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PubMed1982

Inhibitory activity of human urine on calcium oxalate crystal growth: effects of sodium urate and uric acid.

1. Freshly voided urine from healthy subjects was pooled and ultrafiltered (10,000 daltons). The ultrafiltrable and the macromolecular portions were preincubated with calcium oxalate, uric acid and sodium urate crystals and the effects on the inhibitory activity of calcium oxalate crystal growth assessed by monitoring the disappearance of [14C]oxalate from the solution. 2. The inhibitory activity of the ultrafiltrate was higher than that of the urinary macromolecular fraction. Both uninhibited and inhibited crystal growth processes followed second-order kinetics. 3. Calcium oxalate crystals adsorbed almost all the urinary macromolecular inhibitors whereas sodium urate or uric acid crystals adsorbed only 10-20%. 4. In the presence of a metastable solution of calcium oxalate, the incubation of the urinary macromolecular fraction with sodium urate crystals caused a pronounced reduction in the inhibitory activity. A similar effect was seen with uric acid crystals, but to a lesser degree. 5. We conclude that the effect of sodium urate or uric acid crystals alone on naturally occurring urinary macromolecular inhibitors of calcium oxalate crystal growth is weak, but that in the presence of metastable calcium oxalate this is greatly enhanced. A substantial adsorption of the inhibitors on to the crystals is suggested, possibly secondary to epitaxial growth of calcium oxalate on the surface of the urate crystals.

Calcium Oxalate↗
PubMed2006

DNA/Poly(p-aminobenzensulfonic acid) composite bi-layer modified glassy carbon electrode for determination of dopamine and uric acid under coexistence of ascorbic acid.

A nano-composite of DNA/poly(p-aminobenzensulfonic acid) bi-layer modified glassy carbon electrode as a biosensor was fabricated by electro-deposition method. The DNA layer was electrochemically deposited on the top of electropolymerized layer of poly(p-aminobenzensulfonic acid) (Pp-ABSA). Scanning electron microscopy, X-ray photoelectron spectroscopy and electrochemical impedance spectrum were used for characterization. It demonstrated that the deposited Pp-ABSA formed a 2-D fractal patterned nano-structure on the electrode surface, and which was further covered by a uniform thin DNA layer. Cyclic voltammetry and electrochemical impedance spectrum were used to characterize the deposition, and demonstrated the conductivity of the Pp-ABSA layer. The biosensor was applied to the detection of dopamine (DA) and uric acid (UA) in the presence of ascorbic acid (AA). In comparison with DNA and Pp-ABSA single layer modified electrodes, the composite bi-layer modification provided superior electrocatalytic actively towards the oxidation of DA, UA and AA, and separated the originally overlapped differential pulse voltammetric signals of UA, DA and AA oxidation at the bare electrode into three well-defined peaks at pH 7 solution. The peak separation between AA and DA, AA and UA was 176 mV and 312 mV, respectively. In the presence of 1.0 mM AA, the anodic peak current was a linear function of the concentration of DA in the range 0.19-13 microM. The detection limit was 88 nM DA (s/n=3). The anodic peak current of UA was also a linear function of concentration in the range 0.4-23 microM with a detection limit of 0.19 microM in the presence of 0.5 mM AA. The superior sensing ability was attributed to the composite nano-structure. An interaction mechanism was proposed.

Ascorbic Acid↗
PubMed1981

Serum uric acid concentrations and arthralgia among patients treated with pyrazinamide-containing regimens in Hong Kong and Singapore.

The serum uric acid concentrations of patients being treated in Hong Kong and Singapore with a daily regimen consisting of streptomycin, isoniazid, rifampicin and pyrazinamide or a control regimen of daily streptomycin, p-amino-salicylic acid (PAS) and isoniazid were determined by the phosphotungstate method. Arthralgia and elevated serum uric acid levels were encountered only during the period that patients were being treated with pyrazinamide. Although daily treatment with pyrazinamide increased serum uric acid concentrations approximately 2.5-fold, the concentrations of the 6 patients who developed arthralgia were closely similar to those of matched controls without arthralgia. This fails to confirm a previous suggestion that patients with arthralgia might have higher values. Rifampicin appeared not to influence the hyperuricaemic effect of pyrazinamide.

Humans↗
PubMed2005

Interactions of peroxynitrite with uric acid in the presence of ascorbate and thiols: implications for uncoupling endothelial nitric oxide synthase.

