Performance of Ultrasound in the Clinical Evaluation of Gout and Hyperuricemia.

OBJECTIVE: To evaluate monosodium urate (MSU) crystal deposition and related lesions in the joints of patients with gout and hyperuricemia (HUA) using ultrasound. To explore the association between ultrasound findings and clinical features in gout and HUA. METHODS: A total of 202 patients with gout and 43 asymptomatic patients with HUA were included. The clinical data and ultrasonic assessment results were collected and statistically analyzed. RESULTS: Deposition of MSU crystals was found in 25.58% (11/43) of patients with asymptomatic HUA and 76.24% (154/202) of patients with gout. Of the 1,082 joints from patients with gout examined, 33.09% (358/1082) displayed MSU crystal deposition. In the joints with MSU crystal deposition, 77.37% (277/358) had a history of attacks. Among the joints of gouty arthritis, double contour sign (DCS), hyperechoic aggregate (HAG), and tophi were found in 32.65% (159/487), 7.80% (38/487), and 24.64% (120/487) of the joints, respectively. DCS and tophi, but not HAG, increasingly appeared with the extension of gout duration. In patients with more than 15 years of gout history, DCS, Tophi, and HAG were found in 48.18%, 40.00%, and 6.36% of US assessed joints, respectively. In patients with gout, synovial lesion and bone erosion were found in 17.74% (192/1082) and 7.58% (82/1082) of joints, respectively. The synovial lesion was related to HAG, while bone erosion was related to tophi and DCS. Nephrolithiasis was detected in 20.30% (41/202) of patients with gout and 4.65% (2/43) of HUA patients, indicating that nephrolithiasis occurred in more patients with gout than in patients with HUA. CONCLUSION: HAG is an early performance of MSU crystal deposition in joints of gout and HUA. Both DCS and tophi are risk factors for bone erosion. Early urate-lowering therapy (ULT) should be considered in patients with gout, DCS, or tophi.

Ultrasound assessment of skin thickness and stiffness: the correlation with histology and clinical score in systemic sclerosis.

BACKGROUND: Ultrasound is a useful tool to evaluate and quantify skin lesions. Few studies have assessed the criterion validity of skin ultrasound in systemic sclerosis (SSc). The aims of the study were to investigate skin thickness and stiffness using ultrasound and shear wave elastography (SWE) in SSc and to validate skin ultrasound measurements against histological skin thickness. METHODS: A total of 22 patients with diffuse cutaneous SSc (dcSSc), 22 with limited cutaneous SSc (lcSSc), and 22 age- and gender-matched healthy controls were enrolled. Skin thickness and stiffness were measured by B-mode ultrasound with SWE imaging on the bilateral fingers and hands. Additional ultrasound evaluation was carried out in 13 patients (9 dcSSc and 4 lcSSc) on their dorsal forearms, followed by skin biopsy conducted in the same skin areas. Correlations between ultrasound measurements and histological skin thickness and modified Rodnan skin score (mRSS) were investigated using Spearman's correlation. RESULTS: Compared with controls, ultrasound-measured skin thickness and skin stiffness were significantly higher in patients with SSc (p < 0.001) and even higher in those with dcSSc. No clear correlation could be established between ultrasound-determined skin thickness and stiffness at the same site. Ultrasound-measured skin thickness correlated well with histological skin thickness (r = 0.6926, p = 0.009). A weaker association was also observed between histological skin thickness and local mRSS (r = 0.5867, p = 0.050). CONCLUSIONS: Ultrasound is a reliable tool for quantifying skin involvement in SSc. Ultrasound-measured skin thickness showed good agreement with histological skin thickness.

Renal excretion is a cause of decreased serum uric acid during acute gout.

AIMS: To evaluate the fluctuation of serum uric acid (SUA) during acute gout (AG) and explore its potential mechanisms. METHODS: Data such as SUA, urinary uric acid and 24-hour uric acid urinary excretion were collected from 126 patients diagnosed with gout and were analyzed. RESULTS: Serum uric acid was negatively correlated with age in gout patients, and significantly elevated in patients aged ≤50 years. Twenty-four-hour uric acid urinary excretion was affected by SUA, creatinine clearance, age, body mass index and urine volume. In contrast, clearance of uric acid and fractional excretion of uric acid (FEur) were more stable. SUA was significantly downregulated during acute attacks. Of the AG patients, 34.92% had detected SUA <420 µmol/L. Clearance of uric acid and FEur were notably increased in patients during acute attacks, especially in patients with SUA <420 µmol/L. CONCLUSION: This study demonstrated that the level of SUA was remarkably upregulated in young gout patients. Therefore, early onset of gout should be considered of great importance. SUA was downregulated during acute gouty arthritis, which might be associated with increased urinary excretion of uric acid.

