Drug interference with the phosphotungstate uric acid test.
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Identification of allantoin, uric acid, and indoxyl sulfate as biochemical indicators of filth in food packaging by LC.
A liquid chromatographic (LC) method was developed for the determination of allantoin, uric acid, and indoxyl sulfate in mammalian urine contaminated packaging material including paper bagging, corrugated cardboard, grayboard, and burlap bagging. The procedure involves solvent extraction and isolation of the 3 analytes by reversed-phase LC with ultraviolet detection at 225 nm for allantoin and 286 nm for uric acid and indoxyl sulfate. The composition of authentic mammalian urine such as mouse, rat, cat, dog, and human were also determined with regard to the 3 compounds of interest. A linear concentration range of 0.11-20.4, 0.02-10.0, and 0.04-30.0 microg/mL was obtained for allantoin, uric acid, and indoxyl sulfate, respectively. Limits of detection (LOD) and quantitation (LOQ) were 0.0104 and 0.0345 microg/mL for allantoin; 0.0018 and 0.0060 microg/mL for uric acid; and 0.0049 and 0.0165 microg/mL for indoxyl sulfate, respectively. Interday relative standard deviation values for a mixture of standard allantoin, uric acid, and indoxyl sulfate (n = 5) were 0.97, 0.80, and 0.94%, respectively. Analyte composition for 5 types of authentic mammalian urine varied from 0.19-6.88 mg/mL allantoin; 0.08-0.57 mg/mL uric acid; and 0.03-0.78 mg/mL indoxyl sulfate. Analyte content for 8 samples including 2 samples each for paper, cardboard, grayboard, and burlap bagging each contaminated with mouse or rat urine ranged from <LOD to 4,598 microg/gm allantoin; <LOD to 202 microg/gm uric acid; and 17.5 to 616 microg/gm indoxyl sulfate. Recoveries of allantoin, uric acid, and indoxyl sulfate from 11 fortified samples (4 types) for both mouse and rat urine ranged from 28.2 to 114.1 % for allantoin; 32.6 to 123.4% for uric acid; and 52.6 to 118.2% for indoxyl sulfate.
Allantoin↗
Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial.
OBJECTIVE: Gout affects a large fraction of persons with advanced chronic kidney disease, and hyperuricemia may increase the risk of cardiovascular disease. Several hypouricemic agents are contraindicated in patients with end-stage renal disease. Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract. Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid, another organic anion. We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term, randomized, clinical trial comparing sevelamer with calcium-based phosphate binders. METHODS: Two hundred subjects undergoing maintenance hemodialysis were randomly assigned to receive either sevelamer or calcium-based phosphorus binders in an international, multicenter, clinical trial. Data on baseline and end-of-study uric acid concentrations were available in 169 subjects (85%); the change in uric acid concentration from baseline to the end of the study was the outcome of interest. RESULTS: Baseline clinical characteristics, including mean uric acid concentrations, were similar in subjects randomly assigned to receive sevelamer and calcium-based phosphate binders. The mean change in uric acid concentration (from baseline to the end of the study) was significantly larger in sevelamer-treated subjects (-0.64 mg/dl versus -0.26 mg/dl; P = 0.03). The adjusted mean change in uric acid concentration was more pronounced when the effects of age, sex, diabetes, vintage (time since initiation of dialysis), dialysis dose, and changes in blood urea nitrogen and bicarbonate concentrations were considered (-0.72 mg/dl versus -0.15 mg/dl; P = 0.001). Twenty-three percent of sevelamer-treated subjects experienced a study-related reduction in the concentration of uric acid equal to -1.5 mg/dl or more, compared with 10% of calcium-treated subjects (P = 0.02). CONCLUSION: In a randomized clinical trial comparing sevelamer and calcium-based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.
Aged↗
Elevated serum uric acid levels impair coronary microvascular function in patients with idiopathic dilated cardiomyopathy.
In patients with idiopathic dilated cardiomyopathy (IDC), attenuated coronary flow reserve (CFR) and elevated serum uric acid levels have been reported. In this study, we investigated whether increased uric acid levels correlate with the degree of coronary microvascular dysfunction. Serum uric acid levels were measured in 29 patients with IDC (mean age: 57.0+/-10.8 years, 10 female), and each patient also underwent transthoracic echocardiographic examination including CFR measurement. The study population was divided into two groups according to the median CFR value (lower CFR group and higher CFR group). Uric acid levels were significantly higher in the lower CFR group than in the higher CFR group (7.59+/-2.56 vs 4.80+/-0.80 mg/dL, P=0.000). CFR correlated significantly and inversely to serum uric acid (r=-0.570, P=0.001). Logistic regression analysis revealed that uric acid level was the only independent predictor of CFR (B=-1080, P=0.015). We found a possibly clinically important negative association between serum uric acid levels and CFR in patients with IDC.
