

    Wewer, U M; Thornell, L E; Loechel, F

    1997-01-01

    to the laminin beta 2 chain. We found that laminin beta 1 chain was detected at all times during development from 10 weeks of gestation. Laminin beta 2 chain was first detected in 15 to 22-week-old fetal skeletal muscle as distinct focal immunoreactivity in the sarcolemmal basement membrane area of some......We have investigated the distribution of the laminin beta 2 chain (previously s-laminin) in human fetal and adult skeletal muscle and compared it to the distribution of laminin beta 1. Immunoblotting and transfection assays were used to characterize a panel of monoclonal and polyclonal antibodies...... results demonstrate a prominent extrasynaptic localization of laminin beta 2 in the human muscle, suggesting that it may have an important function in the sarcolemmal basement membrane....

  13. Muscle-tendon interaction and elastic energy usage in human walking

    DEFF Research Database (Denmark)

    Ishikawa, Masaki; Komi, Paavo V.; Grey, Michael James;

    2005-01-01

    The present study was designed to explore how the interaction between the fascicles and tendinous tissues is involved in storage and utilization of elastic energy during human walking. Eight male subjects walked with a natural cadence (1.4 +/- 0.1 m/s) on a 10-m-long force plate system. In vivo...... techniques were employed to record the Achilles tendon force and to scan real-time fascicle lengths for two muscles (medial gastrocnemius and soleus). The results showed that tendinous tissues of both medial gastrocnemius and soleus muscles lengthened slowly throughout the single-stance phase......-stance phase. In contrast, the soleus fascicles were lengthened until the end of the single-stance phase. These findings suggest that the elastic recoil takes place not as a spring-like bouncing but as a catapult action in natural human walking. The interaction between the muscle fascicles and tendinous...

  14. Bio-artificial heart as ultimate treatment of end-stage heart failure.

    Science.gov (United States)

    Smit, Francis E; Dohmen, Pascal M

    2014-10-16

    End-stage heart failure is a major health problem, but implementation of guidelines and optimizing medical therapy for this devastating disease should decrease mortality. If optimal conservative therapy is no longer sufficient, a mechanical support system may be required as final destination therapy or as bridge-to-transplant. Since the first heart transplantation in 1967, this therapy has become the criterion standard for end-stage heart failure, but is limited due to organ shortage. Tissue engineering could help overcome this limitation and provide regeneration, remodeling, and growth potential. This so-called bio-artificial heart would be available, created by a decellularized extracellular matrix and seeded with in vitro proliferated autologous cardiovascular cells. Results of the first experimental studies have been promising, but numerous challenges must be met before this procedure will be available.

  15. The Progress of Bioartificial Kidney%生物人工肾的研究新进展

    Institute of Scientific and Technical Information of China (English)

    李清刚

    2001-01-01

    The development of a bioartificial hemofilter and renal tubule assist device with tissue engineering , gene and cell technique were reported. It is possible potential to develope th e wearable or transplantable bioartifical kidney for total replacement of renal f unction by these devices and significantly diminish the morbidity and mortality in patients with acute renal failure or end-stage renal disease.%本文阐述了采用组织工程和基因、细胞技术发展起来的生物人 工 血滤器、生物人工肾小管辅助装置,通过它们可望生产出易携带或可移植的生物人工肾以完 全代替肾功能,减少急性肾功能衰竭或终末期肾病的发病率或病死率。

  16. Evaluation of effect of hybrid bioartificial liver using end-stage liver disease model

    Institute of Scientific and Technical Information of China (English)

    Qing Liu; Zhong-Ping Duan; Chun Huang; Chun-Hui Zhao

    2004-01-01

    AIM: To study the role of hybrid bioartificial liver (HBL) in clearing proinflammatory cytokines and endotoxin in patients with acute and sub-acute liver failure and the effects of HBL on systemic inflammatory syndrome (SIRS) and multipl eorgan dysfunction syndrome (MODS).METHODS: Five cases with severe liver failure (3 acute and 2 subacute) were treated with HBL. The clinical signs and symptoms, total bilirubin (TBIL), serum ammonia,endotoxin TNF-α, IL-6 and prothrombin activity (PTA),cholinesterase (CHE) were recorded before, dudng and after treatment. The end-stage liver disease (MELD) was used for the study.RESULTS: Two patients were bridged for spontaneous recovery and 1 patient was bridged for OLT successfully.Another 2 patients died on d 8 and d 21. The spontaneous recovery rate was 30.0%. PTA and CHE in all patients were significantly increased (P<0.01), while the serum TBIL,endotoxin,TNF-α, IL-6 were decreased. MELD score (mean 43.6) predicted 100% deaths within 3 mo before treatment with HBL. After treatment with HBL, four out of 5 patients had decreased MELD scores (mean 36.6). The MELD score predicted 66% mortalities.CONCLUSION: The proinflammatory cytokines (TNFα, IL6 and endotoxin)can be significantly removed by hybrid bioartificial liver and HBL appears to be effective in blocking SIRS and MODS in patients with acute and sub-acute liver failure. MELD is a reliable measure for predicting short-term mortality risk in patients with end-stage liver disease. The prognostic result also corresponds to clinical outcome.

  17. Impact of Hot and Cold Exposure on Human Skeletal Muscle Gene Expression

    Science.gov (United States)

    Zak, Roksana B.; Shute, Robert J.; Heesch, Matthew W.S.; La Salle, D. Taylor; Bubak, Matthew P.; Dinan, Nicholas E.; Laursen, Terence L.; Slivka, Dustin R.

    2017-01-01

    Many human diseases lead to a loss of skeletal muscle metabolic function and mass. Local and environmental temperature can modulate the exercise-stimulated response of several genes involved in mitochondrial biogenesis and skeletal muscle function in a human model. However, the impact of environmental temperature, independent of exercise, has not been addressed in a human model. Thus, the purpose of this study was to compare the effects of exposure to hot, cold, and room temperature conditions on skeletal muscle gene expression related to mitochondrial biogenesis and muscle mass. METHODS Recreationally trained male subjects (n=12) had muscle biopsies taken from the vastus lateralis before and after 3 h exposure to hot (33 °C), cold (7 °C), or room temperature (20 °C) conditions. RESULTS Temperature had no effect on most of the genes related to mitochondrial biogenesis, myogenesis, or proteolysis (p > 0.05). Core temperature was significantly higher in hot and cold environments compared to room temperature (37.2 ± 0.1 °C, p = 0.001; 37.1 ± 0.1 °C, p = 0.013; 36.9 ± 0.1 °C, respectively). Whole body oxygen consumption was also significantly higher in hot and cold compared to room temperature (0.38 ± 0.01 L·min−1, p < 0.001; 0.52 ± 0.03 L·min−1, p < 0.001; 0.35 ± 0.01 L·min−1, respectively). CONCLUSIONS These data show that acute temperature exposure alone does not elicit significant changes in skeletal muscle gene expression. When considered in conjunction with previous research, exercise appears to be a necessary component to observe gene expression alterations between different environmental temperatures in humans. PMID:28177744

  18. Rotator cuff tear state modulates self-renewal and differentiation capacity of human skeletal muscle progenitor cells.

    Science.gov (United States)

    Thomas, Kelsey A; Gibbons, Michael C; Lane, John G; Singh, Anshuman; Ward, Samuel R; Engler, Adam J

    2017-08-01

    Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC muscle atrophy and fatty infiltration, with lasting damage even after surgical tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle repair in response to injury, but the inability of RC muscles to recover from chronic RCT tear indicates possible deficits in repair mechanisms. Here we investigated if muscle injury state was a crucial factor during human SMP expansion and differentiation ex vivo. SMPs were isolated from muscles in patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears. Despite using growth factors, physiological niche stiffness, and muscle-mimetic extracellular matrix (ECM) proteins, we found that SMPs isolated from human RC muscle with RCT tears proliferated slower but fused into myosin heavy chain (MHC)-positive myotubes at higher rates than SMPs from untorn RCTs. Proteomic analysis of RC muscle tissue revealed shifts in muscle composition with pathology, as muscle from massive RCT tears had increased ECM deposition compared with no tear RC muscle. Together these data imply that the remodeled niche in a torn RCT primes SMPs not for expansion but for differentiation, thus limiting longer-term self-renewal necessary for regeneration after surgical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1816-1823, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. Elastic modulus of orbicularis oculi muscle in normal humans, humans with Graves' eye disease, and cynomolgus monkeys.

    Science.gov (United States)

    Oestreicher, J H; Frueh, B R

    1995-06-01

    We built an experimental apparatus to investigate the passive elastic characteristics of orbicularis oculi muscle and examined specimens from normal humans, humans with stable Graves' eye disease, and cynomolgus monkeys. Stress-strain curves were determined and found to be exponential. The elastic modulus (Young's modulus), analogous to the stiffness of the material, was calculated as a function of strain. Elastic modulus as a function of instantaneous stress was linear. Monkey elastic modulus values were determined, but did not allow meaningful interspecies comparison because of the small sample size. No significant difference was found between normal humans and humans with Graves' eye disease with respect to elastic modulus values.

  20. Differential activation of sympathetic discharge to skin and skeletal muscle in humans.

    Science.gov (United States)

    Vissing, S F

    1997-01-01

    The present work provides insight into the relative contribution of different mechanisms in regulating sympathetic discharge to skin and skeletal muscle in humans. Activation of sympathetic nerve activity during common behaviours such as orthostasis and exercise was shown to be highly selective, depending on the specific sympathetic outflow under study. Regarding orthostasis, data from experiments in this thesis revoked the concept that cardiopulmonary afferents only regulate muscle vascular resistance in the forearm, not in the leg. Also the concept that the cutaneous circulation is under baroreceptor control has been challenged. Unloading cardiopulmonary afferents with lower body negative pressure elicited intensity dependent increases in peroneal sympathetic discharge to skeletal muscle, and increases in forearm and calf vascular resistances. Therefore, it was concluded that cardiopulmonary afferents regulate vascular resistance in skeletal muscle of both forearm and calf, suggesting an important role for these afferents in the reflex adjustments to upright posture. In contrast to muscle sympathetic nerve activity, baroreceptor deactivation with lower body negative pressure had no effect on skin sympathetic nerve activity or skin vascular resistance. However, assumption of upright posture increased skin vascular resistance, this increase was abolished when increased vascular transmural pressure was avoided by elevating the arm. Local cutaneous nerve blockade, but not blockade of efferent sympathetic nerve traffic, abolished the vasoconstrictor response to upright posture. Based on these experiments, it was concluded that baroreceptor afferents do not regulate sympathetic vasoconstrictor outflow to the cutaneous circulation. During upright posture at normothermia cutaneous vasoconstriction is mainly driven by a local reflex. To explain activation of sympathetic outflow during exercise two theories have been proposed. One is that a "central motor command" signal

  1. Gene expression in human skeletal muscle: alternative normalization method and effect of repeated biopsies

    DEFF Research Database (Denmark)

    Lundby, Carsten; Nordsborg, Nikolai; Kusuhara, K.

    2005-01-01

    The reverse transcriptase-polymerase chain reaction (RT-PCR) method has lately become widely used to determine transcription and mRNA content in rodent and human muscle samples. However, the common use of endogenous controls for correcting for variance in cDNA between samples is not optimal. Spec...

  2. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Osada, Takuya; Andersen, Lisbeth Tingsted

    2005-01-01

    In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabolic genes during recovery from exercise, ...

  3. Reconstruction of human swing leg motion with passive biarticular muscle models.

    Science.gov (United States)

    Ahmad Sharbafi, Maziar; Mohammadi Nejad Rashty, Aida; Rode, Christian; Seyfarth, Andre

    2017-04-01

    Template models, which are utilized to demonstrate general aspects in human locomotion, mostly investigate stance leg operation. The goal of this paper is presenting a new conceptual walking model benefiting from swing leg dynamics. Considering a double pendulum equipped with combinations of biarticular springs for the swing leg beside spring-mass (SLIP) model for the stance leg, a novel SLIP-based model, is proposed to explain human-like leg behavior in walking. The action of biarticular muscles in swing leg motion helps represent human walking features, like leg retraction, ground reaction force and generating symmetric walking patterns, in simulations. In order to stabilize the motion by the proposed passive structure, swing leg biarticular muscle parameters such as lever arm ratios, stiffnesses and rest lengths need to be properly adjusted. Comparison of simulation results with human experiments shows the ability of the proposed model in replicating kinematic and kinetic behavior of both stance and swing legs as well as biarticular thigh muscle force of the swing leg. This substantiates the important functional role of biarticular muscles in leg swing. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Assessment of satellite cell number and activity status in human skeletal muscle biopsies

    DEFF Research Database (Denmark)

    Mackey, Abigail; Kjaer, Michael; Charifi, Nadia;

    2009-01-01

    The primary aim of our study was to validate the assessment of myonuclear and satellite cell number in biopsies from human skeletal muscle. We found that 25 type I and 25 type II fibers are sufficient to estimate the mean number of myonuclei per fiber. In contrast, the assessment of satellite cells...

  5. Oxidative phosphorylation in human muscle in patients with ocular myopathy and after general anaesthesia

    NARCIS (Netherlands)

    H.R. Scholte (Hans); E. Agsteribbe (E.); H.F.M. Busch (Herman); T.U. Hoogenraad (T.); F.G.I. Jennekens (Frans G.); B. van Linge (Bert); I.E.M. Luyt-Houwen (I. E M); J.D. Ross (John); M.H.J. Ruiters (M. H J); M.H.M. Verduin (M. H M)

    1990-01-01

    markdownabstractAbstract The fuel preference of human muscle mitochondria has been given. Substrates which are oxidized with low velocity cannot be used to detect defects in oxidative phosphorylation. After general anaesthesia, the oxygen uptake with the different substrates is much lower than aft

  6. Endurance training enhances skeletal muscle interleukin-15 in human male subjects

    DEFF Research Database (Denmark)

    Rinnov, Anders; Yfanti, Christina; Nielsen, Søren

    2014-01-01

    endurance running. With the present study we aimed to determine if muscular IL-15 production would increase in human male subjects following 12 weeks of endurance training. In two different studies we obtained plasma and muscle biopsies from young healthy subjects performing: (1) 12 weeks of ergometer...

  7. Response of growth and myogenic factors in human skeletal muscle to strength training

    NARCIS (Netherlands)

    Liu, Y.; Heinichen, M.; Wirth, K.; Schmidtbleicher, D.; Steinacker, J. M.

    2008-01-01

    Objective: To investigate the response to different strength training techniques of growth and myogenic factors in human skeletal muscle, with particular emphasis on satellite cell (SC) activation. Methods: 24 volunteers were divided into two groups and performed a 6-week strength training (group A

  8. Actovegin, a non-prohibited drug increases oxidative capacity in human skeletal muscle

    DEFF Research Database (Denmark)

    Søndergård, Stine D; Dela, Flemming; Helge, Jørn W

    2016-01-01

    skeletal muscle. Mitochondrial adaptations like this are also seen after a training program in human subjects. Whether this improvement translates into an ergogenic effect in athletes and thus reiterates the need to include Actovegin on the World Anti-Doping Agency's active list remains to be investigated....

  9. Short-latency crossed responses in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend S.

    2015-01-01

    , indicating their existence in humans. The aim of the present study was to investigate whether short-latency crossed-spinal reflexes are present in the contralateral biceps femoris (cBF) muscle following ipsilateral knee (iKnee) joint rotations during a sitting task, where participants maintained a slight pre...

  10. Active controlled muscles in numerical model of human arm for movement in two degrees of freedom

    NARCIS (Netherlands)

    Budziszewski, P.; Nunen, E. van; Mordaka, J.K.; Kȩdzior, K.

    2008-01-01

    This paper describes the development of numerical model of human upper extremity able to perform movements and stabilization tasks in two degrees of freedom as a result of muscle activation controlled by a PID-based controller. These tasks are defined by functions of specified angle for every degree

  11. Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training

    DEFF Research Database (Denmark)

    Alsted, Thomas J; Schweiger, Martina; Nybo, Lars

    2009-01-01

    ) is not changed. Recently, adipose triglyceride lipase (ATGL) was identified as a TG-specific lipase in various rodent tissues. To investigate whether human skeletal muscle ATGL protein is regulated by endurance exercise training, 10 healthy young men completed 8 wk of supervised endurance exercise training...

