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PubMed1982

Anaerobic degradation of uric acid via pyrimidine derivatives by selenium-starved cells of Clostridium purinolyticum.

Clostridium purinolyticum decomposed uric acid via pyrimidine derivatives under selenium starvation conditions. Products were acetate, formate, glycine, ammonia, and CO2. 4,5-Diaminouracil could be identified as an intermediate after converting the labile substance into 6,7-dimethyllumazine. The breakdown of uric acid was inhibited by EDTA. High-pressure liquid chromatography methods have been developed for the simultaneous determination of uric acid, 4,5-diaminouracil, and 6,7-dimethyllumazine. The significance of the new pathway is discussed.

Anaerobiosis↗
PubMed1985

Experimental observations on dissolution of uric acid calculi.

An in vitro model was devised to evaluate the efficacy of the different irrigating solutions utilized for local dissolution of uric acid stones. Tris (hydroxymethyl) aminomethane proved to be several times faster than sodium bicarbonate in dissolving uric acid calculi. The maximal dissolution rate was obtained when the highest pH (10.5) of Tris buffer was used in concentrations at or above 0.2 M. This makes the commercially available THAM-E an optimal choice. Stones averaging 1 cm. in diameter were dissolved in less than 48 hours when this compound was used. Sodium bicarbonate should only be used in solutions with concentrations lower than 0.2 M and pH below 9, if some dissolution is to be attempted. Concentrations and pH's above these levels will coat the stones with hard shells of sodium urate, making it impossible to dissolve them. The in vitro findings were confirmed in vivo in a limited study in pigs with human uric acid calculi surgically placed in their kidneys. Our results indicate how to make the best use of the solutions clinically available in order to obtain total dissolution of uric acid stones in short periods of time. We recommend the use of a 0.3 molar concentration of this buffer (THAM-E) at flow rates of about 50 cc per hour.

Animals↗
PubMed2002

Peroxidase properties of extracellular superoxide dismutase: role of uric acid in modulating in vivo activity.

OBJECTIVE: The cytosolic form of Cu/Zn-containing superoxide dismutase (SOD1) has peroxidase activity, with H2O2 used as a substrate to oxidize other molecules. We examined peroxidase properties of the extracellular form of SOD (SOD3), a major isoform of SOD in the vessel wall, by using recombinant SOD3 and an in vivo model of atherosclerosis. METHODS AND RESULTS: In the presence of HCO3-, SOD3 reacted with H2O2 to produce a hydroxyl radical adduct of the spin trap 5-diethoxyphosphoryl-5methyl-1-pyrroline N-oxide (DEMPO). SOD1 and SOD3 were inactivated by H2O2 in a dose- and time-dependent fashion, and this was prevented by physiological levels of uric acid. To examine the in vivo role of uric acid on SOD1 and SOD3, control and apolipoprotein E-deficient (ApoE(-/-)) mice were treated with oxonic acid, which inhibits urate metabolism. This treatment increased plasma levels of uric acid in control and ApoE(-/-) mice by approximately 3-fold. Although increasing uric acid levels did not alter aortic SOD1 and SOD3 protein expression, aortic SOD1 and SOD3 activities were increased by 2- to 3-fold in aortas from ApoE(-/-) mice but not in aortas from control mice. CONCLUSIONS: These studies show that SOD1 and SOD3 are partially inactivated in atherosclerotic vessels of ApoE(-/-) mice and that levels of uric acid commonly encountered in vivo may regulate vascular redox state by preserving the activity of these enzymes.

Animals↗
PubMed1996

Uric acid lowering effect of oxipurinol sodium in hyperuricemic patients - therapeutic equivalence to allopurinol.

OBJECTIVE: Oxipurinol has been shown to be sufficiently absorbed after oral administration as a rapid release preparation of oxipurinol sodium. We compared the uric acid lowering affect of allopurinol and oxipurinol. METHODS: In a multicenter, randomized, double blind crossover trial in 99 hyperuricemic patients with normal renal function we investigated the uric acid lowering effect of oxipurinol sodium (O) in daily amounts equimolar to 300 mg allopurinol (A). Mean pretreatment plasma uric acid concentrations in groups A/O and O/A were 8.3 +/- 1.4 and 8.7 + /- 1.4 mg/dl, respectively. RESULTS: In group A/O the mean plasma uric acid decreased to 5.4 +/- 1.2 mg/dl with allopurinol treatment, and increased slightly to 5.7 + /- 1.3 mg/dl during the consecutive oxipurinol period. In group O/A plasma uric acid declined to 6.0 +/- 1.4 mg/dl with oxipurinol and was 5.6 + /- 1.3 mg/dl at the end of the allopurinol period. The overall average reduction compared to baseline was 3.0 mg/dl with allopurinol and 2.6 mg/dl with oxipurinol. The difference between the 2 treatments was small but significant (multiple p=0.027,2 tailed). The corresponding mean plasma oxipurinol concentrations were 9.24 mu g/dl at the end of the allopurinol period and 9.9 mu g/dl after treatment with oxipurinol (NS). CONCLUSION: Oxipurinol is well absorbed and sufficiently effective in hyperuricemic patients when administered as a rapid release preparation of oxipurinol sodium. Oxipurinol sodium could be a substitute for allopurinol in hyperuricemic patients and possibly also with new uses for allopurinol.

