Pharmacy and Pharmaceutical Sciences Commons^™

Sitosterolemia: Twenty Years Of Discovery Of The Function Of Abcg5abcg8, Kori Williams, Allison Segard, Gregory A. Graf

Pharmaceutical Sciences Faculty Publications

Sitosterolemia is a lipid disorder characterized by the accumulation of dietary xenosterols in plasma and tissues caused by mutations in either ABCG5 or ABCG8. ABCG5 ABCG8 encodes a pair of ABC half transporters that form a heterodimer (G5G8), which then traffics to the surface of hepatocytes and enterocytes and promotes the secretion of cholesterol and xenosterols into the bile and the intestinal lumen. We review the literature from the initial description of the disease, the discovery of its genetic basis, current therapy, and what has been learned from animal, cellular, and molecular investigations of the transporter in the twenty …

Apolipoprotein E Genotype-Dependent Nutrigenetic Effects To Prebiotic Inulin For Modulating Systemic Metabolism And Neuroprotection In Mice Via Gut-Brain Axis, Lucille M. Yanckello, Jared D. Hoffman, Ya-Hsuan Chang, Penghui Lin, Geetika Nehra, George Chlipala, Scott D. Mcculloch, Tyler C. Hammond, Andrew T. Yackzan, Andrew N. Lane, Stefan J. Green, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: The goal of the study was to identify the potential nutrigenetic effects to inulin, a prebiotic fiber, in mice with different human apolipoprotein E (APOE) genetic variants. Specifically, we compared responses to inulin for the potential modulation of the systemic metabolism and neuroprotection via gut-brain axis in mice with human APOE ϵ3 and ϵ4 alleles.

METHOD: We performed experiments with young mice expressing the human APOE3 (E3FAD mice and APOE4 gene (E4FAD mice). We fed mice with either inulin or control diet for 16 weeks starting from 3 months of age. We determined gut microbiome …

Evaluating Opioid Dispensing Rates Among Pediatrics And Young Adults Based On Cures Data Reporting In California From 2015–2019, Michael T. Phan, Courtney Wong, Daniel M. Tomaszewski, Zeev N. Kain, Brooke Jenkins, Candice D. Donaldson, Michelle Fortier, Sun Yang

Pharmacy Faculty Articles and Research

Background

Receipt of opioid prescriptions in pediatric and young adult patients may be a risk factor for future opioid misuse. Data from prescription drug monitoring programs provide insight on outpatient opioid use. In our study, we analyzed the opioid dispensing rates for pediatrics and young adults in California. Methods

A secondary analysis was performed from 2015–2019 using Controlled Utilization Review and Evaluation System data. This database provides dispensing data of controlled substances in California. Patients younger than 25 years who were prescribed opiates were analyzed by county. We further divided them into two groups (children: ≤14 years; adolescents and young …

Guideline-Directed Heart Failure Therapy In Patients After Left Ventricular Assist Device Implantation, Bailey M. Colvin, James C. Coons, Craig J. Beavers

The VAD Journal

Background: Left ventricular assist devices (LVADs) are used as an advanced therapy option for patients with stage D heart failure. These devices provide mechanical unloading of the heart as either a bridge to transplant or recovery, or as destination therapy. In patients with LVADs, there are emerging data on the use of heart failure guideline-directed medical therapy (GDMT) to improve outcomes. This review describes the current evidence available for the use of neurohormonal blocking agents in patients with LVADs.

Methods: Articles were found using PubMed and web searches for heart failure therapies/neurohormonal blockade and LVADs. Studies were included if they …

Rap1a Overlaps The Age/Rage Signaling Cascade To Alter Expression Of Α‐Sma, P‐Nf‐Κb, And P‐Pkc‐Ζ In Cardiac Fibroblasts Isolated From Type 2 Diabetic Mice, Stephanie D. Burr, James A. Stewart

Faculty and Student Publications

Cardiovascular disease, specifically heart failure, is a common complication for individu-als with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by “active” cardiac fibroblasts (i.e., myofibroblasts) remodeling the extracellular matrix (ECM). Differentiation of fibroblasts to myofibroblasts has been demonstrated to be an outcome of AGE/RAGE signaling. Hyperglycemia causes advanced glycated end products (AGEs) to accu-mulate within the body, and this process is greatly accelerated under chronic diabetic conditions. AGEs can bind and activate their receptor (RAGE) to trigger multiple downstream outcomes, such as altering ECM remodeling, inflammation, and oxidative stress. …

Design Of Topical Ocular Ciprofloxacin Nanoemulsion For The Management Of Bacterial Keratitis, Ahmed Adel Ali Youssef, Chuntian Cai, Narendar Dudhipala, Soumyajit Majumdar

Faculty and Student Publications

Bacterial keratitis (BK) is a critical ocular infection that can lead to serious visual disability. Ciprofloxacin (CIP), moxifloxacin (MOX), and levofloxacin (LFX) have been accepted as monothera-pies by the US Food and Drug Administration for BK treatment. CIP is available commercially at 0.3% w/v concentration as an ophthalmic solution and as an ointment for ocular delivery. Because of solubility issues at physiological pH, CIP precipitation can occur at the corneal surface post instillation of the solution dosage form. Consequently, the ocular bioavailability of CIP is reduced. The ointment dosage form is associated with side effects such as blurred vision, itching, …

Change Management Is A Consideration Beyond The Pandemic, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Pharmacy Practice & Administration

Change management (CM) is a well-organized framework for managing the people side of change. It includes practices, processes, and planned activities designed to facilitate and lead organizations to move from the present state to a desired state. The goal of CM is not to eliminate resistance but to anticipate it, proactively plan for it, continuously manage it, and mitigate the consequences.

