Pharmacology, Toxicology and Environmental Health Commons^™

Parthenolide Blocks Cocaine’S Effect On Spontaneous Firing Activity Of Dopaminergic Neurons In The Ventral Tegmental Area, David Schwarz, Damaris Bloom, Rocío Castro, Oné R. Pagán, C. A. Jiménez-Rivera

Biology Faculty Publications

Chronic cocaine administration leads to catecholamine reuptake inhibition which enhances reward and motivational behaviors. Ventral Tegmental Area dopaminergic (VTA DA) neuronal firing is associated with changes in reward predictive signals. Acute cocaine injections inhibit putative VTA DA cell firing in vertebrates. Parthenolide, a compound isolated from the feverfew plant (Tanacetum parthenium), has been shown to substantially inhibit cocaine’s locomotion effects in a planarian animal model (Pagán et al., 2008). Here we investigated the effects of parthenolide on the spontaneous firing activity of putative VTA DA neurons in anesthetized male rats (250-300g). Single-unit recordings were analyzed after intravenous (i.v.) parthenolide administration …

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation And Cause Cell Cycle Arrest In A Pparγ Independent Manner, Linah Al-Alem, R. Chase Southard, Michael W. Kilgore, Thomas E. Curry

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.

PRINCIPAL FINDINGS: Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no …

National Center For Pharmaceutical Crops, Wei Yuan, Shiyou Li, Zushang Su, Ping Wang

NCPC Presentations

The mission of the National Center for Pharmaceutical Crops is to develop crops for the production of pharmaceutical and other bioactive compounds. The NCPC, located in the Arthur Temple College of Forestry and Agriculture, is the only one of its kind in the U.S. and it seeks to improve human health, revitalize rural economies and enhance U.S. security in strategic pharmaceuticals. This poster provides a background to the department, its functions and activities and notable achievements.

Evaluating The Effectiveness Of A Commercial Portable Air Purifier In Homes With Wood Burning Stoves: A Preliminary Study, Julie Hart, Tony Ward, Terry Spear, Richard Rossi, Ph.D., Nicolas Holland M, Brodie Loushin

Safety Health & Industrial Hygiene

Wood burning for residential heating is prevalent in the Rocky Mountain regions of the United States. Studies have shown that wood stoves can be a significant source of PM2.5 within homes. In this study, the effectiveness of an electrostatic filter portable air purifier was evaluated (1) in a home where a wood stove was the sole heat source and (2) in a home where a wood stove was used as a supplemental heat source. Particle count concentrations in six particle sizes and particle mass concentrations in two particle sizes were measured for ten 12-hour purifier on and ten purifier off …

Estrogen Sulfotransferase (Sult1e1) Expression And Function In Mcf10a-Series Breast Epithelial Cells: Role As A Modifier Of Breast Carcinogenesis And Regulation By Proliferation State, Jiaqi Fu

Wayne State University Dissertations

Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. TaqMan Gene Expression assays were used to profile the mRNA expression of estrogen receptor (ERα and ERβ) and estrogen metabolism enzymes including cytosolic sulfotransferases (SULT1E1, SULT1A1, SULT2A1, and SULT2B1), steroid sulfatase (STS), aromatase (CYP19), 17β-hydroxysteroid dehydrogenases (17βHSD1 and 2), CYP1B1, and catechol-O-methyltransferase (COMT) in an MCF10A-derived lineage cell culture model for basal-like human breast cancer progression and in ERα-positive luminal MCF7 breast cancer cells. Low levels of ERα and ERβ mRNA were present in MCF10A-derived cell lines. SULT1E1 mRNA was more abundant in confluent relative to subconfluent MCF10A …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

Full Issue: Volume 4, Number 2

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Compensatory Renal Hypertrophy, Mitochondria And Redox Status, Bavneet Benipal

Wayne State University Dissertations

A reduction in functional renal mass occurs in humans during aging and severe kidney damage from diseases, injuries, infections and congenital conditions and after nephrectomy. Nephrectomy, or surgical removal of a kidney or a section of a kidney, is performed for treatment of unilateral secondary renal cancer, infections and for kidney transplantation. As a result, the remaining renal tissue undergoes compensatory growth due primarily to hypertrophy, in which both the size and functional capacity of the remaining kidney are increased. Renal compensatory hypertrophy is associated with a series of physiological, morphological and biochemical changes that also have toxicological implications.

