Medicine and Health Sciences Commons^™

Structure-Guided Mutagenesis Reveals The Catalytic Residue That Controls The Regiospecificity Of C6-Indole Prenyltransferases, Ahmed R. Aoun, Nagaraju Mupparapu, Diem N. Nguyen, Tae Ho Kim, Christopher M. Nguyen, Zhengfeiyue Pan, Sherif I. Elshahawi

Pharmacy Faculty Articles and Research

Indole is a significant structural moiety and functionalization of the C−H bond in indole-containing molecules expands their chemical space, and modifies their properties and/or activities. Indole prenyltransferases (IPTs) catalyze the direct regiospecific installation of prenyl moieties on indole-derived compounds. IPTs have shown relaxed substrate flexibility enabling them to be used as tools for indole functionalization. However, the mechanism by which certain IPTs target a specific carbon position is not fully understood. Herein, we use structure-guided site-directed mutagenesis, in vitro enzymatic reactions, kinetics and structural-elucidation of analogs to verify the key catalytic residues that control the regiospecificity of all characterized regiospecific …

Intramuscular Administration Of The Host-Derived Immunostimulant Cpdi-02 Increases Protection Of Outbred Mice And Piglets Against Dermal Mrsa Infection In A Curative Setting And Is Well Tolerated After Repeated Administration, Jason P. Stewart

Theses & Dissertations

Staphylococcus aureus is the most common cause of bacterial skin and soft tissue infections (SSTIs) and the leading cause of hospital-associated infections in the United States. The abundance of S. aureus infections is due, in part, to its virulence factors that suppress host immune system and the development of antibiotic resistance strains such as methicillin-resistant S. aureus (MRSA). In contrast to antibiotics, Host-Directed Therapeutics (HDTs), avoid the pitfalls of antibiotics by targeting the host for immune system rather than targeting the pathogen. This mechanism of action avoids selective evolutionary pressure, which leads to antibiotic resistance and helps the host immune …

Targeted Therapies For Improving The Treatment Of Sonic Hedgehog And Myc Driven Medulloblastoma, Bharti Sethi

Theses & Dissertations

The aim of this thesis to develop a novel potent dual inhibitor to target BDR4/PI3K and MDM2/ XIAP pathways to treat medulloblastoma. A series of new analogs were synthesized, characterized, and evaluated in vitro and in vivo using xenograft and orthotopic mouse models.

In Chapter 1 an overview of Blood brain barrier such as their components, physiology, current drug delivery system and nanomedicines to treat medulloblastoma.

Chapter 2 includes synthesis of new molecule MDP5, targeting both BRD4 and PI3K pathways. We used X-ray crystal structures and molecular modeling approach to confirm the interactions between MDP5 with BD domains from both …

Creation Of Tatde Rlnps For The Excision Of Integrated Hiv-1 Proviral Dna, Mahmudul Hasan

Theses & Dissertations

The persistence of integrated human immunodeficiency virus type 1 (HIV-1) proviral DNA despite combination antiretroviral therapy (ART) is the principal challenge to eliminating HIV-1 infection. This is made ever more complex based on the high viral mutation rates, diversity and resistance profiles. Taken together, these factors present principal obstacles towards any means to eliminate the virus from its infective human host. To address these factors, we have developed and validated a TatDE rLNP RNA delivery system. The system utilizes Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) guide RNAs (gRNAs) to target multiple exons of an integrated proviral HIV-1 (tat_{1-2 …}

Isolated Temazepam Overdose: A Unique Case Of An Unresponsive Female, Eric Doane

Rowan-Virtua Research Day

Cases of acute overdose presenting to the emergency department pose a great challenge given that history can sometimes be limited or at times be inaccurate. While naloxone is routinely given in the field to help reduce opiate’s sedating effects, the routine use of flumazenil has not been routinely adopted in cases of benzodiazepine overdose. This is because, unlike naloxone, there are many medications that act on the GABA receptor, and flumazenil is only specific for binding to the benzodiazepine/GABA receptor. This can lead to an unmasking of other medications that may be co-ingested that also effect the GABA receptor leading …

Case Report And Review: Hawthorne Root Toxicity, James Espinosa, Darren Finn, Alan Lucerna

Rowan-Virtua Research Day

Here we present the case of a patient who purchased a hawthorn root product, Raiz de Tejocote, for weight loss purposes. The side effect profile seen, including a positive digoxin level, are consistent with hawthorn root. This case reinforces the importance of asking a patient about all medications, including over the internet medications.

