Healthy lifestyle counteracts the risk effect of genetic factors on incident gout: a large population-based longitudinal study.

BACKGROUND: Risk genes linked to the development of gout have been identified, and lifestyle factors are related to gout risk. It remains unclear whether healthy lifestyle factors can mitigate the genetic risk of gout. Therefore, we aimed to explore whether and to what extent a healthy lifestyle can mitigate the risk of gout related to genetic factors. METHODS: Within the UK Biobank, 416,481 gout-free participants (aged 37-74) were identified at baseline. Polygenic risk for gout was assessed and categorized as low (lowest tertile), middle (tertile 2), and high (highest tertile). Healthy lifestyle factors included no/moderate alcohol consumption, no smoking, physical activity, and a healthy diet. Participants were categorized into three groups according to their number of healthy lifestyle factors: unfavorable (0 or 1), intermediate (any 2), and favorable (3 or 4). Data were analyzed using Cox proportional hazard models. RESULTS: Over the follow-up (median: 12.1 years), 6206 participants developed gout. Compared to low genetic risk, the hazard ratios (HRs) and 95% confidence intervals (CIs) of gout was 1.44 (1.35-1.54) for middle and 1.77 (1.66-1.89) for high genetic risk. The HRs (95% CIs) of gout were 0.63 (0.59-0.67) for a favorable lifestyle and 0.79 (0.75-0.85) for an intermediate lifestyle, compared to an unfavorable lifestyle. In joint effect analysis, compared to participants with low genetic predisposition and a favorable lifestyle, the HRs (95% CIs) of gout were 2.39 (2.12-2.70)/3.12 (2.79-3.52) in those with middle and high genetic predisposition plus unfavorable lifestyle profiles, and 1.53 (1.35-1.74)/1.98 (1.75-2.24) for those with middle and high genetic predisposition plus favorable lifestyle profiles, respectively. Moreover, compared to an unfavorable lifestyle, the HRs of gout related to a favorable lifestyle was 0.64 (95% CI, 0.56-0.73) for low genetic risk, 0.65 (95% CI, 0.58-0.72) for middle genetic risk, and 0.62 (95% CI, 0.57-0.69) for high genetic risk. There was a significant additive interaction between unfavorable lifestyle and high genetic risk on gout. CONCLUSIONS: Healthy lifestyle was associated with a lower risk of gout and may attenuate the risk of gout related to genetic factors by almost a third.

Consensus Statement Regarding the Efficacy and Safety of Long-Term Low-Dose Colchicine in Gout and Cardiovascular Disease.

Over the last decade, evidence has demonstrated that long-term, low-dose colchicine (0.5 mg daily) is effective for preventing gout flare and cardiovascular (CV) events in a wide range of patients. Given the potentially expanding use of colchicine in CV disease, we here review and update the biologic effects and safety of colchicine based on recent data gathered from bench and pharmacodynamic studies, clinical reports, controlled clinical trials, and meta-analyses, integrated with important studies over the last 50 years, to offer a consensus perspective by experts from multiple specialties familiar with colchicine's long-term use. We conclude that the clinical benefits of colchicine in gout and CV disease achieved at low dose do not sustain serum levels above the upper limit of safety when used in patients without advanced renal or liver disease or when used concomitantly with most medications. Further, data accrued over the last 50 years strongly suggest that the biologic effects of long-term colchicine do not increase the risk of cancer, sepsis, cytopenia, or myotoxicity.

Influence of Short-Term Consumption of Hericium erinaceus on Serum Biochemical Markers and the Changes of the Gut Microbiota: A Pilot Study.

Hericium erinaceus (H. erinaceus) is widely studied as a medicinal and edible fungus. Recent studies have shown that H. erinaceus has protective effects for diseases, such as inflammatory bowel disease and cancer, which are related to gut microbiota. To investigate the benefits of H. erinaceus intake on gut microbiota and blood indices in adulthood, we recruited 13 healthy adults to consume H. erinaceus powder as a dietary supplement. Blood changes due to H. erinaceus consumption were determined by routine hematological examination and characterized by serum biochemical markers. Microbiota composition was profiled by 16S ribosomal RNA gene sequencing. Results showed that daily H. erinaceus supplementation increased the alpha diversity within the gut microbiota community, upregulated the relative abundance of some short-chain fatty acid (SCFA) producing bacteria (Kineothrix alysoides, Gemmiger formicilis, Fusicatenibacter saccharivorans, Eubacterium rectale, Faecalibacterium prausnitzii), and downregulated some pathobionts (Streptococcus thermophilus, Bacteroides caccae, Romboutsia timonensis). Changes within the gut microbiota were correlated with blood chemical indices including alkaline phosphatase (ALP), low-density lipoprotein (LDL), uric acid (UA), and creatinine (CREA). Thus, we found that the gut microbiota alterations may be part of physiological adaptations to a seven-day H. erinaceus supplementation, potentially influencing beneficial health effects.

