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Monosodium urate crystal

Daniela Marotto, Antonella De Santis, Donatella Chessa, Davide Firinu, Stefano Del Giacco
Gout is the most common form of arthritis in adults. It is often associated with other comorbidities, which contraindicate the use of conventional therapies. The discovery of the role of interleukin-1β (IL-1β) in orchestrating the monosodium urate crystal-induced inflammatory response offered new therapeutic prospects to refractory patients, or to those in whom standard therapies are contraindicated. This paper describes a clinical case of a 65-year-old man with chronic tophaceous gouty arthropathy and subintrant flares, who had comorbidities contraindicating the use of conventional gout therapies-to which he did not respond-who was treated with canakinumab, a monoclonal selective inhibitor of IL-1β...
March 9, 2018: Rheumatology and Therapy
Yan Lin, Pei-Gang Liu, Wei-Qing Liang, Yi-Juan Hu, Pan Xu, Jie Zhou, Jin-Bao Pu, Hong-Jian Zhang
BACKGROUND: Gnaphalium affine D. Don is a folk medicine of China believed to be efficacious in the treatment of many ailments, including hyperuricemia and gout. PURPOSE: Based on a previous study, we isolated two flavones, luteolin and luteolin-4'-O-glucoside, from G. affine. Our aim was to assess the potential beneficial effects of treatment and mechanisms of these two flavones on hyperuricemia and acute gouty arthritis. METHODS: The model of potassium oxonate (PO)-induced hyperuricemia and monosodium urate (MSU) crystal-induced inflammation in mice has been established...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Connie B Gilfillan, Sabine Kuhn, Camille Baey, Evelyn J Hyde, Jianping Yang, Christiane Ruedl, Franca Ronchese
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A-diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Sidharth Tandon, Kabir Sardana, Purnima Malhotra, Jasmeet Singh
Asymptomatic, juxta-articular nodules are an uncommon morphology, which is usually diagnosed as xanthomas, calcinosis cutis or rheumatoid nodules. This study was represented as a case of gout, which is a disorder of purine metabolism resulting in elevation of serum uric acid and deposition of monosodium urate crystals within and around joints and manifests clinically as inflammatory arthritis. Urate crystal deposits have also been found in tendons, ligaments, viscera, and the skin, with the term "tophi" being used for the non-articular deposits...
October 2017: Journal of Cutaneous and Aesthetic Surgery
Helen I Keen, Wendy A Davis, Erin Latkovic, Jocelyn J Drinkwater, Johannes Nossent, Timothy M E Davis
AIMS: The prevalence and consequences (articular and extra-articular) of hyperuricemia in type 2 diabetes, especially when asymptomatic (ASH), are incompletely understood. The aim of this study was to use ultrasonography to assess pathology associated with monosodium urate deposition in the joints of well-characterized hyperuricemic patients with type 2 diabetes. METHODS: A subset of 101 participants (mean age 70.4 years, 59.8% males, median diabetes duration 14...
January 5, 2018: Journal of Diabetes and its Complications
Teng Ma, Xiao Liu, Zhifu Cen, Chuan Xin, Mingfeng Guo, Chaoyu Zou, Wenpeng Song, Rou Xie, Kailun Wang, Hong Zhou, Jun Zhang, Zhen Wang, Ce Bian, Kaijun Cui, Jiong Li, Yu-Quan Wei, Jing Li, Xikun Zhou
BACKGROUND: Interleukin-1β (IL-1β) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1β is regulated has not been fully elucidated. Our previous work identified that miR-302b had an important immune regulatory role in bacterial lung infections. This study was conducted to evaluate the function of miR-302b on monosodium urate (MSU) crystal-induced inflammation and its mechanism...
February 26, 2018: Arthritis Research & Therapy
Irving O Estevez-Garcia, Selma Gallegos-Nava, Erika Vera-Pérez, Luis H Silveira, Lucio Ventura-Ríos, Gonzalo Vancini, Cristina Hernández-Díaz, Fausto Sánchez-Muñoz, Martha A Ballinas-Verdugo, Marwin Gutierrez, Carlos Pineda, Pedro Rodriguez-Henriquez, Diana Castillo-Martínez, Luis M Amezcua-Guerra
OBJECTIVE: To assess potential associations among serum cytokines and microRNA (miR) levels with ultrasound (US) findings suggestive of urate deposits in chronic asymptomatic hyperuricemia and gout. METHODS: All participants underwent musculoskeletal US and measurements of serum IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IFN-γ, TNF, MCP-1, and ENA-78, as well as miR-146a, miR-155, and miR-223 levels. RESULTS: Thirty individuals with asymptomatic hyperuricemia, 31 normouricemic controls, and 30 gouty patients were included...
February 18, 2018: Arthritis Care & Research
Yuan Yuan, Chang Liu, Xi Xiang, Tong-Ling Yuan, Li Qiu, Yi Liu, Yu-Bin Luo, Y Zhao, Martin Herrmann
OBJECTIVE: The present study was performed to localize the articular deposition of monosodium urate (MSU) crystal in joints. We compare the detection efficiencies of dual-energy CT (DECT) and ultrasound scans. METHODS: Analyses by DECT and ultrasound were performed with 184 bilateral joints of the lower limbs of 54 consecutive gout patients. All joints were categorized into (1) knee, (2) ankle, (3) MTP1, and (4) MTP2, and sorted into those with and those without detectable MSU deposition...
February 13, 2018: Rheumatology International
Masafumi Nakayama
Inhalation of exogenous crystals such as silica, asbestos, and carbon nanotubes can cause lung fibrosis and cancer. Endogenous crystals such as monosodium urate, cholesterol, and hydroxyapatite are associated with pathogenesis of gout, atherosclerosis, and osteoarthritis, respectively. These crystal-associated-inflammatory diseases are triggered by the macrophage NLRP3 inflammasome activation and cell death. Therefore, it is important to understand how macrophages recognize crystals. However, it is unlikely that macrophages have evolutionally acquired receptors specific for crystals or recently emerged nanoparticles...
2018: Frontiers in Immunology
Águeda Prior-Español, Yaiza García-Mira, Sonia Mínguez, Melania Martínez-Morillo, Laia Gifre, Lourdes Mateo
OBJECTIVE: Septic arthritis is a medical emergency and crystal-induced arthritis is a risk factor for its development. If both occur simultaneously, crystal-induced arthritis may mask the diagnosis of infection and delay antibiotic therapy. METHOD: Retrospective analysis of patients with coexistence of septic and crystal-induced arthritis. We included only patients with isolation of crystals in synovial fluid analysis and positive culture of synovial fluid and/or blood culture...
February 1, 2018: Reumatología Clinica
Sydney C W Tang
As a disease of kings, and the king of diseases, gout is one of the oldest joint diseases known to humans. First described as far back as 2640 B.C., gout is still the most common form of inflammatory arthritis haunting humans in the 21st century. The disease is caused by the chronic elevation of serum uric acid levels above the saturation point for monosodium urate crystal formation. Its incidence is progressively rising even today, but there are also regional and ethnic variations. Finally, the role of genetics is only beginning to be unraveled...
2018: Contributions to Nephrology
Gianni Bellomo, Antonio Selvi
BACKGROUND: Uric acid (UA) is still considered a risk factor, or even a causative agent, for chronic kidney disease (CKD); however, a few, important, clinical questions remain unanswered; in particular: when and whether urate-lowering therapy should be commenced in subjects with asymptomatic hyperuricemia and/or monosodium urate crystals deposition? What is the most appropriate UA target to be achieved and how long does it need to be maintained? How does treatment need be adjusted in patients with chronic kidney disease? SUMMARY: The observational and intervention studies available do not fully answer such questions, and a treatment to target trial is required...
2018: Contributions to Nephrology
M Gamala, S P Linn-Rasker, M Nix, B G F Heggelman, J M van Laar, P C M Pasker-de Jong, J W G Jacobs, R Klaasen
To establish whether dual-energy CT (DECT) is a diagnostic tool, i.e., associated with initiation or discontinuation of a urate lowering drug (ULD). Secondly, to determine whether DECT results (gout deposition y/n) can be predicted by clinical and laboratory variables. Digital medical records of 147 consecutive patients with clinical suspicion of gout were analyzed retrospectively. Clinical data including medication before and after DECT, lab results, and results from diagnostic joint aspiration and DECT were collected...
January 27, 2018: Clinical Rheumatology
Xiaoliang Wang, Shida Yousefi, Hans-Uwe Simon
Necroptosis is a form of regulated necrosis and is dependent on a signaling pathway involving receptor interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL). Necroptosis is considered to have important functions in inflammation and, based on studies with animal disease models, is believed likely to be involved in the pathogenesis of many human inflammatory diseases. In neutrophils, necroptosis has recently been reported to be triggered by tumor necrosis factor (TNF) stimulation, ligation of adhesion receptors, exposure to monosodium urate (MSU) crystals, or phagocytosis of Staphylococcus aureus (S...
