ライフサイエンスコーパス: urate

1 ces were explained by higher levels of serum urate.

2 g of Pseudomonas aeruginosa was inhibited by urate.

3 lds of hydroperoxides were formed by LPO and urate.

4 e (XOR), blocks the oxidation of xanthine to urate.

5 3) for a 0.5mg/dl decrease in measured serum urate.

6 gene have increased concentrations of brain urate.

7 after exposure of S. coelicolor cultures to urate.

8 ubstantial players in the renal excretion of urate.

9 respect to smoking (nicotine), caffeine, and urate.

10 high-affinity interaction with the substrate urate.

11 , respectively, per 1 SD increment in plasma urate.

12 ical consequences of crystallized monosodium urate acutely causing liver/kidney damage or chronically

13 onse to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia co

14 placebo and nifedipine did not affect plasma urate, ADMA, or urine ET-1/creatinine, which reflects re

15 However, urate also possesses antioxidant and neuroprotective pro

16 of monosodium urate (MSU) crystals, soluble urate also primes for inflammatory signals in cells resp

17 showed direction-consistent association with urate among AA.

18 manifestations of these in clinical practice-urate and bone marrow edema detection, metal artifact re

19 es our understanding of how hSLC2A9 mediates urate and fructose transport, providing further informat

20 studies confirm that hSLC2A9 transports both urate and fructose, but it interacts with them in differ

21 ogy Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using stan

22 At gestational day 20, maternal plasma urate and L-cysteine concentrations, and placental level

23 sociated with urate that do not affect serum urate and PD progression.

24 ecS, indicating a direct interaction between urate and PecS.

25 s of the observational association of plasma urate and risk of coronary heart disease.

26 though a positive association between plasma urate and SSB consumption was found, there was no associ

27 ratory and radiographic tests, such as serum urate and synovial fluid crystal analysis and radiograph

28 to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune enc

29 We show here that HucR responds only to urate and, to a lesser extent, to xanthine by attenuated

30 g/dl genetically conferred decrease in serum urate, and 1.05 (95% CI = 1.01-1.10, p = 0.0133) for a 0

31 artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03).

32 ar ATP, excess glucose, ceramides, amyloids, urate, and cholesterol crystals, all of which increase w

33 uded negative associations with raised serum urate, and single studies or studies with conflicting re

34 acterium tumefaciens PecS specifically binds urate, and urate attenuates DNA binding in vitro.

35 n consisting of a nucleophilic attack of the urate anion on the flavin hydroperoxide resulting in the

36 Our findings establish urate as a likely physiological substrate for LPO that w

37 emiological and clinical data has identified urate as a predictor of both reduced risk and favorable

38 As an example, we identified urate as one of these key players mediating the comorbid

39 e reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months)

40 vance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs).

41 e is not the causal agent underlying the SSB-urate association.

42 rmination that GLUT9 and ABCG2 can transport urate at the apical border of proximal tubules implicate

43 mefaciens PecS specifically binds urate, and urate attenuates DNA binding in vitro.

44 show here that all four residues involved in urate binding and propagation of conformational changes

45 at S. coelicolor PecS responds to the ligand urate by attenuated DNA binding in vitro and upregulatio

46 that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigg

47 Elevated urate can cause gout and urolithiasis and is associated

48 Uric acid (urate), carnitine, prostaglandins, conjugated sex steroi

49 n of metabolic substrates such as monosodium urate, ceramide, cholesterol, and glucose can trigger th

50 lar patterns as well as biological crystals (urate, cholesterol, etc.), resulting in expression of IL

51 At physiologically relevant concentrations, urate competed effectively with thiocyanate, the main su

52 A high plasma urate concentration (PUA), related to loss of urate oxid

53 rting the inverse association between plasma urate concentration and dairy consumption should be refl

54 o investigate the association between plasma urate concentration and: a) food items: dairy, sugar-swe

55 Higher plasma urate concentration has been linked to lower risk of Par

56 The urate concentration in the serum was normal but in the u

57 Fetal plasma urate concentration increased significantly during chron

58 Increased circulating plasma urate concentration is associated with an increased risk

59 requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL (the approximate p

60 Mean urate concentration was 283.8+/-72.1 mmol/dL (females: 2

61 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (O

62 Plasma urate concentration was inversely associated with Parkin

63 Urate concentration was measured in plasma.

64 nutrients and food products influence plasma urate concentration, to inform the development of eviden

65 iews the current practice of targeting serum urate concentrations (sUA) in the mid-normal range (roug

66 Serum urate concentrations are highly heritable and elevated s

67 of modified uricases to rapidly reduce serum urate concentrations in patients with otherwise untreata

68 Higher serum urate concentrations predict more favorable prognosis in

69 Serum urate concentrations were 0.69mg/dl lower among individu

70 hat identify an allele associated with lower urate concentrations, and for selected SNPs in other gen

71 smoking, caffeine consumption, higher serum urate concentrations, physical activity, and use of ibup

72 overexpressing the enzyme have reduced brain urate concentrations.

