Pharmacy and Pharmaceutical Sciences Commons^™

Engineering A Mutation In The Heparin Binding Pocket Of The Human Fibroblast Growth Factor, Roshni Patel

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast growth factors (FGFs) are family of proteins that belong to a group of growth factors that are found in mammals and play an important role in angiogenesis, differentiation, organogenesis, and tissue repair. In summary, their main functionality is involved in cell division and proliferation. Because FGFs plays such a vital role in cell proliferation, they are mainly involved in the process of wound healing and injuries. FGF binds to its ligand, heparin—a heavily sulfated glycosaminoglycan. The binding of heparin to FGF occurs through electrostatic interactions, specifically between the negatively charged sulfate groups on heparin and positively charged residues such …

Upregulation Of Antibiotic Activity Of A Streptomyces Sp. Via Co-Cultures With Challenge Pathogens, Anne A. Sung

Honors Scholar Theses

Marine natural product drug discovery has begun to play an important role in the treatment of diseases. Early drug discovery from natural products came primarily from plants, but after the discovery and development of penicillin, scientists started looking at natural products from microorganisms. Numerous natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces, due to their metabolic diversity in the production of biologically active secondary metabolites. Ascidians, also known as tunicates, are marine invertebrates that contain many host-associated microbes. Adult tunicates are sessile, which makes them vulnerable to predators, and thus, they …

The Potentiating Effects Of Acetaminophen On Oxidant Air Pollutant Sensory Irritation And The Onset Of Asthma, Bennett J. Doughty

Honors Scholar Theses

Through its toxic metabolites, acetaminophen can cause oxidative injury in the liver. This damage has not yet been investigated in the respiratory tract. If acetaminophen also causes oxidative stress and injury here, this widely used antipyretic could potentiate the adverse effects of oxidant air pollutants. Thus, the primary goal of this project is to determine if low non-hepatotoxic doses of APAP is correlated with an increase of oxidative stress in the airways, possibly linking APAP to the onset of asthma. Using data that reflected murine breathing patterns, the addition of acetaminophen greatly increased the reflex irritant response to ETS through …

Crizotinib And Ceritinib Induce Apoptosis And Necrosis In Primary Rat Hepatocytes With Distinct Capacity, Alec T. Salminen

Biomedical Engineering Undergraduate Honors Theses

Drug development makes up a major portion of biomedical engineering research interests. The FDA oversees the introduction, experimentation, and implementation of all drugs before market approval is granted. Even after market approval is granted, the FDA continues to monitor the safety of all drugs. Crizotinib and ceritinib are two anaplastic lymphoma kinase (ALK) inhibitors recently approved by the FDA. Both drugs are indicated for treatment of non-small cell lung cancers (NSCLC) with abnormal ALK gene, and they are approved with a companion diagnostic test that determines ALK abnormality. Clinical trial data suggest that crizotinib and ceritinib can cause liver injury, …

Sglt-2 Inhibitors: A Novel Mechanism In Targeting Glycemic Control In Type 2 Diabetes Mellitus, Kobi T. Nathan, Nabila Ahmed-Sarwar, Paul M. Werner

Pharmacy Faculty/Staff Publications

OBJECTIVE: To review the chemistry, pharmacology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, dosing, drug interactions, and administration of canagliflozin, dapagliflozin, and empagliflozin, and comparing the benefit and risk aspects of using these agents in the older adult diabetes patient population.

DATA SOURCES, STUDY SELECTION, DATA EXTRACTION, AND DATA SYNTHESIS: A search of PubMed using the terms "SGLT-2 inhibitors," "canagliflozin," "dapagliflozin," "empagliflozin," "efficacy," and "tolerability" was performed to find relevant primary literature on each of the sodium/glucose cotransporter 2 (SGLT-2) inhibitors currently approved for use in type 2 diabetes. Phase III trials for all agents were included. All English-language articles from 2010 …

Feasibility Test Of The Medacube, Charles Hoffmann, Anne Schweighardt, Kelly Conn, D. Nelson, R. Barbano, F. Marshall, Jack Brown

Pharmacy Faculty/Staff Publications

Poor adherence is a significant barrier to achieve better patient outcomes. Rates of non-adherence approach 40% resulting in 10% of all emergency department visits and 23% of admissions into skilled nursing facilities. Many factors contribute to medication non-adherence including psychological and memory disorders, aging and pill burden. The MedaCube is a medication management system intended to help solve unintentional medication non-adherence. The device is designed to dispense scheduled and as-needed oral medications. The MedaCube provides audio and visual prompts alerting subjects to administer their medications. Caregivers receive notification of missed doses, late doses and refill requests. The null hypothesis is …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

Fellowships In Community Pharmacy Research: Experiences Of Five Schools And Colleges Of Pharmacy, Margie E. Snyder, Caitlin K. Frail, Stephanie A. Gernant, Jennifer L. Bacci, Kim C. Coley, Lauren M. Colip, Stefanie P. Ferreri, Nicholas E. Hagemeier, Melissa Somma Mcgivney, Jennifer L. Rodis, Megan G. Smith, Randall B. Smith

ETSU Faculty Works

Objective To describe common facilitators, challenges, and lessons learned in 5 schools and colleges of pharmacy in establishing community pharmacy research fellowships.

