Deposition Of Uric Acid Crystals Research Articles

Transcutaneous auricular vagus nerve stimulation mitigates gouty inflammation by reducing neutrophil infiltration in BALB/c mice

Gouty inflammation, caused by uric acid crystal deposition, primarily affects tissues around the toe joints and triggers potent inflammatory responses. Current treatments focus on alleviating inflammation and pain using pharmaceutical agents, which can lead to side effects and complications. This has generated interest in non-pharmacological interventions, such as non-invasive vagus nerve stimulation (VNS). In this study, we explored the anti-inflammatory mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of acute gout. Gouty inflammation was induced by injecting monosodium urate (MSU) crystals into the ankle joints of BALB/c mice. The effects of taVNS on the expression of inflammatory cytokines and chemokines in the ankle joint tissue were assessed using real-time quantitative PCR (qPCR), western blotting, histological assessments (H&E staining), and immunohistochemistry (IHC). The role of α7 nicotinic acetylcholine receptors (α7nAChR) was also evaluated by signal blocking. Our findings revealed that MSU significantly elevated gout-associated inflammatory cascades and mediators in the ankle joint. Notably, taVNS at 200 µA and 25 Hz effectively reduced these inflammatory responses, decreasing neutrophil infiltration and chemoattraction within the tissue. taVNS showed significant anti-inflammatory properties by suppressing neutrophil activity, offering a novel therapeutic approach for gout beyond conventional pharmacological methods. Additionally, taVNS holds potential for managing various chronic joint diseases. These results highlight taVNS as a promising non-pharmacological therapy for chronic inflammation.

Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models.

Humans are predisposed to gout because they lack uricase that converts uric acid to allantoin. Rodents have uricase, resulting in low basal serum uric acid. A uricase inhibitor raises serum uric acid in rodents. There were two aims of the study in polycystic kidney disease (PKD): 1) to determine whether increasing serum uric acid with the uricase inhibitor, oxonic acid, resulted in faster cyst growth and 2) to determine whether treatment with the xanthine oxidase inhibitor, oxypurinol, reduced the cyst growth caused by oxonic acid. Orthologous models of human PKD were used: PCK rats, a polycystic kidney and hepatic disease 1 (Pkhd1) gene model of autosomal recessive PKD (ARPKD) and Pkd1RC/RC mice, a hypomorphic Pkd1 gene model. In PCK rats and Pkd1RC/RC mice, oxonic acid resulted in a significant increase in serum uric acid, kidney weight, and cyst index. Mechanisms of increased cyst growth that were investigated were proinflammatory cytokines, the inflammasome, and crystal deposition in the kidney. Oxonic acid resulted in an increase in proinflammatory cytokines in the serum and kidney in Pkd1RC/RC mice. Oxonic acid did not cause activation of the inflammasome or uric acid crystal deposition in the kidney. In Pkd1RC/RC male and female mice analyzed together, oxypurinol decreased the oxonic acid-induced increase in cyst index. In summary, increasing serum uric acid by inhibiting uricase with oxonic acid results in an increase in kidney weight and cyst index in PCK rats and Pkd1RC/RC mice. The effect is independent of inflammasome activation or crystal deposition in the kidney.NEW & NOTEWORTHY This is the first reported study of uric acid measurements and xanthine oxidase inhibition in polycystic kidney disease (PKD) rodents. Raising serum uric acid with a uricase inhibitor resulted in increased kidney weight and cyst index in Pkd1RC/RC mice and PCK rats, elevated levels of proinflammatory cytokines in the serum and kidney in Pkd1RC/RC mice, and no uric acid crystal deposition or activation of the caspase-1 inflammasome in the kidney.

