Disease relevance of uric acid

• In patients with persistent hyperuricemia, regular medication should lower the serum urate concentration to an optimal level [1].
• Asymptomatic elevations of the serum aminotransferase levels (in 13 patients) and the serum urate level (in 10) were also noted, but there was no dose-related hematologic toxicity [2].
• Hypoxanthine and urate concentrations were extremely high in the plasma and urine of the patient with glycogenosis type VII [3].
• We describe a large kindred from northern New York with hereditary nephrolithiasis accompanied by urinary concentrating defects, nephrocalcinosis, renal insufficiency, and renal wasting of potassium, phosphate, calcium, and uric acid [4].
• Dysuria, uric acid crystalluria and hyperuricosuria developed in a child with cystic fibrosis and normal serum uric acid [5].
• Serum uric acid levels are an independent predictor of death in patients at high risk of cardiovascular disease [6].
• Diet soft drink consumption was not associated with serum uric acid levels or hyperuricemia (multivariate P>0.13 for trend) [7].

Psychiatry related information on uric acid

• Relative risks were adjusted for age, physical activity level, and uric acid level [8].
• There was no consistent univariate association of xanthelasma and corneal arcus with smoking, alcohol consumption, blood pressure, obesity, sedentary lifestyle, family history of ischemic heart disease, or glucose and uric acid plasma concentrations [9].
• Elevation of serum uric acid as a clue to alcohol abuse [10].
• Analyses were carried out on eGFR (equation of Modification Diet in Renal Disease study), disorders potentially secondary to kidney dysfunction (hypertension, high serum uric acid, high serum phosphorus/low serum calcium, high serum potassium, cardiovascular disease, anemia), and kidney disease awareness [11].
• Lesch-Nyhan syndrome is a hereditary disorder of purine metabolism causing overproduction of uric acid and neurological problems including spasticity, choreoathetosis, mental retardation, and compulsive self-mutilation [12].

High impact information on uric acid

• With increasing serum concentrations of the biochemical markers of alcohol intake (aspartate aminotransferase, uric acid, and gamma-glutamyl transferase), we observed similar trends in the relative risk of stroke [13].
• Purine nucleoside phosphorylase is a necessary component of the major, if not the sole, pathway for the conversion of purine nucleosides and nucleotides to uric acid [14].
• Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12 [15].
• Urate oxidase (E.C. 1.7.3.3) catalyzes the oxidation of uric acid to allantoin in most mammals except humans and certain primates [16].
• Renal tubular handling of glucose, phosphate, sodium, potassium, uric acid, and amino acids was abnormal, and in vitro uptake of labeled lysine, glycine, and alpha-methyl-D-glucoside by renal cortical slices was impaired [17].

Chemical compound and disease context of uric acid

• These purine metabolites subsequently serve as substrates for the synthesis of uric acid, leading to hyperuricemia [3].
• Ethanol-induced hyperuricemia: evidence for increased urate production by activation of adenine nucleotide turnover [18].
• We conclude that hyperuricemia is a common complication of cyclosporine therapy and is caused by decreased renal urate clearance [19].
• On the basis of this short-term study, the use of a single 300-mg tablet of allopurinol per day appears to be an effective means of lowering the elevated serum urate levels of individuals with gouty hyperuricemia and compares favorably with the results obtained by allopurinol in divided doses [20].
• On the basis of these results, it is suggested that progressive retention of hippuric acid, indoxyl sulfate, and other yet unidentified inhibitors may explain the gradual increase in urinary fractional excretion of urate observed in uremia [21].

Biological context of uric acid

• Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution [15].
• MEASUREMENTS--Obesity (overall and regional), plasma glucose and insulin responses to a 75-g oral glucose load, fasting uric acid concentrations, plasma triglyceride and high-density lipoprotein-cholesterol concentrations, systolic and diastolic blood pressure, insulin-mediated glucose disposal, and urinary uric acid clearance [22].
• This relationship suggests an altered tubular sodium handling and uric acid metabolism consistent with hyperinsulinemia, insulin resistance being the possible pathophysiological link [23].
• Control of blood volume and serum uric acid, appropriate spacing of radiographic studies, and possibly urinary alkalinization and hypouricosuric drugs in high-risk patients are recommended to decrease the incidence and morbidity of contrast-mediated nephropathy [24].
• The kinetics and characteristics of uric acid entry are shown to be the same for hemolysed and normal erythrocytes [25].

Anatomical context of uric acid

• Urate spherulites in gouty synovia [26].
• Uricase is shown to be active within the erythrocytes and to degrade uric acid as rapidly as it enters the cells when high intracellular enzyme concentrations are employed [25].
• Lipoproteins containing apo B are thus a major regulator of neutrophil responses to urate crystals [27].
• The transport mechanism of urate and p-aminohippurate (PAH) was evaluated in microvillus membrane vesicles isolated from the renal cortex of the mongrel dog [28].
• Paradoxical effects of pyrazinoate and nicotinate on urate transport in dog renal microvillus membranes [29].

Associations of uric acid with other chemical compounds

• The uric acid level in the patients receiving hydrochlorothiazide therapy rose from a baseline of 5.9 to 7.5 mg/dL (normal range, 3.0 to 8.0 mg/dL) [30].
• This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate [31].
• However, immunofluorescence microscopy and killing assays using the scavenger uric acid suggest that peroxynitrite is not responsible for macrophage killing of wild-type S. typhimurium [32].
• The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid [31].
• The enzymatic or physical removal of ascorbate or urate and other low molecular weight components did not affect the ability of either fluid to prevent LDL oxidation, and the high molecular weight fraction was as protective as whole serum or SBIF [33].

Gene context of uric acid

• The decrease in mitochondrial respiration in response to LPS and IFN-gamma stimulation was inhibited by the ONOO- scavenger uric acid (100 mumol/L) and by inhibitors of iNOS [34].
• Reduction of STAT1 phosphorylation by ethanol was prevented in the presence of 4MP, DAS, or uric acid, indicating that the oxidative products from ethanol metabolism were partly responsible for suppression of STAT1 phosphorylation [35].
• Adjustment for age, sex, BMI, hypertension, LDL cholesterol, HDL cholesterol, uric acid, C-reactive protein, and IL-6 did not alter these findings [36].
• The association of URAT1 with PDZK1 enhanced urate transport activities in HEK293 cells (1.4-fold), and the deletion of the URAT1 C-terminal PDZ motif abolished this effect [37].
• Familial juvenile hyperuricemic nephropathy (FJHN [MIM 162000]) is an autosomal-dominant disorder characterized by abnormal tubular handling of urate and late development of chronic interstitial nephritis leading to progressive renal failure [38].
• Based on these data, we propose a novel model of transcellular urate transport in the kidney; urate [corrected] is taken up via apically located URAT1 and exits the cell via basolaterally located GLUT9, which we suggest be renamed URATv1 (voltage-driven urate transporter 1) [39].

Analytical, diagnostic and therapeutic context of uric acid

• In men only, higher body mass index and serum uric acid concentration also were independently associated with an elevated risk of pancreatic cancer mortality [40].
• CONTEXT: Although many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for cardiovascular mortality, this relationship remains uncertain [41].
• Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National Health and Nutrition Examination Survey [41].
• Percutaneous nephrostomy and uric acid stones [42].
• In all 14 fibroblast strains from patients showing excessive production of uric acid (groups 3 and 4), rates of purine synthesis de novo and PP-ribose-P concentrations exceeded values for cells from control groups [43].

References