Previous …

High Resolution Hybrid Mass Spectrometry For The Determination Of Marine Biotoxins, Azaspiracids, And Their Biotransformation Products., Zuzana Skrabakova

Theses

Azaspiracids (AZAs), polyether marine toxins, are produced by marine microalgae and accumulate in filter-feeding bivalve molluscs, such as mussels, clams, oysters and scallops, while grazing on phytoplankton, from which they derive nutrition. Although being discovered quite recently, AZAs have caused several human intoxication events and thus became a problem for health authorities and shellfish industries. The rapid development of highly sensitive liquid chromatography multiple tandem mass spectrometry (LC-MS/MS, LC-MS") methods enabled the identification of numerous AZA analogues and added to the control of shellfish contamination. Tandem mass spectrometry techniques, while being highly selective and sensitive for determination of AZAs in …

Electro-Gene Transfer To Skin Using A Noninvasive Multielectrode Array, Siqi Guo, Amy Donate, Gaurav Basu, Cathryn Lundberg, Loree Heller, Richard Heller

Bioelectrics Publications

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection …

The Impact Of Tricaine Methanesulfonate, 2-Phenoxyethanol, And Carvone-Methyl Salicylate On The Innate Immune Response Of Zebrafish (Danio Rerio), Charles R. Wulff

Honors Theses

Anesthesia plays a vital role in the maintenance of aquaculture species, where it is used to minimize stress during complex handling tasks such as transport, assessment, and harvesting. However, anesthetics have been shown to suppress the innate immune response, which could impact immunity and increase risk of infection. Tricaine methanesulfonate (MS-222) and 2-Phenoxyethanol (2-PE) represent two of the most commonly used anesthetics in aquaculture, with R-(+)-carvone, in the form of carvone-methyl salicylate (CMS) has recently been proposed as an alternative anesthetic for food fish. These three anesthetics were used to assess the influence of anesthetics on the immune system of …

An Overview Of New Psychoactive Substances And The Outlets Supplying Them, Cathy Kelleher, Rachel Christie, Kevin Lalor, John Fox, Matt Bowden, Cora O'Donnell

Reports

This report represents the outcome of a review of new psychoactive substances2 within the Irish context, including a review of the outlets that supply these substances. The review was commissioned by the National Advisory Committee on Drugs (NACD) in accordance with Action 14 of the National Drugs Strategy (interim) 2009–2016. Action 14 provides for the monitoring of ‘head shops’3 and other outlets for the sale of psychoactive substances, under the Misuse of Drugs Act 1977 and the Misuse of Drugs (Amendment) Regulations 2007. Researchers at the Centre for Social and Educational Research (CSER) within the School of Social Sciences and …

Novel Inhibitors Of Lysine Specific Demethylase 1 As Epigenetic Modulators, Michael Crowley

Wayne State University Theses

The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 over expression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1, and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a new series of isosteres that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target …

Gene And Environment Interactions Modulate Immune System Influences On Social Behavior, Yubin Zhang

Legacy Theses & Dissertations (2009 - 2024)

Autism is a neurodevelopmental disorder with unknown etiology, affecting about 1 in 110 children in the US. Here, we show that developmental exposure to anti-brain Abs impaired mouse social behaviors. BTBR mice, a mouse strain with high serum anti-brain Abs and behaviors that resemble autism, have more activated splenic B cells, CD4+ T cells (Th1, Th2 and Th17 subsets), and CD4+ T cells with expression of Vb6 chains than B6 mice (the control H-2 identical strain). Elevated numbers of activated (CD25+) CD4+Vb6+ cells also were detected in thymic preparations. All of the immunological and behavioral parameters of BTBR mice were …

The Role Of Androstane Neurosteroids In Alcohol-Mediated Social Behavior, Jason J. Paris

Legacy Theses & Dissertations (2009 - 2024)

Androgenic steroids, such as testosterone, may influence the propensity for aggression in both people and animals. Some of testosterone's effects on aggression may be due, in part, to its metabolic products that are 5á-reduced and 3á-hydroxylated to form, 3á-androstanediol (3á-diol), which can also enhance aggression in mice. Notably, alcohol (EtOH) consumption facilitates aggression in people and animals, particularly among those predisposed to act aggressively. In rats, EtOH can increase 3á-diol in prefrontal cortex, which may facilitate aggression. The present work aimed to elucidate the role of 3á-diol for EtOH-enhanced aggression. We hypothesized that EtOH would enhance inter-male aggression, social dominance, …

The Nasal Toxicity Of The Herbicide 2,6-Dichlorobenzonitrile : Mechanisms And Biomarkers, Fang Xie

Legacy Theses & Dissertations (2009 - 2024)

