Hypertonic saline increases lung epithelial lining fluid glutathione and thiocyanate: two protective CFTR-dependent thiols against oxidative injury

<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis is a debilitating lung disease due to mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) and is associated with chronic infections resulting in elevated myeloperoxidase activity and generation of hypochlorous acid (HOCl). CFTR mutations lead to decreased levels of glutathione (GSH) and thiocyanate (SCN) in the epithelial lining fluid (ELF). Hypertonic saline is used to improve lung function however the mechanism is uncertain.</p> <p>Methods</p> <p>In the present study, the effect of GSH and SCN on HOCl-mediated cell injury and their changes in the ELF after hypertonic saline nebulization in wild type (WT) and CFTR KO mice was examined. CFTR sufficient and deficient lung cells were assessed for GSH, SCN and corresponding sensitivity towards HOCl-mediated injury, in vitro.</p> <p>Results</p> <p>CFTR (-) cells had lower extracellular levels of both GSH and SCN and were more sensitive to HOCl-mediated injury. In vivo, hypertonic saline increased ELF GSH in the WT and to a lesser extent in the CFTR KO mice but only SCN in the WT ELF. Finally, potential protective effects of GSH and SCN at concentrations found in the ELF against HOCl toxicity were examined in vitro.</p> <p>Conclusions</p> <p>While the concentrations of GSH and SCN associated with the WT ELF protect against HOCl toxicity, those found in the CFTR KO mice were less sufficient to inhibit cell injury. These data suggests that CFTR has important roles in exporting GSH and SCN which are protective against oxidants and that hypertonic saline treatment may have beneficial effects by increasing their levels in the lung.</p

Method for Determining Air Side Convective Heat Transfer Coefficient Using Infrared Thermography

Air side convective heat transfer coefficients are among the most important parameters to know when modeling thermal systems due to their dominant impact on the overall heat transfer coefficient. Local air side convective heat transfer coefficients can often prove challenging to measure experimentally due to limitations with sensor accuracy, complexity of surface geometries, and changes to the heat transfer due to the sensor itself. Infrared thermography allows local heat transfer coefficients to be accurately determined for many different surface geometries in a manner which does not impact the results. Moreover, when determining convective heat transfer coefficients for a large number of samples, it is less costly in terms of both time and materials than other experimental methods. The method determines the heat transfer coefficient for an arbitrary region by determining the rate at which the surface temperature changes due to a step change in air temperature. To utilize the method a simple calibration is first done to determine the local thermal time constant under natural convection. Alternatively, if the thermal properties of the object are well known, a model may be used. In subsequent tests, the ratio of thermal time constant to that from the calibration test can be determined. As the material properties of the solid object are unchanged, the convective heat transfer coefficient scales inversely with the thermal time constant. A computer script has been created which automates the entire analysis process with the exception of determining the region of interest. The experimental method has been validated by comparison to other experimental methods, values from literature, and numerical simulations