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[The effect of the injection of water-soluble triiodized monomer contrast media for intravenous urography on glomerular filtration, uricemia and urinary elimination of uric acid in normal subjects].

One mechanism suggested as being the cause of nephrotoxicity following the administration of triiodized contrast media is intratubular urate precipitation. Thirty healthy volunteers were investigated by IVU using three different media. The iodized injections (0,56 g/kg) failed to produce significant modifications of glomerular filtration and were followed by only very moderate variations in blood and urine uric acid levels.

Contrast Media↗

An enzymic assay for uric acid in serum and urine compared with HPLC.

We evaluated a colorimetric method for the assay of uric acid in serum or urine, which utilises a Trinder chromogenic system modified by the inclusion of 2,4,6-tribromo-3-hydroxybenzoic acid for oxidative coupling to p-aminophenazone. Colour development (Amax: 512 nm) is complete within five minutes. Measurement of a sample blank is not needed. The procedure involves pre-incubation with ascorbic acid oxidase and detergent to eliminate interference by ascorbic acid and to abolish turbidity due to lipaemia; this pretreatment was effective up to 1.14 mmol/l ascorbate and up to at least 25 mmol/l triacylglycerol. Interference by icteric sera was insignificant up to about 170 mumol/l bilirubin. The method is linear up to at least 1428 mumol/l. In human serum and urine the procedure correlates well with HPLC and the uricase p-aminophenazone method on the SMAC analyser. Within-run and between-run imprecisions of the enzymic test were higher than for HPLC, but did not exceed 1.2% (CV) and 2.5% (CV), respectively.

Chemical Phenomena↗

Effects of allopurinol on striatal dopamine, ascorbate and uric acid during an acute morphine challenge: ex vivo and in vivo studies.

In the present study in vivo and ex vivo experiments were combined to evaluate the effects of allopurinol on the neurochemical changes induced by an acute morphine challenge (2 mg kg-1, s.c.). In samples from rat striatum, levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), ascorbate (AA), dehydroascorbate (DHAA), hypoxanthine, xanthine and uric acid (UA) were measured. Brain microdialysis experiments were carried out in freely moving rats. Striatal dialysate levels were assayed for DA, DOPAC + HVA, AA and UA using liquid chromatography followed by electrochemical detection. Morphine administration increased the striatal levels of DA metabolites, UA and DHAA and the extracellular concentrations of DA, DOPAC + HVA, UA and AA. Allopurinol (50 mg kg-1 by gavage), an inhibitor of xanthine oxidase which catalyses oxidation of xanthine to UA, decreased basal UA and AA concentrations and the morphine-induced increase in DA metabolites and AA oxidation. Since oxidation of DA and xanthines generates reactive oxygen species (ROS) and AA and UA are the main cellular antioxidants, these findings suggest that: (a) single morphine administration increases DA and xanthine oxidative metabolism with a consequent increase in ROS production, which may account for changes in concentrations of extracellular AA and tissue DHAA; (b) allopurinol decreases morphine-induced DA and xanthine oxidation; (c) UA and AA may act in concert to regulate levels of ROS in the brain.

Allopurinol↗

Selective voltammetric and amperometric detection of uric acid with oxidized diamond film electrodes.

Electrochemically anodized diamond film electrodes were used for selective detection of uric acid (UA) in the presence of high concentrations of ascorbic acid (AA) by differential pulse voltammetry and chronoamperometry. Because the oxidation peak potential for AA is approximately 450 mV more positive than that for UA at anodized diamond electrodes, UA can be determined with very good selectivity. By use of chronoamperometry, linear calibration curves were obtained for UA over the concentration range up to 1 x 10(-6) M in 0.1 M HClO4 solution, with the lowest experimental value measured being 5 x 10(-8) M. This is consistent with the fact that a statistical analysis of the calibration curve yielded a detection limit of 1.5 x 10(-8) M (S/N = 3). AA in less than 20-fold excess does not interfere. The practical analytical utility of the method is demonstrated by the measurement of UA in human urine and serum without any preliminary treatment.

Diamond↗

Association between uric acid and carotid atherosclerosis in elderly persons.

