Pharmacology, Toxicology and Environmental Health Commons^™

Environmental Contaminants, Parasitism, And Neoplasia In White Perch Morone Americana From Chesapeake Bay, Usa, Mark Arnold Matsche

Graduate Theses, Dissertations, and Problem Reports (ETD)

White perch are an abundant demersal fish species in freshwater and oligohaline habitats of the Chesapeake Bay. An avoidance of salinity > 12-15 ppt generally restricts the distribution and movements of fish to within tributaries in the mid to lower Bay, which over time has resulted in the formation of at least three separate stocks in Chesapeake Bay. Sub-populations of white perch that are partially isolated may serve as sentinels of the conditions or stressors in the tributaries in which they reside. Fish are exposed to a variety of environmental contaminants and other anthropogenic stressors that can vary in magnitude based …

The Effect Of Seasonality On Yellow Perch Ecology And Ecotoxicology Within Lake Manganese, Bailey Duxbury

Dissertations, Master's Theses and Master's Reports

Seasonality is a consistent component of aquatic ecosystems yet most fish biological and ecotoxicological studies commonly employ field sampling protocols focused during the warm open water season with minimal emphasis placed on winter sampling, especially for north-temperate latitude ecosystems. Such strategies limit our understanding of poikilotherm biology and ecology during the overwintering seasons. Here, I investigated seasonal changes in yellow perch (Perca flavescens) biology, ecology and ecotoxicology over a one-year period in Lake Manganese. Significant seasonality was observed for metrics including fish energy densities (kJ/g), gonadosomatic indices, whole-body lipid contents, and carbon stable isotope values (δ¹³C). …

What The Covid-19 Crisis Is Telling Humanity, David Wiebers, Valery Feigin

Animal Sentience

The planet is in a global health emergency exacting enormous medical and economic tolls. It is imperative for us as a society and species to focus and reflect deeply upon what this and other related human health crises are telling us about our role in these increasingly frequent events and about what we can do to prevent them in the future.

Cause: It is human behavior that is responsible for the vast majority of zoonotic diseases that jump the species barrier from animals to humans: (1) hunting, capture, and sale of wild animals for human consumption, particularly in live-animal markets; …

Insulin-Like Growth Factor-1 (Igf-1) Impacts P53-Regulated Gene Products In Uvb-Irradiated Human Keratinocytes And Skin Epidermis, Abdulrhaman Mohammed Mohammed Alkawwar

Browse all Theses and Dissertations

Skin cancer is the most prevalent human malignancy and is primarily caused by ultraviolet (UV) wavelengths of sunlight. However, the fact that most skin cancers occur in people over the age of 60 indicates that advantaged age is a second skin cancer risk factor. Why geriatric skin is prone to developing skin cancers is not clear, but several studies have shown that dermal fibroblasts in geriatric skin express lower levels of the hormone insulin-like growth factor-1 (IGF-1) than young adult skin and that deficient IGF-1 signaling negatively impacts how epidermal keratinocytes respond to UVB radiation. A major regulator of the …

Performance Of Mechanical Filters Used In General Ventilation Against Nanoparticles, Clothilde Brochot, Pooya Abdolghader, Fariborz Haghighat, Ali Bahloul

Études primaires

With an equal mass, nanoparticles (NP) have a higher toxicity than particles with the same chemical composition but with larger surface area. However, the toxicological knowledge concerning NP is still insufficient to establish limit values of exposure. To seek the lowest exposure level, filtration is a simple and effective way to capture particles, including NP. According to ANSI/ASHRAE 52.2 standard, ventilation filters efficiency is tested for particles ranging from 0.3 to 10.0 μm. Performances of entire filters for NP are still very limited and particle size of 300 nm (0.3 μm) is commonly used as the most penetrating particle size …

Development Of A Method For Quantification Of Toluene Diisocyanate And Methylenediphenyl Diisocyanate Migration From Polyurethane Foam Sample Surface To Artificial Sweat By Hplc-Uv-Ms, Aleksandra Donchenko, Simon Aubin, Sébastien Gagné, Mark Spence, Livain Breau, Jacques Lesage

Études primaires

The US Environmental protection agency (EPA) has published guidance that includes test procedures for evaluating indoor exposure to chemicals from products. One of the test procedures represents the migration test for evaluating potential dermal exposure from home furniture. Such an evaluation involves the chemical measurement of the sweat which is currently unavailable in the literature. The objective of this project was to develop and validate an analytical method for quantification of migration of 4,4′-methylenediphenyl diisocyanate (MDI), 2,6-toluene diisocyanate (2,6-TDI) and 2,4-toluene diisocyanate (2,4-TDI) from a polyurethane (PU) flexible foam to artificial sweat that meets the recommendations of the EPA test …

