Pharmacy and Pharmaceutical Sciences Commons^™

Development And Validation Of A Sensitive Uplc-Ms/Ms Method For The Quantitation Of [13c]Sucrose In Rat Plasma, Blood, And Brain: Its Application To The Measurement Of Blood-Brain Barrier Permeability, Mohammad K. Miah, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Accurate and reproducible measurement of blood-brain barrier (BBB) integrity is critical in the assessment of the pathophysiology of the central nervous system disorders and in monitoring therapeutic effects. The widely-used low molecular weight marker [14C]sucrose is non-specific in the absence of chromatographic separation. The purpose of this study was to develop and validate a sensitive and reproducible LC-MS/MS method for the analysis of stable isotopemodified [13C12]sucrose in brain, plasma, and blood to determine BBB permeability to sucrose. After addition of internal standard (IS, [13C6]sucrose), the marker and IS were recovered from diluted rat blood, plasma, and brain homogenate by protein …

Phytopharmaceuticals In Mongolia: Past, Present, And Future, Disan Gunbilig, Ulziinyam Rentsendorj

Erforschung biologischer Ressourcen der Mongolei / Exploration into the Biological Resources of Mongolia, ISSN 0440-1298

Over the last two decades, the consumption of medicinal plants has increased in Mongolia. Once banned by the post-revolutionary government, it is now valued by the practitioners of orthodox medicine, government as well as by the society. Yet the scientific community has to give this major and crucial component of traditional Mongolian medicine the attention it deserves, scientific knowledge about biologically active principles within medicinal plants remain poorly unknown. At the same time, due to over exploitation of plants many species are becoming extinct together with invaluable traditional knowledge being lost. For these reasons, there is a certain urgency to …

Purin-6-One Derivatives As Phosphodiesterase-2 Inhibitors, Wei Yuan, Xin-Yun Zhao, Xi Chen, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

A series of purin-6-one derivatives were synthesized, and their in vitro inhibitory activity against phosphodiesterase-2 (PDE2) was evaluated by using a fluorescence polarization assay. Three compounds, that are, 2j, 2p, and 2q, showed significant inhibitory activity against PDE2 with IC₅₀ values of 1.73, 0.18, and 3.43 μM, respectively. Structure-activity relationship (SAR) analysis was performed to explore the relationship between the chemical structures of these compounds and their inhibitory activity. Compounds 2j, 2p, and 2q were further selected for molecular docking study. The docking results suggested that these ligands bind with hydrophobic pockets of …

Bupropion Hydrochloride, Cylie A. Couch

Natural Sciences Student Research Presentations

This is a poster presented at the Natural Sciences Poster Session at Parkland College, which provides the chemical makeup, dosage, and the body's response to r bupropion hydrochloride (Wellbutrin, Zyban), a medication used to treat depression, smoking cessation, and seasonal affective disorder.

Continuous Stationary Phase Gradients For Planar And Column Chromatography, Veeren Dewoolkar

Theses and Dissertations

Surfaces that exhibit a gradual change in their chemical and/or physical properties are termed as surface gradients. Based on the changes in properties they are classified either as physical or chemical gradients. Chemical gradients show variations in properties like polarity, charge, functionality concentration and have found potential applications in fields of biology, physics, biosensing, catalysis and separation science. In this dissertation, surface gradients have been prepared using controlled rate infusion (CRI).

CRI is a simple method in which a surface gradient is formed by carrying out the infusion of organoalkoxysilane in a time-dependent fashion using a set infusion rate. Depending …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Antiviral Peptide Nanocomplexes As Potential Therapeutics For The Treatment Of Infectious Diseases, Jinjin Zhang

Theses & Dissertations

Hepatitis C Virus (HCV) is recognized as a major burden in global public health, which can be further exacerbated by several cofactors such as human immunodeficiency virus (HIV). Currently, there is no vaccine for HCV. The emergence of potent and highly specific direct-acting antivirals (DAA) has marked a new era in HCV therapy, however, the remaining issues like affordability, genotype dependency, and potential resistance still necessitate the development of additional therapeutic approaches to be used instead or in combination with DAA.

Recently, the antiviral peptide C5A (in our studies designated as p1) and its cationic derivative p41 have been identified …

Synthesis Of Medicinally Relevant Thiazolyl Aryl Ketones Under Mild Conditions, Danielle M. Gardner

Health, Human Performance and Recreation Undergraduate Honors Theses

Purpose: The growing amount of clinical resistance observed in current antifungal drugs and in anti-HIV pharmaceuticals is a concern in the medical community. The purpose of this study is to develop a mild synthetic process for biomedically relevant thiazolyl aryl ketones that can be used to develop antifungal and anti-HIV drugs. We hypothesized that the proposed synthetic technique would be more efficient, produce fewer unwanted byproducts, and be more tolerant of functional groups than existing methods.

