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Detection of uric acid in aqueous humor by high pressure liquid chromatography.

The uric acid peak among the compounds in aqueous humor separated by high pressure liquid chromatography was identified by its retention time, the UV absorbance characteristics, and the effect of uricase. The uric acid concentration in the aqueous humor of normal monkey, human eyes with cataract, and human eyes with glaucoma are less than 0.05, 1.7 +/- 0.3, and 3.8 +/- 0.4 respectively. The significance of high uric acid concentration in glaucoma is discussed.

Animals↗

Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease.

Recent experimental findings have led to renewed interest in the possible role of uric acid in the pathogenesis of both hypertension and vascular disease. Often considered an antioxidant, biochemical and in vitro data indicate that noncrystalline, soluble uric acid also can react to form radicals, increase lipid oxidation, and induce various pro-oxidant effects in vascular cells. In vitro and in vivo findings suggest that uric acid may contribute to endothelial dysfunction by inducing antiproliferative effects on endothelium and impairing nitric oxide production. Proinflammatory and proliferative effects of soluble uric acid have been described on vascular smooth muscle cells (VSMCs), and in animal models of mild hyperuricemia, hypertension develops in association with intrarenal vascular disease. Possible adverse effects of uric acid on the vasculature have been linked to increased chemokine and cytokine expression, induction of the renin-angiotensin system, and to increased vascular C-reactive protein (CRP) expression. Experimental evidence suggests a complex but potentially direct causal role for uric acid in the pathogenesis of hypertension and atherosclerosis.

Animals↗

[Uricemia and uric acid quantities in urine under unbalanced diet (author's transl)].

Under exclusive intake of glucose or fat production of uric acid and growth is lowered in male rats. Just the same can be observed in adult animals. Loss in weight and impairment in production of uric acid seem to relate to each other. Growth-inhibition, i.e. weight reduction cannot be the reason for the obviously reduced synthesis of uric acid, because corresponding findings can not be ascertained in protein-fed animals in spite of weight-reduction. These findings suggest that synthesis of uric-acid depends on the intake of amino-acids. Thereby the pool of amino acids would be decisive for the synthesis-rate of nucleic acids. It might be conceivable, that the decrease of uric acid serum concentration during aging relates to the suggestion mentioned above.

Animals↗

[Changes in the blood uric acid levels in patients with retinitis pigmentosa and in rats with hereditary retinal degeneration].

The content of uric acid was measured in the blood of patients suffering from retinitis pigmentosa, as well as in the blood, retina, brain, liver and urine of rats with inherited retinal degeneration in the course of postnatal development. It was found that in the patients with retinitis pigmentosa, the concentration of uric acid in the blood serum was 50% higher as compared to normals. On the 8th day of life the content of uric acid in the blood of the sick rats was equal to 150% as compared to the normal animals. This difference persisted during the subsequent postnatal life. In the rats with inherited retinal degeneration, the content of this purine in the retina, brain and liver was approximately the same as that seen in the normal animals in all the studied periods of life. Meanwhile statistically significant changes in the uric acid content in the sick animals' urine appeared at an age of 1.5-2 months. It is believed that the identical line of changes in the uric acid content in the blood of the sick persons and rats points to similarity of the experimental disease of the animals to the disease in humans.

Animals↗

Growth of Cryptococcus neoformans on uric acid agar.

Effect of certain low molecular nitrogen substances, namely uric acid, eura and creatinine as sole source of nitrogen was studied on 31 strains of Cryptococcus neoformans as well as on a rough looking isolate recovered from the brain of a mouse inoculated with a mucoid strain of C. neoformans. Uric acid as a nitrogen source caused striking alterations in the morphology of C. neoformans. In view of the facts that uric acid is a common end-product of human and animal metabolism, it is abundantly present in the avian faecal matter and is capable of inducing mucoid growth and capsule formation in dry growing non-encapsulated strains or in an otherwise rough looking hypha forming isolate, its role in studying the phylogenesis of C. neoformans and its pathogenicity seems to be an important proposition.

