Pharmacology, Toxicology and Environmental Health Commons^™

Developing A Point-Of-Care Detection Kit For Parkinson’S Disease Using Gold Nanoparticle-Based Lateral Flow Assay, Ali Aljassabi

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease and the fastest-growing neurodegenerative disorder in the world. The major issue with PD is that it takes several years of biological changes until the patient starts to experience physiological symptoms that could affect their daily lives. The major hallmark of PD is the appearance of Lewy body inclusions in the neuron’s cytoplasm, which is rich in a protein called α-Synuclein (α-Syn). Several studies have shown that the levels of α-Syn in blood increase because the excess α-Syn is released from neurons into the bloodstream through extracellular vesicles. …

Utilization Of Detonation Nanodiamonds: Nanocarrier For Gene Therapy In Non-Small Cell Lung Cancer, Allan E. Gutierrez

USF Tampa Graduate Theses and Dissertations

Lung cancer is one of the most prevalent and high mortality cancers in the world. Two different categories of lung cancer are non-small cell lung cancer which makes up 85% of cases, and small cell lung cancer which makes up the remaining 15% of cases. A significant risk factor that can lead to lung cancer is cigarette smoking (CS) however non-smoking cases i.e., secondhand CS, exposure to certain toxins and family history are on the rise. Both the main types of lung cancer have different system of stages, different ranges of treatment, and consequently low survival rates. Unfortunately, detection and …

Pamam- Cyclodextrin Conjugate Upregulates Brain-Derived Neurotropic Factor In Arpe-19 Cells, Gopika Ashokan

USF Tampa Graduate Theses and Dissertations

Background: Traumatic Brain Injury (TBI) is a major contributor to death and disability due to motorvehicle accidents, sports, physical abuse, and battlefield injuries. The primary insult to the brain leads to inflammation, vascular dysfunction, and oxidative stress in the brain as well as in the eye. This leads to loss of Retinal Ganglion Cells (RGCs) and downregulation of Brain derived Neurotopic Factor (BDNF). BDNF is a neurotrophic factor that binds to Tropomyosin Receptor Kinase B (TrkB) receptor to promote cell growth, survival, and differentiation. Current treatment strategies do not promote neuronal regeneration. Therefore, novel treatments are needed to restore vision …

Effect Of Hyperoxia On Cardiac Pathophysiology In Female Guinea Pig Hearts, Chayapatou Chayawatto

USF Tampa Graduate Theses and Dissertations

Hyperoxia is widely implemented in critical care and ICU patients. The administration of a high concentration of inspired oxygen to the lung can unknowingly cause hyperoxia and thereby damaging the lungs and heart due to oxidative stress. Technically, hyperoxia occurs when the patient receives PaO2 > 200 mmHg. Major research focused on hyperoxia-induced lung injury, but nothing is known on its effect on heart. Our lab is the pioneer in understanding the effect of hyperoxia on cardiovascular remodeling using mice model. Previous results show that mice under 72 hours of hyperoxia present severe cardiac pathophysiology. This research uses Guinea pigs, which …

Association Between Use Of Remdesivir And Bradycardia, Gibret Umeukeje

USF Tampa Graduate Theses and Dissertations

Remdesivir received the first emergency use authorization from the FDA for the treatment of COVID-19. Multiple adverse drug reactions (ADR) have been reported since its approval in October 2020. Bradycardia, defined by a decrease in heart rate has been reported as an adverse event for patients receiving remdesivir for COVID-19 treatment. The purpose of the research is to systematically investigate the frequency of occurrence of bradycardia in adults receiving remdesivir using clinical data derived from the FDA Adverse Event Reporting System (FAERS) database. Patients receiving remdesivir were compared to those receiving Paxlovid, Regen-Cov, and Dexamethasone for COVID-19 treatment to see …

Screening Pathological Protein Specific Antibodies As Biomarker Discovery Tools For Neurodegenerative Disease, Yitong Li

