Medicine and Health Sciences Commons^™

Effects Of Human Dopamine Transporter (Dat) Mutations And Novel Allosteric Modulatory Compounds In Disrupting Hiv-1 Tat-Dat Protein Interaction, Pamela Marie P. Quizon

Theses and Dissertations

More than 37 million people are living with HIV worldwide. Despite the widespread use of antiretroviral therapy (ART), up to 70% of HIV-positive individuals suffer from cognitive and behavioral deficits collectively known as HIV-associated neurocognitive disorders (HAND). HIV-mediated damage to the dopaminergic system is a mediating factor in HAND. Dopamine (DA) transporter (DAT)-mediated reuptake is essential for maintaining DA homeostasis. Because most ART cannot efficiently cross the blood-brain barrier (BBB), the brain serves as a viral reservoir that facilitates the spread of infection to microglia and astrocytes. Infected cells shed viral proteins such as Tat, which plays a critical role …

Glia Responsivity In Nicotine Dependence, Adewale Oluwamuyiwa Adeluyi

Theses and Dissertations

Neurons are the primary research target in the exploration and development of novel smoking cessation pharmacotherapies over the years. These research efforts have led to the discovery and development of three FDA-approved smoking cessation aids – nicotine replacement therapy, varenicline, and bupropion, each of which have quantifiable success as smoking cessation aids. However, relapse is still very common and smoking cessation is successful in less than 5% of quit attempts, making paramount the development of novel therapeutics. One untapped therapeutic target are glia, particularly, astrocytes and microglia, which are active participants in the neuroplastic events underlying drug addiction.

First, we …

Investigating The Neural Correlates Of Nicotine Withdrawal Phenotypes In Mice: Involvement Of Creb-Dependent Nrg3-Erbb4 Signaling In Mediating Anxiety-Like Behavior, Miranda Fisher

Theses and Dissertations

Addiction to nicotine and the ability to quit smoking are influenced by genetic factors. Therefore, it is important to understand how genes and drugs of abuse mechanistically impact each other. One well-characterized protein responsible for regulating both response to drugs and gene expression is the transcription factor cAMP response element-binding protein (CREB). Work from our lab indicates that hippocampal specific alterations in CREB signaling and synaptic plasticity underlie certain nicotine withdrawal (WD) phenotypes in a region-specific manner. We found that CREB deletion in the ventral hippocampus (VH), a region known for regulation of mood and emotion, results in amelioration of …

Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown …

Identifying The Enzyme Involved In Vacuolar Atpase Acetylation During Doxorubicin-Induced Cardiotoxicity, Rebecca Dang, Tianqing Peng

Western Research Forum

Doxorubicin is an established anticancer medication infamous for its bright colouration and extremely toxic side effects. Emerging studies support that the imbalance between acetylation and deacetylation disrupts the autophagic flux leading to doxorubicin-induced cardiotoxicity. Vacuolar ATPases are a family of electrogenic proton pumps present on the lysosomal membrane that create an acidic environment for proteases to degrade proteins. Our preliminary study found that acetylated Vacuolar ATPase subunit V₀ D1 levels increased in doxorubicin-injected mouse hearts. However, it is unknown how acetylation of subunit V₀ D1 is modulated and whether this modification plays a role in doxorubicin-induced cardiotoxicity.

The …

Mouse Performance On A Novel Touchscreen Continuous Performance Task Is Dependent On Signaling In The Prelimbic Cortex, Tyler D. Dexter, Daniel Palmer, Amy C. Reichelt, Anita Taksokhan, Lisa M. Saksida, Tim J. Bussey

Western Research Forum

Attention is the cognitive processing that facilitates the ability to target and attend to relevant environmental stimuli, while filtering out irrelevant or distracting stimuli. Control over selective attention is theorized to be dependent on organized neural communication that stems from the medial prefrontal cortex (mPFC). To evaluate selective and sustained attention, mice were trained on the novel touchscreen rodent continuous performance task (rCPT), a task designed to emulate the human CPT. In the rodent version, images are continuously presented on a touchscreen, where mice have been trained to selectively respond to one image type while suppressing responses to all others. …

Co-Located Retail Clinics And Pharmacies: An Opportunity To Provide More Primary Care., Katherine K. Knapp, Keith Yoshizuka, Debra Sasaki-Hill, Rory Caygill-Walsh

