Pharmacology, Toxicology and Environmental Health Commons^™

The Effects Of Aqueous Atorvastatin On Steroidogenesis Of Xenopus Laevis At Environmentally Relevant Concentrations, Jeremy Johnson

Master's Theses

Statin drugs are a class of drug that work to reduce endogenous production of cholesterol by competitively inhibiting 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr) thus inhibiting production of mevalonic acid in the mevalonate pathway. Atorvastatin (Lipitor) is one of the most widely prescribed statin drugs and contamination of wastewater effluent is a growing environmental concern because of the potential to interfere with steroidogenesis in wildlife. Amphibians may be particularly susceptible to the effects of atorvastatin contamination because of their highly permeable integument. I used an amphibian model, Xenopus laevis to test the hypothesis that chronic exposure to low concentrations of atorvastatin …

Investigation Of Riluzole’S Synaptic Protection Mechanism Through Hsf1-Bdnf Axis, Yi Zhang

Theses and Dissertations (ETD)

The FDA-approved amyotrophic lateral sclerosis (ALS) drug Riluzole has great potential in treating Alzheimer’s disease (AD) based on promising animal data as well as its known action on modulating synaptic transmission. However, its detailed mechanism of action is not fully understood. Here, we proposed work aiming to address this aspect via focus- ing on the Heat Shock Factor 1 (HSF1)-dependent mechanisms. We found that Riluzole could increase HSF1 and BDNF (Brain-Derived Neurotrophic Factor) expression both at transcriptional and translational levels. CA1 (Cornu Ammonia, the first region in the hip- pocampal circuit), is its main target. We also demonstrated a protective …

Molecular Responses To Deepwater Horizon Oil Spill Contaminants In Estuarine Fish, Elizabeth Jones

Dissertations

The 2010 Deepwater Horizon (DWH) oil spill resulted in the oiling of approximately 2100 km of shoreline. During that time, resident organisms had to contend with the effects of multiple contaminants and suboptimal environmental conditions. This research examines the molecular effects of DWH oil spill contaminants in estuarine fish (CyprinodonvariegatusandFundulusgrandis) across multiple life stages, contaminant concentrations, and in conjunction with environmental stressors.

Our results indicate that:

1. Oil elicits substantial transcriptional effects across life stages in C. variegatus. In adults, exposure to low concentrations of oil and dispersant results in transcriptional effects related …

Growing On A Scar: Genetic Variation Of Achillea Millefolium Near Meeker, Colorado, Ace Spitzer

Ursidae: The Undergraduate Research Journal at the University of Northern Colorado

Mining operations deposit high concentrations of heavy metals such as lead, cadmium, arsenic, and vanadium into the topsoil of an ecosystem. These toxic metals can affect plant health and behavior, causing local extinction and shifts in ecosystem dynamics. However, genetic analyses of some plants growing on toxic soil conditions indicate higher genetic diversity than would be expected in that environment. Determining the effects of soil pollution on plants is important to determine a species’ utility in conservation and restoration. This investigation compared the genetic diversity of western yarrow (Achillea millefolium, Asteraceae), growing near a mine with vanadium and …

The Effects Of Climate Change On The Ecotoxicology Of Contaminants Of Emerging Concern: Flame Retardants, Contemporary Use Pesticides And Pharmaceuticals Personal Care Products On The Estuarine Grass Shrimp, Palaemontes Pugio, Rajaa Nouri Al-Yassein

Theses and Dissertations

Global Climate Change may adversely affect the environment, increasing water temperature and altered salinity which may affect the toxicity of both legacy pollutants and Contaminants of Emerging Concern (CECs). Acute, 96 hour toxicity tests with adult grass shrimp (Palaemonetes pugio) assessed the effects of CECs (Polybrominated Diphenyl Esther (PBDE) – 47, ibuprofen, bifenthrin, triclosan, and bifenthrin/triclosan mixtures) under Standard Conditions (20°C, 20psu) and different Climate Change Conditions (30°C, and/or35psu) In addition, the grass shrimp microbiome (e.g. Vibrio bacteria) were assessed following acute triclosan exposures at the Maximum Exposure Concentration (MECs) and Minimum Inhibitory Concentration (MICs) under standard conditions. …

Do Rope And Washer Pumps Provide Safe Water And Satisfied Users? A Case Study Piloting New Rural Water Supply Technology In Rumphi District, Malawi., Jacob C. Mkandawire, Mavuto Tembo, Muthi Nhlema, Joel Luhanga, Rochelle H. Holm

Faculty and Staff Scholarship

Innovation is needed to develop rural water supply to support sub-Saharan Africa communities that are hard to reach. The purpose of this study was to critically review rope and washer pumps that have been installed on manually drilled boreholes in 48 communities as part of a pilot project in Rumphi District, Malawi, and which serve as a sustainable source of drinking water from both technical (water quality and functionality) and social (user satisfaction) perspectives. At each water source, an infrastructure checklist was used (n = 48); 10 users were interviewed (n = 472); and, if the pump had water, water …

