Medicine and Health Sciences Commons^™

Role Of Cyclooxygenase-2 In Abdominal Aortic Aneurysms In Mice, Kamalika Mukherjee

Theses and Dissertations--Pharmacy

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease with no available pharmacological treatment. AAA formation reduces the structural integrity of the vessel and increases the susceptibility to rupture. The inflammatory response within human aneurysmal tissue is characterized by increased expression of cyclooxygenase-2 (COX-2). Similarly, in a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, we have shown that COX-2 expression in the abdominal aortic smooth muscle layer increases early in the development of the disease. Furthermore, genetic or pharmacological inactivation of COX-2 prior to disease initiation reduces AAA incidence.

The current study utilized nonhyperlipidemic mice …

Pharmacy-Student Outreach: Bridging The Gap From An Inner-City High School To Pharmacy School, Jennifer L. Mathews, Chirag Dave, Mohammad Mohammad, Gabriela Cipriano, Fang Zhao, Brooke Lowry

Pharmacy Faculty/Staff Publications

A poster describing a program at Thomas A. Edison High School that aimed to educate students on the educational requirements for pharmacy school and career opportunities within the profession.

Personal Impact Of A Service-Learning Medical Missions Elective Course On Pharmacy Student's Attitudes And Values, Christine R. Birnie, Sherry Jimenez

Pharmacy Faculty/Staff Publications

No abstract provided.

Course-Level Curriculum Map Pilot Program, Jane M. Souza, Jennifer Mathews, Amy L. Parkhill

Pharmacy Faculty/Staff Publications

Objective: To pilot a newly developed course level curriculum map that documents course learning outcomes, corresponding teaching activities, assessments, student achievement on assessments, and evidence-based changes made subsequently at the course level.

Method: The newly developed course level curriculum map was piloted in twelve courses involving nine faculty members. Faculty either retroactively recorded data or utilized the map during the semester. At the conclusion of the pilot period, a focus group was conducted during which seven of the faculty members shared experiences and recommendations. Focus group comments were recorded by three people. Recorders’ notes were compared for accuracy and …

Development, Implementation, And Evaluation Of A Pharmaceutical Biotechnology Elective Course In Hybrid Format, Parag Budukh, Christine R. Birnie

Pharmacy Faculty/Staff Publications

No abstract provided.

The Role Of Ω-3 Polyunsaturated Fatty Acids In Programming Inflammation Resolution, Ramil Sapinoro, David Barr, Samuel Slevinski

Pharmacy Faculty/Staff Publications

No abstract provided.

A Continuous Professional Development Process For First-Year Pharmacy Students, Richard O'Brocta, Asim Abu-Baker, Parag Budukh, Mona A. Gandhi, Jill Lavigne, Christine R. Birnie

Pharmacy Faculty/Staff Publications

Objectives. To develop, pilot test, and evaluate a continuous professional development (CPD) process for first-year pharmacy (P1) students.

Design. Students and faculty members were introduced to the important elements of the CPD process via a live training program. Students completed the year-long 4-step CPD cycle by identifying a learning objective, creating a plan, completing the learning activity, evaluating their learning outcome, documenting each step, and meeting with their faculty advisor for feedback and advice.

Assessment. Seventy-five first-year students (100%) successfully completed the CPD process during the 2009-2010 academic year. The students spent an average of 7 hours (range 2 to …

The Potential For Screening For Interpersonal Violence In Community Pharmacies: An Exploratory Study, Marie Barnard

Electronic Theses and Dissertations

Intimate partner violence (IPV) is a public health problem of epidemic proportion; the only known effective health care intervention is routine screening for IPV exposure. Despite professional guidelines for routine screening, this intervention has been poorly adopted. Expansion of screening efforts to the community pharmacy setting provides an opportunity to have a substantial impact on the health, well-being of pharmacy patients. This investigation is the first to examine IPV screening related to the pharmacy environment. An existing measure of physicians' readiness to manage IPV (PREMIS) was adapted for the community pharmacy environment and validated in a national random sample of …

Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.

Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were …

Effects Of In Vivo Hepatic Ischemia-Reperfusion Injury On The Hepatobiliary Disposition Of Rhodamine 123 And Its Metabolites In Isolated Perfused Rat Livers, Ridhi Parasrampuria, Imam H. Shaik, Reza Mehvar

Pharmacy Faculty Articles and Research

Purpose. A few studies have shown that normothermic hepatic ischemia-reperfusion (IR) injury may affect the mRNA and/or protein levels of canalicular transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2). However, the effects of the injury on the functions of these canalicular transporters with respect to the biliary excretion of drugs remain largely unknown. Therefore, the purpose of this study was to investigate the effects of warm hepatic IR on the hepatobiliary disposition of rhodamine 123 (RH-123), a P-gp substrate, and its glucuronidated metabolite (RH-Glu), an Mrp2 substrate, in rats.

Methods. Twenty four or 72 h following a …

Key Opinion Leaders' Views Regarding Emergency Contraception In India, M.E. Khan, Isha Bhatnagar, Deepthi S. Varma, Anvita Dixit

Reproductive Health

This policy brief explores the views of key opinion leaders (KOLs) in the field of reproductive health and family welfare on provision of emergency contraception (ECPs). The study’s objective was to gain a better understanding of how the attitudes and beliefs of KOLs might influence policy and program implementation, either encouraging or opposing ECP promotion and service delivery. Results suggest strong support by the majority of KOLs to continue the sale of ECP as an over-the-counter drug. KOLs also emphasized the importance of comprehending and addressing the main barriers to ECP provision and use: poor knowledge, lack of training, moral …

Providers' Attitudes And Practices Regarding Emergency Contraception In India: Key Findings, M.E. Khan, Isha Bhatnagar, Deepthi S. Varma, Anvita Dixit

Reproductive Health

This policy brief reports key findings of a study in India that explored providers’ knowledge of how emergency contraception (ECP) works and its safety and effectiveness, their perceptions of the frequency of repeat use, their provision of ECP, and their attitudes toward women who seek it. Many of the findings of this study are encouraging. Most providers believed that ECP is an effective and safe method to prevent pregnancy and that it cannot induce abortion, and half supported the over-the-counter provision of ECP. Nevertheless, the study revealed many biases and gaps in knowledge. Recommendations include a number of ways to …

Predictors Of Carbapenem Resistant Gram-Negative Bacteria In A Consortium Of Academic Medical Center Hospitals, Mera Ababneh

Theses and Dissertations

Background: Gram-negative resistance is a growing problem worldwide. It is generally believed that rates of resistant bacteria within a hospital are a function of antibiotic use, resistant organisms brought into the hospital, infection control efforts, and underlying severity of patient illness. The relative contribution of each to a particular resistance phenotype is unclear. P. aeruginosa is responsible for many hospital acquired infections and it may become resistant to carbapenems. In addition, newer threats to the future utility of the carbapenems are carbapenemase-producing K. pneumoniae Purpose: To determine if there is an association between the volume and composition of antibiotic use, …

Identifying Psychological Contract Breaches To Guide Improvements In Faculty Recruitment, Retention, And Development, Gretchen L. Peirce, Shane P. Desselle, Jolaine R. Draugalis, Alan R. Spies, Tamra S. Davis, Mark Bolino

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To identify pharmacy faculty members’ perceptions of psychological contract breaches that can be used to guide improvements in faculty recruitment, retention, and development.

Methods. A list of psychological contract breaches was developed using a Delphi procedure involving a panel of experts assembled through purposive sampling. The Delphi consisted of 4 rounds, the first of which elicited examples of psychological contract breaches in an open-ended format. The ensuing 3 rounds consisting of a survey and anonymous feedback on aggregated group responses.

Results. Usable responses were obtained from 11 of 12 faculty members who completed the Delphi procedure. The final list …

Treating Mentoring Programs As A Scholarly Endeavor, Shane P. Desselle

Faculty Publications & Research of the TUC College of Pharmacy

The author discusses mentoring programs for pharmacy school faculty and the research literature around forming these programs.

Preformulation Characterization And Formulation Development Of Δ9-Tetrahydrocannabinol Prodrugs For Potential Treatment Of Glacuoma, Tushar Hingorani

Electronic Theses and Dissertations

Relationship between smoking marihuana and a drop in intraocular pressure (IOP) was first reported in 1971. Research efforts since then have identified a number of constituents that could be linked to this observation. Delta-9-Tetrahydrocannabinol (THC) was one of the ingredients identified. However, four decades and numerous research efforts since the first observation, it has still not been concluded whether THC is effective in the treatment of glaucoma or not. Current therapy for IOP control in glaucoma, though effective, cannot prevent vision loss completely. Thus, identification of agents that can lower IOP as well as protect the retinal ganglion cells from …

Design And Development Of Drug Delivery Systems For Immediate And Sustained Release Utilizing Hot Melt Extrusion, Abhilasha Singh

Electronic Theses and Dissertations

Polymers have indispensable role in pharmaceutical formulation development. Polymer choice is a critical factor to obtain the desired drug-release profile during formulation development for HME (Hot melt extrusion). Many commercially available, pharmaceutical-grade polymers can be used in HME formulations. The suitable polymer choice facilitates processing in the extruder. When choosing a polymer to use in a formulation, processing conditions and processing attributes of the active pharmaceutical ingredients (APIs) should be considered. The physicochemical and the mechanisms of drug release from drug delivery systems prepared by utilizing HME with various polymeric carriers were investigated. Amorphous forms of API can have as …

Anticancer And Antibiotic Leads From Marine Organis, Bin Wang

Electronic Theses and Dissertations

During the past three decades, the development of marine natural products as drug leads has become a promising avenue for research. As our efforts towards the discovery of anticancer and antibiotic drug leads from marine organisms, modifications of anticancer drug candidate kahalalide F, isolations of new peptides from the mollusk, Elysia rufescens and anticancer drug leads from the NCI repository, as well as chemical regulation of antibiotic production from marine Pseudomonas aeruginosa were investigated. Kahalalide F (KF) is a potent anticancer lead isolated from the herbivorous marine mollusk E. rufescens and its algal diet Bryopsis pennata. Our semisynthesis approach was …

Antimalarials From Plant Pathogenic Fungi, Mallika Kumarihamy

Electronic Theses and Dissertations

The purpose of this study was to discover antimalarial compounds from necrotropic plant pathogenic fungi. Various phytotoxins released by necrotropic plant pathogenic fungi may inhibit the plant-like metabolic pathways in the apicoplast, a chloroplast-like organelle, essential for the survival of apicomplexan parasites, such as Plasmodium which cause malaria in humans. This dissertation describes the isolation, characterization, and biological evaluation of secondary metabolites of eight fungal strains. In addition to the antiplasmodial assay, all the extracts were subjected to phytotoxic, antimicrobial, and cytotoxic bioassays. Isolation of metabolites was performed by chromatographic methods and identification was carried out by spectroscopic and spectrometric …

Tp53 Codon 72 Polymorphism Affects Accumulation Of Mtdna Damage In Human Cells, Serena Altilia, Aurelia Santoro, Davide Malagoli, Catia Lanzarini, Josué Adolfo Ballesteros Álvarez, Gianluca Galazzo, Donald Carl Porter, Paolina Crocco, Giuseppina Rose, Giuseppe Passarino, Igor Roninson, Claudio Franceschi, Stefano Salvioli