A New Method For Investigating Bioequivalence Of Inhaled Formulations: A Pilot Study On Salbutamol, Homa Razaei, Maryam Khoubnasabjafari, Vahid Jouyban-Gharamaleki, Hamed Hamishehkar, Mohammad Reza Afshar Mogaddam, Elaheh Rahimpour, Reza Mehvar, Abolghasem Jouyban

Pharmacy Faculty Articles and Research

Purpose: An efficient, cost-effective and non-invasive test is required to overcome the challenges faced in the process of bioequivalence (BE) studies of various orally inhaled drug formulations. Two different types of pressurized meter dose inhalers (MDI-1 and MDI-2) were used in this study to test the practical applicability of a previously proposed hypothesis on the BE of inhaled salbutamol formulations.

Methods: Salbutamol concentration profiles of the exhaled breath condensate (EBC) samples collected from volunteers receiving two inhaled formulations were compared employing BE criteria. In addition, the aerodynamic particle size distribution of the inhalers was determined by employing next generation impactor. …

An Analysis Of Trends Of Generic Drugs And Biologic Prices In The U.S., Mohammed Jamjoom

Pharmaceutical Sciences (PhD) Dissertations

Introduction: Drug prices are a significant problem for the US healthcare system. Generic and biosimilar market competition reduces drug and biologic prices, results in substantial savings, and improves patient access and outcomes. As the costs of healthcare and prescription drugs continue to rise, the discussion about drug prices has taken a prominent place at the forefront of national discourse. This study assessed impacting trends in prices of generic, biosimilar, and reference products in the US. We also evaluated the effect of the Affordable Care Act (ACA) of 2010 on biologic prices.

Methods: We extracted a list of the new generic …

The Efficacy Of Neuroleptics On Mental Health Disorders, Rathea Hersi

Honor’s College Freeman Research Journal

Mental health disorders affect a lot of people in the world and can be triggered by a wide variety of reasons. The treatment of mental health disorders varies based on the type of disorder one is dealing with, as well as the symptoms that each portrays. While history has changed how people view mental health disorders, it also shows that the models of treatment used have not always been beneficial to the wellness of human beings. Research shows that there are different ways in which mental health disorders affect the brain, which means that a study of the different parts …

Cyclic And Linear Peptides Containing Tryptophan And Arginine Residues As Cell-Penetrating Peptides And Antifungal Agents, Khushbu Bhakta

Pharmaceutical Sciences (MS) Theses

Here, we synthesized a novel group of linear and cyclic amphiphilic peptides containing different sequences of arginine (R) and tryptophan (W) residues. The peptides included a class of cyclic peptides, [R3W3]2, [R3WRW]2, [RWW]4, [WRR]4, [RWRW3]2, and the corresponding linear peptides, (R3WRW)2, (RWW)4, (WRR)4, (RWRW3)2. The peptides were examined as potential molecular transporters and cell-penetrating peptides (CPPs), and their efficiency in delivering cell-impermeable compounds was compared with [WR]5. The peptides showed no significant cytotoxicity in different cell lines (MDA-MB-231, SK-OV-3, and HEK-293) at a concentration of 1 µM and after 3 h of incubation time. The uptake of fluorescence-labeled cargo molecules …

The Implications Of Pharmacogenomics In Oncology, Jean J. Latimer

HPD Articles

No abstract provided.

An Economic And Regulatory Analysis Of Breast Cancer Drugs Approved By The Us Food And Drug Administration, Abdullah Althomali

Pharmaceutical Sciences (MS) Theses

Introduction

Breast cancer is the most common cancer among women and the leading cause of cancer death among women worldwide. The pharmacological options for breast cancer include chemotherapy, hormone therapy, targeted therapy, and immunotherapy, which are used for the prevention or treatment of breast cancer. This study assessed trends in FDA approvals and prices at the market entry of new drugs indicated for breast cancer in the period 1980-2022. The study also evaluated the factors associated with the price of the new breast cancer drugs at market entry.

