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An amperometric uric acid biosensor based on modified Ir-C electrode.

The level of uric acid (UA) has a high relationship with gout, hyperuricemia and Lesch-Nyan syndrome. The determination of UA is an important indicator for clinics and diagnoses of kidney failure. An amperometric UA biosensor based on an Ir-modified carbon (Ir-C) working electrode with immobilizing uricase (EC 1.7.3.3) was developed by thick film screen printing technique. This is the first time to report the utilization of an uricase/Ir-C electrode for the determination of UA by using chronoamperometric (CA) method. The high selectivity of UA biosensor was achieved due to the reduction of H(2)O(2) oxidation potential based on Ir-C electrode. Using uricase/Ir-C as the sensing electrode, the interference from the electroactive biological species, such as ascorbic acid (AA) and UA (might be directly oxidized on the sensing electrode) was slight at the sensing potential of 0.25 V (versus Ag/AgCl). UA was detected amperometrically based on uricase/Ir-C electrode with a sensitivity of 16.60 microAmM(-1) over the concentration range of 0.1-0.8 mMUA, which was within the normal range in blood. The detection limit of UA biosensor was 0.01 mM (S/N=6.18) in pH 7 phosphate buffer solution (PBS) at 37 degrees C. The effects of pH, temperature, and enzymatic loading on the sensing characteristics of the UA biosensor were also investigated in this study.

Biosensing Techniques↗

Effect of oxametacin on endogenous uric acid clearance rate in healthy volunteers.

Oxametacin, a new non steroidal anti-inflammatory compound, with analgesic, antipyretic and anti-inflammatory properties comparable to those of indomethacin, has been claimed to be effective in treatment of acute attacks of gout. The present study comprises an investigation in 8 healthy volunteers of the effect on the endogenous uric acid clearance rate, of oxametacin administered alone or in combination with the conventional hypouricaemic agents benzbromarone or allopurinol. Whether given alone or in combination with these drugs, oxametacin failed to alter the clearance rate of endogenous uric acid. In view of its good tolerance and its possible efficacy in treatment of acute attacks of gout, the present data help to validate use of oxametacin in acute gout.

Adult↗

Maternal and umbilical plasma concentrations of uric acid and oxypurines at delivery in normal and hypertensive pregnancy.

Concentrations of uric acid (UA) and oxypurines (OP) were enzymatically determined in arterial and venous cord plasma, and in maternal plasma at delivery in normal (n = 45) and hypertensive (n = 22) pregnant women. Concentrations of UA in all samples were significantly higher in hypertensive than in normal pregnancies. Concentrations of OP in hypertensive pregnancies showed a nonsignificant increase as compared with normal pregnancies. There were no significant differences between concentrations of UA or OP in paired samples of arterial or venous cord plasma and maternal plasma. This finding suggests an easy transfer of UA and OP across the placenta during labor, which is at variance with earlier experimental data obtained in the pregnant rhesus monkey. The hypothesis is put forward, that labor and delivery could influence the facility of placental transfer of UA and OP.

Female↗

Change in the transport of uric acid under the influence of pyrazinoic acid: in vitro studies with human and rabbit peritoneum.

Bidirectional transport of uric acid (UA) through human and rabbit peritoneum, and its change under the influence of pyrazinoic acid (PA) was investigated in vitro. Fragments of parietal peritoneum were taken from the region of anterior abdominal wall from rabbits (the animal series) and from patients undergoing abdominal operations (the human series). Under control conditions, higher values of the UA transport were found in the rabbit peritoneum in comparison with the human peritoneum, but in both series it was maintained at a constant level throughout the experiment lasting 120 min. In rabbit as well as in human peritoneum it was found that PA depressed about 50% of the UA transport from the interstitial to the mesothelial side, leaving the opposite direction intact. The results obtained in vitro are in agreement with previous observations in a patient undergoing peritoneal dialysis that showed decreased peritoneal UA excretion evoked by pyrazinamide. The comparative analysis proves the rabbit peritoneum to be a good experimental model for further investigations of peritoneal urate transport in man.

Adult↗

[Uric acid metabolism in children with hyperuricosuria].

We treated 39 children with hyperuricosuria (18 boys and 21 girls aged between 6 and 11 years). Treatment consisted of increased fluid intake, low salt and low purine diet and urine alkalization up to pH 6.5-6.8. We have selected two groups of patients with different uric acid [UA] metabolism parameters. In group I (21 children) mean value of serum UA was 2.52 mg/dL, mean urine UA excretion was 13.11 mg/kg/d and UA FE was 21.51%. In group II (18 children) mean value of serum UA was 4.7 mg/dL, mean urine UA excretion was 12.8 mg/kg/d and UA FE was 10.9%. In group I, treatment did not normalize uricosuria (13.57 mg/kg/d), urine pH was elevated (6.56). In group II uricosuria was diminished (8.37 mg/kg/d), urine pH was 6.37. 1. Disturbances of tubular secretion may be suspected in some children with hyperuricosuria and without hypouricemia. 2. The maintenance of urine pH within normal values is the basic of treatment in children with hyperuricosuria. 3. In children suspected of tubular transport disturbances appropriate tests of uric acid metabolism should be performed.

