Pharmacy and Pharmaceutical Sciences Commons^™

Implementing In-House Compounding Of Nimodipine Oral Syringes For Aneurysmal Subarachnoid Hemorrhage Patients., Keaton S Smetana, Kerri J Wilcox, Aaron M Cook

Neuroscience Articles

No abstract provided.

The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl

Senior Honors Theses

Bacterial infections in the United States are becoming increasingly resistant to existing antibiotic treatments. Due to projected increases in resistance and the recent decrease in novel antibacterials, experts have determined that the United States is in the “post-antibiotic era.” The scientific community has failed to resolve resistance despite the continual discovery of new antibiotic compounds. In the past decade, a novel form of cell death called ferroptosis has been implicated in antibiotic treatment by employing the use of nanotechnology. This literature review will describe the problem of bacterial resistance and demonstrate how current research is pioneering a new age of …

Dietary Analysis For Hashimoto’S Thyroiditis: An Integrative Review, Evan Thompson, Alison Hultquist

Master of Science in Nursing Final Projects

Abstract

Hashimoto’s Thyroiditis (HT) is the leading cause of primary hypothyroidism in the United States. In HT, there is an infiltration by lymphocytes which leads to the production of autoantibodies against the thyroid gland. Throughout this integrative review, the aim was to evaluate the effectiveness of micronutrient supplementation and dietary management as adjunct treatments in HT. The purpose was to assist primary care providers in the development of a more holistic plan of care. Literature published within the past seven years was gathered and reviewed from PubMed, CINAHL, and Cochrane Library. Findings indicate that many patients with HT may benefit …

Repurposing Egfr Inhibitors For Oral Cancer Pain And Opioid Tolerance, Maria Daniela Santi, Morgan Zhang, Naijiang Liu, Chi T Viet, Tongxin Xie, Dane D Jensen, Moran Amit, Huilin Pan, Yi Ye

Faculty, Staff and Student Publications

Oral cancer pain remains a significant public health concern. Despite the development of improved treatments, pain continues to be a debilitating clinical feature of the disease, leading to reduced oral mobility and diminished quality of life. Opioids are the gold standard treatment for moderate-to-severe oral cancer pain; however, chronic opioid administration leads to hyperalgesia, tolerance, and dependence. The aim of this review is to present accumulating evidence that epidermal growth factor receptor (EGFR) signaling, often dysregulated in cancer, is also an emerging signaling pathway critically involved in pain and opioid tolerance. We presented preclinical and clinical data to demonstrate how …

Liposome Synthesis And Evaluation In The Hek-293 Cell Line, Christine Skibinski

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Liposomes were synthesized using the thin film method. A lyophilized power of egg-derived phosphatidylcholine, stearylamine, and cholesterol were added to ethanol and dried under argon to form a lipid cake. The lipid cake was rehydrated with dPBS and sonicated at 60°C forming a heterogenous batch of liposomes. Our results revealed the average size of the liposomes, determined by Dynamic Light Scattering, was approximately 223.1nm, while demonstrating a weakly positive zeta-potential of 1.9± 8.07mv. Next, we tested the antitumor action of the liposomes in the HEK-293 cell line via an MTT assay. We observed that the liposomes were able to inhibit …

Tolfenamic Acid Derivatives: A New Class Of Transcriptional Modulators With Potential Therapeutic Applications For Alzheimer’S Disease And Related Disorders, Juanetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ourarhni, Nasser H. Zawia

Pharmacy Faculty Articles and Research

The field of Alzheimer’s disease (AD) has witnessed recent breakthroughs in the development of disease-modifying biologics and diagnostic markers. While immunotherapeutic interventions have provided much-awaited solutions, nucleic acid-based tools represent other avenues of intervention; however, these approaches are costly and invasive, and they have serious side effects. Previously, we have shown in AD animal models that tolfenamic acid (TA) can lower the expression of AD-related genes and their products and subsequently reduce pathological burden and improve cognition. Using TA as a scaffold and the zinc finger domain of SP1 as a pharmacophore, we developed safer and more potent brain-penetrating analogs …

Therapeutic Effects Of Combining Curcumin And Swimming In Osteoarthritis Using A Rat Model, Mona M Saber, Manal Moustafa Mahmoud, Hesham M Amin, Reham M Essam

