[Affinity of Luliconazole for Human Nail Derived Keratin].

Affinity of Luliconazole (LLCZ), an antifungal drug used for topical treatment of onychomycosis in Japan, to nail keratin was demonstrated. Efinaconazole (EFCZ) was used as a reference drug. Drugs at fixed concentrations were added to 4 ml of buffer solution containing 40 mg of nail keratin powder prepared from healthy volunteers or from tinea unguium patients. The mixtures were shaken at 37℃, and adsorption and desorption rates of the drug in nail keratin were measured. Theoretical analysis using the Freundlich adsorption isotherm was applied to eliminate effects of testing conditions on the results. Results showed that compared with EFCZ, LLCZ exhibited high adsorption rates and low desorption rates in nail keratins. These results were verified by Freundlich analysis, in which adsorption coefficient (KadsF) and desorption coefficient (KadsF) of LLCZ were 5-7 times and about 2 times higher than EFCZ, respectively. In addition, antifungal activity against Trichophyton rubrum of the desorbed LLCZ samples was determined using disk diffusion assay. In conclusion, LLCZ is considered to possess high affinity to nail keratin. LLCZ, therefore, can be retained in the nail as a reservoir and continuously desorbed at the infection site to exhibit antifungal activity against pathogenic fungi. The pharmacokinetics of LLCZ in the nail is believed to differ from that of EFCZ. As adsorption and desorption rates of the two drugs in nail keratin tended to be different between healthy volunteers and patients, further detailed study is needed.

CaMKII regulates the strength of the epithelial barrier.

Epithelial cells define the boundary between the outside and the inside of our body by constructing the diffusion barrier. Tight junctions (TJs) of epithelial cells function as barriers against invasion of harmful microorganisms into the human body and free diffusion of water or ions from the body. Therefore, formation of TJs has to be strictly controlled in epithelial cells. However, the molecular mechanisms governing this regulation are largely unknown. In this study, we identified Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) as a regulator of the barrier function of TJs. CaMKII inhibition led to enlargement of TJ-areas and up-regulation of the barrier function. CaMKII inhibition induced excess TJ formation in part by the activation of AMP-activated protein kinase (AMPK) and subsequent phosphorylation of claudin-1. As up-regulation of epithelial barriers is essential for the prevention of chronic inflammatory diseases, the identification of CaMKII as a modulator of TJ function paves the way for the development of new drugs to treat these diseases.