BALB/c-Fcgr2b−/−Pdcd1−/− mouse expressing anti-urothelial antibody is a novel model of autoimmune cystitis

We report the impact of anti-urothelial autoantibody (AUAb) on urinary bladder phenotype in BALB/c mice deficient of the FcγRIIb and PD-1. AUAb was present in serum samples from approximately half of the double-knockout (DKO) mice, as detected by immunofluorescence and immunoblots for urothelial proteins including uroplakin IIIa. The AUAb-positive DKO mice showed degeneration of urothelial plaque and umbrella cells, along with infiltration of inflammatory cells in the suburothelial layer. TNFα and IL-1β were upregulated in the bladder and the urine of AUAb-positive DKO mice. Voiding behavior of mice was analyzed by the Voided Stain on Paper method. 10-week-old and older AUAb-positive DKO mice voided significantly less urine per void than did wild type (WT) mice. Furthermore, administration of the AUAb-containing serum to WT mice significantly reduced their urine volume per void. In summary, this report presents a novel comprehensive mouse model of autoimmune cystitis

Amantadine for Dyskinesias in Parkinson's Disease: A Randomized Controlled Trial

BACKGROUND: Dyskinesias are some of the major motor complications that impair quality of life for patients with Parkinson's disease. The purpose of the present study was to investigate the efficacy of amantadine in Parkinson's disease patients suffering from dyskinesias. METHODS: In this multi-center, double-blind, randomized, placebo-controlled, cross-over trial, 36 patients with Parkinson's disease and dyskinesias were randomized, and 62 interventions, which included amantadine (300 mg/day) or placebo treatment for 27 days, were analyzed. At 15 days after washout, the treatments were crossed over. The primary outcome measure was the changes in the Rush Dyskinesia Rating Scale (RDRS) during each treatment period. The secondary outcome measures were changes in the Unified Parkinson's Disease Rating Scale part IVa (UPDRS-IVa, dyskinesias), part IVb (motor fluctuations), and part III (motor function). RESULTS: RDRS improved in 64% and 16% of patients treated with amantadine or placebo, respectively, with significant differences between treatments. The adjusted odds-ratio for improvement by amantadine was 6.7 (95% confidence interval, 1.4 to 31.5). UPDRS-IVa was improved to a significantly greater degree in amantadine-treated patients [mean (SD) of 1.83 (1.56)] compared with placebo-treated patients [0.03 (1.51)]. However, there were no significant effects on UPDRS-IVb or III scores. CONCLUSIONS: Results from the present study demonstrated that amantadine exhibited efficacious effects against dyskinesias in 60-70% of patients. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000000780