The overall goal of this study is to investigate mechanisms of the potent nasal specific toxicity of the herbicide 2,6-dichlorobenzonitrile (DCBN) in rodents, and to determine whether DCBN could induce similar nasal toxicity in humans. The central hypotheses are 1) that the nasal specific toxicity of DCBN in rodents is mediated by its electrophilic intermediates that are formed through metabolic activation catalyzed by target tissue cytochrome P450 enzymes (P450) and can interfere with stem cell regeneration and differentiation in the olfactory epithelium (OE); and 2) that human nasal tissues are also capable of catalyzing bioactivation of DCBN. The specific aims …

Regulation Of The Aryl Hydrocarbon Receptor And The Signal Transducer And Activator Of Transcription 1 By Long-Term Estrogen Exposure In Breast Carcinoma Cells, Neal Englert

Legacy Theses & Dissertations (2009 - 2024)

The risk of developing breast cancer is known to be associated with a woman's lifetime exposure to estrogens, both endogenous and exogenous. Increased exposure to estrogens stimulates cellular proliferation, which is a widely accepted theory of estrogen receptor positive mammary carcinogenesis. The molecular mechanisms of gene expression regulation in response to long-term estrogen exposure (LTEE) of MCF-7 breast cancer cells were addressed in this study, with a focus on the aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 1 (STAT1).

In Vitro And In Vivo Pharmacodynamic Characterization Of The Novel Plasma Kallikrein Inhibitor Pf-04886847, Dhaval Sanjeev Kolte

Electronic Theses and Dissertations

Plasma kallikrein plays an important role in the pathogenesis of inflammation and thrombosis. Kallikrein cleaves high molecular weight kininogen (HK) to liberate the potent pro-inflammatory peptide bradykinin (BK). BK upon activation of its constitutive B2 receptors on endothelial cells leads to an increase in intracellular Ca2+ level and subsequent production of nitric oxide (NO) and prostacyclin (PGI2), ultimately leading to vasodilation, hypotension, increased vascular permeability and vascular leakage. Further, kallikrein activates the complement system and stimulates neutrophil chemotaxis, aggregation and elastase release. Furthermore, kallikrein mediates the conversion of factor XII (FXII) to activated factor XII (FXIIa) thereby potentiating the intrinsic …

Anaplasmataceae As Human Pathogens : Biology, Ecology And Epidemiology, Marina E. Eremeeva, Gregory A. Dasch

Environmental Health Sciences: Faculty Publications

This review describes the biology, ecology, and epidemiology of known human pathogens in the family Anaplasmataceae that are transmitted by ticks and belong to the genus Anaplasma and genus Ehrlichia. We discuss the current status of diagnosis and surveillance of the diseases they cause, and address the challenges and new perspectives raised due to continuous recognition of new emerging human pathogens in the family Anaplasmataceae.

Scoliosis: Comparative Analysis Of Surgery Vs. Brace Treatment, Jerry Frenkel

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction of this article: The spine, or spinal column, as it is also called, is a complex structure made up of 33 vertebrae (bone segments) arranged vertically in succession from just below the skull to the tailbone. The entire column is broken up into various classes of vertebrae named, from superior to inferior, as cervical, thoracic, lumbar, sacral, and coccygeal. Different forms of spinal deformities that can occur include kyphosis, lordosis and scoliosis (Neuwirth and Osborn 2001). Scoliosis is defined simply in medical terms as a lateral three-dimensional irregular curvature of the spine. The curvature as …

Full Issue: Volume 5, Number 1, Fall 2011

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

The Effects Of Protein Kinase C Inhibitors On Blood Nitric Oxide And Hydrogen Peroxide Release In Ischemia And Reperfusion Injury, Kyle D. Bartol

PCOM Biomedical Studies Student Scholarship

Vascular endothelial dysfunction is a key component initiating oxidative stress in ischemia/reperfusion (I/R). Endothelial dysfunction is characterized by an increase in hydrogen peroxide (H2O2) and a decrease in the bioavailability of nitric oxide (NO). Previous studies using protein kinase C (PKC) inhibitor Gö 6983 or PKC Beta (β) II inhibitor improved cardiac function in myocardial I/R, decreased leukocyte-endothelial interactions and leukocyte superoxide (SO) release and increased endothelial-derived NO release in vitro. This study examined the effects of Gö 6983 or PKC β II inhibitor on realtime H2O2 and NO release in femoral vein I/R in vivo. NO or H2O2 microsensors …

Synthesis, Evaluation And Structural Studies Of Antiproliferative Tubulin-Targeting Azetidin-2-Ones, Niamh O'Boyle, Lisa M. Greene, Orla Bergin, Jean-Baptiste Fichet, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

A series of azetidin-2-ones substituted at positions 2, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerization that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the …

Feedback From Malaysian Pharmacists Who Underwent A 3-Year Period Of Compulsory Service With The Government, Ong Aik Liang, Thomas Paraidathathu

The Thai Journal of Pharmaceutical Sciences

Since 2004, it is mandatory for all new pharmacy graduates in Malaysia to serve the government for a period of 4 years, before they are free to work as registered pharmacists in a sector of their choice, either public or private. With the enactment of th...

