IntroductionIn this study, we aimed to investigate ultrasonographic (US) changes suggestive of gouty arthritis in the hyaline cartilage, joints and tendons from asymptomatic individuals with hyperuricemia.MethodsWe conducted a cross-sectional, controlled study including US examinations of the knees and first metatarsal-phalangeal joints (first MTPJs), as well as of the tendons and enthesis of the lower limbs. Differences were estimated by χ2 or unpaired t-tests as appropriate. Associations were calculated using the Spearman's correlation coefficient rank test.ResultsFifty asymptomatic individuals with hyperuricemia and 52 normouricemic subjects were included. Hyperechoic enhancement of the superficial margin of the hyaline cartilage (double contour sign) was found in 25% of the first MTPJs from hyperuricemic individuals, in contrast to none in the control group (P < 0.0001). Similar results were found on the femoral cartilage (17% versus 0; P < 0.0001). Patellar enthesopathy (12% versus 2.9%; P = 0.01) and tophi (6% versus 0; P = 0.01) as well as Achilles enthesopathy (15% versus 1.9%; P = 0.0007) were more frequent in hyperuricemic than in normouricemic individuals. Intra-articular tophi were found in eight hyperuricemic individuals but in none of the normouricemic subjects (P = 0.003).ConclusionsThese data demonstrate that morphostructural changes suggestive of gouty arthritis induced by chronic hyperuricemia frequently occur in both intra- and extra-articular structures of clinically asymptomatic individuals.

ObjectiveTo develop ultrasound (US) definitions and a US novel scoring system for major salivary gland (SG) lesions in patients with primary Sjögren’s syndrome (pSS) and to test their intrareader and inter-reader reliability using US video clips.MethodsTwenty-five rheumatologists were subjected to a three-round, web-based Delphi process in order to agree on (1) definitions and scanning procedure of salivary gland ultrasonography (SGUS): parotid, submandibular and sublingual glands (PG, SMG and SLG); (2) definitions for the elementary SGUS lesions in patients with Sjögren’s syndrome; (3) scoring system for grading changes. The experts rated the statements on a 1–5 Likert scale. In the second step, SGUS video clips of patients with pSS and non-pSS sicca cases were collected containing various spectrums of disease severity followed by an intrareader and inter-reader reliability exercise. Each video clip was evaluated according to the agreed definitions.ResultsConsensual definitions were developed after three Delphi rounds. Among the three selected SGs, US assessment of PGs and SMGs was agreed on. Agreement was reached to score only greyscale lesions and to focus on anechoic/hypoechoic foci in a semiquantitative matter or, if not possible on a qualitatively (present/absent) evaluation of fatty or fibrous lesions. Intrareader reliability for detecting and scoring these lesions was excellent (Cohen’s kappa 0.81) and inter-reader reliability was good (Light’s kappa 0.66).ConclusionNew definitions for developing a novel semiquantitative US score in patients with pSS were developed and tested on video clips. Inter-reader and intrareader reliabilities were good and excellent, respectively.

BackgroundGout is the most common inflammatory arthropathy of metabolic origin and it is characterized by intense inflammation, the underlying mechanisms of which are unknown. The aim of this study was to evaluate the oxidative stress in human fibroblast-like synoviocytes (FLS) exposed to monosodium urate (MSU) crystals, which trigger an inflammatory process.MethodsHuman FLS isolated from synovial tissue explants were stimulated with MSU crystals (75 μg/mL) for 24 h. Cellular viability was evaluated by crystal violet staining, apoptosis was assessed using Annexin V, and the cellular content of reactive oxygen species (ROS) and nitrogen species (RNS) (O2-, H2O2, NO) was assessed with image-based cytometry and fluorometric methods. In order to determine protein oxidation levels, protein carbonyls were detected through oxyblot analysis, and cell ultrastructural changes were assessed by transmission electron microscopy.ResultsThe viability of FLS exposed to MSU crystals decreased by 30 % (P < 0.05), while apoptosis increased by 42 % (P = 0.01). FLS stimulated with MSU crystals exhibited a 2.1-fold increase in H2O2 content and a 1.5-fold increase in O2- and NO levels. Oxyblots revealed that the spots obtained from FLS protein lysates exposed to MSU crystals exhibited protein carbonyl immunoreactivity, which reflects the presence of oxidatively modified proteins. Concomitantly, MSU crystals triggered the induction of changes in the morphostructure of FLS, such as the thickening and discontinuity of the endoplasmic reticulum, and the formation of vacuoles and misfolded glycoproteins.ConclusionsOur results prove that MSU crystals induce the release of ROS and RNS in FLS, subsequently oxidizing proteins and altering the cellular oxidative state of the endoplasmic reticulum, which results in FLS apoptosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1012-3) contains supplementary material, which is available to authorized users.

Dedicated to Professor Julio Delgado Martín on the occasion of his 70th birthdayAllenes [1] are useful reagents for the [2+2] cycloaddition reaction, [2] which is a powerful process for the synthesis of cyclobutanes. This carbocyclic motif is present in bioactive compounds [3] and has unique reactivity. [4] Gold catalysis triggers the functionalization of allenes [5] and assists several intramolecular allenene reactions [6] which allow the preparation of bicyclic frames that contain cyclobutane motifs. [7] The gold-catalyzed enantioselective intramolecular [2+2] reaction of allenenes has been recently accomplished. [7b, 8] Moreover, racemic versions of related intermolecular processes have been disclosed. [9] An enantioselective version is highly desirable as it would provide a yet unknown and straightforward entry into optically active cyclobutanes from readily available allenamides and alkenes, in a sole synthetic operation. We are pleased to report herein the first asymmetric gold-catalyzed intermolecular allenene[2+2] cycloaddition.At the start of this study, previous work on the goldcatalyzed cyclization of allenamides and alkenes supported a stepwise reaction (Scheme 1). [9] The activation of the allene Scheme 1. Gold-catalyzed [2+2] intermolecular allene-alkene cycloaddition.Scheme 2. Ligands for the intermolecular [2+2] gold(I)-catalyzed enantioselective cycloaddition of the allenamide 1 a and styrene 2 a. Tf = trifluoromethanesulfonyl, Ts = 4-toluenesulfonyl.

Detection of normal findings (i.e., grading of physiological ossification during skeletal maturation and identification of physiological vessels) can be highly reliable by using clear definitions and a standardized acquisition protocol. These data will permit development of a reliable and standardized US approach for evaluating paediatric joint pathologies. This article is protected by copyright. All rights reserved.