Therapeutics Commons^™

Donor Age Effects On The Proliferative And Chondrogenic/Osteogenic Differentiation Performance Of Equine Bone Marrow- And Adipose Tissue Derived Mesenchymal Stem Cells In Culture, Jasmin Bagge

Theses and Dissertations--Veterinary Science

Orthopedic injuries are a major cause of lameness and morbidity in horses. Bone marrow (BM)- and adipose tissue (AT) derived mesenchymal stem cells (MSCs) have shown potential to facilitate the repair of orthopedic injuries and are being used increasingly in veterinary clinics. Presently, the use of MSCs as a therapy for equine patients is most commonly applied as autologous transplants, using BM- and AT-MSCs harvested from the patient shortly after the time of injury. Cell-based therapies are therefore delayed to enable primary cell numbers to be expanded in culture. Of concern, however, are human and rodent studies that have shown …

The Efficacy Of Yoga As An Adjunctive Therapy To Standard Multidisciplinary Care In The Treatment Of Female Patients Presenting With Cognitive Eating Disorder Symptoms, Cassidy Nagle

Capstone Showcase

Introduction: Current treatment of patients exhibiting cognitive eating disorder symptoms is standard multidisciplinary care (SMDC) involving behavioral therapy, medical management and dietetics. Because these symptoms often persist or relapse despite treatment, research has begun to explore adjunctive therapies like yoga for this population. This review will explore seven studies in order to analyze the effect of yoga (I) on cognitive eating disorder symptoms (O) in teenage and adult females (P) when added to SMDC compared to symptom reduction with SMDC alone (C).

Methods: A literature search was conducted in PubMed, Academic Search Ultimate and Google Scholar starting November 2018. Seven …

The Comparative Efficacy Of Amantadine Vs. Lcig Therapy For The Treatment Of Levodopa-Induced Dyskinesia In Patients With Advanced Parkinson's Disease, Katelynn Timony

Capstone Showcase

Introduction: Though levodopa-carbidopa therapy remains the gold standard of Parkinson’s disease (PD) treatment to this day, patients often experience increased dyskinetic activity as a result of long-term treatment; known as levodopa-induced dyskinesia (LID); the mechanism of which is not completely understood. In this review, the efficacy of two adjunct treatments for LID are compared: 1) the concomitant administration of amantadine, an antiviral medication with antidyskinetic properties; and 2) a new form of levodopa administration in the form of an intestinal gel delivered straight via a device much like an insulin pump.

Methods: Two systematic literature searches of primary, peer-reviewed articles …

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 …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Outbreak Of Ebola Virus Disease, Alexandra Dimit, Tiffany Kneuss, Joelle Farano, Haley Armstrong, Jodi Otte, Andrew M. Roecker

Pharmacy and Wellness Review

Ebola virus disease (EVD) has existed as a major health concern with devastating and, many times, fatal symptoms. The recent outbreaks of EVD in West Africa and the Democratic Republic of the Congo (DRC) have incited international concern. In this article, the implications of EVD will be discussed including the etiology, transmission, signs and symptoms, diagnosis and treatment of the disease. In addition to this discussion, the manner in which major health care organizations, including the World Health Organization (WHO), are dealing with treating infected patients and containing spread of the disease will be covered.

Polycystic Ovarian Syndrome And Hyperinsulinemia: Overview And Treatment, Amanda M. Meyer, Lauren D. Bajbus, Sarah E. Drake, Kristen M. Quertinmont, Ashley Overy, Anne Gentry

Pharmacy and Wellness Review

Polycystic ovary syndrome is a prevalent issue in women's health that is associated with hyperinsulinemia and insulin resistance and can lead to long-term health problems. The most highly recommended treatments are diet and lifestyle changes. If these changes alone are not enough, pharmacologic treatments may be employed which include metformin, spironolactone or thiazolidinediones, although more research is needed to fully realize their role. The role of the pharmacist in this disease state includes counseling patients on healthy lifestyle changes, consulting with the physician about prescribing the best medication for each patient, and monitoring therapy adherence in the patient.

Management Of Hypertensive Emergencies In Pediatrics, Jennifer L. Bauer, Jamie L. Amero, Amanda C. Mcdavid, Ryan A. Fischer, Alison L. Huet, Karen L. Kier

Pharmacy and Wellness Review

As hypertension becomes more prevalent in the pediatric population, clinicians are more likely to encounter hypertensive emergencies in children, which require pharmacists and physicians to be educated on the therapeutic options for these emergencies. However, the strict governmental requirements on the testing of these drugs in pediatric patients have limited the amount of available evidence on which to base clinical decisions. This review will highlight the available evidence and preferred treatment options for the management of pediatric hypertensive emergencies.