Investigation of the association between the polymorphism <i>SLC2A9</i> rs2280205 and gout in Vietnamese population

Gout, a predominant form of inflammatory arthritis, is characterized by the deposition of uric acid crystals in joints and other tissues. Genome-wide association studies (GWAS) have established the association between gout and genetic variants of solute carrier family 2 member 9 (SLC2A9). In this study, we assessed the association of the single nucleotide polymorphism SLC2A9 rs2280205 with gout susceptibility in the Vietnamese population. Genomic DNA was extracted from the peripheral blood of 477 samples (160 gout patients and 317 healthy controls). The polymorphism rs2280205 of the SLC2A9 gene was genotyped using the PCR-RFLP method. Results indicated that the allele distribution of this variant was in accordance with Hardy-Weinberg Equilibrium, and the genotype frequencies of rs2280205 GG/GA/AA were 0.65, 0.33, and 0.02, respectively. However, no relation was identified between SLC2A9 rs2280205 and gout in this studied population. This research contributed a preliminary insight into the genetic factors in the development of gout in the Vietnamese population.

Chloroquine inhibits NLRP3 inflammasomes activation and alleviates renal fibrosis in mouse model of hyperuricemic nephropathy with aggravation by a high-fat-diet

Numerous epidemiological studies have demonstrated that hyperuricemia (HUA) is a risk factor for renal diseases and renal fibrosis. Dietary patterns can influence serum urate levels and hyperuricemic nephropathy (HN). NLRP3 inflammasomes play a crucial role in various inflammatory responses and contribute to HN progression. Chloroquine (CQ) is an anti-inflammatory and disease-modifying anti-rheumatic drug (DMARD) utilized in treating autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In this study, we examined the effects and underlying mechanisms of CQ in a high-fat-diet (HFD) exacerbated mouse model of HN. C57BL/6 mice were randomized into either a control group or an HN group (induced by adenine/potassium oxonate treatment), followed by a normal diet or HFD, with or without CQ treatment. Our findings revealed that the HN group exhibited elevated serum levels of blood urea nitrogen (BUN) and creatinine compared to the control group. Additionally, the HN + HFD group displayed increased serum levels of uric acid, BUN, and creatinine relative to the control + HFD group. Moreover, the HFD exacerbated renal uric acid crystal deposition and fibrosis in HN mice compared to a normal diet. CQ ameliorated renal dysfunction, as evidenced by reduced serum creatinine levels, renal fibrosis, and renal tubular injury scores, and significantly decreased NLRP3, ASC, caspase-1, and IL-1β levels in HN mice. These findings suggest that CQ inhibits the activation of NLRP3 inflammasomes and may serve as a potential therapeutic strategy for HN treatment.

The Gouty Kidney: A Reappraisal

This review re-examines the role of crystal deposition in the kidney in view of recent clinical and experimental findings. The involvement of the renal system in gout seems frequent. Indeed, recent studies showed that approximately 25% of patients with gout experience renal failure, defined by estimated glomerular filtration rate <60 mL/min/1.73 m2. The pathophysiology is complex and involves several factors, their respective roles being difficult to dissect. The role of crystal deposition in the kidney was the first suspected, and the concept of gouty microcrystalline nephropathy, also called gouty nephropathy, has been popular, supported by early autopsy studies demonstrating uric acid and urate crystal deposition in the renal medulla of patients with gout, together with features of tubulointerstitial nephritis. Crystal deposition was first considered an important source of renal involvement in gout. After the introduction of urate-lowering drugs and the performance of kidney biopsies, which mainly involved the renal cortex and did not reveal much crystal deposition but rather vascular changes, this concept has been criticized and even dismissed. Thereafter, kidney involvement in gout was considered mainly vascular, related to hypertension and associated comorbidities and later to hyperuricemia. The toxic effects of non-steroidal anti-inflammatory drugs is also an important factor. Modern imaging, especially renal ultrasonography, allows for atraumatic exploration of the kidney and has revealed hyperechogenicity of the renal medulla, suggesting crystalline deposits, in approximately one-third of patients with tophaceous gout. Experimental models of gouty nephropathy have recently demonstrated the pathogenic role of microcrystal deposition in the collecting ducts and parenchyma of the renal medulla. Taken together, these recent findings lead to the re-examination of the pathogenic role of crystal deposition in the renal medulla and testing the effect of urate-lowering drugs on renal features of gouty patients with evidence of renal crystal deposition.