Animals↗

Serum carotenoids and uric acid levels in relation to cancer.

We studied the levels of serum total carotenoids and uric acid in newly diagnosed cancer cases. The levels of carotenoids and uric acid in serum samples from 94 subjects with cancer affecting different sites (21 breast, 26 head and neck, 13 lung, 17 genitourinary and 17 other sites) were compared with those of 92 controls who were matched for age, sex, Quetelet index and smoking history. Mean (+/- SE) levels of carotenoids were significantly lower among the cases than the controls (51.41 +/- 3.32 vs. 102.75 +/- 4.52 micrograms/dl, P < 0.001), when all the different sites were considered together. The mean (+/- SE) uric acid levels among cases and controls were 5.14 +/- 0.16 mg/dl and 4.21 +/- 0.18 mg/dl (P < 0.001), respectively. It was of interest that patients with genitourinary cancer had the lowest serum carotenoids levels, and the highest levels were found in patients with breast cancer. These results are informative but do not establish a causal link. There was no apparent association between serum urate levels and cancer site. The data presented here do not provide support for the protective antioxidant properties of uric acid in cancer.

Adult↗

Deactivation of triplet-excited riboflavin by purine derivatives: important role of uric acid in light-induced oxidation of milk sensitized by riboflavin.

The reactivity of purine derivatives (uric acid, xanthine, hypoxanthine, and purine) toward triplet-excited riboflavin in aqueous solution at pH 6.4 is described on the basis of kinetic (laser flash photolysis), electrochemical (square-wave voltammetry), and theoretical data (density functional theory, DFT). Direct deactivation of triplet-excited riboflavin in aqueous solution, pH 6.4 at 24 degrees C, in the presence of uric acid, xanthine, and hypoxanthine strongly suggests a direct electron transfer from the purine to the triplet-excited riboflavin with k = 2.9 x 10(9) M(-1) s(-1) (DeltaH(++) = 14.7 kJ mol(-1), DeltaS(++) = -15.6 J mol(-1) K(-1)), 1.2 x 10(9) M(-1) s(-1) (DeltaH(++) = 34.3 kJ mol(-1), DeltaS(++) = +45.3 J mol(-1) K(-1)), and 1.7 x10(8) M(-1) s(-1) (DeltaH(++) = 122 kJ mol(-1), DeltaS(++) = +319 J mol(-1) K(-1)), respectively. From the respective one-electron oxidation potentials collected in aqueous solution at pH 6.4 for uric acid (E = +0.686 vs normal hydrogen electrode, NHE), xanthine (E = +1.106 vs NHE), and hypoxanthine (E = +1.654 vs NHE), the overall free energy changes for electron transfer from the quencher to the triplet-excited riboflavin are as follows: uric acid (DeltaG(o) = -114 kJ mol(-1)), xanthine (DeltaG(o) = -73.5 kJ mol(-1)), hypoxanthine (DeltaG(o) = -20.6 kJ mol(-1)), and purine (DeltaG(o) > 0). The inertness observed for purine toward triplet-excited riboflavin corroborates with its electrochemical inactivity in the potential range from 0 up to 2 V vs NHE. These data are in agreement with the DFT results, which show that the energy of the purine highest occupied molecular orbital (HOMO) (-0.2685 arbitrary unit) is lower than the energy of the semioccupied molecular orbital (SOMO) (-0.2557 a.u.) of triplet-excited riboflavin, indicating an endergonic process for the electron-transfer process. The rate-determining step for deactivation by purine derivatives can be assigned to an electron transfer from the purine derivative to the SOMO orbital of the triplet-excited riboflavin. The results show that uric acid may compete with oxygen and other antioxidants to deactivate triplet-excited riboflavin in milk serum and other biological fluids leading to a free radical process.

Animals↗

Direct electrochemistry of uric acid at chemically assembled carboxylated single-walled carbon nanotubes netlike electrode.

