Urinary Uric Acid Levels Research Articles

Toxic studies on biochemical parameters carried out in rats with Serankottai nei, a siddha drug–milk extract of Semecarpus anacardium nut

A toxicological study was carried out in rats with a Siddha preparation, milk extracts of Semecarpus anacardium nuts. The effect of acute (72 h) and subacute (30 days) treatment of the drug with different dosage on liver and kidney functions and hematological parameters were studied. The acute toxicity studies with this drug did not produce mortality at any dose level given (75–2000 mg/kg body weight). No marked adverse alterations were observed in hematological and biochemical parameters during the subacute toxicity studies (50, 100, 250 and 500 mg/kg body weight). In the subacute treatment, the highest dose (500 mg/kg body weight) alone showed a moderate increase in the level of blood glucose, plasma urea, uric acid, and creatinine. In addition, alteration in lipid profiles were observed which may be attributed to the ghee preparation of the drug. Decrease in urinary urea, uric acid and creatinine levels were also observed. Histopathological examination of vital organs showed normal architecture suggesting no morphological disturbances.

Effect on Physiological Variables and Urinary Metabolites following a Single Dermal Application of Sulphur Mustard in Rats

The effect of single dermal application of different doses of sulphur mustard (2,2'-dichlorodiethyl sulphide, SM), i.e.5, 10 and 20 mg/kg body weight on some physiological variables, viz., body weight, intake of food and water, and excretion of excreta and urine was studied for one week. Levels of urinary metabolites, uric acid, urea, protein, creatine and creatinine were measured at 0, 1, 2, and 7 days in albino rats of Wister strain. A progressive dose-dependent fall in body weight was observed from day onwards after SM application. Feed and water intake were reduced significantly. Excretion of urine and exdreta was also affected adversely. The level of uric acid, a metabolite of purine bases, increased 24 hr post-exposure, in a time and dose-dependent manner. Excretion of urea decreased and the level of creatine increased drastically on 7th day. However, urinary excretions of protein and creatinine did not change. The study shows that single application of SM in rats induces a catabolic state.

Biochemical relationship between urine composition and urinary stone formation in stone forming patients.

The precise relationship between urine composition and stone formation has not yet been completely understood. The object of this work is to study some constituents of the urine in stone formers and normal subjects in a trial to correlate stone formation with urine composition. Urinary levels of oxalic acid, uric acid and phosphate were elevated in oxalate, urate and phosphate stone formers, respectively, while in the urine of mixed stone formers both oxalic and uric acids were increased. Urinary levels of ascorbic acid, citric acid and mucopolysaccharides in all groups of patients were significantly higher than the corresponding control levels. Although oxalic acid, uric acid and phosphate concentrations were high in their respective stones, the concentrations of these constituents were nearly the same in the mixed stones. Also Ca2+ concentration was higher in stones of oxalate and mixed stone formers than in stones of urate and phosphate formers. Exceptionally, magnesium was high in stones of phosphate stone formers. It is recommended that urinary contents of oxalate, urate and phosphate have to be minimized to overcome stone recurrence.

Hypouricemic effect of allopurinol and the novel xanthine oxidase inhibitor TEI-6720 in chimpanzees

The hypouricemic effect of a newly synthesized xanthine oxidase / xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid, was investigated and compared with that of allopurinol in male chimpanzees ( n = 3). When allopurinol (10 mg/kg) was administered orally once a day for three consecutive days, it cumulatively reduced serum urate levels by 29.7, 50.1 and 60.2%, 24, 48 and 72 h, respectively, after the initial dose. This effect was dose dependent at doses of 3 and 10 mg/kg. At 3 mg/kg, the mean serum urate levels were 3.1, 2.4, 2.5 and 2.3 mg/dl before and 24, 48 and 72 h, respectively, after the initial dose. Animals treated with 10 mg/kg of allopurinol showed serum urate levels of 3.3, 2.3, 1.6 and 1.3 mg/dl, respectively. The urate-lowering effect of TEI-6720 was then comapred with that of allopurinol at a daily dose of 5 mg/kg ( n = 3). Both compounds caused striking reductions in serum and urinary uric acid levels accompanied by an increase in urinary xanthine levels. These effects of TEI-6720 were more potent than those of allopurinol. TEI-6720 reduced serum urate levels by 55.9, 69.6 and 73.6%, 24, 48 and 72 h, respectively, after the first dose, whereas, the corresponding values after allopurinol were 28.1, 41.6 and 45.1%. These results suggest that the hypouricemic effect of TEI-6720 may be more potent than that of allopurinol in the treatment of hyperuricemia and gout, and that TEI-6720 may become an effective alternative drug.