Literatur Review: Peran konseling gizi dan senam ergonomik dalam menurunkan kadar asam urat pada penderita gout

Gout is a disorder caused by inflammation of the joints due to the deposition of uric acid crystals stored in the joints. The causative factors are age, excessive purine intake, obesity, alcoholic beverages, and lack of physical activity. Various efforts can be made to overcome this, including nutritional counseling and physical activity, such as gymnastics. The study aims to provide descriptive information regarding the effect of nutritional counseling on a low-purine diet and ergonomic gymnastics in reducing uric acid levels in patients with gout. Literature review research was conducted using the keywords "Counseling, Ergonomic Exercise, Uric acid, and Gout" on the Google Scholar search engine and other electronic databases, namely Proquest, BMC, and Cochrane review. Scientific articles are published in national and international journals that can be accessed openly, published between 2010-2020. From these results, 13 articles were selected for review. The literature review was conducted in an unsystematic narrative review. The results of the study state that providing counseling using various media can be one solution to help reduce pain and reduce one's uric acid levels, namely through counseling or nutrition counseling and ergonomic exercises. Counseling can provide insight or knowledge related to a low-purine diet, while ergonomic exercises provide the impact of physical fitness on the patient's health. The combination of providing nutritional counseling and ergonomic exercises can reduce uric acid levels in patients with gout.

Uric Acid Crystal Deposition Triggers Tubule Dilation in Normal Kidneys and Cystogenesis in Polycystic Kidney Disease (PKD)

Uric Acid Crystal Deposition Triggers Tubule Dilation in Normal Kidneys and Cystogenesis in Polycystic Kidney Disease (PKD)

Gout in the course of systemic lupus erythematosus: Literature review and case study report

Gout is one of the relatively common inflammatory diseases of the joints. It is caused by the deposition of uric acid crystals in the tissues, which induces an acute or chronic inflammatory process. Elevated serum uric acid levels are usually found long before symptoms appear, and it is worth emphasizing that not every hyperuricemic patient will ever develop gout symptoms. The onset of gout is characterized by periodic joint inflammation, which may be triggered by various stress factors (trauma, infection), certain medications, dietary mistakes, and excessive exercise. Over time, repeated joint inflammation causes permanent joint damage. Most often, deposits of urate crystals are located in places with poorer blood supply and exposed to increased pressure, such as joints and soft tissues (e.g., auricles). The coexistence of gout and autoimmune diseases is relatively rare. While for many years it was believed that gout was not associated with other systemic connective tissue diseases, gout has been described in the course of systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. The presented systematic review also describes a case of a patient with longlasting systemic lupus erythematosus who was diagnosed with gout.

Febuxostat Improves Uric Acid Levels and Renal Function in Patients with Chronic Kidney Disease and Hyperuricemia: A Meta-Analysis.

Background Uric acid nephropathy, also known as hyperuricemia nephropathy or gouty nephropathy, is characterized by uric acid crystal deposition and inflammatory cell infiltration. Herein, we aimed to demonstrate the role of febuxostat on uric acid levels and renal function in patients with chronic kidney disease and hyperuricemia. Methods Eight databases included were searched for clinical randomized controlled trials. Meanwhile, the confidence interval (CI) of either relative risk or mean difference was set to 95%. Besides, the heterogeneity of the research results is tested by I2. Results Ten studies were ultimately included in this meta-analysis. All of them were considered to be random controlled trials. 10 studies reported the serum uric acid of the test group and the control group, which was significantly lower (SMD: -146.44, 95% Cl: -195.96, -86.93, and P < 0.01) than the control group, EGFR (SMD: 3.21, 95% Cl: 1.17, 5.25, and P < 0.01), serum creatinine (SMD: -15.27, 95% Cl: -20.75, -9.79, and P < 0.01), serum urea nitrogen (SMD: -2.37, 95% Cl: -3.31, -1.61, and P < 0.01), and adverse reactions (OR: 0.74, 95% Cl: 0.32, 1.68, and P = 0.47). Conclusion The results of this study suggest that febuxostat may be effective in patients with CKD with HUA, as evidenced by serum uric acid, creatinine, urea nitrogen, and EGFR. However, large sample, multicenter, low risk of bias clinical studies, as well as basic medical research, are needed.