OBJECTIVE: Several cohort studies have shown a link between serum uric acid (SUA) and subsequent cardiovascular disease. However, such an association did not remain significant after adjusting for concomitant risk factors for atherosclerosis in some studies. Thus, the role of SUA as an independent risk factor remains controversial. We therefore investigated the association between SUA and sclerotic lesions of common carotid atherosclerosis. PATIENTS AND METHODS: We evaluated sclerotic lesions of the common carotid arterial intima-media thickness (IMT) by ultrasonography in 398 men aged 74+/-8 (range, 60-97) years and 521 women aged 75+/-8 (range, 60-104) years. To investigate the relation between SUA and various factors, all subjects were divided into three groups based on the tertile of SUA. RESULTS: Stepwise multiple linear regression analysis using IMT as an objective variable, adjusted by various risk factors as explanatory variables showed that SUA [B, 0.0099; 95% confidence interval (CI), 0.0022-0.0175] was a significant independent contributing factor along with known risk factors such as age, sex, smoking status, systolic blood pressure, diastolic blood pressure, antihypertensive drug use, HDL-cholesterol, and LDL-cholesterol. Multiple logistic regression analysis for carotid IMT as a tertile of SUA and dependent variables showed that the adjusted odds ratio was 1.25 (95% CI, 0.87-1.78) for those in the middle tertile (4.2-5.5 mg/dl), and 1.66 (95% CI, 1.16-2.39) for those in the highest tertile (5.6-14.1 mg/dl) compared to that for subjects in the lowest tertile of SUA levels (0.51-4.1 mg/dl). CONCLUSION: We suggest that SUA is a risk factor or marker for ultrasonographically determined IMT.

Aged↗

Serum uric acid and long-term mortality from stroke, coronary heart disease and all causes.

BACKGROUND: Increased serum uric acid (SUA) levels are linked to obesity, dyslipidemia, diabetes and hypertension. Whether SUA carries a risk for coronary heart disease (CHD) and stroke remains uncertain. DESIGN: A prospective cohort study. METHODS: Of an original cohort of middle-aged workers who were examined in 1963 and followed-up for 23 years, 9125 men, free of CHD at entry, are included in this study. Subjects were divided into quintiles according to baseline SUA levels. Hazard ratios (HR) for all-cause, CHD, and stroke mortality were estimated in SUA quintiles, with the third serving as a referent. RESULTS: During follow-up, 2893 deaths were recorded, including 830 ascribed to CHD and 292 to stroke. The HR for all death [1.22, 95% confidence interval (CI) 1.09-1.37] and CHD (1.29, 95% CI 1.05-1.58) were increased in the upper SUA quintile. Fatal stroke showed a U-shaped relationship as both the upper (HR 1.48, 95% CI 1.02-2.17) and bottom (HR 1.43, 95% CI 0.99-2.08) quintiles were associated with a higher risk. Adjustment for confounders reduced the HR of the upper quintile for all outcomes, but did not attenuate the association of the bottom quintile with stroke (HR 1.52, 95% CI 1.04-2.23). When analysed separately by stroke type, the latter association seemed to be stronger for hemorrhagic (HR 3.27, 95% CI 1.14-9.33) than for ischemic stroke (HR 1.34, 95% CI 0.87-2.05). CONCLUSION: In addition to findings supporting increased mortality among hyperuricemic subjects, we identified an association between low SUA levels and fatal stroke, which deserves further investigation.

Biomarkers↗

[The features of uric acid metabolism in women in climacterium].

The purpose of the study was to establish the prevalence of uric acid (UA) metabolism disturbances as a possible risk factor of urate nephropathy in women of various age groups. The authors carried out a retrospective analysis of 757 case histories and performed uricemia and uricosuria screening in women aged 18 to 69 years. The study revealed significant age-dependent elevation of uricemia, with hyperuricemia (HUE) at the age of 60 to 69 years old. The study also found age-dependent increase of HUE rate with its significant elevation in postmenopausal women (older than 50 years), compared with HUE rate in reproductive age women (18 to 49 years old) -37.9% vs. 11.4%. For the first time the researchers established UA excretion level and found a significant tendency of uricosuria to decrease with age (p < 0.016 between the groups of 40 to 49 and 50 to 59 years old). The highest rate of hyperuricosuria was revealed in women of 40 to 49 years old (22.2%), while in women of 18 to 29 and 60 to 69 years old it was 10.1% to 12.1%. For the first time the authors established the rate of hypouricosuria in women, which culminated in women older than 50 (22% of cases). The increase of HUE rate, which is most prominent in postmenopausal women, is associated with the decrease in UA excretion, accompanied by the decrease of hyperuricosuria rate and increase of hypouricosuria rate. Taking into account high prevalence of UA metabolism disturbances in women older than 50, menopause may be considered a risk factor of HUE and urate nephropathy.

