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Avian vitreous humor concentrations of inosine, hypoxanthine, xanthine, uric acid, uracil and uridine as influenced by age and sex: their relevance as indicators of ante-mortem hypoxia.

An investigation was made to determine the effects of age and sex on postmortem concentrations (mumol/l) of inosine, hypoxanthine, xanthine, uric acid, uracil and uridine in the vitreous humor of chickens (Gallus domesticus). Five male and 5 female chickens were sampled each week from 0-10 weeks of age. Samples were collected at 0 and 24 h postmortem and analysed by HPLC. Hypoxanthine, uric acid and uridine were detected at both 0 and 24 h postmortem whereas inosine, xanthine and uracil were detected only at 24 h postmortem. Neither sex nor the sex X age interaction influenced the concentrations of the compounds investigated (P greater than 0.01). Age had a significant influence on the concentrations of all compounds at 24 h postmortem (P less than 0.0001). At 0 h postmortem, age significantly affected the levels of hypoxanthine and uridine (P less than 0.0001) but not uric acid (P = 0.014). All compounds occurred at higher concentrations at 24 than 0 h postmortem with the exception of uridine at 0 and 1 week of age. Previous studies using data confounded by age and postmortem sampling time have concluded that postmortem vitreous humor hypoxanthine concentration is a useful indicator of antemortem hypoxia. The results of this study cast doubt on that conclusion. Age and postmortem sampling time should be rigorously controlled when conducting quantitative analyses of these compounds in vitreous humor.

Age Factors↗

The effects of short-term vitamin C on plasma bun, uric acid, cholesterol and triglyceride levels.

The effects of daily 0.5 g vitamin C on plasma urea nitrogen, uric acid, cholesterol and triglyceride levels were recorded over a period of one month. There was a significant reduction in plasma cholesterol level (P less than 0.05). There was no significant effect of vitamin C on plasma urea nitrogen, uric acid and triglyceride levels (P greater than 0.05). It was a placebo-controlled trial. The research and control groups were formed of 105 and 47 volunteer university students, respectively. In these groups the mean ages were 20 +/- 0.33 (mean +/- S.E.M.) and 20 +/- 0.49 years, respectively. Mean body mass indices were 22.2 +/- 0.13 and 22.3 +/- 0.19 kg/m2, respectively.

Adult↗

[Interference of noramidopyrin and its derivatives on the dosage of uric acid].

Administration of noramidopyrine or of noramidopyrine-methane-sulfonate interferes with the determination of blood uric acid by both the colorimetric method of Folin-Denis and an enzymatic uricase peroxidase method. This interference which is observed at least during the 24 hours following intravenous administration of noramidopyrine, results in either an increase (Folin-Denis) or a decrease (uricase) of the intensity of the final colour. The same effects are also observed in vitro when one adds noramidopyrine to an aqueous solution of uric acid. Existence of this interference should be taken into consideration especially in the diagnosis, the prognosis and the analgesic treatment of renal lithiasis.

Adult↗

Evaluation of renal handling of uric acid in essential hypertension: hyperuricemia related to decreased urate secretion.

The tubular transport of urate was studied in 40 hypertensive patients and in 20 normal subjects by means of pyrazinamide and benzbromarone tests. There was a marked decrease in urate excretion per nephron in hyperuricemic patients with essential hypertension. Serum uric acid correlated inversely with fractional excretion of urate (r = -0.7450, p less than 0.001). Presecretory and postsecretory reabsorption of urate did not significantly differ between hypertensive patients with high uric acid levels and control subjects. Urate secretion was significantly reduced in hypertensive patients and in those with hyperuricemia showed a twofold decrease. Serum uric acid correlated inversely with tubular secretion of urate (r = -0.7091, p less than 0.001) in hypertensive patients. These findings indicate that impaired tubular secretion of urate is a potential mechanism of hyperuricemia in essential hypertension.

Female↗

[Clearance of oxypurines and uric acid in patients with gout].