Carboxylated single-walled carbon nanotubes (SWCNT) chemically assembled on gold substrate was employed as netlike electrode to investigate the charge-transfer process and electrode process kinetics using uric acid as an example. The electrochemical behavior of uric acid in carboxylated SWCNT system was investigated using cyclic voltammetry, chronoamperometry, and single potential time-based techniques. The properties of raw SWCNT electrode were also studied for comparison purpose. Uric acid has better electrochemical behavior whereas ascorbic acid has no effective reaction on the carboxylated SWCNT electrode. Cyclic voltammograms indicate that the assembled carboxylated SWCNT increases more active sites on electrode surface and slows down the electron transfer between the gold electrode and uric acid in solution. The charge-transfer coefficient (alpha) for uric acid and the rate constant (k) for the catalytic reaction were calculated as 0.52 and 0.43 s(-1), respectively. The diffusion coefficient of 0.5 mM uric acid was 7.5 x 10(-6) cm2 x s(-1). The results indicate that electrode process in the carboxylated SWCNT electrode system is governed by the surface adsorption-controlled electrochemical process.

Ascorbic Acid↗

Changes in urinary uric acid excretion in obstructive sleep apnea before and after therapy with nasal continuous positive airway pressure.

STUDY OBJECTIVE: To assess the utility of urinary uric acid excretion as a marker of nocturnal hypoxia in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after the institution of nasal continuous positive airway pressure (CPAP). DESIGN: Prospective, open. SETTING: Sleep Disorders Laboratory, Veterans Affairs Medical Center. PARTICIPANTS: Thirty consecutive male subjects, 20 with OSAHS and 10 without OSAHS. MEASUREMENTS AND METHODS: Spot morning urine and venous blood samples were obtained in all subjects; samples were also obtained after the application of CPAP in those with OSAHS. Uric acid excretion, normalized to creatinine clearance, was calculated as the product of urinary uric acid and serum creatinine concentrations divided by urine creatinine concentration. In patients with OSAHS, uric acid excretion was 0.55+/-0.1 mg/dL before CPAP therapy and decreased to 0.30+/-0.01 mg/dL after CPAP therapy (p < 0.001). The latter value did not differ significantly from the mean value (0.32+/-0.03 mg/dL) in the control group. Uric acid excretion in OSAHS patients correlated significantly with the apnea-hypopnea index (r=0.42; p<0.0003). CONCLUSION: Uric acid excretion is increased in OSAHS patients and normalizes after CPAP treatment, most likely reflecting differences in tissue oxygenation between the two conditions. Further studies in large number of patients may confirm the usefulness of this simple test for diagnosis and follow-up of patients with OSAHS.

Creatinine↗

Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study.

The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial. For up to 12 years (mean, 4.0) we followed 1720 subjects with essential hypertension. At entry, all subjects were untreated and all were carefully screened for absence of cardiovascular disease, renal disease, cancer, and other important disease. Outcome measures included total cardiovascular events, fatal cardiovascular events, and all-cause mortality. During 6841 person-years of follow-up there were 184 cardiovascular events (42 fatal) and 80 deaths from all causes. In the 4 quartiles of serum uric acid (division points: 0.268, 0.309, and 0.369 mmol/L [4.5, 5.2, and 6.2 mg/dL] in men; 0.190, 0.232, and 0.274 mmol/L [3.2, 3.9, and 4.6 mg/dL] in women), the rate (per 100 person-years) of cardiovascular events was 2.51, 1.48, 2.66, and 4.27, that of fatal cardiovascular events was 0.41, 0.33, 0.38, and 1.23, and that of all-cause deaths was 1.01, 0.55, 0.93, and 2.01, respectively. The relation between uric acid and event rate was J-shaped in both genders. After adjustment for age, gender, diabetes, total cholesterol/HDL cholesterol ratio, serum creatinine, left ventricular hypertrophy, ambulatory blood pressure, and use of diuretics during follow-up, uric acid levels in the highest quartile were associated with increased risk for cardiovascular events (relative risk, 1.73; 95% CI, 1.01 to 3.00), fatal cardiovascular events (relative risk, 1.96; 95% CI, 1.02 to 3.79), and all-cause mortality (relative risk, 1.63; 95% CI, 1.02 to 2.57) in relation to the second quartile. In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.

