Pharmacy and Pharmaceutical Sciences Commons^™

Combinatorial Efficacy Of Antimicrobial Peptides And Silver Ions, Christina Lynne Chrom

Theses and Dissertations

Antimicrobial peptides are produced by multicellular organisms as a defense against competing pathogenic microbes. The mechanism of action for positively charged antimicrobial peptides is widely believed to occur when the positively charged peptide interacts with the negatively charged outer lipid membrane followed by the insertion of the peptide into the membrane. This insertion into the outer or cytoplasmic membranes leads to disruption of membrane integrity. Alternatively, silver based antimicrobials, which have been well known for centuries, are thought to act by inhibiting the proton motive force, the respiratory electron transport chain, and by affecting membrane permeability resulting in cell death. …

Population Pharmacokinetic And Pharmacodynamic Analysis Of Buprenorphine For The Treatment Of Neonatal Abstinence Syndrome, Jason N. Moore, Pharmd, Marc Gastonguay, Susan C. Adeniyi-Jones, Md, David E. Moody, Walter K. Kraft, Md, Facp

Department of Pharmacology and Experimental Therapeutics Posters

Neonatal abstinence syndrome (NAS) is a condition affecting newborns exposed to an opioid in utero. Symptoms of NAS include excessive crying, poor feeding, and disordered autonomic control. Up to 2/3 of infants will require pharmacologic therapies to reach symptom control. Opioids including morphine and methadone are the current first-line treatments. Buprenorphine is being investigated as a treatment of NAS. The purpose of this analysis was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of BUP in infants with NAS.

Poster presented at American Society for Clinical Pharmacology and Therapeutics (ASCPT) 2017 Annual Meeting, March 15-18, 2017 in Washington DC.

Catatonia Secondary To Sudden Clozapine Withdrawal: A Case With Three Repeated Episodes And A Literature Review, John Bilbily, Betsy Mccollum, Jose De Leon

Psychiatry Faculty Publications

A literature search identified 9 previously published cases that were considered as possible cases of catatonia secondary to sudden clozapine withdrawal. Two of these 9 cases did not provide enough information to make a diagnosis of catatonia according to the Diagnostic and Statistical Manual, 5th Edition (DSM-5). The Liverpool Adverse Drug Reaction (ADR) Causality Scale was modified to assess ADRs secondary to drug withdrawal. From the 7 published cases which met DSM-5 catatonia criteria, using the modified scale, we established that 3 were definitive and 4 were probable cases of catatonia secondary to clozapine withdrawal. A new definitive case is …

Utilizing Three Years Of Epidemiological Data From Medical Missions In Cambodia To Shape The Mobile Medical Clinic Formulary, Jeany Kim Jun, Junia S. Koo, Amy Y. Kang, Deborah B. Chien, Albert Shim, Dale Knutson, Eda M. Kim

Pharmacy Faculty Articles and Research

Objective: The purpose of this project was to gather epidemiological data on common diseases and medications dispensed during medical mission teams to Cambodia to shape the mobile medical clinic formulary.

Methods: Data for patients seen during week-long, mobile, medical clinics was collected in Cambodia during Septembers 2012 to 2014. Patient’s gender, age, weight, blood pressure, glucose, pertinent laboratory values, diagnoses, and medications dispensed were collected. Blood pressure and glucose were measured in patients 18 years and above. Data collected onto paper intake forms were transferred onto spreadsheets without patient identifying information and analyzed for aggregate means, common diseases, and most …

Empirical Assessment Of The Impact Of Low-Cost Generic Programs On Adherence-Based Quality Measures, Nathan J. Pauly, Jeffery C. Talbert, Joshua D. Brown

Pharmacy Practice and Science Faculty Publications

In the United States, federally-funded health plans are mandated to measure the quality of care. Adherence-based medication quality metrics depend on completeness of administrative claims data for accurate measurement. Low-cost generic programs (LCGPs) cause medications fills to be missing from claims data as medications are not adjudicated through a patient’s insurance. This study sought to assess the magnitude of the impact of LCGPs on these quality measures. Data from the 2012–2013 Medical Expenditure Panel Survey (MEPS) were used. Medication fills for select medication classes were classified as LCGP fills and individuals were classified as never, sometimes, and always users of …

Polymer Micelle Formulation For The Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy And Pharmacokinetic Studies In Mice, Ji Eun Park, Se-Eun Chun, Derek Alexander Reichel, Jee Sun Min, Su-Chan Lee, Songhee Han, Gongmi Ryoo, Yunseok Oh, Shin-Hyung Park, Heon-Min Ryu, Kyung Bo Kim, Ho-Young Lee, Soo Kyung Bae, Younsoo Bae, Wooin Lee

