Chemicals and Drugs Commons^™

Quantifying The Effect Of A Novel Topical Hyaluronic-Acid Phosphatidylethanolamine Cream On The Epidermis, Caitlin J. Symonette

Electronic Thesis and Dissertation Repository

With aging, keratinocytes have diminished proliferative capacity resulting in atrophic skin with reduced barrier function. This investigation evaluates the effect of daily topical applications of a novel high-molecular weight hyaluronan cream (HA-PE) on keratinocyte renewal and epidermal thickness. Unmodified hyaluronan and HA-PE were mixed separately into a vehicle cream. Each topical formulation was applied daily onto the shaved backs of aged female C57BL6 mice. Full-thickness biopsies of treated skin were obtained for analysis of keratinocyte proliferation, keratinocyte differentiation, and local inflammation at days 1, 5, and 10 of cream application. In addition, a cardiac puncture was performed for serum C-reactive …

Synthesis Of Carbohydrate Functionalized Dendrons For Use As Multivalent Scaffold And In Self-Assembled Structures, Namrata Jain

Electronic Thesis and Dissertation Repository

Carbohydrates are implicated in a large number of biological processes ranging from cell-cell interactions to bacterial and viral infection. Lectins are carbohydrate-binding proteins that are generally specific for certain sugars. However, typical carbohydrate–lectin interactions tend to have very low monomeric binding affinities. In many cases, the binding of saccharide ligands by protein receptors can be improved significantly through the attachment of multiple saccharide residues to a common support. Dendronized polymers constitute a class of macromolecules whose nanoscale size, rigidity, and functionality can be controlled with precision by tuning their molecular architecture. It is hypothesized that due to their large size …

Functional Assessment And Potential Therapeutic Role Of Carbon Monoxide Releasing Molecule-­‐3 In A Rodent Model Of Compartment Syndrome, Al Walid Hamam

Electronic Thesis and Dissertation Repository

Compartment syndrome (CS) is a life and limb threatening condition resulting in long term morbidity. Gold standard treatment of CS is surgical fasciotomy. Long-term morbidity is common post fasciotomy. We tested a gait analysis system (CatWalk™) to see if we could detect functional effects of CS in our rodent model. We also investigated the effects of carbon monoxide releasing molecule-3 (CORM-3) on the function of gait in rodents post CS.

The CatWalkTM system was able to detect abnormalities in a rodent’s gait post CS. CORM-3 was also found to alleviate the functional deficits following CS. Multiple dose but not single …

Genomic Predictors Of Drug Response To The Alpha-Specific Phosphoinositol 3-Kinase (Pi3ka-Alpha) Inhibitor Byl719 In Head And Neck Cancers, Giananthony T. Rizzo

Electronic Thesis and Dissertation Repository

PIK3CA is the only frequently mutated, druggable oncogene in head and neck squamous cell cancer (HNSCC), with PIK3CA point mutations and gene amplification rates of 17.5% and 40% respectively, with higher rates in HPV-positive disease. The objective of this research was to determine the effects of BYL719, an α-specific PI3K inhibitor in HNSCC cell lines.

All cell lines with PIK3CA hotspot point mutations or gene amplifications will be sensitive to BYL719.

Twenty-eight HNSCC cell lines were subjected to increasing concentrations of BYL719 and cell viability was measured over time. Cell lines were screened for activating PIK3CA hotspot mutations and amplifications …

The Effects Of Ocean Acidification And Eutrophication On The Growth, Lipid Composition And Toxicity Of The Marine Raphidophyte Heterosigma Akashiwo., Julia Rose Matheson

Electronic Thesis and Dissertation Repository

Anthropogenic forcing, such as ocean acidification caused by rising carbon dioxide emissions, and eutrophication due to increased nutrient loadings in run-off, are causing major changes to the biogeochemistry of the oceans. As a consequence, coastal phytoplankton are susceptible to altered biogeochemical environments. This study examined the effect of a lower pH and increased levels of nutrients on the common coastal harmful alga, Heterosigma akashiwo. Growth rates, maximal cell yields, neutral lipid accumulation and toxicity of cells grown under various pH and nutrients regimes were measured. H. akashiwo growth was near maximal when grown at lower pH levels. There was …

Development Of Non-Covalent Functionalization Of Carbon Nanotubes For Sirna Delivery, King Sun Siu