The Efficacy Of Ketamine In Adult Patients With Obsessive Compulsive Disorder With Symptoms Refractory To Standard Of Care Treatment., Brooke Thornton

Capstone Showcase

First line pharmacologic treatments for adult patients with Obsessive Compulsive Disorder (OCD) involve selective serotonin/norepinephrine reuptake inhibitors (SSRI/SNRIs). These drug classes often fail to deliver timely relief of symptoms as well as maintain longevity of symptom recurrence. This research analyzed the use of ketamine in adult patients suffering with OCD for the purposes of more efficacious management of symptoms. Although ketamine demonstrated a timelier relief of symptoms in some small clinical studies, its effects were ultimately unable to be sustained long term. Additionally, a wide range of adverse effects including dissociation, and rebound symptoms were observed. As a result, large …

Data Mining Raman Microspectroscopic Responses Of Cells To Drugs In Vitro Using Multivariate Curve Resolution-Alternating Least Squares, David Perezguaita, Guillermo Quintas, Zeineb Farhane, Roma Tauler, Hugh Byrne

Articles

Raman microspectroscopy is gaining popularity for the analysis of time-dependent biological processes such as drug uptake and cellular response. It is a label-free technique which acquires signals from a large variety of components, including cell biomolecules and exogenous compounds such as drugs and nanoparticles, and is commonly employed for in vitro analysis of cells and cell populations with no labelling or staining required. By monitoring the changes to the Raman spectra of the cell as a result of a perturbing agent (e.g. exposure to a drug or toxic agent), one can study the associated changes in cell biochemistry involved in …

Sex Differences In The Mechanisms That Modulate The Neurochemical Effects Of Nicotine, Kevin Uribe

Open Access Theses & Dissertations

Prior behavioral studies in our laboratory revealed that overexpression of the stress peptide, corticotrophin-releasing factor (CRF), in the mesocorticolimbic reward pathway enhanced the reinforcing effects of nicotine. The latter effect was greater in female versus male rats, suggesting that females are uniquely susceptible to the effects of stress on nicotine reinforcement. The goal of this dissertation was to examine the neurochemical mechanisms by which overexpression of CRF in the nucleus accumbens (NAc), a terminal region of the mesocorticolimbic pathway, modulates the behavioral effects of nicotine. Specifically, we examined whether nicotine-induced dopamine levels are altered by CRF overexpression via excitatory (glutamate) …

Topical Photodynamic Therapy Generates Microvesicle Particles, Oladayo Ayobami Oyebanji

Browse all Theses and Dissertations

Photodynamic therapy (PDT) involves the use of light at an appropriate wavelength acting on a photosensitizing chemical to cause cell death via generation of reactive oxygen species. PDT has been useful in the management of skin conditions (like acne, psoriasis) and cancers like superficial skin, esophageal and non-small cell lung cancers. In addition to these therapeutic effects, previous murine studies from our group have demonstrated that topical PDT induces immunosuppression in vivo. Thus, topical PDT of skin can generate systemic effects through unknown mechanisms. Our group showed that PDT induces an immunosuppressive effect which occurs partly via Platelet-Activating Factor Receptor …

The Effects Of Staining Cyanobacteria With Sytoxgreen After Lysis By Freeze-Thaw And Lysis By Ethanol, Samantha Galambos

Williams Honors College, Honors Research Projects

The purpose of this project is to find the effects of staining toxic cyanobacteria with SYTOXGreen after lysis by freeze-thaw and lysis by ethanol. This project will focus on two strains of toxic cyanobacteria known as Aphanizomenon - A. flos-aquae and Planktothrix - P. agardhii. The live and dead cells are observed under blue and red fluorescent light to show the effectiveness of each lysis. It is important that this topic is researched because it is significantly affecting our waterways and sometimes drinking water. We often see that you cannot swim in Lake Erie due to algae, more specifically, these …

Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara

Williams Honors College, Honors Research Projects

I tested the hypothesis that recombinant leptin protein can be introduced to zebrafish in vivo through non-invasive soaking in a solution containing the protein. One way to study various molecules’ effects in vivo is through intraperitoneal or intracerebroventricular injections during the embryonic or larval stage, which is invasive, difficult to administer, and can have a high mortality rate. 48 hours post fertilization (hpf) zebrafish were soaked in a His-tagged recombinant leptin protein solution at 10 nM and 100 nM concentrations (produced by Genscript). After soaking, zebrafish larvae were washed extensively to remove all recombinant protein on their exterior before homogenization. …

