Pharmacology, Toxicology and Environmental Health Commons^™

Exploring The Role Of Insulin Receptor Signaling In Hippocampal Learning And Memory, Neuronal Calcium Dysregulation, And Glucose Metabolism, Hilaree N. Frazier

Theses and Dissertations--Pharmacology and Nutritional Sciences

In the late 90’s, emerging evidence revealed that the brain is insulin-sensitive, highlighted by broad expression of brain-specific insulin receptors and reports of circulating brain insulin. Contemporary literature robustly supports the role of insulin signaling in normal brain function and suggests that insulin-related processes diminish with aging, evidenced by decreased signaling markers, reduced insulin receptor density, and lower levels of insulin transport across the blood-brain barrier. In the context of pathological cognitive decline, clinical trials using intranasal insulin delivery have reported positive outcomes on memory and learning in patients with mild cognitive decline or early-stage Alzheimer’s disease. However, while the …

Dough Properties And Baking Characteristics Of White Bread, As Affected By Addition Of Raw, Germinated And Toasted Pea Flour, Kim A. Millar, Catherine Barry-Ryan, Roisin Burke, Sinead Mccarthy, Eimear Gallagher

Articles

Thermal and non-thermal processing may alter the structure and improve the techno-functional properties of pulses and pulse flours, increasing their range of applications in protein-enhanced foods. The effects of germination and toasting of yellow peas (Pisum sativum) on flour and dough characteristics were investigated. Wheat flour was substituted with raw, germinated and toasted pea flour (30%). The resulting bread-baking properties were assessed. Toasting increased dough water absorption and improved dough stability compared with germinated and raw pea flour (p < 0.05). This resulted in bread loaves with comparable specific volume and loaf density to that of a wheat flour control. Significant correlations between dough rheological properties and loaf characteristics were observed. Addition of pea flours increased the protein content of the breads from 8.4% in the control white bread, to 10.1–10.8% (p < 0.001). Toasting demonstrated the potential to improve the techno-functional properties of pea flour. Results highlight the potential application of pea flour in bread-making to increase the protein content.

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Role Of Mcp-1 And Ccr2 In Ethanol-Induced Damage In The Developing Brain, Kai Zhang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Fetal alcohol spectrum disorders (FASD) are caused by alcohol exposure during pregnancy and is the leading cause of mental retardation. Alcohol exposure during development results in the loss of neurons in the developing brain. The underlying molecular mechanisms are unclear and there currently is no cure for FASD. Ethanol-induced neuronal death is accompanied by neuroinflammation. Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. Using a third trimester equivalent mouse model of ethanol exposure, we found that treatment of Bindarit (MCP-1 synthesis inhibitor) and RS504393 (CCR2 …

The Effect Of Glucose, Adenosine-5’-Triphosphate, And Adenosine On Glucose Transporter 9 Expression In Mdck Cells, Jamras Kanchanapiboon, Thitima Pengsuparp

The Thai Journal of Pharmaceutical Sciences

This study aimed to investigate the effect of glucose, adenosine triphosphate (ATP) and adenosine and their concentration dependence on GLUT9 expression in hyperglycemic conditions. These compounds have been reported to be associated with hyperglycemia i.

Pharmacokinetic Study Of Novel Anthraquinone Analogues, Yuhan Guo

Electronic Theses and Dissertations

Small molecules functioning as negative regulators of MDM2 have been considered as promising anti-cancer agents. A series of novel anthraquinone (AQ) analogues upregulate p53, a well-known tumor suppressor, by inactivating its antagonist protein MDM2. The novel AQ compounds synthesized through the modifications on the rhein scaffold were reported to have successfully arrested tumor growth. To have a better understanding of their underlying metabolism in vivo, pharmacokinetic (PK) studies were performed for the AQ compounds. A selective, accurate and reproducible assay methodology for PK study was set up for each AQ compound. The stabilities of AQ compounds were then evaluated …

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 …

Metal Nanomaterials: Immune Effects And Implications Of Physicochemical Properties On Sensitization, Elicitation, And Augmentation Of Allergic Disease, Katherine Adair Roach

Graduate Theses, Dissertations, and Problem Reports (ETD)

Many allergenic metals are being manufactured in nanoparticulate forms. Although the decreased size profile of metal nanomaterials has been consistently associated with more pronounced lung toxicity compared to larger materials, it is unclear if metal-induced immunotoxic effects exhibit a similar size-dependency.

