Pharmacy and Pharmaceutical Sciences Commons^™

Development Of Novel, Brain Permeable, Mpges-1 Inhibitors For Inflammatory Conditions, Madison Sluter

Theses and Dissertations (ETD)

Prostaglandin E2 (PGE2) is a potent proinflammatory lipid signaling molecule produced downstream of the cyclooxygenase (COX) cascade. The COX pathway has long been implicated for its role in inflammation, with drugs like aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) non-selectively targeting the upstream COX enzymes to suppress inflammation. However, despite displaying potent anti-inflammatory effects it has been demonstrated that when taken chronically, NSAIDs can cause gastrointestinal bleeding. COX-2 selective inhibitors (COXIBs) were then developed to combat the gastrointestinal bleeding induced by nonselective NSAIDs by specifically inhibiting the COX enzyme most infamous for its role in inflammation. Yet, soon after entering …

Characterization, Antibacterial, Antioxidant, Antidiabetic, And Anti-Inflammatory Activities Of Green Synthesized Silver Nanoparticles Using Phragmanthera Austroarabica A. G. Mill And J. A. Nyberg Extract, Shady Swidan, Dina Khodeer, Sarah Shabayek, Ali Nasr, Roaa Khinkar, Mohammed Aldurdunji, Maryam Ramadan, Jihan Badr

Pharmacy

Introduction: Diabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries.

Methods: The plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity.

Results …

Effects Of Disulfiram On The Metabolome Of Mrsa, Surya Teja Naidu

Theses, Dissertations and Capstones

Disulfiram, known as Antabuse®, is an oral drug for the treatment of alcohol dependence. Previous studies have indicated that disulfiram (DSF) exhibits antibacterial effects, particularly against Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Our study delves into the antibacterial mechanism of DSF in MRSA through High-Pressure Liquid Chromatography (HPLC) metabolomics, investigating the underlying mechanism of DSF effects on thiamine and amino acid metabolism. Thiamine pyrophosphate (TPP) plays a crucial role as a cofactor for critical enzymes such as transketolase, pyruvate dehydrogenase, and 2-oxoglutarate dehydrogenase. These enzymes are integral to the carbohydrate metabolism process within bacterial cells. TPP also contributes …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

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 …

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …

Novel Drugs Approved In 2021-2022, Michael Do, Bona Shin, Elaina Lioudis, Emaleigh Munn

Transformative Medicine

This article provides an abbreviated overview of the newly Federal Drug Administration (FDA)approved novel drugs of 2021-2022 with their respective approved indication(s). The FDA serves as the governing body that regularly evaluates and approves medications that will eventually be introduced to the market for routine use. These medications include both drugs that are the same or related to previously approved products (e.g., Extended indications of priorly approved medications) and novel drugs. By definition, a novel drug is an innovative product which serves to improve quality care in patient populations with unmet or advanced medical needs to overall advance patient care …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam

UROP Posters

Tumors may induce tolerogenesis through signaling dendritic cells to produce tolerogenic molecules, such as indoleamine 2, 3-dioxygenase 1 (IDO1). Tumor-associated immunosuppression is associated with higher mortality in patients. Small interfering RNA (siRNA) has been shown to silence specific target genes in the target cell. The siRNA associated with these genes could support a gene knockdown of these immunosuppressors and reduce mortality. Delivery of these therapeutic nucleic acids is difficult in vivo because siRNA is easily broken down inside the cell and the bloodstream through present nucleases. Use of liposome polymers has been reviewed extensively in literature. YSK12-C4, a lipid nanoparticle …

Modulating The Tumor Microenvironment To Improve Immunotherapy Treatments, Lleayem Nazario-Johnson, David Rowley

Senior Honors Projects

Advances in immunotherapy are revolutionizing the treatments of certain cancers, especially those in the blood. However, wider applications for eradicating solid tumors have been slow to emerge. A likely reason is the presence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment that secrete immunosuppressive molecules which attenuate the attack of immune cells. We hypothesize that small molecule Wnt/Beta- Catenin inhibitors can be used to modulate the immunosuppressive actions of MDSCs and increase the effectiveness of immunotherapy treatments, such as with chimeric antigen receptor (CAR) T-cells. The Wnt/Beta-Catenin Pathway has been shown to be a crucial driving force behind the …

Can 3d Printers Create Viable Personalized Therapy In The Treatment Of Diabetes?, Lyla White

Holster Scholar Projects

This study aimed to use 3D printing techniques to create a drug tablet containing two commonly used active ingredients (metformin and glyburide) for treating diabetes in a single pill. The hypothesis was that both drugs can be given in doses not available commercially and that these pills will have appropriate hardness, and extended-release dissolution. I was able to create 48 tablets that contained evenly dispersed active ingredient powder and met the weight requirements with consistency between tablets. Unfortunately, we had to substitute the usual bulk excipient for another because it was incompatible with the metformin and the replacement (mannitol) may …