Faculty Publications

Human TP53 gene is characterised by a polymorphism at codon 72 leading to an Arginine-to-Proline (R/P) substitution. The two resulting p53 isoforms have a different subcellular localisation after stress (more nuclear or more mitochondrial for the P or R isoform, respectively). p53P72 variant is more efficient than p53R72 in inducing the expression of genes involved in nuclear DNA repair. Since p53 is involved also in mitochondrial DNA (mtDNA) maintenance, we wondered whether these p53 isoforms are associated with different accumulation of mtDNA damage. We observed that cells bearing p53R72 accumulate lower amount of mtDNA damage upon rotenone stress with respect …

In Vivo Quantitative Study Of Sized-Dependent Transport And Toxicity Of Single Silver Nanoparticles Using Zebrafish Embryos, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Tanvi Desai, Pavan K. Cherukui, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess distinctive physicochemical properties (e.g., small sizes and high surface area-to-volume ratios) and promise a wide variety of applications, ranging from the design of high quality consumer products to effective disease diagnosis and therapy. These properties can lead to toxic effects, potentially hindering advances in nanotechnology. In this study, we have synthesized and characterized purified and stable (nonaggregation) silver nanoparticles (Ag NPs, 41.6 ± 9.1 nm in average diameter) and utilized early developing (cleavage-stage) zebrafish embryos (critical aquatic and eco- species) as in vivo model organisms to probe the diffusion and toxicity of Ag NPs. We found that single …

Influence Of Prescription Drug Monitoring Programs On Acetaminophen-Related Liver Toxicity, Aaron Barcelo

MPA/MPP/MPFM Capstone Projects

No executive summary.

Design And Synthesis Of Hiv-1 Integrase Inhibitors, Sarah Chajkowski Scarry

Electronic Theses and Dissertations

In recent years, HIV-1 integrase (IN) has emerged as an attractive target for the treatment of human immunodeficiency virus type 1 (HIV-1), the causative pathogen of acquired immuno-deficiency syndrome (AIDS). Several classes of IN inhibitors are known but many of these compounds are toxic, do not show antiviral activity or display decreased potency. Therefore, new classes of potent IN inhibitors are desperately needed. The b-diketo (b-DK) class of compounds has emerged as one of the most successful classes of IN inhibitors. Although several b-DK inhibitors with potent antiviral activity are known, compounds containing b-DK motifs have limitations in drug development. …

Design Synthesis And Biological Evaluation Of Non-Peptide Neuropeptide Ff Ligands, Jessica Valentinas Mankus

Electronic Theses and Dissertations

Neuropeptide FF is an endogenous RF-amide with two receptor subtypes originally described as having anti-opioid characteristics. While peptide work helped to elucidate key features for targeting the subtypes of the neuropeptide FF receptor, non-peptide small molecules offer a more refined tool to discover features that affect selectivity and affinity. Improvements in small molecule ligands for neuropeptide FF support lead development and offer a clearer understanding of the binding pocket of each receptor subtype. Previous work on the lead 4–anilindopiperidine structure clarified a key feature between agonist and antagonist behavior. Early modifications of substituents of the piperidine nitrogen were tolerated and …

Discovery, Isolation, And Identification Of Antimalarials From Fungal Endophytes, Andrekeus Lee

Electronic Theses and Dissertations

We examined fungal endophytes for their ability to inhibit bacterial, fungal and protozoal pathogens. Once antimalarial activity was discovered and confirmed, we sought to isolate and identify the active constituent(s) of our extracts. Bioassay-guided fractionation techniques were used to isolate our active compound, the structure of which was elucidated using 1H- and 13C-NMR. 2D-NMR and LC-MS analyses helped confirm that our endophytes were indeed producing artemisinin. Growth versus production studies were conducted to optimize our growth and extraction conditions while several other variables, like temperature and culture medium, were evaluated in an effort to improve our yields. Artemisinin production under …

Discovery Of Small-Molecule Natural Products That Target Cellular Bioenergetics, Sandipan Datta

