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Muscle atrophy

Navaneetha Santhanam, Lee Kumanchik, Xiufang Guo, Frank Sommerhage, Yunqing Cai, Max Jackson, Candace Martin, George Saad, Christopher W McAleer, Ying Wang, Andrea Lavado, Christopher J Long, James J Hickman
There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units...
February 27, 2018: Biomaterials
Rishibha Sachdev, Karin Kappes-Horn, Lydia Paulsen, Yvonne Duernberger, Catharina Pleschka, Philip Denner, Bishwajit Kundu, Jens Reimann, Ina Vorberg
Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disorder in the elderly with no defined etiology or effective therapy. Endoplasmic reticulum stress and deposition of myostatin, a secreted negative regulator of muscle growth, have been implicated in disease pathology. The myostatin signaling pathway has emerged as a major target for symptomatic treatment of muscle atrophy. Here, we systematically analyzed the maturation and secretion of myostatin precursor MstnPP and its metabolites in a human muscle cell line...
March 15, 2018: Molecular Neurobiology
Floriane Rudwill, Donal O'Gorman, Etienne Lefai, Isabelle Chery, Alexandre Zahariev, Sylvie Normand, Allan F Pagano, Angèle Chopard, Anthony Damiot, Claire Laurens, Leanne Hodson, Emmanuelle Canet-Soulas, Martina Heer, Petra Frings Meuthen, Judith Buehlmeier, Natalie Baecker, Laure Meiller, Guillemette Gauquelin-Koch, Stéphane Blanc, Chantal Simon, Audrey Bergouignan
Context: The effects of energy balanced bed-rest on metabolic flexibility has not been thoroughly examined. Objective: We investigated the effects of 21-days bed-rest, with and without whey protein supplementation, on metabolic flexibility while maintaining energy balance. We further hypothesized protein supplementation mitigates metabolic inflexibility by preventing muscle atrophy. Design & Setting: Randomized cross-over longitudinal study conducted at the German Aerospace Center, Cologne, Germany...
March 12, 2018: Journal of Clinical Endocrinology and Metabolism
Arjun Paudyal, Mark Slevin, Huub Maas, Hans Degens
Denervation leads to significant muscle atrophy, but it is less clear whether 1) loss of capillaries, fibre size and oxidative capacity decline in parallel and 2) the time course of these changes differs between young and old animals. To investigate this, we denervated the left gastrocnemius muscle for 1, 2 or 4 weeks, while the right muscle served as an internal control, in rats that were 5- or 25 months old at the end of the experiment. In the fast part of the gastrocnemius muscle, almost all atrophy had occurred after two weeks (42%) of denervation...
March 12, 2018: Experimental Gerontology
S C Ibeneme, C Ekanem, A Ezuma, N Iloanusi, N N Lasebikan, O A Lasebikan, O E Oboh
BACKGROUND: Depletion of ovarian hormone in postmenopausal women has been associated with changes in the locomotor apparatus that may compromise walking function including muscle atrophy/weakness, weight gain, and bone demineralization. Therefore, handgrip strength (HGS), bone mineral density (BMD) and body composition [percentage body fat mass (%BFM), fat mass (FM), Fat-free mass (FFM) and body mass index (BMI)], may significantly vary and predict WB in postmenopausal women. Consequently, the study sought to 1...
March 15, 2018: BMC Musculoskeletal Disorders
Mariko Nishibe, Yu Katsuyama, Toshihide Yamashita
The motor deficit of the reeler mutants has largely been considered cerebellum related, and the developmental consequences of the cortex on reeler motor behavior have not been examined. We herein showed that there is a behavioral consequence to reeler mutation in models examined at cortex-dependent bimanual tasks that require forepaw dexterity. Using intracortical microstimulation, we found the forelimb representation in the motor cortex was significantly reduced in the reeler. The reeler cortex required a significantly higher current to evoke skeletal muscle movements, suggesting the cortical trans-synaptic propagation is disrupted...
March 13, 2018: Brain Structure & Function
Russell T Hepple
Skeletal muscle atrophy is a hallmark of advancing age that contributes to mobility impairment, physical frailty and increased morbidity in the elderly. This article is protected by copyright. All rights reserved.
