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)

The antioxidant potential of an aqueous extract obtained from Pieris brassicae larvae reared on Brassica oleracea L. var. costata DC was evaluated against 2,2-diphenyl-1-picrylhydrazyl radical and several reactive oxygen species. The results revealed an effective concentration-dependent protective activity against superoxide and hydroxyl radicals, being superior to that of the host plant. In addition, the larvae extract also exhibited a strong inhibitory effect on xanthine oxidase that was not observed for B. oleracea var. costata. A weak scavenging ability was noticed for hypochlorous acid. Several phenolic compounds with complex chemical structures that are hard to synthesize in the laboratory were found in P. brassicae extract. This is the first time that an insect has been tested for its xanthine oxidase inhibitory capacity, which proved to be very high. These findings are interesting considering that they can be used by food or pharmaceutical industries to prevent the oxidation of their products, to increase the dietary supply of antioxidants, or for prevention of free radical-mediated diseases, namely, gout.
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PMID:Pieris brassicae inhibits xanthine oxidase. 1922 75

Febuxostat is a novel, potent, non-purine selective xanthine oxidase inhibitor, which in clinical trials demonstrated superior ability to lower and maintain serum urate levels below 6 mg/dL compared with conventionally used doses of allopurinol. Febuxostat was well tolerated in long term treatment in patients with hyperuricemia including those experiencing hypersensitity/intolerance to allopurinol. Dose adjustment appears unnecessary in patients with mild to moderate renal or liver insufficiency or advanced age. The most common adverse reactions reported were abnormal liver function tests, headache, and gastrointestinal symptoms, which were usually mild and transient. However, whether hepatotoxicity becomes a limitation in the use of febuxostat needs to be determined in further studies. An increased frequency of gout flares occurs for a prolonged period after treatment initiation, as with any aggressive lowering of serum urate, and prolonged prophylaxis with colchicine or NSAIDs is usually required. Febuxostat has been granted marketing authorization by the European Commission in early 2008 for the treatment of chronic hyperuricemia and gout. Febuxostat is the first major treatment alternative for gout in more than 40 years and is a promising alternative to allopurinol, although continued long-term surveillance on safety and efficacy is required.
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PMID:Febuxostat in the management of hyperuricemia and chronic gout: a review. 1933 28

Morinda citrifolia L. (noni), family Rubiaceae, has been used in Polynesia for over 2000 years for its reputed health benefits, one of which is its therapeutic effects on gout (langa e hokotanga hui). However, its healing mechanism has not been elucidated. This study showed that in an in vitro bioassay that Tahitian Noni Juice (TNJ) inhibited xanthine oxidase (XO) concentration dependently. Concentrations of 1, 5 and 10 mg/mL of TNJ inhibited XO by 11%, 113% and 148%, respectively, with an IC50 of 3.8 mg compared with an IC50 of 2.4 microm for allopurinol. Noni fruit juice concentrate (NFJC) also inhibited XO concentration dependently. Concentrations of 1 and 5 mg/mL NFJC inhibited XO in vitro by 184% and 159%, respectively. A 0.1 mg/mL methanol extract (NFJME) from the fractionation of noni fruit puree inhibited XO by 64%. It was elucidated that the noni fruit juice inhibitory effect on XO enzymes is the mechanism by which noni ameliorates gout and gout-like diseases. Further, the results also support the traditional usage of noni in the treatment of gout.
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PMID:Xanthine oxidase inhibiting effects of noni (Morinda citrifolia) fruit juice. 1943 57

Oxidative stress plays an important role in the progression of vascular endothelial dysfunction. The two major systems generating vascular oxidative stress are the NADPH oxidase and the xanthine oxidase pathways. Allopurinol, a xanthine oxidase inhibitor, has been in clinical use for over 40 years in the treatment of chronic gout. Allopurinol has also been shown to improve endothelial dysfunction, reduce oxidative stress burden and improve myocardial efficiency by reducing oxygen consumption in smaller mechanistic studies involving various cohorts at risk of cardiovascular events. This article aims to explain the role of xanthine oxidase in vascular oxidative stress and to explore the mechanisms by which allopurinol is thought to improve vascular and myocardial indices.
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PMID:Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. 1943 71

