Pharmacy and Pharmaceutical Sciences Commons^™

One More Negative Regulator Of Ac6: S-Nitrosylation, Isabella Cattani-Cavalieri, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

"In this issue of the Journal, Maghsoudi and colleagues (pp. 82–96) report a series of studies that delineate the biochemical and pharmacological mechanism of this resistance (4). The study focuses on adenylyl cyclase (AC), an enzyme crucial for pulmonary vasodilation through its action of synthesizing cAMP. There are nine isoforms of AC (AC1–AC9) that are all stimulated by Gs but otherwise are distinct in their regulatory qualities, subcellular localization, and expression profiles throughout the body (5). AC6 plays a significant role in fetal and neonatal lung, especially in pulmonary artery smooth muscle cells, where …

Injectable Formulations For Localized Delivery Of Immunomodulators, Ketki Velankar

Electronic Theses and Dissertations

Dysregulation of immune homeostasis is fundamental to the development of autoimmune disorders. Fibroblastic reticular cells (FRCs) within lymph nodes play crucial roles in forming a microenvironment conducive to immune cell interactions and regulating autoreactive T cells driving autoimmune diseases. Studies have shown the potential of FRCs as a form of personalized cell therapy to correct dysregulated immune responses. Successful translational efforts, however, require the cells to be formulated as injectable suspensions while retaining their native architecture, which is essential for their regulatory functions. The main challenge resides in retaining the native reticular organization of FRCs lost in conventional monolayer cultures …

Uptake Of Extracellular Vesicles Into Brain Endothelial Cells And Development Of Motor Neuron-Derived Extracellular Vesicles For Amyotrophic Lateral Sclerosis, Jhanvi Rajan Jhaveri

Electronic Theses and Dissertations

Extracellular vehicles (EVs) are an emerging class of drug carriers and are primarily reported to be internalized into recipient cells via a combination of endocytic routes such as clathrin-mediated, caveolae-mediated and macropinocytosis pathways. In part one of this thesis, (1) we investigated potential effects of homotypic vs. heterotypic interactions by studying the cellular uptake of homologous EVs (EV donor cells and recipient cells of the same type) vs. heterologous EVs (EV donor cells and recipient cells of different types) and (2) determined the route of EV internalization into low pinocytic/hard-to-deliver cell models such as brain endothelial cells ( …

Delivery Of Mitochondria-Containing Engineered Extracellular Vesicles To The Blood-Brain Barrier For Ischemic Stroke Therapy, Kandarp Dave

Electronic Theses and Dissertations

Ischemic stroke is the second leading cause of death worldwide, and the lack of effective treatment options is an unmet clinical need for stroke survivors. Ischemic stroke-induced oxygen-glucose deprivation (OGD) in the affected brain tissue leads to mitochondrial dysfunction and adenosine triphosphate (ATP) depletion in the brain endothelial cells (BECs) lining the blood-brain barrier (BBB). ATP deprivation in the BECs dysregulates actin cytoskeleton dynamics, resulting in BBB breakdown. Restoration of blood flow (i.e., reperfusion) upon the first-line stroke treatment further leads to BBB breakdown and widens the paracellular spaces between BECs. …

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …

Central Nervous System Antiviral Pharmacology, Sean N. Avedissian

Theses & Dissertations

Soon after viral infection, viruses like Human Immunodeficiency Virus (HIV) and SARS-CoV-2 can disseminate throughout the body and establish reservoirs in the central nervous system (CNS). The persistence of viruses in cells of these reservoirs is a major obstacle to virus eradication. This is due to the abundance of cells/receptors that these viruses utilize to gain entry into cells found at these various reservoir sites. Consequently, these same anatomical sites also may be pharmacologic sanctuaries, as evidenced by concentrations of antiretroviral drugs (ARVs) and antivirals (AVs) that are lower in reservoirs than those in peripheral blood; in some cases, these …

Characterization Of Population Pharmacokinetics And Associated Interindividual Variability Of Drugs Used In Mass Drug Administration Against Lymphatic Filariasis, Abdullah Alshehri