USF Tampa Graduate Theses and Dissertations

With the increase in the average life span, the incidence of neurodegenerative diseases also increases, among which Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common types of neurological disorders. AD and PD share the same pathogenic mechanism that involves a class of proteins called beta-amyloid (Aβ), which, under the induction of some factors, changes from its natural monomeric state to the oligomers containing β-sheet, which is neurotoxic and thus leads to cell damage or apoptosis. This study focused on the selection of antibodies used as biomarkers for AD and PD. The selection of antibodies was based …

Effects Of Exogenous Ketone Therapy On Performance, Cardiorespiration, And Seizure Genesis During Exposure To Hbo2 In The Sprague Dawley Rat, Nicole M. Stavitzski

USF Tampa Graduate Theses and Dissertations

Hyperbaric oxygen (HBO2) is used for clinical HBO2 therapy and in undersea and aerospace medicine. HBO2 is a humanmade extreme environment and protracted exposures can cause several adverse physiological effects on the body. For example, HBO2 increases the partial pressure of oxygen (PO2) in the body leading to redox stress. Redox stress is, in part, a cause of oxygen toxicity that manifests as seizures in its most severe form (central nervous system oxygen toxicity, CNS-OT). This dissertation focuses on strategies to be employed specifically for the warfighter breathing HBO2. Currently, the only way to prevent CNS-OT is to lower the …

Application Of Gold Nanoshells For Photothermal Therapy In Lung Cancer Cells, Yva K. Luc

USF Tampa Graduate Theses and Dissertations

Lung cancer is the leading cause of cancer deaths in the world. For the year 2020, it was estimated 1.8 million deaths were due to lung cancer alone, making it more lethal than breast cancer and prostate cancer combined. For the year 2021, it is estimated 235,760 new cases of lung cancer and 50% will lead to death. The primary cause of lung cancer is due to cigarette smoking, which accounts for 80% of all lung cancer deaths. Lung cancer screening relies on only different methods, biopsy, bronchoscopy, ultrasound, chest x-ray film, and sputum cytology. These techniques are used to …

Evaluating Daily Systemic Betaine Delivery In Alleviating Dry-Amd Pathophysiology, Dawin Khiev

USF Tampa Graduate Theses and Dissertations

MnSod (Sod2) deletion in the retinal pigment epithelium (RPE) of Sod2flox/floxVMD2-cre mice leads to oxidative stress-induced apoptosis of the RPE and photoreceptor cells that show salient features of dry-AMD. The purpose of this study was to investigate the potential antioxidant effect of betaine in protecting retinal health in Sod2flox/floxVMD2-cre mice. Betaine low dose (50mg/Kg Body Weight) and high dose (500mg/kg Body Weight, n=9) were administered intraperitoneally to 8-weeks old male and female Sod2flox/floxVMD2-cre mice daily for four months, while the control group (Sod2flox/floxVMD2-cre mice; n=9) received saline. We used spectral-domain optical coherence tomography (SD-OCT), retinal outer nuclear layer (ONL) thickness …

Quercetin Loaded Nanoparticles For The Treatment Of Dry Eye Disease, Bassma Sami Nashaat Hamed Eltanameli

USF Tampa Graduate Theses and Dissertations

Dry eye disease (DED) is a common condition that affects the eye's anterior surface due to tear deficiency or excessive evaporation. The lack of tears leads to dryness and initiation of an inflammatory response which can irritate the eye and interfere with daily activities. Current treatment depends mainly on artificial tears eye drops which offer temporary relief and require repetitive administration due to frequent blinking. Prescription medications are also available but need around three months to relieve dry eye symptoms. Quercetin is a flavonoid that has an anti-inflammatory and antioxidant effect. However, it suffers from low water solubility and low …

Mitigation Strategies For Central Nervous System Oxygen Toxicity In Rodents: Ketone Metabolic Therapy And Mitochondrial Antioxidant Therapy, Christopher Manuel Hinojo