It has been suggested that uric acid acts as a peroxynitrite scavenger although it may also stimulate lipid peroxidation. To gain insight into how uric acid may act as an antioxidant, we used electron spin resonance to study the reaction of uric acid and plasma antioxidants with ONOO-. Peroxynitrite reacted with typical plasma concentrations of urate 16-fold faster than with ascorbate and 3-fold faster than cysteine. Xanthine but not other purine-analogs also reacted with peroxynitrite. The reaction between ONOO- and urate produced a carbon-centered free radical, which was inhibited by either ascorbate or cysteine. Moreover, scavenging of ONOO- by urate was significantly increased in the presence of ascorbate and cysteine. An important effect of ONOO- is oxidation of tetrahydrobiopterin, leading to uncoupling of nitric oxide synthase. The protection of eNOS function by urate, ascorbate and thiols in ONOO(-)-treated bovine aortic endothelial cells (BAECs) was, therefore, investigated by measuring superoxide and NO using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine (CMH) and the NO-spin trap Fe[DETC]2. Peroxynitrite increased superoxide and decreased NO production by eNOS indicating eNOS uncoupling. Urate partially prevented this effect of ONOO- while treatment of BAECs with the combination of either urate with ascorbate or urate with cysteine completely prevented eNOS uncoupling caused by ONOO-. We conclude that the reducing and acidic properties of urate are important in effective scavenging of peroxynitrite and that cysteine and ascorbate markedly augment urate's antioxidant effect by reducing urate-derived radicals.

Animals↗
PubMed1990

[Significance of blood uric acid determination. Review of the literature].

Determination of the blood uric acid levels is still a weak indicator in the evaluation of the prognosis of fetal distress when compared with materno and feto-placental vascular tests. Its diagnostic and prognostic value in case of maternal gravidic nephropathy could be improved by a specific uricase titration and initial determination at the beginning of the 2nd trimester. Elevated uric acid levels would therefore be undeniably helpful in selecting the form of treatment.

Female↗
PubMed2000

Serum lipid resistance to oxidation and uric acid levels in subjects with Down's syndrome.

In subjects with Down's syndrome (DS) increased oxidative stress and consequent oxidative cell damage have been reported. The aim of this study was to assess whether the excessive production of free oxygen radicals in these subjects can affect the copper-induced lipid oxidation resistance measured in fresh whole serum. Since a significant elevation of serum uric acid levels, which is an efficient hydrophilic antioxidant, has been repeatedly reported in subjects with DS, we studied the association between increased serum uric acid levels and lipid resistance to oxidation measured directly in serum samples by monitoring the change in absorbance at 234 nm. The group of subjects with Down's syndrome consisted of 25 individuals (aged 18+/-5 years). Control group included brothers and sisters of subjects with DS (n = 25, aged 17+/-7 years). In subjects with DS, the serum lipid resistance to oxidation (lag time) was significantly higher than in controls (p<0.05) and a concomitant increase in serum uric acid levels was observed (p<0.001). A significant positive correlation between lag time and serum uric acid concentration was found in subjects with DS (r = 0.48, p<0.05), while the positive correlation in the control group was not significant. The results suggest that increased serum uric acid levels repeatedly observed in subjects with DS may be associated with an enhanced resistance of serum lipids to oxidation which is thought to play an important role in the atherogenic process.

Adolescent↗
PubMed2001

The role of uric acid in protection against peroxynitrite-mediated pathology.

Peroxynitrite, the product of the free radicals nitric oxide and superoxide, has been implicated in the pathogenesis of inflammatory CNS disorders. Uric acid, an effective scavenger of peroxynitrite, is a purine metabolite present at high levels in the serum of hominoids relative to lower-order animals due to the functional deletion of urate oxidase. Raising the normally low levels of uric acid in mice is therapeutic for experimental allergic encephalomyelitis, an animal model of multiple sclerosis. This therapeutic activity of uric acid is associated with the inhibition of peroxynitrite-induced tissue damage, blood-CNS barrier permeability changes, and CNS inflammation. Based on these findings we have concluded that peroxynitrite has an important role in promoting enhanced vascular permeability and inflammatory cell extravasation. We hypothesize that higher uric acid levels in hominoids evolved to protect against this process.

Animals↗
PubMed1988

Increased uric acid clearance in the syndrome of inappropriate secretion of antidiuretic hormone.