Palmatine Protects Against MSU-Induced Gouty Arthritis via Regulating the NF-κB/NLRP3 and Nrf2 Pathways.

PurposeGouty arthritis could be triggered by the deposition of monosodium uric acid (MSU) crystals. Palmatine (PAL), a protoberberine alkaloid, has been proven to possess compelling health-beneficial activities. In this study, we aimed to explore the effect of PAL on LPS plus MSU crystal-stimulated gouty arthritis in vitro and in vivo.MethodsPMA-differentiated THP-1 macrophages were primed with LPS and then stimulated with MSU crystal in the presence or absence of PAL. The expression of pro-inflammatory cytokines and oxidative stress-related biomarkers and signal pathway key targets were determined by ELISA kit, Western blot, immunohistochemistry and qRT-PCR, respectively. In addition, the anti-inflammatory and antioxidant activities of PAL on MSU-induced arthritis mice were also evaluated.ResultsThe results indicated that PAL (20, 40 and 80 μM) dose-dependently decreased the mRNA expression and levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β), IL-6, IL-18 and tumor necrosis factor alpha (TNF-α)). The levels of superoxide dismutase (SOD) and glutathione (GSH) were remarkably enhanced, while the level of malondialdehyde (MDA) was reduced. Western blot analysis revealed that PAL appreciably inhibited NF-κB/NLRP3 signaling pathways through inhibiting the phosphorylation of p-65 and IκBα, blocking the expression of NLRP3, ASC, IL-1β and Caspase-1, as well as enhancing the antioxidant protein expression of Nrf2 and HO-1. In vivo, PAL attenuated MSU-induced inflammation in gouty arthritis, as evidenced by mitigating the joint swelling, and decreasing the productions of IL-1β, IL-6, IL-18, TNF-α and MDA, while enhancing the levels of SOD and GSH. Moreover, PAL further attenuated the infiltration of neutrophils into joint synovitis.ConclusionPAL protected against MSU-induced inflammation and oxidative stress via regulating the NF-κB/NLRP3 and Nrf2 pathways. PAL may represent a potential candidate for the treatment of gouty arthritis.

Renal pathology associated with visceral gout in ducks

Visceral gout is a metabolic disease of birds characterized by deposition of urate crystals in visceral organs. Though occurrence of visceral gout is common in chicken, reports from ducks and descriptions of its renal pathology are scarce. The present study describes visceral gout in Kuttanad duck, a native breed and in a White Pekin duck. A Kuttanad and a White Pekin duck of about one and a half years of age and reared under intensive system and brought for postmortem examination to Department of Veterinary Pathology, College of Veterinary and Animal Sciences, Pookode formed the material for the study. Grossly, visceral organs such as kidney, liver and heart showed diffuse deposition of chalky white material on the surfaces. Ureters were dilated and engorged with urate crystals. Histologically, kidney revealed extensive degeneration of epithelial cells of proximal and distal convoluted tubules with urate crystals in the lumen. Characteristic lesions noticed in kidneys of both cases were glomerular sclerosis, severe interstitial fibrosis causing tubular atrophy and mild infiltration of mononuclear inflammatory cells in the interstitium. This chronic lesion in kidney might be the primary reason for impaired uric acid excretion and deposition of uric acid crystals in various internal organs of the ducks.

