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PubMed2002

Nitrosative stress, uric Acid, and peripheral nerve function in early type 1 diabetes.

The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively NO(x)) were 34.0 +/- 4.9 micro mol/l in the control subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine (NTY) was 13.3 +/- 2.0 micro mol/l in the control subjects and 26.8 +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 in the diabetic patients (P < 0.01). Uric acid was suppressed by 20% in the diabetic patients (P < 0.001). Composite motor nerve conduction velocity for the median, ulnar, and peroneal nerves was decreased in patients with high versus low NTY (mean Z score -0.522 +/- 0.25 versus 0.273 +/- 0.22; P < 0.025). Patients with high NO(x) had decreased sweating, and those with suppressed uric acid had decreased autonomic function. In conclusion, nitrosative stress in early diabetes is associated with suppressed uric acid and deterioration in peripheral nerve function.

Adolescent↗
PubMed1993

Evidence of defective tubular reabsorption and normal secretion of uric acid in the syndrome of inappropriate secretion of antidiuretic hormone.

The mechanisms responsible for the increased renal clearance of uric acid in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are not fully clarified. Studies using either pyrazinamide or probenecid, or both drugs but at an interval of several days, could not undoubtedly distinguish the 'hypersecretory theory' from the one favoring a defect in either post- or presecretory reabsorption. We decided to do a combined pyrazinamide and probenecid test in 5 patients with hyponatremia due to SIADH in order to evaluate more clearly the respective importance of these different pathways. Our results allow the conclusion of a diminished presecretory and mainly postsecretory reabsorption (80 +/- 4.6 and 14 +/- 3% of filtered load, respectively). As far as the secretion of uric acid is concerned (17 +/- 10% of filtered load), we may say that this pathway is adapted to the amount of hypouricemia.

Absorption↗
PubMed1997

Uric acid and ascorbic acid redox ratios in plasma and tracheal aspirate of preterm babies with acute and chronic lung disease.

This study compared plasma redox ratios of uric acid and ascorbic acid in well preterm babies with those with respiratory distress syndrome (RDS) and chronic lung disease (CLD), and investigated the relationship between these ratios and their respective measurements in tracheal aspirate. On day 1 after birth, plasma allantoin and allantoin/uric acid ratio were elevated in CLD (p < .05), and both markers of oxidative stress enabled early prediction of development of CLD (sensitivity and specificity: 54 and 83%, respectively). The relation between allantoin production and oxidative stress is supported by the correlation between the allantoin level and oxygen therapy in both RDS and CLD (p < .05). Reduced and oxidize ascorbic acid in plasma decreased postnatally in all groups and their redox ratio remained stable. Uric acid and ascorbic acid redox ratios were significantly elevated in tracheal aspirates compared to plasma samples (p < .05), and there was a strong positive correlation between both ratios (p < .005). These markers may be useful in monitoring babies with respiratory distress.

Antioxidants↗
PubMed2003

Suppressive effect of viscous dietary fiber on elevations of uric acid in serum and urine induced by dietary RNA in rats is associated with strength of viscosity.

This study was performed to clarify how dietary fiber (DF) with different viscosities would be associated with dietary RNA metabolism. Male Wistar strain rats, four weeks old, were fed diets containing a 3% (w/w) yeast RNA and a 5% (w/w) viscous DF for five days. Viscosity of DF samples used, in order of strength, were xanthan gum (XG) > guar gum (GG) > locust bean gum (LBG) > karaya gum (KG) > pectin (PE) = arabic gum (AG) > CM-cellulose (CMC) = inulin (IN). The serum uric acid concentration in the viscous DF groups significantly decreased as compared with that in the cellulose (CL) group. The urinary excretions of uric acid and allantoin in the respective groups given AG, GG, IN, KG, PE, and XG were significantly suppressed as compared with those in the CL group. The fecal RNA excretion was markedly increased in the IN, KG, PE, and XG groups in comparison to the CL group. The DF with high viscosity significantly suppressed RNA digestion by RNase A and decreased uptakes of 14C-labeled adenosine and adenosine 5'-monophosphate (5'-AMP) in rat jejunum. The results reveal that the suppressive effect of DF on elevation of serum uric acid concentration induced by dietary RNA in rats is associated with the strength of DF viscosity. The mechanism by which this is accomplished is suggested to be attributed to the inhibitions of digestion for dietary RNA and/or absorption of the hydrolyzed compounds.

