Pharmacy and Pharmaceutical Sciences Commons^™

Investigation Of The Sequence-Structure-Activity Relationship In Ponericin L1 From Neoponera Goeldii & Synergistic Interactions Of Ionic Liquids And Antimicrobials To Improve Efficacy, Alexandria S. Senetra

Theses and Dissertations

Non-traditional antimicrobials have been an area of great interest due to the increasing prevalence of antimicrobial resistance (AMR) in bacteria. Antimicrobial peptides (AMPs) & ionic liquids (ILs) are two examples that have been investigated as a potential solution. Most AMPs are naturally derived & exhibit high selectivity against bacterial targets over host cells. The venom-derived peptide, ponericin L1 from Neoponera goeldii, was used to investigate the role of cationic residues & net charge on peptide activity. Using both in vitro & microbiological methods, L1 peptide & derivatives exhibited an alpha-helical conformation with enhanced binding to lipid vesicles containing anionic lipids …

Searching For New Medications For The Treatment Of Alcohol Use Disorder, Harley M. Buechler

Theses and Dissertations

Alcohol use disorder (AUD) affects more than 15 million people in the United States. Current pharmacotherapeutic treatments for AUD are only modestly effective, necessitating the identification of new targets for medications development. In this study, the effects of the D4 receptor antagonist, L-745,870, and the CB1 negative allosteric modulator, PSNCBAM-1, were both tested for effects in ethanol conditioned place preference (CPP) and oral ethanol self-administration. Food-restricted adult male mice were trained in operant chambers to nose poke for delivery of rewards, trained on ascending concentrations of alcohol with descending concentrations of Ensure and water, until the mixture self-administered was 8% …

Parent Responses To Pediatric Pain: The Differential Effects Of Ethnicity On Opioid Consumption, Candice D. Donaldson, Brooke N. Jenkins, Michelle A. Fortier, Michael T. Phan, Daniel M. Tomaszewski, Sun Yang, Zeev N. Kain

Psychology Faculty Articles and Research

Objective

Within the context of the United States opioid epidemic, some parents often fear the use of opioids to help manage their children's postoperative pain. As a possible consequence, parents often do not dispense optimal analgesic medications to their children after surgery, putting their children at risk of suffering from postsurgical pain. The objective of this research was to assess ethnicity as a predictor of both pain and opioid consumption, and to examine how Hispanic/Latinx and Non-Hispanic White parents alter their child's opioid consumption in response to significant postsurgical pain.

Methods

Participants were 254 children undergoing outpatient tonsillectomy and/or adenoidectomy …

Evaluation Of Sodium Valproate Low Dose Efficacy In Radicular Pain Management And It’S Relation With Pharmacokinetics Parameters, Mona Ghasemian, Mohammad Bagher Owlia, Mohammad Hossein Mosaddegh, Masoud Nakhaie Nejad, Seyed Mojtaba Sohrevardi

BioMedicine

Background: Radiculopathy due to lumbar or cervical disc disease is the most common chronic neuropathic pain in adults. The aim of present study was evaluation of low dose of sodium valproate on radicular pain and determining VPA pharmacokinetics.

Materials and Methods: In this double blind randomized placebo control clinical study, 80 patients with established lumbar or cervical radicular pain, have been randomly allocated into two study groups: 40 have received sodium valproate 200 mg/day and Celecoxib 100 mg/day and acetaminophen 500 mg PRN as rescue medication, and second group has received placebo, Celecoxib and acetaminophen. Quantitative assessment of pain was …

Cocaine Hydrolase-Fc Fusion Proteins For Cocaine And Methods For Utilizing The Same, Chang-Guo Zhan, Fang Zheng, Hsin-Hsiung Tai, Xiabin Chen, Liu Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter includes isolated polypeptides that comprise a butyrylcholinestrase (BChE) polypeptide and a second polypeptide. The BChE polypeptide as well as the second polypeptide can be variants and/or fragments thereof. The presently-disclosed subject matter also includes a pharmaceutical composition that comprises the present isolated polypeptide and a suitable pharmaceutical carrier. Further still, methods are provided for treating cocaine-induced conditions, and comprise administering the isolated polypeptide and/or pharmaceutical compositions thereof to an individual.