Setting: Five schools and colleges of pharmacy in the United States.

Practice description: Schools and colleges of pharmacy with existing community partnerships identified a need and ability to develop opportunities for pharmacists to engage in advanced research training.

Practice innovation: Community pharmacy fellowships, each structured as 2 years long and in combination with graduate coursework, have been established at the University of Pittsburgh, Purdue University, East Tennessee State University, University of North Carolina at Chapel Hill, and The …

Hit Identification For Pkcζ Inhibitors: Structure-Based Optimization, Virtual Screening, And Biological Evaluation, Xiaoxin Wu

Theses and Dissertations (ETD)

Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure …

An Investigation Into Formulation And Therapeutic Effectiveness Of Nanoparticle Drug Delivery For Select Pharmaceutical Agents, Dustin Cooper

Electronic Theses and Dissertations

Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug delivery systems. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Furthermore, polymer based, biodegradable nanodelivery has become increasing popular in the field of NP formulation because of their high degree of compatibility and low rate of toxicity. Due to their popularity, commercially available polymers such as poly lactic acid (PLA), poly glycolic acid (PGA) and polylactic-co-glycolic acid (PLGA) are commonly used in the development and design of new nano based delivery …

A Model For The Voltammetric Behaviour Of Tio2 Memristors, John Cassidy, Daryl Fox, Tony Betts

Articles

Abstract A model is solved based on the Nernst Planck equation to calculate the diffusion and migration currents for a species in a thin layer (about 200 nm) confined between two electrodes. This is proposed to account for the current voltage behaviour of a memristor constructed in a similar fashion. At the working electrode, an electroactive species is oxidised and at the counter electrode, the same species is reduced. Upon application of a simple voltammetric waveform, the migration current exhibits a resistance profile at slow scan rates and hysteresis at faster scan rates, indicative of memristor behavior.

Uji Aktivitas Penghambatan Xantin Oksidase Secara In-Vitro Oleh Isolat 6,4’-Dihidroksi-4-Metoksibenzofenon-2-O-Β-D Glukopiranosida(C20h22o10) Yang Diisolasi Dari Mahkota Dewa (Phaleria Macrocarpa (Scheff.) Boerl), Aprilita Rina Yanti Eff, Sri Teguh Rahayu, Resta Dwi Syachfitri

Pharmaceutical Sciences and Research

Hyperuricemia is a condition in which an increasing in uric acid levels abovenormal. Hyperuricemia is a major factor in the development of gout. Gout is adisease caused by the accumulation of monosodium urate crystals in the tissues dueto elevated levels of uric acid. Crown gods (Phaleria macrocarpa (Scheff.) Boerl) is Indonesia native medicinal that has effect such as lowering blood pressure, diabetes mellitus drugand lowering uric acid levels. One of the chemical constituents of this plant is abenzopheneon compound that is 6,4’-dihydroxy-4-metoksi benzofenon-2-O-β-D-glukopiranosida (C20H22O10). Research was conducted to determine the activity of 6,4’-dihydroxy -4-metoksi benzofenon-2-O-β-D-glukopiranosida (C20H22O10) that isolated from Crown …

Uji Aktivitas Antiproliferasi Formula Liposom Ekstrak Etanol Kunyit (Curcuma Domestica) Terhadap Sel Kanker Payudara T47d, Gabriella Pasaribu, Iskandarsyah Iskandarsyah, Erny Sagita

Pharmaceutical Sciences and Research

Breast cancer is one of deadliest diseases in world. Turmeric extract was known to have antiproliferative activity. To minimize its toxicity, turmeric extract was encapsulated with liposome, a vesicle lipid bilayer functioned as cancer drug carrier in body. This research aimed to determine encapsulation effect of turmeric ethanol extract against antiproliferative activity in T47D breast cancer cells through in vitro assay. Liposomes was made using thin layer method and particle size was reduced by extrusion. Materials used are phosphatidylcholine, cholesterol, and turmeric extract. Optimization of liposomes was made in three formulations with different concentrations of extract. Most optimal formulation was …

Pengaruh Pemberian Minyak Atsiri Daun Kemangi (Ocimum Americanum L.) Terhadap ~ Motilitas Usus Mencit Putih Jantan, Dewi Sriyani, Fadlina Chany Saputri

Pharmaceutical Sciences and Research

Kemangi (Ocimum americanum L.) is a well known plant that contains essential oils with citral as a major compound. Citral is reported to have beneficial effect on intestinal motility. In the present study, we investigated the effect of essential oil of kemangi leaves (Ocimum americanum L.) on male DDY mices intestinal motility. Thirty mices were divided into six groups and each group was pretreated with 0,2 ml of 0,5% CMC (negative control), 1 mg/kg BW of atropine sulfate (positive control), 5 mg/kg BW of citral (comparative control), and three dose variation of volatile oil of kemangi leaves (25 mg/kg BW; …

