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PubMed1995

On the significance of brain extracellular uric acid detected with in-vivo monitoring techniques: a review.

The concentration of uric acid [UA] in the extracellular fluid (ECF) estimated with in-vivo voltammetry and microdialysis data is compared for probes of different diameters from the day of implantation (acute) to several days (chronic) or even months after surgery. For small probes (diameter < 160 microns) the acute [UA] of ca. 5 microM decreased significantly to ca. 1 microM under chronic conditions. For larger probes (e.g., 320-microns diameter) the acute [UA] was also ca. 5 microM, but this value significantly increased to ca. 50 microM under chronic conditions. Associated with this difference in [UA], there were parallel differences in the extent of gliosis around the probes. These findings are discussed in terms of possible sources of extracellular UA and their implications for in-vivo monitoring techniques in behaving animals.

Animals↗

PubMed1980

Development and improvement of a commercial uric acid enzymatic determination kit on a centrifugal fast analyzer.

The performance of a uric acid determination kit has been evaluated for five months, under routine conditions, in a General Hospital Biochemical Laboratory. An anomalous increment in fresh serum blanks was noted in the kit when first introduced. This interference, probably due to alcohol dehydrogenase contamination, was corrected by addition of 50 mmol/l (NH4)2SO4 to the reagent. Results obtained with this modified reagent correlate perfectly with those obtained with modified kits by Smith Kline Instruments (SKI), and with many other determination methods. Correlations are discussed and explanations for differences in statistical data are offered. Within run and between run precision data are presented. The kit fits perfectly with the needs of centrifugal fast analyzers and discrete micro analyzers, on account of its speed, reliability and precision.

Alcohol Oxidoreductases↗

PubMed1987

Production of uric acid in cerebrospinal fluid after subarachnoid hemorrhage in dogs: investigation of the possible role of xanthine oxidase in chronic vasospasm.

Based on accumulating evidence of the role of xanthine oxidase (XO) in generating oxygen free radicals and causing tissue damage during ischemia, we examined the possible role of XO in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). After inducing SAH in dogs by two autologous blood injections 2 days apart, chronic vasospasm of the basilar artery was reliably produced. There was a 3.5-fold elevation in uric acid (UA), the product of XO, in the cerebrospinal fluid (CSF) of these animals. Parenteral administration of allopurinol (i.v., 25 mg/kg, every 6 hours), a specific blocker of XO, successfully abolished the elevation in CSF uric acid levels due to SAH. However, angiographic vasospasm measured on Day 7, morphological changes observed by electron microscope, and elevated CSF prostaglandin levels were not altered by the treatment. It can be concluded that the observed activation of the enzyme XO, which is a well-known source of oxygen free radicals in ischemia in various organs, is not playing a major role in the pathogenesis of chronic cerebral vasospasm in this animal.

Allopurinol↗

PubMed1986

Serum uric acid correlates with beta 2-microglobulin in pre-eclampsia.

In order to evaluate renal tubular function, beta 2-microglobulin was measured in serum and urine from 15 patients with severe pre-eclampsia and 13 normal pregnant women. In the pre-eclamptic group, the serum beta 2-microglobulin level was significantly higher (p less than 0.05) and urinary excretion/24h significantly lower (p less than 0.05), than in the normal pregnant group. A positive linear correlation between serum uric acid and beta 2-microglobulin was observed both in the pre-eclamptic group (r = 0.79, p less than 0.001) and in the normal pregnant group (r = 0.58, p less than 0.05). This may indicate that production and renal handling of these two substances are interdependent. Tubular function is reduced in normal pregnancy, whereas increased 'net tubular reabsorption' of uric acid and beta 2-microglobulin occurs in pre-eclampsia. The cause of the observed changes in tubular function is still obscure.

Adult↗

PubMed1975

Synthesis of uric acid in isolated normothermic perfused mongrel and Dalmatian dog kidneys.

