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Articles 391 - 420 of 834

Full-Text Articles in Medical Physiology

Molecular Basis For Activation And Biased Signaling At The Thrombin-Activated Gpcr Proteinase Activated Receptor-4 (Par4), Pierre E. Thibeault, Jordan C. Lesarge, D'Arcy Arends, Michaela Fernandes, Peter Chidiac, Peter B. Stathopulos, Leonard G. Luyt, Rithwik Ramachandran Feb 2020

Molecular Basis For Activation And Biased Signaling At The Thrombin-Activated Gpcr Proteinase Activated Receptor-4 (Par4), Pierre E. Thibeault, Jordan C. Lesarge, D'Arcy Arends, Michaela Fernandes, Peter Chidiac, Peter B. Stathopulos, Leonard G. Luyt, Rithwik Ramachandran

Physiology and Pharmacology Publications

© 2020 Thibeault et al. Proteinase-activated receptor (PAR)-4 is a member of the proteolytically-activated PAR family of G-protein– coupled receptors (GPCR) that represents an important target in the development of anti-platelet therapeutics. PARs are activated by proteolytic cleavage of their receptor N terminus by enzymes such as thrombin, trypsin, and cathepsin-G. This reveals the receptor-activating motif, termed the tethered ligand that binds intramolecularly to the receptor and triggers signaling. However, PARs are also activated by exogenous application of synthetic peptides derived from the tethered-ligand sequence. To better understand the molecular basis for PAR4-dependent signaling, we examined PAR4-signaling responses to a …


Hierarchical Clustering Analyses Of Plasma Proteins In Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based On Differential Levels Of Angiogenic And Inflammatory Biomarkers, Zachary Winder, Tiffany L. Sudduth, David W. Fardo, Qiang Cheng, Larry B. Goldstein, Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Donna M. Wilcock Feb 2020

Hierarchical Clustering Analyses Of Plasma Proteins In Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based On Differential Levels Of Angiogenic And Inflammatory Biomarkers, Zachary Winder, Tiffany L. Sudduth, David W. Fardo, Qiang Cheng, Larry B. Goldstein, Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Agglomerative hierarchical clustering analysis (HCA) is a commonly used unsupervised machine learning approach for identifying informative natural clusters of observations. HCA is performed by calculating a pairwise dissimilarity matrix and then clustering similar observations until all observations are grouped within a cluster. Verifying the empirical clusters produced by HCA is complex and not well studied in biomedical applications. Here, we demonstrate the comparability of a novel HCA technique with one that was used in previous biomedical applications while applying both techniques to plasma angiogenic (FGF, FLT, PIGF, Tie-2, VEGF, VEGF-D) and inflammatory (MMP1, MMP3, MMP9, IL8, TNFα) protein data to …


Δ9-Tetrahydrocannabinol Exposure During Rat Pregnancy Leads To Symmetrical Fetal Growth Restriction And Labyrinth-Specific Vascular Defects In The Placenta., Bryony V Natale, Katarina N Gustin, Kendrick Lee, Alison C Holloway, Steven R Laviolette, David R C Natale, Daniel B Hardy Jan 2020

Δ9-Tetrahydrocannabinol Exposure During Rat Pregnancy Leads To Symmetrical Fetal Growth Restriction And Labyrinth-Specific Vascular Defects In The Placenta., Bryony V Natale, Katarina N Gustin, Kendrick Lee, Alison C Holloway, Steven R Laviolette, David R C Natale, Daniel B Hardy

Physiology and Pharmacology Publications

1 in 5 women report cannabis use during pregnancy, with nausea cited as their primary motivation. Studies show that (-)-△9-tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis, causes fetal growth restriction, though the mechanisms are not well understood. Given the critical role of the placenta to transfer oxygen and nutrients from mother, to the fetus, any compromise in the development of fetal-placental circulation significantly affects maternal-fetal exchange and thereby, fetal growth. The goal of this study was to examine, in rats, the impact of maternal Δ9-THC exposure on fetal development, neonatal outcomes, and placental development. Dams received a daily intraperitoneal …