Electronic Thesis and Dissertation Repository

RNA interference (RNAi) therapy is promising for treating various diseases but the delivery of small interfering RNA (siRNA) is difficult. To overcome the technical difficulties of siRNA delivery, an efficient and targeted delivery of siRNA is required for efficient RNAi therapy. Single-walled carbon nanotubes (CNT) has been used for nucleic acid delivery such as siRNA delivery. It has been found that CNT can gain entry into the cells by a diffusion-like mechanism which was called “nano-needle”. However, the solubility of CNT is low in most of the solvents including water. Functionalization of CNT can be carried out to enhance the …

The Development Of A New Dry Powder Inhaler, Xi Zhang

Electronic Thesis and Dissertation Repository

A new dry powder inhaler (DPI) for respiratory drug delivery was developed. This novel device is characterized by a micro-dose, passive delivery and multiple doses individually sealed in one replaceable disk. The micro-dose delivery system uses only a small amount of excipient, such as 2-3mg lactose, thereby improving the drug delivery efficiency. The passive delivery method eliminates the need for coordination between breath and device actuation such as the pressure metered dose inhaler (pMDI). Finally, 14 doses on a disk reduce the need to frequently change dosage disks. In addition, each dose is effectively protected by a blister package to …

Bio-Identical Hormone Therapy: Understanding Women's Decision-Making Process And Family Physicians' Views, Lemmese Alwatban

Electronic Thesis and Dissertation Repository

This thesis explored women’s and family physicians’ experiences with Bio-identical Hormone Therapy (BHT). It aimed to develop a deeper understanding of women’s decision-making process in choosing this therapeutic modality, and the influence family physicians may have on this process. To capture the phenomenon under study, two complementary and sequential qualitative studies were conducted. The studies involved in-depth interviews with women using BHT and family physicians that care for this population. The collective findings of both studies demonstrated the complexity of menopause care. The findings illuminated the major factors involved in women’s BHT decision-making process. It also offered important information about …

Effects Of Prenatal Testosterone On The Reproductive And Metabolic Neurons Of The Sheep Hypothalamus, Maria Cernea

Electronic Thesis and Dissertation Repository

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting reproductively aged women. Women with PCOS and ewes prenatally exposed to testosterone (T) show similar reproductive and metabolic defects, including anovulatory dysfunctions stemming from abnormal gonadotropin releasing hormone (GnRH) secretion and insulin resistance. For this dissertation, I examined the effects of prenatal T treatment on androgen receptor (AR) and insulin receptor (IR) expression with the reproductive and metabolic neurons of the hypothalamus, the ARC KNDy (co-expressing kisspeptin, neurokinin B/dynorphin), AgRP (agouti-related peptide) and proopiomelanocortin (POMC) neurons, and the preoptic area (POA) kisspeptin neurons, and the GnRH neurons. …

Folate Receptor-Targeting Liposomes For The Delivery Of Antisense Molecules To Cancer Cells, Colin J. Way

Electronic Thesis and Dissertation Repository

RNAi (RNA interference) is emerging as a promising tool for cancer therapy. Small interfering RNA (siRNA) molecules are activated in that pathway to reduce specific tumour cell RNAs that mediate malignancy. SiRNA treatment has been primarily limited to in vitro studies: lack of efficient, preferential in vivo delivery to target cells remains a major obstacle. Many human tumours overexpress folate receptors (FR), and siRNA-mediated reduction of thymidylate synthase (TS) sensitizes tumour cells to anti-TS drugs. I developed a folate-containing cationic liposome to preferentially deliver anti-TS siRNA to FR-expressing human tumour cells. I show, in vitro, that liposome-encapsulated siRNA (but …

Synthesis And Spectroscopic Studies Of Substituted Pyrrolocytidines, Mckenry Charles

Electronic Thesis and Dissertation Repository

This thesis reports work in the area of modified nucleosides for potential use as molecular probes in nucleic acid chemistry. These heterocyclic base surrogates that are capable of canonical base pairing have use in the study of nucleic acid conformation, as reporters of the state of hybridization.^[1]

The synthesis of a 5-phenylpyrrolocytidine was attempted in order to compare its properties with its 6-substituted pyrrolocytidine counterpart. Unfortunately, the 5-substituted pyrrolocytidine was not achieved.

