Pharmacy and Pharmaceutical Sciences Commons^™

Activation Of Thromboxane A2 Receptor (Tp) Increases The Expression Of Monocyte Chemoattractant Protein -1 (Mcp-1)/Chemokine (C-C Motif) Ligand 2 (Ccl2) And Recruits Macrophages To Promote Invasion Of Lung Cancer Cells, Xiuling Li, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Publications

Thromboxane synthase (TXAS) and thromboxane A₂ receptor (TP), two critical components for thromboxane A₂ (TXA₂) signaling, have been suggested to be involved in cancer invasion and metastasis. However, the mechanisms by which TXA₂ promotes these processes are still unclear. Here we show that TXA₂ mimetic, I-BOP, induced monocyte chemoattractant protein -1(MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) expression at both mRNA and protein levels in human lung adenocarcinoma A549 cells stably over-expressing TP receptor α isoform (A549-TPα). The induction of MCP-1 was also found in other lung cancer cells H157 and H460 that express relatively …

Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F. Bjeldanes, Keith Rayburn

Natural Sciences and Mathematics | Faculty Scholarship

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …

Design, Physicochemical Characterization, And Optimization Of Organic Solution Advanced Spray-Dried Inhalable Dipalmitoylphosphatidylcholine (Dppc) And Dipalmitoylphosphatidylethanolamine Poly(Ethylene Glycol) (Dppe-Peg) Microparticles And Nanoparticles For Targeted Respiratory Nanomedicine Delivery As Dry Powder Inhalation Aerosols, Samantha Ann Meenach, Frederick G. Vogt, Kimberly W. Anderson, J. Zach Hilt, Ronald C. Mcgarry, Heidi M. Mansour

Pharmaceutical Sciences Faculty Publications

Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600 …

Defining A Simplified Pharmacophore For Simocyclinone D8 Inhibition Of Dna Gyrase, Lauren Gaskell

Theses and Dissertations

The type II topoisomerase subfamily of enzymes has been clinically targeted by the widely used, broad-spectrum quinolone class of antibacterials. Due to emerging drug-resistant strains of bacteria, the quinolones’ effectiveness is threatened. The natural product simocyclinone D8 (SD8) has shown the ability to inhibit the type II topoisomerase, DNA gyrase, even when mutated to be resistant to the quinolones. In order to determine the pharmacophore required for SD8 binding to DNA gyrase, 16 compounds were synthesized. These compounds were then tested by surface plasmon resonance for their ability to inhibit the DNA – DNA gyrase binding interaction. It was found …

Acclimatization To Chronic Intermittent Hypoxia In Mine Workers: A Challenge To Mountain Medicine In Chile, J. G. Farias, D. Jimenez, J. Osario, A. B. Zepeda, C. A. Figueroa, V. M. Pulgar

Pharmaceutical Sciences

In the past two decades, Chile has developed intense mining activity in the Andes mountain range, whose altitude is over 4,000 meters above sea level. It is estimated that a workforce population of over 55,000 is exposed to high altitude hypobaric hypoxia. The miners work under shift systems which vary from 4 to 20 days at the worksite followed by rest days at sea level, in a cycle repeated for several years. This Chronic Intermittent Hypoxia (CIH) constitutes an unusual condition for workers involving a series of changes at the physiological, cellular and molecular levels attempting to compensate for the …

Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion

STAR Program Research Presentations

Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.

What’S Your Line? Defining Pharmacists' Role In Jejunostomy Tube Medication Administration, Jamie M. Gomes, Pharmd, Gloria M. Espinosa, Pharmd, Brian P. Roslund, Pharmd, Bcps, Joanne Heil, Pharmd, Bcps

Pharmacy Presentations, Posters, and Grand Rounds

Enteral nutrition is preferred over parenteral nutrition in patients with inadequate oral intake for an extended period of time. Enteral feeding helps preserve the functioning of the gastrointestinal (GI) tract. 1 Feeding tubes provide access to the GI tract allowing administration of medication while unable to swallow. Drug therapy is complicated by drug formulation, absorption site, first-pass elimination, as well as the size and placement of the tube.1-3 Medication errors revolving around administration via enteral feeding tubes represent a need for education and implementation of hospital guidelines.