USF Tampa Graduate Theses and Dissertations

Hyperbaric oxygen (HBO2) is a frequently encountered condition in undersea medicine and hyperbaric oxygen therapy (HBOT). The risk of CNS oxygen toxicity (CNS-OT) seizures limits its use in hyperbaric medicine and limits bottom time for diving operations. In this study, we sought to understand the role of reactive oxygen species (ROS) in two mitigation strategies for CNS-OT; ketone metabolic therapy (KMT), which is known to delay onset of CNS-OT seizures, and mitochondria targeted antioxidant therapy (MitoTAT), which has never been tested under HBO2 conditions. We specifically focused on superoxide anions, one of the early reduction products of molecular oxygen, and …

The Effects Of Agrochemical Pesticide Applications On Target And Off-Target Species In Aquatic Ecosystems, Bryan K. Delius

USF Tampa Graduate Theses and Dissertations

The increase in the global human population is driving agricultural expansion, which increases the likelihood and degree by which agrochemicals impact aquatic systems. It is projected that by 2100 the global human population will exceed 11 billion, and to feed the increased human population, the necessary increase in agricultural infrastructure is estimated to double irrigation, nearly triple fertilizer applications, and increase pesticide applications by tenfold. It stands to reason that wetlands impacts from agriculture are also likely to increase as the industry expands its operation to meet the globally growing demand for food.

Wetlands are highly productive habitats that not …

A Study Of Trpa1 Activation Via Covalent Electrophilic Modification Of Cysteines, Thomas A. Parks

USF Tampa Graduate Theses and Dissertations

A subset of sensory nerves called nociceptors are stimulated by noxious stimuli and evoke nocifensive responses in different organ systems. Transient Receptor Potential Ankyrin 1 (TRPA1) is a tetrameric, nonselective, cation channel that initiates the generator potential that evokes afferent signaling in nociceptive nerves. TRPA1 is activated many harmful irritants, such as food chemicals, environmental pollutants, reactive oxygen species and other endogenous mediators. Most TRPA1 agonists have electrophilic properties, which covalently modify cysteine residues on the cytosolic side of the channel. Biochemical studies in our lab have identified four cysteines (C273, C621, C665, C1085) that rapidly bound iodoacetamide (irreversible electrophile); …

Hyperoxia-Induced Cardiac Pathophysiology In Guinea Pig Hearts, Zain Ul Abidin

USF Tampa Graduate Theses and Dissertations

Hyperoxia, is regularly introduced to critically ill patients in ICU. Nevertheless, recent studies have shown the negative effects of this treatment on patients in critical care, including increased rates of lung and cardiac injury and thereby high in-hospital mortality. Large part of the literature related to hyperoxia was majorly focused on lung injury, with no or minimal investigations on cardiac injury. Our lab is the first to investigate the effect of hyperoxia on cardiac pathophysiology in mice and showed that mice exposed to hyperoxia for 3 days demonstrated brady-arrhythmia, cardiac hypertrophy, QTc prolongation along with other electrical remodeling and functional …

Investigating The Novel Role Of Dextromethorphan In Mitigating Oxidative Stress Induced Changes In Retinal Pigment Epithelial Cells (Rpe), Zeinab A. Mohamed

USF Tampa Graduate Theses and Dissertations

Oxidative stress contributes to the degeneration of retinal pigment epithelial (RPE) cells and photoreceptors that lead to the dry form of age-related macular degeneration. Activation of N-Methyl-D-aspartate (NMDA) receptors contributes to the increase of free radicals that induce oxidative stress-induced changes. Our study investigates if Dextromethorphan, an NMDA receptor antagonist, reverses oxidative stress-induced changes in RPE. We used Paraquat and H2O2 as oxidative stress-inducing agents to induce oxidative damage in human ARPE-19 cells. To illustrate the change in cell viability and measure the apoptosis of ARPE-19 cells from oxidative damage, we performed MTT assay and Annexin V-DAPI flow cytometry analysis. …

