Medicine and Health Sciences Commons^™

Extracellular Matrix Proteins And The Liver-Lung Axis In Disease., Veronica L. Massey

Electronic Theses and Dissertations

No abstract provided.

Study Of Novel Nanoparticle Transport And Drug Release For Cancer Treatment., Christopher Gene England 1988-

Electronic Theses and Dissertations

Nano-scale particles sized 10—400 nm administered systemically preferentially extravasate from tumor vasculature due to the enhanced permeability and retention effect. Therapeutic success remains elusive, however, because of inhomogeneous particle distribution within tumor tissue. Insufficient tumor vascularization limits particle transport and also results in avascular hypoxic regions with non-proliferating cells, which can regenerate tissue after nanoparticle-delivered cytotoxicity or thermal ablation. In this study, gold nanoparticles were functionalized with phosphatidylcholine (two-layer) or phosphatidylcholine and HDL (three-layer) in the formation of “layered” nanoparticles. The diffusivity of both two- and three layered colloidal gold nanoparticles and silica gold nanoshells were examined in 3D cell …

Lunasin Reduces The Melanoma Stem Cell Population In Vitro And Inhibits Tumor Proliferation In Vivo., Christopher Paul Shidal

Electronic Theses and Dissertations

Lunasin is a 44 amino acid peptide derived from the soybean seed that has been shown to have cancer chemopreventive and chemotherapeutic properties. In this study, we investigated the potential utility of lunasin as a chemotherapeutic in a melanoma model. Initial studies showed that lunasin has little activity against established melanoma cell lines in vitro using adherent culture methods; however, lunasin’s in vitro activity was significantly higher in non-adherent colony-forming assays in soft agar and oncosphere assays. These results led us to investigate whether lunasin selectively affects cancer initiating cells (CIC) that are known to be present in these melanoma …

Building A Metabolic Bridge Between Glycolysis And Sphingolipid Biosynthesis : Implications In Cancer., Morgan L. Stathem

Electronic Theses and Dissertations

Cancer therapeutics has seen an emergence and re-emergence of two metabolic fields in recent years, namely bioactive sphingolipids and glycolytic metabolism. Anaerobic glycolysis and its role in cancer has been recognized in cancer biology over 90 years. In recent decades, the role of sphingolipids in cancer cell metabolism has gained recognition, notably ceramide’s essential role in programmed cell death and the role of the glucosylceramide synthase (GCS) in chemotherapeutic resistance. Despite this knowledge, a direct link between these two fields has yet to be concretely drawn. Herein, we show that in a model of highly glycolytic cells, generation of the …

Inducible Tumor Difference Between Rapid And Slow Rat Nat2 Congenic Fischer 344 Rats Administered Methyl-Nitrosourea., Marcus W. Stepp

Electronic Theses and Dissertations

Human arylamine N-acetyltransferase 1 (NAT1) is a well-known phase II metabolic enzyme that has been associated with carcinogenesis. Its role in the biotransformation of aromatic and heterocyclic amine carcinogens has been investigated for many years, but more recent investigations focus on a possible endogenous role of human NAT1 in cancer initiation and progression. We conducted in vivo studies using homozygous Fischer 344 rats, congenic at the rat Nat2 locus for high (rapid) and low (slow) activity. Wistar Kyoto inbred rats were used to breed in the slow activity rat Nat2 locus into the Fischer 344 inbred rat, which contains the …

Evaluation Of The Safety And Pharmacokinetic Profile Of The Broad Spectrum Antiviral Lectin Griffithsin., Christopher Lynn Barton

Electronic Theses and Dissertations

Carbohydrate binding agents that target viral envelope glycans are being studied for their potential use as microbicides and antiviral therapeutics. Griffithsin is a lectin originally identified in a red alga Griffithisia sp. Multiple studies have shown that GRFT inhibits HIV-1, Coronaviruses, Hepatitis C, influenza and Ebola virus replication in vitro. This antiviral activity suggests potential uses in chemoprophylaxis and disease treatment. However, safety of GRFT administration has not been extensively studied. In vivo testing--chronic subcutaneous treatment as well as single dose subcutaneous, oral, and intravenous administrations of Griffithsin in Sprague Dawley Rats (Rattus Norvegicus)--was used to assess Griffithsin’s pharmacokinetic properties …

Bone Strength And Architecture : Pharmacological Targeting Of Camkk2 As A Method For Enhancing Bone Quality., Zachary James Pritchard