Patient Education And Coumadin (Warfarin) Therapy: Readmission Rates Pre/Post Coumadin Team Initiation, Rebecca L. Barber

Nursing Theses and Capstone Projects

As a response to the 2011 National Patient Safety Goals (NPSG), a Coumadin Team, consisting of a Physician Chair, Pharmacists, and Registered Nurses, was formed at Mission Health System to focus on International Normalized Ratio (INR) testing, Coumadin dosing, and patient education. The goal of this team has been to identify and eliminate barriers that prevent the stabilization of INRs within the prescribed goal range, and to ensure that all patients receive education about Coumadin therapy in order to prevent harm and reduce readmission rates related to Coumadin therapy. The purpose of this study is to compare readmission rates within …

Micelles: Chemotherapeutic Drug Delivery, Antoine Al-Achi, Jonathon Lawrence

Pharmaceutical Sciences

No abstract provided.

Clinical Effectiveness Of Baclofen For The Treatment Of Alcohol Dependence: A Review, J. G. Leung, J. L. Brennan, J. P. Gagliardi, S. K. Rivelli, A. J. Muzyk

Pharmacy Practice

No abstract provided.

Acclimatization To Chronic Intermittent Hypoxia In Mine Workers: A Challenge To Mountain Medicine In Chile, J. G. Farias, D. Jimenez, J. Osorio, A. B. Zepeda, C. A. Figueroa, V. M. Pulgar

Pharmaceutical Sciences

No abstract provided.

Blood Pressure Homeostasis Is Maintained By A P311-Tgf-Β Axis, K. R. Badri, M. Yue, O. A. Carretero, S. L. Aramgam, J. Cao, S. M. Sharkady, G. H. Kim, G. A. Taylor, K. L. Bryon, L. Schuger

Pharmaceutical Sciences

No abstract provided.

Empiric Guideline-Recommended Weight-Based Vancomycin Dosing And Nephrotoxicity Rates In Patients With Methicillin-Resistant Staphylococcus Aureus Bacteremia: A Retrospective Cohort Study, Ronald G. Hall Ii, Kathleen A. Hazlewood, Sara D. Brouse, Christopher A. Giuliano, Krystal K. Haase, Chistopher R. Frei, Nicolas A. Forcade, Todd Bell, Roger J. Bedimo, Carlos A. Alvarez

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Previous studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB).

Methods

Adults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from …

Developing Community Based Rehabilitation For Cancer Survivors: Organizing For Coordination And Coherence In Practice, Karen La Cour, Malcolm P. Cutchin

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Increasing incidences of cancer combined with prolonged survival have raised the need for developing community based rehabilitation. The objectives of the analysis were to describe and interpret the key issues related to coordination and coherence of community-based cancer rehabilitation in Denmark and to provide insights relevant for other contexts.

Methods

Twenty-seven rehabilitation managers across 15 municipalities in Denmark comprised the sample. The study was designed with a combination of data collection methods including questionnaires, individual interviews, and focus groups. A Grounded Theory approach was used to analyze the data.

Results

A lack of shared cultures among health care …

Biological Characterization Of 3-(2-Amino-Ethyl)-5-[3-(4-Butoxyl-Phenyl)-Propylidene]-Thiazolidine-2,4-Dione (K145) As A Selective Sphingosine Kinase-2 Inhibitor And Anticancer Agent, Kai Liu, Tai L. Guo, Nitai C. Hait, Jeremy Allegood, Hardik I. Parikh, Wenfang Xu, Glen E. Kellogg, Steven Grant, Sarah Spiegel, Shijun Zhang

Medicinal Chemistry Publications

In our effort to develop selective sphingosine kinase-2 (SphK2) inhibitors as pharmacological tools, a thiazolidine-2,4-dione analogue, 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione(K145), was synthesized and biologically characterized. Biochemical assay results indicate that K145 is a selective SphK2 inhibitor. Molecular modeling studies also support this notion. In vitro studies using human leukemia U937 cells demonstrated that K145 accumulates in U937 cells, suppresses the S1P level, and inhibits SphK2. K145 also exhibited inhibitory effects on the growth of U937 cells as well as apoptotic effects in U937 cells, and that these effects may be through the inhibition of down-stream ERK and Akt signaling pathways. K145 also significantly …