  12. EMG-normalised kinase activation during exercise is higher in human gastrocnemius compared to soleus muscle

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Leutert, Robin; Rasmussen, Søren T;

    2012-01-01

    to differential reactive oxygen species (ROS)-scavenging ability or resting glycogen content. To evaluate these parameters in humans, biopsies from soleus, gastrocnemius and vastus lateralis muscles were taken before and after a 45 min inclined (15%) walking exercise bout at 69% VO2(max) aimed at simultaneously...

  13. Bone morphogenetic proteins regulate osteoprotegerin and its ligands in human vascular smooth muscle cells

    DEFF Research Database (Denmark)

    Knudsen, Kirsten Quyen Nguyen; Olesen, Ping; Ledet, Thomas

    2007-01-01

    in the transformation of human vascular smooth muscle cells (HVSMC) to osteoblast-like cells. In this study, we evaluated the effect of BMP-2, BMP-7 and transforming growth factor beta (TGF-beta1) on the secretion and mRNA expression of OPG and its ligands receptor activator of nuclear factor-kappabeta ligand (RANKL...

  14. Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Langberg, Henning; Gemmer, Carsten;

    2002-01-01

    The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quanti...

  15. Clay Modeling as a Method to Learn Human Muscles: A Community College Study

    Science.gov (United States)

    Motoike, Howard K.; O'Kane, Robyn L.; Lenchner, Erez; Haspel, Carol

    2009-01-01

    The efficacy of clay modeling compared with cat dissection for human muscle identification was examined over two semesters at LaGuardia Community College in Queens, NY. The 181 students in 10 sections in this study were randomly distributed into control (cat dissection) and experimental (clay modeling) groups, and the results of the muscle…

  16. The effect of handedness on electromyographic activity of human shoulder muscles during movement

    DEFF Research Database (Denmark)

    Diederichsen, Louise Pyndt; Nørregaard, Jesper; Dyhre-Poulsen, Poul

    2006-01-01

    The aim of the study was to investigate whether there was a difference in the electromyographic (EMG) activity of human shoulder muscles between the dominant and nondominant side during movement and to explore whether a possible side-difference depends on the specific task. We compared the EMG ac...

  17. Protein carbonylation and heat shock proteins in human skeletal muscle: relationships to age and sarcopenia.

    Science.gov (United States)

    Beltran Valls, Maria R; Wilkinson, Daniel J; Narici, Marco V; Smith, Kenneth; Phillips, Bethan E; Caporossi, Daniela; Atherton, Philip J

    2015-02-01

    Aging is associated with a gradual loss of muscle mass termed sarcopenia, which has significant impact on quality-of-life. Because oxidative stress is proposed to negatively impact upon musculoskeletal aging, we investigated links between human aging and markers of oxidative stress, and relationships to muscle mass and strength in young and old nonsarcopenic and sarcopenic adults. Sixteen young and 16 old males (further subdivided into "old" and "old sarcopenic") were studied. The abundance of protein carbonyl adducts within skeletal muscle sarcoplasmic, myofibrillar, and mitochondrial protein subfractions from musculus vastus lateralis biopsies were determined using Oxyblot immunoblotting techniques. In addition, concentrations of recognized cytoprotective proteins (eg, heat shock proteins [HSP], αβ-crystallin) were also assayed. Aging was associated with increased mitochondrial (but not myofibrillar or sarcoplasmic) protein carbonyl adducts, independently of (stage-I) sarcopenia. Correlation analyses of all subjects revealed that mitochondrial protein carbonyl abundance negatively correlated with muscle strength ([1-repetition maximum], p = .02, r (2) = -.16), but not muscle mass (p = .13, r (2) = -.08). Abundance of cytoprotective proteins, including various HSPs (HSP 27 and 70), were unaffected by aging/sarcopenia. To conclude, these data reveal that mitochondrial protein carbonylation increases moderately with age, and that this increase may impact upon skeletal muscle function, but is not a hallmark of (stage-I) sarcopenia, per se. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.

  18. EFFECT OF HEAT PRECONDITIONING BY MICROWAVE HYPERTHERMIA ON HUMAN SKELETAL MUSCLE AFTER ECCENTRIC EXERCISE

    Directory of Open Access Journals (Sweden)

    Norio Saga

    2008-03-01

    Full Text Available The purpose of this study was to clarify whether heat preconditioning results in less eccentric exercise-induced muscle damage and muscle soreness, and whether the repeated bout effect is enhanced by heat preconditioning prior to eccentric exercise. Nine untrained male volunteers aged 23 ± 3 years participated in this study. Heat preconditioning included treatment with a microwave hyperthermia unit (150 W, 20 min that was randomly applied to one of the subject's arms (MW; the other arm was used as a control (CON. One day after heat preconditioning, the subjects performed 24 maximal isokinetic eccentric contractions of the elbow flexors at 30°·s-1 (ECC1. One week after ECC1, the subjects repeated the procedure (ECC2. After each bout of exercise, maximal voluntary contraction (MVC, range of motion (ROM of the elbow joint, upper arm circumference, blood creatine kinase (CK activity and muscle soreness were measured. The subjects experienced both conditions at an interval of 3 weeks. MVC and ROM in the MW were significantly higher than those in the CON (p < 0.05 for ECC1; however, the heat preconditioning had no significant effect on upper arm circumference, blood CK activity, or muscle soreness following ECC1 and ECC2. Heat preconditioning may protect human skeletal muscle from eccentric exercise-induced muscle damage after a single bout of eccentric exercise but does not appear to promote the repeated bout effect after a second bout of eccentric exercise

  19. Characterization of adipocytes derived from fibro/adipogenic progenitors resident in human skeletal muscle

    Science.gov (United States)

    Arrighi, N; Moratal, C; Clément, N; Giorgetti-Peraldi, S; Peraldi, P; Loubat, A; Kurzenne, J-Y; Dani, C; Chopard, A; Dechesne, C A

    2015-01-01

    A population of fibro/adipogenic but non-myogenic progenitors located between skeletal muscle fibers was recently discovered. The aim of this study was to determine the extent to which these progenitors differentiate into fully functional adipocytes. The characterization of muscle progenitor-derived adipocytes is a central issue in understanding muscle homeostasis. They are considered as being the cellular origin of intermuscular adipose tissue that develops in several pathophysiological situations. Here fibro/adipogenic progenitors were isolated from a panel of 15 human muscle biopsies on the basis of the specific cell-surface immunophenotype CD15+/PDGFRα+CD56−. This allowed investigations of their differentiation into adipocytes and the cellular functions of terminally differentiated adipocytes. Adipogenic differentiation was found to be regulated by the same effectors as those regulating differentiation of progenitors derived from white subcutaneous adipose tissue. Similarly, basic adipocyte functions, such as triglyceride synthesis and lipolysis occurred at levels similar to those observed with subcutaneous adipose tissue progenitor-derived adipocytes. However, muscle progenitor-derived adipocytes were found to be insensitive to insulin-induced glucose uptake, in association with the impairment of phosphorylation of key insulin-signaling effectors. Our findings indicate that muscle adipogenic progenitors give rise to bona fide white adipocytes that have the unexpected feature of being insulin-resistant. PMID:25906156

  20. Creatine supplementation does not affect human skeletal muscle glycogen content in the absence of prior exercise.

    Science.gov (United States)

    Sewell, Dean A; Robinson, Tristan M; Greenhaff, Paul L

    2008-02-01

    Due to the current lack of clarity, we examined whether 5 days of dietary creatine (Cr) supplementation per se can influence the glycogen content of human skeletal muscle. Six healthy male volunteers participated in the study, reporting to the laboratory on four occasions to exercise to the point of volitional exhaustion, each after 3 days of a controlled normal habitual dietary intake. After a familiarization visit, participants cycled to exhaustion in the absence of any supplementation (N), and then 2 wk later again they cycled to exhaustion after 5 days of supplementation with simple sugars (CHO). Finally, after a further 2 wk, they again cycled to exhaustion after 5 days of Cr supplementation. Muscle samples were taken at rest before exercise, at the time point of exhaustion in visit 1, and at subsequent visit time of exhaustion. There was a treatment effect on muscle total Cr content in Cr compared with N and CHO supplementation (P exercise. Cr supplementation under conditions of controlled habitual dietary intake had no effect on muscle glycogen content at rest or after exhaustive exercise. We suggest that any Cr-associated increases in muscle glycogen storage are the result of an interaction between Cr supplementation and other mediators of muscle glycogen storage.

  1. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry;

    2011-01-01

    Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) ß-cells.......Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) ß-cells....

  2. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry;

    2011-01-01

    Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells.......Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells....

  3. Detection of chromosomal regions showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Bortoluzzi Stefania

    2004-06-01

    Full Text Available Abstract Background Rhabdomyosarcoma is a relatively common tumour of the soft tissue, probably due to regulatory disruption of growth and differentiation of skeletal muscle stem cells. Identification of genes differentially expressed in normal skeletal muscle and in rhabdomyosarcoma may help in understanding mechanisms of tumour development, in discovering diagnostic and prognostic markers and in identifying novel targets for drug therapy. Results A Perl-code web client was developed to automatically obtain genome map positions of large sets of genes. The software, based on automatic search on Human Genome Browser by sequence alignment, only requires availability of a single transcribed sequence for each gene. In this way, we obtained tissue-specific chromosomal maps of genes expressed in rhabdomyosarcoma or skeletal muscle. Subsequently, Perl software was developed to calculate gene density along chromosomes, by using a sliding window. Thirty-three chromosomal regions harbouring genes mostly expressed in rhabdomyosarcoma were identified. Similarly, 48 chromosomal regions were detected including genes possibly related to function of differentiated skeletal muscle, but silenced in rhabdomyosarcoma. Conclusion In this study we developed a method and the associated software for the comparative analysis of genomic expression in tissues and we identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolar rhabdomyosarcoma representing possible targets for drug treatment and/or development of tumor markers.

  4. Effects of muscle fatigue on the usability of a myoelectric human-computer interface.

    Science.gov (United States)

    Barszap, Alexander G; Skavhaug, Ida-Maria; Joshi, Sanjay S

    2016-10-01

    Electromyography-based human-computer interface development is an active field of research. However, knowledge on the effects of muscle fatigue for specific devices is limited. We have developed a novel myoelectric human-computer interface in which subjects continuously navigate a cursor to targets by manipulating a single surface electromyography (sEMG) signal. Two-dimensional control is achieved through simultaneous adjustments of power in two frequency bands through a series of dynamic low-level muscle contractions. Here, we investigate the potential effects of muscle fatigue during the use of our interface. In the first session, eight subjects completed 300 cursor-to-target trials without breaks; four using a wrist muscle and four using a head muscle. The wrist subjects returned for a second session in which a static fatiguing exercise took place at regular intervals in-between cursor-to-target trials. In the first session we observed no declines in performance as a function of use, even after the long period of use. In the second session, we observed clear changes in cursor trajectories, paired with a target-specific decrease in hit rates.

  5. A comparison of muscle energy models for simulating human walking in three dimensions.

    Science.gov (United States)

    Miller, Ross H

    2014-04-11

    The popular Hill model for muscle activation and contractile dynamics has been extended with several different formulations for predicting the metabolic energy expenditure of human muscle actions. These extended models differ considerably in their approach to computing energy expenditure, particularly in their treatment of active lengthening and eccentric work, but their predictive abilities have never been compared. In this study, we compared the predictions of five different Hill-based muscle energy models in 3D forward dynamics simulations of normal human walking. In a data-tracking simulation that minimized muscle fatigue, the energy models predicted metabolic costs that varied over a three-fold range (2.45-7.15 J/m/kg), with the distinction arising from whether or not eccentric work was subtracted from the net heat rate in the calculation of the muscle metabolic rate. In predictive simulations that optimized neuromuscular control to minimize the metabolic cost, all five models predicted similar speeds, step lengths, and stance phase durations. However, some of the models predicted a hip circumduction strategy to minimize metabolic cost, while others did not, and the accuracy of the predicted knee and ankle angles and ground reaction forces also depended on the energy model used. The results highlights the need to clarify how eccentric work should be treated when calculating muscle energy expenditure, the difficulty in predicting realistic metabolic costs in simulated walking even with a detailed 3D musculoskeletal model, the potential for using such models to predict energetically-optimal gait modifications, and the room for improvement in existing muscle energy models and locomotion simulation frameworks.

  6. TRPC3 Regulates Release of Brain-Derived Neurotrophic Factor From Human Airway Smooth Muscle

    OpenAIRE

    Vohra, Pawan K.; Thompson, Michael A.; Sathish, Venkatachalem; Kiel, Alexander; Jerde, Calvin; Pabelick, Christina M.; Singh, Brij B.; Prakash, Y. S.

    2013-01-01

    Exogenous brain-derived neurotrophic factor (BDNF) enhances Ca2+ signaling and cell proliferation in human airway smooth muscle (ASM), especially with inflammation. Human ASM also expresses BDNF, raising the potential for autocrine/paracrine effects. The mechanisms by which ASM BDNF secretion occurs are not known. Transient receptor potential channels (TRPCs) regulate a variety of intracellular processes including store-operated Ca2+ entry (SOCE; including in ASM) and secretion of factors suc...

  7. Neck posture and muscle activity are different when upside down: a human volunteer study.

    Science.gov (United States)

    Newell, Robyn S; Blouin, Jean-Sébastien; Street, John; Cripton, Peter A; Siegmund, Gunter P

    2013-11-15

    Rollover crashes are dynamic and complex events in which head impacts with the roof can cause catastrophic neck injuries. Ex vivo and computational models are valuable in understanding, and ultimately preventing, these injuries. Although neck posture and muscle activity influence the resulting injury, there is currently no in vivo data describing these parameters immediately prior to a head-first impact. The specific objectives of this study were to determine the in vivo neck vertebral alignment and muscle activation levels when upside down, a condition that occurs during a rollover. Eleven human subjects (6F, 5M) were tested while seated upright and inverted in a custom-built apparatus. Vertebral alignment was measured using fluoroscopy and muscle activity was recorded using surface and indwelling electrodes in eight superficial and deep neck muscles. In vivo vertebral alignment and muscle activation levels differed between the upright and inverted conditions. When inverted and relaxed, the neck was more lordotic, C1 was aligned posterior to C7, the Frankfort plane was extended, and the activity of six muscles increased compared to upright and relaxed. When inverted subjects were asked to look forward to eliminate head extension, flexor muscle activity increased, C7 was more flexed, and C1 was aligned anterior to C7 versus upright and relaxed. Combined with the large inter-subject variability observed, these findings indicate that cadaveric or computational models designed to study injuries and prevention devices while inverted need to consider a variety of postures and muscle conditions to be relevant to the in vivo situation.

  8. GM-CSF production from human airway smooth muscle cells is potentiated by human serum

    Directory of Open Access Journals (Sweden)

    Maria B. Sukkar

    2000-01-01

    Full Text Available Recent evidence suggests that airway smooth muscle cells (ASMC actively participate in the airway inflammatory process in asthma. Interleukin–1β (IL–1β and tumour necrosis factor–α (TNF–α induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1 allergic asthmatic serum (AAS modulates ASMC mediator release in response to IL–1β and TNF–α, and (2 IL–1β/TNF–α prime ASMC to release mediators in response to AAS. IL–5 and GMCSF were quantified by ELISA in culture supernatants of; (1 ASMC pre-incubated with either AAS, non-allergic non-asthmatic serum (NAS or MonomedTM (a serum substitute and subsequently stimulated with IL–1β and TNF–α and (2 ASMC stimulated with IL–1β/TNF–α and subsequently exposed to either AAS, NAS or MonomedTM. IL-1g and TNF–α induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or MonomedTM. IL–1β and TNF–α, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL–1β/TNF–α and serum exposure (AAS or NAS was significantly greater than that following IL–1β /TNF–α and MonomedTM exposure or IL–1β/TNF–α exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage.

