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https://www.readbyqxmd.com/read/29150952/ck-2127107-amplifies-skeletal-muscle-response-to-nerve-activation-in-humans
#1
Jinsy A Andrews, Timothy M Miller, Vipin Vijayakumar, Randall Stoltz, Joyce K James, Lisa Meng, Andrew A Wolff, Fady I Malik
INTRODUCTION: Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-2127107 (CK-107), a next-generation fast skeletal muscle troponin activator (FSTA), in healthy subjects. We tested the hypothesis that CK-107 would amplify the force-frequency response of muscle in humans. METHODS: To assess the force-frequency response, subjects received single doses of CK-107 and placebo in a randomized, double-blind, 4-period, crossover study...
November 18, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/29150943/muscle-regeneration-potential-and-satellite-cell-activation-profile-during-recovery-following-hindlimb-immobilization-in-mice
#2
Maria Guitart, Josep Lloreta, Laura Mañas-Garcia, Esther Barreiro
Reduced muscle activity leads to muscle atrophy and function loss in patients and animal models. Satellite cells (SCs) are postnatal muscle stem cells that play a pivotal role in skeletal muscle regeneration following injury. The regenerative potential, satellite cell numbers, and markers during recovery following immobilization of the hindlimb for seven days were explored. In mice exposed to seven days of hindlimb immobilization, in those exposed to recovery (seven days, splint removal), and in contralateral control muscles, muscle precursor cells were isolated from all hindlimb muscles (fluorescence-activated cell sorting, FACS), and SCs and muscle regeneration were identified using immunofluorescence (gastrocnemius and soleus) and electron microscopy (EM, gastrocnemius)...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150918/central-role-of-transforming-ggrowth-factor-type-beta-1-in-skeletal-muscle-dysfunctions-an-update-on-therapeutic-strategies
#3
Johanna Abrigo, Felipe Simon, Daniel Cabrera, Gonzalo Cordova, Capucine Trollet, Claudio Cabello Verrugio
Among the soluble factors that regulate skeletal muscle function, Transforming Growth Factor type Beta 1 (TGF-b1) is one of the most studied. This factor inhibits myogenesis and regeneration by regulating the activity and function of satellite cells (SCs). Indeed, TGF-b has a central role in muscle pathologies in which there is development of fibrosis and/or atrophy of skeletal muscle. Thus, in this review we present the critical and recent antecedents regarding the mechanisms and cellular targets involved in the effects of TGF-b1 in the muscle, in pathological processes such as the inhibition of regeneration, fibrosis and atrophy...
November 16, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29150696/impact-of-prolonged-overfeeding-on-skeletal-muscle-mitochondria-in-healthy-individuals
#4
Frederico G S Toledo, Darcy L Johannsen, Jeffrey D Covington, Sudip Bajpeyi, Bret Goodpaster, Kevin E Conley, Eric Ravussin
AIMS/HYPOTHESES: Reduced mitochondrial capacity in skeletal muscle has been observed in obesity and type 2 diabetes. In humans, the aetiology of this abnormality is not well understood but the possibility that it is secondary to the stress of nutrient overload has been suggested. To test this hypothesis, we examined whether sustained overfeeding decreases skeletal muscle mitochondrial content or impairs function. METHODS: Twenty-six healthy volunteers (21 men, 5 women, age 25...
