High plasma uric acid (UA) is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. The main causes for higher plasma UA are either lower excretion, higher synthesis or both. Higher waist circumference and the BMI are associated with higher insulin resistance and leptin production, and both reduce uric acid excretion. The synthesis of fatty acids (tryglicerides) in the liver is associated with the de novo synthesis of purine, accelerating UA production. The role played by diet on hyperuricemia has not yet been fully clarified, but high intake of fructose-rich industrialized food and high alcohol intake (particularly beer) seem to influence uricemia. It is not known whether UA would be a causal factor or an antioxidant protective response. Most authors do not consider the UA as a risk factor, but presenting antioxidant function. UA contributes to > 50% of the antioxidant capacity of the blood. There is still no consensus if UA is a protective or a risk factor, however, it seems that acute elevation is a protective factor, whereas chronic elevation a risk for disease. PMID:22475652
Uric acid urine test is performed to check for the amount of uric acid in urine. Urine is collected over a 24 ... testing. The most common reason for measuring uric acid levels is in the diagnosis or treatment of ...
Jiménez, M C; Curhan, G C; Choi, H K; Forman, J P; Rexrode, K M
Elevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. A nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. In matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval (CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. Plasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk. © 2016 EAN.
... products and services. Advertising & Sponsorship: Policy | Opportunities Uric Acid Share this page: Was this page helpful? Also known as: Serum Urate; UA Formal name: Uric Acid Related tests: Synovial Fluid Analysis , Kidney Stone Analysis , ...
Fromonot, J; Deharo, P; Bruzzese, L; Cuisset, T; Quilici, J; Bonatti, S; Fenouillet, E; Mottola, G; Ruf, J; Guieu, R
The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 ± 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 ± 0.5 μmol/L vs 0.53 ± 0.14 μmol/L; p < 0.01), HCys (15 ± 7.6 μmol/L vs 6.8 ± 3 μmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations.
Boban, Mladen; Modun, Darko
The aim of this article is to review the role of uric acid in the context of antioxidant effects of wine and its potential implication to human health. We described and discussed the mechanisms of increase in plasma antioxidant capacity after consumption of moderate amounts of wine. Because this effect is largely contributed by acute elevation in plasma uric acid, we paid special attention to wine constituents and metabolic processes that are likely to be involved in uric acid elevation. PMID:20162741
Simoyi, Melvin F; Falkenstein, Elizabeth; Van Dyke, Knox; Blemings, Kenneth P; Klandorf, Hillar
Urate oxidase is not present in birds yet allantoin, a product of this enzyme, has been measured in birds. Studies were designed to compare the concentrations of plasma purine derivatives in chickens and turkeys fed inosine-supplemented diets. The first study consisted of 12 male chicks that were fed diets supplemented with 0.6 mol inosine or hypoxanthine per kilogram diet from 3- to 6-week-old. Study 2 consisted of 12 turkey poults (toms) fed inosine-supplemented diets (0.7 mol/kg) from 6- to 8-week-old. Plasma allantoin and oxypurines concentrations were measured weekly using high performance liquid chromatography. Plasma uric acid (PUA) in chickens fed inosine-supplemented diets increased from 0.31 to 1.34 mM (P<0.05) at the end of week 2. In turkeys, those fed control diet had 0.17 mM PUA concentration compared to 0.3 mM in those fed the inosine diet at week 2 (P<0.05). Allantoin concentration increased in chickens from week 1 to 2 while a decrease was observed in turkeys (P<0.005) for both treatments. These data show that allantoin is present in turkey and chicken plasma. The presence of allantoin in avian plasma is consistent with uric acid acting as an antioxidant in these species.
Shi, Yuanlu; Williamson, Gary
Elevated plasma uric acid concentration is a risk factor for gout, insulin resistance and type 2 diabetes. Quercetin, a flavonoid found in high levels in onions, tea and apples, inhibits xanthine oxidoreductase in vitro, the final step in intracellular uric acid production, indicating that quercetin might be able to lower blood uric acid in humans. We determined the effects of 4 weeks of oral supplementation of quercetin on plasma uric acid, blood pressure and fasting glucose. This randomised, double-blinded, placebo-controlled, cross-over trial recruited twenty-two healthy males (19-60 years) with baseline plasma uric acid concentration in the higher, but still considered healthy, range (339 (SD 51) µmol/l). The intervention included one tablet containing 500 mg quercetin daily for 4 weeks, compared with placebo, with a 4-week washout period between treatments. The primary outcome was change in concentrations of plasma uric acid after 2 and 4 weeks; secondary outcome measures were changes in fasting plasma glucose, 24-h urinary excretion of uric acid and resting blood pressure. After quercetin treatment, plasma uric acid concentrations were significantly lowered by -26·5 µmol/l (95% CI, -7·6, -45·5; P=0·008), without affecting fasting glucose, urinary excretion of uric acid or blood pressure. Daily supplementation of 500 mg quercetin, containing the bioavailable amount of quercetin as present in approximately 100 g red onions, for 4 weeks, significantly reduces elevated plasma uric acid concentrations in healthy males.