Twenty-eight elderly inpatients with severe hyponatremia were investigated prospectively to determine if fractional uric acid clearance was increased significantly in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) compared with other causes of hyponatremia. The patients were divided into three groups: Group A--hyponatremia due to SIADH, Group B--hyponatremia due to diuretic use, and Group C--hyponatremia possibly due to a number of causes. Serum uric acid was 3.2 +/- 0.4 and 5.3 +/- 0.6 in Groups A and B, respectively (P less than 0.05). Fractional clearance of urate in Groups A and B were 43 +/- 5.1 and 16.7 +/- 1.9, respectively (P less than 0.001). In Group C six of the nine had abnormally increased fractional clearance of uric acid (31.6 +/- 3.8) in addition to accepted biochemical criteria of SIADH. In 10 patients with SIADH, urate clearance measured before water restriction was 40.2 +/- 9.0%, and after serum sodium returned to normal 11.6 +/- 1.5 (P = 0.05). Of the total 28 patients 17 had increased fractional uric acid clearance with biochemical criteria of SIADH, suggesting that this syndrome is a common cause of the increased susceptibility to hyponatremia among older patients.

Aged↗
PubMed1982

A candidate reference method for uric acid in serum. II. Interlaboratory testing.

We describe the interlaboratory testing of a candidate Reference Method (Part I) for uric acid in serum. The method is based on the ultrasound spectrophotometric quantitation of uric acid before and after incubation with uricase. A comprehensive investigation involving 12 laboratories was organized to document the transferability, intra- and interlaboratory precision, and general reliability of the candidate Reference Method. The interlaboratory CV with this method was about 2 to 6% for uric acid concentrations ranging from 0.12 to 0.60 mmol/L. The results detailed here demonstrate that the method can be successfully duplicated among different laboratories.

Evaluation Studies as Topic↗
PubMed1977

Uric acid infarctions in the kidneys of newborn infants. A study on the changing incidence and on oxypurine ratios.

Among 1115 newborns who died during 1957--1976, 136 (12.2%) showed macroscopic renal uric acid infarctions. The incidence depended on the age of the infants and their fluid supply during the first days of life. After introduction of parenteral alkali-glucose infusion in the treatment of perinatal complications, the incidence of renal uric acid infarctions decreased from 19.3% to less than 1.0%. Analysis of the oxypurines in the renal uric acid infarctions of three newborns revealed high percentages of hypoxanthine (31.1%, 21.8% and 11.0%) along with the uric acid. Hypoxanthine ratios above 15% retrospectively point to chronic hypoxia of the newborn.

Age Factors↗
PubMed2006

Uric acid restores endothelial function in patients with type 1 diabetes and regular smokers.

Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.

Acetylcholine↗
PubMed2006

Accuracy of serum uric acid in predicting complications of pre-eclampsia: a systematic review.

BACKGROUND: Pre-eclampsia is one of the largest causes of maternal and fetal mortality and morbidity. Hyperuricemia is often associated with pre-eclampsia. OBJECTIVE: To determine the accuracy with which serum uric acid predicts maternal and fetal complications in women with pre-eclampsia. STUDY DESIGN: Systematic quantitative review of test accuracy studies. SEARCH STRATEGY: We conducted electronic searches in MEDLINE (1951-2004), EMBASE (1980-2004), the Cochrane Library (2004:4) and the MEDION database to identify relevant articles. A hand-search of selected specialist journals and reference lists of articles obtained was then carried out. There were no language restrictions for any of these searches. SELECTION CRITERIA: Two reviewers independently selected the articles in which the accuracy of serum uric acid was evaluated to predict maternal and fetal complications of pre-eclampsia. DATA COLLECTION AND ANALYSIS: Data were extracted on study characteristics, quality and accuracy to construct 2 x 2 tables with maternal and fetal complications as reference standard. Summary likelihood ratios for positive (LR+) and negative LR(-) test results are generated for various threshold levels of uric acid. MAIN RESULTS: There were 18 primary articles that met the selection criteria, including a total of 3913 women and forty-one 2 x 2 tables. In women with pre-eclampsia, a positive test result of uric acid greater than or equal to a 350-micromol/l threshold predicted eclampsia with a pooled likelihood ratio (LR) of 2.1 (95% CI 1.4-3.5), while a negative test result had a pooled LR of 0.38 (95% CI 0.18-0.81). For severe hypertension as the outcome measure, the LRs were 1.7 (95% CI 1.3-2.2) and 0.49 (95% CI 0.38-0.64) for positive and negative test results, respectively, and for caesarean section the LRs were 2.4 (95% CI 1.3-4.7) and 0.39 (95% CI 0.20-0.76). For stillbirths and neonatal deaths the respective LRs were 1.5 (95% CI 0.91-2.6) and 0.51 (95% CI 0.20-1.3). For the prediction of small-for-gestational-age fetus, the pooled LRs were 1.3 (95% CI 1.1-1.7) and 0.60 (95% CI 0.43-0.83) for positive and negative results, respectively. AUTHOR'S CONCLUSION: Serum uric acid is a poor predictor of maternal and fetal complications in women with pre-eclampsia.