The Health Implication And Application Of Silver And Iron Oxide Nanoparticles, Sahar Pourhoseini

Theses and Dissertations

Nanoscience and nanotechnology have successfully created different nanomaterials, which are defined as materials with at least one dimension between 1-100 nm. This small size gives nanomaterials unique and novel properties compared with bulk material, such as a high surface area, specific mechanical, optical and magnetic properties. These novel properties have stimulated the interest of using nanoparticles in a wide range of consumer products and applications including biomedical, pharmaceutical and drug delivery. Silver and iron oxide nanoparticles attracted more attention commercially due to their antibacterial and magnetic properties, respectively. So, the overall objective of this dissertation was: 1) to examine the …

The Wet Bridge Transfer System: An Novel In Vitro Tool For Assessing Exogenous Surfactant As A Pulmonary Drug Delivery Vehicle, Brandon J. Baer

Western Research Forum

Background:

Due to its complex branching structure, direct drug delivery to the remote areas of the lung is a major challenge. Consequently, most therapies, such as those treating pulmonary infection and inflammation, must utilize large systemic dosing, with the potential for adverse side effects. A novel alternative strategy is to use exogenous surfactant, a material capable of distributing throughout the lung, as a pulmonary drug delivery vehicle.

Objective:

Utilize an in vitro transferring system to assess exogenous surfactant (BLES) as a pulmonary delivery vehicle for different therapeutics.

Methods:

An in vitro technique was developed to simultaneously study surfactant delivery and …

To Compare Cyclosporine A Nanoformulations For Their Effectiveness In Reducing Nephrotoxicity, Ilkin Nasirli

USF Tampa Graduate Theses and Dissertations

Cyclosporine (CsA) is one of the main immune-suppressant agents which has been used widely in organ transplantation against graft rejection. However, the low oral bioavailability and the associated adverse effects such as nephrotoxicity are the main drawbacks of current usage of this drug. Thus, purpose of this research is to formulate PLGA nanoparticles of CsA to improve its effectiveness and to reduce the nephrotoxicity induced by the plain drug. CsA-loaded PLGA nanoparticles were prepared by the nanoprecipitation method. Particle size and zeta potential of the formulation was determined and percent drug entrapment were also determined. Quantitative estimation was carried out …

Arts Of Living On A Damaged Planet: Ghosts And Monsters Of The Anthropocene By Anna Lowenhaupt Tsing, Heather Anne Swanson, Elaine Gan, And Nils Bubandt, Randy Lee Cutler

The Goose

Review of Anna Lowenhaupt Tsing, Heather Anne Swanson, Elaine Gan, and Nils Bubandt's Arts of Living on a Damaged Planet: Ghosts and Monsters of the Anthropocene.

Pazopanib Loaded Plga Nanoparticles For The Treatment Of Age-Related Macular Degeneration, Gulimirerouzi Fnu

USF Tampa Graduate Theses and Dissertations

Age-related macular degeneration (AMD) is a reason of severe vision loss worldwide. Pazopanib is a multitargeted tyrosine kinase inhibitor drug that can reduce neovascularization by mainly acting on vascular endothelial growth factor receptor (VEGFR). An intraocular injection to posterior segment of eye of anti-VEGF agent at present represents the cornerstone of therapies for AMD. However, challenges in targeting and delivering drug to eye’s posterior segment well as difficulties arising from repetitive frequent intraocular injections, which requires novel drug delivery method. In this study, pazopanib loaded PLGA‐NPs were prepared and the studied formulation had particle size of 132.1 ± 1.4 nm …

Predicting The Future: Parental Progeny Investment In Response To Environmental Stress Cues, Leah Gulyas, Jennifer R. Powell

Biology Faculty Publications

Environmental stressors can severely limit the ability of an organism to reproduce as lifespan is decreased and resources are shifted away from reproduction to survival. Although this is often detrimental to the organism’s reproductive fitness, certain other reproductive stress responses may mitigate this effect by increasing the likelihood of progeny survival in the F1 and subsequent generations. Here we review three means by which these progeny may be conferred a competitive edge as a result of stress encountered in the parental generation: heritable epigenetic modifications to nucleotides and histones, simple maternal investments of cytosolic components, and the partially overlapping phenomenon …

Environmental Microcystin Targets The Microbiome And Increases The Risk Of Intestinal Inflammatory Pathology Via Nox2 In Underlying Murine Model Of Nonalcoholic Fatty Liver Disease, Sutapa Sarkar, Diana Kimono, Muayad Albadrani, Ratanesh K. Seth, Philip Busbee, Hasan Alghetaa, Dwayne E. Porter, Geoff I. Scott, Bryan Brooks, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh Chatterjee

