Pharmacy and Pharmaceutical Sciences Commons^™

Pde4 Inhibition: A Novel Therapeutic Strategy In Liver Fibrosis., Mohamed Elnagdy

Electronic Theses and Dissertations

Background: Liver fibrosis is accumulation of extracellular matrix (ECM) proteins due to chronic liver injury. Chronic hepatic damage can occur due to multiple causes including, alcohol, non-alcoholic steatohepatitis and chronic viral hepatitis. Liver fibrosis is a critical problem worldwide due to the extremely high incidence of alcohol associated liver damage and chronic viral hepatitis. Moreover, there is no FDA approved therapy for liver fibrosis. Activation and transdifferentiation of quiecent hepatic stellate cells (HSCs) to myofibroblasts (MFBs) is the main event contributing to liver fibrosis. This process involves two phases, the initiation and the perpetuation phases. Hepatocyte injury and inflammatory response …

Muc13 Enhances Colorectal Cancer Metastasis, Kyle Doxtater

Theses and Dissertations (ETD)

Colorectal cancer (CRC) is one of the most prevalent cancer worldwide with a 5% lifetime incidence in developed countries. It is third most common cause of cancer related death in the United States and the second deadliest when men and women are combined. Encouragingly due to changes in dietary lifestyle, screening colonoscopy, and advancement in treatments the mortality has decreased in recent years. Most sporadic CRCs develop from polyploid adenomas and are preceded by intramucosal carcinomas (stage 0), which can progress into more malignant forms. This developmental process is known as the adenoma-carcinoma sequence. Early detection and endoscopic removal are …

Optimizing Empiric Vancomycin Use In Febrile Neutropenia Patients, Nicole Tadros, Erika Dittmar, Radhan Gopalani

All Publications

Introduction: Febrile neutropenia (FN) is a complication of chemotherapy resulting in a temperature 100.4⁰F or greater plus an absolute neutrophil count (ANC) below 500 cells/mm³ or an ANC below 1000 cells/mm³ and expected to decrease below 500 cells/mm³ within 48 hours. Timely administration of broad-spectrum antimicrobial therapy is a cornerstone for the initial management of FN. However, prolonged empiric antimicrobial treatment can lead to resistance and toxicity. National guidelines and published literature do not support vancomycin as a routine part of empiric antimicrobial regimens in FN; it is only recommended in patients with specific clinical indications. This …

Covid-19: The Vaccine Race Continues, L. Hayley Burgess, Carley Castelein, Andrew Rubio, Mandelin K. Cooper

HCA Healthcare Journal of Medicine

Over a year has passed since the discovery of SARS-CoV-2 and the subsequent COVID-19 pandemic. As mitigation efforts continue, COVID-19 has claimed over half a million lives in the United States and 3.1 million lives globally. The development and availability of vaccines delivering immunity to prevent COVID-19 offers hope to end the pandemic.

Emergency use authorizations from the Food and Drug Administration have been issued in the United States for three vaccines, one each from Pfizer-BioNTech, Moderna and Janssen/J&J. Pfizer-BioNTech and Moderna are both mRNA vaccines with efficacy of 95% and 94.1% respectively, while the vector-based vaccine from Janssen/J&J has …

Thyroid Hormone Synthesis Continues Despite Biallelic Thyroglobulin Mutation With Cell Death, Xiaohan Zhang, Aaron P. Kellogg, Cintia E. Citterio, Hao Zhang, Dennis Larkin, Yoshiaki Morishita, Héctor M. Targovnik, Viviana A. Balbi, Peter Arvan

Pharmacy Faculty Articles and Research

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe …

Home Blood Pressure Monitoring To Improve Hypertension Control: A Narrative Review Of International Guideline Recommendations, John Andraos, Luma Munjy, Michael S. Kelly

