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Serum uric acid, inorganic phosphorus, and glutamic-oxalacetic transaminase and blood pressure in carbohydrate-sensitive adults consuming three different levels of sucrose.

12 men and 12 women, classified as carbohydrate-sensitive on the basis of an exaggerated insulin response to a sucrose load, consumed diets containing either 5, 18, or 33% sucrose in a crossover design. The diets simulated the average American diet and consisted of identical natural and processed foods with the exception of a patty. The patty provided the experimental levels of sucrose; the difference was made up by starch. Each level of sucrose was consumed for a 6-week period. Subject body weights were maintained. Fasting serum uric acid and inorganic phosphorus increased as the level of dietary sucrose increased. Diastolic blood pressure was significantly higher when subjects were on the 33% sucrose diet as compared to the 5 and 18% diets. Serum glutamic-oxalacetic transaminase was not affected by diet. In tolerance tests after a sucrose load (2 g/kg body weight), the uric acid response was higher after the 18 and 33% sucrose diets than after the 5% sucrose diet. Serum inorganic phosphorus, which increased significantly with each level of dietary sucrose, decreased following the sucrose load. These results indicate that carbohydrate-sensitive individuals may be affected adversely by the level of sucrose commonly found in the Westernized diet. Since elevated serum uric acid and blood pressure have been identified as risk factors in degenerative diseases, this study suggests that carbohydrate-sensitive individuals should limit their sucrose consumption.

Adult↗

Uric acid renal handling: spontaneous changes and influence of a thiazide alone or associated with triamterene.

The spontaneous changes in renal handling of uric acid, the consequences of methyclothiazide (M) and of a combination of M with three doses of triamterene (25, 50, 75 mg) were assessed in eight normal men, in a ten-week placebo controlled, double-blind study. In untreated subjects, significant correlations were found between blood uric acid (bUA) and UAV, between bUA and FeUA, between FeUA and plasma renin activity (PRA) and between bUA and PRA. Spontaneous variations in bUA and UAV were shown to be predominantly dependent on changes in sodium status. All diuretics significantly increased bUA and decreased FeUA. Under diuretics, bUA kept correlations with FeUA and PRA similar to that observed in untreated subjects indicating that the changes were dependent only on variations in renal transport induced by changes in sodium status. Addition of triamterene to methyclothiazide significantly lessened the thiazide induced abnormalities in UA.

Adult↗

Changes in uric acid during acute infusion of MPP+, 6-OHDA, and FeCl3. A microdialysis study in the substantia nigra of the guinea pig.

Extracellular uric acid levels were measured in the substantia nigra of guinea pigs via microdialysis/liquid chromatography with electrochemical detection (LCED) during infusion (60 min) of N-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA), or iron (III) chloride (FeCl3). Striatal and substantia nigra (SN) tissues were analyzed for uric acid (UA) and dopamine (DA) 3 h postinfusion. MPP+ infusion resulted in an increase in extracellular UA of 222 +/- 6%. The ipsilateral/contralateral ratio of nigral UA tissue levels was significantly increased over vehicle controls. Infusion of 6-OHDA produced an increase of 362 +/- 44% in extracellular UA. No significant changes were seen in UA tissue levels in either the striatum or the SN. Infusion of FeCl3 produced a significant decrease in extracellular nigral UA levels to 21.5 +/- 0.7% of preinfusion levels. The ipsilateral/contralateral ratio of nigral UA tissue levels increased by 38%, whereas the striatal ratio value decreased to 62% of the vehicle control levels. No changes in DA tissue levels were observed in any of the brain regions in the experimental groups. These results indicate that infusion of neurotoxins known to affect dopaminergic cells generates an acute change in UA levels within the nigrostriatal system of guinea pigs.

1-Methyl-4-phenylpyridinium↗

Serum uric acid and multiple sclerosis.

