Musculoskeletal Diseases Commons^™

A Comparison Of 4-Year Total Medical Care Costs, Adverse Outcomes, And Opioid/Prescription Analgesic Use For 3 Knee Osteoarthritis Pain Treatments: Intra-Articular Hyaluronic Acid, Intra-Articular Corticosteroids, And Knee Arthroplasty., John Mackowiak, John T Jones, Vinod Dasa

School of Medicine Faculty Publications

To compare the medical costs associated with treatments for knee osteoarthritis (OA): intra-articular corticosteroids (ICS) and intra-articular hyaluronic acid (IHA) primarily, and ICS/IHA vs knee arthroplasty (TKA) secondarily. This was a retrospective analysis of an insurance claims database. Eligible members had diagnosed OA and no claims for ICS, IHA, or TKA during the 6–18-month look-back period. Cohorts of interest over the 4-year observation period were: patients who received ICS only, those who received IHA only, and those who received TKA only. Outcomes assessed included: (1) total allowed medical costs, (2) claims for pre-specified, treatment-related adverse outcomes and costs, and (3) …

Efficacy And Safety Of Abobotulinumtoxina For Upper Limb Spasticity In Children With Cerebral Palsy: A Randomized Repeat-Treatment Study, Mauricio R. Delgado, Ann Tilton, Jorge Carranzo-Del Rio, Nigar Dursun, Marcin Bonikowski, Resa Aydin, Iwona Maciag-Tymecka, Joyce Oleszek, Edward Dabrowski, Anne-Sophie Grandoulier, Philippe Picaut, The Dysport In Pul Study Group

School of Medicine Faculty Publications

Aim: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP). Method: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2–17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4. Results: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], …

Proteoglycan-4 Regulates Fibroblast To Myofibroblast Transition And Expression Of Fibrotic Genes In The Synovium, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Holly Richendrfer, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo.

Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or …

A Closer Look At Muscle Breakdown: An Overview Of The Causes, Complications, And Diagnostics Of Rhabdomyolysis, Jamie Holchin

Senior Honors Theses

Rhabdomyolysis is the rapid breakdown of myocytes in skeletal muscle. This condition can be triggered by a variety of things including crush injury, drugs, prolonged exercise, and venom. Although the causes can vary, the general pathophysiology of rhabdomyolysis is similar. Increased intracellular calcium ion levels instigate the breakdown of cellular and certain organelle membranes of muscle cells. Reactive oxygen species form, ATP is depleted, and the sarcoplasmic reticulum, which regulates muscle contraction, is also damaged. Necrosis ensues, leading to toxic intracellular components spreading throughout the body. Rhabdomyolysis can then lead to several complications including acute renal injury and heart arrhythmias, …

Cd44 Receptor Mediates Urate Crystal Phagocytosis By Macrophages And Regulates Inflammation In A Murine Peritoneal Model Of Acute Gout, Emira Bousoik, Marwa Qadri, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is a chronic arthritis caused by the deposition of poorly soluble monosodium urate monohydrate (MSU) crystals in peripheral joints. Resident macrophages initiate inflammation in response to MSU mediated by NF-κB nuclear translocation and NLRP3 inflammasome activation. We investigated the role of CD44, a transmembrane receptor, in mediating MSU phagocytosis by macrophages. We used an antibody that sheds the extracellular domain (ECD) of CD44 to study the role of the receptor and its associated protein phosphatase 2A (PP2A) in macrophage activation. We also studied the significance of CD44 in mediating MSU inflammation in-vivo. Cd44^−/− BMDMs showed reduced MSU …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

The Effectiveness Of Cannabidiol In Rheumatic Disease Pain: A Systematic Review, Mary C. Wiczek

All Graduate Theses, Dissertations, and Other Capstone Projects

Cannabinoids have long been a part of human culture and medicine, and more recently have been rediscovered for their potential use in the management of rheumatic disease pain. The objective of this review was to evaluate the known clinical effectiveness of cannabidiol treatment for rheumatic disease related pain. The legality and current regulation of these products was also reviewed to establish the current status of federal and state rules regarding their clinical use. Basic definitions of the terms used to differentiate cannabidiol from other cannabinoid products was also outlined. A systematic literature search was then conducted to explore the current …

Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect. …

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …

Sma-Causing Missense Mutations In Survival Motor Neuron (Smn) Display A Wide Range Of Phenotypes When Modeled In Drosophila, Kavita Praveen, Ying Wen, Kelsey M. Gray, John J. Noto, Akash R. Patlolla, Gregory D. Van Duyne, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of …