Material and Methods

Regulatory data were collected from the FDA website, and …

Renal Toxicity Warnings And Precautions Of Drugs Marketed In The Us, Mohammad Al Ghamdi

Pharmaceutical Sciences (MS) Theses

INTRODUCTION: The use of drugs can lead to renal adverse effects prompting the need to include warnings and precautions on medication labels. Studies evaluating renal warnings and precautions need to be improved. This study assessed the characteristics of FDA renal toxicity warnings and precautions included in the labels of drugs approved by the FDA and marked in the US. The study also evaluated the potential factors of including a boxed warning on a drug label.

METHODS: We extracted the labels of human prescription drugs with renal toxicity boxed warnings and warnings and precautions from the “FDA Label: Full-Text Search of …

The Impact Of Pharmacy Led Education On The Management Of Heart Failure With Preserved Ejection Fraction In The Primary Care Setting, Laura Kays, Ben Rosati, Trevor Laursen, Maurice N. Tran

Providence Pharmacy PGY2 Program at Providence Medical Group 2023

No abstract provided.

Application Of Informatics Tools To Facilitate The Practice Of Precision Medicine With Genomic Testing And Clinical Data, Michael Sayer

Pharmaceutical Sciences (PhD) Dissertations

The practice of precision medicine considers a variety of sources of information to optimize patient care. Factors such as patient demographics, clinical history, and lab test values have well understood effects on treatment outcomes and influence decision making. However, effective inclusion of biomolecular data such as protein expression and DNA sequencing data within the practice of precision medicine needs continued study. Informatics tools offer solutions to allow these complex data sources to be effectively embraced. Utilization of informatics tools to visualize data pertaining to the gene selection practices of pharmacogenomic (PGx) tests effectively communicated large amounts of information into concise …

Starch Granule And Crystalline Structures With Relation To Enzyme Digestibility, Ana Isabel Gonzalez Conde

Graduate Theses and Dissertations

Porous starch produced by enzyme hydrolysis has attracted much attention for its adsorption and delivery properties. Porous starch has been successfully prepared from A-type starch, but not from B-type and C-type starches, which is partly attributed to the surface and crystalline structure. The present study aimed to characterize the role of the crystalline structure and the structure-function relationship impacting the susceptibility of starch with different crystalline polymorphs to amylase digestion. The starches were subjected to chemical modification (acid hydrolysis or surface gelatinization), physical modification (heat-moisture treatment, HMT, or high-pressure processing, HPP) or their combinations prior to amylase digestion, and the …

Longitudinal Assessment Of Pharmacy Student Attitudes Towards Mental Illness, Jessica Dillon

Honors Scholar Theses

Background: Mental health stigma in providers is one of the greatest barriers in effective care in psychiatric patients. When patients feel stigma towards them, they have lower levels of self-esteem and lower medication adherence. When training healthcare providers, specifically pharmacists, it is important to assess the effectiveness of training at reducing stigma levels. Previous studies have shown that didactic teaching does not significantly decrease stigma in pharmacy students. However, other studies have shown that students who participated in psychiatric rotations have less stigma surrounding mental health following the rotation. Currently there are no studies that assess the same students’ stigma …

An Analysis Of The Prevalence Of Over-The-Counter Painkiller Abuse, Benjamin Yanovich, Benjamin Yanovich

Theses/Capstones/Creative Projects

Pain, aches, fever, and discomfort are a part of the lives of many people. For most people, this pain can be managed using over the counter painkillers. OTC medications have a multibillion-dollar market. In the United States, patients can purchase as much of this medication as they desire to treat their pain. This medication can be easily abused and misused unintentionally. Every year, there are thousands of hospitalizations from misuse of these medications, and several cases of death. When taken incorrectly, these helpful medications can cause detrimental effects such as ulcers, kidney failure, and loss of liver function. The max …

Optimizing Collaboration Among Clinical Pharmacy Specialists And Behavioral Health Providers In The Primary Care Setting To Increase Mental Health Access, Ryan Ferris, Christine Doran, Bonnie Jiron, Dara L. Johnson

Providence Pharmacy PGY2 Program at Providence Medical Group 2023

No abstract provided.

