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Positive interference of catecholamine metabolites with quantitation of urinary uric acid by the direct acid ferric-reduction method.

We report the effect of major catecholamine metabolites such as homovanillic acid and vanilmandelic acid, normally present in urine, on quantitation of urinary uric acid by the direct acid ferric-reduction procedure [(Am. J. Clin. Pathol. 60, 691 (1973)]. When aqueous uric acid standards containing a mixture of these two metabolites, in concentrations comparable to those in a normal human 24-h urine, were added to Fe3+-phenanthroline or Fe3+-2,4,6-tripyridyl-s-triazine reaction mixture, the resulting absorbances at 505 or 593 nm considerably exceeded those of standards without such additions. Moreover, quantitation of urinary uric acid by the direct acid ferric-reduction procedure gave values that significantly exceeded those determined by the uricase method. Interference by the two metabolites was eliminated by extracting urine specimens with ethyl acetate before quantitation. Spectral scans revealed that homovanillic acid or vanilmandelic acid alone could also effectively reduce Fe3+-chelator complex and that the effect of these compounds on the analytical reaction was additive.

Homovanillic Acid↗

[Blood uric acid levels in patients with sleep-disordered breathing].

OBJECTIVE: Recurrent hypoxia associated with sleep apnea-hypopnea syndrome (SAHS) leads to an increase in the degradation of adenosine triphosphatase to xanthine and, secondarily, to an increase in uric acid concentrations. The aim of the present study was to determine whether there is a correlation between uric acid levels in peripheral blood and sleep-disordered breathing, independently of known confounding factors. PATIENTS AND METHODS: We carried out a retrospective cross-sectional study of 1135 patients evaluated for suspected SAHS. For all patients, a medical history was taken using a standardized protocol. In addition, biochemical analysis of venous blood and an overnight sleep study (with either conventional polysomnography or home monitoring) were carried out. RESULTS: The mean (SD) concentration of uric acid was 6.31 (1.5) mg/dL, and 36% of patients had concentrations above established normal values for their sex. We found a significant correlation between uric acid levels and some sleep study parameters (number of respiratory events, number of desaturations, or the cumulative percentage of time with oxygen saturation less than 90%). Those patients with more respiratory events (apnea-hypopnea index or respiratory event index >or= 30) had higher uric acid levels than those with mild or no SAHS. However, this difference was not apparent in the univariate analysis of variance, in which body mass index and cholesterol and triglyceride levels were considered confounding factors. CONCLUSIONS: Uric acid levels are positively correlated with the number of obstructive respiratory episodes and oxygen desaturations during sleep, but this correlation seems to be influenced by other factors, such as obesity.

Cross-Sectional Studies↗

Ammonia production from uric acid and its absorption from the caecum of the cockerel.

1. Experiments were done in vitro and in situ in the caeca to measure ammonia production from uric acid and its absorption. 2. When uric acid was introduced into a caecal sac containing mixed caecal micro-organisms 0.77 disappeared in 1 h, with the concomitant appearance of ammonia. 3. Amounts of ammonia produced from added [15N] uric acid in the caeca in situ after 30 min and in caecal medium in vitro after 10 h, were 0.28 and 0.25 respectively of the added 15N. 4. About 0.92 of the ammonia introduced into a caecal sac disappeared from the lumen fluid in 30 min. 5. It is concluded that ammonia is produced from uric acid by caecal micro-organisms and rapidly absorbed.

Ammonia↗

Serum uric acid and hypertension: the Olivetti heart study.