Faculty Publications & Research of the TUC College of Pharmacy

This paper proposes that co-located retail clinics (RCs) and community pharmacies can increase opportunities to provide more accessible, affordable, and patient-friendly primary care services in the United States. RCs are small businesses of about 150-250 square feet with a clientele of about 10-30 patients each day and most frequently staffed by nurse practitioners (NPs). Community pharmacies in the U.S. at ~67,000 far outnumber RCs at ~2800, thereby opening substantial opportunity for growth. Community pharmacies and pharmacists have been working to increase on-site clinical services, but progress has been slowed by the relative isolation from other practitioners. An ideal merged facility …

Marketing Channel Effectiveness Of New Medications/Medical Technology, Hadley Mccormick

Celebration of Learning

This research project will study what marketing platforms/channels are most effective in the dissemination of new medical product news. Many people like myself have an illness/disease that requires daily medication, or require the daily use of a medical device. Due to the increasing influence of Direct to Consumer advertising of pharmaceuticals and the constant development of new medications and devices, patients may now more often go to the doctor with perceptions of what they should do to manage their illness/disease. This study aims to look at how the developers of these medications/medical devices promote their products currently and how certain …

Medications Development For Drug Addiction And Other Neuropsychiatric Disorders, Ariful Islam

Theses and Dissertations

Drug addiction and abuse especially opiate and psychostimulant abuse is a national and global crisis. IBNtxA (3-iodobenzoyl naltrexamine) is a novel mu opioid receptor (MOR) agonist, a naloxone derivative, structurally related to the classical MOR antagonist naltrexone. Recent studies suggest IBNtxA preferentially signals through truncated MOR splice variants, producing a unique pharmacological profile resulting in potent analgesia with reduced side effects. It has been found that M. vaccae has immunoregulatory effects that can prevent stress-induced exaggeration of neuroinflammation in the brain. The purpose of our pilot study is to develop medication for addiction and neuropsychiatric disorders. According to our purpose, …

Molecular Recognition Of M1-Linked Ubiquitin Chains By Native And Phosphorylated Uban Domains, Lina Herhaus, Henry Van Den Bedem, Sean Teng, Innokentiy Maslennikov, Soichi Wakatsuki, Ivan Dikic, Simin Rahighi

Pharmacy Faculty Articles and Research

Although the Ub-binding domain in ABIN proteins and NEMO (UBAN) is highly conserved, UBAN-containing proteins exhibit different Ub-binding properties, resulting in their diverse biological roles. Post-translational modifications further control UBAN domain specificity for poly-Ub chains. However, precisely, how the UBAN domain structurally confers such functional diversity remains poorly understood. Here we report crystal structures of ABIN-1 alone and in complex with one or two M1-linked di-Ub chains. ABIN-1 UBAN forms a homo-dimer that provides two symmetrical Ub-binding sites on either side of the coiled-coil structure. Moreover, crystal structures of ABIN1 UBAN in complex with di-Ub chains reveal a concentration-dependency of …

A 24-Week Double-Blind Placebo-Controlled Study Of The Efficacy And Safety Of The Ampa Modulator S47445 In Patients With Mild To Moderate Alzheimer's Disease And Depressive Symptoms, Eileen M. Bulger, Sylvie Gouttefangeas, Sylvie Bretin, Stéphanie Galtier, Philippe Robert, Vjera Holthoff-Detto, Jeffrey Cummings, Maria Pueyo

School of Medicine Faculty Research

Introduction S47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms. Methods For this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses …

Association Of Naloxone Coprescription Laws With Naloxone Prescription Dispensing In The United States, Minji Sohn, Jeffery C. Talbert, Zhengyan Huang, Michelle R. Lofwall, Patricia R. Freeman

Institute for Pharmaceutical Outcomes and Policy Faculty Publications

Importance: To mitigate the opioid overdose crisis, states have implemented a variety of legal interventions aimed at increasing access to the opioid antagonist naloxone. Recently, Virginia and Vermont mandated the coprescription of naloxone for potentially at-risk patients.

Objective: To assess the association between naloxone coprescription legal mandates and naloxone dispensing in retail pharmacies.