Electronic Theses and Dissertations

Mice lacking or pharmacologically inhibited for calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) have enhanced bone mass and microarchitecture. This enhanced bone mass and architecture is due to changes in osteoblast and osteoclast numbers as well as activity. Whether the enhanced bone mass translated to increased bone quality and strength was further explored by developing a method to directly test the trabecular strength of the distal femur. Micro computed tomography (CT)-based measurement of the length of the epiphysis of the distal femur, aided in its removal, allowing the exposure of the trabecular bone volume used to determine the microarchitecture parameters. Following …

Neurodegeneration-Associated Instability Of Ribosomal Dna., Justin Lauren Hallgren 1981-

Electronic Theses and Dissertations

Homologous recombination-mediated instability of the repetitively organized ribosomal DNA has been proposed as a mediator of cell senescence in yeast triggering the DNA damage response. High individual variability in the content of human ribosomal DNA suggests that this genomic region remained relatively unstable throughout evolution. Therefore, quantitative real time PCR was used to determine the genomic content of ribosomal DNA in post mortem samples of parietal cortex from 14 young and 9 elderly individuals with no diagnosis of a chronic neurodegenerative/neurological disease. In addition, ribosomal DNA content in that brain region was compared between 10 age-matched control individuals and 10 …

The Role Of Pesticides In Non-Alcoholic Fatty Liver Disease (Nafld)., Laila Al-Eryani 1986-

Electronic Theses and Dissertations

NAFLD, the most common form of liver disease worldwide, is caused by various factors including industrial chemicals and pesticides exposure. Annually, 5.2 billion pounds of pesticides are used worldwide and can contribute to liver disease, but their role is modestly studied. We hypothesize that pesticides contaminating food supply can worsen diet-induced steatosis via xenobiotic receptor activation. Two human and two rodent databases were utilized and 85% of the 330 chemicals identified associated with NAFLD were pesticides. Eight were selected for evaluating hepatic receptor activation in vitro. The majority including DDT activated hPXR/CAR and mPXR. DDT (100 mg/kg) was studied in …

Preventive Effect Of Non-Mitogenic Acidic Fibroblast Growth Factor On Diabetes-Induced Testicular Cell Death., Melissa Skibba 1990-

Electronic Theses and Dissertations

Fibroblast growth factor (FGF)-1 was found to protect the heart from oxidative damage, but clinically its long-term use was restricted for its undesirable proliferating activity on cells. Thus a cluster of amino acids responsible for the proliferation were deleted in the native FGF-1 to create a non-mitogenic FGF-1 (nmFGF-1). To assess whether nmFGF-1 protects male germ cells from diabetes-induced apoptotic death, the study employed a murine model of diabetes using multiple low-doses of streptozotocin, followed by nmFGF-1 treatment for 6 months. Diabetic mice showed a decrease in testicular weight and an increase in apoptotic cell death. Treatment with nmFGF-1 alleviated …

Cranberry Metabolites With Urinary Anti-Adhesion Activity, Christina M. Coleman

Electronic Theses and Dissertations

The fruit of the American cranberry (Vaccinium macrocarpon Aiton, Ericaceae) is a comfood and a top selling dietary supplement in the U.S. Cranberry juice is traditionally used for the prevention of urinary tract infections (UTIs), many of which are caused by P-fimbriated Escherichia coli. Human urine produced after cranberry juice consumption can prevent E. coli adhesion, but the urinary metabolites responsible for this activity are currently not known. High-molecular weight components of cranberry juice, specifically proanthocyanidin oligomers (PACs), are currently believed to be responsible for the ability of cranberry juice to prevent UTIs. Cranberry PACs can prevent the adherence of …

Customer Tolerance In Community Pharmacy, Philip Everett Schwab

Electronic Theses and Dissertations

Customers can have an existing relationship with a service provider where they are not satisfied with the services they receive, yet they continue to patronize the service provider. Why does this happen? Why do these customers remain as patrons of service providers that do not meet expectations and that leave these customers with low satisfaction. This dissertation presents the concept of tolerance to explain the retention of customers who are not satisfied with a service provider. Specifically, this dissertation examined the concept of customer tolerance in community pharmacy. Tolerance is an important concept for consideration because regardless of good intentions …

Management Of Breast Cancer In The Medicaid Population, Rohan Mahabaleshwarkar

Electronic Theses and Dissertations

Breast cancer is the second most comcancer and the second leading cause of cancer-related death among women. The current project examined some key issues important for effective breast cancer management in the Medicaid population. Medicaid is one the largest healthcare insurance systems in the US providing coverage to more than 60 million low-income individuals. As a part of this project, three studies were conducted. The first study determined the healthcare burden associated with breast cancer in the form of healthcare use (inpatient, outpatient, and emergency room [ER] visits) and costs associated with the condition in the Medicaid population. Significant healthcare …

