Musculoskeletal System Commons^™

Direct Effects Of Capsaicin On Voltage-Dependent Calcium Channels Of Mammalian Skeletal Muscle, Dmytro Isaev, Tatiana Prytkova, Badarunnisa Mohamed, Mohamed Omar Mahgoub, Keun-Hang Susan Yang, Murat Oz

Pharmacy Faculty Articles and Research

Capsaicin, a naturally occurring polyphenol, is known to affect energy expenditure and muscle fatigue and modulate contractions in skeletal muscle. The L-type Ca²⁺ channels are known to be an important ion channel involved in the various muscle functions and the effect of capsaicin on the skeletal L-type Ca²⁺ channels is currently unknown. In this study, the effects of capsaicin and capsaicin analogs on depolarization-induced Ca²⁺ effluxes through L-type Ca²⁺ channels in transverse tubule membranes from rabbit skeletal muscle and L-type Ca²⁺ currents recorded using the whole-cell patch clamp technique in rat myotubes were examined. Capsaicin, …

Glucocorticoids Rapidly Activate Camp Production Via GΑs To Initiate Non-Genomic Signaling That Contributes To One-Third Of Their Canonical Genomic Effects, Francisco J. Nuñez, Timothy B. Johnstone, Maia L. Corpuz, Austin G. Kazarian, Nicole N. Mohajer, Omar Tliba, Reynold A. Pannettieri Jr., Cynthia J. Koziol-White, Moom Roosan, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Glucocorticoids are widely used for the suppression of inflammation, but evidence is growing that they can have rapid, non-genomic actions that have been unappreciated. Diverse cell signaling effects have been reported for glucocorticoids, leading us to hypothesize that glucocorticoids alone can swiftly increase the 3′,5′-cyclic adenosine monophosphate (cAMP) production. We found that prednisone, fluticasone, budesonide, and progesterone each increased cAMP levels within 3 minutes without phosphodiesterase inhibitors by measuring real-time cAMP dynamics using the cAMP difference detector in situ assay in a variety of immortalized cell lines and primary human airway smooth muscle (HASM) cells. A membrane- impermeable glucocorticoid showed …

Changes In The Utilization Of Osteoporosis Drugs After The 2010 Fda Bisphosphonate Drug Safety Communication, Bander Balkhi, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

Introduction

In October 2010, the US Food and Drug Administration (FDA) issued a safety communication regarding the risks of atypical fractures of the femur, with bisphosphonates drugs. This study evaluated the impact of the bisphosphonates FDA safety communication on the utilization of osteoporosis medications in Medicaid programs.

Methods

Osteoporosis drugs utilization data from the July 2006 to June 2014 were extracted from the national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services (CMS). We performed an interrupted time series analyses to evaluate trends in utilization of osteoporosis drugs before and …

Suppression Of Chrn Endocytosis By Carbonic Anhydrase Car3 In The Pathogenesis Of Myasthenia Gravis, Ailian Du, Shiqian Huang, Xiaonan Zhao, Kuan Fang, Shuangyan Zhang, Jiefang Huang, Xiang Miao, Fulvio Baggi, Rennolds S. Ostrom, Yanyun Zhang, Xiangjun Chen, Congfeng Xu

Pharmacy Faculty Articles and Research

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/ AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis. Using an experimental autoimmune myasthenia gravis animal model and the skeletal muscle cell C2C12, we find that inhibition of CAR3 (the mouse homolog of CA3) promotes CHRN …

Antimicrobial Hydroxyapatite-Gelatin-Silica Composite Pastes With Tunable Setting Properties, Vuk Uskoković, Shreya Ghosh, Victoria M. Wu

Pharmacy Faculty Articles and Research

Bone grafting is one of the commonest surgical procedures, yet all bone substitutes developed so far suffer from specific weaknesses and the search for a bone graft material with ideal physical and biological properties is still ongoing. Calcium phosphate pastes are the most frequently used synthetic bone grafts, yet they (a) often take an impractically long time to set, (b) release the drug content too fast, and (c) do not form pores large enough to accommodate host cells and foster osseointegration. To make up for these deficiencies, we introduced gelatin and silica to pastes composed of 5–15 nm sized hydroxyapatite …

Compartmentalized Camp Responses To Prostaglandin Ep2 Receptor Activation In Human Airway Smooth Muscle Cells, Shailesh R. Agarwal, Kathryn Miyashiro, Htun Latt, Rennolds S. Ostrom, Robert D. Harvey

Pharmacy Faculty Articles and Research

Background and Purpose

Previous studies indicate that prostaglandin EP2 receptors (EP2Rs) selectively couple to adenylyl cyclase type 2 (AC2) in non-lipid raft domains of airway smooth muscle (ASM) cells, where they regulate specific cAMP-dependent responses. The goal of the present study was to identify the cellular microdomains where EP2Rs stimulate cAMP production.