March 13, 2018: Journal of Physiology
Malo Le Hanneur, Andres A Maldonado, Benjamin M Howe, Michelle L Mauermann, Robert J Spinner
BACKGROUND: Several hypotheses have been proposed for the pathophysiology of suprascapular nerve (SSN) palsy, including compression, traction, and nerve inflammation. OBJECTIVE: To provide insight into the pathophysiology of isolated nontraumatic SSN palsy by performing critical reinterpretations of electrodiagnostic (EDX) studies and magnetic resonance (MR) images of patients with such diagnosis. METHODS: We retrospectively reviewed all patients referred to our institution for the past 20 yr with a diagnosis of nontraumatic isolated suprascapular neuropathy who had an upper extremity EDX study and a shoulder or brachial plexus MR scan...
February 26, 2018: Neurosurgery
Jamie S McPhee, James Cameron, Thomas Maden-Wilkinson, Mathew Piasecki, Moi Hoon Yap, David A Jones, Hans Degens
The contributions of fibre atrophy, fibre loss, in situ specific force and voluntary activation to weakness in sarcopenia remain unclear. To investigate, forty older (20 women; age 72±4yrs) and 31 younger adults (15 women, age 22±3yrs) completed measurements. The knee extensor maximal voluntary torque (MVC) was measured as well as voluntary activation, patella tendon moment arm length, muscle volume and fascicle architecture to estimate in situ specific force. Fibre cross-sectional area (FCSA), fibre numbers and connective tissue contents were also estimated from vastus lateralis biopsies...
February 26, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Joo Yong Lee, Kang Su Cho
PURPOSE OF REVIEW: The use of 5-alpha reductase inhibitors (5ARIs) for the treatment of benign prostatic hyperplasia (BPH) and other diseases has been proposed and studied. However, the controversy about its benefits and harms for other diseases has persisted. In this review, we will discuss the newly identified effects of 5ARIs based on recently published studies. RECENT FINDINGS: These drugs are currently recommended in clinical guidelines for BPH. However, the reporting of adverse effects, including sexual dysfunction as well as neurologic, endocrine, and cardiovascular effects, have been controversial...
March 9, 2018: Current Opinion in Urology
Irina Kramerova, Jorge A Torres, Ascia Eskin, Stanley F Nelson, Melissa J Spencer
Mutations in CAPN3 cause autosomal recessive limb girdle muscular dystrophy 2A. Calpain 3 (CAPN3) is a calcium dependent protease residing in the myofibrillar, cytosolic and triad fractions of skeletal muscle. At the triad, it colocalizes with calcium calmodulin kinase IIβ (CaMKIIβ). CAPN3 knock out mice (C3KO) show reduced triad integrity and blunted CaMKIIβ signaling, which correlates with impaired transcriptional activation of myofibrillar and oxidative metabolism genes in response to running exercise...
March 8, 2018: Human Molecular Genetics
Lilian A Martinez Carrera, Elke Gabriel, Colin Donohoe, Irmgard Hölker, Aruljothi Mariappan, Markus Storbeck, Mirka Uhlirova, Jay Gopalakrishnan, Brunhilde Wirth
BICD2 encodes a highly conserved motor adaptor protein that regulates the dynein-dynactin complex in different cellular processes. Heterozygous mutations in BICD2 cause autosomal dominant lower extremity-predominant spinal muscular atrophy-2 (SMALED2). Although, various BICD2 mutations have been shown to alter interactions with different binding partners or the integrity of the Golgi apparatus, the specific pathological effects of BICD2 mutations underlying SMALED2 remain elusive. Here, we show that the fibroblasts derived from individuals with SMALED2 exhibit stable microtubules...
March 8, 2018: Human Molecular Genetics
V Krishnan, N J Patel, J G Mackrell, S A Sweetana, H Bullock, Y L Ma, T H Waterhouse, B C Yaden, J Henck, Q Q Zeng, K Gavardinas, P Jadhav, A Saeed, P Garcia-Losada, D A Robins, C T Benson
We have identified a non-steroidal selective androgen receptor modulator (SARM), termed LY305, that is bioavailable through a transdermal route of administration while highly cleared via hepatic metabolism to limit parent compound exposure in the liver. Selection of this compound and its transdermal formulation was based on the optimization of skin absorption properties using both in vitro and in vivo skin models that supported PBPK modeling for human PK predictions. This molecule is an agonist in perineal muscle while being a weak partial agonist in the androgenic tissues such as prostate...