  9. SREBP inhibits VEGF expression in human smooth muscle cells.

    Science.gov (United States)

    Motoyama, Koka; Fukumoto, Shinya; Koyama, Hidenori; Emoto, Masanori; Shimano, Hitoshi; Maemura, Koji; Nishizawa, Yoshiki

    2006-03-31

    Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate expression of genes encoding enzymes for lipid biosynthesis. SREBPs are activated by HMG-CoA reductase inhibitors (statins). Statins have been also reported to suppress vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells (VSMCs). Therefore, we hypothesized that SREBPs are involved in statin-mediated regulation of VEGF production in VSMCs. SREBP1 was robustly expressed, and was activated by atorvastatin in VSMCs, as demonstrated by increased levels of the mature nuclear form of SREBP1, and increased promoter activities of a reporter containing sterol regulatory elements by atorvastatin. Moreover, overexpression of SREBP1a dose-dependently suppressed VEGF promoter activity. Site-specific mutation or deletion of the proximal Sp1 sites reduced the inhibitory effects of SREBP1a on VEGF promoter activity. These data demonstrated that SREBP1, activated by atorvastatin, suppressed VEGF expression through the indirect interaction with the proximal tandem Sp1 sites in VSMCs.

  10. Development and validation of a bioartificial liver device with fluidized bed bioreactors hosting alginate-encapsulated hepatocyte spheroids.

    Science.gov (United States)

    Figaro, S; Pereira, U; Rada, H; Semenzato, N; Pouchoulin, D; Legallais, C

    2015-08-01

    Acute and acute-on-chronic liver failure are associated to high mortality when transplantation is not possible. The lack of donors has resulted in an important demand for liver support devices. This paper describes the design and validation of a new bioartificial liver (BAL) device including fluidized bed bioreactors hosting alginate-encapsulated hepatocytes spheroids. To ensure the efficacy of the BAL and the safety of the patients, a complex extracorporeal circulation was designed to be compatible with a commercial medical device, the Prismaflex(®) monitor, already used in intensive care units. Preclinical studies on large animal show that the treatment was well tolerated in terms of hemodynamics considerations. A method using non adhesive coating in petri dish led to the production of large amount of viable spheroids in vitro that were further encapsulated to follow up bioartificial liver activity during four days.

  11. Characterization of cyclic AMP accumulation in cultured human corpus cavernosum smooth muscle cells.

    Science.gov (United States)

    Palmer, L S; Valcic, M; Melman, A; Giraldi, A; Wagner, G; Christ, G J

    1994-10-01

    Intracavernous pharmacotherapy relies heavily on the use of vasoactive agents which act by increasing intracellular cAMP levels in human corpus cavernosum smooth muscle. Yet little is known about the cAMP generating system in this tissue, and how it may affect observed patient variability. Thus, the goal of these studies was to better characterize the biochemistry of cAMP formation in human corpus cavernosum smooth muscle, and thus provide more insight into the mechanisms of corporal smooth muscle relaxation in vivo. We studied both receptor and nonreceptor mediated increases in cAMP formation in short-term cultures of human corpus cavernosum smooth muscle cells. Both isoproterenol (ISO) and prostaglandin E1 (PGE1) produced concentration-dependent increases in cAMP, but histamine, serotonin and vasoactive intestinal polypeptide did not. Forskolin, a relatively specific activator of adenylate cyclase, was also a potent stimulant of cAMP formation in these cells. Moreover, there was a direct correlation between the degree of forskolin-induced cAMP accumulation in cultured corporal smooth muscle cells and the magnitude of the forskolin-induced relaxation response of precontracted isolated corporal smooth muscle strips. Prostaglandin E1 and ISO concentration response curves (CRCs) were then assayed in the absence and presence of subthreshold forskolin (0.1 microM.). In the presence of forskolin, the calculated maximal PGE1-induced cAMP accumulation (Emax) was significantly greater than that elicited by PGE1 alone, ISO alone, or ISO + forskolin (p protocol was used to demonstrate that both 80:20 and 70:30 FMRs (but not 95:5 or 90:10), were associated with significantly greater cAMP Emax values than that observed for PGE1 alone (p < or = 0.01). These data provide direct evidence that the degree of cAMP formation in cultured corporal smooth muscle cells is strongly correlated with the magnitude of relaxation of isolated corporal smooth muscle strips. In addition, since

  12. Exercise induces transient transcriptional activation of the PGC-1α gene in human skeletal muscle

    Science.gov (United States)

    Pilegaard, Henriette; Saltin, Bengt; Neufer, P Darrell

    2003-01-01

    Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1α (PGC-1α) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell culture and rodent skeletal muscle. To determine whether PGC-1α transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl-CoA dehydrogenase mRNA, were higher in the trained than the untrained leg prior to exercise. Exercise induced a marked transient increase (P 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1α was greater in the trained leg despite the lower relative workload. Interestingly, exercise did not affect nuclear respiratory factor 1 (NRF-1) mRNA, a gene induced by PGC-1α in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor α, and calcineurin Aα and Aβ mRNA were elevated (≈2- to 6-fold; P < 0.05) at 6 h of recovery in the untrained leg but did not change in the trained leg. The present data demonstrate that exercise induces a dramatic transient increase in PGC-1α transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1α may coordinate the activation of metabolic genes in human muscle in response to exercise. PMID:12563009

  13. Gene expression in human skeletal muscle: alternative normalization method and effect of repeated biopsies.

    Science.gov (United States)

    Lundby, Carsten; Nordsborg, Nikolai; Kusuhara, Keiko; Kristensen, Kristina Møller; Neufer, P Darrell; Pilegaard, Henriette

    2005-10-01

    The reverse transcriptase-polymerase chain reaction (RT-PCR) method has lately become widely used to determine transcription and mRNA content in rodent and human muscle samples. However, the common use of endogenous controls for correcting for variance in cDNA between samples is not optimal. Specifically, we investigated (1) a new normalization method based on determining the cDNA content by the flourophores PicoGreen and OliGreen, (2) effect of repeated muscle biopsies on mRNA gene expression, and (3) the spatial heterogeneity in mRNA expression across the muscle. Standard curves using oligo standards revealed a high degree of sensitivity and linearity (2.5-45 ng; R2>0.99) with OliGreen reagent, as was the case for OliGreen analyses with standard curves constructed from serial dilutions of representative RT samples (R2 >0.99 for a ten times dilution range of a representative reversed transcribed (RT) sample). Likewise, PicoGreen reagent detected the RNA:DNA hybrid content in RT samples with great sensitivity. Standard curves constructed from both double-stranded lambda DNA (1-10 ng) and from serial dilutions of representative RT samples consistently resulted in linearity with R2 >0.99. The present determination of cDNA content in reversed transcribed human skeletal muscle RNA samples by both PicoGreen and OliGreen analyses suggests that these fluorophores provide a potential alternative normalization procedure for human gene expression studies. In addition, the present study shows that multiple muscle biopsies obtained from the same muscle do not influence the mRNA response induced by an acute exercise bout for any of the genes examined.

  14. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle.

    Science.gov (United States)

    Pilegaard, Henriette; Saltin, Bengt; Neufer, P Darrell

    2003-02-01

    Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1alpha (PGC-1alpha) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell culture and rodent skeletal muscle. To determine whether PGC-1alpha transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl-CoA dehydrogenase mRNA, were higher in the trained than the untrained leg prior to exercise. Exercise induced a marked transient increase (P 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1alpha was greater in the trained leg despite the lower relative workload. Interestingly, exercise did not affect nuclear respiratory factor 1 (NRF-1) mRNA, a gene induced by PGC-1alpha in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor alpha, and calcineurin Aalpha and Abeta mRNA were elevated (approximately 2- to 6-fold; P < 0.05) at 6 h of recovery in the untrained leg but did not change in the trained leg. The present data demonstrate that exercise induces a dramatic transient increase in PGC-1alpha transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1alpha may coordinate the activation of metabolic genes in human muscle in response to exercise.

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

    Directory of Open Access Journals (Sweden)

    Kazushige Sasaki

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

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

    Science.gov (United States)

    Blake, Ollie M; Wakeling, James M

    2015-12-01

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

  17. Economy, Movement Dynamics, and Muscle Activity of Human Walking at Different Speeds

    DEFF Research Database (Denmark)

    Raffalt, Peter Christian; Guul, Martin Kjær; Nielsen, A. N.

    2017-01-01

    The complex behaviour of human walking with respect to movement variability, economy and muscle activity is speed dependent. It is well known that a U-shaped relationship between walking speed and economy exists. However, it is an open question if the movement dynamics of joint angles and centre...... healthy males. The muscle activation strategy and walking economy were also assessed. The movement dynamics was investigated using a combination of the largest Lyapunov exponent and correlation dimension. We observed an intermediate stage of the movement dynamics of the knee joint angle and the anterior...

  18. Regulation of PDH in human arm and leg muscles at rest and during intense exercise

    DEFF Research Database (Denmark)

    Kiilerich, Kristian; Birk, Jesper Bratz; Damsgaard, Rasmus

    2008-01-01

    To test the hypothesis that pyruvate dehydrogenase (PDH) is differentially regulated in specific human muscles, regulation of PDH was examined in triceps, deltoid, and vastus lateralis at rest and during intense exercise. To elicit considerable glycogen use, subjects performed 30 min of exhaustive...... arm cycling on two occasions and leg cycling exercise on a third day. Muscle biopsies were obtained from deltoid or triceps on the arm exercise days and from vastus lateralis on the leg cycling day. Resting PDH protein content and phosphorylation on PDH-E1 alpha sites 1 and 2 were higher (P

  19. The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle

    DEFF Research Database (Denmark)

    Helge, Jørn W; Stallknecht, Bente; Pedersen, Bente Klarlund;

    2003-01-01

    In this study, the hypothesis that the release of interleukin (IL)-6 from human muscle is linked to exercise intensity and muscle glucose uptake was investigated. In the overnight fasted state, seven healthy males performed knee extension exercise, kicking with both legs, each at 25 % of maximal...... % and 85 % W(max), respectively) increased with increasing exercise intensity (P ....75 +/- 0.16, 1.07 +/- 0.15 mmol min(-1) thigh(-1) at rest and 25 %, 65 % and 85 % W(max), respectively) increased with increasing exercise intensity (P exercise, arterial catecholamine concentrations were higher (P exercise...

  20. Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

    DEFF Research Database (Denmark)

    Lundby, Carsten; Pilegaard, Henriette; van Hall, Gerrit

    2003-01-01

    ) was unaltered by prolonged hypoxia, in accordance with the notion that HO-1 is an acute stress response protein. In conclusion, our data indicate high-altitude hypoxia may serve as a good model for oxidative stress and that antioxidant genes are not upregulated in muscle tissue by prolonged hypoxia despite......Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen...

  1. A streamlined protocol for extracting RNA and genomic DNA from archived human blood and muscle.

    Science.gov (United States)

    Majumdar, Gipsy; Vera, Santiago; Elam, Marshall B; Raghow, Rajendra

    2015-04-01

    We combined the TRIzol method of nucleic acid extraction with QIAamp columns to achieve coextraction of RNA and genomic DNA from peripheral blood mononuclear cells (PBMCs) and biopsied skeletal muscle, both stored at -80 °C for many months. Total RNA was recovered from the upper aqueous phase of TRIzol. The interphase and organic phases were precipitated with ethanol, digested with proteinase K, and filtered through QIAamp MinElute columns to recover DNA. The combined protocol yielded excellent quality and quantity of nucleic acids from archived human PBMCs and muscle and may be easily adapted for other tissues.

  2. Human muscle fiber type-specific insulin signaling: Impact of obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth; Pedersen, Andreas J T; Birk, Jesper Bratz

    2015-01-01

    /or metabolic enzymes. Pools of type I and II fibers were prepared from biopsies of the vastus lateralis muscles from lean, obese and type 2 diabetic subjects before and after a hyperinsulinemic-euglycemic clamp. Type I fibers compared to type II fibers have higher protein levels of the insulin receptor, GLUT4......-responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS and PDH-E1α) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared to lean and obese subjects. We conclude that human type I...

  3. Autonomic control of heart rate by metabolically sensitive skeletal muscle afferents in humans

    DEFF Research Database (Denmark)

    Fisher, James P; Seifert, Thomas; Hartwich, Doreen

    2010-01-01

    moderate (PEI-M) and high (PEI-H) intensity isometric handgrip performed at 25% and 40% maximum voluntary contraction, under control (no drug), parasympathetic blockade (glycopyrrolate) and beta-adrenergic blockade (metoprolol or propranalol) conditions, while beat-to-beat HR and BP were continuously...... was similarly increased from rest during PEI-M and further elevated during PEI-H (P Collectively, these findings suggest that the muscle metaboreflex increases cardiac SNA during PEI in humans; however, it requires a robust muscle metaboreflex activation to offset the influence...

  4. Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans

    OpenAIRE

    Rhodes, Michael A.; Carraway, Martha Sue; Piantadosi, Claude A.; Reynolds, Crystal M; Cherry, Anne D.; Wester, T. E.; Natoli, Michael J.; Massey, E. Wayne; Moon, Richard E.; Suliman, Hagir B.

    2009-01-01

    Given that the physiology of heme oxygenase-1 (HO-1) encompasses mitochondrial biogenesis, we tested the hypothesis that the HO-1 product, carbon monoxide (CO), activates mitochondrial biogenesis in skeletal muscle and enhances maximal oxygen uptake (V̇o2max) in humans. In 10 healthy subjects, we biopsied the vastus lateralis and performed V̇o2max tests followed by blinded randomization to air or CO breathing (1 h/day at 100 parts/million for 5 days), a contralateral muscle biopsy on day 5, a...

  5. Anatomical study of the arrangement and attachments of the human medial pterygoid muscle.

    Science.gov (United States)

    El Haddioui, Aziz; Bravetti, P; Gaudy, J-F

    2007-03-01

    The authors have studied the medial pterygoid muscle on 179 fresh cadavers using anatomical dissection and magnetic resonance imaging (MRI). The aim of this study was to define the general morphology and architectural organisation of the human medial pterygoid. Plane by plane dissection, anatomical sections in different spatial planes on half heads and isolated blocks demonstrated that the medial pterygoid has different architectural disposition and insertional zones from those which are normally described. The study has shown that the muscle has a typical penniform structure made up of seven alternating muscular/aponeurotic layers and that the tendinous intramuscular sheets were particularly well developed. This allows supporting a future functional study.

  6. Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts

    Science.gov (United States)

    Stump, Craig S.; Short, Kevin R.; Bigelow, Maureen L.; Schimke, Jill M.; Sreekumaran Nair, K.

    2003-06-01

    Mitochondria are the primary site of skeletal muscle fuel metabolism and ATP production. Although insulin is a major regulator of fuel metabolism, its effect on mitochondrial ATP production is not known. Here we report increases in vastus lateralis muscle mitochondrial ATP production capacity (32-42%) in healthy humans (P oxidative phosphorylation in skeletal muscle along with synthesis of gene transcripts and mitochondrial protein in human subjects. Skeletal muscle of type 2 diabetic patients has a reduced capacity to increase ATP production with high insulin levels. cytochrome c oxidase | NADH dehydrogenase subunit IV | amino acids | citrate synthase

  7. Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Venkatachalem Sathish

    2015-06-01

    Full Text Available Aims: Cigarette smoke (CS in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE on 17β-estradiol (E2 signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca2+]i responses to 10µM histamine. Acute exposure to physiological concentrations of E2 decreased [Ca2+]i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E2 on [Ca2+]i was blunted. Acute E2 exposure also decreased store-operated Ca2+ entry and inhibited stromal interaction molecule 1 (STIM1 phosphorylation: effects blunted by CSE. Acute exposure to E2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

  8. Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Mohamad Hafizi Abu Bakar

    2015-05-01

    Full Text Available Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.