The association between serum uric acid and hypertension was evaluated in a sample of male workers in southern Italy enrolled in the Olivetti Heart Study, an ongoing longitudinal epidemiological investigation on risk factors for coronary heart disease carried out at the Olivetti factory in the suburban area of Naples. Participants were screened at baseline (1975) and at five year (1980) and 12 year (1987) follow-up examinations. The present report focuses on 619 male workers for whom information on coronary heart disease risk factors was available both at baseline and 12 year follow-up examination. At baseline, after excluding hypertensive participants (systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP), > or = 90 mmHg and/or on antihypertensive therapy; n = 72), serum uric acid was positively and significantly related to age, SBP, DBP, body mass index (BMI), serum total cholesterol (CHOL) and serum triglycerides (TG) in 547 normotensive participants. At 12 year follow-up examination, hypertension was defined by SBP > or = 140 mmHg and/or DBP > or = 90 mmHg and/or being on antihypertensive therapy. Multiple logistic regression analysis showed an independent positive association between serum uric acid levels and development of hypertension (RR = 1.23, 95% CI = 1.07-1.39; p = 0.011) after adjustment for age, BMI, CHOL and TG. Furthermore, according to more severe degrees of hypertension (SBP > or = 160 mmHg and/or DBP > or = 95 mmHg and/or being on antihypertensive therapy), the relative risk to develop hypertension was still significant (RR = 1.19; CI = 1.01-1.38; p = 0.051).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Chemiluminescence microflow injection analysis system on a chip for the determination of uric acid without enzyme.

A new microflow injection analysis (microFIA) system on a chip coupled with chemiluminescence (CL) for the non-enzymatic determination of uric acid is described. The microFIA system produced by using two transparent poly(methylmethacrylate) (PMMA) chips measured 50 x 40 x 5 mm, the microchannels, etched by CO2 laser, were 200 microm wide and 100 microm deep, and the volume of the reaction area (RA) was about 1.2 microL. The injection pump, with accurate time control, monitored all reagents, including the sample. The uric acid was sensed by the chemiluminescence reaction between luminol and ferricyanide. The linear range of the uric acid concentration was 0.8-30 mg/L and the detection limit was 0.5 mg/L (S/N = 3). The relative standard deviation was 4.42% for 5 mg/L uric acid (n = 8). The proposed method has been successfully applied to the non-separation determination of uric acid in human serum and urine.

Ferricyanides↗

Serum uric acid in essential hypertension: an indicator of renal vascular involvement.

We measured glomerular filtration rate, renal and systemic hemodynamics, and intravascular volume in normotensive subjects and in borderline and established essential hypertensive patients classified according to serum uric acid level. Renal blood flow was lower and renal vascular and total peripheral resistances were increased in patients with high uric acid levels (p < 0.02). Serum uric acid concentration correlated inversely with renal blood flow/m2 body surface area (r = -0.45, p < 0.001) and directly with renal vascular (r = 0.41, p < 0.001) and total (r = 0.38, p < 0.001) resistance. Cardiac output, heart rate, and intravascular volume as well as glomerular filtration rate showed no uric-acid-department pattern. Mild asymptomatic hyperuricemia, therefore, was associated with decreased renal blood flow without affecting glomerular filtration rate. Increased renal vascular and total peripheral resistances reflecting renal and systemic hypertensive vascular disease paralleled the rising serum uric acid levels. These data suggest that heretofore unexplained hyperuricemia in patients with essential hypertension most likely reflects early renal vascular involvement, specially, nephrosclerosis.

Adult↗

Effect of sodium valproate monotherapy on serum uric acid concentrations in ambulatory epileptic children: a prospective long-term study.

PURPOSE: Hyperuricemia has been shown to be related to cardiovascular morbidity and mortality. There is controversial data about the effect of sodium valproate (VPA) monotherapy on serum uric acid concentrations. The purpose of this study was to investigate by a long-term, prospective method, whether treatment with VPA monotherapy may alter serum uric acid concentrations and liver function tests in ambulatory epileptic children. MATERIAL AND METHODS: Serum uric acid concentrations were determined in 28 ambulatory epileptic children before and at 6, 12 and 24 months of VPA monotherapy. Serum concentrations of biochemical markers of liver and renal function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (gamma-GT) and creatinine (Cr) were also measured before and at 6, 12 and 24 months of VPA monotherapy. Serum VPA concentrations remained within the therapeutic range (50-100 mg/L) during the period of study. RESULTS: No statistically significant changes in serum uric acid concentrations were found at 6, 12 or 24 months of treatment. Serum ALT concentrations were significantly increased at 6 and 12 months of treatment, AST concentrations at 6 and 12 months of treatment and LDH concentrations at 12 months of treatment. CONCLUSIONS: VPA monotherapy does not have a significant effect on serum uric acid concentrations in ambulatory epileptic children. Further studies are needed to definitively address whether it would be useful for physicians to routinely check for elevated serum uric acid levels in children treated with VPA.