Antihypertensive Agents↗

Fragmentation of uric acid calculi with the holmium: YAG laser produces cyanide.

BACKGROUND AND OBJECTIVES: To independently test previously reported findings of cyanide evolution under holmium:yttrium aluminum garnet (Ho:YAG) (holmium) lithotripsy of uric acid calculi, determine if this occurs with other forms of intracorporeal lithotripsy, and establish if this occurs due to a photothermal, photochemical, or photoacoustic reaction. STUDY DESIGN/MATERIALS AND METHODS: Human uric acid calculi were fragmented in vitro through exposure to holmium, ultrasound, and electrohydraulic (EHL) energy sources. The following parameters were varied: total laser energy, individual laser pulse energy, ultrasonic energies, and EHL energies. Uric acid powder was suspended in solution and exposed to holmium laser energy in vitro. Serum and irrigant samples from a human patient were collected following intrarenal holmium lithotripsy of a uric acid calculus. All samples were analyzed for hydrogen cyanide (HCN) content. RESULTS: Holmium lithotripsy of solid uric acid calculi produces cyanide. The yield is linearly dependent upon total laser energy delivered. Pulse energy does not affect cyanide yield. Photothermal mechanisms coupling laser energy to the solid crystal lattice are responsible for the production of cyanide. Ultrasound and EHL lithotripsy do not produce cyanide. A clinically insignificant level of cyanide was detected in the blood of a single patient following laser lithotripsy of a uric acid calculus. CONCLUSIONS: Our study confirms that cyanide is produced by a photothermal mechanism during holmium laser lithotripsy of uric acid calculi, and that the amount produced is clinically insignificant.

Holmium↗

Beer, liquor, and wine consumption and serum uric acid level: the Third National Health and Nutrition Examination Survey.

OBJECTIVE: To evaluate the relationship between intakes of beer, liquor, and wine and serum uric acid levels in a nationally representative sample of men and women. METHODS: Using data from 14,809 participants (6,932 men and 7,877 women) age > or =20 years in The Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between intakes of beer, liquor, and wine and serum uric acid levels. Alcohol intake was assessed by a food frequency questionnaire. RESULTS: Serum uric acid levels increased with increasing beer or liquor intake but not with increasing wine intake. After adjusting for age, the difference in serum uric acid levels as compared with no intake increased with increasing beer or liquor intake (P values for trend <0.001), but the association was inverse with increasing wine intake (P for trend <0.001). After adjusting mutually for these alcoholic beverages and for other risk factors for hyperuricemia, including dietary risk factors, the associations were attenuated but remained significant for beer or liquor (multivariate difference per serving per day 0.46 mg/dl [95% confidence interval [95% CI] 0.32, 0.60] and 0.29 mg/dl [95% CI 0.14, 0.45], respectively; both P values for trend <0.01), but not for wine (0.04 mg/dl [95% CI -0.20, 0.11]; P for trend=0.6). CONCLUSION: These data suggest that the effect of individual alcoholic beverages on serum uric acid levels varies substantially: beer confers a larger increase than liquor, whereas moderate wine drinking does not increase serum uric acid levels.

Adult↗

Uric acid in chronic heart failure: a measure of the anaerobic threshold.

