Pharmacology, Toxicology and Environmental Health Commons^™

Halogen Bonding Interactions Of Haloaromatic Endocrine Disruptors And The Potential For Inhibition Of Iodothyronine Deiodinases, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Halogen bonding (XB) is a potential mechanism for the inhibition of the thyroid-activating/deactivating iodothyronine deiodinase family of selenoproteins through interactions with halogenated endocrine disrupting compounds (EDCs). Trends in XB interactions were examined using density functional theory for a series of polyhalogenated dibenzo-1,4-dioxins, biphenyls, and other EDCs with methylselenolate, a simple model of the Dio active site selenocysteine. The strengths of the interactions depend upon the halogen (Br>Cl), the degree of substitution, and the position of the acceptor. In terms of donor-acceptor energies, interactions at the meta position are often the strongest, suggesting a link to the topology of THs, …

Blood Lead Levels In Minority Children: A Case Of Environmental Racism, Erick Rivera

Sociology & Criminal Justice Theses & Dissertations

Racial minorities in the United States have suffered from being disadvantaged. Among these disadvantages is environmental racism. This includes minority communities being ‘sacrifice zones’ for toxic waste and being exposed to lead poisoning. The purpose of this study is to examine differences in blood levels between white children and children of color. This research will follow a bivariate model for the first research question, “Do youth of color (under the age of 18) have higher BLLs than white children?” The bivariate model will look at the relationship between ethno-racial group and BLLs. Specifically, an analysis of variance (ANOVA) will be …

Computational Analysis Of Type 3 Iodothyronine Deiodinase: Potential Inhibitors, Substrate Binding, And Dimer Structure, Eric Scott Marsan

Chemistry & Biochemistry Theses & Dissertations

Thyroid hormones (THs) in mammalian tissues are crucial for development and maintaining metabolic homeostasis. Iodothyronine deiodinases (Dios) remove iodines from THs by a selenocysteine (Sec) residue, which either activates or inactivates them. Halogen bonding (XB) has been proposed to describe the interaction between the Se and I atoms of the T4-Dio complex. Disruption of TH homeostasis by xenobiotics, such as polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) can cause deleterious effects on the endocrine system. Experimental studies have indicated that PBDEs and PCBs could disrupt TH homeostasis by inhibiting Dio through XB formation. However, no current quantitative study exists …

Effects Of Carboxylated Nanodiamonds On Macrophages During And After Differentiation, Maisoun E. Bani Hani

Biological Sciences Theses & Dissertations

Nanodiamonds (ND) are a carbon-based nanomaterial that are increasingly being proposed for developing novel imaging techniques, as carriers of biomolecules and therapeutic drugs, as coatings for implants, and for other biomedical applications. The exceptional chemical, mechanical, and optical properties of ND make this material suitable in a wide range of fields. The application of ND in the biomedical field is attractive but requires more in-depth investigation into the safety of ND and its interactions with different cells and systems. The effects of ND on the immune system are not fully understood or investigated and there are several controverting reports regarding …

Sperm Dna Oxidative Damage And Dna Adducts, Hueiwang Anna Jeng, Chih-Hong Pan, Mu-Rong Chao, Wen-Yi Lin

Community & Environmental Health Faculty Publications

The objective of this study was to investigate DNA damage and adducts in sperm from coke oven workers who have been exposed to polycyclic aromatic hydrocarbons. A longitudinal study was conducted with repeated measurements during spermatogenesis. Coke-oven workers (n =112) from a coke-oven plant served the PAH-exposed group, while administrators and security personnel (n=67) served the control. Routine semen parameters (concentration, motility, vitality, and morphology) were analyzed simultaneously; the assessment of sperm DNA integrity endpoints included DNA fragmentation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo). The degree of sperm DNA fragmentation was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling …

Interactive Effects Of Climate Change With Nutrients, Mercury, And Freshwater Acidification On Key Taxa In The North Atlantic Landscape Conservation Cooperative Region, Alfred E. Pinkey, Charles T. Driscoll, David C. Evers, Michael J. Hooper, Jeffrey Horan, Jess W. Jones, Rebecca S. Lazarus, Harold G. Marshall, Andrew Milliken, Barnett A. Rattner, John Schmerfold, Donald W. Sparling

