Role of diet in hyperuricemia and gout.

BACKGROUND: Gout is the most common form of inflammatory arthritis, affecting 41 million adults worldwide. The global burden of gout has been increasing over the last three decades, yet its management remains suboptimal. The primary aim of this manuscript is to review the impact of various diets such as the DASH, Mediterranean, and low purine diets; weight loss; and individual foods, including alcohol, caffeine, cherry, dairy, high-fructose corn syrup, omega-3 fatty acids, and vitamin C on hyperuricemia and clinical gout outcomes such as flares and tophi. CONCLUSION: Few studies to date have specifically evaluated the effect of various dietary approaches on hyperuricemia among people with gout and on gout-specific outcomes. Overall, the dietary factors appear to have a small effect on serum urate levels, and their impact on the long-term clinical course of gout is uncertain. Limited evidence suggests that avoidance of certain foods and beverages may decrease the frequency of gout flares. Weight loss may be beneficial for prevention as well as treatment of gout. Urate-lowering therapy remains the mainstay of therapy, with diet and dietary factors studied to date playing a limited role in the definitive management of gout.

[Gout]. / La maladie goutteuse.

Gout is a chronic disease due to the deposition of monosodium urate microcrystals in joints and tissues. Its incidence and prevalence are increasing worldwide in close relation with the epidemic of obesity and metabolic syndrome. Gout is related to chronic hyperuricemia that should be treated to ensure the reduction or even the disappearance of acute attacks ("gout flares") and to reduce the size and number of tophi. If arthritis of the first metatarsophalangeal joint is the most typical form, other joints may be affected, including the spine. Demonstration of urate microcrystals arthritis allows diagnosis of gout but, in the absence of possibility of performing joint puncture, imaging may be useful for providing complementary diagnostic elements. Appropriate care is essential to reduce the number of flares and the evolution towards gouty arthropathy but also in terms of public health in order to reduce costs related to this pathology.

HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-κB-MyD88 Signaling Pathway and Disrupting Mitochondrial Function.

Acute gout is an inflammatory response induced by monosodium urate (MSU) crystals. HSP60 is a highly conserved stress protein that acts as a cellular "danger" signal for immune reactions. In this study, we aimed to investigate the role and molecular mechanism of HSP60 in gout. HSP60 expression was detected in peripheral blood mononuclear cells (PBMCs) and plasma of gout patients. The effect and molecular mechanism of HSP60 in gout were studied in MSU crystals treatment macrophages and C57BL/6 mice. JC-1 probe and MitoSOX Red were used to measure the mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS). HSP60 expression was significantly upregulated in the PBMCs and sera of patients with acute gout (AG) compared to those with intercritical gout (IG) or healthy controls (HCs). MSU crystals induced the expression and secretion of HSP60 in the macrophages. HSP60 knockdown or overexpression affects TLR4 and MyD88 expression, IκBα degradation, and the nuclear localization of NF-κB in MSU crystal-stimulated inflammation. Further, HSP60 facilitates MMP collapse and mtROS production and activates the NLRP3 inflammasome in MSU crystal-stimulated macrophages. In MSU crystal-induced arthritis mouse models pretreated with HSP60 vivo-morpholino, paw swelling, myeloperoxidase (MPO) activity, and inflammatory cell infiltration significantly decreased. Our study reveals that MSU crystal stimulates the expression of HSP60, which accelerates the TLR4-MyD88-NF-κB signaling pathway and exacerbates mitochondrial dysfunction.

Study on the diagnosis of gout with xanthine and hypoxanthine.

