Pharmacy and Pharmaceutical Sciences Commons^™

Comparative Metabolism Of Aflatoxin B1 In Two Quail Genera Coturnix Japonica And Callipepla Californica, Sean Moody

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Avian species are highly susceptible to the hepatotoxic mycotoxin aflatoxin B₁ (AFB₁). Domesticated turkeys are exquisitely sensitive, due to a combination of highly-efficient hepatic cytochrome P450 (CYP)-mediated bioactivation, and to dysfunctional alpha-class glutathione S-transferases (GSTAs) which typically detoxify the bioactivated electrophilic metabolite exo-AFB₁-8,9-epoxide (AFBO). Wild turkeys are relatively resistant to AFB₁ in large part due to expression of functional GSTAs. Quail, a related Galliforme, are slightly less sensitive in vivo to AFB₁, but whether this is related to the hepatic metabolic profiles of these two critical enzymes has not been rigorously evaluated. …

Kshv Susceptibility And Transmission Within Tonsillar Specimens, Farizeh Aalam

Pharmaceutical Sciences (PhD) Dissertations

Despite nearly three decades of research, not much is known regarding the early stages of development for KSHV lymphoproliferative disorders, hindering our ability to develop prophylactic measures or effective treatments. This dissertation will focus on the host and viral factors influencing the magnitude and dynamics of KSHV infection in the human tonsil to pave the way for future interventions directed at limiting person-to-person transmission of KSHV.

To understand the contribution of host factors to KSHV susceptibility in B lymphocytes, we generated a library of 40 tonsillar specimens. Our results indicate that the immunological composition of tonsillar lymphocytes varies across our …

Development Of A Combined Feedforward-Feedback Quality Control System For Extended-Release Granules Using A Quality By Design Approach, Yuxiang Zhao

Electronic Theses and Dissertations

Objectives

For a fluid bed film coating process to consistently deliver quality products, its control system needs to be robust against the variability of input materials and environmental disturbances. Presently, limited studies have been reported to understand the effects and interactions of the material attributes, environmental variables, and process parameters on the product in vitro drug dissolution. A control system can be developed with a proper understanding of the coating process, by adjusting the process parameters in feedback and feedforward manners to compensate for the undesired effect caused by disturbances, and ensure consistent product quality.

Methods

The control system was …

Impact Of Clinical And Pharmacogenetic Variables On The Risk Of Fluoropyrimidine-Related Adverse Events Within Ontario, Theodore J. Wigle

Electronic Thesis and Dissertation Repository

Severe life-threatening adverse events are a major limitation of fluoropyrimidine chemotherapy, these events are disastrous for patients and costly to the healthcare system. Identifying patients at high risk for developing adverse events would allow for preventive dose reduction, improving patient outcomes and reducing healthcare cost. This thesis uses data pulled from provincial databases to quantify the adverse event burden of fluoropyrimidines in Ontario. We found that 31% of Ontario patients treated with fluoropyrimidine systemic chemotherapy developed a severe adverse event that requires acute medical care. Patients that required acute medical therapy were significantly costlier to the public system averaging an …

Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei

Pharmaceutical Sciences (PhD) Dissertations

The aim of this thesis was to design, synthesize, and characterize a novel peptide-doxorubicin conjugate, evaluate in vitro stability and cytotoxicity properties of the conjugate and study its mechanism for uptake into the triple-negative breast cancer (TNBC) cells. For the synthesis of the conjugate, first, doxorubicin (Dox) was conjugated to a highly efficient established cross-linker, MCC, to give an intermediate product, MCC-Dox. MCC-Dox was characterized using NMR spectroscopy, mass spectrometry, and RP-HPLC and purified for subsequent reaction. Second, the 11-mer peptide 18-4 (NH₂-CWxEAAYQrFL-CONH₂) with high proteolytic stability and specificity for breast cancer cells was reacted with …

Cost-Effectiveness Analysis Of Tisagenlecleucel, Blinatumomab, And Clofarabine For Treatment Of B-Cell Precursor Acute Lymphoblastic Leukemia, Kamron Lotfi

