Pharmacy and Pharmaceutical Sciences Commons^™

Research News: 2013, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants and contracts recently awarded

Structure Based Identification And Characterization Of Flavonoids That Disrupt Human Papillomavirus-16 E6 Function, Elliot J. Androphy, Jonathan J. Cherry, Anne Rietz, Anna Malinkevich, Yuqi Liu, Meng Xie, Matthew D. Bartolowits, Vincent J. Davisson, James D. Baleja

Department of Medicinal Chemistry and Molecular Pharmacology Graduate Student Publications

Expression and function of the human papillomavirus (HPV) early protein 6 (E6) is necessary for viral replication and oncogenesis in cervical cancers. HPV E6 targets the tumor suppressor protein p53 for degradation. To achieve this, “high-risk” HPV E6 proteins bind to and modify the target specificity of the ubiquitin ligase E6AP (E6 associated protein). This E6-dependent loss of p53 enables the virus to bypass host cell defenses and facilitates virally induced activation of the cell cycle progression during viral replication. Disruption of the interaction between E6 and E6AP and stabilization of p53 should decrease viability and proliferation of HPV positive …

Synthesis Of Novel Azetidines, Amber Thaxton

LSU New Orleans Theses and Dissertations

Azetidine is a four-membered nitrogen-containing heterocyclic ring that has recently received a great deal of attention as a molecular scaffold for the design and preparation of biologically active compounds. Structure-activity studies employing functionalized azetidines have led to the development of variety of drug molecules and clinical candidates encompassing a broad spectrum of biological activities.

Herein, the synthesis a novel series of 3-aryl-3-arylmethoxyazetidines is described. Selected 3-aryl-3-arylmethoxyazetidines were evaluated for their binding affinity to multiple monoaminergic transporters for the potential treatment of methamphetamine addiction. It was discovered that this scaffold exhibits high binding affinity (nM) for both the serotonin and dopamine …

Survey Of Pharmacist-Managed Primary Care Clinics Using Healthcare Failure Mode And Effect Analysis (Hfmea), Ashley H. Meredith, Jasmine Gonzalvo, Darin Ramsey, Alison M. Walton, Zachary Alan Weber, Jessica E. Wilhoite

Department of Pharmacy Practice Faculty Publications

Objectives: The primary objective was to expand upon results of a previously piloted patient perception survey with Healthcare Failure Mode and Effect Analysis (HFMEA), to identify areas within pharmacist-managed clinics needing improvement.

Methods: The survey was adapted for use in pharmacist-managed clinics. Patients completed the survey following regularly scheduled pharmacist appointments. Data were analyzed with a method adapted from HFMEA. Product scores could range from five to 25. A product of five indicates that pharmacists are doing a good job on the items that patients place the most value on, while a product score of 25 indicates that pharmacists are …

Microbicidal Effects Of Α- And Θ-Defensins Against Antibiotic-Resistant Staphylococcus Aureus And Pseudomonas Aeruginosa, Kenneth P. Tai, Karishma Kamdar, Jason Yamaki, Valerie V. Le, Dat Tran, Patti Tran, Michael E. Selsted, Andre J. Ouelette, Annie Wong-Beringer

Pharmacy Faculty Articles and Research

Antibiotic-resistant bacterial pathogens threaten public health. Because many antibiotics target specific bacterial enzymes or reactions, corresponding genes may mutate under selection and lead to antibiotic resistance. Accordingly, antimicrobials that selectively target overall microbial cell integrity may offer alternative approaches to therapeutic design. Naturally occurring mammalian α- and θ-defensins are potent, non-toxic microbicides that may be useful for treating infections by antibiotic-resistant pathogens because certain defensin peptides disrupt bacterial, but not mammalian, cell membranes. To test this concept, clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), including vancomycin heteroresistant strains, and ciprofloxacin-resistant Pseudomonas aeruginosa (Cip^R-PA) were tested for sensitivity to …

Computer Testing To Document Student Achievement Of Learning Outcomes, Richard O'Brocta

Pharmacy Faculty/Staff Publications

In lieu of an abstract, here is the letter's first paragraph:

To the Editor. Every course should have published learning outcomes describing what students should be able to do upon successful completion of the course.1 Assessing how well the students have achieved the learning outcomes for the course is very important as this can provide evidence of learning for the student and a measure of the effectiveness of the course. Evidence of learning is important for accreditation purposes and can provide data that can be used to improve the course.2 Documenting student achievement of outcomes can be …

