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[Dynamics of uric acid concentration in the liver of cockerels subjected to model stress situations induced by fasting].

A model stress situation was created by nutrition deprivation. The experiment was performed with 130 cockerels of the initial breed White Leghorn. The experimental cockerels of the age of 18 to 24 days fasted for 24, 48 and 72 hours. Uric acid was determined in the supernatant of liver homogenate by means of a colorimetrically reductometric method with phospho-wolframic agent. A significant increase in the uric acid concentration in the liver of cockerels was found out during the model stress: the concentration of uric acid increased progressively from the initial 70.25 +/- 8.94 mg per 100 g to 93.15 +/- 9.66 mg per 100 g after 24-hour fasting, to 90.23 +/- 7.84 mg per 100 g after 48-hour fasting and even to 137.04 +/- 15.59 mg per 100 g after three-day fasting of 72 hours. After re-alimentation, the concentrations of uric acid were reduced to physiological values already within 24 hours.

Animals↗

[Plasma levels of the serum antioxidants (uric acid, ceruloplasmin, transferrin) in term and preterm neonates in the first week of life].

Development of serum antioxidants (ceruloplasmin, transferrin, uric acid and bilirubin) an the 1st, 4th, 7th days of life has been evaluated in 50 healthy NGA newborns (25 preterm with 35 +/- 0.6 week of gestational age and 2270 +/- 150 g of weight, 25 a term with 39 +/- 0.8 week of gestational age and 3480 +/- 220 g of weight) and in apparent absence of oxidant stress. The ceruloplasmin values increase from the 1st to 7th days of life and change significantly at the 4th day between a term and preterm newborns (p < 0.01); the transferrin values reduce significantly an the 1st (p < 0.01) and 7th days of life (p < 0.05); the uric acid values reduce in the two groups an the 1st day (p < 0.01). Our results show in the newborn a prevalent antioxidant activity of the studied substances. The plasma levels of uric acid may be compared, in the first week of life, to the hypoxanthine levels as acute ipoxia gauges.

Age Factors↗

[The frequency of gout and other disorders of uric acid metabolism in Dalmatia in comparison with these disorders in Croatia].

According to the literature gout is more frequent in Dalmatia than in continental part of Croatia. Higher average values of uric acid in serum, prevalence of hyperuicaemia as well as uric nephrolithiasis are also seen more frequently in Dalmatia comparing to the continental Croatia. This is probably genetically determined and is connected with metabolic changes of uric acid. Relative isolation of population in Dalmatian where the part of immigrants from other regions since the war started was very small favoured these changes. In addition some exogenous factors contribute in clinical manifestation of uric acid metabolic disturbances. The most important among them are consumption of food rich in nucleoproteins and dehydration in summer period.

Croatia↗

Evaluation of three clinical chemical routine methods for the determination of serum uric acid, by mass fragmentography.

A mass fragmentographic method for assay of serum uric acid was developed and used as a reference method to evaluate the accuracy of different routine methods used in clinical chemistry. [1,3-15N2]Uric acid was added to the serum sample and the mixture was subjected to ion-exchange chromatography. After conversion to the tetra-trimethylsilyl derivative the purified mixture was analyzed by combined gas chromatography-mass spectrometry using a multiple ion detector. Within-series imprecision of the reference method as calculated by means of relative standard deviation was 0.6%. The small difference between calculated and found value obtained in different recovery experiments could be explained by this degree of imprecision. In a comparison between results obtained with the reference method and different routine methods, a significant difference was observed only when using an uricase-oxygen consumption method.

Catalase↗

[Effects of whole-body microwave exposure on the plasma corticosterone, glucose, uric acid and allantoin levels in rats].

To investigate the effects of whole-body microwave exposure on plasma corticosterone, glucose, uric acid and allantoin levels, rats weighing 245-300 g (light group) and 440-510 g (heavy group) were exposed to microwaves with a frequency of 2,450 MHz at the power density of 10 mW/cm2 under an ambient temperature of 21 to 23 degrees C for one hour. Rectal temperatures were increased by 3.4 degrees C in the light group and 1.4 degrees C in the heavy group after microwave exposure. Plasma levels of corticosterone, glucose and uric acid did not change in both groups after microwave exposure. Plasma levels of allantoin increased significantly only in the heavy group after microwave exposure. These results suggest that the plasma levels of allantoin, a metabolite of uric acid, may be useful as a biological variable for assessment of the effects of whole-body microwave exposure in rats. The increase of plasma allantoin level after microwave exposure could not be explained only by the degree of increased rectal temperature caused by hyperthermic effects of microwaves.

