Physical Sciences and Mathematics Commons^™

Synthesis And Characterization Of Hydrazine Derivatives Of Coumarin For Bioorthogonal Chemistry Inside Cells, Akiva J. Grimaldi

Undergraduate Honors Theses

Protein carbonylation is one manifestation of oxidative stress, which is characteristic of many diseases. Our lab has developed several coumarin-hydrazine based fluorescent probes capable of detecting carbonylation in live cells via the formation of hydrazone conjugates. As an effort to expand and improve on these achievements, this work presents new data regarding the synthesis and characterization of three such probes. Two of the probes—julolidine coumarin hydrazide (JCH) and trifluoromethyl coumarin hydrazine (TFCH)—were previously synthesized by our lab. Here, JCH is studied in terms of its reaction speed and fluorescence enhancement in acylhydrazone formation with aldehydes under various conditions and catalytic …

Development Of Novel Therapies Targeting Biochemical Mechanisms To Halt Progression Of Alzheimer’S And Parkinson’S Disease, Caleb Vegh

Electronic Theses and Dissertations

Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are the two most common and devastating neurodegenerative diseases in the world. There is no cure for either disease and current treatments provide only symptomatic relief. Furthermore, current treatments for AD and PD have shown to exhibit adverse side effects when taken over long periods of time. With age being the greatest risk factor for developing AD and PD, the increase in the aging population has the potential to lead to a serious medical/economic crisis due to the amount of time and care required for patients with AD and PD. The exact aetiologias …

The Activity And Structure Of Cu2+-Biomolecules In Disease And Disease Treatment, Darrell Cole Cerrato

USF Tampa Graduate Theses and Dissertations

Despite its relatively low concentration in the human body, copper is an essential transition metal ion. Under normal circumstances, it is a well-regulated trace element that is introduced via diet or environment depending on the organism. Its strong reactivity and binding to some biologically essential chemicals can be detrimental to the host organism. Herein the oxidative chemistry of copper and its possible prevention in humans and agricultural organisms is discussed, as well as the potential avenues as metal-targeting disease treatment via novel-peptide and peptoid products.

In the first study, copper is implicated in the progression and onset of Alzheimer’s disease. …

Assessment Of Oxidative Stress In The Livers Of Rats Exposed To 2-Aminoanthracene For Twelve Weeks, John C. Stagg

Honors College Theses

Diabetes is a chronic illness that affects many people, and it’s thought that environmental exposure to certain compounds may increase its proliferation. In this study, we examine the dietary effects of 2-aminoanthracene (2AA), a polycyclic aromatic hydrocarbon (PAH), in rats, specifically as it relates to oxidative stress. Oxidative stress refers to the imbalance of reactive oxygen species (ROS) and antioxidants in living systems; it has been shown to contribute to type-1 diabetes. To accomplish the study objectives rats were divided into three dietary treatment groups, control (0 mg/kg-2AA), low dose (50 mg/kg-2AA) and high dose (100 mg/kg-2AA). Rats were fed …

Characterizing The Activity Of Antimicrobial Peptides Against The Pathogenic Bacterium Clostridium Difficile In An Anaerobic Environment, Adenrele Mojeed Oludiran

Chemistry & Biochemistry Theses & Dissertations

Clostridium difficile is an anaerobic Gram-positive pathogen with high treatment costs and mortality and very high antibiotic tolerance. Antimicrobial host-defense peptides (HDPs) produced naturally by animal immune systems are promising candidates to develop novel therapies for bacterial infection because they cause oxidative stress that damages multiple targets in bacterial cells, so it is difficult for bacteria to evolve resistance to these attacks.

Piscidins, fish-derived HDPs that can also form complexes with copper (Cu) to enhance their activities, are very active against multiple bacterial species in an aerobic environment. We examined their activity against C. difficile and other species in an …

Study Of 2,5-Diaminoimidazolone, A Mutagenic Product Of Oxidation Of Guanine In Dna, Hannah Catherine J. Pollard

Electronic Theses and Dissertations

2,5-diaminoimidazolone (Iz) is an important product of a 4-electron oxidation of guanine. The present research focuses on the mechanisms of formation of Iz via pathways initiated by guanine oxidation by one-electron oxidants (OEOs) generated by X-ray radiolysis in aqueous solutions. The kinetics of formation and yields of Iz in reactions of native highly polymerized DNA with different OEOs have been compared using an HPLC-based quantitative analysis of low-molecular products generated from the reaction of DNA-bound Iz with primary amines. Mechanisms of Iz formation in DNA have been investigated including oxygen and superoxide dependence as well as the hypothesis that 8-oxo-G, …

Proposed Mechanism Of Alzheimer’S Disease: The Role Of Oxidative Stress A Review Of Scientific Literature, Alicia Monahan