Pharmaceutical Sciences Faculty Publications

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic …

The Pharmacological And Cognitive Effects Of Propranolol On Cd-1 Mice, Jennifer Hindieh

Discovery Day (formerly Post & Beyond)

The Pharmacological and Cognitive Effects of Propranolol on CD-1 Mice Jennifer Hindieh, William Hoefer, Grace Rossi, Christopher McAllister Long Island University Post Campus, Psychology Department, College of Liberal Arts & Sciences Currently, 31 million people in the United States have chronic kidney disease; with high blood pressure being the 2nd leading cause of kidney disease, and about 70 million people in the United States have high blood pressure. The importance of studying the conditions becomes more prevalent as the average individual, of recent times, has a diet consisting of preservatives, artificial ingredients, which in turn leads to a more consistent …

Pharmacological Basis For The Medicinal Use Of Polyherbal Formulation And Its Ingredients In Cardiovascular Disorders Using Rodents, A Malik, Malik Hassan Mehmood, H Channa, Ms Akhtar, Ah Gilani

Department of Biological & Biomedical Sciences

A compound herbal formulation (POL4) has been used in the indigenous system of medicine to treat cardiometabolic disorders like diabetes and associated hypertension. POL4 and most of its constituents have not been studied widely for its therapeutic use in hypertension. This study is aimed to determine the efficacy and possible insight into mechanism(s) for the medicinal use of POL4 and its ingredients in hypertension.

Selective Immunoproteasome Inhibitors With Non-Peptide Scaffolds, Chang-Guo Zhan, Kyung Bo Kim, Vinod Kasam, Na-Re Lee

Pharmaceutical Sciences Faculty Patents

Compounds useful for inhibiting the immunoproteasome have the formula of [image on patent].

Methods and compounds for inhibiting the immunoproteasome, particularly, immunoproteasome inhibitors with non-peptide scaffolds, are described.

Mccrearamycins A-D, Geldanamycin-Derived Cyclopentenone Macrolactams From An Eastern Kentucky Abandoned Coal Mine Microbe, Xiachang Wang, Yinan Zhang, Larissa V. Ponomareva, Qingchao Qiu, Ryan M. Woodcock, Sherif I. Elshahawi, Xiabin Chen, Ziyuan Zhou, Bruce E. Hatcher, James C. Hower, Chang-Guo Zhan, Sean Parkin, Madan K. Kharel, S. Randal Voss, Khaled A. Shaaban, Jon S. Thorson

Center for Pharmaceutical Research and Innovation Faculty Publications

Four cyclopentenone‐containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD‐23‐14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19‐hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α …

Adverse Events And Treatment Discontinuations Of Antimuscarinics For The Treatment Of Overactive Bladder In Older Adults: A Systematic Review And Meta-Analysis, Scott Martin Vouri, Clark D. Kebodeaux, Paul M. Stranges, Besu F. Teshome

Pharmacy Practice and Science Faculty Publications

Introduction

Antimuscarinics should be used with caution in older adults with overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have not specified risk in the elderly, the population at highest risk for AEs. The aim of this review is to explore and evaluate AEs and treatment discontinuations in adults 65 or older taking antimuscarinics for OAB.

Methods

Keywords were searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic …

Reduction Of Cocaine-Induced Locomotor Effects By Enriched Environment Is Associated With Cell-Specific Accumulation Of Δfosb In Striatal And Cortical Subregions, Audrey Lafragette, Michael T. Bardo, Virginie Lardeux, Marcello Solinas, Nathalie Thiriet

Psychology Faculty Publications

Background: Early exposure to enriched environments has been shown to decrease the locomotor effects induced by repeated injections of cocaine and modify basal and cocaine-induced total protein levels of the transcription factor ΔFosB in the whole striatum of mice. In this study, we aimed at characterizing whether the profile of ΔFosB accumulation induced by enriched environments and cocaine would be similar or different in terms of brain areas and cell type.

