Pharmacy and Pharmaceutical Sciences Commons^™

Transforming Growth Factor-Β1 Decreases Β2-Agonist–Induced Relaxation In Human Airway Smooth Muscle, Christie A. Ojiaku, Elena Chung, Vishal Parikh, Jazmean K. Williams, Anthony Schwab, Ana Lucia Fuentes, Maia L. Corpuz, Victoria Lui, Sam Paek, Natalia M. Bexiga, Shreya Narayan, Francisco J. Nunez, Kwangmi An, Rennolds S. Ostrom, Steven S. An, Reynold A. Pannettieri Jr.

Pharmacy Faculty Articles and Research

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β₂-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1–treated HASM cells, ISO evoked markedly lower …

Utility Of Combination Antimicrobial Therapy In Adults With Bloodstream Infections Due To Enterobacteriaceae And Non-Fermenting Gram-Negative Bacilli Based On In Vitro Analysis At Two Community Hospitals, Rachel Foster, Casey Troficanto, P. Brandon Bookstaver, Joseph Kohn, Julie Ann Justo, Majdi Al-Hasan

Faculty Publications

This study examined the utility of combination therapy for bloodstream isolates of Enterobacteriaceae and non-fermenting Gram-negative bacilli (NFGN) from adults at two community hospitals from January 2010 through to June 2015. Changes to in vitro antimicrobial susceptibilities by adding ciprofloxacin or gentamicin to third-generation cephalosporins (3GC) were examined overall and in patients with risk factors for 3GC resistance. Overall ceftriaxone susceptibility among Enterobacteriaceae was 996/1063 (94%) and 247/295 (84%) in patients with 3GC resistance risk factors. Susceptibilities increased marginally by adding ciprofloxacin or gentamicin (mean difference 2.4% (95% CI 1.5, 3.4) and 3.0% (95% CI 2.0, 4.0), respectively, overall and …

Synthesis Of Novel Library Of Cyanopyrrolidinyl Beta-Amino Alcohols And Matrine Alkaloids, Xiaotian Chen

Theses and Dissertations

Cyanopyrrolidines and beta-Amino alcohols are molecular scaffolds that are highly found in commercially available drugs. We developed a multi-step synthetic method to form a novel library of compounds as inhibitors that share both scaffolds toward potent and selective diabetes therapeutics. Despite the ease for the synthesis of Cyanopyrrolidines, the difficulty of forming high selective beta-Amino alcohols is challenging. We successfully find the best condition for the preference of highly selective mono-alkylation and double-alkylation products and produce them with high yield.

Matrine is an alkaloid found in plants from the genus Sophora and can produce some pharmacological effects such as anti-cancer …

Carboxylic Acids Accelerate Acidic Environment-Mediated Nanoceria Dissolution, Robert A. Yokel, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Ligands that accelerate nanoceria dissolution may greatly affect its fate and effects. This project assessed the carboxylic acid contribution to nanoceria dissolution in aqueous, acidic environments. Nanoceria has commercial and potential therapeutic and energy storage applications. It biotransforms in vivo. Citric acid stabilizes nanoceria during synthesis and in aqueous dispersions. In this study, citrate-stabilized nanoceria dispersions (∼4 nm average primary particle size) were loaded into dialysis cassettes whose membranes passed cerium salts but not nanoceria particles. The cassettes were immersed in iso-osmotic baths containing carboxylic acids at pH 4.5 and 37 °C, or other select agents. Cerium atom material …

Icatibant Is Not Helpful For The Treatment Of Ace Inhibitor-Induced Angioedema, Samantha R. Schwartz

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sinert R, Levy P, Bernstein JA, et al. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017; 5(5): 1402-1409. doi: 10.1016/j.jaip.2017.03.003.

Development Of A Novel Loop-Mediated Isothermal Amplification Method To Detect Guiana Extended-Spectrum (Ges) Β-Lactamase Genes In Pseudomonas Aeruginosa, Chika Takano, Mitsuko Seki, Dong Wook Kim, Humphrey Gardner, Robert E. Mclaughlin, Paul E. Kilgore, Kazunari Kumasaka, Satoshi Hayakawa

Department of Pharmacy Practice

Infections caused by multidrug-resistant Pseudomonas aeruginosa in hospitalized patients are often fatal, and nosocomial infections caused by Guiana extended-spectrum (GES) β-lactamase-producing strains are of growing concern. Several genotypes of the GES β-lactamase gene (bla_GES) include a single missense mutation, a change from G to A at nucleotide position 493 (G_493A) that changes glycine to serine; the mutant enzyme exhibits carbapenemase activity. Rapid and reliable identification of drug-resistance is important in clinical settings; however, culture methods remain the gold standard. Conventional and real-time PCR cannot identify carbapenemase-producing genotypes, and direct DNA sequencing is essential. We established …

Self-Care Therapeutics And Non-Prescription Drugs I Php 319, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Implementation Of A Cardiac Transitions Of Care Pilot Program: A Prospective Study Of Inpatient And Outpatient Clinical Pharmacy Services For Patients With Heart Failure Exacerbation Or Acute Myocardial Infarction, Julie A. Murphy, Michelle N. Schroeder, Rachel E. Rarus, Idris Yakubu, Sean O. P. Mckee, Steven J. Martin

Pharmacy Faculty Scholarship

Background:: Pharmacists may assist with reducing 30-day readmission rates for patients with heart failure (HF) exacerbation or acute myocardial infarction (AMI) by promoting medication adherence.