  9. Sustantial Observation on Foot Taeyang Meridian Muscle in Human Lower Limb from a Anatomical Viewpoint

    Directory of Open Access Journals (Sweden)

    Kyoung-Sik Park

    2009-06-01

    Full Text Available Objective : This study was carried to identify the anatomical component of FTMM(Foot Taeyang Meridian Muscle in human lower limb, and further to help the accurate application to real acupuncture. Methods : FTM at the surface of the lower limb was labelled with latex. And cadaver was stripped off to demonstrate muscles, nerves and the others and to display the internal structures of FTMM, being divided into outer, middle, and inner layer. Results : FTMM in human lower limb is composed of muscles, nerves, ligaments etc. The internal composition of the FTMM in human lower limb are as follows : 1 Muscle : Gluteus maximus. biceps femoris, semitendinosus, gastrocnemius, triceps calf, fibularis brevis tendon, superior peroneal retinacula, calcaneofibular ligament, inferior extensor retinaculum, abductor digiti minimi, sheath of flexor tendon at outer layer, biceps femoris, semimembranosus, plantaris, soleus, posterior tibialis, fibularis brevis, extensor digitorum brevis, flexor digiti minimi at middle layer, and for the last time semimembranosus, adductor magnus, plantaris, popliteus, posterior tibialis, flexor hallucis longus, dorsal calcaneocuboidal ligament at inner layer. 2 Nerve : Inferior cluneal nerve, posterior femoral cutaneous n., sural cutaneous n., proper plantar branch of lateral plantar n. at outer layer, sciatic nerve, common peroneal n., medial sural cutaneous n., tibial n. at middle layer, and for the last time tibial nerve, flexor hallucis longus branch of tibial n. at inner layer. Conclusions : This study proves comparative differences from already established studies from the viewpoint of constituent elements of FTMM in the lower limb, and also in the aspect of substantial assay method. We can guess that there are conceptional differences between terms (that is, nerves which control muscles of FTMM and those which pass near by FTMM in human anatomy.

  10. Smooth Muscle Precursor Cells Derived from Human Pluripotent Stem Cells for Treatment of Stress Urinary Incontinence

    Science.gov (United States)

    Wang, Zhe; Li, Yan Hui; Wei, Yi; Green, Morgaine; Wani, Prachi; Zhang, Pengbo; Pera, Renee Reijo; Chen, Bertha

    2016-01-01

    There is great interest in using stem cells (SC) to regenerate a deficient urethral sphincter in patients with urinary incontinence. The smooth muscle component of the sphincter is a significant contributor to sphincter function. However, current translational efforts for sphincter muscle restoration focus only on skeletal muscle regeneration because they rely on adult mesenchymal SC as cell source. These adult SC do not yield sufficient smooth muscle cells (SMCs) for transplantation. We may be able to overcome this limitation by using pluripotent stem cell (PSC) to derive SMCs. Hence, we sought to investigate whether smooth muscle precursor cells (pSMCs) derived from human PSCs can restore urethral function in an animal model generated by surgical urethrolysis and ovariectomy. Rats were divided into four groups: control (no intervention), sham saline (surgery + saline injection), bladder SMC (surgery + human bladder SMC injection), and treatment (surgery + pSMC injection, which includes human embryonic stem cell (hESC) H9-derived pSMC, episomal reprogrammed induced pluripotent stem cells (iPSCs)-derived pSMC, or viral reprogrammed iPSC-derived pSMC). pSMCs (2 × 106 cells/rat) were injected periurethrally 3 weeks postsurgery. Leak point pressure (LPP) and baseline external urethral sphincter electromyography were measured 5 weeks postinjection. Both iPSC-derived pSMC treatment groups showed significantly higher LPP compared to the sham saline group, consistent with restoration of urethral sphincter function. While the difference between the H9-derived pSMC treatment and sham saline group was not significant, it did show a trend toward restoration of the LPP to the level of intact controls. Our data indicate that pSMCs derived from human PSCs (hESC and iPSC) can restore sphincter function. PMID:26785911

  11. Generation of human muscle fibers and satellite-like cells from human pluripotent stem cells in vitro.

    Science.gov (United States)

    Chal, Jérome; Al Tanoury, Ziad; Hestin, Marie; Gobert, Bénédicte; Aivio, Suvi; Hick, Aurore; Cherrier, Thomas; Nesmith, Alexander P; Parker, Kevin K; Pourquié, Olivier

    2016-10-01

    Progress toward finding a cure for muscle diseases has been slow because of the absence of relevant cellular models and the lack of a reliable source of muscle progenitors for biomedical investigation. Here we report an optimized serum-free differentiation protocol to efficiently produce striated, millimeter-long muscle fibers together with satellite-like cells from human pluripotent stem cells (hPSCs) in vitro. By mimicking key signaling events leading to muscle formation in the embryo, in particular the dual modulation of Wnt and bone morphogenetic protein (BMP) pathway signaling, this directed differentiation protocol avoids the requirement for genetic modifications or cell sorting. Robust myogenesis can be achieved in vitro within 1 month by personnel experienced in hPSC culture. The differentiating culture can be subcultured to produce large amounts of myogenic progenitors amenable to numerous downstream applications. Beyond the study of myogenesis, this differentiation method offers an attractive platform for the development of relevant in vitro models of muscle dystrophies and drug screening strategies, as well as providing a source of cells for tissue engineering and cell therapy approaches.

  12. Premature birth is associated with not fully differentiated contractile smooth muscle cells in human umbilical artery.

    Science.gov (United States)

    Roffino, S; Lamy, E; Foucault-Bertaud, A; Risso, F; Reboul, R; Tellier, E; Chareyre, C; Dignat-George, F; Simeoni, U; Charpiot, P

    2012-06-01

    Smooth muscle cells (SMCs) participate to the regulation of peripheral arterial resistance and blood pressure. To assume their function, SMCs differentiate throughout the normal vascular development from a synthetic phenotype towards a fully differentiated contractile phenotype by acquiring a repertoire of proteins involved in contraction. In human fetal muscular arteries and umbilical arteries (UAs), no data are available regarding the differentiation of SMCs during the last trimester of gestation. The objective of this study was to characterize the phenotype of SMCs during this gestation period in human UAs. We investigated the phenotype of SMCs in human UAs from very preterm (28-31 weeks of gestation), late preterm (32-35 weeks) and term (37-41 weeks) newborns using biochemical and immunohistochemical detection of α-actin, smooth muscle myosin heavy chain, smoothelin, and non-muscle myosin heavy chain. We found that the number of SMCs positive for smoothelin in UAs increased with gestational age. Western blot analysis revealed a higher content of smoothelin in term compared to very preterm UAs. These results show that SMCs in human UAs gradually acquire a fully differentiated contractile phenotype during the last trimester of gestation and thus that premature birth is associated with not fully differentiated contractile SMCs in human UAs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Fiber type and metabolic characteristics of lion (Panthera leo), caracal (Caracal caracal) and human skeletal muscle.

    Science.gov (United States)

    Kohn, Tertius Abraham; Burroughs, Richard; Hartman, Marthinus Jacobus; Noakes, Timothy David

    2011-06-01

    Lion (Panthera leo) and caracal (Caracal caracal) skeletal muscle samples from Vastus lateralis, Longissimus dorsi and Gluteus medius were analyzed for fiber type and citrate synthase (CS; EC 2.3.3.1), 3-hydroxyacyl Co A dehydrogenase (3HAD; EC 1.1.1.35), phosphofructokinase-1 (PFK; EC 2.7.1.11), creatine kinase (CK; EC 2.7.3.2), phosphorylase (PHOS; EC 2.4.1.1) and lactate dehydrogenase (LDH; EC 1.1.1.27) activities and compared to human runners, the latter also serving as validation of methodology. Both felids had predominantly type IIx fibers (range 50-80%), whereas human muscle had more types I and IIa. Oxidative capacity of both felids (CS: 5-9 μmol/min/g ww and 3HAD: 1.4-2.6 μmol/min/g ww) was lower than humans, whereas the glycolytic capacity was elevated. LDH activity of caracal (346 ± 81) was higher than lion (227 ± 62 μmol/min/g ww), with human being the lowest (55 ± 17). CK and PHOS activities were also higher in caracal and lion compared to human, but PFK was lower in both felid species. The current data and past research are illustrated graphically showing a strong relationship between type II fibers and sprinting ability in various species. These data on caracal and lion muscles confirm their sprinting behavior.

  14. Studies on adenosine triphosphate transphosphorylases. Human isoenzymes of adenylate kinase: isolation and physicochemical comparison of the crystalline human ATP-AMP transphosphorylases from muscle and liver.

    Science.gov (United States)

    Kuby, S A; Fleming, G; Frischat, A; Cress, M C; Hamada, M

    1983-02-10

    Procedures are described for the isolation, in crystalline form, of the adenylate kinases from autopsy samples of human muscle and from human liver. Weight average molecular weights were determined by sedimentation equilibrium to be 22,000 (+/- 700) and 25,450 (+/- 160) for the human muscle and liver isoenzymes, respectively. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, their molecular weights were estimated to be 21,700 and 26,500 for the muscle and liver enzymes, respectively. Both isoenzymes are accordingly monomeric proteins in their native state. Amino acid analyses are reported here for the normal human liver, calf liver, and rabbit liver adenylate kinases and compared with the normal human muscle, calf muscle, and rabbit muscle myokinases. The liver types as a group and the muscle types as a group show a great deal of homology, but some distinct differences are evident between the liver and muscle enzyme groups, especially in the number of residues of His, Pro, half-cystine, and the presence of tryptophan in the liver enzymes. The normal human liver adenylate kinase, as isolated in this report, has proved to be similar in its properties, if not identical, to the adenylate kinase isolated directly from human liver mitochondria (Hamada, M., Sumida, M., Okuda, H., Watanabe, T., Nojima, M., and Kuby, S. A. (1982) J. Biol. Chem. 257, 13120-13128). Therefore, the liver-type adenylate kinase may be considered a mitochondrial type.

  15. Startle stimuli exert opposite effects on human cortical and spinal motor system excitability in leg muscles

    DEFF Research Database (Denmark)

    Ilic, T V; Pötter-Nerger, M; Holler, I

    2011-01-01

    Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains...... (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of approximately 0.5 mV in the slightly preinervated soleus muscle (SOL). In the second experiment, the startling AS was used to condition the size of the H-reflex in SOL muscle. Mean MEP amplitude...... was calculated for each ISI. The conditioning AS suppressed MEP amplitude at ISIs of 30-80 ms. By contrast, H-reflex amplitude was augmented at ISIs of 100-200 ms. In conclusions, acoustic stimulation exerts opposite and ISI-specific effects on the amplitude of MEPs and H-reflex in the SOL muscle, indicating...

  16. Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise

    DEFF Research Database (Denmark)

    Mikkelsen, U R; Langberg, H; Helmark, I C

    2009-01-01

    exercise in vivo in human skeletal muscle. Eight young healthy males performed 200 maximal eccentric contractions with each leg. An NSAID was infused via a microdialysis catheter into the vastus lateralis muscle of one leg (NSAID leg) before, during, and for 4.5 h after exercise, with the other leg working...... of satellite cells 8 days after exercise. These results suggest that NSAIDs negatively affect satellite cell activity after unaccustomed eccentric exercise.......Despite the widespread consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), the influence of these drugs on muscle satellite cells is not fully understood. The aim of the present study was to investigate the effect of a local NSAID infusion on satellite cells after unaccustomed eccentric...

  17. The motor cortex drives the muscles during walking in human subjects

    DEFF Research Database (Denmark)

    Petersen, Tue Hvass; Willerslev-Olsen, Maria; Conway, B A;

    2012-01-01

    to address if activity arising in the motor cortex contributes to the muscle activity during gait. Nine healthy human subjects walked on a treadmill at a speed of 3.5–4 km h(-1). Seven of the subjects in addition walked at a speed of 1 km h(-1). Significant coupling between EEG recordings over the leg motor...... area and EMG from the anterior tibial muscle was found in the frequency band 24–40 Hz prior to heel strike during the swing phase of walking. This signifies that rhythmic cortical activity in the 24–40 Hz frequency band is transmitted via the corticospinal tract to the active muscles during walking...

  18. IMPROVING METHODOLOGICAL STRATEGIES FOR SATELLITE CELLS COUNTING IN HUMAN MUSCLE DURING AGEING

    Directory of Open Access Journals (Sweden)

    Špela Sajko

    2011-05-01

    Full Text Available Stereological methods, based on the optical disector principle and fluorescent staining, were developed for estimating frequency of satellite cells in skeletal muscles. The parameter NL(sc, fib (number of satellite cells per fibre length was compared with the parameter NN(sc, nucl (the percentage of satellite cell nuclei in all muscle nuclei, most often published in the literature, by applying unbiased sampling and counting procedures and using a confocal microscope. The methods were tested in autopsy samples of four young vs. four old human vastus lateralis muscles. Both parameters NL(sc, fib and NN(sc, nucl declined during ageing. However, it appears that the two parameters cannot be substituted one by the other because the number of nuclei per fibre length tends to be increased during aging. Using the introduced methods, it is more straightforward to estimate NL(sc, fib than NN(sc, nucl.

  19. Phosphatidic acid phosphatase activity in subcellular fractions of normal and dystrophic human muscle.

    Science.gov (United States)

    Kunze, D; Rüstow, B; Olthoff, D; Jung, K

    1985-03-15

    Biopsy samples from normal and dystrophic human muscle (Duchenne type) were fractionated by differential centrifugation and microsomes, mitochondria and cytosol were assayed for phosphatidic acid phosphatase (EC 3.1.3.4) and marker enzymes of mitochondria and cytosol. The activity of phosphatidic acid phosphatase was significantly lower in microsomes and higher in cytosol and mitochondria of dystrophic muscle than in the corresponding subcellular fractions of normal muscle. The results support an explanation of earlier findings that there is reduced G3P incorporation into diglycerides and phosphatidylcholine and a qualitative and quantitative change in the amount of phosphatidylcholine in dystrophic microsomes. The possible reasons for the reduction in the activity of only microsomal PA-P-ase were discussed.

  20. Human and rodent muscle Na(+)-K(+)-ATPase in diabetes related to insulin, starvation, and training

    DEFF Research Database (Denmark)

    Schmidt, T A; Hasselbalch, S; Farrell, P A

    1994-01-01

    , insulin treatment of rats with streptozotocin-induced diabetes induced an increase of 18-26% above control (P muscle [3H]ouabain binding site concentration induced by untreated diabetes to only 2-5%. No significant variation was observed in rat......As determined by vanadate-facilitated [3H]ouabain binding to intact samples, semistarvation and untreated streptozotocin- or partial pancreatectomy-induced diabetes reduced rat soleus muscle Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) concentration by 12-21% (P ... cerebral cortex Na(+)-K(+)-ATPase concentration as a result of diabetes, semistarvation, or insulin treatment. In human subjects, Na(+)-K(+)-ATPase concentration in vastus lateralis muscle biopsies was 17 and 22% greater (P

  1. Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle

    DEFF Research Database (Denmark)

    Gaster, M; Poulsen, P; Handberg, A

    2000-01-01

    GLUT-4 expression in individual fibers of human skeletal muscles in younger and older adults was studied. Furthermore, the dependency of insulin-stimulated glucose uptake on fiber type distribution was investigated. Fiber type distribution was determined in cryosections of muscle biopsies from 8...... younger (29 yr) and 8 older (64 yr) healthy subjects, and estimates of GLUT-4 expression in individual fibers were obtained by combining immunohistochemistry and stereology. GLUT-4 was more abundantly expressed in slow compared with fast muscle fibers in both younger (P ...) subjects. A 25% reduction of GLUT-4 density in fast fibers (P GLUT-4 density in slow fibers were demonstrated in older compared with younger subjects. Insulin-stimulated glucose uptake rates measured by hyperinsulinemic, euglycemic clamp were not correlated with the fraction...