Hypercholesterolemia Accelerates Both The Initiation And Progression Of Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Jing Liu, Hisashi Sawada, Deborah A. Howatt, Jessica J. Moorleghen, Olga A. Vsevolozhskaya, Alan Daugherty, Hong S. Lu Jan 2020

Hypercholesterolemia Accelerates Both The Initiation And Progression Of Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Jing Liu, Hisashi Sawada, Deborah A. Howatt, Jessica J. Moorleghen, Olga A. Vsevolozhskaya, Alan Daugherty, Hong S. Lu

Pharmacology and Nutritional Sciences Faculty Publications

Objective: This study determined whether hypercholesterolemia would contribute to both the initiation and progression of angiotensin (Ang)II-induced abdominal aortic aneurysms (AAAs) in mice.

Methods and Results: To determine whether hypercholesterolemia accelerates the initiation of AAAs, male low-density lipoprotein (LDL) receptor -/- mice were either fed one week of Western diet prior to starting AngII infusion or initiated Western diet one week after starting AngII infusion. During the first week of AngII infusion, mice fed normal diet had less luminal expansion of the suprarenal aorta compared to those initiated Western diet after the first week of AngII infusion. The two groups …


Role Of Atp1a1 In Skeletal Muscle Growth And Metabolism, Laura C. Kutz Jan 2020

Role Of Atp1a1 In Skeletal Muscle Growth And Metabolism, Laura C. Kutz

Theses, Dissertations and Capstones

Skeletal muscle comprises approximately 30% of total body mass, and loss of muscle mass and dysfunctional muscle metabolism are implicated in multiple disease states, including type 2 diabetes, heart failure, and septic shock. As such, understanding the mechanisms of skeletal muscle growth and atrophy, including pharmaceutical targets that may prove safe and effective, is therefore an important goal of current research on skeletal muscle physiology. One potential target in skeletal muscle development and function that has not been fully explored is the Na/KATPase (NKA), especially the α1 isoform. This isoform has a unique signaling function that has previously been shown …


Nanoformulation Of The Superoxide Dismutase Mimic, Mntnbuoe-2-Pyp5+, Prevents Its Acute Hypotensive Response, Sarah L. Schlichte, Svetlana Romanova, Kenichi Katsurada, Elizabeth A. Kosmacek, Tatiana K. Bronich, Kaushik K. Patel, Rebecca E. Oberley-Deegan, Matthew C. Zimmerman Jan 2020

Nanoformulation Of The Superoxide Dismutase Mimic, Mntnbuoe-2-Pyp5+, Prevents Its Acute Hypotensive Response, Sarah L. Schlichte, Svetlana Romanova, Kenichi Katsurada, Elizabeth A. Kosmacek, Tatiana K. Bronich, Kaushik K. Patel, Rebecca E. Oberley-Deegan, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Scavenging superoxide (O2•-) via overexpression of superoxide dismutase (SOD) or administration of SOD mimics improves outcomes in multiple experimental models of human disease including cardiovascular disease, neurodegeneration, and cancer. While few SOD mimics have transitioned to clinical trials, MnTnBuOE-2-PyP5+ (BuOE), a manganese porphyrin SOD mimic, is currently in clinical trials as a radioprotector for cancer patients; thus, providing hope for the use of SOD mimics in the clinical setting. However, BuOE transiently alters cardiovascular function including a significant and precipitous decrease in blood pressure. To limit BuOE's acute hypotensive action, we developed a mesoporous silica nanoparticle …


Postnatal Catch-Up Growth Leads To Higher P66shc And Mitochondrial Dysfunction., Shelby Oke, Gurjeev Sohi, Daniel Barry Hardy Jan 2020

Postnatal Catch-Up Growth Leads To Higher P66shc And Mitochondrial Dysfunction., Shelby Oke, Gurjeev Sohi, Daniel Barry Hardy