Downregulation of Transcription Factor T-Bet as a Protective Strategy in Monosodium Urate-Induced Gouty Inflammation.

Gout is sterile joint inflammation triggered by the damaging effects of monosodium urate (MSU) crystals accumulation. Previous studies suggest transcription factor T-bet plays an important role in inflammatory arthritis. Notably, mice lacking T-bet markedly reduced joint inflammation of rheumatoid arthritis models, however, the involvement of T-bet in gouty inflammation has yet to be clarified. Here, we took advantage of T-bet knockout (KO) mice to investigate the role of T-bet in the pathogenesis of MSU-induced gout inflammation. T-bet KO and wild type (WT) mice were used for models of acute inflammation induced with MSU crystals, including footpad, air pouch and peritonitis models. Inflammatory cytokines and phagocytosis were detected in bone-marrow-derived macrophages (BMDMs) from T-bet KO and WT mice treated with MSU crystals in vitro. In addition, T-bet expression in peripheral blood mononuclear cells (PBMCs) from gout patients was measured, as well as plasma inflammatory cytokines. We found that the levels of interleukin (IL)-17, IL-23, and interferon-γ were reduced, but tumor necrosis factor-α was not, in BMDMs from T-bet KO compared with WT mice after MSU challenge in vitro, as well as MSU phagocytosis. In comparison with WT mice in vivo, the swelling index of T-bet KO mice was significantly decreased in the footpad model. T-bet deficiency also dramatically relieved MSU-induced inflammatory cell infiltration in peritonitis and air pouch models in vivo, and as well as the IL-1ß levels of air pouch lavage fluid (APLF). In addition, plasma IL-17 and IL-23 levels were elevated in acute gout, whereas protein levels of T-bet were downregulated in PBMCs from acute gout patients and intercritical gout treated with MSU crystals in vitro as well. Transcription factor T-bet deficiency protects against MSU-induced gouty inflammation, suggesting that downregulation of T-bet could be a protective strategy and contribute to spontaneous remission of inflammation in acute gout.

Evaluation of Healthy User Effects With Metformin and Other Oral Antihyperglycemia Medication Users in Adult Patients With Type 2 Diabetes.

OBJECTIVES: Healthy user bias, whereby health-seeking patients are more likely to initiate preventive therapies and engage in healthy lifestyle behaviours, is well known in observational studies, particularly with statins. However, its influence in studies of oral antihyperglycemic therapies is unknown. We sought to explore the healthy user effects in metformin users vs. nonusers on various health outcomes that should not be associated with metformin use. METHODS: We conducted a retrospective cohort study using data from Alberta, between 2008 and 2015, to examine the association between metformin use and various health outcomes. RESULTS: We identified 135,301 new users of oral antihyperglycemic agents. The mean age was 55 years, 75,949 (56%) were men and 130,725 (97%) had had at least 1 metformin prescription during a mean follow-up period of 3.4 years. Metformin users were less likely to be involved in accident-related events (adjusted hazard ratio [aHR] 0.90; 95% CI 0.85 to 0.96), were more likely to have preventive screening services (aHR 1.16; 95% CI 1.11 to 1.21), were less likely to experience other clinical events, such as asthma and gout attacks (aHR 0.90; 95% CI 0.84 to 0.97), and had lower risks for all-cause mortality (aHR 0.57; 95% CI 0.51 to 0.63) compared to nonusers. CONCLUSIONS: Our results suggest that metformin users are more likely to initiate preventive therapies and engage in other healthy behaviours. Failure to account for these behaviours may introduce healthy user bias into studies evaluating the effects of oral antihyperglycemic therapies.

The History, Symptoms, Causes, Risk Factors, Types, Diagnosis, Treatments, and Prevention of Gout, Part 2.