The central hypothesis of these studies was that metal nanoparticles cause more pronounced immunomodulatory effects on allergic processes than larger forms of respective metals. Moreover, it was anticipated that, similar to their inflammatory potential in airways, the magnitude of these responses would correlate best with the dose metric of surface area.

The first set of studies utilized fine and …

Detection Of Adsorbed Chlordecone On Microplastics In Marine Sediments In Guadeloupe: A Preliminary Study, Fidji Sandre, Charlotte R. Dromard, Karyn Le Menach, Yolande Bouchon-Navaro, Sébastien Cordonnier, Nathalie Tapie, Hélène Budzinski, Claude Bouchon

Gulf and Caribbean Research

Plastic pollution in the oceans is recognized as a worldwide problem. Since the 1950s, the production of plastics has been increasing and the first reports of microplastics (particles < 500 μm) in the marine environment began to appear in the 1970s. These particles represent a growing environmental problem due to their dispersion in seawater and marine organisms. Additionally, microparticles in general can adsorb pollutants that will then become bioavailable to organisms by being desorbed during digestion, which could be an important pathway for the contamination of organisms. In Guadeloupe and Martinique, an organochlorine pesticide called “chlordecone” was used from 1972 to 1993 in banana plantations and this very persistent pollutant contaminates soils, rivers, and coastal marine areas and accumulates in marine foodwebs. To examine these issues, we had two goals: 1) to assess the contamination of marine sediments by microplastics surrounding Guadeloupe; and 2) to determine the ability of microplastics to adsorb chlordecone, as has been demonstrated for other organochlorine pollutants. To do so, marine sediments were collected in triplicate from 12 sites in coral reef environments around the island. Microplastics from each sample were then enumerated by size, color and shape under a binocular microscope. The results indicate that microplastics are found in all the studied sites and that their distribution could be linked to marine currents or proximity to areas of significant human activities (port activities, agglomeration, etc.). Finally, our preliminary results indicated that chlordecone could be adsorbed onto microplastics, with a concentration ranging from 0.00036—0.00173 µg/µg of microfilter.

Island Invasion: The Silent Crisis In Hawaii, Sophia Janssen

Pomona Senior Theses

Keeping out invasive species may, upon first review, seem like a trivial environmental cry from ecologists and deep environmentalists; a belated wish to return to an undeveloped world where nature was pristine. However invasive species create problems that impact all of us and can have far more severe consequences than changing a stunning landscape. These problems are heightened in islands like Hawaii, where the fragile ecosystems have developed over centuries of evolution and adaptation. The introduction of a disease-carrying mosquito can put the people of Hawaii at risk to many vector-born illnesses and create an epidemic, taking human life. The …

The Effects Of Bisphenol F On Embryonic Cardiac Output In Zebrafish, Kyle Monnot

Williams Honors College, Honors Research Projects

Bisphenol F (BPF) is an analog compound of the xenoestrogen bisphenol A (BPA). BPA utilization has decreased dramatically due to its detrimental effects as an endocrine disrupter. In place of BPA, BPF is growing to be a ubiquitous chemical in epoxy resin manufacturing. Recent research has begun to investigate the possible endocrinal effects of BPF as an analog of BPA. This study was performed to examine the potential effects of BPF exposure on cardiac parameters of zebrafish (Danio rerio) embryos. Embryos were exposed to 50 µg/L BPF for 48 hours, and cardiac parameters (stroke volume, heart rate, and …

Qualitative And Quantitative Analysis Of Therapeutic Solutions Using Raman And Infrared Spectroscopy, Alaa A. Makki, Franck Bonnier, Renaud Respaud, Fatma Chtara, Ali Tfayli, Clovis Tauber, Dominique Bertrand, Hugh Byrne, Elhadi Mohammed, Igor Chourpa

Articles

Anticancer drugs are prescribed and administrated to an increasing number of patients on a daily basis. As a consequence, a number of concerns have been raised about the patient health and safety in the case that the drugs administered are not at the required concentration or even worse not the correct ones. Quality control of therapeutic solutions has therefore been extensively implemented in hospital environments, in order to avoid any failure in the intense workflow faced by administering pharmacists. In the present study, infrared (IR) and Raman spectroscopy have been employed for the analysis of 3 commercially available therapeutic solutions …

