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PubMed2006

Uric acid and endothelial dysfunction in essential hypertension.

Recent epidemiologic and experimental evidence suggests that serum uric acid (UA) is an independent risk factor for cardiovascular and renal diseases. However, endothelial dysfunction is an early predictor of cardiovascular events, particularly in hypertensive patients. For assessment of the association between UA and endothelial function, 217 (108 men, 109 women; aged 48.0 +/- 10.6 yr) white never-treated hypertensive patients were studied. All patients underwent the following procedures: BP measurements, laboratory tests (C-reactive protein [CRP], insulin resistance by homeostasis model assessment, serum creatinine, and UA), and endothelial function evaluated by intra-arterial infusion of acetylcholine (ACh). Serum creatinine, CRP, and maximal vasodilatory response to ACh were related to the UA (all P < 0.0001). In the multiple regression analysis, serum UA ranked as the third correlate of peak of forearm blood flow predictor, after homeostasis model assessment and CRP. The data show an independent link between UA and endothelial function, also in a statistical model that included CRP. In conclusion, the data demonstrate an inverse and significant relationship between UA and ACh-stimulated vasodilation in patients with uncomplicated, untreated essential hypertension, independent of traditional cardiovascular risk factors. Probably, the chronic inflammation that was documented in these patients may be considered the mechanistic link between serum UA and vascular damage.

Adult↗
PubMed2006

Polymorphism of methylenetetrahydrofolate reductase gene (C677T MTHFR) is not a confounding factor of the relationship between serum uric acid level and the prevalence of hypertension in Japanese men.

BACKGROUND: The association between serum uric acid (UA) and the prevalence of hypertension, and the relationship between methylenetetrahydrofolate reductase (MTHFR) polymorphism and hypertension remains unclear. The aim of the present study was to investigate whether the C677T MTHFR mutation genotype (VV) is independently associated with the prevalence of hypertension or blood pressure (BP), and examined any interaction of MTHFR and UA with BP. METHODS AND RESULTS: Participants were randomly selected from all residents (aged 40-69 years) in a rural county of Japan, and the data for the men (n=335) were analyzed. ;Hypertension' was defined as systolic BP >or=140 and/or diastolic BP >or=90 mmHg and/or being administered antihypertensive medication. Serum UA level was independently associated with the prevalence of hypertension (odds ratio (95% confidence interval) =2.7 (1.2-5.9), p=0.047) for the highest tertile of serum UA (>or=398.5 micromol/L (6.7 mg/dl)) vs that of the lowest tertile (<321.2 micromol/L (5.4 mg/dl)), but the MTHFR mutation was not independently associated with prevalence of hypertension or BP. No interaction of the MTHFR mutation and serum UA with BP was found. CONCLUSIONS: The mutation of C677T MTHFR was not independently associated with the prevalence of hypertension or BP levels although serum UA was. Furthermore, the relationship between serum UA and BP was not modulated by the MTHFR mutation in Japanese men.

Adult↗
PubMed2006

[The predictive value of serum advanced fibrinogen and uric acid for acute coronary event risk].

OBJECTIVE: To study the serum advanced fibrinogen (FIB) and uric acid (UA) in predicting acute coronary events risk. METHODS: 264 patients hospitalized with the suspected diagnosis of coronary heart disease (CHD) were divided into 2 groups according to the results of coronary arteriography: acute coronary event group (n = 195, 141 males and 54 females, aged 62 +/- 12, with laboratory and electrocardiogram proven acute myocardial infarction or unstable angina pectoris and obvious stricture of main coronary artery > 75%) and control group (n = 69, 31 males and 38 females, aged 65 +/- 9, without acute coronary event and with normal coronary artery or stricture of branches of coronary artery less than 50%). A week before the coronary arteriography fast peripheral venous blood samples were collected. The blood sugar, blood-lipid, FIB, and UA were determined. RESULTS: The FIB level of the acute coronary event group was 4.09 g/L +/- 1.36 g/L, significantly higher than that of the control group (3.52 g/L +/- 1.37 g/L, P < 0.05). The UA level of the acute coronary event group was 320 micromol/L +/- 91 micromol/L, not significantly different from that of the control group (302 micromol/L +/- 104 micromol/L, P > 0.05). Excluding the influence of age, sex, blood pressure, blood sugar, etc. multivariate analysis showed that FIB was a significant variable associated with acute coronary events, but UA, not entering the regression equation, was not an independent risk factor. When FIB and UA were both at high levels, acute coronary events risk was much higher than when any single index was at a high level. CONCLUSION: High FIB and UA jointly accelerate the development of atherosclerosis. It may be important to use the index of FIB associated with UA to predict acute coronary risk.

