Pharmacology, Toxicology and Environmental Health Commons^™

Apical Testis Structure And The Effects Of Cadmium Treatment On Spermatogenesis In Drosophila, Paulina J. Cardaci

Seton Hall University Dissertations and Theses (ETDs)

The fruit fly Drosophila melanogaster is used extensively as a model for studying molecular, genetic and cellular aspects of human disease and physiology. Our lab has used D. melanogaster and related species to study the structure of the testis stem cell niche, as well as other aspects of spermatogenesis. We previously revealed a novel stem cell niche structure in D. pseudoobscura, a distant relative of D. melanogaster. The signaling center of the D. melanogaster stem cell niche has a well-characterized rosette arrangement of fasciclin-positive cells terms the “hub”. D. pseudoobscura, however, lacks a punctuate hub and instead displays a …

Influence Of Water Hardness On Accumulation And Effects Of Silver In The Green Alga, Raphidocelis Subcapitata, Aarya Venkat, Adriana L. Amerson, Gretchen K. Bielmyer-Fraser

Georgia Journal of Science

Metal pollution from anthropogenic sources can pose a threat to aquatic systems. Silver is released into the environment from various industrial processes. In excess, silver can accumulate and cause adverse effects in aquatic organisms, particularly those in lower trophic levels, such as phytoplankton. Water chemistry parameters, such as hardness, have been shown to modify toxicity of metals because divalent cations compete with the metal for binding sites on the biological membrane. The objective of this study was to assess population growth and silver accumulation in the green alga, Raphidocelis subcapitata, after silver exposure in waters of varying hardness for 7 …

Resveratrol Supplementation Confers Neuroprotection In Cortical Brain Tissue Of Nonhuman Primates Fed A High-Fat/Sucrose Diet, Michel Bernier, Devin Wahl, Ahmed Ali, Joanne Allard, Shakeela Faulkner, Artur Wnorowski, Mitesh Sanghvi, Ruin Moaddel, Irene Alfaras, Julie A. Mattison, Stefano Tarantini, Zsuzsanna Tucsek, Zoltan Ungvari, Anna Csiszar, Kevin J. Pearson, Rafael De Cabo

Pharmacology and Nutritional Sciences Faculty Publications

Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the …

Cardiovascular Effects Evoked By Airway Nociceptive Reflexes In Healthy And Cardiovascular Diseased Rats, Justin Shane Hooper

USF Tampa Graduate Theses and Dissertations

Acute inhalation of airborne pollutants alters cardiovascular function and has been shown to have its greatest affects on individuals with pre-existing cardiovascular disease. Evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the cardiovascular responses evoked by inhalation of AITC (TRPA1 agonist) and capsaicin (TRPV1 agonist) in healthy Sprague Dawley (SD) and Wistar Kyoto (WKY) rats, and cardiovascular diseased Spontaneously Hypertensive (SH) rats. Inhalation of the agonists by healthy SD and WKY rats caused significant bradycardia, atrio-ventricular (AV) block and prolonged PR-Intervals. Inhalation of …

Evaluation Of Pulmonary Function Among Workers Engaged In The Manufacture Of Hydraulic Fracking Ceramic Proppant, Humairat H. Rahman

USF Tampa Graduate Theses and Dissertations

Workers involved in hydraulic fracking processes are exposed to various types of chemicals and dusts in their workplaces, such as proppants, which hold open the fissures created in the fracking process. Recently, ceramic proppants have been developed that may be less hazardous to workers than traditional proppants. Pulmonary function testing of workers producing ceramic proppant was used to assess the potential inhalation hazards of ceramic proppant. Male workers (n = 100) from a producer of ceramic proppant were evaluated with pulmonary function test data collected and evaluated using The American Thoracic Society (ATS) acceptability criteria. A comparison group was selected …

Human Health Risk Characterization Of Petroleum Coke Calcining Facility Emissions, Davinderjit Singh

USF Tampa Graduate Theses and Dissertations

Calcined coke is a high quality carbon material produced by calcining green petroleum coke. Calcining is the process of heating green petroleum coke in a kiln to remove excess moisture, extract all remaining hydrocarbons, and modify the crystalline structure of the coke into a denser, electrically conductive product. The final product, calcined coke, is primarily used to make carbon anodes for the aluminum industry and recarburizing agent for industries such as the steel industry. If not appropriately controlled, the calcining process could lead to excess production of particulate emissions from either handling or storing of raw coke, or from the …

