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The C677 mutation in methylene tetrahydrofolate reductase gene: correlation with uric acid and cardiovascular risk factors in elderly Korean men.

The C677T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene results in elevated homocysteine levels and, presumably, in increased cardiovascular risk. Moreover, elevated homocysteine levels are reportedly associated with high serum uric acid levels. We evaluated the MTHFR genotype and a panel of biochemical, hematological variables, and lifestyle characteristics in 327 elderly Korean men (age range 40-81 yr; mean, 51.87). This study shows that mutation of the MTHFR gene may be a risk for hyperuricemia. The mean uric acid levels for the C/C, C/T and T/T genotypes were 5.54, 5.91 and 6.33 mg/dL, respectively (p=0.000). The T/T genotype was significantly more frequent in subjects with high uric acid levels (p=0.003). Thus, this mutation of the MTHFR gene is implied by the study results to be a risk factor of hyperuricemia in elderly Korean men. However, the relationship between the MTHFR mutation and uric acid metabolism remains unclear. Therefore, further studies are necessary to explain the associated between the MTHFR mutation and elevated uric acid levels, and to examine potential relationships between it and conventional cardiovascular risk factors.

Adult↗

The determination of calcium, glucose, urea and uric acid using the Kodak EKTACHEM multilayer film technology: an evaluation.

Calcium, glucose, urea and uric acid determinations on the "'Kodak Ektachem Four Chemistry Analyzer" were tested for precision and an estimation of the accuracy was performed with our laboratory routine methods using patients' sera and proficiency fluids. Precision -- examined over a period of six weeks -- was very good. Even the very stringent claim of the College of American Pathologists (CAP) -- that analytical dispersion should be less than 1/16th of the normal range -- was fulfilled in almost all control samples. The results from patients' sera measured using both the Ektachem and the routine laboratory methods showed very good correlation. Proficiency fluids tested for calcium, glucose and uric acid all resulted in values well within the assigned interval. Some negative bias was noted for the urea determination however. This could not be completely eliminated even though the samples had been reconstituted with a bicarbonate solution according to the manufacturer's instructions. The linear range of the four determinations was checked: calcium is linear up to 4.2 mmol/l, glucose up to 33 mmol/l, urea up to 60 mmol/l and uric acid up to 1370 mumol/l. Our results confirmed the long-term stability of analyzer and slides to be so high that one calibration per week is sufficient.

Blood Glucose↗

[Uric acid analysis in thalassemia trait carriers].

The results of a uric acid analysis on Beta Thalassaemia Heterozygotes compared with healthy or microcytic non Beta Thalassaemia Heterozygotes are reported. Identical uric acid levels, higher than in the control group, were found in Beta Thalassaemia Heterozygotes: therefore the difference does not appear to be specific for thalassaemic carriers but consequent to increased erythrocytic catabolism in microcytic anemias.

Anemia↗

The effect of trimethoprim on potassium and uric acid metabolism in normal human subjects.

BACKGROUND: Trimethoprim used in combination with other antibiotics, has been implicated in causing hyperkalemia and hypouricemia in patients with acquired immune deficiency syndrome (AIDS). In experimental animal models, trimethoprim has been demonstrated to block sodium channels and Na+-K+-ATPase in the distal nephron and thus impair potassium excretion. Although the data from the experimental models suggest that trimethoprim reduces urinary potassium excretion, the retrospective clinical studies have confounding factors that prevent a rigorous demonstration that the hyperkalemia and hypouricemia are due solely to the effects of trimethoprim on solute excretion. AIM: The purpose of this study was to evaluate the effect of trimethoprim on potassium and uric acid balance in normal human subjects. METHODS: Five normal human subjects were admitted to the general clinical research center and placed on a fixed metabolic diet. After a 4-day control period, the subjects were given trimethoprim (15 mg/kg/day) orally for 5-7 days followed by a 4-day recovery period. Free-flow blood samples and 24-hour urine collections were obtained daily. RESULTS: Treatment with trimethoprim resulted in a significant increase in plasma potassium concentration (4.5 +/- 0.1 versus 3.7 +/- 0.1 mmol/l, p < 0.005) and significant decrease in serum uric acid concentration (3.8 +/- 0.4 versus 5.6 +/- 0.5 mg/dl, p < 0.001). Treatment with trimethoprim significantly increased the urinary excretion of uric acid, but did not significantly decrease potassium excretion during the 7-day treatment period. There was, however, a significant decrease in potassium excretion observed during the first 48 hours of trimethoprim treatment. In one subject where repeat studies were performed using different dosages, the effect on potassium and uric acid levels appeared to be dose-dependent. CONCLUSIONS: Trimethoprim increases plasma potassium concentration probably by reducing urinary potassium excretion. Trimethoprim decreases serum uric acid levels by augmenting urinary uric acid excretion. This uricosuric effect may be due to the ability of trimethoprim to impair urate reabsorption by the urate-anion exchanger in the proximal tubule.