Allantoin↗

Quantification of urinary uric acid in the presence of thymol and thimerosal by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed as an alternative to automated enzymatic analysis of uric acid in human urine preserved with thymol and/or thimerosal. Uric acid (tR = 10 min) and creatinine (tR = 5 min) were separated and quantified during isocratic elution (0.025 M acetate buffer, pH 4.5) from a mu Bondapak C18 column. The uric-acid peak was identified chemically by incubating urine samples with uricase. The thymol/thimerosal peak appeared at 31 min during the washing step and did not interfere with the analysis. We validated the high-performance liquid chromatographic method for linearity, precision and accuracy, and the results were found to be excellent.

Chromatography, High Pressure Liquid↗

Dietary fiber suppresses elevation of uric acid and urea nitrogen concentrations in serum of rats with renal dysfunction induced by dietary adenine.

This study was conducted to examine the effects of several kinds of dietary fiber (DF) with different physical properties on the elevation of uric acid and urea nitrogen concentrations in serum of rats induced by dietary adenine. DF decreased an uptake of 14C-labeled adenine in the rat jejunum in vitro, but the reduction varied with the physical property of DF. Male Wistar rats (3 weeks old) were fed a diet with or without a 0.4% adenine and a 5% DF (cellulose, chitin, chitosan, or xanthan gum) for 20 days. Feeding of adenine in the fiber-free group elevated the concentrations of uric acid, creatinine, and urea nitrogen in serum, but decreased the excretions of these compounds into urine and increased the amounts of 2,8-dihydroxyadenine (2,8-DHA) in kidney and urine. The test DF was found to suppress the elevation of uric acid, creatinine, and urea nitrogen concentrations in serum induced by dietary adenine, and to mitigate the decreased excretions of these compounds into urine and the increased retention of 2,8-DHA in kidney and urine. This phenomenon was remarkable in the xanthan gum group. These results suggest that DF suppresses the elevation of uric acid and urea nitrogen concentrations in serum by attenuating the absorption of dietary adenine.

Adenine↗

Uric acid oxidation by peroxynitrite: multiple reactions, free radical formation, and amplification of lipid oxidation.

Uric acid has been considered to be an efficient scavenger of peroxynitrite but the reaction between urate and peroxynitrite has been only partially characterized. Also, previous studies have indicated that urate may increase peroxynitrite-mediated oxidation of low density lipoprotein (LDL). Here, we examined the reaction between urate and peroxynitrite by combining kinetic, oxygen consumption, spin trapping, and product identification studies; in parallel, we tested the effect of urate upon peroxynitrite-mediated lipid oxidation. Our results demonstrated that urate reacts with peroxynitrite with an apparent second order rate constant of 4.8 x 10(2) M(-1). s(-1) in a complex process, which is accompanied by oxygen consumption and formation of allantoin, alloxan, and urate-derived radicals. The main radical was identified as the aminocarbonyl radical by the electrospray mass spectra of its 5, 5-dimethyl-l-pyrroline N-oxide adduct. Mechanistic studies suggested that urate reacts with peroxynitrous acid and with the radicals generated from its decomposition to form products that can further react with peroxynitrite anion. These many reactions may explain the reported efficiency of urate in inhibiting some peroxynitrite-mediated processes. Production of the aminocarbonyl radical, however, may propagate oxidative reactions. We demonstrated that this radical is likely to be the species responsible for the effects of urate in amplifying peroxynitrite-mediated oxidation of liposomes and LDL, which was monitored by the formation of lipid peroxides and thiobarbituric acid-reactive substances. The aminocarbonyl radical was not detectable during urate attack by other oxidants and consequently it is unlikely to be responsible for all previously described prooxidant effects of uric acid.

Allantoin↗

Plasma uric acid levels in women with cervical intraepithelial neoplasia.

