Pharmacy and Pharmaceutical Sciences Commons^™

The Development Of Preclinical Strategies For Facilitation Of Lead Candidate Selection, Christopher Dale Kulczar

Open Access Dissertations

Chapter 1 details a background of techniques used for modeling the blood-brain barrier (BBB). The BBB represents a diffusive barrier to both paracellular and transcellular movement of many compounds in and out of the brain. The main rate- limiting barriers of the BBB include exclusive tight junctions that prevent the movement of hydrophilic molecules through intercellular gaps, and efflux proteins in the membrane which pump many hydrophobic molecules back into the blood. In addition, the BBB contains metabolizing enzymes, including Cytochrome P450s. This barrier acts to protect the vulnerable tissues of the brain from harmful xenobiotics, but also can serve …

Volumetry Of Low-Contrast Liver Lesions With Ct: Investigation Of Estimation Uncertainties In A Phantom Study, Qin Li, Yongguang Liang, Qiao Huang, Min Zong, Benjamin Berman, Marios A. Gavrielides, Lawrence H. Schwartz, Binsheng Zhao, Nicholas Petrick

United States Food and Drug Administration: Publications

Purpose: To evaluate the performance of lesion volumetry in hepatic CT as a function of various imaging acquisition parameters.

Methods: An anthropomorphic abdominal phantom with removable liver inserts was designed for this study. Two liver inserts, each containing 19 synthetic lesions with varying diameter (6–40 mm), shape, contrast (10–65 HU), and both homogenous and mixed-density were designed to have background and lesion CT values corresponding to arterial and portal-venous phase imaging, respectively. The two phantoms were scanned using two commercial CT scanners (GE 750 HD and Siemens Biograph mCT) across a set of imaging protocols (four slice thicknesses, …

Carriers For The Tunable Release Of Therapeutics: Etymological Classification And Examples, Vuk Uskoković, Shreya Ghosh

Pharmacy Faculty Articles and Research

Introduction—Physiological processes at the molecular level take place at precise spatiotemporal scales, which vary from tissue to tissue and from one patient to another, implying the need for the carriers that enable tunable release of therapeutics.

Areas Covered—Classification of all drug release to intrinsic and extrinsic is proposed, followed by the etymological clarification of the term “tunable” and its distinction from the term “tailorable”. Tunability is defined as analogous to tuning a guitar string or a radio receiver to the right frequency using a single knob. It implies changing a structural parameter along a continuous quantitative scale and …

Regulation Of Cancer Metastasis By Protein Kinase D1: A Global Regulatory Cascade, Aditya Ganju

Theses and Dissertations (ETD)

Protein Kinase D1 (PKD1) is a serine threonine kinase which is downregulated in Prostate, Breast and Colon Cancer. It functions as a tumor suppressor in different cancer cells. Downregulation of PKD1 is known to be associated with aggressiveness of the cancer. PKD1 is known to regulate many key oncogenic signaling pathways such as E-cadherin, β-catenin and Androgen Receptor signaling pathways. Aberrant expression of these oncogenic pathways leads to transformation of cells from normal to malignant phenotype, thereby leading to increased proliferation, growth and metastasis to distant organs of these cancer cells. Literature evidence also points to the fact that E-cadherin …

Mechanism Of Interaction Of Peptide Modified Nanoparticles With Porphyromonas Gingivalis., Ankita Jain

Electronic Theses and Dissertations

Studies suggest that P. gingivalis functions as a keystone pathogen and interacts with primary colonizers in the supragingival biofilm such as S. gordonii. This interaction contributes to the initial colonization of the oral cavity by P. gingivalis and thus represents a potential target for therapeutic intervention. We have identified a peptide (BAR) derived from the streptococcal SspB protein that functions to inhibit P. gingivalis adherence to S. gordonii. In addition, we showed that nanoparticles (NPs) functionalized with BAR inhibit this interaction more potently than free soluble peptide, possibly by promoting interaction with P. gingivalis at higher valency than …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Gathering Steam In Health Care: A Student History, Michael J. Leach

The Transdisciplinary STEAM+ Journal

In this reflection, I demonstrate STEAM in health care by outlining my 15 years as a university student engaged in formal education, extracurricular learning, research, and employment.