Renal synthesis of uric acid (urate) in the dog was demonstrated by use of two isolated kidney preparations during pulsatile perfusion at 37 degrees C with artificial perfusate or with a plasma fraction. During perfusion of mongrel and Dalmatian dog kidneys with 0.5 mg of [14C]xanthine per 100 ml, a mean of 24.3 and 25.4 mug of [14C]urate per minute, respectively, entered either urine or perfusate after its synthesis in the isolated kidney. Approximately 6.2% of the combined extracellular radiolabeled urate formed in the isolated mongrel kidney was excreted in the urine and 15.7% in the urine of isolated Dalmatian dog kidneys. Recirculating the perfusate without the kidney did not convert any radioactively labeled xanthine to urate and therefore the radioactively labeled urate appearing in the urine and recycled perfusate must have been formed in the renal parenchyma. Renal synthesis of urate was blocked by the xanthine oxidase inhibitor allopurinol. In the presence of allopurinol, [14C]xanthine was excreted unchanged into the urine.

Allantoin↗

PubMed2000

Schlieren photography study of energy absorption by uric acid nuclei.

Previous studies using microfocus x-ray radiography on concentric laminated uric acid calculi following in vitro extracorporeal shock-wave lithotripsy (ESWL) has demonstrated the enlargement of the matrix layers. The Schlieren technique was used to verify the hypothesis that the incident energy would be concentrated in the matrix layers by total internal reflection. Because of the rough surface of the stone, the ultrasonic beam (4 MHz) was incident at various angles. At the critical Rayleigh angle (45.9 degrees +/- 0.5 degrees ), the reflected beam consisted of a spectacularly reflected lobe and a reradiated leaky Rayleigh wave. Different critical Lamb angles, theta(L), of 30.8 degrees, 38.1 degrees and 50.8 degrees (experimental uncertainty 0.5 degrees ) were also determined. Depending on the angle of incidence on the stone surface, a Rayleigh wave can be produced and/or one or more layers, as a whole, are set into vibration (Lamb excitation), with the result that shell-like fragments consisting of one or more layers, break off the stones at sites of weaker bonding, as has been noted in previous in vitro lithotripsy experiments by our group.

Absorption↗

PubMed1988

Xanthine and uric acid levels in rat brain following focal ischemia.

Changes of the xanthine and uric acid (UA) levels in rat forebrain following focal cerebral ischemia were studied by reversed-phase HPLC with electrochemical detection. Focal ischemia was induced by occluding the left middle cerebral artery in the rat. The xanthine level in the normal group was 11.50 nmol/g tissue. In the ischemic group, the xanthine concentration in the ischemic hemisphere progressively increased after occlusion and reached a maximum value of 59.42 nmol/g tissue 4 h after operation. The UA level in the normal group was 2.20 nmol/g tissue, whereas in the ischemic group the UA concentration in the ischemic hemisphere gradually increased after occlusion, reaching a value of 38.53 nmol/g tissue 24 h after ischemia. The concentration of UA remained elevated in the ischemic hemisphere until 48 h after occlusion, and reached a maximum value of 38.98 nmol/g tissue. The xanthine and UA levels in the contralateral hemisphere remained unchanged. The xanthine and UA concentrations in the sham-operated group did not show a significant increase after operation. The time course of xanthine and UA levels suggests that in ischemic forebrain UA is formed from xanthine as a product of purine metabolism.

Animals↗

PubMed2002

Effect of fetal number on maternal serum uric acid concentration.

The aim of this study was to examine whether maternal serum uric acid (UA) concentrations are influenced by the number of fetuses and whether this effect is confounded by maternal body mass index (BMI). Medical records of 207 consecutive twin and 69 triplet pregnancies admitted to our high-risk pregnancy unit between 1994 and 1998 were reviewed. Pregnancies complicated by acute or chronic renal diseases, vascular diseases, hypertension, hemolysis, diabetes mellitus, or proteinuria were excluded. The remaining 137 twin and 42 triplet pregnancies were matched with 118 consecutive singleton pregnancies who met the same exclusion criteria and were admitted in the first half of 1998. Each birth order study group was further stratified and compared within three maternal BMI subgroups. Serum UA concentrations were higher in twin and triplet pregnancies compared to singletons (4.6 +/- 1.3, 5.2 +/- 1.2, and 3.8 +/- 0.7 mg%, respectively; p <0.01). These differences in UA concentration persisted after grouping by BMI classes. Serum UA concentration in pregnancy are positively correlated with the number of fetuses. For clinical purpose, the UA cutoff concentration should be adjusted using mean + 2 SD as follows: 5.2, 7.2, and 7.6 for singleton, twin, and triplets, respectively.

