Pharmacology, Toxicology and Environmental Health Commons^™

Design And Synthesis Of Enzalutamide-Isothiocyanate Hybrid Drug As Anti-Prostate Cancer Agent, Siyu Ou

Wayne State University Theses

Isothiocyanate (ITC), such as sulforaphane (SFN), is an active metabolite of dietary glucosinolate from cruciferous vegetables. SFN-rich extracts have been recently tested in recurrent prostate cancer (PCa) patients and notably prolonged PSA doubling time without Grade 3 adverse events. One of the anti-PCa mechanisms of SFN is to inhibit HDAC6, which further triggering androgen receptor (AR) degradation. We have incorporated ITC to the chemical scaffold of enzalutamide (Enz) to create Enz-ITC hybrid molecules with an intention to intracellularly deliver ITC to AR-Hsp90-HDAC6 complex and therefore improving anti-PCa efficacy of both parental drugs. Two Enz-ITCs and one Enz-ITC N-acetyl cysteine (NAC) …

Impact Of Cefazolin Co-Administration With Vancomycin To Reduce Development Of Vancomycin Intermediate Staphylococcus Aureus, Nivedita Birbahadur Singh

Wayne State University Theses

IMPACT OF CEFAZOLIN CO-ADMINISTRATION WITH VANCOMYCIN TO REDUCE DEVELOPMENT OF VANCOMYCIN INTERMEDIATE STAPHYLOCOCCUS AUREUS

by

NIVEDITA B SINGH

August 2106

Advisor: Dr. Michael J. Rybak

Major: Pharmaceutical sciences

Degree: Masters of Science

Objective: Development of resistance in S. aureus has been a big concern in the treatment of infections caused by the organism. The line of therapy used today has a disadvantage of slowly developing cross-resistance for antibiotics such as DAP secondary to prior VAN exposure. Therefore, alternative therapy is needed to prevent the emergence of VAN resistance and cross-resistance to other antibiotics. The primary aim of this experiment is …

Targeted Delivery Of Nrf2 Sirna Using Modular Polymeric Micellar Nanodelivery System For Efficient Target Gene Knockdown In Hepatocellular Carcinoma, Shaimaa Mohamed Ibrahim Yousef

Wayne State University Theses

Tumor selective drug delivery as well as chemotherapy associated multi drug resistance (MDR) pose tremendous hurdles for effective cancer therapy. In this regard, designing multifunctional nanocarriers loaded with drug/gene payloads and engineered with tumor targeting ligands can serve as a modular platform for targeted drug/gene delivery. In this study we undertook the synthesis of a self-assembling block copolymer constructed using poly(styrene-co-maleic anhydride, partial iso-octyl ester) (SMAPIE) and branched polyethylenimine (PEI) as building blocks and evaluated its micelle forming ability, siRNA complexation and siRNA delivery potentials. In addition, we engineered galactosamine decorated nanomicelles using modular “click” chemistry based approaches for evaluating …

Dendrimer-Coated Iron Oxide Theranostic Nanoparticles For Cancer Imaging And Therapy, Duy Khanh Luong

Wayne State University Theses

The bleak prognosis for patients diagnosed with metastatic cancer along with the low therapeutic efficacy and the recurrence of cancer in conventional chemotherapy are prompting clinical medicine to adopt a new strategy to detect cancer in early stage and to deliver the anticancer drugs specifically to tumor site to enhance therapeutic efficiency and minimize side effects. The aim of this study is to design a theranostic nanocarrier consisting of iron oxide nanoparticles (SPIONs) for magnetic resonance imaging (MRI) and Polyamidoamine dendrimers conjugated with folic acid (FA-PAMAM) for active targeted delivery of a highly potent but extremely lipophilic anticancer compound 3,4-difluorobenzylidene …

Corporate Social Responsibility/Sustainability Reporting Among The Fortune Global 250: Greenwashing Or Green Supply Chain?, John K. Lewis

Faculty and Staff - Articles & Papers

The sustainability reporting efforts of MNCs who are members of the Fortune Global 250 (FG250) was investigated. The focus was on sustainability reporting by MNCs of supply chain impacts. The reporting of FG250 MNCs was examined to determine if greenwashing was occurring or whether MNCs had committed to operating a green supply chain. A mixed methodology was used consisting of quantitative analysis of twenty-five MNC CSR/sustainability reports which were randomly selected from the FG250 listing. Qualitative analysis using content analysis was also conducted on the reports. Both methodologies concentrated on the sustainability reporting of the selected MNCs in regard to …

Full Issue: Volume 9, Number 2

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

The Influence Of Abiotic Factors On The Uptake And Elimination Of 3-Trifluoromethyl-4-Nitrophenol By Larval Sea Lamprey (Petromyzon Marinus), Benjamin Livingston Hlina