Development Of A Method For The Detection And Quantification Of Various Benzodiazepines And Z-Drugs In Human Blood And Qualitative Identification In Urine Samples Using Liquid Chromatography Mass Spectrometry (Lc-Ms/Ms), Haley Michel

Williams Honors College, Honors Research Projects

This method developed in the toxicology department at the Cuyahoga County Medical Examiner’s Office (CCMEO) detects 40 benzodiazepines and metabolites along with several z-drugs in blood and urine by liquid chromatography tandem mass spectrometry. A sample amount of 0.5 mL was used to detect analytes in postmortem drug facilitated sexual assault and impaired driving cases. Twenty-nine analytes met criteria for quantification while the remaining 14 were used as qualitative indicators. Bias and precision results for quality controls met criteria, staying within ±15% except for clonazolam and etizolam which were within ±20%. Quantitative reporting criteria which included dilution integrity was met …

Multiple Genotoxic Agents Activate Atr Kinase Signaling In Quiescent Human Cells, Mariyyah Ahmed O. Madkhali

Browse all Theses and Dissertations

The ATR protein kinase is activated in response to DNA damage and other forms of genotoxic stress caused by both environmental carcinogens and anti-cancer drugs. However, much of our understanding of ATR kinase function is limited to proliferating cells in which DNA replication stress is the primary signal for ATR activation and where the major regulatory targets of ATR signaling are proteins involved in DNA synthesis and cell cycle progression. Here we have used HaCaT keratinocytes maintained in a non-replicating, quiescent state in vitro to examine how cell killing by different genotoxic agents is impacted by cell growth status and …

Role Of Exercise In Macrophage Polarization Of Perivascular Adipose Tissue And Adipose Tissue Inflammation In Hypertensive Mice Model, Venkata Sai Usha Sri Polaki

Browse all Theses and Dissertations

Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. It can lead to severe health complications and increase the risk of heart disease, stroke, and sometimes death. Perivascular adipose tissue (PVAT) is known as the adipose tissue (AT) surrounding all the blood vessels and plays a critical role in the pathogenesis of the vascular disease. In vascular pathologies, PVAT increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. Macrophages have been found to accumulate in PVAT during hypertension, which might be involved …

Identification Of New Metabolic Mutations In The Fission Yeast Schizosaccharomyces Pombe That Sensitize The Cell To Hydroxyurea, Alaa Mahdi

Browse all Theses and Dissertations

Cancer is a life-threatening illness and innovative research is therefore required to fuel the development of new anti-cancer therapies. As an anti-proliferative drug, hydroxyurea (HU) has been used in the treatment of various neoplastic and non-neoplastic diseases such as sickle cell anemia, psoriasis, and viral infections. HU is a well-known inhibitor of ribonucleotide reductase (RNR), an enzyme that generates dNTPs for DNA replication and repair. In our genetic screen in fission yeast looking for mutants with defects in checkpoint response, we also found a set of mutants that are highly sensitive to HU but with a functional checkpoint response. It …

Effects Of Creatine And Nicotinamide On Experimentally Induced Senescence In Dermal Fibroblasts, Avinash Satyanarayan Mahajan

Browse all Theses and Dissertations

Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce Insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation found in sunlight. Our group has determined that the lack of IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of skin cancer in geriatric patients. The present studies were designed to test the hypothesis that pro-energetics like creatine monohydrate and nicotinamide …

Host Abundance Correlates With Gulf War Illness Symptom Persistence Via Nlrp3-Mediated Neuroinflammation And Decreased Brain-Derived Neurotrophic Factor, Diana Kimono, Dipro Bose, Ratanesh K. Seth, Ayan Mondal, Punnag Saha, Patricia Janulewicz, Kimberly Sullivan, Stephen Lasley, Ronnie Horner, Nancy Klimas, Saurabh Chatterjee

Faculty Publications

Neurological disorders are commonly reported among veterans who returned from the Gulf war. Veterans who suffer from Gulf War illness (GWI) complain of continued symptom persistence that includes neurological disorders, muscle weakness, headaches, and memory loss, that developed during or shortly after the war. Our recent research showed that chemical exposure associated microbial dysbiosis accompanied by a leaky gut connected the pathologies in the intestine, liver, and brain. However, the mechanisms that caused the symptoms to persist even 30 years after the war remained elusive to investigators. In this study, we used a rodent model of GWI to investigate the …

