Pharmacy and Pharmaceutical Sciences Commons^™

“The Role Of Artificial Intelligence In The Pharmaceutical Field: Enhancing Therapeutic Outcomes And Repurposing Through The Acceleration Of Drug Discovery”, Tonivie Valeriano

[Archive] Belmont University Research Symposium (BURS)

The development of new drugs and their repurposing have considerably benefited the field of pharmacy. It will not only affect the pharmaceutical sector but also its diverse facets of health will be significantly influenced. Yet, the development of innovative medical treatments necessitated a lengthy period of expectancy for human survival. Individual survival rates were decreasing over time before the development of the treatment. Humanity has a limited lifespan. Moreover, investments in new drugs often go unnoticed because of the prolonged and complex process of drug research and development (R&D). In the future of pharmacy, artificial intelligence will continue to have …

Near-Neutral Balanced Selection Theory (Nnbst): Implication On The Molecular Evolution Of Sars-Cov-2 And Zika Virus, Nicholas J. Paradis

Graduate Student and Postdoctoral Fellow Symposium

Virus pandemics have significantly impacted human welfare and development. Understanding the true molecular evolution of viruses is critical for preventing future pandemics and developing the next-generation drugs and vaccines. Unfortunately, viruses exhibiting constant genomic substitution rates (GSRs) despite increasing vaccinations and human infections (SARS-CoV-2) and viruses under seemingly extreme conservation (ZIKV) paints a confusing picture of viral evolution, and the main evolutionary theories (Selectionist Theory, Kimura’s Neutral Theory) cannot explain their molecular evolution. Here, we developed a first-principle model, c/u, to characterize reproductive fitness changes in viruses based on variations in the nucleotide/codon mutation rate (c) with respect to the …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Characterizing Antibiotic Regimen Modification Behavior, Patient Characteristics, And Outcomes For Patients With Gram-Negative Bacterial Infections, A Retrospective Single-Center Study, Jason Yamaki, Mirna Mikhail, Richard Beuttler, Philip Robinson, Emre Yücel, Alexandre H. Watanabe

Pharmacy Faculty Articles and Research

Few studies describe the frequency of antibiotic regimen modification behaviors in the acute care setting. We sought to ascertain patient and treatment characteristics, details of regimen modification, and clinical outcomes with antibiotic modifications. This retrospective study included patients admitted to Hoag Memorial Hospital from 1 January 2019–31 March 2021 with a complicated infection caused by a Gram-negative organism resistant to extended-spectrum cephalosporins or with the potential for resistance (AmpC producers). A total of 400 patients were included. The predominant sources were bloodstream (33%), urine (26%), and respiratory (24%), including patients with multiple sources. The most isolated organisms were Pseudomonas spp. …

A Highly Selective Mpges-1 Inhibitor To Block Abdominal Aortic Aneurysm Progression In The Angiotensin Mouse Model., Lauren M Weaver, Madeline J Stewart, Kai Ding, Charles D. Loftin, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

Abdominal aortic aneurysm (AAA) is a deadly, permanent ballooning of the aortic artery. Pharmacological and genetic studies have pointed to multiple proteins, including microsomal prostaglandin E₂ synthase-1 (mPGES-1), as potentially promising targets. However, it remains unknown whether administration of an mPGES-1 inhibitor can effectively attenuate AAA progression in animal models. There are still no FDA-approved pharmacological treatments for AAA. Current research stresses the importance of both anti-inflammatory drug targets and rigor of translatability. Notably, mPGES-1 is an inducible enzyme responsible for overproduction of prostaglandin E₂ (PGE₂)-a well-known principal pro-inflammatory prostanoid. Here we demonstrate for the first …

Mechanistic Investigation Of C—C Bond Activation Of Phosphaalkynes With Pt(0) Complexes, Roberto M. Escobar, Abdurrahman C. Ateşin, Christian Müller, William D. Jones, Tülay Ateşin