Effects Of Canagliflozin On Renal And Urinary Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Db/Db Diabetic Mice, Unmesha Hemant Thanekar

Browse all Theses and Dissertations

Diabetes is one of the major causes of chronic kidney disease (CKD) which could lead to end-stage renal disease. Angiotensin-II (Ang-II), a major bioactive peptide of renin angiotensin system (RAS) plays a pivotal role in the pathogenesis and progression of diabetic nephropathy. The reno-degenerative effects of Ang-II can be partially counteracted by Ang (1-7). Therefore, Ang (1-7) forming enzymes, angiotensin converting enzyme 2 (ACE2) and neprilysin (NEP), are hypothesized to have reno-protective effects. In our previous studies, we have demonstrated increased renal shedding of ACE2 and NEP in the urine of type-2 diabetic mice which was attenuated by normalizing hyperglycemia …

Kinetics Of Microvesicle Particle Release In Keratinocytes, Pariksha Thapa

Browse all Theses and Dissertations

Microvesicle particles (MVPs) are subcellular particles that could be involved in inter-cellular communication because they carry various bioactive substances including cytokines. Previous studies from our lab has shown that that the lipid mediator Platelet-activating Factor (1-alkyl-2-acetyl-glycerophosphocholine; PAF) and ultraviolet B radiation (UVB) enhances the release of MVP in various cell types like primary keratinocytes, epithelial cell lines, and murine skin. We hypothesized that there may be synergistic increases in MVP release after combination of treatment of keratinocytes with UVB and PAF agonist (CPAF)/phorbol ester (PMA). The combination treatment significantly increases MVP and cytokine release at 4 to 8 hours time …

Identification Of New Metabolic Mutations That Enhance The Cell-Killing Effect Of Hydroxyurea, A Clinically Used Drug With Multiple Implications, Rittu Elsa Samuel

Browse all Theses and Dissertations

Cancer is one of the leading causes of death and a worldwide health issue. Intensive studies have been conducted in the past to unearth new anti-cancer agents. One such anti-proliferative drug is hydroxyurea (HU). HU has been used in clinics for ≥ 100 years to treat various neoplastic and non-neoplastic diseases. Although newer agents have been developed, as a WHO-enlisted essential medicine, it remains the staple drug for the management of chronic myeloproliferative disorders and sickle cell anemia. A better understanding of the HU-induced cell death may improve or expand the therapeutic spectrum of this clinically important drug. HU arrests …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …

Two-Dimensional Correlation Analysis Of Raman Microspectroscopy Of Subcellular Interactions Of Drugs In Vitro, Hugh Byrne, Franck Bonnier, Zeineb Farhane

Articles

Two-dimensional (2D) correlation analysis is explored to data mine the time evolution of the characteristic Raman microspectroscopic signatures of the subcellular responses of the nucleoli of human lung cancer cells to the uptake of doxorubicin. A simulated dataset of experimental control spectra, perturbed with systematically time-dependent spectral changes, constituted by a short-term response which represents the initial binding of the drug in the nucleolus, followed by a longer term response of the organelle metabolism, is used to validate the analysis protocol. Applying 2D correlation analysis, the in phase, synchronous correlation coefficients are seen to contain contributions of both response profiles, …

Raman Spectroscopy Of Blood Plasma Samples From Breast Cancer Patients At Different Stages., H. F. Nargis, H. Nawaz, A. Ditta, T. Mahmood, N. Rashid, M. Muddassar, M. I. Majeed, H. N. Bhatti, M. Saleem, K. Jilani, Franck Bonnier, Hugh Byrne

Articles

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy.

