Pharmacology, Toxicology and Environmental Health Commons^™

The Establishment Of A Fibroblastic Cell Line From Yellow Perch (Perca Flavescens) And Its Potential Applications In Toxicology, Katelin W. Spiteri

Theses and Dissertations (Comprehensive)

This thesis describes the establishment, characterization and potential toxicological applications of YPF5, a yellow perch cell line. YPF5 is a fibroblastic cell line derived from the caudal fin of yellow perch. This cell line has been maintained for over 2 years. Cultures have been passaged over 60 times, and successfully cryopreserved and thawed. YPF5 is grown at room temperature in Leibovitz-15 (L-15) media, supplemented with 10% fetal bovine serum and 3% penicillin-streptomycin. The origin of YPF5 has been confirmed as Perca flavescens through “DNA Barcoding” and reaffirmed through Karyotyping (2n = 48) as per literature reported karyology for percidae including …

Effects Of Salinity And Dissolved Organic Matter On Cu Toxicity To Americamysis Bahia In Estuarine Environments, Rabia Nasir

Theses and Dissertations (Comprehensive)

As salinity increases the geochemical speciation of Cu is altered as a result of organic/inorganic complexation/competition. Such salinity changes may further challenge the osmoregulatory capabilities of euryhaline organisms. This chemical-biological interaction complicates the understanding of the impacts of Cu in estuarine waters. Dissolved organic matter (DOM) has been widely established to be an important modifier of Cu toxicity in freshwaters however its effectiveness in modulating Cu toxicity across the range of salinities that occur in estuarine conditions has not been studied in a systematic manner. Site to site differences in DOM quality with respect to the potential for toxicity mitigation …

Distribution And Elimination Of 3-Trifluoromethyl-4-Nitrophenol (Tfm) By Sea Lamprey (Petromyzon Marinus) And Non-Target, Rainbow Trout (Oncorhynchus Mykiss) And Lake Sturgeon (Acipenser Fulvescens), Michael W. Le Clair

Theses and Dissertations (Comprehensive)

The pesticide, 3-trifluoromethyl-4-nitrophenol (TFM), has been highly successful in the control of sea lamprey (Petromyzon marinus) populations in the Great Lakes. Treatments with TFM involve applying it to streams, where it targets larval sea lamprey which live burrowed in the stream substrate. While the toxic mechanism of TFM has been elucidated, and its effects on sea lamprey described, its effects on non-target fish species such as rainbow trout (Oncorhynchus mykiss) and lake sturgeon (Acipenser fulvescens) are not as well understood. The present work demonstrated that rainbow trout show a great capacity to detoxify the lampricide using glucuronidation, when exposed to …

Recovery From Acute Toluene Intoxication Is Facilitated By The Nmda Receptor Co-Agonist D-Serine, But Not The Gabaa Receptor Antagonist Picrotoxin, Susan R. Samuel-Herter

Theses and Dissertations (Comprehensive)

Toluene is a volatile solvent found in many household products and when intentionally inhaled results in intoxication. In rats, acute inhalation of toluene results in sedation and neurological impairments, with marked increases in ambulation and vertical behaviour during the recovery period. Previous in vitro research has shown that toluene may exert its effects by inhibiting NMDA receptors, and / or by activating GABA_A receptors. To test whether modulation of these receptors are also implicated in the changes in motor behaviour and neurological impairments resulting from toluene vapour inhalation, rats were injected with the NMDA receptor co-agonist D-serine (1000 mg/kg …

Addressing Public Health Risks Of Persistent Pollutants Through Nutritional Modulation And Biomimetic Nanocomposite Remediation Platforms, Bradley J. Newsome

Theses and Dissertations--Chemistry

Due to their relative chemical stability and ubiquity in the environment, chlorinated organic contaminants such as polychlorinated biphenyls (PCBs) pose significant health risks and enduring remediation challenges. Engineered nanoparticles (NPs) provide a novel platform for sensing/remediation of these toxicants, in addition to the growing use of NPs in many industrial and biomedical applications, but there remains concern for their potential long-term health effects. Research highlighted herein also represents a transdisciplinary approach to address human health challenges associated with exposure to PCBs and NPs. The objectives of this dissertation research are two-fold, 1) to develop effective methods for capture/sensing and remediation …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

The Role Of Surface Chemistry In The Toxicity Of Manufactured Cerium Dioxide Nanomaterials To Caenorhabditis Elegans, Emily Kay Oostveen