Biological Sciences Faculty Publications

The North Atlantic Landscape Conservation Cooperative LCC (NA LCC) is a public-private partnership that provides information to support conservation decisions that may be affected by global climate change (GCC) and other threats. The NA LCC region extends from southeast Virginia to the Canadian Maritime Provinces. Within this region, the US National Climate Assessment documented increases in air temperature, total precipitation, frequency of heavy precipitation events, and rising sea level, and predicted more drastic changes. Here, we synthesize literature on the effects of GCC interacting with selected contaminant, nutrient, and environmental processes to adversely affect natural resources within this region. Using …

Re: Pierce Et Al. Diacetyl And 2,3-Pentanedione Exposures Associated With Cigarette Smoking: Implications For Risk Assessment Of Food And Flavoring Workers Crit Rev Toxicol, 2014; 44(5): 420-435, Muge Akpinar-Elci, Omur Cinar Elci

Center for Global Health Publications

We were greatly dismayed by Pierce et al.’ s report on the associations between exposure to Diacetyl and 2,3-pentanedione and cigarette smoking (Pierce et al. 2014). It stated that “ Diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/flavoring workers who smoke. ” Based on this finding, the authors suggested that “ previous claims of a significant exposure – response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded because none of the investigations considered or quantified the non-occupational diacetyl exposure from cigarette smoke, yet all the cohorts evaluated had considerable smoking …

Study Of Charge-Dependent Transport And Toxicity Of Peptide-Functionalized Silver Nanoparticles Using Zebrafish Embryos And Single Nanoparticle Plasmonic Spectroscopy, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess unusually high surface area-to-volume ratios and surface-determined physicochemical properties. It is essential to understand their surface-dependent toxicity in order to rationally design biocompatible nanomaterials for a wide variety of applications. In this study, we have functionalized the surfaces of silver nanoparticles (Ag NPs, 11.7 ±+2.7 nm in diameter) with three biocompatible peptides (CALNNK, CALNNS, CALNNE) to prepare positively (Ag-CALNNK NPs^+ζ), negatively (Ag-CALNNS NPs^−2ζ), and more negatively charged NPs (Ag-CALNNE NPs^−4ζ), respectively. Each peptide differs in a single amino acid at its C-terminus, which minimizes the effects of peptide sequences and serves as …

Embryo And Gamete Development Upon Exposure To Cca Components: Cro3, Cuo, And As2o5, Nerbana Talaat-Elsebaei Mahmoud

Theses and Dissertations in Biomedical Sciences

Production of functional gametes and healthy embryos is essential for proliferation of all vertebrates, especially humans. Many compounds have toxic effects on developing gametes and embryos among which are chromium trioxide (CrO₃), cupric oxide (CuO) and arsenic pentaoxide (As₂O₅) as a mixture (CCA) or individually. Controversy surrounding the safety of CCA-treated wood centers primarily on the toxicity of its components and the potential for these metals to be released from the wood.

The aim of this research is to test the hypothesis that CCA components have deleterious effects on embryo development, oocyte maturation and …

Recognizing Toxic Species In Aquatic Habitats: A Potential Concern In Lake Management, Mikolaj Kokocinski, Harold G. Marshall

Biological Sciences Faculty Publications

The importance of distinguishing toxic and non-toxic algal species is becoming a more common problem for management decisions associated with various freshwater and estuarine habitats. An example is given where two dinoflagellates, originally unidentified as closely resembling the toxin producing Pfiesteria spp., have been compared to these species. In order to clarify any relationship to Pfiesteria spp., scanning electron microscopy was used to determine the plate tabulation patterns of these dinoflagellates and make comparisons to the tabulation present in Pfiesteria spp. The results indicated significant differences in the plate tabulations of these taxa to distinguish them from Pfiesteria …

The Standardized Fish Bioassay Procedure For Detecting And Culturing Actively Toxic Pfiesteria, Used By Two Reference Laboratories For Atlantic And Gulf Coast States, Joann M. Burkholder, Harold G. Marshall, David W. Seaborn, Nora J. Deamer-Melia

