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 …

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 …

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 …

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 …

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 …

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 …

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 …

Chemical Investigation Of Antarctic Marine Organisms & Their Role In Modern Drug Discovery, Jacqueline Lee Fries

USF Tampa Graduate Theses and Dissertations

The chemicals produced by biological systems, whether proteins, peptides, or terpenes, will always provide an intriguing topic for researchers. Invisibly controlling every aspect of nature, these molecules are responsible for life, evolution, and death. Specifically, here is described the secondary metabolites produced by Antarctic marine organisms as well as others, and how they are used to defend or attract other animals while potentially providing health benefits to mankind. This is done through collection, extraction, and separation of individual specimens. The respective mixtures of compounds after isolation are then analyzed via spectroscopic methods such as nuclear magnetic resonance spectroscopy, mass spectrometry, …

Statistical Analysis, Modeling, And Algorithms For Pharmaceutical And Cancer Systems, Bong-Jin Choi

USF Tampa Graduate Theses and Dissertations

The aim of the present study is to develop a statistical algorithm and model associ- ated with breast and lung cancer patients. In this study, we developed several statistical softwares, R packages, and models using our new statistical approach.

In the present study, we used the five parameters logistic model for determining the optimal doses of a pharmaceutical drugs, including dynamic initial points, an automatic process for outlier detection and an algorithm that develops a graphic user interface(GUI) program. The developed statistical procedure assists medical scientists by reducing their time in determining the optimal dose of new drugs, and can …

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …