Radiation dermatitis (RD) is the most common acute side effect of breast irradiation. More than a century following the therapeutic utilisation of X-rays, potent preventative and therapeutic options are still lacking. Non-invasive physical plasma (NIPP) is an emerging approach towards treatment of various dermatological disorders. In this study, we sought to determine the safety and feasibility of a NIPP device on RD. Thirty patients undergoing hypofractionated whole-breast irradiation were included. Parallel to radiation treatment, the irradiated breast was treated with NIPP with different application regimens. RD was assessed during and after NIPP/radiation, using clinician- and patient-reported outcomes. Additionally, safety and feasibility features were recorded. None of the patients was prescribed topical corticosteroids and none considered the treatment to be unpleasant. RD was less frequent and milder in comparison with standard skin care. Neither NIPP-related adverse events nor side effects were reported. This proven safety and feasibility profile of a topical NIPP device in the prevention and treatment of RD will be used as the framework for a larger intrapatient-randomised double-blind placebo-controlled trial, using objective and patient-reported outcome measures as an endpoint.
The bile acid-sensitive ion channel (BASIC) is a member of the Deg/ENaC family of ion channels that is activated by bile acids. Despite the identification of cholangiocytes in the liver and unipolar brush cells in the cerebellum as sites of expression, the physiological function of BASIC in these cell types is not yet understood. Here we used a cholangiocyte cell line, normal rat cholangiocytes (NRCs), which expresses BASIC to study the role of the channel in epithelial transport using Ussing chamber experiments. Apical application of bile acids induced robust and transient increases in transepithelial currents that were carried by Na+ and partly blocked by the BASIC inhibitor diminazene. Genetic ablation of the BASIC gene in NRC using a CRISPR-cas9 approach resulted in a decrease of the bile acid-mediated response that matched the diminazene-sensitive current in NRC WT cells, suggesting that cholangiocytes respond to bile acids with a BASIC-mediated Na+ influx. Taken together, we have identified BASIC as a component of the cholangiocyte transport machinery, which might mediate a bile acid-dependent modification of the bile and thus control bile flux and composition.
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