Evaluation Of Wait Times For Pediatric Patients Receiving Chemotherapy, Kristin M. Held Wheatley Pharmd, Bcop, Rachael Gerstein Pharmd

Department of Pharmacy

No abstract provided.

Artificial Intelligence–Powered Smartphone App To Facilitate Medication Adherence: Protocol For A Human Factors Design Study, Don Roosan, Jay Chok, Mazharul Karim, Anandi V. Law, Andrius Baskys, Angela Hwang, Moom Roosan

Pharmacy Faculty Articles and Research

Background: Medication Guides consisting of crucial interactions and side effects are extensive and complex. Due to the exhaustive information, patients do not retain the necessary medication information, which can result in hospitalizations and medication nonadherence. A gap exists in understanding patients’ cognition of managing complex medication information. However, advancements in technology and artificial intelligence (AI) allow us to understand patient cognitive processes to design an app to better provide important medication information to patients.

Objective: Our objective is to improve the design of an innovative AI- and human factor–based interface that supports patients’ medication information comprehension that could potentially …

Rethinking Fda Regulation Of Complex Products, Philip E. Alford

Minnesota Journal of Law, Science & Technology

No abstract provided.

Efficient Cocaine Degradation By Cocaine Esterase-Loaded Red Blood Cells, Luigia Rossi, Francesca Pierigè, Marco Agostini, Noemi Bigini, Veronica Termopoli, Yingting Cai, Fang Zheng, Chang-Guo Zhan, Donald W. Landry, Mauro Magnani

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Recombinant bacterial cocaine esterase (CocE) represents a potential protein therapeutic for cocaine use disorder treatment. Unfortunately, the native enzyme was highly unstable and the corresponding mutagenized derivatives, RBP-8000 and E196-301, although improving in vitro thermo-stability and in vivo half-life, were a partial solution to the problem. For cocaine use disorder treatment, an efficient cocaine-metabolizing enzyme with a longer residence time in circulation would be needed. We investigated in vitro the possibility of developing red blood cells (RBCs) loaded with RBP-8000 and E196-301 as a biocompatible system to metabolize cocaine for a longer period of time. RBP 8000 stability within human …

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …

Redox-Sensitive Nanocomplex For Targeted Delivery Of Melittin, Bei Cheng, Peisheng Xu

Faculty Publications

Although peptide therapeutics have been explored for decades, the successful delivery of potent peptides in vitro and in vivo remains challenging due to the poor stability, low cell permeability, and off-target effects. We developed a redox sensitive polymer-based nanocomplex which can efficiently and stably deliver the peptide drug melittin for cancer therapy. The nanocomplex selectively targets cancer cells through lactobionic acid mediated endocytosis and releases melittin intracellularly upon the trigger of elevated redox potential. In vivo study proved that the targeted nanocomplex shows excellent potency in inhibiting tumor growth in a xenograft colon cancer mouse model. Thus, the polymer/melittin nanocomplexes …

Suspected Malignant Hyperthermia And The Application Of A Multidisciplinary Response, Laura Ebbitt, Eric Johnson, Brooke Herndon, Kristina Karrick, Aric Johnson

Pharmacy Practice and Science Faculty Publications

Purpose: Malignant hyperthermia (MH) is a critical and potentially life-threatening emergency associated with inhaled anesthetic and depolarizing neuromuscular blocker administration. This is a single center’s response to MH. Summary: When signs of MH are observed, a page for “anesthesia STAT-MH crisis” is called, triggering a multidisciplinary response, including the deployment of a Malignant Hyperthermia Cart. The MH cart and the delegation of duties allows nurses, physicians and pharmacists to quickly understand their role in the stabilization, transition and recovery of a suspected MH patient. Conclusion: This case highlights the importance of multi-disciplinary involvement in these rare, but potentially fatal, cases.

