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A comparative study of the concentrations of hypoxanthine, xanthine, uric acid and allantoin in the peripheral blood of normals and patients with acute myocardial infarction and other ischaemic diseases.

The aim of this study was the elucidation of the role of the xanthine oxidoreductase in the purine metabolism in ischaemic diseases of man. The serum concentrations of hypoxanthine, xanthine, uric acid and allantoin were determined in peripheral blood samples from patients with angina pectoris, cerebral insult and myocardial infarction with thrombolytic therapy and were compared with the concentrations obtained for healthy males and females. No significant differences were observed for the serum hypoxanthine concentrations, xanthine concentrations, the sum (hypoxanthine+xanthine) and the ratio (xanthine/hypoxanthine) between the healthy males, healthy females, the patients suffering from angina pectoris and the patients suffering from cerebral insult. An increase of the serum xanthine concentration in patients with myocardial infarction indicates a significant metabolic involvement of xanthine oxidoreductase in this disease and therefore a possible role in the development of tissue damage in the postischaemic phase due to oxygen radicals generated by the oxidase activity of this enzyme. The serum concentrations of uric acid and allantoin showed no differences between any of the studied groups. Study of the non-enzymatic oxidation of uric acid to allantoin by oxygen radicals, a relevant radical-scavenging mechanism in other diseases, provided no indication of an increased concentration of oxygen radicals due to the xanthine oxidoreductase reaction or other radical-producing mechanisms.

Adult↗

Effect of apolipoprotein E polymorphism on serum uric acid levels in healthy subjects.

BACKGROUND: We have previously shown that apolipoprotein E (apo E-) polymorphism may affect serum creatinine concentration and predicted glomerular filtration rate in healthy individuals. On the other hand, there are limited data regarding the possible influence of apo E- polymorphism on serum uric acid (SUA) levels. METHODS: Two hundred ninety (148 male, 142 female) apparently healthy white individuals were studied. apo E- genotypes, serum lipid parameters including apolipoproteins, insulin resistance using the homeostasis model assessment (HOMA) as a marker, serum and urine creatinine levels, and serum and urine uric acid concentration were determined in all participants. RESULTS: The apo E-2 allele was associated with lower serum levels of total cholesterol, higher levels of triglycerides and apo E-, and increased serum creatinine concentration compared with the apo E-3 and apo E-4 alleles in our population. Furthermore, the apo E-2 allele was associated with higher SUA levels (321.3+/-101.1 micrmol/L [5.4+/-1.7 mg/dL]) compared with the apo E-3 allele (261.8+/-89.2 micromol/L [4.4+/-1.5 mg/dL]; p= .012) and the apo E-4 allele (243.9+/-65.4 micromol/L [4.1+/-1.1 mg/dL]; p= .010), whereas the apo E-2 allele was associated with a nonsignificantdecrease in the fractional renal excretion of uric acid (FEUA) compared with the apo E-3 and apo E-4 alleles (7.9+/-2.2% vs 8.7+/-4.2% vs 8.9+/-5.1%, respectively; p = .53). These observations remained statistically significant when the effect of apo E- polymorphism on SUA levels was adjusted for gender, age, systolic and diastolic blood pressure, body mass index, serum creatinine, and triglyceride and apo E- levels, as well as for HOMA index and FEUA. CONCLUSIONS: Our data provide evidence, for the first time, that the apo E-2 allele is independently associated with increased SUA levels in healthy individuals.

Aged↗

Serum leptin is associated with serum uric acid concentrations in humans.

This cross-sectional study aimed to evaluate the relationship between leptin and the cluster of abnormalities often referred to as the metabolic syndrome. The serum leptin concentration, body mass index (BMI), percent body fat, total fat mass (FM), waist and hip circumference, waist to hip ratio (WHR), prevalence of hypertension, and triglyceride (TG), lipoprotein, and uric acid concentration were determined in 86 type 2 diabetic (n = 59) and healthy (n = 27) subjects. Multiple regression analyses showed that the estimates of total body obesity (BMI, percent body fat, and total FM), sex, and serum uric acid concentration are independently associated with the serum leptin concentration. The finding of a positive correlation between serum leptin and uric acid levels suggests that leptin could be a pathogenic factor responsible for hyperuricemia in obesity.

Adipose Tissue↗

Astroglia-mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity.