Tobramycin Disposition In The Lung Following Airway Administration, Min Li

Theses and Dissertations

Tobramycin disposition following airway administration was evaluated by meta-analysis of human data in the literature and, experimentally, using a realistic ex vivo model, the isolated perfused rat lung preparation (IPRL). Pulmonary bioavailability of inhaled tobramycin in published studies was re-evaluated separately for CF and healthy adults, with the drug’s intrinsic pharmacokinetic (PK) parameters obtained from intravenous (IV) studies in the literature. While large variations in tobramycin’s clearance precluded accurate assessment of its bioavailability, the results were indicative of substantial pulmonary absorption, in spite of its hydrophilic and poly cationic properties. To explore its disposition kinetics and mechanisms following airway administration, …

Evaluation Of The Appropriate Weaning Of Neonatal Morphine Solution (Nms) In The Treatment Of Neonatal Abstinence Syndrome (Nas) And Its Effect On Length Of Stay (Los), Nicole Hollinger, Pharmd Candidate, Christopher Hvisdas, Pharmd Candidate, Maria Samohod, Md Candidate, Tara E. Decerbo, Pharmd, Janet Larson, Md, Kristin Mckenna, Md, Lindsey Roke, Pharmd

Pharmacy Presentations, Posters, and Grand Rounds

Purpose: Neonates suffering from NAS receive NMS to treat withdrawal symptoms associated with this disease. Frequent NMS dosing and close monitoring are required to ensure adequate symptom control and prevent adverse events. Maximum dose achieved, titration, severity of disease, and variance in in-utero exposure to addictive drugs all contribute to length of stay. The primary objective of this drug utilization evaluation is to assess adherence to current institutional guidelines for titrating neonates and infants off NMS and to identify opportunities for improvement to potentially decrease length of stay in this population.

Methods: A retrospective chart review of neonates …

Anticancer Properties Of Distinct Antimalarial Drug Classes, Rob Hooft Van Huijsduijnen, R. Kiplin Guy, Kelly Chibale, Richard K. Haynes, Ingmar Peitz, Gerhard Kelter, Margaret A. Phillips, Jonathan L. Vennerstrom, Yongyuth Yuthavong, Timothy N. C. Wells

Journal Articles: Pharmaceutical Sciences

We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin …

Characterization Of Prophylactic Antiemetic Regimens In Pediatric Patients Receiving Moderately And Highly Emetogenic Chemotherapy, Jessica Degiacomo Pharmd, Kristin M. Held Pharmd, Bcop

Department of Pharmacy

No abstract provided.

Synthesis Of Novel Ciprofloxacin Analogues And Evaluation Of Their Anti-Proliferative Effect On Human Cancer Cell Lines, Narva Suresh, Hunsur Nagendra Nagesh, Kondapalli Venkata Govri Chandra Sekhar, Anil Kumar, Amir Nasrolahi Shirazi, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized (1H NMR, 13C NMR and LCMS) and evaluated for their inhibitory activity on the proliferation of human caucasian acute lymphoblastic leukemiacells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin analogues 3t at 50 µM showed comparable potency to doxorubicin (10mol) in all three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35% selectively over other two cell lines. Cancer is a leading cause of death worldwide. It is a group of diseases characterized by uncontrolled growth. Cancer …

Attenuation Of Parenteral Nutritionassociated Liver Disease By Omega-3 Long-Chain Polyunsaturated Fatty Acids, Emma Monique Tillman

Theses and Dissertations (ETD)

No abstract provided.

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Acquisition Of Medication For Short-Term Medical Mission Trips, Christine R. Birnie

Pharmacy Faculty/Staff Publications

In lieu of an abstract, here is the article's first paragraph:

Each year, increasing numbers of pharmacists and pharmacy students participate in medical mission trips around the world. The Christian Pharmacist Fellowship International (CPFI) partners with Global Health Outreach (GHO) to ensure that one or two pharmacists are included on each of their multi-disciplinary medical trips. Over the past years, the number of pharmacists participating on these trips has increased from 20 pharmacists in 2002 to 78 pharmacists in 2012.¹ In recent years, pharmacy students have also become active team members, and several schools are now organizing medical mission …

The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The voltage dependence of charges in voltage-sensitive proteins, typically displayed as charge versus voltage (Q-V) curves, is often quantified by fitting it to a simple two-state Boltzmann function. This procedure overlooks the fact that the fitted parameters, including the total charge, may be incorrect if the charge is moving in multiple steps. We present here the derivation of a general formulation for Q-V curves from multistate sequential models, including the case of infinite number of states. We demonstrate that the commonly used method to estimate the charge per molecule using a simple Boltzmann fit is not only inadequate, but in …

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang, Lin Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

Binding, Transcytosis And Biodistribution Of Anti-Pecam-1 Iron Oxide Nanoparticles For Brain-Targeted Delivery, Mo Dan, David B. Cochran, Robert A. Yokel, Thomas D. Dziubla

Pharmaceutical Sciences Faculty Publications

OBJECTIVE: Characterize the flux of platelet-endothelial cell adhesion molecule (PECAM-1) antibody-coated superparamagnetic iron oxide nanoparticles (IONPs) across the blood-brain barrier (BBB) and its biodistribution in vitro and in vivo.

