Pharmacology, Toxicology and Environmental Health Commons^™

Urinary Excretion Of (1-3)-Beta-D-Glucans., Debra K. Head

Electronic Theses and Dissertations

(1→3)-β-D-Glucans are carbohydrate polymers that are present in the cell wall of various fungi and bacteria; they are pathogen associated molecular patterns that circulate during infection and modulate immunity. Our laboratory has previously established the pharmacokinetics of intravenously and orally administered glucans; the present studies investigated the renal excretion of (1→3)-β-D-glucans following intravenous and oral administration. Three fluorescently-labeled glucans were administered to adult male rats in the presence or absence of toxic challenge. Urine specimens were collected and analyzed by fluorescence spectroscopy, size-exclusion chromatography and GPC/MALLS. 71 ± 3% of fluorescence remained in the >5K MWCO fraction; this fraction showed …

Down-Regulation Of Ppargamma1 Suppresses Cell Growth And Induces Apoptosis In Mcf-7 Breast Cancer Cells, Yekaterina Y. Zaytseva, Xin Wang, R. Chase Southard, Natalie K. Wallis, Michael W. Kilgore

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARgamma has been identified as a potential target for breast cancer therapy based on the fact that its activation by synthetic ligands affects the differentiation, proliferation, and apoptosis of cancer cells. However, the controversial nature of current studies and disappointing results from clinical trials raise questions about the contribution of PPARgamma signaling in breast cancer development in the absence of stimulation by exogenous ligands. Recent reports from both in vitro and in vivo studies …

Borderline Personality Disorder: An Overview Of History, Diagnosis And Treatment In Adolescents, Linah Al-Alem, Hatim A. Omar

Pharmacology and Nutritional Sciences Faculty Publications

Borderline personality disorder (BPD) is a cluster B personality disorder. It is characterized by erratic behaviors, emotional instability and one of its hallmarks is self injurious behavior, which starts in adolescence. Patients with BPD are difficult to treat, most have a history of child sexual abuse, about a quarter present with sexual abuse from a caretaker. Although personality disorders are diagnosed only in adults, BPD manifests itself in adolescence in the form of uncontrollable anger, self mutilations, dissociation and other such behaviors. Hence, there is a growing number of scientists discussing the possibility of diagnosing BPD in adolescents. Here, we …

Ecological Niche Of The 2003 West Nile Virus Epidemic In The Northern Great Plains Of The United States, Michael Wimberly, Michael B. Hildreth, Stephen P. Boyte, Erik Lindquist, Lon Kightlinger

United States Public Health Resources

Background: The incidence of West Nile virus (WNv) has remained high in the northern Great Plains compared to the rest of the United States. However, the reasons for the sustained high risk of WNv transmission in this region have not been determined. To assess the environmental drivers of WNv in the northern Great Plains, we analyzed the county-level spatial pattern of human cases during the 2003 epidemic across a seven-state region.
Methodology/Principal Findings: County-level data on WNv cases were examined using spatial cluster analysis, and were used to fit statistical models with weather, climate, and land use variables as predictors. …

Pgrmc1: A New Biomarker For The Estrogen Receptor In Breast Cancer, Rolf J. Craven

Pharmacology and Nutritional Sciences Faculty Publications

Estrogen receptor (ER) status is a critical biomarker in breast cancer, in large part because the ER is the target of tamoxifen and similar drugs. In the previous issue of Breast Cancer Research, Neubauer and colleagues used a proteomic approach to identify proteins that are differentially regulated by ER in breast tumors. The authors showed that ER-negative tumors have elevated levels of PGRMC1 (progesterone receptor membrane component-1), a hormone receptor component and binding partner for P450 proteins. In contrast, PGRMC1 was phosphorylated in ER-positive tumors. The staining patterns of ER and PGRMC1 were mutually exclusive in breast tumor sections, and …

Blood Pressure Lowering And Vasomodulator Effects Of Piperine, Syed Intasar Husain Taqvi, Abdul Jabbar Shah, Anwar Gilani