The clearance of uric acid, hypoxanthine and xanthine has been examined in gouty patients and in normal subjects comparatively to the creatinine clearance. The clearance of the three purine compounds was lower in the gouty patients, while the creatinine clearance showed a normal behavior. These results indicate that either the tubular excretion or the carriers of the considered metabolites probably undergo specific alterations in the gout.

Adult↗

Effect of splanchnicotomy on the renal excretion of uric acid in anaesthetized dogs.

The renal excretion of uric acid was examined during acute i.v. urate (Ua) loading on unilaterally splanchnicotomized ("renal denervation") anaesthetized mongrel dogs. Glomerular filtration rate (GFR) in general was not different in innervated and denervated kidneys, whereas urine flow (V) and urinary excretion of sodium (UNaV) on the splanchnicotomized side were significantly increased at any plasma concentration of Ua. The excretion (UUaV) and tubular transport (TUa) of urate calculated for unit GFR were considerably increased and depressed, respectively, at normal plasma Ua level and during minor urate loading (plasma concentration up to 4.7 mg%). Above this plasma level, i.e. up to 24.6 mg%, no difference in net urate reabsorption between intact and sympathectomized organs was found. It is suggested that both reabsorption and secretion of Ua in denervated kidneys are diminished.

Anesthesia↗

Cerebrospinal fluid levels of uric acid in dogs and the effect of allopurinol.

Uric acid (UA) levels in cerebrospinal fluid (CSF) were measured in 15 dogs and the entrance and effect of allopurinol, a specific inhibitor of enzyme xanthine oxidase (XO), in brain were measured by sampling CSF in dogs. Allopurinol was administered intravenously 25 mg/kg every 6 h for 48 h. Drug level as well as UA level in plasma and CSF was measured by high-performance liquid chromatography. A significant concentration of allopurinol was achieved in CSF and a remarkable suppression of CSF UA level was observed at all time points measured. Decrease of UA in CSF level was more pronounced than in plasma, and was not considered secondary to suppression of systemic XO activity. Therefore the regimen employed was proven to be sufficient to suppress XO activity in the subarachnoid space, and drug concentration observed in CSF during this period (5 micrograms/ml) is considered to be in the therapeutic range.

Allopurinol↗

Experience with percutaneous nephrostomy, extracorporeal shock wave lithotripsy and chemolysis in the treatment of obstructive uric acid stones.

Intravenous pyelography (IVP), retrograde ureteral catheterization and percutaneous nephrostomy (PCN) have been used to locate radiolucent stones during ESWL in an X-ray localization system lithotripter. We also used an alternative method combining PCN, ESWL and chemolysis to treat 8 obstructive uric acid stones. The average number of shock wave pulses was 1,725 (range 1,000-2,000), the generator voltage of the HM-3 Dornier lithotripter was 20-22 kV, and the local chemolysis lasted 4 days (range 2-7). All radiolucent uric acid stones were successfully disintegrated. Of the 8 patients treated, 5 were completely free of stones and the other 3 had insignificant residual stones after 3 months. Three patients who developed fever during local chemolysis with 0.1 M sodium bicarbonate solution were managed conservatively without severe sequelae. Only 1 patient retained a PCN tube after discharge. Because PCN can provide a path for local chemolysis and better localization, it is especially helpful in treating obstructive uric acid stones.

Bicarbonates↗

Uric acid and inflammatory markers.