The objective of this study was to determine the association of plasma levels of uric acid, an endogenous antioxidant, in women with cervical intraepithelial neoplasia (CIN), while controlling for the confounding effects of human papillomavirus (HPV) infection, age, smoking, and use of oral contraception. Plasma-reduced and oxidized uric acid levels were determined in 650 women by high-performance liquid chromatography, employing electrochemical technique. The findings demonstrated that 1) plasma-reduced uric acid (PRUA) levels in women with CIN (n = 311) were significantly lower (P < 0.05) compared with women in a control group (n = 339); 2) according to multiple logistic regression analysis, PRUA levels were negatively (P = 0.0113) and HPV infection were positively associated (P < 0.0001) with CIN, after controlling for the confounding effects of the studied factors; 3) according to multiple regression analysis, there was a 31% decrease in CIN risk for each incremental increase of 1mg/dl of PRUA; and 4) according to polychotomous logistic regression analysis, independent of HPV infection, PRUA level was inversely associated with the histopathological graded severity of CIN. We have previously reported decreased plasma levels of exogenous antioxidants, for example, vitamins C and E, in women with CIN independent of HPV infection. The data suggest that plasma deficiencies of several antioxidants in HPV-infected uterine cervical tissue may create an oxidative environment that renders the tissue susceptible to free radical damage. It may be speculated that chronic free radical-induced tissue damage in the context of persistent HPV infection may be involved in the pathogenesis of CIN.

Adult↗

Association of serum uric acid with all-cause and cardiovascular disease mortality and incident myocardial infarction in the MONICA Augsburg cohort. World Health Organization Monitoring Trends and Determinants in Cardiovascular Diseases.

Because previous findings have been inconsistent, we explored the association of serum concentrations of uric acid with all-cause and cardiovascular disease mortality and myocardial infarction prospectively. We used data from 1,044 men who are members of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) Augsburg cohort. The men, 45-64 years of age in 1984-1985, were followed through 1992. There were 90 deaths, 44 of which were related to cardiovascular disease; 60 men developed incident nonfatal or fatal myocardial infarction. We estimated hazard rate ratios from Cox proportional hazard models. Uric acid levels > or =373 micromol/liter (fourth quartile) vs < or =319 micromol/liter (first and second quartile) independently predicted all-cause mortality [hazard rate ratio = 2.8; 95% confidence interval (CI) = 1.6-5.0] after adjustment for alcohol, total cholesterol/high-density lipoprotein cholesterol ratio, hypertension, use of diuretic drugs, smoking, body mass index, and education. The adjusted risk of cardiovascular disease mortality was 2.2 (95% CI = 1.0-4.8), and that of myocardial infarction was 1.7 (95% CI = 0.8-3.3). Although residual confounding cannot be excluded, our results are among the few, in men, demonstrating a strong positive association of elevated serum uric acid with all-cause mortality. Future investigations may be able to evaluate whether uric acid contributes independently to the development of cardiovascular disease or is simply a component of the atherogenic metabolic condition known as the insulin resistance syndrome.

Cardiovascular Diseases↗

Effects of uric acid in aqueous phase on neutrophil alkaline phosphatase.

In vitro effects of uric acid (2-6-8 trioxypurine) on purified human neutrophil alkaline phosphatase were studied. A marked activation of the enzyme catalyzed reaction is observed. This activation is dose and pH dependent and not influenced by dialysis. Uric acid can form a stable complex with alkaline phosphatase, whose biochemical characteristics (heat stability, reactivity towards some inhibitors) are significantly modified.

Adult↗

Renal handling of uric acid in gout: impaired tubular transport of urate not dependent on serum urate levels.

Metabolic studies were conducted in 56 patients with primary gout and in ten normal subjects to assess differences in the tubular transport mechanisms of urate. Renal handling of uric acid was examined by means of pyrazinamide and probenecid tests at increased and pharmacologically reduced serum urate concentrations in both groups. Patients with gout showed similar serum urate levels and glomerular filtration rates than controls at both serum urate levels. Pyrazinamide decreased urinary uric acid excretion to less than 1.0% of the urate filtered load in both groups at increased and diminished serum urate concentrations. The maximum uricosuric response promoted by probenecid at high serum urate levels was (mean +/- SD) 3,707 +/- 443 micrograms/min/1.73 m2 in controls and 2,215 +/- 738 micrograms/min/1.73 m2 in patients with gout (P less than 0.01). Forty-four patients had a daily uric acid excretion rate below 700 mg/1.73 m2, and all of them showed a diminished uricosuric response to probenecid. When serum urate was reduced in normal subjects and 30 patients to a mean of 2.1 and 2.3 mg/dL, respectively, probenecid elicited a significantly lower urate excretion rate in gout (532 +/- 202 micrograms/min/1.73 m2) than in controls (922 +/- 136 micrograms/min/1.73 m2; P less than 0.01). Among these 30 patients examined in their basal state and at decreased serum urate levels, uric acid excretion following probenecid was normal in six and diminished in 24 in both situations. The difference between maximum uricosuria and basal urate excretion was not increased in gouty patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Disposition and uric acid lowering effect of oxipurinol: comparison of different oxipurinol formulations and allopurinol in healthy individuals.