Entrustable Professional Activities (Epas) For Global Health, David R. Steeb, Tina P. Brock, Sarah A. Dascanio, Paul K. Drain

Faculty and Student Publications

Purpose As global health education and training shift toward competency-based approaches, academic institutions and organizations must define appropriate assessment strategies for use across health professions. The authors aim to develop entrustable professional activities (EPAs) for global health to apply across academic and workplace settings. Method In 2019, the authors invited 55 global health experts from medicine, nursing, pharmacy, and public health to participate in a multiround, online Delphi process; 30 (55%) agreed. Experts averaged 17 years of global health experience, and 12 (40%) were from low-to middle-income countries. In round one, participants listed essential global health activities. The authors used …

Clinical Pharmacology And Dosing Regimen Optimization Of Neonatal Opioid Withdrawal Syndrome Treatments, Fei Tang, Chee M. Ng, Henrietta S. Bada, Markos Leggas

Pharmaceutical Sciences Faculty Publications

In this paper, we review the management of neonatal opioid withdrawal syndrome (NOWS) and clinical pharmacology of primary treatment agents in NOWS, including morphine, methadone, buprenorphine, clonidine, and phenobarbital. Pharmacologic treatment strategies in NOWS have been mostly empirical, and heterogeneity in dosing regimens adds to the difficulty of extrapolating study results to broader patient populations. As population pharmacokinetics (PKs) of pharmacologic agents in NOWS become more well-defined and knowledge of patient-specific factors affecting treatment outcomes continue to accumulate, PK/pharmacodynamic modeling and simulation will be powerful tools to aid the design of optimal dosing regimens at the patient level. Although there …

Will The Covid-19 Pandemic Finally Fuel Drug Repurposing Efforts?, Anna Chen, Shivangi Patel, Matthew Alcusky, Vittorio Maio

College of Population Health Faculty Papers

No abstract provided.

Biologically Guided Isolation And Admet Profile Of New Factor Xa Inhibitors Fromglycyrrhiza Glabraroots Usingin Vitroandin Silicoapproaches, Reham S. Ibrahim, Rahma S. R. Mahrous, Rasha M. Abu El-Khair, Samir A. Ross

Faculty and Student Publications

Selective factor Xa inhibitors effectively block coagulation cascade with a broader therapeutic window than multitargeted anticoagulants. They have evolved as a crucial part of prevention and treatment of thromboembolic diseases and in therapeutic protocols involved in many clinical trials in coronavirus disease 2019 (COVID-19) patients. Biologically-guided isolation of specific FXa inhibitors from licorice (Glycyrrhiza glabra) root extract furnished ten flavonoids. By detailed analysis of their1H,13C NMR and MS data, the structures of these flavonoids were established as 7,4′-dihydroxyflavone (1), formononetin (2), 3-R-glabridin (3), isoliquiritigenin (4), liquiritin (5), naringenin 5-O-glucoside (6), 3,3′,4,4′-tetrahydroxy-2-methoxychalcone (7), liquiritinapioside (8) and the two isomers isoliquiritigenin-4′-O-β-d-apiosylglucoside (9) …

Preclinical Evaluation Of Artesunate As An Antineoplastic Agent In Ovarian Cancer Treatment, Anthony Mcdowell Jr., Kristen S. Hill, Joseph Robert Mccorkle, Justin W. Gorski, Yilin Zhang, Ameen A. Salahudeen, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

BACKGROUND: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment.

METHODS: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq …

Bacterial Vaccines Deficient In The 2-C-Methyl-D-Erythritol-4-Phosphate Pathway And Methods Of Preparation And Use Thereof, Keith Bahjat, Yoshinobu Koguchi, Alejandro F Alice

Technology Transfer - Patents

The present invention relates to the preparation and use in primates of whole organismvaccines in which the MEP pathway is disrupted such that synthesis of HMBPP by the bacterial cells is substantially blocked. The data provided demonstrates that, when bacteria or other vaccine vectors that comprise an active MEP pathway are used in vaccine methods, the .gamma..delta. T cell response dominates, potentially clearing the vaccine strain via .gamma..delta. T cell-mediated killing of vector infected antigen presenting cells and reducing its utility as a stimulator of a productive adaptive immune response, specifically priming or boosting of CD4.sup.+ and CD8.sup.+ .alpha..beta. T …

Stability Evaluation Of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect Of Solvents And Storage Conditions, Christopher Ross, Basir Syed, Joanna Pak, Vishal Jhanji, Jason Yamaki, Ajay Sharma

