Low-dose intralesional injection of 5-fluorouracil and triamcinolone reduces tissue resident memory T cells in chronic eczema

BACKGROUND Tissue resident memory T(TRM)cells have been reported to play a significant role in the pathogenesis and relapse of chronic eczema.AIM To compare the efficacy and safety of the intralesional injection of 5-fluorouracil(5-FU)and triamcinolone(TA)with those associated with TA alone for the treatment of chronic eczema.METHODS A total of 168 patients were randomized to 5-FU+TA or TA groups and received a one-time intralesional injection of 5-FU+TA or TA only.Biopsies were collected before and 2 wk after treatment for evaluation of histopathological changes.All patients were followed up monthly for up to 1 year.RESULTS No serious adverse event was observed in either group.Although the mean atopic dermatitis severity index scores and effective rates were comparable between the two groups after 2 wk of treatment,the relapse rate was significantly lower in the 5-FU+TA group than in the TA group.Histological examination showed significantly fewer CD8^(+)and CD103^(+)T cells but not CD4^(+)T cells in the 5-FU+TA group.CONCLUSION One-time intralesional injection of 5-FU+TA is effective and safe for chronic eczema treatment and can further reduce the retention of T_(RM) cells in the lesional skin and the relapse rate of chronic eczema.

Pharmacological kinetics of BmK AS, a sodium channel site 4-specific modulator on Na_v1.3

Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations （10, 100, and 500 nmol/L）. Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.