Genetic Mutations Of KCa2.3 And KCa3.1 Channels Affect Ca2+ Sensitivity, Razan Orfali

Pharmaceutical Sciences (PhD) Dissertations

The Ca²⁺-activated potassium channels K_Ca channels are a unique family of potassium channels activated by intracellular calcium. K_Ca channels are critical for maintaining K⁺ homeostasis and modulate several physiological processes, from the firing properties of neurons to the control of the transmitter release. The Ca²⁺ sensitivity of these channels allows intracellular Ca²⁺ to regulate the electrical activity of the cell membrane. Increased Ca²⁺ sensitivity of K_Ca channels caused by gain of function mutations (GOF) in the KCNN genes results in a broad spectrum of human channelopathies, including Zimmermann- Laband syndrome (ZLS), …

Johnson & Johnson Strategic Audit, Hannah Headley, Lucy Peterkin, Ryan Nyffeler, Joshua Wiemers, Bailey Birkholtz

Honors Program: Senior Projects (Public)

Johnson & Johnson (J&J) is a healthcare company that generates economic value from its three core business segments: Consumer Health, Pharmaceuticals, and Medical Devices. Recent innovations include new pharmaceutical products, remote clinical trials, automated patient recruitment, improved scientific and digital literacy amongst employees, and innovative digitized models for supply chain planning. J&J has a competitive edge in R&D efficiency, with a 4.35 return on research capital ratio. Sociocultural, technological, and economic factors will play a large role in changing the pharmaceutical industry environment, and J&J is well positioned to benefit from sources of growth such as the increase in aging …

Pkpd-Model Based Preclinical Characterization Of The Activity Of Spectinamide 1599 Against Mycobacterial Subpopulations. And The Identification Of Potential Partners For Combination Therapy, Zaid Hanif Temrikar

Theses and Dissertations (ETD)

Tuberculosis is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent prior to COVID19. Mycobacterium tuberculosis (Mtb) is the causative agent of TB. The interaction between Mtb and the immune system leads to development of diverse environmental niches and physiology within the lung of the TB patients. Mtb is thought to adapt and thrive in such an environment by transforming to different phenotypic variants. Such variants are difficult to kill and are thought to prolong TB pharmacotherapy. Spectinamide 1599 is a synthetic modification of spectinomycin that has demonstrated excellent …

Osteoporosis Is Underdiagnosed And Undertreated In Patients With Fragility Femoral Neck And Vertebral Compression Fractures, Philip Zakko, Lauren Eberhardt, Madeline Declercq, Ahyoung Park, Megan Audet, Daniel Park

Conference Presentation Abstracts

Background/Introduction

Femoral neck (FNF) and vertebral compression fractures (VCF) are common fragility fractures (FF) in the elderly population. Defined as fractures from low-energy trauma, FF are diagnostic of osteoporosis and require treatment. The purpose of this study was to assess whether patients were appropriately diagnosed and treated for osteoporosis following fragility FNF and VCF.

Materials/Methods

A retrospective chart review was performed at a single-institution from 1/1/2017 to 12/31/2020 on consecutive patients who sustained fragility FNF treated with closed reduction percutaneous pinning, hemiarthroplasty, or total hip arthroplasty or VCF treated with kyphoplasty. Patients <50 years of age, who sustained a high-energy or a non-osteoporotic pathologic fracture, were treated non-operatively, or deceased within one-year post-op were excluded. Preoperative demographics, ASA, CCI, smoking, alcohol, and glucocorticoid use were obtained. Diagnosis and treatment of osteoporosis, including dual-energy X-ray absorptiometry (DEXA) scans, calcium, vitamin D, bisphosphonates, denosumab, and alternative treatments (teriparatide, calcitonin, raloxifene, estrogen) were assessed pre-op and within one-year post-op. Subsequent FF were recorded.

Results

Of 593 patients, 276 FNF and 94 …

The Association Of Long Working Hours And The Use Of Prescription Sedatives Among U.S. Workers., Emmanuel Ezekekwu

Electronic Theses and Dissertations

BACKGROUND: Meeting the needs of a round-the-clock and globalized society has led to an increase in long working hours. This trend has been accompanied by a corresponding rise in sleep disorders and subsequent use of sedating medications. Overtime hours have been associated with adverse health outcomes such as cardiovascular diseases, symptoms of psychological distress, and health behaviors, including risky intake of alcohol and smoking. Hence, the main objectives of this three-paper dissertation were to examine the multi-faceted relationship between working hours, the use of prescription sleep aids, the onset of psychological distress, and the use of health care services. METHODS: …

