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Muscle relaxent

Jeffrey J Widrick, Matthew Alexander, Benjamin Sanchez, Devin Gibbs, Genri Kawahara, Alan Beggs, Louis Kunkel
Sapje zebrafish lack the protein dystrophin and are the smallest vertebrate model of Duchenne muscular dystrophy (DMD). Their small size makes them ideal for large-scale drug discovery screens. However, the extent that sapje mimic the muscle dysfunction of higher vertebrate models of DMD is unclear. We used an optical birefringence assay to differentiate affected dystrophic sapje larvae from their unaffected siblings and then studied trunk muscle contractility at 4-7 days post fertilization. Preparation cross-sectional area (CSA) was similar for affected and unaffected larvae, yet tetanic forces of affected preparations were only 30-60% of normal...
October 7, 2016: Physiological Genomics
Pieter Uvin, Maarten Albersen, Ine Bollen, Maarten Falter, Emmanuel Weyne, Loes Linsen, Hanna Tinel, Peter Sandner, Trinity J Bivalacqua, Dirk Jmk De Ridder, Frank Van der Aa, Bert Brône, Koenraad Van Renterghem
OBJECTIVES: To evaluate the expression of the Rho/Rho associated protein kinase (ROCK) pathway in corpus cavernosum of patients with severe erectile dysfunction (ED) compared to healthy human corpus cavernosum, and to test the functional effects of two Rho Kinase Inhibitors (RKI) on erectile tissue of patients with severe ED, not responding to phosphodiesterase type 5 inhibitors (PDE5-i). PATIENTS AND METHODS: Human corpus cavernosum samples were obtained after consent from individuals undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for qPCR)...
October 20, 2016: BJU International
Luca Fusi, Valentina Percario, Elisabetta Brunello, Marco Caremani, Pasquale Bianco, Joseph D Powers, Massimo Reconditi, Vincenzo Lombardi, Gabriella Piazzesi
KEY POINTS: Myosin filament mechanosensing determines the efficiency of the contraction by adapting the number of switched ON motors to the load. Accordingly, the unloaded shortening velocity (V0 ) is already set at the end of the latency relaxation (LR), ∼10 ms after the start of stimulation, when the myosin filament is still in the OFF state. Here the number of actin-attached motors per half-myosin filament (n) during V0 shortening imposed either at the end of LR or at the plateau of the isometric contraction is estimated from the relation between half-sarcomere compliance and force during the force redevelopment after the shortening...
October 20, 2016: Journal of Physiology
Riccardo Bientinesi, Cesare Mancuso, Maria Martire, Pier Francesco Bassi, Emilio Sacco, Diego Currò
Voltage-gated type 7 K(+) (KV7 or KCNQ) channels regulate the contractility of various smooth muscles. With this study, we aimed to assess the role of KV7 channels in the regulation of human detrusor contractility, as well as the gene and protein expression of KV7 channels in this tissue. For these purposes, the isolated organ technique, RT-qPCR, and Western blot were used, respectively. XE-991, a selective KV7 channel blocker, concentration-dependently contracted the human detrusor; mean EC50 and Emax of XE-991-induced concentration-response curve were 14...
October 19, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
T A Lewandowski
Carisoprodol is a widely prescribed muscle relaxant and is also a drug known to be a subject to abuse. Despite the fact that carisoprodol has been available for prescription since 1959, a number of gaps in our knowledge of the toxicokinetics of this common drug exist. For example, the volume of distribution (Vd) for carisoprodol in humans has not been reported. A two-compartment pharmacokinetic model describing carisoprodol metabolism and that of the primary metabolite, meprobamate, was developed to better understand the pharmacokinetics of this drug...
October 10, 2016: Human & Experimental Toxicology
Thashi Chang, Bethan Lang, Angela Vincent
BACKGROUND: Stiff person syndrome is a highly disabling, progressive autoimmune disorder of the central nervous system characterized by muscle rigidity and spasms. Stiff person syndrome is rare, but is believed to be under diagnosed with only 14 cases been reported among a 1.7 billion population in South Asia. We report the first authenticated case from Sri Lanka. CASE PRESENTATION: A 55-year-old Sri Lankan female presented with difficulty in walking and recurrent falls due to progressive muscular rigidity in her lower limbs and trunk with superimposed muscle spasms that occurred in response to unexpected noise, startle or emotional upset...