Sexual Dimorphism In Rat Vascular Function Of Type I And Type Ii Diabetes: Role Of Edrfs, Roshanak Rahimian

Science Seminar Series

Dr. Roshanak Rahimian, professor of physiology and pharmacology in the Thomas J. Long School of Pharmacy and Health Sciences will tell us about her work on understanding the mechanisms underlying the interaction of sex and diabetes in vasculature.

Over the past decade, diabetes and obesity have reached epidemic levels in developed countries, and has become one of the most serious and challenging health problems in the 21st century. Several studies suggest that diabetes affects male and female vascular beds differently. However, the mechanisms underlying the interaction of sex and diabetes in vasculature remain to be investigated. We have shown that …

Bis-Quaternary Ammonium Salts As Pain Modulating Agents, Joseph R. Holtman, Peter A. Crooks, Linda Phyliss Dwoskin, J. Michael Mcintosh

Pharmaceutical Sciences Faculty Patents

Provided are methods for using his-quaternary ammonium compounds to treat inflammatory pain, neuropathic pain and nociceptive pain.

Design, Synthesis, And Evaluation Of Dasatinib-Amino Acid And Dasatinib-Fatty Acid Conjugates As Protein Tyrosine Kinase Inhibitors, Rakesh Tiwari, Alex Brown, Neda Sadeghiani, Amir Nasrolahi Shirazi, Jared Bolton, Amanda Tse, Gennady M. Verkhivker, Keykavous Parang, Gongqin Sun

Pharmacy Faculty Articles and Research

Derivatives of dasatinib were synthesized via esterification with 25 carboxylic acids including amino acids and fatty acids by extending the inhibitor to interact with more diverse sites and to improve specificity. Dasatinib-L-arginine derivative (Das-R, 7) was the most potent of the inhibitors tested with IC50 values of 4.4 nM, <0.25 nM, and <0.45 nM against Csk, Src, and Abl kinases, respectively. The highest selectivity ratio obtained in our study, 91.4 Csk/Src belonged to compound 18 (Das-C10) with an IC50 of 3.2 μM for Csk compared to 35 nM for Src. Furthermore, many compounds displayed increased selectivity toward Src, as compared with Abl. Compounds 15 (Das-E) and 13 (Das-C) demonstrated the largest gains (10.2 and 10.3 Abl/Src IC50 ratios). Das-R (IC50 = 2.06 μM) was significantly more potent than Das (IC50 = 26.3 μM) against Panc-1 cells while they both showed an IC50 < 51.2 pM against BV-173 and K562 cells. Molecular modeling and binding free energy simulations revealed a good agreement with the experimental results and rationalized differences in selectivity of the studied compounds. Integration of experimental and computational approaches in the design and biochemical screening of dasatinib derivatives facilitated rational engineering and diversification of dasatinib scaffold, providing useful insights into mechanisms of kinase selectivity.

Decreasing Cost Associated Medication Nonadherence, Shawn E. Raymond

Doctor of Nursing Practice Scholarly Project

An Abstract of the Scholarly Project by

Shawn E. Raymond

Medication cost is a major contributor for patient medication nonadherence. Take in the fact that a large population lives in poverty, many cannot afford to pay the retail prices associated with purchasing their medications. By incorporating wholesale medications into a charitable health clinic, the reduced cost of medications for treatment of both acute and chronic illnesses could be passed on to those in need thereby decreasing cost associated medication nonadherence. Nurse Practitioners in the state of Kansas are not afforded the privilege to purchase, repackage and distribute or resell wholesale …

Moseying Along At The Fda, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Causal Inference For Biomedical Research Php/Sta 592, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Proteasome Inhibitors, Kyung Bo Kim, Venod Kasam, Wooin Lee, Dong-Eun Kim, Zachary Miller, Chang-Guo Zhan, Do-Min Lee

Pharmaceutical Sciences Faculty Patents

To see this patent's abstract, please download it.