  2. Inflammatory and protein metabolism signaling responses in human skeletal muscle after burn injury.

    Science.gov (United States)

    Merritt, Edward K; Cross, James M; Bamman, Marcas M

    2012-01-01

    Severe burn injuries lead to a prolonged hypercatabolic state resulting in dramatic loss of skeletal muscle mass. Postburn muscle loss is well documented but the molecular signaling cascade preceding atrophy is not. The purpose of this study is to determine the response to burn injury of signaling pathways driving muscle inflammation and protein metabolism. Muscle biopsies were collected in the early flow phase after burn injury from the vastus lateralis of a noninjured leg in patients with 20 to 60% TBSA burns and compared with uninjured, matched controls. Circulating levels of proinflammatory cytokines were also compared. Immunoblotting was performed to determine the protein levels of key signaling components for translation initiation, proteolysis, and tumor necrosis factor/nuclear factor kappa B (NFκB)and interleukin (IL)-6/STAT3 signaling. Burn subjects had significantly higher levels of circulating proinflammatory cytokines, with no difference in muscle STAT3 activity and lower NFκB activity. No differences were found in any translational signaling components. Regarding proteolytic signaling in burn, calpain-2 was 47% higher, calpastatin tended to be lower, and total ubiquitination was substantially higher. Surprisingly, a systemic proinflammatory response 3 to 10 days postburn did not lead to elevated muscle STAT3 or NFκB signaling. Signaling molecules governing translation initiation were unaffected, whereas indices of calcium-mediated proteolysis and ubiquitin-proteasome activity were upregulated. These novel findings are the first in humans to suggest that the net catabolic effect of burn injury in skeletal muscle (ie, atrophy) may be mediated, at least during the early flow phase, almost entirely by an increased proteolytic activity in the absence of suppressed protein synthesis signaling.

  3. Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy.

    Science.gov (United States)

    Palma, Eleonora; Reyes-Ruiz, Jorge Mauricio; Lopergolo, Diego; Roseti, Cristina; Bertollini, Cristina; Ruffolo, Gabriele; Cifelli, Pierangelo; Onesti, Emanuela; Limatola, Cristina; Miledi, Ricardo; Inghilleri, Maurizio

    2016-03-15

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons that leads to progressive paralysis of skeletal muscle. Studies of ALS have revealed defects in expression of acetylcholine receptors (AChRs) in skeletal muscle that occur even in the absence of motor neuron anomalies. The endocannabinoid palmitoylethanolamide (PEA) modified the clinical conditions in one ALS patient, improving muscle force and respiratory efficacy. By microtransplanting muscle membranes from selected ALS patients into Xenopus oocytes, we show that PEA reduces the desensitization of acetylcholine-evoked currents after repetitive neurotransmitter application (i.e., rundown). The same effect was observed using muscle samples from denervated (non-ALS) control patients. The expression of human recombinant α1β1γδ (γ-AChRs) and α1β1εδ AChRs (ε-AChRs) in Xenopus oocytes revealed that PEA selectively affected the rundown of ACh currents in ε-AChRs. A clear up-regulation of the α1 subunit in muscle from ALS patients compared with that from non-ALS patients was found by quantitative PCR, but no differential expression was found for other subunits. Clinically, ALS patients treated with PEA showed a lower decrease in their forced vital capacity (FVC) over time as compared with untreated ALS patients, suggesting that PEA can enhance pulmonary function in ALS. In the present work, data were collected from a cohort of 76 ALS patients and 17 denervated patients. Our results strengthen the evidence for the role of skeletal muscle in ALS pathogenesis and pave the way for the development of new drugs to hamper the clinical effects of the disease.

  4. Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy

    Science.gov (United States)

    Palma, Eleonora; Reyes-Ruiz, Jorge Mauricio; Lopergolo, Diego; Roseti, Cristina; Bertollini, Cristina; Ruffolo, Gabriele; Cifelli, Pierangelo; Onesti, Emanuela; Limatola, Cristina; Miledi, Ricardo; Inghilleri, Maurizio

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons that leads to progressive paralysis of skeletal muscle. Studies of ALS have revealed defects in expression of acetylcholine receptors (AChRs) in skeletal muscle that occur even in the absence of motor neuron anomalies. The endocannabinoid palmitoylethanolamide (PEA) modified the clinical conditions in one ALS patient, improving muscle force and respiratory efficacy. By microtransplanting muscle membranes from selected ALS patients into Xenopus oocytes, we show that PEA reduces the desensitization of acetylcholine-evoked currents after repetitive neurotransmitter application (i.e., rundown). The same effect was observed using muscle samples from denervated (non-ALS) control patients. The expression of human recombinant α1β1γδ (γ-AChRs) and α1β1εδ AChRs (ε-AChRs) in Xenopus oocytes revealed that PEA selectively affected the rundown of ACh currents in ε-AChRs. A clear up-regulation of the α1 subunit in muscle from ALS patients compared with that from non-ALS patients was found by quantitative PCR, but no differential expression was found for other subunits. Clinically, ALS patients treated with PEA showed a lower decrease in their forced vital capacity (FVC) over time as compared with untreated ALS patients, suggesting that PEA can enhance pulmonary function in ALS. In the present work, data were collected from a cohort of 76 ALS patients and 17 denervated patients. Our results strengthen the evidence for the role of skeletal muscle in ALS pathogenesis and pave the way for the development of new drugs to hamper the clinical effects of the disease. PMID:26929355

  5. Contributions of skin and muscle afferent input to movement sense in the human hand.

    Science.gov (United States)

    Cordo, Paul J; Horn, Jean-Louis; Künster, Daniela; Cherry, Anne; Bratt, Alex; Gurfinkel, Victor

    2011-04-01

    In the stationary hand, static joint-position sense originates from multimodal somatosensory input (e.g., joint, skin, and muscle). In the moving hand, however, it is uncertain how movement sense arises from these different submodalities of proprioceptors. In contrast to static-position sense, movement sense includes multiple parameters such as motion detection, direction, joint angle, and velocity. Because movement sense is both multimodal and multiparametric, it is not known how different movement parameters are represented by different afferent submodalities. In theory, each submodality could redundantly represent all movement parameters, or, alternatively, different afferent submodalities could be tuned to distinctly different movement parameters. The study described in this paper investigated how skin input and muscle input each contributes to movement sense of the hand, in particular, to the movement parameters dynamic position and velocity. Healthy adult subjects were instructed to indicate with the left hand when they sensed the unseen fingers of the right hand being passively flexed at the metacarpophalangeal (MCP) joint through a previously learned target angle. The experimental approach was to suppress input from skin and/or muscle: skin input by anesthetizing the hand, and muscle input by unexpectedly extending the wrist to prevent MCP flexion from stretching the finger extensor muscle. Input from joint afferents was assumed not to play a significant role because the task was carried out with the MCP joints near their neutral positions. We found that, during passive finger movement near the neutral position in healthy adult humans, both skin and muscle receptors contribute to movement sense but qualitatively differently. Whereas skin input contributes to both dynamic position and velocity sense, muscle input may contribute only to velocity sense.

  6. Architectural analysis and predicted functional capability of the human latissimus dorsi muscle.

    Science.gov (United States)

    Gerling, Michael E; Brown, Stephen H M

    2013-08-01

    The latissimus dorsi is primarily considered a muscle with actions at the shoulder, despite its widespread attachments at the spine. There is some dispute regarding the potential contribution of this muscle to lumbar spine function. The architectural design of a muscle is one of the most accurate predictors of muscle function; however, detailed architectural data on the latissimus dorsi muscle are limited. Therefore, the aim of this study was to quantify the architectural properties of the latissimus dorsi muscle and model mechanical function in light of these new data. One latissimus dorsi muscle was removed from each of 12 human cadavers, separated into regions, and micro-dissected for quantification of fascicle length, sarcomere length, and physiological cross-sectional area. From these data, sarcomere length operating ranges were modelled to determine the force-length characteristics of latissimus dorsi across the spine and shoulder ranges of motion. The physiological cross-sectional area of latissimus dorsi was 5.6±0.5 cm2 and normalized fascicle length was 26.4±1.0 cm, indicating that this muscle is designed to produce a moderate amount of force over a large range of lengths. Measured sarcomere length in the post-mortem neutral spine posture was nearly optimal at 2.69±0.06 μm. Across spine range of motion, biomechanical modelling predicted latissimus dorsi acts across both the ascending and descending limbs of the force-length curve during lateral bend, and primarily at or near the plateau region (where maximum force generation is possible) during flexion/extension and axial twist. Across shoulder range of motion, latissimus dorsi acts primarily on the plateau region and descending limbs of the force length curve during both flexion/extension and abduction/adduction. These data provide novel insights into the ability of the latissimus dorsi muscle to generate force and change length throughout the spine and shoulder ranges of motion. In addition, these

  7. Muscular strategy shift in human running: dependence of running speed on hip and ankle muscle performance.

    Science.gov (United States)

    Dorn, Tim W; Schache, Anthony G; Pandy, Marcus G

    2012-06-01

    Humans run faster by increasing a combination of stride length and stride frequency. In slow and medium-paced running, stride length is increased by exerting larger support forces during ground contact, whereas in fast running and sprinting, stride frequency is increased by swinging the legs more rapidly through the air. Many studies have investigated the mechanics of human running, yet little is known about how the individual leg muscles accelerate the joints and centre of mass during this task. The aim of this study was to describe and explain the synergistic actions of the individual leg muscles over a wide range of running speeds, from slow running to maximal sprinting. Experimental gait data from nine subjects were combined with a detailed computer model of the musculoskeletal system to determine the forces developed by the leg muscles at different running speeds. For speeds up to 7 m s(-1), the ankle plantarflexors, soleus and gastrocnemius, contributed most significantly to vertical support forces and hence increases in stride length. At speeds greater than 7 m s(-1), these muscles shortened at relatively high velocities and had less time to generate the forces needed for support. Thus, above 7 m s(-1), the strategy used to increase running speed shifted to the goal of increasing stride frequency. The hip muscles, primarily the iliopsoas, gluteus maximus and hamstrings, achieved this goal by accelerating the hip and knee joints more vigorously during swing. These findings provide insight into the strategies used by the leg muscles to maximise running performance and have implications for the design of athletic training programs.

  8. Distribution of inspiratory drive to the external intercostal muscles in humans

    Science.gov (United States)

    De Troyer, André; Gorman, Robert B; Gandevia, Simon C

    2003-01-01

    The external intercostal muscles in humans show marked regional differences in respiratory effect, and this implies that their action on the lung during breathing is primarily determined by the spatial distribution of neural drive among them. To assess this distribution, monopolar electrodes were implanted under ultrasound guidance in different muscle areas in six healthy individuals and electromyographic recordings were made during resting breathing. The muscles in the dorsal portion of the third and fifth interspace showed phasic inspiratory activity with each breath in every subject. However, the muscle in the ventral portion of the third interspace showed inspiratory activity in only three subjects, and the muscle in the dorsal portion of the seventh interspace was almost invariably silent. Also, activity in the ventral portion of the third interspace, when present, and activity in the dorsal portion of the fifth interspace were delayed relative to the onset of activity in the dorsal portion of the third interspace. In addition, the discharge frequency of the motor units identified in the dorsal portion of the third interspace averaged (mean ± s.e.m.) 11.9 ± 0.3 Hz and was significantly greater than the discharge frequency of the motor units in both the ventral portion of the third interspace (6.0 ± 0.5 Hz) and the dorsal portion of the fifth interspace (6.7 ± 0.4 Hz). The muscle in the dorsal portion of the third interspace started firing simultaneously with the parasternal intercostal in the same interspace, and the discharge frequency of its motor units was even significantly greater (11.4 ± 0.3 vs. 8.9 ± 0.2 Hz). These observations indicate that the distribution of neural inspiratory drive to the external intercostals in humans takes place along dorsoventral and rostrocaudal gradients and mirrors the spatial distribution of inspiratory mechanical advantage. PMID:12563017

  9. Fluid shifts and muscle function in humans during acute simulated weightlessness

    Science.gov (United States)

    Hargens, A. R.; Tipton, C. M.; Gollnick, P. D.; Mubarak, S. J.; Tucker, B. J.; Akeson, W. H.

    1983-01-01

    The acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surface reflex time were studied in eight supine human subjects who were placed in a 5 degrees head-down tilt position for 8 hr. Results show a cephalic fluid shift from the legs as indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. The interstitial fluid pressure in the tibialis anterior muscle and subcutaneous tissue of the lower leg was found to fall significantly, while other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. The total water content of the soleus muscle was unchanged during the head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged, while the triceps surae reflex time associated with plantar flexion movement slowed slightly. These results demonstrate a dehydration effect of head-down tilt on muscle and subcutaneous tissue of the lower leg that may affect muscle function.

  10. Mapping ECoG channel contributions to trajectory and muscle activity prediction in human sensorimotor cortex

    Science.gov (United States)

    Nakanishi, Yasuhiko; Yanagisawa, Takufumi; Shin, Duk; Kambara, Hiroyuki; Yoshimura, Natsue; Tanaka, Masataka; Fukuma, Ryohei; Kishima, Haruhiko; Hirata, Masayuki; Koike, Yasuharu

    2017-01-01

    Studies on brain-machine interface techniques have shown that electrocorticography (ECoG) is an effective modality for predicting limb trajectories and muscle activity in humans. Motor control studies have also identified distributions of “extrinsic-like” and “intrinsic-like” neurons in the premotor (PM) and primary motor (M1) cortices. Here, we investigated whether trajectories and muscle activity predicted from ECoG were obtained based on signals derived from extrinsic-like or intrinsic-like neurons. Three participants carried objects of three different masses along the same counterclockwise path on a table. Trajectories of the object and upper arm muscle activity were predicted using a sparse linear regression. Weight matrices for the predictors were then compared to determine if the ECoG channels contributed more information about trajectory or muscle activity. We found that channels over both PM and M1 contributed highly to trajectory prediction, while a channel over M1 was the highest contributor for muscle activity prediction. PMID:28361947

  11. Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes.

    Science.gov (United States)

    Albers, Peter H; Pedersen, Andreas J T; Birk, Jesper B; Kristensen, Dorte E; Vind, Birgitte F; Baba, Otto; Nøhr, Jane; Højlund, Kurt; Wojtaszewski, Jørgen F P

    2015-02-01

    Skeletal muscle is a heterogeneous tissue composed of different fiber types. Studies suggest that insulin-mediated glucose metabolism is different between muscle fiber types. We hypothesized that differences are due to fiber type-specific expression/regulation of insulin signaling elements and/or metabolic enzymes. Pools of type I and II fibers were prepared from biopsies of the vastus lateralis muscles from lean, obese, and type 2 diabetic subjects before and after a hyperinsulinemic-euglycemic clamp. Type I fibers compared with type II fibers have higher protein levels of the insulin receptor, GLUT4, hexokinase II, glycogen synthase (GS), and pyruvate dehydrogenase-E1α (PDH-E1α) and a lower protein content of Akt2, TBC1 domain family member 4 (TBC1D4), and TBC1D1. In type I fibers compared with type II fibers, the phosphorylation response to insulin was similar (TBC1D4, TBC1D1, and GS) or decreased (Akt and PDH-E1α). Phosphorylation responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS, and PDH-E1α) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared with lean and obese subjects. We conclude that human type I muscle fibers compared with type II fibers have a higher glucose-handling capacity but a similar sensitivity for phosphoregulation by insulin.