January 25, 2018: Cell Death & Disease
Simon M Chatfield, Kathrin Grebe, Lachlan W Whitehead, Kelly L Rogers, Thomas Nebl, James M Murphy, Ian P Wicks
Neutrophil extracellular traps (NETs) and the cell death associated with it (NETosis) have been implicated in numerous diseases. Mechanistic studies of NETosis have typically relied on nonphysiological stimuli, such as PMA. The human disease of gout is caused by monosodium urate (MSU) crystals. We observed that DNA consistent with NETs is present in fluid from acutely inflamed joints of gout patients. NETs also coat the crystals found in uninflamed tophi of chronic gout patients. We developed a quantitative, live cell imaging assay, which measures the key features of NETosis, namely, cell death and chromatin decondensation...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kuang-Hui Yu, Der-Yuan Chen, Jiunn-Horng Chen, Shih-Yang Chen, Shyh-Ming Chen, Tien-Tsai Cheng, Song-Chou Hsieh, Tsu-Yi Hsieh, Pai-Feng Hsu, Chang-Fu Kuo, Mei-Chuan Kuo, Hing-Chung Lam, I-Te Lee, Toong-Hua Liang, Hsiao-Yi Lin, Shih-Chang Lin, Wen-Pin Tsai, Gregory J Tsay, James Cheng-Chung Wei, Chung-Han Yang, Wen-Chan Tsai
Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis...
January 24, 2018: International Journal of Rheumatic Diseases
Cory Iverson, Andrew Bacong, Sha Liu, Scott Baumgartner, Torbjörn Lundström, Jan Oscarsson, Jeffrey N Miner
This study assesses the efficacy and exposure-response relationship of omega-3-carboxylic acids (OM-3 CA) in models of crystal-based inflammation. Human THP-1 macrophages and primary peripheral blood mononuclear cells exposed to multiple inflammatory crystal types were used to determine the anti-inflammatory potential of omega-3 (OM-3) fatty acids in vitro. Anti-inflammatory effects of OM-3 CA in vivo were tested in rat monosodium urate (MSU) crystal air pouch and rat knee intra-articular MSU injection models...
January 19, 2018: Scientific Reports
(no author information available yet)
Gout is the most common form of inflammatory arthritis and its incidence in the UK has steadily increased from 1.5% in 1997 to 2.5% in 2012.1,2 It is characterised by deposition of monosodium urate crystals in joints and tissues and usually presents with intermittent painful attacks followed by long periods of remission.3 It has been suggested that the management of gout in the UK remains suboptimal.1 In 2004, we concluded that there was a woeful lack of evidence to guide treatment or prophylaxis for gout, particularly with regard to choice of drug or doses...
January 2018: Drug and Therapeutics Bulletin
Aida Marcotti, Ana Miralles, Eduardo Dominguez, Eliseo Pascual, Ana Gomis, Carlos Belmonte, Elvira de la Peña
The mechanisms whereby monosodium urate (MSU) crystals deposition in gout activate nociceptors to induce joint pain are incompletely understood. We tried to reproduce the signs of painful gouty arthritis, injecting into the knee joint of rats suspensions containing amorphous or triclinic, needle MSU crystals. The magnitude of MSU-induced inflammation and pain behavior signs was correlated with the changes in firing frequency of spontaneous and movement-evoked nerve impulse activity recorded in single knee joint nociceptor saphenous nerve fibers...
January 9, 2018: Pain
Mariela Castelblanco, Jérôme Lugrin, Driss Ehirchiou, Sonia Nasi, Isao Ishii, Alexander So, Fabio Martinon, Nathalie Busso
A variety of stimuli, including monosodium urate (MSU) crystals, activate the NLRP3 inflammasome, and this activation involves several molecular mechanisms including xanthine oxidase (XO) upregulation and mitochondrial dysfunction. Upon oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 becomes active and cleaves the proinflammatory cytokine IL-1β into its active secreted form. Hydrogen sulfide (H2S), a gasotransmitter mainly produced by cystathionine γ-lyase (CSE) in macrophages, could modulate inflammation...
December 26, 2017: Journal of Biological Chemistry
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