Adolescent↗

Relationship of plasma uric acid to plasma lipids and lipoproteins in subjects with peripheral vascular disease.

Hyperuricaemia and hyperlipidaemia (elevated fasting plasma cholesterol or triglycerides) were frequently found in 219 males and 63 females with peripheral vascular disease (PVD). The subjects were divided into sexes and the uric acid, cholesterol and triglyceride concentration adjusted for the effects of age and obesity by multiple regression analysis. Followig this no significant relationship was found between uric acid and cholesterol or triglyceride. When the males with PVD were divided into lipoprotein types it was found that those who were normo-lipoproteinaemics or who had type IV hyperlipoproteinaemia (HLP) had a significantly higher mean uric acid level. The other types had a mean uric acid concentration similar to that found in 25 healthy normolipoproteinaemic males. The discrepancy between this result and the lack of correlation between uric acid and triglyceride noted above is presumably due to the complex effects of age and obesity. In the females no significant increase in the mean uric acid concentration was found in any of the lipoprotein groups.

Body Weight↗

Effect of minidose aspirin on renal function and renal uric acid handling in healthy young adults.

Minidose aspirin (60-325 mg/day) has been widely used in the prevention and treatment of cardiovascular and cerebrovascular diseases. However, studies on the effects of minidose aspirin on renal handling of uric acid and renal function are limited. We studied the effect of aspirin at 60 mg/day (n = 18) and 300 mg/day (n = 14) on uric acid handling and renal function in healthy subjects. The subjects were evaluated weekly during 2 weeks of aspirin therapy, and again 1 week after aspirin was discontinued. Aspirin at both dosages decreased the fractional excretion of uric acid. However, aspirin at 300 mg/day, but not 60 mg/day, significantly decreased uric acid clearance and creatinine clearance by the end of the second week of aspirin therapy. Despite these changes, serum uric acid and serum creatinine remained constant. The uric acid clearance, but not the creatinine clearance, returned to baseline value 1 week after aspirin therapy was discontinued. As aspirin at 60 mg/day showed no suppressive effect on renal function, it may be better for long-term use.

Journal Article↗

Simultaneous determination of creatine, uric acid, creatinine and hippuric acid in urine by high performance liquid chromatography.

A simple method for the simultaneous determination of creatine, uric acid, creatinine and hippuric acid in urine using reversed-phase high performance liquid chromatography was described. Chromatography was performed on a Nova-Pak C18 (3.9 x 150 mm) column with a mobile phase of 0.02 mol/L KH2PO4, and UV detection at 220 nm. The recoveries of creatine, uric acid, creatinine and hippuric acid were 103.13, 99.86, 98.26 and 98.24%, respectively. The calibration curves were linear within the concentration range of 2-200 micrograms/mL for creatine, uric acid and hippuric acid, and 2-400 micrograms/mL for creatinine. The detection limits of the method were 0.69, 0.21, 0.10 and 0.095 microgram/mL for creatine, uric acid, creatinine and hippuric acid, respectively. This method has been applied to the analysis of urine samples from normal subjects and some patients.

Chromatography, High Pressure Liquid↗

Chemiluminescent in vitro estimation of the inhibitory constants of antioxidants ascorbic and uric acids in Fenton's reaction in urine.