Pharmacy Faculty Articles and Research

Home blood pressure monitoring (HBPM) is a convenient way to assess out-of-office blood pressure control and is recommended by numerous international guidelines to aid clinicians in the diagnosis and management of essential hypertension. Although available guidelines recommend the use of HBPM in patients receiving antihypertensive medication, their specific recommendations regarding optimal monitoring schedule, duration, and clinician interpretation of home blood pressure readings may differ among guidelines. Purpose: The purpose of this article is to review available international hypertension guideline recommendations related to the use of HBPM to improve hypertension control among patients receiving antihypertensive therapy. We also briefly highlight …

Improving Antibiotic Prescribing For Acute Respiratory Illnesses, Laurinia Hunter

Student Scholarly Projects

Practice Problem: Unwarranted antibiotic prescribing practices when treating acute respiratory illnesses contribute to the national health threat of antibiotic resistance.

PICOT: In a pediatric outpatient setting for patients ages 6-25 who have no documented uncontrolled comorbidities, presenting with an acute respiratory illness (P), does provider utilization of clinical guidelines, and patient and (caregivers) utilization of educational pamphlets, to collectively develop a plan of care (I), compared to providers and patients who do not utilize such strategies(C) result in a reduction in antibiotics prescribed for acute respiratory illnesses (O) in a 6-week timeframe (T)?

Evidence: The evidence reviewed reported the utilization …

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

Undergraduate Honors Thesis Projects

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

Genetic Mechanisms Of Transcriptional Regulation In Childhood Acute Lymphoblastic Leukemia, Xujie Zhao

Theses and Dissertations (ETD)

Introduction. Advances in genomic profiling and sequencing studies have identified germline and somatic variations that are associated with childhood ALL, improving our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL). Recent genome-wide association studies (GWAS) have identified germline genetic variations of ARID5B and, more recently, IGF2BP1 that are associated with susceptibility to ALL. Genome-wide sequencing studies also discovered a new ALL subtype characterized of ZNF384-mediated chromosomal translocations, providing new insights into genetic heterogeneity in childhood ALL. However, the underlying mechanism by which these genetic variants contribute to the transcriptional regulatory circuitries of ALL is still poorly understood. …

Categorization Of Marketed Artificial Tear Formulations Based On Their Ingredients: A Rational Approach For Their Use, Avani Kathuria, Kiumars Shamloo, Vishal Jhanji, Ajay Sharma

Pharmacy Faculty Articles and Research

Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations contain a variety of active ingredients, biologically active excipients, and preservatives. Many of these formulations are also available as preservative-free. This study was conducted to inspect artificial tear formulations currently marketed in the United States for their active ingredients, biologically relevant excipients, and preservatives. The marketed artificial tears were examined at various US retail pharmacy chains and using the manufacturers’ website to compile information about active ingredients, inactive ingredients, and …

Nanomaterials As Novel Cardiovascular Theranostics, Rajasekharreddy Pala, Subhaswaraj Pattnaik, Siddhardha Busi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular diseases (CVDs) are a group of conditions associated with heart and blood vessels and are considered the leading cause of death globally. Coronary heart disease, atherosclerosis, myocardial infarction represents the CVDs. Since CVDs are associated with a series of pathophysiological conditions with an alarming mortality and morbidity rate, early diagnosis and appropriate therapeutic approaches are critical for saving patients’ lives. Conventionally, diagnostic tools are employed to detect disease conditions, whereas therapeutic drug candidates are administered to mitigate diseases. However, the advent of nanotechnological platforms has revolutionized the current understanding of pathophysiology and therapeutic measures. The concept of combinatorial therapy …

Guideline-Directed Heart Failure Therapy In Patients After Left Ventricular Assist Device Implantation, Bailey M. Colvin, James C. Coons, Craig J. Beavers

The VAD Journal

Background: Left ventricular assist devices (LVADs) are used as an advanced therapy option for patients with stage D heart failure. These devices provide mechanical unloading of the heart as either a bridge to transplant or recovery, or as destination therapy. In patients with LVADs, there are emerging data on the use of heart failure guideline-directed medical therapy (GDMT) to improve outcomes. This review describes the current evidence available for the use of neurohormonal blocking agents in patients with LVADs.