November 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/29150671/urothelial-cancer-proteomics-provides-both-prognostic-and-functional-information
#5
Guillermo de Velasco, Lucia Trilla-Fuertes, Angelo Gamez-Pozo, Maria Urbanowicz, Gustavo Ruiz-Ares, Juan M Sepúlveda, Guillermo Prado-Vazquez, Jorge M Arevalillo, Andrea Zapater-Moros, Hilario Navarro, Rocio Lopez-Vacas, Ray Manneh, Irene Otero, Felipe Villacampa, Jesus M Paramio, Juan Angel Fresno Vara, Daniel Castellano
Traditionally, bladder cancer has been classified based on histology features. Recently, some works have proposed a molecular classification of invasive bladder tumors. To determine whether proteomics can define molecular subtypes of  muscle invasive urothelial cancer (MIUC) and allow evaluating the status of biological processes and its clinical value. 58 MIUC patients who underwent curative surgical resection at our institution between 2006 and 2012 were included. Proteome was evaluated by high-throughput proteomics in routinely archive FFPE tumor tissue...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150470/platelet-rich-plasma-in-achilles-tendon-healing-2-path-2-trial-protocol-for-a-multicentre-participant-and-assessor-blinded-parallel-group-randomised-clinical-trial-comparing-platelet-rich-plasma-prp-injection-versus-placebo-injection-for-achilles-tendon-rupture
#6
Joseph Alsousou, David J Keene, Philippa A Hulley, Paul Harrison, Susan Wagland, Christopher Byrne, Michael Maia Schlüssel, Susan J Dutton, Sarah E Lamb, Keith Willett
BACKGROUND: Achilles tendon injuries give rise to substantial long-lasting morbidity and pose considerable challenges for clinicians and patients during the lengthy healing period. Current treatment strategies struggle to curb the burden of this injury on health systems and society due to lengthy rehabilitation, work absence and reinjury risk. Platelet-rich plasma (PRP) is an autologous preparation that has been shown to improve the mechanobiological properties of tendons in laboratory and animal studies...
November 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/29150450/aerobic-power-and-flight-capacity-in-birds-a-phylogenetic-test-of-the-heart-size-hypothesis
#7
Roberto F Nespolo, César González-Lagos, Jaiber J Solano-Iguaran, Magnus Elfwing, Alvaro Garitano-Zavala, Santiago Mañosa, Juan Carlos Alonso, Jordi Altimiras
Flight capacity is one of the most important innovations in animal evolution; it only evolved in insects, birds, mammals and the extinct pterodactyls. Given that powered flight represents a demanding aerobic activity, an efficient cardiovascular system is essential for the continuous delivery of oxygen to the pectoral muscles during flight. It is well known that the limiting step in the circulation is stroke volume (the volume of blood pumped from the ventricle to the body during each beat), which is determined by the size of the ventricle...
November 17, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29150445/the-antiapoptotic-protein-hax-1-mediates-half-of-phospholamban-s-inhibitory-activity-on-calcium-cycling-and-contractility-in-the-heart
#8
Philip A Bidwell, Kobra Haghighi, Evangelia G Kranias
The antiapoptotic protein HS-associated protein X-1 (HAX-1) localizes to sarcoplasmic reticulum (SR) in the heart and interacts with the small membrane protein phospholamban (PLN), inhibiting the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a) in the regulation of overall calcium handling and heart muscle contractility. However, because global HAX-1 deletion causes early lethality, how much endogenous HAX-1 contributes to PLN's inhibitory activity on calcium cycling is unknown. We therefore generated a cardiac-specific and inducible knockout mouse model...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29150436/microvesicles-derived-from-human-wharton-s-jellymesenchymal-stem-cells-ameliorate-ischemia-reperfusion-induced-renal-fibrosis-by-releasing-from-g2-m-cell-cycle-arrest
#9
Wenxia Chen, Yongbin Yan, Chundong Song, Ying Ding, Tao Du
Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI), however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator HGF or inhibitor U0126 was administrated, respectively. Tubular cell proliferation and apoptosis were identified by Ki67 or TUNEL immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin (α -SMA) staining were used for assessing renal fibrosis...