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a common debilitating degenerative disease of the elderly. We aimed to study the therapeutic effects of combining curcumin and swimming in monosodium iodoacetate (MIA)-induced OA in a rat model. The rats were divided into 5 groups (n = 9). Group 1 received saline and served as a control group. Groups 2-5 were injected intra-articularly in the right knee with 100 μL MIA. One week later, groups 3 and 5 were started on daily swimming sessions that gradually increased to 20-mins per session, and for groups 4 and 5, oral curcumin was administered at a dose of 200 …

Oral Dosages Of The Nsaid Aspirin Decreased The Growth Rate Of Species Found In The Human Gut Microbiome Including Akkermansia Muciniphila, Bacteroides Fragilis, Clostridium Sordellii, And Clostridium Difficile, Wyatt H. Greenbaum, Garrett J. Greenbaum, Anna Spiezio

PANDION: The Osprey Journal of Research and Ideas

Over past few decades, new insight has been revealed in the scientific community about the importance of the human gut microbiome relating to general health. It is known that imbalances in the species that reside in the human gut can cause organism-wide problems in humans. When prescribing or injecting oral medications, the thought of the downstream effects on the gut microbiome are not always considered. By exposing known healthy members of the gut; Akkermansia muciniphila, Bacteroides fragilis, Clostridium sordellii, and Clostridium difficile to the Aspirin, this study attempted to provide insight into the effects of the drug on bacterial growth. …

Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal

The Undergraduate Research Journal

Diadema savignyi spine extract in an experimental setup using L929 cell line in vitro. The cell metabolic activity of L929 cells is tested through an MTT assay. The sea urchin spine extract is applied to the cells in two concentrations: 100 μg/ml (136% viability) and 200 μg/ml (95% viability). The bioactive components of the sea urchin spine are identified via GC-MS, and the antioxidant and anti-inflammatory activities are evaluated using catalase assay (CAT), glutathione (GSH), and nitric oxide (NO) tests. Results show that the GC-MS identified bioactive components including the anti-inflammatory and anti-irritant bisabolol oxide and the pro-inflammatory oleic acid. …

Equine In Vivo Metabolite Profiling Of The Selective Androgen Receptor Modulator Lgd-3303 For Doping Control, Malin Nilsson Broberg, Heather Knych, Ulf Bondesson, Curt Pettersson, Börje Tidstedt, Scott Stanley, Mario Thevis, Mikael Hedeland

UK CARES Faculty Publications

LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg⋅kg 1 LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizing ultra-high performance liquid …

Sirna Drug Delivery Across The Blood–Brain Barrier In Alzheimer's Disease, Muhammad Imran Sajid, Fahad Sultan Sheikh, Faiza Anis, Nourina Nasim, Rachita K. Sumbria, Surya M. Nauli, Rakesh K. Tiwari

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a few FDA-approved drugs that provide modest symptomatic benefits and only two FDA-approved disease-modifying treatments for AD. The advancements in understanding the causative genes and non-coding sequences at the molecular level of the pathophysiology of AD have resulted in several exciting research papers that employed small interfering RNA (siRNA)-based therapy. Although siRNA is being sought by academia and biopharma industries, several challenges still need to be addressed. We comprehensively report the latest advances in AD pathophysiology, druggable targets, ongoing clinical trials, and the siRNA-based approaches across the blood–brain barrier for addressing …

Application Of Natural Polysaccharides And Their Novel Dosage Forms In Gynecological Cancers: Therapeutic Implications From The Diversity Potential Of Natural Compounds, Yi Li, Chuanlong Zhang, Lu Feng, Qian Shen, Fudong Liu, Xiaochen Jiang, Bo Pang

Faculty, Staff and Student Publications

Cancer is one of the most lethal diseases. Globally, the number of cancers is nearly 10 million per year. Gynecological cancers (for instance, ovarian, cervical, and endometrial), relying on hidden diseases, misdiagnoses, and high recurrence rates, have seriously affected women's health. Traditional chemotherapy, hormone therapy, targeted therapy, and immunotherapy effectively improve the prognosis of gynecological cancer patients. However, with the emergence of adverse reactions and drug resistance, leading to the occurrence of complications and poor compliance of patients, we have to focus on the new treatment direction of gynecological cancers. Because of the potential effects of natural drugs in regulating …

Studies On The Leukocyte-Associated Ig-Like Inhibitory Receptor-1 Signaling Pathway In T Lymphocytes, Chidi Zacheaus

Theses and Dissertations (ETD)

