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Skeletal muscle relaxant

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https://www.readbyqxmd.com/read/28097712/force-generation-by-titin-folding
#1
Zsolt Mártonfalvi, Pasquale Bianco, Katalin Naftz, György G Ferenczy, Miklós Kellermayer
Titin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force-dependent folding mechanisms, here we manipulated skeletal-muscle titin molecules with high-resolution optical tweezers. In force-clamp mode, after quenching the force (<10 pN), extension fluctuated without resolvable discrete events...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28097532/medication-overuse-in-chronic-pain
#2
REVIEW
Eric S Hsu
PURPOSE OF REVIEW: Chronic pain is usually managed by various pharmacotherapies after exhausting the conservative modalities such as over-the-counter choices. The goal of this review is to investigate current state of opioids and non-opioid medication overuse that includes NSAIDs, skeletal muscle relaxants, antidepressants, membrane stabilization agents, and benzodiazepine. How to minimize medication overuse and achieve better outcome in chronic pain management? RECENT FINDINGS: Although antidepressants and membrane stabilization agents contribute to the crucial components for neuromodulation, opioids were frequently designated as a rescue remedy in chronic pain since adjunct analgesics usually do not provide instantaneous relief...
January 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28097207/upper-arm-and-cardiac-magnetic-resonance-imaging-in-duchenne-muscular-dystrophy
#3
Lasya Gaur, Alexander Hanna, W Patricia Bandettini, Kenneth H Fischbeck, Andrew E Arai, Ami Mankodi
We analyzed quantitative maps of T1 and T2 relaxation times and muscle fat fraction measurements in magnetic resonance imaging of the upper arm skeletal muscles and heart in ambulatory boys with Duchenne muscular dystrophy and age-range-matched healthy volunteer boys. The cardiac-optimized sequences detected fatty infiltration and edema in the upper arm skeletal muscles but not the myocardium in these Duchenne muscular dystrophy boys who had normal ejection fraction. Imaging the heart and skeletal muscle using the same magnetic resonance imaging methods during a single scan may be useful in assessing relative disease status and therapeutic response in clinical trials of Duchenne muscular dystrophy...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28091624/paracrine-cross-talk-between-skeletal-muscle-and-macrophages-in-exercise-by-pgc-1%C3%AE-controlled-bnp
#4
Regula Furrer, Petra S Eisele, Alexander Schmidt, Markus Beer, Christoph Handschin
Activation of resident and infiltrating immune cells is a central event in training adaptation and other contexts of skeletal muscle repair and regeneration. A precise orchestration of inflammatory events in muscle fibers and immune cells is required after recurrent contraction-relaxation cycles. However, the mechanistic aspects of this important regulation remain largely unknown. We now demonstrate that besides a dominant role in controlling cellular metabolism, the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) also has a profound effect on cytokine expression in muscle tissue...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067669/targeting-deregulated-ampk-mtorc1-pathways-improves-muscle-function-in-myotonic-dystrophy-type-i
#5
Marielle Brockhoff, Nathalie Rion, Kathrin Chojnowska, Tatiana Wiktorowicz, Christopher Eickhorst, Beat Erne, Stephan Frank, Corrado Angelini, Denis Furling, Markus A Rüegg, Michael Sinnreich, Perrine Castets
Myotonic dystrophy type I (DM1) is a disabling multisystemic disease that predominantly affects skeletal muscle. It is caused by expanded CTG repeats in the 3'-UTR of the dystrophia myotonica protein kinase (DMPK) gene. RNA hairpins formed by elongated DMPK transcripts sequester RNA-binding proteins, leading to mis-splicing of numerous pre-mRNAs. Here, we have investigated whether DM1-associated muscle pathology is related to deregulation of central metabolic pathways, which may identify potential therapeutic targets for the disease...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28065835/nmr-investigation-of-the-isolated-second-voltage-sensing-domain-of-human-nav1-4-channel
#6
A S Paramonov, E N Lyukmanova, M Yu Myshkin, M A Shulepko, D S Kulbatskii, N S Petrosian, A O Chugunov, D A Dolgikh, M P Kirpichnikov, A S Arseniev, Z O Shenkarev
Voltage-gated Na(+) channels are essential for the functioning of cardiovascular, muscular, and nervous systems. The α-subunit of eukaryotic Na(+) channel consists of ~2000 amino acid residues and encloses 24 transmembrane (TM) helices, which form five membrane domains: four voltage-sensing (VSD) and one pore domain. The structural complexity significantly impedes recombinant production and structural studies of full-sized Na(+) channels. Modular organization of voltage-gated channels gives an idea for studying of the isolated second VSD of human skeletal muscle Nav1...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28060254/quantitative-magnetic-resonance-imaging-of-skeletal-muscle-disease
#7
Bruce M Damon, Ke Li, Richard D Dortch, E Brian Welch, Jane H Park, Amanda K W Buck, Theodore F Towse, Mark D Does, Daniel F Gochberg, Nathan D Bryant
Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization...
