Superficial cell desquamation followed by differentiation of newly exposed superficial cells induces regeneration of the urinary bladder epithelium, urothelium. In the present work, chitosan was evaluated as a new inducer of urothelial cell desquamation, in order to study the regeneration of mouse urothelial cells in vivo. Intravesical application of chitosan dispersion caused complete removal of only the superficial layer of cells within 20 min of treatment. Differentiation of the new superficial layer was followed by the appearance and distribution of three urothelial differentiation markers, tight junction protein ZO1, cytokeratin 20 and the maturation of the apical plasma membrane. The arrangement of ZO1 into continuous lines in individual cells of the intermediate layer was already found after 10 min of chitosan application, when desquamation had just started. The appearance of the apical membrane changed from microvillar to typically scalloped within 20 min of regeneration, while complete arrangement of the cytokeratin 20 network took 60 min. These findings provide a new perspective on the rate of the differentiation process in the urothelium and make chitosan a new and a very controllable tool for studies on urothelial regeneration.
Background: Several factors have been shown to affect psoriasis pathogenesis, clinical presentation and treatment response. Objectives: The aim of this study was to investigate the potential relationship between patients’ baseline characteristics and the efficacy of calcipotriol-betamethasone ointment in patients with mild to moderate plaque psoriasis and to evaluate whether the efficacy is consistent across subgroups. Method: Using data from the therapeutic equivalence study on patients with plaque psoriasis, post hoc analyses were performed to evaluate the impact of baseline demographic and disease characteristics, habits and comorbidities on the response to treatment with calcipotriol-betamethasone ointment. Results: Body mass index (BMI) and obesity were each independently associated (univariate analysis, p < 0.05) with reduction in modified Psoriasis Area and Severity Index (mPASI) and PASI75 (≥75% improvement in mPASI from baseline). Increased body weight is more common in patients with late-onset psoriasis. There was a significant trend for lower response rates with increasing BMI (p = 0.007) and obesity (p = 0.003). The odds of achieving PASI75 is 2.3 times lower for obese compared to normal-weight subjects.If patients with obesity or hypertension were treated with calcipotriol-betamethasone, they were still more likely to achieve PASI75 after 4-week treatment compared to vehicle (p < 0.001). Conclusion: Increased BMI and obesity present risk factors for reduced treatment effectiveness. Importantly, the efficacy of calcipotriol-betamethasone ointment was consistent in all subgroups.
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