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Studies on the impaired metabolism of uric acid in obese subjects: marked reduction of renal urate excretion and its improvement by a low-calorie diet.

Uric acid metabolism was investigated in 27 overweight subjects, 11 men (176 +/- 30 percent of ideal body weight) and 16 women (169 +/- 20 percent of ideal body weight). They were all hospitalized and treated with low-calorie diets (1,500-800 kcal/day) with gradual reduction of total calorie intake; exercise therapy (walking, and riding a bicycle ergometer) was added to this regimen afterwards. On admission, serum levels of uric acid were significantly elevated to 9.2 +/- 1.9 mg/dl in males (control 5.1 +/- 0.8 mg/dl) (P less than 0.001) and 6.8 +/- 1.9 mg/dl in females (control 4.4 +/- 1.0 mg/dl) (P less than 0.001), while the ratios (percentages) of uric acid clearance (CuA) to creatinine clearance (Ccr) were significantly reduced to 4.0 +/- 2.1 percent in males (control 10.8 +/- 2.2 percent) (P less than 0.001) and 5.2 +/- 3.1 percent in females (control 11.8 +/- 2.9 percent) (P less than 0.001). Urinary urate excretions were also lower in obese subjects than in controls. These data suggest that hyperuricemia in obese people is mainly attributed to an impaired renal clearance of uric acid rather than overproduction. In the course of weight reduction by a low-calorie diet, CuA/Ccr ratios gradually rose up to almost normal levels and serum levels of uric acid fell without significant changes in creatinine clearance. This increase of CuA/Ccr ratio was also preserved after starting exercise therapy. The normalization of urate excretion was observed even at the phase when their body weight was not fully reduced. Although the underlying mechanism of the impaired urate excretion in obese patients and its improvement during weight reduction is as yet unclear, hyperuricemia associated with obesity can be treated very well only with appropriate diet therapy and in most cases there is no need for drug therapy.

Adolescent↗

[Inherited disorders of uric acid metabolism--classification, enzymatic- and DNA-diagnosis].

Uric acid is the end product of purine metabolism in human. Then, the enzymatic abnormalities, concerning purine metabolism, cause disorders of uric acid metabolism including hyperuricemia and hypouricemia. The superactivity of 5-phosphoribosyl-pyrophosphate (PRPP) synthetase and deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) caused hyperuricemia. In glycogen storage diseases of type I, III, V, and VII, decreased energy supply induces hyperuricemia by accelerating ATP degradation. Deficiencies of xanthine oxidase (XO), purine nucleoside phosphorylase (PNP), and PRPP were reported causing hypouricemia. Many methods for DNA-diagnosis were developed including Southern blot, Northern blot, PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism), PCR-RFLP (restriction fragment length polymorphism), and allele specific oligonucleotide hybridization etc.

Adenosine Triphosphate↗

Serum uric acid levels in normal pregnancy with observations on the renal excretion of urate in pregnancy.

Serum uric acid estimations were performed in 106 healthy pregnant women during early, middle, and late pregnancy, using an automated colorimetric method. The mean serum uric acid level was significantly lower during early and middle pregnancy than that of 64 age-matched female controls. The serum uric acid level was not significantly different in late pregnancy from the control group. Studies of the daily urinary urate excretion in 31 pregnant women showed normal urinary urate excretion in early pregnancy and enhanced renal loss of urate in middle and late pregnancy. It appears that the renal clearance of urate in pregnancy is high, especially in the middle period when the serum level is low in spite of the increased production of uric acid by the foetus.

Adolescent↗

Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study.

