Medicine and Health Sciences Commons^™

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapies In Cystic Fibrosis: A Retrospective Evaluation Of A Nationwide Specialty Pharmacy Database, Zumi Mehta

Electronic Theses and Dissertations

Background: Cystic fibrosis (CF) is a progressive, genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with CF experience excessive mucus build up and infections leading to complications in the pancreas, lungs, and other organs. There has been a paradigm shift in the treatment of CF with the introduction of CFTR modulator therapies and given their high acquisition cost, assessing their economic burden along with the adherence rate of patients is imperative. Objective: (i) To assess the utilization of CFTR modulator therapies in a specialty pharmacy CF patient population and (ii) to calculate …

Screening For Iron-Deficiency Anemia In The Pediatric Population (Ages 1-17) In Gonaïves, Haiti, Cara Rose Fratianni

Doctor of Nursing Practice Final Manuscripts

Abstract

Purpose: The purpose of this pilot project is to screen for iron-deficiency anemia in pediatric patients (ages 1-17) in a primary school in Gonaïves, Haiti. Patients with anemia will be treated with oral supplemental iron for a period of four weeks according to WHO guidelines (WHO, 2011). All students will be treated empirically for helminths per WHO guidelines, unless treated elsewhere in the last six months (WHO, 2017). Nutritional status will also be assessed using MUAC according to WHO guidelines (2017).

Background Summary: Malnutrition contributes significantly to the problem of iron-deficiency anemia, with one in four children exhibiting stunting …

Does Long-Term Proton Pump Inhibitor Use Pump Up Your Risk Of Adverse Effects?, Hindu Rao, Jelena Lewis

Pharmacy Faculty Articles and Research

"Many studies have linked proton pump inhibitor (PPI) use to several adverse effects including Clostridium difficile-associated diarrhea, community-acquired pneumonia, bone fractures, and nutritional deficiencies.1 Other reports have linked PPI use with chronic kidney disease, cognitive decline, myocardial infarction (MI), stroke, and even death.1,2,3 Many patients take PPIs chronically and may be concerned about the risk of these side effects. This poses a challenge for healthcare providers as safety data has been primarily based on retrospective and observational studies. Thus, the fears associated with long term PPI therapy can create confusion, result in extended patient visits, and lead to under-prescribing PPIs …

Expansion Of Medication Therapy Management Services To Rural Sites For Patients With An Employer-Sponsored Health Plan, Taylor Thooft Pharmd

Theses and Dissertations

Previous literature supports that pharmaceutical care provider in the ambulatory care setting can improve clinical, economic, and humanistic outcomes for recipients, and when utilized in employer-provided health plans can lead to reduced spending on healthcare costs by employers. A large health system in central Minnesota offers an Employee Medication Therapy Management (MTM) benefit that offers further financial incentives to meet with an MTM Pharmacist for a comprehensive review of one’s medications. Currently, this program is underutilized due to both lack of awareness of the program and geographic for employees in the wester region of the health system. This project sought …

Vascular Risk Reduction In Obesity Through Reduced Granulocyte Burden And Improved Angiogenic Monocyte Content Following Bariatric Surgery., David A Hess, Justin Z Trac, Stephen A Glazer, Daniella C Terenzi, Adrian Quan, Hwee Teoh, Mohammed Al-Omran, Deepak L Bhatt, C David Mazer, Ori D Rotstein, Subodh Verma

Physiology and Pharmacology Publications

Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair. We also describe that, at 3 months following bariatric surgery, systemic inflammatory burden was reduced and pro-angiogenic macrophage precursor content was improved in subjects …

Overexpression Of Mig-6 In The Cartilage Induces An Osteoarthritis-Like Phenotype In Mice, Melina Bellini, Michael A. Pest, Manuela Miranda-Rodrigues, Ling Qin, Jae Wook Jeong, Frank Beier

Physiology and Pharmacology Publications

© 2020 The Author(s). Background: Osteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of the articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the epidermal growth factor receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of the articular cartilage, and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in the cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study. Methods: Utilizing knee joints from cartilage-specific Mig-6-overexpressing (Mig-6 over/over ) mice (at multiple time points), we …

A Role For Retinoids In The Treatment Of Covid-19?, Steven E. Trasino

Publications and Research

The 2020 global outbreak of the novel coronavirus (SARS-CoV-2 or COVID-19) is a serious threat to international health, and thus, there is an urgent need for discoverynof novel therapies or use of repurposed drugs that can make a significant impact on slowing the spread of the virus. Type 1 interferons (IFN-I) are a family cytokines of the early innate immune response to viruses that are being tested against SARSCoV- 2. However, coronaviruses similar to SARS-CoV-2 can suppress host IFN-I antiviral responses. Retinoids are a family molecules related to vitamin A that possess robust immune-modulating properties, including the ability to increase …

Keep Taking Your Ace Inhibitors And Arbs During The Covid 19 Pandemic, Robert C. Speth

HPD Articles

No abstract provided.

Understanding Elements Involved In Active Racial And Ethnic Minority Recruitment Practices For Biopharmaceutical-Sponsored Clinical Trials: A Socio-Ecological Qualitative Inquiry, Rebecca Rae Johnson

Seton Hall University Dissertations and Theses (ETDs)

Inequitable participation in clinical trials continues to be a problem, and trial populations do not always reflect the demographics of the population that the investigational product will ultimately be treating. Because genetic differences between racial and ethnic groups affect the safety and efficacy of new treatments, it is important that standard of care decisions are made based on a representative population. The purpose of this study is to understand the socio-ecological elements that are involved in the active implementation of racial and ethnic minority recruitment practices for biopharmaceutical-funded trials in the United States. This general qualitative study was both descriptive …

Prediction Of Drug-Drug Interaction Potential Using Machine Learning Approaches, Joseph Scavetta

Theses and Dissertations

Drug discovery is a long, expensive, and complex, yet crucial process for the benefit of society. Selecting potential drug candidates requires an understanding of how well a compound will perform at its task, and more importantly, how safe the compound will act in patients. A key safety insight is understanding a molecule's potential for drug-drug interactions. The metabolism of many drugs is mediated by members of the cytochrome P450 superfamily, notably, the CYP3A4 enzyme. Inhibition of these enzymes can alter the bioavailability of other drugs, potentially increasing their levels to toxic amounts. Four models were developed to predict CYP3A4 inhibition: …

Comparative Antiviral Activity Of Remdesivir And Anti-Hiv Nucleoside Analogs Against Human Coronavirus 229e (Hcov-229e), Keykavous Parang, Naglaa Salem El-Sayed, Assad J. Kazeminy, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. …

Iv Amiodarone Vs Iv Sotalol For The Use In Postoperative Junctional Ectopic Tachycardia (Jet): A Randomized Study, Tanner Isaacson

Research Days

No abstract provided.

Assessing The Effect Of Chronic Dopamine Receptor 2 Blockade As A Potential Model Of Secondary Negative Symptoms In Rats Using The Fr5/Chow Feeding Choice Task, Cyrene Nicholas

Honors Scholar Theses

Haloperidol, a dopamine (DA) D2 receptor antagonist, is an antipsychotic drug which is commonly used to treat schizophrenia and other psychiatric disorders. These disorders are often characterized by elevated striatal dopamine, which is speculated to have a role in producing positive symptoms such as hallucinations, delusions, and paranoia, as well as symptoms related to motivational salience and reward prediction. Individuals with schizophrenia also exhibit negative symptoms, such as amotivation, anergia, fatigue, and apathy among others. While some negative symptoms of schizophrenia are inherent to the pathophysiology, other negative symptoms are hypothesized to be partially induced by chronic exposure to antipsychotic …

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy For Bloodstream Infections Secondary To Enterobacter, Serratia, And Citrobacter Species, Caroline Derrick, P. Brandon Bookstaver, Zhiqiang K. Lu, Christopher M. Bland, S. Travis King, Kayla R. Stover, Kathey Rumley, Shawn H. Macvane, Jenna Swindler, Scott Kincaid, Trisha Branan, David Cluck, Benjamin Britt, Kelly E. Pillinger, Bruce M. Jones, Virginia Fleming, V. Paul Dimondi, Sandy Estrada, Brad Crane, Brian Odle, Majdi N. Al-Hasan, Julie Ann Justo

Faculty Publications

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of …

Proteoglycan-4 Regulates Fibroblast To Myofibroblast Transition And Expression Of Fibrotic Genes In The Synovium, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Holly Richendrfer, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo.

Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or …

Selective Autophagy Maintains The Aryl Hydrocarbon Receptor Levels In Hela Cells: A Mechanism That Is Dependent On The P23 Co-Chaperone, Yujie Yang, William K. Chan

School of Pharmacy Faculty Articles

The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after ligand activation. Recently, we discovered that HeLa cells can modulate the AHR levels via protein degradation without exogenous treatment of a ligand, and this degradation is particularly apparent when the p23 content is down-regulated. Inhibition of autophagy by a chemical agent (such as chloroquine, bafilomycin A1, or 3-methyladenine) increases the AHR protein levels in HeLa cells whereas activation …

Commentary: Phytocannabinoids As Therapeutic Agents To Combat Chronic Gingival Disease., Nick Narek Ohanian

Pacific Journal of Health

The therapeutic potential of cannabis has been harnessed for thousands of years yet the United States Food and Drug Administration (FDA) has still not approved cannabis as a safe or effective drug. The FDA has, however, approved the manufacturing of pharmaceutical drugs, which contain a “synthetic version of a substance that is present in the marijuana” and other compounds that mimic its action. A search of the US National Library of Medicine and National Institute of Health for keywords “CBD” and “Periodontitis” together yields only 2 publications. Although the current State and Federal regulations on the use of cannabis for …

Lipid Bilayer-Integrated Spp1 Connector Protein Nanopore And Spp1 Connector Protein Variants For Use As Lipid Bilayer-Integrated Nanopore, Peixuan Guo, Shaoying Wang

Pharmaceutical Sciences Faculty Patents

A conductive channel-containing membrane includes a membrane layer, and a SPPl connector polypeptide variant that is incorporated into the membrane layer to form an aperture through which conductance can occur when an electrical potential is applied across the membrane. A method of sensing a molecule, such as a polypeptide or nucleic acid molecule, makes use of the conductive channel- containing membrane. A method of DNA sequence makes use of the conductive channel-containing membrane.

Ocular, Neural, And Cellular Biodistribution Of Multifunctional Antioxidants, Damian Daszynski

Theses & Dissertations

Aging is a complex biological process which stems from a growing imbalance between the regenerative capacity of an organism and endogenous as well as exogenous damaging factors. This imbalance leads to the slow deterioration of individual cells, organs, and eventually the entire organism. The free radical theory of aging combines the evolutionary and mechanistic aspects of aging, postulating that the innate process is caused by deleterious, irreversible, and inevitable changes in biological systems caused by oxidative damage that accumulates over the lifespan. Evidence of this phenomenon is supported by the pathogenesis of age-related diseases, such as age-related macular degeneration and …

Delivery For Hydrophobic Drugs For Treating Pancreatic Cancer, Saud Almawash

Theses & Dissertations

Purpose The aim of this study was to determine whether coadministration of hedgehog (Hh) pathway inhibitor cyclopamine (CYP) and microtubule stabilizer docetaxel (DTX) as polymer-drug conjugates, methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonategraft- dodecanol-graft-cyclopamine) (P-CYP) and methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-docetaxel) (P-DTX) could synergistically inhibit orthotopic pancreatic tumor growth in NSG mice.

Methods P-DTX and P-CYP were synthesized from mPEGb- PCC through carbodiimide coupling reaction and characterized by 1H–NMR. The micelles were prepared by film hydration and particle size was measured by dynamic light scattering (DLS). Cytotoxicity, apoptosis and cell cycle analysis of P-DTX and P-CYP were evaluated in MIA PaCa-2 cells. In vivo efficacy …

Smart Delivery Of Genes And Drugs For Treatment Of Cancer, Feng Lin

Theses & Dissertations

The ineffective delivery of genes and drugs have become a big obstacle for the treatment of cancer, due to either poor stability or low aqueous solubility. In the first part, A ROS responsive polymer named poly(ethylene glycol)–poly[aspartamidoethyl(p-boronobenzyl)diethylammonium bromide] (PEG-B-PAEBEA) was developed for codelivery miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) for the treatment of pancreatic ductal adenocarcinoma (PDAC), since tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis, and invasion is significant downregulated while Polo-like kinase 1 (PLK1) closely associated with short survival rates of pancreatic cancer patients is remarkably upregulated . In part 2, …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