Faculty Publications

With increased climate change pressures likely to influence harmful algal blooms, exposure to microcystin, a known hepatotoxin and a byproduct of cyanobacterial blooms can be a risk factor for NAFLD associated comorbidities. Using both in vivo and in vitro experiments we show that microcystin exposure in NAFLD mice cause rapid alteration of gut microbiome, rise in bacterial genus known for mediating gut inflammation and lactate production. Changes in the microbiome were strongly associated with inflammatory pathology in the intestine, gut leaching, tight junction protein alterations and increased oxidative tyrosyl radicals. Increased lactate producing bacteria from the altered microbiome was associated …

A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter

Department of Biological Sciences Publications

Background: A rapid in-house TM4 mycobacteriophage-based assay, to identify multidrug resistance against various anti-tuberculosis drugs, using the fast-growing Mycobacterium smegmatis mc² 155 in a microtiter plate format was evaluated, based on phage viability assays. Methods: A variety of parameters were optimized before the study including the minimum incubation time for the drugs, phage and M. smegmatis mc² 155 to be in contact. An increase in phage numbers over 2 h was indicative that M. smegmatis mc² 155 is resistant to the drugs under investigation, however when phage numbers remained static, M. smegmatis mc² 155 found to …

Method Development And Validation For The Determination Of Designer Benzodiazepines In Blood By Lc-Ms/Ms, Victoria Mei

Student Theses

The misuse of designer benzodiazepines, as an alternative to prescription benzodiazepines and for drug-facilitated sexual assaults, has emerged as a growing threat, due in part to the ease of purchasing these drugs on the internet at low prices. Causing concern for safety, is the lack of dosage information resulting in users self-medicating, often leading to unintended overdoses, coma, or death at higher doses. With limited published data regarding quantification of designer benzodiazepines in forensic cases, a method was validated for the determination of thirteen and screening for two designer benzodiazepines in blood, in addition to a limited number of common …

Health Disparities Among South Asians: Is Food Insecurity The Missing Link?, Valentina Chawdhury

Electronic Theses, Projects, and Dissertations

Objective: Food insecurity among South Asians in the US is a public health issue. Food insecure adults face a plethora of adverse outcomes and research shows that individuals with ancestral origins from South Asia have a higher susceptibility rate for cardiovascular disease after migrating to urban environments. As such, the goal of this study was to research possible barriers South Asians face when creating cultural dishes in the US.

Methods: This was a convergent parallel mixed-methods analysis to understand how South Asians feel about food insecurity. Pricing and availability of cultural food items were obtained from South Asian and Western …

Developmental Expression Of The Cytosolic Sulfotransferases In Human Liver., Sarah Dubaisi, Joseph A. Caruso, R Gaedigk, Carrie A. Vyhlidal, Philip C. Smith, Ronald N. Hines, Thomas A. Kocarek, Melissa Runge-Morris

Manuscripts, Articles, Book Chapters and Other Papers

The liver is the predominant organ of metabolism for many endogenous and foreign chemicals. Cytosolic sulfotransferases (SULTs) catalyze the sulfonation of drugs and other xenobiotics, as well as hormones, neurotransmitters, and sterols, with consequences that include enhanced drug elimination, hormone inactivation, and procarcinogen bioactivation. SULTs are classified into six gene families, but only SULT1 and SULT2 enzymes are expressed in human liver. We characterized the developmental expression patterns of SULT1 and SULT2 mRNAs and proteins in human liver samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR), RNA sequencing, and targeted quantitative proteomics. Using a set of prenatal, infant, and …

Development And Validation Of A Lc-Ms/Ms Method For Detection And Quantification Of 18 Antidepressants In Whole Blood, Linda Kim

Student Theses

Antidepressants are one of the most commonly prescribed drugs in America, with researchers reporting one in six Americans take some form of psychiatric drugs-mostly antidepressants (NBC News, 2016). Antidepressants are often present in combination with other drugs in suicides and drug-related deaths, so a sensitive and specific method to detect and quantify antidepressants is necessary. We developed a method for the detection and quantification of 18 different antidepressants in whole blood, with a range of 2.5-900 ng/mL and LOQ of 2.5 ng/mL. Three hundred uL of blood was used and the analytes were extracted using solid-phase extraction and analyzed by …

Fouling And Aging In Membrane Filtration : Hybrid Afm-Based Characterization, Modelling And Reactive Membrane Design, Wanyi Fu