Theses and Dissertations (Comprehensive)

The backbone of sea lamprey (Petromyzon marinus) control in the Great Lakes is the use of the piscicide, 3-trifluoromethyl-4-nitrophenol (TFM), which is applied to streams containing larval sea lampreys. However, TFM effectiveness can be influenced by abiotic factors such as pH and temperature, which fluctuate daily and seasonally. The objectives of this thesis were to evaluate the influence of pH, temperature, and season on the toxicity, uptake, and elimination of TFM by larval sea lamprey. Radio-labeled TFM (¹⁴C-TFM) was used to determine how TFM uptake rates varied at different water pHs or temperatures during exposure to …

Nickel And Copper Mixture Toxicity To Daphnia In Soft Water, Prachi Deshpande

Theses and Dissertations (Comprehensive)

Industrially important metals, such as Cu and Ni, sometimes are present at elevated concentrations in lakes, including those in the Sudbury, ON region. Although they are essential metals, their divalent-cation state (Cu²⁺ and Ni²⁺) can be toxic at high concentrations in the water. The free-ion toxicity of each of these metals has been studied in isolation, but rarely as a mixture. The economic importance of Cu²⁺ and Ni²⁺ makes them essential to study in the context of mixture toxicity. The objectives were to: (1) determine Cu and Ni mixture toxicity to Daphnia through acute LC50 …

The Sublethal Physiological Effects Of Exposure To Copper And Silver Mixtures On Rainbow Trout (Oncorhynchus Mykiss), Wesley Truong

Theses and Dissertations (Comprehensive)

The mechanisms behind metal-metal interactions in freshwater environments are currently not well understood. Freshwater environments consist of many different types of metals, from those naturally present such as copper (Cu) and those that originate from anthropogenic sources like silver (Ag). Both Cu and Ag use apical sodium (Na⁺) channels for uptake into the gills of freshwater fish. In the gills, the mechanisms of Cu²⁺ and Ag⁺ toxicity appear to be similar to one another, which is by inhibiting Na⁺ /potassium (K⁺)- adenosine triphosphatase (NKA) and carbonic anhydrase (CA). Inhibition of NKA and CA …

Phosphodiesterase Inhibition As A Mechanism Of Ion Channel Modulation By Celecoxib, Christina Jean Robakowski

Master's Theses

The overall objective of this thesis work is to determine the mechanism by which celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells. The central hypothesis of the project is that celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells through inhibition of phosphodiesterase 4 (PDE4, which catalyzes the breakdown of cyclic adenosine monophosphate (cAMP)), thereby activating a cAMP/protein kinase A (PKA) signaling pathway. The aims of this thesis targeted different points in the cAMP/PKA pathway with pharmacological interventions using whole cell perforated patch clamp electrophysiology and biochemical methods.

The data suggest multiple mechanisms by which celecoxib could …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

Assessing Public Health Burden Associated With Exposure To Ambient Black Carbon In The United States, Ying Li, Daven K. Henze, Darby Jack, Barron H. Henderson, Patrick L. Kinney

ETSU Faculty Works

Black carbon (BC) is a significant component of fine particulate matter (PM_2.5) air pollution, which has been linked to a series of adverse health effects, in particular premature mortality. Recent scientific research indicates that BC also plays an important role in climate change. Therefore, controlling black carbon emissions provides an opportunity for a double dividend. This study quantifies the national burden of mortality and morbidity attributable to exposure to ambient BC in the United States (US). We use GEOS–Chem, a global 3-D model of atmospheric composition to estimate the 2010 annual average BC levels at 0.5 x 0.667° …

Impact Of A Diesel Spill On Macroinvertebrate Communities In Ponds In S.E. Alabama, Usa, Katie E. Winkles

Theses and Dissertations

In this study, macroinvertebrate communities were examined to determine an indication of the water quality in ponds on a wetlands property after a diesel spill. In 2012, a train derailed, and at least 3000 gallons of diesel fuel leached into a small pond of the wetlands. Even after clean-up attempts there remains major concerns that the contamination spread throughout the wetlands. This concern led to the present study. Macroinvertebrates were the chosen focus due to their sensitivity to changes in the environment. Two field trials were conducted in which Hester-Dendy multiplate samplers were placed in ponds to allow macroinvertebrates to …

The Role Of Renal Replacement Therapy In The Management Of Pharmacologic Poisonings, Aibek E. Mirrakhimov, Aram Barbaryan, Adam Gray, Taha Ayach

