Pharmacology, Toxicology and Environmental Health Commons^™

Solvants Verts : Fondements, Santé, Sécurité, Environnement Et Substitution, Denis Bégin, Caroline Couture, Michel Gérin, Maximilien Debia

Rapports de recherche scientifique

L’utilisation de solvants dans de nombreuses applications (dégraissage, nettoyage, décapage, imprimerie, peintures, adhésifs, fabrication de produits pharmaceutiques) constitue une préoccupation majeure. En effet, un grand nombre d’entre eux sont associés à des effets nocifs, tant sur la santé et la sécurité des travailleurs (brûlure, cancer, dermatite, encéphalopathie, fœtotoxicité, polynévrite) que sur l’environnement et la santé de la population générale (précurseurs de smog, pollution des eaux, couche d’ozone). Par ailleurs, de plus en plus d’entreprises veulent prendre le virage vert, c.-à-d. faire en sorte que leurs activités et leurs produits s’inscrivent dans la démarche du développement durable. C’est dans ce contexte …

Novel Strategies To Overcome Carboplatin Resistance In Triple Negative Breast Cancer Using Patient Derived Xenografts, Mohammad A. Al Zubi

Theses and Dissertations

Triple-negative breast cancer (TNBC) patients have a poor prognosis and rely on chemotherapeutic treatment as standard of care. Often, they develop chemotherapy resistance, which leaves them without more therapeutic options, like targeted therapy. New models have been developed to test targeted inhibitors in human tumors, and they are known as patient-derived xenografts (PDX). These tumors are obtained from patients, then established and maintained in mice where they areused for tumor studies. In this work, we characterized 14 PDXs for their primary tumor growth rate and investigated metastatic propensity using spontaneous and experiment metastasis models. We utilized RNA-sequencing to characterize contributions …

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 …

Toxic Trace Elements In Follicular Fluid, Oxidative Stress, And In Vitro Fertilization (Ivf) Outcomes, Celeste Danielle Butts

Legacy Theses & Dissertations (2009 - 2024)

Exposures to environmental contaminants, including non-essential toxic trace elements, may be associated with in vitro fertilization (IVF) outcomes. Follicular fluid (FF) envelops the developing oocyte, offering a “snapshot” of the oocyte microenvironment. FF may better estimate trace element concentrations associated with IVF outcomes than more commonly employed blood and urine biomarkers of exposure. Hence, FF concentrations of four widespread non-essential toxic trace elements (arsenic, mercury, cadmium, and lead) were investigated in relation to a spectrum of IVF endpoints in n=56 women undergoing IVF. Antioxidant activity was explored as an intervening variable and dietary exposure sources of non-essential toxic trace elements …

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 …

Environmental Governance For Whom? Examining The Political, Institutional, Fiscal, And Legal Determinants Of State Environmental Agency Budget Policy In The Us, Andrew R. Duggan

Theses and Dissertations

Budgets are a prospective tool of governance, and appropriations are a planning vehicle reflecting: bureaucracies’ values, complex interactions, collective preferences, political influences, and available resources. Research spanning 30 years finds that environmental pollution is a key determinant of environmental budgets in the US, though myriad factors, actors, and subsystems are important to consider. Due to federalism and devolution of responsibilities and authorities, environmental governance falls largely to the states. While the dynamics that shape state environmental budget policy have received scholarly interest, theoretically-driven examinations of environmental appropriations remain limited within the public budgeting and environmental policy literature.

Using panel data …

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 …

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

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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 …

Measuring Functional Brain Recovery In Regenerating Planarians By Assessing The Behavioral Response To The Cholinergic Compound Cytisine, Oné R. Pagán, Debra L. Baker, Sean Deats, Mary O'Brien, Rochelle Dymond, Gabriella Demichele

Biology Faculty Publications

Planarians are traditional model invertebrates in regeneration and developmental biology research that also display a variety of quantifiable behaviors useful to screen for pharmacologically active compounds. One such behavior is the expression of seizure-like movements (pSLMs) induced by a variety of substances. Previous work from our laboratory showed that cocaine, but not nicotine, induced pSLMs in intact but not decapitated planarians. Interestingly, as decapitated planarians regenerated their heads, they gradually recovered their sensitivity to cocaine. These results suggested a method to assess planarian brain regeneration and a possible way of identifying compounds that could enhance or hold back brain regeneration. …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

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 …

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). …

Topical Photodynamic Therapy Generates Microvesicle Particles, Oladayo Ayobami Oyebanji

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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 …

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 …

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 …