Department of Biological & Biomedical Sciences

This study was aimed to explore underlying mechanism(s) of cardiovascular effects of piperine. Intravenous administration of piperine caused a dose-dependent (1 to 10 mg/kg) decrease in mean arterial pressure (MAP) in normotensive anesthetized rats, the next higher dose (30 mg/kg) did not cause any further change in MAP. The fall in blood pressure (BP) was followed by small increase in MAP after each dose. In Langendorrf's rabbit heart preparation, piperine caused partial inhibition and verapamil caused complete inhibition of force and rate of ventricular contractions and coronary flow. In rabbit aortic rings, piperine inhibited high K(+) (80 mM) precontractions and …

Acquisition De Modèles Pour L’Étude De L’Absorption Percutanée Des Substances Chimiques : Cellules De Diffusion À Flux Continu, Claude Viau, Suzanne Leroux, Ross Thuot, Sophie Lim

Rapports de recherche scientifique

Dans les milieux de travail où des substances chimiques sont utilisées, celles-ci peuvent se retrouver dans l’air. Les employés peuvent donc y être exposés par le fait de la respiration. C’est d’ailleurs pour ça que le règlement sur la santé et la sécurité du travail donne des valeurs limites d’exposition dans l’air pour près de 700 substances chimiques. Mais il est aussi possible d’être exposé par le contact des substances avec la peau. Quand on veut savoir à quel point un travailleur peut absorber des substances dans son organisme de cette manière, on doit savoir trois choses principales :

• la …

Maturational Changes In Myosin Light Chain Kinase Activity In Ovine Carotids, Elisha Raju Injeti

Loma Linda University Electronic Theses, Dissertations & Projects

Vascular reactivity changes dramatically during postnatal maturation due in large part to developmental changes in myofilament calcium sensitivity. Recent findings suggest that reactivity of the thick filament component of calcium sensitivity is upregulated in fetal compared to adult arteries. In light of these findings, the present study tests the hypothesis that upregulation of fetal thick filament reactivity is due to upregulation of myosin light chain kinase (MLCK) activity. To test this hypothesis, MLCK abundance and its activity is measured in intact arteries. The results indicate that MLCK abundance is 6.03 ± 0.96 fold greater in adult than in fetal arteries. …

Nanoengineered Templates For Controlled Delivery Of Bioactive Compounds, Nalinkanth Ghone Veerabadran

Doctoral Dissertations

The significance of any drugs, therapeutic proteins, or any bioactive compounds, is based not only on their effects on diseases but also on how specifically, how readily, how controllable and how prolonged their effects on the disease without having any side effects. Thus the techniques involved in the drug encapsulation and its controlled release for a longer duration of time form one of the important processes of drug reformulation. In recent years nanoparticles have created overwhelming attention for delivering drugs by nanoencapsulation. The smaller size of nanoparticles has longer circulation time and higher cellular uptake when compared with larger size …

Genome-Wide Compensatory Changes Accompany Drug Selected Mutations In The Plasmodium Falciparum Crt Gene, Hongying Jiang, Jigar J. Patel, Ming Yi, Jianbing Mu, Jinhui Ding, Robert Stephens, Roland Cooper, Michael T. Ferdig, Xin-Zhuan Su

Collected Faculty Scholarship

Mutations in PfCRT (Plasmodium falciparum chloroquine-resistant transporter), particularly the substitution at amino acid position 76, confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. Moreover, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). Reemergence of CQ sensitive parasites after cessation of CQ use indicates that changes in PfCRT are deleterious to the parasite. Some CQR parasites, however, persist in the field and grow well …

The Guacamole Fund Presents...