Pharmaceutical Sciences (MS) Theses

Acute lymphoblastic leukemia (ALL) is a common type of adolescent and young adult leukemia in the United States (U.S.). Patients who are refractory or relapsed after receiving two or more lines of systemic therapy have the option of taking tisagenlecleucel. Due to the high cost of this treatment, a cost-effectiveness analysis was performed to assess the treatments for tisagenlecleucel, clofarabine combination, and blinatumomab. Objectives

The objective of this study is to evaluate the cost-effectiveness of tisagenlecleucel; clofarabine, etoposide, cyclophosphamide; and blinatumomab for the treatment of relapse- refractory ALL for adolescents and young adults from the U.S. health care payer perspective. …

Establishing The Role Of Dc-Sign And Glycoprotein H For Kshv Entry In B Lymphocytes, Nancy Palmerin

Pharmaceutical Sciences (MS) Theses

Kaposi sarcoma-associated herpesvirus, also known as KSHV or HHV-8, is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. KSHV is known to cause four types of malignancies: endothelial-based Kaposi Sarcoma (KS), two rare B cell- based lymphomas; Primary effusion lymphoma, Multicentric Castleman’s disease and a recently characterized inflammatory disorder called KSHV-associated inflammatory cytokine syndrome(KICS). Unfortunately, all of the diseases associated with KSHV infection are fatal, and to this day there is no known cure. The purpose of this study is to understand the viral entry process of KSHV in tonsil-derived B lymphocytes. This study will …

Modulation Of Antibacterial Activity And Cytotoxicity In Amphipathic Cyclic Peptide [R4w4] Using Histidine Substitution, Ryan Stueber

Pharmaceutical Sciences (MS) Theses

Antibiotics have been the gold standard frontline defense against bacterial infections for decades. At the same time, these infecting bacteria have continued to evolve to resist developed antibiotics in an almost endless cycle. As such, we aim to take an alternative approach utilizing antimicrobial peptides (AMPs) as a means to end this cycle. [R4W4] is among known AMPs that demonstrated antimicrobial activity against methicillin-resistant staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 2.67 μg/mL. This peptide had notably effective antimicrobial activity, especially relative to linear (R4W4). However, it displayed a concerning level of cytotoxicity; eliciting a human embryonic …

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were …

Hybrid Cyclic-Linear Cell-Penetrating Peptides Containing Alternative Positive And Hydrophobic Residues As Molecular Transporters, Sorour Khayyatnejad Shoushtari

Pharmaceutical Sciences (MS) Theses

The cell membrane properties create a significant obstacle in intracellular delivery of cell-impermeable and negatively charged molecules. Amphiphilic cyclic peptides containing alternative arginine and tryptophan such as [WR]₅ have been shown to enhance the transport of cargo molecules across the cell membrane. Herein, we report the synthesis and biological evaluation of a novel series of hybrid cyclic-linear peptides containing alternative positive and hydrophobic amino acids on the ring and side-chain [(RW)₅]K(RW)_X (X=1-5) to compare their molecular transporter efficiency. The peptides were synthesized through Fmoc solid-phase peptide synthesis. Final compounds were purified by a reversed-phase HPLC (High …

Deprescribing In The Hospice Population, Who Is Eligible And Who Is Agreeable: A Quality Improvement Project, Ashlee Nicole Smith

Doctor of Nursing Practice Final Manuscripts

Current evidence recommends and supports deprescribing medications to reduce polypharmacy in the hospice population. The project aim was to determine accurate percentages of deprescribing at three time periods: before hospice admission, at hospice enrollment, and four weeks post hospice enrollment. This project was a retrospective review of the medication administration record (MAR) of patients admitted into Sharp Hospice from a Sharp Healthcare facility. Sharp Hospice, in California, USA, admitted 164 patients during August 2020. Of those, 34 patients were eligible for inclusion in this retrospective quality improvement review. Prior to discharge from a Sharp facility, the percentage of target medications …

The Effects Of Dexmedetomidine On Preventing/Decreasing Severity Of Delirium When Given To Surgical Intensive Care Unit Patients: A Systematic Review Of Randomized Control Trials, Lindsey Hettish