Febuxostat is a new non-purine xanthine oxidase inhibitor that is more potent than allopurinol 300 mg daily. In two Phase III trials, significantly more febuxostat-treated gout patients met the primary endpoint [serum urate (sUA) <6 mg/dl (<360 mumol/l) at the last three visits] (48 and 53% with 80 mg; 65 and 62% with 120 mg), compared with those receiving allopurinol 300 mg (22 and 21%; P < 0.001 in both studies). Febuxostat was more effective than allopurinol in the subset with impaired renal function; no dose adjustment is required in mild-to-moderate renal impairment. Long-term extension studies confirmed the efficacy and tolerability of febuxostat. In patients who achieved the sUA target of 6 mg/dl (360 mumol/l), the incidence of gout flares fell steadily and tophi resolved in many patients. The incidence of adverse events such as dizziness, diarrhoea, headache and nausea with febuxostat was similar to allopurinol. The incidence of cardiovascular side-effects (Antiplatelet Trialists Collaboration events) was numerically higher with febuxostat than with allopurinol, but this was not statistically significant. Co-administration of febuxostat with AZA or 6-mercaptopurine is not recommended. Prophylaxis (colchicine and/or NSAIDs) against acute attacks should be used for at least the first 6 months, since early mobilization flares were observed in the clinical trials. In conclusion, febuxostat is more effective than allopurinol 300 mg daily in reducing sUA levels <6 mg/dl (360 mumol/l), the target recommended by EULAR, and offers a new option for the long-term treatment of gout.
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PMID:Febuxostat: a new treatment for hyperuricaemia in gout. 1944 78

Febuxostat (Uloric--Takeda), a xanthine oxidase inhibitor, has been approved by the FDA for chronic management of hyperuricemia in patients with gout. It is the first drug marketed for treatment of gout in 40 years. Febuxostat is structurally unrelated to allopurinol, the only other commercially available inhibitor of xanthine oxidase. Xanthine oxidase inhibitors decrease serum urate concentrations by decreasing urate synthesis.
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PMID:Febuxostat (Uloric) for chronic treatment of gout. 1944 87

The prevalence of gout has been increasing in epidemic proportions over the last several decades. Hyperuricemia has been shown to be associated with metabolic syndrome and to be an independent risk factor for cardiovascular disease. Associations between hyperuricemia, obesity and aging have provided an impetus in recent years to develop alternative methods of treating hyperuricemia and gout. Febuxostat is a new non-purine xanthine oxidase inhibitor indicated for chronic gout. Febuxostat has been shown to quickly and effectively lower serum urate levels in patients with chronic gout. This manuscript will review febuxostat, its pharmacokinetics and pharmacodynamics, efficacy and adverse events and use in patients with comorbid conditions. The review will also summarize the phase III trials leading up to the drug's approval by both the European Commission in 2008 and the U.S. FDA in 2009. Possible implications the medication may have in the future on gout and hyperuricemia will also be discussed.
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PMID:Febuxostat: a new agent for lowering serum urate. 1949 90

