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Under constant exposure, receptors are pulled off the cell surface and become less responsive over time (receptor desensitization). Higher doses maintain more signal against that fade

Chronic alcohol ingestion alters the expression and interaction of essential components of the tight junctions, including claudin-1, claudin-5, claudin-7, occludin, and zonula occludens-1, resulting in a five-fold increase in pulmonary epithelial permeability (79, 105107)

Duration of treatment was five times the half-life of each agent and the placebo was matched accordingly