MO427SAFE USE OF ALLOPURINOL TO TREAT ACUTE URIC ACID NEPHROPATHY IN PREGNANCY: A CASE REPORT

Abstract Introduction Acute uric acid nephropathy (UAN) is characterized by acute kidney injury (AKI) due to uric acid crystal precipitation within the distal tubules and collecting ducts. We present a young woman, with a history of hyperuricaemia, who was treated with allopurinol for acute UAN during her first pregnancy. She also continued allopurinol treatment during her second pregnancy for prevention of further acute UAN. To the author’s knowledge, this is the first case report of biopsy-confirmed acute UAN during pregnancy. Case report A 20 year old woman, who was 13 weeks pregnant, was admitted with AKI. Past medical history included chronic kidney disease (CKD) and gout since the age of 17. She had an extensive family history of CKD and gout (without diagnosis, despite genetic testing). She had been on daily allopurinol 300mg, but this was stopped 8 weeks prior by her rheumatology team due to concerns about teratogenicity. At that time serum creatinine was at her baseline of 100 μmol/L (normal range 50-120 μmol/L) and serum uric acid had been 740 μmol/L (normal range 140-360 μmol/L). On admission, she felt well and was euvolemic. Serum creatinine was now 352 μmol/L and her serum uric acid level was 1720 μmol/L, with an elevated urine uric acid to creatinine ratio of 1.1. She underwent renal biopsy, which showed significant deposition of uric acid crystals in the renal tubules, confirming a diagnosis of acute UAN. She was given intravenous fluids. The uncertainties of allopurinol use in pregnancy were discussed with her, and she was restarted on allopurinol 200 mg daily. Over the next 3 weeks, serum uric acid decreased to 470 μmol/L and serum creatinine to 116 μmol/L. She was maintained on allopurinol during her pregnancy and delivered a healthy baby girl. She was advised against further pregnancies due to increased risk of maternal and fetal complications. However, three years later she presented at 15 weeks’ gestation. After a discussion regarding the potential teratogenic effects of allopurinol versus the risk of recurrent severe AKI due to acute UAN if it was again discontinued, she chose to continue allopurinol. The pregnancy proceeded without complication. Her daughters are now 8 and 5 years old. They do not have any congenital malformations, though both have mild to moderate learning difficulties. Discussion Allopurinol is approved for the treatment of hyperuricaemia outside of pregnancy, but given it interrupts purine synthesis there is a biologically plausible concern regarding teratogenicity. However, in our patient with long-standing hyperuricaemia it was the discontinuation of allopurinol that precipitated AKI due to the resultant crystal formation when serum uric acid reached very high levels. Biopsy confirmation of acute UAN was vital in this case, given the possibility of missing an alternative diagnosis and the risks of giving empirical allopurinol therapy. Once the diagnosis for her severe AKI was confirmed, it was clear our patient would benefit from uric acid lowering therapy. Our patient had two healthy girls despite using allopurinol from week 16 in her first pregnancy and throughout her second pregnancy. Unfortunately, both girls have mild to moderate learning needs, though it is unprovable whether allopurinol was causative as no study has followed up long term outcomes after foetal exposure during pregnancy.

MO491ASSOCIATION BETWEEN SERUM URIC ACID LEVEL AND CHRONIC KIDNEY DISEASE INCIDENCE STRATIFIED BY SEX IN MIDDLE-AGED ADULTS

