Objective
A number of congenital conditions include oxidative stress as a phenotypic hallmark, in spite of very distinct genotypic assets. These disorders include three rare, lifethreatening conditions, i.e. ataxia telangiectasia (AT), Fanconi's anaemia (FA), and xeroderma pigmentosum (XP), as well as two frequent congenital conditions, Down's syndrome (DS) and cystic fibrosis (CF). All of these disorders generate severe biomedical and social handicaps in their progression. A clinical feature shared by these disorders is cancer proneness, while other manifestations include early ageing, neurological symptoms or malformations. The onset of oxidative stress has been related to excess formation or defective detoxyfication of reactive oxygen species (ROS). This can arise from either the abnormal expression or inducibility of ROS-detoxyfying enzymes, or by defective absorption of nutrient antioxidants. Resulting oxidative injury has been characterised through: i. DNA, protein or lipid oxidative damage; ii. excess ROS formation (in vitro and ex vivo); iii. sensitivity to oxygenrelated toxicity, and iv. improvement of cellular defects by either hypoxia or antioxidants. Investigations conducted so far have focussed on individual disorders and have utilised a range of different methodologies; this has has lead to a number of unanswered questions regarding the role(s) for oxidative stress in these disorders. Thus, comparative studies are required which should focus on selected indicators for oxidative stress based on homogeneous methods, facilities and personnel. The ensuing information is expected to provide relevant insights into the pathogenesis of each individual condition, with possible consequences into the studies of ageing and cancer.
Objectives:
l. To evaluate some selected indicators of oxidative stress in AT, FA, XP, DS and CF.
2. To determine the activities and regulation of Cu,ZnSOD, MnSOD, catalase and GPx.
3. To evaluate ultrastructure and some selected functions of blood cells. 4. To evaluate the apoptotic propensity of peripheral blood mononuclear (PBMN) cells.
5. To relate the data to clinical history and to the genetic asset.
Key-words: oxidative stress, reactive oxygen species, congenital diseases, chromosomal instability, cancer proneness, ageing, handicap
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- humanities history and archaeology history
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Coordinator
I-80078 Pozzuoli
Italy
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