Sensitive, Selective And Extraction-Free Spectrophotometric Determination Of Lamotrigine In Pharmaceuticals Using Two Sulphonthalein Dyes, K. B. Vinay, H. O., N. Rajendraprasad, K. Basavaiah

The Thai Journal of Pharmaceutical Sciences

Two direct, simple, sensitive and rapid extraction-free spectrophotometric methods have been developed for the determination of lamotrigine (LMT) in pure form and in its dosage forms. The methods are based on formation of ion-pair complex between the dru...

Genotoxin-Induced Acetylation Of The Werner Syndrome Protein (Wrn) And Effect On Its Dna Metabolic Function, Enerlyn Meliza Lozada Santiago

University of Kentucky Doctoral Dissertations

Loss of function of the WRN protein causes the genetic disorder Werner Syndrome that is characterized by increased cancer and premature aging. WRN belongs to the RecQ helicase family that plays key roles in preventing genome instability. In response to treatment with genotoxins, WRN is subject to post-translational modification. The relationship of post-translational modification of WRN with its function in DNA metabolism is unknown. There is accumulating evidence suggesting that WRN contributes to the maintenance of genomic integrity through its involvement in DNA replication. Consistent with this notion, WS cells are sensitive to DNA replication inhibitors and DNA damaging agents …

Pharmacotherapy Safety And Efficacy In Adolescent Smoking Cessation, Jennifer Lincoln

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine whether or not pharmacotherapy is a safe and effective treatment option for smoking cessation in adolescents

Small Gtp-Binding Proteins In Insulin Secretion, Bhavaani Jayaram

Wayne State University Dissertations

Type 2 diabetes mellitus is marked by a substantial beta-cell failure which is characterized by defective insulin secretion and resistance to insulin. Understanding the molecular events leading to Glucose-stimulated insulin secretion [GSIS] might serve as therapeutic potential towards diabetes. GSIS involves interplay between small G-proteins and their regulatory factors. Herein, I tested the hypothesis that Arf nucleotide binding site opener [ARNO], a guanine nucleotide exchange factor [GEF] for the small G-protein Arf6, mediates the activation of Arf6, and that ARNO/Arf6 signaling axis, in turn, controls the activation of downstream effectors. Salient features of my study are: [i] ARNO/Arf6 is expressed …

Mechanisms Of Regulation Of Islet Function By Nadph Oxidase, Ismail Syed

Wayne State University Dissertations

Glucose stimulated insulin secretion (GSIS) involves a series of metabolic and cationic events, leading to translocation of insulin-laden secretory granules from a distal site toward the plasma membrane for fusion and release of insulin into circulation. Vesicular transport and fusion events are tightly regulated by signals which coordinate between vesicle- and membrane-associated docking proteins. It is now being accepted that reactive oxygen species [ROS] plays a second messenger role in islet â-cell function. Further, evidence from multiple laboratories suggests a tonic increase in ROS generation is necessary for GSIS and fatty acid-induced insulin secretion. On the other hand, excessive ROS …

Response Of Monovalent Cation Transporters To Pro-Apoptotic Protein Kinase C Modulators In Human Lens Epithelial Cells, Michael Anthony Lepera

Browse all Theses and Dissertations

Protein kinase inhibition by staurosporine causes apoptotic volume decrease involving potassium (K) channels in immortalized human B3 lens epithelial cells (LECs). Here, the effect of two pro-apoptotic protein kinase C (PKC) inhibitors [12-O-tetradecanoyl-phorbol-13-acetate (TPA) and chelerythrine (CET)] were studied on membrane K transport in a fetal human LEC line (FHL124) by western blotting, immunofluorescence, ion flux, ATP, apoptosis, and biotinylation assays. Long term TPA exposure (0-6 h) inhibited 75% of Na-K-2Cl cotransport (NKCC). In contrast, short term (0-20 min) exposure to 50 μM CET reduced Na/K pump and NKCC by >90% and >70%, respectively, without retrieval from the membrane into …