Uric acid (UA) has been demonstrated to reduce damage to neurons elicited by oxidative stress. However, our studies utilizing cultures derived from embryonic rat spinal cord indicate that an astroglia-mediated mechanism is involved in the effects of UA to protect neurons from glutamate toxicity. The damage elicted by glutamate to neurons in a mixed culture of spinal cord cells can be reversed by UA. Furthermore, addition of UA after the termination of glutamate exposure suggests that UA plays an active role in mediating neuroprotection rather than purely binding peroxynitrite, as previously thought. Importantly, in pure neuron cultures from the same tissue, UA does not protect against glutamate toxicity. Addition of astroglia to the pure neuron cultures restores the ability of UA to protect the neurons from glutamate-induced toxicity. Our results also suggest that glia provide EAAT-1 and EAAT-2 glutamate transporters to protect neurons from glutamate, that functional EAATs may be necessary to mediate the effects of UA, and that treatment with UA results in upregulation of EAAT-1 protein. Taken together, our data strongly suggest that astroglia in mixed cultures are essential for mediating the effects of UA, revealing a novel mechanism by which UA, a naturally produced substance in the body, may act to protect neurons from damage during insults such as spinal cord injury.

Analysis of Variance↗

Urocanic acid isomers are good hydroxyl radical scavengers: a comparative study with structural analogues and with uric acid.

UV-exposure of the epidermis leads to the isomerisation of trans-UCA into cis-UCA as well as to the generation of hydroxyl radicals. This study shows by means of the deoxyribose degradation test that UCA isomers are more powerful hydroxyl radical scavengers than the other 4-(5-)substituted imidazole derivatives, such as histidine, though less powerful than uric acid. UCA, present in relatively high concentrations in the epidermis, may well be a major natural hydroxyl radical scavenger.

Deoxyribose↗

Platelets and uric acid in the prediction of preeclampsia.

Fifty-four pregnancies that were subsequently complicated by preeclampsia had platelet parameters and uric acid levels measured during pregnancy. The expected fall in platelet count and rise in platelet volume parameters and uric acid levels beyond those that occur in normal pregnancy were seen only in the week before delivery.

Blood Platelets↗

Bioassay of aldosterone antagonists in normal human subjects: a relationship between the level of plasma uric acid before treatment and apparent drug responses.

The activity of single doses of SC-23992, a new aldosterone antagonist, and spironolactone in reversing the effects of fludrocortisone on urinary electrolyte composition in normal subjects was compared with that of placebo in a double-blind crossover study. 2 SC-23992 (50 mg) and spironolactone (125 mg) each significantly increased sodium excretion and the sodium : potassium (Na/K) ratio, and decreased potassium excretion, when compared with placebo. The response to the two active drugs did not differ significantly. 3 The urine Na/K ratio, and log10 Na/K, in response to spironolactone correlated negatively with the level of plasma uric acid measured 12 h before treatment. Similar trends were present after SC-23992 and placebo treatments. 4 It is suggested that the correlations between plasma uric acid and apparent drug response reflect a correlation between plasma uric acid and the aldosterone secretion rate in normal subjects. The sensitivity of this method of bioassay may be improved by suppressing endogenous aldosterone prior to medication.

Adult↗

[Why Dalmatians excrete uric acid. Causes and consequences of a classical metabolic disorder].

After introducing into developmental aspects of "Dalmatian dog research" uric acid excretion is explained on the basis of new results by the loss of a specific transport system in liver cell membranes. Therefore, uricase which is present in normal activities is supplied only to a limited extent with uric acid for the transformation into the easily soluble allantoin. As indicated by feeding experiments, the plasma urate level is increased from about 32 mumol/l (no purine intake) up to 150-200 mumol/l at very high levels of purine intake. Thus, the influence of nutrition on plasma urate level is extraordinary. The diseases urate-urolithiasis and "bronze syndrome" associated with dalmatian urate metabolism are characterized in view of the typical pattern of the diseases and of the therapeutical and prophylactical measures to be taken.

Allantoin↗

Serum uric acid and hemorheology in borderline hypertensives and in subjects with established hypertension and left ventricular hypertrophy.