Design, Setting, and Participants: This was a population-based, state-level cohort study. The sample included all prescriptions dispensed for naloxone in the retail pharmacy setting contained in IQVIA's national prescription audit, which represents 90% of all retail pharmacies in the United States. The unit of observation was state-month …

Modification And Characterization Of Chloro-Sugar Derivatives As Anti-Bacterial Agents, Mansi Jani

Theses and Dissertations

Sucralose is an artificial sugar substitute which is most commonly used sweetener among other artificial sweeteners. It is derived from sucrose through a complex chemical process that selectively substitutes three atoms of chlorine for three hydroxyl groups on sucrose molecule, which have shown some inhibition of bacterial growth in gut. The goal of the project was to substitute halide in sucralose in a way that it sustains potential anti-bacterial activity along with sweetening effect, which can be then incorporated into mouthwash formulation. Sucralose is very stable molecule and it also has other physico-chemical advantages which are suitable for our anticipated …

An In Silico Study Of G Protein-Coupled-Receptor Activation, Specifically In The Corticotropin Releasing Factor Receptor And The Glucagon-Like Peptide Receptor, Nicolas Angelo Scorese

Theses and Dissertations

The drug discovery process is an extremely long and expensive process that modern computational methods help to alleviate. Through the use of computational methods, we provide information and insight into the activation methods of class B GPCRs so that future drugs can be developed to have less side effects. The first study focuses on the corticotropin releasing factor receptor, which is a good drug target for anxiety and depression. A mechanism of activation was theorized which focuses less on molecular switches (as has been the focus of several papers) and more on large scale conformation at the intracellular region of …

Effect Of Hyperoxia On Type-1 Diabetic Mouse Model, Samuel Ignatious Bolleddu

USF Tampa Graduate Theses and Dissertations

Administration of Hyperoxia (>90 % oxygen) is a pervasive intervention to supplement respiratory needs in patients admitted in ICU/critical care units. Current literature suggests that prolonged use of Hyperoxia therapy is directly associated with in-hospital mortality. The exact reason for this high mortality under Hyperoxia is unknown. Recent explorations in Dr. Panguluri lab identified that dysregulation of Kv channels plays a vital role in the pathophysiology of Hyperoxia-induced pulmonary and cardiac complications using animal models. The proposed research will focus on the part of Hyperoxia in generating cardiotoxicity and ventricular remodeling in the type-1 diabetes patients using the Akita, …

A Systematic Review Of The Evidence Behind Use Of Reduced Doses Of Acetaminophen In Chronic Liver Disease, Anne Schweighardt, Katherine Juba

Pharmacy Faculty/Staff Publications

Acetaminophen is among the most commonly used nonopioid analgesics, but significant variation exists in its prescribing practices for cirrhosis patients. Our primary objective was to describe the quality of evidence supporting or refuting the use of acetaminophen in patients with hepatic dysfunction. A comprehensive literature review of PubMed, Cochrane Library, Web of Science, and International Pharmaceutical Abstracts using the search terms “acetaminophen,” “paracetamol,” “chronic liver disease,” “cirrhosis,” and “hepatic disease” for studies describing changes in acetaminophen metabolism in patients with hepatic dysfunction was conducted. Twelve studies and four abstracts were included. Ten studies and three abstracts were pharmacokinetic studies. Two …

June 2019, Randy Curry, Cindy Brooks

RURAL ROCKS

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

A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter

Department of Biological Sciences Publications

Background: A rapid in-house TM4 mycobacteriophage-based assay, to identify multidrug resistance against various anti-tuberculosis drugs, using the fast-growing Mycobacterium smegmatis mc² 155 in a microtiter plate format was evaluated, based on phage viability assays. Methods: A variety of parameters were optimized before the study including the minimum incubation time for the drugs, phage and M. smegmatis mc² 155 to be in contact. An increase in phage numbers over 2 h was indicative that M. smegmatis mc² 155 is resistant to the drugs under investigation, however when phage numbers remained static, M. smegmatis mc² 155 found to …

Patient And Student Experience On An Interprofessional Hotspotting Team, Steven Elsesser, Md, Elizabeth Feeney, Bsn, Katherine Petty, Spt, Kevin Shaloo, Spt, Nancy Tang, Pharmd

JCIPE Posters

The purpose of the Student Hotspotting initiative is to identify these individuals, understand their barriers and intervene by:

• Connecting them with community resources
• Improving coordination and communication between both providers and the patient
• Empowering these individuals to better manage their health