AIMS: The role of uric acid (UA) in the process of atherosclerosis and atherotrombosis is controversial. Epidemiological studies have recently shown that UA may be a risk factor for cardiovascular diseases and a negative prognostic marker for mortality in subjects with pre-existing heart failure. METHODS AND RESULTS: We evaluate a relationship between UA levels and several inflammatory markers in 957 subjects, free of severe renal failure, from a representative Italian cohort of persons aged 65-95. Plasma levels of UA and white blood cell (WBC) and neutrophil count, C-reactive protein, interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6r), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-alpha) were measured. Complete information on potential confounders was collected using standard methods. WBC (P=0.0001), neutrophils (P<0.0001), C-reactive protein (P<0.0001), IL-1ra (P<0.0001), IL-6 (P=0.0004), sIL-6r (P=0.002), IL-18 (P<0.0001), TNF-alpha (P=0.0008), and the percentage of subjects with abnormally high levels of C-reactive protein (P=0.004) and IL-6 (P=<0.0001) were significantly higher across UA quintiles. After adjustment for age, sex, behaviour- and disease-related confounders, results were virtually unchanged. In subjects with UA within the normal range, UA was significantly and independently associated with neutrophils count, C-reactive protein, IL-6, IL-1ra, IL-18, and TNF-alpha, whereas non-significant trends were observed for WBC (P=0.1) and sIL-6r (P=0.2). CONCLUSION: A positive and significant association between UA and several inflammatory markers was found in a large population-based sample of older persons and in a sub-sample of participants with normal UA. Accordingly, the prevalence of abnormally high levels of C-reactive protein and IL-6 increased significantly across UA quintiles.

Aged↗

Comparison of ticrynafen and probenecid in patients with elevated uric acid levels.

Ticrynafen, 125--250 mg/day was compared with probenecid 0.5--1.0 g/day in patients with elevated serum uric acid values in a randomized, double-blind crossover study. Each treatment period lasted 12 weeks. The mean reduction in serum uric acid from 9.4 +/- 1.2 to 6.22 +/- 1.2 mg/dl (33.8%) during ticrynafen was greater (p less than 0.01) than that from 9.46 +/- 1.1 to 7.0 +/- 1.3 mg/dl (26%) during probenecid treatment. There were slight increases in serum creatinine and BUN and decreases in body weight during ticrynafen treatment. There were no statistically significant changes in serum electrolytes. The hypouricemic effect of ticrynafen was well maintained during its subsequent open-label administration for 18 months without any deterioration of renal function.

Aged↗

Haemorrhage-induced release of noradrenaline, 5-hydroxytryptamine and uric acid in the supraoptic nucleus of the rat, measured by microdialysis.

Concentrations of monoamines and metabolites and uric acid were measured in sequential 15-min microdialysis samples taken from the area of the supraoptic nucleus (SON) in 9 urethane-anaesthetized rats. A decrease in blood pressure of 40 mm Hg was induced by withdrawing 3-4 ml of blood from an indwelling jugular catheter. This decreased blood pressure was maintained for 30 min and produced a significant rise in the concentrations of noradrenaline (NA) and its metabolite 4-hydroxy-3-methoxyphenylethan-1,2-diol (MHPG) and also in 5-hydroxytryptamine (5-HT) and the purine metabolite uric acid (UA). When blood pressure was returned to normal by replacing the withdrawn blood, the concentrations of NA, MHPG, 5-HT and UA returned to pre-haemorrhage levels within 15 min. No significant changes in concentrations of dopamine and its metabolites were found, and in 7 control animals sampled 1.5-2 mm away from the SON, in the area of the olfactory tubercle, concentrations of NA, MHPG, 5-HT and UA were not significantly altered by haemorrhage-induced decreases in blood pressure.

Animals↗

A candidate reference method for the determination of uric acid in serum based on high performance liquid chromatography, compared with an isotope dilution-gas chromatography-mass spectrometer method.

A method based on isocratic high performance liquid chromatography (HPLC) with UV detection at 292 nm is proposed as a candidate reference method for the determination of uric acid. Data obtained by this method are compared with those from an isotope dilution-gas chromatography-mass spectrometric method (ID-GC-MS), using [1,3-15N2]uric acid as internal standard and selected mass detection at m/z = 456 and m/z = 458. The inaccuracy of the ID-GC-MS method is maximally 0.4% for NBS-SRM-909 control sera with a concentration of 483 mumol/l. The coefficient of variation between days is 0.26%-0.80% and 0.37-0.90% for 14 control sera from other suppliers. The maximum bias of the HPLC method is 0.6%, and the coefficient of variation between days is 0.31%-0.65% for NBS-SRM-909 control sera. The coefficient of variation between days for the other 14 control sera tested is 0.35%-0.66%. Comparison of the HPLC method with the reference ID-GC-MS method resulted in a coefficient of correlation of r = 0.9998 (n = 14). The concentration of uric acid in the tested control sera ranged from 160 to 624 mumol/l.