Research Symposium

Carbon–carbon (C–C) bond activation has gained increased attention as a direct method for the synthesis of pharmaceuticals. Due to the thermodynamic stability and kinetic inaccessibility of the C–C bonds, however, activation of C–C bonds by homogeneous transition-metal catalysts under mild homogeneous conditions is still a challenge. Most of the systems in which the activation occurs either have aromatization or relief of ring strain as the primary driving force. The activation of unstrained C–C bonds of phosphaalkynes does not have this advantage. This study employs Density Functional Theory (DFT) calculations to elucidate Pt(0)-mediated C–CP bond activation mechanisms in phosphaalkynes. Investigating the …

Real-Time Camp Dynamics In Live Cells Using The Fluorescent Camp Difference Detector In Situ, Isabella Cattani-Cavalieri, Jordyn Margolis, Camelia Anicolaesei, Francisco J. Nuñez, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

cAMP Difference Detector In Situ (cADDis) is a novel biosensor that allows for the continuous measurement of cAMP levels in living cells. The biosensor is created from a circularly permuted fluorescent protein linked to the hinge region of Epac2. This creates a single fluorophore biosensor that displays either increased or decreased fluorescence upon binding of cAMP. The biosensor exists in red and green upward versions, as well as green downward versions, and several red and green versions targeted to subcellular locations. To illustrate the effectiveness of the biosensor, the green downward version, which decreases in fluorescence upon cAMP binding, was …

Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).

Methods

Eight-month-old female 3xTg-AD mice were injected intraperitoneally with …

The Prevalence Of Gram-Negative Bacteria With Difficult-To-Treat Resistance And Utilization Of Novel Β-Lactam Antibiotics In The Southeastern United States, Y. Vivian Tsai, P. Brandon Bookstaver Pharm.D., Joseph Kohn, Julie Ann Justo, Darrell Childress, Stefanie Stramel, Douglas Slain, Patrick Tu, Mary Joyce B. Wingler, Bruce M. Jones, Daniel T. Anderson, Megan M. Seddon, David A. Cretella, Joshua Eudy, Hana Winders, Kayla Antosz Pharm.D., Pamela Bailey, Majdi N. Al-Hasan

Faculty Publications

Objective:

To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel β-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design:

Retrospective, multicenter, cohort. Setting:

Ten hospitals in the southeastern United States. Methods:

GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel β-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) …

Association Between Expedited Review Designations And The Us Or Global Burden Of Disease For Drugs Approved By The Us Food And Drug Administration, 2010–2019: A Cross-Sectional Analysis, Matthew J. Jackson, Gregory Vaughan, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Pharmaceutical innovation can contribute to reducing the burden of disease in human populations. This research asks whether products approved by the US Food and Drug Administration (FDA) from 2010 to 2019 and expedited review programmes incentivising development of products for serious disease were aligned with the US or global burden of disease.

Limonene Exerts Anti-Inflammatory Effect On Lps-Induced Jejunal Injury In Mice By Inhibiting Nf-Κb/Ap-1 Pathway, Sarmed H. Kathem, Yasameen Sh. Nasrawi, Shihab H. Mutlag, Surya M. Nauli

Pharmacy Faculty Articles and Research

The human gastrointestinal system is a complex ecosystem crucial for well-being. During sepsis-induced gut injury, the integrity of the intestinal barrier can be compromised. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, disrupts the intestinal barrier, contributing to inflammation and various dysfunctions. The current study explores the protective effects of limonene, a natural compound with diverse biological properties, against LPS-induced jejunal injury in mice. Oral administration of limonene at dosages of 100 and 200 mg/kg was used in the LPS mouse model. The Murine Sepsis Score (MSS) was utilized to evaluate the severity of sepsis, while serum levels of urea and …

Implementing Services For Pediatric Cystic Fibrosis Treatment In A Community Hospital., Paige Grube, Heather Nichols, Sarah Ferrell Pharmd, Denise Gilham Pnp, Allyson Gaylor Pharmd, Bcpps, Karen Dunkelberger Bs Pharm, Mshi, Cpps

Pharmacy Residency

This project aimed to describe how the pharmacy department prepared to care for pediatric patients with cystic fibrosis, a new population being cared for at the institution.