December 18, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28043117/rocuronium-bromide-inhibits-inflammation-and-pain-by-suppressing-nitric-oxide-production-and-enhancing-prostaglandin-e2-synthesis-in-endothelial-cells
#8
Sang Bin Baek, Mal Soon Shin, Jin Hee Han, Sang Woong Moon, Boksoon Chang, Jung Won Jeon, Jae Woo Yi, Jun Young Chung
PURPOSE: Rocuronium bromide is a nondepolarizing neuromuscular blocking drug and has been used as an adjunct for relaxation or paralysis of the skeletal muscles, facilitation of endotracheal intubation, and improving surgical conditions during general anesthesia. However, intravenous injection of rocuronium bromide induces injection pain or withdrawal movement. The exact mechanism of rocuronium bromide-induced injection pain or withdrawal movement is not yet understood. We investigated whether rocuronium bromide treatment is involved in the induction of inflammation and pain in vascular endothelial cells...
December 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/28027523/preparation-characterization-and-in-vivo-evaluation-of-a-formulation-of-dantrolene-sodium-with-hydroxypropyl-%C3%AE-cyclodextrin
#9
Mengmeng Chen, Qijuan Wu, Juan Jiang, Xin Jin, Shuang Liu, Miao Wang, Chunjie Zhao
Dantrolene sodium (Da) is an effective skeletal muscle relaxant. However, its pharmacological effects are severely limited owing to its poor solubility and low oral bioavailability. In order to solve these problems, an inclusion complex using hydroxypropyl-β-cyclodextrin (HP-β-CD) to improve the oral bioavailability of Da was prepared successfully by freeze-drying. The prepared complex was characterized by Powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy (FTIR) and evaluated by a dissolution test and a pharmacokinetic study...
December 19, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27932789/the-maintenance-ability-and-ca-2-availability-of-skeletal-muscle-are-enhanced-by-sildenafil
#10
Mei Huang, Keon Jin Lee, Kyung-Jin Kim, Mi Kyoung Ahn, Chung-Hyun Cho, Do Han Kim, Eun Hui Lee
Sildenafil relaxes vascular smooth muscle cells and is used to treat pulmonary artery hypertension as well as erectile dysfunction. However, the effectiveness of sildenafil on skeletal muscle and the benefit of its clinical use have been controversial, and most studies focus primarily on tissues and organs from disease models without cellular examination. Here, the effects of sildenafil on skeletal muscle at the cellular level were examined using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca(2+) imaging experiments and cellular and biochemical studies...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27904817/transitional-vertebra-and-spina-bifida-occulta-related-with-chronic-low-back-pain-in-a-young-patient
#11
Maryam Kundi, Maham Habib, Sumbal Babar, Asif K Kundi, Salman Assad, Amjad Sheikh
Bertolotti's syndrome (BS) must be considered as a differential diagnosis in a young patient presenting with low back pain (LBP). We present a case of a 26-year-old male complaining of mild chronic LBP for six years, radiating to his left thigh for the past six months. He has been taking non-steroidal anti-inflammatory drugs (NSAIDs) with skeletal muscle relaxants for pain relief. The X-ray and computed tomography (CT) imagings showed congenital enlargement of the left transverse process of the fifth lumbar (L5) vertebra forming pseudo-articulation with the sacrum and unilateral pars interarticularis defect at the L4 level on the left side, respectively...
