Pharmacy and Pharmaceutical Sciences Commons^™

Study Of Iridium Catalyzed N-Alkylation Of Urea With Benzyl Alcohols, Majed Abdullah Bajaber

LSU New Orleans Theses and Dissertations

The solvent-free (Cp*IrCl2)2 catalyzed N-alkylation of urea with benzyl alcohol has been studied. A variety of reaction conditions were studied and optimized to produce a high yield (82%) of N,N-dibenzylurea. A series of substituted benzyl alcohols were examined at the optimal reaction conditions. However, the preparation of substituted benzyl urea derivatives using conditions optimized for benzyl alcohol gave poor yields or intractable mixtures.

Investigation Of The Response And Repair Of Replication, Kathryn Brady

Theses and Dissertations

When a mammalian cell suffers DNA damage, DNA damage signaling responses and repair pathways are invoked. The phosphorylation of histone variant H2AX (γH2AX) and of replication protein A (pRPA) are two well-documented damage signals, marking double strand breaks and stalled replication forks, respectively. Inhibitors of thymidylate synthase (TS) and ribonucleotide reductase (RNR) are chemotherapeutics that act by depriving cells of the deoxynucleotides necessary for DNA synthesis, which causes damage. The response and repair pathways activated by these chemotherapeutics have been studied for a number of years but there remain unanswered questions as to how cancer cells perceive this damage, the …

Six1 Overexpression Promotes Epithelial– Mesenchymal Transition And Malignant Progression In Models Of Cervical And Colon Cancer, Hanwen Xu

Theses and Dissertations

Inappropriate expression of embryonic genes, particularly homeodomain transcription factors, contributes to tumorigenesis and tumor progression. The overexpression of Six1, a member of the Six family of homeodomain transcription factors, has been found in various human cancers, and is associated with tumor progression and metastasis. We have previously determined that the expression of SIX1 mRNA increased during in vitro progression of human papillomavirus type 16 (HPV16)- immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. However, the mechanism(s) of how Six1 promotes HPV16- mediated transformation remain unknown. In this study, we explored the role of Six1 at early stages and late …

Effects Of Hiv-1 Tat Protein On Structure, Function And Trafficking Of The Dopamine Transporter, Narasimha Murty Midde

Theses and Dissertations

The alarming rise in HIV-1 associated neurocognitive disorder (HAND) is, at least in part, associated with HIV-1 viral proteins shed from infected macrophages, including transactivator of transcription (Tat) despite the success of anti-retroviral therapies. The dopamine (DA) system is greatly involved in the progression of HAND and is influenced by psychostimulants like cocaine. The DA transporter (DAT), a key regulator of neurocognitive functions, is a major molecular target for both Tat and cocaine. Our lab previously reported that exposure to Tat decreases DA uptake through allosteric regulation and alters cocaine binding sites in DAT.

In this research project the hypothesis …

Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the …

The Role Of Ape/Ref-1 In Hepatocellular Carcinoma Progression, Zhen Yang, Sun Yang, Bobbye J. Misner, Feng Liu-Smith, Frank L. Meyskens

Pharmacy Faculty Articles and Research

Hepatocellular carcinoma (HCC) is responsible for a third of the estimated cancer-caused deaths worldwide. To deeply understand the mechanisms controlling HCC progression is of primary importance to develop new approaches for treatment. Apurinic/apyrimidinic endonuclease-1/redox effector factor 1 (APE/Ref-1) has been uncovered elevated in various types of cancer, including HCC. Additionally, HCC progression is always correlated with elevated copper (Cu). Our previous data demonstrated that Cu treatment initiated APE/Ref-1 expression and its downstream targets. Therefore, we hypothesized that APE/Ref-1 may be involved in HCC progression through mediating the effect of Cu to its signaling cascades. Following different treatments, human HCC cell …

Exploring The Effect Of Solution Speciation On Crystallization Outcome, David M. Harvey, Arjun Kalra, Tonglei Li

The Summer Undergraduate Research Fellowship (SURF) Symposium

In the field of pharmaceuticals, the crystallization process significantly impacts the purity, morphology and polymorphism of active pharmaceutical ingredients (API), all of which are important in drug development. Polymorphism is the existence of more than one solid-state form of the same chemical entity. Tolfenamic acid (TFA), a Non-Steroid Anti-inflammatory drug (NSAID), has been shown to exhibit a unique physical phenomenon called concomitant polymorphism, whereby two polymorphs crystallize from the solution simultaneously. From previous work, it has been established that solution speciation i.e. the presence of monomers or dimers of TFA in solution is concentration and temperature dependent. This study correlates …

Effect Of Twin Screw Granulator Process Parameters On Granule Attributes, Haosheng Xu, Ridade Sayin, James Litster