BACKGROUND: Hyperuricemia is the only biochemical index in the classification of acute gouty arthritis in American Rheumatism Association 1977 and the main basis of clinical diagnosis for most doctors. However, nearly half of the time gout occurs without hyperuricemia, especially in an acute attack，which leads to an urgent need to find a new substitute diadynamic criteria of gout. Xanthine and hypoxanthine, as precursors of uric acid, have been reported to be high in gout patients with hyperuricemia and presumed to be gout biomarkers. OBJECTIVES: To further explore the possibility of xanthine and hypoxanthine to be gout biomarkers as substitutes for uric acid. METHODS: A reversed-phase HPLC-UV method was employed for simultaneous quantitative detection of uric acid (UA), xanthine (X), and hypoxanthine (HX) in gout patients' (with and without hyperuricemia) and healthy persons' serum. RESULTS: The xanthine and hypoxanthine concentrations in gout patients with hyperuricemia and without hyperuricemia are higher than in healthy persons with a P < 0.001. CONCLUSIONS: This study supplements previous researches by confirming that xanthine and hypoxanthine are significantly elevated in gout patients' serum especially in patients' with normouricemia, which supported xanthine and hypoxanthine may have clinical application for the diagnosis of gout.

Beneficial Properties of Phytochemicals on NLRP3 Inflammasome-Mediated Gout and Complication.

Gouty arthritis is characterized by the precipitation of monosodium urate (MSU) crystals in the joint. Pro-inflammatory cytokine IL-1ß is a critical manifestation in response to MSU crystals attack. IL-1ß secretion is dependent on the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Abnormal activation of the NLRP inflammasome is related to cellular oxidative stress. However, recent studies have illustrated that phytochemicals with potent antioxidant activity exert inhibitory effects on NLRP3 inflammasome-mediated diseases. This review focuses on the current findings of studies on the NLRP3 inflammasome and the proposed mechanisms that MSU crystals trigger inflammation via activation of the NLRP3 inflammasome. We also summarized the potential use of phytochemicals on NLRP3 inflammasome-mediated diseases, suggesting that phytochemicals can further prevent acute gout attack.

[Nutritional therapy of gout]. / Ernährungstherapie bei Gicht.

Nutrition and nutritional behaviours have been found to play a major role in the development of gout. Studies show that body mass index (BMI), as well as excessive intake of alcoholic beverages, meat, soft drinks and fruit juices increase the risk of developing gout. Similarly, dairy products and coffee have been seen to decrease the risk of hyperuricemia and gout, as they increase the excretion of uric acid. Flares of gout are often caused by large meals and high alcohol consumption. Each additional intake of meat portion per day increases the risk of gout by 21 %. Taking total alcohol consumption into account, the risk of gout increases after one to two standard drinks. In contrast to previous assumptions purine-rich plant foods like legumes and vegetables do not increase the risk of gout. The current dietary guidelines take into account nutritional factors, which not only consider purine intake, but also their endogenous production and their influence on renal excretion. A balanced diet based on the Swiss healthy eating guideline pyramid as well as the Mediterranean diet is appropriate for this patient population. The treatment of gout is multi-faceted, since this patient population presents other comorbidities such as obesity, diabetes mellitus, dyslipidemia and hypertension. Collectively, these risk factors are diet dependent and require a treatment strategy that is centered on modifying one's nutrition and nutritional behaviours. The aim of such therapy is to educate the patient as well as treat the accompanying comorbidities with the goal of decreasing serum uric acid values. Motivated patients require consultation and follow-up care in order to be able to actively decrease the serum uric acid.

Study on the anti-gout activity of chlorogenic acid: improvement on hyperuricemia and gouty inflammation.

Gout is a metabolic disorder associated with hyperuricemia resulting in the deposition of monosodium urate (MSU) crystals in joints and tissues. Lowering serum uric acid (Sur) levels and anti-inflammation are highly essential in treating gout. Chlorogenic acid (CA), as one of the most abundant polyphenols in the Chinese medicines, has been rarely reported to have an anti-gout effect. The model of potassium oxonate (PO)-induced hyperuricemia in mice and MSU crystal-induced inflammation in rats has been established in this study. The potential beneficial effects and mechanisms of CA on hyperuricemia and gouty arthritis were elucidated. The results demonstrated that CA significantly decreased the Sur level by inhibiting the xanthine oxidase (XOD) activity but not increasing the urinary uric acid (Uur) level. In addition, CA also exhibited the effect of suppressing paw swelling. Further investigation indicated that CA improved the symptoms of inflammation induced by MSU crystals by inhibiting the production of proinflammatory cytokines including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The present study suggests that CA may have a considerable potential for development as an anti-gouty arthritis agent for clinical application.