Drug Candidates Targeting Hsp90/Cdc37 For The Treatment Of Neurodegenerative Disease, Ryan Martin

USF Tampa Graduate Theses and Dissertations

Neurodegenerative disease refers to the death of specific populations of neurons that canresult in dementia, loss of voluntary muscle motility, and other abnormalities. Two major neurodegenerative diseases are Alzheimer’s disease (AD) and Parkinson’s disease (PD), which are linked to abnormalities in Tau and a-synuclein proteins, respectively. Currently, there is no cure for these diseases. Our group and others have shown that chaperone proteins play a critical role in the processing of Tau and a-synuclein. The inhibition of the Hsp90/Cdc37 chaperone complex is shown to affect the levels of these two proteins. Hence, we hypothesized that a drug molecule, conglobatin (Cb), …

Glutathione-S-Transferase Mu 1 (Gstm1) Gene Augmentation Attenuated Oxidative Stress Induced Changes In Retinal Pigment Epithelium Cells (Rpe), Riddhi Sandeep Vichare

USF Tampa Graduate Theses and Dissertations

Purpose: Loss of Retinal Pigment Epithelial (RPE) cells and photoreceptors leads to Age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly worldwide. Oxidative stress-mediated damage is one of the factors that impair the survival of RPE and photoreceptors in dry-AMD. We sought to determine the role of human Glutathione S-Transferase Mu-1 (GSTM1) in protecting RPE cells from oxidative stress-induced changes.

Method: We cloned human GSTM1 cDNA with P2A tag into a lenti-plasmid vector and later made a lentivector to express GSTM1. After that, we infected human retinal pigment epithelial cells (ARPE-19), screened stable ARPE-19 cells …

Dendriplex - Cyclodextrin Conjugates For Gene Delivery To Retina, Durga Deepak Puro

USF Tampa Graduate Theses and Dissertations

Gene therapy holds promise for treating a wide range of diseases including cancer and several other polygenic and monogenic disorder arising in different organs. Due to its immune privilege nature, eye is an ideal organ for gene therapy,as various visual pathologies arise from gene defect and can lead to partial or complete vision loss. The last decade, several nanoparticles have been developed and tested for their transfection efficiency in vitro and in vivo. Among them, dendrimers with small size, good physicochemical properties and endosomal escape activity have shown high transfection efficiency in various cell lines. In an attempt to further …

Hepatobiliary Polycyclic Aromatic Hydrocarbons In Pelagic Fishes Of The Gulf Of Mexico, Madison R. Schwaab

USF Tampa Graduate Theses and Dissertations

Fisheries populations and their ecosystems are negatively impacted by both chronic and acute inputs of pollutants, including oil spills such as the Deepwater Horizon platform blowout in 2010 in the Gulf of Mexico (GoM). After Deepwater Horizon, toxicological studies of demersal fishes of the northern GoM were undertaken to characterize impacts and to establish baseline contaminant levels in the aftermath of the spill. In this study, I quantify polycyclic aromatic hydrocarbon (PAH) concentrations in eight pelagic fish species to demonstrate oil exposure differences between species, region and time. Analysis of biliary PAH metabolite equivalents using high performance liquid chromatography was …

A Health Evaluation Of Gulf Of Mexico Golden Tilefish (Lopholatilus Chamaeleonticeps) And Red Snapper (Lutjanus Campechanus) Following The Deepwater Horizon Oil Spill, Kristina Leigh Deak

USF Tampa Graduate Theses and Dissertations

A lack of baseline heath indices for offshore Gulf of Mexico (GoM) teleosts complicated impact assessments of the Deepwater Horizon (DWH) oil spill. While measurement of contaminant levels in fish after a pollution event can document exposure, such data fail to provide meaningful information about how this contact affects an animal's physiology. Controlled exposure studies have highlighted the utility of biomarkers that may indicate deleterious, long-lasting effects of pollutant exposure on various life stages of fish, however, their extrapolation to wild-caught, non-model species is challenging. In an increasingly chemically-saturated environment, it can also be difficult to separate the influence of …