Physiology and Pharmacology Publications

Epidemiological data suggest an inverse relationship between birth weight and long-term metabolic deficits, which is exacerbated by postnatal catch-up growth. We have previously demonstrated that rat offspring subject to maternal protein restriction (MPR) followed by catch-up growth exhibit impaired hepatic function and ER stress. Given that mitochondrial dysfunction is associated with various metabolic pathologies, we hypothesized that altered expression of p66Shc, a gatekeeper of oxidative stress and mitochondrial function, contributes to the hepatic defects observed in MPR offspring. To test this hypothesis, pregnant Wistar rats were fed a control (20% protein) diet or an isocaloric low protein (8%; LP) diet …


Quantification Of Joint Blood Flow By Dynamic Contrast-Enhanced Near-Infrared Spectroscopy: Application To Monitoring Disease Activity In A Rat Model Of Rheumatoid Arthritis, Seva Ioussoufovitch, Laura B. Morrison, Lise Desjardins, Jennifer A. Hadway, Keith St Lawrence, Ting Yim Lee, Frank Beier, Mamadou Diop Jan 2020

Quantification Of Joint Blood Flow By Dynamic Contrast-Enhanced Near-Infrared Spectroscopy: Application To Monitoring Disease Activity In A Rat Model Of Rheumatoid Arthritis, Seva Ioussoufovitch, Laura B. Morrison, Lise Desjardins, Jennifer A. Hadway, Keith St Lawrence, Ting Yim Lee, Frank Beier, Mamadou Diop

Physiology and Pharmacology Publications

No abstract provided.


Seen In Science: Lgbtq+ Inclusivity In Anatomy & Physiology Texts, Harshini Sirvisetty, Kat Ray King, Linda Catherine Fuselier Jan 2020

Seen In Science: Lgbtq+ Inclusivity In Anatomy & Physiology Texts, Harshini Sirvisetty, Kat Ray King, Linda Catherine Fuselier

Undergraduate Arts and Research Showcase

Biology is unique from other science disciplines in that concepts taught in core classes can inform our student’s understanding of sex and gender. A biology major encounters lessons on sex determination, sexual reproduction, and sex characteristics in their courses. The language used in these units matters. It is imperative that educators consider how the language, examples, and content that we use in classrooms drive (or not) inclusivity for gender- and sexuality-diverse (GSD) (aka LGBTQ+) individuals. We chose to analyze four college-level human anatomy/physiology (AP) textbooks for GSD population inclusivity. We adopted a queer theory framework to critically examine how sex, …


The Effects Of An Inflammasome Inhibitor Olt1177 On The Development Of Ischemic Heart Failure, Joseph S. Aliaga Jan 2020

The Effects Of An Inflammasome Inhibitor Olt1177 On The Development Of Ischemic Heart Failure, Joseph S. Aliaga

Theses and Dissertations

Thesis Abstract

THE EFFECTS OF AN INFLAMMASOME INHIBITOR OLT1177 ON THE DEVELOPMENT OF ISCHEMIC HEART FAILURE

By Joseph S. Aliaga, BS

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2020

Background: Evidence suggests that prolonged and enhanced pro-inflammatory signaling, modulated by the NLRP3 inflammasome, plays a crucial role in the pathophysiology of several different types of cardiovascular diseases such as acute myocardial infarction (AMI), adverse ventricular remodeling, and heart failure (HF). Consequently, we hypothesize that attenuating the enhanced inflammatory response using a pharmacological NLRP3 …


The Role Of Interleukin-18 In Myocardial Ischemia/Reperfusion, Yogesh Dhakal Jan 2020

The Role Of Interleukin-18 In Myocardial Ischemia/Reperfusion, Yogesh Dhakal

Theses and Dissertations

Acute Myocardial Infarction (AMI) is one of the leading causes of morbidity for cardiovascular diseases (CVDs) in the western world. While mortality rates for AMI has reduced in the last 20 years due to advancements in clinical interventions, patients who have an AMI are significantly more likely to develop heart failure (HF) in the following years. Reperfusion of the ischemic tissue is a necessary procedure to restore blood delivery to cardiomyocytes, minimize myocardial dysfunction, and reduce infarct size. Still, the step of reperfusion itself induces myocardial damage in a phenomenon known as reperfusion injury. Considering that the degree of myocardial …