Adult↗
PubMed1994

[Spectrophotometric determination of uric acid in serum using a titanium (IV)-porphyrin complex].

Aqueous solution of oxo[5,10,15,20-tetra(4-pyridyl)porphyrinato]titanium (IV) complex, a Ti-TPyP reagent, was found to be very useful for the spectrophotometric determination of hydrogen peroxide. The reagent (lambda max 432 nm) reacts with hydrogen peroxide to form a monoperoxocomplex, resulting in a significant decrease of the absorbance at 432 nm. The decrease (delta A) in absorbance was proportional to the concentration of hydrogen peroxide. The Ti-TPyP reagent was successfully applied to the assay of uric acid in the serum, using uricase to produce hydrogen peroxide through enzymatic oxidation. Using only 5 microliters serum, a linear relationship was obtained between delta A and uric acid concentration in the serum ranging from 5 x 10(-6) to 1 x 10(-3) M. The apparent molar delta A of uric acid was 2.2 x 10(5) M-1 cm-1. The relative standard deviation of repeated runs (n = 8) was 2.8% at 3.77 x 10(-4) M uric acid. The analytical recovery of uric acid (5 x 10(-4) M) added to the serum was 96.8 to 105.0%. No pre-concentration and deproteinization were required to determine uric acid in the serum by the present method because of the high sensitivity and selectivity of the Ti-TPyP reagent for hydrogen peroxide.

Gout↗
PubMed2006

An in vitro study on the free radical scavenging capacity of ergothioneine: comparison with reduced glutathione, uric acid and trolox.

BACKGROUND: Treatment of oxidative stress-related pathologies is a possible therapeutical strategy for the future. Natural product with antioxidant properties could trigger this goal. The aim of this in vitro study was to assess the antioxidant activity of the natural product ergothioneine (EGT), a compound of plant origin, which is assimilated and conserved by mammals in erythrocytes, kidney, seminal fluid and liver. METHODS: We measured the antioxidant activity of EGT as its ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid (KMBA) by hydroxyl radical, peroxyl radicals and peroxynitrite. The results are expressed as total oxyradical scavenging capacity (TOSC) units. Glutathione (GSH), uric acid and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), the water-soluble analog of vitamin E, were used as the reference antioxidants. RESULTS: EGT was the most active scavenger of free radicals as compared to classic antioxidants as GSH, uric acid and trolox. In particular, the highest antioxidant capacity exhibited by EGT vs. peroxyl radicals (5.53 +/- 1.27 units) resulted 25% higher than the value obtained with the reference antioxidant trolox (4.4 +/- 0.6 units, P < 0.01). The scavenging capacity of EGT towards hydroxyl radicals (0.34 +/- 0.09 units) was 60% higher, as compared to uric acid (0.21 +/- 0.04 units, P < 0.001), which represent the reference antioxidant vs. hydroxyl radicals. Finally, EGT showed the highest antioxidant activity also towards peroxynitrite (5.2 +/- 1.0 units), with a scavenging capacity 10% higher than that of uric acid (4.7 +/- 0.9 units, P < 0.05). CONCLUSIONS: This study showed that EGT has potent intrinsic anti-hydroxyl, anti-peroxyl and anti-peroxynitrite radicals antioxidant activity, as compared to classic molecules with antioxidant capacity as GSH, trolox and uric acid. This appears of interest, given the increasing use of non-vitamins cocktails for therapeutical approaches to many oxidative-induced pathologies.

Butyrates↗
PubMed2005

Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis.

