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Skeletal muscle relaxant

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
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
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
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
Akira Hanashima, Ken Hashimoto, Yoshihiro Ujihara, Takeshi Honda, Tomoko Yobimoto, Aya Kodama, Satoshi Mohri
Connectin, also called titin, is the largest protein with a critical function as a molecular spring during contraction and relaxation of striated muscle; its mutation leads to severe myopathy and cardiomyopathy. To uncover the cause of this pathogenesis, zebrafish have recently been used as disease models because they are easier to genetically modify than mice. Although the gene structures and putative primary structures of zebrafish connectin have been determined, the actual primary structures of zebrafish connectin in heart and skeletal muscles remain unclear because of its large size and the PCR amplification-associated difficulties...
October 7, 2016: Gene
Yukiko Mori, Satoshi Yamashita, Mai Kato, Teruaki Masuda, Koutaro Takamatsu, Toshihide Kumamoto, Ryogen Sasaki, Yukio Ando
Myotonia congenita is a non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction caused by a mutation in the gene encoding skeletal muscle chloride channel-1 (CLCN1). We encountered a case of Thomsen disease with ptosis. A short tau inversion recovery MR imaging demonstrated high-intensity lesions in the levator palpebrae superioris muscles. Molecular genetic testing revealed a heterozygosity for the c.1439C>A (p.P480H) mutation in the CLCN1 gene...
September 3, 2016: Neuromuscular Disorders: NMD
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
Natalia A Koubassova, Sergey Y Bershitsky, Michael A Ferenczi, Theyencheri Narayanan, Andrey K Tsaturyan
Contraction of skeletal and cardiac muscle is controlled by Ca(2+) ions via regulatory proteins, troponin (Tn) and tropomyosin (Tpm) associated with the thin actin filaments in sarcomeres. In the absence of Ca(2+), Tn-C binds actin and shifts the Tpm strand to a position where it blocks myosin binding to actin, keeping muscle relaxed. According to the three-state model (McKillop and Geeves Biophys J 65:693-701, 1993), upon Ca(2+) binding to Tn, Tpm rotates about the filament axis to a 'closed state' where some myosin heads can bind actin...
September 17, 2016: European Biophysics Journal: EBJ
Tahira Assad, Rafeeq Alam Khan
Currently available anxiolytics cause numerous adverse effects and show craving and tolerance during long term treatment. Currently traditional medicines have been re-evaluated widely through work on various plant species. Numerous plants in traditional system show pharmacological activity with unlimited prospective for therapeutic use. Hence we planned to evaluate the effect of methanol extract of T. foenum-graecum L. seeds on anxiety, sedation and motor coordination in mice at different doses following 15 days of oral feeding...
September 17, 2016: Metabolic Brain Disease
Melissa M Derner, Courtney A Linhart, LeeAnna M Pederson, Sarith M Saju, Alyssa M Heiden, Lisa A Wohlford, Michael T Swanoski, M Nawal Lutfiyya
OBJECTIVE: The Beers criteria list skeletal muscle relaxants (SMR) as inappropriate for individuals 65 years of age and older because of anticholinergic effects, sedation, and risk of falls/fractures. Patients 65 years of age and older presenting to U.S. primary care clinics for injury, prescribed an SMR, are at risk for these events. SMR prescribing patterns in older adults with injury have not been well studied at the population level. Using nationally representative data, the prevalence of older adults prescribed an SMR presenting to U...
September 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
Gunchan Paul, Gautam L Parshotam, Rajneesh Garg
Soma (Carisoprodol) is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma) withdrawal resembling NMS that was a diagnostic dilemma...
July 2016: Journal of Anaesthesiology, Clinical Pharmacology
Tomohiro Nakamura, Shunya Takagi, Takafumi Kamon, Ken-Ichi Yamasaki, Toshia Fujisato
Tissue-engineered skeletal muscles were potentially useful as physiological and biochemical in vitro models. Currently, most of the similar models were constructed without tendons. In this study, we aimed to develop a simple, highly versatile tissue-engineered muscle with artificial tendons, and to evaluate the contractile, histological and molecular dynamics during differentiation. C2C12 cells were embedded in a cold type-І collagen gel and placed between two artificial tendons on a silicone sheet. The construct shrank and tightly attached to the artificial tendons with differentiation, finally detaching from the silicone sheet within 1 week of culture onset...
September 9, 2016: Journal of Bioscience and Bioengineering
Savina Tincheva, Bilyana Georgieva, Tihomir Todorov, Alexey Savov, Slavena Tsaneva, Ivan Litvinenko, Vanyo Mitev, Albena Todorova
Myotonia congenita type Becker is an autosomal recessive nondystrophic skeletal muscle disorder, caused by mutations in the CLCN1 gene. The disease is characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Here we report the results from molecular genetic testing of 6 families, referred for sequencing of the CLCN1 gene. The disease causing mutations were detected in 5 of the cases, representing diverse type of nucleotide changes: nonsense (p.Arg894*), splice-site (c...