73 were higher among persons with greater serum urate concentrations.

74 ny genetic loci associated with raised serum urate concentrations.

75 rol disease manifestations related to tissue urate crystal deposition.

76 ndent neutrophil recruitment in a monosodium urate crystal inflammatory murine peritonitis model.

77 Analogously, monosodium urate crystal-induced neutrophil migration to the tibiof

78 familial cold autoinflammatory syndrome and urate crystal-induced peritonitis.

79 ent understanding of the interaction between urate crystals and key cellular components of the gouty

80 ytidylic acid or a combination of monosodium urate crystals and Mycobacterium smegmatis was effective

81 ent-activating structures such as monosodium urate crystals and zymosan was not affected by BCD.

82 and the inflammatory response to monosodium urate crystals are translating into potential new treatm

83 itis, caused by the deposition of monosodium urate crystals in and around the joints.

84 wever, tophi and tissue stores of monosodium urate crystals resolve slowly, particularly in patients

85 inflammation, NLRP3 activation by monosodium urate crystals similarly increased IL-6.

86 peritonitis model of gout, using monosodium urate crystals to activate NLRP3, 15d-PGJ2 caused a sign

87 ion of the NLRP3 inflammasome in response to urate crystals, ATP and lipotoxic fatty acids.

88 In contrast, LPS, monosodium urate crystals, or M. smegmatis alone had no activity.

89 s was also observed in a model of monosodium urate crystals-induced inflammation.

90 crystals but not in response to LPS or other urate crystals.

91 centrations of fructose stimulate redox- and urate-dependent inflammatory mediators in proximal tubul

92 d did not increase during 15 wk of sustained urate depletion.

93 Notably, urate dissociates PecS from cognate DNA, allowing transc

94 ucial site that could directly interact with urate during transport.

95 tained in this region, is a hitherto unknown urate efflux transporter.

96 A urate-elevating agent is currently under investigation a

97 and strengthen the rationale for developing urate-elevating strategies as potential disease-modifyin

98 pidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disa

99 The Safety of Urate Elevation in PD (SURE-PD) study, a randomized, dou

100 7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to

101 Monosodium urate enhanced CD86 and OX40L expression on DCs, indepen

102 sms by which these genetic variants regulate urate excretion and serum urate levels.

103 r targets for the design of drugs to enhance urate excretion and the genetic variants that predispose

104 which underscores the importance of reduced urate excretion as opposed to increased endogenous produ

105 e hSLC2A9; however, Ile-335 is necessary for urate/fructose trans-acceleration exchange to occur.

106 n(III)tetrakis(4-benzoic acid)porphyrin, and urate had no protective effects, supplementation of the

107 Plasma urate has been consistently associated with a lower risk

108 allopurinol and febuxostat lowering of serum urate have once again raised the tantalizing possibility

109 s an essential protein that mainly regulates urate/hexose homeostasis in human kidney and liver.

110 e than Prx1 to hyperoxidation caused by both urate hydroperoxide and hydrogen peroxide.

111 erefore, Prx1 and Prx2 are likely targets of urate hydroperoxide in cells.

112 Urate hydroperoxide is a product of the oxidation of uri

113 Oxidation of Prxs by urate hydroperoxide might affect cell function and be pa

114 The formation of urate hydroperoxide might be a key event in vascular inf

115 n data suggest that the oxidation of Prx2 by urate hydroperoxide occurs by a three-step mechanism, wh

116 Urate hydroperoxide oxidized Prx2 from intact erythrocyt

117 Urate hydroperoxide oxidizes glutathione and sulfur-cont

118 cytosolic 2-Cys Prx1 and Prx2 revealed that urate hydroperoxide oxidizes these enzymes at rates comp

119 ns such as bicarbonate, lactate, citrate and urate in a variety of bio-fluids.

120 ome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking.

121 support a neuroprotective role of endogenous urate in dopaminergic neurons and strengthen the rationa

122 of 11 loci previously associated with serum urate in EA individuals, 10 of 11 lead single-nucleotide

123 of a causal role for triglyceride in raising urate in men (P(Corrected)=0.018).