Adult↗

PubMed2022

Uric Acid Levels Are Associated with Bone Mineral Density in Mexican Populations: A Longitudinal Study.

Background: Inconsistent epidemiological evidence between uric acid (UA) and bone mineral density (BMD) has been observed. Therefore, we evaluated the association between UA and BMD in Mexican adults. Methods: This analysis was conducted on 1423 participants from the Health Workers Cohort Study. We explored cross-sectional associations using linear regression and longitudinal associations using fixed-effects linear regression by sex and age groups (<45 and ≥45 years). Results: In females <45 years old, the cross-sectional analysis showed that UA levels were positively associated with total hip BMD. However, in the longitudinal analysis, we observed a negative association with the femoral neck and lumbar spine BMD. In contrast, in males <45 years old, we found an increase in total hip and femoral neck BMD in the groups with high levels of UA in the longitudinal association. On the other hand, in females ≥45 years old, we observed a longitudinal association between UA and loss of BMD at different sites. We did not observe an association between UA levels and BMD in males ≥45 years old. Conclusions: Our results suggest higher serum UA levels are associated with low BMD at different skeletal sites in Mexican females. Further studies are needed to delineate the underlying mechanisms behind this observation.

Male↗

PubMed1995

Influence of two amounts of dietary casein on uric acid, sodium urate, and ammonium urate urinary activity product ratios of healthy beagles.

Casein has been used as a protein source in diets designed to dissolve canine ammonium urate uroliths and to prevent their recurrence, because it contains fewer purine precursors than do many other sources of protein. However, an important question is whether reduced quantities of dietary casein have any benefit in modifying saturation of urine with urates. To answer this question, activity product ratios of uric acid, sodium urate, and ammonium urate were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of consumption of a 10.4% protein, casein-based (10.4% casein) diet and a 20.8% protein, casein-based (20.8%casein) diet. Significantly lower 24-hour urinary excretions of ammonia and phosphorus were observed when dogs consumed the 10.4% casein diet. These results suggest that use of the 10.4% casein diet in protocols designed for dissolution and prevention of uric acid, sodium urate, and ammonium urate uroliths in dogs may be beneficial.

Ammonia↗

PubMed1975

Colorimetric, enzymatic, and liquid-chromatographic methods for serum uric acid compared.

We describe high-performance liquid chromatography in conjunction with electrochemical detection as a possible reference method for serum uric acid. Separation was effected on a column packed with "Vydac" strong anion-exchange resin, with use of a detection potential of +0.80 V vs. an Ag/AgCl reference electrode. Results were linearly related to concentration up to 1.0 g/liter, and no interferences were seen. Assay of human sera gave within-run and day-to-day coefficients of variation of 0.83% and 1.1%, respectively; analytical recoveries averaged 100%. Comparison of the new procedure (x) with the phosphotungstate and uricase methods (y) showed the following linear regression and correlation coefficients for results: y equal 0.963x + 0.219 (r = 0.995), and y = 0.991x + 0.165 (r = 0.999), respectively. As compared to these methods, the procedure we describe is more accurate, because of the selective detection system based on retention time and redox potential. Samples can be analyzed at the rate of 20/h. No deproteinization is required.

Chromatography, Ion Exchange↗

PubMed1980

High uric acid as an indicator of cardiovascular disease. Independence from obesity.

In three groups of patients, we investigated the hypothesis that body weight is not the factor underlying the relation between hyperuricemia and cardiovascular disease. Among 111 subjects with asymptomatic hyperuricemia followed for 108 months, atherosclerotic heart disease (ASHD) developed in six; their mean was 77.4 kg (172 pounds) compared with 79.7 kg (177 pounds) in the remainder; in 25 of the 111 patients hypertension developed; their mean weight was not significantly higher than that of the remainder. Among 156 patients with established gout followed for 133 months, clinical atherosclerosis developed in 25 after a mean of 95 months; their mean weight was 78.3 kg (174 pounds) contrasted with 79.7 kg (177 pounds) in those 81 of the remaining patients who had a weight recorded with 75 +/- 12 months after their initial attack of gout. Among 1,356 men aaged 60 to 69 years who had their serum uric acid recorded in 1967, subsequent deaths from cardiovascular disease showed a stepwise increase when deaths were arranged according to the serum uric acid levels but not when they were arranged according to body weight. Hyperuricemia thus predicts future cardiovascular disease independently of body weight.