  12. Potential therapeutic effects of branched-chain amino acids supplementation on resistance exercise-based muscle damage in humans

    Directory of Open Access Journals (Sweden)

    da Luz Claudia R

    2011-12-01

    Full Text Available Abstract Branched-chain amino acids (BCAA supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE-derived biochemical markers of muscle soreness (creatine kinase (CK, aldolase, myoglobin, soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

  13. A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes

    Directory of Open Access Journals (Sweden)

    Iwamuro Masaya

    2012-12-01

    Full Text Available Abstract Background Bioartificial liver systems, designed to support patients with liver failure, are composed of bioreactors and functional hepatocytes. Immunological rejection of the embedded hepatocytes by the host immune system is a serious concern that crucially degrades the performance of the device. Induced pluripotent stem (iPS cells are considered a desirable source for bioartificial liver systems, because patient-derived iPS cells are free from immunological rejection. The purpose of this paper was to test the feasibility of a bioartificial liver system with iPS cell-derived hepatocyte-like cells. Methods Mouse iPS cells were differentiated into hepatocyte-like cells by a multi-step differentiation protocol via embryoid bodies and definitive endoderm. Differentiation of iPS cells was evaluated by morphology, PCR assay, and functional assays. iPS cell-derived hepatocyte-like cells were cultured in a bioreactor module with a pore size of 0.2 μm for 7 days. The amount of albumin secreted into the circulating medium was analyzed by ELISA. Additionally, after a 7-day culture in a bioreactor module, cells were observed by a scanning electron microscope. Results At the final stage of the differentiation program, iPS cells changed their morphology to a polygonal shape with two nucleoli and enriched cytoplasmic granules. Transmission electron microscope analysis revealed their polygonal shape, glycogen deposition in the cytoplasm, microvilli on their surfaces, and a duct-like arrangement. PCR analysis showed increased expression of albumin mRNA over the course of the differentiation program. Albumin and urea production was also observed. iPS-Heps culture in bioreactor modules showed the accumulation of albumin in the medium for up to 7 days. Scanning electron microscopy revealed the attachment of cell clusters to the hollow fibers of the module. These results indicated that iPS cells were differentiated into hepatocyte-like cells after culture

  14. Investigation of the Intra- and Inter-Limb Muscle Coordination of Hands-and-Knees Crawling in Human Adults by Means of Muscle Synergy Analysis

    Directory of Open Access Journals (Sweden)

    Xiang Chen

    2017-05-01

    Full Text Available To investigate the intra- and inter-limb muscle coordination mechanism of human hands-and-knees crawling by means of muscle synergy analysis, surface electromyographic (sEMG signals of 20 human adults were collected bilaterally from 32 limb related muscles during crawling with hands and knees at different speeds. The nonnegative matrix factorization (NMF algorithm was exerted on each limb to extract muscle synergies. The results showed that intra-limb coordination was relatively stable during human hands-and-knees crawling. Two synergies, one relating to the stance phase and the other relating to the swing phase, could be extracted from each limb during a crawling cycle. Synergy structures during different speeds kept good consistency, but the recruitment levels, durations, and phases of muscle synergies were adjusted to adapt the change of crawling speed. Furthermore, the ipsilateral phase lag (IPL value which was used to depict the inter-limb coordination changed with crawling speed for most subjects, and subjects using the no-limb-pairing mode at low speed tended to adopt the trot-like mode or pace-like mode at high speed. The research results could be well explained by the two-level central pattern generator (CPG model consisting of a half-center rhythm generator (RG and a pattern formation (PF circuit. This study sheds light on the underlying control mechanism of human crawling.

  15. GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Jessen, Niels; Pedersen, Steen Bønløkke

    2006-01-01

    Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, but the underlying GH signaling pathways have not been studied in vivo in humans. We investigated GH signaling in biopsies from muscle and abdominal fat obtained 30 (n = 3) or 60 (n...... in vivo model may be used to study the mechanisms subserving the actions of GH on substrate metabolism and insulin sensitivity in muscle and fat....

  16. Differences in the interaction of acetylcholine receptor antibodies with receptor from normal, denervated and myasthenic human muscle.

    OpenAIRE

    Lefvert, A. K.

    1982-01-01

    The interaction of acetylcholine receptor antibodies with different kinds of human skeletal muscle receptor was investigated. The reaction of most receptor antibodies was strongest with receptor from a patient with myasthenia gravis and with receptor from denervated muscle. Results obtained with these receptors were well correlated. The binding of most receptor antibodies to receptor from functionally normal muscle was much weaker and also qualitatively different. In a few patients with moder...

  17. Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta

  18. Muscle contractile properties as an explanation of the higher mean power output in marmosets than humans during jumping.

    Science.gov (United States)

    Plas, Rogier L C; Degens, Hans; Meijer, J Peter; de Wit, Gerard M J; Philippens, Ingrid H C H M; Bobbert, Maarten F; Jaspers, Richard T

    2015-07-01

    The muscle mass-specific mean power output (PMMS,mean) during push-off in jumping in marmosets (Callithrix jacchus) is more than twice that in humans. In the present study it was tested whether this is attributable to differences in muscle contractile properties. In biopsies of marmoset m. vastus lateralis (VL) and m. gastrocnemius medialis (GM) (N=4), fibre-type distribution was assessed using fluorescent immunohistochemistry. In single fibres from four marmoset and nine human VL biopsies, the force-velocity characteristics were determined. Marmoset VL contained almost exclusively fast muscle fibres (>99.0%), of which 63% were type IIB and 37% were hybrid fibres, fibres containing multiple myosin heavy chains. GM contained 9% type I fibres, 44% type IIB and 47% hybrid muscle fibres. The proportions of fast muscle fibres in marmoset VL and GM were substantially larger than those reported in the corresponding human muscles. The curvature of the force-velocity relationships of marmoset type IIB and hybrid fibres was substantially flatter than that of human type I, IIA, IIX and hybrid fibres, resulting in substantially higher muscle fibre mass-specific peak power (PFMS,peak). Muscle mass-specific peak power output (PMMS,peak) values of marmoset whole VL and GM, estimated from their fibre-type distributions and force-velocity characteristics, were more than twice the estimates for the corresponding human muscles. As the relative difference in estimated PMMS,peak between marmosets and humans is similar to that of PMMS,mean during push-off in jumping, it is likely that the difference in in vivo mechanical output between humans and marmosets is attributable to differences in muscle contractile properties.

  19. Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Frøsig, Christian; Kjøbsted, Rasmus

    2017-01-01

    Insulin resistance is a major health risk and although exercise clearly improves skeletal muscle insulin sensitivity, the mechanisms are unclear. Here we show that initiation of a euglycemic hyperinsulinemic clamp four hours after single-legged exercise in humans increased microvascular perfusion...... and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand.......Insulin resistance is a major health risk and although exercise clearly improves skeletal muscle insulin sensitivity, the mechanisms are unclear. Here we show that initiation of a euglycemic hyperinsulinemic clamp four hours after single-legged exercise in humans increased microvascular perfusion...... the insulin stimulated increase in microvascular perfusion in both legs and abrogated the greater glucose uptake in the exercised compared with the rested leg. Skeletal muscle phosphorylation of TBC1D4 Ser(318) and Ser(704) and glycogen synthase activity were greater in the exercised leg before insulin...

  20. Otilonium bromide inhibits calcium entry through L-type calcium channels in human intestinal smooth muscle.

    Science.gov (United States)

    Strege, P R; Evangelista, S; Lyford, G L; Sarr, M G; Farrugia, G

    2004-04-01

    Otilonium bromide (OB) is used as an intestinal antispasmodic. The mechanism of action of OB is not completely understood. As Ca(2+) entry into intestinal smooth muscle is required to trigger contractile activity, our hypothesis was that OB blocked Ca(2+) entry through L-type Ca(2+) channels. Our aim was to determine the effects of OB on Ca(2+), Na(+) and K(+) ion channels in human jejunal circular smooth muscle cells and on L-type Ca(2+) channels expressed heterologously in HEK293 cells. Whole cell currents were recorded using standard patch clamp techniques. Otilonium bromide (0.09-9 micromol L(-1)) was used as this reproduced clinical intracellular concentrations. In human circular smooth muscle cells, OB inhibited L-type Ca(2+) current by 25% at 0.9 micromol L(-1) and 90% at 9 micromol L(-1). Otilonium bromide had no effect on Na(+) or K(+) currents. In HEK293 cells, 1 micromol L(-1) OB significantly inhibited the expressed L-type Ca(2+) channels. Truncation of the alpha(1C) subunit C and N termini did not block the inhibitory effects of OB. Otilonium bromide inhibited Ca(2+) entry through L-type Ca(2+) at concentrations similar to intestinal tissue levels. This effect may underlie the observed muscle relaxant effects of the drug.

  1. Optimizing the measurement of mitochondrial protein synthesis in human skeletal muscle.

    Science.gov (United States)

    Burd, Nicholas A; Tardif, Nicolas; Rooyackers, Olav; van Loon, Luc J C

    2015-01-01

    The measurement of mitochondrial protein synthesis after food ingestion, contractile activity, and/or disease is often used to provide insight into skeletal muscle adaptations that occur in the longer term. Studies have shown that protein ingestion stimulates mitochondrial protein synthesis in human skeletal muscle. Minor differences in the stimulation of mitochondrial protein synthesis occur after a single bout of resistance or endurance exercise. There appear to be no measurable differences in mitochondrial protein synthesis between critically ill patients and aged-matched controls. However, the mitochondrial protein synthetic response is reduced at a more advanced age. In this paper, we discuss the challenges involved in the measurement of human skeletal muscle mitochondrial protein synthesis rates based on stable isotope amino acid tracer methods. Practical guidelines are discussed to improve the reliability of the measurement of mitochondrial protein synthesis rates. The value of the measurement of mitochondrial protein synthesis after a single meal or exercise bout on the prediction of the longer term skeletal muscle mass and performance outcomes in both the healthy and disease populations requires more work, but we emphasize that the measurements need to be reliable to be of any value to the field.

  2. Firing rate modulation of human motor units in different muscles during isometric contraction with various forces.

    Science.gov (United States)

    Seki, K; Narusawa, M

    1996-05-06

    To examine the factors affecting the control of human motor units, rate coding strategies of the motor units were investigated in upper limb and intrinsic hand muscles during voluntary isometric contraction of steady force levels up to 80% of maximal voluntary contraction. Numerous spike trains from single motor units were recorded from the m. first dorsal interosseous (FDI) and the m. biceps brachii (BB) of eight human subjects by means of tungsten micro-electrodes, and the mean firing rate (MFR) was calculated for each subject and inter-individual comparisons made. The MFRs of the FDI were larger than that of the BB at the higher force level, and substantial differences were not found between these muscles at the lower force level. The slope of the linear regression line of MFRs vs. exerted forces for the FDI was more than twice that for the BB. Therefore, isometric force control of the FDI depends more on the rate coding strategy. The difference in rate coding between the FDI and BB motor units may be determined by factors other than muscle fiber composition, because both muscles are known to possess a similar composition of fiber types. Possible mechanisms underlying these characteristics of rate coding strategy are considered in this report.

  3. Sexual dimorphism in the histologic organization of the muscle fibers in human tongue.

    Science.gov (United States)

    de Campos, Deivis; Jotz, Geraldo Pereira; Heck, Layana; Xavier, Léder Leal

    2014-07-01

    Tongue movements are critical for speech, swallowing, and respiration; and tongue dysfunction could lead to dysarthria, dysphagia, and obstructive sleep apnea, respectively. Our current understanding of the contributions of specific tongue muscles (TOs) to precise movement patterns is limited. Likewise, there is still little information regarding the orientation of histologic muscle fibers of the tongue in humans, especially between men and women. Thus, the aim of this study was to compare the histologic organization in the tongue of men and women. Ten tongues were studied in human specimens obtained from necropsies (five men and five women). The muscles were analyzed using histology, and the morphometric parameters were measured using Image Pro-Plus Software (Image Pro-Plus 6.0; Media Cybernetics, Silver Spring, MD). Slices were obtained from the anterior, median, and posterior parts of the tongue. We classified and estimated the percentages of transverse (T), oblique (O), and longitudinal (L) fibers in the tongue. To quantify the percentage of fibers in each category in the tongue, the shape coefficient (Shape Z) was estimated. Statistical differences were found between the orientation of the muscle fibers of men and women only for the middle region of the tongue. The middle region of the tongue in women compared with men has a smaller difference in the variation of the percentage of fibers T (P=0.0004), O (P=0.0006), and L (P=0.0013). These morphologic findings are probably related to physiological differences.

  4. Effect of contraction intensity on sympathetic nerve activity to active human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Daniel eBoulton

    2014-06-01

    Full Text Available The effect of contraction intensity on muscle sympathetic nerve activity (MSNA to active human limbs has not been established. To address this, MSNA was recorded from the left peroneal nerve during and after dorsiflexion contractions sustained for two minutes by the left leg at ~10, 25 and 40 %MVC. To explore the involvement of the muscle metaboreflex, limb ischaemia was imposed midway during three additional contractions and maintained during recovery. Compared with total MSNA at rest (11.5 ± 4.1 mv.min-1, MSNA in the active leg increased significantly at the low (21.9 ± 13.6 mv.min-1, medium (30.5 ± 20.8 mv.min-1 and high (50.0 ± 24.5 mv.min-1 intensities. This intensity-dependent effect was more strongly associated with increases in MSNA burst amplitude than burst frequency. Total MSNA then returned to resting levels within the first minute of recovery. Limb ischaemia had no significant influence on the intensity-dependent rise in MSNA or its decline during recovery in the active leg. These findings reveal intensity-dependent increases in total MSNA and burst amplitude to contracting human skeletal muscle that do not appear to involve the muscle metaboreflex.

  5. Composition and adaptation of human myotendinous junction and neighboring muscle fibers to heavy resistance training.

    Science.gov (United States)

    Jakobsen, J R; Mackey, A L; Knudsen, A B; Koch, M; Kjaer, M; Krogsgaard, M R

    2016-10-26

    The myotendinous junction (MTJ) is a common site of strain injury and yet understanding of its composition and ability to adapt to loading is poor. The main aims of this study were to determine the profile of selected collagens and macrophage density in human MTJ and adjoining muscle fibers, and to investigate whether heavy exercise loading would alter this profile. Fifteen individuals scheduled for anterior cruciate ligament repair surgery were randomized into three groups: control, acute or 4 weeks heavy resistance training. MTJ samples were collected from the semitendinosus and gracilis muscles and were sectioned and stained immunohistochemically for collagen types I, III, VI, XII, XIV, XXII, Tenascin-C and CD68. Macrophage density and distribution was evaluated and the amount of each collagen type in muscle and MTJ was graded. Collagen XXII was observed solely at the MTJ, while all other collagens were abundant at the MTJ and in muscle perimysium or endomysium. The endomysial content of collagen XIV, macrophages and Tenascin-C increased following 4 weeks of training. These findings illustrate the heterogeneity of collagen type composition of human MTJ. The increase in collagen XIV following 4 weeks of training may reflect a training-induced protection against strain injuries in this region. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis.

    Science.gov (United States)

    Welvaart, W N; Paul, M A; van Hees, H W H; Stienen, G J M; Niessen, J W M; de Man, F S; Sieck, G C; Vonk-Noordegraaf, A; Ottenheijm, C A C

    2011-08-01

    Recent studies proposed that mechanical inactivity of the human diaphragm during mechanical ventilation rapidly causes diaphragm atrophy and weakness. However, conclusive evidence for the notion that diaphragm weakness is a direct consequence of mechanical inactivity is lacking. To study the effect of hemidiaphragm paralysis on diaphragm muscle fiber function and structure in humans, biopsies were obtained from the paralyzed hemidiaphragm in eight patients with hemidiaphragm paralysis. All patients had unilateral paralysis of known duration, caused by en bloc resection of the phrenic nerve with a tumor. Furthermore, diaphragm biopsies were obtained from three control subjects. The contractile performance of demembranated muscle fibers was determined, as well as fiber ultrastructure and morphology. Finally, expression of E3 ligases and proteasome activity was determined to evaluate activation of the ubiquitin-proteasome pathway. The force-generating capacity, as well as myofibrillar ultrastructure, of diaphragm muscle fibers was preserved up to 8 wk of paralysis. The cross-sectional area of slow fibers was reduced after 2 wk of paralysis; that of fast fibers was preserved up to 8 wk. The expression of the E3 ligases MAFbx and MuRF-1 and proteasome activity was not significantly upregulated in diaphragm fibers following paralysis, not even after 72 and 88 wk of paralysis, at which time marked atrophy of slow and fast diaphragm fibers had occurred. Diaphragm muscle fiber atrophy and weakness following hemidiaphragm paralysis develops slowly and takes months to occur.