November 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29150283/transcutaneous-neuromuscular-electrical-stimulation-may-be-beneficial-in-the-treatment-of-premature-ejaculation
#10
Ilan Gruenwald, Ege Can Serefoglu, Tal Gollan, Shmuel Springer, Gideon Meiry, Boaz Appel, Arik Shechter
Approximately 20-30% of sexually active men suffer from Premature Ejaculation (PE), but the pathophysiology still remains unclear and the current available treatments for PE are unsatisfying. Considering the role of rhythmic bulbospongiosus and ischiocavernosus Muscles contractions on the ejaculatory reflex, we hypothesize that weakening this muscles via inhibiting it's contractions by Application of Neuromuscular Electrical Stimulation prior to the planned sexual activity, may have a beneficial effect in the treatment of PE...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150270/m-biceps-femoris-a-wolf-in-sheep-s-clothing-the-downside-of-a-lower-limb-injury-prevention-training
#11
Thomas Ertelt, Thomas Gronwald
Both, hamstring and ACL injuries are among the most typical injuries, particularly in change of direction and high speed running sports. They're also difficult to treat. Therefore, in the past few years, sports medicine practitioners and exercise scientists have mainly been focusing on the development and implementation of preventive programs in order to reduce the number of lower limb injuries, mainly by improving knee alignment. A number of studies have been able to prove the success of these training interventions, which are mainly addressing sensorimotor abilities and plyometric activities...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150241/targeting-interleukin-1%C3%AE-protects-from-aortic-aneurysms-induced-by-disrupted-transforming-growth-factor-%C3%AE-signaling
#12
Francesco Da Ros, Raimondo Carnevale, Giuseppe Cifelli, Dario Bizzotto, Manuel Casaburo, Marialuisa Perrotta, Lorenzo Carnevale, Iolanda Vinciguerra, Stefania Fardella, Roberta Iacobucci, Giorgio M Bressan, Paola Braghetta, Giuseppe Lembo, Daniela Carnevale
Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor β (TGF-β) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) in SMCs...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29150087/dexmedetomidine-methadone-ketamine-versus-dexmedetomidine-methadone-alfaxalone-for-cats-undergoing-ovariectomy
#13
Rocio Fernandez-Parra, Chiara Adami, Thomas Dresco, Thomas M Donnelly, Luca Zilberstein
OBJECTIVE: To compare the duration, quality of anaesthesia and analgesia, and quality of recovery of dexmedetomidine and methadone combined with either ketamine or alfaxalone. STUDY DESIGN: Randomized, prospective clinical trial. ANIMALS: A group of 44 healthy client-owned cats presenting for ovariectomy. METHODS: Cats were randomly assigned to one of the two treatment groups: DAM (n=22), which was administered intramuscularly (IM) dexmedetomidine (15 μg kg(-1)), methadone (0...
May 27, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/29149851/identification-of-gaa-variants-through-whole-exome-sequencing-targeted-to-a-cohort-of-606-patients-with-unexplained-limb-girdle-muscle-weakness
#14
Katherine Johnson, Ana Töpf, Marta Bertoli, Lauren Phillips, Kristl G Claeys, Vidosava Rakocevic Stojanovic, Stojan Perić, Andreas Hahn, Paul Maddison, Ela Akay, Alexandra E Bastian, Anna Łusakowska, Anna Kostera-Pruszczyk, Monkol Lek, Liwen Xu, Daniel G MacArthur, Volker Straub
BACKGROUND: Late-onset Pompe disease is a rare genetic neuromuscular disorder caused by a primary deficiency of α-glucosidase and the associated accumulation of glycogen in lysosomal vacuoles. The deficiency of α-glucosidase can often be detected using an inexpensive and readily accessible dried blood spot test when Pompe disease is suspected. Like several neuromuscular disorders, Pompe disease typically presents with progressive weakness of limb-girdle muscles and respiratory insufficiency...
November 17, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29149696/clearance-of-plasmin-pn-1-complexes-by-vascular-smooth-muscle-cells-in-human-aneurysm-of-the-ascending-aorta
#15
Kamel Boukais, Luciano F Borges, Laurence Venisse, Ziad Touat, Déborah François, Véronique Arocas, Guillaume Jondeau, Paul Declerck, Marie-Christine Bouton, Jean-Baptiste Michel
Plasminogen is a circulating zymogen which enters the arterial wall by radial, transmural hydraulic conductance, where it is converted to plasmin by tissue plasminogen activator t-PA on an activation platform involving S100A4 on the vascular smooth muscle cell (vSMC) membrane. Plasmin is involved in the progression of human thoracic aneurysm of the ascending aorta (TAA). vSMCs protect the TAA wall from plasmin-induced proteolytic injury by expressing high levels of antiproteases. Protease nexin-1 (PN-1) is a tissue antiprotease belonging to the serpin superfamily, expressed in the vascular wall, and is able to form a covalent complex with plasmin...