Physiological Effects During Aerobatic Flights On Science Astronaut Candidates, Pedro Llanos, Diego M. Garcia Jan 2020

Physiological Effects During Aerobatic Flights On Science Astronaut Candidates, Pedro Llanos, Diego M. Garcia

Publications

Spaceflight is considered the last frontier in terms of science, technology, and engineering. But it is also the next frontier in terms of human physiology and performance. After more than 200,000 years humans have evolved under earth’s gravity and atmospheric conditions, spaceflight poses environmental stresses for which human physiology is not adapted. Hypoxia, accelerations, and radiation are among such stressors, our research involves suborbital flights aiming to develop effective countermeasures in order to assure sustainable human space presence. The physiologic baseline of spaceflight participants is subject to great variability driven by age, gender, fitness, and metabolic reserve. The objective of …


Physiological Effects On Scientist Astronaut Candidates: Hypobaric Training Assessment, Pedro Llanos, Diego Garcia Jan 2020

Physiological Effects On Scientist Astronaut Candidates: Hypobaric Training Assessment, Pedro Llanos, Diego Garcia

Publications

This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model …


Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer Jan 2020

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 …


Glp-1 Mediated Diuresis And Natriuresis Are Blunted In Heart Failure And Restored By Selective Afferent Renal Denervation, Kenichi Katsurada, Shyam Sundar Nandi, Hong Zheng, Xuefei Liu, Neeru M. Sharma, Kaushik K. Patel Jan 2020

Glp-1 Mediated Diuresis And Natriuresis Are Blunted In Heart Failure And Restored By Selective Afferent Renal Denervation, Kenichi Katsurada, Shyam Sundar Nandi, Hong Zheng, Xuefei Liu, Neeru M. Sharma, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity.

METHODS: HF was induced in rats by coronary artery ligation. The direct recording of afferent renal nerve activity (ARNA) with intrapelvic injection of GLP-1 and total …


Will Pitch Velocity Remain Consistent Throughout A Competitive Baseball Season Following Blood Flow Restriction: An Observational Study, Mackenzie Marie Evans Jan 2020

Will Pitch Velocity Remain Consistent Throughout A Competitive Baseball Season Following Blood Flow Restriction: An Observational Study, Mackenzie Marie Evans

Graduate Theses, Dissertations, and Problem Reports (ETD)

Context: Blood flow restriction (BFR) has previously been used in a rehabilitation setting to decrease the external load applied to post-surgical patients and those with chronic debilitating conditions. BFR in a performance context has been explored minimally, particularly as it applies to baseball pitching over time. Objective: The purpose of this study was to retrospectively investigate the trend in throwing velocity of fastballs with BFR implementation over one competitive season. Design: This study was a retrospective longitudinal design on pitching velocity of fastballs throughout a competitive season. Setting: The data collection and analysis was completed at …


Artificial Reverse Shoulder Arthroplasty Joint Project, Michael Rosen, Bailei Hoyng Jan 2020

Artificial Reverse Shoulder Arthroplasty Joint Project, Michael Rosen, Bailei Hoyng

Williams Honors College, Honors Research Projects

This proposed project will be developing an artificial reverse shoulder arthroplasty joint that focuses on improvements to the Zimmer Biomet Comprehensive Reverse System by freating a unique feature, or features, to the humeral component that focuses on the prevention of dislocation by not limiting the range of motion of men from ages 45 to 65 years.

