Pharmacology, Toxicology and Environmental Health Commons^™

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 …

To Compare Cyclosporine A Nanoformulations For Their Effectiveness In Reducing Nephrotoxicity, Ilkin Nasirli

USF Tampa Graduate Theses and Dissertations

Cyclosporine (CsA) is one of the main immune-suppressant agents which has been used widely in organ transplantation against graft rejection. However, the low oral bioavailability and the associated adverse effects such as nephrotoxicity are the main drawbacks of current usage of this drug. Thus, purpose of this research is to formulate PLGA nanoparticles of CsA to improve its effectiveness and to reduce the nephrotoxicity induced by the plain drug. CsA-loaded PLGA nanoparticles were prepared by the nanoprecipitation method. Particle size and zeta potential of the formulation was determined and percent drug entrapment were also determined. Quantitative estimation was carried out …

Pazopanib Loaded Plga Nanoparticles For The Treatment Of Age-Related Macular Degeneration, Gulimirerouzi Fnu

USF Tampa Graduate Theses and Dissertations

Age-related macular degeneration (AMD) is a reason of severe vision loss worldwide. Pazopanib is a multitargeted tyrosine kinase inhibitor drug that can reduce neovascularization by mainly acting on vascular endothelial growth factor receptor (VEGFR). An intraocular injection to posterior segment of eye of anti-VEGF agent at present represents the cornerstone of therapies for AMD. However, challenges in targeting and delivering drug to eye’s posterior segment well as difficulties arising from repetitive frequent intraocular injections, which requires novel drug delivery method. In this study, pazopanib loaded PLGA‐NPs were prepared and the studied formulation had particle size of 132.1 ± 1.4 nm …

A Retrospective Study Of The Opioid Epidemic And Fentanyl Related Overdose Fatality Cases In A Florida West Coast Medical Examiner District Population, Anne Terese Powell

USF Tampa Graduate Theses and Dissertations

Opioids are scheduled by the propensity for misuse and abuse with a high rate of dependency and risk of fatal overdose. Opioids can be divided into different classes, including, natural, synthetic, and semi-synthetic. Opiates are naturally occurring and come directly from the opium poppy plant; whereas the semi synthetics opioids are chemical modifications of the poppy plant. Synthetic opioids attach to the opioid receptor but contain no part of the poppy plant. The increased variety and frequency in opioid prescriptions contributed to an opioid epidemic in the United States which is still on going.

According to the CDC, the opioid …

Nanoparticle Synthesis For Glucose-Loaded Mesoporous Silica And Sucrose Hydrolysis Strategies For Bioanalyte Detection Applications Using A Personal Glucose Meter, Xiomar Emauel Bustos Perez

USF Tampa Graduate Theses and Dissertations

Point-of-care (POC) tests are a reliable, portable, easy to use, and more affordable alternative to regular laboratory diagnostic tests. They bypass the necessity of expensive equipment, human labor, and technical expertise. The personal glucose meter (PGM) is a POC device that measures glucose levels in blood. Lately, the PGM have been used as a tool to detect other bioanalytes in different applications. There are two analytes which POC detection would be beneficial for patients: creatinine and tacrolimus. Creatinine is used to calculate glomerular filtration rate, a measurement of kidneys function that can help to diagnose kidney failure, and other nephropathies. …

A New Approach To The Development Of An Rsv Anti-Viral Targeted Nanocarrier For Dual Inhibition Of Viral Infection And Replication, Anthony N. Singer

USF Tampa Graduate Theses and Dissertations

Respiratory Syncytial Virus (RSV) is a potentially life-threatening respiratory pathogen that infects approximately 64 million children and immunocompromised adults globally per year. Currently, there is a need for prophylactic and therapeutic approaches effective against primary and secondary RSV infections. This project focuses on the development of a simple, smart, and scalable anti-RSV nanotherapeutic that combines novel cellular antiviral defense mechanisms targeting the inhibition of viral fusion and replication. An ICAM-1 targeted liposomal nanocarrier will be synthesized and coated with a layer of chitosan containing the anti-fusion HR2-D peptide as an extracellular defense mechanism. Additionally, chitosan complexed to dual expressing short …