BACKGROUND: It has been suggested throughout the past fifty years that serum uric acid concentrations can help predict the future risk of coronary heart disease (CHD), but the epidemiological evidence is uncertain. METHODS AND FINDINGS: We report a "nested" case-control comparison within a prospective study in Reykjavik, Iceland, using baseline values of serum uric acid in 2,456 incident CHD cases and in 3,962 age- and sex-matched controls, plus paired serum uric acid measurements taken at baseline and, on average, 12 y later in 379 participants. In addition, we conducted a meta-analysis of 15 other prospective studies in eight countries conducted in essentially general populations. Compared with individuals in the bottom third of baseline measurements of serum uric acid in the Reykjavik study, those in the top third had an age- and sex-adjusted odds ratio for CHD of 1.39 (95% confidence interval [CI], 1.23-1.58) which fell to 1.12 (CI, 0.97-1.30) after adjustment for smoking and other established risk factors. Overall, in a combined analysis of 9,458 cases and 155,084 controls in all 16 relevant prospective studies, the odds ratio was 1.13 (CI, 1.07-1.20), but it was only 1.02 (CI, 0.91-1.14) in the eight studies with more complete adjustment for possible confounders. CONCLUSIONS: Measurement of serum uric acid levels is unlikely to enhance usefully the prediction of CHD, and this factor is unlikely to be a major determinant of the disease in general populations.

Age Factors↗
PubMed2001

Serum uric acid is not an independent risk factor for coronary heart disease.

Many large epidemiologic studies have confirmed a positive association between raised serum uric acid and risk of coronary heart disease or cardiovascular disease, both in the general population and among hypertensive patients. There is much controversy concerning the role of uric acid as an independent risk factor in the development of coronary heart disease because serum uric acid is related to many of the established etiologic risk factors for cardiovascular disease that could confound the observed association. This review finds little support for an independent causal role for serum uric acid in the development of coronary heart disease.

Coronary Disease↗
PubMed1982

Furosemide-induced increase in urinary and peritoneal excretion of uric acid during peritoneal dialysis in patients with chronic uremia.

Intermittent peritoneal dialysis was performed in 17 patients with chronic uremia in order to observe the effect of furosemide added to the dialysate on urinary and peritoneal elimination of uric acid. Two kinds of dialysate were used: moderately hypertonic (osmolality, 431.2 mOsm/kg of water) and slightly hypertonic (osmolality, 368.9 Osm/kg of water). Significant increases in urine volume, urinary and peritoneal excretion of uric acid, and renal and peritoneal clearances were found. The increase in urinary excretion of uric acid exceeded that of urine volume. These findings were interpreted to be the result of furosemide action on renal function after being transferred through the peritoneum into the blood stream with the concomitant increase in the uric acid shift from the circulation into the peritoneal cavity. We concluded that the addition of furosemide is useful in increasing uric acid elimination in patients with chronic uremia.

Diuresis↗
PubMed1982

Serum uric acid as a marker of pregnancy-induced hypertension.

A prospective longitudinal study was conducted, looking at the changes in serum uric acid during pregnancy in women who were normotensive at initial presentation. In our sample of 78 women having a total of 88 singleton pregnancies, 13 developed pregnancy-induced hypertension during labour only, whilst a further 6 developed hypertension during pregnancy. Women who developed hypertension had significantly higher uric acid levels than women who remained normotensive throughout. However, there was an appreciable overlap between the groups. Women with essential hypertension showed similar changes. We conclude that the serum uric acid level is an unreliable indicator of developing hypertension in the individual woman. However, a rapidly rising uric acid level should be viewed with caution.

Adult↗
PubMedDate not supplied

[Urinary excretion of calcium, uric acid and citrate in healthy children and adolescents].

OBJECTIVE: To obtain regional reference values for calcium, uric acid and citrate urinary excretion and establish a correlation between those excretions in 24-hour urine sample and single urine sample for their use in clinical practice. METHODS: A hundred and twenty-five healthy children and adolescents were randomly chosen and submitted to the following protocol: clinical examination, biochemical analysis of blood, blood cell count, parathormone, 24-hour urine, fasting urine sample and stool test. RESULTS: The maximum value of calcium excretion in 24-hour urine was 3.75 mg/kg; in mg/dl of the glomerular filtration rate, it was 0.10; and for the calcium/creatinine (mg/dl) ratio in the fasting urine sample was 0.25. Positive correlation was observed between calcium excretion in the 24-hour urine and the fasting sample (mg/dl and mg/dl of glomerular filtration rate). The maximum values of uric acid excretion in 24-hour urine were 600, 450, and 320 mg and 13, 15 and 18 mg/kg for adolescents, school and preschool children, respectively; in mg/dl of glomerular filtration rate, in the fasting urine sample, it was 0.47. Positive correlation was observed for the uric acid excretion in 24-hour urine and fasting urine samples. The mean values for the citrate excretion in 24-hour urine were 1.6, 1.1 and 0.5 mmol for adolescents, school and preschool children, respectively; for citrate/creatinine ratio, in the fasting urine sample the mean value was 0.3. CONCLUSIONS: The calcium and uric acid excretion in 24-hour urine showed correlation with those in the fasting urine sample, which allows their use for metabolic diagnosis, population studies and follow-up of patients with hypercalciuria and hyperuricosuria without voiding control; the citrate/creatinine ratio in the fasting urine sample can be used for controlling patients with hypocitraturia.

