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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gout is a disease of antiquity but is increasing once again in prevalence despite availability of reasonably effective treatments. This may be related to a combination of factors, including diet, obesity, and diuretic use. Allergic reactions, noncompliance, drug interactions, and sometimes inefficacy all limit the effective use of current hypouricemic agents. There are new treatments for gout on the horizon, including febuxostat, a nonpurine inhibitor of xanthine oxidase with a potentially better combination of efficacy and side effects than allopurinol. Diagnostic progress is being made in that ultrasound may offer a noninvasive means of diagnosing tophaceous deposits in and around joints. The increasing prevalence of gout means that dermatologists will see more cutaneous manifestations of gout, including tophi, draining sinus tracts, panniculitis, and dystrophic calcifications.
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PMID:Metabolic diseases: gout. 1711 68

Mechanistic and therapeutic advances in gout have been moving swiftly in the past decade. Clinically, the disease is changing in character. This review discusses several of the pertinent recent developments in understanding gout and in novel therapeutics for the disease. Subjects addressed include the role of URAT1-mediated renal proximal tubule epithelial cell urate anion reabsorption in hyperuricemia. We discuss the therapeutic limitations of allopurinol and uricosurics and the potential applications of novel xanthine oxidase inhibitors and of recombinant uricase preparations. Last, we summarize understanding of the central role of the early induced innate immune response in gouty inflammation, which has suggested the potential value of new strategies for treating gouty inflammation by targeting caspase-1 or IL-1beta.
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PMID:Gout in 2006: the perfect storm. 1712 96

We studied the bioactivities of constituents from two tropical medicinal plants, Cunila spicata and Hyptis fasciculata. These plants found in Brazil belong to the Labiatae family. Four known compounds obtained from these herbs were identified as 3alpha, 24-dihydoxylurs-12-en-28-oic acid, betulinic acid, aurantiamide acetate, and aurantiamide benzoate by spectroscopic means. 3alpha, 24-Dihydoxylurs-12-en-28-oic acid has potent inhibitory activity against Streptococcus salivarius, Streptococcus pneumoniae, Streptococcus pyogenes, and Porphyromomas gingivalis. Aurantiamide benzoate exhibited moderate inhibitory activity against xanthine oxidase. It was clarified that herbs Cunila spicata and Hyptis fasciculata are effective against bronchitis and gout.
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PMID:[Biological activity tests of chemical constituents from two Brazilian Labiatae plants]. 1726 60

In 2003, the uricosuric drug benzbromarone was withdrawn from the market. The first alternative drug of choice was the xanthine oxidase inhibitor allopurinol. The purpose was to (1) investigate the efficacy of allopurinol (standard dosage) compared with previous treatment with benzbromarone; and (2) investigate the combination therapy allopurinol-probenecid as an effective alternative treatment compared with previous benzbromarone treatment. A prospective, open study was carried out in a cohort of 51 gout patients who discontinued benzbromarone therapy because of market withdrawal. Patients were given 200-300 mg allopurinol (stage 1). When allopurinol failed to attain the target serum urate (sUr) levels <or=0.30 mmol/l, probenecid 1,000 mg/day was added (stage 2). Treatment with benzbromarone monotherapy (range: 100-200 mg/day; mean 138 mg/day) resulted in 92% of patients reaching target levels sUr <or= 0.30 mmol/l with a decrease of 61[11]% compared to baseline. In stage 1, 32 patients completed treatment with allopurinol monotherapy (range 200-300 mg/day; mean 256 mg/day), which resulted in 25% of patients attaining sUr target levels. Decrease in sUr levels was 36[11]%, which was significantly less compared to treatment with benzbromarone (p < 0.001). In stage 2, 14 patients received allopurinol-probenecid combination therapy, which resulted in 86% of patients attaining target sUr levels (after failure on allopurinol monotherapy), which was comparable to previous treatment with benzbromarone (p = 0.81). Decrease in sUr levels was 53[9]% (CI 95%: 48-58%), which was a non-significant difference compared to previous treatment with benzbromarone (p = 0.23). Benzbromarone is a very effective antihyperuricemic drug with 91% success in attainment of target sUr levels <or=0.30 mmol/l. Allopurinol 200-300 mg/day was shown to be a less potent alternative for most selected patients to attain target sUr levels (13% success). In patients failing on allopurinol monotherapy, the addition of probenecid proves to be an effective treatment strategy for attaining sUr target levels (86% success).
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PMID:Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients. 1730 59