Evaluation Of Cytotoxicity Profile And Intracellular Localisation Of Doxorubicin-Loaded Chitosan Nanoparticles, Gabriele Dadalt Souto, Zeineb Farhane, Esen Efeoglu, Alan Casey, Jennifer Mcintyre, Hugh Byrne

Articles

In the emerging field of nanomedicine, targeted delivery of nanoparticle encapsulated active pharmaceutical ingredients (API) is seen as a potential significant development, promising improved pharmacokinetics and reduced side effects. In this context, understanding the cellular uptake of the nanoparticles and subsequent subcellular distribution of the API is of critical importance. Doxorubicin (DOX) was encapsulated within chitosan nanoparticles to investigate its intracellular delivery in A549 cells in vitro. Unloaded (CS-TPP) and doxorubicin-loaded (DOX-CS-TPP) chitosan nanoparticles were characterised for size (473±41 nm), polydispersity index (0.3±0.2), zeta potential (34±4 mV), drug content (76±7 µM) and encapsulation efficiency (95±1%). The cytotoxic response to …

Effect Of An Improved Biomass Stove On Acute Lower Respiratory Infections In Young Children In Rural Nepal: A Cluster-Randomised, Step-Wedge Trial, James M. Tielsch, Joanne Katz, Subarna K. Khatry, Laxman Shrestha, Patrick N. Breysse, Scott L. Zeger, +5 Additional Authors

Global Health Faculty Publications

Background

Acute lower respiratory infections (ALRI) are an important cause of death in young children in low income countries. High concentrations of fine particulate matter (PM2.5) indoors caused by open burning of biomass are associated with risk of ALRI. However, improved biomass stoves reduce emissions and might reduce the incidence of lower respiratory illness. A cluster-randomised, step-wedge, community-based trial was conducted to estimate the eff ect that a change from open burning of biomass to improved biomass stoves could have on rates of ALRI in children younger than 36 months in a rural area of southern Nepal.

Methods

Households were …

Fipronil Promotes Adipogenesis Via Ampkα-Mediated Pathway In 3t3-L1 Adipocytes, Quancai Sun, Jeremy Yang, Kyong-Sup Yoon, John M. Clark, Yeonhwa Park

SIUE Faculty Research, Scholarship, and Creative Activity

Emerging evidence suggests that organochlorine, organophosphorus and neonicotinoid insecticide exposure may be linked to the development of obesity and type 2 diabetes. However, there is no knowledge of the potential influence of fipronil, which belongs to the phenylpyrazole chemical family, on obesity. Thus, the goal of this study was to determine the role of fipronil in adipogenesis using 3T3-L1 adipocytes. Fipronil treatment, at 10 mM, increased fat accumulation in 3T3-L1 adipocytes as well as promoted key regulators of adipocyte differentiation (CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor gamma-γ), and key regulators of lipogenesis (acetyl-CoA carboxylase and fatty acid synthase). The …

Phantom Limb Pain, Stephanie J. Stockburger, Mandakini Sadhir, Hatim A. Omar

Pediatrics Faculty Publications

Phantom limb pain is pain that is perceived in a part of the body which is no longer present. It is estimated that 80 percent of amputees experience phantom limb pain. Although the term is “phantom limb pain” the feeling is often more of a burning, twisting, itching, or pressure sensation than pain. The exact mechanism of phantom limb pain is unknown although proposed mechanisms include pain origination from either the central nervous system or the peripheral nervous system. Since the exact mechanism of phantom limb pain is unknown, treating this pain may be difficult. Treatments include pharmacological and nonpharmacological. …

Anticonvulsant And Procognitive Properties Of Novel Histamine H3 Receptor Antagonists In Male Adult Rats, Ali Kassem Saad

Theses

To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic and procognitive drugs, aromatic ether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced seizure models in male adult rats having phenytoin (PHT) and valproic acid (VPA) as the reference antiepileptic drugs, pitolisant (PIT) as the standard H3R antagonist/inverse agonist, and donepezil (DOZ) as a reference procognitive drug. Among the H3R ligands (1-12) tested in the current project, H3R …

Inquiry Into The Implementation Of Bush’S Executive Order 13211 And The Impact On Environmental And Public Health Regulation, Elizabeth Ann Glass Geltman, Gunwant Gill, Miriam Jovanovic