The anaerobic threshold (AT) is a measure of the balance between aerobic and anaerobic cellular metabolism. Hyperuricemia occurs in conditions that involve an imbalance between cellular oxygen consumption and carbon dioxide production, such as chronic heart failure (CHF). We therefore hypothesized that in CHF, serum uric acid might be related to the AT. Patients with CHF (n=40, aged 58.7+/-1.9 years; New York Heart Association Class I-IV; maximal oxygen consumption [MVO2], 18.7+/-01.1 mL/kg/min; left ventricular ejection fraction, 26%+/-2%) and 10 age-matched healthy controls underwent measurement of the serum uric acid level at rest and assessment of the AT. This was derived from MVO2 and the regression slope relating minute ventilation to carbon dioxide output (VE - VCO2) during a maximal treadmill exercise test. Compared with the healthy controls, patients with CHF had a lower AT (11.8+/-0.7 v 16.9+/-1.1 mL/kg/min, P < .001) and a higher serum uric acid concentration (493.8+/-22.4 v 308.7+/-21.5 micromol/L, P < .001). In univariate analyses of the CHF group, the AT correlated with serum uric acid (r=-.56, P < .001; AT=19.93 - (0.016 x uric acid), R2=.31, P < .001) and plasma creatinine (r=-.43, P < .01), but not with the diuretic dose. In stepwise regression analyses of the CHF group, serum uric acid emerged as a predictor of the AT (standardized coefficient=-.56, P < .001), whereas the diuretic dose and plasma creatinine failed to enter into the final models (multiple R2=.31, P < .001). In conclusion, in CHF there is an inverse relationship between the AT and the resting serum uric acid concentration. This is consistent with the known links between uric acid production and the imbalance in aerobic/anaerobic metabolism that occur in CHF. These findings provide the basis for using the simple measurement of the serum uric acid level as a surrogate measure of the AT.

Anaerobiosis↗

Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension.

We examined the relation of serum creatinine and uric acid to mortality and cardiovascular disease in older (aged >/=60 years) Chinese patients with isolated systolic hypertension (systolic/diastolic blood pressure >/=160/<95 mm Hg). We used Cox regression to correlate outcome with baseline serum creatinine and uric acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in the placebo-controlled Systolic Hypertension in China (Syst-China) TRIAL: Median follow-up was 3 years. In multiple Cox regression analysis with adjustment for gender, age, active treatment, and other significant covariates, serum creatinine was significantly associated with a worse prognosis. The relative hazard rates (95% CIs) associated with a 20-micromol/L increase in serum creatinine for all-cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27, P=0.003), 1.15 (1.01 to 1.31, P=0.03), and 1.37 (1.13 to 1.65, P=0.001), respectively. In a similar analysis, which also accounted for serum creatinine, serum uric acid was also significantly and independently associated with excess mortality of cardiovascular disease and stroke. The relative hazard rates associated with a 50-micromol/L increase of serum uric acid were 1.14 (1.02 to 1.27, P=0.02) for cardiovascular mortality and 1.34 (1.14 to 1.57, P<0.001) for fatal stroke. In conclusion, in older Chinese patients with isolated systolic hypertension, serum creatinine and serum uric acid were predictors of mortality.

Age Factors↗

Effect of fenofibrate on uric acid metabolism in Japanese hyperlipidemic patients.

Forty Type IIb or IV hyperlipidemic patients (serum triglyceride concentrations were higher than 150 mg/dl) were treated with fenofibrate (300 mg/day) for 12 weeks. Lipid profile and uric acid metabolism were evaluated before and after the treatment; the serum concentrations of total cholesterol and triglyceride respectively decreased from 224 +/- 41.9 mg/dl to 199 +/- 35.2 mg/dl and from 205 +/- 71.7 mg/dl to 134 +/- 67.5 mg/dl (p < 0.001). The uric acid concentrations in the serum also significantly decreased from 7.0 +/- 1.58 mg/dl to 5.2 +/- 1.57 mg/dl (p < 0.001). Fenofibrate treatment did not cause any change in the serum xanthine and hypoxanthine concentrations. Instead the urinary concentrations of uric acid decreased from 7.0 +/- 1.58 mg/dl to 5.2 +/- 1.57 mg/dl (p < 0.01), while the clearance ratio of uric acid and creatinin increased from 6.1 +/- 2.56 to 9.9 +/- 3.87 (p = 0.02) by the fenofibrate treatment. Fenofibrate decreases uric acid concentrations in the serum not as a result of inhibition of uric acid production but by increasing the urinary excretion of uric acid.