We have investigated the disposition and plasma uric acid lowering effect of oxipurinol in ten healthy individuals following oral administration of three different formulations of oxipurinol and of allopurinol in equimolar doses. The reduction of plasma uric acid was clearcut up to 48 h. As estimated from plasma AUC0-infinity, Cmax, tmax, tlag, and urinary drug excretion, a conventional rapid release preparation of oxipurinol sodium was clearly superior to oxipurinol as free acid and to enteric coated microtablets of oxipurinol sodium. Plasma oxipurinol concentrations following a single dose of the conventional formulation of oxipurinol sodium were approximately 25% lower than those observed after an equimolar dose (300 mg) of allopurinol, but mean Cmax reached the value reported to be necessary for 90% inhibition of xanthine oxidase. Since prolonged administration will result in accumulation of oxipurinol because of its slow elimination, this type of oxipurinol formulation can be expected to meet the therapeutic requirements for a drug to lower plasma uric acid.

Administration, Oral↗

[Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].

Lasting normalisation of uric acid levels after treatment of patients with gout and hyperuricaemia with a combination of 300 mg allopurinol and 60 mg benzbromarone A total of 210 patients (163 men, 47 women) with gout and hyperuricaemia was treated for three months with daily doses of 300 mg allopurinol and 60 mg benzbromarone. During the course of treatment, the uric acid levels decreased to 4.3 +/- 1.3 mg/dl in male, and 4.4 +/- 1.3 mg/dl in female patients. Both of these levels differ significantly from the initial levels (p less than 0.001). Three months after discontinuation of treatment, uric acid levels were 5.7 +/- 1.2 mg/dl in women, and 5.9 +/- 1.4 mg/dl in men, levels that again differed significantly from the initial levels (p less than 0.001); both levels were, however, within the therapeutic range of below 6.4 mg/dl.

Allopurinol↗

Ischemia/reperfusion alters uric acid and ascorbic acid levels in liver.

Tissue damage in ischemia/reperfusion injury may be mediated by oxidative stress caused by reactive oxidant species. Since such reactive species are difficult to measure directly, changes in antioxidant concentrations are often used as an indication of oxidative stress. In this study, microdialysis membranes were inserted into the livers of anesthetized rats to determine the effects of ischemia/reperfusion on the extra-cellular concentrations of two antioxidants, uric acid and ascorbic acid. Total hepatic ischemia was induced for 30 min by clamping the portal triad and was followed by 60 min of reperfusion. Uric acid and ascorbic acid concentrations were measured in microdialysis perfusates by high-performance liquid chromatography with electrochemical detection. Initial uric acid and ascorbic acid concentrations were high after insertion of membranes into the liver and decreased rapidly within 90 min (P < 0.001; ANOVA with repeated measures). Uric acid concentrations increased over 300% after ischemia and by 600% during the first 30 min of reperfusion (n = 8; P < 0.05). Ascorbic acid concentrations were 60% higher than controls after ischemia and 90% higher during the first 30 min of reperfusion (n = 8; P < 0.05). Alterations in concentrations of these redox-active molecules may be associated with oxidative stress in liver extracellular fluid during ischemia/reperfusion.

Animals↗

Incorporation of 15N from glycine into uric acid in gout: a follow-up study.

Over-incorporation of 15N-labeled glycine into uric acid indicates over-production of uric acid by de novo purine biosynthesis. This metabolic aberration, though considered to be inborn (3), may be modified by changing of life style, aging and long-term therapy. In the patient under study, the protracted use of allopurinol seems to have played the most important role. Aging contributed to a certain extent, and changing life style was the least significant factor.

Adult↗

Estimation of decision criteria for the uric acid concentration for the early diagnosis of gestosis.

An increase of the serum uric acid concentration of pregnant women can indicate an EPH gestosis with a high risk. Above a uric acid level of 270 mumol/l (and of 315 mumol/l after the 32nd. week of pregnancy) and gestosis has become moderate. An increased risk for mother and fetus must then be assumed. This decision point is estimated by comparing three techniques: The ROC-curve-method and the determination of the maximal efficiency and of the maximal information content.

Female↗