Serotonin 5-Ht2a And 5-Ht2c Receptors Regulate Rat Maternal Behavior Through Distinct Behavioral And Neural Mechanisms, Jun Gao, Lina Nie, Yu Li, Ming Li

Department of Psychology: Faculty Publications

Serotonin 5-HT_2A and 5-HT_2C receptors play important yet distinctive roles in the regulation of rat maternal behavior. The present study investigated their neural substrates and explored the possible behavioral mechanisms (i.e., behavioral organization or maternal motivation). Sprague-Dawley postpartum females were microinjected with either a selective 5-HT_2A agonist (TCB-2, 0.4 or 4.0 μg/side) or a 5-HT_2C agonist (MK212, 2.5 or 5.0 μg/side) into the medial prefrontal cortex (mPFC) or ventral tegmental area (VTA). Ten and 60 min later, their maternal activities were observed in the home cage; and their motivational responses towards pups were examined in a …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

Surfacant Contamination Alters Freshwater Phytoplankton Community Composition, William H. Hodge

College of Graduate Studies: Theses & Dissertations

Pollution from cleaning and personal care products enter freshwater systems and have the potential to alter phytoplankton abundance and diversity. Alkyl polyglucoside (APG), a widely used foaming agent in detergents, decreases phytoplankton abundance, but whether sensitivity to APG is affected by taxonomic identity and/or the presence of competitors is unclear. Establishing taxon-specific responses to APG is important, because taxa differ in nutritional quality and palatability for zooplankton grazers.

Chapter one describes comparisons between how individual phytoplankton communities respond to the same range of APG concentrations to test hypotheses that: 1) chemical concentration determines how individual taxa respond to APG; 2) …

Characterization Of Cardiovascular Risk Factors People Living With Hiv In A Veteran Population, Veronica Taylor, Joe Castillo, Daniel Tassone Pharmd, Bcps

Graduate Research Posters

Background: CVD is the leading cause of death in PLWH. HIV positive individuals have a 1.5-2-fold greater risk of CVD compared to uninfected individuals, even if complete viral load suppression is achieved. HIV-associated CVD has tripled over the past 20 years, yet scant data is available describing this population. We have characterized CVD risk factors and treatment in PLWH in order to assess and improve cardioprotective treatment.

Methods: A retrospective EMR review was conducted for HIV positive patients enrolled at the McGuire VAMC between 12/2018 and 12/2019. Patients were excluded if labs were older than one year from follow-up. …

Novel Post-Translational Modification And Function Of Fus: The Relevance To Amyotrophic Lateral Sclerosis, Alexandra Arenas

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by the preferential death of motor neurons. Approximately 10% of ALS cases are familial and 90% are sporadic. Fused in Sarcoma (FUS) is a ubiquitously expressed RNA binding protein implicated in familial ALS and frontotemporal dementia (FTD). FUS is ubiquitously expressed in cells and has a variety of functions in the nucleus and cytoplasm. FUS mutations in the nuclear localization sequence (NLS) causes mislocalization of FUS in the cytoplasm, where it can undergo liquid-liquid phase separation and become stress granules or protein inclusions. Although FUS inclusion bodies can be found in …

In Vitro Assessment Of Deleterious Impacts Of Organomodified Nanoclays And Their Incinerated Byproducts On Human Cells, Andrew Philip White

Graduate Theses, Dissertations, and Problem Reports (ETD)

Organomodified nanoclays (ONCs: i.e., smectite clays with different organic coatings), act as nanofillers in applications ranging from automotive, to aerospace, and biomedical implementations. Because of their large utilization, ONC industry is projected to be a U.S. $3.3 billion industry by 2023. However, emerging studies showed that ONCs and ONC-nanocomposites could harbor health risks upon pulmonary exposure and along their life cycle, namely during synthesis, handling, use, manipulation, and disposal. Specifically, the potential for exposure and adverse effects on human health primarily includes release of dry particulate during handling, manipulation, release during use, and release during the end-of-life disposal or recycling …

The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry …

Characterization Of Proteins Found In Serum And Sputum Samples From Ventilator Associated Pneumonia Patients, Hima Priya Yenuga