Adult↗

Preliminary investigations on a new disposable potentiometric biosensor for uric acid.

In this paper, uricase, catalase, and electron mediator were coimmobilized on the surface of the tin oxide (SnO2)/indium tin oxide (ITO) glass, to develop a disposable potentiometric uric acid biosensor. The SnO2/ITO glass was employed as a pH sensor, fabricated by sputtering SnO2 thin films on the ITO glass. 3-Glycidyloxypropyltrimethoxysilane (GPTS) was utilized to immobilize uricase, catalase and the electron mediator (ferrocenecarboxylic acid, FcA) on the sensing window. The experimental results reveal that the optimal weight ratio of uricase, FcA to catalase (CAT) is 4:1:2. The sensor responds linearly between 2 mg/dl and 7 mg/dl at pH 7.5, in 20 mM of test solution, with a correlation coefficient of 0.99213. Accordingly, no significant interference was observed when interfering substances, glucose, urea and ascorbic acid, were added to the uric acid solution. Moreover, the recorded voltage was relatively constant during the first 28 days of measurement. Consequently, a potentiometric uric acid biosensor was realized with the advantages of low cost and simple fabrication.

Biosensing Techniques↗

Stereospecificity of conversion of uric acid into allantoic acid by enzymes of Canadida utilis.

1. Allantoinase [EC 3.5.2.5] was isolated from cells of Candida utilis and unpurified by chromatography on columns of DEAE-cellulose and Sephadex G-200 after treatment with urea to remove urate oxidase [EC 1.7.3.3.]. 2. The purified allantoinase catalyzed the hydrolysis of allantoin into allantoic acid. However, only half of the allantoin produced from uric acid by urate oxidase was converted. The rest of the allantoin was unchanged, and showed a negative optical rotation. 3. On the other hand, the combined action of crude urate oxidase and allantoinase resulted in nearly complete conversion of uric acid into allantoic acid. Furthermore, the unpurified allantoinase preparation hydrolyzed racemic allantoin to allantoic acid completely. 4. These results indicate that the urate oxidase produces racemic allantoin from uric acid and that the allantoinase attacks only allantoin of positive optical rotation. The results also suggest that allantoin racemase is present in the yeast cells.

Amidohydrolases↗

Uric acid metabolism in therapy of glycogen storage disease type I.

Factors which may explain lower serum uric in a new therapy of patients with glycogen storage disease (GSD) type I have been studied. [1-14C]Glycine incorporation into urine uric acid was 0.68% of the injected dose during a 6-day period of frequent high carbohydrate feedings, 0.40% with the same diet and nocturnal nasogastric feeding by Vivonex, and 0.18% in a control patient with GSD type III. Fractional renal uric acid excretion in the patient with GSD type I increased from 11.3% to 26.3% after beginning nocturnal nasogastric feeding of Vivonex. Red cell phosphoribosylpyrophosphate leve,ls were not changed by the therapy. Addition of Vivonex nocturnal feedings to frequent high carbohydrate feedings (1) decreased the accelerated de novo purine synthesis to a level still higher than control and (2) increased fractional renal uric acid excretion.

Child↗

Correlations of serum lipids, uric acid, and albumin among mothers, offspring, and siblings in Taipei, Taiwan.