The development of the this project will utilize the Food and Drug Administration (FDA) medical device design process. This project will involve a total of four Biomedical Engineering students from the University of Akron. Two students, Michael and Bailei, are in the Honors college …


An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski Jan 2020

An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski

Theses and Dissertations

Organ transplants are a necessary intervention for many diseases that result in end stage organ failure. The donation pool cannot match the demands of the transplant list, so expanding the pool to include donation after cardiac death (DCD) is desired. However, there are increased odds of graft failure and ischemic cholangiopathy leading to inferior outcomes when DCD livers are used. Ischemic cholangiopathy consists of multiple diffuse strictures and fibrosis of the bile ducts leading to a loss of epithelialization and fibrosis. The cellular mechanism is proposed to be epithelial-to-mesenchymal transition (EMT). TGF-�� is seen as a key initiator of EMT, …


Connectivity Differences Between Gulf War Illness (Gwi) Phenotypes During A Test Of Attention, Tomas Clarke, Jessie Jamieson, Patrick Malone, Rakib U. Rayhan, Stuart Washington, John W. Vanmeter, James N. Baraniuk Dec 2019

Connectivity Differences Between Gulf War Illness (Gwi) Phenotypes During A Test Of Attention, Tomas Clarke, Jessie Jamieson, Patrick Malone, Rakib U. Rayhan, Stuart Washington, John W. Vanmeter, James N. Baraniuk

Department of Mathematics: Faculty Publications

One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise. One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention …


Trade-Offs Between Survival And Reproduction In Starvation-Selected Drosophila Melanogaster, Tammara Beeghly Dec 2019

Trade-Offs Between Survival And Reproduction In Starvation-Selected Drosophila Melanogaster, Tammara Beeghly

UNLV Theses, Dissertations, Professional Papers, and Capstones

Evolutionary outcomes are demonstrated by traits that affect an organism’s schedule of reproduction and survival. These life history traits are reflected in an organism’s physiology, development and behavior. Environmental changes, such as availability of nutritional resources, can profoundly affect evolutionary outcomes of individuals and populations. When shortages arise, there will be trade-offs in the allocation of resources, where one trait prevails at the expense of another.

In the laboratory, we can mimic conditions in nature and study the specific effects of the conditions that we re-create. In our case, over 100 generations of Drosophila melanogaster have been selected for starvation …


An Analysis Of Abdominal Stability Following Hyperthermic Exercise In Euhydrated And Dehydrated Conditions, Carli Ceckanowicz Dec 2019

An Analysis Of Abdominal Stability Following Hyperthermic Exercise In Euhydrated And Dehydrated Conditions, Carli Ceckanowicz

Honors Scholar Theses

Core stability is essential for maintaining safety and optimizing performance during exercise and sport. The purpose of this study is to analyze how heat and hydration status (euhydrated USG<1.025 or dehydrated USG>1.025) can impair trunk stability in males and females (in both follicular and luteal phases) using the Trunk Stability Test (TST). Participants complete three blocks of 30 minutes of hyperthermic (35±1.299 oC and 49.418±5.0329% relative humidity) treadmill exercise. Exercise intensity is equivalent to 15 minutes at either 11W/kg or 7W/kg and the following 15 minutes at either 7W/kg or 4W/kg, respectively, based on individual heat production data. TST data will …


The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan Dec 2019

The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan

Electronic Theses and Dissertations

Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in …


Exposure To The Rxr Agonist Sr11237 In Early Life Causes Disturbed Skeletal Morphogenesis In A Rat Model, Holly Dupuis, Michael Andrew Pest, Ermina Hadzic, Thin Xuan Vo, Daniel B. Hardy, Frank Beier Oct 2019

Exposure To The Rxr Agonist Sr11237 In Early Life Causes Disturbed Skeletal Morphogenesis In A Rat Model, Holly Dupuis, Michael Andrew Pest, Ermina Hadzic, Thin Xuan Vo, Daniel B. Hardy, Frank Beier

Physiology and Pharmacology Publications

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. …


Sciatic Nerve Cut And Repair Using Fibrin Glue In Adult Mice, Erica T. Akhter, Travis M. Rotterman, Arthur W. English, Francisco J. Alvarez Sep 2019