Abstract Background and Aims While previous studies have reported the association between serum uric acid (SUA) and chronic kidney disease (CKD) incidence, the sex differences in this association remain controversial. Therefore, we examined the association between SUA levels and CKD incidence in middle-aged adults stratified by sex using data from a large-scale health check-up. Method We analyzed information from the JMDC database, which included the annual health check-up data of Japanese employees and their dependents aged &amp;lt;75 years. Among those individuals, we analyzed data from 138,511 individuals without CKD, kidney disease, or a history of cardiovascular disease at baseline. CKD was defined as an estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2 and/or proteinuria. We divided the participants into 9 and 7 groups according to SUA levels for men and women, respectively. A Cox model was applied to assess the adjusted hazard ratios (HRs) for CKD incidence in each SUA level group using an SUA concentration of 4.0–4.9 mg/dL as the reference after adjusting for age, body mass index, current or ex-smoker, current or ex-drinker, diabetes mellitus, dyslipidemia, systolic blood pressure, use of anti-hyperuricemic drugs, and baseline eGFR. Results The mean participant age was 44.1 years, and 29.6% were women. The mean SUA levels were 5.9 mg/dL and 4.1 mg/dL in men and women, respectively. During the mean follow-up period of 4.68 years, 12,589 participants developed CKD. The age-standardized incidence rates for CKD were 17.88/17.80 per 1000 person-years in men/women with SUA concentrations of 4.0–4.9 mg/dL, 209.76 per 1000 person-years in men with SUA ≥11.0 mg/dL, and 73.38 per 1000 person-years in women with SUA ≥ 9.0 mg/dL. The fully adjusted HRs (95% confidence interval [CI], P value) for CKD incidence in the groups with SUA concentrations of &amp;lt;4.0, 10.0–10.9, and ≥11.0 mg/dL compared with those with SUA of 4.0–4.9 mg/dL among men were 1.13 (1.01–1.26, P=0.030), 1.98 (1.32–2.97, P=0.0010), and 3.74 (1.68–8.35, P=0.0013), respectively. In women, the fully adjusted HRs for CKD incidence in the groups with SUA concentrations of &amp;lt;4.0, 8.0–8.9, and ≥9.0 mg/dL were 1.08 (1.01–1.16, P=0.032), 2.39 (1.07–5.35, P=0.034), and 3.20 (0.80–12.8, P=0.10), respectively. Similar results were observed when we performed the sensitivity analysis excluding 8,411 individuals with hypertensive treatment from the main analysis. The HRs for the outcomes caused by the onset of eGFR &amp;lt;60 mL/min/1.73 m2 or proteinuria separately were similar to those for the main results. Conclusion The results of the present study demonstrated an increased risk of CKD in men with SUA concentrations of &amp;lt;4.0 and ≥10.0 mg/dL and &amp;lt;4.0 and ≥8.0 mg/dL in women compared to those with SUA concentrations of 4.0–4.9 mg/dL after adjusting for various covariates. Both high and low SUA levels were risk factors for CKD in middle-aged men and women. Hyperuricemia was demonstrated to cause renal injury due to the intraluminal deposition of uric acid crystals in the renal collecting duct. Hyperuricemia may also induce endothelial dysfunction, activation of the renin-angiotensin system, and induction of inflammation and stimulation of vascular smooth muscle cell proliferation by the induction of cyclooxygenase-2. However, as uric acid is one of the most important antioxidants in human plasma, low SUA levels may increase the risk of CKD incidence through decreased antioxidant activity. These mechanisms are implicated in the pathogenesis of CKD caused by high and low SUA levels. In addition, the SUA levels and ranges associated with increased risks of CKD incidence differed by sex.

Loganin Alleviates Gout Inflammation by Suppressing NLRP3 Inflammasome Activation and Mitochondrial Damage.

Gout is a type of inflammatory arthritis caused by the deposition of monosodium uric acid (MSU) crystals in tissues. The etiology of gout is directly linked to the NLRP3 inflammasome, since MSU crystals are NLRP3 inflammasome activators. Therefore, we decided to search for a small-molecule inhibitor of the NLRP3 inflammasome for the prevention of gout inflammation. We found that loganin suppressed MSU crystals-induced caspase-1 (p20) and interleukin (IL)-1β production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks formation in mouse primary macrophages, showing its ability to inhibit the NLRP3 inflammasome. In an air pouch inflammation model, oral administration of loganin to mice prevented MSU crystals-induced production of mature IL-1β and IL-18 in air pouch exudates, resulting in decreased neutrophil recruitment. Furthermore, oral administration of loganin suppressed MSU crystals-induced gout inflammation in a mouse foot gout model, which was accompanied by the inhibition of the NLRP3 inflammasome. Loganin blocked de novo synthesis of mitochondrial DNA in air pouches and foot tissues injected with MSU crystals. Consistently, loganin prevented MSU crystals-induced mitochondrial damage in macrophages, as it increased mitochondrial membrane potential and decreased the amount of mitochondrial reactive oxygen species. These data demonstrate that loganin suppresses NLRP3 inflammasome activation by inhibiting mitochondrial stress. These results suggest a novel pharmacological strategy to prevent gout inflammation by blocking NLRP3 inflammasome activation and mitochondrial dysfunction.