UNLABELLED: Peroxynitrite (PN) has been implicated in multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis. Uric acid (UA) serum levels of MS patients, a natural scavenger of PN, were found lowered in some recent studies. OBJECTIVE/PURPOSE: The objective of our study was to correlate UA serum levels and several clinical parameters of MS. We also tried to investigate serum UA changes during treatment with immunomodulating or immunosuppressing drugs in the last 6 months. PATIENTS AND METHODS: We measured UA serum levels in 190 patients with MS and 58 age and gender matched patients with inflammatory (IND) and non-inflammatory diseases (NIND) studied as control groups. UA levels were correlated with clinical parameters as type of the disease, duration, disability, magnetic resonance imaging (MRI) activity and female gender. RESULTS: In the overall MS group, patients were found to have significantly lower mean serum uric acid levels compared with the IND (p = 0.0029) and the NIND group (p < 0.0001). UA serum concentrations were not inversely correlated with duration of the disease (p = 0.87), with disability as assessed by Expanded Disability Status Scale (EDSS) score (p = 0.67) and MRI activity (p = 0.36). Treatment with immunomodulating or immunosuppressing drugs had no influence in UA levels (p = 0.85). Patients with Clinically Isolated Syndromes (CIS) were found to have significantly lower UA concentrations compared with IND and NIND patients (p = 0.009 and <0.001, respectively). CONCLUSIONS: Our findings suggest that lower serum UA levels in MS patients may represent a primary, constitutive loss of protection against nitric oxide and the development of CNS inflammation and tissue damage may not have a direct effect to UA serum levels. They also provide support that the earlier increase of UA serum levels might be beneficial in the future treatment of MS.

Adolescent↗

Moderate alcohol consumption reduces urinary 8-hydroxydeoxyguanosine by inducing of uric acid.

Recent studies suggest that moderate alcohol consumption is associated with a low risk of cancer, coronary heart disease, and other diseases. Most of these diseases are considered to be related to the action of reactive oxygen species (ROS) at certain stages of disease progression. However, considerable evidence exists indicating that ethanol generates ROS in vivo. Thus, the reduced risk of disease as a result of alcohol consumption seems to contradict evidence suggesting the induction of ROS by ethanol. In the present study, we investigated whether oxidative stress was induced in moderate alcohol drinkers. We measured the total urinary biopyrrins and 8-hydroxydeoxyguanosine (8-OHdG) levels as a systemic oxidative stress marker and an oxidative DNA damage marker, respectively. Serum uric acid was also measured as an alcohol-induced antioxidant. We compared total urinary biopyrrins and 8-OHdG levels among groups with different alcohol habits. The results showed that total biopyrrins levels increased with the amount of alcohol consumed, but that the level of 8-OHdG significantly decreased with the amount of alcohol consumed. The decrease in 8-OHdG levels seemed to be associated with increasing levels of uric acid. Judging from the increasing level of total biopyrrins, alcohol may induce ROS. ROS may then cause cell damage in liver, as suggested by the positive correlation between the total biopyrrins levels and the serum GOT, GPT, and gammaGTP levels. However, since ROS may be more effectively counteracted by uric acid in organs other than the liver, DNA damage may be suppressed rather than induced. Accordingly, moderate alcohol consumption seems to have the overall effect of reducing DNA damage, as shown by the decrease in urinary 8-OHdG levels observed in our study.

8-Hydroxy-2'-Deoxyguanosine↗

[Vesical uric acid lithiasis in a child with renal hypouricemia].

We report a 12-month-old boy with renal hypouricemia who presented with crying due to obstructing vesicourethral uric acid stones. Metabolic study revealed persistent acidic urine with normal blood pH, and hypouricemia (1.4-1.7 mg/dl) with an increased ratio of uric acid clearance to creatinine clearance (24-32 %). Pyrazinamide produced no response but the patient showed a positive response to benzbromarone. These findings were consistent with a presecretory defect. No other tubular dysfunctions, such as renal glycosuria, aminoaciduria or phosphaturia were found. The patient underwent surgical treatment and was subsequently treated with potassium citrate. After a 2-year follow-up, he remains asymptomatic, despite persistent hyperuricosuria. To our knowledge, this is the youngest reported case of renal hypouricemia and lithiasis.