(1) For patients with chronic symptomatic hyperuricaemia who fail to respond to a low purine diet, allopurinol is the standard drug used to prevent complications. This xanthine oxidase inhibitor can, in rare instances, cause severe skin reactions. Probenecid, a uricosuric agent, with which there is also long experience, is a second-line option; (2) Febuxostat, another xanthine oxidase inhibitor, is now authorized for the treatment of hyperuricaemia; (3) Two randomised double-blind trials in 762 and 1072 patients tested various doses of febuxostat compared with a standard dose of allopurinol (33 mg/day). Febuxostat normalised uric acid levels more frequently than allopurinol. However, overall, more patients suffered gout attacks with febuxostat than with allopurinol during the first two months of treatment, despite preventive measures (30-35% versus 22%). Between 3 and 6 months of treatment neither drug reduced the incidence of gout attacks more effectively than placebo. After one year of treatment about two-thirds of patients suffered gout attacks, with no difference between the febuxostat and allopurinol groups; (4) In these trials there were more premature treatment withdrawals with febuxostat than with allopurinol; (5) The adverse effects of febuxostat are poorly documented, especially cardiac, hepatic, haematological and thyroid disorders. In the short term, severe cardiac disorders, based on a composite endpoint, were 4 to 5 times more frequent with febuxostat than with allopurinol. Treatment withdrawals due to hepatic disorders were more frequent with febuxostat than with allopurinol (2.8% versus 0.4%). The relative frequency of severe cutaneous disorders with febuxostat and allopurinol is not known; (6) Clinical evaluation does not include any head-to-head trials of febuxostat versus probenecid; (7) In practice, patients with hyperuricaemia should continue to receive allopurinol as first-line treatment, and probenecid as second-line treatment if allopurinol is ineffective.
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PMID:Febuxostat: new drug. Hyperuricaemia: risk of gout attacks. 1958 22

Allopurinol as an effective inhibitor of the enzyme xanthine oxidase (XO) has been used for several decades for the treatment of patients with gout and hyperuricemia. Because the inhibition of XO limits the formation of radical oxygen species as well as uric acid (UA) production, allopurinol has been used experimentally for the treatment of conditions associated with ischemia and reperfusion (I/R) injury.Although there have been many ischemic organs treated in the laboratory with allopurinol, the heart has been of particular interest. Therefore, we emphasize our attention to the administration of XO inhibitors such as allopurinol on cardiac I/R as well as cardiac failure. Experimental data also support allopurinol as a possible consideration for biochemical support after acute myocardial infarction. Anker and associates (Circulation. 2003;107:1991-1997) have observed a direct correlation between uric acid levels and mortality in treated heart failure patients. Anker and associates showed a 100% mortality rate in patients with UA levels 800 micromol/L or less over a period of 3 years. Comparing this to a 27% mortality rate in patients with UA levels 400 micromol/L or less over a period of 10 years, it seems that the suppression of XO activity ameliorates myocardial inefficiency, and poor vascular flow may present innovative contributions to the future treatment of I/R heart failure patients. Our review focuses on the role of allopurinol on ischemic hearts as well as those with added chronic heart failure.
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PMID:Allopurinol, xanthine oxidase, and cardiac ischemia. 1979 15

Xanthine oxidase (XO) is responsible for the pathological condition called gout. Inhibition of XO activity by various pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidine-4-one derivatives was assessed and compared with the standard inhibitor allopurinol. Out of 10 synthesized compounds, two compounds, viz. 3-amino-6-(2-hydroxyphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3b) and 3-amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3g) were found to have promising XO inhibitory activity of the same order as allopurinol. Both compounds and allopurinol inhibited competitively with comparable Ki (3b: 3.56 microg, 3g: 2.337 microg, allopurinol: 1.816 microg) and IC(50) (3b: 4.228 microg, 3g: 3.1 microg, allopurinol: 2.9 microg) values. The enzyme-ligand interaction was studied by molecular docking using Autodock in BioMed Cache V. 6.1 software. The results revealed a significant dock score for 3b (-84.976 kcal/mol) and 3g (-90.921 kcal/mol) compared with allopurinol (-55.01 kcal/mol). The physiochemical properties and toxicity of the compounds were determined in silico using online computational tools. Overall, in vitro and in silico study revealed 3-amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3g) as a potential lead compound for the design and development of XO inhibitors.
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PMID:Synthesis and biological activity of pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives: in silico approach. 2000 Dec 74


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