Pharmacy and Pharmaceutical Sciences Commons^™

Simulating Molecular Mechanisms Of The Mdm2-Mediated Regulatory Interactions: A Conformational Selection Model Of The Mdm2 Lid Dynamics, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Diversity and complexity of MDM2 mechanisms govern its principal function as the cellular antagonist of the p53 tumor suppressor. Structural and biophysical studies have demonstrated that MDM2 binding could be regulated by the dynamics of a pseudo-substrate lid motif. However, these experiments and subsequent computational studies have produced conflicting mechanistic models of MDM2 function and dynamics. We propose a unifying conformational selection model that can reconcile experimental findings and reveal a fundamental role of the lid as a dynamic regulator of MDM2-mediated binding. In this work, structure, dynamics and energetics of apo-MDM2 are studied as a function of posttranslational modifications …

Impact Of An Elective Course On Pharmacy Students’ Attitudes, Beliefs, And Competency Regarding Medicare Part D, Suzanne M. Galal, Rajul A. Patel, Huong K. Thai, Christine M. Phou, Mark P. Walberg, Joseph A. Woelfel, Sian M. Carr-Lopez, Emily K. Chan

School of Pharmacy Faculty Articles

Objective. To determine the impact of an elective course on pharmacy students’ perceptions, knowledge, and confidence regarding Medicare Part D, medication therapy management (MTM), and immunizations.

Design. Thirty-three pharmacy students were enrolled in a Medicare Part D elective course that included both classroom instruction and experiential training.

Assessment. Students’ self-reported confidence in and knowledge of Part D significantly improved upon course completion. End-of-course student perceptions about the relative importance of various aspects of MTM interventions and their confidence in performing MTM services significantly improved from those at the beginning of the course. Students’ confidence in performing immunizations also increased significantly …

Conditioned Response Evoked By Nicotine Conditioned Stimulus Preferentially Induces C-Fos Expression In Medial Regions Of Caudate-Putamen, Sergios Charntikov, Matthew E. Tracy, Changjiu Zhao, Ming Li, Rick A. Bevins

Department of Psychology: Faculty Publications

Nicotine has both unconditioned and conditioned stimulus properties. Conditioned stimulus properties of nicotine may contribute to the tenacity of nicotine addiction. The purpose of this experiment was to use neurohistochemical analysis of rapidly developing c-Fos protein to elucidate neurobiological loci involved in the processing of nicotine as an interoceptive conditioned stimulus (CS). Rats were injected (SC) in an intermixed fashion with saline or nicotine (16 sessions of each) and placed in conditioning chambers where they were given one of the three conditions depending on group assignment: (a) nicotine paired 100% of the time with intermittent access to sucrose (nicotine-CS condition), …

Structural Properties Of Thermoresponsive Poly(N-Isopropylacrylamide)-Poly(Ethyleneglycol) Microgels, J. Clara-Rahola, A. Fernandez-Nieves, B. Sierra-Martin, A. B. South, L. Andrew Lyon, J. Kohlbrecher, A. F. Barbero

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The application of RNA interference to treat disease is an important yet challenging concept in modern medicine. In particular, small interfering RNA (siRNA) have shown tremendous promise in the treatment of cancer. However, siRNA show poor pharmacological properties, which presents a major hurdle for effective disease treatment especially through intravenous delivery routes. In response to these shortcomings, a variety of nanoparticle carriers have emerged, which are designed to encapsulate, protect, and transport siRNA into diseased cells. To be effective as carrier vehicles, nanoparticles must overcome a series of biological hurdles throughout the course of delivery. As a result, one promising …

Enantioselective Demethylation: The Key To The Nornicotine Enantiomeric Composition In Tobacco Leaf, Bin Cai

Theses and Dissertations--Plant and Soil Sciences

Nicotine and nornicotine are the two main alkaloids that accumulate in Nicotiana tabacum L. (tobacco), and nornicotine is the N-demethylation metabolite of nicotine. Nicotine is synthesized in the root, and probably primarily in the root tip. Both nicotine and nornicotine exist as two isomers that differ from each other by the orientation of H atom at the C-2' position on the pyrrolidine ring. (S)-nicotine is the dominant form in tobacco leaf and the enantiomer fraction of nicotine (EF_nic), the fraction of (R)-enantiomer over the total nicotine, is approximately 0.002. Despite considerable efforts to elucidate nicotine and nornicotine …