Child↗

[Significance of uric acid concentration in the serum for the early recognition of the risk of EPH gestosis].

102 patients with EPH-gestosis in different stages of severity and 29 patients with normal pregnancy were examined regularly in a longitudinal study. 54 clinical and laboratory parameters were continuously measured. The concentration of uric acid in serum has proven to be the most important parameter in the early detection of the risk of gestosis. This serum concentration correlates with blood pressure and in individual cases shown to be of additional predictive value. Significant differences, compared to normal pregnancy, exist already in the 17th to the 24th week. Until now these differences had been described for a much later period. Other laboratory parameters have not been useful at this early stage in the detection of likely development of EPH-gestosis. Hyperuricemia is primarily due to the isolated reduction of uric acid clearance by normal glomerular filtration rate. Thus it is assumed that hyperuricemia is an indication of renal cortical blood flow dysfunction which parallels the decreased perfusion of the placenta.

Eclampsia↗

Is the plasma uridine level a marker of the overproduction of uric acid?

To determine whether the plasma level of uridine can be used to identify patients with gout, the plasma concentration of uridine was determined in patients with gout and normal subjects. Plasma uridine was significantly higher in patients with gout than in normal subjects. It was also significantly higher in patients with gout of the overexcretion (of uric acid) type than in those with gout of the underexcretion type. Plasma uridine was used to classify gout patients into underexcretion and overexcretion types, with a diagnostic accuracy of 92.5%. Results indicate that the plasma uridine concentration may be a marker of uric acid production and can be used to separate hyperuricemia into the overexcretion and underexcretion types.

Adult↗

Uric acid levels in sera from patients with multiple sclerosis.

The levels of uric acid (UA), a natural peroxynitrite scavenger, were measured in sera from 240 patients with multiple sclerosis (MS) and 104 sex- and age-matched control patients with other neurological diseases (OND). The mean serum UA concentration was lower in the MS than in the OND group, but the difference did not reach the level of statistical significance (P = 0.068). However, the mean serum UA level from patients with active MS (202.6 + 67.1 mumol/l) was significantly lower than that in inactive MS patients (226.5 + 78.6 mumol/l; P = 0.046) and OND controls (P = 0.007). We found a significant inverse correlation of serum UA concentration with female gender (P = 0.0001), disease activity (P = 0.012) and duration (P = 0.017), and a trend towards an inverse correlation with disability as assessed by EDSS score, which did not reach statistical significance (P = 0.067). Finally, multivariate linear regression analyses showed that UA concentration was independently correlated with gender (P = 0.0001), disease activity (P = 0.014) and duration of the disease (P = 0.043) in MS patients. These findings suggest that serum UA might serve as a possible marker of disease activity in MS. They also provide support to the potential beneficial therapeutic effect of radical-scavenging substances in MS.

Adolescent↗

Effect of aging on serum uric acid levels: longitudinal changes in a large Japanese population group.

BACKGROUND: Serum uric acid (SUA) is related not only to an increased risk of gout, but also to an increased risk of cardiovascular diseases. However, real age-related changes in SUA remain unknown. METHODS: Longitudinal population-based study of epidemiological follow-up data of SUA, body mass index (BMI), and alcohol intake was conducted at a health examination center between 1989 and 1998. The subjects were 80,506 Japanese office workers or their families (50,157 men and 30,349 women) with an average age of 44.5 years for the men and 43.7 years for the women. RESULTS: SUA increased with age in all birth cohorts examined in men, and in women except for the youngest birth cohort (1960-1969). BMI and alcohol consumption positively contributed to the longitudinal changes of SUA. However, SUA also increased with age in the model controlled for BMI and alcohol consumption. There were birth cohort effects of SUA; at most ages, there were higher SUA levels in younger cohorts in men and lower SUA levels in younger cohorts in women, respectively. CONCLUSIONS: SUA levels in men and women increased with advancing age, despite changes in drinking and in the BMI. There are birth cohort effects for SUA levels in the Japanese population.

Adult↗

Serum uric acid and risk of ischemic stroke: the ARIC Study.

