Pharmacy and Pharmaceutical Sciences Commons^™

Development Of A Cx46 Targeting Strategy For Cancer Stem Cells, Erin E. Mulkeans-Hubert, Luke A. Torre-Healy, Daniel J, Silver, Jennifer T. Eurich, Defne Bayik, Emily Serbinowski, Masahiro Hitomi, John Zhou, Bartlomiej Przychodzen, Renliang Zhang, Samuel A. Sprowls, James S. Hale, Tyler J. Alban, Artem Berezovsky, Brent A. Bell, Paul R. Lockman, Babal K. Jha, Justin D. Lathia

Faculty & Staff Scholarship

Gap-junction-mediated cell-cell communication enables tumor cells to synchronize complex processes. We previously found that glioblastoma cancer stem cells (CSCs) express higher levels of the gap junction protein Cx46 compared to non-stem tumor cells (non-CSCs) and that this was necessary and sufficient for CSC maintenance. To understand the mechanism underlying this requirement, we use point mutants to disrupt specific functions of Cx46 and find that Cx46-mediated gap-junction coupling is critical for CSCs. To develop a Cx46 targeting strategy, we screen a clinically relevant small molecule library and identify clofazimine as an inhibitor of Cx46-specific cell-cell communication. Clofazimine attenuates proliferation, self-renewal, and …

Crystal Structure Of The Mitochondrial Protein Mitoneet Bound To A Benze-Sulfonide Ligand, Werner J. Geldenhuys, Timothy E. Long, Pushkar Saralkar, Toshio Iwasaki, Rasia A. A. Nuñez, Rajesh R. Nair, Mary E. Konkle, Michael A. Menze, Mark V. Pinti, John M. Hollander, Lori A. Hazlehurst, Aaron R. Robart

Faculty & Staff Scholarship

MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remains elusive. Here we report the crystal structure of the soluble domain of human mitoNEET with a sulfonamide ligand, furosemide. Exploration of the high-resolution crystal structure is used to design mitoNEET binding molecules in a pilot study of molecular probes for use in future development of mitochondrial targeted therapies for a wide variety …

Metabolic Modulation Predicts Heart Failure Tests Performance, Daniel Contaifer Jr., Leo F. Buckley, George Wohlford, Naren G. Kumar, Joshua M. Morriss, Asanga D. Ranasinghe, Salvatore Carbone, Justin M. Canada, Cory Trankle, Antonio Abbate, Benjamin W. Van Tassell, Dayanjan S. Wijesinghe

Pharmacotherapy and Outcomes Science Publications

The metabolic changes that accompany changes in Cardiopulmonary testing (CPET) and heart failure biomarkers (HFbio) are not well known. We undertook metabolomic and lipidomic phenotyping of a cohort of heart failure (HF) patients and utilized Multiple Regression Analysis (MRA) to identify associations to CPET and HFBio test performance (peak oxygen consumption (Peak VO₂), oxygen uptake efficiency slope (OUES), exercise duration, and minute ventilation-carbon dioxide production slope (VE/VCO₂ slope), as well as the established HF biomarkers of inflammation C-reactive protein (CRP), beta-galactoside-binding protein (galectin-3), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP)). A cohort of 49 patients with …

Efficacy Of Sodium Polystyrene Sulfonate In Hyperkalemia, Rajandeep Kaur Pharmd, Dustin D Linn Pharmd, Bcps, Bcccp

Parkview Pharmacy Department

Poster Presentation

Background:

Clinically significant hyperkalemia, defined as potassium ≥ 6.0 mEq/L can be a life-threatening, and urgent lowering of serum potassium is needed to prevent life-threatening arrhythmias. There are many potential causes of hyperkalemia including acute or chronic kidney disease, medications (e.g. ACE-inhibitors), and rhabdomyolysis among other causes.

Market Claims And Efficacy Information In Direct‐To‐Consumer Prescription Drug Print Advertisements, Kathryn J. Aikin Phd, Kevin R. Betts Phd, Aysha Keisler Phd, Kathryn Schaefer Ziemer Phd

United States Food and Drug Administration: Publications

This study examined the impact of “New” and “#1 Prescribed” market claims and quantitative efficacy information on perceptions of a hypothetical prescription drug in a direct‐to‐consumer (DTC) print advertisement. We examined two market claims (New and #1 Prescribed), two efficacy levels (higher and lower), and a control condition without this information. Participants with diabetes were randomized to review one ad version and asked their perceptions of the ad's message, the drug's benefits, side effects and risks, doctors' opinions about the drug, and behavioral intention to use the drug, as well as recall and recognition of drug benefits and risks. Results …

Youth Perception Of Harm And Addictiveness Of Tobacco Products: Findings From The Population Assessment Of Tobacco And Health Study (Wave 1), David R. Strong, Karen Messer, Martha White, Yuyan Shi, Madison Noble, David B. Portnoy, Alexander Persoskie, Annette R. Kaufman, Kelvin Choi, Charles Carusi, Maansi Bansal-Travers, Andrew Hyland, John Pierce

United States Food and Drug Administration: Publications

Purpose: We provide a US national assessment of youth perceptions of the harm and addictiveness of six separate tobacco products, identifying a continuum of perceived harm associated with a range of products in relation to patterns of current use, former use, and susceptibility to use tobacco products.