Sciatic Nerve Cut And Repair Using Fibrin Glue In Adult Mice, Erica T. Akhter, Travis M. Rotterman, Arthur W. English, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injury (PNI) is an excellent model for studying neural responses to injury and elucidating the mechanisms that can facilitate axon regeneration. As such, several animal models have been employed to study regenerative mechanisms after PNI, including Aplysia, zebrafish, rabbits, cats and rodents. This protocol describes how to perform a sciatic nerve injury and repair in mice, one of the most frequently used models to study mechanisms that facilitate recovery after PNI, and that takes advantage of the availability of many genetic models. In this protocol, we describe a method for using fibrin glue to secure the proximal …


Drug Interactions And Pharmacogenetic Factors Contribute To Variation In Apixaban Concentration In Atrial Fibrillation Patients In Routine Care, Markus Gulilat, Denise Keller, Bradley Linton, A. Demetri Pananos, Daniel Lizotte, George K. Dresser, Jeffrey Alfonsi, Rommel G. Tirona, Richard B. Kim, Ute I. Schwarz Sep 2019

Drug Interactions And Pharmacogenetic Factors Contribute To Variation In Apixaban Concentration In Atrial Fibrillation Patients In Routine Care, Markus Gulilat, Denise Keller, Bradley Linton, A. Demetri Pananos, Daniel Lizotte, George K. Dresser, Jeffrey Alfonsi, Rommel G. Tirona, Richard B. Kim, Ute I. Schwarz

Physiology and Pharmacology Publications

Factor Xa-inhibitor apixaban is an oral anticoagulant prescribed in atrial fibrillation (AF) for stroke prevention. Its pharmacokinetic profile is known to be affected by cytochrome P450 (CYP)3A metabolism, while it is also a substrate of the efflux transporters ATP-binding cassette (ABC)B1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein, BCRP). In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2, ABCB1, CYP3A4*22, CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average …


Targeting Pathogenic Lafora Bodies In Lafora Disease Using An Antibody-Enzyme Fusion, M. Kathryn Brewer, Annette M. Uittenbogaard, Grant L. Austin, Dyann M. Segvich, Anna Depaoli-Roach, Peter J. Roach, John J. Mccarthy, Zoe R. Simmons, Jason A. Brandon, Zhengqiu Zhou, Jill Zeller, Lyndsay E. A. Young, Ramon C. Sun, James R. Pauly, Nadine M. Aziz, Bradley L. Hodges, Tracy R. Mcknight, Dustin D. Armstrong, Matthew S. Gentry Jul 2019

Targeting Pathogenic Lafora Bodies In Lafora Disease Using An Antibody-Enzyme Fusion, M. Kathryn Brewer, Annette M. Uittenbogaard, Grant L. Austin, Dyann M. Segvich, Anna Depaoli-Roach, Peter J. Roach, John J. Mccarthy, Zoe R. Simmons, Jason A. Brandon, Zhengqiu Zhou, Jill Zeller, Lyndsay E. A. Young, Ramon C. Sun, James R. Pauly, Nadine M. Aziz, Bradley L. Hodges, Tracy R. Mcknight, Dustin D. Armstrong, Matthew S. Gentry

Molecular and Cellular Biochemistry Faculty Publications

Lafora disease (LD) is a fatal childhood epilepsy caused by recessive mutations in either the EPM2A or EPM2B gene. A hallmark of LD is the intracellular accumulation of insoluble polysaccharide deposits known as Lafora bodies (LBs) in the brain and other tissues. In LD mouse models, genetic reduction of glycogen synthesis eliminates LB formation and rescues the neurological phenotype. Therefore, LBs have become a therapeutic target for ameliorating LD. Herein, we demonstrate that human pancreatic α-amylase degrades LBs. We fused this amylase to a cell-penetrating antibody fragment, and this antibody-enzyme fusion (VAL-0417) degrades LBs in vitro and dramatically reduces LB …


White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups, Omar M. Al-Janabi, Christopher E. Bauer, Larry B. Goldstein, Richard R. Murphy, Ahmed A. Bahrani, Charles D. Smith, Donna M. Wilcock, Brian T. Gold, Gregory A. Jicha Jul 2019