Publications and Research

Executive Order 13211, promulgated in 2001, requires the federal government to consider the impact of federal action on energy independence as part of the George W. Bush’s National Energy Policy. This law review examines whether EO 13211 was used to curtail environmental protection and natural resource conservation. The article begins with a review of the procedure required of federal agencies under EO 13211 and its associated documents. The paper then examines case law and published federal rulemaking proceedings and examines how federal agencies apply tests to evaluate the potential energy effect. The study concludes that EO 13211 strikes a reasonable …

Examining Mechanism Of Toxicity Of Copper Oxide Nanoparticles To Saccharomyces Cerevisiae And Caenorhabditis Elegans, Michael Joseph Mashock

Dissertations (1934 -)

Copper oxide nanoparticles (CuO NPs) are an up and coming technology increasingly being used in industrial and consumer applications and thus may pose risk to humans and the environment. In the present study, the toxic effects of CuO NPs were studied with two model organisms Saccharomyces cerevisiae and Caenorhabditis elegans. The role of released Cu ions during dissolution of CuO NPs in growth media were studied with freshly suspended, aged NPs, and the released Cu2+ fraction. Exposures to the different Cu treatments showed significant inhibition of S. cerevisiae cellular metabolic activity. Inhibition from the NPs was inversely proportional to size …

Expansion Of The Knockdown Resistance Frequency Map For Human Head Lice (Phthiraptera: Pediculidae) In The United States Using Quantitative Sequencing, K J. Gellatly, S Krim, D J. Palenchar, K Shepherd, Kyong-Sup Yoon, C J. Rhodes, S H. Lee, J M. Clark

SIUE Faculty Research, Scholarship, and Creative Activity

Pediculosis is a prevalent parasitic infestation of humans, which is increasing due, in part, to the selection of lice resistant to either the pyrethrins or pyrethroid insecticides by the knockdown resistance (kdr) mechanism. To determine the extent and magnitude of the kdr-type mutations responsible for this resistance, lice were collected from 138 collection sites in 48 U.S. states from 22 July 2013 to 11 May 2015 and analyzed by quantitative sequencing. Previously published data were used for comparisons of the changes in the frequency of the kdr-type mutations over time. Mean percent resistance allele frequency (mean % RAF) values across …

Assessment Of The Role Of Poly (Adp-Ribose) Polymerase In Drug-Induced Cardiomyopathy, Alexis I. Brinkerhoff

USF Tampa Graduate Theses and Dissertations

Drug-induced cardiotoxicity has resulted in a thorough evaluation of patient doses, treatments, and rehabilitation. One of the most commonly prescribed chemotherapeutic agents is cyclophosphamide. The active metabolite, acrolein, is one of the most potent inducers of cardiomyopathy. In this study, research was conducted on the H9c2 (2-1) cardiomyocyte cell line derived from the embryonic myocardium of rattus norvegicus to assess its competency for evaluation of the change in poly (ADP-ribose) polymerase (PARP) activity. The application of this model to study the effects of acrolein on PARP activation was chosen as an ideal determinant of cell damage produced by nitrogen mustards. …

Assessment Of Acrolein-Induced Toxicity Using In-Vitro Modeling To Evaluate The Role Of Parp Inhibitors In Reducing Cytotoxicity, Kristina Marie Harand

USF Tampa Graduate Theses and Dissertations

Acrolein is an electrophilic α, β-unsaturated aldehyde. Additionally, acrolein is a metabolite of the antineoplastic alkylating agent cyclophosphamide and is implicated in off-target effects, including to bladder hemorrhagic cystitis and cyclophosphamide-induced cardiotoxicity, both of which have led to serious secondary iatrogenic injury during and following chemotherapy. At low concentrations acrolein inhibits cell proliferation without inducing apoptosis, while at high concentrations may result in secondary apoptosis promotion. This investigation assessed the role of the enzyme poly (ADP-ribose) polymerase (PARP) in acrolein induced toxicity using the established toxicological H9c2 (2-1) cardiomyoblast in vitro model. H9c2 (2-1) cells were plated in 24-well plates …

Chemotherapeutic Efficiency Of Drugs In Vitro: Comparison Of Doxorubicin Exposure In 3d And 2d Culture Matrices, Alan Casey, Mahmoud Gargotti, Franck Bonnier, Hugh Byrne