Inflammation is a natural process in which the immune system concertedly responds to pathogens and abnormal cell growth to protect the host. For an efficient/effective immune response that circumvents tissue atrophy, a delicate balance between stimulatory and inhibitory mechanisms is essential for the proper functioning of the immune system. Immuno-receptor Tyrosine-based Inhibitory Motif (ITIM)-bearing receptors in immune cells, including T lymphocytes, play a major role in preventing autoimmune responses. Leukocyte-associated Ig-like Inhibitory Receptor 1 (LAIR-1) is one of ITIM-bearing receptors. The mechanism by which LAIR-1 attenuates T-cell response has yet to be completely understood. In this study, I investigated a …

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 …

Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …

Development And Validation Of An Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry Method To Investigate The Plasma Pharmacokinetics Of A KCa2.2/KCa2.3 Positive Allosteric Modulator In Mice, Mohammad Asikur Rahman, Devaraj Venkatapura Chandrashekar, Young-Woo Nam, Basir Syed, David Salehi, Hamidreza Montazeri Aliabadi, Miao Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Rationale

There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of K_Ca2.2/K_Ca2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently developed positive allosteric modulator of K_Ca2.2/K_Ca2.3 channels (compound 2q) in mouse plasma.

Methods

Mouse plasma samples (10 μL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar …

Magnetic Resonance Image-Based Estimates Of Hepatic Blood Flow In Children With And Without Obesity; Implications For Physiologically-Based Pharmacokinetic Models, Yoon Cho, Sherwin S. Chan, Chance S. Friesen, Valentina Shakhnovich

Research Days

Background: Physiologically based pharmacokinetic models for simulating drug pharmacokinetics are useful to guide drug dosing for pediatric patients. Hepatic blood flow could be a useful variable to use in these models.

Objectives/Goal: In this study, we explored 2-D phase contrast non-invasive magnetic resonance imaging (MRI) to measure hepatic blood flow in children with and without obesity.

Methods/Design: In this IRB-approved study, we imaged pediatric patients with abdominal MRI with 2D phase contrast imaging of the descending aorta (AO) at the diaphragm, the inferior vena cava (IVC) at the right atrium, and inferior to hepatic drainage above the renal vein confluence …

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang

Pharmaceutical Sciences Faculty Publications

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced …

One Immune System Plays Many Parts: The Dynamic Role Of The Immune System In Chronic Pain And Opioid Pharmacology, Sanam Mustafa, Juliana E Bajic, Benjamin Barry, Samuel Evans, Kariel R Siemens, Mark R Hutchinson, Peter M Grace

Faculty, Staff and Student Publications

The transition from acute to chronic pain is an ongoing major problem for individuals, society and healthcare systems around the world. It is clear chronic pain is a complex multidimensional biological challenge plagued with difficulties in pain management, specifically opioid use. In recent years the role of the immune system in chronic pain and opioid pharmacology has come to the forefront. As a highly dynamic and versatile network of cells, tissues and organs, the immune system is perfectly positioned at the microscale level to alter nociception and drive structural adaptations that underpin chronic pain and opioid use. In this review, …

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …

Well-Being Content Inclusion In Pharmacy Education Across The United States And Canada, Elizabeth Buckley, Simi Gunaseelan, Benjamin D Aronson, Heidi N Anksorus, Victoria Belousova, Tram B Cat, Kristine M Cline, Stacey D Curtis, Christina E Deremer, David Fuentes, Mckenzie S Grinalds, Seena L Haines, Hannah E Johnson, Karen Kopacek, Jessica M Louie, Nkem P Nonyel, Natasha Petry, Shawn Riser Taylor, Suzanne C Harris, Cheryl A Sadowski, Anandi V Law

Faculty, Staff and Student Publications

Objective. To describe the landscape of well-being content inclusion across schools and colleges of pharmacy in the United States and Canada through identification of content implementation, incorporation, and assessment.

Methods. A cross-sectional survey was distributed to all accredited schools and colleges of pharmacy in the United States (n=143) and Canada (n=10). Survey questions included curricular and cocurricular timing, frequency, assessment strategies, and support for well-being initiatives, using a framework of eight dimensions (pillars) of wellness to categorize content.

