Pharmacology, Toxicology and Environmental Health Commons^™

The Role Of Surface Chemistry In The Toxicity Of Manufactured Cerium Dioxide Nanomaterials To Caenorhabditis Elegans, Emily Kay Oostveen

Theses and Dissertations--Plant and Soil Sciences

Manufactured CeO₂ nanomaterials (CeO₂-MNMs) are used for a wide variety of applications including diesel fuel additives and chemical/mechanical planarization media. To test the effects of CeO₂-MNM surface coating charge on to model organism Caenorhabditis elegans, we synthesized 4 nm CeO₂ with cationic (DEAE-), anionic (CM-), and neutral (DEX) coatings. In L3 nematodes exposed for 24 hours, DEAE-CeO₂ induced lethality at lower concentrations than CM- or DEX-CeO₂. Feeding slightly decreased CeO₂ toxicity, regardless of coating. In L2 nematodes exposed for 48 hours with feeding, DEAE-CeO₂ caused lethality at the …

The Efficacy Of Prostaglandin Synthase Inhibition On Attenuating Pressure Overload Induced Cardiac Remodeling, Krishna T. Nagalla

Electronic Theses and Dissertations

Chronic hypertension has long been known to cause left ventricular remodeling. Although previous studies pointed towards inflammation as the pathological driver of cardiac remodeling, the exact mechanistic pathway associated with pressure overload-induced cardiac remodeling remains to be elucidated. In order to address this issue, we designed this study to determine pathways associated with pressure overload induced cardiac remodeling and identify therapeutic targets to attenuate this maladaptive cardiac remodeling. Rats with surgically constricted abdominal aorta were used as an animal model for pressure overload and associated Left ventricular (LV) structure and functional changes were measured by pressure-volume admittance catheterization. Human cardiac …

Dual Delivery Systems Based On Polyamine Analog Benspm As Prodrug And Gene Delivery Vectors, Yu Zhu

Wayne State University Dissertations

Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range …

Bystander Effects Due To Neutrons, And Low-Dose Hyper-Radiosensitivity To Gamma Rays In Human Cells Using Cytogenetics, Isheeta Seth

Wayne State University Dissertations

Chapter 2:

Micronuclei have been used extensively in studies as an easily-evaluated indicator of DNA damage but little is known about their association with other types of damage such as nucleoplasmic bridges and nuclear buds. Radiation-induced clastogenic events were evaluated via the cytokinesis-block micronucleus assay in two normal human lymphoblastoid cell lines exposed to neutrons or gamma radiation. Micronuclei, nucleoplasmic bridges and nuclear buds were enumerated by recording the coincident presence of these endpoints within individual cells, and the associations among these three endpoints were evaluated for all treatment conditions. The common odds ratios for micronuclei and nucleoplasmic bridges were …

Adenosine A2b Receptor Effects On Post-Mi Remodeling And Cardiac Fibroblast Function, Enbo Zhan

Wayne State University Dissertations

Adenosine A_2B receptor (A_2BR) appear to contribute to chronic inflammation. This receptor is highly expressed in macrophages and cardiac fibroblasts, cells which play key roles in inflammation and healing following myocardial infarction (MI). A_2BR have been shown to induce collagen production and promote organ fibrosis, although the reports of A_2BR role on MI are limited and conflicting. The results of cardiac fibroblast (CF) studies however suggest that non-selective A_2BR stimulation inhibits collagen expression. The hypothesis of the present study was that deletion of A_2BR reduces adverse remodeling in post-MI, …

Investigation Of Pyrrolizidine Alkaloids In Foods Using Liquid Chromatography Mass Spectrometry, Caroline Griffin

Theses

Pyrrolizidine Alkaloids (PAs) are known plant toxins which can cause hepatic veno-occlusive disease (HVOD) in both humans and livestock when ingested. Although PAs are primarily known for their hepatotoxicity they also induce genotoxicity, carcinogenicity and pneumotoxicity. PAs are consumed through plants as food, for medicinal purposes, or as contaminants of agricultural crops. Aside from ingesting the plants directly PA exposure may occur through the consumption of honey produced by bees that visit PA-containing plants or by drinking milk produced by animals that have consumed PA-containing plants. Possible PA contamination in our food chain is a potential health risk.

To assess …

The Development Of Liquid Chromatography Mass Spectrometry Methods For The Analysis Of Cyanobacterial Toxins In Environmental Freshwaters, Brian Anthony Dineen

Theses

Cyanobacteria, also known as blue-green algae, are a common component of many freshwater and marine ecosystems and have a potential to produce several different classes of biotoxins. The most common class of cyanobacterial toxins are the microcystins (MCs) and cylindrospermopsins (CYLs). MCs are cyclic heptapeptides that display potent hepatotoxicity and are tumour promoters. CYLs are alkaloids that are cytotoxic and can cause illness and display hepatotoxic effects in animals and humans. Worldwide, these toxins have caused fatal poisonings to animals, birds and fish. Several incidents of human intoxications have been reported and the presence of these toxins in environmental waters …

Characterization Of Small Conductance Calcium-Activated Potassium Channels In A Human Lens Epithelium Cell Line (B3), Wedad Ali Saqar