Adolescent↗

Serum uric acid levels and risk for acute ischaemic non-embolic stroke in elderly subjects.

BACKGROUND: Elevated serum uric acid (SUA) levels have been proposed as an independent risk factor for cardiovascular (CV) morbidity and mortality. Recent evidence suggests that treatments with a hypouricaemic action have a favourable effect on CV event prevention. OBJECTIVES: The association between SUA and acute ischaemic/non-embolic stroke was assessed in a population-based case-control study in the prefecture of Ioannina, Epirus, Greece. SUBJECTS AND METHODS: A total of 163 patients aged older than 70 years (88 men and 75 women) admitted due to a first-ever-in-a-lifetime acute ischaemic/non-embolic stroke and 166 volunteers (87 men and 79 women) without a history of CV disease were included. The association between SUA and stroke was determined by multivariate logistic regression modelling after adjusting for potential confounding factors. RESULTS: Stroke patients showed higher concentrations of SUA compared with controls (333.1+/-101.1 micromol L(-1) vs. 285.5+/-83.3 micromol L(-1); P<0.001). In univariate analysis elevated SUA levels were associated with increased risk for ischaemic stroke [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.21-1.64, P<0.0001]. Compared to patients with SUA levels in the lowest quintile, those within the highest quintile had a 2.8-time increase in the odds of suffering an ischaemic stroke (OR 2.81, 95% CI 1.67-4.73, P<0.001). This association was strong even after controlling for gender, age, body mass index, the presence of hypertension and diabetes mellitus, drug treatment and lipids (OR 2.90, 95% CI 1.59-5.30, P=0.001). CONCLUSION: Elevated SUA is associated with an increased risk for acute ischaemic/non-embolic stroke in a strictly defined population of elderly individuals independently of concurrent metabolic derangements. This association may need to be considered when treating the elderly.

Aged↗

Dichlorobenzoquinone chloroimine colorimetry of uric acid in urine.

In this nonenzymatic colorimetric method, dichlorobenzoquinone chloroimine is used as a color reagent to measure uric acid in urine. This method is less subject to the interferences that make enzymatic methods unreliable and is inexpensive, simple, and fast.

Benzoquinones↗

Phentermine/Topiramate in Obese, Diabetic Uric Acid Stone Formers: An Open-Label Randomized Feasibility Trial.

PURPOSE: The purpose of this study was to determine whether medical treatment of obesity, diabetes, and low urine pH with combination phentermine/topiramate affects uric acid (UA) kidney stone burden. MATERIALS AND METHODS: Participants with obesity, diabetes mellitus, normal renal function, urine pH < 5.8, and stone analysis &#x2265; 80% UA were block randomized (2:1 ratio) to phentermine 18.75 mg/topiramate 100 mg vs pragmatic controls for an 18-month, prospective, open-label feasibility study with dose escalation. The primary outcome was change in CT stone volume. Secondary outcomes included medication adherence; patient safety; and change in anthropometrics, laboratory studies, and body composition. RESULTS: Nineteen participants (age 62.1 &#xb1; 9.8 years; 68% male; mean BMI = 36.3 &#xb1; 2.9 kg/m2) were randomized, and 15 completed the study with 73% pill adherence and no serious adverse events. Stone volume by intention-to-treat analysis fell by 52% in the intervention group and rose by 8.6% in the control group (P = .10), with per-protocol analysis demonstrating statistically significant stone volume reduction (P = .02). At study end and compared with means of controls, the intervention group had greater weight loss (-10.2 vs +2.9 kg), reduction in hemoglobin A1c levels (-0.2 vs +0.5), lower 24-hour urine citrate (309 &#xb1; 81 vs 951 &#xb1; 782 mg), and lower UA supersaturation (0.7 &#xb1; 1.1 vs 1.8 &#xb1; 1.0), along with higher 24-hour urine pH (6.2 &#xb1; 0.5 vs 5.5 &#xb1; 0.4) and calcium phosphate supersaturation (0.9 &#xb1; 0.8 vs 0.2 &#xb1; 0.1; all P < .05). CONCLUSIONS: Among obese participants with diabetes mellitus and UA nephrolithiasis, phentermine/topiramate was well tolerated and demonstrated significant stone burden reductions by per-protocol analysis. The intervention group also had greater weight loss, higher urinary pH, and lower hemoglobin A1c and urinary citrate levels. These data provide a framework to study the impact of this novel alternative UA therapy on a wider range of patients with obesity and diabetes.