Intranasal Delivery Of Therapeutics Targeted To Csf And Brain, Prashanth Manda

Electronic Theses and Dissertations

Blood-brain barrier and blood-cerebrospinal fluid barrier limit the systemic delivery of therapeutics to the brain and cerebrospinal fluid (CSF) respectively. Therapeutic agents targeting CNS are currently being administered by invasive routes which are not patient compliant and do not allow frequent administration. Intranasal delivery of therapeutics to target CSF and brain is a noninvasive route of administration which is patient compliant and allows frequent administration. In the current study, the plausibility of delivering ziconotide and cefotaxime to CSF and brain respectively via intranasal pathway using barrier modulating agents like chitosan was investigated. The ability of chitosan to enhance the permeation …

Secondary Metabolite Production By An Endophytic Bacillus Sp. From Platanus Occidentalis, Michael C. James

Electronic Theses and Dissertations

Endophytes are bacterial and fungal microbes that live inside of plant tissue without causing disease. Endophytes have applications in many industries including the pharmaceutical and food industries as producers of natural products. This potential was demonstrated by investigating the natural product production from a Bacillus amyloliquefaciens endophyte of Platanus occidentalis using a combination of MALDI-IMS, LC-MS, MS-MS, and NMR methods, by purifying nicotianamine from soy flour, and by reviewing natural product inhibitors of the hepatitis C virus (HCV). The secondary metabolite production of the endophytic B. amyloliquefaciens was investigated under a variety of fermentation conditions. It was discovered that the …

Pharmacists' Preparedness For Acute Medical Emergencies, James W. Parrett

Electronic Theses and Dissertations

Purpose/Objectives: This project studied how prepared community pharmacists are to respond to acute medical emergencies, as well as their perceived efficacy in addressing these situations. Specifically, it considered what training pharmacists have for responding to medical emergencies, what emergency medical equipment pharmacies have on-hand, the frequency that medical emergencies occur within pharmacies, and the types of emergencies encountered. It also measured self and collective efficacy of pharmacists in responding to medical emergencies within their pharmacy to determine if differences in self-efficacy or collective efficacy exist. Methods: This study utilized a cross-sectional, non-experimental, descriptive design via a self-administered, Internet-based survey distributed …

Solubility Enhancement And Precipitation Inhibition Of Poorly Water Soluble Compounds Utilizing Hot Melt Extrusion Technology, Jiannan Lu

Electronic Theses and Dissertations

Soluplus® (SOL), a graft amorphous copolymer, composed of polyethylene glycol, vinyl acetate and vinylcaprolactam in a ratio of 13: 30: 57, was utilized to prepare solid dispersions containing felodipine (FEL) or ketoconazole (KTZ) using hot-melt extrusion technology. The melting point depression approach was utilized to determine the miscibility and solubility of the model compounds within Soluplus® , of which felodipine demonstrated higher solubility when compared to ketoconazole (14% vs 4.3% w/w) at room temperature (298K). Moreover, the solubility parameters of FEL, KTZ and SOL were calculated as 21.76, 26.51 and 21.64, respectively.

Polarized light microscopy, Fourier transform infrared spectroscopy (FT-IR), …

Solubility Enhancement Via Melt Extrusion: Drug-Polymer Solubility, Physicochemical Characterization And Quality By Design, Ketaki Patwardhan

Electronic Theses and Dissertations

Many new drugs developed face oral delivery challenges and absorption due to poor biopharmaceutical properties. Formation of solid dispersions is a very widely applied technique for solubility enhancement of water insoluble drugs. In order to form stable solid dispersions it is important to select appropriate excipients that will maintain the drug in its amorphous form for an extended period of time. Selection of appropriate excipients is critical during the development of stable amorphous solid dispersions. The solubility parameter concept has been explored for theoretically identifying the excipients that will be suitable based on the structure of the active. In this …

Structure, Synthesis And Biological Activity Of Harmful Algal Bloom Toxins From Karlodinium Sp. And Exploration Of Microbial Derived Natural Products, Amanda Leigh Waters

Electronic Theses and Dissertations

This work features natural products isolated from both the marine and microbial environments. Part I focuses on the elucidation of toxins from harmful algal blooms (HAB). The HAB dinoflagellate Karlodinium veneficum produces a harmful suite of molecules identified as the karlotoxins (KmTx) that have been implicated in massive fish kills pan-globally. Nine new karlotoxin congeners were isolated from various Karlodinium blooms around the world and utilizing the structure of KmTx2 were characterized using overlaid 2D NMR techniques. Due to the contrasting conformational differences between KmTx and the closely related amphidinols, the absolute configuration of KmTx was further evaluated by extensive …