Our patient (DW) lives in a close-knit, 4-generation household that just welcomed their newest member: a black-and-white kitten

DW is a 61 year-old female who recently received orthotopic heart transplant. Her comorbidities include sleep apnea, GERD, OA, chronic pain syndrome, COPD and a history of a CVA

We identified 3 main barriers to address with DW

• Transportation difficulties
• Management …

Preclinical Evaluation Of An Unconventional Ruthenium‐Gold‐ Based Chemotherapeutic: Rance‐1, In Clear Cell Renal Cell Carcinoma, Benelita Elie, Karen Hubbard, Yuriy Pechenyy, Buddhadev Layek, Swayam Prabha, Maria Contel

Publications and Research

Background: There are few effective treatments for patients with advanced clear cell renal cell carcinoma (CCRCC). Recent findings indicate that ruthenium‐gold containing compounds exhibit significant antitumor efficacy against CCRCC in vitro affecting cell viability as well as angiogenesis and markers driving those 2 phenomena. However, no in vivo preclinical evaluation of this class of compounds has been reported.

Methods: Following the dose‐finding pharmacokinetic determination, NOD. CB17‐Prkdc SCID/J mice bearing xenograft CCRCC Caki‐1 tumors were treated in an intervention trial for 21 days at 10 mg/kg/72h of RANCE‐1. At the end of the trial, tumor samples were analyzed for histopathological and …

“Smoking Evolved?” Perceptions And Use Of Juul Products Amongst College Students, Ty Meka

Sociology Between the Gaps: Forgotten and Neglected Topics

No abstract provided.

Small‐Molecule Activators Of Glucose‐6‐Phosephate Dehydrogenase (G6pd) Bridging The Dimer Interface, Andrew G. Raub, Sunhee Hwang, Naoki Horikoshi, Anna D. Cunningham, Simin Rahighi, Soichi Wakatsuki, Daria Mochly-Rosen

Pharmacy Faculty Articles and Research

We have recently identified AG1, a small-molecule activator that functions by promoting oligomerization of glucose-6- phosphate dehydrogenase (G6PD) to the catalytically competent forms. Biochemical experiments indicate activation of G6PD by the original hit molecule (AG1) is noncovalent and that one C2-symmetric region of the G6PD homodimer is important for ligand function. Consequently, the disulfide in AG1 is not required for activation of G6PD and a number of analogs were prepared without this reactive moiety. Our Study supports a mechanism of action whereby AG1 bridges the dimer interface at the structural nicotinamide adenine dinucleotide phosphate (NADP+)-binding sites of two interacting G6PD …

A Multivalent Kaposi Sarcoma-Associated Herpesvirus-Like Particle Vaccine Capable Of Eliciting High Titers Of Neutralizing Antibodies In Immunized Rabbits, David H. Mulama, Lorraine Z. Mustvunguma, Jennifer Totonchy, Peng Ye, Joslyn Foley, Gabriela M. Escalante, Esther Rodriguez, Ramina Nabiee, Murali Muniraju, Felix Wussow, Anne K. Barasa, Javier Gordon Ogembo

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.1, gB, and gH/gL) into a single multivalent KSHV-like particle (KSHV-LP). Purified KSHV-LPs were similar in size, shape, and morphology to KSHV virions. Vaccination of rabbits with adjuvanted KSHV-LPs generated strong glycoprotein-specific antibody responses, and purified immunoglobulins from KSHV-LP-immunized rabbits neutralized KSHV infection in epithelial, endothelial, fibroblast, and B …

Diagnosis, Treatment And Follow Up Of Acute Pulmonary Embolism: Consensus Practice From The Pert Consortium, Belinda Rivera-Lebron, Michael Mcdaniel, Kamran Ahrar, Abdulah Alrifai, David M. Dudzinski, Christina Fanola, Danielle Blais, David Janicke, Roman Melamed, Kerry Mohrien, Elizabeth Rozycki, Charles B. Ross, Andrew J. Klein, Parth Rali, Nicholas R. Teman, Leoara Yarboro, Eugene Ichinose, Aditya M. Sharma, Jason A. Bartos, Mahir Elder, Brent Keeling, Harold Palevsky, Soophia Naydenov, Parijat Sen, Nancy Amoroso, Josanna M. Rodriguez-Lopez, George A. Davis, Rachel Rosovsky, Kenneth Rosenfield, Christopher Kabrhel, James Horowitz, Jay S. Giri, Victor Tapson, Richard Channick, Pert Consortium