Theses and Dissertations--Plant and Soil Sciences

Manufactured CeO₂ nanomaterials (CeO₂-MNMs) are used for a wide variety of applications including diesel fuel additives and chemical/mechanical planarization media. To test the effects of CeO₂-MNM surface coating charge on to model organism Caenorhabditis elegans, we synthesized 4 nm CeO₂ with cationic (DEAE-), anionic (CM-), and neutral (DEX) coatings. In L3 nematodes exposed for 24 hours, DEAE-CeO₂ induced lethality at lower concentrations than CM- or DEX-CeO₂. Feeding slightly decreased CeO₂ toxicity, regardless of coating. In L2 nematodes exposed for 48 hours with feeding, DEAE-CeO₂ caused lethality at the …

Atrazine In Maternal Drinking Water Supply Below The Federal Maximum Contaminant Level And Risk Of Preterm Birth, Small For Gestational Age, Cryptorchidism And Hypospadias, Daniel Rice

Legacy Theses & Dissertations (2009 - 2024)

The prevalence of preterm birth, small for gestational age (SGA), and hypospadias has been increasing for several decades in the U.S resulting in significant morbidity and mortality and direct costs to society. Drinking water provides a mechanism for prolonged chronic exposure to environmental contaminants but is one of the least assessed environmental exposures in pregnancy and birth outcomes. To test the hypothesis that maternal exposure to atrazine through drinking water during pregnancy, or one or more trimesters of gestation, is associated with an increased risk of preterm birth, small for gestational age, cryptorchidism and hypospadias a retrospective cohort study was …

Comparative Study Of Postmortem Blood, Urine And Vitreous Humor Methamphetamine, Rungtip Narapanyakul, Wichian Tungtananuwat, Patramon Yongpanich, Theerin Sinchai, Nantana Thong-Ra-Ar, Somsong Lawanprasert

The Thai Journal of Pharmaceutical Sciences

Methamphetamine (MA) is a highly addictive and toxic central nervous system stimulant. Urine samples are used as evidences of MA abuse under the Narcotics Laws, whereas blood samples are specimens for investigation of MA poisoning. However, both specimen...

Understanding The Medication Experiences Of Thai Patients Attending A Medication Therapy Management Clinic, Phantipa Sakthong, Win Winit-Watjana, Rungpetch Sakulbumrungsil

The Thai Journal of Pharmaceutical Sciences

The study aimed to explore Thai patients' medication experiences in five domains, i.e., attitudes, understanding, expectations and wants, concerns, and convenience of medicine use. This cross-sectional descriptive study was carried out using a qualitativ...

Evaluation Of Antioxidant And Free Radical Scavenging Activities Of Different Fractions Of Pterospermum Suberifolium Leaf Extract, Dibyajyoti Saha, Swati Paul

The Thai Journal of Pharmaceutical Sciences

The study was aimed an evaluating the antioxidant activities of the various leaf extracts (ethyl acetate, n- butanol and chloroform) of Pterospermum suberifolium by using various in vitro antioxidant assays. The total polyphenols were also determined spe...

The Effects Of 1, 3, & 7 Trisubstituted And 8-Cyclopentyl Alkylxanthines On Respiration In Newborn Rats, Nathan Creel Davidson

Masters Theses

Methylxanthines have been shown to be promising respiratory stimulants in newborns suffering from recurrent apnea. The respiratory stimulant effects of methylxanthines are most likely due to their antagonism of adenosine receptors. These drugs have been shown to stimulate respiration in newborn rats in doses in excess of 10 mg/kg body weight. Structure-activity studies have shown that methylxanthines not only differ in the antagonism of A₁ and A₂ adenosine receptors but also, as a consequence of their different chemical structures, differ in potency as respiratory stimulants. To assess this, two potent A₁ adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and …

Wastewater Influent And Effluent Concentrations Of 17 Beta-Estradiol: A Study Of The Influence Of A University Community And The Risk To Environmental Health, Kyle Heffron

Masters Theses

The concentration of 17β-estradiol (E2) was measured through stages of wastewater treatment at a central Illinois wastewater treatment plant (WWTP). E2 concentration was quantified using a competitive enzyme linked immunosorbent assay (ELISA). The concentration of E2 was compared with demographic effects of a university, physical parameters of the wastewater (dissolved oxygen, pH, and temperature) and daily influent and effluent flow rates. Effluent concentrations ranged from 0 to 25.3 ng L^-1 with an average discharge of 3.6 ng L^-1. E2 concentration was shown to increase at the start of each university semester, however, this trend was not observed …

Effect Of The Broad-Spectrum Caspase Inhibitor Q-Vd-Oph On Neurodegeneration And Neuroinflammation Of Sarin Exposed Mice, Ekta J. Shah