Gout

Gout is a metabolic process characterized by the deposition of uric acid crystals in various tissues of the body. Pathogenesis of gout is based on the accumulation of uric acid salts and its reduced renal elimination, leading to an increase in its concentration in the blood. Clinically, gout manifests itself in the form of recurrent attacks of arthritis with the formation of tophi. Development of renal pathology is also noted against the background of arthritis. The disease is more common among men, however, recently, cases of lesions of women are not rare. Prevalence of gout increases with age. Medicines that affect the pathogenetic mechanism of the disease are used for the treatment, as well as drugs for symptomatic treatment.

Consumption of 100% Tart Cherry Juice Reduces Serum Urate in Overweight and Obese Adults

ABSTRACTBackgroundGout is a frequently occurring, complex rheumatologic form of inflammatory arthritis caused by the accumulation of serum uric acid (sUA) and deposition of uric acid crystals in the joints and tissues of the body. Hyperuricemia is also a significant independent risk factor for all-cause and cardiovascular morbidity and mortality and is associated with hypertension, diabetes, obesity, and osteoarthritis. However, patient adherence to prescribed urate-lowering therapies ranges from 20% to 70%, suggesting that other additional strategies, such as dietary intervention with specific, efficacious foods or beverages, may be necessary to mitigate the risk of arthritis, as well as other comorbidities. Tart cherry juice (TCJ) has been used for decades by some for gout based largely on anecdotal evidence of its efficacy and its antioxidant and anti-inflammatory properties.ObjectivesWe designed this study to test the effect of TCJ on uricemia, lipidemia, glycemia, and inflammation in at-risk overweight and obese humans with a specific hypothesis that TCJ consumption would reduce sUA concentrations.MethodsIn this randomized, placebo-controlled crossover study, we recruited overweight and obese participants with body mass index (BMI) >25.0 kg/m2 (n = 26, 18 women/8 men, 41 ±11 y; BMI 31.3 ± 6.0; 12 obese, 14 overweight) to consume 240 mL/d (8 oz/d) of either TCJ or placebo beverage, for 4 wk each with a 4-wk intervening washout period followed by 4 wk of the alternate beverage.ResultsTCJ significantly reduced sUA concentration by 19.2% (P < 0.05) and reduced by 19.4% (P = 0.09) and 6.3% (P = 0.08) proinflammatory high-sensitivity C-reactive protein and monocyte chemoattractant protein-1, respectively. The participants in this study displayed risk ratios indicating increased cardiovascular disease risk and insulin resistance but no differences in the pre- and postintervention groups of either placebo or TCJ groups.ConclusionCollectively, the data suggest that 100% TCJ reduces sUA concentrations, mitigating hyperuricemia associated with gouty arthritis. This trial was registered at clinicaltrials.gov as NCT03636529.

The application of dual-energy computed tomography in the diagnosis of musculoskeletal disorders: a review of current concepts and applications.

With the assistance of innovations in scanner engineering and software design, dual-energy computed tomography (DECT) is an advanced imaging method that has been developed over the last decade. With its unique ability to differentiate materials by their atomic number, DECT has opened new perspectives in imaging. The principal advantages of DECT over conventional CT in the musculoskeletal setting relate to the additional information provided regarding tissue composition, artifact reduction and image optimization. In musculoskeletal imaging, uric acid material decomposition images can help identify articular deposition of uric acid crystals (in addition to the detection of uric acid renal stones). Material separation can also help detect bone marrow edema on CT in the case of trauma, algoneurodystrophy, inflammation (osteitis) or malignant bone marrow infiltrates, such as metastases. DECT also offers means to reduce the radiation exposure of patients by replacing multiphase exams with more specific single acquisitions. The first part of this article reviews the basic principles and technical aspects of DECT. The second part focuses on applications of DECT to musculoskeletal imaging including that of gout and other crystal-induced arthropathies, virtual non-calcium images for the study of bone marrow lesions, the study of collagenous structures, as well as the detection of hemosiderin and metal particles.

Gout - asymptomatic hyperuricemia with/without asymptomatic monosodium urate crystal deposition: To be treated or not?

