Tolfenamic acid lowers the levels of the amyloid precursor protein (APP) and amyloid beta (Aβ) when administered to C57BL/6 mice by lowering their transcriptional regulator specificity protein 1 (SP1). To determine whether changes upstream in the amyloidogenic pathway that forms Aβ plaques would improve cognitive outcomes, we administered tolfenamic acid for 34 days to hemizygous R1.40 transgenic mice. Following the characterization of cognitive deficits in these mice, assessment of spatial learning and memory functions revealed that treatment with tolfenamic acid attenuated long-term memory and working memory deficits, determined using Morris water maze (MWM) and the Y-maze. These improvements occurred within a shorter period of exposure than that seen with clinically approved drugs. Cognitive enhancement was accompanied by reduction in the levels of the SP1 protein (but not mRNA), followed by lowering both the mRNA and protein levels of APP, and subsequent Aβ levels. These findings provide evidence that tolfenamic acid can disrupt the pathological processes associated with AD and are relevant to its scheduled biomarker study in AD patients.

No abstract

Purpose: Vision-threatening ocular inflammation can be a devastating complication of granulomatosis with polyangiitis (GPA). Here we performed a retrospective observational study to describe the safety and efficacy of treating scleritis and uveitis with either cyclophosphamide or rituximab in GPA. Methods: A chart review of patients diagnosed with GPA-associated scleritis or uveitis, treated with either cyclophosphamide or rituximab as the final therapy at our clinic, was conducted. A total of 1 year of follow-up visits was required for inclusion in the study. Results: Thirteen patients (19 eyes) suffering from GPA-associated scleritis and/or uveitis were identified. As the final therapy, rituximab was administered to 9 patients and cyclophosphamide to 4. Mean duration of follow-up was 55 months (range 16–23 months). Remission was observed in all patients. Three patients had a flare of scleritis after the completion of therapy, and they were restarted on their respective agents. One patient had a flare of retinal vasculitis during rituximab therapy. One patient on cyclophosphamide experienced transient leukopenia. No adverse side effects of rituximab were noted throughout the course of treatment. Conclusions: Cyclophosphamide and rituximab are safe and effective agents for controlling scleritis and uveitis associated with GPA, with eventual progression towards steroid-sparing remission.