Other Pharmacy and Pharmaceutical Sciences Commons^™

Influences Of Host Cytokine Signaling On Kshv Infection In Tonsil-Derived B Lymphocytes, Nedaa Alomari

Pharmaceutical Sciences (PhD) Dissertations

Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of kaposi sarcoma. It is also associated with the B cell lymphoproliferative disorders, primary effusion lymphoma (PEL), multicentric Castleman disease (MCD) and KSHV inflammatory cytokine syndrome (KICS). Existing research reveals that KSHV has developed numerous strategies to alter host cytokine signaling activities to facilitate viral persistence and escape host immune surveillance.

Despite three decades of research, there are still many questions in this field awaiting further investigation. This dissertation will investigate host cytokines as factors influencing the establishment of KSHV infection in the human tonsil. We have identified and characterized different cytokines …

Prg4/Cd44/Pp2a Signaling Axis: A Significant Regulator Of Gout Arthritis, Sandy Elsayed

Pharmaceutical Sciences (PhD) Dissertations

Introduction: Gout is a common chronic arthritis caused by monosodium urate (MSU) crystal deposition in joints leading to activation of synovial resident macrophages and downstream production of interleukin-1b (IL-1b). Xanthine oxidase (XO) catalyzes purines into uric acid (UA) and reactive oxygen species (ROS) that activate NLRP3 inflammasome. Protein phosphatase-2A (PP2A) may be involved in regulating inflammatory pathways in macrophages. Proteoglycan 4 (PRG4) and its receptor CD44 and its transducer PP2A signaling axis play a biologically significant role in regulating urate crystal inflammation.

Methods: Monocytes and macrophages were primed with TLR2 agonist and stimulated with MSU crystals. Fingolimod (PP2A …

Anti-Inflammatory And Analgesic Effects Of Highly Selective Microsomal Prostaglandin E2 Synthase-1 (Mpges-1) Inhibitors, Madeline Stewart

Theses and Dissertations--Pharmacy

Lipid messenger prostaglandin E2 (PGE₂) is a prostanoid that plays a key role in the generation of the inflammatory response. Currently available non-steroid anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX)-1 and/or COX-2, all with significant cardiovascular, cerebrovascular, and gastrointestinal risks that have limited their utilization. Microsomal PGE₂ synthase 1 (mPGES-1), an inducible enzyme responsible for overproduction of PGE₂, may be a more promising target for a new type of anti-inflammatory drug without the adverse effects associated with the COX-1/2 inhibition. There have been extensive efforts to design and discover inhibitors targeting mPGES-1. Unfortunately, within the previously …

Investigating The Use Of Mpges-1 Inhibitors For The Treatment Of Abdominal Aortic Aneurysms, Lauren M. Weaver

Theses and Dissertations--Pharmacy

The cardiovascular field is still searching for a treatment for abdominal aortic aneurysms (AAA). This inflammatory disease is a deadly, permanent ballooning of the aortic artery. It often goes undiagnosed until a late stage where associated rupture has a high mortality rate. Surgery is the only option available to patients, but it is risky. There are currently no FDA-approved pharmacological treatments for AAA available. Historically, drugs that have been examined in interventional clinical trials for treatment of AAA were repurposed therapeutics. Novel treatments have been unable to reach the clinic, stalling out in pre-clinical studies. Exceedingly few murine studies have …

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 …

Genetic And Pharmacogenetics Associations Of Cancer Disparities In Appalachia, Nan Lin

Theses and Dissertations--Pharmacy

Individuals residing in Appalachian regions have significant health disparities, including higher cancer incidence and mortality rates. Previous studies have addressed the impact of socioeconomic status and environmental risk factors on Appalachia cancer disparities, while few studies have evaluated genetic risk factors.

Germline whole exome sequencing samples from 7,078 individuals with cancer (759 Appalachians) were evaluated. Demographics and relatedness were assessed using KING. Ethnicity was verified by principal component analysis using TRACE, which included 6,034 individuals (85%) of European genetic ancestry. After QC filtering, 5,980 individuals were analyzed. To assess the overall predisposition of hereditary disease, gene level frequency of likely …

Bioinformatic Analysis Of Proteomic And Genomic Data From Nsclc Tumors On Prognostic And Predictive Factors Of Immunotherapy Treatment, Mark Wuenschel