The Eleanor Mann School of Nursing Undergraduate Honors Theses

The purpose of this systematic review was to integrate research evidence from studies published from 2010 to 2020 on the relationship between administration of dexmedetomidine and severity/prevalence of postprocedural delirium in patients in the surgical intensive care unit. In this review, clinical trial studies were recovered by searching the MEDLINE Complete and PubMed databases and utilizing MeSH terminology search. The MeSH terms utilized to search for applicable articles on PubMed included: “intensive care units” or “critical care” or “critical care nursing”, and “delirium”, “dexmedetomidine”, and “surgical procedures, operative”. On MEDLINE Complete, the search terms utilized were “ICU or intensive care …

Effects Of Strong Oxidants Present In Acer Spp. On Hemolysis Methemoglobin Production In Equine Erythrocytes, Gabrielle Mcgeorge, Jeffrey Lehman

Undergraduate Honors Thesis Projects

Maple toxicosis is a deadly condition affecting equines after they have ingested wilted leaves of the genus Acer (i.e., maple species). It is characterized by hemolytic anemia and methemoglobinemia. Although the toxins responsible for causing toxicosis have not been identified, they are thought to be strong oxidants. The objective of this study is to determine the effect of eight compounds (galloyl derivatives) found in Acer spp. on hemolysis and methemoglobin production in bioassays with equine erythrocytes. Seven of the compounds are known constituents of Acer spp. that are commercially available. One of the compounds--acertannin--was isolated and characterized from leaf extracts …

Preformulation Studies For The Preparation Of Amorphous Solid Dispersions, Hemanth Kumar Mamidi

Theses and Dissertations

The major challenges in the formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion (HME) are the selection of an ideal polymeric carrier, optimization of HME processing conditions, and screening of the physical stability of the ASDs. Addressing these challenges using traditional approaches require extensive experimentation and large amounts of active pharmaceutical ingredients (API) which may not be feasible during the initial stages of product development. Therefore, there is a need to develop material-sparing techniques for the successful formulation of ASDs. The objective of the present study was to develop material-sparing techniques that can be used as pre-formulation tool during …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Nmr-Based Characterization Of A Glucan Isolated From Ganoderma Lucidum, Alysia Gonzales

Electronic Theses and Dissertations

Ganoderma lucidum is a polypore fungus commonly known as Lingzhi, Youngji or Reishi mushroom in East Asia. It is frequently marketed as an herbal supplement and often utilized as traditional Chinese medicine. Our research comprises the structural investigation of the principal polysaccharide from this fungus. After proper purification, the fungal glucan was subjected to multiple experiments of NMR spectroscopy, including 1D 1H and 13C, 2D; 1H-1H COSY, 1H-1H TOCSY, 1H-1H NOESY, 1H-13C HSQC, 1H-1H Phase Sensitive-TOCSY, and 1H-13C TOCSY-HSQC NMR spectra. Data has confirmed that this fungal polysaccharide contains residues of glucose (91.31%) as major, galactose (4.99%), and mannose (3.69%) …

Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy

Graduate Theses, Dissertations, and Problem Reports

Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of the plasma cells. MM is a relatively rare cancer that accounts for about 1.8% of all cancers and is the second most common hematologic malignancies, and despite the advancement from untreatable to treatable malignancy, it is yet incurable. Calcium ions (Ca²⁺) play an important role as second messengers in regulating a plethora of physiological and pathological processes, hence cytoplasmic Ca²⁺ is tightly regulated with strict spatial and temporal control to initiate, maintain, and terminate appropriate signaling pathways and phenotypes including cellular proliferation, cell cycle …

The Development Of A Cancer-Targeting Peptide-Drug Conjugate For The Treatment Of Melanoma, Cassandra Dill

Pharmaceutical Sciences (MS) Theses

Cancer is an ongoing global pandemic which has caused a dramatic shift in research priorities. One of the most aggressive and difficult to treat has invariably remained metastatic melanoma. Although encompassing only 4% of overall skin cancer diagnoses, chances for recovery were slim until recent revolutionary development of immunotherapy adding to its regimen spectrum. This is due to its resistance to many standard-of-care treatment methods, along with its relatively high-metastatic potential. Within the past decade, eight new targeted and immune checkpoint inhibitors have gained FDA approval. The median life survival has increased significantly from 9 months to over 2 years …