Browse all Theses and Dissertations

Small conductance calcium-activated potassium (SK) channels belong to the family of K+ channels. They play a significant role in cell volume regulation and in lens homeostasis, and thus are associated with cataract formation. This study was designed to demonstrate the presence of the four different isoforms of SK channels (SK1, SK2, SK3, and SK4) in human lens epithelial (HLE)-B3 cell line using Western blot (WB), immunofluorescence (IF), and reverse transcriptase coupled to the polymerase chain reaction (RT-PCR). Cataract formation involves SK-mediated K+ loss and gain of Na+ ions by lens cells. Further, it has been shown in previous studies that …

Inactivation Of At1a Receptors Attenuate Lactate Accumulation And Improve Cardiac Performance And Acid-Base Homeostasis During Endurance Exercise, Ahmad Mohammed Alhajoj

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Angiotensin Type 1 (AT1) receptors are involved in cardiovascular pathology. Losartan, the AT1 receptor blocker, in combination with exercise has been shown to be effective in improving cardiac performance. The goal of the study was to investigate the role of AT1a receptors on cardiac function, and exercise tolerance in response to aerobic exercise using AT1a receptor knockout (AT1aKO) mice. An exercise wheel system was used for the exercise paradigm. Male (C57BL/6) wild type (WT) and AT1aKO mice were randomly assigned to four groups: WT control (n=6), WT exercise (WTEX, n=8), AT1a KO (KO) control (n=5), and AT1a KO exercise (KOEX, …

Early Increase Of Cd11c In Human Monocyte-Derived Dendritic Cells In The Presence Of A/California/07/2009 (H1n1pdm), Amber M. Braddock

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Influenza A continues to cause significant morbidity and mortality. Vaccine production time, viral antigenic variability and low vaccine efficacy contribute to the annual pandemics and seasonal epidemics. A better understanding of human immune responses to influenza A could result in more effective vaccines. Dendritic cells (DCs) play an important role in the initiation of immune responses. Populations of B lymphocytes secrete protective antibodies but the role of different populations of B cells in the protective response is unknown. In this thesis we developed assays to determine subclasses of influenza specific antibodies. Mononuclear cells were assessed using flow cytometry to identify …

The Modulatory Role Of Circulating Microvesicles In Endothelial Progenitor Cell Function Is Altered In T2dm, Hala Mustafa Ammar

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Circulating microvesicles (cMVs) are the extracellular MVs released from the cells in the blood and on the vascular wall. Our previous study demonstrates that cMVs of diabetic mouse are detrimental to endothelial progenitor cells (EPCs), which are known to be very important for maintaining normal endothelial function and structure. In this study, we compared the levels of circulating EPCs and EPC-derived MVs (EPC-MVs) in diabetic and healthy subjects. Also, the migration ability, apoptosis rate and reactive oxygen species (ROS) production of EPCs cultured from diabetic and healthy subjects were determined. More importantly, we evaluated whether cMVs from healthy subjects (ch-MVs) …

Expression, Characterization, Cloning And Functional Impact Of Slc12a5 In The Endocrine Pancreas, Shams Kursan

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The Slc12a5 gene encodes the neuron-specific electroneutral K+Cl- cotransporter-2 (KCC2), a constitutively active Cl- extruder. In mature neurons, KCC2 functionally predominates over other members of the Slc12a family, particularly the Na+K+2Cl- cotransporter-1 (NKCC1), a ubiquitous Cl- loader. Therefore, KCC2 keeps and maintains the intracellular chloride concentration ([Cl-]i) below values predicted by thermodynamic equilibrium and in doing so, KCC2 plays a key role in neuron physiology: it makes possible the inhibitory action of neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine. Neurons and insulin-secreting pancreatic ß-cells share many genes and functions. Indeed, neuron-specific genes have been also found in ß-cells whereas …

Effect Of The Broad-Spectrum Caspase Inhibitor Q-Vd-Oph On Neurodegeneration And Neuroinflammation Of Sarin Exposed Mice, Ekta J. Shah

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Organophosphates (OP) cause CNS hyperstimulation resulting in seizures, convulsions and brain damage. Sarin is a toxic nerve agent used in Syria, the Gulf War and in terrorist attacks in Japan. Exposure to sarin is associated with presence of dead neurons, activation of astrocytes, microglia and neuroinflammation. Since, cell death and neuroinflammation are found in sarin exposed animals, we evaluated the efficacy of Q-VD-OPh, a broad spectrum caspase inhibitor that prevents cell death and has anti-inflammatory properties. Currently, treatment for sarin exposures is effective only if administered within 30-40 minutes of exposure. In this study, adult female C57BL/6 mice were subjected …

Increased Urinary Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Type 2 Diabetic Patients, Sridevi Gutta