Objective:: To determine the change in 30-day readmission rates for patients with HF exacerbation or AMI after implementation of a "high-touch" standard of care.

Methods:: Patients admitted with HF exacerbation, non-ST-segment elevation AMI, or ST-segment elevation AMI from August 1, 2013, to June 30, 2015, were included in this prospective study. Patients were educated while in the inpatient setting and followed up in the outpatient setting through telephone contact and scheduling a medication therapy management …

Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Chromone/Aza-Chromone Fused Α-Aminophosphonates As Src Kinase Inhibitors, S. Bapat, N. Viswanadh, M. Mujahid, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, M. Karthikeyan, M. Muthukrishnan, Renu Vyas

Pharmacy Faculty Articles and Research

A series of novel chromone/aza-chromone fused α-aminophosphonate derivatives were synthesized in good yields using silica chloride as the catalyst. All the synthesized compounds were tested for their c-Src kinase inhibitory activity. Aza-chromone compound showed Src kinase inhibition with an IC50 value of 15.8 µM. The compounds were subjected to molecular docking and dynamics simulations to study the atomic level interactions with an unphosphorylated proto-oncogenic tyrosine protein kinase Src (PDB code 1Y57) as well as phosphorylated tyrosine protein kinase Src (PDB code 2H8H). Docking and molecular dynamic results revealed phosphorylated Src tyrosine kinase protein better results than unphosphorylated tyrosine Src kinase …

Carbapenem-Resistant Enterobacteriaceae Infections: A Review Of Epidemiology And Treatment Options, Julie Harting

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Use Of Aloe Vera In Cancer Radiation: An Updated Comprehensive Review, Carrie-Jo E. Farrugia, Elizabeth Sutton Burke, Mariah E. Haley, Komul T. Bedi, Mona A. Gandhi

Doctoral External Publications

Introduction: Many cancer patients require radiation therapy and often experience adverse effects including erythema, itching, and pain. Aloe vera has been studied for its potential use in the prevention and treatment of radiation related adverse effects as it possesses a variety of properties and is considered an antioxidant and anti-inflammatory agent. Multiple controlled trials have been performed in order to evaluate the efficacy of aloe vera for the prevention and treatment of radiation side effects. Previous systematic reviews have examined the use of aloe vera for radiation-induced skin reactions, however updated literature now includes the use of aloe vera in …

Daptomycin Dosing In Obese Patients: Analysis Of The Use Of Adjusted Body Weight Versus Actual Body Weight, Ashley N. Fox, Winter J. Smith, Katherine E. Kupiec, Stephanie J. Harding, Beth H. Resman-Targoff, Stephen B. Neely, Bryan P. White, Ryan E. Owens

Pharmacy Faculty Publications and Presentations

Background: Food and Drug Administration-approved daptomycin dosing uses actual body weight, despite limited dosing information for obese patients. Studies report alterations in daptomycin pharmacokinetics and creatine phosphokinase elevations associated with higher weight-based doses required for obese patients. Limited information regarding clinical outcomes with alternative daptomycin dosing strategies in obesity exists. Objective: This study evaluates equivalency of clinical and safety outcomes in obese patients with daptomycin dosed on adjusted body weight versus a historical cohort using actual body weight. Methods: This retrospective, single center study compared equivalency of outcomes with two onesided tests in patients with body mass index >30 kg/m2 …

A Rational Approach For Creating Peptides Mimicking Antibody Binding, Sameer Sachdeva, Hyun Joo, Jerry Tsai, Bhaskara Jasti, Xiaoling Li

School of Pharmacy Faculty Articles

This study reports a novel method to design peptides that mimic antibody binding. Using the Knob-Socket model for protein-protein interaction, the interaction surface between Cetuximab and EGFR was mapped. EGFR binding peptides were designed based on geometry and the probability of the mapped knob-sockets pairs. Designed peptides were synthesized and then characterized for binding specificity, affinity, cytotoxicity of drug-peptide conjugate and inhibition of phosphorylation. In cell culture studies, designed peptides specifically bind and internalize to EGFR overexpressing cells with three to four-fold higher uptake compared to control cells that do not overexpress EGFR. The designed peptide, Pep11, bound to EGFR …

Estradiol Modulation Of The Renin-Angiotensin System And The Regulation Of Fear Extinction, Jenna N Parrish, Megan L Bertholomey, Hong W Pang, Robert Charles Speth, Mary M Torregrossa