Methods: Articles were found using PubMed and web searches for heart failure therapies/neurohormonal blockade and LVADs. Studies were included if they …

Stability Evaluation Of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect Of Solvents And Storage Conditions, Christopher Ross, Basir Syed, Joanna Pak, Vishal Jhanji, Jason Yamaki, Ajay Sharma

Pharmacy Faculty Articles and Research

Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus keratitis and other ocular infections. Vancomycin ophthalmic drops are not commercially available and require compounding. The present study was designed to investigate the stability of vancomycin ophthalmic drops in normal saline, phosphate-buffered saline (PBS), and balanced salt solution (BSS) while stored at room temperature or under refrigeration. Vancomycin ophthalmic drops (50 mg/mL) were aseptically prepared from commercially available intravenous powder using PBS, BSS, and saline. Solutions were stored at room temperature and in a refrigerator for 28 days. The vancomycin stability was tested by a microbiology assay and high-performance liquid …

Anti-Inflammatory Effects Of Α7-Nicotinic Ach Receptors Are Exerted Through Interactions With Adenylyl Cyclase-6, Simeng Zhu, Shiqian Huang, Guofang Xia, Jin Wu, Yan Shen, Ying Wang, Rennolds S. Ostrom, Ailian Du, Chengxing Shen, Congfeng Xu

Pharmacy Faculty Articles and Research

Background and purpose

Alpha 7 nicotinic acetylcholine receptors (CHRNA7) suppress inflammation through diverse pathways in immune cells, so is potentially involved in a number of inflammatory diseases. However, the detailed mechanisms underlying CHRNA7’s anti‐inflammatory effects remain elusive.

Experimental approach

The anti‐inflammatory effects of CHRNA7 agonists in both murine macrophages (RAW 264.7) and bone marrow‐derived macrophages (BMDM) stimulated with LPS were examined. The role of adenylyl cyclase 6 (AC6) in Toll‐like Receptor 4 (TLR4) degradation was explored via overexpression and knockdown. A mouse model of chronic obstructive pulmonary disease was used to confirm key findings.

Results

Anti‐inflammatory effects of CHRNA7 were …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Pharmacist-Led Programs To Increase Statin Prescribing: A Narrative Review Of The Literature, Mary Elkomos, Raha Jahromi, Michael S. Kelly

Pharmacy Faculty Articles and Research

Statins are lipid-lowing medications shown to reduce cardiovascular events and are recommended for specific patient populations at elevated risk of atherosclerotic cardiovascular disease (ASCVD). Despite the demonstrated efficacy of statins for reducing ASCVD risk, and guidance on which populations should receive statin therapy, a substantial portion of eligible patients are not prescribed statin therapy. Pharmacists have attempted to increase the number of eligible patients receiving appropriate statin therapy through a variety of interventions and across several clinical settings. In this article, we highlight multiple studies evaluating the effectiveness of pharmacist-led interventions to improve statin use. A total of seven studies …

Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. Mccormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe

Pharmacotherapy and Outcomes Science Publications

Aims: Platelet rich plasma (PRP) has been used in tissue repair to treat numerous inflammatory pathophysiologies. Recent studies have elucidated that the bioactive lipid fraction of PRP significantly contributes towards the resolution of inflammation. There has been great interest in how therapeutics could modulate the PRP lipidome to formulate a more pro-resolving matrix. Many of the pathways used to produce either pro-resolving or pro-inflammatory lipids are shared between ω-3 and ω-6 polyunsaturated fatty acids (PUFA). Here, we explored the separate and interacting effects acute exogenous ω-3 PUFA supplementation and aspirin had on the lipidome of PRP within 6 hours.