Biological Sciences Faculty Publications

In the absence of purified standards of toxins from Pfiesteria species, appropriately conducted fish bioassays are the "gold standard" that must be used to detect toxic strains of Pfiesteria slop. from natural estuarine water or sediment samples and to culture actively toxic Pfiesteria. In this article, we describe the standardized steps of our fish bioassay as an abbreviated term for a procedure that includes two sets of trials with fish, following the Henle-Koch postulates modified for toxic rather than infectious agents. This procedure was developed in 1991, and has been refined over more than 12 years of experience in …

The Effect Of Illicit Drugs On The Cardiovascular And Hormonal Responses In Pregnant Rabbits, Andrea Alana Chambliss

Biological Sciences Theses & Dissertations

The purpose of this study is to determine the effect of acute administration of heroin and ecgonine methyl ester (EME) on renin and atrial natriuretic peptide (ANP) secretion in time dated New Zealand White rabbits. Thirteen rabbits were studied. Arterial blood pressure and pCOz, increased significantly from a control value of 80 ± 8 mmHg and 30 ± 2 mmHg respectively to 93 ± 18 mmHg and 31 ± 1 mmHg. pO₂ decreased from 99 ± 8 mmHg to 90 ± 11 mmHg 10 minutes after heroin administration. EME caused arterial blood pressure to significantly increase from a control …

Monitoring Results For Pfiesteria Piscidida And Pfiesteria-Like Organisms From Virginia Waters In 1998, Harold G. Marshall, David W. Seaborn, Jennifer Wolny

Virginia Journal of Science

Results of an extensive 1998 monitoring program for the presence of Pfiesteria-like organisms (PLO) in Virginia estuaries indicate these dinoflagellates are widely distributed in both the water column, and as cysts in the sediment, however Pfiesteria piscicida was not detected at this time. The highest concentrations of PLO were in estuaries along the Virginia shore line of the Potomac River, and in western Chesapeake Bay estuaries from the Little Wicomico River to the Rappahannock River. The most common PLO included Cryptoperidiniopsis sp. and Gymnodinium galatheanum. The lowest PLO concentrations were at ocean side locations. PLO were also …

Pfiesteria Piscicida And Dinoflagellates Similar To Pfiesteria, Harold G. Marshall

Biological Sciences Faculty Publications

Pfiesteria pisiccida is a microscopic, unicellular organism that is classified as both a mixotrophic and heterotrophic dinoflagellate, which has been associated with both fish deaths and a cause of human illness (Burkholder et al., 1992; Glasglow et al., 1995; Burkholder and Glasgow, 1997). This species possesses a complex life cycle that includes motile forms (e.g. zoospores, gametes, amoebae) and a cyst stage that may remain dormant in the sediment (Burkholder et al, 1995b). Pfiesteria piscicida is known to have toxin and non-toxin producing populations, where cyst transformation into the toxic motile zoospores may be initiated by the presence of certain …

Monitoring Results For Pfiesteria Piscidida And Pfiesteria-Like Organisms From Virginia Waters In 1998, Harold G. Marshall, David W. Seaborn, Jennifer Wolny

Biological Sciences Faculty Publications

Results of an extensive 1998 monitoring program for the presence of Pfiesteria-like organisms (PLO) in Virginia estuaries indicate these dinoflagellates are widely distributed in both the water column, and as cysts in the sediment, however Pfiesteria piscicida was not detected at this time. The highest concentrations of PLO were in estuaries along the Virginia shore line of the Potomac River, and in western Chesapeake Bay estuaries from the Little Wicomico River to the Rappahannock River. The most common PLO included Cryptoperidiniopsis sp. and Gymnodinium galatheanum. The lowest PLO concentrations were at ocean side locations. PLO were also …

Water Quality Relationships To Concentrations Of Pfiesteria-Like Organisms In Virginia Estuaries For 1998, Everett P. Weber, Harold G. Marshall

Virginia Journal of Science

A series of statistical analyses were performed to identify the relationship between abundance of dinoflagellates grouped as Pfiesteria-like organisms and a set of 25 water quality variables from May through October of 1998 at 41 estuarine locations. Although regions were identified in relation to seasonal density of cells present, there were no strong relationships to specific water quality variables. Factors that may have influenced these results included: a) several species were included in the group analyzed and this composite did not respond as a unit to changing environmental conditions; b) cell concentrations were low and there were a large …

Mouse Embryo Development In The Presence Of Capsaicin, Carlos Santiago Villar-Gosalvez

