Pharmacy and Pharmaceutical Sciences Commons^™

Coffee Beverage, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Vesicular Monoamine Transporter-2 Inhibitor Jpc-141 Prevents Methamphetamine-Induced Dopamine Toxicity And Blocks Methamphetamine Self-Administration In Rats, Cassie M. Chandler, Justin R. Nickell, A. George Wilson, John P. Culver, Peter A. Crooks, Michael T. Bardo, Linda P. Dwoskin

Psychology Faculty Publications

Previous research has demonstrated therapeutic potential for VMAT2 inhibitors in rat models of methamphetamine use disorder. Here, we report on the neurochemical and behavioral effects of 1-(2-methoxyphenethyl)-4-phenethypiperazine (JPC-141), a novel analog of lobelane. JPC-141 potently inhibited (Ki = 52 nM) [3H]dopamine uptake by VMAT2 in striatal vesicles with 50 to 250-fold greater selectivity for VMAT2 over dopamine, norepinephrine and serotonin plasmalemma transporters. Also, JPC-141 was 57-fold more selective for inhibiting VMAT2 over [3H]dofetilide binding to hERG channels expressed by HEK293, suggesting relatively low potential for cardiotoxicity. When administered in vivo to rats, JPC-141 prevented the METH-induced reduction in striatal dopamine …

The Impact Of Pdcd4, A Translation Inhibitor, On Drug Resistance, Qing Wang, Hsin-Sheng Yang

Markey Cancer Center Faculty Publications

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

Association Between Opioid-Benzodiazepine Trajectories And Injurious Fall Risk Among Us Medicare Beneficiaries., Grace Hsin-Min Wang, Juan M. Hincapie-Castillo, Walid F. Gellad, Bobby L. Jones, Ronald I. Shorr, Seonkyeong Yang, Debbie L. Wilson, Jeannie K. Lee, Gary M. Reisfield, Chian K. Kwoh, Chris Delcher, Khoa A. Nguyen, Christopher A. Harle, Zachary A. Marcum, Wei-Hsuan Lo-Ciganic

Pharmacy Practice and Science Faculty Publications

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate injurious fall risk (e.g., falls and fractures) compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious fall risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated the time to first injurious falls …

A Highly Selective Mpges-1 Inhibitor To Block Abdominal Aortic Aneurysm Progression In The Angiotensin Mouse Model., Lauren M Weaver, Madeline J Stewart, Kai Ding, Charles D. Loftin, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

Abdominal aortic aneurysm (AAA) is a deadly, permanent ballooning of the aortic artery. Pharmacological and genetic studies have pointed to multiple proteins, including microsomal prostaglandin E₂ synthase-1 (mPGES-1), as potentially promising targets. However, it remains unknown whether administration of an mPGES-1 inhibitor can effectively attenuate AAA progression in animal models. There are still no FDA-approved pharmacological treatments for AAA. Current research stresses the importance of both anti-inflammatory drug targets and rigor of translatability. Notably, mPGES-1 is an inducible enzyme responsible for overproduction of prostaglandin E₂ (PGE₂)-a well-known principal pro-inflammatory prostanoid. Here we demonstrate for the first …

Neuroimmune Response And Neurodegeneration In Adolescent Rats Following Binge Alcohol Exposure, Catherine Van Doorn

Theses and Dissertations--Pharmacy

Studies of adolescent drinking show a distinct prevalence of binge drinking, including at extreme levels, and this type of drinking has been identified as increasing risk of developing an Alcohol Use Disorder (AUD). Additionally, females suffer greater levels of harm from binge drinking and AUD and in an abbreviated timeline compared to males. Neuroimmune reactivity, specifically with microglial reactivity following binge drinking, may influence the sex differences seen in negative alcohol-related health disparities.