Factors Influencing Pharmacists’ Decision To Report Adverse Events Related To Dietary Supplements, Ali M. Alhammad

Theses and Dissertations

Background: The increasing consumption of dietary supplements (DS) has drawn the attention of regulatory agencies, researchers and healthcare professionals. The US Food and Drug Administration (FDA) does not require premarketing assessment of DS considering them safe unless proven otherwise. However, the reporting rate of DS adverse events (DS-AE) is low. Objective: To describe pharmacists’ attitudes and knowledge of DS and DS information resources, and to determine the importance of selected attributes in pharmacists’ decisions to report a DS-AE. Methods: A convenience sample of practicing pharmacists in Virginia was surveyed using a web-based self-administered questionnaire. A conjoint analysis exercise was developed …

Mechanism Of Action Of A Novel Antifungal Compound, Amber Ward

Honors Theses

Opportunistic fungal infections have become problematic in recent years. There has been an emergence of new fungal pathogens, development of antifungal resistance, and increasing prevalence. In addition, toxicity, resistance, and lack of efficacy as a single agent limit the effectiveness of current antifungal drugs. Therefore, new drugs targeting new pathways are greatly needed. An analog derived from the marine natural product phloeodictine, analog PHL5-34A, was identified as having strong in vitro antifungal activity. In this study, its mechanism of action (MOA) was investigated in the model yeast, Saccharomyces cerevisiae. This study made use of a collection of 166 yeast mutants …

The Effect Of N-Trans-P-Coumaroyl Tyramine On Indomethacin-/Diclofenac-Mediated-Cytotoxicity In Breast Cancer Cells., Angkana Wongsakul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Indomethacin (INDO) and diclofenac (DIC) are non-steroidal anti-inflammatory (NSAIDs) have been reported their anticancer potential. Their cytotoxicity could be increased when combining with certain natural compounds such as piperine in Piper plants. N-trans-p-coumaroyltyramine (TCT) (a coumaric acid derivative) was also found at significant amount in these plants and other commonly used in traditional medicine. This study determined the potentiative effect of TCT on NSAIDs (INDO and DIC) induced cytotoxicity in MCF-7 breast cancer cells, and the underlying mechanisms. Combination of TCT with either NSAIDs or various ER stressors at their non-cytotoxic concentrations were able to reduce cell viability in MCF-7 …

An Expanded Age Range For Meningococcal Meningitis: Molecular Diagnostic Evidence From Population-Based Surveillance In Asia, Soon Kim, Dong Kim, Bai Dong, Jung Kim, Dang Anh, Paul E. Kilgore

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

To understand epidemiologic patterns of meningococcal disease in Asia, we performed a retrospective molecular analysis of cerebrospinal fluid (CSF) specimens collected in prospective surveillance among children aged < 5 years of age in China, South Korea, and Vietnam.

Methods

A total of 295 isolates and 2,302 CSFs were tested by a meningococcal species- and serogroup-specific polymerase chain reaction (PCR) assay targeting the Neisseria meningitidis (Nm) ctrA gene. Multi-locus sequence typing (MLST) was performed in Nm gene amplification analysis and incidence rates for meningococcal meningitis were estimated.

Results

Among 295 isolates tested, 10 specimens from Vietnam were confirmed as serogroup B and all were Sequence Type (ST) 1576 by MLST. …

Designing Direct And Indirect Factor Xa Inhibitors, Rami Al-Horani

Theses and Dissertations

Anticoagulants are the basis for treatment and prevention of thrombotic diseases. The currently available medicines are associated with a wide range of adverse reactions that mandates developing new anticoagulants. Several lines of evidence support the superiority of factor Xa (FXa) as a promising target to develop novel anticoagulants. This work focuses on the design of direct and indirect FXa inhibitors using an interdisciplinary approach. As indirect FXa inhibitors, a focused library of tetrasulfated N–arylacyl tetrahydroisoquinoline (THIQ) nonsaccharide allosteric antithrombin activators was designed, synthesized, and biochemically evaluated to establish their structure–activity relationship (SAR). An N–arylacyl THIQ analog having carboxylate at position–3, …