Toxicology Commons^™

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 …

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 …

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 …

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 …

Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud

Electronic Theses and Dissertations

Background: Periodontal diseases are globally prevalent inflammatory disorders that affect ~47% of U.S adults. Porphyromonas gingivalis (Pg) has been identified as a “keystone” pathogen that disrupts host-microbe homeostasis and contributes to the initiation and progression of periodontitis. Pg associates with oral streptococci in supragingival plaque and this interaction represents a potential target for therapeutic intervention. Previously our group developed a peptide (designated BAR), that potently inhibits Pg/Streptococcus gordonii (Sg) adherence in vitro and Pg virulence in a murine model of periodontitis. While efficacious, BAR (SspB Adherence Region) provided transient inhibition and required higher concentrations of BAR to disrupt established …

A Retrospective Study Of The Opioid Epidemic And Fentanyl Related Overdose Fatality Cases In A Florida West Coast Medical Examiner District Population, Anne Terese Powell

USF Tampa Graduate Theses and Dissertations

Opioids are scheduled by the propensity for misuse and abuse with a high rate of dependency and risk of fatal overdose. Opioids can be divided into different classes, including, natural, synthetic, and semi-synthetic. Opiates are naturally occurring and come directly from the opium poppy plant; whereas the semi synthetics opioids are chemical modifications of the poppy plant. Synthetic opioids attach to the opioid receptor but contain no part of the poppy plant. The increased variety and frequency in opioid prescriptions contributed to an opioid epidemic in the United States which is still on going.

According to the CDC, the opioid …

Residues Of Thiamethoxam And Mefenoxam In Vegetative And Floral Tissue Of Soybean At The Early Reproductive Stage Resulting From Seed Treatments, Carolina Camargo, Daniel D. Snow, Sathaporn Onanong, Thomas Hunt, Blair Siegfried

Department of Entomology: Faculty Publications

Thiamethoxam with mefenoxam is the most widely used neonicotinoid insecticide/fungicide mixture applied to soybean (Glycine max [L]) as seed treatments. Based on the systemic nature of thiamethoxam and mefenoxam, residues of this insecticide/fungicide mixture may be present in soybean vegetative and floral tissue and negatively impact beneficial insects. Although neonicotinoids are often applied in combination with systemic fungicides, the research on ecological risks of neonicotinoids has been focused on the analysis of these compounds without considering their interaction with other agrochemicals. The objective of this study was to identify the concentration of thiamethoxam and mefenoxam in soybean flowers and …

Effects Of Harvest Time On The Aroma Of White Wines Made From Cold-Hardy Brianna And Frontenac Gris Grapes Using Headspace Solid-Phase Microextraction And Gas Chromatography-Mass Spectrometry-Olfactometry, Somchai Rice, Madina Tursumbayeva, Matthew Clark, David Greenlee, Murlidhar Dharmadhikari, Anne Fennell Dr, Jacek A. Koziel

Agronomy, Horticulture and Plant Science Faculty Publications

The Midwest wine industry has shown a marked increase in growers, hectares planted, wineries, and wine production. This growth coincides with the release of cold-hardy cultivars such as Brianna and Frontenac gris, in 2001 and 2003, respectively. These white grape varieties account for one-third of the total area grown in the state of Iowa. It is generally accepted that the wine aroma profile plays a crucial role in developing a local, sustainable brand. However, the identity of Brianna/Frontenac Gris-based wine aromas and their link to the grape berry chemistry at harvest is unknown. This study aims to preliminarily characterize key …

Biogenic Volatiles Emitted From Four Cold-Hardy Grape Cultivars During Ripening, Somchai Rice, Devin L. Mauer, Anne Fennell, Murlidhar Dharmadhikari, Jacek A. Koziel

Agronomy, Horticulture and Plant Science Faculty Publications

In this research dataset, we summarize for the first time volatile organic compounds (VOCs) emitted in vivo from ripening wine grapes. We studied four cold-hardy cultivars grown in the Midwestern U.S.: St. Croix, Frontenac, Marquette, and La Crescent. These cultivars have gained popularity among local growers and winemakers, but still very little is known about their performance compared with long-established V. vinifera grapes. Volatiles were collected using two novel approaches: biogenic emissions from grape clusters on a vine and single grape berries. A third approach was headspace collection of volatiles from crushed grapes. Solid-phase microextraction (SPME) was used to collect …

A Mechanistic Study Of The Teratogenic Potential Of 4-O-Methylhonokiol (Mh) On Japanese Medaka (Oryzias Latipes), Santu Kumar Singha