The goal of this research was to measure in vitro the inhibitory constants of the antioxidants ascorbic and uric acid in urine, with lucigenin enhanced chemiluminescence (CL) in Fenton's system. Maximum CL emission is registered in urine containing H2O2 (5.10(-4) M), Fe2+ (5.10(-5) M), EDTA (5.10(-5) M), and chemical enhancer lucigenin (10(-4) M) at pH 5.5 and 36 degrees C. Ascorbic acid exhibits up to 4-fold stronger antioxidant effect than uric acid. The constants of antioxidant inhibition in urine were measured at concentrations 10(-3) and 10(-4) M: for ascorbic acid, 5.92 +/- 0.04 and 24.05 +/- 1.82 micromol.sec(-1); for uric acid, 1.60 +/- 0.02 and 21.45 +/- 0.97 micromol.sec(-1), respectively. Three phases of CL kinetics of urine are well observed: spontaneous CL (0-10 sec), fast flash of CL (10-50 sec), and latent period (50-300 sec). The antioxidant efficiency of ascorbic and uric acids in the final stage of catabolic processes in the body is discussed.

Acridines↗

Effect of deafferentation on the levels of uric acid in the spinal cord of the rat.

In previous studies we reported that the rat spinal cord contains relatively high levels of uric acid and that the levels in a rat model of bilateral chronic pain, experimental adjuvant arthritis. In this report we evaluate the changes in UA in the unilaterally deafferented rat, a preparation which has also been used to study chronic pain. Uric acid was measured by high-pressure liquid chromatography with electrochemical detection in the spinal cord of rats that underwent unilateral, multiple cervical dorsal rhizotomy. Compared to control and sham-operated rats, there was a significant increase in the level of uric acid in the dorsal quadrant of the spinal cord ipsilateral to the dorsal rhizotomy. This increase was present at 1 and 4 weeks after surgery. At 1 week, we also observed a small but statistically insignificant increase in uric acid levels in the dorsal quadrant contralateral to the deafferentation and in sham-operated rats. Four weeks after surgery the levels of UA in all regions except for the deafferented dorsal quadrant returned to normal. The possibility was raised that the changes in uric acid reflect an increase in purinergic metabolism in the spinal cord secondary to the increased activity of the dorsal horn neurons that occurs with deafferentation.

Afferent Pathways↗

Iron(III) chloride injection increases nigral uric acid in guinea-pig.

The present study was carried out to determine if iron chloride (FeCl3) injections into the substantia nigra of guinea-pigs produced changes in nigro-striatal uric acid levels. Two-weeks following unilateral injection of FeCl3 (185 nmol Fe3+), ipsilateral uric acid levels were increased 176% over contralateral levels in the substantia nigra. No effect on striatal uric acid levels was observed. Iron chloride injection produced a 74% depletion of dopamine levels in the ipsilateral striatum. Ipsilateral/contralateral ratios were significantly decreased for striatal dopamine and significantly increased for nigral uric acid when compared with saline-injected controls. The results of this work indicate that FeCl3 injections into the substantia nigra of guinea-pigs produce a significant, localized increase in tissue uric acid levels two weeks after treatment.

Animals↗

Simultaneous determination of uric acid and creatinine in plasma by reversed-phase liquid chromatography.

Because numerous substances, endogenous compounds as well as xenobiotics, interfere with determination of uric acid and creatinine, we have devised a more nearly specific method by which we can simultaneously determine uric acid and creatinine in plasma by "high-performance" liquid chromatography. We used a mobile phase of ammonium acetate (30 mmol/L) and methanol (156 mmol/L) at pH 7.0 and a flow rate of 1 mL/min. We used a C18 reversed-phase column, and measured absorbance at 235 nm, the wavelength corresponding to the absorption maximum of uric acid and creatinine. Uric acid and creatinine could be determined in less than 5 min by directly injecting plasma diluted fivefold; use of a precolumn eliminated the need for deproteinization. We evaluated the precision, recovery, linearity, specificity, and limit of detection of the method and we checked for analytical interference by 37 currently used drugs. We compared results with those obtained by routine and reference methods.

Autoanalysis↗

Familial renal hypouricaemia: two additional cases with uric acid lithiasis.

Two families are reported affected with hereditary renal hypouricaemia associated with uric acid lithiasis. The propositi of both families were found also to have hyperabsorptive hypercalciuria. Based on the study of the effect of pyrazinamide and probenecid on uric acid excretion in both propositi, it is suggested that the defect in uric acid reabsorption is most probably at the pre-secretory site.

