Cystic fibrosis (CF) is caused by defective cyclic AMP-dependent cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Therefore, CF epithelial cells fail to transport, Cl(-) and water. Furthermore, the cessation of Cl(-) efflux across the apical membrane of CF pancreatic and biliary duct cells reduces HCO(3) (-) secretion as well. In CF epithelial cells activation of calcium-dependent Cl(-) channels might substitute for impaired CFTR function and restore Cl(-) and/or HCO(3) (-) secretion. ATP-mediated stimulation of P2Y and P2X purinergic receptors causes an increase in cytosolic Ca(2+) concentration ([Ca(2+)](i)). Effects of ATP are influenced by external zinc, pH and Na(+) concentrations. In low Na(+), alkaline environment, ATP and zinc induce a sustained and reproducible Ca(2+) signal because of P2X receptor mediated Ca(2+) influx from the extracellular space. Importantly, the increase in [Ca(2+)](i) stimulates anion secretion of nasal epithelia in CF mouse models suggesting that targeting P2X receptors might have beneficial effects in CF therapy.

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Background: The pH of the airway surface liquid (ASL) plays a pivotal role in maintaining the proper function of the respiratory epithelium. In patients with cystic fibrosis (CF) acidic ASL has been observed. Thus, alkalinization of ASL itself might be beneficial in CF. The aim of this study was to investigate the role of extracellular pH (pH_o) on the alternative Ca²⁺-activated Cl^- channels (CaCCs) in CF airway epithelial cells. Methods: The [Ca²⁺]_i and viability of CF airway epithelial cells (IB3-1) were assessed using Fluo-3/AM and YO-PRO-1 fluorescent dyes, respectively. Ion currents were detected in whole-cell configuration using the patch clamp technique. Results: Extracellular alkalinization (pH_o 8.2) stimulated Ca²⁺ entry and inward currents in low Na⁺ containing medium. The inward currents were blocked by the removal of extracellular Ca²⁺, chelating cytosolic Ca²⁺, as well as by the application of niflumic acid and DIDS. While Zn²⁺ promoted sustained Ca²⁺ entry in pH_o-dependent manner, it inhibited the anion conductance. The low external Na⁺ concentrations and alkaline pH_o were well tolerated by the cells. Conclusions: Stimulation of CaCCs could be achieved by alkalinization of the extracellular environment in CF airway epithelial cells. Zn²⁺ directly blocked, however indirectly enhanced the activity of Cl^- conductance.

Basal cell carcinoma is the most common malignant tumor of the periocular region with local aggressive growth and extensive destruction. The histological subtypes of periocular basalioma, the recurrence rates and resection border relationships were analyzed and the results were compared with basaliomas from other body regions. The results of gender and age distribution, histological subtypes, recurrence rates and resection border relationships were evaluated using the χ(2)-test. The results showed a significantly higher recurrence rate (p < 0.01) for the periocular region compared to other body regions and the incidence of periocular basalioma was higher in women (p < 0.05). In addition the rarer histological subtypes were more commonly found in this region compared to other body regions (p < 0.01).

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