BANK1 alters B cell responses and influences the interactions between B cells and induced T regulatory cells in mice with collagen-induced arthritis.

BACKGROUND: Functional variants of the B cell gene, B cell scaffold protein with ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility, but their influences on B cell responses are unclear. Moreover, the function of induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen-induced arthritis (CIA) model is unknown. This study was performed to investigate the roles of BANK1 in CIA and the interaction between B cells and iTregs. METHODS: The changes in BANK1 mRNA and protein levels and their correlation with disease severity in CIA were determined. Next, the antigen-presenting function and autoantibody production in B cells were evaluated by co-culture with effector T cells and iTregs, respectively, both in vitro and in vivo. Then, the mechanisms underlying these interactions were studied by adding neutralizing antibodies or transwell inserts and by adoptive transfer to B-cell-depleted CIA mice. RESULTS: The BANK1 level decreased in the peripheral blood, spleen and lymph nodes of CIA mice, particularly during the acute stage of arthritis, and exhibited negative correlation with disease severity and autoantibody production. B cell responses were enhanced by this decrease. B cells from CIA mice (CIA-B cells) promoted iTreg differentiation, proliferation and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) expression. Meanwhile, BANK1 expression in CIA-B cells increased after co-culture with iTregs, limiting B cell responses. All these interactions depended on cell contact with CTLA-4-overexpressing iTregs but were independent of CTLA-4 cytokine. CONCLUSION: Decreased BANK1 expression promotes B cell responses, resulting in an increased antigen presentation ability and autoantibody production that subsequently influences the communication between B cells and iTregs through a cell-contact-dependent and CTLA-4- cytokine-independent mechanism in CIA mice.

Sirt1 ameliorates systemic sclerosis by targeting the mTOR pathway.

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation and fibrosis. Our previous research has indicated that Sirtuin1 (Sirt1) plays a role in the regulation of TNF-α-induced inflammation; however, whether Sirt1 may inhibit the progress of SSc by blocking inflammation remains unknown. OBJECTIVE: We aimed to investigate the function of Sirt1 in SSc. METHODS: The function and its mechanism of Sirt1 were evaluated in fibroblasts or scleroderma mice. The expression of Sirt1 and cytokines was analyzed using real-time PCR, western blot, ELISA and immunohistochemistry. RESULTS: We determined that fibroblasts of SSc patients were activated to exhibit inflammation. Sirt1, activated by resveratrol (Res), ameliorated cutaneous inflammation and fibrosis in bleomycin (BLM)-induced scleroderma mice. An improvement in mammalian target of rapamycin (mTOR) was identified in the fibroblasts of SSc patients and the skin lesions of BLM mice. Rapamycin, an mTOR specific inhibitor, substantially inhibited the induced inflammation and fibrosis. The enhancement of mTOR expression in the skin lesions of the BLM-treated mice was significantly inhibited by Sirt1 activation. However, in both the BLM-treated cells and mice, Res exerted an inhibitory function on the expression of inflammatory factors, and collagen was diminished following mTOR knockdown. These findings suggest that Res may inhibit inflammation and fibrosis via mTOR. CONCLUSION: The modulation of Sirt1 activity may represent a potential therapeutic method for SSc. The mechanism may involve the inhibition of mTOR phosphorylation, whereas mTOR activity was shown to be a pathogenic culprit of SSc.

New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions.

OBJECTIVES: New interleukins (ILs), especially members of IL-1 and IL-12 families, have recently been reported to be involved in the development and regulation of autoimmune and inflammatory diseases. In this study, we aimed to explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis (PsA). METHODS: Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs) were recruited. Blood samples were obtained for detecting the levels of ILs, IL-12/23p40, and tumor necrosis factor α (TNF-α). The severity of skin lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and receptor activator of nuclear factor-κB ligand) and numbers of osteoclast precursors were evaluated. Radiographic features of affected joints in these patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Correlations among levels of these ILs, Ps, and PsA disease activities and bone erosions were studied. RESULTS: Ps and PsA patients had higher serum levels of TNF-α, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had higher serum levels of IL-36α and IL-38 than patients with Ps vulgaris or HCs. Increased serum levels of IL-36α were positively correlated with PASI. CONCLUSION: Certain ILs were elevated in the circulation of patients with Ps and PsA, which might contribute to the pathogenesis of skin lesions and arthritis.

The effect of resveratrol on the recurrent attacks of gouty arthritis.

