Oestradiol enhances in vitro the histamine release induced by embryonic histamine-releasing factor (EHRF) from uterine mast cells

The relationship between maternal hormones and factors secreted by the implanting embryo is still controversial. We have analysed the in-vitro effect of oestradiol and human embryo-derived histamine-releasing factor (EHRF) on histamine release from rat uterine mast cells. Rat uterine mast cells which were preincubated with oestradiol and then challenged with human EHRF gave histamine release values two- to threefold higher than those without preincubation. The enhancement observed was time- and temperature-dependent. A similar enhancement was obtained with human sensitized basophils but not with rat peritoneal mast cells. Oestradiol, used as a direct challenge, did not induce any histamine release from either rat uterine or peritoneal mast cells, or from human sensitized basophils. Oestradiol preincubation also enhanced the histamine release induced by anti-IgE but did not enhance the histamine release induced by substance P or compound 48/80, two secretagogues that are not mediated by IgE. Moreover, uterine fragments derived from rats at various oestrus phases, with different amounts of endogenous oestrogen, were challenged in vitro with EHRF. The release of histamine by mast cells was higher at the proestrus and preimplantation phases than at dioestrus. All these findings suggest that the interaction of oestradiol with rat uterine mast cells was capable of enhancing in vitro the histamine releasing effect of EHR

Secukinumab for the treatment of palmoplantar psoriasis: a 2-year, multicenter, real-life observational study

Background Palmoplantar psoriasis is difficult to treat and often recalcitrant to conventional therapies. Clinical trials have demonstrated the efficacy and safety of secukinumab for this debilitating psoriasis form, but real-life evidence is currently limited. Therefore, here we described the outcomes of patients treated with secukinumab in clinical practice. Research Design and Methods This was a real-life, retrospective, observational study involving patients with palmoplantar psoriasis treated with secukinumab (300 mg, subcutaneously) at seven dermatologic clinics in Italy. Treatment effectiveness was evaluated based on the changes of the Psoriasis Area and Severity Index (PASI) and palmoplantar (pp) PASI during treatment and by recording safety and tolerability issues over 104 weeks. Results Forty-three patients initiated treatment with secukinumab. Previous treatments included topical and systemic therapies; half of patients had already tried one or more biologics. Secukinumab improved mean PASI rapidly and substantially with a 78.2% decrease at 16 weeks. Mean ppPASI also improved substantially, but more gradually, with reductions of 55.0% and 79.3% at 16 and 104 weeks, respectively. Approximately half of patients achieved complete skin clearance at 40 weeks. Secukinumab was well tolerated and no relevant treatment-related adverse events were reported. Conclusions Secukinumab appears to be effective for the treatment of palmoplantar psoriasis also in the real-life setting