Adult↗
Nocturnal increase of urinary uric acid:creatinine ratio. A biochemical correlate of sleep-associated hypoxemia.
Sleep-associated hypoxemia may result in tissue hypoxia and increased production and excretion of adenosine triphosphate (ATP) degradation intermediates and uric acid. Urinary uric acid:creatinine(UA:Cr) ratio is a convenient method for estimating uric uric acid excretion. We measured the overnight changes in urinary UA:Cr ratio in 17 patients with documented sleep-associated hypoxemia, 13 control patients who remained normoxemic during polysomnography, and 14 normal volunteers. The urinary UA:Cr ratio increased overnight in patients with sleep-associated hypoxemia (+31.2 +/- 10.9%), whereas it decreased in the control patients with negative sleep studies (-13.6 +/- 4.6%; p less than or equal to 0.01) and in the normal volunteers (-23.2 +/- 5.8%). Repeat polysomnography revealed interval resolution of sleep-associated hypoxemia in 2 patients and significant improvement in a third. In every case, this clinical improvement was accompanied by a decrease in the overnight change in UA:Cr ratio. We report that urinary UA:Cr ratio increased overnight in a nonhomogeneous group of patients with sleep-associated hypoxemia.
Adult↗
Highly sensitive flow detection of uric acid based on an intermediate regeneration of uricase.
The principle of the signal amplification of a uric acid sensor based on dithiothreitol (DTT)-mediated intermediate regeneration of uricase was applied to a flow-injection system with an immobilized uricase reactor and a DTT-containing carrier. Highly sensitive detection for nM to microM order of uric acid was achieved when 10 mM TRIS-HCl buffer (pH 10.0) containing 20 mM DTT was used as a carrier at 0.6 ml min-1 and 37 degrees C. The sensitivity of the uric acid was much improved over a batch method using a uricase membrane-coupling electrode, and the detection limit (ca. peak current 8 nA) of uric acid was found to be down to 3 x 10(-10) M (amplification factor; more than 10,000). This chemically amplified flow-system is very useful for the direct assay of uric acid in highly diluted biological fluids (urine and serum) without complicated pretreatment of the samples, because this sensor has the potential to detect trace amounts (nM to microM) of uric acid in highly diluted body fluids in which the concentration of interfering constituents was decreased to negligible levels. Good correlation was observed between this system and conventional spectrophotometry. The immobilized uricase reactor could be re-used for at least 4 months of repeated analysis without loss of activity and was stable if stored at 4 degrees C in 10 mM TRIS-HCl buffer, pH 9.0.
Dithiothreitol↗
Elevated serum uric acid levels in gestational hypertension are correlated with insulin resistance.
The purpose of this study was to assess a possible correlation between insulin resistance and uric acid levels in gestational hypertension (GH) and preeclampsia. Fourteen pregnant, nondiabetic women with either GH (n = 7) or preeclampsia (n = 7) and nine pregnant healthy controls in the third trimester were enrolled onto the study. Fasting serum was collected and insulin sensitivity was determined by Homeostasis Model Assessment based on the algorithm developed by Turner and colleagues. Serum samples were also analyzed for creatinine and uric acid levels. Insulin resistance and uric acid levels were compared between hypertensive and control pregnant women, and the association between these two variables was calculated. There were no significant differences in mean age, weight, body mass index, and glucose challenge test between all hypertensive patients and controls. Significant differences were revealed in insulin sensitivity between hypertensive and nonhypertensive pregnant women (45 +/- 31.2% vs. 79.7 +/- 33%; p = 0.018). In our study, uric acid levels were not significantly higher for hypertensive patients (5.46 +/- 0.85 vs. 4.53 +/- 1.4 mg/dL in controls; p = 0.06). The elevated serum uric acid levels were highly correlated to insulin resistance in patients with GH. In contrast, uric acid levels did not correlate with insulin sensitivity in patients with preeclampsia and controls. Insulin resistance is associated with the elevated uric acid levels found in nonproteinuric gestational hypertensive disease.
Adult↗
[Serum uric acid concentration and anticonvulsant therapy in childhood].