Effect of Orange Juice Consumption on Urinary Stone Risk Factors

The value of orange juice consumption in kidney stone prevention was examined in 8 healthy men and 3 men with documented hypocitraturic nephrolithiasis. They underwent 3 phases of a metabolic study, a placebo phase and 2 treatment phases in which they ingested either 1.2 1. orange juice (containing 60mEq. potassium and 190mEq. citrate per day) with meals or potassium citrate tablets (60mEq. per day) with water and meals. Compared to potassium citrate, orange juice delivered an equivalent alkali load and caused a similar increase in urinary pH (6.48 versus 6.75 from 5.71) and urinary citrate (952 versus 944 from 571mg. per day). Therefore, orange juice, like potassium citrate, decreased urinary undissociated uric acid levels and increased the inhibitor activity (formation product) of brushite (calcium phosphate). However, orange juice increased urinary oxalate and did not alter calcium excretion, whereas potassium citrate decreased urinary calcium without altering urinary oxalate. Thus, orange juice lacked the ability of potassium citrate to decrease urinary saturation of calcium oxalate. Overall, orange juice should be beneficial in the control of calcareous and uric acid nephrolithiasis.

Changes in serum and urinary uric acid levels in normal human subjects fed purine-rich foods containing different amounts of adenine and hypoxanthine.

The effect of ingesting some purine-rich foods (beef liver, haddock fillets and soybeans) on uric acid metabolism was investigated in 18 male subjects with no history of gout or kidney disorder. In a crossover design, three isoenergetic and isonitrogenous meals were fed to volunteers during a 3-week period. Only the content of uricogenic bases (adenine and hypoxanthine) varied among the test meals. Ingestion of all experimental meals caused an increase in serum uric acid levels at 120 minutes and this increase was more marked (about twofold) with haddock and soybean ingestion. In all groups, the postprandial serum uric acid levels at 240 minutes were lower than those obtained at 120 minutes, but still remained elevated in comparison to the fasting level. The test foods had little or no effect on serum and urinary creatinine values. As expected, 24-hour urinary uric acid excretion was similar for the three test meals due to the isonitrogenous load of proteins and purines. Assessment of each purine base content rather than the total purine content of foods should be considered in future recommendations for hyperuricemic individuals.

Molybdenum in the Premature Infant

The molybdenum (Mo) levels in the plasma and urine of 30 premature and 15 full-term infants have been compared with the Mo intakes and urine uric acid excretion (uric acid/creatinine ratio) produced by the Mo enzyme xanthine oxidase. The Mo intakes of full-term infants were 41 +/- 14 nmol/kg/day (mean +/- SEM). In the premature group breast milk supplied significantly less Mo (4.3 +/- 0.4 nmol/kg/day) than infant formulas (101 +/- 31 nmol/kg/day) or premature formula (255 +/- 13 nmol/kg/day). When fed breast milk, the preterm infants displayed similar or higher plasma and urine Mo and urine uric acid levels than formula-fed infants. For the whole preterm group a significant correlation was determined for urine Mo levels and Mo intakes as well as for plasma Mo and uric acid excretion. The bioavailability of breast milk Mo seems to be higher than formula Mo according to the Mo levels and to their statistical link with uric acid excretion which could be proposed as a functional index of Mo status. These parameters displayed similar values in breast milk-fed prematures and control full-term infants. The Mo needs of formula-fed premature newborns remain to be defined using complete balance trials.