Articles

The interest in the use of 3D matrices for in vitro analysis, with a view to increasing the relevance of in vitro studies and reducing the dependence on in vivo studies, has been growing in recent years. Cells grown in a 3D in vitro matrix environment have been reported to exhibit significantly different properties to those in a conventional 2D culture environment. However, comparison of 2D and 3D cell culture models have recently been noted to result in differing responses of cytotoxic assays, without any associated change in viability. The effect was attributed to differing conversion rates and effective concentrations …

Comparison Of Protein Phosphatase Inhibition Assay With Lc-Ms/Ms For Diagnosis Of Microcystin Toxicosis In Veterinary Cases, Caroline E. Moore, Jeanette Juan, Yanping Lin, Cynthia L. Gaskill, Birgit Puschner

Veterinary Diagnostic Laboratory Faculty Publications

Microcystins are acute hepatotoxins of increasing global concern in drinking and recreational waters and are a major health risk to humans and animals. Produced by cyanobacteria, microcystins inhibit serine/threonine protein phosphatase 1 (PP1). A cost-effective PP1 assay using p-nitrophenyl phosphate was developed to quickly assess water and rumen content samples. Significant inhibition was determined via a linear model, which compared increasing volumes of sample to the log-transformed ratio of the exposed rate over the control rate of PP1 activity. To test the usefulness of this model in diagnostic case investigations, samples from two veterinary cases were tested. In August …

Combination Of Vatalanib And A 20-Hete Synthesis Inhibitor Results In Decreased Tumor Growth In An Animal Model Of Human Glioma, Adarsh Shankar, Asm Iskander, Meenu Jain, Tom Mikkelsen, Austin M. Guo, Ali Arbab

NYMC Faculty Publications

BACKGROUND: Due to the hypervascular nature of glioblastoma (GBM), antiangiogenic treatments, such as vatalanib, have been added as an adjuvant to control angiogenesis and tumor growth. However, evidence of progressive tumor growth and resistance to antiangiogenic treatment has been observed. To counter the unwanted effect of vatalanib on GBM growth, we have added a new agent known as N-hydroxy-N'-(4-butyl-2 methylphenyl)formamidine (HET0016), which is a selective inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis. The aims of the studies were to determine 1) whether the addition of HET0016 can attenuate the unwanted effect of vatalanib on tumor growth and 2) whether the treatment …

Xenoestrogens From Household Plastics Bind Estrogen Receptors And Affect Cell Proliferation, Susan G. Hurley, Brett R. Lackey, Patricia L. Tate, Sandra L. Gray

Journal of the South Carolina Academy of Science

Xenoestrogens are “foreign” chemicals or compounds that interact with estrogen receptors as either agonists or antagonists to interfere with endocrine system function. Xenoestrogens include phytoestrogens, pesticides, industrial by- products and synthetic estrogens. In this study, consumer plasticware, including baby bottles and food storage containers, were found to release xenoestrogenic compounds that bound to ERα and ERβ and affected cell proliferation.

Thromboxane A2 And Tp Receptors: A Trail Of Research, Well Traveled, Perry V. Halushka Phd, Md

Journal of the South Carolina Academy of Science

This article was written is response to a request from the editor-in-chief as a result of my receiving the Governor’s Award in Scientific Awareness. My goal is to provide a glimpse into a 40 plus year research career that was predominately focused on the role of thromboxane A₂ and its receptor (TP) in physiologic and pathophysiologic processes in the cardiovascular system. It also enumerates the lessons learned along the way that may lead to a productive research career. Those lessons were; Perseverance, Think out of the box, Challenge the dogma, Take risks, Failure is not a bad thing, Focus, …

Extracorporeal Membrane Oxygenation (Ecmo) For Severe Toxicological Exposures: Review Of The Toxicology Investigators Consortium (Toxic)., G S. Wang, R Levitan, T J. Wiegand, Jennifer Lowry, R F. Schult, S Yin, Toxicology Investigators Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for …

Glyphosate Induces Neurotoxicity In Zebrafish, Nicole M. Roy, Bruno Carneiro, Jeremy Ochs

Biology Faculty Publications

Glyphosate based herbicides (GBH) like Roundup^® are used extensively in agriculture as well as in urban and rural settings as a broad spectrum herbicide. Its mechanism of action was thought to be specific only to plants and thus considered safe and non-toxic. However, mounting evidence suggests that GBHs may not be as safe as once thought as initial studies in frogs suggest that GBHs may be teratogenic. Here we utilize the zebrafish vertebrate model system to study early effects of glyphosate exposure using technical grade glyphosate and the Roundup^® Classic formulation. We find morphological abnormalities including cephalic and …