BACKGROUND: Despite abundant epidemiologic evidence, the role of elevated serum uric acid level as a cardiovascular risk factor is controversial. We assessed the predictive value of serum uric acid levels for cardiovascular and overall mortality. METHODS: A population-based prospective cohort study was performed of 1423 middle-aged Finnish men initially without cardiovascular disease, cancer, or diabetes. The main outcome measure was death from cardiovascular disease and any cause. RESULTS: The mean follow-up was 11.9 years. There were 157 deaths during follow-up, of which 55 were cardiovascular. In age-adjusted analyses, serum uric acid levels in the upper third were associated with a greater than 2.5-fold higher risk of death from cardiovascular disease than levels in the lower third. Taking into account cardiovascular risk factors and variables commonly associated with gout increased the relative risk to 3.73. Further adjustment for factors related to the metabolic syndrome strengthened the risk to 4.77. Excluding the 53 men using diuretics did not alter the results. In age-adjusted analyses, men with serum uric acid levels in the upper third were 1.7-fold more likely to die of any cause than men with levels in the lower third. Adjustment for further risk factors strengthened the association somewhat. CONCLUSIONS: Serum uric acid levels are a strong predictor of cardiovascular disease mortality in healthy middle-aged men, independent of variables commonly associated with gout or the metabolic syndrome. Serum uric acid measurement is an easily available and inexpensive risk marker, but whether its relationship to cardiovascular events is circumstantial or causal remains to be answered.

Biomarkers↗

Assay for uric acid level in rat striatum by a reagentless biosensor based on functionalized multi-wall carbon nanotubes with tin oxide.

A novel reagentless amperometric uric acid biosensor based on functionalized multi-wall carbon nanotubes (MWCNTs) with tin oxide (SnO2) nanoparticles has been developed. This was successfully applied to assay uric acid levels from an in vivo microdialysis sampling. Compared with unfunctionalized or traditional carboxylic acid (-COOH)-functionalized MWCNTs, the MWCNTs-SnO2 electrode exhibited higher electrocatalytic oxidation to uric acid. Here, MWCNTs-SnO2 may act as an efficient promoter, and the system exhibited a linear dependence on the uric acid concentration over the range from 1.0 x 10(-7) to 5.0 x 10(-4) mol L(-1). In addition, there was little ascorbic acid interference. The high sensitivity of the MWCNTs-SnO2 modified enzyme electrode enabled the monitoring of trace levels of uric acid in dialysate samples in rat striatum.

Animals↗

Serum uric acid levels in obese children and adolescents: linkage to testosterone levels and pre-metabolic syndrome.

Hyperuricemia is part of the "metabolic syndrome". The aim of this study was to investigate the regulation and role of serum uric acid in the cardiovascular risk factor profile of obese children and adolescents. Serum levels of uric acid and selected risk factors and hormones were determined in 269 children aged 10.0-15.9 years with a BMI >90th percentile (mean 24.0 kg/m2, SD 5.43). Stepwise regression adjusted for age and sex revealed that testosterone (p < 0.0001), BMI (p < 0.0001), systolic blood pressure (p < 0.0017), triglycerides (p < 0.0345) and cholesterol/HDL ratio (p < 0.0393) were positively correlated with serum uric acid and accounted for 42.1% of the variance. Additional regression models with the same set of variables indicated that uric acid contributed significantly to levels of cholesterol/HDL, total cholesterol, BMI and systolic blood pressure, respectively. These results suggest a not yet described impact of androgens in the regulation of serum uric acid in obese children and adolescents. Furthermore, they show that uric acid is a reliable indicator for the "pre-metabolic syndrome" in obese youths.

Adolescent↗

Quantitative measurements of the urinary excretion of creatinine, uric acid, hypoxanthine and xanthine, uracil, cyclic AMP, and cyclic GMP in healthy newborn infants.

Serum creatinine, uric acid, and hypoxanthine and xanthine concentrations were determined in 17 mother-infant pairs at the time of delivery. Creatinine and uric acid levels were nearly similar, but hypoxanthine and xanthine were more than twice as high in the blood of the infants than in the blood of their mothers. In the same newborns the urinary excretion of creatinine, uric acid, hypoxanthine and xanthine, uracil, cAMP, and cGMP was measured on the first and fourth day of life. Creatinine, uracil, and cAMP increased, hypoxanthine and xanthine, and cGMP decreased, whereas the output of uric acid was nearly the same on both days. Correlations of the excreted substances to each other were calculated.