Dissertations

Membrane filtration has been extensively used in water and wastewater treatment, desalination, dairy making, and biomass/water separation. However, membrane fouling, aging and insufficient removal efficiency for dissolved organic matters remain major challenges for wider industrial applications. In order to tackle these challenges, this doctoral dissertation investigates mechanisms of membrane fouling and development of antifouling membrane filtration technologies. Specifically, four major research areas are explored: (i) nanoscale physicochemical characterization of the chemically modified polymeric membranes; (ii) quantitative modelling between membrane properties and membrane fouling and defouling kinetics; (iii) development of quantitative structure-activity relationships for membranes that undergo thermal and chemical aging …

Gmp Environmental Risks, Control And Monitoring Pbs 426, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Simultaneous Determination Of Fourteen Antipsychotic Drugs In Whole Blood By Solid Phase Extraction And Liquid Chromatography Tandem Mass Spectrometry, Theresa M. Dawe

Student Theses

Anti-psychotic drugs are commonly prescribed to patients to treat several mental conditions, such as bipolar, schizophrenia, and manic-depressive disorder. The analysis of anti-psychotic drugs in blood is a common practice in clinical and forensic toxicology, to monitor drug treatment (therapeutic drug monitoring) or to explain the cause of the impairment or intoxication in human performance and in postmortem cases. However, most of the current studies have been performed in plasma, and a limited number in blood. We developed and validated a method to confirm and quantify a panel of commonly prescribed anti-psychotic drugs in whole blood using solid phase extraction …

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of …

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of …

A Pharmacokinetic Model Of Lead Absorption And Calcium Competitive Dynamics, Anca R. Radulescu

Biology and Medicine Through Mathematics Conference

No abstract provided.

Novel Antiviral Effect Of A Small Molecule Onc201 And Its Potential Application In Hiv-1 Eradication, Runze Zhao

Theses & Dissertations

Despite the success of antiretroviral therapy (ART), eradication of HIV-1 from brain reservoirs remains elusive. HIV-1 brain reservoirs include perivascular macrophages that are behind the blood-brain barrier and difficult to access by ART. Macrophages express transcription factor FOXO3a and the TNF superfamily cytokine TRAIL, which are known to target HIV-1-infected macrophages for viral suppression. ONC201 is a novel and potent FOXO3a activator capable of inducing TRAIL. It can cross the blood-brain barrier, and has shown an antitumor effect in clinical trials. We hypothesized that activation of FOXO3a/TRAIL by ONC201 will reduce the size of HIV-1 brain reservoirs. Using primary human …

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …

Development Of Long-Acting Nanoformulated Abacavir Protides, Zhiyi Lin, Howard E. Gendelmant

Theses & Dissertations

Combination antiretroviral therapy (cART) for treatment of human immunodeficiency virus (HIV) infection demands life-long regimen adherence. Treatment interruptions lead to a lack of virologic control and the emergence of viral mutations and drug resistance. To address these, our laboratory developed long-acting (LA) parenteral administered nanoformulated abacavir prodrug (NMABC) by formulating myristoylated abacavir (MABC) with poloxamer 407 as stabilizer, which sustained ABC levels for up to 2 weeks with low levels of active drug metabolite (CBV-TP). To more significantly extend the apparent half-life of ABC and improve its antiretroviral activities, we developed second generation long-acting ABC prodrugs by ProTide technologies. This …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Modulation Of Estrogen Metabolism And Prevention Of Pathologies, Bodhisattwa Mondal

Theses & Dissertations

Estrogens have been implicated in non-cancerous pathologies such as Fuchs Endothelial Corneal Dystrophy (FECD), and accumulating evidence suggests estrogen genotoxicity leads to initiation of multiple types of cancer among Caucasian populations. These studies were mono-racial, and restoration of estrogen metabolism imbalance using naturally occurring compounds were not definitive. Therefore, the role of estrogen metabolism in FECD, in cancer initiation among African American (AA) populations, its modulation by environmental toxicant arsenic trioxide (As₂O₃), and by antioxidants polydatin (PD) and resveratrol were explored.

In human breast epithelial non-transformed MCF10A cells, As₂O₃ – induced cytotoxicity was …

Herbicide Toxicity To Non-Target Aquatic Organisms Does Not Increase In Mixtures With Surfactants, Courtney L. Telfort

Honors College Theses

Agricultural herbicides enter aquatic environments after rain events where they affect microscopic aquatic plants (phytoplankton) and animals (zooplankton) that form the base of aquatic food webs. Atrazine, an herbicide with low solubility in water, is often mixed with surfactants such as alkyl polyglucoside (APG) to improve effectiveness. Although APG has low-toxicity, a potential drawback to increased atrazine solubility is greater adverse effects on aquatic organisms. I hypothesized that atrazine and APG decrease phytoplankton abundance more than atrazine alone. Specifically, I predicted phytoplankton abundance should 1) decrease with increasing concentrations of the mixture compared to the same atrazine concentrations individually, and …