Humans↗

Rate of weight loss after vertical banded gastroplasty in morbid obesity: relationship to serum lipids and uric acid.

The relationship between postoperative weight loss after vertical banded gastroplasty in morbidly obese patients and preoperative serum triglycerides, cholesterol, HDL-cholesterol, uric acid and fasting plasma glucose was evaluated. The rate of weight loss, calculated as a percentage of original weight, was determined at three and six months after surgery. There was a significant correlation between rate of weight loss at three months and preoperative serum uric acid (r = -0.60, p less than 0.01). and also with the total cholesterol: HDL-cholesterol ratio (r = 0.61, P less than 0.01). At six months, the rate of weight loss correlated with preoperative serum triglycerides (r = -0.54, p less than 0.02) and total cholesterol: HDL cholesterol ratio (r = 0.44, p less than 0.05). The reasons for the predictive value of these biochemical parameters is unknown and deserves further study.

Adult↗

Electroconvulsive shock increases interstitial concentrations of uric acid in the rat brain.

This study examined the effects of electroconvulsive shock (ECS) on striatal interstitial concentrations of the purine metabolite uric acid (UA) using microdialysis in freely moving rats. UA increased to about 200% of baseline following ECS. Intense seizure activity induced by the convulsant agent flurothyl also resulted in a two-fold increase of UA concentrations suggesting that the ECS-induced UA increase is related to the seizure activity per se. Local administration of tetrodotoxin or perfusion with a Ca(2+)-free solution failed to affect the basal or the ECS-induced increase in UA concentrations. These data indicate that both the basal and the stimulated interstitial concentrations of uric acid are not dependent upon neuronal activity and exocytotic release. The UA response to ECS appears to be refractory to a second ECS delivered 2 but not 24 h after the first. Intrastriatal infusion of allopurinol (1 mM), an inhibitor of UA synthesis, decreased basal UA concentrations to 26% but did not influence the ECS-induced UA increase. Systemic injection of allopurinol (20 mg/kg, i.p.) decreased basal UA concentrations to 25% and prevented the ECS-induced UA elevation. ECS also increased serum concentrations of UA to almost 200% of baseline. Allopurinol (20 mg/kg, i.p.) markedly decreased serum UA concentrations to non-detectable levels and completely abolished the ECS-induced increase. The estimated concentration difference between blood and brain interstitial UA strongly suggests that ECS-induced increase in brain interstitial UA concentrations is of peripheral origin possibly due to disruption of the blood brain barrier during seizure activity.

Administration, Topical↗

Enzymatic method for assaying uric acid in serum with a new tetrazolium salt produces water-soluble formazan dye.

OBJECTIVES: To apply an enzymatic method for assaying uric acid in serum based on the uricase (EC 1.7.3.3)-catalase (EC 1.11.1.6)-formaldehyde dehydrogenase (FADH, EC 1.2.1.46) coupled with the new tetrazolium salt producing a water-soluble formazan dye as an indicator system. Unlike the traditional tetrazolium salts, e.g., iodonitrotetrazolium (INT) and nitrotetrazolium blue (NTB), the corresponding formazan dye produced did not absorb to the test tube and the reaction cells of the analyzer. Moreover, this formazan dye had a higher water solubility and more sensitivity. DESIGN AND METHODS: A two electron reduction of tetrazolium salt with NADH, produced by the uricase-catalase-FADH reaction, was mediated by an electron carrier, 1-methoxy PMS. The generation of formazan, monitored at 440 nm, was proportional to the concentration of uric acid in serum. The sensitivity of this method was about 1.5 times that of the peroxidase-TOOS [N-ethyl-N-(2-hydroxy-3-sulfopropyl)-m-toluidine] method. The assay was evaluated with TBA-80FR.NEO biochemical analyzer. The average within-run and between-day imprecision (CV) were 0.75-2.44% and 3.20-3.33%, respectively. RESULTS: Results of the proposed method (y) correlated well with those determined by the conventional chromogen method (x): y = 0.970 x - 0.018 mmol/L (Sy l x = 0.019 mmol/L, r = 0.993, n = 67). CONCLUSIONS: We also present data showing that the method is rapid, relatively free of interference, and amenable to automation.

