Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An unusual case of a patient with a gouty tophus in the middle ear is presented. The patient had no clinical or laboratory signs of hyperuricaemia. The findings in the middle ear are discussed with reference to current knowledge of the pathogenesis of gout.
HNO 1990 Dec
PMID:[Gout tophus of the middle ear]. 208 74

Symmetric, sometimes monstrous fat deposits occur in this rare benign disease. They can extend from the neck to the shoulders and from the mandible to the clavicle. The authors have treated 3 patients during the last 4 years. One of them was sent as an inpatient with the diagnosis of lymphadenitis. The aetiology is unknown. Some metabolic disorders (gout, diabetes mellitus, hypertriglyceridemia) are discussed as causes. Alcoholism seems to be an important factor. Surgical removal of the fat deposits is the therapy of choice despite the tendency to recur which is described in the literature.
HNO 1984 Sep
PMID:[Madelung's disease--the problem of treating benign growths of the adipose tissue]. 650 Oct 10

Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO) produced by lipopolysaccharide-stimulated cells of a mouse monocyte line. In this study, we used uric acid to treat experimental allergic encephalomyelitis (EAE) in the PLSJL strain of mice, which develop a chronic form of the disease with remissions and exacerbations. Uric acid administration was found to have strong therapeutic effects in a dose-dependent fashion. A regimen of four daily doses of 500 mg/kg uric acid was required to promote long-term survival regardless of whether treatment was initiated before or after the clinical symptoms of EAE had appeared. The requirement for multiple doses is likely to be caused by the rapid clearance of uric acid in mice which, unlike humans, metabolize uric acid a step further to allantoin. Uric acid treatment also was found to diminish clinical signs of a disease resembling EAE in interferon-gamma receptor knockout mice. A possible association between multiple sclerosis (MS), the disease on which EAE is modeled, and uric acid is supported by the finding that patients with MS have significantly lower levels of serum uric acid than controls. In addition, statistical evaluation of more than 20 million patient records for the incidence of MS and gout (hyperuricemic) revealed that the two diseases are almost mutually exclusive, raising the possibility that hyperuricemia may protect against MS.
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PMID:Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. 943 51

Peroxynitrite, a biological oxidant formed from the reaction of nitric oxide with the superoxide radical, is associated with many pathologies, including neurodegenerative diseases, such as multiple sclerosis (MS). Gout (hyperuricemic) and MS are almost mutually exclusive, and uric acid has therapeutic effects in mice with experimental allergic encephalomyelitis, an animal disease that models MS. This evidence suggests that uric acid may scavenge peroxynitrite and/or peroxynitrite-derived reactive species. Therefore, we studied the kinetics of the reactions of peroxynitrite with uric acid from pH 6.9 to 8.0. The data indicate that peroxynitrous acid (HOONO) reacts with the uric acid monoanion with k = 155 M(-1) s(-1) (T = 37 degrees C, pH 7.4) giving a pseudo-first-order rate constant in blood plasma k(U(rate))(/plasma) = 0.05 s(-1) (T = 37 degrees C, pH 7.4; assuming [uric acid](plasma) = 0.3 mM). Among the biological molecules in human plasma whose rates of reaction with peroxynitrite have been reported, CO(2) is one of the fastest with a pseudo-first-order rate constant k(CO(2))(/plasma) = 46 s(-1) (T = 37 degrees C, pH 7.4; assuming [CO(2)](plasma) = 1 mM). Thus peroxynitrite reacts with CO(2) in human blood plasma nearly 920 times faster than with uric acid. Therefore, uric acid does not directly scavenge peroxynitrite because uric acid can not compete for peroxynitrite with CO(2). The therapeutic effects of uric acid may be related to the scavenging of the radicals CO(*-)(3) and NO(*)(2) that are formed from the reaction of peroxynitrite with CO(2). We suggest that trapping secondary radicals that result from the fast reaction of peroxynitrite with CO(2) may represent a new and viable approach for ameliorating the adverse effects associated with peroxynitrite in many diseases.
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PMID:Reaction of uric acid with peroxynitrite and implications for the mechanism of neuroprotection by uric acid. 1077 20

Hyperuricemia has been labeled both a risk factor and marker for cardiovascular pathology in addition to being associated with gout and kidney disease. Uric acid in vitro acts as a potent antioxidant capable of scavenging hydroxy radicals and peroxynitrite and reacting with nitric oxide. Some clinical studies have provided evidence that, in vivo, uric acid is oxidized under conditions associated with high oxidant stress and may spare other antioxidants such as ascorbic acid. The plasma level of uric acid is controlled by the rates of production and excretion or degradation of uric acid. Under most circumstances, it is the renal clearance of uric acid which primarily determines the plasma concentration. Many factors of exogenous and endogenous origin can influence renal tubular absorption and secretion of uric acid. We suggest that renal urate clearance is not haphazard but regulated by an unknown signal that is issued in response to the level of oxidative stress. Since much cardiovascular pathology is now believed to have an inflammatory component and is associated with enhanced production of free radicals, the accompanying hyperuricemia may be viewed as a compensatory response of potential benefit.
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PMID:Renal regulation of plasma total antioxidant capacity. 1139 10