Theses and Dissertations--Pharmacy

Recent lung cancer research has led to advancements in molecular immunology, resulting in development of small molecule inhibitors, or immune checkpoint inhibitors, that propagate an anti-tumor T cell response. Despite increased overall and progression-free survival with reduced adverse effects compared to traditional chemotherapy, treating advanced stage lung adenocarcinoma patients remains non-curative, and evidence of non-responders or tumor recurrence to immune checkpoint inhibitor therapy is growing. Also, compared to traditional chemotherapy, there is a lower percentage of patients who respond to small molecule inhibitors. In this analysis of proteomic and genomic data from The Cancer Proteome Atlas and Global Data Commons …

Investigation Of Folate-Poly(Glutamic Acid)/Polyethylenimine/Dna Complexes For In Vitro Gene Delivery, Caleb Akers

Theses and Dissertations--Pharmacy

Gene therapy is currently being studied as a treatment for a variety of indications, including cancer, infectious disease, and cardiovascular diseases, among others. While many of the early treatments in the field involved the use of viral delivery methods, various safety, ethical, and financial concerns limit the potential uses of this methodology. As such, more recent research has focused on developing non-viral delivery platforms to alleviate some of the issues inherent in viral delivery. Recently, the release of the COVID-19 vaccines from Pfizer and Moderna represents a promising use of non-viral delivery as both utilized a lipid-based delivery vector.

Despite …

An Epidemiological And Pharmacokinetic-Pharmacodynamic Investigation Into The Impact Of Carbapenem-Resistant Enterobacterales, Justin Clark

Theses and Dissertations--Pharmacy

Background: According to the 2019 CDC Antibiotic Resistance Threats Report, more than 2.8 million antibiotic-resistant infections occur in the United States each year, leading to more than 35,000 deaths. Among the most urgent threats identified by the CDC are carbapenem-resistant Enterobacterales (CRE). Despite efforts to control the spread of these organisms, the number of estimated cases between 2012 and 2017 remained stable. In 2017, an estimated 13,100 hospitalized cases of CRE led to approximately 1,100 deaths and $130 million attributable healthcare costs. This dissertation seeks to address this issue from both a pharmacokinetic/pharmacodynamic and epidemiological perspective.

Methods: We evaluated the …

Studies Of Polypharmacy And Medication Therapy Management In Population-Based Cohorts, Ximena A. Oyarzun Gonzalez

Theses and Dissertations--Epidemiology and Biostatistics

According to the United States Census Bureau, 16.8% of the population was 65 years and older in 2021, and it is expected that by 2060 that number will increase to about 30% (about 114 million people). Aging is associated with physiological changes in all systems of the body. These changes impact the pharmacodynamics and pharmacokinetic characteristics of drugs. Furthermore, older adults usually have several chronic conditions, which increases their exposure to medications. Increased vulnerability combined with increasing exposure puts elderly people at higher risk for drug interactions and adverse events.

Charlesworth et al. (2014) found that the prevalence of polypharmacy, …

Elafibranor Modulates Ileal Macrophage Polarization To Restore Intestinal Integrity In Nash: Potential Crosstalk Between Ileal Il-10/Stat3 And Hepatic Tlr4/Nf-Κb Axes, Andrew Hakeem, Mohamed M. Kamal, Rasha A. Radwan, Basma A. Abdelrahman, Olfat A. Hammam, Mohey M. Elmazar, Aiman S. El-Khatib, Yasmeen M. Attia

Pharmacy

Experimental and clinical evidence implicate disrupted gut barrier integrity in provoking innate immune responses, specifically macrophages, towards the progression of non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptors (PPARs), a subset of the nuclear receptor superfamily, act to fine-tune several metabolic and inflammatory processes implicated in NASH. As such, the current study was carried out to decipher the potential role of dual PPAR α/δ activation using elafibranor (ELA) on ileal macrophage polarization (MP) and its likely impact on the liver in a NASH setting. To achieve this aim, an in vitro NASH model using fat-laden HepG2 cells was first used to validate …

Gender Differences In Administration Of Tpa In Treatment Of Ischemic Stroke, Christina Annerino

CURE Proceedings

As medicine and pharmacology advance through the years, new life-saving treatments are studied or discovered every day, and a medical emergency is no longer a death sentence. Even with conditions as serious as ischemic stroke, there is hope for survival and rehabilitation with the ‘clot-busting’ drug, tissue plasminogen activator, colloquially known as ‘tPA’. tPA is a thrombolytic agent, a substance that acts on fibrin in clots to dissolve them so they can no longer cause ischemia in blood vessels that results in a stroke. (Vega, 2022). tPA is an extremely effective treatment for ischemic stroke, demonstrated in 2013 by a …

Identifying Unexpected Inflammation Resulting From Drug-Drug Interactions, Keegan Jolly