Gouty arthritis is characterized by inflammation induced by monosodium urate (MSU) crystal deposition, which is resulted by an increase of serum urate concentration. The management of gout, especially the recurrent acute attacks of chronic gouty arthritis, is still a problem to be resolved. In this study, we aimed to develop the preventive and therapeutic effect of resveratrol on gouty arthritis. MSU was used to induce gouty arthritis in the foot pad of C57BL/6 mice. Yeast polysaccharide and potassium oxonate were used to induce hyperuricemia in Kunming mice. Resveratrol was intraperitoneal injected to the mice in the treatment group. The pad inflammation and the level of serum uric acid were investigated to estimate the effect of resveratrol in gouty arthritis. Hyperuricemia was significantly detected in the mice treated with yeast polysaccharide and potassium oxonate, and gouty arthritis was successfully induced with MSU in mice. We further identified that resveratrol inhibited pad swelling and pad 99mTc uptake in gouty mice. Moreover, serum uric acid level was also decreased by resveratrol in hyperuricemia mice. This study highlighted that resveratrol might be applied to prevent the recurrent acute attack of gouty arthritis because of its inhibition of articular inflammation and down-regulation of serum uric acid.

Role of the NLRP3 inflammasome in the transient release of IL-1ß induced by monosodium urate crystals in human fibroblast-like synoviocytes.

BACKGROUND: To investigate whether monosodium urate (MSU) crystals induce interleukin (IL)-1ß in human fibroblast-like synoviocytes (FLS), and whether the NLRP3 inflammasome is involved in the inflammatory mechanism. METHODS: Human FLS isolated from explants of synovial tissue were stimulated with MSU crystals (0.001 to 0.5 mg/ml) for different time course (6 hours to 48 hours). The expressions of IL-1ß, IL-6, TNF-α and NLRP3 were evaluated with ELISA, Western blot and quantitative real-time PCR. RESULTS: Exposure of FLS to MSU crystals transiently induced a significant increase in IL-1ß expression in culture medium with a peak at 6 h. The mRNA level of IL-1ß in the FLS cells had a similar pattern at this time point. Changes in IL-6 and TNF-α expression were not observed. Simultaneously, intercellular pro-IL-1ß was detected at 6 h. Furthermore, MSU crystals also induced NLRP3 mRNA and protein expression at 6 h to 48 h after MSU treatment. CONCLUSIONS: MSU crystals directly increased IL-1ß and intercellular NLRP3 expression in FLS cells. It is suggested that the NLRP3 inflammasome may be associated with IL-1ß in FLS treated with MSU. Altogether, MSU could induce production and release of IL-1ß through the NLRP3 inflammasome in human synoviocytes.

The effect of resveratrol on the recurrent attacks of gouty arthritis.

Gouty arthritis is characterized by inflammation induced by monosodium urate crystal (MSU) deposition, which is resulted by increase of serum urate concentration. The management of gout, especially the recurrent attacks of chronic gouty arthritis, is still a problem to be resolved. In this study, we aimed to develop the preventive and therapeutic effects of resveratrol on gouty arthritis. Monosodium urate crystal (MSU) was used to induce gouty arthritis in foot pad of C57BL/6 mice. Yeast polysaccharide and potassium oxonate were used to induce hyperuricemia in Kunming mice. Resveratrol was intraperitoneally injected to the mice in the treatment group. Article inflammation and serum uric acid level were investigated to estimate the effect of resveratrol in gout. Yeast polysaccharide and potassium oxonate were used to induce hyperuricemia in mice, and MSU to induce gouty arthritis. We identified that resveratrol inhibited foot swelling and inflammation-associated 99mTc uptake in gouty mice. Moreover, serum uric acid level was also decreased by resveratrol in hyperuricemia mice. This study highlighted that resveratrol might be applied to prevent the recurrent attack of gouty arthritis because of its inhibition of articular inflammation and down-regulation of serum uric acid.

T follicular helper cells and regulatory B cells dynamics in systemic lupus erythematosus.

T follicular helper (Tfh) cells aid effector B cells, and augment autoimmunity, whereas the role of Tfh cells on regulatory B (Breg) cells in systemic lupus erythematosus (SLE) is not known. The aim of this study is to investigate the percentage of Breg cells in SLE, and the role of Tfh cells on Breg cells. First, we demonstrated the presence of Breg cells in SLE peripheral blood mononuclear cells and in involved skins. Both the percentage of circulating Breg cells and the ability to produce interleukin-10 (IL-10) were elevated in SLE patients. The percentage of Breg cells increased during SLE flares and decreased following disease remission. Second, Tfh cell expansion was not only related to autoantibody production but also correlated with the increased percentage of Breg cells. Third, in vitro studies revealed that Tfh cell-derived IL-21 could promote IL-10 production and Breg cell differentiation. In conclusions, these data imply that SLE flares may be linked to the expansion of Tfh cells and that Breg cells are increased in a regulatory feedback manner. Thus, SLE development may be associated with the complex regulation of Tfh cells and diverse B cell subsets.

[Comprehensive analysis on variation of cardiac enzyme and troponin induced by acute organophosphorous poisoning].