Uji Penghambatan Xantin Oksidase Secara In Vitro Ekstrak Kulit Rambutan, Nurul Eka Putri, Rissyelly Rissyelly, Marista Gilang Mauldina

Pharmaceutical Sciences and Research

Hyperuricemia is a condition have higher uric acid levels that can cause a cumulation uric acid crystals in the tissues. Xanthine oxidase is an enzyme which catalyze the oxidation of hypoxanthine into xanthine and into uric acid.Therefore, the inhibition of xanthine oxidase will reduce ammount of uric acid. This research aims to determine xanthine oxidase inhibition activity and also to identify chemical constituent group of extract rambutan (Nephelium lappaceum Linn.) skin. Rambutan fruit skin was extracted by graded maceration using a three solvent, based on polarity the solvent are n-hexane, ethyl acetate and methanol. The test of inhibition xanthine oxidase …

Karakterisasi Dan Stabilitas Fisik Mikroemulsi Tipe A/M Dengan Berbagai Fase Minyak, Endang Wahyu Fitriani, Erlina Imelda, Christina Kornelis, Christina Avanti

Pharmaceutical Sciences and Research

This research consists of formulation, characterization and physical stability of the microemulsion of water-in-oil type. On the microemulsion, VCO, palm oil, olive oil and soybean oil were used as oil phase, aqua demineralisata used as the aqueous phase, a combination of Span® 80 and Tween® 80 as a surfactant and propanol as cosurfactant. Each formula was three times replication done and determined the physical characteristics including organoleptic observations, measurements of density, droplet, viscosity, flow properties, and pH. Determination of physical characteristics was done at the beginning of the microemulsion formed and after 5 weeks storage at room temperature. The physical …

Structural Dynamics Of A Methionine Γ-Lyase For Calicheamicin Biosynthesis: Rotation Of The Conserved Tyrosine Stacking With Pyridoxal Phosphate, Hongnan Cao, Kemin Tan, Fengbin Wang, Lance Bigelow, Ragothaman M. Yennamalli, Robert Jedrzejczak, Gyorgy Babnigg, Craig A. Bingman, Andrzej Joachimiak, Madan K. Kharel, Shanteri Singh, Jon S. Thorson, George N. Phillips Jr.

Pharmaceutical Sciences Faculty Publications

CalE6 from Micromonospora echinospora is a (pyridoxal 5′ phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. We report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acidcomplex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structuralanalysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis and holoenzyme maturation.

Peptidomimetic Small Molecules Disrupt Type Iv Secretion System Activity In Diverse Bacterial Pathogens, Carrie L. Shaffer, James A.D. Good, Santosh Kumar, K. Syam Krishnan, Jennifer A. Gaddy, John T. Loh, Joseph Chappell, Fredrik Almqvist, Timothy L. Cover, Maria Hadjifrangiskou

Pharmaceutical Sciences Faculty Publications

Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85) that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA) and peptidoglycan into gastric epithelial cells. In …

S100a4 Drives Non-Small Cell Lung Cancer Invasion, Associates With Poor Prognosis, And Is Effectively Targeted By The Fda-Approved Anti-Helminthic Agent Niclosamide, Rachel L. Stewart, Brittany L. Carpenter, Dava S. West, Teresa Knifley, Lili Liu, Chi Wang, Heidi L. Weiss, Tamas S. Gal, Eric B. Durbin, Susanne M. Arnold, Kathleen L. O'Connor, Min Chen

Markey Cancer Center Faculty Publications

S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer have not been properly explored. Using established lung cancer cell lines, we demonstrate that S100A4 knockdown reduces cell proliferation, invasion and three-dimensional invasive growth, while overexpression of S100A4 increases invasive potential. In patient-derived tissues, S100A4 is preferentially elevated in lung adenocarcinoma. This elevation is associated with lymphovascular …

Hiding Inside? Intracellular Expression Of Non-Glycosylated C-Kit Protein In Cardiac Progenitor Cells, Huilin Shi, Christopher A. Drummond, Xiaoming Fan, Steven T. Haller, Jiang Liu, Deepak Malhotra, Jiang Tian

Pharmaceutical Science and Research

Cardiac progenitor cells including c-kit(+) cells and cardiosphere-derived cells (CDCs) play important roles in cardiac repair and regeneration. CDCs were reported to contain only small subpopulations of c-kit(+) cells and recent publications suggested that depletion of the c-kit(+) subpopulation of cells has no effect on regenerative properties of CDCs. However, our current study showed that the vast majority of CDCs from murine heart actually express c-kit, albeit, in an intracellular and non-glycosylated form. Immunostaining and flow cytometry showed that the fluorescent signal indicative of c-kit immunostaining significantly increased when cell membranes were permeabilized. Western blots further demonstrated that glycosylation of …