Aged↗

PubMed2005

Insulin neuroprotection against oxidative stress in cortical neurons--involvement of uric acid and glutathione antioxidant defenses.

In this study we investigated the effect of insulin on neuronal viability and antioxidant defense mechanisms upon ascorbate/Fe2+-induced oxidative stress, using cultured cortical neurons. Insulin (0.1 and 10 microM) prevented the decrease in neuronal viability mediated by oxidative stress, decreasing both necrotic and apoptotic cell death. Moreover, insulin inhibited ascorbate/Fe2+-mediated lipid and protein oxidation, thus decreasing neuronal oxidative stress. Increased 4-hydroxynonenal (4-HNE) adducts on GLUT3 glucose transporters upon exposure to ascorbate/Fe2+ were also prevented by insulin, suggesting that this peptide can interfere with glucose metabolism. We further analyzed the influence of insulin on antioxidant defense mechanisms in the cortical neurons. Oxidative stress-induced decreases in intracellular uric acid and GSH/GSSG levels were largely prevented upon treatment with insulin. Inhibition of phosphatidylinositol-3-kinase (PI-3K) or mitogen-induced extracellular kinase (MEK) reversed the effect of insulin on uric acid and GSH/GSSG, suggesting the activation of insulin-mediated signaling pathways. Moreover, insulin stimulated glutathione reductase (GRed) and inhibited glutathione peroxidase (GPx) activities under oxidative stress conditions, further supporting that insulin neuroprotection was related to the modulation of the glutathione redox cycle. Thus, insulin may be useful in preventing oxidative stress-mediated injury that occurs in several neurodegenerative disorders.

Aldehydes↗

PubMed1996

Simultaneous determination of adenosine, inosine, hypoxanthine, xanthine, and uric acid in microdialysis samples using microbore column high-performance liquid chromatography with a diode array detector.

In the myocardial interstitial space, adenosine and its metabolites are important markers of ischemia, regulators of blood flow, and may produce cardioprotection against ischemia. A fast and sensitive method to assess the concentrations of adenosine and its metabolites is necessary to determine their involvement in mediating these effects. A method for the simultaneous determination of adenosine, inosine, hypoxanthine, xanthine, and uric acid in the interstitial fluid of the canine myocardium was developed using microdialysis, microbore column high-performance liquid chromatography, and a photo diode array detector (DAD). The microdialysis samples were injected directly onto a microbore C18 reverse-phase column without any prior sample preparation. Use of a DAD in this method provided many advantages. First, a DAD allowed the simultaneous detection of UV absorbance at multiple wavelengths, allowing the detection of each compound at their maximal UV absorbance. Further, the full UV absorption spectrum was recorded for each detected peak, confirming peak purity and identity. Using a microbore HPLC column and detection of UV absorbance at the maximal absorbance for each compound improve the sensitivity for all compounds. The detection limit of these compounds is 50 fmol (signal-to-noise ratio, S/N = 3). This method is useful in analyzing the temporal effect of a prolonged period of myocardial ischemia and reperfusion upon interstitial adenosine, inosine, hypoxanthine, xanthine, and uric acid concentrations in an in vivo canine model.

Adenosine↗

PubMed2006

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

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early prediction of pre-eclampsia may be used to target high-risk women for effective preventative treatments. Hyperuricemia is associated with pre-eclampsia and it has been tested in early pregnancy for its ability to predict the later onset of the disease. OBJECTIVE: To systematically review the accuracy of determining serum uric acid before the 25th gestational week in predicting pre-eclampsia. METHODS: We searched Medline, Embase, Cochrane Library, Medion, bibliographies of review articles and eligible primary studies, and contacted experts in the field. Language restrictions were not applied. Reviewers working independently selected studies, extracted data and assessed validity according to eight criteria. Sensitivities and specificities were plotted in a Receiver Operating Characteristic plot. RESULTS: We identified five primary articles, with a total of 572 women, including 44 who developed pre-eclampsia. Study populations differed clinically, with incidences ranging from 3.4% to 40.1%. Sensitivity ranged from 0.0% to 55.6% and specificity ranged from 76.9% to 94.9%. Clinical heterogeneity and poor reporting precluded sensible pooling of data. In particular, consecutive entry of eligible women, blind assessment of the reference standard, and treatment to prevent pre-eclampsia were poorly reported. CONCLUSION: Contrary to previous reviews, we conclude that there is currently insufficient evidence to draw firm conclusions about the accuracy of serum uric acid determination in predicting pre-eclampsia.