Gout is a common chronic arthritis that can lead to significant disability. Gout is one of the few rheumatological conditions that can be diagnosed with certainty, has a known cause and can be cured with appropriate therapy. Hypouricaemic agents reduce uric acid concentrations through inhibiting uric acid production (allopurinol) or enhancing uric acid excretion (probenecid, benzbromarone). Allopurinol is the most commonly used hypouricaemic agent but at recommended doses often fails to reduce adequately uric acid concentrations and prevent acute attacks of gout. The use of probenecid is limited by lack of efficacy in renal impairment. In the last few years, new agents in the management of hyperuricaemia and gout have become available. Febuxostat, a new xanthine oxidase inhibitor, is an effective hypouricaemic agent although further data are required for patients with renal impairment and other significant medical conditions. Rasburicase, a recombinant uricase (which catalyses the conversion of uric acid to the more readily excreted allantoin) is available for prevention of tumour lysis syndrome. However, its repeated use, as would be required in chronic gout, is limited by antigenicity. A less antigenic PEGylated uricase can rapidly reduce serum uric acid concentrations and promote resorption of tophi. However, further information with regard to the long-term risks and benefits of these agents is required. These agents may ultimately be used in the short term to rapidly deplete urate stores (induction therapy) followed by long-term therapy with an alternative hypouricaemic agent to prevent subsequent accumulation of uric acid (maintenance therapy).
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PMID:Emerging therapies in the long-term management of hyperuricaemia and gout. 1738 67

Uric acid is the end-product of purine catabolism. Hyperuricaemia is implicated in disorders such as gout and urolithiasis and recent epidemiological evidence suggests an association between increasing uric acid levels and increased cardiovascular morbidity and mortality. A direct causal role remains to be established but recent studies of losartan, atorvastatin and fenofibrate suggest that uric acid reduction contributes to attenuation of cardiovascular risk. Furthermore, several small studies of xanthine oxidase inhibition (the most common method of uric acid reduction) have shown improvements in measures of cardiovascular and endothelial function of a similar magnitude to those of other proven preventative strategies. This review introduces the epidemiological data, discusses strategies to lower uric acid and outlines the available clinical trial data supporting uric acid reduction as a potential and novel method of reducing the burden of cardiovascular disease.
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PMID:Uric acid reduction: a new paradigm in the management of cardiovascular risk? 1762 23

Hyperuricemia and gout appear to be rapidly increasing worldwide and frequently cause symptoms of metabolic syndrome. Dietary flavonoids have their potential beneficial effects on human health. In the present study, 15 flavonoids (quercetin, morin, myricetin, kaempferol, icariin, apigenin, luteolin, baicalin, silibinin, naringenin, formonoetin, genistein, puerarin, daidzin and naringin dihydrochalcone) were selected to investigate for their hypouricemic action in mice. Oral administration of quercetin, morin, myricetin, kaempferol, apigenin and puerarin at 50 and 100 mg/kg for 3 d was able to elicit hypouricemic actions in hyperuricemic mice induced by potassium oxonate. Luteolin, formonoetin and naringenin showed the significant effects only at 100 mg/kg. Quercetin, puerarin, myricetin, morin and kaempferol significantly reduced liver uric acid level in hyperuricemic animals. In addition, quercetin, morin, myricetin, kaempferol and puerarin exhibited significant inhibition on the liver xanthine oxidase (XOD) activities. It seems to be likely that these flavonoids reduce serum urate levels by mainly inhibiting XOD activity. However, the hypouricemic effect of apigenin observed seemed not to parallel with the changes in liver uric acid level and liver XOD activity, implying that apigenin might act via other mechanisms apart from inhibiting enzyme activity simply. Analysis of the chemical structure showed that a planar structure with the hydroxyl groups played a crucial role in hypouricemic activity of flavonoids. The exact mechanism of the hypouricemic action of flavonoids in vivo should be investigated in the future.
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PMID:Hypouricemic action of selected flavonoids in mice: structure-activity relationships. 1766 19