October 19, 2016: Curēus
https://www.readbyqxmd.com/read/27879676/calcium-dyshomeostasis-in-tubular-aggregate-myopathy
#12
REVIEW
Jong-Mok Lee, Satoru Noguchi
Calcium is a crucial mediator of cell signaling in skeletal muscles for basic cellular functions and specific functions, including contraction, fiber-type differentiation and energy production. The sarcoplasmic reticulum (SR) is an organelle that provides a large supply of intracellular Ca(2+) in myofibers. Upon excitation, it releases Ca(2+) into the cytosol, inducing contraction of myofibrils. During relaxation, it takes up cytosolic Ca(2+) to terminate the contraction. During exercise, Ca(2+) is cycled between the cytosol and the SR through a system by which the Ca(2+) pool in the SR is restored by uptake of extracellular Ca(2+) via a specific channel on the plasma membrane...
November 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27879195/the-pharmacokinetic-comparison-and-bioequivalence-evaluation-of-two-10-mg-baclofen-formulations-in-healthy-male-subjects%C3%A2
#13
Sumin Yoon, SeungHwan Lee, Kyung-Sang Yu, Sung-Vin Yim, Bo-Hyung Kim
BACKGROUNDS: Baclofen is used as a skeletal muscle relaxant for multiple sclerosis patients. It depresses the transmission of monosynaptic and polysynaptic reflex by stimulating GABAβ (gamma-aminobutyric acid) receptors. OBJECTIVES: The aim of this study was to compare the pharmacokinetic characteristics of two 10-mg baclofen formulations and to assess bioequivalence. METHODS: A randomized, single-dose, two-period, two-sequence crossover study was conducted in healthy male subjects...
November 23, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27869319/the-ca-2-sensitizer-ck-2066260-increases-myofibrillar-ca-2-sensitivity-and-submaximal-force-selectively-in-fast-skeletal-muscle
#14
Darren T Hwee, Arthur J Cheng, James J Hartman, Aaron C Hinken, Ken Lee, Nickie Durham, Alan J Russell, Fady I Malik, Håkan Westerblad, Jeffrey R Jasper
Skeletal muscle dysfunction occurs in many diseases and can lead to muscle weakness and premature muscle fatigue. Here we show that the fast skeletal troponin activator, CK-2066260, counteracts muscle weakness by increasing troponin Ca(2+) affinity, thereby increasing myofibrillar Ca(2+) sensitivity. Exposure to CK-2066260 resulted in a concentration-dependent increase in the Ca(2+) sensitivity of ATPase activity in isolated myofibrils and reconstituted hybrid sarcomeres containing fast skeletal muscle troponin C...
November 21, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27862560/noninvasive-assessment-of-age-gender-and-exercise-effects-on-skeletal-muscle-initial-experience-with-t1-%C3%AF-mri-of-calf-muscle
#15
Xin-Gui Peng, Yuancheng Wang, Shijun Zhang, Yingying Bai, Hui Mao, Gao-Jun Teng, Shenghong Ju
PURPOSE: To prospectively investigate age- and gender-related changes in the fast-twitch (tibialis anterior, TA) and slow-twitch (soleus, SOL) skeletal muscle of healthy rats and volunteers and to compare the exercise-related difference in health volunteers with T1 ρ magnetic resonance imaging (MRI). MATERIALS AND METHODS: In all, 18 rats and 70 humans were involved in this study. For the animal study, T1 ρ relaxation times were measured in the TA and SOL rat muscle with a 3...
November 9, 2016: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/27861245/selective-impairment-of-blood-pressure-reduction-by-endothelial-nitric-oxide-synthase-dimer-destabilization-in-mice
#16
Tatsiana Suvorava, Stephanie Pick, Georg Kojda
OBJECTIVES: Endothelial dysfunction and oxidative stress are associated with hypertension but whether endothelial superoxide may play a role in the early development of essential hypertension remains uncertain. We investigated whether endothelial nitric oxide synthase (eNOS)-derived endothelial oxidative stress is involved in the regulation of SBP. METHODS: Wild-type eNOS [mice with endothelium-specific overexpression of bovine endothelial NO-synthase (eNOS-Tg)] or a novel dimer-destabilized eNOS-mutant harboring a partially disrupted zinc-finger [mice with endothelium-specific overexpression of destabilized bovine eNOS destabilized by replacement of Cys 101 to Ala (C101A-eNOS-Tg)] was introduced in C57BL/6 in an endothelial-specific manner...