Adenosine Monophosphate↗
PubMed1996

Labelling of uric acid and allantoin in different purine organs and urine of the rat.

We studied the incorporation of 14C-formate into uric acid and allantoin in different organs (liver, lung, kidney, spleen), isolated hepatocytes, perfused liver and urine of the rat. Allantoin had a higher specific radioactivity than uric acid after 14C-formate load in the liver in vivo. This was found to be a strictly hepatic phenomenon and not due to the influence of other tissues.

Allantoin↗
PubMed1977

The effect of kind of carbohydrate in the diet and use of oral contraceptives on metabolism of young women. I. Blood and urinary lactate, uric acid, and phosphorus.

Six oral contraceptive (OC) users and six control subjects consumed diets in which 43% of the calories came from either sucrose or starch for 4 weeks in a cross-over design. Kind of carbohydrate in the diet had no effect on blood lactate response to a sucrose load, but lactate response of OC users was greater than that of control subjects. Kind of carbohydrate in the diet did not affect urinary lactate excretion after a sucrose load; however, OC users excreted more lactate than did controls and there was a significant interaction between dietary carbohydrate and OC use. Serum uric acid levels were significantly higher when the sucrose diet was consumed, but levels were not affected by OC use. Serum phosphorus levels were not affected by kind of carbohydrate in the diet but were higher in control subjects than in OC users and there was a significant interaction between diet and OC use. There were no significant differences in urinary uric acid and phosphorus excretions after sucrose loads or in 24-hr urinary excretions of uric acid, phosphorus, or urea due to kind of carbohydrate in the diet or OC use.

Adult↗
PubMed1994

Effect of allopurinol on uric acid levels and brain cell membrane Na+,K(+)-ATPase activity during hypoxia in newborn piglets.

Oxygen-free radicals generated by xanthine oxidase during hypoxia-ischemia may result in cellular injury through harmful effects on membrane phospholipids. The present study investigated the effect of administration of allopurinol, an inhibitor of xanthine oxidase, on free-radical generation and brain cell membrane injury during hypoxia by inhibiting the breakdown of hypoxanthine to uric acid. Brain cell membrane Na+,K(+)-ATPase activity and lipid peroxidation products (conjugated dienes and fluorescent compounds) were determined as indices of brain membrane function and structure. Cerebral oxygenation was continuously monitored during hypoxia by 31P-NMR spectroscopy. Plasma and brain tissue levels of uric acid were measured to evaluate xanthine oxidase activity and purine degradation. Na+,K(+)-ATPase activity decreased significantly in both hypoxic groups; however, the allopurinol-treated hypoxic group showed a smaller decrease than the untreated hypoxic group (47.3 +/- 4.9 vs. 42.0 +/- 2.7 mumol Pi/mg protein/h, P < 0.05), respectively. Conjugated dienes increased significantly in the untreated hypoxic compared to control animals (0.070 +/- 0.045 vs. 0.004 +/- 0.006 mumol/g brain, P < 0.05), with the allopurinol-treated animals having intermediate values (0.053 +/- 0.039 mumol/g brain). Fluorescent compounds were lower in the allopurinol-treated hypoxic group compared to the untreated hypoxic group (0.79 +/- 0.19 vs. 1.06 +/- 0.60 micrograms/quinine sulfate/g brain, P < 0.05). Measurements of serum and brain tissue uric acid were significantly lower during hypoxia in the allopurinol-treated compared to the untreated group (30.3 +/- 15.6 vs. 45.7 +/- 10.6 microM (P < 0.05) and 1.69 +/- 0.97 vs. 4.27 +/- 2.37 nmol/g (P < 0.05), respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗
PubMedDate not supplied

[Serum uric-acid and serum lipids. Statistical correlations. Report of 1 000 cases (author's transl)].