The purpose of this study was to investigate the correlations of serum lipids, uric acid, and albumin, among mothers (n = 111), offspring (n = 208), and siblings (n = 57) in Taipei, Taiwan. Analytical items included serum triglyceride, serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, and albumin. Statistical analysis was performed according to the SAS UNIVARIATE procedure; while regression coefficient, parent-offspring regressions, paired-comparison and heritability were estimated. These results show higher heritabilities of four types of serum lipids, uric acid and albumin between mothers and testers (bYX) or siblings (bZX) by parent-offspring regression analysis. Regression coefficients (bYX) of six characters were significantly different (p < 0.05-0.01). Regression coefficients (bZX) for total cholesterol, low-density lipoprotein cholesterol, uric acid, and albumin were significantly different (p < 0.05-0.01), showing the result of genetic control, because their heritabilities were very high at 0.75-1.0, 0.77-1.0, 0.96-1.0, and 0.48-0.82, respectively. This study disclosed that the serum lipids of children in Taipei, Taiwan were significantly correlated with that of parents, which may be attributed to the result of genetic control.

Child↗

Characterization of a uricase from Bacillus fastidious A.T.C.C. 26904 and its application to serum uric acid assay by a patented kinetic uricase method.

An intracellular uricase from Bacillus fastidious A.T.C.C. 26904 was characterized and evaluated for serum uric acid assay by a patented kinetic uricase method. The active uricase was 151 kDa by gel filtration through Sephadex G-200. Both SDS/PAGE and matrix-assisted laser-desorption ionization-time-of-flight MS resolved a single polypeptide with a molecular mass of approx. 36.0 kDa. The N-terminal sequence was AERTMFYGKGDV. The optimum pH for this uricase ranged from 9.0 to 10.5. At pH 9.2, the Km (Michaelis-Menten constant) was 204+/-14 micromol/l (n=8) and the Ki (inhibition constant) for xanthine was 41+/-7 micromol/l (n=5). By analysing the data monitored within 5 min at 0.03 unit/ml uricase, this kinetic uricase method gave linear response to uric acid in reaction solution from 1.3 to 60 micromol/l. Aside from other common errors, 30 micromol/l xanthine in the reaction solution caused no error in this kinetic uricase method, while it caused negative error in the indirect equilibrium method by peroxidase-coupled assay of H2O2. Uric acid in clinical sera by this kinetic uricase method (Ck) closely and positively correlated with that from the indirect equilibrium method (Ce) (Ck = 0.008+1.081 x Ce, r>0.990, n=99). However, Bland-Altman analysis suggested inconsistency between Ck and Ce. These results indicated that this kinetic uricase method using this uricase was reliable for serum uric acid assay with enhanced resistance to xanthine besides other common errors.

Amino Acid Sequence↗

Simultaneous determination of guanine, uric acid, hypoxanthine and xanthine in human plasma by reversed-phase high-performance liquid chromatography with amperometric detection.

A reversed-phase high-performance liquid chromatographic method with amperometric detection is described for the separation and quantification of uric acid, guanine, hypoxanthine and xanthine. The isocratic separation of a standard mixture of the compounds was achieved in 5 min on a Spherisorb 5 C18 reversed-phase column, with a mobile phase of NaH2PO4 (300 mmol dm-3, pH 3.0)-methanol-acetonitrile-tetrahydrofuran (97.8 + 0.5 + 1.5 + 0.2). Uric acid, guanine, hypoxanthine and xanthine were completely separated, with detection limits in the range 2-20 pmol per injection. The effect of pH and the composition of the mobile phase on the separation are described. The hydrodynamic voltammograms of these compounds were recorded at a glassy carbon electrode. The linear range of the calibration graph for each compound was: uric acid, 1-5000 mumol dm-3; guanine, 0.5-2000 mumol dm-3; hypoxanthine, 0.1-500 mumol dm-3 and xanthine, 0.5-5000 mumol dm-3. The within- and between-day precision was good. The uric acid and hypoxanthine content in human plasma was measured using the proposed method. Good recoveries of uric acid (97.9-103%), hypoxanthine (98.0-99.2%), guanine (96.0-98.3%) and xanthine (96.0-102%) were obtained from human plasma. The results of electrochemical detection were in good agreement with those of UV detection.

