Pharmacology, Toxicology and Environmental Health Commons^™

Impact Of Diabetes On Ace/Ace2 Balance And Angiotensin Ii Type 1 Receptor Expression In Db/Db Diabetic Mice, Malav Navinchandra Madhu

Browse all Theses and Dissertations

Alterations in the renin-angiotensin system (RAS) are considered to be crucial for the development of diabetic complications like hypertension and nephropathy. Our previous work demonstrated role of AT1 receptors (AT1R) in the development of hypertension in db/db diabetic mice. The aim of this study was to test the hypothesis that there is upregulation of renal AT1R and imbalance in renal ACE/ACE2 homeostasis in db/db mice. In addition, we hypothesize that treatment with an anti-hyperglycemic or an AT1R blocker will correct this imbalance. Five week old control and db/db mice were housed in metabolic cages for 24 hour collection of urine. …

Characterization Of Infectivity And Pathogenesis Of Partially Reconstructed 1918 And Highly Pathogenic Avian Influenza Viruses In The Balb/C Mouse Model, John Allen Pyles

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Influenza viruses are consistently responsible for an average of 20,000 deaths and 114,000 hospitalizations per year. To a great extent, these viruses always stay one step ahead of the available vaccines and people's immunity year after year because they have the ability to either mutate part of their genetic material, or to be transmitted from one species to another. That same genetic variability explains why highly pathogenic influenza viruses emerge that cause great mortality over several countries resulting in pandemics. Highly pathogenic strains of influenza A virus have emerged occasionally in recent history, producing pandemics such as the one in …

Tcdd-Induced Modulation Of The Hs1,2 Enhancer Within The 3'Immunoglobulin Heavy Chain Regulatory Region, Tharu M. Fernando

Browse all Theses and Dissertations

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin that inhibits immunoglobulin (Ig) gene expression in mice. Transcriptional regulation of the Ig heavy chain (IgH) involves the 3'IgH regulatory region (3'IgH RR). The murine 3'IgH RR consists of four enhancers (hs3A, hs1,2, hs3B, and hs4), which are homologous to the human 3'IgH RR enhancers (hs3, hs1,2, and hs4). In humans, a polymorphism of the hs1,2 enhancer, resulting in a varying number of tandem repeats of a 53 bp sequence, has been correlated with autoimmune diseases like IgA nephropathy and Celiac disease. The repeated sequence contains a kB and DRE binding site. Previous …

Identification Of Potential Protein Biomarkers Of Low Level Kidney Degradation, Christopher Lee Woolard

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The purpose of this research was the identification of potential dose-dependent and time-dependent serum protein biomarkers of low level kidney degradation in a rat model. Potential biomarkers were evaluated based on differential protein expression between control and dosed samples in rat serum. Proteins of interest demonstrated upregulation at a minimum 1.5 fold increase in protein concentration control versus dosed sample. In order to identify common biomarkers of kidney decrement, three nephrotoxins were chosen to target specific locations of the kidney: 1) D-Serine, which causes necrosis of the proximal straight tubules, 2) Puromycin, an antibiotic that degrades the Glomerular Basement Membrane …

Novel Neuroprotectants For Sarin Plus Cbdp Induced Convulsions, Kaushal V. Joshi

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Sarin, also known as Sarin (German agent B) is classified as a weapon of mass destruction. Sarin (O-isopropyl methyl phosphonofluoridate) is a highly toxic nerve agent originally produced for chemical warfare and has been used in terrorist activities. Sarin is an extremely potent acetylcholinesterase inhibitor with high specificity and affinity for the enzyme. High sarin doses causes death due to anoxia resulting from airway obstruction, weakness of the muscles of respiration, respiratory failure and convulsions. Current treatments are still not effective at protecting against long term effects following exposure. A current approach aims to counteract the increased glutamatergic and cholinergic …

A Discourse On The Public Nature Of Research In Contemporary Life Science: A Law-Policy Proposal To Promote The Public Nature Of Science In An Era Of Academia-Industry Integration, Michael J. Malinowski

Journal Articles

This article addresses the impact of integration of academia, industry, and government on the public nature of research. The article concludes that, while the integration has benefited science immensely, regulatory measures should be taken to restore the public nature of research in an age of integration.

Using The World Wide Web To Educate And Inform The Public About Risk And Agricultural Biotechnology, Douglas A. Golick, Robert D. Peterson, Leon G. Higley

Department of Entomology: Faculty Publications

The University of Nebraska and AgBios, Inc. launched the AgBiosafety website (http://agbiosaftzy.unl.edu) with the purpose of educating the public about agricultural biotechnology risk and safezy issues through science-based content. This article discusses the creation ofthe website, its components, and data gathered from usage statistics and a web-delivered survey. Also included is a discussion of the results ofdata gathered and recommendations for future web-based educational efforts in biotechnology safety and risk assessment.

Flavonoid Glycosides From The Leaves Of Uvaria Rufa With Advanced Glycation End-Products Inhibitory Activity, Khanittha Deepralard, Kazuko Kawanishi, Masataka Moriyasu, Thitima Pengsuparp, Rutt Suttisri

The Thai Journal of Pharmaceutical Sciences

Prolonged hyperglycemia in diabetic patients leads to the formation of advanced glycation end-products (AGEs) in their body tissues, which contribute to the development and progression of diabetic complications and aging. Preliminary screening of the eth...

