Unexpected Formation and Potent Antioxidant Activity of Macrocyclic Dimers Containing Disulfide and Selenide Groups.

During attempts to prepare spirodithiaselenuranes as GPx mimetics, a series of unexpected dimeric macrocycles was obtained, each containing two selenide and two disulfide moieties in rings ranging from 18- to 26-membered. The products showed potent GPx-like activity in an NMR assay based on their ability to catalyze the reduction of hydrogen peroxide with benzyl thiol. The high catalytic activity was attributed to transannular effects during selenide to selenoxide oxidation. This redox process was also characterized by an induction period that indicated autocatalysis in the formation of an intermediate selenoxide from the oxidation of the corresponding selenide.

Clinical and serological analysis of patients with positive anticyclic citrullinated Peptide antibodies referred through a Rheumatology Central Triage System.

OBJECTIVE: Anticitrullinated protein antibodies (ACPA) are a highly specific and sensitive biomarker for the diagnosis of rheumatoid arthritis (RA). Some patients who were found to have a positive ACPA test were referred to our Rheumatology Central Triage (CT; Calgary, Alberta, Canada) for assessment by a rheumatologist. The objectives of our study were to determine the clinical accuracy of ACPA in establishing a diagnosis of RA in a real-time clinical setting. METHODS: Cases that met 3 criteria were included in the study: (1) referred to the CT over 3 calendar years (n = 20,389), (2) reason for referral was a positive ACPA test (n = 568), and (3) evaluated by a certified rheumatologist (n = 314). An administrative serological database was used to retrieve specific ACPA results. RESULTS: Of patients referred through our CT for evaluation of a positive ACPA test, 57.6% received a diagnosis of RA; the remainder had a variety of other diagnoses, some of which might be considered early RA (9%). The predictive values of ACPA for the diagnosis of RA were increased when rheumatoid factor (RF) results were included in the analysis. When definite and possible RA were combined and the prevalence of moderate/high ACPA was compared to all other individuals, the positive and negative predictive values for moderate/high ACPA for RA were 74.3% and 68.4%, respectively. CONCLUSION: About 58% of patients with a positive ACPA referred through a triage system for a rheumatologist opinion received a diagnosis of RA at their first visit. RF provides additional useful information to guide the diagnosis and urgency of referral.

Autoantibodies to Dense Fine Speckles in Pediatric Diseases and Controls.

OBJECTIVE: Autoantibodies to the dense fine speckled 70 kDa antigen (DFS70) are reported to be more common in individuals who do not have an antinuclear antibody (ANA)-associated rheumatic disease (AARD) than in patients with AARD. The frequency of anti-DFS70 antibodies has been thoroughly studied in adult but not in pediatric populations. The primary objective of this observational study was to determine the frequency of anti-DFS70 in pediatric AARD and reference cohorts. METHODS: Sera from 743 children with AARD and related conditions, and 345 samples from reference cohorts (healthy children and those being investigated for AARD) were studied for anti-DFS70 autoantibodies as measured by a chemiluminescence immunoassay. A de-identified administrative database was used to retrieve demographic, serologic, and clinical data. RESULTS: Anti-DFS70 antibodies were seen in 2.1% of healthy children and in 4.5% of sera from pediatric individuals referred for ANA testing. The frequency of anti-DFS70 was highest in juvenile localized scleroderma (LS; 4/29, 13.8%), juvenile dermatomyositis (JDM; 2/11, 18.2%), childhood systemic lupus erythematosus (cSLE; 19/331, 5.7%), diffuse cutaneous systemic sclerosis (1/22, 4.5%), celiac disease (2/49, 4.1%), and juvenile idiopathic arthritis (JIA; 5/202, 2.5%). Of note, anti-DFS70 antibodies were observed in 3/26 children (11.5%) with uveitis and JIA-associated uveitis. CONCLUSION: The frequency of anti-DFS70 autoantibodies in healthy pediatric subjects is within the lower range of that reported in adults. Anti-DFS70 antibodies can be found in childhood SSc and cSLE, but has a remarkably high frequency in children with LS, JDM, and uveitis.