Results. Descriptive data analyses were applied to 99 completed surveys (65%), 89 (62%) in the United States and 10 (100%) in Canada. …

Naltrexone-Bupropion Combinations Do Not Affect Cocaine Self-Administration In Humans, Sean D Regnier, William W Stoops, Joshua A Lile, Joseph L Alcorn, B Levi Bolin, Anna R Reynolds, Lon R Hays, Abner O Rayapati, Craig R Rush

Faculty, Staff and Student Publications

The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder. Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, 80 …

Recent Advances In Psychopharmacology: From Bench To Bedside Novel Trends In Schizophrenia, Asim A Shah, Syed Z Iqbal

Faculty, Staff and Students Publications

Research in the field of psychopharmacology is ongoing to develop novel compounds which can revolutionize the treatment of psychiatric disorders. The concept of bench-to-bedside is a tedious process, transforming the initial research performed in the laboratories into novel treatment options. Schizophrenia (SCZ) is a chronic psychiatric illness with significant morbidity and mortality. SCZ not only presents with psychotic symptoms including hallucinations and delusions but also with negative and cognitive symptoms. The negative symptoms include the diminished ability to express emotions, loss of pleasure, and motivation with minimal social interactions. Conventional antipsychotics primarily target positive symptoms with minimal therapeutic benefits for …

The Science Of Oral Carbapenems, Landon Olsen, Daniel J. Yang, Aiyi Chen, Thahn-Liem Vu, H. Stephen Lee

Annual Research Symposium

No abstract provided.

Sulopenem For The Treatment Of Complicated And Uncomplicated Bacterial Urinary Tract Infection (Uti), Aiyi Chen, Thanh-Liem Vu, Daniel J. Yang, Landon Olsen

Annual Research Symposium

No abstract provided.

Evaluation Of Antifungal Efficacy In The Treatment Of Candida Auris Bloodstream Infections, Monique Busacay, Kaylee Putney, Rebecca Jayakumar

Annual Research Symposium

No abstract provided.

Adverse Infusion-Related Event Severity In Oncology Patients Receiving Chemotherapy Agents Vs. Immunotherapy Agents, Tayler Hutto

Annual Research Symposium

In recent years, immunotherapy investigational drugs in cancer research has been underway in treating multiple forms of cancer due to a lower side effect profile and decreased severe infusion-reaction risk compared to conventional chemotherapy agents. The purpose of this study was to determine the infusion reaction severity among patients receiving either chemotherapy treatment or immunotherapy agents based on the CTCAE (Common Terminology Criteria for Adverse Events) scale to improve patient care outcomes.

In this intent-to-treat, retrospective observational study, a survey of patients throughout 10 Intermountain Healthcare infusion clinics was conducted to obtain documentation on patients who had received chemotherapy and/or …

Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and …

The Roles Of Cyp1a2 And Cyp2d In Pharmacokinetic Profiles Of Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine And Its Metabolites In Mice, Xuan Qin, Cen Xie, John M Hakenjos, Kevin R Mackenzie, Shelton R Boyd, Mercedes Barzi, Karl-Dimiter Bissig, Damian W Young, Feng Li

Faculty, Staff and Students Publications

Duloxetine (DLX) is widely used to treat major depressive disorder. Little is known about the mechanistic basis for DLX-related adverse effects (e.g., liver injury). Human CYP1A2 and CYP2D6 mainly contributes to DLX metabolism, which was proposed to be involved in its adverse effects. Here, we investigated the roles of Cyp1a2 and Cyp2d on DLX pharmacokinetic profile and tissue distribution using a Cyp1a2 knockout (Cyp1a2-KO) mouse model together with a Cyp2d inhibitor (propranolol). Cyp1a2-KO has the few effects on the systematic exposure (area under the plasma concentration-time curve, AUC) and tissue disposition of DLX and its primary metabolites. Propranolol dramatically increased …

Loss-Of-Function KCa2.2 Mutations Abolish Channel Activity, Young-Woo Nam, Mohammad Asikur Rahman, Grace Yang, Razan Orfali, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium channels subtype 2 (K_Ca2.2, also called SK2) are operated exclusively by a Ca²⁺-calmodulin gating mechanism. Heterozygous genetic mutations of K_Ca2.2 channels have been associated with autosomal dominant neurodevelopmental disorders including cerebellar ataxia and tremor in humans and rodents. Taking advantage of these pathogenic mutations, we performed structure-function studies of the rat K_Ca2.2 channel. No measurable current was detected from HEK293 cells heterologously expressing these pathogenic K_Ca2.2 mutants. When co-expressed with the K_Ca2.2_WT channel, mutations of the pore-lining amino acid residues (I360M, Y362C, G363S …