Aged↗
PubMed2005

Does uric acid have a pathogenetic role in graft dysfunction and hypertension in renal transplant recipients?

BACKGROUND: Uric acid (UA) may play a pathogenetic role in hypertension and kidney disease. We explored the prevalence of hyperuricemia and the relationship of UA to graft function and hypertension in prevalent renal transplant recipients (RTR). METHODS: Baseline and follow-up data were collected on 90 RTR (mean age 51 yrs, 53% male, median transplant duration 7 years). Graft function was estimated using MDRD Study Equation 7. RESULTS: At baseline, 70% RTR had hyperuricemia (UA >7.0 mg/dl (0.42 mmol/L) in men and >6.0 mg/dl (0.36 mmol/L) in women) compared to 80% after 2.2 years (P=0.06). UA was not associated with blood pressure (BP) level but was higher in RTR with a history of hypertension compared to those without (8.6+/-1.8 vs. 7.3+/-2.2 mg/dl, [0.51+/-0.11 vs. 0.43+/-0.13 mmol/L], P=0.003) and in RTR on > or =3 antihypertensive medications compared to those taking less (9.1+/-1.6 vs. 7.6+/-1.8 mg/dL, [0.54+/-0.1 vs. 0.45+/-0.11 mmol/L], P<0.001). A history of hypertension was independently predictive of UA (beta 0.06, [95% CI 0.02 to 0.10], P=0.007) in addition to sex, cyclosporine dose, prednisolone dose, estimated glomerular filtration rate (eGFRMDRD) and beta-blocker therapy. UA was independently predictive of follow-up eGFRMDRD (beta -22.2 [95% CI -41.2 to -3.2], P=0.02) but did not predict change in eGFRMDRD over time. UA was independently associated with requirement for antihypertensive therapy (beta 0.34, [95% CI 1.05 to 1.90], P=0.02). CONCLUSIONS: Hyperuricemia is common in RTR and is associated with need for antihypertensive therapy and level of graft function.

Adult↗
PubMed2005

[Study of serum uric acid changes after experimental pulmonary thromboembolism in rats].

OBJECTIVE: To study the change in serum uric acid (UA) after acute pulmonary thromboembolism (PTE) in rats and its value on the diagnosis of PTE. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into PTE group (n=34) and control group (n=30). Experimental PTE was induced in 34 rats by injection of auto-blood clots into the jugular vein (4 rats died and 30 survived), and another group of 30 rats underwent sham operation. Serum UA, partial pressure of oxygen in artery (PaO(2)), mean pulmonary arterial pressure (mPAP) and right ventricular pressure (RVP) were monitored on 1,4,7,14 and 28 days (n=6 per time point) after the operation. Lung tissue was harvested for histologic analysis using hematoxylin and eosin (HE) staining. RESULTS: Local hemorrhage in alveoli and inflammatory cell infiltration in interstitial tissue could be found microscopically within 1 week after PTE. The alveolar structure recovered and inflammatory cells in interstitial tissue decreased 7 days after PTE. Serum UA was higher in PTE group during 1-7 days after operation than in sham group (all P<0.05). PaO(2) was depressed markedly on 1,4 and 7 days after PTE (P<0.05 or P<0.01), and serum UA was negatively correlated with PaO(2) (r=-0.638, P<0.001); Serum UA returned to baseline 1 week after PTE, along with improvement of PaO(2) and alveolar hemorrhages. mPAP and RVP were not elevated in both groups. CONCLUSION: Serum UA content increases after experimental PTE in rats, and it may serve as a potential indicator of the severity and efficacy of treatment of PTE, but its clinical value need to be investigated.