Renal sonography in long standing Lesch-Nyhan syndrome

The Lesch-Nyhan syndrome is an x-linked defect of purine metabolism resulting in its classical form in major neurodevelopmental abnormality, hyperuricaemia, and hyperuricosuria. Uric acid calculi and crystalluria are common. Allopurinol is the main method of reducing serum and urinary uric acid levels, but results in xanthinuria and oxypurinoluria, both of which may cause crystal nephropathy and calculi. The variable ultrasonic appearances of multiple calculi and increased medullary echogenicity in four cases of long-standing treated disease and the nature of the renal disorder, which is at least partially iatrogenic, are described.

海綿腎の臨床的検討

Thirty eight patients with medullary sponge kidney (MSK) were detected (4.3%) in 881 patients with urolithiasis diagnosed by drip infusion pyelography in 12 years from January 1974 to December 1985. Those with MSK were studied clinically and as to metabolism of urolithiasis. The results obtained were as follows: 1) Age distribution of the patients with MSK was the same as that of general stone formers. 2) Hematuria was observed in 20 patients (52.6%) and pyuria in 7, in whom 4 were positive by urine culture (E. coli in 3 and P. mirabilis in 1) and 2 of them had infective stones. 3) Renal function of the patients examined by PSP test (20 patients) and creatinine clearance test (21 patients) was normal in all of the patients but three with ureteral caliculi. Concentration tests performed by Fishberg method (12 patients) were disturbed in half of them. 4) Affected lesions wer detected at more than three pyramides in each kidney and the bilaterals were found in 32 patients (84.2%) and at less than two pyramides in each kidney and the unilateral or the bilaterals were shown in the other 6. 5) When urinary levels of calcium, phosphate, uric acid and citrate using 24 hours urine were compared with 37 patients with MSK and 100 general stone formers, there was no difference in hypercalciuria and hyperuricosuria accounting for the frequency of the patients with MSK and the general stone formers, but there was a tendency of increased frequency about hyperphosphaturia and hypocitraturia in the patients with MSK.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in Uricogenic Effects of Dietary Purine Bases, Nucleosides and Nucleotides in Rats

The uricogenic effects of dietary free purines (adenine, guanine, hypoxanthine and xanthine), their nucleosides (adenosine, monophosphate, guanosine monophosphate and inosine monophosphate) were studied in rats. Casein-based diets (20% protein) supplemented with 30 mmol/kg diet of each of the free purine base, nucleoside or nucleotide were fed to male Sprague-Dawley rats (100 +/- 5 g) for 14 d. Addition of adenine resulted in less weight gain than in controls, greater kidney weight, greater urine volume and higher levels of blood urea nitrogen, serum uric acid, creatinine and allantoin but lower urinary levels of allantoin, uric acid and creatinine. The adenine diet also caused nephropathy characterized by nephromegaly and deposition of crystals. A microscopic examination of the kidneys revealed deposition of crystals mainly in the lumen of convoluted tubules of the cortex. Feeding of diets containing other purine bases, nucleosides and nucleotides had no adverse effects on kidney weight or structure, urine volume, serum uric acid or creatinine. Urinary allantoin excretion, however, was greater in rats fed hypoxanthine, xanthine, nucleoside and nucleotide diets than in control rats. Adenine produced adverse effects only when fed in the free form and not when fed as the nucleoside or nucleotide, suggesting a metabolic significance for free adenine in predicting hyperuricemic effects of foods.