Browse all Theses and Dissertations

Organophosphates (OP) cause CNS hyperstimulation resulting in seizures, convulsions and brain damage. Sarin is a toxic nerve agent used in Syria, the Gulf War and in terrorist attacks in Japan. Exposure to sarin is associated with presence of dead neurons, activation of astrocytes, microglia and neuroinflammation. Since, cell death and neuroinflammation are found in sarin exposed animals, we evaluated the efficacy of Q-VD-OPh, a broad spectrum caspase inhibitor that prevents cell death and has anti-inflammatory properties. Currently, treatment for sarin exposures is effective only if administered within 30-40 minutes of exposure. In this study, adult female C57BL/6 mice were subjected …

Increased Urinary Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Type 2 Diabetic Patients, Sridevi Gutta

Browse all Theses and Dissertations

Chronic Kidney Disease (CKD) has reached epidemic proportions affecting more than 20 million adults in the US. CKD is routinely diagnosed and defined as reduced glomerular filtration rate (GFR), increased urinary albumin creatinine ratio (UACR) or both. Diabetes, hypertension and obesity share a major part in causing CKD. Angiotensin (1-7) (Ang (1-7)) is a vasodilator that plays an important renoprotective role in the renin angiotensin system, counteracting the vasoconstrictor and proliferative effects of Ang II. ACE2 and NEP which form Ang (1-7) by degrading Ang II and Ang I, respectively. A Disintegrin and Metalloproteinase (ADAM) 17, which is responsible for …

Epigenetic Changes After Prenatal Environmental Tobacco Smoke Exposure And Asthma, Sonja Christensen

Graduate Student Theses, Dissertations, & Professional Papers

Allergic asthma affects over 300 million people worldwide. Multiple factors have been shown to alter an individuals' susceptibility to this allergic airway disease such as exposure to polycyclic aromatic hydrocarbons (PAHs), endotoxin, and environmental tobacco smoke (ETS). Prenatal exposure to these contaminants, especially ETS, has been shown to increase risk for an individuals’ asthma risk, however, the mechanism by which this happens is still unknown. Epigenetic alterations, particularly DNA methylation patterns, have been introduced as a proposed mechanism. The goals of this project were to use a house dust mite (HDM) murine model of asthma to determine the methylation alterations …

An Environmental Toxic Model Of Parkinson's Disease: The Fruit Fly, Jennene Lyda

Graduate Student Theses, Dissertations, & Professional Papers

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with no known specific cause; although genetic risk factors and/or environmental exposure are thought to be involved. The etiology of PD is currently unknown, although the combination of non-genetic components such as environmental exposures, the accumulation of exposure, and gene-environment interactions are thought to play a major role. However, despite this knowledge it is important to develop better models that parallel PD pathophysiology to further understand the mechanisms underlying dopaminergic neuron (DaN) damage. The use of mammalian models to study the degenerative processes in PD has been the most common …

Inactivation Of At1a Receptors Attenuate Lactate Accumulation And Improve Cardiac Performance And Acid-Base Homeostasis During Endurance Exercise, Ahmad Mohammed Alhajoj

Browse all Theses and Dissertations

Angiotensin Type 1 (AT1) receptors are involved in cardiovascular pathology. Losartan, the AT1 receptor blocker, in combination with exercise has been shown to be effective in improving cardiac performance. The goal of the study was to investigate the role of AT1a receptors on cardiac function, and exercise tolerance in response to aerobic exercise using AT1a receptor knockout (AT1aKO) mice. An exercise wheel system was used for the exercise paradigm. Male (C57BL/6) wild type (WT) and AT1aKO mice were randomly assigned to four groups: WT control (n=6), WT exercise (WTEX, n=8), AT1a KO (KO) control (n=5), and AT1a KO exercise (KOEX, …

Early Increase Of Cd11c In Human Monocyte-Derived Dendritic Cells In The Presence Of A/California/07/2009 (H1n1pdm), Amber M. Braddock

Browse all Theses and Dissertations

Influenza A continues to cause significant morbidity and mortality. Vaccine production time, viral antigenic variability and low vaccine efficacy contribute to the annual pandemics and seasonal epidemics. A better understanding of human immune responses to influenza A could result in more effective vaccines. Dendritic cells (DCs) play an important role in the initiation of immune responses. Populations of B lymphocytes secrete protective antibodies but the role of different populations of B cells in the protective response is unknown. In this thesis we developed assays to determine subclasses of influenza specific antibodies. Mononuclear cells were assessed using flow cytometry to identify …

Expression, Characterization, Cloning And Functional Impact Of Slc12a5 In The Endocrine Pancreas, Shams Kursan

