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Assessment and pharmacological correction of abnormalities in bicarbonate (HCO3-) and muc
     
 
Author(s) : de Jonge H and Caldrer S
Address : Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam; Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata Verona 
Erasmus University Medical Center, Universitaria Integrata Verona
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Background. Most physiological assays used for CF diagnosis and as a biomarker in clinical trials measure CFTR-dependent chloride but not bicarbonate transport. Recent studies however reveal that defective bicarbonate rather than chloride transport is the primary cause of impaired mucociliary clearance in the airways and luminal obstruction in the GI tract in CF.

Hypothesis and objectives. Our major aims were (i) development of new protocols to measure bicarbonate transport in rectal biopsies and intestinal organoids from healthy controls and CF patients; (ii) ex vivo testing of CFTR correctors and potentiators for their ability to restore bicarbonate secretion in these models; (iii) validating the concept that CFTR functional variants associated with pancreatitis and sinusitis but not CF have a specific bicarbonate permeation defect.

 
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