Animals↗
PubMed2005

Uric acid, left ventricular mass index, and risk of cardiovascular disease in essential hypertension.

Elevated serum uric acid (UA) is frequently encountered in individuals with hypertension, but whether the relationship between UA and cardiovascular events is circumstantial or causal remains to be answered. We examined the association between serum UA and left ventricular mass index (LVMI) and investigated prospectively whether the combination of UA and LVMI can predict the incidence of cardiovascular disease (CVD) in asymptomatic subjects with essential hypertension. A total of 619 subjects (mean age, 61 years; 52% female) free of prior CVD were included in this study. A significant association between UA and LVMI was also confirmed in multiple regression analysis (male: F=4.29, P<0.04; female: F=4.24, P<0.05). During follow-up (mean, 34 months), 28 subjects (14 female) developed CVD including myocardial infarction, angina pectoris, congestive heart failure, cerebral infarction, and transient cerebral ischemia. Sex-specific median values were used to separate the higher group from the lower group of UA and LVMI. Kaplan-Meier curves showed a significantly poorer survival rate in the group with higher UA and LVMI (LVMI, male: >126.9, female: >112.0 g/m2; UA, male: >374.7, female: >303.3 micromol/L; log-rank chi2=13.18; P<0.01). Multivariate Cox regression analysis showed that the combination of higher UA and LVMI was an independent predictor for CVD events (hazard ratio, 2.38; P<0.03). Our findings demonstrate that UA is independently associated with LVMI and suggest that the combination of hyperuricemia combined with left ventricular hypertrophy is an independent and powerful predictor for CVD. The association between UA and CVD events may be introduced in part because of a direct association of UA with LVMI.

Cardiovascular Diseases↗
PubMed2005

The controversial role of serum uric acid in essential hypertension: relationships with indices of target organ damage.

The role of serum uric acid (SUA) in the context of adverse cardiovascular events in hypertensive subjects is controversial. Additionally, the relationship between SUA and indices of target organ damage is not well defined in this setting. Towards this end, we studied 842 consecutive nondiabetic patients with stage I-II essential hypertension (office blood pressure=148/95 mmHg, aged 53.4 years), referred to our outpatient hypertensive unit within a period of 4 years. According to the urinary albumin excretion (UAE), the study population was classified into those with microalbuminuria [MA(+), UAE=20-200 mg/24 h, n=222] and those without MA [MA (-), UAE< 20 mg/24 h, n=620]. Moreover, according to the presence of left ventricular hypertrophy (LVH) the participants were subdivided into two additional groups: [LVH (+), n=305 and LVH (-), n=537]. SUA levels were higher by 0.4 mg/dl, (P=0.04) in group MA (+) compared with the group MA (-), while no difference was observed between groups LVH (+) and LVH (-) (P=NS). In the entire population, SUA was correlated with body mass index (BMI) (r=0.17, P<0.001), waist/hip ratio (r=0.3, P<0.001), office systolic blood pressure (SBP) (r=0.14, P<0.05), triglycerides levels (r=0.25, P<0.001), UAE (r=0.35, P<0.001) and HDL (r=-0.26, P<0.001). Multiple regression analysis demonstrated that SUA was significantly related with BMI, office SBP and UAE (P<0.05). In conclusion, increased SUA levels are associated with MA but not with LVH in essential hypertensive subjects. Whether these inter-relationships may elucidate the clinical positioning of augmented SUA in this setting remains to be clarified in future studies.

Albuminuria↗
PubMed2003

Simultaneous electrochemical determination of xanthine and uric acid at a nanoparticle film electrode.

A sensitive electrochemical method was developed for simultaneous determination of uric acid (UA) and xanthine (XA) at a glassy carbon electrode modified with multi-wall carbon nanotubes (MWNTs) film. The oxidation peak currents of UA and XA were increased at the MWNTs film electrode significantly. The experimental parameters, which influence the peak currents of UA and XA, such as the amount of MWNTs on the glassy carbon electrode, the pH of the solution, accumulation time, and scan rate, were optimized. Under optimum conditions, the peak currents were linear to the concentration of UA over the wide range from 1 x 10(-7) mol L(-1) to 1 x 10(-4) mol L(-1) and to that of XA over the wide range from 2 x 10(-8) mol L(-1) to 2 x 10(-5) mol L(-1). The interferences studies showed that the MWNTs-modified electrode exhibited excellent selectivity in the presence of ascorbic acid, dopamine, and hypoxanthine. The proposed procedure was successfully applied to detect UA and XA in human serum without any preliminary treatment.