Distribution and correlations of serum uric-acid, cholesterol, triglycerides and lipoproteins were sought in this paper. Blood triglycerides and blood cholesterol in males were found significantly higher in patients with hyperuricaemia than in normo-uricaemic subjects. This elevation was reflected in the electrophoresis by a significant elevation of the bêta and pre-bêta lipoproteins correlated with hyperuricaemia. Partial correlations between age and serum uric-acid have been also demonstrated.

Age Factors↗
PubMedDate not supplied

Uric acid levels and platelet function in humans. An in-vivo ex-vivo study.

Platelet function (aggregation by ADP, adrenaline, collagen and circulating platelet aggregates) before, during and after dietary induction of hyperuricemia (ribonucleic acid, 3 g/day) was studied in five healthy volunteers to assess the relationship between uric acid level and platelet function. In the same subjects, during a second period of ribonucleic acid diet, the acute and chronic effects of a hypo-uricemizing agent, allopurinol, were assessed. No significant correlation was detected between platelet function and uricemia either in the absence or in the presence of pharmacological treatment with allopurinol. On the basis of these results, the well known relationship between uric acid levels and ischemic heart disease does not appear to be mediated by an exaggerated platelet function.

Adult↗
PubMed2001

Uric acid inhibits liver phosphorylase a activity under simulated in vivo conditions.

We have reported that glycogen synthesis and degradation can occur in vivo without a significant change in the amount of phosphorylase a present. These data suggest the presence of a regulatable mechanism for inhibiting phosphorylase a activity in vivo. Several effectors have been described. AMP stimulates, whereas ADP, ATP, and glucose inhibit activity. Of these effectors, only the glucose concentration changes under normal conditions; thus it could regulate phosphorylase a activity in vivo. We previously have reported that, when all of these effectors were present at physiological concentrations, the net effect was no change in phosphorylase a activity. Addition of caffeine, an independent inhibitor of activity, to the above effectors not only resulted in inhibition but also restored a glucose concentration-dependent inhibition. Because uric acid is an endogenous xanthine derivative, we decided to determine whether it had an effect on phosphorylase a activity. Independently, uric acid did not affect activity; however, when added at a presumed physiological concentration in combination with AMP, ADP, ATP, and glucose, it inhibited activity. A modest but not statistically significant glucose concentration-dependent inhibition was also present. Thus uric acid may play an important role in regulating phosphorylase a activity in vivo.

Adenine Nucleotides↗
PubMed2003

Bilateral uric acid nephrolithiasis and ureteral hypertrophy in a free-ranging river otter (Lontra canadensis).

We report the first case of uric acid nephrolithiasis in a free-ranging river otter (Lontra canadensis). A 7 yr old male river otter collected from the Skagit River of western Washington (USA) had bilateral nephrolithiasis and severely enlarged ureters (one of 305 examined [0.33%]). The uroliths were 97% uric acid and 3% protein. Microscopic changes in the kidney were confined to expansion of renal calyces, minor loss of medullary tissue, and multifocal atrophy of the cortical tubules. No inflammation was observed in either kidney or the ureters. The ureters were enlarged due to marked hypertrophy of smooth muscle plus dilation of the lumen. Fusion of the major calyces into a single ureteral lumen was several cm distal to that of two adult male otters used as histopathologic control specimens. This case report is part of a large contaminant study of river otters collected from Oregon and Washington. It is important to understand diseases and lesions of the otter as part of our overall evaluation of this population.

Animals↗
PubMed1992

Measurement of low-molecular-weight antioxidants, uric acid, tyrosine and tryptophan in plaques and white matter from patients with multiple sclerosis.