In antiepileptic treated adults a decrease of serum uric acid concentration was reported. In contrast to these findings we did not find a general decrease of uric acid concentration in 233 studied epileptic children and juveniles treated with antiepileptic drugs. But we found a significant decrease of uric acid concentration in epileptic children and juveniles treated with carbamazepine in monotherapy as well as in combined treatment. Rather increased uric acid serum concentration were found in primidone and valproate monotherapy. In the studied age groups only carbamazepine seems to be able to diminish uric acid concentration. The underlying mechanisms are unknown.
Adolescent↗
New ultraviolet (340 nm) method for assay of uric acid in serum or plasma.
We propose a novel enzymatic method for assay of uric acid at 340 nm, which eliminates several disadvantages of both the colorimetric and enzymatic methods now in common use. Here, uric acid is catalytically oxidized to allantoin and hydrogen peroxide. The peroxide is reacted with ethanol in the presence of catalase to form acetaldehyde and water, and the acetaldehyde is reduced by NADH in the presence of alcohol dehydrogenase to ethanol. The decrease in absorbance at 340 nm caused by oxidation of NADH is directly proportional to the concentration of uric acid in the sample. Measurement of the change in absorbance between 20 and 200 s eliminates the need for a serum blank measurement. Absorbance and concentration are linearly related to 120 mg of uric acid per liter. The new method was compared with the uricase method in which decomposition of uric acid at 293 nm is directly measured. The results for the 47 patients' sera so examined can be expressed by the linear equation y340 = 1.0078x293 + 0.122 (r = 0.9984).
Alcohol Oxidoreductases↗
Intermittent elevation of serum urate and 24-hour urinary uric acid excretion.
OBJECTIVES: Serum urate concentrations fluctuate throughout the day, and may be subject to variation with time. However, monthly variation of urinary uric acid excretion has not been investigated. This prompted us to investigate serum urate and 24-h urinary uric acid excretion in healthy men. METHODS: Serum urate and creatinine and 24-h urinary uric acid and creatinine were measured at monthly intervals throughout a 12-month period in 12 healthy men (aged 23-61 yr) from July 2002 to June 2003. RESULTS: The mean age of the 12 healthy men was 35.3+/-10.5 yr (median 33, range 23-61), and they had mean serum urate concentration 7.1+/-1.1 mg/dl (range 4.6-10.4), mean serum creatinine 1.0+/-0.1 mg/dl (range 0.8-1.3) and mean 24-h urinary uric acid excretion 651+/-189 mg/day/1.73 m(2) (median 623, range 389-1565). Approximately 20.1 and 20.7% of the measurements displayed above normal serum urate level and daily urinary uric acid excretion of more than 800 mg, respectively. CONCLUSIONS: The data presented here demonstrate individual variations in serum urate levels and 24-h urinary uric acid excretions in healthy men with serial measurement. Transient hyperuricaemia and hyperuricosuria are more common than expected, and both transitory and monthly variations are important factors to consider when evaluating the influence of other factors upon serum urate levels and urinary uric acid excretion. Further studies are needed to confirm these results using larger populations.
Adult↗
Mass spectrometric method for detecting carbon 13 enrichment introduced by folate coenzymes in uric acid.
Using [2-13C]uric acid as a test material, we developed a mass spectrometric procedure that detects and estimates the difference in 13C enrichment at the positions of carbons 2 and 8 of the purine ring. This method could replace radiochemical methods and could trace the incorporation of carbon fragments into the purine ring from 13C-labeled metabolites in humans.
Carbon Isotopes↗
[The influence of uric acid on the calcium oxalate stone formation (author's transl)].
Statistic analysis of data from 209 calcium oxalate stone patients and 42 stone-free patients pertinent to the concentration and excretion of uric acid in urine and of uric acid levels in the serum yielded no significant difference between the two groups. Only 17% of the calcium oxalate stone patients suffered from hyperuricuria and hyperuricemia was found only in 15% of these patients. Based on these findings, our in-vitro experiments as to the influence of uric acid on calcium oxalate stone formation yielded the following results: firstly, precipitates in urine form only at uric acid concentrations which in-vivo are rate exceptions humans, and secondly, the precipitates at pH 5.5--6.0 always contain uric acid, and a precipitation of calcium oxalate only is never observed. From the experiments one has to conclude that there exists no "salting-out effect" of uric acid on calcium oxalate in urine but rather that precipitate formation reflects the individual solution- and crystallization characteristics of the precipitating compounds.
Calcium Oxalate↗
Gender difference in the concentration of the antioxidant uric acid in human nasal lavage.