Food, drink, and herbs: alternative therapies and gout.

Gout was first recognized as a distinct clinical entity in antiquity. Our understanding of the epidemiology and treatment of gout has evolved over millennia intertwined with observations about social class and plant and animal sources of food, beverages and medicines. Investigators have identified various aspects of diet that relate to gout risk and recurrence. Some of our most useful medications for the treatment of gout were developed from herbal precursors. Traditional dietary recommendations for gout patients have included limiting high purine meat and alcohol consumption. More recent work suggests diets leading to weight loss through calorie and carbohydrate reductions may be effective for lowering serum urate levels, as well as the risk of gout.

Maori experiences and perceptions of gout and its treatment: a kaupapa Maori qualitative study.

INTRODUCTION: The prevalence of gout among Maori is one of the highest in the world. This study explores the perceptions, understanding and treatment of gout among Maori. METHODS: A qualitative general inductive approach was used, guided by kaupapa Maori principles. Participants included 12 Maori aged 48-79 years with gout. Semi-structured interviews were undertaken, taped and transcribed. Themes were identified from transcripts. FINDINGS: Participants described overwhelming sufferance due to gout, which was sometimes considered inevitable. All participants believed or had been informed that gout is caused by food and/or drink. This led to feelings of self-blame and blame from partners and employers. Whanau (family) were a resource for information and a support when independence was limited. Rongoa (traditional medicine) played a role in the lives of rural but not urban participants. Many reported stoicism, putting up with pain and putting others before themselves, as the 'Maori way'. Medicines used for gout management were predominantly non-steroidal anti-inflammatory drugs, colchicine and prednisone, with allopurinol only playing a role late in the disease. Medications were often poorly understood and consequently improperly used. Relationships with health professionals were important, but cultural, financial and time barriers impaired access and understanding. Gout had a huge, negative impact on the lives of participants. CONCLUSION: The quality of lives of many people with gout could be improved by better understanding through educational campaigns for health professionals and the community. Culturally sensitive health care systems and a paradigm shift in gout management and early preventive treatment are needed.

Recent advances in management of gout.

Incidence and prevalence of gout have markedly increased over the last few decades in keeping with the rise in prevalence of obesity and metabolic syndrome. Until recently, management of gout in patients with associated metabolic syndrome and comorbid illnesses such as renal impairment was difficult because of limited treatment options. However, significant progress has been made in the last few years, with introduction of new treatments such as interleukin-1 antagonists for management of acute gout, and febuxostat and pegloticase for chronic gout. The association of gout with alcohol, dietary purines and fructose ingestion has been confirmed in large prospective studies, thus enabling the clinician to now provide evidence-based advice to patients. Recent efficacy and safety data favour lower over higher doses of colchicine, and oral corticosteroids over non-steroidal anti-inflammatory drugs for patients with acute gout. Local ice therapy might help to differentiate gout from other forms of inflammatory arthritis, and supplementation with vitamin C help to reduce risk of gout. Several other drugs with rational mechanisms of action are in the pipeline, and likely to be introduced over the next few years. A new era has thus begun in the field of gout.

Update on the management of hyperuricemia and gout.

Gout is the most common inflammatory arthritis in the United States, with more than three million sufferers. Management of gout has changed relatively little in the past 50 years, despite the fact that many gout patients have contraindications to one or more currently available gout therapies. However, recent insights into gout pathophysiology suggest that time is ripe for a change. This article reviews recent updates in the management of gout, including new insights into dietary management that may permit better control of hyuperuricemia. Also reviewed are the biological and clinical data behind newly-developed drugs for gout that are likely to receive serious consideration for FDA approval, and clinical use, in the foreseeable future.

TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation.

Microcrystals of calcium pyrophosphate dihydrate (CPPD) and monosodium urate (MSU) deposited in synovium and articular cartilage initiate joint inflammation and cartilage degradation in large part by binding and directly activating resident cells. TLRs trigger innate host defense responses to infectious pathogens, and the expression of certain TLRs by synovial fibroblasts has revealed the potential for innate immune responses to be triggered by mesenchymally derived resident cells in the joint. In this study we tested the hypothesis that chondrocytes also express TLRs and that one or more TLRs centrally mediate chondrocyte responsiveness to CPPD and MSU crystals in vitro. We detected TLR2 expression in normal articular chondrocytes and up-regulation of TLR2 in osteoarthritic cartilage chondrocytes in situ. We demonstrated that transient transfection of TLR2 signaling-negative regulator Toll-interacting protein or treatment with TLR2-blocking Ab suppressed CPPD and MSU crystal-induced chondrocyte release of NO, an inflammatory mediator that promotes cartilage degeneration. Conversely, gain-of-function of TLR2 in normal chondrocytes via transfection was associated with increased CPPD and MSU crystal-induced NO release. Canonical TLR signaling by parallel pathways involving MyD88, IL-1R-associated kinase 1, TNF receptor-associated factor 6, and IkappaB kinase and Rac1, PI3K, and Akt critically mediated NO release in chondrocytes stimulated by both CPPD and MSU crystals. We conclude that CPPD and MSU crystals critically use TLR2-mediated signaling in chondrocytes to trigger NO generation. Our results indicate the potential for innate immunity at the level of the articular chondrocyte to directly contribute to inflammatory and degenerative tissue reactions associated with both gout and pseudogout.

Lead nephropathy, gout, and hypertension.

The EDTA (calcium disodium edetate) lead mobilization test revealed lead as the probable cause of renal disease in industrial lead workers and in patients with gout or essential hypertension. The data reviewed here demonstrate persistence of lead nephropathy in the contemporary scene despite the introduction of modern industrial and environmental exposure standards. Renal function and biopsy studies showed that lead nephropathy is a chronic tubulointerstitial renal disease with modest proteinuria which frequently presents with hyperuricemia, gout and hypertension. Only evaluation of body lead stores by either the EDTA lead mobilization test or by x-ray fluorescence is helpful in diagnosing lead nephropathy. While chelation therapy is safe and helpful in reversing early lead nephropathy, the best treatment is prevention. These studies further raise the possibility that chronic environmental lead poisoning and associated renal disease and hypertension may be a more widespread problem than suspected. Assessment of the true extent of chronic lead poisoning requires large scale epidemiological studies.

Gout of the rich and famous.

A number of sources on the subject of gout, and particularly its role in history, were consulted. Highlights are presented to illustrate popular conceptions of the social implications of gout. It is indicated that the consequences of this affliction may be disastrous to empires, yet are not always viewed as entirely negative for individual sufferers.

New trends in psychosomatic research.

Advances in physiological psychology and neuroendocrinology, together with epidemiological studies, have added new dimensions to psychosomatic research. Psychological influences still are accepted as exacerbators or trigger mechanisms, if less often as causes. Theories of psychosomatics which connected specific personality profiles with specific psychosomatic illnesses have lost favor, and multifactorial explanations, which include heredity, environment, social class, life stress, endocrines, brain areas, neurohormones, and immunological mechanisms, are new areas of research. Research methods have become more sophisticated scientifically, particularly in the selection and size of samples tested, and the variety of situations investigated. Psychological reactions to illness in general, terminal disease, and death, and psychological experiences of pain, in addition to variable effects of psychotherapeutic methods and psychotherapists' personality, are identifiable but unquantified influences which seem acceptable as contributors to, if not causes of, psychophysiological disorders.