Prevalence Of Prescription Opioid Abuse In Patients With Pain, Samuel Godana, Ankoor Biswas, Nebiyu Biru, Abraham Getenet, Biana Leybishkis

Journal of Patient-Centered Research and Reviews

Background: Studies showed that 20% to 30% of opioid analgesic drugs prescribed for chronic pain in the United States are misused, while the rate of opioid addiction is approximately 10%. The study describes methods to identify high-risk behavior and forward recommendations to decrease opioid abuse.

Purpose: To assess prevalence and correlate multiple variables with opioid abuse and to forward appropriate recommendation to decrease the prevalence of opioid abuse in the primary care setting.

Methods: A prospective study was conducted at a primary health care clinic, Aurora Sinai Medical Center (Milwaukee, WI). Over 6 months, a total of 49 consecutive patients …

An Interdisciplinary Process Change: Conversion Of Picc Line Capping Solution From Heparin To Normal Saline, Angela Colella, Brandon Bodager, Frank Spexarth, Natalie Mcdonough, Deb Kastenholz, Paul Grebe

Journal of Patient-Centered Research and Reviews

Background: Heparin-induced thrombocytopenia (HIT) and HIT with thrombosis syndrome (HITTS) are serious conditions. Patients are at increased risk for developing HIT/HITTS with any exposure to heparin, even intravenous line flushes. Patients may be exposed to heparin multiple times each day when they have a peripherally inserted central catheter (PICC) that is flushed and capped with heparin. At Aurora Health Care, heparin is the standard capping solution for PICCs, but with a recent switch to positive pressurized caps, normal saline may be a capping option that reduces patient exposure to heparin.

Purpose: To reduce heparin exposure at a single hospital by …

Treatment Of A Chemoresistant Neuroblastoma Cell Line With The Antimalarial Ozonide Oz513., Don W. Coulter, Timothy R. Mcguire, J. Graham Sharp, Erin M. Mcintyre, Yuxiang Dong, Xiaofang Wang, Shawn Gray, Gracey R. Alexander, Nagendra K. Chatuverdi, Shantaram Joshi, Xiaoyu Chen, Jonathan L. Vennerstrom

Journal Articles: Pharmacy Practice

BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c.

METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing's Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. …

Method And System For Producing Triterpenes, Joe Chappell, Thomas D. Niehaus, Shigeru Okada, Timothy P. Devarenne, David Watt

Pharmaceutical Sciences Faculty Patents

A method and system are provided for the production of triterpene including methylated triterpenes. The method and system include isolated nucleic acid sequences encoding triterpene methyltransferases such as triterpene methyltransferases 1, 2, 3. Advantageously, the method and system includes transgenic plant cells via an expression vector for triterpene methyltransferase and optionally various triterpene synthase and prenyltransferase all with tags directing these enzymes to the chloroplast of the transgenic plant cells for using the chloroplast methyl erythritol phosphate (MEP) pathway in the triterpene biogenesis.

Effects Of Antibiotic Mixtures Across Marine Intertidal Trophic Levels: Examining Environmentally-Relevant Contaminant Concentrations, Jaclyn Rebecca Teixeira

Dissertations and Theses

Approximately 48% of Americans use prescription drugs within each 30-day period, and there are signs this trend is increasing. Although many studies track pharmaceuticals’ fates in contaminating waterways, only fairly recent efforts have examined the potential impacts of these drugs on non-target organisms. The antibiotics sulfamethoxazole and trimethoprim, often prescribed together to treat bacterial infections, have been detected worldwide in marine and estuarine environments at concentrations up to 700-800 ng/L each. Toxic effects of these drugs have been identified in freshwater organisms, with synergistic effects observed in short-term studies of mixtures of the two; however, little research has examined possible …

Legislative Solutions To Narcotic And Drug Addiction, Joseph R. Corso

The Catholic Lawyer

No abstract provided.