Synthesis Of Aromatic Fluorinated Ketones For Evaluation At The Gaba Receptor, Madeline Griffin

Honors Theses

GABA is a neurotransmitter that inhibits the excitation of neurons. Targeting this specific receptor has the potential to inhibit the central nervous system and possibly treat addiction, anxiety, or mood disorders. Previous research has shown that fluorinated ketones can have valuable applications in the medicinal chemistry of addiction. Some fluorinated ketones have shown activity at the GABA receptor. The main goal of this project was to synthesize aromatic fluorinated ketones for biological evaluation at the GABA_B receptor. Another goal was to compare both the monofluorinated and difluorinated analogues synthesized in order to quantify differences in activity from fluorination state. …

Improving Diabetes Self-Management Developing A Patient Decision Aid To Improve Patient Education, Morgan Baker

Honors Theses

Type 2 diabetes is a complex disease that affects a large population of people. It is imperative that efforts are made to develop more effective and inclusive treatment strategies for patients with this condition. A promising approach being studied is the utilization of community pharmacists to individualize and implement diabetes self-management training and education. The objective of this study is to develop a preliminary version of a patient decision aid (PDA) designed to evaluate patient knowledge and behavior towards diabetes self-management for use in the community pharmacy setting. The study design used to achieve this objective was a cross-sectional survey …

Regulating Neuronal Growth With Structurally Defined Glycans, Gabriella D. Hartman

Honors Theses

Chondroitin sulfate proteoglycans (CSPGs) and keratan sulfate proteoglycans (KSPGs) play an important role in neural development. Aggrecan, a CSPG, operates in the neural extracellular matrix where it negatively regulates neurite outgrowth to prevent aberrant process formation. Unfortunately, this aggrecan or CSPG-rich/KSPG-rich barrier can also prevent neuronal regeneration, which contributes to the inability to repair brain and spinal cord injuries. Removal of CSPGs and KSPGs has been shown to increase neurite outgrowth. We extend these findings by testing the ability of structurally-defined glycans to outcompete aggrecan and allow neurite outgrowth. Our overall goal is to determine if there is a particular …

The Teaching Of Performance Enhancing Drugs In U.S. Schools And Colleges Of Pharmacy, Sara Dorothy Green

Honors Theses

The teaching of performance enhancing drugs in U.S. schools and colleges of pharmacy is necessary to better help patients who are athletes especially those who compete in high-level athletics such as the Olympics or the National Collegiate Athletic Association (NCAA). There is no master list for banned substances, they differ for each organization and have many exceptions. Pharmacists can play a key role in preventing unintentional disqualifications of athletes as there are many medications considered performance enhancing drugs including some supplements and stimulants. For example, commonly used cold medications may contain pseudoephedrine hydrochloride, a banned substance in the world of …

Studies Of Salvinorin-Based Antagonists To Elucidate Pertinent Interactions For Kappa Opioid Receptor Antagonism, Madeline Keane

Honors Theses

Opioid abuse, leading to addiction and related deaths, has created a chronic epidemic in the United States for the past 30 years. This crisis has sprung from reliance on the prescription of opioid analgesics as the primary method for the management of pain in the 1990s. At that time, these drugs, specifically Purdue Pharma’s OxyContin, were marketed as non-addictive. Due to this systemic minimization of the addictive properties of opioid analgesics, as prescription rates increased, opioid-related mortality rates climbed. This epidemic continues to be pervasive, as opioid-related overdose resulted in 47,600 deaths in 2017. In addition to the opioid epidemic, …

Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks

Honors Theses

Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I concluded …

Impacts Of Embryonic Exposure To Cannabidiol Or ∆9-Tetrahydrocannabinol On Zebrafish (Danio Rerio) Frailty In F0 And F1 Generations, Anika Faruque

Honors Theses

Exposure to cannabinoids during critical development periods has increased with epileptic children being commonly prescribed CBD for seizures and pregnant women taking it recreationally. Many studies have been done on the possible benefits and drawbacks of cannabinoid exposure on the human brain, but not much is known about how it can affect the developing brain long-term. To see the potential adverse effects of cannabinoid exposure during critical stages of development and discover potential developmental origins of disease in consuming cannabinoids during embryogenesis, zebrafish embryos (6-96 hours post fertilization) were exposed to varying concentrations of CBD (0.02, 0.1, 0.5 µM), THC …