Pharmacy and Pharmaceutical Sciences Commons^™

The Effects Of Nicotine In The Neonatal Quinpirole Rodent Model Of Psychosis: Neural Plasticity Mechanisms And Nicotinic Receptor Changes, Daniel J. Peterson, W. Drew Gill, John M. Dose, Donald B. Hoover, James R. Pauly, Elizabeth D. Cummins, Katherine C. Burgess, Russell W. Brown

Pharmaceutical Sciences Faculty Publications

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal’s lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1–21. Animals were given …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Comparing The Effectiveness Of Using Educational Booklet Or Brief Video On Patients’ Knowledge, Perceptions And Willingness To Participate In Placebo-Controlled Clinical Trials, Khalid F. Almoaikel, Dennis Raisch, Matthew Borrego, Mike Sather, Mark Holdsworth

Pharmaceutical Sciences ETDs

Background and Objectives: Limited knowledge about clinical trials can influence a patient’s willingness to participate in medical research. For placebo-controlled clinical trials, it is more difficult to recruit patients compared to clinical trials without a placebo arm. Thus, educating individuals about clinical trials and placebos can potentially improve their perceptions about clinical trials and might increase their willingness to enroll in them. The study objectives include:

1) To design educational interventions (a booklet and a video) to improve a patient’s knowledge of placebo controlled clinical trials.

2) To compare the impact of the educational interventions (booklet, video or both) on …

Comparative Evaluation Of Three Pharmaceutical Medications And White Willow Bark, Jazzmin Washington

Undergraduate University Honors Capstones

Pharmaceuticals have become a big business today. However, the costs of medications are continuously increasing, due to several factors such as an increased demand. This is one of the many reasons herbal remedies continue to be used; 80% of the world still uses herbal medicine as their primary form of treatment. Due to this, one must evaluate and compare herbal remedies to their pharmaceutical counterparts to ensure that individuals have the same quality of medicine. Different brands of commercial aspirin were compared to its herbal counterpart, white willow bark, to validate their similarities in chemical structure. This project will serve …

One-Pot Syntheses And Characterizations Of “Click-Able” Polyester Polymers For Potential Biomedical Applications, James F. Beach Ii

Electronic Theses & Dissertations

In this study, a synthetic polyester polymer was designed using polyethylene glycol, sorbitol, glutaric acid and 4-pentynoic acid as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by Novozyme-435, an enzyme suitable for polyesterification of biocompatible compounds. The progress of the reaction was monitored with respect to time and vacuum exposure, with samples being subjected to standard characterization protocols. Polymers with high molecular weight and water solubility were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to cancer cells. This was achieved by employing a solvent diffusion method, wherein the polymer …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

Discovery Of A Diaminopyrimidine Flt3 Inhibitor Active Against Acute Myeloid Leukemia, Jamie A. Jarusiewicz, Jae Yoon Jeon, Michele C. Connelly, Yizhe Chen, Lei Yang, Sharyn D. Baker, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

Profiling of the kinase-binding capabilities of an aminopyrimidine analogue detected in a cellular screen of the St. Jude small-molecule collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure–activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological profiling demonstrated that compound 5e shows characteristics suitable for further preclinical development.

Pediatric Leukemia: Diagnosis To Treatment–A Review, Samantha C. Bernard, Ehab H. Abdelsamad, Paisley A. Johnson, Daniel L. Chapman, Madhukiran Parvathaneni

Faculty Works

Leukemia is cancer of the blood and bone marrow, it is the most common cancer found in children and is found to be more than one fourth of pediatric cancers. It causes white blood cells to become abnormal and the body to become weak. This deficiency in the immune system reduces the body's ability to fight infection or simple airborne illnesses, causing extensive treatment of common pathogens and cancer treatment. The present review covers all topics, from diagnosis to treatment of pediatric leukemia, as well as the stages of growth and physiological changes throughout the process. As leukemia has a …

Targeted Delivery Of Drug Combinations Via Nanocarriers For Cancer Treatment, Kruti Soni