Calibration↗
PubMed2006

Pre-analytical factors affecting ascorbic and uric acid quantification in human plasma.

We have recently described a new capillary electrophoresis assay to measure serum ascorbic and uric acids in which a baseline separation of peaks was obtained in less than 4 min by using a 60.2 cm x 75 microm uncoated capillary with a 100 mmol/L sodium borate running buffer pH 8. Since during sample preparation AA is rapidly oxidized, we employed our new capillary electrophoresis method to analyze the pre-analytical factors affecting its stability. In particular we evaluated how the standard mix preparation, the blood collection (plasma EDTA or serum) and the plasma protein precipitation influence the results of analysis. Our data suggest that standard ascorbate must be dissolved in a solution containing cysteine and EDTA in order to avoid oxidation and that EDTA blood collection is better than serum for AA measurement. Moreover, the type and the quantity of the precipitating compound are critical parameters to obtain a complete recovery of analytes. We performed AA and UA analysis in 32 healthy volunteers with the optimized experimental conditions by using our capillary electrophoresis method and a reference CE assay. Obtained data were compared to Bland-Altman test to verify the accuracy of our CZE method.

Ascorbic Acid↗
PubMed2000

Effect of caecectomy on growth, moisture in excreta, gastrointestinal passage time and uric acid excretion in growing chicks.

1. The effect of caecectomy on nitrogen utilisation and excretion was examined in growing chicks fed on a commercial diet. 2. Caecectomy had no significant effect on food intake or body weight gain. 3. Caecectomy caused significantly higher moisture content in excreta (P<0.01). 4. Gastrointestinal passage time of digesta was significantly shorter in caecectomised chicks than in control chicks (P<0.05). 5. Caecectomy tended to improve nitrogen utilisation rate in growing chicks. 6. The treatment significantly decreased uric acid excretion (P<0.01) and excretory uric acid-N/total nitrogen excretion (P<0.01). 7. It is concluded that the effects of caecectomy on nitrogen metabolism in growing chicks are similar to those in adult chickens.

Animals↗
PubMed1984

Use of computerized tomography in the delineation of uric acid calculi.

Computerized tomography without injection of contrast material was used to detect the presence of uric acid stones within the kidney in 10 patients. In contrast to the lucent appearance on conventional urography the stones are dense on computerized tomography. The technique is useful to differentiate lucent stones from renal pelvic tumors. Additionally, stone dissolution can be monitored with sequential computerized tomography studies.

Adult↗
PubMed2005

[The fibrinolytic system in uric acid dysmetabolism].

The subjects of the study were 50 first-degree relatives of patients with uric acid (UA) dysmetabolism. The subjects were divided into three groups: 15 with hyperuricosuria and normal UA blood level (group 1), 17--with hyperuricosuria and hyperuricemia (group 2), and 18--with hyperuricemia and lowered UA clearance (group 3). All of them displayed inhibited urine fibrinolytic activity (UFA) and reduced urokinase activity. The degree of UFA inhibition correlated with urokinase activity (r = 0.60) and grew from group 1 to group 3; the subjects in the latter had maximal manifestations of tubulointerstitial nephritis, which suggests that disorder of the local fibrinolytic mechanisms plays an important role in the development and progress of urate tubulointerstitial renal lesion. No changes of blood fibrinolysis were observed.

Diabetes Mellitus↗
PubMed2005

Serum uric acid and cardiovascular disease: recent developments, and where do they leave us?