Coloring Agents↗

Value of the urinary uric acid to creatinine ratio in term infants with perinatal asphyxia.

The diagnosis of perinatal asphyxia is often inexact and present techniques for assessing its severity are unsatisfactory. The purpose of this study was to describe prospectively the value of the urinary uric acid to creatinine (UA/Cr) ratio in showing increased uric acid excretion in early spot urine samples for the identification of perinatal asphyxia, and to assess the relationship between the urinary UA/Cr ratio and the severity of hypoxic-ischemic encephalopathy. Twenty-seven fullterm infants with perinatal asphyxia were compared with 40 healthy controls. The UA/Cr ratio was higher in the asphyxiated group when compared with controls (2.11 +/- 0.83 vs 0.72 +/- 0.39 P < 0.001). Furthermore, there was a correlation between the UA/Cr ratio and the severity of the encephalopathy (r = 0.84; P < 0.001). The UA/Cr ratio was found to be a good, simple screening test for the early assessment of perinatal asphyxia.

Asphyxia Neonatorum↗

Slightly radiopaque uric acid calculi: impact upon therapeutic considerations?

Ten patients with slightly radiopaque urinary calculi were treated by percutaneous litholapaxy or even open surgery. The stone analysis revealed uric acid as the main stone composite suggesting that these patients should have been treated by oral litholysis alone alkalinizing the urine and decreasing uric acid levels with allopurinol. CT density measurements proved that concrements with HE less than 600 can be successfully dissolved by oral medication alone. Twenty-four patients were subsequently treated by oral citrate alkalinizing the spontaneous urine to pH 6.8-7.2 dissolving even large staghorns within 6-8 weeks. CT density measurements have become a routine diagnostic procedure when poorly radiopaque calculi are found on the standard plain film. The patient can thus be spared invasive treatment which is unnecessary in most cases.

Aged↗

Effects of acute exercise on the levels of iron, magnesium, and uric acid in liver and spleen tissues.

In this study, we investigated the effects of acute exercise on tissue levels of iron, magnesium, and uric acid of rats. Twenty adult Wistar albino rats were used for the study. They were divided into two groups: controls (n=10) and the study group (n=10). The study group was left into a small water pool and allowed to do swimming exercise for 30 min while controls rested. All of the animals were sacrificed, and their livers and spleens removed and homogenized immediately. The iron, magnesium, and uric acid levels of the homogenates were measured by an autoanalyzer (ILAB 900, Italy) with commercial kits from the same company. Results were evaluated by the Mann-Whitney U-test. According to our results, the liver iron levels increased significantly with exercise, whereas spleen iron levels decreased significantly (p<0.05) compared to controls. We found no significant differences in the levels of the other two parameters with exercise. These results show that the iron distribution in organs changes with exercise.

Animals↗

Biorhythm in the renal excretion of electrolytes and uric acid in healthy subjects.