Pharmacy Faculty Articles and Research

Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus keratitis and other ocular infections. Vancomycin ophthalmic drops are not commercially available and require compounding. The present study was designed to investigate the stability of vancomycin ophthalmic drops in normal saline, phosphate-buffered saline (PBS), and balanced salt solution (BSS) while stored at room temperature or under refrigeration. Vancomycin ophthalmic drops (50 mg/mL) were aseptically prepared from commercially available intravenous powder using PBS, BSS, and saline. Solutions were stored at room temperature and in a refrigerator for 28 days. The vancomycin stability was tested by a microbiology assay and high-performance liquid …

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …

Interactions Of Neuroimmune Signaling And Glutamate Plasticity In Addiction, Cassandra D. Gipson, Scott Rawls, Michael D. Scofield, Benjamin M. Siemsen, Emma O. Bondy, Erin E. Maher

Family and Community Medicine Faculty Publications

Chronic use of drugs of abuse affects neuroimmune signaling; however, there are still many open questions regarding the interactions between neuroimmune mechanisms and substance use disorders (SUDs). Further, chronic use of drugs of abuse can induce glutamatergic changes in the brain, but the relationship between the glutamate system and neuroimmune signaling in addiction is not well understood. Therefore, the purpose of this review is to bring into focus the role of neuroimmune signaling and its interactions with the glutamate system following chronic drug use, and how this may guide pharmacotherapeutic treatment strategies for SUDs. In this review, we first describe …

Selecting An Anti-Malarial Clinical Candidate From Two Potent Dihydroisoquinolones, Yizhe Chen, Fangyi Zhu, Jared T. Hammill, Gloria Holbrook, Lei Yang, Burgess Freeman, Karen L. White, David M. Shackleford, Kathleen G. O'Loughlin, Susan A. Charman, Jon C. Mirsalis, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

BACKGROUND: The ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. The process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles is described.

METHODS: The compounds were tested to define their physicochemical properties including kinetic and thermodynamic solubility, partition coefficient, permeability, ionization constant, and binding to plasma proteins. Metabolic stability was assessed in both microsomes and hepatocytes derived …

Anti-Inflammatory Effects Of Α7-Nicotinic Ach Receptors Are Exerted Through Interactions With Adenylyl Cyclase-6, Simeng Zhu, Shiqian Huang, Guofang Xia, Jin Wu, Yan Shen, Ying Wang, Rennolds S. Ostrom, Ailian Du, Chengxing Shen, Congfeng Xu

Pharmacy Faculty Articles and Research

Background and purpose

Alpha 7 nicotinic acetylcholine receptors (CHRNA7) suppress inflammation through diverse pathways in immune cells, so is potentially involved in a number of inflammatory diseases. However, the detailed mechanisms underlying CHRNA7’s anti‐inflammatory effects remain elusive.

Experimental approach

The anti‐inflammatory effects of CHRNA7 agonists in both murine macrophages (RAW 264.7) and bone marrow‐derived macrophages (BMDM) stimulated with LPS were examined. The role of adenylyl cyclase 6 (AC6) in Toll‐like Receptor 4 (TLR4) degradation was explored via overexpression and knockdown. A mouse model of chronic obstructive pulmonary disease was used to confirm key findings.

Results

Anti‐inflammatory effects of CHRNA7 were …

Pace Yourself: Impact Of Covid-19 On Patient-Centered Care Experience, Kristen Wilhite, Mikael D. Jones, Clark D. Kebodeaux

Pharmacy Practice and Science Faculty Publications

(1) Background: The outbreak of the novel coronavirus, COVID-19, forced colleges of pharmacy to implement new online learning methodologies to ensure that students could complete required courses. This transition was especially acute for laboratory simulation courses that require students to practice professional skills. This study aims to compare student assessment performance within a simulation-based laboratory course for students who completed the module prior to and after the online transition. (2) Methods: This study was a retrospective cohort comparison of student outcome performance with two distinct content delivery methods. Students were organized into two tracks at the beginning of the semester …

Valtoco® (Diazepam Nasal Spray) For The Acute Treatment Of Intermittent Stereotypic Episodes Of Frequent Seizure Activity, Elyse M. Cornett, Sam N. Amarasinghe, Alexis Angelette, Tunde Abubakar, Adam M. Kaye, Alan David Kaye, Elisa E. Neuchat, Ivan Urits, Omar Viswanath

School of Pharmacy Faculty Articles

Valtoco® is a new FDA-approved nasal spray version of diazepam indicated for the treatment of acute, intermittent, and stereotypic episodes of frequent seizure activity in epilepsy patients six years of age and older. Although IV and rectal diazepam are already used to treat seizure clusters, Valtoco® has less variability in plasma concentration compared to rectal diazepam. Furthermore, the intranasal administration of Valtoco® is more convenient and less invasive than rectal or IV diazepam, making it ideal for self-administration outside of a hospital setting. Multiple clinical trials have taken place comparing Valtoco® to the oral, rectal, and IV forms of diazepam. …