Cystic Fibrosis (CF) is the most common autosomal recessive disease affecting the Caucasian population. This devastating disease is caused by any one of 1500 mutations identified in the Cystic Fibrosis Transmembrane Regulator Conductance (cftr) gene. Chronic inflammation is a hallmark of CF and it affects all systems including respiratory, gastrointestinal, reproductive and skeletal. Although the exact molecular link between the CFTR dysfunction and various phenotypes remains to be delineated, many phenotypes seem to be linked to inadequate nutritional absorption of essential fatty acids and vitamins, which leads to an imbalance between the essential fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA). The skeletal system does not only serve as mechanical support, but also functions as an active organ that regulates balance and interactions between both local and systemic hormones, cytokines and prostaglandins. Previously our laboratory has shown that fenretinide [ N-(4-hydroxyphenyl) retinamide] corrects the essential fatty acid imbalance. We hypothesized that correcting the DHA/AA ratio in the plasma of Cftr-KO mice could avoid the early-onset osteoporosis. This thesis presents our novel results describing how fenretinide prevents osteoporosis. We found that twice a week treatment with fenretinide over a period of four weeks dramatically increased trabecular bone volume and quality in Cftr-KO mice. The results of this thesis strongly suggest that fenretinide might have potential for the treatment of cystic fibrosis patients by preventing the reduction of trabecular bone mineral density.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.101740 |
| Date | January 2007 |
| Creators | Saeed, Zienab Sahar. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | © Zienab Sahar Saeed, 2007 |
| Relation | alephsysno: 002599030, proquestno: AAIMR32856, Theses scanned by UMI/ProQuest. |
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