Pharmacology, Toxicology and Environmental Health Commons^™

The Proton-Coupled Folate Transporter: Biology And Therapeutic Applications To Cancer, Sita Desmoulin

Wayne State University Dissertations

Folates are essential cofactors of tumor cell proliferation and survival required for nucleotide biosynthesis and amino acid metabolism. In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. Unfortunately, the efficacy of many clinically approved antifolates is limited by a lack of tumor selectivity. Facilitative transport of folates into mammalian cells is achieved by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). As PCFT is a folate-proton symporter with an acidic pH optimum, PCFT may provide a mechanism for targeting cytotoxic antifolates to tumors, based on their acidic microenvironments. To establish the …

Analogues Of The Epoxy Resin Monomer Diglycidyl Ether Of Bisphenol F: Effects On Contact Allergenic Potency And Cytotoxicity, Niamh O'Boyle, Tamara Delaine, Kristina Luthman, Andreas Natsch, Ann-Therese Karlberg

Articles

Diglycidyl ethers of bisphenol A (DGEBA) and bisphenol F (DGEBF) are widely used as components in epoxy resin thermosetting products. They are known to cause occupational and non-occupational allergic contact dermatitis. The aim of this study is to investigate analogues of DGEBF with regard to contact allergy and cytotoxicity. A comprehensive knowledge of the structural features that contribute to the allergenic and cytotoxic effects of DGEBF will guide the development of future novel epoxy resin systems with reduced health hazards for those coming into contact with them. It was found that the allergenic effects of DGEBF were dependent on its …

Calcium Montmorillonite Clay Reduces Urinary Biomarkers Of Fumonisin B₁ Exposure In Rats And Humans, Abraham Robinson, Natalie M. Johnson, A. Strey, John F. Taylor, Alicia Marroquin-Cardona, N. J. Mitchell, Evans Afriyie-Gyawu, Nii-Ayi Ankrah, Jonathan H. Williams, Jia-Sheng Wang, Pauline E. Jolly, R. J. Nachman, Timothy D. Phillips

Environmental Health Sciences: Faculty Publications

Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB1 (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB1 in …

Maternal Immune Dysregulation In The Pathogenesis Of Neurodevelopmental Disorders: Interleukin-6 As A Central Mechanism And Therapeutic Target Of Flavonoids, Ellisa Carla Parker-Athill

USF Tampa Graduate Theses and Dissertations

Activation of the maternal immune system and resultant maternal cytokine expression due to prenatal infection has been implicated as a significant contributor to the pathology of neuropsychiatric and neurodevelopmental disorders such as schizophrenia and Autism Spectrum Disorder (ASD). Increased maternal interleukin-6 (IL-6) expression, observed clinically and in animal models of prenatal infection, and resultant activation of key signaling pathways, has been shown to be a biological indicator of pathology, and a central component of the pathological mechanism. In animal models of prenatal infection and clinically in pregnancy disorders hallmarked by immunological irregularities and increased IL-6 expression, inhibition of IL-6 has …

Modulating The Pharmacokinetics Of Bioflavonoids, Adam John Smith

USF Tampa Graduate Theses and Dissertations

One of the largest obstacles in drug development is to overcome solubility and bioavailability problems. Preformulation strategies such as nanoparticle formation are often employed but sometimes create new issues and are limited in their effectiveness and applications. Since the majority of drugs are marketed and sold as solid forms, drug delivery systems are not always desirable. This is where solid-state chemistry becomes important. Traditional solid-state chemistry approaches are often successful but are sometimes too restrictive and cannot be applied to certain compounds. Cocrystals have emerged as an alternative solid-state technique that can be applied to a broad range of compounds. …

Mutation In The Plasmodium Falciparum Crt Protein Determines The Stereospecific Activity Of Antimalarial Cinchona Alkaloids, Carol E. Griffin, Jonathan M. Hoke, Upeka Samarakoon, Junhui Duan, Jianbing Mu, Michael T. Ferdig, David C. Warhurst, Roland A. Cooper

Biological Sciences Faculty Publications

The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (-)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (-)-isomers in vitro and in vivo against Plasmodium falciparum malaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal potency order of quinine and quinidine toward P. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured the in …

Extinction Risk And Bottlenecks In The Conservation Of Charismatic Marine Species, Loren Mcclenachan, Andrew B. Cooper, Kent E. Carpenter, Nicholas K. Dulvy

Biological Sciences Faculty Publications

The oceans face a biodiversity crisis, but the degree and scale of extinction risk remains poorly characterized. Charismatic species are most likely to gar- ner greatest support for conservation and thus provide a best-case scenario of the status of marine biodiversity. We summarize extinction risk and diagnose impediments to successful conservation for 1,568 species in 16 families of marine animals in the movie Finding Nemo. Sixteen percent (12–34%) of those that have been evaluated are threatened, ranging from 9% (7–28%) of bony fishes to 100% (83–100%) of marine turtles. A lack of scientific knowledge impedes analysis of threat status …

Compositional Determinants Of The Pharmacological Actions Of Heparins, Angel Lee Gray-Shah

Dissertations

This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).