White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups, Omar M. Al-Janabi, Christopher E. Bauer, Larry B. Goldstein, Richard R. Murphy, Ahmed A. Bahrani, Charles D. Smith, Donna M. Wilcock, Brian T. Gold, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and …


Self-Directed Down-Regulation Of Auditory Cortex Activity Mediated By Real-Time Fmri Neurofeedback Augments Attentional Processes, Resting Cerebral Perfusion, And Auditory Activation, Matthew Sherwood, Jason G. Parker, Emily E. Diller, Subhashini Ganapathy, Kevin B. Bennett, Carlos R. Esquivel, Jeremy T. Nelson Jul 2019

Self-Directed Down-Regulation Of Auditory Cortex Activity Mediated By Real-Time Fmri Neurofeedback Augments Attentional Processes, Resting Cerebral Perfusion, And Auditory Activation, Matthew Sherwood, Jason G. Parker, Emily E. Diller, Subhashini Ganapathy, Kevin B. Bennett, Carlos R. Esquivel, Jeremy T. Nelson

Neuroscience, Cell Biology & Physiology Faculty Publications

In this work, we investigated the use of real-time functional magnetic resonance imaging (fMRI) with neurofeedback training (NFT) to teach volitional down-regulation of the auditory cortex (AC) using directed attention strategies as there is a growing interest in the application of fMRI-NFT to treat neurologic disorders. Healthy participants were separated into two groups: the experimental group received real feedback regarding activity in the AC; the control group was supplied sham feedback yoked from a random participant in the experimental group and matched for fMRI-NFT experience. Each participant underwent five fMRI-NFT sessions. Each session contained 2 neurofeedback runs where participants completed …


System Dynamics To Investigate Opioid Use And Chiropractic Care For Chronic Musculoskeletal Pain, Marion Mcgregor, Alexandra Nielsen, Chadwick Chung, Mark Fillery, Wayne Wakeland, Silvano Mior Jun 2019

System Dynamics To Investigate Opioid Use And Chiropractic Care For Chronic Musculoskeletal Pain, Marion Mcgregor, Alexandra Nielsen, Chadwick Chung, Mark Fillery, Wayne Wakeland, Silvano Mior

Complex Systems Faculty Publications and Presentations

Objective: The purpose of this investigation was to create a system dynamics (SD) model, including published data and required assumptions, as a tool for future research identifying the role of chiropractic care in the management of chronic, nonmalignant pain in a Canadian population. Methods: We present an illustrative case description of how we evaluated the feasibility of conducting a large-scale clinical trial to assess the impact of chiropractic care in mitigating excessive opioid use in Canada. We applied SD modeling using current evidence and key assumptions where such evidence was lacking. Modeling outcomes were highlighted to determine which potential …


Poly(Ester Amide) Particles For Controlled Delivery Of Celecoxib, Ian J. Villamagna, Trent N. Gordon, Mark B. Hurtig, Frank Beier, Elizabeth R. Gillies Jun 2019

Poly(Ester Amide) Particles For Controlled Delivery Of Celecoxib, Ian J. Villamagna, Trent N. Gordon, Mark B. Hurtig, Frank Beier, Elizabeth R. Gillies

Physiology and Pharmacology Publications

© 2019 Wiley Periodicals, Inc. Many potential pharmacological treatments for osteoarthritis can result in undesirable side effects due to the systemic administration of drugs, making the direct delivery of drugs to joints an attractive alternative. Poly(ester amide)s (PEAs) have been shown to exhibit promising properties for the development of particle-based intra-articular delivery vehicles. However, a limited range of PEA structures has been investigated. In this study, we prepared and characterized the properties of two different PEA particles composed of l-phenylalanine, sebacic acid, and either 1,4-butanediol or 1,8-octanediol (PBSe and POSe, respectively). The anti-inflammatory drug celecoxib (CXB) was encapsulated into the …