Browse all Theses and Dissertations

Ventilator associated pneumonia (VAP) is the most common nosocomial infection leading to increased mortality in ICU patients. The main goal of this project was to evaluate and analyze a number of different biomarkers of disease that may be involved in the transition to pneumonia in patients on ventilators. Patients in this study were in the ICU, required greater than or equal to 48 hours of mechanical ventilation, and had a Clinical Pulmonary Infection Score greater than or equal to 6. For this study we recruited 16 subjects who were on ventilator for more than 48 hours, obtained serum and sputum …

Implication Of Mirna-149 In Platelet-Activating-Factor-Receptor-Mediated Effects On Lung Cancer Growth And Treatment Efficacy, Shreepa J. Chauhan

Browse all Theses and Dissertations

Lung cancer remains the leading cause of cancer-related deaths, with low response rates to the current treatment options, indicating the need to explore potential factors, involved in lung cancer growth or impeding the efficacy of therapeutic agents. Studies, including ours, have shown the critical roles of a G-protein coupled, platelet-activating factor-receptor (PAF-R) in augmenting tumor growth or limiting therapy effectiveness in various experimental cancer models via mechanisms involving the secretion of microvesicle particles (MVPs). However, the effects of PAF-R pathway with microRNAs (miRs) have not been studied. In particular, while miR-149 has been shown to play oncogenic roles in other …

On Site Comparison Of The Osha 42, Asset Ez4-Nco, Iso-Chek, Dan And Cip10 Methods For Measuring Toluene Diisocyanate (Tdi) At A Polyurethane Foam Factory, Simon Aubin, El Mekki Hamdi, Audrey Joly, Philippe Sarazin, Jacques Lesage, Livain Breau, Mark Spence, Sébastien Gagné

Études primaires

Because of the semi-volatile nature of diisocyanates (being airborne in both physical vapor and particulate phases), their high reactivity and low occupational exposure limits, diisocyanate exposure evaluation has been challenging for industrial hygienists and laboratories. The objective of this study was to compare the toluene diisocyanate (2,4 and 2,6 isomers, TDI) concentration measured by five methods in a flexible polyurethane foam factory using different collection or derivatization approaches. The methods used were: OSHA 42 modified (filter, 1-(2-pyridyl)piperazine) (OSHA), Asset EZ4-NCO (denuder and filter, dibutylamine) (Asset), Iso-Chek (double-filter, 9-(N-methylaminomethyl) anthracene and 1,2-methoxyphenylpiperazine), DAN (filter, 1,8-diaminonaphthalene), and CIP10 (centrifugation, 1,2-methoxyphenylpiperazine). Particle real-time …

On-Site Comparison Of The Osha 47, Asset Ez4-Nco, Iso-Chek, Dan, And Cip10 Methods For Measuring Methylene Diphenyl Diisocyanate (Mdi) At An Oriented-Strand Board (Osb) Factory, Simon Aubin, El Mekki Hamdi, Audrey Joly, Philippe Sarazin, Jacques Lesage, Livain Breau, Mark Spence, Sébastien Gagné

Études primaires

Diisocyanates are occupational contaminants and known sensitizers causing irritation (skin and respiratory tract) as well as occupational asthma. Because of their physicochemical properties (semi-volatile and high reactivity) and low occupational limits, diisocyanate exposure evaluation is still a challenge nowadays for industrial hygienists and laboratories. The objective of this study was to compare the methylene diphenyl diisocyanate (MDI) concentrations measured by five methods using different collection or derivatization approaches in an oriented-strand board (OSB) factory. The methods used were: OSHA 47 (filter, 1-(2-pyridyl)piperazine) (OSHA), Asset EZ4-NCO (denuder and filter, dibutylamine) (Asset), Iso-Chek (double-filter, 9-(N-methylaminomethyl) anthracene and 1,2-methoxyphenylpiperazine), DAN (filter, 1,8-diaminonaphthalene), and …

Pulmonary Immune Responses To Respirable Elongate Mineral Particles Of Asbestiform And Non-Asbestiform Morphologies, Timur Khaliullin

Graduate Theses, Dissertations, and Problem Reports (ETD)

Inhalation exposure to asbestiform elongate mineral particles (EMPs) may cause pulmonary fibrosis, lung and pleural cancer. At the same time, epidemiological evidence for non-asbestiform EMP pathogenicity is scarce, with little if any risk of cancer, but consistent findings of pneumoconiosis and increased mortality. Globally, conditions caused by asbestos exposures contribute most to the occupational cancer burden and are responsible for the increasing mortality for occupational respiratory diseases. Immunological components of the fiber-induced lesions are extremely understudied, partly due to the lack of comparable test articles. In this study I utilized respirable preparations of asbestiform and non-asbestiform riebeckite and tremolite to …