Medicine and Health Sciences Commons^™

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 …

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 …

Bone Strength And Distal Femur Trabecular Thickness In Sleep Deprived Ovariectomized Rats Treated With Zoledronate, Erin Nolte, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Osteoporosis is a disease that causes the density and quality of bone to be decreased, which can increase the risk of fracture by 40%. 1 in 3 women over the age of 50 will be affected by osteoporosis. This study aimed to show how bone strength and distal femur trabecular thickness might be affected by Zoledronate and sleep-deprivation in estrogen-deficient rats. Wistar female rats were ovariectomized to contrive postmenopausal estrogen-deficiency. The rats were separated into 4 groups. The control group (C, n=4) was given an intraperitoneal (IP) injection of 0.45 mL of 0.9% saline, were housed in standard conditions permitting …

Budesonide Enhances Agonist-Induced Bronchodilation In Human Small Airways By Increasing Camp Production In Airway Smooth Muscle, Cynthia J. Koziol-White, Timothy B. Johnstone, Maia L. Corpuz, Gaoyuan Cao, Sarah Orfanos, Vishal Parikh, Brian Deeney, Omar Tliba, Rennolds S. Ostrom, Ian Dainty, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

The non-genomic mechanisms by which glucocorticoids modulate β₂ agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E₂ (PGE₂), cholera toxin (CTX) or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE₂, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation …

Individuals With Recurrent Low Back Pain Exhibit Significant Changes In Paraspinal Muscle Strength After Intramuscular Fine Wire Electrode Insertion, Szu-Ping Lee, Vincent Dinglasan, Anthony Duong, Russell Totten, Jo Armour Smith

Physical Therapy Faculty Articles and Research

Objective

To examine how insertion and presence of intramuscular fine‐wire electromyography electrodes (IFWE) in lumbar multifidus affect paraspinal muscle strength, endurance, and activation in persons with and without recurrent lower back pain (RLBP) during activities that require high levels of muscle contraction.

Design

Case‐control with randomization of conditions.

Setting

Clinical Research Laboratory.

Participants

Forty participants age 18‐40 were recruited (18 female; mean age = 25.5 yr); 20 with a history of RLBP were compared to a matching control group of 20 without RLBP.

Interventions

Each participant was tested under three conditions over three sessions. On Session 1, the baseline condition, …

Effects Of Obesity And Fall Risk On Gait And Posture Of Community-Dwelling Older Adults, Thurmon E. Lockhart, Christopher W. Frames, Rahul Soangra, Abraham Lieberman

Physical Therapy Faculty Articles and Research

Epidemiological studies link increased fall risk to obesity in older adults, but the mechanism through which obesity increases falls and fall risks is unknown. This study investigates if obesity (Body Mass Index: BMI>30 kg/m2) influenced gait and standing postural characteristics of community dwelling older adults leading to increased risk of falls. One hundred healthy older adults (age 74.0±7.6 years, range of 56-90 years) living independently in a community participated in this study. Participants’ history of falls over the previous two years was recorded, with emphasis on frequency and characteristics of falls. Participants with at least two falls in the …

Nuclear Magnetic Resonance Solution Structure And Functional Behavior Of The Human Proton Channel, Monika Bayrhuber, Innokentiy Maslennikov, Witek Kwiatkowski, Alexander Sobol, Christoph Wierschem, Cédric Eichmann, Lukas Frey, Roland Riek

Pharmacy Faculty Articles and Research

The human voltage-gated proton channel [Hv1⁽¹⁾ or VSDO⁽²⁾] plays an important role in the human innate immune system. Its structure differs considerably from those of other cation channels. It is built solely of a voltage-sensing domain and thus lacks the central pore domain, which is essential for other cation channels. Here, we determined the solution structure of an N- and C-terminally truncated human Hv1 (Δ-Hv1) in the resting state by nuclear magnetic resonance (NMR) spectroscopy. Δ-Hv1 comprises the typical voltage-sensing antiparallel four-helix bundle (S1–S4) preceded by an amphipathic helix (S0). The solution structure corresponds to an intermediate …

A Method To Concatenate Multiple Short Time Series For Evaluating Dynamic Behaviour During Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Gait variability is a sensitive metric for assessing functional deficits in individuals with mobility impairments. To correctly represent the temporal evolution of gait kinematics, nonlinear measures require extended and uninterrupted time series. In this study, we present and validate a novel algorithm for concatenating multiple time-series in order to allow the nonlinear analysis of gait data from standard and unrestricted overground walking protocols. The fullbody gait patterns of twenty healthy subjects were captured during five walking trials (at least 5 minutes) on a treadmill under different weight perturbation conditions. The collected time series were cut into multiple shorter time series …

Does Variability Of Footfall Kinematics Correlate With Dynamic Stability Of The Centre Of Mass During Walking?, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

A stable walking pattern is presumably essential to avoid falls. Stability of walking is most accurately determined by the short-term local dynamic stability (maximum Lyapunov exponent) of the body centre of mass. In many studies related to fall risk, however, variability of step width is considered to be indicative of the stability of the centre of mass during walking. However, other footfall parameters, in particular variability of stride time, have also been associated with increased risk for falling. Therefore, the aim of this study was to investigate the association between short-term local dynamic stability of the body centre of mass …

Fluorometholone Modulates Gene Expression Of Ocular Surface Mucins, Jonathan Taniguchi, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose

Mucins are vital to keep the ocular surface hydrated. Genes encoding for mucins contain a glucocorticoid response element. The purpose of this study was to evaluate the effect of fluorometholone, a glucocorticoid receptor agonist used in the management of dry eye, on the gene expression of conjunctival and corneal epithelial cell mucins.

Methods

Stratified cultures of human conjunctival and corneal epithelial cells were exposed to 25, 50 and 100 nM of fluorometholone alone or in presence of mifepristone, a glucocorticoid receptor antagonist. The mRNA was isolated from the cells and reverse transcribed to cDNA. The cDNA was used for …

Transforming Growth Factor-Β1 Decreases Β2-Agonist–Induced Relaxation In Human Airway Smooth Muscle, Christie A. Ojiaku, Elena Chung, Vishal Parikh, Jazmean K. Williams, Anthony Schwab, Ana Lucia Fuentes, Maia L. Corpuz, Victoria Lui, Sam Paek, Natalia M. Bexiga, Shreya Narayan, Francisco J. Nunez, Kwangmi An, Rennolds S. Ostrom, Steven S. An, Reynold A. Pannettieri Jr.

Pharmacy Faculty Articles and Research

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β₂-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1–treated HASM cells, ISO evoked markedly lower …