Theses and Dissertations in Biomedical Sciences

Capsaicin is the pungent agent found in hot peppers of the Capsicum genus. It is a potent neurotoxin that stimulates the degranulation and degeneration of C-afferent neurons. Capsaicin is widely used as a food condiment and medicine. Human exposure of capsaicin can exceed levels shown to be neurotoxic in laboratory animals. Additionally, capsaicin can cross the blood/placenta barrier and affect an embryo in utero. In order to assay the potential for toxicity to human embryos, mouse embryos were exposed to capsaicin and the effect of the capsaicin on embryo development was measured. Embryos were co-cultured in Krebs medium with 1% …

Evaluation Of Toxicity, Bioavailability And Speciation Of Lead, Zinc And Cadmium In Mine/Mill Wastewaters, Mujde Erten-Unal, Bobby G. Wixson, Nord Gale, Jerry L. Pitt

Civil & Environmental Engineering Faculty Publications

The toxicity of common compounds of lead, cadmium and zinc was evaluated in waters similar to that found in the world's largest lead producing area in Missouri. Static, acute toxicity tests were performed using fathead minnows (Pimephales promelas) and water fleas (Daphnia magna) respectively. Test organisms were subjected to varying amounts of sulfide, carbonate, chloride and sulfate salts of lead, zinc and cadmium mixed in hard, alkaline waters typical to this region. Median lethal concentrations were calculated using nominal versus measured metal concentrations. Measured metal concentrations included four different metal fractionation (extraction/filtration) techniques at different pH …

Effect Of Cocaine On Rabbit Renin Angiotensin System: Cocaine Detection In Adult And Fetal Tissue And Adult Plasma Using Ion Mobility Spectrometry, Barbara Belinda Guinn

Biological Sciences Theses & Dissertations

Ion mobility spectrometry (IMS) was used to detect cocaine and/or the metabolite ecgonine methyl ester (EME) in tissue and plasma samples from male, maternal, and fetal New Zealand White (NZW) rabbits. EME was consistently detected in all adult plasma samples 5 minutes after the injection of cocaine hydrochloride (cocaine•HCI, 2 mg/kg). EME was also in the liver, kidneys, testicles, and ovaries. Five minutes after the injection of cocaine•HCI, the male arterial pressure (MAP) increased from a mean control value of 79 ± 3.2 mmHg to 88 ± 4.1 mmHg, and the pCO₂ increased from a control value of28 ± …

Lead Activation Of A Developmentally Regulated Calcium Channel In Rat Hippocampal Nerve Terminals, Troy E. Rhodes

Theses and Dissertations in Biomedical Sciences

Low level lead (Pb²⁺) exposure may produce lasting deficits in learning and memory by altering calcium (Ca²⁺) dependent processes. Isolated presynaptic nerve terminals from rat hippocampus were loaded with the intracellular (Ca²⁺) indicator Fura-2. The changes in cytoplasmic free calcium ([Ca²⁺]_i) were measured by stopped-flow fluorescence spectroscopy following depolarization with elevated potassium on a millisecond time scale (Lentzner et al., 1992). Depolarization promoted a rapid increase in Ca²⁺_i which occured in two kinetically distinguishable phases: a fast component, representing the activity of rapidly inactivating Ca²⁺ channels (τ …

Comparison Of Positive Screening And Confimatory Results From Federally Mandated Drug Testing Of Urine, Mary M. Stuck

Community & Environmental Health Theses & Dissertations

The purpose of this study was to analyze the accuracy of FDA approved immunoassays for the detection of drug positive urine samples.

Federal civilian employees are tested under the strict protocol of the Department of Health and Human Services mandatory guidelines for federal workplace drug testing programs. The guidelines provide for a two instrument testing protocol for the analysis of urine samples. The first is an FDA approved immunoassay. Samples which test positive on this screening immunoassay are then submitted for confirmatory testing with the "gold standard" gas chromatography/mass spectrometry.