Health Outcomes And Utilization Associated With Renal Diseases In Patients With Cancer In The United States, Mitisha Dedhia

Theses and Dissertations

Background: Adverse events and impairments associated with cancer and its treatments causes worse outcomes. Increased incidence of renal diseases among cancer patients is of particular concern. Objective: To determine the risk factors for renal disease in cancer patients and compare healthcare costs, utilization and health-related quality of life (HRQoL) of cancer patients with a renal disease and cancer patients without renal diseases. Methods: Medical Expenditure Panel Survey files from 2009 – 2018 for cancer patients was used for this study. Multiple logistic regression, generalized linear model, Poisson regression and multiple linear regression for analyses after adjusting for demographic, socioeconomic and …

Reward-Related Effects Of Amphetamines Administered By Electronic Cigarette, Lucas Wohler

Theses and Dissertations

While e-cigarette vaporizers are primarily used for the delivery of nicotine, they can also be used to administer a wide range of other substances of abuse including stimulants such as d-amphetamine and methamphetamine. Methamphetamine and prescription amphetamines are widely abused throughout the United States and across the world leading us to believe there may be abuse potential with vaping methamphetamine as vaping becomes increasingly popular. In the present study, methamphetamine and amphetamine vapor were assessed using vapor capture methods. The vapor samples were then analyzed using liquid chromatography mass spectroscopy (LC-MS). Three experiments were carried out to examine the abuse …

Viral Factors Influencing Early Infection Events During Ex-Vivo Kshv Infection, Ramina Nabiee

Pharmaceutical Sciences (PhD) Dissertations

The enigma of Kaposi Sarcoma Herpes Virus infection, and its persistence despite a quarter century of research on the virus, has given rise to an immediate need for addressing fundamental questions about basic immunology and virology knowledge regarding this virus. Kaposi Sarcoma Herpes Virus (KSHV), also known as Human Herpesvirus 8 (HHV8), is the etiological agent of Kaposi Sarcoma (KS) and other lymphoproliferative cancers, such as Multicentric Castleman’s Disease (MCD), Primary Effusion Lymphoma (PEL), and a newly discovered rare disease called KSHV Inflammatory Cytokines Syndrome (KICS). Epidemic KS, also known as AIDS-KS, is the most common cancer in untreated HIV …

Sleep And Health-Related Quality Of Life Among Persons With Parkinson’S Disease And Their Caregiverssleep And Health-Related Quality Of Life Among Persons With Parkinson’S Disease And Their Caregivers, Sushmitha Inguva

Electronic Theses and Dissertations

This dissertation aimed at filling gaps in the body of Parkinson’s disease (PD) and sleep literature by synthesizing and appraising current knowledge on the influence of sleep on health-related quality of life (HRQoL) in persons with Parkinson’s (PWP) and their caregivers, conducting a psychometric evaluation of a HRQoL instrument among PWP, and applying a novel method to assess the dyadic relationship between sleep and HRQoL in PWP and their caregivers. First, the systematic literature review results showed that nocturnal and diurnal sleep problems among PWP are strong predictors of their HRQoL. Additionally, studies that focused on caregiver outcomes showed that …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Understanding The Variable Drivers Of Toxicity For The Broad Class Of Carbon Nanotubes And Nanofibers From U.S. Facilities, Kelly E. Fraser

Graduate Theses, Dissertations, and Problem Reports

Pulmonary exposure to carbon nanotubes or nanofibers (CNT/F) is known to induce inflammation, toxicity, or tumorigenesis, and is a concern in the occupational setting. U. S. facility employees are at risk of inhalation exposure of multi-walled carbon nanotubes and carbon nanofibers during primary and secondary manufacturing. To date, only one MWCNT, Mitsui-7 has been classified as possibly carcinogenic to humans (Group 2B), while all other materials were subsequently categorized as unclassifiable (Group 3). This class of material has recently been listed as a high priority to the International Agency for Research on Cancer due to this significant knowledge gap. Furthermore, …