Aged↗

Postmortem changes in uric acid and ascorbic acid in human cerebral cortex tissues excised after cardiac death.

There has been no report on the determination of uric acid (UA) in human brain and heart tissues. UA and ascorbic acid (AA) in human cerebral cortex and heart tissues excised after cardiac death have been studied by reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection (ECD). It has been found that the levels of AA and UA in the human cerebral cortex tissues tend to decrease and increase, respectively, after cardiac death as a function of time between death and forensic operation. In addition, it has been found that there is no special relationship between UA levels in human heart tissues and time after cardiac death, also that the UA levels in the heart are high as compared with those in human cerebral cortex tissues. We have emphasized that the HPLC-ECD method is useful in determining UA and AA in mammalian tissues by one-time chromatography to gain a better understanding of the relationship between disease and serum urate level.

Ascorbic Acid↗

[Changes in serum uric acid concentration after defined physical stress].

The influence of two variants of strength training on serum level of uric acid was examined in four weightlifters. In a pilot study a remarkable increase was found in both after maximum strength orientated squats and after power-related strength training. The results were discussed in terms of different kinds of recruitment of motor units, the time structure of examined movements and the arthritis urica as a typical disturbance of the purine nucleotid metabolism.

Adult↗

Two successive pregnancies in a woman with xanthinuria: unexpected increase in serum uric acid levels.

Two successive pregnancies were observed in a patient with xanthinuria. In each of them, maternal serum uric acid (SUA) level rose progressively during the third trimester, reaching a subnormal value just before delivery. The level of UA was slightly higher in arterial cord blood than in maternal blood. There was no difference between levels in arterial and venous cord blood. It is suggested that xanthine oxydase may be present in the placenta.

Adult↗

Dopamine and uric acid act as antioxidants in the repair of DNA radicals: implications in Parkinson's disease.

Dopamine (DA) and uric acid (UA) have been found to undergo a protective reaction effecting the fast chemical repair of oxidative free-radical damage to DNA. This antioxidant reaction does not occur with normal concentrations of other, more abundant, antioxidants and our findings suggest that DA and UA are important for the preservation of the DNA in certain brains cells per se. These studies point to the need for drugs that undergo a similar antioxidant reaction with DNA radicals to prevent or arrest DNA damage associated with Parkinson's disease when the levels of DA and UA fall.

Animals↗

A sensitive determination of uric acid in serum using uricase/catalase/formaldehyde dehydrogenase coupled with formate dehydrogenase.

We developed and evaluated an assay for serum uric acid based on the uricase (EC 1.7.3.3)-catalase (EC 1.11.1.6)-formaldehyde dehydrogenase (FADH, EC 1.2.1.46) method coupled with formate dehydrogenase (formate:NAD oxidoreductase, FDH, EC 1.2.1.2). Formate dehydrogenase from Pseudomonas oxalaticus catalyzes the formation of NADH from formate produced by FADH. Owing to the NADH and formate oxidase activity of the FDH itself, the full reaction curve is not linear, but gradually decreases. The formation of NADH is not stoichiometric with formate removal, but is strictly proportional to it. To overcome this decrease of extinction, we added hydroxylamine hydrochloride to the FDH. The sensitivity of the full reaction in the presence of FDH was about 1.8 times that without FDH. Analysis with a Cobas Bio centrifugal analyzer revealed a linearity of up to 3.56 mmol/L. The uricase-catalase-alcohol dehydrogenase method correlated well with the uricase-peroxidase-chromogen method. Our method is more sensitive than other methods.

Aldehyde Oxidoreductases↗