Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis

Amitriptyline is a pleiotropic tricyclic antidepressant, which has anti-oxidant and anti-inflammatory properties. We tested whether amitriptyline might be useful in the treatment of chronic renal disease using the mouse model of unilateral ureteral obstruction. Amitriptyline caused a significant reduction of interstitial fibrosis, determined by Masson's staining, with minimal myofibroblast formation and macrophage infiltration following ureteral obstruction. Using quantitative PCR we found that this treatment significantly reduced the expression of key molecular markers of progressive tubulointerstitial injury such as osteopontin, MCP-1, ICAM-1, and TGF-beta 1 compared to their level in a saline-treated control group. Sublethal X-irradiation or mycophenolate mofetil, treatments that reduce inflammation, were comparable to amitriptyline in the reduction of interstitial fibrosis and macrophage infiltration. These studies in animals suggest that amitriptyline is worth testing as a therapeutic agent that might preserve renal function by blocking inflammation and renal fibrosis

The V109G polymorphism in the p27 gene is associated with endometriosis

Objective: To investigate the prevalence of the p27 gene polymorphism in women with endometriosis.Study design: Transversal case-control study. Genomic DNA was extracted from cells collected from buccal swabs. the p27 V109G polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Brazilian population.Results: We analysed the 104 patients and 109 control subjects. the distribution of genotype and allele frequencies of p27 V109G polymorphism was significantly different between the endometriosis cases and healthy women (p = 0.016 and 0.002). Women who had at least one mutated allele presented twofold chances for endometriosis development (OR = 1.9; 95% Cl, 1.120-3.343).Conclusion: the polymorphic variant at codon 109 of the p27 gene seems to be associated with higher risk of endometriosis development. (C) 2009 Elsevier Ireland Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Med, Dept Gynecol, Pelv Pain & Endometriosis Unit, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Gynecol, Pelv Pain & Endometriosis Unit, BR-04039032 São Paulo, BrazilFAPESP: 06.58214-2Web of Scienc