Differing Functions Of Atr Kinase In Human Epidermal Keratinocytes Exposed To Ultraviolet B Radiation, Kavya Shaj

Browse all Theses and Dissertations

Ataxia-telangiectasia and Rad-3 related (ATR) is a DNA damage response protein kinase that is upregulated in various cancer cell types and has key roles in cell cycle progression, DNA repair and apoptosis. Small molecule ATR kinase inhibitors are of importance as antineoplastic agents because they sensitize cancer cells to DNA damaging chemotherapy drugs. However, only a few studies have looked at the effects of ATR kinase inhibitors on non-replicating cells, which constitute the majority of cells in the human body and have suggested an opposite, pro-apoptotic role for ATR kinase signaling in non-replicating cells in comparison to a pro-survival function …

Effect Of Endothelial Progenitor Cell-Derived Exosomes On High Glucose And Hypoxia/ Reoxygenation-Induced Injury Of Astrocytes, Manasi Suchit Halurkar

Browse all Theses and Dissertations

In this study, we tested the protective effects of EPC-EXs (endothelial progenitor cell derived exosomes) and miR-126 EPC-EXs (microRNA-126 EPC-EXs) on the astrocytes injured by HG (high glucose) plus H/R (hypoxia/reoxygenation) model. At first, we determined the concentration and time dependent uptake of EPC-EXs by astrocytes. It was also found that the EPC-EXs were uptaken via macropinocytosis, caveolin-dependent and clathrin-mediated pathways in astrocytes. Furthermore, the astrocyte cell line was injured through the HG + H/R model. EXs, isolated by ultracentrifugation from the EPC culture supernatant were co-incubated with the injured cells. It was found that EPC-EXs and miR-126 EPC-EXs decrease …

Multigenerational Genomic And Epigenetic Effects Of Manufactured Silver Nanomaterials In Caenorhabditis Elegans, Anye Wamucho

Theses and Dissertations--Toxicology and Cancer Biology

There has been an increase in the incorporation of silver nanomaterials into consumer products due to their antimicrobial properties. Therefore there is potential for silver nanoparticles (Ag-NPs) to leach out into the environment during different life-cycle stages of these nanomaterial-containing products. Concern about the toxicity of Ag-NPs has led to investigations into their toxic effects on a variety of organisms mainly using acute and sub-chronic, single-generation exposures. The focus of this project was to understand the effects of long-term continuous multigenerational exposure to AgNO₃ and Ag-NPs in both pristine and environmentally transformed forms, on the model organism, Caenorhabditis elegans …

Negative Effects Of Common Herbicides On Non-Target Invertebrates, Debbi Albanese

College of Graduate Studies: Theses & Dissertations

Three herbicide formulations, Roundup® Ready to Use Weed and Grass Killer, Bayer Advanced Southern Weed Killer for Lawns and Pure 20% Vinegar Solution were directly applied to eggs of four species of butterflies, Danaus plexippus, Papilio cresphontes, Papilio polyxenes and Papilio troilus. Roundup and Bayer Advanced containing 2,4-D, mecoprop-p and dicamba significantly reduced hatch success in all four species. Lethal and sublethal effects of these herbicides on the earthworm, Eisenia andrei, was also examined. Direct contact by E. andrei with a heavy dose of the herbicides applied to tops of soil 24 hours prior was lethal to earthworms. …

Synthesis Of N-Heterocyclic Molecules And Their Applicability Towards Ion Sensing: Polymeric Chemosensors, Aikohi M. Ugboya

College of Graduate Studies: Theses & Dissertations

Critical to biological and environmental processes are anions because often times their relative concentration in our body can be an indicator of one’s well-being. Therefore, highly sensitive and cost-efficient methods for ions recognition is necessary for human health. In recent times, polymeric chemosensors have become a vital tool for sensing ions because of its higher sensitivity and good mechanical properties compared to their monomeric counterparts. These sensors are designed to produce a measurable response in the presence of a targeted ion such as an electrochemical or optical signal. The unique structure and the photophysical properties of the 1,2,3-triazole core coupled …

Investigating The Antiviral Effects Of Vig-3 From Rainbow Trout, Shanee Herrington-Krause

Theses and Dissertations (Comprehensive)

Rainbow trout is the most farmed fish in Ontario, and thus is economically important to the province. Despite this, there is a lack of understanding regarding fish innate immunity, specifically with regards to interferon-stimulated genes (ISGs) and their antiviral effector functions. ISGs are the workhorses of the innate antiviral response, operating together to limit each step of virus replication. The Viral Hemorrhagic Septicemia Virus (VHSV) induced gene (Vig)-3 is a newly identified ISG within many fish species and is homologous to ISG-15 in mammals. It is a small ubiquitin-like protein inducible by type I interferon (IFN-I), and is suggested to …