Cesarean Section↗

[Influence of dietary habits and body weight on blood uric acid in the elderly].

Influence of dietary habits, body weight on blood uric acid was studied in 416 elderly people. The result showed that level of blood uric acid in the people who had habits of drinking alcohol, tea and taking hot foods was higher than that who never had those habits (P < 0.05 or 0.01). It also showed that level of blood uric acid was significantly increased in the over-weight or obesity people (P < 0.05). The hyperuricemia incidence in the over-weight or obesity people is 27.4 per cent, and it is 2 times and 3.4 times of the people with ideal weight and weak-weight, respectively. It is suggested that the patients with gout or hyperuricemia give up drinking alcohol, tea and taking hot foods for their health. Reducing body weight is one of the effective measures to prevent and treat gout or hyperuricemia in the elderly.

Aged↗

Relation between serum uric acid and plasma adenosine levels in women with preeclampsia.

The aim of this study was to examine the relationship between plasma adenosine and serum uric acid levels in women with preeclampsia. Maternal arterial blood sampling was performed to measure serum uric acid and plasma adenosine levels in 20 pregnant women complicated by preeclampsia and 22 normal pregnant women at 33-38 weeks of gestation. The average plasma adenosine levels were 0.31 +/- 0.12 micromol/l in the normal pregnant group and 0.45 +/- 0.11 micromol/l in the preeclampsia group. The mean serum uric acid level in women with preeclampsia was 5.9 +/- 0.60 mg/dl, significantly higher than in the normal pregnant women (4.4 +/- 0.69 mg/dl). Positive correlations were found between serum uric acid and plasma adenosine levels in both the group with (r(2) = 0.38, p < 0.05) and the group without (r(2) = 0.54, p < 0.05) preeclampsia. There was also a significant correlation between serum uric acid and plasma adenosine levels on the whole (r(2) = 0.59, p < 0.05). Our results suggest that increased adenosine is a contributing source of preeclamptic hyperuricemia.

Adenosine↗

The effect of normal pregnancy upon the renal handling of uric acid.

Twenty-four women were investigated serially during and after normal pregnancy. Plasma uric acid concentration appeared to be inversely related to uric acid clearance under infusion conditions, and comparison with simultaneous inulin clearance suggested an alteration in renal function resulting in increased 'net tubular reabsorption' of uric acid as pregnancy progressed. No difference was detected between primigravidae and multigravidae. The implications of these changes are discussed with reference to the renal handling of uric in pre-eclampsia.

Adult↗

Use of azure-D2 for the measurement of uric acid in serum.

It has been suggested that achieving a chromogenic endpoint with an absorbance read at 600 nm or greater will reduce the degree of spectral interference in many colorimetric methods. We have examined a uricase/peroxidase-based system utilising a novel oxygen acceptor (azure-D2) as chromogen which produces a chromophor with an absorbance which can be measured at 600 nm (Synermed). Results (median, range, mumol/l) obtained on patient sera (n = 113) using the Synermed method (297; 38-847) were lower than those obtained using a 293 nm uricase method (Du Pont Ltd., 312; 62-874) (p < 0.001, Synermed = -16.709 + 1.0065 Du Pont). Within- and between-batch CV's were < 3% in all cases. Results obtained in one external quality assessment scheme (WEQAS) were significantly lower (p < 0.001) than the method group mean (Synermed = -17.298 + 1.0056 WEQAS) but in a second scheme (NEQAS) results did not differ significantly (p > 0.05) from the method group mean (Synermed = -29.315 + 1.0570 NEQAS). Bilirubin had a negative effect (p < 0.0001; 300 mumol/l producing a 23 mumol/l reduction in uric acid) and haemoglobin had a small positive effect (p < 0.05; 5 g/l increasing uric acid by 8 mumol/l) on the assay. Lipaemia did not interfere (p > 0.05) but both ascorbic acid (100 mumol/l reducing uric acid by 68 mumol/l) and N-acetylcysteine (3 mmol/l reducing uric acid by 95 mumol/l) had significant negative effects (p < 0.0001 in both cases). Uraemic serum had no effect on the assay (p > 0.05) but serum storage for 72 hours at room temperature resulted in a significant (p < 0.0005) increase in measured uric acid. The Synermed method is a precise and accurate assay for serum uric acid. However, although generally showing low levels of spectral interference, chemical interferences in the assay from antioxidant components of serum may be problematic. This paper shows that the use of longer wavelengths of detection can reduce the significance of common spectral interferences.