January 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/27857962/functional-analysis-of-ryr1-variants-linked-to-malignant-hyperthermia
#17
Jeremy Stephens, Anja H Schiemann, Cornelia Roesl, Dorota Miller, Sean Massey, Neil Pollock, Terasa Bulger, Kathryn Stowell
Malignant hyperthermia manifests as a rapid and sustained rise in temperature in response to pharmacological triggering agents, e.g. inhalational anesthetics and the muscle relaxant suxamethonium. Other clinical signs include an increase in end-tidal CO2, increased O2 consumption, as well as tachycardia, and if untreated a malignant hyperthermia episode can result in death. The metabolic changes are caused by dysregulation of skeletal muscle Ca(2+) homeostasis, resulting from a defective ryanodine receptor Ca(2+) channel, which resides in the sarcoplasmic reticulum and controls the flux of Ca(2+) ions from intracellular stores to the cytoplasm...
April 2016: Temperature: Multidisciplinary Biomedical Journal
https://www.readbyqxmd.com/read/27815532/highly-selective-inhibition-of-myosin-motors-provides-the-basis-of-potential-therapeutic-application
#18
Serena Sirigu, James J Hartman, Vicente José Planelles-Herrero, Virginie Ropars, Sheila Clancy, Xi Wang, Grace Chuang, Xiangping Qian, Pu-Ping Lu, Edward Barrett, Karin Rudolph, Christopher Royer, Bradley P Morgan, Enrico A Stura, Fady I Malik, Anne M Houdusse
Direct inhibition of smooth muscle myosin (SMM) is a potential means to treat hypercontractile smooth muscle diseases. The selective inhibitor CK-2018571 prevents strong binding to actin and promotes muscle relaxation in vitro and in vivo. The crystal structure of the SMM/drug complex reveals that CK-2018571 binds to a novel allosteric pocket that opens up during the "recovery stroke" transition necessary to reprime the motor. Trapped in an intermediate of this fast transition, SMM is inhibited with high selectivity compared with skeletal muscle myosin (IC50 = 9 nM and 11,300 nM, respectively), although all of the binding site residues are identical in these motors...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27799519/piperine-s-mitigation-of-obesity-and-diabetes-can-be-explained-by-its-up-regulation-of-the-metabolic-rate-of-resting-muscle
#19
Leonardo Nogara, Nariman Naber, Edward Pate, Marcella Canton, Carlo Reggiani, Roger Cooke
We identify a target for treating obesity and type 2 diabetes, the consumption of calories by an increase in the metabolic rate of resting skeletal muscle. The metabolic rate of skeletal muscle can be increased by shifting myosin heads from the super-relaxed state (SRX), with a low ATPase activity, to a disordered relaxed state (DRX), with a higher ATPase activity. The shift of myosin heads was detected by a change in fluorescent intensity of a probe attached to the myosin regulatory light chain in skinned skeletal fibers, allowing us to perform a high-throughput screen of 2,128 compounds...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27793139/a-short-term-statin-treatment-changes-the-contractile-properties-of-fast-twitch-skeletal-muscles
#20
Antoine Boulanger Piette, Sébastien S Dufresne, Jérôme Frenette
BACKGROUND: Cumulative evidence indicates that statins induce myotoxicity. However, the lack of understanding of how statins affect skeletal muscles at the structural, functional, and physiological levels hampers proper healthcare management. The purpose of the present study was to investigate the early after-effects of lovastatin on the slow-twitch soleus (Sol) and fast-twitch extensor digitorum longus (EDL) muscles. METHODS: Adult C57BL/6 mice were orally administrated with placebo or lovastatin [50 mg/kg/d] for 28 days...
October 28, 2016: BMC Musculoskeletal Disorders
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