Congenital Diaphragmatic Hernia (CDH) is a severe birth defect that
affects approximately 1 in 3,000 newborns. The etiology of CDH is
largely unknown. The clinical presentation is variable, but is usually
characterized by cardiopulmonary distress caused by underdevelopment of
the lungs and the pulmonary vasculature. In this thesis we have reviewed
the current knowledge on the role of nutrition, life style factors and
genes in human CDH. In part I, the epidemiological studies, we
demonstrated that newborns with CDH have significantly lower levels of
retinol and retinol-binding protein (RBP) in cord blood as compared to
healthy newborns. Levels in case and control mothers were comparable.
However, we found a lower intake of vitamin A in case mothers with
normal weight during pregnancy. Although a relationship with the
methylation pathway has been hypothesized, we could not identify a
difference between case and control newborns in the cord blood levels of
homocysteine, s-adenosyl methionine (SAM) and S-adenosyl homocysteine
(SAH).
In part II, the molecular biological studies, we describe a model to
study human lung development and the role of hypoxia–related factors in
lung development. This model can be used to manipulate lung growth by
pharmacological agents or signaling molecules such as vitamin A
derivatives. Further, we studied the expression of metabolic actors of
the vitamin A pathway in human, rat and rabbit lung. We demonstrated
that the vitamin A pathway is disturbed in the lung of human CDH, but
probably at a different level than in the animal models of CDH.http://repub.eur.nl/res/pub/21415/101124_Beurskens%2C%20Leonardus%20Wilhelmus%20Josephus%20Elisabeth.pdf
No comments:
Post a Comment