Theses & Dissertations

Combination therapy is preferred over monotherapy to treat cancer as it can show better therapeutic outcomes and also delay the onset of resistance by targeting multiple cell-survival pathways in cancer cells. Rationally developed combinations with monoclonal antibodies and small molecule drugs in the form of antibody-drug conjugates or antibody nanoparticle conjugates allow us to take advantage of the cellular targeting of the potent cytotoxic agents, thereby widening the scope for dose reduction while maintaining the required therapeutic response. This can in turn improve patient tolerability by reducing the off target toxicities. For the therapy of ErbB2 positive breast cancer, the …

Delivery Of Small Molecule And Rna For The Treatment Of Type 1 Diabetes And Prostate Cancer, Di Wen

Theses & Dissertations

The aim of this thesis is to develop combination therapy using a small molecule and RNA including siRNA, shRNA, or miRNA inhibitor for the treatment of type 1 diabetes and prostate cancer. New amphiphilic biodegradable polymers capable of co-delivering small hydrophobic molecules and RNAs or human bone marrow-derived mesenchymal stem cell (hBMSC) for co-delivery of an shRNA and a miRNA inhibitor were used as drug delivery platform. The drug delivery properties were evaluated in vitro and in vivo islet transplantation, subcutaneous and orthotopic prostate cancer models.

In Chapter 1, an overview of prostate cancer, the role of miRNA and …

Sleep Deprivation And Voluntary Alcohol Consumption In Adult Rats, Charles M. Cowan Ii

Masters Theses, 2010-2019

Alcohol is a psychoactive drug with a large userbase among adults across the globe. However, alcohol use also reduces the quality of sleep in the user. Historically, research has focused on the effects of alcohol on sleep architecture, but recent research has started to examine the effects of sleep deprivation on alcohol consumption. This research examines the effects of sleep deprivation on voluntary alcohol consumption in adult rats. Twelve Sprague Dawley rats were given ad libitum access to food, alcohol (7% solution), and water for the duration of this study. Subjects were then placed into non-moving forced exercise wheels to …

Pediatric Hematology/Oncology Outpatient Care: The Effect Of A Standardized Collaborative Medication Reconciliation Process, Traci R. Pulliam

Evidence-Based Practice Project Reports

Pediatric patients are at an increased risk for medication errors and can benefit from processes that facilitate and promote medication safety (Stone et al., 2010). Medication reconciliation (Med Rec) is a valuable tool in improving patients’ medication safety and reducing adverse drug events (The Joint Commission, 2015). The purpose of this evidence-based practice (EBP) project was to improve the accuracy of the Med Rec process in a Midwestern pediatric hematology/oncology outpatient clinic by developing, promoting, and evaluating a standardized, collaborative Med Rec process. The Stetler EBP model guided the implementation of the intervention, with the goal of integrating current evidence …

High-Content Screening Of Clinically Tested Anticancer Drugs Identifies Novel Inhibitors Of Human Mrp1 (Abcc1), Brian G. Perterson, Kee W. Tan, Bremansu Osa-Andrews, Surtaj H. Iram

Chemistry and Biochemistry Faculty Publications

Multidrug resistance protein 1 (MRP1/ABCC1), an integral transmembrane efflux transporter, belongs to the ATP-binding cassette (ABC) protein superfamily. MRP1 governs the absorption and disposition of a wide variety of endogenous and xenobiotic substrates including various drugs across organs and physiological barriers. Additionally, its overexpression has been implicated in multidrug resistance in chemotherapy of multiple cancers. Here, we describe the development of a high content imaging-based screening assay for MRP1 activity. This live cell-based automated microscopy assay is very robust and allows simultaneous detection of cell permeable, non-toxic and potent inhibitors. The validity of the assay was demonstrated by profiling a …

Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori

Senior Honors Projects

The genomes of living organisms are under constant bombardment from various sources, including chemical modification stemming from processes within the organisms themselves or from exogenous agents, and from radiation. These sources of genomic damage may induce structural changes in the genome’s most basic functional units, the nucleotides that comprise DNA. Damage to an organism’s DNA may result in the production of dysfunctional or nonfunctional proteins. Failure to repair such damage may result in the compounding of successive mutations within the organism’s genome, the pathogenesis of cancer and various genetic disorders in humans. To ensure their viability, organisms have developed unique …

Evaluating The Safety And Efficacy Of Classical Greek And Roman Treatments Compared To Modern Treatment, Morgan A. Wynes

Senior Honors Projects

Classical Greek and Roman civilizations survived for centuries and have greatly influenced the civilizations that have succeeded them. The treatments of diseases of both civilizations changed over time as physicians and philosophers such as Hippocrates and Galen developed a better understanding of the human body. Some of the treatments for disease used in ancient Greece and Rome remain in use today.