Some pyrazolo[3,4-d]pyrimidines, structurally related with allopurinol, a well known xanthine oxidase inhibitor, clinically used in the therapy of gout, have also been reported as potent inhibitors of xanthine oxidase and the growth of several human tumour cell lines. Considering the potential interest of this family of compounds, the aim of the present study was to synthesise and provide a full chemical characterization of new N-aryl-5-amino-4-cyanopyrazole derivatives and their corresponding pyrazolo[3,4-d]pyrimidines. Their biological activity pertaining to the xanthine oxidase inhibition and effect on the growth of three tumour cell lines (MCF-7, NCI-H460, and SF-268) are also provided. With only one exception, the synthesised compounds showed no effect on the growth of the three tumour cell lines. However, a strong xanthine oxidase inhibitory activity was observed for almost all pyrazolo[3,4-d]pyrimidines tested, revealing some of them IC(50) values below 1 microM. The results of the molecular docking studies of these compounds, against xanthine oxidoreductase are also described, providing an atomistic explanation of the differences in the inhibitory efficiency. MEP calculations were used to explain different inhibitory efficiency of similar inhibitors.
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PMID:Synthesis of N-aryl-5-amino-4-cyanopyrazole derivatives as potent xanthine oxidase inhibitors. 1769 32

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a genetic disease of purine metabolism resulting in uric acid overproduction. Allopurinol, which inhibits the enzyme xanthine oxidase and reduces uric acid synthesis, is widely used for the treatment of gout and uric acid overproduction. The aim of the study was to analyze the long-term efficacy and safety of allopurinol in patients with HPRT deficiency. Nineteen patients (13 with Lesch-Nyhan syndrome and 6 with partial HPRT deficiency) were treated with allopurinol (mean dose, 6.4 mg/kg body weight per day; range, 3.7-9.7 mg/kg body weight per day) and followed up for at least 12 months (mean follow-up, 7.6 years). The efficacy of allopurinol was evaluated by serial measurement of purine metabolic parameters and renal function as well as by clinical manifestations. Safety was assessed by recording adverse events. Treatment with allopurinol normalized serum urate level in all patients and resulted in a mean reduction in serum urate of 47%. Allopurinol treatment was associated with a mean 74% reduction in urinary uric acid-to-creatinine ratio. In contrast, allopurinol treatment increased mean hypoxanthine and xanthine urinary excretion rates 5.4- and 9.5-fold, respectively, compared with baseline levels. The decrease in uric acid excretion in complete and partial HPRT-deficient patients was not accompanied by a stoichiometric substitution of hypoxanthine and xanthine excretion rates. Allopurinol-related biochemical changes were similar in patients with either complete or partial HPRT deficiency. Renal function remained stable or improved with treatment. Three patients had urolithiasis during allopurinol treatment. In 2 patients, xanthine stones were documented and they required allopurinol dose adjustments aimed at reducing excessive oxypurine excretion rates. No allopurinol hypersensitivity reactions occurred. Neurologic manifestations were not influenced by allopurinol therapy. In conclusion, allopurinol is efficacious and generally safe for the treatment of uric acid overproduction in patients with HPRT deficiencies. Xanthine lithiasis, developing as a consequence of allopurinol therapy, should be preventable by adjustment of allopurinol dose.
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PMID:Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency. 1769 59

The recognition that uric acid plays a significant role in cardiac function has been slow to be appreciated. About 50 years ago it was recognized that gout and high uric acid levels were often a marker for coronary heart disease, Since then the literature has contained several hundred studies which have demonstrated a great deal of the physiology of xanthine oxidase inhibition. A reduction in xanthine oxidase improves cardiac output, improves endothelial function, reduces myocardial infarct size, reduces inflammation, reduces myocardial oxidative stress and platelet adhesiveness. It seems logical that these effects would be beneficial to patients with congestive heart failure. A large placebo controlled trial with Allopurinol seems very likely to demonstrate that this old fashioned drug provides a new found benefit.
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PMID:Xanthine oxidase inhibitors the unappreciated treatment for heart failure. 1822 Jul 28


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