Internal Medicine Faculty Publications

Pharmacologic toxicities are common and range from mild to life-threatening. The aim of this study is to review and update the data on the role of renal replacement therapy (RRT) in the management of various pharmacologic poisonings. We aim to provide a focused review on the role of RRT in the management of pharmacological toxicities. Relevant publications were searched in MEDLINE with the following search terms alone or in combination: pharmacologic toxicity, hemodialysis, hemofiltration, renal replacement therapy, toxicology, poisonings, critical illness, and intensive care. The studies showed that a pharmacologic substance should meet several prerequisites to be deemed dialyzable. These …

Synthesis And Biochemical Evaluation Of 3-Phenoxy-1,4-Diarylazetidin-2-Ones As Tubulin-Targeting Antitumor Agents, Thomas F. Greene, Shu Wang, Lisa M. Greene, Seema M. Nathwani, Jade K. Pollock, Azizah M. Malebari, Thomas Mccabe, Brendan Twamley, Niamh O'Boyle, Daniela M. Zisterer, Mary J. Meegan

Articles

Structure-activity relationships for a series of 3-phenoxy-1,4-diarylazetidin-2-ones were investigated leading to the discovery of a number of potent antiproliferative compounds, including trans-4-(3-hydroxy-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (78b) and trans-4-(3-amino-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (90b). X-ray crystallography studies indicate the potential importance of the torsional angle between the 1-phenyl ‘A’ ring and 4-phenyl ‘B’ ring for potent antiproliferative activity, and that a trans configuration between the 3-phenoxy and 4-phenyl rings is generally optimal. These compounds displayed IC₅₀ values of 38 nM and 19 nM respectively in MCF-7 breast cancer cells, inhibited the polymerization of isolated tubulin in vitro, disrupted the microtubular …

Heavy Metal Accumulation In Urban Soil: A Phytoextraction Method Review, Diane M. Nelson

Dissertations, Master's Theses and Master's Reports

Lead (Pb), cadmium (Cd), and arsenic (As) are three common non-essential heavy metals found in urban soils and can prove toxic to animals, humans, and some plants at low concentrations. The main exposure pathways of heavy metals in humans are through ingestion and inhalation of soil particles and ingestion of contaminated food. When dealing with contaminated soil in urban environments, activities like urban gardening can increase the likelihood of these exposure pathways, so heavy metal toxicity from contaminated soil can become a greater risk with the increased interest in urban agriculture. The US EPA created target concentrations for these heavy …

Simple And Rapid Spectrophotometric Method For Quality Determination Of Roselle (Hibiscus Sabdariffa), Tasamaporn Sukwattanasinit, Jankana Burana-Osot, Uthai Sotanaphun

The Thai Journal of Pharmaceutical Sciences

A simple and rapid spectrophotometric method has been developed to determine the quality of roselle (Hibiscus sabdariffa). The absorbance at 530 nm (coloring intensity) and the ratio between the absorbances at 380 and 530 nm (degradation index) of its 5...

An Investigation Of Juvenile Alewife (Alosa Pseudoharengus) Habitat Use And Growth Using Natural Markers, Gregory Norman Labonte Ms

All Student Scholarship

This research attempts to connect patterns in growth and migration of an anadromous species. The goal of this research was to understand habitat movements and growth of juvenile alewives (Alosa pseudoharengus) in the Penobscot Estuary and Bay through the use of otolith microchemistry, otolith growth increments, and a laboratory stable isotope turnover study. Understanding the connection between growth and movement of juvenile alewives may lead to more accurate and sophisticated conservation and restoration methods for anadromous species.

Unique Behavioral And Neurochemical Effects Induced By Repeated Adolescent Consumption Of Caffeine-Mixed Alcohol In C57bl/6 Mice., Meridith T. Robins, Julie Lu, Richard M. Van Rijn

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug …

Interaction Of Na+/K+ Atpase With Bcl-2 Proteins: Isolated Enzyme Vs Epithelial Cell Extracts, Chandra Kumar Maharjan

Browse all Theses and Dissertations

The nearly complete inhibition of Na+/K+ ATPase (NKA) in fetal human lens (FHL) epithelial cells by chelerythrine (CHE), a Bcl-2 homology (BH)3-mimetic quaternary benzophenanthridine alkaloid was proposed to be the consequence of CHE binding at a BH1-like hydrophobic groove at the cytosolic aspect of NKA. This conclusion was based on in silico analysis showing at least two motifs in the N-terminal domain of NKA’s a1 subunit- i) aa 59-71 (ARAAEILARDGPN) and ii) aa 42-48 (DELHRKY) homologous to the BH1 and BH3 motifs of Bcl-2 (B-cell lymphoma) respectively, leading to a novel hypothesis that NKA could interact with these proteins by …