Female↗

PubMed2006

Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population.

OBJECTIVE: Human urate transporter 1 (hURAT1) is a member of the organic anion transporter family (SLC22A12) that mainly regulates tubular urate reabsorption. Loss-of-function mutations result in idiopathic hypouricemia. The present case-control study was designed to analyze whether hURAT1 might also be a candidate gene for hyperuricemia with primary reduced renal urate excretion. METHODS: DNA samples from 389 individuals with reduced fractional excretion of uric acid (FEUA) (< or =6.5%) and from 263 controls (FEUA >6.5%) were sequenced. Genotype frequencies between groups were compared by Cochran-Armitage trend test. RESULTS: Significantly different genotype distributions could be demonstrated for the -788 T >A (promoter; P = 0.014), the C258T (exon 1; P = 0.006), and the C426T (exon 2; P = 0.0002) polymorphisms, but not for the T1309C (exon 8) and the +18 C >T (intron 9) polymorphisms. The strongest association with reduced FEUA was observed for the C426T polymorphism, with odds ratios (ORs) of 1.59 and 2.54 (P = 0.0002) for the CT and TT genotypes, respectively. Adjusted values for FEUA in the C426T genotype, were significantly reduced decreasing to 7.3%, 6.7%, and 6.3% in individuals with the CC, CT, and TT genotypes, respectively (P = 0.004). Haplotypes were constructed from the -788 T >A, C258T, and C426T polymorphisms. Individuals carrying at least 1 ACT haplotype (n = 349) had a significantly higher risk for reduced FEUA than individuals without any ACT haplotype (n = 303) (OR 1.39, P = 0.041). CONCLUSION: These results indicate that polymorphisms in the N-terminus of the hURAT1 gene were significantly associated with reduced renal uric acid excretion. The main regulating factor seems to be located close to the C426T polymorphism or is in strong linkage disequilibrium.

Adult↗

PubMed1982

[Long-term treatment and prevention of uric acid urolithiasis with allopurinol].

29 patients (20 male and 9 female, average age 55 years), suffering from uric acid-urolithiasis were treated with Zyloric-U over a period of 8 to 20 months. Two of them had side effects (cutaneous symptoms). In all other cases the stones were dissolved or diminuated. Chemical analysis demonstrated a significant reduction of serum uric acid as well as a decrease of calcium secretion in the urine. Yet the urine-pH of 5 remained unchanged. In some cases, if the patients excreted gravel and if the level of uric acid was not lowered sufficiently the dose was raised to twice 300 mg. A report of the follow-up of these patients shall be published later.

Aged↗

PubMed2002

Dietary fiber suppresses elevations of uric acid and allantoin in serum and urine induced by dietary RNA and increases its excretion to feces in rats.

This study was performed to examine the effects of several kinds of dietary fibers (DF) with different physical properties on dietary RNA metabolism. Male Wistar strain rats, 4 wk old, were fed diets with or without a 3% yeast RNA and a 5% DF (cellulose, chitin, chitosan, inulin, and xanthan gum) for 20 d (Experiment 1) or 5 d (Experiment 2). Feeding DF tested lowered the serum uric acid and allantoin concentrations and the urinary excretions of their compounds and increased the amount of RNA excreted into the feces compared with fiber-free. The water-holding capacity and nucleotide adsorption of chitin and chitosan in acidic solutions were higher than those of cellulose. The digestion rate of RNA by RNase A in vitro was found to be lower in the DF tested than in fiber-free. The decrease was remarkable in chitosan and xanthan gum. The uptakes of 14C-labeled adenosine and adenosine 5'-monophosphate (5'-AMP) in the rat jejunum were markedly decreased in regard to chitosan and xanthan gum in comparison with the fiber-free. These phenomena suggest that DF with high viscosity is more strongly associated with the suppression of RNA digestion by RNase A and the depression of the uptake of purine compounds to jejunum. The present results reveal that the elevation of serum uric acid concentration induced by dietary RNA can be suppressed by DF in rats.

Adsorption↗