Off-Target Based Drug Repurposing Using Systems Pharmacology, Brent M. Kuenzi

USF Tampa Graduate Theses and Dissertations

The goal of this study was to identify novel drug repurposing opportunities in cancer by utilizing the off-target profiles of clinically relevant kinase inhibitors. This was based on the observation that the global target profiles of compounds are largely ignored and that many compounds have activity that cannot be explained by their cognate target alone. Additionally, by utilizing clinically relevant compounds, any results would hold a high potential for eventual clinical implementation. We utilized a systems pharmacology approach utilizing cell viability-based drug screening to identify compounds with beneficial off-target activity and then using chemical and phosphoproteomics in order to elucidate …

Signal Detection Of Adverse Drug Reaction Using The Adverse Event Reporting System: Literature Review And Novel Methods, Minh H. Pham

USF Tampa Graduate Theses and Dissertations

One of the objectives of the U.S. Food and Drug Administration is to protect the public health through post-marketing drug safety surveillance, also known as Pharmacovigilance. An inexpensive and efficient method to inspect post-marketing drug safety is to use data mining algorithms on electronic health records to discover associations between drugs and adverse events.

The purpose of this study is two-fold. First, we review the methods and algorithms proposed in the literature for identifying association drug interactions to an adverse event and discuss their advantages and drawbacks. Second, we attempt to adapt some novel methods that have been used in …

A Historical Assessment Of Asbestos Exposure, Abatement Methods And Containment Efficacy During Asbestos Containing Material Removal Activities At A Large Federal Facility, Daniel A. Newfang

USF Tampa Graduate Theses and Dissertations

Asbestos sampling and monitoring data, starting from 2003, located in a large federal facility’s Asbestos Air Database Management (AADM) repository will be queried and analyzed on airborne asbestos fiber concentrations generated from abatement activities of asbestos-containing materials (ACM) and asbestos-containing building materials (ACBM). Historically, concerns expressed by personnel outside of the containment areas, whether adjacent to or quite a distance from the asbestos abatement activities present operational challenges for the project manager, potential angst and uneasiness to personnel residing next to the abatement activity as well as programmatic concerns to the building/facility managers. The concerned individuals working outside the abatement …

Identifying New Treatment Options And Risk Factors For Type 2 Diabetes: The Potential Role Of Thymoquinone And Persistent Organic Pollutants, Shpetim Karandrea

USF Tampa Graduate Theses and Dissertations

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, which develops as a consequence of peripheral insulin resistance and defective insulin secretion from pancreatic β-cells. A high calorie diet coupled with physical inactivity are known risk factors for the development of T2DM; however, these alone fail to account for the rapid rise of the disease. Recent attention has turned to the role of environmental pollutants in the development of metabolic diseases. PBDEs (polybrominated diphenyl ethers) are environmental pollutants that have been linked to the development of type 2 diabetes (T2D), however, the precise mechanisms are not …

Distribution Of Polybrominated Diphenyl Ethers Among Demographic Categories, Giorvanni Merilis

USF Tampa Graduate Theses and Dissertations

Polybrominated Diphenyl Ethers (PBDEs) are flame retardants widely used within the United States in various products such as plastics, electronics, textiles and furniture. With an increase in production and usage, PBDEs have recently emerged as a contaminant of concern. Due to their chemical structure, PBDEs have the propensity to bioaccumulate in mammals. In fact, elevated PBDE concentrations have been recorded in human breast milk. Due to the potential widespread exposure to PBDEs, this study investigates human blood concentrations of PBDEs generated through the 2003-2004 National Health and Nutrition Examination Survey. Through the use of statistical modeling, a comparison of mean …

Therapeutic Modulation Of Cancer Metabolism With Dichloroacetate And Metformin, Nathan Patrick Ward

USF Tampa Graduate Theses and Dissertations

The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin’s reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in the VM-M3 model of GBM. We demonstrated that metformin potentiated DCA-induced superoxide production and that this was required for enhanced cytotoxicity towards VM-M3 cells with the combination. Similarly, rotenone enhanced oxidative stress resultant …

The Optimization Of The Nuclear Protein In Testis (Nut) Antibody And Its Importance And Impact In The Pathology Lab, Lindsey Martinez