The relationship between serum uric acid (SUA) and cardiovascular disease has been controversial. Here we review recent literature assessing whether hyperuricemia is an independent risk factor for adverse cardiovascular outcomes. Studies from the past 6 years evaluating the association of SUA with cardiovascular disease were identified through MEDLINE, EMBASE, and Cochrane library searches, bibliography cross-referencing, and review articles. Twenty-one cohort studies in healthy and high-risk patients with cardiovascular disease were identified and reviewed. In studies of high-risk patients, in which more overall events were recorded, 10 of 11 studies were supportive of an independent association. In 10 studies of healthy patients, 6 suggested an independent association of SUA with adverse cardiovascular outcomes. Increasing SUA is likely an independent risk factor for cardiovascular disease in high-risk individuals. However, the magnitude of excess risk attributable to high SUA is likely to be small in healthy individuals. Trials of SUA-lowering therapy in hyperuricemic patients evaluating the effect on cardiovascular outcomes are justified in high-risk patients.

Cardiovascular Diseases↗
PubMed2006

Can cerebrospinal fluid uric acid levels differentiate intraventricular hemorrhage from traumatic tap?

OBJECTIVE: To measure blood and cerebrospinal fluid (CSF) uric acid (UA) levels of neonates with intraventricular hemorrhage (IVH), and to examine whether or not UA can be used to differentiate traumatic tap from IVH. MATERIAL AND METHODS: The control group (n = 19, group I) consisted of neonates presenting with signs requiring analysis of CSF but whose CSF indices proved to be normal. Traumatic taps (n = 15, group II) were mimicked by adding 2 drops of homologous blood to normal CSF samples. The IVH group (n = 21, group III) consisted of neonates who had been diagnosed by cranial ultrasonography or computed tomography scans. Data are presented as median (range). RESULTS: There was no significant difference between groups with respect to serum UA levels. While no significant difference was observed between CSF UA levels of the control [0.6 (0.1-1.8) mg/dl] and traumatic tap group [0.5 (0.3-1.1) mg/dl], the IVH group [1.6 (0.7-6.9) mg/dl] was found to have significantly higher CSF UA levels than groups I and II. Furthermore, although there were significant correlations between serum and CSF UA levels in the control and traumatic tap groups, no correlation was observed in the IVH group. CONCLUSION: CSF UA levels are increased in neonates with IVH and they may be used to differentiate a real hemorrhage from a traumatic tap.

Brain Injuries↗
PubMed1990

An enzymatic assay for the colorimetric and fluorimetric determination of uric acid in sera.

The methods described in this paper are based on the uricase catalyzed oxidation of uric acid to allantoine and hydrogen peroxide. By making use of the catalytic activity of peroxidase the generated H2O2 is measured either spectrophotometrically with 3-methyl-benzothiazoline-2-one hydrazone (MBTH) and 3-dimethylaminobenzoic acid (DMAB) (M1) or fluorimetrically with tyramine (M2) or L-tyrosine (M3). The methods are simple, sensitive and selective. The procedures developed can be rapidly and readily performed on patient serum samples without deproteinization using 100 microliters and 5 microliters for colorimetric and fluorimetric assay, respectively.

Colorimetry↗
PubMed1971

Uric acid dihydrate in bird urine.

X-ray diffraction analysis shows that the white excrement from a budgerigar, consists mainly of uric acid dihydrate. Initially this material is in the form of a smectic (or cholesteric) phase, which transforms to the normal crystalline phase either on aging or on removal of the minor (soluble) constituents of the excrement with water or dilute acids.

Animals↗
PubMed2005

Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia.

Beyond allopurinol and the well-established uricosuric drugs, several other agents can decrease serum uric acid (SUA) levels, such as losartan, fenofibrate and some non-steroidal anti-inflammatory drugs (NSAIDs). Some of these drugs increase renal urate excretion. Hyperuricaemia and gout are common problems (at least 1% of Western men are affected by gout). Raised SUA levels increase the incidence of acute gout and renal calculi. Hyperuricaemia may also predict an increased risk of vascular events. Therefore, lowering SUA levels is of clinical relevance. In this review we consider the effect on SUA levels of drugs that are prescribed for indications other than treating hyperuricaemia. These drugs may obviate the need for specific treatment (e.g. allopurinol) aimed at lowering SUA levels. Furthermore, because hyperuricaemic patients may already be on several drugs (e.g. due to associated dyslipidaemia, hypertension and/or arthritis) compliance may be improved by avoiding additional medication. The potential for adverse effects associated with polypharmacy would also be decreased.

Angiotensin II Type 1 Receptor Blockers↗