Native American Forum on Nuclear Issues

Special Bonnie Raitt Benefit Tickets

Use Of Monoclonal ∆-9-Tetrahydrocannabinol Antibodies Chemically Bound To A Polystyrene Surface Using Glutaraldehyde For The Purpose Of Extracting ∆-9-Tetrahydrocannabinol And ∆-9-Tetrahydrocannabinol Carboxylic Acid From Postmortem Whole Blood Samples For Analysis By Gas Chromatography Mass Spectrometry, Thomas Sidney Pittman

Dissertations

Quantitations of drugs and their respective metabolites in postmortem blood samples using gas chromatographic instrumentation is a primary analytical practice used to determine if drugs played a role in or were the cause of a victim's death. Postmortem blood samples often prove difficult to work with due to interfering substances formed during the putrefaction process. Attempts to eliminate interfering substances with present day extraction methods can be time-consuming, costly and often ineffective when dealing with drugs that exhibit toxicity or impairment at very low concentrations. This study was conducted using monoclonal antibodies chemically bound to a polystyrene surface to extract …

Iron(Iii)-Salophene: An Organometallic Compound With Selective Cytotoxic And Anti-Proliferative Properties In Platinum-Resistant Ovarian Cancer Cells, Thilo S. Lange, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Carolyn Mccourt, Laurent Brard

Chemistry Faculty Publications and Presentations

Background: In this pioneer study to the biological activity of organometallic compound Iron(III)-salophene (Fe-SP) the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovariancancer cell lines were investigated.

Methodology/Principal Findings: Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma) cell lines at concentrations between 100 nM and 1 μM, while the viability of HeLa cells (epithelial cervix adenocarcinoma) or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed …

Nrc’S Decision Process: Judging The Safety Of A Proposed Repository, Janet Kotra

Native American Forum on Nuclear Issues

Abstract:

-Provide an overview of the role of the U.S. Nuclear Regulatory Commission (NRC) at Yucca Mountain

-Describe the process NRC will use to decide whether or not to authorize construction of a repository at Yucca Mountain

-Explain options and highlight important milestones that apply to Tribes as potential participants in NRC’s process

Fighting Nuclear Waste At Skull Valley, Margene Bullcreek

Native American Forum on Nuclear Issues

Abstract:

-Reasons We Oppose Nuclear Waste

-Sovereignty

-Traditional values must be protected

-Protect sacredness of our culture, plants,

animals, air, and water

-Affects on community health

-Protect reservation and homeland

-To protect the air and water

-To protect future generations

-Environmental Justice

Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh

Publications and Research

Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8–19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI2 microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression …

Respiratory Effects Of 1-Propylxanthine On Neonatal Rats, Amanda Hance

Student Honors Theses

Neonatal apnea is commonly treated by methylxanthines like caffeine or theophylline, but these drugs have the potential to create serious side effects. As an alternative, a new xanthine analog, 1-propylxanthine (1-PX), was recently synthesized at Eastern Illinois University. The respiratory effects of 1-PX were investigated in 4- to 7-day-old rats to determine if 1-PX could be a respiratory stimulant. Each rat was placed in a heated body plethysmograph, and its respiratory rate and volume were measured using a flow transducer, pneumotachograph, and Power Lab data acquisition system. After a 10-min control period, the rat was given a s.c. dose of …

Development And Recycling Of Novel Arsenic Removal Technology, Morgan Jones

Mahurin Honors College Capstone Experience/Thesis Projects

As of 2006, the U.S. Environmental Protection Agency (EPA) changed the Maximum Contaminant Level (MCL) for arsenic from 50 parts per billion (ppb), to 10ppb because of links to cancer. Current remediation technologies are expensive; therefore, this change will result in increased economic pressure on rural communities with high levels of arsenic in their drinking water. Lowering of the standard has spurred the development of a novel remediation technology that has shown the ability to reduce arsenic in drinking water at the source, with the added benefit of low-cost disposal of a stable and benign waste product in ordinary landfills. …

Cannabinoids: A Novel Treatment Strategy For Retinal Neurodegenerative Disorders, Sandeep Samudre

Theses and Dissertations in Biomedical Sciences

Synthetic and naturally occurring cannabinoids are known to decrease intraocular pressure (IOP). Glaucomatous damage to the retina and optic nerve progresses even after therapy to maintain normal intraocular pressure (IOP). Topical application of cannabinoids decreases IOP while not affecting blood pressure or heart rate. Based upon their effects on other tissues, we hypothesize that these analogs reduce IOP and may also confer direct neuroprotective effects on the retina, possibly via CB1 and/or CB2 receptors. The purpose of this study is to determine if the newly synthesized CB agonists, lipid soluble O-1812 (CB 1), and water soluble O-2545 (CB 1