English Abstract↗
PubMed1995

Biosensor based on chemiluminescence for serum uric acid determination.

A biosensor based on luminol chemiluminescent reaction and immobilized uricase column for serum uric acid determination has been developed. The response time by the sensor for various concentrations of serum uric acid was 47 sec with a 17-microliters sample volume at 40 samples per hr. The linear range of standard curve was from 1 mg/dL up to 20 mg/dL of serum uric acid. The imprecision within a day was 3.22% to 4.36%. The day-to-day imprecision was 6.18% to 7.80%. The recovery rate by the method was 93% to 109%. Compared with the standard colorimetric method employed, the enzymatic kit revealed that the linear regression and correlation coefficient were Y = 0.4 + 0.938x and r = 0.9909, respectively. The immobilized uricase column retained 94% of its original activity even after over 2000 runs for five and half months of continual usage.

Biosensing Techniques↗
PubMed1968

Anhydrous uric acid: nature and occurrence of a new form of urinary calculi.

A second form of anhydrous uric acid has been found in urinary calculi; it is probably derived as an artifact from uric acid dihydrate during storage. It has been prepared in the laboratory by desiccation of uric acid dihydrate. Mixtures of these two substances sometimes give x-ray powder patterns that resemble that of xanthine on weak photographs, but are distinguishable by their infrared spectra.

Anhydrides↗
PubMed1996

[Serum levels of uric acid, lipids and glucose in essential hypertension].

In 48 men, 42, 1 +/- 8.8 yrs old, with untreated mild essential hypertension, serum uric acid, total cholesterol triglycerides and glucose were examined at 8 a.m after 16 hour overnight fasting. All patients were overweight, with body mass index: 26.9 +/- 2.4 kg/m2, (normal value: 19-24.9); serum uric acid 293.1 +/- 89.3 mmol/l; cholesterol 6.3 +/- 1.4; triglycerides 2.0 +/- 1.3 and glucose 5.4 +/- 0.9 mmol/l. File out of 48 (10.4%) patients had hyperuricemia, nine (18.7%) had hypercholesterolemia, twenty (41.7%) had hypertriglyceridemia and 19 (39.6%) had hyperglycemia. Significant correlation between serum uric acid and triglycerides only (r = 0.35; p < 0.01), was found. A correlation exists between the diastolic blood pressure and cholesterol (r = 0.35; p < 0.01); as well as, between mean arterial blood pressure and cholesterol (r = 0.34; p < 0.02). Only three out of 48 (6.2%) patients with hypertension had all four biochemical parameters above normal levels. Our results suggest that interrelation of all these metabolic disorders are important in essential hypertension, and especially the association of high serum uric acid and triglyceride level.

Adult↗
PubMedDate not supplied

[The blood level of uric acid as a risk factor in transient cerebral ischemic attacks and in non-embolic acute cerebral infarct].

The serum uric acid level has been determined in 300 patients, both males and females. 125 of these suffered from transient cerebral ischaemic attacks and 175 from atherothrombotic brain infarction. The values obtained were compared with those determined, with the same technique, in a control group of patients with neurologic diseases, chosen at random, and with no clinical finding or historical data of cerebrovascular and/or cardiac disease. No significant statistical difference has been observed between the mean serum uric acid level in the patients with transient ischaemic attacks, or brain infarction, and the control group. All the patients examined were divided according to sex and age. As far as sex was concerned, males suffering from cerebral transient or completed focal ischaemia, had on average a lower serum uric acid level compared to the control group. The opposite happened with females. As far as age was concerned, significantly high serum uric acid levels, compared to the control group, were observed in women with either transient ischaemic attacks or brain infarction, but only in those whose age range was between 50 and 60. In conclusion, from this study, hyperuricemia does not appear to be a high risk factor in ischaemic cerebrovascular diseases.