Theses & Dissertations

Lymphatic filariasis (LF) is a mosquito-borne filarial infection that affects the lymphatic system. The progression of the disease is associated with severe comorbidities and social stigma among patients. The World Health Organization has categorized the disease as a public health problem, and it has been targeted by mass drug administration (MDA) campaigns over the past two decades. Several preventive chemotherapies have been used in MDA campaigns against LF, including a combination of three anti-filarial drugs (IDA therapy): albendazole (ALB), diethylcarbamazine (DEC), and ivermectin (IVM). Other antiparasitic drugs, such as moxidectin (MOX), are still under investigation for their activity against LF. …

Synthesis And Characterization Of An Activity-Based Probe To Isolate And Quantify Adduct Formation In Ntsr1 Trt., Aadarsh Khairnar

Theses & Dissertations

Targeted radionuclide therapy (TRT) has emerged as a promising cancer treatment by offering precise delivery of radioisotopes to cancer cells via molecular targets. Recent advancements in the small molecule TRTs offer efficient targeting and rapid clearance, reducing off-target toxicity. The Neurotensin receptor 1 (NTSR1) targeted small molecule antagonist 3BP-227 when labeled with [¹⁷⁷Lu], has demonstrated effective tumor targeting but suffers from rapid washout from the target cancer cell, limiting its therapeutic potential.

To enhance tumor retention and therapeutic efficacy of the NTSR1-targeted TRT, the Garrison laboratory has developed a novel approach utilizing cysteine cathepsins (CCs) and the E64 …

Pharmacokinetics And Tissue Distribution Of A Lipid-Based Extended-Release Nano-Formulation Of Mo-Oh-Nap Tropolone To Enhance Pulmonary Delivery For The Treatment Of Pulmonary Metastatic Osteosarcoma, Wafaa N. Aldhafiri

Theses & Dissertations

Osteosarcoma is the most common primary bone tumor in children and adolescents. Metastasis is prevalent in 25% of patients, at diagnosis, with the lungs being the most common metastatic site. Pulmonary metastatic osteosarcoma is a significant therapeutic challenge with a 5-year survival rate of ≤30%. Patients with pulmonary metastatic disease at diagnosis receive the same standard of care as patients with local disease, which hasn’t changed over the past 30 years. The treatment and prevention of pulmonary metastatic osteosarcoma represents a significant critical and unmet need.

MO-OH-Nap tropolone is a novel small molecule with cytotoxic activity across multiple human osteosarcoma …

Unmc Quick Checks: An “Opt-Out” Model For Health Profession Student Appointments With Mental Health Counseling Services, Hannah K. Tandon Md, Taylor J. Kratochvil Md, Ms, Katherine L. Keiser Ms, Limhp, Nicole J. Kent Bs, Kaitlyn E. Schultis Bs, Jeffrey W. Knapp Msw, Jeffrey P. Gold

Innovations in Health Sciences Education Journal

Background: Health professions trainees experience high rates of anxiety and depression but are often reluctant to seek help. Institutional outreach during pre-clinical training may identify vulnerable students, improve resource awareness, and destigmatize psychological counseling. The University of Nebraska Medical Center (UNMC) Quick Check program is a novel opt-out program connecting health professions students to mental health counselors.

Objective: The purpose of this study was to evaluate student perceptions and utilization of mental health resources after participation in the UNMC Quick Check program.

Methods: For this limited pilot study, second-year pharmacy students were assigned to UNMC Quick Check appointments with UNMC …

Advancement In In-Silico Drug Discovery From Virtual Screening Molecular Dockings To De-Novo Drug Design Transformer-Based Generative Ai And Reinforcement Learning, Dony Ang

Computational and Data Sciences (PhD) Dissertations

The field of drug discovery has seen remarkable advancements over the past few decades, transitioning from traditional experimental methods to highly sophisticated computational approaches. One of the pivotal techniques in this evolution is virtual screening, which utilizes molecular docking to predict the interaction between small molecules and target proteins. This method has significantly accelerated the initial stages of drug discovery by enabling the high-throughput screening of large chemical libraries. By simulating the binding affinity and stability of potential drug candidates, virtual screening has become a cornerstone in identifying promising compounds for further development.