October 18, 2016: BMC Research Notes
Josef Donnerer, Ingrid Liebmann
Allyl isothiocyanate (AITC, mustard oil, 50-200 µmol/l), depending on specific dosages, inhibited the cholinergic twitch response in the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. AITC also induced short-lasting contractile responses, and decreases of the basal tone of the LMMP strip at low concentrations and increases at high concentrations. Hexamethonium, a blocker of nicotinic ganglionic transmission, was able to prevent the AITC-evoked inhibitory effect, an effect that was also observed with the opioid antagonist naloxone...
October 19, 2016: Pharmacology
Deepesh Pandey, Daijiro Tori, Yohei Nomura, Dan Berkowitz, Lewis Romer
OBJECTIVE: Kruppel Like Factor 15 (KLF15) has recently been shown to be critical for activation of proinflammatory processes in vascular smooth muscle and atherogenesis. Although KLF15 is abundantly expressed in vascular endothelium there is a significant lack of knowledge regarding the role of KLF15 in the regulation of vascular endothelial function. Here we tested the hypothesis that KLF15 is a critical regulator of Arg2 transcription in hypoxia exposed human pulmonary microvascular endothelial cells (HPMEC) and that it plays critical role in pathogenesis of pulmonary hypertension (PHTN)...
September 2016: Journal of Hypertension
Anthony Heagerty
There is now a considerable body of evidence to suggest that the fat cells that surround blood vessels (perivascular adipose tissue, PVAT) can influence profoundly arterial tone by releasing vasodilator adipokines which can act locally in a paracrine fashion. In healthy lean individuals the primary vasodilator released appears to be adiponectin and there is a complex interation between autonomic nerve firing in PVAT and the release of nitric oxide from adipocytes and an increased bioavailability of adiponectin...
September 2016: Journal of Hypertension
Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Justin Parreno, Sneha Raju, Po-Han Wu, Rita A Kandel
Chondrocyte culture as a monolayer for cell number expansion results in dedifferentiation whereby expanded cells acquire contractile features and increased actin polymerization status. This study determined whether the actin polymerization based signaling pathway, myocardin-related transcription factor-a (MRTF-A) is involved in regulating this contractile phenotype. Serial passaging of chondrocytes in monolayer culture to passage 2 resulted in increased gene and protein expression of the contractile molecules alpha-smooth muscle actin, transgelin and vinculin compared to non-passaged, primary cells...
October 14, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Li-Jie Wang, Wei-Dong Liu, Liang Zhang, Ke-Tao Ma, Lei Zhao, Wen-Yan Shi, Wen-Wen Zhang, Ying-Zi Wang, Li Li, Jun-Qiang Si
Niflumic acid (NFA) is a novel gap junction (GJ) inhibitor. The aim of the present study was to investigate the effect of NFA on GJ communication and the expression of connexin (Cx) in vascular smooth muscle cells (VSMCs) of mesenteric arterioles of spontaneously hypertensive rats (SHR). Whole‑cell patch clamp recording demonstrated that NFA at 1x10‑4 M significantly inhibited the inward current and its effect was reversible. The time for charging and discharging of cell membrane capacitance (Cinput) reduced from 9...
September 26, 2016: Molecular Medicine Reports
Ho Sung Lee, Young Joo Lee, Yoon Hee Chung, Moo Yeol Lee, Sung Tae Kim, Sung Kwon Ko, Mariko Momoi, Yutaka Kondoh, Fumio Sasaki, Ji Hoon Jeong
BACKGROUND: Progressed tissue culture techniques have allowed us to easily obtain mass products of tissue-cultured mountain ginseng over 100 yr old (TCMG-100). We investigated the effects of TCMG-100 extract on erectile function using in vitro and in vivo studies. METHODS: To examine the relaxation effects and mechanisms of action of TCMG-100 on rabbit cavernosal strips evaluated in an organ bath. To investigate the long-term treatment effect of TCMG-100, 8-wk administration was performed...