Calibration↗

Typing of uric acid level in cerebrospinal fluid in neurological and psychiatric diseases.

The increasing number of latent and manifest hyperuricemia is important concerning differential diagnosis in neurological and psychiatric diseases. The pathological importance of hyperuricemia in these diseases is particularly unknown. The possibility of a physiological regulative function of uric acid in central nervous system may be discussed. Therefore uric acid typing in cerebrospinal fluid were made of 173 patients with neurological and psychiatric diseases. On an average the uric acid level in cerebrospinal fluid is 1:10 of the blood uric acid level. In advanced age a lower level could be found. High level for example were found after L-Dopa treatment and epileptical seizures. These results and possible pathophysiological correlation to the correspondant diseases are discussed.

Humans↗

Relationship between aldosterone and sodium, potassium, and uric acid clearance in cirrhosis with and without ascites.

We have suggested that cirrhotic patients with high uric acid clearances had an increased effective vascular volume. This hypothesis was tested by studying the relationship between the excretion of uric acid, sodium, potassium, and aldosterone in cirrhosis. In 29 consecutive cirrhotic patients, of whom 17 had ascites, and in a control group, the logarithm of urinary sodium and aldosterone excretion highly correlated in control (r = -0.79, p less than 0.001) and cirrhotic patients without (r = -0.72, p less than 0.01) and with (r = -0.80, p less than 0.001) ascites. The regression line significantly shifted to the left in the cirrhotic patients (p less than 0.001). The urinary ratio K/K + Na also correlated with urinary aldosterone in controls (r = +0.66, p less than 0.001) and in cirrhotic patients (r = +0.77, p less than 0.001); this regression line shifted to the right in cirrhosis patients (p less than 0.02). The fractional uric acid excretion significantly correlated with urinary aldosterone only in cirrhotic patients (r = -0.76, p less than 0.001). These data confirmed the existence of hypoaldosteronism in many cirrhotic patients and are consistent with tubular hypersensitivity to aldosterone and emphasize the major role of the effective vascular volume in the control of urid acid clearance in cirrhosis.

Adult↗

SERUM URIC ACID LEVELS OF HEALTHY CAUCASIAN, CHINESE AND HAIDA INDIAN MALES IN BRITISH COLUMBIA.

Because previous studies have shown that serum uric acid levels are higher in members of the Filipino and Maori races than in Caucasians, and because gout seemed unexpectedly common in the Chinese population of Vancouver, a study of serum uric acid levels in Caucasian, Chinese and Haida Indian males was undertaken. The serum uric acid levels of 200 Caucasian, 100 Chinese and 237 Haida Indian males were determined by the ultraviolet spectrophotometric method of Dubbs, which gives a result 0.5 mg. % below that of the more commonly employed method of Grayzel. The mean level of the Caucasians was 4.55 mg. % and that of the Haida Indians 4.41 mg. %; in contrast, the Chinese mean was 5.44 mg. %, a significantly higher figure than the means of the other two groups. No explanation for this finding can be given at present.

Asian People↗

A selective voltammetric method for uric acid detection at beta-cyclodextrin modified electrode incorporating carbon nanotubes.

A beta-cyclodextrin-coated electrode incorporating carbon nanotubes was constructed and applied to the detection of uric acid in the presence of high concentration of ascorbic acid. The major obstacle of the overlapped oxidation potential of ascorbic acid was overcome owing to the distinct ability of the carbon nanotubes-modified electrode to yield a large anodic peak difference ca. 400 mV. The sensitive detection of uric acid has been further improved by the formation of a supramolecular complex between beta-cyclodextrin and uric acid. A linear calibration curve was obtained for 5 x 10(-7) to 5 x 10(-5) M in 0.2 M HAc-NaAc buffer (pH 4.5) with correlation coefficient of 0.998 and detection limit of 0.2 microM. The practical analytical application was illustrated by a selective measurement of uric acid in human urine without any preliminary treatment.