Methods: We used mice expressing the eGFP protein in D1 receptor positive (D1R(+)) neurons to determine whether ΔFosB induced by enriched environment or cocaine injections (5×15 mg/kg) would occur …

Efficacy And Tolerability Of Adjunctive Brivaracetam In Patients With Prior Antiepileptic Drug Exposure: A Post-Hoc Study., Ali A. Asadi-Pooya, Michael R. Sperling, Steve Chung, Pavel Klein, Anyzeila Diaz, Sami Elmoufti, Jimmy Schiemann, John Whitesides

Department of Neurology Faculty Papers

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV …

Quetiapine Misuse And Abuse: Is It An Atypical Paradigm Of Drug Seeking Behavior?, Sean Hyungwoo Kim, Gayoung Lee, Eric Kim, Hyejin Jung, Jongwha Chang

Institute for Pharmaceutical Outcomes and Policy Faculty Publications

Recent case reports in medical literatures suggest that more and more second-generation atypical antipsychotics (AAs) have been prescribed for off-label use; quetiapine (Brand name: Seroquel^®) showed increase in its trend for off-label use. Little is known about the reasons behind this trend, although historical sedative and hypnotic prescription patterns suggest that despite relatively superior safety profiles of quetiapine (especially for movement disorders), it may be used for treating substance abuse disorder. In addition, recent studies have shown a strong potential for misuse and abuse (MUA) of quetiapine beyond Food and Drug Administration-approved indications. This includes drug-seeking behaviors, such …

February 2017, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Nucleosome Repositioning During Differentiation Of A Human Myeloid Leukemia Cell Line, Vladimir B. Teif, Jan-Philipp Mallm, Tanvi Sharma, David B. Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L. Olins, Donald E. Olins

Pharmaceutical Sciences Faculty Publications

Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of epichromatin (surface chromatin adjacent to the nuclear envelope). Nucleosome positions changed genome-wide, exhibiting a specific class of alterations involving nucleosome loss in extended (∼1kb) regions, pronounced in enhancers and promoters. Genes that lost nucleosomes at their …

Inhibition Of Cdk8 Mediator Kinase Suppresses Estrogen Dependent Transcription And The Growth Of Estrogen Receptor Positive Breast Cancer, Martina S. Mcdermott, Alexander A. Chumanevich, Chang-Uk Lim, Jiaxin Liang, Mengqian Chen, Serena Altilia, David Oliver, James M. Rae, Michael Shtutman, Hippokratis Kiaris, Balázs Győrffy, Igor Roninson, Eugenia Broude

Faculty Publications

Hormone therapy targeting estrogen receptor (ER) is the principal treatment for ER-positive breast cancers. However, many cancers develop resistance to hormone therapy while retaining ER expression. Identifying new druggable mediators of ER function can help to increase the efficacy of ER-targeting drugs. Cyclin-dependent kinase 8 (CDK8) is a Mediator complex-associated transcriptional regulator with oncogenic activities. Expression of CDK8, its paralog CDK19 and their binding partner Cyclin C are negative prognostic markers in breast cancer. Meta-analysis of transcriptome databases revealed an inverse correlation between CDK8 and ERα expression, suggesting that CDK8 could be functionally associated with ER. We have found that …

Oled Loki As A Catalyst For Tertiary Amine And Hydroxamate Glycosylation, Ryan R. Hughes, Khaled A. Shaaban, Jianjun Zhang, Hongnan Cao, George N. Phillips Jr., Jon S. Thorson

Center for Pharmaceutical Research and Innovation Faculty Publications

We describe the ability of an engineered glycosyltransferase (OleD Loki) to catalyze the N‐glycosylation of tertiary‐amine‐containing drugs and trichostatin hydroxamate glycosyl ester formation. As such, this study highlights the first bacterial model catalyst for tertiary‐amine N‐glycosylation and further expands the substrate scope and synthetic potential of engineered OleDs. In addition, this work could open the door to the discovery of similar capabilities among other permissive bacterial glycosyltransferases.

Mechanisms Of Modulation Of Brain Microvascular Endothelial Cells Function By Thrombin., Eugen Brailoiu, Megan M. Shipsky, Guang Yan, Mary E. Abood, G. Cristina Brailoiu

College of Pharmacy Faculty Papers

Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca

Compounds Including Cox Inhibitor Moiety And Enhanced Delivery Of Active Drugs Using Same, Audra Stinchcomb, Kyung Bo Kim, Ragotham Reddy Pinninti, Priyanka Ghosh, Kalpana S. Paudel

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter includes compounds including a cyclooxygenase enzyme inhibitor moiety and a moiety derived from a drug of interest. In some embodiments, the drug of interest is an opioid. In some embodiments, the compound includes a diclofenac moiety and a naltrexone or naltrexol moiety. The compounds allow for enhanced delivery rates across skin.