Long-Term Treatment of Calcium Nephrolithiasis with Potassium Citrate

The long-term effects of potassium citrate therapy (usually 20 mEq. 3 times daily during 1 to 4.33 years) were examined in 89 patients with hypocitraturic calcium nephrolithiasis or uric acid lithiasis, with or without calcium nephrolithiasis. Hypocitraturia caused by renal tubular acidosis or chronic diarrheal syndrome was associated with other metabolic abnormalities, such as hypercalciuria or hyperuricosuria, or occurred alone.Potassium citrate therapy caused a sustained increase in urinary pH and potassium, and restored urinary citrate to normal levels. No substantial or significant changes occurred in urinary uric acid, oxalate, sodium or phosphorus levels, or total volume. Owing to these physiological changes, uric acid solubility increased, urinary saturation of calcium oxalate decreased and the propensity for spontaneous nucleation of calcium oxalate was reduced to normal. Therefore, the physicochemical environment of urine following treatment became less conducive to the crystallization of calcium oxalate or uric acid, since it simulated that of normal subjects without stones.Commensurate with the aforementioned physiological and physicochemical changes the treatment produced clinical improvement, since individual stone formation decreased in 97.8 per cent of the patients, remission was obtained in 79.8 per cent and the need for surgical treatment of newly formed stones was eliminated. In patients with relapse after other treatment, such as thiazide, the addition of potassium citrate induced clinical improvement.Thus, our study provides physiological, physicochemical and clinical validation for the use of potassium citrate in the treatment of hypocitraturic calcium nephrolithiasis and uric acid lithiasis with or without calcium nephrolithiasis.

The Incidence of Cystinuria in Japan

Screening tests for cystinuria were done in approximately 110,000 children and students. The rates of discovery were chemical cystinuria 920 to 1, cystine crystalluria 16,000 to 1 and homozygous cystinuria 18,000 to 1 (8,000 to 1 if a correction was made by the rates of performances of secondary screening and urinary amino acid assay). No stone formation was observed in a 7-year followup of 6 patients considered to be homozygotes. A correlation was observed between urinary cystine and urinary uric acid levels in 39 cases of chemical cystinuria.

Pharmacokinetic and pharmacodynamic studies of tienilic acid in healthy volunteers.

A simple and reliable HPLC method for the determination of tienilic acid ((TA) Selacryn, Selcryn, Diflurex, Ticrynafen) and its alcoholic metabolite in plasma and urine has been developed. In 8 healthy adult volunteers the plasma and urinary levels of tienilic acid and its alcoholic metabolite, and plasma and urinary levels of sodium, creatinine and uric acid were measured after oral administration of tienilic acid 250 mg. The pharmacokinetic parameters found differed only slightly from those reported in the literature, as there was faster absorption and a shorter half-life. TA is probably excreted by a saturable renal tubular transport mechanism. The pharmacodynamic effects of tienilic acid developed quickly, the uricosuric effect being very impressive and the natriuretic effect moderate. These effects disappeared in about 8 h. An inverse relationship was found between the starting plasma uric acid level in an individual and the maximal uric acid clearance - the higher the plasma uric acid level, the lower was the maximum effect. Plasma tienilic acid level and natriuretic effect were correlative within individuals and intra-individually (p less than 0.05). Urinary tienilic acid level and natriuretic effect were correlated, too (p less than 0.05 to p less than 0.001), but only intraindividually. No correlation between drug level and uricosuric effect was found.

Uric acid: Effects on serum and urine levels in patients receiving intravenous dextrose, fat, and/or amino acid solutions

Parenteral dextrose/amino acid solutions reduce serum uric acid levels when infused into patients. To elucidate the mechanism further, 53 patients with invasive bladder cancer were selected for study. Patients received either amino acids alone ( n = 13), 5% dextrose + amino acids ( n = 15), 5% dextrose in water ( n = 13), 25% dextrose + amino acids ( n = 7), or fat 10% + amino acids ( n = 5). All patients received 2500 ml intravenously for 3 days preop and 3000 ml for at least 7 days postop containing 1.4 g AA/kg/day; after Day +7 oral intake was allowed. No patient had gout. Serial serum uric acid levels and daily 24-hr urine uric acid and creatinine levels were measured. There were no significant differences among intravenous groups in: mean patient age, percentage ideal body weight, duration of operation, operative blood loss, fluid-blood replacement, or serum and urine creatinine levels. Mean serum uric acid levels decreased postoperatively in all groups. The mean change in serum uric acid levels from Day −3 to Day +7 was significantly different between the D5/AA group (2.3 ± 0.2 mg/dl) and the AA/H 2O group (1.1 ± 0.4 mg/dl) and between the D25/AA group (2.8 ± 0.6 mg/dl) and the AA/H 2O and D5W (1.4 ± 0.3 mg/dl) group. This significant change in mean serum uric acid levels with infusion of 5 and 25% dextrose with amino acids occurred without increased uricosuria compared to the other groups of patients.