Adult↗

Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans.

D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal range were small and were of short duration. Consistent with earlier observations on fructose, the increase of plasma uric acid was associated with a slight decrease of plasma phosphorus and a slight increase of magnesium. The daily ingestion of D-tagatose for 8 weeks had no effect on fasting plasma magnesium, phosphorus, cholesterol, triglycerides, glycosylated hemoglobin, glucose, and insulin levels. The ingestion of three 25-g doses per day for a period of 8 weeks resulted in varying amounts of flatulence in seven of the eight subjects, and some degree of diarrhea in six subjects. D-tagatose holds promise as a sweetener with no adverse clinical effects observed in these studies.

Blood Pressure↗

Purine metabolism in high and low uric acid lines of chickens: phosphoribosylpyrophosphate (PRPP) synthetase activities and PRPP pool sizes.

Phosphoribosylpyrophosphate synthetase activities were examined in liver and kidney tissues of two genetic lines of chickens selected for their plasma uric acid levels. Previous work demonstrated that the high uric acid line (HUA) has significantly greater de novo uric acid synthesis rates in kidney tissue compared to the low uric acid line (LUA). In addition, xanthine dehydrogenase activity in liver and kidney tissues was significantly higher in the HUA compared to the LUA line. The activity of PRPP synthetase, which provides a key substrate for the rate limiting step in de novo purine biosynthesis, was found to be significantly elevated (P less than 0.05) in liver and kidney tissues of the HUA line. The mean value of kidney PRPP synthetase activity was 30.2 +/- 0.7 nmole PRPP and 19.1 +/- 1.6 nmol PRPP produced/mg protein/hr, respectively, for the HUA and LUA lines. The PRPP pool size in kidney tissue was also significantly higher in the HUA line. The mean level of PRPP was 319.8 +/- 37.2 pmole/g of wet tissue compared to 176.7 +/- 12.4 pmole PRPP/g of wet tissue in the LUA line. The mean values of liver PRPP synthetase activities were 11.4 +/- 0.6 nmole PRPP and 9.0 +/- 0.4 nmole PRPP produced/mg protein/hr, respectively, for the HUA and LUA lines. The PRPP pool size in liver tissues was significantly higher in the HUA line as well. The mean level of PRPP was 550.7 +/- 72.5 pmole/g of wet tissue compared to 313.6 +/- 31.4 pmole PRPP/g of wet tissue in the LUA line. The enzyme from the HUA birds does not differ from controls with respect to Michaelis constants, inhibition phenomena, and phosphate activation. The increased PRPP synthetase activity found in HUA tissues may be due to structural alterations of the molecule resulting in an enzyme with a greater Vmax, an increase in the amount of enzyme protein, or a lowered level of a nondialyzable inhibitor.

Adenosine Triphosphate↗

Diet effect on activity product ratios of uric acid, sodium urate, and ammonium urate in urine formed by healthy beagles.

Urine activity product ratios of uric acid, sodium urate, and ammonium urate and urinary excretion of metabolites were determined in 24-hour samples produced by 6 healthy Beagles during periods of consumption of a low-protein, casein-based diet (diet A) and a high-protein, meat-based diet (diet B). Comparison of effects of diet A with those of diet B revealed: significantly lower activity product ratios of uric acid (P = 0.025), sodium urate (P = 0.045), and ammonium urate (P = 0.0045); significantly lower 24-hour urinary excretion of uric acid (P = 0.002), ammonia (P = 0.0002), sodium (P = 0.01), calcium (P = 0.005), phosphorus (P = 0.0003), magnesium (P = 0.01), and oxalic acid (P = 0.004); significantly (P = 0.0001) higher 24-hour urine pH; and significantly (P = 0.01) lower endogenous creatinine clearance. These results suggest that consumption of diet A minimizes changes in urine that predispose dogs to uric acid, sodium urate, and ammonium urate urolithiasis.

Animals↗