Senior Honors Projects

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that has become the sixth leading cause of death in the United States. The most notable neuropathological hallmarks of AD are the accelerated accumulation of β-amyloid deposits around neurons and the accumulation of neurofibrillary tangles (NFT) within neurons. These abnormalities block proteasome function, inhibit mitochondrial function, alter biometal levels, stimulate inflammatory processes, disrupt synaptic communication, and ultimately result in cell death. Mitochondrial dysfunction has been cited as an underlying cause of AD pathologies, specifically by enhancing the production and accumulation of β-amyloid. Once the β-amyloid oligomers form, they disrupt the Ca^{2+ …}

Contribution Of New Thiol Antioxidant In The Treatment Of Acetaminophen Toxicity, Ahdab Naeem Khayyat

Doctoral Dissertations

"Acetaminophen (N-acetyl-p-aminophenol, APAP) is one of the most widely used over-the-counter antipyretic analgesic medications. It is safe at therapeutic doses, but an overdose can result in severe hepato-nephrotoxicity, a leading cause of drug-induced acute liver failure in the U.S. Although a few different mechanisms have been proposed for APAP-induced toxicity, a significant amount of evidence has pointed to the potential involvement of oxidative stress in acetaminophen toxicity. Depletion of glutathione (GSH) is one of the initiating steps in APAP-induced toxicity; therefore, one strategy for restricting organ damage is to restore GSH levels by using GSH prodrugs like N-acetylcysteine (NAC). Although …

Kinetics Of Formation And Oxidation Of 8-Oxo-7,8-Dihydroguanine (8oxog), Derrick Ampadu Boateng

Electronic Theses and Dissertations

8-oxo-7,8-dihydroguanine (8oxoG) is one of the most important base lesions formed during oxidative damage of DNA. The aim of the present research was to investigate the effects of DNA concentration, G content, and the nature of oxidizing species on the kinetics of 8oxoG in model DNA solutions by using HPLC. The experimentally obtained yields of 8oxoG were typically in the range of 2-2.5% of total concentration of guanine. The ratios of the rate constant of hole diffusion in DNA to the rate constant of conversion of the hole into 8oxoG (k_d/k_r) were calculated from the experimental …

Effects Of Oxidative Stress On J774 Macrophages, Katelyn Chessier

Senior Honors Projects

No abstract provided.

Addressing Public Health Risks Of Persistent Pollutants Through Nutritional Modulation And Biomimetic Nanocomposite Remediation Platforms, Bradley J. Newsome

Theses and Dissertations--Chemistry

Due to their relative chemical stability and ubiquity in the environment, chlorinated organic contaminants such as polychlorinated biphenyls (PCBs) pose significant health risks and enduring remediation challenges. Engineered nanoparticles (NPs) provide a novel platform for sensing/remediation of these toxicants, in addition to the growing use of NPs in many industrial and biomedical applications, but there remains concern for their potential long-term health effects. Research highlighted herein also represents a transdisciplinary approach to address human health challenges associated with exposure to PCBs and NPs. The objectives of this dissertation research are two-fold, 1) to develop effective methods for capture/sensing and remediation …

Oxidative Damage To Dna In Alzheimer's Disease, Sony Soman

Theses and Dissertations--Chemistry

Previous studies from our laboratory and others show a significant increase in levels of both nuclear and mitochondrial DNA and RNA oxidation in vulnerable brain regions in the progression of Alzheimer’s disease (AD). Although total DNA oxidation is increased in AD it remains unclear whether oxidative damage is widespread throughout the genome or is concentrated to specific genes. To test the hypothesis that specific genes are more highly oxidized in the progression of AD, we propose to quantify the percent oxidative damage in genes coding for proteins shown to be altered in the progression of AD using quantitative/real-time polymerase chain …

Environmentally Persistent Free Radicals (Epfrs) In Pm₂.₅ : Their Contribution To Hydroxyl Radical Formation And Atmospheric Transformation, William Micheal Gehling, Jr.

LSU Doctoral Dissertations

Previous research demonstrated environmentally persistent free radicals (EPFRs) will form on particulate surfaces under combustion conditions (temperature range of 150-400 °C) from reactions of organic precursors with redox-active transition metals. With an understanding of how these EPFRs form, it is necessary to determine how they behave in a natural environment after emission. To better understand this, the nature of EPFRs in ambient PM2.5 under simulated atmospheric conditions was investigated. Ambient PM2.5 samples were collected at a roadside ambient monitoring site near heavy interstate traffic and major industrial activity. The EPFR concentration and general radical structure were determined with EPR spectroscopy. …

A Novel Microfluidic Enrichment Technique For Carbonylated Proteins, Bryant C. Hollins

Doctoral Dissertations

Proteins are the building blocks of cells in living organisms, and are composed of amino acids. The expression of proteins is regulated by the processes of transcription and translation. Proteins undergo post-translational modifications in order to dictate their role physiologically within a cell.

Not all post-translational modifications are beneficial for the protein or the cell. One type of post-translational modification, called carbonylation, irreversibly places a carbonyl group onto an amino acid residue, most commonly proline, lysine, arginine, and threonine. This modification can have severe consequences physiologically, including loss of solubility, loss of function, and protein aggregation.

Carbonylated proteins have commonly …

Investigations Of Oxidative Stress Effects And Their Mechanisms In Rat Brain After Systemic Administration Of Ceria Engineered Nanomaterials, Sarita S. Hardas

Theses and Dissertations--Chemistry

Advancing applications of engineered nanomaterials (ENM) in various fields create the opportunity for intended (e.g. drug and gene delivery) or unintended (e.g. occupational and environmental) exposure to ENM. However, the knowledge of ENM-toxicity is lagging behind their application development. Understanding the ENM hazard can help us to avoid potential human health problems associated with ENM applications as well as to increase their public acceptance. Ceria (cerium [Ce] oxide) ENM have many current and potential commercial applications. Beyond the traditional use of ceria as an abrasive, the scope of ceria ENM applications now extends into fuel cell manufacturing, diesel fuel additives …

Investigations Into Modulation Of Brain Oxidative Stress By Various Interventions, Jessica Lynn Harris

Theses and Dissertations--Chemistry

In this thesis study we examined glycogen synthase kinase-3β (GSK-3β) and its effects over Nrf2 and Pin 1 as it relates to Alzheimer’s disease (AD). AD is a neurodegenerative disease characterized by a prolonged high oxidative environment. Transcription factor Nrf2 is vital in the brain’s defense against oxidative insults through its up-regulation of over 100 antioxidants. Depletion of the brain’s antioxidant defense system results in intolerance to an oxidative environment, contributing to the progression of AD. The regulatory Pin 1 protein promotes cellular homeostasis, and when down-regulated results in increased deposits of neurofibrillary tangles (NFTs) and amyloid-β (Aβ) plaques, the …

Synthetic And Mechanistic Studies Of Coupling Reactions Involving C-H Bond Activation, Ki Hyeok Kwon

Dissertations (1934 -)

Transition metal-catalyzed C-C bond forming reactions involving C-H bond activation have been shown to be effective methods for functionalization of unreactive compounds. Since Murai's pioneering work on ruthenium-catalyzed regioselective arene-to-alkene coupling reactions, a number of well-defined, late transition metal catalysts have been shown to mediate regioseletive C-C bond forming reaction involving C-H bond activation. Recently, late transition metal complexes have also been found to catalyze the regioselective coupling reaction of nitrogen containing compounds with alkenes as well as sp3 bond insertions and oxidative coupling reaction of aimdes. The catalytic C-C bond forming reaction involving C-H bond activation would provide simple …

Semen Quality And Chemical Oxidative Stress; Quantification And Remediation, Saleem Ali Bani-Hani

ETD Archive

The necessary multi-step process to prepare human semen for assisted reproduction (AR) such as in vitro fertilization (IVF) is known to induce oxidative stress in human spermatozoa and subsequent damage to the integrity of their cell components and, thus, to their function. Literature reports have viewed this as a potential link with the high frequency of birth defects among the IVF babies. In this work, we studied the effect of incubation and centrifugation on human sperm quality using established AR protocols. We found that in vitro incubation and centrifugation (20 min at 220g) of sperm generally degrade sperm quality in …

In Vivo Oxidative Stress In Alzheimer Disease Brain And A Mouse Model Thereof: Effects Of Lipid Asymmetry And The Single Methionine Residue Of Amyloid-Β Peptide, Miranda Lu Bader Lange

University of Kentucky Doctoral Dissertations

Studies presented in this dissertation were conducted to gain more insight into the role of phospholipid asymmetry and amyloid-β (Aβ)-induced oxidative stress in brain of subjects with amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). AD is a largely sporadic, age-associated neurodegenerative disorder clinically characterized by the vast, progressive loss of memory and cognition commonly in populations over the age of ~65 years, with the exception of those with familial AD, which develop AD symptoms as early as ~30 years-old. Neuropathologically, both AD and FAD can be characterized by synapse and neuronal cell loss in conjunction with accumulation of …

Experimental Design, Synthesis And Application Of Molecular Micelle Modified Polymeric Nanoparticles For Drug Delivery Systems And Free Radical Detection, Gabriela M. Ganea Visser

LSU Doctoral Dissertations

Biodegradable and biocompatible polymeric nanoparticles such as poly (lactide-co-glycolide) (PLGA) nanoparticles have been extensively studied as drug delivery systems for a variety of pharmaceutical agents. Nanoparticle surface properties are primarily determined by the emulsifiers used in the synthesis process, which have a significant impact on nanoparticle physico-chemical and biological properties. Anionic amino acid – based molecular micelles were used in the emulsification process to prepare monodisperse, small (below 100 nm) PLGA nanoparticles with a well defined spherical shape. Such molecular micelle – modified nanoparticles were used as drug carriers for delivery of antioxidants. Thymoquinone is a natural antioxidant, and an …