The levels of the antioxidants ascorbic acid, cysteine, reduced glutathione and alpha-tocopherol, of the free-radical marker uric acid and of the amino acids tyrosine and tryptophan were measured by means of high-pressure liquid chromatography in plaques, adjacent white matter and distant white matter from patients with multiple sclerosis, and in central nervous system tissue from patients without neurological diseases. Cholesterol and DNA were also determined, to check demyelination and cellularity. Uric acid was increased and glutathione correspondingly decreased in plaques; alpha-tocopherol was lowest in plaques and highest in distant white matter in all cases. Ascorbic acid, cysteine, tyrosine and tryptophan were not significantly changed in any tissue. The results provide evidence supporting the involvement of free radicals in multiple sclerosis.

Adult↗
PubMed2006

[Study on the independent association of uric acid levels with peripheral arterial disease in Chinese patients with coronary heart disease].

OBJECTIVE: To evaluate the relationship between uric acid (UA) and peripheral arterial disease (PAD) in Chinese patients with coronary heart disease (CHD). METHODS: UA levels and PAD were evaluated in 3251 Chinese hospitalized patients with CHD (age > or = 50 years). PAD was diagnosed when the ankle-brachial index was < 0.9 but patients with an ankle-brachial index of > 1.4 were excluded because of false negative rate. Potential confounding variables with P < 0.10 were adjusted for multivariate analysis. RESULTS: In univariate analysis, UA levels were higher in patients with PAD than in those without PAD (349.80 micromol/L +/- 128.45 micromol/L vs. 323.00 micromol/L +/- 110.72 micromol/L, P < 0.001). Rate of hyperuricemia in patients with PAD and without PAD were 31.62% and 22.48% (P < 0.001) respectively. Prevalence rates of PAD for quintiles of UA level were 23.2%, 27.4%, 36.1%, 43.2% and 72.7%, respectively (P-trend < 0.05). With UA level as a continuous variable, the multivariate-adjusted odds ratio for PAD was 1.002 (95% confidence interval: 1.001 - 1.002) (P < 0.001). The optimal cut-off point for UA as determined by the receiver operating characteristic curve, was 227.2 micromol/L. The sensitivity and specificity at this cut-off point were 84.6% and 20.3%, respectively. The area under curve was 0.521 (95% confidence interval: 0.504 - 0.547) and the multivariate-adjusted odds ratio for PAD for UA above this level was 1.292 (95% confidence interval: 1.047 - 1.596) (P < 0.01). The results, however, after exclusion those cases who used diuretics, were similar. CONCLUSION: Elevated uric acid level seemed a significant and independent risk factor for PAD in Chinese hospitalized patients with CHD (age > or = 50 years).

Analysis of Variance↗
PubMed2001

DNA oxidatively damaged by chromium(III) and H(2)O(2) is protected by the antioxidants melatonin, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, resveratrol and uric acid.

Chromium (Cr) compounds are widely used industrial chemicals and well known carcinogens. Cr(III) was earlier found to induce oxidative damage as documented by examining the levels of 8-hydroxydeoxyguanosine (8-OH-dG), an index for DNA damage, in isolated calf thymus DNA incubated with CrCl(3) and H(2)O(2). In the present in vitro study, we compared the ability of the free radical scavengers melatonin, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), resveratrol and uric acid to reduce DNA damage induced by Cr(III). Each of these scavengers markedly reduced the DNA damage in a concentration-dependent manner. The concentrations that reduced 8-OH-dG formation by 50% (IC(50)) were 0.10 microM for both resveratrol and melatonin, and 0.27 microM for AFMK. However, the efficacy of the fourth endogenous antioxidant, i.e. uric acid, in terms of its inhibition of DNA damage in the same in vitro system was about 60--150 times less effective than the other scavengers; the IC(50) for uric acid was 15.24 microM. These findings suggest that three of the four antioxidants tested in these studies may have utility in protecting against the environmental pollutant Cr and that the protective effects of these free radical scavengers against Cr(III)-induced carcinogenesis may relate to their direct hydroxyl radical scavenging ability. In the present study, the formation of 8-OH-dG was likely due to a Cr(III)-mediated Fenton-type reaction that generates hydroxyl radicals, which in turn damage DNA. Once formed, 8-OH-dG can mutate eventually leading to cancer; thus the implication is that these antioxidants may reduce the incidence of Cr-related cancers.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