Plasma and urine uric acid levels: heritability estimates and correlation with IQ.

Plasma and urine uric acid levels were measured in 37 pairs of twins aged 11 or 12 years and their parents. Effect of age differed between sexes and between plasma and urine. Assuming linear regression on age, the uric acid levels were adjusted for a fixed age, then standardized with mean 0 and standard deviation 1. The standardized values for plasma yielded a high MZ twin correlation (0.8429) a high mid-parent-offspring regression (0.7516) and a high parent-offspring regression (0.5100). Because of a high husband-wife correlation (0.3771) a model was used for estimating parameters, where effects of assortative mating and/or common within-family environment were incorporated. In plasma two sets of estimates were obtained: VA/VP=0.7064, 0.3251; VD/VP=0.1010, 0.1769; and VEC (variance due to common within-family environment)/VP=0.0362, 0.3416. In urine VA/VP=0.4125, VD/VP=0.3556 and VEC/VP=−0.1106. It was concluded that heritability of uric acid level was not less than 0.3 in plasma and not less than 0.4 in urine. The plasma uric acid level and IQ was positively correlated (between 0.17 and 0.34), but not significant.

The degradation of nucleic acids in, and the removal of breakdown products from the small intestines of steers.

1. Nucleic acids and breakdown products were estimated in digesta taken from different sites in the small intestines of slaughtered steers given different diets. Amounts passing different sites were compared using cellulose as a non-digestible marker. The validity of this marker was checked with chromic oxide in some experiments. In other experiments, nucleic acids or derivatives were infused into the proximal duodenum of steers receiving diets of approximately equal proportions of flaked maize and hay. The amounts disappearing during passage through the small intestine were estimated using polyethylene glycol (PEG) as a non-absorbable marker. 2. In the slaughter experiments the amounts of nucleic acids entering the small intestine varied with the type of diet. RNA and DNA disappeared on average, to extents of 89% and 80% respectively between the abomasum and the terminal ileum, irrespective of the diet. RNA disappearance occurred almost entirely in the proximal quarter of the small intestine, whereas that of DNA extended further along the tract. 3. Nucleic acid degradation in the upper small intestine was accompanied by the transient appearance of adenosine, guanosine and pyrimidine nucleosides. These products were in greatest concentration in digesta from the first quarter of the small intestine and had generally completely disappeared by the terminal ileum. 4. Of the different substances infused into the smnall intestine, free nucleic acids were removed to extents greater than 97%, adenine, guanine and uracil had completely disappreaed, thymine and xanthine to approximately 80% and 95% and hypoxanthine and cytosine to only 51% and 48% respectively. The nucleosides adenosine and cytidine were also completely removed in the small intestine but were replaced, in part, by the catabolic products inosine plus hypoxanthine or cytosine respectively. Other nucleosides were removed to approximately half the extent of the correspoonding bases. 5. Serum and urine allantoin and uric acid levels were related to the amounts of purines entering the small intestines in free or bound form.

Hyperuricemia induced by some antihypertensives and uricosuric drugs in oxonate-treated rats.