All Master's Theses

Adverse drug events result in nearly 1.3 million emergency room visits per year in the United States of America. As much as 30% of these adverse events are a result of drug-drug interactions (DDI’s). There is a gap in knowledge concerning these DDI outcomes especially when it comes to inflammation. Inflammation is linked to a variety of chronic health conditions and non-infectious diseases such as cancer. Purpose: The goal of this study was to examine how many active drug ingredients from FDA’s Adverse Event Reporting System (FAERS), when combined (in groups of two or more), elicit an inflammatory response …

Right Treatment Wrong Time: Immunotherapy Administration Post-Radiotherapy Decreases Tumor Burden In A Preclinical Model Of Brain Metastasis, Kathryn Elizabeth Blethen

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in-depth literature review of methods to modulate the blood-brain and blood-tumor barriers to increase drug delivery and efficacy in brain metastases, (b) evaluated the effects of whole-brain radiation therapy on the blood-brain barrier in immunocompetent and immunocompromised mouse models and proposed a mechanism by which the immune response to radiation disrupts the blood-brain barrier, and (c) developed a syngeneic lung cancer brain metastasis model to determine the impact of coordinated immunotherapy administration with radiotherapy. The blood-brain barrier is an impediment to drug delivery to the brain. The inherent leakiness of the blood-tumor barrier does not …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …

Formulation Of Pectin-Based Double Layer-Coated Tablets Containing Dexamethasone And Probiotics For Inflammatory Bowel Disease, Erny Sagita, Ronaldo Ongki Winata, Raditya Iswandana

Pharmaceutical Sciences and Research

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition in the colon that includes ulcerative colitis and Crohn’s disease. Dexamethasone is a steroid anti-inflammatory drug that can be used in IBD therapy. This study aims to obtain an optimum formulation of a dexamethasone drug delivery system for IBD treatment and to investigate its release profile based on an in vitro dissolution test. Dexamethasone was formulated as a double-coated tablet in combination with a probiotic L. acidophilus and B. longum mixture (1:1). The core tablets were produced using the wet granulation method, after which they were coated with pectin 4% b/v …

Phytochemical Analysis, Antioxidant And Cytotoxic Activity Of Lannea Egregia Engl. & K. Krause Stem Bark Extracts, Seide M. Akoro, Mutiat A. Omotayo, Oyinlade C. Ogundare, Stemon A. Akpovwovwo, Gbemileke P. Bello

Pharmaceutical Sciences and Research

This study investigates the phytochemical contents, antioxidants and cytotoxic activities of Lannea egregia Engl. & K. Krause stem bark extracts. Secondary metabolites were extracted using n-hexane, ethyl acetate, and ethanol by successive maceration. The concentrated extracts were subjected to preliminary phytochemical screening using standard procedures. The crude flavonoid was obtained from the plant material using Harborne’s method and then profiled using high-performance liquid chromatography (HPLC). The antioxidant activities of the plant extract were assessed using reducing power assay and DPPH scavenging activity, while the cytotoxic activity was determined using the brine shrimp lethality assay. The crude extract of n-hexane or …

The Potential Application Of Clitoria Ternatea For Cancer Treatment, Anita Purnamayanti, Krisyanti Budipramana, Marisca Evalina Gondokesumo

Pharmaceutical Sciences and Research

The Clitoria ternatea flower, known as bunga telang in Indonesia, is commonly mixed with food and beverages to provide a natural blue colour. Aside from its popular culinary use, it is a traditional medicine in Indonesia for diseases in the eyes, urinary tract and skin, as well as functioning as an anti-toxin. Furthermore, recent advances in science and technology have revealed that the C. ternatea flower contains a high level of polyphenol compounds that possess anticancer activity, including saponins, tannins, steroids, triterpenoids, kaempferol, and quercetin. This review aims to identify and analyse recent articles regarding the phytochemical activities of C. …

Characterisation And Antibacterial Activity Of Green Tea Extract-Enriched Solid Goat’S Milk Soap, Uswatun Chasanah, Dian Ermawati, Dwi Putri Utami, Angela Nora Hayati

Pharmaceutical Sciences and Research

Solid goat’s milk soap is organic and beneficial for the health and appearance of the skin. One of the components in green tea known to display antibacterial activities is epigallocatechin gallate (ECGC). In this study, the effects of solid goat’s milk soap containing 1%, 2%, and 4% green tea extract on the growth of Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis were examined. The soap was characterized for its organoleptic, pH, free fatty acid, alkalinity, water content, foam stability, and hardness. In addition, an in vitro antimicrobial test was performed utilising the well-diffusion method. The findings revealed that all the …