Serum uric acid (SUA) but also hemorheological parameters such as hematocrit (Hct) and whole blood viscosity (WBV) are markers of cardiovascular risk. Increased blood cell volume is one of the known causes of hyperuricemia. We therefore aimed to investigate the relationship between SUA and hemorheology in untreated borderline hypertensive young men (n = 67) and in subjects with established hypertension and left ventricular hypertrophy (n = 40) examined when they had been without treatment for 2 weeks. We found positive correlations between SUA and Hct (r = 0.46, p < 0.0001), hemoglobin (Hgb) (r = 0.40, p = 0.001), mean blood pressure (BP) (r = 0.39, p = 0.001) and body weight (r = 0.26, p = 0.036) in the borderline hypertensive young men. No relation between SUA and glucose disposal rate (GDR) assessed with hyperinsulinemic isoglycemic glucose clamp appeared (r = -0.06, p = 0.633). Multiple regression analysis showed that 33% of the variation in SUA could be explained by BP and Hct. We also found positive correlations between SUA and Hgb (r = 0.40, p = 0.011) and body weight (r = 0.42, p = 0.006) and an inverse trend with GDR (r = -0.27, p = 0.087) in the subjects with established hypertension. Multiple regression showed that 32% of the variation in SUA was explained by Hgb and body weight. These data suggest that hemorheology may be involved in the uric acid metabolism in borderline as well as in established hypertensives. Hemorheology may possibly be a link between SUA and cardiovascular risk. There was no relation between SUA and insulin resistance in these hypertensive groups.

Adolescent↗

Glycation-induced inactivation of aspartate aminotransferase, effect of uric acid.

Glycation is common posttranslational modification of proteins impairing their function, which occurs during diabetes mellitus and aging. Beside extracellular glycation of long-lived proteins, intracellular modifications of short-lived proteins by more reactive sugars like fructose are possible. The process includes free oxygen radicals (glycoxidation). In an attempt to reduce glycoxidation and formation of advanced glycation products (AGE), influence of 0.2-1.2 mM uric acid as endogenous antioxidant on glycoxidation of purified pig heart aspartate aminotransferase (AST) by 50 mM and 500 mM D-fructose in vitro was studied. Uric acid at 1.2 mM concentration reduced AST activity decrease and formation of total AGE products caused by incubation in vitro of the enzyme with sugar up to 25 days at 37 degrees C. The results thus support the hypothesis that uric acid has beneficial effects in controlling protein glycoxidation. The in vitro system AST-fructose proved to be a useful tool for investigation of glycation process.

Aspartate Aminotransferases↗

[Analysis of uric acid and oxypurines in normal subjects and in gout patients].

The behavior of plasma and urine oxypurines (hypoxanthine and xanthine) and of uric acid has been studied in normal subjects and in gout patients. Oxypurines and uric acid were increased in the plasma of gout patients but only the urinary excretion of hypoxanthine was higher in this group. The interpretation of the observed variations is discussed.

Adult↗

Simultaneous determination of inosine, hypoxanthine, xanthine, and uric acid and the effect of metal chelators.

We describe a sensitive, reproducible method for the simultaneous determination of the ATP catabolites inosine, hypoxanthine, xanthine, and uric acid in biological samples and organ perfusate using reverse-phase chromatography and multiwavelength detection at 254, 270, and 292 nm. Sample preparation includes precipitating proteins with perchloric acid, neutralizing the sample, passing the supernatant over a polyethyleneimine column, and analyzing the collected fractions by high-performance liquid chromatography. Addition of metal chelators to the perchloric acid resulted in increased values for xanthine, hypoxanthine, and uric acid. The method was sensitive (limit of detection, 0.08 nmol on column; S/N = 4) and linear over the range 0.5-30 microM. Precision and accuracy of the method were evaluated for lung tissue and lung perfusate. Coefficients of variation ranged from 2.8 to 6.1% for perfusate and from 1.7 to 12.6% for tissue. Recoveries for all compounds exceeded 90%. We applied this method to rat lung tissue, lung perfusate, and rat and human blood. Advantages of this method are simultaneous quantitation with excellent sensitivity of all compounds, simplified peak identification by using multiwavelength detection, and improved accuracy by preventing loss of compounds with metal chelators.

Adenosine Triphosphate↗

[Plasma renin activity, creatinine and uric acid in the serum of patients with essential hypertension].

The authors examined the plasma renin activity (PRA), serum uric acid and creatinine in 53 patients with essential hypertension (EH). They recorded low renin EH in 28%, normorenin EH in 53% and high-renin EH in 19% of the hypertensive patients. Assessment of basal PRA levels does not suffice for the classification of EH because the PRA response after stimulation is not related to its basal values. The authors found significantly higher levels of serum creatinine in low-renin EH. They did not confirm a relationship between PRA and the uric acid serum level in any form of EH.