Recent Advances Spark Significant Guideline Change: Antiretroviral Therapy (Art) At High Cd4+ Counts In The Treatment Naïve Patient, Joshua Ilenin, Kelly Fargo, Lisa Berni, Kristen Thatcher, Caitlin Swann, Andrew Roecker

Pharmacy and Wellness Review

Human immunodeficiency virus (HIV) targets CD4+ lymphocytes, a critical component to proper functioning of the human immune system. HIV is a significant public health concern, having resulted in over 27 million deaths since its discovery. Currently, several different treatment options exist, with combination antiretroviral therapy (ART) at the forefront. Despite the success of ART therapy, there are number of problems, including poor patient compliance. Due to this, the appropriate time to initiate therapy in the treatment naïve patient is under continuous scrutiny. Recently, several trials have demonstrated evidence suggesting that initiating ART at high CD4+ counts in the treatment naïve …

Evolution Of Acute Ischemic Stroke Treatment As Supported By Clinical Trials, Savya S. Shukla, Brian F. Baigorri Md, Roberto I. Fourzali Md, Yafell Serulle Md

Radiology

No abstract provided.

Role Of The Pharmacist In Improving Treatment For Children With Concurrent Gastrointestinal And Autism Spectrum Disorders, Whitney R. Henry, Kaitlin A. Sanders, Jenna L. Schaffner, Leslie M. Hart, Whitney N. Detillion, Anne F. Gentry

Pharmacy and Wellness Review

Over the last several years, a noteworthy association between gastrointestinal (GI) disorders and autism spectrum disorders (ASD) has been documented, although no large population-based studies exist. GI disorders in ASD children may stem from the underlying behavioral, communication, sensory or neurological issues intrinsic to the autistic disorder itself; therefore, the incorporation of alternative therapies, including behavioral modification, may be compelling treatment additions to the GI care traditionally recommended in children. To improve GI symptoms and quality of life in ASD children, a multidisciplinary approach is optimal, with pharmacists playing an active role in determining appropriate pharmacotherapy. Although there is a …

Iron Pill-Induced Gastropathy In Elderly Patients: A Case Series Report, Isin Y. Comba Md, Richard Henriquez, Sundeep Kumar, Ruthvik Srinvasa-Murthy, Maria Wallis-Crespo, Lakhinder Bhatia Md, Joshua Shultz

Gastroenterology

Introduction: Iron deficiency anemia is a global health problem with an estimated two billion cases worldwide. Oral iron supplementation is considered the first line treatment. However, recent studies favor the use of short-term IV iron especially in patients with drug tolerance and efficacy concerns. In this report, we present three cases of iron pill gastropathy in patient's whose clinical courses were complicated by gastric erosion, ulcer or gastrointestinal (GI) bleeding. All of our patients had a history of iron deficiency anemia and were being treated with oral ferrous sulfate.

Case Description/Methods: The first case involved a 72-year-old male with multiple …

Non-Incarcerated Inguinal Hernia With Sigmoidal Diverticulitis, Umair J. Khan, Ali Hassan, Kingsley Dah, M Lambing, P Mathew

Internal Medicine

Introduction: Abdominal wall hernia is defined as a protrusion of a part or whole organ through the wall of a cavity. Inguinal hernias account for 75% of abdominal wall hernias, with a lifetime risk of 27% in men and 3% in women. Indirect inguinal hernia account for 80% of total inguinal hernias. A wide variety of pathological processes can present as inguinal hernias however, large reducible inguinal hernias are quite rare. Recent studies have associated abdominal wall hernia with colonic diverticulosis, a term referred to as herniosis. This association suggests that an underlying connective tissue disorder could be a common …

Peripheral Nerve Stimulator For Treating Nummular Headaches And Occipital Neuralgia, Bruce Dixon Do, Stephen Pyles Md, Ettore Crimi Md

Anesthesiology

No abstract provided.

Effects Of Dabigatran In Mouse Models Of Aging And Cerebral Amyloid Angiopathy, Neethu Michael, Mher Mahoney Grigoryan, Kelley Kilday, Rachita K. Sumbria, Vitaly Vasilevko, Joanne Van Ryn, David H. Cribbs, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants. We analyzed whether the anticoagulant dabigatran produces cerebral microhemorrhage (the pathological substrate of MRI-demonstrable cerebral microbleeds) or intracerebral hemorrhage in aged mice with and without hemorrhage-predisposing angiopathy. We studied aged (22 months old) Tg2576 (a model of CAA) and wild-type (WT) littermate mice. Mice received either dabigatran etexilate (DE) …

Prediction Of Anal Cancer Recurrence After Chemoradiotherapy Using Quantitative Image Features Extracted From Serial (18)F-Fdg Pet/Ct, Michael Chuong

All Publications

No abstract provided.