Dispersion Medium Modulates Oxidative Stress Response Of Human Lung Epithelial Cells Upon Exposure To Carbon Nanomaterial Samples, Eva Herzog, Hugh Byrne, Maria Davoren, Alan Casey, Albert Duschl, Gertie Janneke Oostingh

Articles

Due to their large specific surface area, the potential of nanoparticles to be highly reactive and to induce oxidative stress is particularly high. In addition, some types of nanoparticles contain transition metals as trace impurities which are known to generate reactive oxygen species (ROS) in biological systems. This study investigates the potential of two types of single-walled carbon nanotube samples, nanoparticulate carbon black and crocidolite asbestos to induce ROS in lung epithelial cells in vitro. Carbon nanotube and carbon black samples were used as produced, without further purification or processing, in order to best mimic occupational exposure by inhalation of …

Raman Spectroscopy: A Potential Platform For The Rapid Measurement Of Carbon Nanotube-Induced Cytotoxicity, Peter Knief, Colin Clarke, Eva Herzog, Maria Davoren, Fiona Lyng, Aidan Meade, Hugh Byrne

Articles

In this study the suitability of Raman spectroscopy for the determination of carbon nanotube mediated toxicity on human alveolar carcinoma epithelial cells (A549) is explored. The exposure of this cell line represents the primary pathway of exposure in humans, that of inhalation. Peak ratio analysis demonstrates a dose dependent response which correlates to previous toxicological studies. Principal component analysis is employed to further classify cellular response as a function of dose and to examine differences between spectra as a function of exposed concentration. To further illustrate the potential of Raman spectroscopy in this field, Partial Least Squares (PLS) regression and …

Insights Into Expression, Cellular Localization, And Regulation Of Supernatant Protein Factor, A Putative Regulator Of Cholesterol Biosynthesis, Elzbieta Ilona Stolarczyk

University of Kentucky Doctoral Dissertations

SPF (Supernatant Protein Factor) is a cytosolic protein that stimulates at least two enzymes in the cholesterol biosynthetic pathway: squalene monooxygenase and HMGCoA reductase. The mechanism of action has not been established but may be related to lipid transfer between intracellular membranes.

There are three human genes for SPF: SEC14L2 (SPF1), SEC14L3 (SPF2) and SEC14L4 (SPF3). The present study differentiates these closely related genes by evaluating their tissue-specific and relative expression levels. SPF1 mRNA was found to be most abundant in liver, mammary gland and stomach. SPF2 showed negligible expression in all tissues tested; SPF3 expression pattern was similar to …

Lipid Signaling In Brain Aging And Alzheimer's Disease: Pharmacologically Targeting Cholesterol Synthesis, Transport And Metabolism, James Lucas Searcy

University of Kentucky Doctoral Dissertations

The role cholesterol plays in the brain has long been underappreciated even though the brain contains a disproportionately high percentage of body cholesterol. Recent studies have found a link between the dysregulation of lipid metabolism and the risk of acquiring Alzheimer’s disease (AD) as well as a predisposition to cognitive decline. The goal of these studies was to elucidate the possible role lipid metabolism plays in pathological and normal brain aging by pharmacologically manipulating lipid metabolism and determining effects on key hippocampal biomarkers of AD and age-related cognitive decline. One series of experiments used an agonist (TO901317) to the liver …

First Approaches To Standard Protocols And Reference Materials For The Assessment Of Potential Hazards Associated With Nanomaterialss, Gordon Chambers, Hugh Byrne, Iseult Lynch, Micheal Riediker, Hans Bouwmeester, Hans Marvin, Alan Casey, Markus Berges, Martin Clift, Teresa Fernandez, Lise Fjellsbo, Lucienne Juillerat, Gert Roebben, Christoph, Klein, Qinglan Wu, Vince Hackley, Jean-Pierre Kaiser, Wolfganag Kreyling, Michael Garner, Peter Hatto,, Kenneth Dawson

Articles

All new technologies have an inherent risk, which is typically assessed alongside the development of applications of the technology. This is also the case for nanotechnology: a key concern in the case of engineered nanomaterials (ENMs) is that due to their very small size, NMs can reach areas such as the cell that are inaccessible to other materials, such as implants and drugs. As a result of their large surface area, NMs may be more reactive than other larger materials. The large physical and chemical variability of NMs, and the fact that small changes can have large consequences, mean that …

When Every Drop Counts: The Public Health Impact Of Drought, Steven Konkel

Environmental Health Planning and Policy

No abstract provided.

Evaluating Acute Toxicity Of Cadmium To Chironomid Using Hemoglobin As A Molecular Biomarker, Jun Taek Oh

Seton Hall University Dissertations and Theses (ETDs)

Effects of cadmium (Cd), a heavy metal contaminant, on hemoglobin were investigated in aquatic midge fly larvae of the Family, Chironomidae. In this study, chironomid populations from one polluted site, Kearny Marsh, New Jersey, two reference sites, North East Creek, and Bass Harbor, ME, and a laboratory population were taxonomically identified and tested for their sensitivity to Cd. Heavy metals in tissue, water and sediment were analyzed using Atomic Absorption Spectroscopy. Water quality at each site was assessed by measuring pH, dissolved oxygen (DO), oxidation-reduction potential ( eH), salinity and temperature. Hemoglobin proteins in individual larvae were easily detected using …

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

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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