Electronic Theses and Dissertations

Molecular-targeted antitumor therapy has found favor in antitumor drug discovery programs. Hypoxia (< 5% oxygen) is a comfeature of solid tumors and hypoxia-inducible factor-1 (HIF-1) represents an important antitumor target. Bioenergetic homeostasis is typically altered in tumor cells and HIF-1 plays an important role to produce a glycolytic phenotype. Glycolysis inhibitors are an emerging class of potential tumor-selective adjuvant therapeutic agents. Natural product aerobic glycolysis inhibitors may enhance the effectiveness of current therapies. Mitochondrial oxidative phosphorylation inhibitors in botanical dietary supplements (BDS) possess a potential health hazard which should be identified and appropriately regulated. Chapter one briefly reviews the molecular-targeted natural product antitumor drug discovery process. Descriptions of tumor hypoxia, HIF-1, HIF-1 regulatory pathways and the effect of HIF-1 on tumor cell bioenergetics are presented. Cellular bioenergetic pathways and natural products that inhibit HIF-1 by interfering with cellular bioenergetics are discussed. Mitochondriotoxic small-molecule natural products reported previously are further reviewed. Chapter two discusses the effect of chromatographic media on molecular-targeted antitumor drug discovery. A panel of crude extracts was eluted through columns of various chromatographic media using a step gradient method. Total recoveries from the various columns and various elution protocols were compared and statistically analyzed. The crude extracts and column eluates were evaluated for HIF-1 inhibitory activity. Chapter three discusses the development of a bioenergetics-based screening method to screen crude extracts for glycolysis inhibitors. Crude extracts (10,648) were screened and seven hits (hit rate 0.72%) were identified. Bioassay-guided isolation of Moronobea coccinea crude extract resulted in isolation of a protonophoric compound moronone (1) (false positive). The structure of 1 was determined by a combination of spectroscopic and spectrometric means. The protonophoric compounds must be rapidly dereplicated for successful discovery of glycolysis inhibitors. Chapter four discusses the screening of BDS products and pure compounds for mitochondrial uncouplers or electron transport chain inhibitors. The blue cohosh (Caulophyllum thalictroides) extract and three saponins cauloside A (3), saponin PE (4) and cauloside C (5) permeabilize the mitochondrial membrane. Sesamin (6) and guggulsterol III (7) and guggul (Commiphora wightii) extract inhibit mitochondrial complex I. These extracts and compounds are cytotoxic in nature.

Development Of Novel Thermosensitive Polymers For Bioresponsive Drug Delivery, Vivek Kumar Garripelli

Electronic Theses and Dissertations

Stimuli-responsive polymers have already shotremendous promise in controlled and self-regulated drug delivery. Successful construction of responsive polymers requires amalgamation of chemical, physical and biological principles. For careful therapy, a great deal of advantages offered by stimuli-responsive polymers is essential. A small or modest change in the environmental condition (e.g. temperature, pH, light) brings a sharp change in the properties of the responsive polymers. 'Smart' drug delivery systems utilize these principles to mimic the biological response behavior to a certain extent. Synthetic polymers incorporated with stimuli-responsive behavior would be amenable to overcome some of the systemic and intracellular delivery barriers. Development …

Metabolism And Pharmacokinetics In The Development Of New Therapeutics For Cocaine And Opioid Abuse, Pradeep Kumar Vuppala

Electronic Theses and Dissertations

Cocaine and opioid abuse are a major public health concern and the cause of significant morbidity and mortality worldwide. The development of effective medication for cocaine and opioid abuse is necessary to reduce the impact of this issue upon the individual and society. The pharmacologic treatment for drug abuse has been based on one of the following strategies: agonist substitution, antagonist treatment, or symptomatic treatment. This dissertation is focused on the role of metabolism and pharmacokinetics in the development of new pharmacotherapies, CM304 (sigma-1 receptor antagonist), mitragynine and 7-hydroxymitragynine (μ-opioid receptor agonists), for the treatment of drug abuse. The affinity …

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 …