“Pinkalicious": Outer Membrane Vesicles Isolated From Pseudoalteromonas Rubra Carry Prodigiosin Antibiotics As Cargo, Margaret Hill

Senior Honors Projects

Astrangia poculata, the state coral of Rhode Island, is susceptible to infection by Vibrio coralliilyticus RE22, which is a common marine pathogen affecting various invertebrate species. The settlement of coral larvae prior to the establishment of colonies is mediated by crustose coralline algae (CCA). This process may be induced by CCA-associated protective bacteria that colonize corals in early metamorphosis; furthermore, such bacteria potentially have downstream effects in the susceptibility of corals to pathogens. Strains of Pseudoalteromonas rubra isolated from CCA have been shown to induce larval settlement of tropical corals. We hypothesize that P. rubra induces the settlement of …

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, …

Beyond Use Date (Bud) Determination Of Ambroxol Hydrochloride Syrup By High-Performance Liquid Chromatography – Uv/Vis Detector, Catur Jatmika, Raditya Iswandana, Indah Dewi Lestari

Pharmaceutical Sciences and Research

Ambroxol HCl is a mucolytic agent often used to treat respiratory disorders associated with excess mucus secretion. This study aims to determine the beyond-use date (BUD) of ambroxol HCl syrup on the market based on analysis of the decrease in drug content using High-Performance Liquid Chromatography (HPLC) – UV/Vis detector. The HPLC conditions were reversed-phase with a C18 column, mobile phase containing acetonitrile - phosphate buffer 0.05 M pH 4.5 (60:40) at a flow rate of 1.0 ml/min using UV detection at 248 nm. To determine BUD, five syrup preparations (brands) obtained from the Jakarta area were analyzed in triplicate. …

Synthesis Of Ferrous Fumarate From Indonesian Iron Sand And In Vivo Body Weight Gain Test In Rats, Taufiq Indra Rukmana, Felicia Natalia Kurniadi, Harmita Harmita

Pharmaceutical Sciences and Research

Iron deficiency anemia (IDA) is a health problem in Indonesia. Prevention and treatment of IDA is carried out by giving fortified foods and oral iron therapy. Both can use ferrous fumarate which is made with reacting bivalent iron and disodium fumarate. Bivalent iron can be obtained from iron sand in Indonesia. This study aims to synthesize ferrous fumarate from Indonesian iron sand, which is from Malang, Sukabumi, and Cianjur area, and to determine its absorption through in vivo body weight gain test in male Wistar white rats (Rattus norvegicus). First, ferrous fumarate was synthesized through reaction of ferrous …

Utilization Of Spent Arabica Coffee Grounds As Raw Material For Activated Charcoal In Liquid Bath Soap Formulation, Hilda Maysarah, Lydia Septa Desiyana, Siti Nurzuhra, Didi Nurhadi Illian

Pharmaceutical Sciences and Research

Arabica coffee (Coffea arabica) is one of the most popular coffees among Acehnese, an ethnic group from Aceh, Indonesia. The amount of coffee consumed is directly proportional to the amount of coffee waste produced. Spent coffee grounds are the residue obtained during the brewing process. Spent coffee grounds can be utilized by converting them into active charcoal adsorbents. This study aimed to produce activated charcoal from spent arabica coffee grounds (SACG), to utilize it as an active ingredient in the liquid bath soap formulations, and to determine the best formula. The characterization of activated charcoal was conducted and …

Solid Dispersion Technology For Improving The Solubility Of Antiviral Drugs, Maria Elvina Tresia Butar-Butar, Nasrul Wathoni, Hestiary Ratih, Yoga Windhu Wardhana

Pharmaceutical Sciences and Research

Most drugs, including antiviral drugs, show low solubility in water, which affects dissolution, bioavailability, and therapeutic effectiveness. Therefore, many antiviral drugs are given in very large doses. One of the efforts to overcome these problems is the application of solid dispersions in which polymers and surfactants can trap drug molecules that are in the amorphous phase. Drugs in a hydrophilic carrier will increase wettability, water absorption capacity, and porosity of particles, so that the drug is released better. This review article will discuss the development of technology in solid-state, how solid dispersion overcomes the lack of solubility and the rate …