Adult↗
PubMed1992

Chemodissolution of urinary uric acid stones by alkali therapy.

Experience with chemodissolution of uric acid stones in 30 patients is presented. Chemodissolution was achieved either with infusion of 0.16 M i.v. lactate or oral sodium bicarbonate, in addition to liberal fluid intake and allopurinol wherever indicated. In some cases direct chemodissolution by in situ irrigation with sodium bicarbonate solution was done after an initial percutaneous nephrostomy. Seven patients presented with acute obstructive anuria. In this group, 5 of them had bilateral obstructive calculi, while 2 had unilateral obstruction in a solitary kidney. The latter 2 had complete recovery following intravenous lactate therapy. Of the 5 presenting with bilateral obstruction, 2 patients had complete response to chemodissolution, whereas the remaining 3 had only a partial response requiring surgery for ultimate salvage. In this group I, 6 patients are doing well with a normal serum creatinine at 3 months to 4 years follow-up, while 1 patient has a serum creatinine, stabilised at 3.2 mg%. In the second group, 23 patients presented with non-obstructing urinary stones. Flank pain was the commonest complaint and a concomitant history of gout was present in 6 patients. Hyperuricaemia was detected in 12 and hyperuricosuria in 19. All cases were managed by high fluid intake and oral sodium bicarbonate, with self-monitoring of urine pH, which was kept between 6.5 and 7.0. Allopurinol was administered in cases having hyperuricaemia and/or hyperuricosuria. Systemic alkali therapy in the form of intravenous molar lactate or sodium bicarbonate is effective and safe both in obstructive anuria and non-obstructive urinary uric acid stones.

Aged↗
PubMed2004

Nitric oxide, lipid peroxides, and uric acid levels in pre-eclampsia and eclampsia.

The aim was to study the role of nitric oxide (NO), lipid peroxides (LPX), and uric acid in pre-eclampsia and eclampsia. Plasma levels of NO metabolites (nitrite+nitrate), malonyldialdehyde (MDA), and uric acid and erythrocyte MDA levels were compared between normal pregnant, pre-eclamptic, and eclamptic pregnant women in third trimester. Student's t-test was used for statistical evaluation. Plasma NO metabolites levels were higher in eclamptic group (35.7 +/- 16.5 micromol/liter, p < 0.05) but not in pre-eclamptic group (22.1 +/- 10.8 micromol/liter) than control group (18.8 +/- 6.9 micromol/liter). Plasma MDA and uric acid concentrations were higher in preeclamptic (4.4 +/- 1.7 nmol/ml, p < 0.05; 0.45 +/- 0.11 mmol/liter, p < 0.05, respectively) and eclamptic (5.8 +/- 1.9 nmol/ml, p < 0.05; 0.47 +/- 0.12 mmol/liter, p < 0.05) groups compared with control group (3.0 +/- 1.3 nmol/ml; 0.35 +/- 0.06 mmol/liter). Erythrocytes MDA concentrations were higher only in eclamptic group (174.4 +/- 62 nmol/gHb, p < 0.05) than control group (139.2 +/- 49.5 nmol/gHb). These results suggest that NO, LPX, and uric acid are important factors in the pathogenesis of pre-eclampsia and eclampsia, and that NO production and LPX are directly related to the severity of disease.

Adult↗
PubMed1985

Determination of uric acid in human serum by isotope dilution-mass spectrometry. Definitive methods in clinical chemistry, III.

A method for the measurement of uric acid in human serum by isotope dilution-mass spectrometry is described. The analytical procedure consists of the following steps: Addition of [1,3-15N2]uric acid to the serum sample; ion exchange chromatography on AG1-X2; formation of the trimethylsilyl derivative; gas liquid chromatography-mass spectrometry (GC-MS), selected ion monitoring (SIM) at m/z-values 456 and 458; calculation of the amount of uric acid in the serum sample from the isotope ratio, as measured by GC-MS. The accuracy of the method is obtained by the use of the highly specific technique of selected ion recording in combination with the exact control of recovery as performed by the isotope dilution procedure. On the basis of the high accuracy of the isotope dilution-mass spectrometry technique, the method presented here may be proposed as a definitive method in clinical chemistry. The imprecision of the method was estimated by measuring replicates in 18 lyophilised serum pools on different occasions. The coefficient of variation proved to be between 0.6 and 1.1% in the concentration range of 200 to 500 mumol/l. The lower limit of detection (ratio of signal to noise 3:1) of SIM was about 10 ng uric acid per sample.

Chromatography, Ion Exchange↗