Azure Stains↗

Serum uric acid levels in normal pregnancy.

Sixty-four patients were assessed throughout pregnancy to determine normal serum uric acid levels (mean +/- 2SD). Serum uric acid levels increased significantly from early pregnancy levels of 0.13-0.33 nmol/L to levels of 0.18-0.45 mmol/L at full-term (p less than 0.005). Factors implicated in uric acid homeostasis contributing to these changes are discussed.

Adolescent↗

Simultaneous determination of uric acid and ascorbic acid at a ferrocenium-thioglycollate modified electrode.

Self-assembled monolayers (SAMS) of chemisorbed thioglycollate on a gold electrode surface have been used as a base interface for the electrostatic adsorption of ferrocenium ion. Electrochemical impedance spectra (EIS) and cyclic voltammetry (CV) were used to evaluate the electrochemical properties of the supramolecular film. The bare gold electrode failed to distinguish the oxidation peaks of ascorbic acid (AA) and uric acid (UA) in phosphate buffer solution (PBS, pH 7.0), while the ferrocenium-thioglycollate modified electrode could separate them efficiently. In differential pulse voltammetric measurements, the prepared gold electrode could separate AA and UA signals, allowing the simultaneous determination of AA and UA. Under optimal conditions and within the linear range of 1.0 x 10(-6) to 5.0 x 10(-4) M, the detection limits of AA and UA achieved were 2.0 x 10(-7) and 1.0 x 10(-7) M, respectively. The applicability of the prepared electrode was demonstrated by measuring AA and UA in human urine without any pretreatment.

Journal Article↗

Uric acid as a prognostic factor for survival time: a prospective cohort study of terminally ill cancer patients.

The aim of this prospective cohort study was to determine whether serum uric acid level is useful as a predictor of survival in terminally ill cancer patients. One hundred eighteen terminally ill cancer patients, including 63 (53.4%) males, were categorized into four groups by serum uric acid levels and followed up until death or to the end of the study. Cox's proportional hazard model was adopted to evaluate the joint effect of some clinicobiological variables on survival. From an initial model containing 51 variables, a final parsimonious model was obtained by means of a stepwise method. Repetitive dispersion analysis was performed for serum uric acid level in 39 subjects for 3 weeks until death. During the study period, 113 (95.76%) subjects expired, and the median survival time was 14 days. In univariate analysis, survival time of the fourth highest group (> or =7.2mg/dL) was significantly shorter than that of the others (hazard ratio (HR)=2.784, P<0.001). After adjustment for low performance status, moderate to severe pain, prolonged prothrombin time, hypocholesterolemia, and high lactate dehydrogenase (LDH) level, high serum uric acid level (> or =7.2mg/dL) was significantly and independently associated with short survival time (HR=2.637, P=0.001). Serum uric acid levels were also significantly increased between the first and the second week before death. These findings suggest that serum uric acid level can be useful in predicting life expectancy in terminally ill cancer patients.

Adult↗

[Determination of uric acid by chemiluminescence].