Decreasing Unintentional Pregnancies For Tennesseans, Paula M. Todd

Electronic Theses and Dissertations

In 2018, 49% of all pregnancies in the United States were unintended, with women with a lower- income status being five times more likely to experience an unplanned pregnancy. Tennessee has a high rate of unintended pregnancies, particularly among the uninsured, low-income, and rural teen populations; some 22% of these unintended pregnancies end in abortion. Oral or transdermal contraceptives that are affordable and accessible for women of childbearing age can reduce unintentional pregnancies. The addressed gap in clinical practice was that contraceptives are not currently available over the counter in Tennessee pharmacies without a prescription, which necessitates a costly medical …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Opioid And Naloxone Training In A Rural School District, Allyson C. Waldron

UNLV Theses, Dissertations, Professional Papers, and Capstones

The opioid epidemic is a national health emergency in the United States, with over 128 people dying each day due to an opioid overdose. It is estimated that 4.3 million people over the age of 12 use opioids without a medical need, and 1.3 million youth ages 12-17 use opioids inappropriately. Drug overdose deaths have become the leading cause of accidental death in the United States, prompting the U.S. Surgeon General and the World Health Organization to advise that more Americans have access to naloxone and understand how to use this life-saving drug correctly. Naloxone is an opioid antagonist, used …

Anti‑Estrogenic And Anti‑Aromatase Activities Of Citrus Peels Major Compounds In Breast Cancer, Maha Salama, Dina Mahmoud Elkersh, Shahira M. Ezzat, Yasmeen Attiaa, Engy A. Mahrous, Mohey Elmazar

Pharmacy

Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling …

Drug Delivery Systems: Exploring Rheological Properties And Therapeutic Effect Of 5-Fu Chitosan Gel For Topical Wound Healing, Samuel Tetteh-Quarshie

Theses, Dissertations and Capstones

Diabetic skin wound is a common complication of diabetes that occurs in about 15% of diabetic patients and often requires prolonged hospitalization for its management and treatment. Natural polymers are used for wound dressing due to their biological adhesiveness, non-toxicity, and biodegradable nature. 5-Fluorouracil (FU) has been shown to alter adipokine expression which is implicated in cutaneous wound repair. Thus, our overall objective was to investigate the utility of chitosan (CS) gel for topical delivery of 5-FU to treat diabetic wounds. We prepared chitosan gel (2% w/w) in serial dilutions of 5-FU (25μg/mL, 2.5μg/mL, 0.25μg/mL, and 0.025μg/mL) and evaluated their …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations and Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Veru-111 As An Oral Tubulin Inhibitor Suppressing Triple-Negative Breast Cancer And Evaluation Of Novel Tubulin Inhibitors For Cancer Therapy, Shanshan Deng

Theses and Dissertations (ETD)

Triple negative breast cancer (TNBC) has aggressive clinical features strongly associated with poorer overall prognosis and higher mortality rates relative to other molecular subtypes. FDA-approved drugs, such as paclitaxel, are effective in treating TNBC. Yet, treatment failure is commonly observed due to the development of acquired chemoresistance, which remains a clinical challenge for TNBC therapy.

Vitamin D Levels Affect Survival In A Bcr-Abl Acute Lymphoblastic Leukemia Mouse Model But Do Not Cause Vitamin-Drug Interactions, Kavya Annu

Theses and Dissertations (ETD)

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of vitamin D (VD3) status on systemic exposure and efficacy of chemotherapeutic agents that are CYP3A substrates. We employed VD3 sufficient and deficient mice to perform pharmacokinetics (PK) and anti-leukemic efficacy studies.

First, using hCYP3A4 transgenic mouse model we evaluated the intestinal, hepatic and renal expression …

Cyclosporine Shows Benefit As Compared To Methotrexate For Treatment Of Pediatric Atopic Dermatitis Refractory To Topical Medications When Rapidity Of Clinical Response Is Of Key Importance To The Patient, Connor R. Buechler, Steven Daveluy Md

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. European Journal of Pediatrics. 2012;172(3):351-356. https://doi.org10.1007/s00431-012-1893-3 for a pediatric patient with severe atopic dermatitis.