Influence Of Gut Microbiome On Obesity In Western-Style Dietary Practices Versus Other Diets: A Systematic Review, Keely A. Niemeyer, Doris I. Buezo, Loren Landeros, Karina Corral

OSRI Journal of Student Research and Innovation

BACKGROUND: The human gut is home to a microbiome that has a complex relationship to human health. Like the human genome project, microbiome is catching the attention of researchers who seek new methods to combat obesity and negative health outcomes associated with it.

OBJECTIVES: This systematic review aims to distinguish the impact of a Western diet on gut health verses a plant-based diet.

DATA SOURCES: EBSCOHost library databases inclusive of CINAHL plus, ScienceDirect, and PubMed using keywords to better understand the correlation of dietary practices and microbiome balance.

STUDY ELIGIBILITY: Criteria that include diet, current research, and scholarly peer reviewed …

The Wet Bridge Transfer System: An Novel In Vitro Tool For Assessing Exogenous Surfactant As A Pulmonary Drug Delivery Vehicle, Brandon J. Baer

Western Research Forum

Background:

Due to its complex branching structure, direct drug delivery to the remote areas of the lung is a major challenge. Consequently, most therapies, such as those treating pulmonary infection and inflammation, must utilize large systemic dosing, with the potential for adverse side effects. A novel alternative strategy is to use exogenous surfactant, a material capable of distributing throughout the lung, as a pulmonary drug delivery vehicle.

Objective:

Utilize an in vitro transferring system to assess exogenous surfactant (BLES) as a pulmonary delivery vehicle for different therapeutics.

Methods:

An in vitro technique was developed to simultaneously study surfactant delivery and …

Investigating Neuroinflammation And Demyelination In The Nervous System Of Twitcher Mice By The Use Of Immunohistochemistry, Irene Wilson

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Neuroinflammation and demyelination are the hallmark lesions of the Twitcher mouse—the model of Krabbe Disease. By analyzing hemibrains and sciatic nerves via immunohistochemistry, we supported the microglial hypothesis that early activation of microglial cells, macrophages, and globoid cells in the nervous system of Twitcher mice results in specific cellular polarization states that may contribute to myelin loss. The influx of activated macrophages seen in both the central and peripheral nervous systems at days 21 and 17, respectively, accounted for this polarization. Using selected M1 and M2 markers, YKL-40, and GPNMB and CD206, respectively, we proved that microglial cells and macrophages …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Prophylactic Use Of Lmwh Vs Ufh In Pe Patients, Kyleigh Grieshaber, Barbara Mcclaskey

Posters

As a result of deep vein thrombosis (DVT), a pulmonary embo­lism (PE) can occur which creates a blockage in the body’s pulmonary circulation, leading to cell death. PE is the third leading cause of death in the U.S., while being the most common, most preventable cause of death in hospitalized patients. Understanding the signs and symptoms of PE is essential in order to save patients’ lives. The objective of this research study was to compare the prophylactic use of Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH) in patients effected with PE. Information for this research project was gathered …

Successful Extracorporeal Membrane Oxygenation In The Management Of Acute Respiratory Distress Syndrome And Cardiopulmonary Collapse Secondary To Amniotic Fluid Embolism, Sumon Roy, Nishit A. Biniwale, Venkata S. Pendela, Patricia Oates, Katrina Wojciechowski, Scott C. Feitell

The VAD Journal

Amniotic fluid embolism (AFE) is one of the most devastating complications of pregnancy that typically manifests as acute cardiopulmonary collapse during delivery or in the postpartum period. The potential role of extracorporeal membrane oxygenation (ECMO) as a management technique in severe cases of AFE remains largely unknown given the limited literature available. In this report, we present the first case, to our knowledge, of successful implementation of ECMO as a life-saving measure in a case of hemorrhagic shock due to postpartum bleeding complicated by severe AFE leading to acute respiratory distress syndrome (ARDS) ultimately requiring tracheostomy. Hemodynamic decompensation is often …

Management Of Patients With Brain Metastases From Non-Small Cell Lung Cancer And Adverse Prognostic Features: Multi-National Radiation Treatment Recommendations Are Heterogeneous, Minesh Mehta

All Publications

No abstract provided.

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 …

The Promises And Challenges Of Erythropoietin For Treatment Of Alzheimer's Disease, Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood–brain barrier (BBB) and negative hematopoietic effects are the two …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …

Genomic Prediction Of Relapse In Recipients Of Allogeneic Haematopoietic Stem Cell Transplantation., J Ritari, K Hyvärinen, S Koskela, M Itälä-Remes, R Niittyvuopio, A Nihtinen, U Salmenniemi, M Putkonen, L Volin, T Kwan, T Pastinen, J Partanen

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …