Pharmacy and Pharmaceutical Sciences Commons^™

Striving For Appropriate Antibiotic Use: A Biomarker Initiative, And Outcomes Associated With Azithromycin Exposure, Amanda Gusovsky

Theses and Dissertations--Pharmacy

The introduction of antibiotics into clinical practice is considered the greatest medical breakthrough of the 20^thcentury. However, the use of antibiotics can contribute to the development of resistance. In the United States (U.S.), approximately 2.8 million people are infected with antibiotic-resistant bacteria each year, and more than 35,000 people die as a result. Moreover, some antibiotics are known to cause cardiac side effects including QT prolongation, hypotension, and ventricular arrythmias. The U.S. Centers for Disease Control and Prevention (CDC) defines appropriate antibiotic use as the effort to use “the right antibiotic, at the right dose, for the right …

Modeling The Bidirectional Relationship Between Shared-Patient Physician Networks And Patient Longitudinal Treatment Patterns: Application To Physician Risky-Prescribing, Xin Ran

Dartmouth College Ph.D Dissertations

Risky-prescribing is a pressing public health concern in the United States. Opioids, benzodiazepines, and non-benzodiazepine sedative-hypnotics (sedative-hypnotics) are three commonly-prescribed but potentially risky drug groups, prescribed alone or in combination. Physician shared-patient networks provide a unique perspective in studying physician network characteristics and structures, as well as their association with the delivery of health care. Understanding how physician shared-patient networks are related to their prescribing may inform network-based interventions targeting risky-prescribing, which is yet to be fully studied.

We investigated patient receipt of risky prescriptions and physician risky-prescribing intensity through the scope of shared-patient networks. We used retrospective Medicare insurance …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

Synthesis And Characterization Of D5-Barbarin For Use In Barbarin-Related Research, Sucheta Kudrimoti, Jacob Machin, Adedamola S. Arojojoye, Samuel G. Awuah, Rodney Eisenberg, Clara Fenger, George Maylin, Andreas F. Lehner, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d₅-barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D₅-barbarin synthesis commenced with production of d₅-2-oxo-2-phenylacetaldehyde oxime (d₅-oxime) from d₅-acetophenone via butylnitrite in an ethoxide/ethanol solution. This d₅-oxime was then reduced with lithium aluminum …

Perturbation Modeling For Molecular Design Of Protein Tyrosine Kinase Inhibitors Using Unsupervised Machine Learning, Keerthi Krishnan

Computational and Data Sciences (MS) Theses

The field of computational drug discovery and development has grown, with the aid of new computational tools for novel molecule discovery. In specific, generative deep learning models have excelled as tools to aid in navigating the large space of known molecules and in the creation of new molecules. These models are fed various representations of molecules as inputs and learn to perform a variety of things, such as the optimization of these molecules towards a targeted property. Ultimately, these generative learning models allow us to build bridges between chemical and continuous spaces to understand the compromise between invoking small incremental …

Jatropha Tanjorensis A Flora Of Southeast Nigeria: Isolation And Characterization Of Naringenin And Validation Of Bio-Enhanced Synergistical Activity Of Α- Tocopherol Toward Clinical Isolates Of Resistant Bacterial, Ikechukwu Kingsley Ijoma, Vincent Ishmael Egbulefu Ajiwe

Makara Journal of Science

Jatropha tanjorensis is among the rich floras of Southeast Nigeria and used by ethnic people to treat infections and manage health conditions. Ethnomedicine has long been employed in the treatment of ailments caused by bacterial pathogens. Studies showed that the incorporation of synthetic α-tocopherol to an antibacterial agent improves its activity. However, knowledge about the antibacterial-enhanced activity of plant-based α-tocopherols, especially those isolated from Jatropha tanjorensis, is limited because of the different bioactivities of synthetic and natural α-tocopherols. To determine the phytochemicals in J. tanjorensis, we carried out the structural elucidation of its leaf extracts. Naringenin and α-tocopherol …

Managing Risk And Knowledge: Frameworks To Guide Knowledge-Enabled Technology Transfer, Martin Lipa Dr, Anne Greene

Level 3

Technology transfer is not only about the transfer of technology, but also about the transfer of knowledge, as evidenced by definitions of KM within the biopharma industry and beyond. However, knowledge transfer is often not well structured and its effectiveness – in particular for tacit knowledge (i.e., know how) – is an opportunity for improvement which can lead to many benefits. This article profiles recent research into the topic of improving knowledge transfer during technology transfer and presents several recently developed frameworks for improving such. The article furthermore explains how the frameworks can be co-deployed in support of robust knowledge …

Steps Towards Digital Transformation In The Pharmaceutical Manufacturing Landscape Knowledge-Enabled Technology Transfer, Anne Greene Professor, Martin Lipa Dr

Level 3

No abstract provided.

Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg

All Faculty Scholarship for the College of the Sciences

C-fused γ-lactam-lactones are resident in several bioactive molecules, including anticancer agents such as omuralide. In this embodiment, we report mild conditions for the catalytic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids. The use of dichloromethane as the solvent and Ph₃PS as the catalyst led to predominant 6-endo-trig cyclization and furnished the trans-fused-γ-lactam-δ-lactones. The transformation is modular, regioselective, chemoselective, and diastereoselective. The γ-lactam-δ-lactones bear angular quaternary benzylic stereocenters, which is noteworthy since the presence of a quaternary carbon in bioactive small molecules often promotes an element of conformational restriction that imparts potency, selectivity, and metabolic stability. The …

Emerging Technologies: Empowering People To Capture, Share And Transfer Tacit Knowledge, Donncadh J. Nagle, Melanie J. Adams

Level 3

ICH Q10 was published in 2008, and presented a model for an effective Pharmaceutical Quality System (PQS). However, the industry still has some way to go in embracing and implementing its principles in order to achieve greater product realisation, to establish and maintain a state of control, and to facilitate continual improvement.

ICH Q10 introduced us to two key enablers: Knowledge Management (KM) and Quality Risk Management (QRM).^[1] While the pharmaceutical industry has made progress in implementing the principles of QRM since 2008, there has been significantly slower progress in implementing knowledge management practices. However, there may be solutions …

Will Reducing Drug Prices Slow Innovation?, Gregory Vaughan, Fred Ledley

Mathematical Sciences Faculty Publications

The pharmaceutical industry has long argued that high drug prices reflect the high cost of innovation and that reducing drug prices would necessarily slow the pipeline of new drugs. These arguments have been bolstered by studies of large pharmaceutical companies showing statistical associations between the projected market size or revenue for pharmaceutical products and research & development (R&D) activity. Our analysis recognizes the increasingly important role of small biopharmaceuticals in drug development , companies that typically have little revenue and negative earnings, but are now responsible for more than 40% of new drug approvals. We examine the relationship between changes …

The Design Of A Pcr-Based Assay To Detect And Isolate The Serine Palmitolytransferase Gene From Environmental Bacteria, Lana Taylor

Honors Theses

Sphingolipids are a natural class of lipids that function as structural elements of cell membranes and signaling molecules for important cellular activities such as cell growth, differentiation, apoptosis, recognition, and adhesion. These lipids can be found universally in eukaryotic cells as well as some species of bacteria, such as those found in the human gut microbiome and in the environment in soils. Though sphingolipid production is rare in bacteria, both eukaryotic and prokaryotic sphingolipid biosynthesis begin with the condensation of serine and palmitoyl CoA into 3-ketodihydrosphingosine catalyzed by the enzyme serine palmitoyltransferase (SPT). In recent years, several studies have shown …

Covid Synergy: A Machine Learning Approach Uncovering Potential Treatment Combinations For Sars-Cov-2, Jason Eden Sanchez

Open Access Theses & Dissertations

For more than two years, the COVID-19 pandemic has upended the lives of billions of individualsworldwide leading to disruptions in healthcare, the economy and society at large. As the pandemic enters its third year, the human impact cannot be overstated and the need to develop effective pharmaceuticals remains. Though there currently exits FDA-approved medications for COVID-19, the emergence of novel variants, such as Omicron, highlights the importance of discovering new therapies which will continue to be effective regardless of the pandemicâ??s progression. Because discovering new medications is a costly and timeintensive endeavor, my approach entails drug repurposing to test medications …

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

A Meshless Approach To Computational Pharmacokinetics, Anthony Matthew Khoury

Doctoral Dissertations and Master's Theses

The meshless method is an incredibly powerful technique for solving a variety of problems with unparalleled accuracy and efficiency. The pharmacokinetic problem of transdermal drug delivery (TDDD) is one such topic and is of significant complexity. The locally collocated meshless method (LCMM) is developed in solution to this topic. First, the meshless method is formulated to model this transport phenomenon and is then validated against an analytical solution of a pharmacokinetic problem set, to demonstrate this accuracy and efficiency. The analytical solution provides a locus by which convergence behavior are evaluated, demonstrating the super convergence of the locally collocated meshless …

A Proposed Treatment Of Mixed Connective Tissue Disease By Competitive Inhibition Of Autoantibodies, Thomas Russell

Senior Honors Theses

Mixed Connective Tissue Disease is an autoimmune disease characterized by Raynaud’s phenomenon and arthritis among other symptoms. It is primarily caused by antibodies that target the U1-RNP 70K peptide. The treatment proposed in this paper uses competitive inhibition to prevent the binding of the anti-U1-RNP 70K antibodies with the U1-RNP 70K peptide. A method for testing the designed treatment in silico is proposed using AutoDock Vina docking software.

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen

CSB and SJU Distinguished Thesis

An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be the protein of …

Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen

CSB and SJU Distinguished Thesis

Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has killed an …

Reliever-Triggered Inhaled Glucocorticoid In Black And Latinx Adults With Asthma, Alex Colon

Annual Research Symposium

No abstract provided.

A Quantitative Analysis Of The Efficacy Of Various Essential Oils Against The Sars Cov-2 Virus, Elizabeth Wagstaff, Chandrelyn Kraczek, Jack Brandon Lopez

Annual Research Symposium

A poster presentation and abstract for the Roseman Symposium. The project focuses on testing 3 essential oil blends and two disinfectants containing an essential oil blend against SARS CoV-2 in response to the COVID-19 pandemic. The project procedure involves plaque assays, disinfection, and neutralization techniques.

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov

Chemistry & Biochemistry Faculty Publications

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …

Patients With Obesity And A History Of Metformin Treatment Have Lower Influenza Mortality: A Retrospective Cohort Study, Tammy H. Cummings, Joseph Magagnoli Ph.D., Ms, James W. Hardin, S. Scott Sutton

Faculty Publications

Background: Obesity is a risk factor for the development of influenza by leading to a chronic inflammatory state and T-cell dysfunction. Based upon preclinical research, metformin has influenza activity by restoring T-cell function and improving the immune response. Objective: We aimed to evaluate the potential drug repurposing of metformin for the management of influenza among patients with obesity utilizing national claims data in an electronic health record database. Methods: The VA Informatics and Computing Infrastructure (VINCI) was utilized to obtain individual-level information on demographics, administrative claims, and pharmacy dispensation. A cohort was created among individuals with laboratory confirmed diagnosis of …

Swosu Research And Scholarly Activity Fair 2022, Swosu Office Of Sponsored Programs

SWOSU Research and Scholarly Activity Fair Programs

On behalf of Southwestern Oklahoma State University, welcome to the Thirtieth Research and Scholarly Activity Fair! We are proud to host students and faculty from universities and community colleges from across the state at this meeting of scholars. Research and scholarly activity ranging from Business Administration, Education and Professional Studies, Fine Arts and Design, Liberal Arts, and Mathematics and Science.
.
.
.

