Sonographic Tophi and Inflammation Are Associated With Carotid Atheroma Plaques in Gout

Objective: Gout and cardiovascular disease are closely related, but the mechanism connecting them remains unknown. This study aims to explore whether urate crystal deposits and inflammation (assessed by ultrasound) are associated with carotid atherosclerosis.Methods: We included consecutive patients with crystal-proven gout newly presenting to a tertiary rheumatology unit. Patients under urate-lowering treatment were excluded. Ultrasound assessment was performed during intercritical periods. Musculoskeletal scans evaluated six joints and four tendons for urate crystal deposits (double contour, aggregates, and tophi), and power Doppler (PD) signal (graded 0–3) as a marker of local inflammation. The sum of locations showing deposits or a positive PD signal (≥1) was registered. Carotids were scanned for increased intima-media thickness (IMT) and atheroma plaques, according to the Mannheim consensus. Associations were analyzed using logistic regression.Results: The study included 103 patients showing sonographic crystal deposits at the examined locations (mean sum 9.9, minimum 2); tophi were the most frequent. Two-thirds of participants presented a positive PD signal (30.1% grade 2–3). In the carotid scans, 59.2% of participants showed atheroma plaques, and 33.0% increased IMT. Tophi (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.03–1.50) and a positive PD signal (OR 1.67; 95% CI 1.09–2.56) were significantly associated with atheroma plaques, while an increased IMT showed no sonographic association.Conclusion: Sonographic crystal deposits and subclinical inflammation were consistently observed in patients with intercritical gout. Tophi and a positive PD signal were linked to carotid atherosclerosis. Our findings may contribute to understanding the complex relationship between gout and atherosclerosis.

Galectin-9 Regulates Monosodium Urate Crystal-Induced Gouty Inflammation Through the Modulation of Treg/Th17 Ratio

Gout is caused by depositing monosodium urate (MSU) crystals within the articular area. The infiltration of neutrophils and monocytes drives the initial inflammatory response followed by lymphocytes. Interestingly, emerging evidence supports the view that in situ imbalance of T helper 17 cells (Th17)/regulatory T cells (Treg) impacts the subsequent damage to target tissues. Galectin-9 (Gal-9) is a modulator of innate and adaptive immunity with both pro- and anti-inflammatory functions, dependent upon its expression and cellular location. However, the specific cellular and molecular mechanisms by which Gal-9 modulates the inflammatory response in the onset and progression of gouty arthritis has yet to be elucidated. In this study, we sought to comprehensively characterise the functional role of exogenous Gal-9 in an in vivo model of MSU crystal-induced gouty inflammation by monitoring in situ neutrophils, monocytes and Th17/Treg recruited phenotypes and related cyto-chemokines profile. Treatment with Gal-9 revealed a dose-dependent reduction in joint inflammation scores, knee joint oedema and expression of different pro-inflammatory cyto-chemokines. Furthermore, flow cytometry analysis highlighted a significant modulation of infiltrating inflammatory monocytes (CD11b+/CD115+/LY6-Chi) and Th17 (CD4+/IL-17+)/Treg (CD4+/CD25+/FOXP-3+) cells following Gal-9 treatment. Collectively the results presented in this study indicate that the administration of Gal-9 could provide a new therapeutic strategy for preventing tissue damage in gouty arthritic inflammation and, possibly, in other inflammatory-based diseases.

In situ Synthesized Monosodium Urate Crystal Enhances Endometrium Decidualization via Sterile Inflammation During Pregnancy

High level of uric acid (UA) is the major origin of gout, and is highly associated with various pregnant complications, such as preeclampsia and gestational diabetes. However, UA’s level and role in the very early stage of pregnancy has not been uncovered. This study aims to investigate the relevance of serum UA and decidualization, an essential process for the establishment and maintenance of pregnancy in women and mice during the early stage of pregnancy. In this study, we first proved that expression level of UA synthase xanthine dehydrogenase (XDH) is highly increased along with decidualization of endometrial stromal cells in both in vitro and in vivo models. Furthermore, serum and endometrial levels of UA are higher in mice with decidualized uterin horn and in vitro decidualized stromal cells. The existence of monosodium urate (MSU) crystal was also confirmed by immunostaining. Next, the roles of MSU on decidualization were explored by both in vitro and in vivo models. Our data shows MSU crystal but not UA enhances the decidualization response of endometrial stromal cells, via the upregulation of inflammatory genes such Ptgs2 and Il11. inhibiting of Cox-2 activity abolishes MSU crystal induced higher expression of decidualization marker Prl8a2. At last, in women, we observed enriched expression of XDH in decidua compare to non-decidualized endometrium, the serum level of UA is significantly increased in women in very early stage of pregnancy, and drop down after elective abortion. In summary, we observed an increased serum UA level in the early stage of women’s pregnancy, and proved that the increased level of UA results from the expressed XDH in decidualizing endometrium of both human and mouse, leading to the formation of MSU crystal. MSU crystal can enhance the decidualization response via inflammatory pathways. Our study has uncovered the association between UA, MSU, and decidualization during the early stage of pregnancy.

Use of ammonium chloride to prevent urolithiasis in sheep

ABSTRACT Urolithiasis has a high incidence among confined sheep. It is multifactorial and may cause economic damage. Our aim was to determine the capacity of urinary acidification using ammonium chloride in sheep. Twenty-five 3-month-old male sheep were confined and randomly divided into three groups; the G200 and G500 groups received 200mg/kg/GW and 500mg/kg/GW of ammonium chloride daily for 56 consecutive days, respectively, whereas the CG group did not receive ammonium chloride. Sampling times and clinical evaluation were performed weekly, starting from the 14th day of confinement (M1 or immediately before administering ammonium chloride) until the 17th day (M9) of the feedlot. Hemogasometry, biochemical examination of serum urea and creatinine concentration and ultrasound evaluation of the urinary tract were performed. The urinalysis indicated a higher incidence of ammonium magnesium phosphate crystals at the beginning of the study, showing a migration to urate crystal formation, mainly in the G500 group because of urinary acidification. No hemogasometric, serum biochemistry, ruminal fluid, or ultrasonographic changes were observed. Urinary acidification was achieved and maintained after M7 during the administration of ammonium chloride in the G500 group, but not in the other study groups.