October 24, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29149346/novel-pathways-of-endocrine-disruption-through-pesticides-interference-with-human-mineralocorticoid-receptors
#16
Jianyun Zhang, Xin Huang, Hongling Liu, Weiping Liu, Jing Liu
Mineralocorticoid receptor (MR) is one member of the steroid receptor family. In addition to its important role in Na+/K+ homeostasis, MR is reported as a tumor-suppressor in carcinogenesis. So far, little was known about the ability of pesticides to interfere with MR. In this study, a total of 43 pesticides and/or metabolites were investigated for their potential effects on human MR. None of the tested pesticides exhibited MR agonistic potency, while 16 compounds showed antagonistic activities. Further investigations indicated that these 16 chemicals individually antagonized aldosterone-induced alkaline phosphatase expression in vascular smooth muscle cells and aldosterone-inhibited hepatocellular carcinoma cell proliferation at higher concentrations, and the mixture of these 16 pesticides at environmentally relevant concentrations significantly disrupted MR activity...
November 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29148852/sildenafil-citrate-improves-the-delivery-and-anticancer-activity-of-doxorubicin-formulations-in-a-mouse-model-of-breast-cancer
#17
Khaled Greish, Maryam Fateel, Sara Abdelghany, Nanitha Rachel, Houman Alimoradi, Moiz Bakhiet, Ahmed Alsaie
Sildenafil is an approved drug for the treatment of erectile dysfunction. The drug exerts its action through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. In this work, we tested whether the aforementioned effects of Sildenafil on tumor vasculatures could result in an improvement of anticancer drug concentration in tumor tissues, and hence improve its anticancer effect. Sildenafil when added to doxorubicin showed synergistic anticancer activity against 4T1 breast cancer cells in vitro...
November 17, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29148568/intrathecal-baclofen-in-dyskinetic-cerebral-palsy-effects-on-function-and-activity
#18
Meta N Eek, Kristina Olsson, Karin Lindh, Berit Askljung, Magnus Påhlman, Olle Corneliusson, Kate Himmelmann
AIM: To investigate the effect of intrathecal baclofen (ITB) on function and activity in dyskinetic cerebral palsy (CP). METHOD: A retrospective cohort study of records from 25 children (15 males, 10 females; mean age 10y 11mo, SD 4y 9mo). Five were classified in Gross Motor Function Classification level IV and 20 in level V. Parents were interviewed about activities in daily life, sitting, communication, pain, sleep, and gross and fine motor function. Differences before and 1 year after ITB were graded as positive, no change, or negative...
November 17, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/29148138/artificial-walking-technologies-to-improve-gait-in-cerebral-palsy-multichannel-neuromuscular-stimulation
#19
Jessica Rose, Katelyn Cahill-Rowley, Erin E Butler
Cerebral palsy (CP) is the most common childhood motor disability and often results in debilitating walking abnormalities, such as flexed-knee and stiff-knee gait. Current medical and surgical treatments are only partially effective in improving gait abnormalities and may cause significant muscle weakness. However, emerging artificial walking technologies, such as step-initiated, multichannel neuromuscular electrical stimulation (NMES), can substantially improve gait patterns and promote muscle strength in children with spastic CP...
November 2017: Artificial Organs
https://www.readbyqxmd.com/read/29148135/cadence-tracking-and-disturbance-rejection-in-functional-electrical-stimulation-cycling-for-paraplegic-subjects-a-case-study
#20
Lucas O da Fonseca, Antônio P L Bó, Juliana A Guimarães, Miguel E Gutierrez, Emerson Fachin-Martins
Functional electrical stimulation cycling has been proposed as an assistive technology with numerous health and fitness benefits for people with spinal cord injury, such as improvement in cardiovascular function, increase in muscular mass, and reduction of bone mass loss. However, some limitations, for example, lack of optimal control strategies that would delay fatigue, may still prevent this technology from achieving its full potential. In this work, we performed experiments on a person with complete spinal cord injury using a stationary tadpole trike when both cadence tracking and disturbance rejection were evaluated...
November 2017: Artificial Organs
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