Gout, a common and complex form of inflammatory arthritis, is characterized by abnormally elevated levels of uric acid in the blood. The most current estimate from the Centers for Disease Control and Prevention shows an increase from 52.5 million to 54.4 million people in the U.S. have arthritis or one of the rheumatic diseases. There are over 100 rheumatic diseases and conditions. In the U.S., the most common types of arthritis or rheumatic diseases are osteoarthritis, gout, fibromyalgia, and rheumatoid arthritis, in that order according to prevalence. This article focuses on gout. Gout can be effectively treated and managed with a combination of medication (manufactured and/or compounded) and self-management strategies. Part 1 of this 2-part article provided the definition of gout and a brief history of gout. Part 2 continues the discussion of gout and includes examples of compounded formulations used in the treatment of gout.

Goals of gout treatment: a patient perspective.

To assess the goals of gout treatment from a patient perspective, a convenience sample of consecutive patients with doctor-diagnosed gout seen at a community-based outpatient clinic were invited. Sex-stratified nominal groups were conducted until saturation was achieved. Responses were collected verbatim, discussed, and rank-ordered by each participant. Thirty-six patients with doctor-diagnosed gout participated in 12 nominal groups: 6 male only, 5 female only, and 1 group with both. Mean age was 61.9 years (SD, 12.3); mean gout duration was 13.3 years (SD, 12.5); 53% were men, 64% African-American, 42% retired, 47% currently married, 87% were using either allopurinol and/or febuxostat, and 40% had had no gout flares in the last 6 months. The top 5 treatment goals accounted for 91% of all votes and included the following: (1) prevent and better manage flare-ups and improve function (25%), (2) eliminate flare-ups/disease remission (30%), (3) diet and activity modification/lifestyle change (13%), (4) patient education and public awareness (12%), and (5) medication management and minimization of side effects (11%). When examining the top-rated concern for each nominal group, the first two goals were nominated by four groups each, diet/activity modification and medication management by 1 group each, and patient education by 3 groups. There were no differences evident by sex in top-ranked treatment goal. People with gout identified and rank-ordered treatment goals relevant to them. Providers of gout care need to be cognizant of these goals. Disease management concordant with these treatment goals might lead to a more satisfied, informed patient.

The History, Symptoms, Causes, Risk Factors, Types, Diagnosis, Treatments, and Prevention of Gout, Part 1.

Gout, a common and complex form of inflammatory arthritis, is characterized by abnormally elevated levels of uric acid in the blood. It is estimated that 52.5 million people in the U.S. have arthritis or one of the rheumatic diseases, according to the Centers for Disease Control and Prevention. There are over 100 rheumatic diseases and conditions. In the U.S., the most common types of arthritis or rheumatic diseases are osteoarthritis, gout, fibromyalgia, and rheumatoid arthritis, in that order according to prevalence. This article focuses on gout. Although there is no cure for gout, the disease can be effectively treated and managed with a combination of medication (manufactured and/or compounded) and self-management strategies.

Low-Purine Diet Is More Effective Than Normal-Purine Diet in Reducing the Risk of Gouty Attacks After Sleeve Gastrectomy in Patients Suffering of Gout Before Surgery: a Retrospective Study.

BACKGROUND: Obese patients with preoperative gout often suffer of gouty attacks after bariatric surgery (BS), probably due to the lack of an adequate postoperative diet. OBJECTIVES: The objectives of the study are to assess whether sleeve gastrectomy (SG) is effective in reducing the frequency of gouty attacks and also whether a postoperative low-purine diet (LPD) may further reduce these attacks as compared to a normal-purine diet (NPD) in a series of patients suffering of gout before SG. METHODS: In this retrospective study, we measured and compared total body weight (TBW), body mass index (BMI), uric acid levels (UAL), anti-gout medication (allopurinol) requirements, and frequency in gouty attacks in 40 patients that underwent SG and who received either a LPD (n = 24) or NPD (n = 16). Compliance in following the prescribed diet was assessed in both groups study. RESULTS: Before surgery, LPD and NPD patients had hyperuricemia and were receiving allopurinol. One year after SG, LPD and NPD groups showed a significant decrease in serum UAL (p < 0.001 and p = 0.00175, respectively). However, serum UAL decreased more significantly with the LPD compared to the NPD (p < 0.001). Furthermore, while NPD group showed a significant decrease in allopurinol requirements (p = 0.00130) and on the frequency in gouty attacks (p < 0.001), LPD group were off allopurinol therapy and had no gouty attacks 12 months after SG. Both groups showed high compliance in following the prescribed diets. CONCLUSION: LPD is more effective in reducing the frequency of gouty attacks after SG compared with NPD in patients suffering of gout before surgery.