A notable application of virtual screening was …

Development Of A Novel Drug Delivery Platform To Treat Hiv-Associated Neurocognitive Disorder, Lina Zhou

Alternative Theses and Dissertations (AETDs)

Despite the significant reduction in HIV prevalence and improvement in life expectancy achieved through the availability of widespread antiretroviral therapy (ART), there remains no definitive cure for HIV. Further, HIV infects the brain as early as eight days after initial peripheral infection leading to neuroHIV and subsequently neuronal damage and cognitive impairment. HIV can enter the brain through several mechanisms, including the migration of infected immune cells (Trojan Horse Mechanism), direct infection of endothelial cells, and cytokine-mediated disruption of the blood-brain barrier (BBB). Consequently, HIV-associated neurocognitive disorder (HAND) remains a significant challenge in the ART era, with an estimated prevalence …

Enhancing The Anticancer Effects Of Apiaceae Spice Phytochemicals., Jared Lee Scott

Electronic Theses and Dissertations

Breast cancer (BC) is a leading contributor to the death of women and is the most common type of cancer. Many chemotherapy drugs are developed from plants, and some plant extracts can exhibit significant anticancer activities while also having less toxic side effects. The Apiaceae plant family consists of several species that are used as culinarily spices which have demonstrated antioxidant, chemopreventive, and anticancer activities. The encapsulation of anticancer phytochemicals into naturally produced membrane-bound nanoparticles known as exosomes could improve their systemic distribution and efficacy. Exosomes are involved in cell-to-cell communication through the delivery of proteins, nucleic acids, and small …

Access To Medicines For Parkinson's Disease In Kenya: A Qualitative Exploration, Natasha Fothergill-Misbah, Juzar Hooker, Judith Kwasa, Richard Walker

Internal Medicine, East Africa

Background: The accessibility of Parkinson’s disease medicines is limited across sub-Saharan Africa,which can have negative health, social and financial consequences for people with Parkinson’s disease andtheir families. However, there is a stark gap in the literature regarding the impact of poor access to medicineson individuals.

Objectives: The study objective was to understand the accessibility of Parkinson’s disease medicines in Kenyafrom the perspective of people with Parkinson’s disease, their caregivers and neurologists.MethodsMethods: In-depth qualitative interviews were conducted with 55 people with Parkinson’s disease, 23 caregiversand 8 neurologists to understand their experience regarding challenges with accessing Parkinson’s diseasemedicines and the health, social …

Diesel Exhaust Particles Alter Mitochondrial Bioenergetics And Camp Producing Capacity In Human Bronchial Epithelial Cells, Isabella Cattani-Cavalieri, Marina Trombetta-Lima, Hong Yan, Ana L. Manzano-Covarrubias, Hoeke A. Baarsma, Asmaa Oun, Melissa Mol Van Der Veen, Emily Oosterhout, Amalia M. Dolga, Rennolds S. Ostrom, Samuel Santos Valenca, Martina Schmidt

Pharmacy Faculty Articles and Research

Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown.

Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24–72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of …

Impact Of A Pharmacist-Led Hcv Treatment Program At A Federally Qualified Health Center, Jerika T. Lam, Sharon Xavioer

Pharmacy Faculty Articles and Research

Pharmacists are key players who can help to eliminate the hepatitis C virus (HCV) epidemic in the United States. This pilot retrospective study evaluated the impact of a pharmacist-led HCV treatment program in a federally qualified health center (FQHC) primary care clinic setting. The primary outcome was to assess sustained virologic response (SVR) rates 12 weeks after patients were initiated and completed their oral direct acting antiviral (DAA) treatment regimens. Methods: This pilot retrospective study included historical analyses of patients who received DAA treatment in the pharmacist-led HCV treatment program in a FQHC clinic between 1 January 2019 and 31 …

Comments Re: Draft Nih Intramural Research Program Policy: Promoting Equity Through Access Planning, Fred Ledley M.D., Edward Zhou Pharmd., Paula Chaves Da Silva Ph.D.