Methods: Prior to each of the ketone reactions, the necessary salt was synthesized by mixing thiazole and 9-bromofluorene neat in a reaction tube heated …

Design And Synthesis Of Novel Chloroquine-Based Antimalarials, Kevin Vincent Murphy

Dissertations and Theses

Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite Plasmodium falciparum. Victims usually contract the disease through a mosquito vector. Chloroquine is a chemotherapeutic that was introduced in the 1940s. For many years the drug was the foremost treatment of malaria, being effective and producing few side effects. Unfortunately, tolerance to chloroquine developed when the parasite evolved a resistance mechanism. Newer drugs have been developed and implemented, but these medicines also show a decreasing effect with continued administration. …

Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen

Dissertations and Theses (Open Access)

The past decade has witnessed an era of RNA biology; despite the considerable discoveries nowadays, challenges still remain when one aims to screen RNA-interacting small molecule or RNA-interacting protein. These challenges imply an immediate need for cost-efficient while predictive computational tools capable of generating insightful hypotheses to discover novel RNA-interacting small molecule or RNA-interacting protein. Thus, we implemented novel computational models in this dissertation to predict RNA-ligand interactions (Chapter 1) and RNA-protein interactions (Chapter 2).

Targeting RNA has not garnered comparable interest as protein, and is restricted by lack of computational tools for structure-based drug design. To test the potential …

An Information Privacy Examination Of The Practices Of Pharmaceutical Companies Regarding Use Of Information Collected Through Their Websites, Shonda Dellena Brown

CCAC Theses and Dissertations

Consumers have begun to take a more proactive approach to their healthcare by accessing pharmaceutical companies Websites to obtain health and drug information, support groups, rebates, coupons, as well as free drug trials. In exchange for these benefits, companies require consumers to voluntarily disclose information. However, research has shown that consumers continue to be concerned about how their information is managed, used, and distributed by companies, especially if accessed via the Web. To date, there has been limited empirical research to examine the actual online practices of companies when it comes to privacy, especially those of pharmaceutical companies. Using Delphi …

Swosu Research And Scholarly Activity Fair 2015, Jason L. Johnson

SWOSU Research and Scholarly Activity Fair Programs

Welcome to the Twenty-Second SWOSU Research and Scholarly Activity Fair! On display today are 103 presentations involving 169 student researchers, writers, performers, and artists, and 40 faculty sponsors encompassing scholarly activity from the Departments of: Accounting, Computer Science, and Entrepreneurship; Art, Communication, and Theatre; Biological Sciences; Chemistry and Physics; Education; Engineering Technology; Finance, Management, and Marketing; Language and Literature; Music; Nursing and Allied Health; Pharmaceutical Sciences; Psychology; and Social Sciences.

Modeling, Optimization, And Sensitivity Analysis Of A Continuous Multi-Segment Crystallizer For Production Of Active Pharmaceutical Ingredients, Bradley James Ridder

Open Access Dissertations

We have investigated the simulation-based, steady-state optimization of a new type of crystallizer for the production of pharmaceuticals. The multi-segment, multi-addition plug-flow crystallizer (MSMA-PFC) offers better control over supersaturation in one dimension compared to a batch or stirred-tank crystallizer. Through use of a population balance framework, we have written the governing model equations of population balance and mass balance on the crystallizer segments. The solution of these equations was accomplished through either the method of moments or the finite volume method. The goal was to optimize the performance of the crystallizer with respect to certain quantities, such as maximizing the …

Expression Of The Nkcc2a Cotransporter In Mouse Central Nervous System, Katherine E. Fahy, James B. Lucot, Hayo Castrop, Mauricio Di Fulvio

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

Na-K-2Cl cotransporter 2A (NKCC2A), also known as the bumetanide-sensitive cotransporter 1 (BSC1), transports Na+, K+ and Cl- with a stoichiometry of 1:1:2. NKCC2A is considered a kidney specific cotransporter. It is abundantly expressed in apical membrane of the tubular cells in the thick ascending limb of the loop of Henle (TALH) and in the macula densa. However, NKCC2 has also been found at low levels in different cells, including insulin-secreting ones. This secondary active transporter uses the energy stored in the electrochemical gradients of Na and K maintained by the Na/K-ATPase located on the basolateral membrane of the TALH. The …

Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver

Theses and Dissertations--Pharmacy

Methamphetamine (METH) abuse is a serious problem in the United States and worldwide. The reward experienced by METH users is due to the increase in extracellular dopamine (DA) concentrations caused by an interaction between METH and the DA transporter (DAT) as well as the Vesicular Monoamine Transporter-2 (VMAT2). The reward felt by users of METH leads to further use of the drug and subsequent abuse. The current project examined the ability of three novel series of lobelane analogs to interact with a binding site on the Vesicular Monoamine Transporter-2 (VMAT2) in an attempt to inhibit the effects of METH. Lobelane …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

A Molecular-Level View Of The Physical Stability Of Amorphous Solid Dispersions, Xiaoda Yuan

Theses and Dissertations--Pharmacy

Many pharmaceutical compounds being developed in recent years are poorly soluble in water. This has led to insufficient oral bioavailability of many compounds in vitro. The amorphous formulation is one of the promising techniques to increase the oral bioavailability of these poorly water-soluble compounds. However, an amorphous drug substance is inherently unstable because it is a high energy form. In order to increase the physical stability, the amorphous drug is often formulated with a suitable polymer to form an amorphous solid dispersion. Previous research has suggested that the formation of an intimately mixed drug-polymer mixture contributes to the stabilization …

Security Of Eprescription: Security Of Data At Rest In Prescription Exchange Services Vs On Mobile Devices, Kyaw Kyaw Htat, Patricia A. H. Williams, Vincent Mccauley

Australian eHealth Informatics and Security Conference

One area of healthcare that has moved more quickly than others in adopting electronic transfer of information is prescribing in the primary care environment. Several Acts and Regulations have been repealed and amended at Commonwealth and State levels to enable this progress over the past decade, as medication provision is a strictly controlled area of healthcare. Further, numerous standards and specifications have been developed and adopted to support and safeguard the regulatory changes and facilitate the electronic transfer of prescriptions. However, the current model of electronic prescription transfer comes with a substantial price tag for ongoing use. With the Nation’s …

Predicting Aqueous Solubility Of Pharmaceutical Agents By Solid Dispersion Prepared By Solvent Evaporation Method, Karthik Reddy Patlolla

University of the Pacific Theses and Dissertations

Solubility of active pharmaceutical agents is a crucial process that determines drug absorption and ultimately its bioavailability. Many of the new therapeutically beneficial compounds discovered are lipophilic requiring various solubility enhancement strategies to improve their solubility. Among these strategies, solubility enhancement using solid dispersions is a leading method. To obtain a desirable increase in the solubility of a poorly-soluble compound, a good understanding of the molecular descriptors influencing the enhancement of solubility is essential. Therefore, the major research objective was to determine the descriptors which significantly influence the solubility enhancement by solid dispersions. After enhancing the solubility of selected poorly-soluble …

Metal Organic Frameworks (Mofs) And Porous Organic Polymers (Pops) For Heterogeneous Asymmetric Catalysis, Youngran Ji

USF Tampa Graduate Theses and Dissertations

The administration of enantiopure drugs brings advantages such as improved efficacy, more predictable pharmacokinetics and reduced toxicity from the point of view of the pharmaceutical area.[1] For this reason, a tremendous amount of supply and demand for enantiomeric pure compounds has been shown not only in market, but industry and academia.[^2-4] According to the industry publication Genetic Engineering and Biotechnology News (GEN) in 2014, 22 billion dollars were accounted for enantiopure form of drugs such as Sovaldi® (Sofosbuvir), Crestor® (Rosuvastatin), and Advair® (fluticasone/salmeterol).

The fact that one enantiomer can be pharmacologically effective whereas the other enantiomer can be …

Reference Material Development For Paralytic Shellfish Poisoning Toxins And Associated Analytical Applications, Stephen Burrell

Doctoral

Food poisoning incidences relating to marine biotoxins are a global phenomenon and have the potential to severely impact the aquaculture industry. As a result, and as a legislative requirement in the European Union (EU), many countries have implemented monitoring programmes for these compounds but their success relies on the availability of certain quality assurance tools, two of which are reference materials (RMs) and proficiency testing. The limited amounts of RMs, in particular matrix certified reference materials (CRMs) for paralytic shellfish poisoning (PSP) toxins has been a limiting factor in the implementation of alternatives to the mouse bioassay for routine monitoring …

Inhibition Of The Thioesterase Activity Of Human Fatty Acid Synthase By 1,4- And 9,10-Diones, Herman H. Odens

Faculty Works

Fatty acid synthase (FASN) is the enzyme that synthesizes fatty acids de novo in human cells. Although FASN is generally expressed at low levels in most normal tissues, its expression is highly upregulated in many cancers. Consistent with this notion, inhibition of FASN activity has demonstrated potential to halt proliferation and induce cell death in vitro and to block tumor growth in vivo. Consequently, FASN is widely recognized as a valuable therapeutic target. In this report, we describe a variety of 1,4-quinones and 9,10- anthraquinones, including several natural compounds and some newly synthesized compounds, that potently inhibit the thioesterase (TE) …

