Pharmacology, Toxicology and Environmental Health Commons^™

Use Of Phage Display Libraries To Select For B-Cell Receptor-Specific Peptides Of Chronic Lymphocytic Leukemia Cells, Richard M. Chou

Browse all Theses and Dissertations

Peptides with high affinity to the B-cell receptor (BCR) fused to a toxin could be an effective therapy for Chronic Lymphocytic Leukemia (CLL) patients. We screened captured BCR of a CLL patient with peptides from 7 and 12-mer phage display libraries, using two strategies. Lymphocytes from two patients diagnosed with CLL expressing two different unmutated VH genes (VH 1-3 and VH4-34, respectively) were used. Membrane BCRs were obtained from patient CLL cells by lysis, identified by western blot, semi-quantified and screened with phage libraries. The first strategy involved using patient VH4-34 BCRs which were captured using goat anti-human IgM to …

Light-Limited Access To Fructose Alters Metabolic Function And Adipose Tissue Catecholaminergic Activity In Mice, Naima Salem Rodwan

Browse all Theses and Dissertations

Consumption of high levels of fructose produces glucose intolerance, sympathetic nervous system activation, and renal dysfunction. A diet high in fructose may play a role in the worldwide epidemic of obesity and diabetes. The aim of this study was to test the hypothesis that time (light/dark) limited access to fructose influences body fat, metabolic function, and adipose tissue catecholaminergic activity in mice. Male C57BL/6 mice were given standard chow and assigned to one of three groups: Control (n=10, water 24h); FL (n=11, 10% fructose solution during 12h light period); and FD (n=10, 10% fructose solution during 12h dark period). Metabolic …

Enhanced Angiotensin Ii-Induced Cardiac And Aortic Remodeling In Ace2 Knockout Mice, Mahmoud Alghamri

Browse all Theses and Dissertations

Activation of the renin angiotensin system (RAS) is a well-known driving force, governing the aggravation and progression of CVD and associated target organ damage. Angiotensin (Ang) converting enzyme 2 (ACE2), a new member within the RAS family, was first cloned from the ventricle of patient with heart failure. ACE2 was shown to be upregulated under pathological conditions. We hypothesize that loss of ACE2 negatively affects cardiac function and exacerbates hypertrophic cardiomyopathy and aortic remodeling in response to Ang II. Eight weeks old ACE2 knock out (KO) and wild type (WT) mice were infused with Ang II s.c. (1000 ng/kg/min for …

Bioavailability, Bioaccumulation, And Trophic Transfer Of Trace Metals In The Tims Branch-Steed Pond Tributary, Paul Gethyn Edwards

Masters Theses

The Department of Energy's (DOE) Savannah River Site (SRS) is a 777 km² former nuclear weapon material production and current research facility located along the Savannah River in west-central South Carolina. In 1954, direct environmental discharges were released from "M-Area", a fuel and aluminum-clad Uranium (U) nuclear reactor target manufacturing facility through a drainage ditch into the Tims Branch-Steed Pond water system. The wastewater discharges released into Tims Branch contained large volumes of inorganic wastes including depleted and natural U, aluminum (Al), and Nickel (Ni) along with smaller quantities of mercury (Hg), lead (Pb), copper (Cu), chromium (Cr), and …

Investigations Of Oxidative Stress Effects And Their Mechanisms In Rat Brain After Systemic Administration Of Ceria Engineered Nanomaterials, Sarita S. Hardas

Theses and Dissertations--Chemistry

Advancing applications of engineered nanomaterials (ENM) in various fields create the opportunity for intended (e.g. drug and gene delivery) or unintended (e.g. occupational and environmental) exposure to ENM. However, the knowledge of ENM-toxicity is lagging behind their application development. Understanding the ENM hazard can help us to avoid potential human health problems associated with ENM applications as well as to increase their public acceptance. Ceria (cerium [Ce] oxide) ENM have many current and potential commercial applications. Beyond the traditional use of ceria as an abrasive, the scope of ceria ENM applications now extends into fuel cell manufacturing, diesel fuel additives …

Quercetin And Derivatives As Butyrylcholinesterase Inhibitors, Siriluk Sontadsakul, Anchisa Prakongsantikul, Worawan Kitphati, Jaturong Pratuangdejkul, Veena Nukoolkam

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Biological Activities Of A Patented Mix Extract From Fruits Of Phyllanthus Emblica And Zanthoxylumlimonella, Buppachart Potduang, Bundit Fungsin, Isara Keeta, Natthachest Ketmanee, Anintitha Intharungsri, Sitthiphong Soradech, Cholticha Niwaspragrit, Sayan Tanpanich

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Anti-Periodontal Bacterial Activity Of Oxyresveratrol, Waranvoo Phoolcharoen, Sireerat Sooampon, Boonchoo Sritularak, Kittisak Likhitvitayawuid, Jintakom Kuvatanasuchati, Prasit Pavasant

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Microemulsion Formulation Of Angelica Sinensis Root Extract On Clove Oil /Nonionic Surfactant/ Water Mixture, Pichaya Ukosaramik, Prasan Tangyuenyongwatana, Rathapon Asasutjarit

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

The Effects Of Extended Access To Methamphetamine Self-Administration On Dopaminergic Markers In The Striatum, Joe Luevano

Open Access Theses & Dissertations

Methamphetamine (METH) abuse is a persistent problem in the U.S. and abroad. Escalation of METH use among independent users occurs for a variety of physiological and psychological reasons. Methamphetamine dependence may be attributed to the rewarding effect of this drug via the dopaminergic systems of the central nervous system (CNS). The presence of METH in the CNS increases synaptic release of dopamine. This increase in dopaminergic neurotransmission is thought to be directly attributed to the rewarding effects of METH. Following METH use, compensatory changes have been found to occur in the dopaminergic system during various periods of abstinence. It is …

Kv7 K+ Channels In Airway Smooth Muscle Cells As Target For Asthma Therapy, Priyanka Prakash Kakad

Master's Theses

Airway hyperresponsiveness (AHR) is an important etiological feature of asthma, the molecular mechanisms of which are poorly understood, thus preventing development of specific and effective therapies. We investigate the role played by Kv7 voltage-activated potassium channels in the pathophysiology of AHR and evaluate the significance of their regulation in treatment of asthma. Our studies provide the first evidence for expression of multiple Kv7 channels in guinea pig and human airways and demonstrate that the expression of Kv7 channels is reduced in allergen-sensitized guinea pig airways. Our ex vivo functional studies reveal that clinically available Kv7 channel activators attenuate the bronchoconstrictor …

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 …

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 …