Ascorbic Acid↗

Thin layer chromatographic method for the detection of uric acid: collaborative study.

A collaborative study has been completed on an improved method for the detection and confirmation of uric acid from bird and insect excreta. The proposed method involves the lithium carbonate solubilization of the suspect excreta material, followed by butanol-methanol-water-acetic acid thin layer chromatography, and trisodium phosphate-phosphotungstic acid color development. The collaborative tests resulted in 100% detection of uric acid standard at the 50 ng level and 75% detection at the 20-25 ng level. No false positives were reported during tests of compounds similar to uric acid. The proposed method has been adopted official first action; the present official final action method, 44.161, will be retained for screening purposes.

Animals↗

Serum lipid, uric acid and glucose levels in urban black males doing manual or clerical work.

Serum lipid, uric acid and glucose levels were measured in four groups of Black male factory workers 1 hour after an oral glucose load. These groups comprised non-obese manual, obese manual, non-obese clerical and obese clerical workers. Obese men had significantly higher serum uric acid, total cholesterol and triglyceride levels and lower high=density lipoprotein (HDL) cholesterol levels than non-obese men. Serum glucose and low-density lipoprotein (LDL) cholesterol values were also higher in obese than in non-obese men, but the differences were not significant. Clerical workers had higher levels than manual workers for most of the biochemical variables measured, but only in the case of uric acid was the difference significant. Possible reasons for the fact that the effect of occupation on the variables was slight are briefly discussed.

Adult↗

[Update of a selected technique for uric acid determination in plasma and serum. Experimental study and value of derivative spectrophotometry].

A critical study of the candidate reference method for evaluation of uric acid in plasma proposed by the American Association of Clinical Chemistry is followed by testing in six laboratories. The dispersion of results is wide (CV greater than 5%). The importance of turbidity remaining after the deproteinization by trichloracetic acid is clearly demonstrated. This turbidity is really not reproducible from an operation to another one on the same serum. It is very likely responsible of the great dispersion of the results. After that, other deproteinization methods are tried. Ultrafiltration and ultracentrifugation give both defect errors because uric acid is in part bound to proteins. So it is necessary to find another technic which cancels the effects of turbidity on the absorbance readings in the ultra-violet domain. Experimental studies showed that uric acid may be evaluated with a good accuracy by derivative spectrophotometry, in lipid solutions as well as in cloudy ones. Turbidity was created by intralipid suspension additions. Various parameters hitting the method were examined (linearity, smoothing window...), taking as criterion the measure of overloaded serums at different levels. At last, the method is successfully transferred in several sites. In the case of blood serum, the respective influences of derivation and of repetition of final centrifugations are studied in order to estimate the effect of remaining turbidity. By the use of derivative spectrophotometry the improvement of the method of evaluation of uric acid proposed by A.A.C.C. is very noticeable; it reduces the variation coefficient between sites to less than 2%.

Animals↗

Dissolution of ureteral uric acid calculi with local litholytic irrigation.

This study was designed to evaluate the efficacy of local litholytic irrigation (LLI) in the treatment of ureteral uric acid calculi. Fourteen cases of ureteral uric acid calculi were diagnosed by abdominal plain radiography (KUB), retrograde urography, ultrasonography (B-mode ultrasound), spiral computerized tomography(CT) and blood biochemical examinations. A ureteral catheter was passed retrogradely across ureteral calculi by cystoscopy. LLI with tromethamine-E (THAM-E) was performed via the ureteral catheter after the improvement of renal function and general situation and the control of urinary tract infection under the condition of intravenous application of antibiotics. The irrigation rate varied from 1000 to 1500 ml per day. Retrograde pyelography demonstrated complete dissolution of all the stones, 13 cases within 10 days and 1 within 12 days. Mild hematuria was observed in the majority of the cases and temporary aggravated lumbago in 1 case, with no other side effects. It is concluded that LLI is a practical and effective method in the treatment of ureteral uric acid calculi for its advantages of shorter duration,lower cost, less physical suffering and no severe complications.

Adult↗