Gout is not a new disease for clinicians; nevertheless, there are still many secrets awaiting discovery for improving knowledge with respect to uric acid metabolism and monosodium urate crystal-induced inflammation. This review of the literature will focus on new insights on the pathogenesis of idiopathic hyperuricemia, and on secondary hyperuricemia and gout. There are also important advances on the pathophysiology of acute gout, especially as a self-limited process (switch from monocyte to macrophage, peroxisome proliferator activated receptor-gamma, and nitric oxide), but also of chronic gouty arthropathy. Armaments for treating hyperuricemia and gout may be already improved by losartan or fenofibrate and, in the future, by urate oxydase-polyethylene glycol 20 and renal handling regulatory molecules. Finally, control of hyperuricemia may also be considered in the prevention and treatment of cardiovascular disease.
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PMID:Hyperuricemia and gout. 1274 16

To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.
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PMID:Consumption of cherries lowers plasma urate in healthy women. 1277 24

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE. Epidemiological studies have shown that MS and gout are almost mutually exclusive diseases. Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission. Inosine, a uric acid precursor, can be used to raise uric acid levels in serum and may provide some benefit in MS patients. A small study of ten patients with progressive MS has demonstrated some improved function in three of them and no sign of progression or relapse in the other. However, this study does not justify a recommendation for use of inosine in MS patients yet. At present, uric acid can solely be regarded as a marker of disease activity in MS. In addition, the current knowledge of uric acid and MS supports hypotheses which predict a positive effect of radical scavengers in MS.
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PMID:[Uric acid and multiple sclerosis]. 1549 14

The role of nitric oxide (NO) in the antinociceptive effect of indomethacin was assessed in the pain-induced functional impairment model in the rat (PIFIR model), a model of inflammatory and chronic pain similar to that observed in clinical gout. Oral administration of indomethacin (5.6 mg/kg), a nonselective cyclooxygenase inhibitor, significantly decreased the nociceptive response elicited by uric acid injected into the knee joint of the right hind limb (2.0+/-3.0 and 149.7+/-18.0 area units [au], in the absence and the presence of indomethacin, respectively). This effect of indomethacin was reduced in nearly 50% by local pretreatment with the nonselective inhibitor of NO synthase, N G-L-nitro-arginine methyl ester (L-NAME) (72.9+/-10.7 vs. 149.7+/-18.0 au, P<0.05). On the other hand, local administration of L-arginine (a NO synthase substrate) or sodium nitroprusside (a non-enzymatic NO donor) each increased in almost 40% the antinociceptive effect of indomethacin (230.9+/-12.6 and 226.6+/-9.7 vs. 149.7+/-18.0 au, P<0.05), whereas D-arginine (the inactive isomer of arginine) had no effect on the indomethacin antinociceptive response (208.0+/-34.9 vs. 149.7+/-18.0 au). These results suggest that, the antinociceptive effect of indomethacin involves, at least in part, the NO-cyclic GMP pathway at peripheral level.
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PMID:Peripheral involvement of the nitric oxide-cGMP pathway in the indomethacin-induced antinociception in rat. 1549 94

Kaempferia parviflora Wall. ex Baker, is one of the plants in the Zingiberaceae family, locally known in Thai as kra-chai-dam. The rhizome of this plant has been used for treatment of gout, apthous ulcer and abscesses. Since K. parviflora rhizomes have long been used for treatment of inflammation and possessed marked nitric oxide (NO) inhibitory activity (IC(50)=7.8microg/ml), we thus investigated the inhibitory activity of compounds isolated from this plant against lipopolysaccharide (LPS)-induced NO release in RAW264.7 cells. From bioassay-guided fractionation of K. parviflora, seven methoxyflavones were isolated from the hexane fraction and were tested for their anti-inflammatory effects. Among the isolated compounds, compound 5 (5-hydroxy-3,7,3',4'-tetramethoxyflavone) exhibited the highest activity against NO release with an IC(50) value of 16.1microM, followed by 4 (IC(50)=24.5microM) and 3 (IC(50)=30.6microM). Compound 5 was also tested on LPS-induced prostaglandin E(2) (PGE(2)) and tumor necrosis factor-alpha (TNF-alpha) releases from RAW264.7 cells. It was revealed that 5 showed appreciable inhibitory effect on PGE(2) release (IC(50)=16.3microM), but inactive on TNF-alpha (IC(50)>100microM). These findings may support the use in Thai traditional medicine of K. parviflora for treatment of inflammatory-related diseases through the inhibition of NO and PGE(2) releases but partly due to that of TNF-alpha.
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PMID:Effects of compounds from Kaempferia parviflora on nitric oxide, prostaglandin E2 and tumor necrosis factor-alpha productions in RAW264.7 macrophage cells. 1872 83


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