The Summer Undergraduate Research Fellowship (SURF) Symposium

Twin screw wet granulation has been considered as an efficient and effective technique of manufacturing granules (agglomerates made up of small particles) and has been widely applied in pharmaceutical industry. However, narrow granule size distributions are difficult to achieve. This study aims to elucidate the effect of process parameters such as liquid feed rate and screw configuration on the granule attributes through granule characterization. The methods used are sieve analysis (for size distribution), liquid distribution (determining the dye concentration in the granules) and density and porosity (percentage gas volume in the granule) analyses. A sieve shaker is used to divide …

Electrochemical Investigations Of Benzanthrone, Antonio Trevino, Kefa Karimu Onchoke

Undergraduate Research Conference

No abstract provided.

Self-Study In Patient Safety And Quality Improvement To Enhance Student Experience In Interprofessional Case Competition, M. Lisa Pagnucco, Erin Maggie Jones, James Walrath, Danielle Cropley, Lindsay Robusto, Nora Asamoah, Leslie Ochs

2014 Interprofessional Student Advisory Team (IPSAT) Case Competition

Objective: The Interprofessional Student Advisory Team (IPSAT) at the University of New England (UNE) organized its 2nd interprofessional student case competition, modeled after the CLARION competition from the University of Minnesota. Completion of an online certificate in patient safety and quality improvement from the Institute for Healthcare Improvement (IHI) Open School was added as a pre-requisite to participation in the 2014 competition. Completion of this program was predicted to improve student preparedness and confidence and facilitate interprofessional teamwork during their case preparation.

Conclusions: Survey results indicate an increase in student confidence and preparedness for interprofessional teamwork during the 2014 UNE …

Evaluation And Revision Of An Introduction To Experiential Rotations Course, Eliza A. Dy, Sarah Nisly

Scholarship and Professional Work – COPHS

The objectives of this study were to evaluate the perceived student value of topics taught in Butler University’s Introduction to Experiential Rotations (RX500) course, implement course revisions to address any perceived weaknesses, and to reassess the course following implementation of those course revisions. Advanced Pharmacy Practice Experience (APPE) students from Butler University’s 2012 doctorate of pharmacy class were initially surveyed to assess the perceived usefulness and design of RX500. Based on the findings of the initial data, course revisions were developed and implemented for the following semester’s RX500 course. In order to assess for potential changes in the perceived value …

Inducible Tumor Difference Between Rapid And Slow Rat Nat2 Congenic Fischer 344 Rats Administered Methyl-Nitrosourea., Marcus W. Stepp

Electronic Theses and Dissertations

Human arylamine N-acetyltransferase 1 (NAT1) is a well-known phase II metabolic enzyme that has been associated with carcinogenesis. Its role in the biotransformation of aromatic and heterocyclic amine carcinogens has been investigated for many years, but more recent investigations focus on a possible endogenous role of human NAT1 in cancer initiation and progression. We conducted in vivo studies using homozygous Fischer 344 rats, congenic at the rat Nat2 locus for high (rapid) and low (slow) activity. Wistar Kyoto inbred rats were used to breed in the slow activity rat Nat2 locus into the Fischer 344 inbred rat, which contains the …

Building A Metabolic Bridge Between Glycolysis And Sphingolipid Biosynthesis : Implications In Cancer., Morgan L. Stathem

Electronic Theses and Dissertations

Cancer therapeutics has seen an emergence and re-emergence of two metabolic fields in recent years, namely bioactive sphingolipids and glycolytic metabolism. Anaerobic glycolysis and its role in cancer has been recognized in cancer biology over 90 years. In recent decades, the role of sphingolipids in cancer cell metabolism has gained recognition, notably ceramide’s essential role in programmed cell death and the role of the glucosylceramide synthase (GCS) in chemotherapeutic resistance. Despite this knowledge, a direct link between these two fields has yet to be concretely drawn. Herein, we show that in a model of highly glycolytic cells, generation of the …

Persistent Hepatic Structural Alterations Following Nanoceria Vascular Infusion In The Rat, Michael T. Tseng, Qiang Fu, Khoua Lor, G. Rafael Fernandez-Botran, Zhong-Bin Deng, Uschi M. Graham, D. Allan Butterfield, Eric A. Grulke, Robert A. Yokel

Chemistry Faculty Publications

Understanding the long-term effects and possible toxicity of nanoceria, a widely utilized commercial metal oxide, is of particular importance as it is poised for development as a therapeutic agent based on its autocatalytic redox behavior. We show here evidence of acute and subacute adverse hepatic responses, after a single infusion of an aqueous dispersion of 85 mg/kg, 30 nm nanoceria into Sprague Dawley rats. Light and electron microscopic evidence of avid uptake of nanoceria by Kupffer cells was detected as early as 1 hr after infusion. Biopersistent nanoceria stimulated cluster of differentiation 3⁺ lymphocyte proliferation that intermingled with nanoceria-containing …

In Vivo Processing Of Ceria Nanoparticles Inside Liver: Impact On Free-Radical Scavenging Activity And Oxidative Stress, Uschi M. Graham, Michael T. Tseng, Jacek B. Jasinski, Robert A. Yokel, Jason M. Unrine, Burtron H. Davis, Alan K. Dozier, Sarita S. Hardas, Rukhsana Sultana, Eric A. Grulke, D. Allan Butterfield

Pharmaceutical Sciences Faculty Publications

The cytotoxicity of ceria ultimately lies in its electronic structure, which is defined by the crystal structure, composition, and size. Despite previous studies focused on ceria uptake, distribution, biopersistance, and cellular effects, little is known about its chemical and structural stability and solubility once sequestered inside the liver. Mechanisms will be presented that elucidate the in vivo transformation in the liver. In vivo processed ceria reveals a particle-size effect towards the formation of ultrafines, which represent a second generation of ceria. A measurable change in the valence reduction of the second-generation ceria can be linked to an increased free-radical scavenging …

Pharmacists' And Patients' Perceptions Of Role Of Pharmacist In Discharge Process, Ravi Teja Vempati

All Theses

The objective of this study was to identify the perceptions of both patients and pharmacists about the pharmacist's role in the hospital discharge process. In order to do this, observations were conducted with the patients and interviews were conducted with both patients and pharmacists. During the interviews, both the patients and pharmacists were asked about the pharmacist's role in the hospital discharge process. The interviews were qualitatively analyzed using the in vivo technique. Four high-level themes emerged from this study: Current role of a pharmacist in the hospital, Ideal role of a pharmacist in the discharge process, Pharmacists' perceptions of …

Antidepressant Effects Of The Nts1 Agonist Pd149163 In The Forced Swim Test, Lawrence Carey Iv

All NMU Master's Theses

Neurotensin is a neuropeptide that influences monoaminergic neurotransmission in areas of the brain involved in the pathophysiology of depression. The forced swim test is a commonly used screening model for putative antidepressant medications. Drugs that have antidepressant effects in humans reliably decrease the time animals spend in an immobile posture in the forced swim test without increasing general locomotor activity as measured in an open field test. The present study sought to examine the effects of the neurotensin NTS₁ receptor agonist PD149163 and the tricyclic antidepressant drug imipramine on immobility in the forced swim test and on locomotor activity …

Radiation-Induced Genomic Instability And Line-1 Hypomethylation In Radiographers, Yoon Hee Cho

University Grant Program Reports

Genomic instability is an important factor in cancer induced by ionizing radiation. Global DNA hypomethylation has been recently proposed as a potential biomarker for cancer risk through genomic instability. However the association between low-dose ionizing radiation exposure and DNA methylation changes is unclear. This study aimed to understand the epigenetic mechanisms associated with low-level radiation exposure and radiation-induced genomic instability (RIGI) among industrial radiographers.

Bone Strength And Architecture : Pharmacological Targeting Of Camkk2 As A Method For Enhancing Bone Quality., Zachary James Pritchard

Electronic Theses and Dissertations

Mice lacking or pharmacologically inhibited for calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) have enhanced bone mass and microarchitecture. This enhanced bone mass and architecture is due to changes in osteoblast and osteoclast numbers as well as activity. Whether the enhanced bone mass translated to increased bone quality and strength was further explored by developing a method to directly test the trabecular strength of the distal femur. Micro computed tomography (CT)-based measurement of the length of the epiphysis of the distal femur, aided in its removal, allowing the exposure of the trabecular bone volume used to determine the microarchitecture parameters. Following …

Evaluation Of The Safety And Pharmacokinetic Profile Of The Broad Spectrum Antiviral Lectin Griffithsin., Christopher Lynn Barton

Electronic Theses and Dissertations

Carbohydrate binding agents that target viral envelope glycans are being studied for their potential use as microbicides and antiviral therapeutics. Griffithsin is a lectin originally identified in a red alga Griffithisia sp. Multiple studies have shown that GRFT inhibits HIV-1, Coronaviruses, Hepatitis C, influenza and Ebola virus replication in vitro. This antiviral activity suggests potential uses in chemoprophylaxis and disease treatment. However, safety of GRFT administration has not been extensively studied. In vivo testing--chronic subcutaneous treatment as well as single dose subcutaneous, oral, and intravenous administrations of Griffithsin in Sprague Dawley Rats (Rattus Norvegicus)--was used to assess Griffithsin’s pharmacokinetic properties …