AIMS: Since serum uric acid (UA) is strongly associated with cardiovascular risk factors, it has been debated whether serum UA is a stroke risk factor or whether UA may be simply "marking" subjects with other, causal risk factors. We therefore investigated the relation between UA and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS AND RESULTS: Of 15,792 ARIC participants, 13,413 who were free of recognized stroke or coronary heart disease (CHD) at baseline and had a baseline UA measurement were included in the analysis. We followed the participants for ischemic stroke incidence (N=381) over 12.6 years. Although serum UA was independently and positively related to ischemic stroke incidence when we adjusted for age, sex, race, and education, the positive relation was weakened when additionally adjusted for possible confounding variables. The positive multivariate-adjusted association between serum UA and ischemic stroke was observed among subjects not using diuretics (adjusted relative hazard in the highest quartile versus the lowest: relative hazard (RH)=1.49; 95% confidence interval (CI): 1.00-2.23) (P for trend: 0.02), but not among diuretic users (P for interaction: 0.08). CONCLUSION: Our findings suggest that UA is an independent predictor of ischemic stroke among subjects not using diuretics, but that elevated UA itself may not cause ischemic stroke.

Biomarkers↗

Serum uric acid level increases in proportion to the severity of pulmonary thromboembolism.

Serum uric acid (UA) has been proposed as a marker for impaired oxidative metabolism and the present study investigated whether serum UA level increases in proportion to the severity of pulmonary thromboembolism (PTE) in 193 patients. Serum UA was repeatedly measured after treatment of PTE in 76 patients. Right heart catheterization was performed in a subgroup of patients (n=104). Serum UA on admission was significantly elevated in patients with acute PTE (6.2+/-2.3 mg/dl) and those with chronic PTE (7.0+/-2.1 mg/dl) compared with age-matched controls (4.5+/-0.9 mg/ml). In particular, serum UA was markedly higher in the 27 patients who died during hospitalization than in the remaining survivors (8.3+/-2.2 vs 6.5+/-2.2 mg/dl, p<0.001). In acute PTE, serum UA negatively correlated with cardiac output, but not significantly with mean pulmonary arterial pressure. In chronic PTE, serum UA negatively correlated with cardiac output and positively correlated with mean pulmonary arterial pressure. Serum UA significantly decreased from 6.7+/-2.0 to 5.8+/-1.9 mg/dl with treatment, associated with an increase in cardiac output and in PaO2. Serum UA increases in proportion to the severity of PTE, and thereby may serve as a potential indicator of the efficacy of treatment of PTE.

Acute Disease↗

Postmortem serum uric acid and creatinine levels in relation to the causes of death.

Serum uric acid (UA) and creatinine (Cr) mainly derive from skeletal muscle tissues. Although, remarkable postmortem stability of the serum levels has been reported, there appears to be very poor knowledge of the diagnostic value in investigation of death, except for uremia. The aim of the present study was to evaluate postmortem serum UA and Cr levels using 395 forensic autopsy cases, in comparison with blood urea nitrogen (BUN), for investigation of the pathophysiology of death with special regard to the causes of death involving possible skeletal muscle damage, e.g. due to hypoxia, heat or agonal convulsions. Cr and BUN showed relatively good topographic stability in the cadaveric blood, whereas, UA was often much higher in the right heart blood than in the left heart and peripheral blood, independent of postmortem intervals. Moderate to marked elevation of Cr and BUN accompanied with hyperuricemia was observed in delayed death. In the acute death cases (survival time <30 min), UA, especially in the right heart blood, showed a considerable elevation in mechanical asphyxiation and drowning. The Cr level in fire victims with a lower carboxyhemoglobin (COHb) level (<60%) was significantly higher than in those with the possible fatal level (>60%). A similar elevation of Cr was observed in fatalities from heat stroke and methamphetamine (MA) poisoning. The observations suggested that hyperuricemia in acute death may be indicative of advanced hypoxia and that elevated Cr level may reflect the skeletal muscle damage, especially due to thermal influence.

Autopsy↗

Prognostic usefulness of serum uric acid after acute myocardial infarction (the Japanese Acute Coronary Syndrome Study).

Serum uric acid (UA) levels reflect circulating xanthine oxidase activity and oxidative stress production. Hyperuricemia has been identified in patients who have congestive heart failure and is a marker of poor prognosis in such patients. We investigated the relation between serum UA levels and Killip's classification suggestive of the severity of heart failure and whether hyperuricemia influences mortality of patients who have acute myocardial infarction (AMI). Using the Japanese Acute Coronary Syndrome Study database, we evaluated 1,124 consecutive patients who were hospitalized within 48 hours of onset of symptoms of AMI from January to December 2002. There was a close relation between serum UA concentration and Killip's classification. Patients who developed short-term adverse events had high UA concentrations. Serum UA levels, Killip's class, age, and peak creatine phosphokinase level were significant predictors of long-term mortality. The hazard ratio for patients in the highest quartile of UA was 3.7 compared with those in the lowest quartile for death after AMI after adjustment for independent factors that were related to mortality. The combination of the best UA cutoff (447 micromol/L) for predicting survival based on receiver-operating characteristics analysis and Killip's class significantly predicted the prognosis of acute and long-term AMI-related complications. In conclusion, our results suggest that hyperuricemia after AMI is associated with the development of heart failure. Serum UA level is a suitable marker for predicting AMI-related future adverse events, and the combination of Killip's class and serum UA level after AMI is a good predictor of mortality in patients who have AMI.

