Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 140-156). Also available in print.

published_or_final_version / Anatomy / Master / Master of Philosophy

Statins induce beneficial vascular effects. How statins induce beneficial vascular effects is yet to be determined. Here we examine Simvastatin and vascular endothelial growth factor (VEGF) acting through the phosphoinositide 3-kinase (PI3K) pathway in human coronary artery endothelial cells (HCAEC). While Simvastatin and VEGF both activated mediators in the PI3K pathway, the proteins and the rates of activation were not always consistent. This suggests that although Simvastatin and VEGF share a common PI3K pathway in HCAEC and similar vascular effects, the agonists diverge in the induction of cellular signaling cascades. Simvastatin also was shown to induce phosphoinositide 3, 4, 5-triphosphate (PIPS) organization and PI3K p110 gamma (y) perinuclear localization. Beneficial, non-lipid lowering effects of statins may occur through the PI3K pathway through activation of distinct mediators from those of VEGF. Better understanding of the pathways associated with statins is necessary for the discovery of better treatments for cardiovascular disease (CVD). / Department of Biology

[Truncated abstract] One of the barriers to understanding and preventing proliferative diabetic retinopathy in humans has been the lack of an appropriate animal model. Historically dog, rat and mouse models of diabetic retinopathy have been studied but none of these exhibit the later changes of proliferative diabetic retinopathy. Animals can be rendered diabetic by surgical pancreatectomy or the use of chemicals such as allozan or streptozotocin or by feeding of a high galactose diet. Alternatively, spontaneous rodent models of diabetes have been examined such as the BB rat, KK mouse or NOD mouse. However, in each case the retinal vascular changes observed are those of early nonproliferative diabetic retinopathy comprising at most saccular microaneurysms, increased thickness of the capillary basement membrane, acellular capillaries and pericyte ghosts. … Fluorecein angiography of this transgenic line clearly demonstrates the presence of leaky new vessels, by the appearance of leakage spots scattered throughout the retina from 1 month of age. These mice constitute a valuable model of diabetic retinopathy. Neovascularization in this animal model is induced by VEGF as in human diabetic retinopathy. The source of VEGF in human diabetic retinopathy is the ischemic inner retina. In this transgenic model the source of VEGF are the photoreceptor cells, which are situated just underneath the inner retina. The neovascularization is not dependent on a particular developmental stage and there is no spontaneous regression of new vessels. Thus any results generated in this model are highly relevant to human diabetic retinopathy.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Additional advisors: Susan Bellis, Vladimir Fast, Chi-Tsou Huang, Donald Muccio. Description based on contents viewed June 23, 2009; title from PDF t.p. Includes bibliographical references.

Thesis (M.S.)--Florida State University, 2004. / Advisor: Dr. Teng Ma, Florida State University, College of Engineering, Dept. of Chemical and Biomedical Engineering. Title and description from dissertation home page (viewed Jan 12, 2005). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 161-178).

The development of new multiphoton absorbing materials has attracted the attention of researchers for the last two decades. The advantages that multiphoton absorbing materials offer, versus their one-photon absorbing counterparts, rely on the nature of the nonlinearity of the absorption process, where two photons are absorbed simultaneously offering increased 3D resolution, deeper penetration, and less photobleaching and photodamage as a result of a more confined excitation. The applications of efficient two-photon absorbing materials have been extensively expanding into the fields of photodynamic therapy, microscopy, and optical data storage. One of the fields where an increased interest in multiphoton absorbing materials has been most evident is in bioimaging, in particular, when different cellular processes and organelles need to be studied by fluorescence microscopy. The goal of this research was to develop efficient two-photon absorption (2PA) compounds to be used in fluorescence bioimaging, meaning that such compounds need to posses good optical properties, such as high fluorescence quantum yield, 2PA cross section, and photostability. In the first chapter of this dissertation, we describe the synthesis and structural characterization of a new series of fluorescent donor–acceptor and acceptor-acceptor molecules based on the fluorenyl ring system that incorporated functionalities such as alkynes and thiophene rings, through efficient Pd-catalyzed Sonogashira and Stille coupling reactions, in order to increase the length of the conjugation in our systems. These new molecules proved to have high two-photon absorption (2PA), and the effect of these functionalities on their 2PA cross section values was evaluated. Finally, their use in two-photon fluorescence microscopy (2PFM) imaging was demonstrated. iii One of the limitations of the compounds described in Chapter 1 was their poor water solubility; this issue was addressed in Chapter 2. The use of micelles in drug delivery has been shown to be an area of increasing interest over the last decade. In the bioimaging field, it is key to have dye molecules with a high degree of water solubility to enable cells to uptake the dye. By enclosing a hydrophobic dye in Pluronic® F-127 micelles, we developed a system that facilitates the use of 2PA molecules (typically hydrophobic) in biological systems for nonlinear biophotonic applications, specifically to image the lysosomes. Furthermore, we report in this chapter the efficient microwave-assisted synthesis of the dye used in this study. In addition, linear photophysical and photochemical parameters, two-photon absorption (2PA), and superfluorescence properties of the dye studied in Chapter 2, were investigated in Chapter 3. The steady-state absorption, fluorescence, and excitation anisotropy spectra of this dye were measured in several organic solvents and aqueous media. In Chapter 4, we describe the preparation and the use of an efficient and novel twophoton absorbing fluorescent probe conjugated to an antibody that confers selectivity towards the vascular endothelial growth factor receptor 2 (VEGFR-2) in porcine aortic endothelial cells that express this receptor (PAE-KDR). It is known that this receptor is overexpressed in certain cancer processes. Thus, targeting of this receptor will be useful to image the tumor vasculature. It was observed that when the dye was incubated with cells that do not express the receptor, no effective binding between the bioconjugate and the cells took place, resulting in very poor, nonspecific fluorescence images by both one and two-photon excitation. On the other hand, when the dye was incubated with cells that expressed VEGFR-2, efficient imaging of the cells was obtained, even at very low concentrations (0.4 μM). Moreover, incubation of the bioconjugate iv with tissue facilitated successful imaging of vasculature in mouse embryonic tissue