OBJECTIVE: To discuss the diagnostic value of cardiac enzyme and troponin in acute organophosphorus pesticide poisoning (AOPP). METHODS: A retrospective study was performed in the document published in domestic journals and PubMed from 1979 to 2010. The data of the cardiac enzyme and troponin were collected. Statistical analysis was conducted with one-way ANOVA and rank sum test. 2129 cases with AOPP were enrolled. RESULTS: The levels of creatine kinase (CK), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) in milder, moderate and severe poisoning groups were significantly elevated compared by the healthy control group (P < 0.05). The differences were also dramatic among three patients groups (P < 0.05). The ratios of CK-MB to CK in both moderate and severe groups were significantly lower than in healthy controls (P < 0.05). The levels of CK, CK-MB and cTnI were higher especially in patients with intermediate myasthenic syndrome (IMS) than patients without IMS. Meanwhile, the levels of CK and CK-MB were elevated in patients with respiratory failure compared by non-failure ones, but decreased in the ratios of CK-MB to CK (P < 0.05). CONCLUSIONS: The elevation of CK and CK-MB in serum could not be judged as the criteria of myocardial damage in AOPP, the ratio of CK-MB to CK were more valuable; the value of cTnI in myocardial damage was still in suspect. CK, CK-MB and cTnI could be used as auxiliary criteria of AOPP classification.

[Meta-analysis of the effectiveness of plasma exchange in treatment of severe and acute organophosphate poisoning].

OBJECTIVE: To discuss the effectiveness of severe and acute organophosphate poisoning (AOPP) treated with plasma exchange in China. METHODS: Researches about effectiveness of severe AOPP treated with plasma exchange were analyzed by Review Manager 4.2 and fixed effect model of meta-analysis method were used. RESULTS: Six trials including 433 patients were identified. Treatment group including 211 patients adopted traditional physician therapy plus plasma exchange, and control group including 222 patients received physician therapy only. The case-fatality rate of the treatment group was lower than the control one [RR=0.30, 95%CI (0.19-0.49), P<0.01]. CONCLUSION: Plasma exchange can improve the cure rate of severe AOPP.

[Different therapeutic efficacy of pralidoxime chloride PAM-Cl on AChE against acute toxicity of methamidophos, dichlorvos and omethoate].

OBJECTIVE: To observe the treatments on the patients with acute methamidophos dichlorvos (DDV) and omethoate poisoning and provide the reliable basis for the rational treatments on these three organophosphorus pesticides poisoning. METHODS: 101 patients with AOPP in 7 hospitals were divided into three groups: Group A, 59 patients with acute methamidophos poisoning, Group B, 32 patients with acute DDV/dipterex (DEP) poisoning, Group C, 10 patients with acute omethoate/dimethoate poisoning. The levels of erythrocyte AChE and the therapeutic efficacies of pralidoxime chloride (PAM-Cl) were compared among the three groups. RESULTS: The AChE activities of all the three groups were inhibited on level of (9.12 +/- 7.99) U/g Hb (group A), 7.32 +/- 4.62 U/g Hb (group B) and (12.01 +/- 9.53) U/g Hb (group C), among which no significant difference was found (P > 0.05). All the patients recovered from acute cholinergic excitation or crisis after the treatment of PAM-Cl. The erythrocyte AChE activities were obviously reactivated in group A three hours later after admission to hospital, each on level of (11.37 +/- 8.67) U/g Hb, (12.51 +/- 6.98) U/g Hb, (15.90 +/- 7.31) U/g Hb, (18.33 +/- 4.78) U/g Hb and (18.91 +/- 7.00) U/g Hb at the 12th, 24th, 48th, 72nd hour and discharge (P < 0.05), and the upgrade tendency was continuous. AChE activities in group B were also reactivated after treatment, each on level of (8.91 +/- 5.89) U/g Hb, (1.31 +/- 6.61) U/g Hb, (13.00 +/- 7.55) U/g Hb, (14.22 +/- 7.80) U/g Hb, (12.78 +/- 7.07) U/g Hb and (16.87 +/- 7.06) U/g Hb at the 3rd, 12th, 24th, 48th, 72nd hour and discharge, but the upgrade tendency turned slowly after 12 hours, the inhibited AChE activities were not reactivated in group C from the beginning to the end. CONCLUSION: After the treatment of PAM-Cl, the AChE activities of the patients with acute methamidophos poisoning could be continuously reactivated, the AChE activities of the patients with acute DDV/DEP poisoning could also be reactivated in 12 hours, and then keep stable, but the AChE activities of the patients with acute omethoate/dimethoate poisoning could not be reactivated. However, PAM-Cl has therapeutic efficacy against acute toxicity of all the three organophosphorus pesticides. Oximes should be vigorously used in the treatment of AOPP, including acute omethoate/dimethoate poisoning.