The entire respiratory tract is continually exposed to a variety of oxidants, of which a large percentage may react within the nasal passages. In the secretions lining the human nasal cavity uric acid has been shown to be the only low molecular weight antioxidant present in abundance. Because this uric acid originates in the plasma, it is possible that factors affecting the levels of plasma uric acid will also alter the levels recovered in lavage fluids. Lavage fluid from 15 men (20-68 years) and 11 women (20-59 years) were collected using a modified Foley catheter which allowed each subject to supply a basal lavage (saline removed immediately after instillation) and an "accrued' lavage (saline left in situ for 5 min) from each nasal cavity. Lavage fluids were assayed for protein, lysozyme and uric acid. The levels of protein and lysozyme in the recovered fluids were found not to be affected by subject age or gender. Uric acid, however, was found to have a weak negative (r2 = -0.685 basal and -0.62 accrued) correlation with age in women, but no such correlation was noted in men. Also, the levels of uric acid in women (1.3 +/- 0.3 microM/L basal and 4.5 +/- 0.6 microM/L accrued) were found to be lower than those seen in men (3.1 +/- 0.6 microM/L basal and 8.4 +/- 1.3 microM/L accrued) (p = 0.0681 and 0.0394 respectively). It is concluded that women have lower levels of uric acid in lavage fluids than men, with subject age also possibly affecting lavage uric acid. It is also proposed that such factors which lead to decreased levels of uric acid may be related to individual sensitivity to inhaled oxidants such as ozone.
Adult↗
Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National Health and Nutrition Examination Survey.
CONTEXT: Although many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for cardiovascular mortality, this relationship remains uncertain. OBJECTIVE: To determine the association of serum uric acid levels with cardiovascular mortality. DESIGN AND SETTING: Cross-sectional population-based study of epidemiological follow-up data from the First National Health and Nutrition Examination Survey (NHANES I) from 1971-1975 (baseline) and data from NHANES I Epidemiologic Follow-up Study (NHEFS). PARTICIPANTS: A total of 5926 subjects who were aged 25 to 74 years and had serum uric acid level measurements at baseline. MAIN OUTCOME MEASURES: Ischemic heart disease mortality, total cardiovascular mortality, and all-cause mortality, compared by quartiles of serum uric acid level. RESULTS: In an average of 16.4 years of follow-up, 1593 deaths occurred, of which 731 (45.9%) were ascribed to cardiovascular disease. Increased serum uric acid levels had a positive relationship to cardiovascular mortality in men and women and in black and white persons. Deaths due to ischemic heart disease in both men and women increased when serum uric acid levels were in the highest quartile compared with the lowest quartile (men, >416 vs <321 micromol/L; risk ratio, 1.77 [95% confidence interval [CI], 1.08-3.98]; women, >333 vs <238 micromol/l; risk ratio, 3.00 [95% CI, 1.45-6.28]). Cox regression analysis showed that for each 59.48-micromol/L increase in uric acid level, cardiovascular mortality and ischemic heart disease mortality increased. Hazard ratios for men were 1.09 (95% CI, 1.02-1.18) and 1.17 (95% CI, 1.06-1.28), and for women were 1.26 (95% CI, 1.16-1.36) and 1.30 (95% CI, 1.17-1.45), respectively, after adjustment for age, race, body mass index, smoking status, alcohol consumption, cholesterol level, history of hypertension and diabetes, and diuretic use. Further analysis, stratifying by cardiovascular risk status, diuretic use, and menopausal status, confirmed a significant association of uric acid and cardiovascular mortality in all subgroups except among men using diuretics (n=79) and men with 1 or more cardiovascular risk factors (n=1140). CONCLUSION: Our data suggest that increased serum uric acid levels are independently and significantly associated with risk of cardiovascular mortality.
Adult↗
The determinants and prognostic significance of serum uric acid in elderly patients of the European Working Party on High Blood Pressure in the Elderly trial.
Determinants and risks associated with serum uric acid were investigated in 822 elderly hypertensive patients treated with hydrochlorothiazide and triamterene or placebo. Pretreatment serum uric acid levels were significantly higher in men than in women and had positive correlation with serum creatinine. After adjustment for serum creatinine, positive correlations of serum uric acid with body weight and fasting blood glucose in women and with serum cholesterol in men were significant. During follow-up, serum uric acid increased significantly in the treated patients, but remained unchanged in the placebo group. Total, cardiovascular, and noncardiovascular mortality were unrelated to initial serum uric acid levels. One placebo patient and seven treated patients developed gout. Of those seven, most were male patients and had significantly higher serum levels of uric acid and creatinine than the other patients. Gender and renal function were the major determinants of serum uric acid in elderly hypertensive patients.