Adult↗

Urine composition in type 2 diabetes: predisposition to uric acid nephrolithiasis.

Type 2 diabetes is a risk factor for nephrolithiasis in general and has been associated with uric acid stones in particular. The purpose of this study was to identify the metabolic features that place patients with type 2 diabetes at increased risk for uric acid nephrolithiasis. Three groups of individuals were recruited for this outpatient study: patients who have type 2 diabetes and are not stone formers (n = 24), patients who do not have diabetes and are uric acid stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants provided a fasting blood sample and a single 24-h urine collection for stone risk analysis. Twenty-four-hour urine volume and total uric acid did not differ among the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH than NV. Urine pH inversely correlated with both body weight and 24-h urine sulfate in all groups. Urine pH remained significantly lower in patients with type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate (P < 0.01). For a given urine sulfate, urine net acid excretion tended to be higher in patients with type 2 diabetes versus NV. With increasing urine sulfate, NV and patients with type 2 diabetes had a similar rise in urine ammonium, whereas in UASF, ammonium excretion remained unchanged. The main risk factor for uric acid nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body mass and increased acid intake can contribute to but cannot entirely account for the lower urine pH in patients with type 2 diabetes.

Adult↗

[Serum uric acid as a prognostic parameter in prenatal monitoring of gestoses].

A correlation between gestosis and increase of serum uric acid level has been known for a longtime. From the 6th month of pregnancy we found significantly increased values in all hypertensive pregnant women. In the 7th and 8th month of pregnancy there was a high significant deviation in gestoses second degree (classification of the organisation gestosis). In the two last months of pregnancy all gestoses deviated high significantly from the uric acid level in serum of the normal collective. There is a correlation between pathologically increased mean uric acid values in the 9th and 10th lunar month and increased systolic and diastolic blood pressure values. The uric acid level in pregnant women with gestosis, whose illness or its consequences led to cesarean section, is significantly higher than in patients with normal delivery. In accordance with literature we could not find a limit above the fetus dies. In our opinion determination of plasma uric acid in late pregnant hypertensive women is one additional parameter calculating both maternal prognosis and fetal risk.

Female↗

Gender differences in the relationships of serum uric acid with fasting serum insulin and plasma glucose in patients without diabetes.

OBJECTIVE: To explore gender differences in the relationship of serum uric acid levels with fasting serum insulin and fasting plasma glucose concentrations among an adult Chinese nondiabetic population in Kinmen, Taiwan. METHODS: A total of 7,483 nondiabetic subjects (4,265 women, 3,218 men, aged 30 to 89 years) were involved in a community based epidemiologic study. Those with known or newly diagnosed diabetes were excluded. Overnight fasting blood samples were drawn for serum uric acid, glucose, insulin, lipid, and other biochemical measurements. Demographic and clinical variables including body mass index (weight/height2), waist-to-hip ratio, and blood pressure were measured and documented during face-to-face interviews with structured questionnaires. RESULTS: Stratified analyses revealed that (1) serum uric acid levels were positively associated with hyperinsulinemia and HOMA-insulin resistance in both men and women after adjusting for hypertriglyceridemia, hypertension, obesity, and plasma glucose levels; and (2) serum uric acid levels were more strongly associated with hyperinsulinemia and plasma glucose levels in women than in men. CONCLUSION; Hyperuricemia was positively associated with hyperinsulinemia among patients of both sexes without diabetes. Elevated levels of uric acid should alert physicians to the possibility of insulin resistance. The serum uric acid level was associated with insulin resistance and plasma glucose levels more strongly in females than in males in our study population.

Adult↗