METHODS: Anti-PECAM-1 IONPs and IgG IONPs were prepared and characterized in house. The binding affinity of these nanoparticles was investigated using human cortical microvascular endothelial cells (hCMEC/D3). Flux assays were performed using a hCMEC/D3 BBB model. To test their immunospecificity index and biodistribution, nanoparticles were given to Sprague Dawley rats by intra-carotid infusion. The capillary depletion method was used to elucidate their distribution between the BBB and brain parenchyma.

RESULTS: Anti-PECAM-1 …

Alcohol And Medication Use In Community-Dwelling Older Adults: Understanding The Effect Of Alcohol And Central Nervous System-Acting Medications On The Risk For Falls, Maitreyee Mohanty

Theses and Dissertations

Introduction: Aging, comorbid conditions, and use of medications render older adults more susceptible to alcohol-disease or alcohol-drug interactions that may lead to harmful outcomes. In this dissertation project the risk profile of alcohol and medications use among older adults was investigated. Considering the rise in CNS-acting medication use and the adverse effect profile linked to CNS-acting medications, it was also of interest to find if older adults were at risk of falling due to interactions between alcohol and CNS-acting medication. Objectives: The objectives were as follows: 1) to determine the prevalence, pattern and factors associated with at-risk drinking, 2) to …

Minimizing Part D Costs For Medicare Beneficiaries: Not Just A Drop In The Bucket, Rajul A. Patel, Kate M. O'Dell, Kim-Anh Vo, Tiffany Chu, Kenneth Wang, Shu Lu, Joseph A. Woelfel, Sian M. Carr-Lopez, Suzanne M. Galal, Berit Gundersen

School of Pharmacy Faculty Presentations

Background: Although Medicare Part D has been largely successful in providing prescription drug coverage for Medicare beneficiaries, many continue to be burdened with unnecessary out-of-pocket (OOP) costs. Objective: This study sought to identify the frequency and impact of cost-lowering strategies used to assist Medicare beneficiaries with their Part D drug costs. Methods: Twelve outreach events were conducted in 6 different cities throughout Northern/Central California during the 2013 Medicare open enrollment period. During each event, trained student pharmacists under the supervision of licensed pharmacists assisted beneficiaries to minimize their OOP costs. Individualized assistance included: optimization of the beneficiary's Part D plan, …

Medicare Part D Prescription Drug Costs And Plan Satisfaction As A Function Of Student Pharmacists' Assistance, Rajul A. Patel, Kate M. O'Dell, Kenneth Wang, Shu Lu, Tiffany Chu, Kim-Anh Vo, Sian M. Carr-Lopez, Joseph A. Woelfel, Suzanne M. Galal, Berit Gundersen

School of Pharmacy Faculty Presentations

Background: Beneficiaries can become overwhelmed by the myriad of Medicare Part D (MPD) plans that offer prescription drug coverage. Poor choice and increased out-of-pocket (OOP) costs can be reduced through annual plan reevaluation. Objective: To examine beneficiaries' plan satisfaction and MPD drug costs as a function of prior assistance from trained student pharmacists. Methods: Twelve outreach events, nine at the same location as the previous year, were held throughout Northern/Central California during October-November 2012. Trained student pharmacists, at each event, identified the MPD plan best meeting a beneficiary's needs based on their current medications and personal preferences (e.g., preferred pharmacy). …

Cyclin E Induction And Oncolytic Replication Of E1b-Deleted Adenoviruses., Pei-Hsin Cheng

Electronic Theses and Dissertations

Virus-mediated oncolysis has been considered as a new and promising cancer therapeutic approach. Although adenoviruses (Ads) with deletion of E1b55K preferentially replicate in cancer cells and have been used in numerous cancer treatments, the selective replication mechanism of this kind of virus still remains controversial. The lack of a well-established studies focusing on possible mechanisms enabling tumor selectivity of oncolytic Ads has hindered the further development of virotherapies and limits their clinical applications. Therefore, uncovering the molecular basis behind the tumor-killing phenomena will fill critical gaps in our understanding of the oncolytic adenovirology. Previously our laboratory has demonstrated that Ad …

Pharmacy Law Brief: Pharmacy Law Exam For Licensure, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …

Empowering Students With Assessment Data, Jane M. Souza, Karen D.C. Bobak

Pharmacy Faculty/Staff Publications

Students’ perspective on assessment may be limited to summative grades for semester performance. However, providing access to data tracking their progress formatively could empower them to be more proactive in preparing for success. Examples of empowering students through access to data will be shared from two campuses. One campus will demonstrate how requiring students to reflect on longitudinal reports of their performance on learning outcomes can assist in targeting their studies. The second campus will exhibit how assessment data can be linked to peer mentoring. Participants will strategize how to engage students actively in the use of assessment data.