Biomarkers↗
PubMed1998

Estimation of the flow of microbial nitrogen to the duodenum using urinary uric acid or allantoin.

Data were collected from six experiments using duodenally cannulated Holstein dairy cows (88 combinations of cow and period) to evaluate the relationship between urinary purine metabolites and microbial N flow. Experiments evaluated the effects of dietary factors on microbial N production, which included 1) varying concentrations of ruminally degradable protein and nonstructural carbohydrates, 2) supplemental sources of protected amino acids, 3) grass silage treated with fibrolytic enzymes, 4) bacterial inoculation of corn silage, and 5) ruminal starch availability as affected by corn silages of varying maturity. The coefficient of determination for individual experiments that measured the relationship between microbial N flow and allantoin or uric acid excretion in urine ranged from 0.01 to 0.68 and 0.02 to 0.82, respectively. Across all experiments, the coefficients of determination between microbial N flow and allantoin or uric acid excretion in urine were r2 = 0.002 and 0.11, respectively. Removal of data from one experiment improved the overall coefficient of determination between microbial N flow and urinary uric acid to r2 = 0.32. Urinary allantoin excretion across experiments was negatively correlated with microbial N flow, but urinary allantoin excretion within experiments was positively correlated with microbial N flow. Uric acid excretion in urine was positively correlated with microbial N flow across and within experiments, except for one experiment. Our data demonstrate that uric acid excretion in urine can be used to predict microbial N production, except in early lactation, and that urinary allantoin excretion cannot be used to predict microbial N production accurately among cows at different stages of lactation.

Allantoin↗
PubMed1980

Methodological principles in the enzymatic determination of substrates illustrated by the measurement of uric acid.

The enzymatic method of Haeckel for the determination of uric acid in serum has been used to compare three different kinetic approaches with the corresponding equilibrium (end-point) procedure. The kinetic methods were: measurement of the difference in absorbance between two pre-selected fixed instants during the course of the reaction under first-order conditions; measurement of the initial rate of reaction at substrate concentrations sufficiently low for first-order kinetics to apply, and determination of initial rate with substrate concentrations approximating to, or greater than, the Michaelis constant (pseudo-zero order kinetics). In the third method results were obtained by solving the Michaelis-Menten equation. The results emphasise the superiority of the two-point kinetic approach, which is apparent even when the timed absorbance values are obtained from an analogue signal displayed on a recorder chart. Conditions are described for the determination or uric acid in serum according to this principle.

Clinical Enzyme Tests↗
PubMed2005

Uric acid and transplantation.

Hyperuricemia is a common complication in organ transplant recipients, and frequently is associated with chronic cyclosporine immunosuppressive therapy. Kidney and heart transplant recipients are prone to develop posttransplant hyperuricemia. Risk factors for hyperuricemia include decreased glomerular filtration rate (GFR), diuretic use, and preexistent history of hyperuricemia. The influence of hyperuricemia in patient and graft survival is unclear because uric acid is not usually considered a common risk factor for cardiovascular disease that affects graft and patient survival. However, there have been small studies that have suggested that control of uric acid levels contributes to recovery of renal function (in heart and liver transplant recipients) and in an improvement in GFR in renal transplant recipients. Despite controversies in the need for hyperuricemia treatment in transplant patients, strategies to decrease uric acid levels includes a decrease or avoidance of cyclosporine treatment, adequacy of antihypertension treatment, avoidance of diuretics, nutritional management, and use of uric acid-decreasing agents. In this article we review the incidence and risk factors for the development of posttransplant hyperuricemia, discuss the influence of different immunosuppressive agents on uric acid metabolism, and suggest some alternative treatments for posttransplant hyperuricemia. We also consider that uric acid should be considered as a potential risk factor for renal allograft nephropathy or for renal dysfunction in nonrenal transplant recipients, as well as a comorbid factor for a decrease in patient and graft survival.