Polyphenols Profile Of Pomegranate Leaves And Their Role In Green Synthesis Of Silver Nanoparticles, Noha Swilam, Khaled Nematallah

Pharmacy

The current study reports on polyphenols profile of pomegranate leaves (PL) Punica granatum grown in Egypt and exhibiting their role in development of an eco-friendly method of green synthesis of silver nanoparticles (AgNPs). PL aqueous alcohol extract was fractionated, the major phenolic compound was isolated from the polyphenols rich fraction (ethyl acetate fraction) and identified by conventional and spectroscopic methods of analysis as ellagic acid. Furthermore, the fraction was standardized and analysed using UPLC-PDA-UV and LC–MS-MS techniques revealing tentative identification of 23 polyphenolic compounds, quantifying ellagic acid as 43.14 ± 0.57 μg/mg of the fraction. AgNPs were successfully synthesized with …

Acute And Chronic Dosing Of A High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody In Mice, Demi M. Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C. Zambon, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as brain drug-delivery vectors has revealed the effect of dosing regimen, valency, and affinity on brain uptake, TfR expression, and Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous dosing in mice. The effects of a high-affinity bivalent TfRMAb with a murine constant region, without a fusion partner, following extravascular dosing in mice are, however, not well characterized. Here we elucidate the plasma pharmacokinetics and safety of a high-affinity bivalent …

Two C-Terminal Sequence Variations Determine Differential Neurotoxicity Between Human And Mouse Α-Synuclein, Natalie Landeck, Katherine E. Strathearn, Daniel Ysselstein, Kerstin Buck, Sayan Dutta, Siddhartha Banerjee, Zhengjian Lv, John D. Hulleman, Jagadish Hindupur, Li-Kai Lin, Sonal Padalkar, Lia A. Stanciu, Yuri L. Lyubchenko, Deniz Kirik, Jean-Christophe Rochet

Journal Articles: Pharmaceutical Sciences

BACKGROUND: α-Synuclein (aSyn) aggregation is thought to play a central role in neurodegenerative disorders termed synucleinopathies, including Parkinson's disease (PD). Mouse aSyn contains a threonine residue at position 53 that mimics the human familial PD substitution A53T, yet in contrast to A53T patients, mice show no evidence of aSyn neuropathology even after aging. Here, we studied the neurotoxicity of human A53T, mouse aSyn, and various human-mouse chimeras in cellular and in vivo models, as well as their biochemical properties relevant to aSyn pathobiology.

METHODS: Primary midbrain cultures transduced with aSyn-encoding adenoviruses were analyzed immunocytochemically to determine relative dopaminergic neuron viability. …

Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]₄ and c[WR]₅ consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in the …

Lipocalin-2 Deficiency May Predispose To The Progression Of Spontaneous Age-Related Adiposity In Mice, Keya Meyers, María López, Joanna Ho, Savannah Wills, Srujana Rayalam, Shashidharamurthy Taval

PCOM Scholarly Works

Lipocalin-2 (Lcn2) is an innate immune protein elevated by several orders of magnitude in various inflammatory conditions including aging and obesity. Recent studies have shown that Lcn2 is secreted by adipocytes in response to inflammation and is categorized as a new adipokine cross-linking innate immunity and metabolic disorders including obesity. However, the involvement of Lcn2 and its function during the progression of obesity is largely unknown. Recently, browning of white adipose tissue (WAT) has gained attention as a therapeutic strategy to combat obesity. Herein, we have shown that treatment of mature 3T3-L1 adipocytes with recombinant Lcn2 (rec-Lcn2) resulted in the …

Effect Of High Glucose On Ocular Surface Epithelial Cell Barrier And Tight Junction Proteins, Saleh M. Alfuraih, Ashley Barbarino, Christopher Ross, Kiumars Shamloo, Vishal Jhanji, Miao Zhang, Ajay Sharma

Pharmacy Faculty Articles and Research

PURPOSE. Patients with diabetes mellitus are reported to have ocular surface defects, impaired ocular surface barrier function, and a higher incidence of corneal and conjunctival infections. Tight junctions are critical for ocular surface barrier function. The present study was designed to investigate the effect of high glucose exposure on human corneal and conjunctival epithelial cell barrier function and tight junction proteins.

METHODS. Human corneal and conjunctival epithelial cells were exposed to 15 mM and 30 mM glucose for 24 and 72 hours. The barrier function was measured using transepithelial electrical resistance (TEER). The cell migration was quantified using scratch assay. …

Everything Is Science: A Free City-Wide Science Festival, Jarrod W. Creameans, Michelle G. Pitts, Olivia White, Kellen M. Greenwell, Kristie Colón, Sylvie Garneau-Tsodikova, Vincent J. Venditto

Pharmaceutical Sciences Faculty Publications

A week-long, city-wide science festival called Everything is Science (EiS) was developed to educate the community in an informal manner. The festival serves as a platform for presenters from diverse professions to give engaging talks (without PowerPoint slides) to the public, free of charge, in restaurants and bars around town. Over 350 people attended the events over 5 days with 33 presenters. Surveys completed by attendees and session coordinators indicate strong support for this festival. Altogether, the EiS festival serves as a no-cost method to engage with the community and improve science literacy with potential for adoption in other cities.