The first set of experiments sought to examine a marker of microglial reactivity, TSPO, in adolescent females and males and found the sexes displayed different temporal and …

A Closer Look At The Humanistic Aspects Of The Opioid Epidemic And Its Implications For Pharmaceutical Ethics And Law, Eriel Burns

Gaines Fellow Senior Theses

This paper elucidates the humanistic elements of this crisis, that is, the ethical challenges it poses and the role of culture in it. The opioid crisis disturbs several bioethics principles as indicated by the fact that it burgeoned out of the health care system as opposed to the illicit environments of the underground market. The book Dreamland by investigative journalist and storyteller, Sam Quinones encapsulates the complexity of the opioid epidemic through research and interviews with important figures related to the crisis such as physicians, people with opioid use disorder, and pharmaceutical sales representatives, among others. Quinones details that the …

Beer, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

The Role Of Microglia In Sex- And Region-Specific Blood-Brain Barrier Integrity During Nicotine Withdrawal, Mohit Kumar, Jack V. Keady, Surya P. Aryal, Marissa Hessing, Christopher I. Richards, Jill R. Turner

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Smoking is the largest preventable cause of death and disease in the United States, with ,5% of quit attempts being successful. Microglia activation and proinflammatory neuroimmune signaling in reward neuro- circuitry are implicated in nicotine withdrawal symptomology. Microglia are integral regulators of blood-brain barrier (BBB) functionality as well; however, whether the effects of nicotine withdrawal on microglia function impact BBB integrity is unknown.

METHODS: Mice were treated with chronic nicotine (12 mg/kg/day) and subjected to 48 hours nicotine withdrawal. Regional BBB permeability, together with messenger RNA and protein expression of tight junction proteins, were assessed. PLX5622 chow was used …

Wine, Sparkling, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Wine, Other, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Table B: Generally Recognized As Safe (Gras) Food Additives Containing Aluminum, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Mineral, Spring, Table, And Bottled Water, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Liquors And Spirits, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Wine, Red, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Wine, White, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Table D: Aluminum-Containing Additives Allowed By The Eu And Fao/Who, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Table C: Some Other Fda-Approved Sources Of Aluminum In Food, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Table E: Aluminum Lakes Of Permitted Colors Allowed By The European Union, Robert Yokel

Aluminum in Beverages and Foods: A Compilation

No abstract provided.

Investigating The Use Of Serious Games For Cancer Control Among Children And Adolescents: Scoping Review, Sunghak Kim, Ebling Library, Olufunmilola Abraham

Pharmacy Practice and Science Faculty Publications

Background: Effective health care services that meet the diverse needs of children and adolescents with cancer are required to alleviate their physical, psychological, and social challenges and improve their quality of life. Previous studies showed that serious games help promote people’s health. However, the potential for serious games to be used for successful cancer control for children and adolescents has received less attention.

Objective: This scoping review aimed to map the use of serious games in cancer prevention and cancer care for children and adolescents, and provide future directions for serious games’ development and implementation within the context of cancer …

Biodegradable Nanoparticles Targeting Circulating Immune Cells Reduce Central And Peripheral Sensitization To Alleviate Neuropathic Pain Following Spinal Cord Injury., Michael N. Saunders, Kate V. Griffin, Irina Kalashnikova, Daniel Kolpek, Dominique R. Smith, Eiji Saito, Brian J. Cummings, Aileen J. Anderson, Lonnie D. Shea, Jonghyuck Park

Pharmaceutical Sciences Faculty Publications

Neuropathic pain is a critical source of comorbidity following spinal cord injury (SCI) that can be exacerbated by immune-mediated pathologies in the central and peripheral nervous systems. In this article, we investigate whether drug-free, biodegradable, poly(lactide- co -glycolide) (PLG) nanoparticle treatment mitigates the development of post-SCI neuropathic pain in female mice. Our results show that acute treatment with PLG nanoparticles following thoracic SCI significantly reduces tactile and cold hypersensitivity scores in a durable fashion. Nanoparticles primarily reduce peripheral immune-mediated mechanisms of neuropathic pain, including neuropathic pain-associated gene transcript frequency, transient receptor potential ankyrin 1 nociceptor expression, and MCP-1 (CCL2) chemokine …

Recent Trends In Stimulant Prescribing In Kentucky, 2021-2023, Jordan Shannon

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Abstract

Introduction

Prescription stimulants have a long history of clinical use dating as far back as the 1930s. In the United States stimulant prescribing rates have steadily climbed over the last 3 decades. The primary objective is to describe recent (2021-2023) prescribing trends of stimulant medications in the Commonwealth of Kentucky

Methods

Prescription data collected from Kentucky’s prescription drug monitoring (PDMP) database known as the Kentucky All Schedule Prescription Electronic Reporting System (KASPER). Annual and quarterly trends in stimulant prescribing between 2021-2023 were calculated, examined by age, sex, and geographic location.

