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Mougenot P Namane C Fett E Camy F Dadji-Faïhun R Langot G Monseau C Onofri B Pacquet F Pascal C Crespin O Ben-Hassine M Ragot JL Van-Pham T Philippo C Chatelain-Egger F Péron P Le Bail JC Guillot E Chamiot-Clerc P Chabanaud MA Pruniaux MP Schmidt F Venier O Nicolaï E Viviani F 《Bioorganic & medicinal chemistry letters》2012,22(7):2497-2502
A novel class of DGAT1 inhibitors containing a thiadiazole core has been discovered. Chemical optimization lead to inhibitors of human DGAT1 with an appropriate ADME profile and that show in vivo activity in target tissues. 相似文献
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Tiphaine Bihouée Gregory Bouchaud Julie Chesné David Lair Camille Rolland-Debord Faouzi Braza Marie-Aude Cheminant Philippe Aubert Guillaume Mahay Christine Sagan Michel Neunlist Sophie Brouard Marie Bodinier Antoine Magnan 《Respiratory research》2014,15(1)
Background
Atopic march refers to the typical transition from a food allergy in early childhood to allergic asthma in older children and adults. However the precise interplay of events involving gut, skin and pulmonary inflammation in this process is not completely understood.Objectives
To develop a mouse model of mixed food and respiratory allergy mimicking the atopic march and better understand the impact of food allergies on asthma.Methods
Food allergy to ovalbumin (OVA) was induced through intra-peritoneal sensitization and intra-gastric challenge, and/or a respiratory allergy to house dust mite (HDM) was obtained through percutaneous sensitization and intra-nasal challenges with dermatophagoides farinae (Der f) extract. Digestive, respiratory and systemic parameters were analyzed.Results
OVA-mediated gut allergy was associated with an increase in jejunum permeability, and a worsening of Der f-induced asthma with stronger airway hyperresponsiveness and pulmonary cell infiltration, notably eosinophils. There was overproduction of the pro-eosinophil chemokine RANTES in broncho-alveolar lavages associated with an enhanced Th2 cytokine secretion and increased total and Der f-specific IgE when the two allergies were present. Both AHR and lung inflammation increased after a second pulmonary challenge.Conclusion
Gut sensitization to OVA amplifies Der f-induced asthma in mice. 相似文献24.