PURPOSE: Our community hospital was recently charged with providing care for pediatric people with cystic fibrosis (PwCF). Pediatric PwCF generally need a higher level of care than is required by other pediatric patients cared for at our institution. This project aimed to prepare the pharmacy department to care for this specialized population safely and efficiently.

SUMMARY: The implementation process was divided into 3 phases to accomplish the larger purpose. These phases were as …

A Novel Micropeptide, Slitharin, Exerts Cardioprotective Effects In Myocardial Infarction, Ahmed G. E. Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán

Pharmacy Faculty Articles and Research

Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type.

Experimental design: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction.

Results: We identified a novel 24-amino acid micropeptide …

Six-Month Report Assessing The Feasibility And Effectiveness Of Amniotic Membrane Injections In Patients With Short, Anterior, Urethral Strictures, Nicholas Pryde, Jack Vernocke, Aron Liaw, Michael Sessine, Nivedita Dhar

Medical Student Research Symposium

Introduction: Urethral stricture treatment has high recurrence rates and adjunct injectable agents have been explored. Amniotic membranes (AM) promote apoptosis of pro-inflammatory cells, prevent differentiation of pro-fibrotic cells, and decrease scar formation. These tissues generated interest in reconstructive urethral surgery. Thus, we performed urethral dilation combined with micronized AM injection in urethral scar tissue for treatment of urethral stricture.

Materials and Methods: Adult males with strictures ≤12Fr in diameter and ≤2 cm in length, International Prostate Symptom Score (IPSS) ≥11 and maximum flowrate <15 ml/s. Reconstituted 100mg micronized AM was injected at the time of urethral dilation. Primary study end point was anatomical success (≥14Fr by cystoscopy) at 6 months. Secondary end points were questionnaires, flow rate, and post void residual. Outcomes assessed at baseline, 5 days, 14 days, 3 months, and 6 months post-injection. Safety was analyzed.

Results: Ten men, mean age of 52 ± 15 years, were included. There were 7 patients with …

Adherence To Sb5195 Naloxone Distribution Requirements At Discharge From The Emergency Department, E Stewart, J Delfeld, J Mckay, J Corhei, Kailyn Elliot

Providence Nursing Research Conference 2023 – Present

Background: Washington State, mirroring a national crisis, experienced a surge in opioid-related deaths, with 17,502 fatalities from 2007 to 2021. This trend aligns with the U.S.'s broader opioid epidemic, marked by 70,000 drug overdose deaths in 2017, data show overdose deaths involving opioids increased from an estimated 70,029 in 2020 to 80,816 in 2021. Overdose deaths were from synthetic opioids, primarily fentanyl. In response, empowering registered nurses (RNs) in emergency departments (EDs) to issue Nurse-Initiated Orders (NIO) for patients to discharge from the hospital with physical naloxone pre-pack kits to be used in the community, an opioid antagonist, has …

Considering Returns On Federal Investment In The Negotiated “Maximum Fair Price” Of Drugs Under The Inflation Reduction Act: An Analysis, Edward W. Zhou, Paula G. Chaves Da Silva, Debbie Quijada, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

The Inflation Reduction Act (IRA) of 2022 contained landmark provisions authorizing government to negotiate a “maximum fair price” for selected Medicare Part D drugs considering the manufacturer’s research and development costs, federal support for discovery and development, the extent to which the drugs address unmet medical needs, and other factors. This working paper describes federal investment in the discovery and development of the ten drugs selected for price negotiation in the first year of the IRA as well as the health value created through Medicare Part D spending on these drugs. We identified $11.7 billion in NIH funding for basic …

January / February / March 2024, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the January, February, and March issue of Rural Rocks from the SWOSU College of Pharmacy.