Elevation of serum uric acid level without clinically visible arthritis (known as asymptomatic hyperuricemia) is not traditionally considered to be gout disease, but only a possible cause of it, even though it may be accompanied by tissue uric acid crystal deposition. On the other hand, gout is traditionally recognized as recurrent, overt arthritis, visible only after a long period of time due to uric acid accumulation in joints. Advanced imaging techniques have substantially changed the perception of this problem, identifying gout as a low-grade chronic inflammatory disease from the very beginning, visible only by phases of acute arthritis attacks. According to ultrasonography, uric acid crystal hyperechoic aggregates (tophi) are seen not only in the symptomatic gout disease phase, but also in the preceding ? asymptomatic (latent) ? gout phase. New perception of the problem was approved by the recently described NETs (neutrophil extracellular traps) phenomenon. Also, hyperuricemia has recently been identified as a systemic disorder, responsible not only for the apparent gout arthritis, but also for the renal and cardiovascular disease occurrence and progression. Positive effect of urate-lowering therapy (xanthine oxidase inhibitors and uricosurics) on hypertension and chronic kidney disease indicates a possibility of its utility in asymptomatic hyperuricemia and asymptomatic gout therapy, apart from the use in clinically manifested gout treatment and for certain conditions, such as tumor lysis syndrome.

Detection of uric acid crystal deposition by ultrasonography and dual-energy computed tomography: A cross-sectional study in patients with clinically diagnosed gout.

The aim of our study was to compare the performance of ultrasonography (US) and dual-energy computed tomography (DECT) in detecting the crystal deposition at lower extremity joints in patients with gout. The correlation of imaging findings with microscopic findings was further assessed whenever aspiration is available.We recruited consecutive patients who were presented with arthritis of lower extremity from January 2012 to December 2014. All the patients underwent DECT and US scan of bilateral knees, ankles, and feet. Synovial fluid was obtained by aspiration from an acute inflammatory joint if possible.Finally, 60 patients fulfilling the 1977 gout classification criteria were included in our study. We found that US can detect significantly more patients with crystal deposition than DECT (81.7% vs 56.7%, by US and DECT, respectively, P < .001). The frequency of urate crystal deposition detected by US at MTP1, knee, and ankle joints regions was 56.7%, 63.3%, and 51.7%, respectively. The percentage of positivity of double contour sign on US was 33.3%, 48.3%, and 41.7% at the joints mentioned above, respectively. There was a good correlation between ultrasound and synovial fluid analysis in detecting crystal deposition (κ = 0.87, P = .001), while the agreement between DECT and synovial fluid analysis was just fair (κ = 0.28, P = .02).The sensitivity of US in detecting urate crystal deposition in lower extremity joints was higher than DECT. The superiority was more obvious in knee and MTP1 joints. US should be considered as the first choice of image examinations when diagnosing gout.

Suppression of NLRP3 inflammasome by oral treatment with sulforaphane alleviates acute gouty inflammation.

The aetiology of gout is closely linked to the deposition of monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we investigated whether oral administration of an NLRP3 inhibitor would be effective to attenuate the symptoms of gout. The effects of oral administration with sulforaphane (SFN) were examined in two mouse models of acute gout induced by injection of MSU crystals into footpads or air pouch. The production of caspase-1 (p10) and IL-1β was examined by immunoblotting and ELISA as hallmarks of NLRP3 inflammasome activation. Oral administration of SFN attenuated MSU crystal-induced swelling and neutrophil recruitment in a mouse foot acute gout model, correlating with the suppression of the NLRP3 inflammasome activation in foot tissues. Consistently, oral administration of SFN blocked MSU-crystal-induced activation of the NLRP3 inflammasome in a mouse air pouch gout model. SFN suppressed NLRP3 inflammasome activation induced by MSU crystals, adenosine triphosphate and nigericin but not by poly(dA:dT) in primary mouse macrophages, independent of the reactive oxygen species pathway. SFN inhibited ligand-independent activation of the NLRP3 inflammasome, suggesting that SFN may act directly on the NLRP3 inflammasome complex. Oral administration of SFN effectively alleviated acute gouty inflammation by suppression of the NLRP3 inflammasome. Our results provide a novel strategy in which oral treatment with SFN may be beneficial in preventing acute attacks of gout.