A novel chemiluminescence method for the determination of uric acid based on its inhibitory effect on the catalysis of Co2+ for the oxidation of luminol by H2O2 is described. The proposed method is simple, very sensitive and inexpensive. The decrease of cheniluminescence intensity is linearly correlated with uric acid concentration. The calibration graph is linear over the range of 1.0 x 10(-10) - 7.0 x 10(-6) mol x L(-1) and the detection limit is 1.1 x 10(-11) mol x L(-1). The relative standard deviation (RSD) for 5.0 x 10(-8) is 1.9% (n=4). The method has been successfully applied to the determination of uric acid in human urine and serum samples.

Catalysis↗

Serum uric acid and risk of coronary heart disease: Atherosclerosis Risk in Communities (ARIC) Study.

PURPOSE: Approximately half of previous studies on serum uric acid have reported it to be an independent risk factor for coronary heart disease (CHD). We tested this hypothesis in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: A total of 13,504 healthy middle-aged men and women were followed prospectively for up to eight years. We identified 128 fatal and nonfatal CHD events in women and 264 in men. RESULTS: The age-, race-, and ARIC field center-adjusted relative risk of CHD for sex-specific quartiles of serum uric acid were 1.0, 1.39, 1.08, and 2.35 in women (p for trend = 0.009) and 1.0, 1.03, 0.89, and 1.21 in men (p for trend = 0.44), respectively. However, serum uric acid was correlated positively with many risk factors, and after multivariable adjustment, there was little evidence of an association of uric acid with CHD in either sex. CONCLUSIONS: Our results are not consistent with serum uric acid being an independent risk factor for CHD.

Aged↗

Impact of sodium-potassium citrate therapy on the circadian rhythm of urinary uric acid and urate saturation in normal individuals.

The circadian rhythm of the urinary saturation of uric acid, sodium acid urate, and ammonium acid urate was studied in 5 normal healthy male volunteers before and during 5 days of treatment with sodium-potassium citrate (1 g t.i.d., 1 g q.i.d., or 3 g t.i.d.). Urinary saturation was estimated on the relative supersaturation scale of Marshall and Robertson. Uric acid relative supersaturation varied during the day (mean +/- SD: -1.297 +/- 1.763) and peaked above the formation product between 5:30 and 8:00 am. The peak level was reduced (but not significantly) by each treatment regimen in comparison with the control day. Overall, critical supersaturation with uric acid was noted in 46 (13%) out of 345 urine specimens, occurring mostly (83%) between 5:30 and 8:00 am. The sodium acid urate relative supersaturation also varied during the day (mean +/- SD: 0.329 +/- 0.305) and peaked below the formation product between 8:00 and 10:30 am. It was increased by each regimen (significantly by the 3 g t.i.d. regimen), but mostly remained in or below the metastable zone. The ammonium acid urate relative supersaturation also varied (mean +/- SD: 0.087 +/- 0.301) and peaked below the formation product between 5:30 and 8:00 am. The level was decreased by each regimen and remained in or below the metastable zone throughout the day. In conclusion, the early morning period was the time with the highest risk of urinary uric acid supersaturation, but this supersaturation could be reduced (although not significantly) by treatment with alkali citrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Elevated serum uric acid levels during treatment with antihypertensive drugs.

An increase in serum uric acid levels has been observed both during treatment with diuretics and beta-blockers. The increase during treatment with beta-blockers seems in most cases to be of no clinical importance and is not a reason for serum uric acid determinations of subjects who have no symptoms indicating hyperuricaemia. During treatment with diuretics in those doses which have been commonly used previously, e.g. hydrochlorothiazide or chlorthalidone greater than or equal to 50 mg/d, an increase on an average of about 90 mumol/l is to be expected. When low-dose diuretics are used (e.g. hydrochlorothiazide or chlorthalidone less than or equal to 25 mg/d) about half of this increase might be anticipated. It is recommended that serum uric acid levels should be studied after starting antihypertensive treatment with diuretics.

Adrenergic beta-Antagonists↗