Results

Stimulant prescribing increased by ~15% where the majority …

Investigating A New Drug Target In Alzheimer’S Disease: Nox2, Tiffany Adams

Theses and Dissertations--Pharmacy

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disease with neuropathological changes in the blood-brain barrier that offers possible therapeutic targets. Oxidative stress is one driving factor for AD. NADPH oxidase 2 (NOX2) in the capillary endothelium produces reactive oxygen species, leading to oxidative stress-mediated blood-brain barrier dysfunction. We hypothesized that using a specific NOX2 inhibitor, PhoxI2, has the potential to reduce reactive oxygen species and repair amyloid-β (Aβ)-driven blood-brain barrier leakage in an AD mouse model.

Methods: For this study, 5xFAD (Familiar Alzheimer Disease) mice were treated with vehicle or PhoxI2, a NOX2 inhibitor. Techniques utilized were Enzyme-Linked Immunosorbent Assay …

Design Of Kappa Opioid Receptor Agonists For Potential Treatment Of Multiple Sclerosis, Lindsay Kornberger

Theses and Dissertations--Pharmacy

Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system characterized by demyelination and neuroinflammation. There is currently no cure for MS. There is a critically unmet need for the development of pharmacotherapies that can induce remyelination promoting both repair and recovery. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating pharmacotherapies. KOR activation has been shown to promote functional recovery and remyelination preclinically. However, typical KOR agonists like U50,488 have limitations such as sedation and dysphoria limiting their use. This necessitates further development of new KOR agonists that maintain …

Sensitizing Keap1 Loss Non-Small Cell Lung Cancer To Artesunate Anti-Cancer Activity, Keng Hee Peh

Theses and Dissertations--Pharmacy

Lung cancer is the global leading cause of cancer related death. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer diagnoses conferring a significant disease burden. However, certain mutations in tumor suppressors such as Kelch-like ECH-associated protein 1 (KEAP1) confers resistance to standard of care therapy in NSCLC. KEAP1 is known to regulate multiple cellular processes such as oxidative stress response and anti-apoptotic pathways. Furthermore, KEAP1 loss of function in NSCLC is associated with poorer clinical outcomes and there are no currently approved therapies for KEAP1 loss NSCLC and represents an unmet clinical need. Artesunate (Art) demonstrated anti-cancer …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Pharmacy Involvement In Increased Access To Opioid Treatment Programs, Catherine O'Rourke

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The opioid epidemic still affects many Americans today. Despite approved medication treatments for opioid use disorder (OUD), a majority of the population with OUD have not received treatment. Since pharmacists are the most accessible health care professional and had an important role providing care during the COVID-19 pandemic, there has been a push to expand pharmacists’ scope of practice. The primary purpose of this investigation was to identify the benefits and barriers to community pharmacist-led treatment of OUD. The secondary purpose was to determine whether pharmacist participation in opioid treatment programs (OTPs) or office based opioid treatment (OBOT) would be …

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized By Polycationic Complexation, Preye Mike Agbana, Ji Eun Park, Piotr G. Rychahou, Kyung-Bo Kim, Younsoo Bae

Markey Cancer Center Faculty Publications

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previ- ously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanopar- ticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ …

Nudcl2 Is Required For Cytokinesis By Stabilizing Rcc2 With Hsp90 At The Midbody, Xiaoyang Xu, Yuliang Huang, Feng Yang, Xiaoxia Sun, Rijin Lin, Jiaxing Feng, Mingyang Yang, Jiaqi Shao, Xiaoqi Liu, Tianhua Zhou, Shanshan Xie, Yuehong Yang

Markey Cancer Center Faculty Publications

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for success- ful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mam- malian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinu- cleation, and midbody disorganization. Using iTRAQ-based …

A Gold-Based Inhibitor Of Oxidative Phosphorylation Is Effective Against Triple Negative Breast Cancer, R. Tyler Mertens, Jong Hyun Kim, Samuel Ofori, Chibuzor Ngozi Olelewe, Paul J. Kamitsuka, Gunnar F. Kwakye, Samuel G. Awuah

Markey Cancer Center Faculty Publications

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mito- chondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its thera- peutic potential following systemic …