In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was …

The Effect Of Cadmium Exposure On Repeat Swimming Performance And Recovery In Rainbow Trout (Oncorhynchus Mykiss), Brown Trout (Salmo Trutta) And Lake Whitefish (Coregonus Clupeaformis), Jessie L. Cunningham

Theses and Dissertations (Comprehensive)

Swim performance provides a measure of the integrated metabolic costs of sub-lethal exposure to stressors, including Cd. While the impacts to sustained swimming performance in Cd exposed fish have already been characterised, effects to repeat swimming ability have not. This thesis identifies the effects of sub-lethal waterborne Cd exposure on ionoregulatory function, repeat swimming ability, anaerobic metabolism and stress response in rainbow trout (Oncorhynchus mykiss), brown trout (Salmo trutta) and lake whitefish (Coregonus clupeaformis).

Repeat swim trials included an initial swim to 85% of the U_crit of control fish and a recovery period …

Studies On Waterborne Cadmium Exposure To Lymnaea Stagnalis In Varying Water Qualities And The Development Of A Novel Tissue Residue Approach, Nish M. Pais

Theses and Dissertations (Comprehensive)

Recent studies have shown that the use of bioaccumulation (tissue residues) as a predictor for toxic effects for metals is a flawed concept.Adams et al. (2010) suggested a novel tissue residue approach (TRA) in which bioaccumulation in resistant organismsis related to toxic effects in sensitive organisms. The goal of this thesis was to test these assumptions in relation to Cd exposure using the great pond snail, Lymnaea stagnalis by developing and improving the understanding of Cd accumulationin aquatic invertebrates.

The relationship between Cd bioaccumulation and its toxicity was studied in L. stagnalisusing acute (96h) and chronic (one month) …

Effects Of 17Α-Ethinylestradiol (Ee2) On Reproductive Endocrine Status In Mummichog (Fundulus Heteroclitus) Under Differing Salinity And Temperature Conditions, Esteban Gillio Meina

Theses and Dissertations (Comprehensive)

Waterborne exposure to 17α-ethinylestradiol (EE₂), a synthetic estrogen, has previously been shown to decrease reproductive endocrine status in the estuarine killifish or mummichog (Fundulus heteroclitus macrolepidotus; northern subspecies). To evaluate if variations in salinity or temperature holding conditions modify the effects of EE₂ on gonad size, plasma reproductive steroid levels, and gonadal steroidogenesis, mummichog were exposed in vivo for 14 days to 0, 50 and 250 ng/L EE₂ in 0, 16 and 32 ppt salinity at 18°C and to 0 and 250 ng/L EE₂ at 10, 18 and 26°C at 16 ppt salinity. …

The Chronic Toxicity Of Titanium Dioxide Nanoparticles To The Freshwater Amphipod Hyalella Azteca, Gurkirpal S. Malhi

Theses and Dissertations (Comprehensive)

There has been an increased use of metal-oxide nanoparticles in both commercial and consumer products. The use of these products and waste generated during manufacture may ultimately be released into the aquatic environment and the potential for these contaminants to cause impacts must be assessed. This study examines the effect of titanium dioxide (TiO₂) nanoparticles (NPs) on Hyalella azteca. Chronic toxicity exposures were conducted in 400mL of spiked test solution and contained 20 neonates. Samples collected for characterization of Ti in TiO₂ NP exposure solutions were digested using ammonium persulfate as an oxidizing agent and dissolved …

A Survey Of Selected Pharmaceuticals And Personal Care Products In A Binational River And Their Effects On A Member Of Its Zooplankton Community, Plationus Patulus (Rotifera), Diana Angelica Martinez Gomez

Open Access Theses & Dissertations

The presence of 9 selected PPCPs (acetaminophen, caffeine, cotinine, codeine, fluoxetine, erythromycin, ciprofloxacin, sulfamethazine, and trimethoprim) was surveyed in water samples collected at four sites along the middle Rio Grande during two flow regimes (irrigation and non-irrigation). Water collection for PPCPs analyses were conducted from August 2010 through September 2011. Three of the sites were located upstream, in, and downstream of the El Paso, TX/Ciudad Juárez, MX metroplex. Site selection was based on their proximity to the metroplex and due to the fact that the Rio Grande in this region is an effluent receiver water system (IBWC, 2011). The fourth …