Polychlorinated Biphenyls, Organochlorine Pesticides, And Polycyclic Aromatic Hydrocarbons In Snapper (Family Lutjanidae) From Cuba And The Wider Gulf Of Mexico, Brigid E. Carr

USF Tampa Graduate Theses and Dissertations

The Snapper species assemblage is economically and environmentally important to all three countries bordering the Gulf of Mexico (GoM). Polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were investigated in seven snapper species located in the GoM, with a specific focus on the those caught along the northwestern coast of Cuba. Hepatic samples were processed using QuEChERs extraction methodology and analyzed using gas chromatography with tandem mass spectrometry (GC-MS/MS). Nearly all fish included in this study contained detectable amounts of all three groups of these contaminants, regardless of location, and across all regions of the Gulf, indicating …

Hyaluronic Acid Coated Targeted Lipid Micellar Nanoparticle As A Delivery Vehicle For Lapatinib And Ketoconazole In Egfr Mutated Lung Cancer, Nadia Tasnim Ahmed

USF Tampa Graduate Theses and Dissertations

Background: According to the American Cancer Society, lung cancer was accountable for over 142,000 deaths in the USA in 2019. Common mutations related to lung cancer mainly occur in TP53, EGFR, and KRAS genes. Lapatinib is a small molecule tyrosine kinase inhibitor which acts reversibly on both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Overexpression of EGFR leads to increased production and signaling of proteins that cause upregulation of cellular proliferation, cholesterol synthesis and resistance to apoptosis. Ketoconazole is an imidazole antifungal agent which works principally by inhibiting the enzyme cytochrome P450 14α-demethylase (CYP51A1) …

Transcriptome Studies On The Toxicity Of Silica Nanoparticles, Shih-Yi Hsu

USF Tampa Graduate Theses and Dissertations

Nanotechnology enables more precise harmony in health condition via reducing the dosage amount, improving the delivery of hydrophobic drugs, more specific targeting to the cancerous sites, and so on. Nevertheless, issues regarding the toxicity of nanotechnology have begun to call for attention several decades later after the innovation of nanotechnology. Tools about risk management of nanotechnology have been developed, but recently not much evidence recognizes the toxicity of nanoparticles (NPs) except for some animal studies, which demonstrated organ damage after the exposure to NPs. Toxicogenomic approach refers to the method utilizing gene expression to evaluate the chemical toxicity. Databases as …

Orally Administered Nanoscale Drug Delivery System For Colorectal Cancer, Bhavya Shah

USF Tampa Graduate Theses and Dissertations

Mithramycin-A (Mit-A) is a US Food and Drug Administration (FDA) approved chemotherapeutic agent that is used for the treatment of testicular cancer. According to previous studies, Mit-A has shown promising results in targeting colorectal cancer (CRC) and cancer stem cells (CSCs) which are responsible for a highly invasive and metastatic forms of CRC. The use of Mit-A as chemotherapy is limited in CRC due to its toxicity. To minimize its toxicity, we have developed an orally delivered nanoscale drug delivery system by which Mit-A can be delivered using biocompatible and biodegradable materials. Mit-A nanoparticles were prepared using Poly(lactic-co-glycolic acid) as …

Luciferase Reporter Crc Cell Line For Bioluminescence Imaging In Orthotopic Tumor Model, Pratik Chopade

USF Tampa Graduate Theses and Dissertations

CRC is the second most common type of cancer in women and the third most common type of cancer in men. It accounts for 9.7% of all cancers in terms of people diagnosed. Measuring the real-time effect of chemotherapeutic drugs has been a major obstacle in developing a tumor model mouse. Tracking the regression of cancer cells after chemotherapy could be an effective way to resolve this issue. Therefore, cancer cells expressing the constitutive luciferase reporter gene can be a potential solution. The biggest advantage of the luciferase (Luc) reporter is that it is detectable at very low concentrations in …