Browse all Theses and Dissertations

The Slc12a5 gene encodes the neuron-specific electroneutral K+Cl- cotransporter-2 (KCC2), a constitutively active Cl- extruder. In mature neurons, KCC2 functionally predominates over other members of the Slc12a family, particularly the Na+K+2Cl- cotransporter-1 (NKCC1), a ubiquitous Cl- loader. Therefore, KCC2 keeps and maintains the intracellular chloride concentration ([Cl-]i) below values predicted by thermodynamic equilibrium and in doing so, KCC2 plays a key role in neuron physiology: it makes possible the inhibitory action of neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine. Neurons and insulin-secreting pancreatic ß-cells share many genes and functions. Indeed, neuron-specific genes have been also found in ß-cells whereas …

Caracterizacíon De Las Particulas Ultrafinas En Suspension Generadas Por La Soldadura De Planchas De Acero, João F. Gomes

João F Gomes

No abstract provided.

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Dartmouth Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.

Studies On Two Polyherbal Formulations (Zpto And Zto) For Comparison Of Their Antidyslipidemic, Antihypertensive And Endothelial Modulating Activities, Nauman Aziz, Malik Hassan Mehmood, Anwarul Hassan Gilani

Department of Biological & Biomedical Sciences

Background

Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs.

Methods

To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and …

Toxic And Repellent Effects Of Pyrethroids Used In Orchards On The Honey Bee, Apis Mellifera L. (Hymenoptera: Apidae), Erin M. Ingram

Department of Entomology: Dissertations, Theses, and Student Research

Managed honey bee colonies provide valuable pollination services and are rented by fruit orchards to improve fruit quality and yield. The placement of colonies in this agricultural setting increases the possibility of exposure to pyrethroids used for broad-spectrum pest control in orchards. Although highly toxic to bees, pyrethroids are believed to pose a relatively low hazard due to their low application rates in the field as well as their contact repellent properties. Previous studies have noted a decrease in foraging visits following pyrethroid application possibly preventing bees from acquiring a lethal dose in the field.

This research quantified behaviors associated …

The Imperative Of Conserving California's Foothill Oak Woodlands, Lauren Phillips

Social Sciences

No abstract provided.

Repeated Asenapine Treatment Produces A Sensitization Effect In Two Preclinical Tests Of Antipsychotic Activity, Rongyin Qin, Yingzhu Chen, Ming Li

Department of Psychology: Faculty Publications

Among several commonly used atypical antipsychotic drugs, olanzapine and risperidone cause a sensitization effect in the conditioned avoidance response (CAR) and phencyclidine (PCP)- induced hyperlocomotion paradigms – two well established animal tests of antipsychotic drugs, whereas clozapine causes a tolerance effect. Asenapine is a novel antipsychotic drug recently approved for the treatment of schizophrenia and manic disorders. It shares several receptor binding sites and behavioral features with other atypical antipsychotic drugs. However, it is not clear what type of repeated effect (sensitization or tolerance) asenapine would induce, and whether such an effect is transferrable to other atypicals. In this study, …

Comparison Of Theophylline And 8-Cyclopentyltheophylline On The Heart Rates Of Neonatal Rats, Stephanie Arnold

Undergraduate Honors Theses

Neonatal apnea is a serious condition that affects the health of infants, especially those born prematurely. To stimulate breathing, methylxanthine drugs, such as theophylline and caffeine, are administered to reverse this condition in humans and avoid the use of breathing-assistance equipment. These drugs cause stimulation of the central nervous system and the heart, however, both detrimental side effects in preterm infants. Antagonism of adenosine receptors is the proposed mechanism of methylxanthine action. Synthetic chemists have produced xanthine analogs with increased affinity for adenosine receptors that could lead to respiratory stimulation while reducing cardiostimulant effects. For this study, theophylline and 8-cyclopentyltheophylline …

Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel

Dissertations & Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy. High levels of Bcl-2 and IAP family proteins are responsible for apoptotic-resistance and accumulation of mature CLL lymphocytes in bone-marrow, lymph nodes and peripheral blood. Besides pro-survival proteins, supporting stromal cells as well as soluble factors in the microenvironment of bone-marrow and lymph nodes provide survival advantage to CLL leukemic cells.

Though the stromal – leukemia cell interactions has been studied extensively, in-depth-knowledge on the regulation of apoptotic pathway proteins in the context of microenvironment is still limited. To address this, the first part of our study focused on comprehensive analysis of …

The Eps Matrix As An Adaptive Bastion For Biofilms: Introduction To Special Issue, Alan Decho

Faculty Publications

No abstract provided.

The Eps Matrix As An Adaptive Bastion For Biofilms: Introduction To Special Issue, Alan W. Decho

Faculty Publications

No abstract provided.