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

Data were collected from 10 experiments with duodenally cannulated Holstein dairy cows (271 combinations of cow and period) to evaluate the relationship between milk purine metabolites and microbial nitrogen flow. Experiments evaluated the effects of dietary factors on microbial N production and included: 1) supplemental sources of ruminally protected amino acids; 2) grass silage treated with fibrolytic enzymes; 3) bacterial inoculation of corn silage; 4) a comparison of corn and barley grain; 5) ruminal starch availability as affected by corn silages of varying maturity; and, 6) ruminal starch availability as affected by corn silages harvested at varying chop length and with or without mechanical processing. The coefficient of determination for individual experiments for the relationship between microbial nitrogen flow and allantoin or uric acid excretion in milk ranged from -0.01 to 0.77 and -0.06 to 0.22 respectively. Across all experiments, the coefficients of determination between microbial nitrogen flow and allantoin or uric acid excretion in milk were r2 = 0.09 and 0.01 respectively. Milk allantoin output was used to develop a prediction equation estimating microbial nitrogen flow to the duodenum. The greatest predictive value (r2 = 0.25) relationship was observed across non-bST experiments and included the factors of allantoin excretion, milk yield, dry matter intake, and days in milk. When milk yield was included in the model, the predictive value improved (r2 = 0.44). Based on these data, milk uric acid excretion alone cannot be used to predict microbial N production accurately [corrected].

Allantoin↗
PubMed1989

Plasma urea, creatinine, uric acid, albumin, and total protein concentrations before and after 15-, 25-, and 42-km contests.

One hundred fourteen volunteers (34 +/- 8 years) took part in an endurance training study to be completed after 18-20 months with a marathon. Ultimately, 60 males and 18 females achieved that goal. The training program, carefully supervised, was divided into three periods with a maximum of 45, 70, and 110 km/week training volume and concluded with contests of 15, 25, and 42.2 km, respectively. The competitive distance always exceeded the maximal distance covered in any previous training session. Three days before and 3 and 5 days after each race 35 subjects were selected to perform a progressive treadmill test and the remaining subjects participated in field tests of 400 and 1000 m. Before and after three contests of 15, 25, and 42.195 km the plasma concentration of urea, creatinine, uric acid, albumin, and total protein were determined. Both sexes demonstrated an increase of the plasma concentrations of urea, creatinine, and uric acid after the contests. Plasma albumin concentration decreased 2 days after the contests and total protein did not change. In females the decrease of the elevated plasma urea concentration after the marathon from the 1st day to the 3rd day post-exercise was faster than in males. The increase of plasma creatinine and uric acid concentrations were hardly dependent on the contest's distance.

Adult↗
PubMed1987

Serum uric acid in renovascular hypertension: reduction following surgical correction.

Mild hyperuricemia in patients with essential hypertension reflects early renal vascular involvement. This report describes a retrospective analysis of 28 patients with unilateral renal arterial disease and hypertension who underwent surgical treatment. Following surgical repair of the arterial lesion: systolic pressure decreased from 188 +/- 25 to 146 +/- 21 mm Hg (p less than 0.001); diastolic pressure decreased from 108 +/- 4 to 87 +/- 6 mm Hg (p less than 0.001), and serum uric acid and creatinine concentrations decreased from 7.0 +/- 1.1 to 6.1 +/- 1.4 mg/dL and from 1.3 +/- 0.3 to 1.0 +/- 0.3 (p less than 0.02 and p less than 0.03, respectively). The reduced serum potassium levels, reflecting hyperaldosteronism, increased after surgical treatment (p less than 0.003). The 28 patients were classified in three groups according to previous therapy: group I (14 patients) had been treated with a centrally active adrenergic agonist or a beta adrenergic receptor blocking agent; group II (7 patients) had been treated with a diuretic, and group III (7 patients) had never received antihypertensive therapy. Serum uric acid concentrations were similar in each of the three groups and decreased significantly in each group after correction of the renal artery stenosis. These data strengthen our previous observations and further suggest that serum uric acid concentration may be useful as an index of renal vascular involvement in hypertension.

Adult↗