Methods: …

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 …

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

Pharmaceutical Sciences (MS) Theses

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

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

Actividades Profesionales Reservadas En Argentina: Orígenes Y Actualidad / Reserved Professional Activities In Argentina: Origins And Current Situation, Cintia E. Citterio, Héctor Targovnik

Pharmacy Faculty Articles and Research

En Argentina, la Ley de Educación Superior (LES; Ley 24.521, 1995) establece que hay profesiones cuyo ejercicio puede comprometer el interés público poniendo en riesgo de modo directo la salud, la seguridad, los derechos, los bienes o la formación de los habitantes, y las mismas están contempladas en el artículo 43 de la LES. Sólo aquellas actividades que realicen estos profesionales y que implican un riesgo rigurosamente directo, se denominan actividades profesionales reservadas. Pero… ¿Cuál es la diferencia entre actividades profesionales reservadas y alcances de los títulos? ¿Y cómo se establecen? El objetivo de este trabajo es analizar el significado …

From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest

Graduate Theses, Dissertations, and Problem Reports (ETD)

Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …

Investigations On Novel Cyp26a1/B1 Inhibitor, Dx308: Using Atra Response As A Theraputic Target For Traumatic Brain Injury And Parkinson’S Disease, Jacob Morgan Leatherwood

Graduate Student Theses, Dissertations, & Professional Papers

Neurodegenerative diseases (NDs) take a wide spectrum of pathologies and have a tendency to present themselves later in life. Neurodegenerative diseases affect 6 million Americans annually with ~1 million currently living with Parkinson’s disease (PD). One of the greatest contributors to the pathogenesis of neurodegenerative diseases is the occurrence of a traumatic brain injury (TBI) during life.

All-trans-retinoic acid (atRA) is the active metabolite of Vitamin A. The retinoic acid pathway is known to be activated following TBI and is reduced in PD patients. Previous studies found a decrease in inflammation and behavioral deficits following administration of Vitamin …

Impact Of 17-Beta Estradiol And Moderate-Intensity Exercise On Mesenteric Arterial Function Of Uc Davis Type-2 Diabetes Mellitus Rats, Md Rahatullah Razan

University of the Pacific Theses and Dissertations

The studies in this dissertation were designed to investigate the impacts of estrogen (17-β estradiol/E2) and moderate-intensity exercise (MIE) on the mesenteric arterial (MA) function of the University of California Davis type-2 diabetes mellitus (UCD-T2DM) Rat model. Our recent report suggests that diabetes impairs MA vasorelaxation in both sexes of the UCD-T2DM model. Particularly, we reported that MA from prediabetic male rats showed a greater impairment compared to that in prediabetic females. However, when females become diabetic, they exhibit a greater vascular dysfunction than males. Therefore, the aim of the first study was to investigate whether female sex hormone, specifically …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

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

Theses and Dissertations

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

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

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

Graduate Theses, Dissertations, and Problem Reports (ETD)

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

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

Graduate Theses, Dissertations, and Problem Reports (ETD)

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

Social Media Self-Regulation And The Rise Of Vaccine Misinformation, Ana Santos Rutschman

All Faculty Scholarship

This essay examines the main characteristics and shortcomings of mainstream social media responses to vaccine misinformation and disinformation. Parts I and II contextualize the recent expansion of vaccine information and disinformation in the online environment. Part III provides a survey and taxonomy of ongoing responses to vaccine misinformation adopted by mainstream social media. It further notes the limitations of current self-regulatory modes and illustrates these limitations by presenting a short case study on Facebook—the largest social media vehicle for vaccine-specific misinformation, currently estimated to harbor approximately half of the social media accounts linked to vaccine misinformation. Part IV examines potential …

Importance Of Awareness Of Adverse Drug Reaction Reporting During The Covid-19 Pandemic, Heather Ellis, Hale Z. Toklu

HCA Healthcare Journal of Medicine

Health care professionals hold the responsibility of reporting any adverse drug reactions in order to learn about new therapy and how best to safely care for our patients. The information derived from case publications and FDA MedWatch reports are essential to accumulate information and increase awareness for the possible risks of new drugs.