March 12, 2018: Andrology
Cristina Basso, Kalliopi Pilichou, Barbara Bauce, Domenico Corrado, Gaetano Thiene
Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disease characterized by myocardial atrophy and fibrofatty replacement of the ventricular myocardium, at risk of sudden cardiac death, particularly in the young and athletes. Because there is no "gold standard" to reach the diagnosis of AC, multiple categories of diagnostic information have been combined, including imaging, electrocardiographic changes, arrhythmias, tissue characterization, and family history. However, the routine use of contrast-enhanced cardiac magnetic resonance increasingly revealed left dominant AC, a variant that is not well addressed in the diagnostic criteria and still escapes clinical identification...
April 2018: Heart Failure Clinics
Anna Fabis-Strobin, Miroslaw Topol, Jaroslaw Fabis, Kryspin Niedzielski, Michal Podgorski, Lukasz Strobin, Michal Polguj
INTRODUCTION: Although the pathomechanism of isolated infraspinatus atrophy (ISA) in throwing sports is known to be traction, it is unclear why only some players are affected. One likely explanation is that the infraspinatus pulling force exerted by its contracture generate the compressive resultant component force (Fn) compressing the lateral trunk of the suprascapular nerve (LTSN) against the edge of scapular spine. This paper makes two key assumptions (1) the course of LTSN in relation to the scapular spine, defined as the suprascapular-scapular spine angle (SSSA) is the key individual anatomical feature influencing the Fn magnitude, and thus potentially ISA development (2) SSSA is correlated with scapular notch type...
March 9, 2018: Surgical and Radiologic Anatomy: SRA
U Plöckinger, V Prasad, A Ziagaki, N Tiling, A Poellinger
BACKGROUND: Pompe disease (PD) is an autosomal recessive, lysosomal storage disease due to a mutation of the acid α-glucosidase (GAA) gene. In adult patients, PD is characterized by slowly progressive limb-girdle and trunk myopathy and restrictive respiratory insufficiency. Enzyme replacement therapy (ERT) is available, improving or stabilizing muscle-function in some and slowing deterioration in other patients. Unfortunately, there is no biomarker available to indicate therapeutic efficacy and/or disease activity...
March 9, 2018: Human Genomics
Hao Yin, Guang Han, Qiang Li, Xuejun He, Congyang Wang
OBJECTIVE: This research aimed to gain a better understanding of the relationship between cervical posterior open-door laminoplasty on axial symptoms, the net cross-sectional area of paraspinal muscles, and the degree of pimelosis. METHOD: A retrospective study was conducted on a consecutive series of 37 patients who had underwent cervical posterior open-door laminoplasty + lateral mass fixation and bone graft fusion between January 2015 and July 2015. All patients received postoperative examinations at 6 months and 18 months after the operation...
March 9, 2018: Zeitschrift Für Orthopädie und Unfallchirurgie
Mohammad Javad Ebrahimi, Abbas Aliaghaei, Mahdi Eskandarian Boroujeni, Fariba Khodagholi, Gholamhoussein Meftahi, Mohammad Amin Abdollahifar, Houssein Ahmadi, Samira Danyali, Mahtab Daftari, Yousef Sadeghi
Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD...
March 8, 2018: Neurotoxicity Research
Áine B Collins, John F Mee, Peter D Kirkland
Schmallenberg virus (SBV) and Akabane virus (AKAV) are teratogenic Simbu serogroup Orthobunyaviruses. Embryonated chicken egg models (ECE) have been used to study the pathogenicity and teratogenicity of Simbu viruses previously, however to date no such studies have been reported for SBV. Hence, the aims of this study were to investigate if ECE are susceptible to experimental SBV infection, and to evaluate the pathogenicity and teratogenicity of SBV and AKAV in ECE models. Two studies were conducted. In Study A, SBV (106...
March 2018: Veterinary Microbiology
T Patzer
BACKGROUND: In a progredient rotator cuff tear with tendon retraction, fatty infiltration and atrophy of rotator cuff muscles the humerus cannot be centered and stabilized sufficiently in the glenohumeral joint. This leads to rotator cuff defect arthropathy as an eccentric osteoarthritis with acetabularization and wear of the acromion, as well as of the glenoid. INDICATION: A painful pseudoparalysis of the shoulder indicates the implantation of a reversed total shoulder arthroplasty (rTSA) to reduce pain and restore active motion...
March 7, 2018: Der Orthopäde
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