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Chronic Kidney Disease (CKD) has reached epidemic proportions affecting more than 20 million adults in the US. CKD is routinely diagnosed and defined as reduced glomerular filtration rate (GFR), increased urinary albumin creatinine ratio (UACR) or both. Diabetes, hypertension and obesity share a major part in causing CKD. Angiotensin (1-7) (Ang (1-7)) is a vasodilator that plays an important renoprotective role in the renin angiotensin system, counteracting the vasoconstrictor and proliferative effects of Ang II. ACE2 and NEP which form Ang (1-7) by degrading Ang II and Ang I, respectively. A Disintegrin and Metalloproteinase (ADAM) 17, which is responsible for …

The Establishment Of A Fibroblastic Cell Line From Yellow Perch (Perca Flavescens) And Its Potential Applications In Toxicology, Katelin W. Spiteri

Theses and Dissertations (Comprehensive)

This thesis describes the establishment, characterization and potential toxicological applications of YPF5, a yellow perch cell line. YPF5 is a fibroblastic cell line derived from the caudal fin of yellow perch. This cell line has been maintained for over 2 years. Cultures have been passaged over 60 times, and successfully cryopreserved and thawed. YPF5 is grown at room temperature in Leibovitz-15 (L-15) media, supplemented with 10% fetal bovine serum and 3% penicillin-streptomycin. The origin of YPF5 has been confirmed as Perca flavescens through “DNA Barcoding” and reaffirmed through Karyotyping (2n = 48) as per literature reported karyology for percidae including …

Effects Of Salinity And Dissolved Organic Matter On Cu Toxicity To Americamysis Bahia In Estuarine Environments, Rabia Nasir

Theses and Dissertations (Comprehensive)

As salinity increases the geochemical speciation of Cu is altered as a result of organic/inorganic complexation/competition. Such salinity changes may further challenge the osmoregulatory capabilities of euryhaline organisms. This chemical-biological interaction complicates the understanding of the impacts of Cu in estuarine waters. Dissolved organic matter (DOM) has been widely established to be an important modifier of Cu toxicity in freshwaters however its effectiveness in modulating Cu toxicity across the range of salinities that occur in estuarine conditions has not been studied in a systematic manner. Site to site differences in DOM quality with respect to the potential for toxicity mitigation …

Distribution And Elimination Of 3-Trifluoromethyl-4-Nitrophenol (Tfm) By Sea Lamprey (Petromyzon Marinus) And Non-Target, Rainbow Trout (Oncorhynchus Mykiss) And Lake Sturgeon (Acipenser Fulvescens), Michael W. Le Clair

Theses and Dissertations (Comprehensive)

The pesticide, 3-trifluoromethyl-4-nitrophenol (TFM), has been highly successful in the control of sea lamprey (Petromyzon marinus) populations in the Great Lakes. Treatments with TFM involve applying it to streams, where it targets larval sea lamprey which live burrowed in the stream substrate. While the toxic mechanism of TFM has been elucidated, and its effects on sea lamprey described, its effects on non-target fish species such as rainbow trout (Oncorhynchus mykiss) and lake sturgeon (Acipenser fulvescens) are not as well understood. The present work demonstrated that rainbow trout show a great capacity to detoxify the lampricide using glucuronidation, when exposed to …

Effects Of Anti-Inflammatory Foods On Hyperglycemia In Type-1 Diabetics, Primrose Martin, Michelle Chino

McNair Poster Presentations

Based on a case study administered by Dr. Charlotte Gerson, an IDDM patient referred to as R.H. reversed hyperglycemic symptoms within ten weeks while adhering to a diet of mainly vegetables and some low-glycemic index fruits. R.H. also ingested mineral supplements and underwent multiple coffee enemas each day (Gerson & Bishop, 2007, p. 56). This self-study hypothesizes that diet alone has a positive correlation coefficient with hyperglycemic blood glucose levels in type-1 diabetics (IDDM). Conducting this self-study contributes information to the limited research and database of alternative methods for managing IDDM hyperglycemia, and provides candid documentation of the effects that …

Epoxy Resin Monomers With Reduced Skin Sensitizing Potency, Niamh F. O'Boyle, Ida B. Niklasson, Ali R. Tehrani-Bagda, Tamara Delaine, Krister Holmberg, Kristina Luthman, Ann-Therese Karlberg

Articles

Epoxy resin monomers, including diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to cause widespread contact allergy. This research describes a number of alternative epoxy resin monomers, designed with the aim of reducing the skin sensitizing potency whilst maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, assessed for skin sensitizing potency using the in vivo murine local lymph node assay, and tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. All the novel epoxy resin monomers had decreased skin …

Novel Compounds As Potential Alzheimer's Disease Therapeutics And Inhibitors Of The Nlrp3 Inflammasome, Jeremy E. Chojnacki

Theses and Dissertations

Alzheimer’s disease is a devastating neurodegenerative disorder and the leading cause of dementia. The disease manifests via several pathologies including neuroinflammation, oxidative stress, metal ion dyshomeostasis, and cell death. To address the multifaceted nature of this disorder, the design of several diverse compounds, targeting many pathological effects, was generated. First, a series of compounds based on curcumin and diosgenin were synthesized following the bivalent design strategy. Two compounds were discovered to have neuroprotective ability, anti-oxidative function, and anti-Aß oligomerization (AßO) properties. A second set of molecules was also designed, wherein a hybrid compound strategy was utilized. Three hybrids were to …