CISI Publication

We commend the NIH initiative to require that licensees of technologies that enable discovery or development of FDA-approved products arising from the NIH intramural program to include an Access Plan to promote “product affordability, availability, acceptability, and sustainability” and recognition that such protections are essential to ensuring a “return on taxpayers' investment in biomedical research.” Recognizing the complexity of anticipating appropriate terms for products that are in pre-clinical or early clinical development at the time of licensing, we also support the proposal that the Access Plan be submitted in late-stage clinical development, though we argue that …

Formative Research About Shared Decision Making In The Treatment Of Opioid Use Disorder In Pregnant Women, Ruth Jeminiwa, Phd, Fadel Dadabaev, Pharmd, Heeyoung Kim, Pharmd, Caroline Popielaski, Pharmd, Sohyeon Park, Pharmd, Meghan Gannon, Phd Msph, Diane Abatemarco, Phd, Msw, Ronald Myers, Phd, Dsw

College of Pharmacy Posters

Background

• Shared Decision Making (SDM) is an evidence-based practice that involves a discussion between a health care professional and patient to reach a mutual agreed upon treatment plan.(1)
• A recent nationally-representative study indicates that only 39% of physicians use SDM for 50% or fewer Pregnant Women with Opioid Use Disorders (PWOUD).(2)
• Little is known about factors that affect SDM among PWOUD. This research project aimed to address this knowledge gap.

Transitions Of Care Practice Models: Innovations Across Different Health Settings, Laressa Bethishou, Noah Fang

Pharmacy Faculty Articles and Research

"Being discharged from a hospital may be a joyous occasion for a patient with a long length of stay, but this process may also be riddled with medication issues. With a deluge of new medications, unclear instructions, and new costs that may be unaffordable, many patients face challenges that are all too common. Additionally, the medication list may be fraught with discrepancies of missing or inaccurate home medications, duplicate therapies of new medications prescribed, or drug-drug interactions of old and new medications.

Pharmacists and pharmacy personnel who support patients during transitions of care (TOC) are very familiar with the consequences …

The Role Of Pharmacy In Supporting Safe And Effective Transitions Of Care, Laressa Bethishou

Pharmacy Faculty Articles and Research

Goal To inform pharmacists and pharmacy technicians of the importance of and processes for conducting transitions of care when patients are moving among healthcare settings.
Summary A narrative review of recent events and research into transitions of care (TOCs) — the movement of patients from one healthcare setting to another. To be conducted safely and effectively, the entire patient care team must optimize patient care and communicate up-to-date information among its members. As the medication experts on the healthcare team, pharmacists are well poised to receive and share information that impacts medication use and patient safety. Pharmacy technicians can play …

Developing Public-Private R&D Consortia To Accelerate Alzheimer’S Disease Drug Development, Joel West, Paul Olk

Management: Faculty Scholarship

Efforts to accelerate Alzheimer's disease (AD) drug development have been spurred on by the creation of open science, public-private R&D consortia. An R&D consortium provides an improved structure for generating and disseminating AD knowledge across a range of organizations while also aligning their interests. Drawing from archival and interview data collected on 46 public-private R&D consortia focused wholly or in part on AD, we uncover two important innovations: the creation of novel consortium types that facilitate coordination beyond the individual consortium, and the practice of organizations joining multiple consortia. Collectively these innovations provide member organizations with different pathways for advancing …

Antitumor Activity Of A Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting Lgr5 In Preclinical Models Of Neuroblastoma, Jianghua Tu, Yukimatsu Toh, Adela M Aldana, Jake J Wen, Ling Wu, Joan Jacob, Li Li, Sheng Pan, Kendra S Carmon, Qingyun J Liu

Faculty, Staff and Student Publications

Neuroblastoma (NB) is a cancer of the peripheral nervous system found in children under 15 years of age. It is the most frequently diagnosed cancer during infancy, accounting for ~12% of all cancer-related deaths in children. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a membrane receptor that is associated with the primary tumor formation and metastasis of cancers in the gastrointestinal system. Remarkably, high levels of LGR5 are found in NB tumor cells, and high LGR5 expression is strongly correlated with poor survival. Antibody-drug conjugates (ADCs) are monoclonal antibodies that are covalently linked to cell-killing cytotoxins to deliver the payloads …

Utilizing Biosimilars To Help Increase Patients Access And Minimize The Financial Burden Of Health Care System In Egypt, Doaa M. Abd-El-Rady, Iman A. El-Baraky, Samar F. Farid

Bulletin of Faculty of Pharmacy Cairo University

Background: Biologics have provided enhanced clinical advantages, but at expense of enormous expenditures. The exorbitant expense of biologics was somewhat mitigated by the development of biosimilars. But biosimilars market access is still recessed in many countries including Egypt. To achieve biosimilars market sustainability, countries need to evaluate the health economic barriers that biosimilars face in gaining market access.

