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Regulation of inflammation and angiogenesis in the cornea
Inflammation and angiogenesis, the growth of new blood vessels from pre-existing ones, are involved in tumor growth, ocular diseases and wound healing. In ocular angiogenesis, new pathological vessels grow into a specific eye tissue, leak fluid, and disrupt vision. The development of safe and effective therapies for ocular angiogenesis is of great importance for preventing blindness, given that current treatments have limited efficacy or are associated with undesirable side effects. The search for alternative treatment targets requires a deeper understanding of inflammation and how it can lead to angiogenesis in the eye in pathologic situations. This thesis provides new insights into the reg...
Aseptic Loosening of Orthopedic Implants
Aseptic loosening is the main cause of failure of orthopedic prostheses. With no pharmaceuticals to prevent or mitigate periprosthetic bone degradation, a surgery to replace the loose implant with a new one is the only choice to restore patients’ function. Most studies on mechanisms for aseptic loosening investigate wear debris particle-induced osteolysis. However, pathological loading conditions around unstable implants can also trigger osteoclast differentiation and bone loss. In the first study, global gene expression changes induced by mechanical instability of implants, and by titanium particles were compared in a validated rat model for aseptic loosening. Microarray analysis showed t...
Inhibitors of corneal inflammation and angiogenesis
Pathologic angiogenesis is involved in cancer and several blinding conditions such as wet age-related macular degeneration, proliferative retinopathies and corneal neovascularization. In these dieseases, the angiogenic triggers are hypoxia and inflammation, and both involve the main angiogenic mediator, which is Vascular Endothelial Growth Factor (VEGF). Among available treatments, anti-VEGF often shows limited or temporary efficacy, while steroids are potentially responsible for many side-effects. This thesis presents a series of linked studies aimed at elucidating the early pathologic changes leading to inflammation and corneal neovascularization, and how various treatments affect this pro...
Investigating mechanisms of angiogenesis in health and disease using zebrafish models
Angiogenesis, the growth of blood vessels from an existing vasculature, can occur by sprouting from preexisting vessels or by vessel splitting (intussusception). Pathological angiogenesis drives choroidal neovascularization (CNV) in age related macular degeneration (AMD) which is commonly restricted under the retinal pigment epithelium (RPE), called occult CNV, but may also involve vessels penetrating through the RPE into the sub-retinal space. Pathological vessels are poorly developed, insufficiently perfused and highly leaky, phenotypes that are considered to drive disease progression and lead to poor prognosis. Currently, a number of anti-angiogenic drugs exists, the majority of which tar...
African Kingships in Perspective
First published in 1977, African Kingships in Perspective deals comparatively and analytically with the dynamics of change in monarchical settings. It examines the variant responses of African kingships to the challenge of modernity and political centralisation, and to assess their successes and failures in the face of rapid social change. The analysis is based on eight case studies: Ethiopia, Buganda, Ankole, Rwanda, Burundi, Ijebu Ode, Swaziland and Lesotho – covering a wide range of historical experiences and social settings. By looking at the relative staying power and adaptability of these traditional polities, the editor reveals the structural regularities behind variations of cultur...