Intellectual Property And Public Health – A White Paper, Ryan G. Vacca, James Ming Chen, Jay Dratler Jr., Thomas Folsom, Timothy S. Hall, Yaniv Heled, Frank A. Pasquale, Elizabeth A. Reilly, Jeffery Samuels, Katherine J. Strandburg, Kara W. Swanson, Andrew W. Torrance, Katharine A. Van Tassel

Faculty Scholarship

On October 26, 2012, the University of Akron School of Law’s Center for Intellectual Property and Technology hosted its Sixth Annual IP Scholars Forum. In attendance were thirteen legal scholars with expertise and an interest in IP and public health who met to discuss problems and potential solutions at the intersection of these fields. This report summarizes this discussion by describing the problems raised, areas of agreement and disagreement between the participants, suggestions and solutions made by participants and the subsequent evaluations of these suggestions and solutions. Led by the moderator, participants at the Forum focused generally on three broad …

Early Alzheimer's And Parkinson's Disease Pathology In Urban Children: Friend Versus Foe Responses—It Is Time To Face The Evidence, Lilian Calderón-Garcidueñas, Maricela Franco-Lira, Antonieta Mora-Tiscareño, Humberto Medina-Cortina, Ricardo Torres-Jardon, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascularrelated sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPrc), alpha-synuclein, and beta-amyloid could …

Exposure To Urban Air Pollution And Bone Health In Clinically Healthy Six-Year-Old Children, Lilian Calderón-Garcidueñas, Antonieta Mora-Tiscareño, Maricela Franco-Lira, Ricardo Torres-Jardon, Bernardo Pena-Cruz, Carolina Palacios-López, Hongtu Zhu, Linglong Kong, Nicolas Mendoza-Mendoza, Hortencia Montesinoscorrea, Lina Romero, Gildardo Valencia-Salazar, Michael Kavanaugh, Silvestre Frenk

Biomedical and Pharmaceutical Sciences Faculty Publications

Air pollution induces systemic inflammation, as well as respiratory, myocardial and brain inflammation in children. Peak bone mass is influenced by environmental factors. We tested the hypothesis that six-year-olds with lifetime exposures to urban air pollution will have alterations in inflammatory markers and bone mineral density (BMD) as opposed to low-polluted city residents when matched for BMI, breast feeding history, skin phototype, age, sex and socioeconomic status. This pilot study included 20 children from Mexico City (MC) (6.17 years ± 0.63 years) and 15 controls (6.27 years ± 0.76 years). We performed full paediatric examinations, a history of outdoor exposures, …

Novel Dicarboxylate Selectivity In An Insect Glutamate Transporter Homolog, Hui Wang, Avi M. Rascoe, David Charles Holley, Eric Gouaux, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Mammals express seven transporters from the SLC1 (solute carrier 1) gene family, including five acidic amino acid transporters (EAAT1-5) and two neutral amino acid transporters (ASCT1-2). In contrast, insects of the order Diptera possess only two SLC1 genes. In this work we show that in the mosquito Culex quinquefasciatus, a carrier of West Nile virus, one of its two SLC1 EAAT-like genes encodes a transporter that displays an unusual selectivity for dicarboxylic acids over acidic amino acids. In eukaryotes, dicarboxylic acid uptake has been previously thought to be mediated exclusively by transporters outside the SLC1 family. The dicarboxylate selectivity was …

Brain Immune Interactions And Air Pollution: Macrophage Inhibitory Factor (Mif), Prion Cellular Protein (Prpc), Interleukin-6 (Il-6), Interleukin 1 Receptor Antagonist (Il-1ra), And Interleukin-2 (Il-2) In Cerebrospinal Fluid And Mif In Serum Differentiate Urban Children Exposed To Severe Vs. Low Air Pollution, Lilian Calderón-Garcidueñas, Janet V. Cross, Maricela Franco-Lira, Mariana Aragón-Flores, Michael Kavanaugh, Ricardo Torres-Jardon, Chih-Kai Chao, Charles Thompson, Jing Chang, Hongtu Zhu, Amedeo D'Angiulli

Biomedical and Pharmaceutical Sciences Faculty Publications

Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile …