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PubMed2001

The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on serum uric acid levels and potassium homeostasis in hypertensive renal transplant recipients treated with CsA.

BACKGROUND: The angiotensin II (AT II) type I receptor antagonist losartan has been reported to increase urinary uric acid and potassium excretion. These effects might be beneficial in cyclosporin (CsA)-treated renal transplant recipients, who frequently suffer from hyperuricaemia and hyperkalaemia. METHODS: In this prospective, open, randomized, two-way cross-over study we included 13 hypertensive CsA-treated patients after renal transplantation and administered either the angiotensin-converting enzyme (ACE) inhibitors enalapril or losartan. Laboratory parameters, 24-h urinary protein excretion, and mean 24-h arterial blood pressure (MAP) were checked after 3 weeks treatment with enalapril, after a wash-out period of 2 weeks, and before and after a 3-week treatment course with losartan. RESULTS: Both drugs slightly reduced MAP (losartan from 97+/-6 to 94+/-9 and enalapril to 93+/-8 mmHg). Serum potassium levels significantly increased during enalapril therapy (from 4.3+/-0.5 to 4.8+/-0.4 mmol/l, P<0.05), as did, although not significantly, uric acid concentrations (from 7.8+/-1.9 to 8.2+/-1.8 mg/dl, P=0.5). Losartan, on the contrary, only mildly affected serum potassium (4.3+/-0.5 vs 4.5+/-0.5 mmol/l, P=0.25) and serum uric acid decreased (from 7.8+/-2.4 to 7.3+/-1.8 mg/dl, P=0.6). Serum aldosterone and urinary aldosterone excretion were significantly reduced only during ACE inhibitor treatment, which might explain the variable effects on potassium homeostasis. CONCLUSION: Losartan may be a useful agent to reduce blood pressure and serum uric acid levels in renal transplant recipients treated with CSA: Furthermore, in this high-risk population, the effects on serum potassium levels are less marked with losartan than with enalapril.

Aged↗
PubMed2025

Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.

BACKGROUND: Uric acid (UA) is the terminal product of purine metabolism. Elevated serum uric acid (SUA) levels, resulting from excessive synthesis or impaired excretion, are link to chronic inflammatory stress and increased risks of colorectal, breast, and prostate cancers. Hyperuricemia triggers a cascade of proinflammatory and oxidative responses, establishing a microenvironment conducive to tumorigenesis. AIM OF REVIEW: This review synthesizes evidence on how hyperuricemia drive inflammation and cancer transformation from global foundational research and clinical practice, elucidate UA metabolism as potential therapeutic strategy for inflammation-associated malignancies. KEY SCIENTIFIC CONCEPTS OF REVIEW: Hyperuricemia-induced oxidative stress, DNA damage and genomic instability, while simultaneously activating proinflammatory signaling pathways. These interconnected pathways establish a persistent, proinflammatory microenvironment that fosters the transition from inflammation to cancer. Therapeutic strategies targeting UA metabolism (including pharmacologic interventions and dietary modifications) may mitigate chronic low-grade inflammation and reduce the cancer risk associated with hyperuricemia. Dysregulated UA metabolism emerges as a critical modulator linking chronic inflammation with oncogenesis.

Humans↗
PubMed2005

The association between serum ferritin and uric acid in humans.

OBJECTIVE: Urate forms a coordination complex with Fe(3+) which does not support electron transport. The only enzymatic source of urate is xanthine oxidoreductase. If a major purpose of xanthine oxidoreductase is the production of urate to function as an iron chelator and antioxidant, a system for coupling the activity of this enzyme to the availability of catalytically-active metal would be required. We tested the hypothesis that there is an association between iron availability and urate production in healthy humans by correlating serum concentrations of ferritin with uric acid levels. MATERIALS AND METHODS: The study population included 4932 females and 4794 males in the National Health and Nutrition Examination Survey III. They were 20 years of age or older and in good health. RESULTS: Serum concentrations of ferritin correlated positively with uric acid levels in healthy individuals (R(2) = 0.41, p<0.001). This association was independent of an effect of gender, age, race/ethnic group, body mass, and alcohol consumption. CONCLUSIONS: The relationship between serum ferritin and uric acid predicts hyperuricemia and gout in groups with iron accumulation. This elevation in the production of uric acid with increased concentrations of iron could possibly reflect a response of the host to diminish the oxidative stress presented by available metal as the uric acid assumes the empty or loosely bound coordination sites of the iron to diminish electron transport and subsequent oxidant generation.

Adult↗
PubMed2002

Uric acid is a genuine metabolite of Penicillium cyclopium and stimulates the expression of alkaloid biosynthesis in this fungus.

On searching for endogenous, low-molecular-weight effectors of benzodiazepine alkaloid biosynthesis in Penicillium cyclopium uric acid was isolated from ethanolic or autoclaved mycelial extracts of this fungus. The isolation was based on a three-step high-pressure liquid chromatography procedure guided by a microplate bioassay, and uric acid was identified by mass spectrometry and the uricase reaction. Conidiospore suspensions that were treated with this compound during the early phase of outgrowth developed emerged cultures with an enhanced rate of alkaloid production. Uric acid treatment did not increase the in vitro measurable activity of the rate-limiting biosynthetic enzyme, cyclopeptine synthetase. However, these cultures displayed a reduced rate of uptake of the alkaloid precursor L-phenylalanine into the vacuoles of the hyphal cells as assayed in situ. It is suggested that the depressed capacity of vacuolar uptake caused by the contact of outgrowing spores with uric acid liberated from hyphal cells results in an enhanced availability of the precursor L-phenylalanine in the cytoplasm and thus accounts at least in part for the increase in alkaloid production.

Anti-Bacterial Agents↗
PubMed1977

Serum uric acid level of Thai individuals in comparison with the nutritional status and some other physical and biochemical parameters.

Serum uric acid levels were measured in a total of 287 adults of Thai origin in Bangkok and the rural area. Mean values and range were found to exceed slightly serum uric acid concentration as reported from western countries. There was no significant difference between the Bangkok group and the group from the rural area but males and females differed significantly in their serum uric acid levels. A significant positive correlation to the ratio between weight to height as an index of the nutritional status was found.

Adult↗
PubMed1982

Uric acid determinations: reversed-phase liquid chromatography with ultraviolet detection compared with kinetic and equilibrium adaptations of the uricase method.

A reversed-phase liquid-chromatographic procedure is presented for quantitation or uric acid in human serum, with absorbance measured at 292 nm. The mobile phase was sodium acetate (35 mmol/L, pH 5.0)/acetonitrile (9/1 by vol). Complete precipitation of serum proteins was obtained by mixing serum (50-500 microL) with an equal volume of acetonitrile, and the precipitate was removed by centrifugation. Aliquots (20 microL) of the supernate were injected directly into the liquid chromatograph, which was adjusted so that the absorbance reading of the uric acid peak was as high as possible. Routinely, a full-scale deflection of 1.28 absorbance units was used. The within-run precision (CV) was 0.6% for a serum uric acid concentration of 227 mumol/L and day-to-day precision over a 15-day period was 0.8% for uric acid of 345 mumol/L. No interferences from related compounds were observed. We compared results by this method with those by kinetic (aca, Du Pont) and equilibrium adaptations (Ames kit; Nyco-test, Nyegaard; and Monotest, Boehringer Mannheim) of uricase methods. The method we report is simple, and can be used in a fully automatic liquid-chromatographic system.

Chromatography, High Pressure Liquid↗
PubMed1988

Progesterone increases glomerular filtration rate, urinary kallikrein excretion and uric acid clearance in normal women.

In pregnancy there is a rise in glomerular filtration rate (GFR), plasma aldosterone levels, uric acid clearance and urinary kallikrein excretion. In toxemia all the above parameters tend to decrease. Progesterone has a diuretic effect which is usually related to aldosterone antagonism. We administered progesterone to normal women and observed that GFR, uric acid clearance and kallikrein excretion increased significantly, GFR from 103.0 +/- 13.7 ml/min to 118.0 +/- 18.0 ml/min (P less than 0.01), uric acid clearance from 9.0 +/- 3.6 ml/min to 14.3 +/- 4.0 ml/min (P less than 0.01), and urinary kallikrein excretion from 165 +/- 156 mU to 432 +/- 220 mU (P less than 0.01). Natriuresis and potassium excretion also increased from 15.9 +/- 6.4 mEq to 33.4 +/- 10.9 mEq (P less than 0.01) and from 7.6 +/- 2.7 mEq to 14.0 +/- 5.4 mEq, (P less than 0.01), respectively, suggesting that in this situation aldosterone antagonism is not relevant to explain the diuretic effects of progesterone.

Female↗
PubMed2002

Plasma 5'-nucleotidase activities and uric acid levels in women with pre-eclampsia.

The present study investigated plasma activity of 5'-nucleotidase, a key enzyme in the production of adenosine, in pre-eclampsia, and evaluated the relationship between changes in 5'-nucleotidase activity, and levels of uric acid, endproduct of the purine metabolism, and the severity of pre-eclampsia. We measured plasma 5'-nucleotidase activities and uric acid levels in women with 18 normal pregnancies, mild and severe pre-eclampsia. In mild and severe pre-eclampsia, plasma 5'-nucleotidase activities and uric acid levels were significantly increased compared with those in normal pregnancy (p < 0.05). Plasma 5'-nucleotidase activity increased according to increases in uric acid levels and the severity of pre-eclampsia. These results suggest that increased plasma 5'-nucleotidase activity may, at least in part, be related to changes in purine metabolism in pre-eclampsia.

5'-Nucleotidase↗
PubMed2003

Leptin might be a regulator of serum uric acid concentrations in humans.

Increased serum urate concentration is a frequent finding in patients with hypertension. Since hyperuricemia is associated with obesity, renal disease, hyperlipidemia, and atherosclerosis, whether or not serum urate is a cardiovascular risk factor per se has remained elusive. The subjects were 210 Turkish male and 210 female adults over 20 years of age. None had diabetes mellitus, endocrine diseases, or renal or hepatic disease, and those receiving antihypertensive drugs, systemic corticosteroids, or lipid-lowering drugs were excluded. Height, weight, blood pressure, serum glucose, lipid profiles, serum insulin, DHEA-SO4, and leptin were measured in the morning after an overnight fast. Women had significantly higher mean leptin (20.3 +/- 0.88 ng/mL vs 5.78 +/- 0.39 ng/mL, P < 0.001) and lower mean uric acid (248.03 +/- 4.76 micromol/L vs 311.6 +/- 5.35 micromol/L, P < 0.001), triglyceride (1.42 +/- 0.06 mmol/L vs 1.61 +/- 0.06 mmol/L, P < 0.001), and DHEA-SO4 (3.02 +/- 0.17 micromol/L vs 4.43 +/- 0.19 micromol/L, P < 0.001) concentrations than men, even when adjusted for BMI. On univariate correlation analysis, leptin showed the strongest association with BMI in both sexes and also correlated significantly with BMI, insulin, uric acid, glucose, total cholesterol, and triglycerides in males and BMI, insulin, uric acid, total cholesterol, apo B, and creatinine in females after adjustment for age and BMI. A statistical model containing creatinine, leptin, insulin, and triglycerides accounted for 34% of the variance in serum uric acid levels in men, whereas another consisting of creatinine, triglycerides, leptin, SBP, and insulin explained 42% of the variance in serum uric acid in women. The present study suggests that leptin could be one of the possible candidates for the missing link between obesity and hyperuricemia. Our study may also suggest that hyperuricemia is not only a metabolic end product but also a marker of a major pressor or pathogenic mechanism underlying the hypertension in obesity.

Adult↗
PubMed2003

Petroleum pollution bioremediation using water-insoluble uric acid as the nitrogen source.

The biodegradation of hydrocarbon pollutants in open systems is limited by the availability of a utilizable nitrogen source. This limitation can be overcome by using uric acid. Enrichment cultures grown on crude oil-uric acid media yielded mixed and pure cultures that degraded petroleum. In a simulated open system, uric acid bound to crude oil and was available for bacterial growth and petroleum biodegradation.

Acinetobacter↗
PubMed1996

[Metabolism of purine nucleotides and the production of uric acid].

The molecular and biochemical aspects of purine nucleotide biosynthesis through de novo and salvage pathways, the production of uric acid, and their regulation mechanisms are reviewed for further understanding of hyperuricemia and gout. The metabolic rate of purine nucleotide biosynthesis is chiefly determined by the regulation of the de novo pathway, especially amidophosphoribosyltransferase and PRPP synthetase, and the accumulation of uric acid results from the acceleration of de novo biosynthesis and catabolism of purine nucleotide or the decrease in urinary excretion of uric acid. Moreover, several enzyme mutations of purine nucleotide metabolism are also clinically important including gout with hyperactive HPRT and the deficiency of HPRT (Lesch-Nyhan syndrome), adenylosuccinate lyase, xanthine oxidase, APRT, PNP, or ADA (SCID) with gene therapy.

Amidophosphoribosyltransferase↗
PubMed1999

Is serum uric acid a risk factor for coronary heart disease?

The role of uric acid as an independent risk factor in the development of coronary heart disease (CHD) has been questioned as serum urate is related to many of the established etiological risk factors for cardiovascular disease which could confound the observed association. This review assesses the role of elevated serum uric acid as an independent role for coronary heart disease.

Biomarkers↗
PubMed1993

Diffusion kinetics of urea, creatinine and uric acid in blood during hemodialysis. Clinical implications.

In order to elucidate some conflicting data reported in the literature the diffusion kinetics between red blood cells (RBC) and plasma during dialysis were studied for urea, creatinine and uric acid. Several complementary studies were performed. According to our results urea diffuses very rapidly from RBC to plasma and is almost at equilibrium at the dialyser outlet; thus the extraction of urea during dialysis is from both plasma and RBC. On the other hand creatinine and uric acid hardly diffuse at all from RBC to plasma during blood transit through the hemodialyser and these solutes are thus extracted mainly from plasma. As a consequence an important in-vitro equilibration process occurs for both solutes in blood drawn at the dialyser outlet; the equilibration rate is greatly temperature-dependent and to achieve complete equilibrium at room temperature, up to 6 to 12 hours were needed for creatinine and 2 to 3 hours for uric acid. Moreover, in the case of creatinine, but not for uric acid, a RBC/plasma disequilibrium was also found in blood drawn at the dialyser inlet; this finding is in contrast with previous reports and suggests that with high-efficiency dialysis modalities the interval between two successive RBC transits through the dialyser may be insufficient for complete equilibration of slowly equilibrating solutes. The clinical implications of these findings with respect to the in-vivo dialyser performance and clearance determinations are discussed.

Creatinine↗
PubMed1992

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.

Adenine↗
PubMed1995

Relation of serum uric acid to mortality and ischemic heart disease. The NHANES I Epidemiologic Follow-up Study.

Although hyperuricemia is frequently found among persons with ischemic heart disease, its importance as a risk factor remains uncertain. The authors examined this relation among 5,421 persons in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study; baseline data were collected in 1971-1975 and follow-up was through 1987. No associations were seen among men, but, among women, the serum uric acid level was predictive of mortality from all causes and from ischemic heart disease. These associations persisted even after excluding the first 10 years of follow-up and were independent of use of antihypertensive agents and diuretics, diastolic blood pressure, overweight, and other characteristics. A dose-response relation was evident for mortality from ischemic heart disease: each 1-mg/dl change in uric acid (about two thirds of the standard deviation) among women increased the rate by 1.48 (95% confidence interval 1.3-1.7). Furthermore, as compared with women who had a uric acid level < 4 mg/dl, those with a level > or = 7 mg/dl had a 4.8-fold (95% confidence interval 1.9-12) higher rate of ischemic heart disease mortality. In contrast, the uric acid level showed a weaker relation with disease incidence among women, with a rate ratio of 1.14 for each 1-mg/dl change. Although the biologic mechanism is unclear, further investigation into the possible role of uric acid in the development of ischemic heart disease is needed.

Adult↗
PubMed1990

Analysis of uric acid transport in renal tubules using benzbromarone and pyrazinamide.

Both the benzbromarone loading test alone and the pyrazinamide suppression test combined with the benzbromarone loading test were performed in four healthy male volunteers to examine the renal handling of uric acid and to demonstrate whether benzbromarone selectively blocks postsecretory reabsorption. On the basis of the four-component theory, equations of four states of fractional uric acid clearance were constructed: 1) the control state, the states of 2) benzbromarone loading, 3) pyrazinamide suppression and 4) both pyrazinamide suppression and benzbromarone loading. As a result, presecretory reabsorption, tubular secretion and postsecretory reabsorption of uric acid were calculated to be about 93-98%, 30-44% and 79-92%, respectively. In addition, it was calculated that benzbromarone inhibited postsecretory reabsorption selectively. Because of the selectivity of the action site of benzbromarone in renal tubules, this loading test is considered to reflect uric acid transport more precisely than tests using probenecid.

Benzbromarone↗
PubMed2005

Effects of Rebixiao granules on blood uric acid in patients with repeatedly attacking acute gouty arthritis.

OBJECTIVE: To observe the clinical effect of Rebixiao granule (RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therapeutic mechanism. METHODS: Ninety repeatedly attacking acute gouty arthritis patients were divided into the treated group (n = 60) and control group (n = 30). The treated group was treated with RBXG, and the control group was treated with Futalin tablets (diclofenac sodium). The baseline treatment including good rest, low purine diet, sufficient water drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine 600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage to establish the animal models. RESULTS: The clinical effective rate of the treated group was 95.0% and that of the control 90.0%. Good therapeutic effects were won, insignificant difference (P > 0.05)was shown between the two groups. However, the cure rate of the treated group was 26.7% while that of the control group was 10.0%, with significant difference (P < 0.01) shown between them. The treated group had its blood uric acid lowered, which was significantly different (P < 0.05) from that of the control group. The animal experiment indicated that all the three groups treated with different dosages of RBXG, as well as the Ash bark and Smilax glabra rhizome groups had their blood uric acid content reduced in the hyperuricemic mice. CONCLUSION: RBXG has a quicker initiation and better treatment effects than sole anti-inflammatory and analgesic agents on the treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic or adverse reactions and therefore good for long-term administration and likely to be a safe TCM preparation to control the symptoms and reduce the onsets of repeatedly attacking of acute gouty arthritis. The animal experiment shows that both the compound preparation and part of the single ingredients in the recipe have the function of reducing blood uric acid. However, the compound recipe has better therapeutic effects, proving to be superior to single drugs.

Acute Disease↗