Agency monthly drug testing summaries, required under the DHHS guidelines …

The Evaluation Of Succinylcholine Chloride For Harmful Effects Upon Early-Stage Mouse Embryos, Francis Warren Prescott

Biological Sciences Theses & Dissertations

Succinylcholine (SCh) chloride is a depolarizing neuromuscular blocking agent used to paralyze patients for surgical procedures. Over 1,800 clinical observations of newborn infants have demonstrated that succinylcholine does not cross the placenta in quantities detrimental to fetuses (Kolstad, et al., 1957, Bakhoum, et al., 1957, Hodges, et al., 1959, Duffield, et al., 1958, Dennis, et al., 1954, 1956, McNab, 1955, Coleman, et al., 1956, Lund, 1953). Later investigations which involved comparison of blood levels of SCh in the mother to those in fetuses bolstered the finding that SCh fails to cross the placenta in significant amounts (Moya and Kvisselgaard, 1961, …

Toxin Producing Phytoplankton In Chesapeake Bay, Harold G. Marshall

Biological Sciences Faculty Publications

Three diatoms and nine dinoflagellates, known to be associated with toxin production, have been identified within Chesapeake Bay. Over the past several decades this number has increased to its present level so that they now represent approximately 1.7% the total number of phytoplankton species reported for the Bay.

Validation Of A Bag Sampling Method For 1,3-Butadiene, Lori Eckenrode

Community & Environmental Health Theses & Dissertations

At this time there is no NIOSH approved means for bag sampling 1,3-butadiene. An attempt was made to use the application of cold (0°F) to inhibit the reactivity of the gas prior to analysis. The State of California Air Resources Board has an approved method for the gas chromatographic analysis of 1,3-butadiene from stationary sources. The method was utilized in the application of industrial hygiene monitoring of affected workers. The application of cold was found to be ineffective at inhibiting the highly reactive nature of 1,3-butadiene. Analyte losses were too great to classify the method as an accurate measure of …

Development And Standardization Of A Short-Term Assay For Evaluating Polluted Estuarine And Coastal Environments: The Medaka Embryo-Larval Assay, Michael Frederick Helmstetter

OES Theses and Dissertations

The eggs of the Japanese medaka (Oryzias latipes) were employed in a number of studies to develop a routine, standardized assay which can assess the acute and sublethal impacts of individual toxicants and complex mixtures. The eggs of this Cyprinodont minnow were topically treated with each toxicant or mixture dissolved in membrane permeable dimethylsulfoxide (DMSO) solvent. Nine chemicals were initially evaluated with two, pentachlorophenol (PCP) and tributyltin chloride (TBTCl), subsequently selected for extensive evaluations of salinity tolerance and the accuracy of the topical exposure method for representing a typical immersion exposure. The amount of material actually penetrating the eggs was …

Reactions Of Organic N-Chloramines In The Gastric Fluid Of The Rat, Kathryn E. Mazina

Chemistry & Biochemistry Theses & Dissertations

Using chlorine as a drinking water disinfectant may have potential health effects due to its reactivity with organic amino nitrogen compounds found in the stomach. Organic N-chloramines have been shown to form in the stomachs of laboratory rats. The possible reactions of N-chloramines in the stomach fluid were examined in this study using a model radiolabeled N-chloramine. ³⁶Cl-N-Chloropiperidine, was synthesized and purified to remove ³⁶Cl-chloride. Stomach fluid was obtained from Sprague-Dawley rats which had been first fasted for 24 or 48 hours and then administered 3 mL of deionized water. Different concentrations of radiolabeled chloramine were reacted with …

The Effects Of Tri-O-Cresyl Phosphate On 2',3'-Cyclicnucleotide-3'-Phosphohydrolase Activity In Neural And Non-Neural Tissue Of The Rat, Mark K. Schlager

Chemistry & Biochemistry Theses & Dissertations

A total of 44 Long-Evans rats received 5.7 g/kg tri-O-cresyl phosphate (TOCP) orally every 3 days for 6 days. A second group of 13 rats received 4.6 g/kg orally every 3 days for 6 days. Animals were administered atropine sulfate (10 mg/kg) intraperitoneally every 6 hours or as needed to alleviate cholinergic symptoms. Ten control animals were given corn oil orally. Eight rats (18%) survived the 5.7 g/kg dose regimen and 5 rats (38%) survived the 4.6 g/kg dose regimen. Surviving rats were killed at 30-33 days post-dose. Signs of delayed neuropathy included ataxia and motor impairment.

The CNP activity …