The …

The Influence Of Citrate, Maltolate And Fluoride On The Gastrointestinal Absorption Of Aluminum At A Drinking Water-Relevant Concentration: A 26Al And 14C Study, Yuzhao Zhou, Wesley R. Harris, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

The objectives were to test the null hypotheses that (1) citrate, maltolate, and fluoride do not significantly influence oral Al bioavailability, C_max or T_max at an Al dose relevant to drinking water exposure; and (2) Al citrate and maltolate are absorbed intact from the gastrointestinal tract. Male Fisher rats were given 1 ml of solution intra-gastrically containing 1 nCi ²⁶Al (65 nmol total Al) as the Al³⁺ ion, or as complexes with ¹⁴C-citrate, ¹⁴C-maltolate or fluoride, during concurrent ²⁷Al iv infusion. Blood was repeatedly collected for serum ²⁶Al, total Al and ^{14 …}

Three Models Of Anthrax Toxin Effects On The Map-Kinase Pathway And Macrophage Survival, Daniel J. Schneider

Theses and Dissertations

Lethal factor (LF), a component of anthrax toxin, is the primary virulence factor that allows Bacillus anthracis to evade the immune response by blocking the activation of mitogen-activated protein kinase (MAPK) enzymes. This research modifies three published MAPK models to reflect this signal inhibition and to estimate a first-order reaction rate by fitting the models to published viability data for two macrophage cell lines cultured with the LF-producing Bacillus anthracis-Vollum1B strain. One model appears to be ill-suited for this purpose because not all relevant MAPK components could be integrated into the inhibition equations. Despite different underlying parameters and values, the …

Characterization Of A Fluorescent Protein Reporter System, Sandra J. Dias

Theses and Dissertations

Chemical and biological threats are ever present and attacks have occurred throughout the world in both war and peace-time. Multiple government agencies, academia, and private industry are developing detection capabilities to address such threats. The research presented in this paper supports development of a modular synthetic biology based system that detects and reports the presence of a threat agent. Synthetic biology builds upon past research in genetic engineering and seeks to combine broad applications within biotechnology in novel ways. This basic research project will help to demonstrate a proof-of-concept design which will guide future studies on the development of a …

In Vitro Toxicity Of Aluminum Nanoparticles In Human Keratinocytes, Stephanie Mccormack-Brown

Theses and Dissertations

Nanotechnology promises to be the defining technology of the 21st century. At an annual investment of $1B, it provides significant contributions to manufacturing, medicine, energy conservation, and the environment. Nanoparticles are structures with at least one dimension in the 1 to 100 nanometer (nm) range. DoD and US Air Force interest in aluminum nanoparticles (AL NPs) stems from its ability to enhance combustion jet fuel, thus increasing fuel efficiency. The addition of AL NPs to JP-8 may pose a unique dermal hazard to aircraft maintenance workers. There is no published data on AL NP toxicity effects on human skin. This …

In Vitro Toxicity And Inflammation Response Induced By Copper Nanoparticles In Rat Alveolar Macrophages, Brian M. Clarke

Theses and Dissertations

Nanotechnology is a thriving industry and has the potential to benefit society in numerous ways. However, not all environmental and human health concerns of nanomaterials have been addressed. Thus, the purpose of this research was to investigate the toxicity and inflammation potential (using cytokines TNF-alpha and IL-6 as indicators) of various sized copper nanoparticles (40, 60, and 80 nm) in rat alveolar macrophages. Toxicity measurements were accomplished by means of in vitro techniques and toxicity mechanisms were studied by measuring reactive oxygen species (ROS) production. In addition, cytokine measurements used enzyme-linked immunosorbent assay (ELISA) methods. Results show copper nanoparticles as …

Optimization Of Therapeutic Strategies For Organophosphate Poisoning, Gregory G. Seaman