'Shi Han Quan' natural soda water prevents development of gout.

PURPOSE: This study aimed to explore the regulatory mechanism of the natural soda Shi Han Quan (SHQ) in the development of gout. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with monosodium urate (MSU) for 24 h to induce acute gouty inflammation in vitro. HUVECs were divided into four groups: ddH2 O group, ddH2 O + MSU group, 1/2 ddH2 O +1/2 SHQ + MSU group, and SHQ + MSU group. The effects of SHQ on cell viability, concentration and expression of intercellular adhesion molecule-1 (ICAM-1), and MSU-induced release of interleukin (IL)-1ß and IL-6 were investigated. Additionally, cell viability and ICAM-1 concentration and expression were detected after HUVECs were incubated with the culture supernatant of THP-1 cells that had been treated with phorbol 12-myristate 13-acetate (PMA), MSU and SHQ for 24 h. RESULTS: The viability of HUVECs was significantly decreased with increasing transfection concentrations of MSU, and MSU treatment resulted in a significant increase of the concentration and expression of ICAM-1. In addition, SHQ improved the MSU-induced decrease in cell viability and alleviated MSU-mediated increase in ICAM-1 levels. Moreover, SHQ decreased MSU-induced release of IL-1ß and IL-6. After HUVECs were incubated with the culture supernatant of THP-1 cells that had been treated with PMA, MSU and SHQ for 24 h, SHQ also markedly alleviated the effects of MSU, such as by increasing cell viability and decreasing ICAM-1 levels. CONCLUSIONS: Drinking natural soda water may have a significant role in preventing gouty inflammation.

Prevention and Management of Complications During Robotic-assisted Laparoscopic Radical Prostatectomy Following Comprehensive Planning: A Large Series Involving a Single Surgeon.

AIM: To report a series of 1,000 patients treated by a single surgeon using robotic-assisted laparoscopic radical prostatectomy (RALP) and to show how to prevent and manage complications of the procedure. PATIENTS AND METHODS: Complication rates were prospectively assessed in a series of 1,000 consecutive patients who underwent RALP (group I, cases 1-200; IIa, 201-400; IIb, 401-600; IIIa, 601-800; and IIIb, 801-1000). Preoperative evaluation focused on patients' history of gout, use of drugs that can influence clotting time, and cardiopulmonary problems. Magnetic resonance imaging (MRI) was routinely performed. Operative difficulty was assessed based on the following variables: neoadjuvant hormonal therapy (NHT), obesity [body mass index (BMI) >30 kg/m(2)], prostate volume >70 g, presence of a large median lobe with intravesical protrusion >1 cm, previous transurethral resection of the prostate, previous pelvic surgery, previous extended pelvic lymph node dissection (EPLND), and salvage robotic radical prostatectomy (SRP). RESULTS: Operative difficulty tended to increase significantly with greater age, higher American Society of Anesthesiologists' anesthetic/surgical risk class scores, increased BMI, and more advanced clinical stage. The number of cases with NHT, obesity, previous pelvic surgery, EPLND, and SRP significantly increased from early to later groups of patients. Conversely, significantly less blood loss occurred in later groups of patients (group I, 179 ml to 97 ml in group IIIb; p<0.001). The need for blood transfusions gradually reduced from 3.5% to 0.5% in groups I and IIIb, respectively (p=0.022). The total complication rate was 6.4% (64/1,000; surgical/medical=5%/1.4%). Complication rates decreased significantly: 12%, 6%, 6%, 4%, and 4% in groups I, IIa, IIb, IIIa, and IIIb, respectively (p=0.003). The most common complications were blood transfusion and bowel problems (11/1,000=1.1%). CONCLUSION: Assessed in terms of groups of 200 cases, the surgeon's learning curve for RALP showed significantly fewer complications even as the operative difficulty of cases increased. The keys to preventing complications were meticulous preoperative evaluation of patients, MRI planning, and a dedicated robotic team for performing RALP. Early diagnosis and management of complications are paramount in patients who present any deviation from the normal postoperative course and clinical care pathway.

Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study.

BACKGROUND: Gout gives rise to increased risk of cardiovascular events. Gout attacks can be effectively prevented with urate lowering drugs, and allopurinol potentially reduces cardiovascular risk. What target level of urate is required to reduce cardiovascular risk is not known. OBJECTIVES: To investigate the effect of achieving target plasma urate with allopurinol on cardiovascular outcomes in a case-control study nested within long-term users of allopurinol. METHODS: We identified long-term users of allopurinol in Funen County, Denmark. Among these, we identified all cases of cardiovascular events and sampled 4 controls to each case from the same population. The cases and controls were compared with respect to whether they reached a urate target below 0.36 mmol/l on allopurinol. The derived odds ratios were controlled for potential confounders available from data on prescriptions, laboratory values and in- and outpatient contacts. RESULTS: No association between treatment-to-target urate level and cardiovascular events were found (adjusted odds ratio of 1.01, 95% confidence interval 0.79-1.28). No significant effect was seen in any subgroup defined by age, gender, renal function, allopurinol dose or the achieved urate level. Overall, the doses of allopurinol used in this study were low (mean ≈ 140 mg/day). CONCLUSION: We were unable to demonstrate a link between achieved urate level in patients treated with allopurinol and risk of cardiovascular events. Possible explanations include that allopurinol doses higher than those used in this study are required to achieve cardiovascular risk reduction or that the cardiovascular effect of allopurinol is not mediated through low urate levels. It remains to be seen whether allopurinol has a dose-response relationship with cardiovascular events at higher doses.

Hyperuricemia is associated with an increased prevalence of atrial fibrillation in hospitalized patients with type 2 diabetes.

PURPOSE: Hyperuricemia/gout and atrial fibrillation (AF) are two pathological conditions that are highly prevalent in type 2 diabetes and share multiple cardiovascular risk factors. However, the relationship between elevated levels of serum uric acid and risk of AF in type 2 diabetes is currently poorly known. METHODS: We studied a hospital-based sample of 842 (male/female = 463/379) patients with type 2 diabetes discharged from our Division of Endocrinology during 2007-2011. Hyperuricemia was defined as a serum uric acid level >7 mg/dl for men and >6 mg/dl for women or allopurinol use. The diagnosis of AF was confirmed in affected participants on the basis of ECGs and medical history by experienced cardiologists. RESULTS: Overall, 243 (28.9 %) patients had hyperuricemia and 91 (10.8 %) patients had persistent or permanent AF. Compared with those with normal serum uric acid levels, patients with hyperuricemia had a remarkably greater prevalence of AF (20.6 vs. 7.1 %; p < 0.001). Hyperuricemia was significantly associated with an increased risk of prevalent AF (odds ratio 3.41, 95 % CI 2.19-5.32; p < 0.001). Adjustments for age, sex, smoking, hemoglobin A1c, hypertension status, chronic kidney disease, chronic obstructive pulmonary disease and previous histories of hyperthyroidism, ischemic heart disease and valvular heart diseases did not weaken this association (adjusted-odds ratio 6.27, 95 % CI 1.82-21.5; p < 0.01). CONCLUSIONS: These results indicate that hyperuricemia is associated with an increased prevalence of AF in hospitalized patients with type 2 diabetes, independently of multiple risk factors and potential confounders.

Guía dietética para pacientes con hiperuricemia y gota agar / Dietary guide for patients with hyperuricaemia and drop agar

Gota proviene del latin Gutta es un término acuñado en el siglo V que significa exceso o derrame de flema por exceso de vino, comida y sexo. Llamada "Rey de las enfermedades yenfermedad de reyes" fue uno de los primeros desordenes reumáticos en ser reconocidos como entidad clínic a. Es la artritis por deposito de microcri s tales más común debida a desequilibrio en el metabolismo de las purinas que conlleva a hiperuricemia y el depósito de cristales de urato monosódico, caracterizada por ser de inicio monoarticular, que a fecta con mayor frecuencia la primera articulación metatarso de pie y que progresa en su forma crónica a poliarticular, asociada a destrucción progresiva y a la formación de tofos, falla renal y enfermedad cardiovascular. Predomina sexo masculino, su pr evalencia se calcula de 0.08% a nivel mundial, aumentando la frecuencia de sus ataques con el alto contenido de carnes, mariscos, cervezas y bebidas espirituosas. El objetivo de la presente revisión bibliográfica es proporcionar una guía dietética para lo s médicos enfatizando y destacando su contenido de purinas en alimentos de uso cotidiano en la población guatemalteca, para obtener un mejor control de la artritis gotosa y disminuir la frecuencia de sus ataques ...(AU)