A Compromised Liver Alters Pcb Toxicity And Nutrient Metabolism, Jazmyne D. L. Barney

Theses and Dissertations--Toxicology and Cancer Biology

Environmental contamination is a public health concern. In particular persistent organic pollutants like Polychlorinated Biphenyls (PCBs) have been associated with multiple chronic inflammatory diseases, including non-alcoholic fatty liver disease (NAFLD). NAFLD prevalence has steadily increased and is expected to continue to rise with an estimated 25% of the world’s population and 80-100 million people affected in the United States alone. Importantly, the liver is the primary site for endobiotic and xenobiotic metabolism, hence its proper function is critical for the body’s response to innate and extrinsic molecules. One way to combat the deleterious effects of PCB toxicity and fatty liver …

The Measles Vaccine, Ben Albrecht

A with Honors Projects

This honors project reviews the development of the measles vaccine, and the controversial and debunked research that led to a decrease in vaccinations and an increase in the illness.

Ground Ingredients: Analysis Of Lead Exposure In The California Condor’S (Gymnogyps Californianus) Ground Foraging Habitat, Evan Michael Mcwreath

Graduate Theses, Dissertations, and Problem Reports (ETD)

The California Condor (Gymnogyps californianus) is a critically endangered species that reached its nadir in 1987 with a population of 27 birds in the wild. Intensive management efforts have been implemented to aid the condors’ recovery, however, anthropogenic factors, like use of lead ammunition, continue to cause fatalities in this vulnerable population. Lead toxicosis, which is responsible for approximately 40% of all condor deaths since 1992, is one of the most significant threats to condors. In birds lead poisoning leads to neurological dysfunction, reproductive impairment, immune suppression, gastrointestinal disturbance, anemia, and ultimately increased vulnerability to predation, starvation, and infection. For …

Acute And Repeated Effects Of Synthetic Cannabinoid Agonism And Cannabinoid Receptor 1 Positive Allosteric Modulation, Kristen R. Trexler

Graduate Theses, Dissertations, and Problem Reports (ETD)

Recent years have seen a rise in the diversity and use of synthetic cannabinoids. Currently, there is little known about the effects of specific synthetic cannabinoid compounds. As such, little research has been done evaluating the acute and chronic effects of synthetic cannabinoid administration or the development of tolerance and withdrawal. The present study aimed, in part, to evaluate the acute and repeated effect of a third-generation synthetic cannabinoid, AB-FUBINACA. Mice were treated with AB-FUBINACA (0.1-3 mg/kg, i.p.) or vehicle and were tested repeatedly in the tetrad battery of assays, which included tests of catalepsy, antinociception, hypothermia, and locomotor activity. …

Effects Of E-Cigarette Flavoring Chemicals On Human Macrophages And Bronchial Epithelial Cells, Anna Manzi Morris

Graduate Theses, Dissertations, and Problem Reports (ETD)

E-cigarettes and vapes are relatively new devices which are popular among young adults and teens. These devices vaporize an “e-liquid” for the user to inhale, which typically contains a mixture of propylene glycol (PG), vegetable glycerin (VG), varying concentrations of nicotine, and flavoring chemicals. Due to these flavoring chemicals being intended for ingestion as a food additive, their respiratory health effects are not well understood. Thousands of e-cigarette flavors are available on the market, many of which have the potential for toxicity. The majority of e-liquid flavoring chemicals (ELFCs) have not been tested for inhalation safety. In this study, we …

The Acute Effect Of Propanil On Reproductive Hormones, Ovarian Gene Expression And Splenic Cells In C57bl/6 Female Mice, Malia Danielle Berg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Earlier evidence indicates exposure to propanil, a post-emergent herbicide used on rice and wheat fields, increases the number of antibody-secreting cells (ASC) in the spleen of mice after immunization with heat-killed Streptococcus pneumoniae (HKSP, 2x10⁸ CFU). Interestingly, an intact hypothalamic-pituitary-gonadal (HPG) axis is required for this immune response assessed on day 7-10 after immunization in female mice. Hence, an overarching premise is that propanil arbitrates the connection between the reproductive and immune system by altering the concentration of hormones involved in the HPG axis, which may then affect the populations of splenic cells. Hypotheses were tested with C57Bl/6 female …