Consider Real Costs Before Implementing A 340b Program, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Pharmacy Practice & Administration

The 340B drug pricing program was created to improve access to outpatient medications for low-income and underinsured r uninsured patients. It has exponentially grown with the expansion of the definition of a covered entity and the change to allow multiple contract pharmacies. Still, there are debates about the program’s financial impact and whether the discounts are passed along to enough underinsured or uninsured patients.

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …

Methods For Using Nhanes For Exposure Estimates, Heather R. Campbell, Robert A. Lodder

Pharmaceutical Sciences Faculty Publications

The National Health and Nutrition Examination Survey (NHANES) is a scheme of studies with the objective of measuring the health and nutritional status of adults and children in the United States. The survey is unique in that it has a clinical component (NCT00005154), and combines interviews and physical examinations into its data sets. NHANES is an important program of the National Center for Health Statistics (NCHS). NCHS is a unit of the Centers for Disease Control and Prevention (CDC) and has the responsibility for producing vital and health statistics for the United States. Data from the NHANES studies …

Afatinib For The Treatment Of Egfr Mutation-Positive Nsclc: A Review Of Clinical Findings, R. Donald Harvey, Val R. Adams, Tyler Beardslee, Patrick Medina

Pharmacy Practice and Science Faculty Publications

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors represent the standard of care in patients with EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC). The availability of several EGFR tyrosine kinase inhibitors approved for use in the first-line or later settings in NSCLC warrants an in-depth understanding of the pharmacological properties of, and clinical data supporting, these agents. The second-generation, irreversible ErbB-family blocker, afatinib, has been extensively studied in the context of EGFRm+ NSCLC. Results from the LUX-Lung 3 and 6 studies showed that afatinib was more active and better tolerated than chemotherapy in patients with tumors …

Empirical Fluoroquinolones Versus Broad-Spectrum Beta-Lactams For Gram-Negative Bloodstream Infections In The Absence Of Antimicrobial Resistance Risk Factors, Majdi N. Al-Hasan, Alyssa P. Gould, Chelsea Drennan, Olivia Hill, Julie Ann Justo, Joseph Kohn, P Brandon Bookstaver

Faculty Publications

OBJECTIVES: Increasing antimicrobial resistance rates limit empirical antimicrobial treatment options for Gram-negative bloodstream infections (GN-BSI). However, antimicrobial resistance may be predicted based on patient-specific risk factors using precision medicine concepts. This retrospective, 1:2 matched cohort examined clinical outcomes in hospitalized adults without major risk factors for antimicrobial resistance receiving empirical fluoroquinolones or broad-spectrum beta-lactams (BSBL) for GN-BSI at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 2010 through June 2015. METHODS: Multivariable logistic regression was used to examine early treatment failure at 72-96 h from GN-BSI. Cox proportional hazards regression was used to examine 28-day mortality and hospital length …

Patterns And Predictors Of Older Adult Medicare Part D Beneficiaries’ Receipt Of Medication Therapy Management, Antoinette B. Coe, Omolola A. Adeoye-Olatunde, Deborah L. Pestka, Margie Snyder, Alan Zillich, Karen B. Farris, Joel F. Farley

Department of Pharmacy Practice Faculty Publications

Background

Medicare Part D medication therapy management (MTM) includes an annual comprehensive medication review (CMR) as a strategy to mitigate suboptimal medication use in older adults.

Objectives

To describe the characteristics of Medicare beneficiaries who were eligible, offered, and received a CMR in 2013 and 2014 and identify potential disparities.

Methods

This nationally representative cross-sectional study used a 20% random sample of Medicare Part A, B, and D data linked with Part D MTM files. A total of 5,487,343 and 5,822,188 continuously enrolled beneficiaries were included in 2013 and 2014, respectively. CMR use was examined among a subset of 620,164 …

Cosmetovigilance: A New Concept For Residency Curriculum, Jennifer Jones, Hale Z. Toklu

HCA Healthcare Journal of Medicine

Primary care physicians need to incorporate “cosmetovigilance” into their post-graduate curriculum to increase their residents’ awareness of the adverse reactions induced by the use of cosmetic products, as well as promoting good reporting behavior.