This project was designed to assess the safety and efficacy of classical Greek and Roman medicinal treatments and compare them to modern day treatments. The first step of the project was to identify classical diseases with telltale symptoms that …

Comparison Of Pharmaceutical Calculations Learning Outcomes Achieved Within A Traditional Lecture Or Flipped Classroom Andragogy, H. Glenn Anderson Jr., Lisa Frazier, Stephanie L. Anderson, Robert B. Stanton, Chris Gillette, Kim Broedel-Zaugg, Kevin W. Yingling

Pharmacy Practice & Administration

Objective. To compare learning outcomes achieved from a pharmaceutical calculations course taught in a traditional lecture (lecture model) and a flipped classroom (flipped model).

Methods. Students were randomly assigned to the lecture model and the flipped model. Course instructors, content, assessments, and instructional time for both models were equivalent. Overall group performance and pass rates on a standardized assessment (Pcalc OSCE) were compared at six weeks and at six months post-course completion.

Results. Student mean exam scores in the flipped model were higher than those in the lecture model at six weeks and six months later. Significantly more students passed …

Effects Of Sodium-Glucose Cotransporter 2 Inhibitors On 24-Hour Ambulatory Blood Pressure: A Systematic Review And Meta-Analysis, William L. Baker, Leo F. Buckley, Michael S. Kelly, John D. Bucheit, Eric D. Parod, Roy Brown, Salvatore Carbone, Antonio Abbate, Dave L. Dixon

Pharmacy Faculty Articles and Research

Background-—Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycemic agents that improve glycemic control by increasing glycosuria. Additional benefits beyond glucose lowering include significant improvements in seated clinic blood pressure (BP), partly attributed to their diuretic-like actions. Less known are the effects of this class on 24-hour ambulatory BP, which is a better predictor of cardiovascular risk than seated clinic BP.

Methods and Results-—We performed a meta-analysis of randomized, double-blind, placebo-controlled trials to investigate the effects of SGLT2 inhibitors on 24-hour ambulatory BP. We searched all studies published before August 17, 2016, which reported 24-hour ambulatory …

A1c Reduction And Weight Loss In A Veteran Population Using Glp-1-Ras, Shelby L. Beutel Darrow

Undergraduate Honors Thesis Collection

Background: Diabetes mellitus is a metabolic disorder defined by high blood glucose. Glucagon-like peptide-1 receptor agonists (GLP-1-RAs) are a newer class of medications that offer potential 2 to 3 kg weight loss and a 1% to 1.5% decrease in A1c. At the Indianapolis Veterans Affairs Medical Center (VAMC), GLP-1-RAs are non-formulary.

Objectives: Primary outcomes included mean change in weight, body mass index (BMI) and A1c in VAMC patients. Secondary outcomes included the comparison to published values, analysis of insulin needs, and analysis of GLP-1-RA discontinuation reasons.

Methods: Indianapolis VAMC patients ages 18-80 with type 2 diabetes who started a GLP-1-RA …

Application Of Fluoroquinolone Resistance Score In Management Of Complicated Urinary Tract Infections, Ansal Shah, Julie Ann Justo, P Brandon Bookstaver, Joseph Kohn, Helmut Albrecht, Majdi N. Al-Hasan

Faculty Publications

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively …

Toxic And Essential Trace Element Content Of Commonly Administered Pediatric Oral Medications, Robert A. Yokel, Sarah E. Seger, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

OBJECTIVES: The aim of this study was to test the hypothesis that commonly administered pediatric oral medications are a significant source of toxic elements. The concentrations of 16 elements were determined in 14 frequently used pediatric oral medications.

METHODS: Samples were prepared for analysis by dilution or nitric acid microwave-assisted digestion and analyzed by inductively coupled plasma mass spectrometry. The intake of each element from administration for 1 week of the medication's maximum recommended daily dose to 6-month-olds was calculated and compared to an exposure guideline for that element. Exposure guidelines used for adverse effects were minimal risk levels, oral …