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Articles 1 - 16 of 16
Full-Text Articles in Toxicology
Evaluation Of Pulmonary Toxicity To Inhaled Erbium Oxide Nanoparticles In Golden Syrian Hamsters, Randy Liang
Evaluation Of Pulmonary Toxicity To Inhaled Erbium Oxide Nanoparticles In Golden Syrian Hamsters, Randy Liang
Theses and Dissertations
Erbium oxide nanoparticles (Er2O3 NPs) are used in various products from simple pottery to semiconductors and such usage leads to an elevated risk of accidental occupational exposure. In the present study, the pulmonary toxicity of Er2O3 NPs was assessed by examining tissues and bronchoalveolar lavage fluid (BALF) from the lungs of Golden Syrian Hamsters following inhalation exposure. The study’s goal was to determine the severity and mechanism of toxicity upon exposure to inhaled Er2O3 NPs. Animals were divided into 4 groups all being exposed for 4 hours a day for 8 days: Group-1: room air, Group-2: vehicle control (water), Group-3: …
Evaluation Of The Mechanism Of Cell Death After Exposure To Amorphous Silicon Dioxide Nanoparticles In Rat Pleural Mesothelial Cells And Golden Syrian Hamsters, Rachel P. Renda
Theses and Dissertations
Amorphous Silicon Dioxide Nanoparticles (SiO2 NPs) are widely used in the industrial processes, chemical, and cosmetics industries. Amorphous SiO2 NPs are abundant in the earth’s crust and can be released into the air through industrial and manufacturing activities. Such particles are overlooked and not as commonly studied when compared to their crystalline counterpart. Amorphous SiO2 NPs are pulmonary toxicants; however, the mechanism of toxicity is uncertain. In the current study, toxicity was assessed using both in vitro and in vivo systems to understand a possible mechanism of cell death. Rat Pleural Mesothelial Cells (RPMCs) were exposed to 50-800 μg/ml SiO2 …
Prevention Of Inflammation-Associated Neurodegeneration: Assessing The Efficacy Of N,N-Dimethylacetamide (Dma) In Lipopolysaccharide (Lps)-Induced Neuroinflammation Using C57bl/6 Mice, Teeshavi Devi Acosta
Prevention Of Inflammation-Associated Neurodegeneration: Assessing The Efficacy Of N,N-Dimethylacetamide (Dma) In Lipopolysaccharide (Lps)-Induced Neuroinflammation Using C57bl/6 Mice, Teeshavi Devi Acosta
Theses and Dissertations
Neurological function is closely linked to both longevity and quality of life. While some degree of neurodegeneration occurs naturally with aging, pathological neurodegeneration leads to devastating functional decline. The mechanisms underlying these processes remain incompletely understood; however, neuroinflammation is recognized as a key driver of neuronal dysfunction and death. Emerging evidence indicates that neuroinflammatory cascades can precede and potentiate hallmark features of neurodegenerative diseases, including synaptic loss and cognitive decline observed in Alzheimer’s disease (AD). Activation of the NF-κB signaling pathway contributes to amyloid beta (Aβ) peptide production, further amplifying a cycle of inflammation and neuronal injury. Preclinical work from …
Improving The Safety Of N,N-Dimethylacetamide As A Potential Treatment For Preterm Birth Using A Vaginal Nanoformulation, Asad Mir
Theses and Dissertations
With no available treatment for preterm birth, the field of reproductive medicine has been repurposing small molecule candidates into vaginal nanoformulations as potential treatments for the condition. The commercial solvent N,N-Dimethylacetamide (DMA) has previously been shown to delay and prevent inflammation-induced preterm birth in a mouse model. A vaginal nanoformulation of DMA loaded into a self-nanoemulsifying drug delivery system (SNEEDS) was studied to see if it can also be efficacious. A side by-side histological comparison was done in the more pertinent tissues of the reproductive tract between the traditional formulation of DMA given intraperitoneally (IP) and the vaginal nanoformulation of …
The Effects Of Exosomes In Lead And Lps Induced Inflammation In Microglia, Yitzchak Lax
The Effects Of Exosomes In Lead And Lps Induced Inflammation In Microglia, Yitzchak Lax
Theses and Dissertations
Exosomes are membrane bound subcellular vesicles formed through membrane budding of a cell and play important roles in cell-cell communication. Studies have demonstrated inflammatory changes in various cell types depending on the etiology of the exosomes such as exosomes from cancer cells or exosomes derived from mesenchymal stem cells. The purpose of this study was to determine the inflammatory consequences of exosomes in microglial cells following exposure to lead, lipopolysaccharides (LPS) and lead+LPS. The cultured mouse microglial cells were treated at 0.01 μM, 0.1 μM and 1 μM of lead,- three environmentally relevant levels and LPS was used at 10 …
Identification Of Pharmacophore Modifications That Enhance Bmp-Receptor Agonism, An Investigation To Understand The Development Of Potential Therapeutic Interventions, Maleka T. Stewart
Identification Of Pharmacophore Modifications That Enhance Bmp-Receptor Agonism, An Investigation To Understand The Development Of Potential Therapeutic Interventions, Maleka T. Stewart
Theses and Dissertations