Methods: A retrospective budget impact analysis was conducted to compare the cost of biosimilars to that of their reference biologics from Egyptian regulatory perspective over a five-year period (2018-2022). Time series forecasting analysis was conducted to predict the cost savings …

Exploring Global Disparities In Tuberculosis Treatment And Outcomes: A Scoping Review Of Gender-Based Perspectives And Implications For Women’S Health, Colin Gordy, Dylan Barker, Marie Barnard, Sudeshna Roy

Faculty and Student Publications

This scoping review aims to explore the gender-specific disparities and highlight the unique disadvantages faced by women in the context of Tuberculosis (TB). By mapping the existing literature on women's experiences with TB, this review seeks to uncover the underlying factors contributing to these disparities and identify gaps in the current understanding. The goal is to inform future research and policymaking, ultimately improving TB prevention, treatment, and outcomes for women worldwide. Recognizing and addressing the specific needs and challenges of women is essential for achieving equitable and effective TB control.

Medicare Drug Price Negotiation Program Draft Guidance, Fred Ledley M.D., Edward Zhou Pharmd, Paula Chaves Da Silva Ph.D.

CISI Publication

This comment focuses on Section 50.1, provisions 1 & 3 of the draft guidance regarding the negotiation of a “maximum fair price” under the Inflation Reduction Act (IRA), research and development (R&D) costs of the primary manufacturer, and prior federal financial support for novel therapeutic discovery and development. Specifically, we argue that a negotiated, “maximum fair price” must consider both public sector (federal) and private sector (manufacturer) investments and provide returns to both commensurate with the scale and risk of their investments. This comment addresses three issues and makes specific recommendations regarding each:

1. In negotiating a “maximum fair price,” both …

Using A Modified Delphi Panel To Develop Best Practices In Course Evaluations Of Teaching., Ma. Emmanuelle (Ella) Domingo Vogt Pharmd, Robert D. Beckett Pharmd, Monica Miller Pharmd, Ms, Alex N. Issacs Pharmd, Ms

Parkview Pharmacy Department

Presented at AACP Annual Meeting. Boston, MA: July 2024.

This study generated best practices colleges of pharmacy should employ when conducting student evaluations of teaching and courses.

The Impact And Potential Of Digital Health Technologies, Craig Kimble, Thomas Pile, Alberto Coustasse

Pharmacy Practice & Administration

Digital technologies and smart devices are now used in every aspect of our lives. Further innovation in the digital health realm is growing and has the potential to reduce inefficiencies in the health care system by sharing health data with providers, decreasing costs related to unnecessary health care visits and improving patients’ quality of life and clinical outcomes by better tailoring treatment to the individual’s health needs.

Summer 2024 Edition, Southwestern Oklahoma State University

The Sig

GREETINGS FROM THE DEAN'S OFFICE!

Since the last edition of The Sig there has been great progress on the construction of the Jerry & Margaret Hodge College of Pharmacy and Rural Health Center. After calling the third floor of the CPP building home for 50 years, it is exciting to see our new home emerge at the corner of North Davis and Caddo with concrete being poured and steel beams hoisted into place with a crane.

Prenatal Tetrahydrocannabinol And Cannabidiol Exposure Produce Sex-Specific Pathophysiological Phenotypes In The Adolescent Prefrontal Cortex And Hippocampus, Daniel Hardy, Mohammed Sarikahya, Kendrick Lee, Sebastian Vanin, Andrea Kocsis, Steven Laviolette

Data and Test Instruments

Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (Δ9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, …

Data-Driven Drug Repurposing For Immune System-Related Diseases, Sabyasachi Mohanty

Department of Biochemistry: Dissertations, Theses, and Student Research

In this research, we explore a data-driven approach for drug repurposing to enhance the immunomodulatory effect by integrating pattern-based search and genome-scale metabolic modeling. This research helps to find a solution to the preexisting problems of drug discovery which includes expenses and a high amount of time consumption. By leveraging the pre-existing data of the approved drugs to identify the major metabolic pathway changes, we can find new drugs with similar effects with less off-target effects.

The focus on the immune system modulating drugs is due to the high prevalence of immune system-involved diseases and the growing demand for effective …