Adult↗

[Effect of cyclosporine on plasma levels of uric acid in patients treated with bone marrow transplantation].

In patients treated with cyclosporine, an increase in the incidence of goiter has been demonstrated. This agent produces changes in the lipidic metabolisms, among which the increase in VLDL stands put. Given that the hyperlipemia more frequently associated to hyperuricemia is the increase of such lipoprotein, we decided to study the behaviour of plasmatic uric acid in patients receiving treatment with cyclosporine. The study was conducted in patients with bone marrow transplant undergoing immunosuppressive therapy, considering the effect of cyclosporine as the only drug or following a scheme of mixed immunosuppression associated to prednisone. We observed a reversible increase in the plasmatic levels of uric acid in patients treated with cyclosporine, which was positively correlated to an increase in VLDL triglycerides. Hence, the cyclosporine produced an increase of uric acid which was neither observed when associated to prednisone nor in the group of self-transplanted patients.

Bone Marrow Transplantation↗

Time course of urinary excretion of intraportal ammonia as uric acid and ammonia in chickens fed low- or high-protein diet.

15N-ammonia was intraportally infused for 6 hr into chickens fed 5% or 20% protein diet to examine the time course of urinary excretion of intraportal ammonia and dietary effects on it. Urinary ammonia increased linearly for the first hour to the same extent in both dietary groups and thereafter further in the low-protein group. Urinary uric acid derived from the intraportal ammonia adaptively increased and reached a steady state level within 1.5 hr. This level was four times higher in the high-protein group. The infused ammonia was excreted into urine as both ammonia and uric acid, in relatively high proportions in the chickens fed the low-protein diet but was almost all excreted as uric acid in those fed the high-protein diet.

Ammonia↗

[Significance of serum uric acid determination for the early detection of complications of hypertensive pregnancy in primigravidae].

In 100 healthy primigravidae the concentration of serum uric acid was examined in a prospective longitudinal study between the 12th and 40th gestational week. Serum uric acid increased continuously and was elevated significantly in 9 women who developed toxaemia of late pregnancy at the 16th, 32nd, and 36th week of pregnancy. If serum concentration are higher than 220 mumol/l or 241 mumol/l in the 32nd gestational week they were considered for a increased risk of developing a hypertensive complication. Sensitivity, specificity and the predictive value of a "positive test" were low in the 16th (22 or 20%) and 32nd (16 or 17%) week of pregnancy. The predictive value of a "negative test" was relative high in the 16th and 32nd week with 93 or 90% respectively 95 or 92%.

Adolescent↗

High-protein diets in hyperlipidemia: effect of wheat gluten on serum lipids, uric acid, and renal function.

BACKGROUND: The metabolic effects of diets high in vegetable protein have not been assessed despite much recent interest in the effect of soy proteins in reducing serum cholesterol. OBJECTIVE: We assessed the metabolic effects of diets high in vegetable protein (specifically, wheat gluten) on serum lipids, uric acid concentrations, and renal function. DESIGN: Twenty hyperlipidemic men and women consumed isoenergetic test (high-protein) and control metabolic diets for 1 mo in a randomized crossover design. In the high-protein diet, 11% of the total dietary energy from starch in the control bread was replaced by vegetable protein (wheat gluten), resulting in 27% of total energy from protein compared with 16% in the control diet. In other respects, the 2 diets were identical. RESULTS: Compared with the control, the high-protein diet resulted in lower serum concentrations of triacylglycerol (by 19.2 +/- 5.6%; P = 0.003), uric acid (by 12.7 +/- 2.0%; P < 0.001), and creatinine (by 2.5 +/- 1.1%; P = 0.035) and higher serum concentrations of urea (by 42.2 +/- 5.8%; P < 0.001) and a higher 24-h urinary urea output (by 99.2 +/- 17.2%; P < 0.001). No significant differences were detected in total or HDL cholesterol or in the renal clearance of creatinine. LDL oxidation, assessed as the ratio of conjugated dienes to LDL cholesterol in the LDL fraction, was lower with the high-protein diet (by 10.6 +/- 3.6%; P = 0.009). CONCLUSIONS: High intakes of vegetable protein from gluten may have beneficial effects on cardiovascular disease risk by reducing oxidized LDL, serum triacylglycerol, and uric acid. Further studies are required to assess the longer-term effects on renal function.

Adult↗