Aged↗
Serum uric acid and the renin-angiotensin system in hypertension.
To study whether the renin-angiotensin system is related to hyperuricemia in hypertension, the serum concentration of uric acid was determined in 96 patients with various types of hypertension and various degrees of plasma renin activity (PRA). In malignant hypertension, both PRA and the serum uric acid level were higher than in essential hypertension; but in primary aldosteronism or desoxycorticosterone-excess hypertension, they were lower than in the essential type. In renovascular hypertension, PRA was higher than in essential hypertension, but the serum uric acid levels were similar. There were no differences in PRA and serum uric acid concentration between Cushing's syndrome and essential hypertension. The serum uric acid level in high-renin essential hypertension was higher than in either the normal-renin or the low-renin type. There was a significant correlation between serum uric acid concentration and PRA in the basal state, and between the change in PRA and the change in serum uric acid induced by administration of furosemide. Apparently the close correlation between the renin-angiotensin system and the concentration of serum uric acid is related to changes in extracellular fluid volume, although an intrarenal effect of angiotensin II cannot be excluded.
Adolescent↗
[Association between serum uric acid and triglyceride in a Chinese community].
OBJECTIVE: To Study the association between the level of serum uric acid and triglyceride in a Chinese population. METHODS: In 1999, a cross-sectional study was carried out in a natural population of Beijing, using stratified-random sampling method. Serum uric acid and triglyceride were measured in 1239 subjects. RESULTS: The prevalence of hypertriglyceridemia significantly increased with increased level of serum uric acid among both the men and women. After adjusting BMI, HOMA index and alcohol consumption level with stratified methods, the incidence of hypertriglyceridemia increased with increasing level of basal serum uric acid in different levels of BMI, HOMA index and alcohol consumption. After adjusting gender, age, BMI, HOMA index, total cholesterol, smoking and alcohol consumption, the results of multivariate logistic regression analyses indicated that the odds ratio for hypertriglyceridemia as compared with the lowest quartile of serum uric acid was 1.26 (P = 0.28) for the second quartile, 1.88 (P = 0.002) for the third quartile, and 3.36 (P < 0.001) for the highest quartile. CONCLUSIONS: Serum uric acid level was strongly associated with triglyceride independent of age, genders, smoking, alcohol consumption, obesity and insulin resistance.
Adult↗
Relationship of uric acid concentration to cardiovascular risk factors in young men. Role of obesity and central fat distribution. The Verona Young Men Atherosclerosis Risk Factors Study.
OBJECTIVE: To examine the relationships of serum uric acid concentration with several risk factors of cardiovascular diseases (CVD). SUBJECTS: 957 men 18 y old participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. MEASUREMENTS: Body mass index (BMI), waist/hip ratio (WHR), serum uric acid, serum lipids, blood pressure, fasting insulin and behavioural variables. RESULTS: Serum uric acid concentration showed positive associations with BMI (r = 0.24; P < 0.0001), WHR (r = 0.19; P < 0.0001) and serum triglyceride levels (r = 0.19; P < 0.0001); it was also significantly correlated to systolic (r = 0.08; P < 0.01) and diastolic (r = 0.11; P < 0.001) blood pressure, fasting insulin (r = 0.11; P < 0.001), total (r = 0.12; P < 0.001) and LDL cholesterol (r = 0.10; P < 0.01) plasma concentrations. Life-style characteristics, such as smoking and physical activity did not show any significant association, while daily alcohol intake was positively associated with uric acid concentration (r = 0.09; P < 0.01). While the adjustment for fasting insulin did not substantially change these results, the magnitude of the correlations between uric acid and CVD risk factors markedly decreased when allowance was made for BMI and WHR. Only triglycerides maintained an independent correlation with uric acid levels (r = 0.17; P < 0.0001). In multivariate regression analysis, serum triglycerides, BMI and WHR (at borderline significance) were independent positive predictors of uric acid (R2 of the model 0.122, P < 0.001), while fasting insulin concentration did not give any independent contribution to explain the variability uric acid levels. CONCLUSIONS: These data indicate that, already in young, essentially health subjects, hyperuricaemia associates with several components of the so-called insulin resistance syndrome, thus suggesting that increased levels of uric acid might be another member of this syndrome. In addition, these data suggest that obesity and central body fat distribution, rather than hyperinsulinaemia/insulin resistance, play a major role in linking hyperuricaemia with CVD risk factors clustering in the insulin resistance syndrome. Nevertheless, hypertrigliceridemia is related to hyperuricemia independently of obesity and central body fat distribution.
Adipose Tissue↗