Aged↗

Relationship of serum uric acid to measures of endothelial function and atherosclerosis in healthy adults.

Although uric acid (UA) is considered as an antioxidant, the relationship between serum UA levels and cardiovascular diseases is not clear yet. Higher brachial artery resting diameter (BD), impaired brachial artery flow-mediated dilatation (FMD), increased carotid intima-media thickness (IMT), decreased aortic distensibility (AoD), and increased aortic stiffness index (AoSI) and elastic modulus (AoEM) are predictors for development and/or progression of atherosclerosis. In this study, BD, FMD, carotid IMT, AoD, AoSI and AoEM were studied in healthy subjects with UA concentrations in physiological range. One hundred 24 healthy volunteers between 26 and 55 years of age were included in this study. Each subject had a serum UA levels in normal range. Carotid IMT, BD and brachial FMD were measured by means of high-resolution vascular ultrasound. AoD, AoSI, AoEM were examined by transthoracic echocardiography. Endothelium-dependent dilatation (EDD) was assessed by establishing reactive hyperemia and endothelium-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. Although carotid IMT and EDD were significantly correlated with UA concentrations (r = 0.346, p < 0.0001; r = -0.255, p < 0.05, respectively), EID measurements were not significantly correlated with serum UA concentrations (r = - 0.105, p > 0.05). In addition, AoSI and AoEM were significantly correlated with serum UA levels (r = 0.368, p < 0.0001; r = -0.366, p < 0.0001, respectively), and there was a significant inverse correlation between AoD and serum UA concentrations (r = -0.366, p < 0.0001). Furthermore, in multivariate analysis, we found that serum UA concentrations were correlated with increased carotid IMT, reduced FMD and increased aortic stiffness independent of other cardiovascular risk factor (beta = 256, p = 0.002; beta = -193, p = 0.03; beta = 0.295, p < 0.0001, respectively). In healthy subjects, increased serum UA concentrations, even in physiological range, are a risk factor for increased carotid IMT, reduced FMD and increased aortic stiffness independent of other cardiovascular risk factor, and other factors related to the metabolic syndrome.

Adult↗

Application of a novel 1,1'-dimethylferricinium dye for the determination of uric acid in urine.

Water-soluble 2-hydroxypropyl-beta-cyclodextrin (Hp-beta-CyD), a cyclic and nonreducing oligosaccharide was used to enclose a hydrophobic guest molecule 1,1'-dimethylferrocene (DMF) to form a water-soluble yellow complex. At high concentrations (300 mM), Hp-beta-CyD enclosed up to 100 mM DMF. The yellow complex was electrochemically oxidized (platinum vs Ag/AgCl poised at +450 mV) to form a blue dye, 1,1'-dimethylferricinium (DMF+). This is a one-electron transfer process and the ferricinium cation formed exhibited an absorption peak at 650 nm. The concentrated DMF+ was stable for at least 4 mo at 4 degrees C and insensitive to a wide pH variation (pH 2-11). Application of the novel DMF+ complex as a colorimetric dye for the determination of uric acid in urine was successfully demonstrated. The reaction between the dye and uric acid is almost instantaneous and decrease in absorbance caused by the reduction of 1,1'-dimethylferricinium to 1,1'-dimethylferrocene can be followed at 650 nm. The results obtained agreed well with those of the reference reversed-phase HPLC method.

2-Hydroxypropyl-beta-cyclodextrin↗

Effect of storage time on red blood cell membrane permeability to creatinine and uric acid.

Although there is considerable evidence that blood storage affects red blood cell viability, deformability, and geometry, available data on the effect of blood storage on solute transport across the red blood cell membrane are highly limited. The authors used a stirred ultrafiltration device, with direct cell-free fluid sampling through a semipermeable ultrafiltration membrane, to obtain accurate data on red blood cell membrane permeability to both creatinine and uric acid. Results for influx and efflux experiments can be adequately explained by a passive transport mechanism. The red blood cell membrane permeability to uric acid increased substantially during storage, whereas trends in creatinine permeability were less clear and suggested possible differences between solute efflux and influx experiments. These results provide important insights into the physical and biochemical changes that occur in the red blood cell membrane during storage and also have important implications for analyses of solute removal in hemodialysis.

Blood Preservation↗