Hydrophobic Interactions Between The Ha Helix And S4‐S5 Linker Modulate Apparent Ca2+ Sensitivity Of Sk2 Channels, Young-Woo Nam, Meng Cui, Razan Orfali, Adam Viegas, Misa Nguyen, Eman H. M. Mohammed, Khalid Zoghebi, Simin Rahighi, Keykavous Parang, Miao Zhang

Pharmacy Faculty Articles and Research

Aim

Small‐conductance Ca²⁺‐activated potassium (SK) channels are activated exclusively by increases in intracellular Ca²⁺, that binds to calmodulin constitutively associated with the channel. Wild‐type SK2 channels are activated by Ca²⁺ with an EC50 value of ~0.3 μM. Here, we investigate hydrophobic interactions between the HA helix and the S4‐S5 linker as a major determinant of channel apparent Ca²⁺ sensitivity.

Methods

site‐directed mutagenesis, electrophysiological recordings and molecular dynamic (MD) simulations were utilized.

Results

Mutations that decrease hydrophobicity at the HA‐S4‐S5 interface lead to Ca²⁺ hyposensitivity of SK2 channels. Mutations that increase hydrophobicity result in …

Epigenetic Diet To Modulate Immune Response Against Sars-Cov-2, Andika Andika, Risa Ahdyani, Linda Erlina, Azminah Azminah, Arry Yanuar

Pharmaceutical Sciences and Research

The COVID-19 pandemic has spread to various parts of the world and caused many deaths. The victims are infected by SARS-CoV-2, a new type of coronavirus that has appeared since December 2019 and caused respiratory symptoms, fever, coughing, and shortness of breath. In addition to social distancing, wearing masks and washing hands, diet is important as a defense of the body against SARS-CoV-2. In this review, researchers conducted epigenetic diet studies that could potentially inhibit SARS-CoV-2, and can be consumed and used on a daily basis.

Antioxidant And Elastase Inhibitor Potential Of Petals And Receptacle Of Rose Flower (Rosa Damascena), Evi Mawarni, Chrismis Novalinda Ginting, Linda Chiuman, Ermi Girsang, Rr. Anisa Siwianti Handayani, Wahyu Widowati

Pharmaceutical Sciences and Research

Free radicals can cause damage to cells or tissues, autoimmune diseases, degenerative diseases, or cancer. Therefore, the body needs important substances, namely antioxidants that can help protect the body by reducing negative effect from free radicals. Rose flower (Rosa damascena) has anthocyanin pigment which belongs to flavonoid group which has a function as antioxidant or free radical scavenger. This study aims to determine antioxidant and anti-elastase potentials of rose petals and receptacles. The method used in this study was a qualitative phytochemical test to determine the compounds contained in the Rose Petal Extract (RPE) and Rose Receptacle Extract (RRE), ABTS …

Hypusination Of Eif5a Regulates Cytoplasmic Tdp-43 Aggregation And Accumulation In A Stress-Induced Cellular Model, Shayna Smeltzer, Zainuddin Quadri, Abraian Miller, Frank Zamudio, Jordan Hunter, Nicholas J.F. Stewart, Sheba Saji, Daniel C. Lee, Dale Chaput, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

TAR DNA-binding protein 43 (TDP-43) is a nuclear RNA/DNA binding protein involved in mRNA metabolism. Aberrant mislocalization to the cytoplasm and formation of phosphorylated/aggregated TDP-43 inclusions remains the hallmark pathology in a spectrum of neurodegenerative diseases, including frontotemporal disorders and Alzheimer's disease. Eukaryotic Translation Initiation Factor 5A undergoes a unique post-translation modification of lysine to hypusine (K50), which determines eIF5A binding partners. We used a sodium arsenite-induced cellular stress model to investigate the role of hypusinated eIF5A (eIF5A^HypK50) in governing TDP-43 cytoplasmic mislocalization and accumulation in stress granule. Our proteomics and functional data provide evidence that eIF5A interacts …