The synthesis of five nucleosides based on the pyrrolocytidine scaffold was reported. Their synthesis was achieved through the tandem Sonogashira/annulations reaction between 5-iodocytidine derivatives and …

Optimization Of Chiral Separation Of Nadolol By Simulated Moving Bed Technology, Nesma Nehad Hashem

Electronic Thesis and Dissertation Repository

Simulated Moving Bed (SMB) technology has gained increasing attention as one of the most powerful techniques for chromatographic separations due to its cost-effectiveness and efficiency. Application of SMB technology is especially important in the pharmaceutical industry for production of enantiopure drugs, as required under strict FDA regulations, to avoid possible adverse effects of racemic drugs. In this study, the performance of the SMB process in separation of racemic nadolol on a perphenyl carbamoylated beta cyclodextrin (β-CD) stationary phase was investigated. The equilibrium dispersive model coupled with bi-Langmuir adsorption isotherm and lumped kinetic approximation, constitute the mathematical model used to simulate …

Experimental And Computational Analysis Of The Structure And Dynamics Of Intrinsically Disordered Proteins, Elio Anthony Cino

Electronic Thesis and Dissertation Repository

Intrinsically disordered proteins (IDPs) are abundant in cells and have central roles in

protein-protein interaction networks. Many are involved in cancer, aging and

neurodegenerative diseases. The structure and dynamics of IDPs is intimately related to their

interactions with binding partners. Because IDPs are inherently flexible and do not have a

single conformation, conventional methods and conditions for determining structure and

dynamics of globular proteins may not be directly applicable. Nuclear magnetic resonance

(NMR) spectroscopy is one of the primary techniques characterizing the structures and

dynamics of IDPs, but one cannot rely solely on NMR data. A primary aim of this …

Nrf2 Activation By Dimercaptopropanol Attenuates Mutant Huntingtin Toxicity, Kyle M. Dailey

Electronic Thesis and Dissertation Repository

Huntington’s disease (HD) is a fatal neurodegenerative disorder resulting from the expansion of a trinucleotide repeat within the HD gene. At the cellular level mutant HTT (mHTT) aggregates perturb cellular metabolism, intracellular trafficking and mitochondrial function, resulting in the increased production of reactive oxygen species (ROS) an event closely linked with nerve cell death. Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-sensitive transcription factor responsible for transcribing neuroprotective genes under the control of the antioxidant response element (ARE), which work to counteract high intracellular ROS levels. I have identified significant increases in cell viability, NRF2 nuclear localization, and …

Design And Syntheses Of Novel Quenchers For Fluorescent Hybridization Probes, Mohamed Moustafa

Electronic Thesis and Dissertation Repository

Since most of human diseases are related to genetic mutations, during the past two decades, identification of such mutations has attracted much attention. Detection of these mutations is mainly based hybridization with the complementary reporter probes.

Nucleic acids detection takes place by changing either the reporter’s fluorescence intensity or the colour of its fluorescence. The use of fluorescent probes for nucleic acid detection has attracted much attention due to its efficiency, the ease of synthesis and availability of commercial reporters that facilitates the probe synthesis. Nowadays, most of nucleic acid detection using fluorescent probes relies on quenching of fluorescence by …

Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean

Electronic Thesis and Dissertation Repository

Tumor and metastasis formation are not cell autonomous phenomena, but rather an evolution of disease within and responding to the host environment. Metastatic spread from a primary tumor occurs as a result of a complex interplay between tumor cells and the host, wherein tumor cells must escape the primary tumor, enter the host vasculature, travel to and arrest in a distant tissue and survive and grow in that new organ. It is known that cells that progress through these stages must both escape and exploit host systems, yet the mechanisms used are not fully understood. Therefore, the goal of this …

Design And Syntheses Of Fluorescent Cytosine Analogues, David W. Dodd

Electronic Thesis and Dissertation Repository

The avid hybridization of peptide nucleic acid (PNA) to DNA and RNA along with the molecule’s biological stability has led it to be used in both antisense and antigene capacities. PNA acts against translation via a steric blockade mechanism. It is therefore reasonable to assume that increased heteroduplex stability could lead to increased potency. Two ways of doing this were explored. I) N-Terminal attachment of a platinous chloride chelating moiety to PNA complementary to Xenopus noggin was synthesized with the objective of selective, covalent platination of the target transcript in vivo. Phenotypes consistent with knockdown of the selected …