October 2016: Neuromuscular Disorders: NMD
Dean L Mayfield, Bradley S Launikonis, Andrew G Cresswell, Glen A Lichtwark
There are high mechanical demands placed on skeletal muscles in movements requiring rapid acceleration of the body or its limbs. Tendons are responsible for transmitting muscle forces, but, due to their elasticity, can manipulate the mechanics of the internal contractile apparatus. Shortening of the contractile apparatus against the stretch of tendon affects force generation according to known mechanical properties, however, the extent to which differences in tendon compliance alter force development in response to a burst of electrical impulses is unclear...
September 8, 2016: Journal of Experimental Biology
Joseph T Horsfall, Jon E Sprague
Combining opioids with benzodiazepines and skeletal muscle relaxants ("The Holy Trinity") has been reported to potentiate the "high". Through unique interactions with co-localized μ-opioid and GABAA receptors, the combined use of these agents induce a synergistic increase in dopamine in the nucleus accumbens (NAc) and depression of respiration. The inhibition of GABA release mediated by μ1 -opioid receptor activation results in a subsequent increase in dopamine in the NAc. Benzodiazepines activate the GABAA R to suppress respiration in the medullary respiratory centers...
August 23, 2016: Basic & Clinical Pharmacology & Toxicology
Orazio Palmieri, Tommaso Mazza, Antonio Merla, Caterina Fusilli, Antonello Cuttitta, Giuseppina Martino, Tiziana Latiano, Giuseppe Corritore, Fabrizio Bossa, Orazio Palumbo, Lucia Anna Muscarella, Massimo Carella, Paolo Graziano, Angelo Andriulli, Anna Latiano
Idiopathic achalasia is characterized by the absence of peristalsis secondary to loss of neurons in the myenteric plexus that hampers proper relaxation of the lower esophageal sphincter. Achalasia can be considered a multifactorial disorder as it occurs in related individuals and is associated with HLA class II genes, thereby suggesting genetic influence. We used microarray technology and advanced in-silico functional analyses to perform the first genome-wide expression profiling of mRNA in tissue samples from 12 achalasia and 5 control patients...
2016: Scientific Reports
Katherine Bootsma, Martha M Fitzgerald, Brandon Free, Elizabeth Dimbath, Joe Conjerti, Greg Reese, Dominik Konkolewicz, Jason A Berberich, Jessica L Sparks
Interpenetrating network (IPN) hydrogel materials are recognized for their unique mechanical properties. While IPN elasticity and toughness properties have been explored in previous studies, the factors that impact the time-dependent stress relaxation behavior of IPN materials are not well understood. Time-dependent (i.e. viscoelastic) mechanical behavior is a critical design parameter in the development of materials for a variety of applications, such as medical simulation devices, flexible substrate materials, cellular mechanobiology substrates, or regenerative medicine applications...
July 22, 2016: Journal of the Mechanical Behavior of Biomedical Materials
Leonardo Nogara, Nariman Naber, Edward Pate, Marcella Canton, Carlo Reggiani, Roger Cooke
In the super-relaxed state of myosin, ATPase activity is strongly inhibited by binding of the myosin heads to the core of the thick filament in a structure known as the interacting-heads motif. In the disordered relaxed state myosin heads are not bound to the core of the thick filament and have an ATPase rate that is 10 fold greater. In the interacting-heads motif the two regulatory light chains appear to bind to each other. We have made single cysteine mutants of the regulatory light chain, placed both paramagnetic and fluorescent probes on them, and exchanged them into skinned skeletal muscle fibers...
2016: PloS One
Bruce M Damon, Ke Li, Nathan D Bryant
Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multifaceted pathology. The goals of this chapter are to describe and evaluate the use of quantitative magnetic resonance imaging (MRI) methods to characterize muscle pathology. The following criteria are used for this evaluation: objective measurement of continuously distributed variables; clear and well-understood relationship to the pathology of interest; sensitivity to improvement or worsening of clinical status; and the measurement properties of accuracy and precision...
2016: Handbook of Clinical Neurology
R Emilova, D Z Dimitrova, M Mladenov, N Hadzi-Petrushev, T Daneva, P Padeshki, R Schubert, M Chichova, L Lubomirov, D Simeonovska-Nikolova, H Gagov
This study aims to reveal the reason for the increased force of 5-hydroxytryptamine-induced contraction of endothelium-denuded skeletal muscle arteries of diabetic rats in the presence of perivascular adipose tissue (PVAT). Our data on rat gracilis arteries show that i) PVAT of skeletal muscle arteries of healthy and diabetic rats releases hydrogen peroxide (H(2)O(2)), ii) higher concentrations of 5-hydroxytryptamine increase the production of H(2)O(2) in PVAT; iii) an enhanced PVAT production of H(2)O(2) is the main, if not the only, reason for the sensitization of arterial contraction to 5-hydroxytriptamine-induced contraction in diabetes and iv) endothelium antagonizes the effect of PVAT-derived H(2)O(2)...
July 15, 2016: Physiological Research
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