Electronic Theses and Dissertations

An additional goal of this project was to characterize the Wnt/β-catenin signaling pathway to unravel the adverse potential of MH on the cardiovascular system (CVS). Our study suggested that MH-mediated cardiovascular injury may be caused due to upregulation of some major components of the Wnt/β-catenin pathway through expression of excessive pro-inflammatory mediators. Moreover MH decreased expression of ErbB3 and NRG-2 suggesting impaired cardiac structure. MH exposure caused a slow heartbeat blood occlusion absence of blood circulation decreased hatching efficiency and increased mortality in medaka embryos in a concentration- and time-dependent manner. MH might cause blood vessel occlusion by increasing the …

A California Without Rodenticides: Challenges For Commensal Rodent Management In The Future, Niamh Quinn, Sylvia Kenmuir, Laura Krueger

Human–Wildlife Interactions

Rodenticides are an essential tool in the integrated pest management of infestations of commensal rodents (Rattus norvegicus, R. rattus, and Mus musculus). With the introduction of Assembly Bill 1788, the California Ecosystems Protection Act of 2019, California is potentially facing a future with new restrictions on the use of anticoagulant rodenticides to manage commensal rodents in urban areas. Assembly Bill 1788 has been proposed specifically to protect predators from anticoagulant rodenticide poisoning and seeks to restrict the application of second-generation anticoagulant rodenticides (SGARs) for use in many urban and non-urban areas of California, USA. Exclusion and cultural …

Prevention Of Crystalline Silica-Induced Inflammation By The Anti-Malarial Hydroxychloroquine, Rachel Dawn Burmeister

Graduate Student Theses, Dissertations, & Professional Papers

Exposure to inhaled crystalline silica (cSiO2) is common in occupations where there is cutting, milling, or grinding of cSiO2 containing material. The Occupational Safety and Health Administration estimates that over 2 million workers may be exposed to inhaled cSiO2 in the United States. Inhalation of cSiO2 causes acute and chronic inflammation and may lead pulmonary diseases such as silicosis, as well as an increased risk of developing autoimmune diseases.Unfortunately, treatment of cSiO2-induced lung diseases is limited and primarily focused on supportive care.

Inflammation caused by cSiO2 begins when, cSiO2 particles are phagocytized by alveolar macrophages. Interaction between the particle and …

Epitranscriptomic Writer Systems And Codon Bias Regulate The Response To Environmental Stress, Andrea Leonardi

Legacy Theses & Dissertations (2009 - 2024)

Epitranscriptomic marks in the form of enzyme-catalyzed modifications to RNA nucleosides can be important regulators of translation and play integral roles in the response to stress. Dynamic changes in tRNA modification status can regulate the translation of stress response proteins whose transcripts have distinct codon biases. The epitranscriptomic writer Alkylation repair homolog 8 (ALKBH8) plays a crucial part in the translation of codon biased transcripts, as it regulates stop codon recoding, which is a specialized form of translation used to generate selenoproteins. ALKBH8 modifies the wobble uridine of selenocysteine tRNA (tRNASec) to promote the decoding of an internal UGA codon …

The Independent And Combined Effects Of Hypoxia And Tributyltin On The Eastern Oyster, Crassostrea Virginica, Ann Fairly Barnett

Electronic Theses and Dissertations

Oysters are vital to the health of estuarine ecosystems and provide critical ecosystem services, such as water quality improvement, nursery habitat for commercially important fisheries, and shoreline stabilization. Despite their ecological and economic importance, oyster reefs are exposed to many stressors, and oyster populations in Mississippi have declined dramatically in recent years. The present study focuses on the effects of hypoxia and tributyltin (TBT) on the Eastern oyster, Crassostrea virginica. Hypoxic events are increasingly comin coastal ecosystems worldwide, and TBT is a legacy toxicant once used as an antifoulant. The effects of these stressors were assessed on adult oysters deployed …

Exploration Of Sonic Hedgehog Gene Expression In Fathead Minnows (Pimephales Promelas), Brooke Renee Greiner

Undergraduate Honors Theses

Pollutants, as a result of wastewater treatments, have been shown to have negative impacts on aquatic ecosystems. To better understand the possible consequences caused by effluents on ecosystems, it is important to examine ecotoxicology data. One of the most commonly used species for water quality testing is the fathead minnow, Pimephales promelas. Ecotoxicology can then be taken one step further to understand the effects of pollutants on a molecular level. Previous research had identified effluents as causes for abnormal minnow fin morphology. In order to collect additional data on development, tanks with fathead minnows were placed at the Charleston …

Ultrafine Black Carbon: A Cumulative Assessment On The Physiology Of Lung - Derived Cells, M Esther Salinas