Experimental Approach

FRET-based cAMP biosensors were targeted to different subcellular locations of primary human ASM cells. The Epac2-camps biosensor, which expresses throughout the cell, was used to measure bulk cytoplasmic responses. Epac2-MyrPalm and Epac2-CAAX were used to measure responses associated with lipid raft and non-raft regions of the …

Reduction Of Friction By Recombinant Human Proteoglycan 4 In Il-1Α Stimulated Bovine Cartilage Explants, Katherine M. Larson, Ling Zhang, Khaled A. Elsaid, Tannin A. Schmidt, Braden C. Fleming, Gary J. Badger, Gregory D. Jay

Pharmacy Faculty Articles and Research

A boundary lubricant attaches and protects sliding bearing surfaces by preventing interlocking asperity-asperity contact. Proteoglycan-4 (PRG4) is a boundary lubricant found in the synovial fluid that provides chondroprotection to articular surfaces. Inflammation of the diarthrodial joint modulates local PRG4 concentration. Thus, we measured the effects of inflammation, with Interkeukin-1α (IL-1α) incubation, upon boundary lubrication and PRG4 expression in bovine cartilage explants. We further aimed to determine whether the addition of exogenous human recombinant PRG4 (rhPRG4) could mitigate the effects of inflammation on boundary lubrication and PRG4 expression in vitro.

Cartilage explants, following a 7-day incubation with IL-1α, were tested …

Multifunctional Hydroxyapatite And Poly(D,L-Lactide-Co-Glycolide) Nanoparticles For The Local Delivery Of Cholecalciferol, Nenad Ignjatović, Vuk Uskoković, Zorica Ajduković, Dragan Uskoković

Pharmacy Faculty Articles and Research

Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery …

Nanoparticles Of Cobalt-Substituted Hydroxyapatite In Regeneration Of Mandibular Osteoporotic Bones, Nenad Ignjatović, Zorica Ajduković, Vojin Savić, Stevo Najman, Dragan Mihailović, Perica Vasilijević, Zoran Stojanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic …

Nanosized Hydroxyapatite And Other Calcium Phosphates: Chemistry Of Formation And Application As Drug And Gene Delivery Agents, Vuk Uskoković, Dragan Uskoković

Pharmacy Faculty Articles and Research

The first part of this review looks at the fundamental properties of hydroxyapatite (HAP), the basic mineral constituent of mammalian hard tissues, including the physicochemical features that govern its formation by precipitation. A special emphasis is placed on the analysis of qualities of different methods of synthesis and of the phase transformations intrinsic to the formation of HAP following precipitation from aqueous solutions. This serves as an introduction to the second part and the main subject of this review, which relates to the discourse regarding the prospects of fabrication of ultrafine, nanosized particles based on calcium phosphate carriers with various …

Human Cytomegalovirus Chemokine Receptor Us28-Induced Smooth Muscle Cell Migration Is Mediated By Focal Adhesion Kinase And Src, Daniel N. Streblow, Jennifer Totonchy, Patsy Smith, Ryan Melnychuk, Laurel Hall, Dora Pancheva, Martine Smit, Paola Casarosa, David D. Schlaepfer, Jay A. Nelson

Pharmacy Faculty Articles and Research

The human cytomegalovirus-encoded chemokine receptor US28 induces arterial smooth muscle cell (SMC) migration; however, the underlying mechanisms involved in this process are unclear. We have previously shown that US28-mediated SMC migration occurs by a ligand-dependent process that is sensitive to proteintyrosine kinase inhibitors. We demonstrate here that US28 signals through the non-receptor protein-tyrosine kinases Src and focal adhesion kinase (FAK) and that this activity is necessary for US28-mediated SMC migration. In the presence of RANTES (regulated on activation normal T cell expressed and secreted), US28 stimulates the production of a FAK Src kinase complex. Interestingly, Src co-immunoprecipitates with US28 in …

Synthesis And Characterization Of Hydroxyapatite-Collagen Biocomposite Materials, Vuk Uskoković, Nenad Ignjatović, Nadejda Petranović

Pharmacy Faculty Articles and Research

Hydroxyapatite-collagen composite is a prosperous biomaterial in reconstructive surgery for the reparation of defects within human hard tissue. Within this research, three-dimensional blocks of HAp/collagen composite biomaterial were synthesized by homogenizing the HAp/collagen mixture by cold and hot (T=60oC) pressing (P=49 MPa). The changes in the system were followed by using thermal analysis (DSC & TGA), FT-IR spectroscopy and scanning electron microscopy (SEM). The identification and kinetic analysis of appearing phase transition were done. FT-IR spectrum of the biocomposite shows that neither cold nor hot pressing had significant influence on the individual components of the composite. SEM of the fracture …