Theses and Dissertations

The National Preparedness Vision requires the U.S. be prepared to prevent, protect against, respond to, and recover from all hazards associated with a chemical attack. Results of this study demonstrate that we cannot protect service members and first responders as required following a nerve agent attack. The research presented herein aimed to construct a physiologically based pharmacokinetic model to determine optimal therapeutic strategies for organophosphate (nerve agent) poisoning. The constructed model integrated organophosphates and two antidotes, atropine and oximes. Model results reasonably mirrored literature data and anecdotal observations of organophosphate poisoning. Results suggest a symptoms-based dosing strategy of atropine and …

The Α1d-Adrenergic Receptor Is Expressed Intracellularly And Coupled To Increases In Intracellular Calcium And Reactive Oxygen Species In Human Aortic Smooth Muscle Cells, Mary L. García-Cazarín, Jennifer L. Smith, Kyle A. Olszewski, Dan F. Mccune, Linda A. Simmerman, Robert W. Hadley, Susan D. Kraner, Michael T. Piascik

Pharmacology and Nutritional Sciences Faculty Publications

Background: The cellular localization of the α_1D-adrenergic receptor (α_1D-AR) is controversial. Studies in heterologous cell systems have shown that this receptor is expressed in intracellular compartments. Other studies show that dimerization with other ARs promotes the cell surface expression of the α_1D-AR. To assess the cellular localization in vascular smooth muscle cells, we developed an adenoviral vector for the efficient expression of a GFP labeled α_1D-AR. We also measured cellular localization with immunocytochemistry. Intracellular calcium levels, measurement of reactive oxygen species and contraction of the rat aorta were used as measures of …

Factors That Influence The Distribution Of Antibiotic Resistant Bacteria In The Mud River, Wv, Timothy Shaun Dotson

Theses, Dissertations and Capstones

Background: Prior studies of the Ohio and Mud Rivers have shown that fecal contamination alone does not explain the distribution of antibiotic resistant bacteria (ARB) in surface waters. The objectives of this study were to determine effects on the distribution of ARB in the Mud.

Methods: Water samples and physical parameters were collected twice per season in spring through fall at 12 sites on the Mud River. Aliquots were plated on R2A agar and R2A agar plus individual antibiotics for the enumeration of total cultivable bacteria, and cultivable bacteria resistant to ciprofloxacin, virginiamycin, or tetracycline respectively. The IDEXX Quanti-Tray/2000™ method …

The Aridity Of Grace: Community And Ecofeminism In Barbara Kingsolver's Animal Dreams And Prodigal Summer, Richard M. Magee

English Faculty Publications

In both Animal Dreams and her later novel Prodigal Summer, Kingsolver constructs narratives of community inhabited by characters with a vivid awareness of the natural world and the threats to that world; furthermore, both novels feature strong female characters who long for a more harmonious life within nature. The novels develop and present forthright ecofeminist themes, with the women in the texts representing ideals of ecologically sensitive living who seek to educate their communities about threats to the environment and the defenses against those threats.

Kingsolver's ecofeminist vision, however, is frequently complicated and contradictory; just as the desert landscape …

Plaster Creek Watershed Management Plan, Fishbeck, Thompson, Carr, & Huber, Inc.

Watershed Reports

The quality of Plaster Creek is influenced by many factors, such as human activities within the Plaster Creek Watershed (Watershed), physical and biological characteristics of the natural resources, and the management of those resources. This document provides an overview of these diverse aspects of the Watershed, including detailed information about the sources and causes of watershed pollution, recommendations needed to address impairments, and steps to implement the recommendations.

Combination Of Natural Variability Estimation With Real Time Measurement For Mushroom Shelf Life Assessment., Leixuri Aguirre

Doctoral

The shelf life of mushrooms (Agaricus bisporus) is affected by the natural variability of the produce which influences the perishable vegetable quality. One of the main causes of this variability is non-homogeneity in the product maturity at harvest, resulting in each vegetable batch being at a different stage of senescence. The present work aims to study a new approach to improve the assessment of the shelf life of mushrooms (Agaricus bisporus) taking into account this variability. The study of variability involved the: i) study of the shelf life, quality parameters and variability of the mushrooms and modelling these experimental laboratory …