USF Tampa Graduate Theses and Dissertations

Optimization in immunohistochemistry is often a time consuming and complex process. There are a varying array of moving parts to consider all while preserving the sensitivity and specificity of the test. When optimizing an antibody it is important to consider the fixation of the tissue and the type of epitope retrieval that would be best suited for the test. The dilution of the primary antibody is a key marker for the efficiency and effectiveness of the laboratory protocol. The purpose of this study was to produce an optimized antibody for the nuclear protein in testis to detect NUT midline carcinoma …

Hypercapnic Hyperoxia Increases Free Radical Production And Cellular Excitability In Rat Caudal Solitary Complex Brain Slice Neurons, Geoffrey Edward Ciarlone

USF Tampa Graduate Theses and Dissertations

The caudal solitary complex (cSC) is a cardiorespiratory integrative center in the dorsal medulla oblongata that plays a vital role in the central CO₂-chemoreceptive network. Neurons in this area respond to hypercapnic acidosis (HA) by a depolarization of the membrane potential and increase in firing rate, however a definitive mechanism for this response remains unknown. Likewise, CO₂-chemoreceptive neurons in the cSC respond to hyperoxia in a similar fashion, but via a free radical mediated mechanism. It remains unknown if the response to increased pO₂ is merely an increase in redox signaling, or if it’s the …

Hormone Replacement Therapy (Hrt) Modulates Peripheral And Central Auditory System Processing With Aging, Tanika Williamson

USF Tampa Graduate Theses and Dissertations

After the findings were reported for the Women’s Health Initiative (WHI) study in the past decade, there has been a significant decline in the overall use of hormone replacement therapy (HRT) among women. However, there are still millions of middle-aged, menopausal women in the U.S. who are currently undergoing hormone therapy. Their reasons for continuing treatment include relief of severe menopausal symptoms, aid in the management of osteoporosis and reduction in the risk of colon cancer (Ness et al., 2005). The purpose of the following investigation was to evaluate the impact of HRT on the central and peripheral auditory systems …

The Influence Of Oxygen Tension And Glycolytic And Citric Acid Cycle Substrates In Acrolein-Induced Cellular Injury In The Differentiated H9c2 Cardiac Cell Model, Jayme Coyle

USF Tampa Graduate Theses and Dissertations

Most in vitro systems employ the standard cell culture maintenance conditions of 95 % air with 5 % CO2 to balance medium pH, which translates to culture oxygen tensions of approximately 20 % - above the typical ≤ 6 % found in most tissues. The current investigation, therefore, aims to characterize the effect of maintenance and toxicant exposure with a particular focus on the α,β-unsaturated aldehyde, acrolein, in the presence of physiologically relevant oxygen tension using a differentiated H9c2 cardiomyoblast subclone. H9c2 cells were maintained separately in 20.1 and 5 % oxygen, after which cells were differentiated for five days, …

A Caenorhabditis Elegans Model To Detect Developmental Teratogens With Adverse Reproductive And Metabolic Effects, Alexis Ann Killeen

USF Tampa Graduate Theses and Dissertations

Obesity is a current epidemic in the United States. Greater than one third of adults and nearly one fifth of children are classified as obese (Ogden, 2014). Increased awareness of this problem has triggered interest into the potentially causal agents in our environment. These agents, termed obesogens, are a type of teratogen hypothesized to work during embryonic development by programming offspring to store excess fat. A type of teratogen, obesogens are also typically reprotoxic, affecting germline development and embryonic viability. These noxious teratogens span a variety of different chemical classes including estrogen mimics, metals and metalloids, biocides, and even voluntary …

Leukemia Inhibitory Factor As A Neuroprotective Agent Against Focal Cerebral Ischemia, Stephanie Davis

USF Tampa Graduate Theses and Dissertations

Previous publications from this laboratory demonstrated that administration of leukemia inhibitory factor (LIF) (125 µg/kg) to young, male Sprague-Dawley rats at 6, 24, and 48 h after middle cerebral artery occlusion (MCAO) reduced infract volume, improved sensimotor skills, and alleviated damage to white matter at 72 h after the injury. In vitro studies using cultured oligodendrocytes (OLs) showed that LIF (200 ng/ml) also protects against 24 h of oxygen-glucose deprivation through activation of Akt signaling and upregulation of the antioxidant enzymes peroxiredoxin IV and metallothionein III. Other groups have demonstrated that LIF reduces neurodegeneration in animal models of disease, but …