Arsenic Analysis: Comparative Arsenic Groundwater Concentration In Relation To Soil And Vegetation, Rominna E. Valentine Vecorena

Electronic Theses, Projects, and Dissertations

Arsenic (As) is a toxic semi-metallic element found in groundwater, soils, and plants. Natural and anthropogenic sources contribute to the distribution of arsenic in the environment. Arsenic’s toxic and mobile behavior is associated with its speciation ability. There are two types of arsenic available to the environment, inorganic and organic arsenic. Of the two, inorganic arsenic is more toxic to humans and more mobile in the environment. Two inorganic compounds responsible for arsenic contamination are trivalent arsenite, As (III), and pentavalent arsenate, As (V). Trivalent arsenate is considered to be more soluble, toxic, and mobile than pentavalent arsenate. Arsenic’s absorptive …

Chemical Investigation Of Antarctic Marine Organisms & Their Role In Modern Drug Discovery, Jacqueline Lee Fries

USF Tampa Graduate Theses and Dissertations

The chemicals produced by biological systems, whether proteins, peptides, or terpenes, will always provide an intriguing topic for researchers. Invisibly controlling every aspect of nature, these molecules are responsible for life, evolution, and death. Specifically, here is described the secondary metabolites produced by Antarctic marine organisms as well as others, and how they are used to defend or attract other animals while potentially providing health benefits to mankind. This is done through collection, extraction, and separation of individual specimens. The respective mixtures of compounds after isolation are then analyzed via spectroscopic methods such as nuclear magnetic resonance spectroscopy, mass spectrometry, …

Acellular Reactivity Of Polymeric Dendrimer Nanoparticles As An Indicator Of Oxidative Stress In Vitro, Marcus Maher, Humza Khalid, Hugh Byrne

Articles

The need for rapid and cost effective pre-screening protocols of the toxicological response of the vast array of emerging nanoparticle types is apparent and the emerging consensus on the paradigm of oxidative stress by generation of intracellular reactive oxygen species as a primary source of the toxic response suggests the development of acellular assays to screen for nanoparticle surface reactivity. This study explores the potential of the monoamine oxidase A (MAO-A) enzyme based assay with polymeric dendrimers as cofactors and serotonin as substrate, which generates H₂O₂, quantified by the conversion of the Carboxy-H₂DCFDA dye …

Gene Expression Microarray Data From Human Microvascular Endothelial Cells Supplemented With A Low Concentration Of Niacin, Nica M. Borradaile, Jennifer M. Hughes-Large

Physiology and Pharmacology Publications

The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors [1]. Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA) values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, …

Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate …

Tom Curran, Phd, Frs, Named Executive Director Of Children's Research Institute, Children's Mercy Hospital

Our Story Continues

Tom Curran, PhD, FRS, has been named Chief Scientific Officer and Executive Director of the Children’s Mercy Children’s Research Institute (CRI), effective Feb. 1 [2016]

The Children’s Research Institute at Children’s Mercy Kansas City was established last year to build on the hospital’s century-long history in pediatric research and to focus the hospital’s future research efforts in four key areas:

• Pediatric Genomic Medicine
• Clinical Pharmacology
• Health Services and Outcomes
• Health Care Delivery

Structural Dependence Of The In Vitro Cytotoxicity, Oxidative Stress And Uptake Mechanisms Of Poly(Propylene Imine) Dendritic Nanoparticles, Humza Khalid, Sourav Prasanna Mukherjee, Luke O'Neill, Hugh Byrne

Articles

The in vitro cytotoxic and intracellular oxidative stress responses to exposure to poly (propylene imine) (PPI) dendritic nanoparticles of increasing generation (number of repeated branching cycles) (G0-G4) were assessed in an immortal non-cancerous human keratinocyte cell-line (HaCaT). Confocal fluorescence microscopy with organelle staining was used to explore the uptake and intracellular trafficking mechanisms. A generation and dose dependent cytotoxic response was observed, increasing according to generation and therefore number of surface amino groups. A comparison of the cytotoxic response of G4 PPI and the related G4 Poly (amido amine) dendrimer indicates that the PPI with the same number of surface …