October 2016: Journal of Ginseng Research
Aparna Shukla, Shilpi Misra
CONTEXT: Clinical need for a nondepolarizing agent with a rapid onset time and a brief duration of action has led to the development of rocuronium bromide. AIMS: The aim of this study was to evaluate optimal dose of rocuronium bromide for intubation and to compare the onset time, duration of action, intubating conditions, and hemodynamic effects of two doses of rocuronium bromide. SETTINGS AND DESIGN: A prospective, randomized, double-blind study...
September 2016: Anesthesia, Essays and Researches
Hussein I El-Subbagh, Adel S El-Azab, Ghada S Hassan, Shahenda M El-Messery, Alaa A-M Abdel-Aziz, Kamal E H El-Taher
The synthesis, biological evaluation and molecular modeling study of 6,7-dihydro-[1,3,4] thiadiazolo[3,2-a][1,3]diazepine analogues as new class of neuromuscular blocking agents are described. The new compounds act via competitive mechanism with ACh which could be reversed by the anticholinesterase - Physostigmine. Compounds GS-53 (30) and AAH1 (33) induced dose-dependent neuromuscular blockade with onset time of 3 and 10 min, ED50 0.15 and 0.36 mmol/kg i.p., respectively, in rats. Compound 30 proved to be as twice as potent as 33 with rapid onset and shorter duration (P < 0...
September 30, 2016: European Journal of Medicinal Chemistry
M Hirschvogel, M Bassilious, L Jagschies, S M Wildhirt, M W Gee
A model for patient-specific cardiac mechanics simulation is introduced, incorporating a 3-dimensional finite element model of the ventricular part of the heart which is coupled to a reduced-order 0-dimensional closed-loop vascular system, heart valve and atrial chamber model.The ventricles are modeled by a nonlinear orthotropic passive material law. The electrical activation is mimicked by a prescribed parametrized active stress acting along a generic muscle fiber orientation. Our activation function is constructed such that the start of ventricular contraction and relaxation as well as the active stress curve's slope are parameterized...
October 15, 2016: International Journal for Numerical Methods in Biomedical Engineering
Y S Prakash
Airway structure and function are key aspects of normal lung development, growth and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, COPD and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and finally, interactions with other airway cell types such as epithelium, fibroblasts and nerves...
October 14, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Jillian M Cavallari, Tara S Jawaro, Nadia I Awad, Patrick J Bridgeman
Glucagon, a hormone secreted by pancreatic alpha cells, causes bronchial smooth muscle relaxation by activating the synthesis of cyclic adenosine monophosphate. It was studied in the 1980s and 1990s as a treatment option for the management of asthma but has since not been evaluated. Data to support its use are limited, but it may serve as a last-line agent for refractory asthma exacerbation. Here we describe 4 cases in which intravenous glucagon was used to manage severe, refractory asthma exacerbation in the emergency department...
September 30, 2016: American Journal of Emergency Medicine
Malek Kammoun, Philippe Pouletaut, Francis Canon, Malayannan Subramaniam, John R Hawse, Muriel Vayssade, Sabine F Bensamoun
As transforming growth factor (TGF)-β inducible early gene-1 is highly expressed in skeletal muscle, the effect of TIEG1 gene deletion on the passive mechanical properties of slow and fast twitch muscle fibers was analyzed. Twenty five muscle fibers were harvested from soleus (Sol) and extensor digitorum longus (EDL) muscles from TIEG1-/- (N = 5) and control (N = 5) mice. Mechanical tests were performed on fibers and the dynamic and static stresses were measured. A viscoelastic Hill model of 3rd order was used to fit the experimental relaxation test data...
2016: PloS One
Marcin Kunecki, Wojciech Płazak, Tomasz Roleder, Jolanta Biernat, Tomasz Oleksy, Piotr Podolec, Krzysztof Stanisław Gołba
BACKGROUND: Ischemic preconditioning (IPC) and postconditioning (POC) are the novel strategies of attaining cardioprotection against ischemia/reperfusion (I/R) injury. Previous studies suggested the role of opioid pathway, however the class of opioid receptors responsible for this effect in humans remains unknown. The aim of the study was to assess the influence of opioids on simulated I/R injury outcomes in the human myocardium. METHODS: Trabeculae of the human right atrium were electrically driven in organ bath and subjected to simulated I/R injury...
October 13, 2016: Cardiology Journal
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