Open Access Theses & Dissertations

Combustion-derived nanomaterials are noxious ultrafine (<100 nm) aerosolized by-products generated by human activity. They pose threats to pulmonary health due to their small size, allowing them to penetrate deep into the alveolar regions causing detrimental responses downstream. Indeed, an examination between nanocarbon particle exposure and poor pulmonary health via cellular behavior was needed. I hypothesized that low-dose and long-term administrations of carbonaceous nanoparticles contribute to respiratory conditions by irritating lung-derived cells. Responses to ultrafine black carbon (UBC), a key component of airborne pollutants, by human lung A549 and murine lung LA4 epithelial cells, human peripheral-blood monocytes THP1, and murine macrophages RAW264.7 were investigated. These lines were chosen because epithelial cells and mononuclear cells (monocytes and macrophages) are the first to come in contact with inhaled particulate matter (PM) and contribute to stress and inflammation of pulmonary tissues. The cells were first plated on day zero and fed fresh UBC suspended in culture media on days one, four, and seven. The exposure regimen included three different low-level concentrations of UBC. On day ten, all cells were prepared for subsequent assays. Effects on cellular viability revealed that UBC was modestly cytotoxic while ATPase and esterase activity (termed enzyme vitality for the purpose of this study) were significantly diminished in a dose-dependent manner. Additionally, beta-galactosidase proportionally increased with UBC concentration compared to untreated cells, indicating that cellular senescence was promoted across all cell types. Multiple markers of oxidative stress were subsequently measured, showing non-uniform trends and displaying moderate accumulation of oxidative damage, contingent upon cell line and UBC treatment. However, a significant induction of inner mitochondrial membrane depolarization of human UBC-treated cells was observed; an aberrant cell-cycle progression was found across all cells. The implemented regimen of UBC exposure elicited an imbalance of free (reduced) glutathione, altered mitochondrial potential, and abnormal cell-cycle activity. This method demonstrated that modifications across both species induced changes to cellular fitness overall. The data supported that compounding nanosized black carbon exposure could negatively affect overall pulmonary cell health by distinctively modifying intracellular activity. Additionally, we further surmised that sustained exposure to nanocarbon could impair innate immunity. Therefore, reactive oxygen species (ROS), reactive nitrogen species (RNS), and cytokine levels upon continuous administrations to 3.0 μg/mL UBC after brief challenges to microbial proxies were assessed; on day 9, the cells were succumbed to three different microbial insults (LPS, Poly I:C, and Zymosan). On day 10, measurements demonstrated a moderate accumulation of oxidative stress, conditional to each cell type. Thus, UBC plus microbe approach triggered pro-oxidant levels and cytokine production across different cell types and diminished phagocytic response by murine macrophages. Based on the results, ultrafine-PM exposure may impair inflammatory function in response to pathogenic infections. In summation, our findings indicated that additive nanosized UBC in combination with microbe-like challenges may compromise cellular behavior, suggesting potential ways by which inhalation of ultrafine-PM may contribute to or exacerbate poor pulmonary health.

Development Of Mithramycin Analogues With Improved Efficacy And Reduced Toxicity For Treatment Of Ets-Dependent Tumors In Ewing Sarcoma And Prostate Cancer, Joseph Michael Eckenrode

Theses and Dissertations--Pharmacy

Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor …

Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction, Ahmed Hamish Neamah Al-Darraji

Theses and Dissertations--Pharmacology and Nutritional Sciences

Introduction: Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Induced by cardiomyocyte death, MI initiates a prolonged and uncontrolled inflammatory response which impairs the healing process. Immune cells, such as macrophages, play a central role in organizing the early post-MI inflammatory response and the subsequent repair phase. Two activation states of macrophages have been identified with distinct and complementary functions (inflammatory vs. reparatory). This bimodal pattern of macrophage activation is an attractive therapeutic target to favorably resolve post-MI inflammation and enhance recovery. It has been demonstrated that azithromycin (AZM), a commonly used antibiotic with immunomodulatory effects, …

Behavioral Impairment Following Gestational Exposure To Titanium Dioxide Nanomaterial Aerosols In Male And Female Rats, Matthew Leland Eckard

Graduate Theses, Dissertations, and Problem Reports (ETD)

Engineered nanomaterials (ENMs) are beginning to be recognized as hazardous to human and animal health. Titanium dioxide (TiO2) is primarily used as a whitening agent in paints, plastics, and sunscreens. While relatively inert in its bulk form, nano-TiO2 (diameter) can produce prolonged inflammation and oxidative stress in target tissue. Recently, the potential for nano-TiO2 to cause neuroinflammation and damage has heightened concerns about its continued use. One important concern is that nano-TiO2, and other metal oxide ENMs, may affect fetal neurodevelopment. Accordingly, it is imperative to screen ENMs, like TiO2, for possible neurotoxicity following developmental exposures. The current set of …