Bone morphogenetic proteins (BMPs) are the largest subfamily of the Transforming Growth Factor (TGF)-ß superfamily. BMPs are renowned for their pivotal role in cellular functions such as cell growth, apoptosis, and differentiation. Yet, BMPs have also been attributed to the maintenance of adult tissue homeostasis. BMPs elicit physiological function at the cell membrane via a heterotetrameric complex composed of two Type I and two Type II serine-threonine kinase BMP receptors. Activation of BMP transmembrane receptors results in activation of either canonical (Smad-dependent) and/or non-canonical (Smad-independent) signaling. Given the physiological importance of this intricate communication between receptor activation and induction of …
Pharmacokinetic Modeling Of Metonitazene And Isotonitazene Using In Vitro And In Vivo Models And Comparison To Human Postmortem Casework, Justine P. Sorrentino
Pharmacokinetic Modeling Of Metonitazene And Isotonitazene Using In Vitro And In Vivo Models And Comparison To Human Postmortem Casework, Justine P. Sorrentino
Theses and Dissertations
Metonitazene and isotonitazene are two benzimidazole opioids that are contributing to the opioid crisis nationwide. Limited pharmacokinetic data has been published on these nitazene compounds, therefore this study sought to determine if these two structurally similar opioids would have comparable half-lives and clearance utilizing in vitro and in vivo models. Using the data determined in the pharmacokinetic study, and by testing human postmortem cases, this study aimed to inform interpretation of these drugs detected in human casework. Sample analysis for all aspects of the study was performed utilizing LC/MS/MS. In vitro pharmacokinetics of both drugs were examined using a human …
Streptozotocin-Induced Diabetes Increases Kidney Toxicity In Rats Exposed To Ochratoxin A, Belkys Gonzalez
Streptozotocin-Induced Diabetes Increases Kidney Toxicity In Rats Exposed To Ochratoxin A, Belkys Gonzalez
Theses and Dissertations
Due to the rising occurrence of diabetes in the population and the prevalence of OTA exposure via ingestion of contaminated foodstuffs, there is a need to assess the possible renal interaction of a diabetic disease state in concurrence with OTA exposure. Sprague Dawley rats were treated with streptozotocin to induce experimental diabetes and then orally exposed to 0.5 mg/kg body weight OTA once a day for 21 days. Renal biomarkers and light microscopy were evaluated to assess the interaction between diabetic nephropathy and OTA exposure. LLC-PK1 proximal tubule cells were used as an in vitro model to assess the potential …
Exposure To Dithiocarbamate Fungicide Ziram Results In Hepatic And Renal Toxicity In Long-Evan Rats, Jeffrey Chen
Exposure To Dithiocarbamate Fungicide Ziram Results In Hepatic And Renal Toxicity In Long-Evan Rats, Jeffrey Chen
Theses and Dissertations
Ziram is a broad spectrum fungicide that is used on a variety of crops. It has been shown to display a wide array of toxicological effects, however, there is still a scarcity of mechanistic data regarding how it facilitates those effects. One of its presumed mechanisms of toxicity is due to the production of oxidative stress. However, whether the production of oxidative stress is due to its dimethyldithiocarbamate backbone, its metal moiety, or a combination of both, is still unknown. Contributing to the production of oxidative stress is ziram’s ability to alter essential metal homeostasis through transchelation of other essential …
Determination Of Genetic Variation In Opioid-Resistant Hospice Patients Using A Pharmacogenomics Approach, Daniel Bianculli
Determination Of Genetic Variation In Opioid-Resistant Hospice Patients Using A Pharmacogenomics Approach, Daniel Bianculli
Theses and Dissertations
Managing pain requires a delicate balance between the advantages of opioid analgesia and the possible adverse effects. This balance becomes even more difficult in hospice and palliative care environments where dosage regimens are frequently ambiguous. Some hospice patients experience opioid resistance, in which opioids no longer produce an analgesic effect on a patient. Evidence-based analyses frequently omit this vulnerable population, resulting in a need for concrete procedures. The emergence of pharmacogenomic analysis and personalized treatment presents a solution to this problem by using each patient's genomic data to interpret opiate dosing. This pharmacogenomic study aimed to single nucleotide polymorphisms (SNPs) …
Evaluation Of Microglia’S Structural Variations Within An Organotypic Hippocampal Slice Model After Regionalized Toxic Injury, Jesus Antonio Trejos
Evaluation Of Microglia’S Structural Variations Within An Organotypic Hippocampal Slice Model After Regionalized Toxic Injury, Jesus Antonio Trejos
Theses and Dissertations