Chromatography, High Pressure Liquid↗

Changes of plasma uric acid levels in horses after galloping.

Two horses were alternately galloped and cantered at 48 h intervals in a cross over trial. Galloping produced a rise in plasma lactic and uric acids. The lactic acid decreased in concentration whereas the uric acid increased in the hour after exercise. Plasma phosphate levels were depressed 1 h after galloping. There was no significant variation in these parameters after cantering. Possible reasons for these changes are discussed.

Animals↗

Vitamin C, uric acid, and glutathione gradients in murine stratum corneum and their susceptibility to ozone exposure.

The stratum corneum has been recognized as the main cutaneous oxidation target of atmospheric ozone (O3), a major part of photochemical smog. This study reports the presence and distribution of vitamin C, glutathione, and uric acid in murine stratum corneum, and evaluates their susceptibility to acute environmental exposure to O3. Based on tape stripping and a modified extraction method with high performance liquid chromatography electrochemical analysis, we detected vitamin C (208.0 +/- 82.5 pmol per 10 consecutive pooled tapes), glutathione (283.7 +/-96.3), and uric acid (286.4 +/-47.1) in murine stratum corneum as compared with only 16.5 +/- 1.4 pmol alpha-tocopherol. Vitamin C, glutathione (both p < 00.001), and urate (p < 0.01) were found to exhibit a gradient with the lowest concentrations in the outer layers and a steep increase in the deeper layers. To investigate the effect of O3 exposure on hydrophilic antioxidants, we exposed SKH-1 hairless mice to O3 concentrations of 0, 0.8, 1, and 10 p.p.m., and stratum corneum was analyzed before and after exposure. Whereas mock exposure with 0 p.p. m. for 2 h had no significant effect, O3 doses of 1 p.p.m. for 2 h and above showed depletion of all three antioxidants. Vitamin C was decreased to 80% +/- 15% of its pretreatment content (p < 0.05), GSH to 41% +/- 24% (p < 0.01), and uric acid to 44% +/- 28% (p < 0.01). This report demonstrates the previously unrecognized role of hydrophilic antioxidants in the stratum corneum and provides further evidence that O3 induces oxidative stress in this outer skin layer.

Animals↗

Survey of metabolic reserves, stored uric acid, and water content from field populations of subterranean termites (Isoptera: Rhinotermitidae) from Georgia.

Total levels of uric acid, soluble proteins, lipid, glycogen, and body water were determined for Reticulitermes flavipes (Kollar) workers 24-72 h after field collection. In addition, levels of biological molecules were compared for termites collected from the same inspection ports within 24 h after field collection, and after laboratory captivity of 6 or 9 mo. Uric acid content, described in a previous study as steadily accumulating in R. flavipes termites in captivity, was found to be low or undetectable in workers tested after 6 or 9 mo in the laboratory.

Animals↗

Adaptation of blank-corrected methods for measurement of total and conjugated bilirubin and uric acid to the centrifugal analyzer.

The blank-corrected determination in serum of total and conjugated bilirubin and of uric acid has been adapted to the centrifugal analyzer. Bilirubin is measured by a modified Jendrassik and Grof procedure; uric acid is determined kinetically by using a reaction based on reduction of ferric ion, including a uricase-treated blank. Sensitivity and precision of both methods are excellent, and results compare well with those obtained by commonly used procedures.

Autoanalysis↗

Uric acid lithiasis in the Sudan.

Fifty-seven per cent of Urinary Calculi in the Sudan contain Uric Acid, 20 per cent in the pure form and 37 per cent mixed with other constituents mainly calcium oxalate. The peak age presentation of urolithiasis is 30-40 years with more prediliction to males than females. An earlier study documented a high incidence of hyperuricaemia in Sudanese people. It is probable that "voluntary dehydration" and hyperuricaemia acting together may help in the formation of uric acid stones on the surface of which other crystals mainly calcium oxalate may be deposited to form the bigger calculi which are commonly encountered in this country.

Adolescent↗