Faculty Articles

Post-traumatic stress disorder (PTSD) is more prevalent in women than men, yet much remains to be determined regarding the mechanism underlying this sex difference. Clinical and preclinical studies have shown that low estradiol levels during extinction of fear conditioning in rodents (i.e., cue exposure therapy in humans) leads to poor extinction consolidation and increased fear during extinction recall. The renin-angiotensin system (RAS) is also associated with stress-related pathologies, and RAS antagonists can enhance extinction consolidation in males. However, less is known about how estradiol and the RAS converge to alter fear extinction consolidation in females. Since estradiol downregulates the RAS, …

Pharmacological Properties Of Chromobacterium Violaceum Violacein At The Human Serotonin 2c Receptor, Letimicia S. Fears, Mary E. Curtis, Terrance L. Johnson, Hugh M. Fentress

Biology Faculty Research

The monoamine neurotransmitter serotonin (5-HT) plays a role in many physiological responses by interacting with various receptor subtypes. The 5-HT_2C receptor subtype is a 7-transmembrane, G protein-coupled receptor (GPCR) that is involved in neuronal excitability, spatial learning, mood, and appetite. The microorganism Chromobacterium violaceum produces a purple pigment, violacein, which can be extracted and purified. Violacein has antibiotic, antileishmanial, antifungal and antitumoral properties in various cancer cell lines. Violacein is derived from the amino acid tryptophan as is 5-HT and therefore, the two have similar chemical structures. However, no one has reported the activity of violacein at 5-HT receptors. …

Src Family Kinase Inhibitors Block Translation Of Alphavirus Subgenomic Mrnas, Rebecca Broeckel, Sanjay Sarkar, Nicholas A. May, Jennifer Totonchy, Craig N. Kreklywich, Patricia Smith, Lee Graves, Victor R. Defilippis, Mark T. Heise, Thomas E. Morrison, Nathaniel Moorman, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Alphaviruses are arthropod-transmitted RNA viruses that can cause arthralgia, myalgia, and encephalitis in humans. Since the role of cellular kinases in alphavirus replication is unknown, we profiled kinetic changes in host kinase abundance and phosphorylation following chikungunya virus (CHIKV) infection of fibroblasts. Based upon the results of this study, we treated CHIKV-infected cells with kinase inhibitors targeting the Src family kinase (SFK)–phosphatidylinositol 3-kinase (PI3K)–AKT–mTORC signaling pathways. Treatment of cells with SFK inhibitors blocked the replication of CHIKV as well as multiple other alphaviruses, including Mayaro virus, O’nyong-nyong virus, Ross River virus, and Venezuelan equine encephalitis virus. Dissecting the effect of …

Treatment Of Pulmonary Hypertension, Lissette Bauza

All Publications

No abstract provided.

Pharmacological Management Of Cystic Fibrosis - Exploring The Therapeutic Advancements In Cystic Fibrosis, Jessica Justiz

All Publications

No abstract provided.

Telepharmacy: The Future Of Pharmacy Services, Monica Tadros

All Publications

No abstract provided.

I Can't Breathe - Cystic Fibrosis, Mayret Gonzalez

All Publications

No abstract provided.

Update On Anticoagulation Agents And Reversals, Carolyn Ruiz

All Publications

No abstract provided.

Beyond The Hospital Doors - The Future Of Transitions Of Care, Lorena Berrios Caldero

All Publications

No abstract provided.

The Latest And Greatest On Usp 797/800 - An Update, Alyssa Donadio

All Publications

No abstract provided.

Update On Epilepsy - Newer Treatment Options, Kamarena Sankar

All Publications

No abstract provided.

Updates In The Treatment Of Alzheimer's Disease, Nothing To Forget About, Jessica Greenwood

All Publications

No abstract provided.

Where Are We With Marijuana And The Smoking Truth About Vaping?, Lorenzo Porras Jr.

All Publications

No abstract provided.

Abuse And Misuse Of Stimulants For Adhd, Rita Chamoun

All Publications

No abstract provided.

Biosynthetic And Synthetic Strategies For Assembling Capuramycin-Type Antituberculosis Antibiotics, Ashley L. Biecker, Xiaodong Liu, Jon S. Thorson, Zhaoyong Yang, Steven G. Van Lanen

Pharmaceutical Sciences Faculty Publications

Mycobacterium tuberculosis (Mtb) has recently surpassed HIV/AIDS as the leading cause of death by a single infectious agent. The standard therapeutic regimen against tuberculosis (TB) remains a long, expensive process involving a multidrug regimen, and the prominence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains continues to impede treatment success. An underexplored class of natural products—the capuramycin-type nucleoside antibiotics—have been shown to have potent anti-TB activity by inhibiting bacterial translocase I, a ubiquitous and essential enzyme that functions in peptidoglycan biosynthesis. The present review discusses current literature concerning the biosynthesis and chemical synthesis of capuramycin …

Cytochrome P450s And Uses Thereof, Joseph Chappell, Lyle F. Ralston

Pharmaceutical Sciences Faculty Patents

The invention relates to isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention relates to uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.

Cytochrome P450s And Uses Thereof, Joseph Chappell, Lyle F. Ralston

Pharmaceutical Sciences Faculty Patents

The invention relates to isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention relates to uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.