Medicine and Health Sciences Commons^™

Genetic Exploration Of Hereditary Immune Diseases, Cheng Tian

Theses and Dissertations (ETD)

An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases, rheumatoid arthritis and systemic sclerosis are two of them. My study focuses on these two diseases. Our hypothesis is that mutated genes lead to autoimmune diseases that cause the immune system to attack the human body. The mutated genes cause the gene expression levels to change which fail to properly regulate the body's functions, resulting in immune system diseases. I used existing mouse models to improve the understanding of these two diseases.

The first …

Development Of Multiple Microemulsion Eye Drops For Sustained Release Of New Glaucoma Drug, Doaa Nabih Ahmed Maria

Theses and Dissertations (ETD)

Persistent or repeated elevation of intraocular pressure (IOP) is a primary risk factor of visual field loss in glaucoma, therefore IOP reduction is the first-line therapeutic option in the disease management. Unfortunately, the current therapies are associated with a lot of deficiencies including several daily dosing, reduced efficacy and systemic side effects all of which resulted in poor patient compliance. Previously we have identified Calcium voltage-gated channel auxiliary subunit Alpha2delta 1 gene (Cacna2d1) as a novel modulator of IOP and confirmed that pregabalin targeted CACNA2D1 in eye tissues (ciliary body and trabecular meshwork) to lower IOP in a …

Understanding The Impact Of Bcrp And Pgp Efflux Transporters On The Disposition Of Their Endogenous, Xenobiotic And Dietary Substrates, Samit Ganguly

Theses and Dissertations (ETD)

Breast Cancer Resistant Protein (BCRP) and P-glycoprotein (PGP) are membrane-bound efflux transporters that transport multiple chemical classes of compounds and act as barriers to tissue permeability, thereby regulating tissue exposure of their substrates. The role of these transporters in therapeutic resistance of their xenobiotic substrates due to their expression and efflux function at target organs/tissues, especially in brain and intestine, is well established, which has fueled investigation toward identification of their inhibitors. Multiple clinically used drugs and dietary chemicals have been reported to inhibit these transporters and potentially increase the exposure of concomitantly administered BCRP and/or PGP substrates, which might …

Somatic Mutation Detection In Leukemia-Derived Circulating Dna: Utility In Monitoring Clonal Dynamics And Disease Response In Pediatric Acute Lymphoblastic Leukemia, Sarah Hisham Abdelaziz Youssef

Theses and Dissertations (ETD)

Despite the improved outcome associated with current treatment strategies ofpediatric acute lymphoblastic leukemia (ALL), relapse still represents a major challenge. Pediatric ALL demonstrates branched evolution in response to selective pressure exerted by therapy; relapse founder clones emerge from pre-leukemic clones or minor subclones present at diagnosis. It is hence crucial to develop biomarkers capable of tracking subclones throughout therapy. Current practices for monitoring disease response in leukemia rely on the analysis of BM biopsy sample at specific time points throughout therapy. Not only the invasiveness of the BM biopsy hinders the sequential sampling, but also, the currently implied techniques are …

Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley

Theses and Dissertations (ETD)

Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - …

Rheological Studies Of Injectable Thermoresponsive Biodegradable Hydrogels And Porcine Ocular Tissues, Chandana Reddy Damera

Theses and Dissertations (ETD)

This research has evaluated the rheological properties of two types of materials which include (i) semi-synthetic polymer-based injectable hydrogels [P(NIPAAm-co-DEX-Lactate HEMA) and P(NIPAAm-co-HA-AEMA)], and (ii) biological tissues (porcine ocular tissues).

A series of thermoresponsive and biodegradable in situ hydrogel based on N-isopropyacrylamide (NIPAAm) monomer and hydrolytically degradable oligolactate Dextran-lactate-HEMA or Hyaluronic acid (HA)-AEMA macromer were investigated as encapsulation matrices (scaffolds) for DPSCs/ADSCs and assess their applicability in dental/retinal tissue engineering. The rheological properties of the hydrogels were strongly dependent on the reaction conditions and composition of the hydrogels. Both the hydrogels exhibited linear viscoelasticity, and the values of storage moludus …

Characterization Of The Hepatotoxicity Of Rifampicin And Isoniazid, Christopher T. Brewer

Theses and Dissertations (ETD)

In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase of protoporphyrin ix (PPIX), the penultimate heme precursor. Excess PPIX is believed to bind to bile acids, precipitate in bile canaliculi, and form bile plugs leading to cholestasis fol owed by liver injury. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to up-regulate Alas1 but down-regulate Fech protein levels in mice; however the mechanism of isoniazid mediated heme synthesis …