Identification Of Snps Associated With Multiple Antibiotic Resistance Genes In Eight Clinical Variants Of Enterococcus Faecium., Krishna S. Karia

USF Tampa Graduate Theses and Dissertations

The evolution of multi drug resistant (MDR) bacteria has been well documented these last decade, suggesting that resistance to antibiotics is most commonly associated to single nucleotide polymorphism (SNPs) mutation. To this aim, several molecular methods have been performed to elucidate SNPs in the increasing number of resistant microorganisms. Early detection of MDR bacteria has become of prime necessity in order to combat the disease and ensure public health. Therefore, this research was conducted to screen for SNP mutations correlated to drug resistance in some nosocomial MDR bacteria strains donated from Moffitt Cancer Center (MCC) hospital. Blood, stool, urine, and …

A Micro-Nano Particle System For Sustained Drug Release In Lung Cancer Therapy, Heta N. Jadhav

USF Tampa Graduate Theses and Dissertations

Lung cancer remains the leading cause of cancer-related mortality in men and women worldwide (National Comprehensive Cancer Network). Hence, developing an effective new therapy to treat lung cancer is under intense investigation. Specifically, the sustained release of a drug in lung tumors is critically important. Previous studies at the USF have shown that telmisartan exhibits synergistic properties when combined with Actinomycin-D for lung cancer treatment. The objective of this study is to develop a novel micro/nano system consisting of lipids and chitosan polymers that would be able to deliver Tel directly to the lungs and release its payloads in a …

Sunitinib-Loaded Mpeg-Pcl Micelles For The Treatment Of Age-Related Macular Degeneration, Jarriaun D. Streets

USF Tampa Graduate Theses and Dissertations

Age-related Macular Degeneration, or AMD will be responsible for the vision impairment of more than 5 million late-aged adults in the next 30 years. Current treatment options include frequent intravitreal injections which report high levels of pain resulting in a low patient compliance. However, there are methods of drug delivery that can decrease the amount of intravitreal injections by sustaining drug release. Polymeric micelles, specifically MPEG-PCL have reported superb biocompatibility and more efficient ways of delivering anti-VEGF drugs such as Sunitinib to the posterior segment of the eye. In this study, the novel micellar formulation exhibited an average DLS particle …

Synthesis Of A Targeted Ph Responsive Nanoparticle For Controlled Release Of Actinomycin D, Alejandro Jesus Gonzalez

USF Tampa Graduate Theses and Dissertations

Out of all cancer diagnosis’s, lung cancer has the highest mortality in both sexes making it the leading cause of cancer deaths. Current therapeutic and clinical methods fail to successfully treat the disease, contributed to the development of multi-drug resistance (MDR). Hence, new therapies are needed that can exploit the tumor microenvironment (TME) to target Cancer Stem Cells (CSC). CSCs constitute a key population of the TME, promoting hypoxia, low intracellular pH, and angiogenesis. Actinomycin D (ACD) is a potent CSC inhibitor, but due to its high toxicity and lack of specificity towards cancer cells presents a need for a …

Functional Significance Of Endothelial Sigma-1 Receptors In Vascular Reactivity And Barrier Function, Zeinab Y. Motawe

USF Tampa Graduate Theses and Dissertations

The sigma-1 receptor (σ1) is a single 25 kD polypeptide that acts as a chaperone protein residing primarily in the endoplasmic reticulum Its interaction with mitochondria at the mitochondria-associated ER membrane domain is well-documented. Following activation, σ1 binds to the inositol trisphosphate receptor (Hayashi & Su), and modulates intracellular calcium homeostasis. Also, the activated σ1 modulates plasma membrane receptors and ion channel functions, and may regulate cellular excitability. Further, σ1 affects trafficking of lipids and proteins essential for neurotransmission, cell growth and motility. Activation of σ1 provides neuroprotection and cardio-protection in various models. Examples of neuroprotection include but not limited …