124 on, findings suggesting that basal levels of urate in mice do not appreciably protect against oxidati

125 The authors examined plasma urate in relation to Parkinson's disease in the biracial

126 sation analysis implicates a causal role for urate in the development of coronary heart disease, but

127 e, p-cresol sulfate, kynurenine, creatinine, urate) include two "drug" transporters of the organic an

128 a normally in response to ATP and monosodium urate, indicating that caspase-11 is engaged by a non-ca

129 a significant longitudinal genotype x serum urate interaction effect, consistent in direction with t

130 ere conducted to assess gene variant x serum urate interaction effects on magnetic resonance imaging-

131 ation study to identify gene variant x serum urate interaction effects on the striatal (123) I-ioflup

132 We now demonstrate that urate is a good substrate for bovine LPO.

133 ions are highly heritable and elevated serum urate is a key risk factor for gout.

134 Taken together, our data show that urate is a ligand for PecS and suggest that urate serves

135 We have previously shown that urate is a ligand for the Deinococcus radiodurans-encode

136 Since production of urate is associated with generation of reactive oxygen s

137 Serum urate is highly heritable, yet association studies of si

138 lipid or protein oxidation, we conclude that urate is not a major factor controlling oxidative stress

139 The physiological function of urate is poorly understood.

140 findings do not support the hypothesis that urate is strongly associated with lower rates of Parkins

141 Urate is the end product of purine metabolism in humans,

142 conserved in PecS homologs, suggesting that urate is the ligand for PecS.

143 etes among persons with hyperuricemia (serum urate level >7 mg/dL vs. </=7.0 mg/dL) were 1.87 (95% co

144 [95% CI] 0.6, 1.9), 0.15 mg/dl in the serum urate level (95% CI 0.07, 0.24), and 3.2% in the prevale

145 Genetic profile combined with serum urate level can be used to predict disease severity and

146 mary definition of hyperuricemia was a serum urate level of >7.0 mg/dl for men and >5.7 mg/dl for wom

147 nome-wide significant interaction with serum urate level to predict striatal dopamine transporter den

148 or each) vs placebo, and cerebrospinal fluid urate level was greater in both inosine groups (P = .006

149 After adjusting for serum urate level, the association between diuretic use and go

150 ported physician diagnosis of gout and serum urate level.

151 onfounders and tested for mediation by serum urate level.

152 reased risk and may be a surrogate for lower urate levels (associated with faster progression in mani

153 High blood urate levels (hyperuricemia) have been found to be a sig

154 oral allopurinol reduced serum and striatal urate levels 4-fold and 1.3-fold, respectively, it did n

155 ed positive associations between circulating urate levels and cardiometabolic diseases, causality rem

156 ed one novel locus in association with serum urate levels and experimentally characterize the novel G

157 e conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidat

158 on on chromosome 4 that associate with serum urate levels and gout, a consequence of elevated urate l

159 Urate-lowering therapy decreases serum urate levels and reduces risk for acute gout attacks.

160 mization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes me

161 Overall, allopurinol lowered urate levels but did not exacerbate dopaminergic neuron

162 However, a 1 SD increase in serum urate levels due to the genetic score was associated wit

163 Serum urate levels have been associated with risk for and prog

164 eotide polymorphisms known to regulate serum urate levels in association with various vascular and no

165 ive in raising serum and cerebrospinal fluid urate levels in early PD.

166 larly in men, to be partly related to higher urate levels in middle-aged blacks.

167 t support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF.

168 Decreasing serum urate levels may not translate into risk reductions for

169 Whereas the high serum urate levels observed in patients with gout predispose t

170 Although lower urate levels reduce risk for recurrent acute attacks, tr

171 The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher i

172 Mean urate levels were 5.04 mg/dL for cases (n = 101) and 4.8

173 The mean serum urate levels were 6.14 mg/dl among men and 4.87 mg/dl am

174 ymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess

175 , recurrence, intermediate outcomes of serum urate levels, and harms.

176 ed as preventive measures as these can lower urate levels, as well as the risk of gout and some of it

177 Serum urate levels, increased by 1 SD due to the genetic score

178 Gout is caused by elevated serum urate levels, which can be treated using inhibitors of t

179 Gout is caused by elevated serum urate levels, which can be treated using inhibitors of t

180 rters that have modest or no effect on serum urate levels.

181 idence of a causal protective effect of high urate levels.

182 an association mediated by a change in serum urate levels.

183 variants regulate urate excretion and serum urate levels.

184 e levels and gout, a consequence of elevated urate levels.