Effects of antihypertensive and uricosuric drugs were studied on the plasma and urinary levels of uric acid in oxonate-treated rats. We made use of animals with a catheterized aorta to successfully collect blood samples and this procedure simplified the evaluation of progressive changes of plasma uric acid, under successive loading with potassium oxonate. The plasma uric acid level of the oxonate-treated rats was increased even with a single administration of diuretic chlorothiazides, furosemide, diazoxide and also uricosuric drugs such as tienilic acid and probenecid. On the other hand, a wellmaintained plasma uric acid level was also produced by exogenously administered uric acid in rats which had been given allopurinol and potassium oxonate. Diazoxide, tienilic acid and probenecid increased the plasma uric acid, while diuretic chlorothiazides did not. Furosemide tended to decrease the plasma uric acid level at the early stage of administration to rats treated with allopurinol, oxonate and uric acid, but increased these levels several hours later when the effect was studied by uric acid loading test wit rats treated with allopurinol and oxonate. These effects also appeared as changes in the urine-excreted uric acid. Thus, the oxonate-treated rats demonstrated an acutely induced hyperuricemia not only with certain antihypertensives, but also with uricosuric drugs. The utility of these procedures for evaluating the hyperuricemic and uricosuric effects of drugs is discussed.

Hyperuricemia Induced by Some Antihypertensives and Uricosuric Drugs in Oxonate-Treated Rats

Effects of antihypertensive and uricosuric drugs were studied on the plasma and urinary levels of uric acid in oxonate-treated rats. We made use of animals with a catheterized aorta to successively collect blood samples and this procedure simplified the evaluation of progressive changes of plasma uric acid, under successive loading with potassium oxonate. The plasma uric acid level of the oxonate-treated rats was increased even with a single administration of diuretic chlorothiazides, furosemide, diazoxide and also uricosuric drugs such as tienilic acid and probenecid. On the other hand, a wellmaintained plasma uric acid level was also produced by exogenously administered uric acid in rats which had been given allopurinol and potassium oxonate. Diazoxide, tienilic acid and probenecid increased the plasma uric acid, while diuretic chlorothiazides did not. Furosemide tended to decrease the plasma uric acid level at the early stage of administration to rats treated with allopurinol, oxonate and uric acid, but increased these levels several hours later when the effect was studied by uric acid loading test with rats treated with allopurinol and oxonate. These effects also appeared as changes in the urine-excreted uric acid. Thus, the oxonate-treated rats demonstrated an acutely induced hyperuricemia not only with certain antihypertensives, but also with uricosuric drugs. The utility of these procedures for evaluating the hyperuricemic and uricosuric effects of drugs is discussed.

Uricosuric properties of diflunisal in man.

1 The uricosuric effect of diflunisal was studied in eleven normal subjects. 2 Urine and serum uric acid levels were measured and used to assess the effect. 3 Diflunisal caused statistically significant decreases in serum uric acid levels and increases in uric acid clearance at 250 and 375 mg twice daily. 4 Diflunisal taken on an empty stomach caused epigastric discomfort in the high dose group which was obviated when the drug was taken with meals. 5 Diflunisal caused no abnormalities in the measured haematological, urological or biochemical parameters.

CHANGES OF BLOOD METABOLITES IN HORSES AFTER RACING, WITH PARTICULAR REFERENCE TO URIC ACID

Changes in concentration of a number of blood metabolites in 30 thoroughbred horses were recorded after an 1110 metre race. No significant changes occurred in blood urea or aspartate aminotransferase during the three hours after racing. Plasma sodium, potassium and calcium levels were increased immediately after racing but had returned to normal one hour after racing. Plasma phosphate showed a significant fall in concentration one hour after racing. Creatinine and lactic acid concentrations were elevated ten minutes after racing and although they subsequently decreased, the level of lactic acid was still significant one hour later. Uric acid levels were well above resting levels at ten minutes after racing but rose even more in the subsequent hour. Urinary uric acid levels were also elevated during this time. Three hours after racing some horses still had elevated plasma uric acid levels and all of them showed a significant rise in creatine phosphokinase. The possible physiological basis of these findings is discussed.