Gout Suppressants↗
PubMed1988

Changes in plasma lipids and uric acid with sodium loading and sodium depletion in patients with essential hypertension.

The short-term effects of manipulating dietary salt intake on plasma levels of cholesterol, lipoproteins and uric acid were studied in two groups of patient with essential hypertension. With dietary salt restriction in 8 patients (10 g to 2 g salt/day for five days), plasma total cholesterol, esterified cholesterol, beta-lipoprotein, low density lipoprotein and uric acid rose significantly. With salt repletion (2 g salt/day to 20 g/day for five days) in 17 patients, plasma total cholesterol, esterified cholesterol, beta-lipoprotein, low density lipoprotein and uric acid fell significantly. Total/HDL cholesterol ratio increased significantly with salt restriction and decreased significantly with repletion. However, very low density lipoprotein, HDL-cholesterol, triglyceride, phospholipid, chylomicron and non-esterified fatty acid were not influenced by the changes in salt intake. These results indicate that the severe restriction of dietary salt raises plasma cholesterol and uric acid levels in patients with essential hypertension in the short term.

Blood Pressure↗
PubMed1997

Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases.

Glutamate-mediated excitotoxicity is associated with adenosine triphosphate (ATP) degradation and generation of oxygen radicals. Hypoxanthine and lactate depict energetic impairment, while xanthine and uric acid reflect activity of radical producing xanthine oxidase. Cerebrospinal fluid (CSF) glutamate, hypoxanthine, lactate, xanthine, and uric acid were investigated in neurological patients. In multiple sclerosis, myelopathy, stroke, epilepsy and viral meningitis glutamate, hypoxanthine, xanthine, and uric acid are increased 2-3-fold compared to controls. Lactate is only elevated in meningitis. Normal lactate dehydrogenase (LDH) levels and absent correlation between the albumin ratio and neurochemical parameters exclude an artificial increase due to cell lysis and barrier damage. Absent correlation between neurochemical parameters within each patient group is most likely related to preserved glial and neuronal uptake mechanisms. CSF hypoxanthine, xanthine, and uric acid levels appear superior to lactate in reflecting glutamate-mediated excitotoxicity in neurological patients.

Adult↗
PubMed2006

J-shaped mortality relationship for uric acid in CKD.

BACKGROUND: Hyperuricemia is a common feature in patients with chronic kidney disease (CKD). Hyperuricemia has been associated with increased cardiovascular mortality in the general population, but less is known about this association in patients with CKD. METHODS: To explore possible associations of serum uric acid with all-cause mortality and comorbidity in patients with CKD, we studied 294 incident patients with CKD stage 5 (185 men; age, 53 +/- 12 years) starting renal replacement therapy with a median glomerular filtration rate of 6.4 mL/min/1.73 m(2) (0.11 mL/s/1.73 m(2); range, 0.8 to 14.3 mL/min/1.73 m(2) [0.01 to 0.24 mL/s/1.73 m(2)]). Survival was determined from the day of examination and during a mean follow-up period of 27 months (range, 3 to 72 months); 94 patients died. Patients were divided into 3 groups based on serum uric acid levels (low quintile, 3 middle quintiles, and high quintile). RESULTS: In a nonadjusted analysis, patients in the high quintile, followed by patients in the low quintile, had greater all-cause mortality compared with patients in the 3 middle quintiles (log-rank test chi-square, 6.8; P = 0.03). After adjusting for age, sex, glomerular filtration rate, cholesterol level, phosphate level, C-reactive protein level, cardiovascular disease, diabetes mellitus, diuretics, and allopurinol treatment, the association showed a "J-shaped" association with hazard ratios of 1.96 (confidence interval, 1.10 to 3.48; P = 0.02) for the high quintile and 1.42 (confidence interval, 0.76 to 2.66; P = not significant) for the low quintile. Moreover, uric acid levels correlated positively with levels of triglycerides, phosphate, C-reactive protein, and intracellular adhesion molecule 1 and negatively with levels of calcium, high-density lipoprotein cholesterol, and apolipoprotein A. CONCLUSION: Serum uric acid levels showed a J-shaped association with all-cause mortality, with the lowest risk in the 3 middle quintiles. Moreover, uric acid level was associated with calcium/phosphate metabolism, dyslipidemia, and inflammation.

Adult↗