Methods: We evaluated youth respondents (N=13,651) ages 12–17 from Wave 1 (2013–2014) of the Population Assessment of Tobacco and Health (PATH) Study. Analyses (2015–2016) focused on refining mea- sures of perceived harm for each product and delineating youth characteristics (demographic, tobacco use status) associated with beliefs about the harmfulness and addictiveness of tobacco …

Associations Of Risk Factors Of E-Cigarette And Cigarette Use And Susceptibility To Use Among Baseline Path Study Youth Participants (2013–2014), Michael D. Sawdey, Hannah R. Day, Blair Coleman, Lisa D. Gardner, Sarah E. Johnson, Jean Limpert, Hoda T. Hammad, Macieji L. Goniewicz, David B. Abrams, Cassandra A. Stanton, Jennifer L. Pearson, Annette R. Kaufman, Heather L. Kimmel, Cristine D. Delnevo, Wilson M. Compton, Maansi Bansal-Travers, Raymond S. Niaura, Andrew Hyland, Bridget K. Ambrose

United States Food and Drug Administration: Publications

Introduction: Improved understanding of the distribution of traditional risk factors of cigarette smoking among youth who have ever used or are susceptible to e-cigarettes and cigarettes will inform future longitudinal studies examining transitions in use.

Methods: Multiple logistic regression analysis was conducted using data from youth (ages 12–17 years) who had ever heard of e-cigarettes at baseline of the PATH Study (n = 12,460) to compare the distribution of risk factors for cigarette smoking among seven mutually exclusive groups based on ever cigarette/e-cigarette use and sus- ceptibility status.

Results: Compared to committed never users, youth susceptible to e-cigarettes, cigarettes, or …

Selection And Consumption Of Lunches By National School Lunch Program T Participants, Janet G. Peckham, Jaclyn D. Kropp, Thomas A. Mroz, Vivian Haley-Zitlin, Ellen M. Granberg

United States Food and Drug Administration: Publications

The Healthy, Hunger-Free Kids Act of 2010 requires schools participating in the National School Lunch Program (NSLP) to offer a variety of healthy food options each day. Using digital photography data collected from two suburban elementary schools in the spring of 2013, we examine NSLP participant's selection and consumption of all five NSLP lunch components ((1) milk, (2) vegetable, (3) fruit, (4) meat/meat alternate (MA), and (5) grain). We use logit regressions to analyze the selection of the various lunch components by race/ethnicity, gender, grade, and household income level. In addition, ordinary least squares regressions are used to analyze the …

Examining The Role Of Menthol Cigarettes In Progression To Established T Smoking Among Youth, James Nonnemaker, Shari P. Feirman, Anna Macmonegle, Bridget K. Ambrose, Kia J. Jackson, Megan J. Schroeder, Alexandria A. Smith, William Ridgeway, Olga Rass

United States Food and Drug Administration: Publications

Background: Menthol, a flavoring compound added to cigarettes, makes cigarettes more appealing to youth and inexperienced smokers and increases cigarettes' abuse liability. However, limited studies are available on menthol's role in smoking progression.

Methods: To assess the association between menthol in cigarettes and progression to established smoking, we used five waves of data from the Evaluation of Public Education Campaign on Teen Tobacco Cohort Study, a nationally representative longitudinal survey of U.S. youth conducted as part of “The Real Cost” evaluation. We used discrete time survival analysis to model the occurrence of two event outcomes—progression to established, current smoking and …

Modeling Of Excitatory Amino Acid Transporters And Clearance Of Synaptic Cleft On Millisecond Time Scale, Denis M. Shchepakin, Leonid Kalachev, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Excitatory Amino Acid Transporters (EAATs) operate over wide time scales in the brain. They maintain low ambient concentrations of the primary excitatory amino acid neurotransmitter glutamate, but they also seem to play a significant role in clearing glutamate from the synaptic cleft in the millisecond time-scale process of chemical communication that occurs between neurons. The detailed kinetic mechanisms underlying glutamate uptake and clearance remain incompletely understood. In this work we used a combination of methods to model EAAT kinetics and gain insight into the impact of transport on glutamate dynamics in a general sense. We derive reliable estimates of the …

Protective Actions Of Oxytocin On Aortic Wistar And Shr Vsmcs, Varun Kumar Soti

Student Theses, Dissertations and Capstones

Background. Oxytocin, known as a female reproductive hormone, has emerged as a cardiovascular hormone showing cardioprotective effects, for instance, negative chronotropic and inotropic effects and ANP release in cardiomyocytes and endothelium. However, oxytocin’s effect in VSMCs remains to be explored. Objectives. This study had three goals: characterizing oxytocin’s effect on proliferation, inflammation, oxidative stress, and vasocontraction pathway in Wistar VSMCs; determining oxytocin’s effect on Ang II; describing oxytocin’s effect and its interaction with Ang II in SHR VSMCs. Methods: Aortic VSMCs were isolated from Wistar rats and SHRs. Hemocytometer, MTT and 3H-Thymidine incorporation assays, and flow cytometry were employed for …

