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Filename: drivers/Session_files_driver.php
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File: /home/orthodiedw/nutridatabase/application/controllers/Articles.php
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Filename: drivers/Session_files_driver.php
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File: /home/orthodiedw/nutridatabase/application/controllers/Articles.php
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Filename: drivers/Session_files_driver.php
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Filename: drivers/Session_files_driver.php
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Filename: Session/Session.php
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File: /home/orthodiedw/nutridatabase/application/controllers/Articles.php
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Filename: Session/Session.php
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Filename: Session/Session.php
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File: /home/orthodiedw/nutridatabase/application/controllers/Articles.php
Line: 7
Function: __construct
File: /home/orthodiedw/nutridatabase/index.php
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Le trinitrate de glycéryle (GTN) a été largement utilisé pour le traitement de l'angine de poitrine, une affection pathologique se manifestant par une douleur à la poitrine résultant d'un apport sanguin insuffisant au cœur. La conversion métabolique de GTN, un promédicament à base d’oxyde nitrique (NO), induit une vasodilatation et améliore le flux sanguin. Les patients développent une tolérance au GTN après plusieurs semaines d'utilisation continue, limitant ainsi les possibilités de traitement à long terme. La cause mécanistique de la tolérance aux nitrates est relativement inconnue. Nous avons développé un modèle de culture cellulaire de tolérance aux nitrates qui utilise des isotopes stables pour mesurer le métabolisme du (15) N3-GTN en (15) N-nitrite. Nous avons effectué une métabolomique globale pour identifier le mécanisme de la tolérance aux nitrates induite par le GTN et pour élucider le rôle protecteur de la vitamine C (acide ascorbique). Les analyses métabolomiques ont révélé que le GTN altérait le métabolisme des purines ainsi que les ATP et GTP intracellulaires appauvris. La xanthine oxydase (XO) inactivée par le GTN, une enzyme essentielle à la bioactivation métabolique du GTN en NO. L'acide ascorbique a empêché l'inactivation de XO, entraînant une augmentation de la production de NO à partir de GTN. Nos études suggèrent que l’acide ascorbique est capable d’empêcher la tolérance aux nitrates en protégeant le XO, mais pas l’aldéhyde déshydrogénase (une autre enzyme bioactivante du GTN), contre l’inactivation induite par le GTN. Nos résultats fournissent une explication mécanistique aux effets bénéfiques précédemment observés de l'acide ascorbique dans le traitement aux nitrates.
Source: https://www.ncbi.nlm.nih.gov/pubmed/30319419