The same 8 subjects were investigated twice within 4 months with regard to variations in the renal clearance of uric acid, creatinine, sodium, potassium, chloride and osmolarity. After a 48-hour stabilization period, clearance values were determined at 2-hourly intervals for 12 hours. Food and fluid intake remained the same for the duration of the studies. The calculation of excretory fractions was based on creatinine clearance as an approximate of glomerular filtration rate. With the exception of creatinine clearance, all the variations tended to decrease during the morning and to exhibit distinct increases in the early afternoon. The maximal excretion fraction coincided with maximal clearance values. The following minimal and maximal clearance values were recorded: uric aicd 4,7-12,7 ml/min; creatinine 131-179 ml/min; Na+ 1,1-2,9 ml/min; K+ 6,6-16,5 ml/min; Cl- 1,4-3,5 ml/min; osmolarity 2,6-3,9 ml/min. The excretion fractions varied from 3,3 to 8,0% (uric acid); 0,7 to 1,8% (Na+); 5,4 to 1,08% (K+); 1,0 to 2,2% (Cl-) and 1,7 to 2,3% (osmolarity). The results of this investigation strongly suggest that clinical trials designed to evaluate the influence of drugs on renal clearances should not be conducted without an appropriate control phase.

Adult↗

An in situ atomic force microscopy study of uric acid crystal growth.

Kidney stones are heterogeneous polycrystalline aggregates that can consist of several different building blocks. A significant number of human stones contain uric acid crystals as a crystalline component, though the molecular-level growth of this important biomaterial has not been previously well-characterized. In the present study, in situ atomic force microscopy (AFM) is used to investigate the real-time growth on the (100) surface of uric acid (UA) single crystals as a function of fundamental solution parameters. Layer-by-layer growth on UA (100) was found to be initiated at screw dislocation sites and to proceed via highly anisotropic rates which depend on the crystallographic direction. The smallest b-steps exhibited minimum heights corresponding to two molecular layers, while fast-moving c-steps more commonly showed monolayer heights. Growth kinetics measured under a range of flow rates, supersaturation levels, and pH values reveal linear trends in the growth kinetics, with faster growth attained in solutions with higher supersaturation and/or pH. The calculated kinetic parameters for UA growth derived from these experiments are in good agreement with the values reported for other crystal systems.

Crystallization↗

Differential effects of dietary flaxseed protein and soy protein on plasma triglyceride and uric acid levels in animal models.

The effect of dietary soy protein and flaxseed meal on metabolic parameters was studied in two animal models, F344 rats with normal lipid levels and obese SHR/N-cp rats with elevated levels of cholesterol and triglyceride. The rats were fed AIN 93 diet differing only in the source of protein. The rats were fed either 20% casein, 20% soy protein or 20% flaxseed meal. Plasma was analyzed for cholesterol, triglyceride, uric acid, blood urea nitrogen (BUN), creatinine and total protein. In both strains of rats, flaxseed meal significantly decreased plasma cholesterol and triglyceride concentrations. The effect of soy protein on lipids was not as striking as that of flaxseed meal. Flaxseed meal also lowered uric acid in F344 rats and BUN in SHR/N-cp rats. Since cholesterol, triglyceride and uric acid are independent risk factors for cardiovascular disorders, our data show that both flaxseed meal and soy protein may have beneficial effects. Which chemical constituent(s) of flaxseed meal or soybean is (are) responsible for the beneficial effects need to be identified.

Journal Article↗

[Uric acid determination in dilute serum with an enzyme electrochemical and enzyme-free sensor].

The paper describes the development of electrochemical methods for analytical determination of uric acid basing on amperometric sensors: with an uricase enzyme electrode, termed "electrochemical-enzymatic" method; with an enzyme-free electrode by indication of the anodic oxidation of uric acid, termed "electrochemical" method. The comparison of analytical quality of both methods shows a sufficient specificity, precision, and accuracy. They show a good correlation with regard to the specific uricase-catalase reference method (UCM): yelectr./enz. = (0.943 xUCM + 19.8) mu mol/l; r = 0.9948 yelectr. = (0.964 xUCM + 6.31) mu mol/l; r = 0.9917 The analysis by the "electrochemical" method can be done with a higher frequency of samples per hour completely without need of enzyme. Both methods are principally suitable for an application in analytic biochemical laboratories.

Electrochemistry↗