Gota comes from Latin Gutta is a term coined in the fifth century that means excess or spill of phlegm for excess wine, food and sex. Called "King of diseases and disease of kings" was one of the first rheumatic disorders to be recognized as a clinical entity. Arthritis is the most common microcritical deposit due to imbalance in the metabolism of purines that leads to hyperuricemia and the deposition of monosodium urate crystals, characterized by monoarticular initiation, which most often occurs with the first metatarsal joint. standing up and progressing in its form chronic to polyarticular, associated with progressive destruction and the formation of tophi, renal failure and cardiovascular disease. Male sex predominates, its pr evance is estimated at 0.08% worldwide, increasing the frequency of its attacks with the high content of meats, seafood, beers and spirits. The aim of this bibliographical review is to provide a dietary guide for physicians emphasizing and highlighting their content of purines in foods of daily use in the Guatemalan population, to obtain a better control of gouty arthritis and to reduce the frequency of their attacks. .. (AU)

Lifestyle and dietary habits of patients with gout followed in rheumatology settings.

Diet and lifestyles modification are core aspects of the non-pharmacological management of gout, but a poor consistency with suggested guidelines is reported. This study aimed to investigate dietary and lifestyle habits of patients with gout followed in rheumatology settings. Data were retrieved from the baseline dataset of the KING study, a multicentre cohort study of patients with gout followed in rheumatology settings. Dietary habits were assessed with the Italian National Institute of Statistics (ISTAT) food-frequency questionnaire and compared with reported data about general population. The relative increase of exposure was estimated by standardized prevalence ratios adjusted for gender, age and geographical distribution. The study population included 446 patients, with a mean age of 63.9 years and a M/F ratio of 9:1. Compared to the Italian population, gouty patients showed a higher prevalence of obesity [1.82 (1.52-2.18)] and a higher consumption of wine [1.85 (1.48-2.32)] and beer [2.21 (1.68-2.90)], but a lower prevalence of smoking and a lower intake of liquor. They showed a lower intake of red meat [0.80 (0.71-0.91)], but a similar intake of other tested dietary factors. Gouty patients' lifestyle is still partially different from the recommended.

Monosodium urate crystal induced macrophage inflammation is attenuated by chondroitin sulphate: pre-clinical model for gout prophylaxis?

BACKGROUND: Chondroitin Sulphate (CS), a natural glycosaminoglycan of the extracellular matrix, has clinical benefit in symptomatic osteoarthritis but has never been tested in gout. In vitro, CS has anti-inflammatory and positive effects on osteoarthritic chondrocytes, synoviocytes and subchondral bone osteoblasts, but its effect on macrophages is unknown. The purpose of our study was to evaluate the in vitro effects of CS on monosodium urate (MSU)-stimulated cytokine production by macrophages. METHODS: THP-1 monocytes were differentiated into mature macrophages using a phorbol ester, pretreated for 4 hours with CS in a physiologically achievable range of concentrations (10-200 µg/ml) followed by MSU crystal stimulation for 24 hours. Cell culture media were analyzed by immunoassay for factors known to be upregulated during gouty inflammation including IL-1ß, IL-8 and TNFα. The specificity of inflammasome activation by MSU crystals was tested with a caspase-1 inhibitor (0.01 µM-10 µM). RESULTS: MSU crystals ≥10 mg/dl increased macrophage production of IL-1ß, IL-8 and TNFα a mean 7-, 3- and 4-fold respectively. Induction of IL-1ß by MSU was fully inhibited by a caspase-1 inhibitor confirming inflammasome activation as the mechanism for generating this cytokine. In a dose-dependent manner, CS significantly inhibited IL-1ß (p = 0.003), and TNFα (p = 0.02) production from macrophages in response to MSU. A similar trend was observed for IL-8 but was not statistically significant (p = 0.41). CONCLUSIONS: CS attenuated MSU crystal induced macrophage inflammation, suggesting a possible role for CS in gout prophylaxis.

Prevention of comorbidity and acute attack of gout by uric acid lowering therapy.

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA≥6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.