Supply Is Not Limulus: Research Review Of Horseshoe Crab Conservation In The Face Of Intense Pharmaceutical Demand, Zoya Galeev

University Honors Theses

Horseshoe crabs are being used by the pharmaceutical industry to conduct endotoxin tests using LAL derived from the organism’s blood to ensure safe medical practice. Their annual collection and bleeding, while not always leading to mortality, affects horseshoe crab behavior and health. This research seeks to understand how the American horseshoe crab, L. polyphemus, is being used by pharmaceutical agencies and the implications that their harvesting has on the industry and the conservation of the species. Studies were collected from the past decade across two databases, Web of Science (WOS) and PubMed, to assess present conservation techniques to reduce …

Repurposing Of Us-Fda-Approved Drugs As Negative Modulators Of Ubiquitin Specific Protease-7 (Usp7), Seema Zadi, Sumaira Javaid, Atia-Tul-Wahab, Humaira Zafar, Muhammad Awais, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of …

Substance Use Disorder (Sud)- The Impact Of Sud In Utah, Amber Escobedo

Annual Research Symposium

Substance use disorder (SUD) is a manageable mental disorder that causes affected individuals to lose control over their use of substances such as drugs or alcohol. The cost of this disorder leads to the loss of billions of dollars each year. The purpose of this study is to explore ways to minimize the cost SUD bring to Utah and the United States.

Pharmacist Interventions Increase Uptake Of Pneumonia Vaccination In At-Risk Populations: A Review., Kaitlyn Hinton

Annual Research Symposium

Pneumonia is a large burden to healthcare costs and a large cause of hospitalization (Hayes, BH. Chest. 2018, 153(2), 427), and bacterial pneumonia can be prevented through vaccination. While pediatric vaccinations are routinely given, an additional dose is required for adults 65+ years of age or otherwise immune compromised, including diabetics. Only 22.2% of Immunocompromised patients and 65% of the elderly population have received the extra dose (Hung, MC. CDC. 2022). With pharmacist interventions, these vaccination rates could increase significantly. The purpose of this study was to conduct a review of the literature to identify interventions that have yielded higher …

Medication Errors Among Als Providers In The Prehospital Setting, Cody Vaughn Gibson, Victor Jimenez Jr

Annual Research Symposium

EMS providers administer a variety of medications to patients in the prehospital environment, and while there are numerous published studies on medication errors pertaining to the hospital environment, there are comparatively fewer studies which focus on the prehospital environment. Therefore, the purpose of this survey is to investigate the type and frequency of medication errors occurring in the prehospital environment.

Evaluation Of Novel Therapeutic Agents For The Treatment Of Chronic Dry Eyes, Lilian Huynh, Evonie Villarete, Surajit Dey

Annual Research Symposium

Dry eye disease (DED) is a multifactorial ocular condition, where disrupted tear film stability and ocular surface inflammation affected between 5% to 34% of the worldwide population in 2015 and posed a challenge to conventional ophthalmic treatments. Recent advances have led to potential novel therapeutics aiming to alleviate symptoms and improve patient outcomes.

A Cost Variation Analysis Of Various Statin Preparations Available In The Egyptian Market, Radwa Ahmed Ibrahim, Marwa G. Elhennawy, Samar F. Farid

Bulletin of Faculty of Pharmacy Cairo University

Introduction: Dyslipidemia is one of the main risk factors for cardiovascular diseases. Statin preparations are the most effective lipid-lowering preparations that reduce the risk of mortality related to cardiovascular diseases. In the Egyptian market, various statin preparations have different strengths and prices. Aim: The current study aims to assess the percentage of cost variations among different statin medications in the Egyptian market. Methods: This is a cost variation study conducted from November to December 2022. The data were collected by using the Egyptian master on therapeutic drugs, edition 2022, and from the Egyptian Drug Database (DDB) website. The maximum and …

Analysis Of Us Food And Drug Administration New Drug And Biologic Approvals, Regulatory Pathways, And Review Times, 1980–2022, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio, John H. Powers Iii

Pharmacy Faculty Articles and Research

U.S. laws enacted since 1983 have aimed to enhance the development and marketing of new pharmaceutical products. We thoroughly characterized all new molecular entities, therapeutic biologics, and gene and cell therapies approved by the US Food and Drug Administration (FDA) during the period 1980–2022 in the context of these laws and regulations. Throughout the study period, the FDA approved 1355 new pharmaceutical products. The median FDA review time decreased from 26.6 months prior to the Prescription Drug User Fee Act (1992), which authorized the FDA to collect fees from drug companies to 9.9 months after the Food and Drug Administration …

Quantifying Community-Based Pharmacy Student Operational And Clinical Rotation (Ippe) Activities., Kenneth Kunke, Phillip Lawrence, C. Leiana Oswald, Erin Johanson, Michelle Hon

Annual Research Symposium

The purpose of this study is to identify and describe trends in the quantity and proportion of operational and clinical activities performed by students on introductory (IPPE) rotations.