Sincerely, SWOSU Office of Sponsored Programs and URSAC

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Investigating The Physical Stability Of Amorphous Pharmaceutical Formulations, Travis W. Jarrells

Theses and Dissertations--Pharmacy

Amorphous formulations, including amorphous solid dispersions (ASDs), consisting of the active pharmaceutical ingredient (API) intimately mixed in a polymeric matrix, are an attractive formulation approach to improve drug delivery, dissolution, and solubility. However, an amorphous API in an ASD is in a higher energy state compared to the crystalline drug and results in most ASDs being inherently unstable. The polymer helps to stabilize the amorphous drug against crystallization such that the resulting homogenous mixture maintains its solubility advantage relative to the crystalline form. One challenge of ASDs is that the presence of impurities including crystals or residual solvent, variations in …

Development Of Accurate And Efficient Computational Methodologies For Predicting Protein-Ligand And Protein-Protein Binding Free Energies, Alexander Hamilton Williams

Theses and Dissertations--Pharmacy

Computational modeling is an invaluable tool in the drug discovery process either for small ligand or protein therapeutics. The widespread availability of protein X-Ray Crystal and Cryo-Electron Microscopy (Cryo-EM) structures has allowed for more accurate molecular dynamics (MD) simulations that are not reliant on methods such as homology modeling, which may produce structures that require significant computational time to demonstrate their stability. In this thesis we describe several novel methodologies for the computationally efficient modeling of protein/ligand and protein/protein complexes that may be employed within both large-scale virtual screenings and lead compound optimization. These methodologies may also be utilized in …

Peripherally Restricted Opioid Conjugates And Its Use As Pharmacological Probes And Potential Therapeutics, Md Tariqul Haque Tuhin

University of the Pacific Theses and Dissertations

Opioid-induced constipation (OIC) is one of the major adverse effects of opioid analgesics used by millions of patients each year. While progress has been made, there remains a significant unmet medical need in the treatment of OIC. Major gaps remain in our understanding of the role of the gastrointestinal tract and central nervous system (CNS) in precipitating OIC. For the last four decades, numerous investigations to study the sites of action of opioid analgesics have utilized peripherally acting mu-opioid receptor antagonists (PAMORAs), which have been incorrectly believed to have limited penetration across the blood-brain barrier (BBB). Several preclinical and clinical …

The Vagabond Flourine Atom Revisited: Dissociative Photoionization Of Tri- And Pentafluoropropene, Jessica K. De La Cruz

University of the Pacific Theses and Dissertations

Photoelectron Photoion Coincidence (PEPICO) Spectroscopy studies on two unsaturated hydrofluorocarbons (HFCs), also known as hydrofluoroolefines (HFOs), are presented here. Previously, the Sztáray group has studied the dissociation of trans-1,3,3,3-tetrafluoroprop-1-ene (ElixClean), which is a fourth-generation refrigerant and propellant and has lower global warming potential than its precursors. My study is an extension of the ElixClean study as it aims to explore how the different number of fluorine atoms impact the dissociation reactions of these molecules. Both 3,3,3-trifluoropropene (TFP) and cis-1,2,3,3,3- pentafluoropropene (PFP) are also utilized as propellants and refrigerants.Measurements were carried out with remote access to the CRF-PEPICO (combustion reactions followed …

Gc/Ms And Lc/Ms Approaches To Chemical Communication In Plants And Marine Cyanobacteria, Carolyn Keim

University of the Pacific Theses and Dissertations

Natural products are small organic compounds synthesized by living organisms including plants, animals, and microbes. These fall into one of two categories, primary metabolites are required for survival, but secondary metabolites usually play a more accessory role. Extracts from organisms have proven to be useful to humans throughout history. Prior to evidence-based western medicine practices, natural products were the only source of medicine and remain as a treatment source for underdeveloped nations. Today, natural products have either been approved by or have served as the template for many FDA approved drugs. Based on a survey of all FDA approved drugs …