185 es for an equivalent increase in circulating urate levels.

186 ators to determine the priority of trials of urate lowering for the prevention of coronary heart dise

187 Novel approaches to urate lowering have led to mechanism-based therapies suc

188 e strategies for both gouty inflammation and urate lowering.

189 new US Food and Drug Administration-approved urate-lowering drugs for gout in the past 40 years.

190 Currently available urate-lowering drugs include allopurinol and probenecid.

191 a on the efficacy and safety of the approved urate-lowering drugs, allopurinol and febuxostat.

192 an be achieved in some patients with current urate-lowering drugs, but new drugs now under investigat

193 tioxidant benefit offsetting its detrimental urate-lowering effect.

194 ient education, self-management training and urate-lowering medication titration.

195 ifestyle advice, monitoring and titration of urate-lowering medications have been implemented to impr

196 In addition, new urate-lowering medications to be used alone or in combin

197 To discuss currently available urate-lowering therapeutic options for gout in the Unite

198 oms, targeting interleukin-1beta, as well as urate-lowering therapies including uricase and inhibitor

199 Moderate-strength evidence suggests that urate-lowering therapy (allopurinol or febuxostat) reduc

200 Urate-lowering therapy decreases serum urate levels and

201 ACP recommends against initiating long-term urate-lowering therapy in most patients after a first go

202 ic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control

203 ttacks by at least half in patients starting urate-lowering therapy, and moderate-strength evidence i

204 preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxi

205 during the initial period of treatment with urate-lowering therapy, with a favorable safety profile.

206 For those with moderate to severe gout, urate-lowering treatment can eliminate acute attacks of

207 5 urate-lowering treatment strategies were evaluated: no t

208 opurinol or febuxostat is a suitable initial urate-lowering treatment.

209 n allopurinol (300 mg/day, titrated to serum urate <6 mg/dl).

210 vascular disease, and that lowering of serum urate may assist in control of hypertension.

211 These data support the previous finding that urate may be a protective factor against Parkinson's dis

212 e-rich vegetables intake for lowering plasma urate may be ineffectual, despite current recommendation

213 dual inhibitor PF-562271 reduced monosodium urate-mediated peritonitis, a disease model used for stu

214 been known about the genetic determinants of urate metabolism and susceptibility to gout in the gener

215 e whole-body metabolism, and that enterocyte urate metabolism could potentially be targeted to modula

216 The mechanism by which monosodium urate monohydrate (MSU) crystals intracellularly activat

217 ged tissues release uric acid and monosodium urate (MSU) crystals as important endogenous danger sign

218 how the endogenous danger signal monosodium urate (MSU) crystals can alter macrophage functions.

219 form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in

220 edispose them to the formation of monosodium urate (MSU) crystals, soluble urate also primes for infl

221 f gout patients upon encountering monosodium urate (MSU) crystals.

222 ly solely on the documentation of monosodium urate (MSU) crystals.

223 ly solely on the documentation of monosodium urate (MSU) crystals.

224 ML by arsenic trioxide suppressed monosodium urate (MSU)-induced IL-1beta production, suggesting that

225 We found that uric acid (monosodium urate [MSU]) crystals induce a proinflammatory profile i

226 xogenous delivery of UA crystals (monosodium urate, MSU) restored the allergic phenotype.

227 Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and

228 e therapy generates H(2)O(2) while depleting urate, offering an in vivo test of the antioxidant hypot

229 tudy, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian ran

230 e, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear

231 scavenger Tiron, the peroxynitrite scavenger Urate, or the eNOS inhibitor L-NAME and these effects as

232 ase kinase kinase in Magnaporthe oryzae, and urate oxidase (designated ClUrase) were functionally cha

233 Recombinant urate oxidase (rasburicase) is a newer agent that direct

234 We have isolated a urate oxidase (uox) mutant of Arabidopsis thaliana that

235 jugation assay, two sites (W160 and D112) of urate oxidase (Uox), a model therapeutic protein, were s

236 Urate oxidase (Uox), a therapeutic enzyme for treatment

237 Exemplified with urate oxidase (UOx), the enzyme used for hyperuricemia t

238 evolutionary disruption of the gene encoding urate oxidase (UOx).

239 e and stand in contrast to the mechanisms of urate oxidase and (1H)-3-hydroxy-4-oxoquinaldine 2,4-dio

240 AD), contrasting with all previously studied urate oxidase enzymes, which have no cofactor requiremen

241 rate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect hum

242 HpxO is a flavin-dependent urate oxidase that catalyzes the hydroxylation of uric a

243 rum UA levels to 0 by infusing a recombinant urate oxidase.