Nanoemulsion Formulation Of Pregabalin For Enhanced Nose To Brain Delivery And Biological Tracking Using Radiolabeling With 99mtc, Hend Fayez, Adli A. Selim, Rehab N. Shamma, Hassan M. Rashed

Bulletin of Faculty of Pharmacy Cairo University

Pregabalin is a γ-aminobutyric acid analogue used for the treatment of neuropathic pain, seizures, and anxiety disorders. After oral administration, its level of brain penetration is rather modest. In this research, pregabalin was formulated successfully as a nanoemulsion. To track the biodistribution of pregabalin nanoemulsion in vivo, radiolabelling of pregabalin using 99mTc was performed. The different factors affecting radiolabeling yield were studied and radiolabelling yield of 92.6 % was achieved. A biological evaluation was performed in Swiss Albino mice through comparing biodistribution of intranasal (IN) 99mTc-pregabalin nanoemulsion with intravenous (IV) 99mTc-pregabalin solution at different time intervals. Biodistribution results show a …

Tbi And Tau Loss-Of-Function Both Affect Naïve Ethanol Sensitivity In Drosophila, Gregg Roman

Faculty and Student Publications

Traumatic brain injury (TBI) is associated with alcohol abuse and higher ethanol sensitivity later in life. Currently, it is poorly understood how ethanol sensitivity changes with time after TBI and whether there are sex-dependent differences in the relationship between TBI and ethanol sensitivity. This study uses the fruit fly Drosophila melanogaster to investigate how TBI affects alcohol sensitivity and whether the effects are sex-specific. Our results indicate that flies have a significantly higher sensitivity to the intoxicating levels of ethanol during the acute phase post-TBI, regardless of sex. The increased ethanol sensitivity decreases as time progresses; however, females take longer …

Cannabidiol Exposure During Rat Pregnancy Leads To Labyrinth-Specific Vascular Defects In The Placenta And Reduced Fetal Growth, Daniel B. Hardy, David R C Natale, Kendrick Lee

Physiology and Pharmacology Publications

Introduction: Cannabis use is increasing among pregnant people, and cannabidiol (CBD), a constituent of cannabis, is often perceived as ‘‘natural’’ and ‘‘safe’’ as it is non-intoxicating. In utero, cannabis exposure is associated with negative health outcomes, including fetal growth restriction (FGR). The placenta supplies oxygen and nutrients to the fetus, and alterations in placental development can lead to FGR. While there has been some investigation into the effects of D9-THC, there has been limited investigation into the impacts of in utero gestational CBD exposure on the placenta. Methods: This study used histological and transcriptomic analysis of embryonic day (E)19.5 rat …

Share Cannabidiol Exposure During Gestation Leads To Adverse Cardiac Outcomes Early In Postnatal Life In Male Rat Offspring., Daniel B. Hardy, Steven R. Laviolette, Kendrick Lee, David Rc Natale

Physiology and Pharmacology Publications

Introduction: Studies indicate that *7% of pregnant individuals in North America consume cannabis in pregnancy. Pre-clinical studies have established that maternal exposure to D9-tetrahydrocannabinol (THC; major psychoactive component in cannabis) leads to fetal growth restriction and impaired cardiac function in offspring. However, the effects of maternal exposure to cannabidiol (CBD; major non-euphoric constituent) on cardiac outcomes in offspring remain unknown. Therefore, our objective is to investigate the functional and underlying molecular impacts in the hearts of offspring exposed to CBD in pregnancy. Methods: Pregnant Wistar rats were exposed to either 3 or 30mg/kg CBD or vehicle control i.p. daily from …