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 …

Biophysical Characterization Of The First Four Metal-Binding Domains Of Human Wilson Disease Protein, Alia V.H. Hinz

Dissertations

Wilson disease protein (WLNP) is a P_1b-type ATPase crucial for maintaining copper homeostasis in humans. Mutations in this protein result in the autosomal recessive disorder Wilson disease, a condition characterized by copper accumulation in the liver and brain. WLNP provides copper for incorporation into cuproproteins and exports excess copper into the bile for excretion. There are six metal-binding domains (MBDs) in WLNP, found within the first 650 amino acids of this 1,465 amino acid protein. Though each MBD has a different amino acid sequence, all MBDs possess a similar ferredoxin fold with a conserved hydrophobic core and a …

Design, Synthesis And Biological Evaluation Of Novel Compounds With Cns-Activity Targeting Cannabinoid And Biogenic Amine Receptors, Alexander M. Sherwood

LSU New Orleans Theses and Dissertations

This work seeks to contribute to the discipline of neuropharmacology by way of structure activity relationship from the standpoint of an organic chemist. More specifically, we sought to develop robust synthetic methodology able to efficiently produce an array of compounds for the purpose of systematic evaluation of their interaction with specific sights within the central nervous system (CNS) in order to better understand the mind and to develop drugs that may have beneficial effects on neurological function.

The focus of these studies has been toward the development of novel molecules, using a structure-activity relationship approach, that exhibit binding affinity at …

Analysis Of Ligand Bias In Functional Studies Involving The Allosteric Modulation Of G Protein- Coupled Receptors, Frederick J. Ehlert, Michael T. Griffin

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Introduction

The affinity constants of a ligand for active and inactive states of a receptor ultimately determine its capacity to activate downstream signaling events. In this report, we describe a reverse-engineering strategy for estimating these microscopic constants.

Methods

Our approach involves analyzing responses measured downstream in the signaling pathway of a G protein-coupled receptor under conditions of allosteric modulation and reduced receptor expression or partial receptor inactivation. The analysis also yields estimates of the isomerization constant of the unoccupied receptor, the sensitivity constant of the signaling pathway, and the more empirical parameters of the receptor population including the observed affinities …

Nudging The Fda, W. Nicholson Price Ii, I. Glenn Cohen

Law Faculty Scholarship

[Excerpt] "The FDA’s regulation of drugs is frequently the subject of policy debate, with arguments falling into two camps. On the one hand, a libertarian view of patients and the health care system holds high the value of consumer choice. Patients should get all the information and the drugs they want; the FDA should do what it can to enforce some basic standards but should otherwise get out of the way. On the other hand, a paternalist view values the FDA’s role as an expert agency standing between patients and a set of potentially dangerous drugs and potentially unscrupulous or …

Quantitative Mass Spectrometric Investigations Of Protein Biomarkers: Serum Thymidine Kinase 1 And Human Osteopontin, Morse Faria

Theses and Dissertations

Mass spectrometry is being increasingly used in biomarker research mainly due to its ability to achieve high selectivity coupled with high sensitivity. This dissertation focuses on quantitative mass spectrometric investigations of two protein biomarkers i.e. serum thymidine kinase 1 (TK1) and human osteopontin (OPN).

First part of this research was focused on developing a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for measuring the activity of TK1 in serum by monitoring the conversion of a TK1 specific exogenous substrate, 3’-deoxy-3’-fluorothymidine (FLT), to its mono-phosphorylated form 3’-deoxy-3’-fluorothymidine monophosphate (FLT-MP). A method to quantify FLT-MP on LC-MS/MS was developed and …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Rat Hippocampal Responses Up To 90 Days After A Single Nanoceria Dose Extends A Hierarchical Oxidative Stress Model For Nanoparticle Toxicity, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

Ceria engineered nanomaterials (ENMs) have very promising commercial and therapeutic applications. Few reports address the effects of nanoceria in intact mammals, let alone long term exposure. This knowledge is essential to understand potential therapeutic applications of nanoceria in relation to its hazard assessment. The current study elucidates oxidative stress responses in the rat hippocampus 1 and 20 h, and 1, 7, 30 and 90 days following a single systemic infusion of 30 nm nanoceria. The results are incorporated into a previously described hierarchical oxidative stress (HOS) model. During the 1-20 h period, increases of the GSSG: GSH ratio and cytoprotective …