Pathogenesis of Gout

Arthritis Research Centre of Canada, University of British Columbia, Vancouver, British Columbia, Canada.
Annals of internal medicine (Impact Factor: 17.81). 11/2005; 143(7):499-516. DOI: 10.7326/0003-4819-143-7-200510040-00009
Source: PubMed


The disease burden of gout remains substantial and may be increasing. As more scientific data on modifiable risk factors and comorbidities of gout become available, integration of these data into gout care strategy may become essential, similar to the current care strategies for hypertension (163) and type 2 diabetes (164). Recommendations for lifestyle modification to treat or to prevent gout are generally in line with those for the prevention or treatment of other major chronic disorders (32). Thus, the net health benefits from these general healthy lifestyle recommendations (32) are expected to be even larger among many patients with gout, particularly those with coexisting insulin resistance syndrome, diabetes, obesity, and hypertension. Weight control, limits on red meat consumption, and daily exercise are important foundations of lifestyle modification recommendations for patients with gout or hyperuricemia and parallel recommendations related to prevention of coronary heart disease, diabetes, and certain types of cancer. Patients with gout could consider using plant-derived ω-3 fatty acids or supplements of eicosapentaenoic acid and docosahexarioic acid instead of consuming fish for cardiovascular benefits. The recent recommendation on dairy consumption for the general public would also be applicable for most patients with gout or hyperuricemia and may offer added benefit to individuals with hypertension, diabetes, and cardiovascular disorders. Further risk-benefit assessments in each specific clinical context would be helpful. Daily consumption of nuts and legumes as recommended by the Harvard Healthy Eating Pyramid (32) may also provide important health benefits without increasing the risk for gout. Similarly, a daily glass of wine may benefit health without imposing an elevated risk for gout, especially in contrast to beer or liquor consumption. These lifestyle modifications are inexpensive and safe and, when combined with drug therapy, may result in better control of gout. Effective management of gout risk factors (for example, hypertension) and the strategic choice of certain therapies for comorbid conditions may also aid gout care. For example, antihypertensive agents with uricosuric properties (for example, losartan [165] or amlodipine [86]) could have a better risk-benefit ratio than diuretics for hypertension in hypertensive patients with gout. Similarly, the uricosuric property of fenofibrate (165) may be associated with a favorable risk-benefit ratio among patients with gout and the metabolic syndrome. The recently elucidated molecular mechanism of renal urate transport has several important implications in conditions that are associated with high urate levels. In particular, the molecular characterization of the URAT1 anion exchanger has provided a specific target of action for well-known substances affecting urate levels. Genetic variation in these renal transporters or upstream regulatory factors may explain the genetic tendency to develop conditions associated with high urate levels and a patient's particular response to medications. Furthermore, the transporters themselves may serve as targets for future drug development. Finally, advances in our understanding of crystal-induced inflammation indicate that gout shares many pathogenetic features with other chronic inflammatory disorders. Some newly available potent anti-inflammatory medications (including biological agents that are indicated for other conditions) may have therapeutic potential in selected subsets of patients with gout, although the high costs of biological agents would probably prevent their widespread use in gout. Anti-inflammatory agents for gout (including colchicine) are typically used to treat acute gout or to reduce the risk for rebound gout attacks during the initiation of urate-lowering therapy but do not lower serum levels of uric acid. The long-term safety profile of these agents needs to be clarified, including the potential consequences of chronic hyperuricemia with such anti-inflammatory treatment.