Classification Of Plants According To Their Heavy Metal Content Around North Mara Gold Mine, Tanzania: Implication For Phytoremediation, N. Mganga, Mlk Manoko, Z. K. Rulangaranga

Tanzania Journal of Science

Plants like other living organisms respond differently under different environmental conditions. An elevated level of heavy metals is one of the stresses which results into three classes of plants depending on their heavy metal content. The classes of plant species according to their accumulated heavy metals around North Mara Gold Mine were not known. To study such classes, a line transect of 700m long was established opposite the gold mine wastes. A total of eight sampling points were systematically established each after every 100m in that transect. Fifteen plant species were sampled; at least one species per sampling point. Approximately …

Living With Emerging Contaminants: Proteomics Of 4-Nonylphenol Exposed Arrow Goby (Clevelandia Ios), Sarah Emily Johnson

Master's Theses

Alkylphenol ethoxylates (APEs) are widely used in industrial and household products as surfactants. APEs degrade into more toxic ethoxylates, such as 4-nonylphenol (NP), which has been shown to be an endocrine disruptor and enhance the growth of tumor cells. Nonylphenol is wider spread in Pacific estuaries than originally thought. Organisms in Morro Bay, California contain some of the highest concentrations of NP reported, while containing few other contaminants. As a benthic mud-dwelling fish, the arrow goby (Clevelandia ios) may be exposed to high levels of NP due to high contaminant sequestration rates in anaerobic mud. While ecotoxicology suggests …

Degradation Of Atrazine By White Rot And Soil Fungi, Gerald Presley

Undergraduate Honors Theses

The widespread use of atrazine in agriculture has lead to an abundance of this toxic chemical in the environment. Fungi that have the ability to degrade atrazine into less toxic products have been identified and used in the remediation of atrazine. In this study atrazine degradation in a defined liquid media was characterized in a diverse group of white rot basidiomycete and deuteromycete soil fungi. Atrazine did not have an effect on fungal growth although each species produced a different amount of biomass in culture. Statistical analysis showed that biomass production was an important factor in determining the amount of …

Modelling Β2ar Regulation, Sharat J. Vayttaden

Dissertations and Theses (Open Access)

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models …

An Evaluation Of Coating Material Dependent Toxicity Of Silver Nanoparticles, Thilini Upekshika Silva

Electronic Theses and Dissertations

Silver nanoparticles (AgNPs) synthesized using numerous types of coating materials may exhibit different toxicity effects. The study evaluated coating material dependent toxicity by selecting 3 types of AgNP synthesis methods with different coating materials (citrate, polyvinyl pyrrolidone, and branched polyethyleneimine, coated AgNPs as citrate-AgNPs, PVP-AgNPs, and BPEI-AgNPs respectively). Two acute aquatic toxicity tests were performed; 48hr D. magna and MetPLATE E. coli toxicity tests. Significantly different toxicity effects were observed in D. magna test exhibiting lethal median concentrations (LC50) for citrate-AgNPs, PVP-AgNPs, and BPEI AgNPs respectively as, 2.7, 11.2, and 0.57μg/L. Median inhibitory concentrations (EC50) for MetPLATE tests were 1.27, …

Store-Operated Calcium Channels In The Function Of Intracardiac Neurons, Timetria Bonds

USF Tampa Graduate Theses and Dissertations

Proper autonomic regulation of mammalian cardiac function is dependent upon very complex and precise communication among the intracardiac ganglia and individual neurons within the ganglia. An array of neuromodulators is found within the ganglia that direct neuronal activity by modulating the movement of calcium. The current study determines that opioidergic agonists, which have been found to contribute to severe cardiac disease states and intracellular calcium mobilization, are also responsible for changes in the function of the intracardiac neuron via their effects on store-operated calcium channels (SOCs).

Previous studies suggest that phosphorylation plays a role in SOC regulation. Using Fura-2 calcium …

Mountains Of Injustice : Social And Environmental Justice In Appalachia, Michele Morrone, Geoffrey L. Buckley

Ohio University Press Open Access Books

Research in environmental justice reveals that low-income and minority neighborhoods in our nation’s cities are often the preferred sites for landfills, power plants, and polluting factories. Those who live in these sacrifice zones are forced to shoulder the burden of harmful environmental effects so that others can prosper. Mountains of Injustice broadens the discussion from the city to the country by focusing on the legacy of disproportionate environmental health impacts on communities in the Appalachian region, where the costs of cheap energy and cheap goods are actually quite high.

Through compelling stories and interviews with people who are fighting for …