Investigating Intermolecular Interactions In Crystalline Aspirin Using Cdft, Nicholas Turner, Tonglei Li, Mingtao Zhang

The Summer Undergraduate Research Fellowship (SURF) Symposium

Drugs today are widely administered in their crystalline form, namely via tablets and capsules. The crystal structure of a drug molecule affects important drug qualities such as solubility, bioavailability, shelf life, and compaction properties. In order to form a basis for crystal structure prediction, it is necessary to first understand how intermolecular interactions cause molecules to pack in certain ways. Being able to predict and perhaps even control a drug molecule’s crystal structure will lead to the development of higher quality drugs that perform more consistently. Scientists and engineers do not fully understand the reasons for a molecule assuming a …

Investigation Of Major Intermolecular Interactions In 7,8-Dihydrobenzo(K)Phenanthridin-6(5h)-One Crystal Using Quantum Calculations And Crystallographic Visualization Programs, Zhiwei Liao, Tonglei Li, Mingtao Zhang

The Summer Undergraduate Research Fellowship (SURF) Symposium

Currently, tablets and capsules are the most common ways of delivering drugs. The active pharmaceutical ingredients and excipients used to make those tablets and capsules are in their crystalline form generally. However, a single molecule can form multiple different crystal structures because of different packing arrangements of the molecules. These different crystal structures have identical chemical composition but different properties such as solubility, density, stability, etc. This phenomenon is called polymorphism. Occurrence of polymorphism could be a disaster for both patients and pharmaceutical companies, as the drug could lose its efficacy due to changes in properties. Studying intermolecular interactions in …

An Institution Wide Interdisciplinary Protocol For Improving The Recognition And Treatment Of Sepsis In Patients Presenting To The Emergency Department, Glenn Oettinger, Pharmd, Bcps

Pharmacy Presentations, Posters, and Grand Rounds

Objectives of this presentation were to describe our severe sepsis protocol, tools for sepsis identification, management, and staff education, as well as results of our research demonstrating the impact of this initiative on mortality.

Presented at: UHC Annual Conference 2013 in Atlanta, GA

36 PowerPoint slides.

Mechanism Of Amyloid Β-Protein Dimerization Determined Using Single-Molecule Afm Force Spectroscopy., Zhengjian Lv, Robin Roychaudhuri, Margaret M. Condron, David B. Teplow, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Aβ42 and Aβ40 are the two primary alloforms of human amyloid β-protein (Aβ). The two additional C-terminal residues of Aβ42 result in elevated neurotoxicity compared with Aβ40, but the molecular mechanism underlying this effect remains unclear. Here, we used single-molecule force microscopy to characterize interpeptide interactions for Aβ42 and Aβ40 and corresponding mutants. We discovered a dramatic difference in the interaction patterns of Aβ42 and Aβ40 monomers within dimers. Although the sequence difference between the two peptides is at the C-termini, the N-terminal segment plays a key role in the peptide interaction in the dimers. This is an unexpected finding …

Mechanism Of Amyloid Β-Protein Dimerization Determined Using Single-Molecule Afm Force Spectroscopy., Zhengjian Lv, Robin Roychaudhuri, Margaret M Condron, David B. Teplow, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Aβ42 and Aβ40 are the two primary alloforms of human amyloid β-protein (Aβ). The two additional C-terminal residues of Aβ42 result in elevated neurotoxicity compared with Aβ40, but the molecular mechanism underlying this effect remains unclear. Here, we used single-molecule force microscopy to characterize interpeptide interactions for Aβ42 and Aβ40 and corresponding mutants. We discovered a dramatic difference in the interaction patterns of Aβ42 and Aβ40 monomers within dimers. Although the sequence difference between the two peptides is at the C-termini, the N-terminal segment plays a key role in the peptide interaction in the dimers. This is an unexpected finding …

Physiological And Pharmacokinetic Effects Of Oral 1,3-Dimethylamylamine Administration In Men, Brian Schilling, Kelley Hammond, Richard Bloomer, Chaela Presley, Charles Yates

Kinesiology and Nutrition Sciences Faculty Research

No abstract provided.