Pharmacy Practice and Science Faculty Publications

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute …

Torsades De Pointes And Qt Prolongation Associations With Antibiotics: A Pharmacovigilance Study Of The Fda Adverse Event Reporting System, Chengwen Teng Pharm.D., Ph.D., Elizabeth A. Walter, Daryl Kevin S. Gaspar, Obiageri O. Obodozie-Ofoegbu, Christopher R. Frei

Faculty Publications

Introduction: Macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone are known to be associated with Torsades de pointes/QT prolongation (TdP/QTP). Other antibiotics may also lead to TdP/QTP, but no study has systemically compared TdP/QTP associations for many available antibiotics.

Objectives: The objective of this study was to evaluate the association between TdP/QTP and many available antibiotics using the FDA Adverse Event Report System (FAERS).

Methods: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs) …

Building A Rotation Syllabus Using Legos: Learning Experience Goals & Objectives, Radhan Gopalani

All Publications

No abstract provided.

A Community Pharmacy Elective Course Utilizing A Service Development Project To Foster Innovation And Creative Thinking, Danielle Mayer, Pharmd, Bcacp

College of Pharmacy Posters

Course Description

Innovations in Community Pharmacy Practice is a 2-credit hour course offered to pharmacy students in the spring of the third professional year.

Teaching methods

• Group discussions
• Case study activity
• Self-reflection
• Group project

The focus of this course is the evolving role of the community pharmacist in delivering direct patient care services. Students learn the basics of creating a business plan and utilize these principles to create their own business plan for a new or enhanced service that could be implemented at a community pharmacy site. This is a hands-on, project- based course, designed to foster innovation, entrepreneurship, and …

Impact Of High Volume Energy Drink Consumption On Electrocardiographic And Blood Pressure Parameters: A Randomized Trial, Sachin A. Shah, Andy H. Szeto, Raechel Farewell, Allen Shek, Dorothy Fan, Kathy N. Quach, Mouchumi Bhattacharyya, Jasmine Elmiari, Winny Chan, Kate O'Dell, Nancy Nguyen, Tracey J. Mcgaughey, Javed M. Nasir, Sanjay Kaul

School of Pharmacy Faculty Articles

Background Energy drinks have been linked to an increase in emergency room visits and deaths. We aim to determine the impact of energy drinks on electrocardiographic and hemodynamic parameters in young healthy volunteers. Methods and Results A randomized, double-masked, placebo-controlled, crossover study was conducted in healthy volunteers. Participants consumed 32 oz of either energy drink A, energy drink B, or placebo within 60 minutes on 3 study days with a 6-day washout period in between. The primary end point of QT c interval and secondary end points of QT interval, PR interval, QRS duration, heart rate, and brachial and central …

Investigating Trail Sensitivity In Platinum-Resistant Ovarian Cancer, Nicholas Pathoulas

All College Thesis Program, 2016-2019

Ovarian cancer is the deadliest gynecologic malignancy in the United States. While these tumors may have a promising initial response to platinum-based chemotherapies, the patient’s prognosis is commonly hindered by the development of platinum resistant cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been implicated as a potential treatment for many cancers based on its tumor selective nature. Combination therapies with TRAIL and platinum drugs have been shown to increase apoptosis and have been used in a variety of clinical trials, which have thus far failed to pass phase II.1 Researchers have not yet elucidated the complex mechanism(s) of TRAIL …

Interventions To Increase Uptake Of The Human Papillomavirus Vaccine In Unvaccinated College Students: A Systematic Literature Review, Marie Barnard, Anna C. Cole, Lori Ward, Emily Gravlee, Mariah L. Cole, Caroline Compretta

Faculty and Student Publications

© 2019, American Association of Colleges of Pharmacy. All rights reserved. The Committee was charged with the responsibility for examining the need for change in pharmacy education and the models of leadership that would enable that change to occur across the academy. They also examined the question of faculty wellbeing in a time of change and made several recommendations and suggestions regarding both charges. Building upon the work of the previous Academic Affairs Committee, the 2018-19 AAC encourages the academy to implement new curricular models supporting personalized learning that creates engaged and lifelong learners. This will require transformational leadership and …