  7. Expression of cytosolic 5' nucleotidase does not correlate with expression of oxidative metabolism marker: myoglobine in human skeletal muscles

    Institute of Scientific and Technical Information of China (English)

    Katarzyna Lechward; Kinga Tkacz-Stachowska

    2009-01-01

    Our previous studies had shown that eytosolic 5'nucleotidase-I (eN-I) is expressed in several tissues in pigeons, including brain and several different skeletal muscles. We observed that cN-I mRNA levels varied among different pigeon muscles. Initial quantification of the differences revealed that ~5-10 times more of cN-I transcript was present in red, oxidative muscles (breast muscle and gastrocnemius) than in white ones,composed of glycolytic fibers (biceps brachii). We had found this observation very intriguing and decided to compare human skeletal muscles distribution of cN-I with the type of oxygen metabolism. Our screen involved 60 samples of several human muscles and we assayed the correlation between the amount of tran-scripts of cN-I and myoglobine, which we took as a measure of oxidative-slow twitch fibers. Our question was whether in humans, cN-I presence in skeletal muscles was related to their fiber composition. If that was the case, then cN-I expression could serve as a tool to assess the percentage of oxidative fibers in any given human muscle sample, where myogiobine expression could not be readily measured. After quantification of expression of both genes, we concluded that there was no correlation between expression of cN-I and fiber type. Therefore, contrary to the pigeon muscles, cN-Idid not reflect the ratio of oxidative fibers to the total mass of the muscle sample in humans. That difference indicated that there were certain mechanisms that dif-ferentially regulated the expression of cN-I in muscle tissues of mammals and lower vertebrates.

  8. Does ankle joint power reflect type of muscle action of soleus and gastrocnemius during walking in cats and humans?

    Science.gov (United States)

    Cronin, Neil J; Prilutsky, Boris I; Lichtwark, Glen A; Maas, Huub

    2013-04-26

    The main objective of this paper is to highlight the difficulties of identifying shortening and lengthening contractions based on analysis of power produced by resultant joint moments. For that purpose, we present net ankle joint powers and muscle fascicle/muscle-tendon unit (MTU) velocities for medial gastrocnemius (MG) and soleus (SO) muscles during walking in species of different size (humans and cats). For the cat, patterns of ankle joint power and MTU velocity of MG and SO during stance were similar: negative power (ankle moment×angular velocitypower (generation of mechanical energy) was found during MTU shortening. This was also found for the general fascicle velocity pattern in SO. In contrast, substantial differences between ankle joint power and fascicle velocity patterns were observed for MG muscle. In humans, like cats, the patterns of ankle joint power and MTU velocity of SO and MG were similar. Unlike the cat, there were substantial differences between patterns of fascicle velocity and ankle joint power during stance in both muscles. These results indicate that during walking, only a small fraction of mechanical work of the ankle moment is either generated or absorbed by the muscle fascicles, thus confirming the contribution of in-series elastic structures and/or energy transfer via two-joint muscles. We conclude that ankle joint negative power does not necessarily indicate eccentric action of muscle fibers and that positive power cannot be exclusively attributed to muscle concentric action, especially in humans.

  9. Effect of muscle contraction levels on the force-length relationship of the human Achilles tendon during lengthening of the triceps surae muscle-tendon unit.

    Science.gov (United States)

    Sugisaki, Norihide; Kawakami, Yasuo; Kanehisa, Hiroaki; Fukunaga, Tetsuo

    2011-07-28

    Findings from animal experiments are sometimes contradictory to the idea that the tendon structure is a simple elastic spring in series with muscle fibers, and suggest influence of muscle contraction on the tendon mechanical properties. The purpose of the present study was to investigate the influence of muscle contraction levels on the force-length relationship of the human Achilles tendon during lengthening of the triceps surae muscle-tendon unit. For seven subjects, ankle dorsiflexion was performed without (passive condition) and with contraction of plantar flexor muscles (eccentric conditions, at 3 contraction levels) on an isokinetic dynamometer. Deformation of the Achilles tendon during each trial was measured using ultrasonography. The Achilles tendon force corresponding to the tendon elongation of 10mm in the passive condition was significantly smaller than those in the eccentric conditions (p<0.05 or p<0.01). Within the eccentric conditions, the Achilles tendon force corresponding to the tendon elongation of 10mm was significantly greater in the maximal contraction level than those in submaximal eccentric conditions (p<0.05 or p<0.01). In addition, the tendon stiffness was greater in higher contraction levels (p<0.05 or p<0.01). Present results suggest that the human tendon structure is not a simple elastic spring in series with muscle fibers.

  10. Anabolic processes in human skeletal muscle: restoring the identities of growth hormone and testosterone.

    Science.gov (United States)

    West, Daniel W D; Phillips, Stuart M

    2010-10-01

    that we believe are more important for stimulating hypertrophy in human skeletal muscle. Clarifying both the role of hormones in regulating muscle mass as well as the underlying basis for adaptation of skeletal muscle to resistance exercise will hopefully enhance and support the prescription of resistance exercise as an integral component of a healthy lifestyle.

  11. Strenuous resistance exercise effects on magnetic resonance diffusion parameters and muscle-tendon function in human skeletal muscle.

    Science.gov (United States)

    Yanagisawa, Osamu; Kurihara, Toshiyuki; Kobayashi, Naoyuki; Fukubayashi, Toru

    2011-10-01

    To assess the effects of strenuous exercise on magnetic resonance diffusion parameters and muscle-tendon complex function in skeletal muscle. Six men performed ankle plantar flexion exercises with eccentric contraction. The fractional anisotropy (FA), λ(1) , λ(2) , λ(3) , mean diffusivity (MD), and T(2) values in the triceps surae muscles were measured by magnetic resonance diffusion tensor and spin-echo imaging. Passive torque of plantar flexors, maximal voluntary isometric plantar flexion torques (MVIP), and Achilles tendon stiffness during MVIP were measured by combined ultrasonography and dynamometry. Plasma creatine kinase and muscle soreness were also assessed. These parameters were measured before and 1-8 days postexercise. The medial gastrocnemius exhibited significantly decreased FA 2-5 days after, increased λ(2) 3 days after, and increased λ(3) 2 and 3 days after exercise. This muscle also showed significantly increased MD and T(2) values 3 days postexercise. MVIP significantly decreased 2 and 3 days postexercise, while passive torque significantly increased 2 days postexercise. Creatine kinase and muscle soreness increased 3-5 days and 1-5 days postexercise, respectively. Exercise-induced muscle damage manifested as significant changes in muscle diffusion parameters with muscle-tendon complex dysfunction and delayed-onset muscle soreness. Copyright © 2011 Wiley-Liss, Inc.

  12. Discrepancies between Skinned Single Muscle Fibres and Whole Thigh Muscle Function Characteristics in Young and Elderly Human Subjects

    Directory of Open Access Journals (Sweden)

    Hyunseok Jee

    2016-01-01

    Full Text Available We aimed to analyse the mechanical properties of skinned single muscle fibres derived from the vastus lateralis (VL muscle in relation to those of the whole intact thigh muscle and to compare any difference between young and older adults. Sixteen young men (29.25±4.65 years, 11 older men (71.45±2.94 years, 11 young women (29.64±4.88 years, and 7 older women (67.29±1.70 years were recruited. In vivo analyses were performed for mechanical properties such as isokinetic performance, isometric torque, and power. Specific force and maximum shortening velocity (Vo were measured with single muscle fibres. Sex difference showed greater impact on the functional properties of both the whole muscle (p<0.01 and single muscle fibres than aging (p<0.05. Sex difference, rather than aging, yielded more remarkable differences in gross mechanical properties in the single muscle fibre study in which significant differences between young men and young women were found only in the cross-sectional area and Vo (p<0.05. Age and sex differences reflect the mechanical properties of both single muscle fibres and whole thigh muscle, with the whole muscle yielding more prominent functional properties.

  13. Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

    Science.gov (United States)

    Putney, S; Herlihy, W; Royal, N; Pang, H; Aposhian, H V; Pickering, L; Belagaje, R; Biemann, K; Page, D; Kuby, S

    1984-12-10

    A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

  14. Changes in satellite cells in human skeletal muscle after a single bout of high intensity exercise

    DEFF Research Database (Denmark)

    Crameri, Regina M; Langberg, Henning; Magnusson, Peter

    2004-01-01

    desmin or dystrophin, were not observed, and hence did not appear to induce the expression of either N-CAM or FA1. We therefore propose that satellite cells can be induced to re-enter the cell growth cycle after a single bout of unaccustomed high intensity exercise. However, a single bout of exercise......No studies to date have reported activation of satellite cells in vivo in human muscle after a single bout of high intensity exercise. In this investigation, eight individuals performed a single bout of high intensity exercise with one leg, the contralateral leg being the control. A significant...... increase in mononuclear cells staining for the neural cell adhesion molecule (N-CAM) and fetal antigen 1 (FA1) were observed within the exercised human vastus lateralis muscle on days 4 and 8 post exercise. In addition, a significant increase in the concentration of the FA1 protein was determined...

  15. 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

    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......, 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...... MPs inhibited MPC fusion while anti-inflammatory MPs strongly promoted MPC differentiation by increasing their commitment into differentiated myocytes and the formation of mature myotubes. Furthermore, the in vivo time course of expression of myogenic and MP markers was studied in regenerating human...

  16. Exercise-induced increase in maximal in vitro Na-K-ATPase activity in human skeletal muscle

    DEFF Research Database (Denmark)

    Juel, Carsten; Nordsborg, Nikolai Baastrup; Bangsbo, Jens

    2013-01-01

    The present study investigated whether the maximal in vitro Na,K-ATPase activity in human skeletal muscle is changed with exercise and whether it was altered by acute hypoxia. Needle biopsies from 14 subjects were obtained from vastus lateralis before and after 4 min of intense muscle activity...

  17. Repeatability of Corticospinal and Spinal Measures during Lengthening and Shortening Contractions in the Human Tibialis Anterior Muscle

    NARCIS (Netherlands)

    Tallent, Jamie; Goodall, Stuart; Hortobagyi, Tibor; Gibson, Alan St Clair; French, Duncan N.; Howatson, Glyn

    2012-01-01

    Elements of the human central nervous system (CNS) constantly oscillate. In addition, there are also methodological factors and changes in muscle mechanics during dynamic muscle contractions that threaten the stability and consistency of transcranial magnetic stimulation (TMS) and perpherial nerve s

  18. Type ⅡB human skeletal muscle fibers positively correlate with bone mineral density irrespective to age

    Institute of Scientific and Technical Information of China (English)

    Wing-Hoi Cheung; Wing-Sze Lee; Ling Qin; Ning Tang; Vivian Wing-Yin Hung; Kwok-Sui Leung

    2010-01-01

    Background Age-associated decrease in type ⅡA/B human skeletal muscle fibers was detected in human biopsies in our previous study. The relationship between change in muscle fiber typing and bone mineral density (BMD) is, however,unknown either cross-sectionally or longitudinally. We therefore conducted a cross-sectional study to investigate their correlation using human muscle biopsies.Methods Forty human subjects aged (53.4±20.2) years were recruited. Histomorphometric parameters of their muscle biopsies were measured by ATPase staining and image analysis, including average area percentage, fiber number percentage, mean fiber area, and area percentage of connective tissues. Hip and spine BMD was measured by dual-energy X-ray absorptiometry. Partial correlation with adjusting age was performed.Results Type ⅡB muscle fiber was found positively correlated with hip BMD irrespective to age and demonstrated significantly stronger relationship with BMD among all fiber types, in terms of its cross-sectional area (r=0.380, P=0.029)and size (r=0.389, P=0.025). Type ⅡA muscle fibers associated with hip BMD in mean fiber area only (r=0.420, P=0.015).Conclusions Type ⅡB muscle fiber may play an important role in maintaining bone quality. This may also be a relatively more sensitive fiber type of sarcopenia and osteoporosis. These findings further consolidate the muscle-bone relationship.

  19. Serotonin and Histamine Therapy Increases Tetanic Forces of Myoblasts, Reduces Muscle Injury, and Improves Grip Strength Performance of Dmdmdx Mice

    Directory of Open Access Journals (Sweden)

    Volkan Gurel

    2015-11-01

    Full Text Available Duchenne muscular dystrophy (DMD is a recessive X-linked fatal disorder caused by a mutation in the dystrophin gene. Although several therapeutic approaches have been studied, none has led to substantial long-term effects in patients. The aim of this study was to test a serotonin and histamine (S&H combination on human skeletal myoblasts and Dmdmdx mice for its effects on muscle strength and injury. Normal human bioartificial muscles (BAMs were treated, and muscle tetanic forces and muscle injury tests were performed using the MyoForce Analysis System. Dmdmdx mice, the murine model of DMD, were administered serotonin, histamine, or S&H combination twice daily for 6 weeks, and functional performance tests were conducted once a week. The S&H combination treatment caused significant increases in tetanic forces at all time points and concentrations tested as compared to the saline controls. Dose response of the BAMs to the treatment demonstrated a significant increase in force generation at all concentrations compared to the controls after 3 to 4 days of drug treatment. The highest 3 concentrations had a significant effect on lowering contractile-induced injury as measured by a reduction in the release of adenylate kinase. Histamine-only and S&H treatments improved grip strength of Dmdmdx mice, whereas serotonin-only treatment resulted in no significant improvement in muscle strength. The results of this study indicate that S&H therapy might be a promising new strategy for muscular dystrophies and that the mechanism should be further investigated.

  20. Microdialysis and the measurement of muscle interstitial K+ during rest and exercise in humans

    DEFF Research Database (Denmark)

    Green, Stefan Mathias; Bülow, J; Saltin, B

    1999-01-01

    medialis muscle of four humans during rest and static plantar flexion exercise. At rest, Ki+ was 3.9-4.3 mmol/l when the perfusate flow was 2 or 5 microl/min. During exercise, Ki+ increased from 6.9 +/- 0.4 to 7.5 +/- 0.3 mmol/l at low to high intensity and declined to 5.2 +/- 0.3 mmol/l after exercise...

  1. Temperature Changes During Therapeutic Ultrasound in the Precooled Human Gastrocnemius Muscle

    OpenAIRE

    1994-01-01

    Therapeutic ultrasound is frequently employed as a deep heating rehabilitation modality. It is administered in one of three ways: a) ultrasound with no preceding treatment, b) ultrasound on preheated tissues, or c) ultrasound on precooled tissues. The purpose of this study was to investigate the effect of ultrasound treatments on the tissue temperature rise of precooled human gastrocnemius muscle. Sixteen male subjects had a 23-gauge hypodermic needle microprobe inserted 3 cm deep into the me...

  2. Accurate Quantitation of Dystrophin Protein in Human Skeletal Muscle Using Mass Spectrometry

    OpenAIRE

    Brown, Kristy J; Marathi, Ramya; Fiorillo, Alyson A; Ciccimaro, Eugene F.; Sharma, Seema; Rowlands, David S.; Rayavarapu, Sree; Nagaraju, Kanneboyina; Eric P. Hoffman; Hathout, Yetrib

    2012-01-01

    Quantitation of human dystrophin protein in muscle biopsies is a clinically relevant endpoint for both diagnosis and response to dystrophin-replacement therapies for dystrophinopathies. A robust and accurate assay would enable the use of dystrophin as a surrogate biomarker, particularly in exploratory Phase 2 trials. Currently available methods to quantitate dystrophin rely on immunoblot or immunohistochemistry methods that are not considered robust. Here we present a mass spectrometry based ...

  3. Retraction: Pid1 Induces Insulin Resistance in Both Human and Mouse Skeletal Muscle during Obesity

    OpenAIRE

    Bonala, Sabeera; McFarlane, Craig; Ang, Jackie; Lim, Radiance; Lee, Marcus; Chua, Hillary; Lokireddy, Sudarsanareddy; Sreekanth, Patnam; Shing Leow, Melvin Khee; Meng, Khoo Chin; Shyong, TAI E; Lee, Yung Seng; Peter D. Gluckman; Sharma, Mridula; Kambadur, Ravi

    2013-01-01

    Obesity is associated with insulin resistance and abnormal peripheral tissue glucose uptake. However, the mechanisms that interfere with insulin signaling and glucose uptake in human skeletal muscle during obesity are not fully characterized. Using microarray, we have identified that the expression of Pid1 gene, which encodes for a protein that contains a phosphotyrosine-interacting domain, is increased in myoblasts established from overweight insulin-resistant individuals. Molecular analysis...