2019 Edition, Southwestern Oklahoma State University

The Sig

The Sig Newsletter from the Southwestern Oklahoma State University College of Pharmacy - 2019 Edition

A Preliminary Investigation Towards The Risk Stratification Of Allogeneic Stem Cell Recipients With Respect To The Potential For Development Of Gvhd Via Their Pre-Transplant Plasma Lipid And Metabolic Signature, Daniel Contaifer Jr., Catherine H. Roberts, Naren Gajenthra Kumar, Ramesh Natarajan, Bernard J. Fisher, Kevin Leslie, Jason Reed, Amir A. Toor, Dayanjan S. Wijesinghe

Pharmacotherapy and Outcomes Science Publications

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unrelated donor SCT, or autologous SCT. Blood samples were taken following conditioning and prior to transplant on day 0 and the …

College Of Pharmacy 2019, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Time To Achievement Of Mean Arterial Pressure Goal In Patients With Septic Shock Based On Initial Norepinephrine Dose, Meagan R. Ellinger Pharmd, Dustin D Linn Pharmd, Bcps, Bcccp, Michael Todt Pharmd, Bccp

Parkview Pharmacy Department

Poster Presentation

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada / Poster # 11-133

Objective: Evaluate whether the initial norepinephrine dose in septic shock patients is associated with the time to achievement of MAP goal

Evaluation Of An Adjusted Body Weight Based Heparin Protocol, Jenna Deininger Pharmd, Elizabeth Meisberger Pharmd, Bcps, Kris Howard Pharmd, Bcps

Parkview Pharmacy Department

Poster Presentation

2019 ASHP Midyear Clinical Meeting/ Las Vegas, Nevada/ Poster 11-136

Objective: Determine the efficacy and safety of a pharmacist-driven adjusted body weight protocol for therapeutic intravenous (IV) heparin dosing in patients of all weights in a community health system.

U.S. Adult Perceptions Of The Harmfulness Of Tobacco Products: Descriptive T Findings From The 2013–14 Baseline Wave 1 Of The Path Study, Geoffrey T. Fong, Tara Elton-Marshall, Pete Driezen, Annette R. Kaufman, K. Michael Cummings, Kelvin Choi, Jonathan Kwan, Amber Koblitz, Andrew Hyland, Maansi Bansal-Travers, Charles Carusi, Mary E. Thompson

United States Food and Drug Administration: Publications

Introduction: This study is the first nationally representative survey of U.S. adults (18+) to examine perceptions of the relative harms of eight non-cigarette tobacco products.

Methods: Data are from Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study Adult Questionnaire, a nationally representative study of 32,320 adults in the United States conducted from September 2013 to December 2014.

Results: 40.7% of adults believed that electronic cigarettes were less harmful than cigarettes, and 17.8% of adults believed that hookah was less harmful than cigarettes. Those less knowledgeable about the health risks of smoking were more likely to believe …

The Scientific Problems With Using Non-Human Animals To Predict Human Response To Drugs And Disease, Ray Greek, Lisa A. Kramer

Pharmacology and Animal Models in Research Collection

Every year, and in countries around the world, significant time and resources are devoted to the noble cause of developing drugs to treat and cure human disease. With rare exception, drug interventions cannot reach commercialization without safety and efficacy having first been demonstrated in animal models. The intention of regulations, which require the use of animal models in such contexts, is to ensure that only safe and effective drugs end up being used by patients. Similarly, it is standard practice for researchers to employ animal models in their attempts to understand the way diseases present and progress in humans. Unfortunately, …

Intranasal Delivery Of Insulin By Nanoemulsion System, Darshana Mahendrakumar Shah

Theses and Dissertations

The main objective of this research was to develop an o/w nanoemulsion dosage form of insulin for intranasal delivery where insulin is loaded into the oil phase of the nanoemulsion for enhanced absorption. When loaded into the lipid droplets (oil phase), insulin can be protected from enzymatic degradation, can permeate through the mucus gel barrier in a comparatively efficient manner and can be absorbed through transcellular permeation along with paracellular route. To incorporate lipophilicity to insulin molecule, several complexes of insulin with various amphiphiles were developed to load it into the oil phase. The cytotoxicity of these amphiphiles and the …

Efficacy Of Statin Therapy In The Elderly, Alyssa M. B. White, Hillary R. Mishcon, John Redwanski, Ronald D. Hills Jr

Pharmacy Student Posters

Statins are one of the most heavily prescribed medications. The 2018 ACC/AHA guidelines support statin therapy for most older adults, but recommendations are less clear for those over 75. The literature was systematically reviewed for evidence of the efficacy of statin treatment in different patient populations. Significant evidence was found supporting a decreasing association between low-density lipoprotein cholesterol (LDL-C) and mortality as well as decreasing statin efficacy with increasing age. The consequences of unnecessary statin therapy can be severe for older adults. Improved methods for evaluating atherosclerotic cardiovascular disease (ASCVD) risk, such as using negative markers to help identify those …