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Available from: Anthony M Reginato, Oct 09, 2015
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    • "Their concentrations may affect human health and act as biomarkers for various diseases (Ascherio et al., 2009; Burtis & Ashwood, 2001; Choi, Mount, & Reginato, 2005; Chonchol et al., 2007; Dehghan, van Hoek, Sijbrands, Hofman, & Witteman, 2008; Gagliardi, Miname, & Santos, 2009; Harper, 1977; Heinig & Johnson, 2006; Kassirer, 1971; Krishnan, Kwoh, Schumarcher, & Kuller, 2007; Lapsia et al., 2012; Lin et al., 2011; Mouton & Holder, 2006). The abnormal high concentrations of uric acid in human plasma and urine are associated with several diseases, such as gouty arthritis, hyperuricemia, hypertension, pneumonia, type 2 diabetes, cardiovascular disease and kidney damage (Ascherio et al., 2009; Burtis & Ashwood, 2001; Choi et al., 2005; Chonchol et al., 2007; Dehghan et al., 2008; Gagliardi et al., 2009; Harper, 1977; Heinig & Johnson, 2006; Kassirer, 1971; Krishnan et al., 2007; Lapsia et al., 2012; Lin et al., 2011; Mouton & Holder, 2006). Creatinine, quantitatively excreted in the urine, is nonenzymatically formed from intracellular creatine and phosphocreatine in muscles. "
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    ABSTRACT: Creatinine (Cr), uric (UA) and ascorbic acid (AA) are common constituents in human fluids. Their abnormal concentrations in human fluids are associated with various diseases. Thus, apart from the endogenous formation in human body, it is also important to examine their sources from food products. In this study, a rapid and accurate HILIC method was developed for simultaneous determination of Cr, UA and AA in bovine milk and orange juice. Milk samples were pretreated by protein precipitation, centrifugation and filtration, followed by HPLC separation and quantification using a Waters Spherisorb S5NH2 column. The developed method has been successfully applied to determine the concentration of UA, AA and Cr in milk and fruit juice samples. The milk samples tested were found to contain UA and creatinine in the concentration range of 24.1-86.0 and 5.07-11.2μgmL(-1), respectively. The orange juices contain AA over 212μgmL(-1). Copyright © 2015 Elsevier Ltd. All rights reserved.
    Food Chemistry 09/2015; 182. DOI:10.1016/j.foodchem.2015.02.142 · 3.39 Impact Factor
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    • "According to this higher concentrations of uric acid may be response to the higher levels of xanthine oxidase activity and to the oxidative stress, which is characteristic for many vascular disease states [38]. The overactivity of XO results in a condition known as gout [39], a common rheumatic disease and an acute inflammatory arthritis [40]. The treatment for hyperuricemia and gout is either increasing the excretion of uric acid or reducing the uric acid production. "
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    ABSTRACT: Xanthine oxidase (XO) is an important enzyme catalyzing the hydroxylation of hypoxanthine to xanthine and xanthine to uric acid which is excreted by kidneys. Excessive production and/or inadequate excretion of uric acid results in hyperuricemia. This paper presents a detailed review of methods of isolation, determination of xanthine oxidase activity, and the effect of plant extracts and their constituents on it. Determining the content and activities of XO can be used for diagnostic purposes. Testing inhibition of XO is important for detection of potentially effective compounds or extracts that can be used to treat diseases that are caused by increased activity of XO. In vitro bioassays are used to examine test material for XO inhibition, as inhibitors of XO may be potentially useful for the treatment of gout or other XO induced diseases. Several authors reported on the XO inhibitory potential of traditionally used medicinal plants.
    02/2015; 2015:1-8. DOI:10.1155/2015/294858
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    • "Gout is a common form of arthritis1 with many sufferers, comprising about 3 million people in the USA2 and 0.7 million in the UK.3 Moreover, gout accounts for 4 million outpatient visits each year,4 resulting in a considerable economic burden.5 "
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    ABSTRACT: The aims of this study were to investigate the most effective combination of physical forces from laser, electroporation, and reverse iontophoresis for noninvasive transdermal extraction of uric acid, and to develop a highly sensitive uric acid biosensor (UAB) for quantifying the uric acid extracted. It is believed that the combination of these physical forces has additional benefits for extraction of molecules other than uric acid from human skin. A diffusion cell with porcine skin was used to investigate the most effective combination of these physical forces. UABs coated with ZnO2 nanoparticles and constructed in an array configuration were developed in this study. The results showed that a combination of laser (0.7 W), electroporation (100 V/cm(2)), and reverse iontophoresis (0.5 mA/cm(2)) was the most effective and significantly enhanced transdermal extraction of uric acid. A custom-designed UAB coated with ZnO2 nanoparticles and constructed in a 1×3 array configuration (UAB-1×3-ZnO2) demonstrated enough sensitivity (9.4 μA/mM) for quantifying uric acid extracted by the combined physical forces of laser, electroporation, and RI. A good linear relationship (R (2)=0.894) was demonstrated to exist between the concentration of uric acid (0.2-0.8 mM) inside the diffusion cell and the current response of the UAB-1×3-ZnO2. In conclusion, a new approach to noninvasive transdermal extraction and quantification of uric acid has been established.
    International Journal of Nanomedicine 06/2014; 9(1):3069-76. DOI:10.2147/IJN.S65674 · 4.38 Impact Factor
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