  4. Force depression following muscle shortening in sub-maximal voluntary contractions of human adductor pollicis.

    Science.gov (United States)

    Rousanoglou, Elissavet N; Oskouei, Ali E; Herzog, Walter

    2007-01-01

    Mechanical properties of skeletal muscles are often studied for controlled, electrically induced, maximal, or supra-maximal contractions. However, many mechanical properties, such as the force-length relationship and force enhancement following active muscle stretching, are quite different for maximal and sub-maximal, or electrically induced and voluntary contractions. Force depression, the loss of force observed following active muscle shortening, has been observed and is well documented for electrically induced and maximal voluntary contractions. Since sub-maximal voluntary contractions are arguably the most important for everyday movement analysis and for biomechanical models of skeletal muscle function, it is important to study force depression properties under these conditions. Therefore, the purpose of this study was to examine force depression following sub-maximal, voluntary contractions. Sets of isometric reference and isometric-shortening-isometric test contractions at 30% of maximal voluntary effort were performed with the adductor pollicis muscle. All reference and test contractions were executed by controlling force or activation using a feedback system. Test contractions included adductor pollicis shortening over 10 degrees, 20 degrees, and 30 degrees of thumb adduction. Force depression was assessed by comparing the steady-state isometric forces (activation control) or average electromyograms (EMGs) (force control) following active muscle shortening with those obtained in the corresponding isometric reference contractions. Force was decreased by 20% and average EMG was increased by 18% in the shortening test contractions compared to the isometric reference contractions. Furthermore, force depression was increased with increasing shortening amplitudes, and the relative magnitudes of force depression were similar to those found in electrically stimulated and maximal contractions. We conclude from these results that force depression occurs in sub

  5. Expression of human IAP-like protein in skeletal muscle: a possible explanation for the rare incidence of muscle fiber apoptosis in T-cell mediated inflammatory myopathies.

    Science.gov (United States)

    Li, M; Dalakas, M C

    2000-07-01

    In Polymyositis (PM) and sporadic Inclusion Body Myositis (s-IBM), the CD8(+) cytotoxic T cells invade the muscle membrane and release perforin and granzyme B to induce cell death. Although granzyme B is a direct activator of executioner caspases, there is no convincing evidence of apoptosis in the muscle fibers of these patients. To search for an explanation, we examined the muscle expression of the human IAP-Like Protein (hILP), an evolutionarily conserved cell death suppressor, that exerts major anti-apoptotic effects by inhibiting the executioner caspases. Muscle biopsy specimens from patients with inflammatory myopathies and controls were studied with: (a) immunocytochemistry using antibodies against hILP and caspase-3 in single and double-labeled confocal laser microscopy; (b) immunoblotting of muscle extracts immunoreacted with anti-hILP antibodies; and (c) subcellular fractionation of muscle lysates immunoreacted with antibodies against hILP. We found that hILP is expressed on the sarcolemmal region and co-localizes with dystrophin. Caspase-3 is undetectable. Subcellular fractionation of the muscle specimens confirmed that hILP is a membrane-associated protein. By immunoblotting, the 57 kD hILP was abundantly expressed in the normal as well as the diseased muscles. We conclude that in s-IBM and PM the expression of hILP, a major cell death suppressor, on the muscle membrane may prevent the induction of apoptosis by the autoinvasive cytotoxic T cells on the cell surface, by inhibiting the caspase activation.

  6. Communication channel modeling of human forearm with muscle fiber tissue characteristics.

    Science.gov (United States)

    Zhang, Shuang; Pun, Sio Hang; Mak, Peng Un; Qin, Yu-Ping; Liu, Yi-He; Vai, Mang I

    2016-09-14

    Human-Body Communication (HBC) is a wireless communication method using the human body tissue as a transmission medium for signals. This paper on the basis of human muscle fiber tissues' characteristics, it is first proposed to establish the analytical model of galvanic coupling human-body communication channel. In this model, the parallel and the transverse electrical characteristics of muscular tissue are fully considered, and the model accurately presents the transmission mechanism of galvanic coupling human-body communication signals in the channel. At last, through compare with the experimental results and calculation results, the maximum error of the model is 22.4% and the average error is 14.2% within the frequency range.

  7. Detection of histidine decarboxylase mRNA in human vascular smooth muscle and endothelial cells.

    Science.gov (United States)

    Tippens, A S; Gruetter, C A

    2004-06-01

    The objective of this study was to investigate histamine synthesis capability of human vascular smooth muscle and endothelial cells by detecting histidine decarboxylase (HDC) mRNA. HDC catalyzes exclusively the formation of histamine in mammalian cells. Experiments utilizing nested reverse transcription-polymerase chain reaction (nRT-PCR) were conducted to detect the presence of HDC mRNA. Human aortic smooth muscle cells (HAoSMC) and human aortic endothelial cells (HAEC) were cultured and RNA was extracted and amplified using two sets of HDC-specific primers. Rat liver and kidney RNA were isolated and amplified to serve as positive and negative controls, respectively. Gel electrophoresis of HAoSMC, HAEC and liver mRNA revealed bands coinciding with an expected product size of 440 base pairs. Sequence analysis revealed that the observed bands were the appropriate HDC amplicons. These findings are the first to indicate the presence of HDC mRNA in vascular smooth muscle cells and confirm the presence of HDC mRNA in endothelial cells which is consistent with an ability of these cell types to synthesize histamine in the vascular wall.

  8. Simulation of muscle and adipose tissue deformation in the passive human pharynx.

    Science.gov (United States)

    Carrigy, Nicholas B; Carey, Jason P; Martin, Andrew R; Remmers, John E; Zareian, Ali; Topor, Zbigniew; Grosse, Joshua; Noga, Michelle; Finlay, Warren H

    2016-01-01

    Quantifying the contribution of passive mechanical deformation in the human pharynx to upper airway collapse is fundamental to understanding the competing biomechanical processes that maintain airway patency. This study uses finite element analysis to examine deformation in the passive human pharynx using an intricate 3D anatomical model based on computed tomography scan images. Linear elastic properties are assigned to bone, cartilage, ligament, tendon, and membrane structures based on a survey of values reported in the literature. Velopharyngeal and oropharyngeal cross-sectional area versus airway pressure slopes are determined as functions of Young's moduli of muscle and adipose tissue. In vivo pharyngeal mechanics for small deformations near atmospheric pressure are matched by altering Young's moduli of muscle and adipose tissue. The results indicate that Young's moduli ranging from 0.33 to 14 kPa for muscle and adipose tissue matched the in vivo range of area versus pressure slopes. The developed anatomical model and determined Young's moduli range are expected to be useful as a starting point for more complex simulations of human upper airway collapse and obstructive sleep apnea therapy.

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

    Directory of Open Access Journals (Sweden)

    Charles eAffourtit

    2015-07-01

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

  10. Characterization of MR-1, a Novel Myofibrillogenesis Regulator in Human Muscle

    Institute of Scientific and Technical Information of China (English)

    Tian-Bo LI; Xiu-Hua LIU; Shuang FENG; Yang HU; Wei-Xi YANG; Yue HAN; Yi-Guang WANG; Li-Min GONG

    2004-01-01

    The actin-myosin contractile apparatus consists of several thick filament and thin filament proteins.Specific regulatory mechanisms are involved in this highly ordered process.In this paper,we reported the identification and characterization of a novel myofibrillogenesis regulator,MR-l.The MR-lgene was cloned from human skeletal muscle cDNA library by using a strategy that involves EST data base searching,PCR and RACE.The MR-l gene is located on human chromosome 2q35 and encodes a 142 aa protein.Northern blot revealed that the mRNA level of MR-1 was highest in the skeletal muscle and certain level of MR-1 expression was also observed in heart,liver and kidney.Immunohistochemical assay confirmed that the MR-l protein existed in human myocardial myofibrils.It was found by yeast two-hybrid screening and confirmed by in vitro binding assay that MR-1 could interact with sarcomeric proteins,such as myosin regulatory light chain,myomesin 1 and β-enolase.These studies suggested that MR-I might play a regulatory role in the muscle cell and it was worth investigating further.

  11. Postmortem muscle protein degradation in humans as a tool for PMI delimitation.

    Science.gov (United States)

    Pittner, Stefan; Ehrenfellner, Bianca; Monticelli, Fabio C; Zissler, Angela; Sänger, Alexandra M; Stoiber, Walter; Steinbacher, Peter

    2016-11-01

    Forensic estimation of time since death relies on diverse approaches, including measurement and comparison of environmental and body core temperature and analysis of insect colonization on a dead body. However, most of the applied methods have practical limitations or provide insufficient results under certain circumstances. Thus, new methods that can easily be implemented into forensic routine work are required to deliver more and discrete information about the postmortem interval (PMI). Following a previous work on skeletal muscle degradation in the porcine model, we analyzed human postmortem skeletal muscle samples of 40 forensic cases by Western blotting and casein zymography. Our results demonstrate predictable protein degradation processes in human muscle that are distinctly associated with temperature and the PMI. We provide information on promising degradation markers for certain periods of time postmortem, which can be useful tools for time since death delimitation. In addition, we discuss external influencing factors such as age, body mass index, sex, and cause of death that need to be considered in future routine application of the method in humans.

  12. Genetic complementation of human muscle cells via directed stem cell fusion.

    Science.gov (United States)

    Gonçalves, Manuel A F V; Swildens, Jim; Holkers, Maarten; Narain, Anjali; van Nierop, Gijsbert P; van de Watering, Marloes J M; Knaän-Shanzer, Shoshan; de Vries, Antoine A F

    2008-04-01

    Duchenne muscular dystrophy (DMD) is caused by mutations in the X chromosome-linked DMD gene, which encodes the sarcolemma-stabilizing protein-dystrophin. Initial attempts at DMD therapy deployed muscle progenitor cells from healthy donors. The utilization of these cells is, however, hampered by their immunogenicity, while those from DMD patients are scarce and display limited ex vivo replication. Nonmuscle cells with myogenic capacity may offer valuable alternatives especially if, to allow autologous transplantation, they are amenable to genetic intervention. As a paradigm for therapeutic gene transfer by heterotypic cell fusion we are investigating whether human mesenchymal stem cells (hMSCs) can serve as donors of recombinant DMD genes for recipient human muscle cells. Here, we show that forced MyoD expression in hMSCs greatly increases their tendency to participate in human myotube formation turning them into improved DNA delivery vehicles. Efficient loading of hMSCs with recombinant DMD was achieved through a new tropism-modified high-capacity adenoviral (hcAd) vector directing striated muscle-specific synthesis of full-length dystrophin. This study introduces the principle of genetic complementation of gene-defective cells via directed cell fusion and provides an initial framework to test whether transient MyoD synthesis in autologous, gene-corrected hMSCs increases their potential for treating DMD and, possibly, other muscular dystrophies.

  13. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise.

    Science.gov (United States)

    Pilegaard, Henriette; Osada, Takuya; Andersen, Lisbeth T; Helge, Jørn W; Saltin, Bengt; Neufer, P Darrell

    2005-08-01

    In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabolic genes during recovery from exercise, 9 male subjects (aged 22-27) completed 75 minutes of cycling exercise at 75% Vo2 max on 2 occasions, consuming either a high-carbohydrate (HC) or low-carbohydrate (LC) diet during the subsequent 24 hours of recovery. Nuclei were isolated and tissue frozen from vastus lateralis muscle biopsies obtained before exercise and 2, 5, 8, and 24 hours after exercise. Muscle glycogen was restored to near resting levels within 5 hours in the HC trial, but remained depressed through 24 hours in the LC trial. During the 2- to 8-hour recovery period, leg glucose uptake was 5- to 15-fold higher with HC ingestion, whereas arterial plasma free fatty acid levels were approximately 3- to 7-fold higher with LC ingestion. Exercise increased (P < .05) transcription and/or mRNA content of the pyruvate dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, carnitine palmitoyltransferase I, hexokinase II, peroxisome proliferator activated receptor gamma coactivator-1 alpha, and peroxisome proliferator activated receptor alpha. Providing HC during recovery reversed the activation of pyruvate dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, and carnitine palmitoyltransferase I within 5 to 8 hours after exercise, whereas providing LC during recovery elicited a sustained/enhanced increase in activation of these genes through 8 to 24 hours of recovery. These findings provide evidence that factors associated with substrate availability and/or cellular metabolic recovery (eg, muscle glycogen restoration) influence the transcriptional regulation of metabolic genes in skeletal muscle of humans during recovery from exercise.

  14. The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts.

    Directory of Open Access Journals (Sweden)

    Maléne E Lindholm

    2016-09-01

    Full Text Available Regularly performed endurance training has many beneficial effects on health and skeletal muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein-coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal muscle memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity.

  15. Skeletal muscle fat metabolism after exercise in humans: influence of fat availability.

    Science.gov (United States)

    Kimber, Nicholas E; Cameron-Smith, David; McGee, Sean L; Hargreaves, Mark

    2013-06-01

    The mechanisms facilitating increased skeletal muscle fat oxidation following prolonged, strenuous exercise remain poorly defined. The aim of this study was to examine the influence of plasma free fatty acid (FFA) availability on intramuscular malonyl-CoA concentration and the regulation of whole-body fat metabolism during a 6-h postexercise recovery period. Eight endurance-trained men performed three trials, consisting of 1.5 h high-intensity and exhaustive exercise, followed by infusion of saline, saline + nicotinic acid (NA; low FFA), or Intralipid and heparin [high FFA (HFA)]. Muscle biopsies were obtained at the end of exercise (0 h) and at 3 and 6 h in recovery. Ingestion of NA suppressed the postexercise plasma FFA concentration throughout recovery (P increase in whole-body fat oxidation during the 6-h period for HFA (52.2 ± 4.8 g) relative to NA (38.4 ± 3.1 g; P muscle malonyl-CoA and acetyl-CoA carboxylase (ACC)β phosphorylation, suggesting mechanisms other than phosphorylation-mediated changes in ACC activity may have a role in regulating fat metabolism in human skeletal muscle during postexercise recovery. Despite marked changes in plasma FFA availability, no significant changes in intramuscular triglyceride concentrations were detected. These data suggest that the regulation of postexercise skeletal muscle fat oxidation in humans involves factors other than the 5'AMP-activated protein kinase-ACCβ-malonyl-CoA signaling pathway, although malonyl-CoA-mediated regulation cannot be excluded completely in the acute recovery period.

  16. Visualization and quantitation of GLUT4 translocation in human skeletal muscle following glucose ingestion and exercise.

    Science.gov (United States)

    Bradley, Helen; Shaw, Christopher S; Bendtsen, Claus; Worthington, Philip L; Wilson, Oliver J; Strauss, Juliette A; Wallis, Gareth A; Turner, Alice M; Wagenmakers, Anton J M

    2015-05-11

    Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in part as a result of the translocation of glucose transporter 4 (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4 redistribution from intracellular stores to the PM in response to glucose feeding and exercise. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of ten insulin-sensitive men in the basal state and following 30 min of cycling exercise (65% VO2 max). Muscle biopsy samples were also taken from a second cohort of ten age-, BMI- and VO2 max-matched insulin-sensitive men in the basal state and 30 and 60 min following glucose feeding (75 g glucose). GLUT4 and dystrophin colocalization, measured using the Pearson's correlation coefficient, was increased following 30 min of cycling exercise (baseline r = 0.47 ± 0.01; post exercise r = 0.58 ± 0.02; P GLUT4 clusters were partially depleted following 30 min cycling exercise, but not 30 min after glucose feeding. This study has, for the first time, used immunofluorescence microscopy in human skeletal muscle to quantify increases in GLUT4 and dystrophin colocalization and depletion of GLUT4 from large and smaller clusters as evidence of net GLUT4 translocation to the PM.

  17. How muscle fiber lengths and velocities affect muscle force generation as humans walk and run at different speeds.

    Science.gov (United States)

    Arnold, Edith M; Hamner, Samuel R; Seth, Ajay; Millard, Matthew; Delp, Scott L

    2013-06-01

    The lengths and velocities of muscle fibers have a dramatic effect on muscle force generation. It is unknown, however, whether the lengths and velocities of lower limb muscle fibers substantially affect the ability of muscles to generate force during walking and running. We examined this issue by developing simulations of muscle-tendon dynamics to calculate the lengths and velocities of muscle fibers