244 tration on the second virial coefficient for urate oxidase.

245 biochemically that HpxO is an FAD-dependent urate oxidase.

246 In rodents, functional UOx catalyzes urate oxidation to allantoin.

247 efficiently eliminate H(2)O(2) derived from urate oxidation to prevent cell injury in vitro; during

248 During urate oxidation, LPO was diverted from its peroxidase cy

249 B consumption was positively associated with urate (p = 0.008), however, energy-adjusted fructose int

250 ctose intakes were inversely associated with urate (p = 0.008, p = 0.003, p = 0.0007, respectively).

251 rich vegetables was not associated to plasma urate (p = 0.38).

252 sted fructose intake was not associated with urate (p = 0.66).

253 from commonly interfering compounds such as urate, paracetamol and l-ascorbate.

254 elevant to therapeutic efforts targeting the urate pathway.

255 d recombinant uricase to directly catabolize urate (pegloticase).

256 cent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those

257 d-type mice, and in both in vivo (monosodium urate peritonitis) and in vitro models of inflammation.

258 ted oxidative damage due to the reduction in urate, protein carbonyl levels, a marker of oxidative da

259 Urate-related compounds are therapeutic candidates in ne

260 kers urinary S-sulphocysteine, xanthine, and urate returned to almost normal concentrations in all ty

261 Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups

262 oximal tubule cells, where it mediates renal urate secretion.

263 urate is a ligand for PecS and suggest that urate serves a novel function in signaling the colonizat

264 emonstrates that the I335V mutant transports urate similarly to the wild type hSLC2A9; however, Ile-3

265 sUA could improve the elimination of tissue urate stores and achieve better control of disease in pa

266 ies have associated elevated levels of serum urate (SU) with triglycerides and risk of heart disease.

267 hronic disease resulting from elevated serum urate (SU).

268 ave led to mechanism-based therapies such as urate synthesis inhibitors (febuxostat is already FDA ap

269 ing the principle of treating the patient to urate target.

270 polymorphisms in other genes associated with urate that do not affect serum urate and PD progression.

271 In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P<

272 l data link higher levels of the antioxidant urate to a reduced risk of developing Parkinsons disease

273 unctional studies were conducted using (14)C-urate transport assays in mammalian Chinese hamster ovar

274 (14)C-urate transport assays showed reduced urate transport fo

275 (14)C-urate transport assays showed reduced urate transport for the G65W URAT1 mutant.

276 , Ser-35 and Phe-365, are also important for urate transport kinetics.

277 directed mutagenesis resulted in 53% reduced urate transport rates compared to wild-type ABCG2 (P < 0

278 e of recent progress in the understanding of urate transport systems.

279 Furthermore, Trp-110 is a critical site for urate transport.

280 Genetic studies of urate transportation and of uromodulin-related nephropat

281 e of sex hormones in the regulation of ABCG2 urate transporter and its potential implications for the

282 olic syndrome in mice lacking the enterocyte urate transporter Glut9 (encoded by the SLC2A9 gene).

283 es including uricase and inhibitors of renal urate transporter proteins.

284 CNPs upstream of the urate transporter SLC2A9 on chromosome 4p16.1 are associ

285 as recently identified as an important human urate transporter, and a common mutation, a Gln to Lys s

286 myeloma and identification of GLUT9 being a urate transporter, are key advances underscoring the nee

287 SLC2A9, a urate transporter, influences uric acid levels.

288 acity hexose transporter and a high capacity urate transporter.

289 Combined with their activities as urate transporters and their strong associations with se

290 nd for selected SNPs in other genes encoding urate transporters that have modest or no effect on seru

291 ught to determine whether lowering levels of urate using allopurinol results in exacerbated neurotoxi

292 n peroxide was added to saliva, oxidation of urate was dependent on its concentration and peroxidase

293 Urate was oxidized by LPO to produce the electrophilic i

294 In controls (n = 504), plasma urate was positively associated with age, body mass inde

295 of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelia

296 s ratios between extreme quartiles of plasma urate were 0.4 (95% confidence interval: 0.2, 0.8) in th

297 Further, IS and urate were found to be independent predictors of change

298 by each of ascorbate, N-acetylcysteine, and urate when compared to alpha-TOH.

299 can be efficiently attenuated by the ligand urate, which also quenches the intrinsic fluorescence of

300 etermined rate constants for the reaction of urate with compound I (k1 = 1.1 x 10(7) M(-1) s(-1)) and