The dendritic cells of the CNS, the microglia (MG), are an initiation point of the immunological response within the post blood-brain barrier (BBB) compartment. Microglia morphology drastically changes in response to cell stress to a much different non-dendritic morphology. This investigation postulates that if the first MG responses to toxic injury are isolated and studied in greater morphological detail there is much to be learned about MG metamorphosis from a baseline (M2) to an activated (M1) state. The organotypic hippocampal slice was the experimental setting used to investigate microglial response to toxic injury. This isolates dendritic cellular responses and associated …
Combined Cytotoxicity Of The Herbicide Glyphosate And The Fungicide Mancozeb In Mouse Neuroblastoma Cells, Heidi Ebid
Combined Cytotoxicity Of The Herbicide Glyphosate And The Fungicide Mancozeb In Mouse Neuroblastoma Cells, Heidi Ebid
Theses and Dissertations
The herbicide glyphosate and the fungicide mancozeb are globally applied on a variety of agricultural crops. Residues of both pesticides are frequently detected in food and water. Combined exposure to both compounds is therefore possible. Glyphosate and mancozeb have been separately investigated in previous studies and were shown to induce neurotoxicity. The current study investigates the cytotoxicity of different glyphosate and mancozeb combinations including mixture of mancozeb + glyphosate, combination of mancozeb followed by glyphosate and combination of glyphosate followed by mancozeb and compares neurotoxicity seen with the combinations to that of glyphosate or mancozeb using mouse neuroblastoma Neuro-2a cells. …
Exploring The Dual Role Of Vegf165 In Bleomycin Induced Lung Injury And Recovery In A Aav Mice Model, Igor Ban
Exploring The Dual Role Of Vegf165 In Bleomycin Induced Lung Injury And Recovery In A Aav Mice Model, Igor Ban
Theses and Dissertations
Pulmonary fibrosis (PF) poses a significant challenge in respiratory medicine due to its complex etiology and progression characterized by excessive lung scarring, leading to compromised pulmonary function. The multifaceted roles of Vascular Endothelial Growth Factor A (VEGF-A) and specifically its isoform VEGF-A165 are critical in this context, given their involvement in angiogenesis, lymphangiogenesis, and tissue repair. The dual nature of VEGF-A165, promoting angiogenesis and potentially exacerbating or mitigating fibrosis, underscores its significance in both the progression and recovery phases of PF. Our work, explores the nuanced functions of VEGF-A165 using AAV1 as a gene delivery vector to overexpress this growth …
Mancozeb Exposure Results In Oxidative Stress And Disruption Of Mitochondrial Complexes Iii & Iv In Transformed Human Colon Cells, Amanda Dhaneshwar
Mancozeb Exposure Results In Oxidative Stress And Disruption Of Mitochondrial Complexes Iii & Iv In Transformed Human Colon Cells, Amanda Dhaneshwar
Theses and Dissertations
The ethylene bisdithiocarbamate pesticides, a subclass of the dithiocarbamate pesticides, are broad spectrum organometallic fungicides used on a variety of crops. The fungicide Mancozeb is comprised of an ethylene bisdithiocarbamate backbone complexed to the metals manganese and zinc. Ingestion of food containing pesticide residue and occupational exposure are common routes of Mancozeb exposure. Previous work demonstrated that Mancozeb exposure to HT-29 colon cancer cells resulted in cytotoxicity, apoptosis, and disruption of mitochondrial complex I, II, and V activity. The current study investigated the effect of Mancozeb exposure on mitochondrial complex III and IV activity and oxidative stress parameters in the …
Cytotoxicity Of Copper (Ii) Octanoate On Mouse Hippocampal Astrocytes, Ali A. Shohatee
Cytotoxicity Of Copper (Ii) Octanoate On Mouse Hippocampal Astrocytes, Ali A. Shohatee
Theses and Dissertations
Copper, as an essential trace element, is crucial for various biological processes but has also been utilized as a constituent of various pesticides for decades. Copper (II) octanoate is a pesticide utilized as a fungicide and is approved for use in the production of certified organic foods. Previous studies have implicated copper as an inducer of oxidative stress and activator of the Nrf2-ARE pathway. Nrf2 is essential in regulating the transcription of various genes to alleviate toxicity such as those involved in glutathione synthesis and detoxification. Due to the limited toxicological data, this study into the potential induction of oxidative …
Dithiocarbamates Mancozeb And Disulfiram Induce Striated Muscle Myopathy And Neuropathy In Long-Evans Rats, Olivia Stephenson
Dithiocarbamates Mancozeb And Disulfiram Induce Striated Muscle Myopathy And Neuropathy In Long-Evans Rats, Olivia Stephenson
Theses and Dissertations
Mancozeb (MZ), an ethylene bis-dithiocarbamate complexed with the metals manganese and zinc, is a broad-spectrum fungicide used primarily on orchards and vineyards. Disulfiram (DS, Antabuse®), a diethyldithiocarbamate, is an FDA-approved drug used for alcohol aversion therapy. Both dithiocarbamates (DTCs) have shown neurological effects including motor impairment, muscle weakness, and hind-limb paralysis, although the mechanism of toxicity is not understood. The purpose of this study is to determine how these neurotoxic compounds are damaging striated muscle of rats. Adult, male Long-Evans rats were administered either 250mg/kg MZ or 750mg/kg DS via oral gavage 3x/week for four weeks. Animals were euthanized 24 …