Pharmacogenomics Cascade Testing (Phact): A Novel Approach For Preemptive Pharmacogenomics Testing To Optimize Medication Therapy, Don Roosan, Angela Hwang, Moom Roosan

Pharmacy Faculty Articles and Research

The implementation of pharmacogenomics (PGx) has come a long way since the dawn of utilizing pharmacogenomic data in clinical patient care. However, the potential benefits of sharing PGx results have yet to be explored. In this paper, we explore the willingness of patients to share PGx results, as well as the inclusion of family medication history in identifying potential family members for pharmacogenomics cascade testing (PhaCT). The genetic similarities in families allow for identifying potential gene variants prior to official preemptive testing. Once a candidate patient is determined, PhaCT can be initiated. PhaCT recognizes that further cascade testing throughout a …

Crnas And Sugammadex Use: A Qualitative Analysis, Natalia Izquierdo Bsn, Rn, Emily Mancewicz Bsn, Rn

Grace Peterson Nursing Research Colloquium

Background: The availability of Sugammadex has increased options for Certified Registered Nurse Anesthetists’ (CRNAs) and their choice of neuromuscular reversal agents, however administration is impacted by a variety of provider and institutional factors.

Objectives: The purpose of this study was to examine and describe the personal and institutional factors impacting the use of Sugammadex in Illinois by CRNAs.

Method: A qualitative study design using an open-ended survey yielded 209 responses. The three main themes that emerged were 1) Why CRNAs choose to use or avoid Sugammadex 2) How CRNAs dose Sugammadex and 3) Practice variations existing within the clinical setting. …

Cytokine Storm In Covid-19: An Overview, Mechanism, Treatment Strategies, And Stem Cell Therapy Perspective, Nuriza Ulul Azmi, Meidi Utami Puteri, Donny Lukmanto

Pharmaceutical Sciences and Research

Coronavirus disease 2019 (COVID-19) is the disease caused by the highly transmittable novel coronavirus (SARS-CoV-2) infections. The disease was found at the end of December 2019, in Wuhan, China, and quickly spread worldwide with a higher mortality rate compared to the previous coronavirus disease. Cytokine plays an important role in the inflammatory response against coronavirus infection. However, in severely ill patients with COVID-19, an excessive amount of cytokine serum level (cytokine storm) has been associated with the aggravation of coronavirus disease leading to acute respiratory distress syndrome (ARDS). Thus, the management of the cytokine storm could be the key to …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

The Development Of Novel Apurinic/Aprymidinic Endonuclease/Redox-Factor 1 Inhibitors For The Treatment Of Human Melanoma, Bella Sharifi

Pharmaceutical Sciences (MS) Theses

Apurinic/apyrimidinic DNA repair endonuclease-1 (APE1), first recognized as an important DNA excision repair enzyme, is also known as Redox Factor-1 (Ref-1) involved in the activation of many nuclear transcription factors in both redox-dependent and independent manner. It has been well-documented that the overexpression of APE/Ref-1 contributes to the development of chemo-resistance and is associated with tumor progression in many human malignancies [1].

Our previous study in melanoma demonstrated that the development of novel inhibitors targeting the redox regulation domain of APE/Ref-1 is a promising strategy for melanoma treatment. To date, limited successes have been reported in developing novel …

Genetic Variations In A Cytochrome P450 Enzyme And The Effects On Clopidogrel Bioactivation And Metabolism, Maryanne Ventura, Lauren Desko, Kimberly Gathers, Ashley Overy, David Kisor

Pharmacy and Wellness Review

Clopidogrel, the top prescribed antiplatelet medication for individuals who have experienced a myocardial infarction or cerebral vascular accident or who have peripheral arterial disease, is administered orally as a prodrug. It relies on hepatic metabolism through cytochrome P450 enzymes for conversion to its active form. Current research shows that allelic variation m the gene coding for CYP2C19 is the main factor contributing to the variability of response associated with clopidogrel treatment. Through the promotion of genetic testing for variability in the CYP2C19 gene and competently interpreting test results, pharmacists have the opportunity to use these findings to significantly impact clopidogrel …

Pharmacogenomics: Your Medical Identity, Hilary Stewart, Lisa Berni, Tyler Bulcher, Joel Rittenhouse, Ryan W. Naseman, Jon E. Sprague

Pharmacy and Wellness Review

Pharmacogenomics, the fusion of pharmacology and genomics, shows strong potential to solve many of today's dosing problems. lnter-patient dosing requirements, mainly due to genetic variability between patients, represent significant challenges for prescribers. Certain receptors, drug-targeted proteins, drug-transport mechanisms and drug-metabolizing enzymes are genetically established. Hence, any defect, absence or abnormality in the gene could alter how an affected individual will respond to a given drug. Due to advancements in technology, health care professionals who utilize pharmacogenomics may assess a patient's genetic profile and determine a predicted response to specific medications. This may result in potentially optimal dosing at the onset …

Metformin And Cancer: Pharmacoepidemiology Considerations, Sarah Kradel, Christina Spinaris, Victoria Pennington, Adam Trimble, Lara Long, Natalie Dipietro

Pharmacy and Wellness Review

No abstract provided.