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Uric acid test system. 862.1775 Section 862.1775....1775 Uric acid test system. (a) Identification. A uric acid test system is a device intended to measure uric acid in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis...
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Uric acid test system. 862.1775 Section 862.1775....1775 Uric acid test system. (a) Identification. A uric acid test system is a device intended to measure uric acid in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis...
Hartman, S; Taleb, S A; Geng, T; Gyenai, K; Guan, X; Smith, E
Plasma uric acid (PUA) is a consensus physiological biomarker for many phenotypes in vertebrates because it is a reliable indicator for processes such as oxidative stress and tubular function. In birds, it is considered a major antioxidant and is also the primary endproduct of nitrogen metabolism. Despite this importance, knowledge of baseline levels of PUA in physiologically normal birds, including the turkey, Meleagris gallopavo, is limited. Here, we compared PUA levels in a total of 106 apparently normal male and female birds at 8 and 32 wk of age from 5 strains of the domestic turkey, including Bourbon Red, Narragansett, Blue Slate, Royal Palm, and Spanish Black. Though differences in PUA were not significant at 8 and 32 wk of age, BW, variety, and sex effects were highly significant. When adjusted for BW, female birds had, on average, a higher PUA per kilogram of BW than male birds. When adjusted for both sex and BW, Royal Palm birds had the lowest average PUA, and Blue Slate had the highest PUA. Results of these investigations represent the first comparative analysis of PUA in physiologically normal turkey varieties. They suggest that differences in basal plasma levels of uric acid in physiologically normal turkeys are influenced by sex, weight, and genetic background but may be independent of age.
Kamel, K S; Cheema-Dhadli, S; Shafiee, M A; Davids, M R; Halperin, M L
A 46-year-old female had a history of recurrent uric acid stone formation, but the reason why uric acid precipitated in her urine was not obvious, because the rate of urate excretion was not high, urine volume was not low, and the pH in her 24-h urine was not low enough. In his discussion of the case, Professor McCance provided new insights into the pathophysiology of uric acid stone formation. He illustrated that measuring the pH in a 24-h urine might obscure the fact that the urine pH was low enough to cause uric acid to precipitate during most of the day. Because he found a low rate of excretion of NH(4)(+) relative to that of sulphate anions, as well as a high rate of citrate excretion, he speculated that the low urine pH would be due to a more alkaline pH in proximal convoluted tubule cells. He went on to suspect that there was a problem in our understanding of the function of renal medullary NH(3) shunt pathway, and he suggested that its major function might be to ensure a urine pH close to 6.0 throughout the day, to minimize the likelihood of forming uric acid kidney stones.
Scheepers, Lieke E J M; Boonen, Annelies; Pijnenburg, Wieke; Bierau, Jörgen; Staessen, Jan A; Stehouwer, Coen D A; Thijs, Carel; Arts, Ilja C W
Elevated serum uric acid concentration has been associated with high blood pressure (BP) and hypertension. A putative underlying mechanism is the accumulation of reactive oxygen species when uric acid is generated by an increased enzyme activity of xanthine oxidase (XO). The aims of the present study were to investigate the associations between plasma uric acid concentration, purine metabolite ratios, as proxies for increased XO activity, and SBP and DBP in school-age children. Cross-sectional analyses were performed in 246 children (46% boys; mean age 7.1 years) from the Dutch KOALA Birth Cohort Study. Purine metabolites were determined with ultra-performance liquid chromatography-tandem mass spectrometry. During a home visit, a nurse collected a blood sample and measured BP three times; in addition, parents measured their child's BP on three consecutive days, in the morning and evening. Generalized estimating equations were used for analyses while controlling for variables such as sex, age, BMI, physical activity, and dietary intake. In multivariable analysis, uric acid (per SD of 38 μmol/l) was associated with DBP z-scores [sβ 0.07; confidence interval (CI), 0.01-1.14], but not with SBP z-scores. Higher ratios of uric acid/xanthine (per SD of 138) (sβ 0.09; CI, 0.01-0.17) and xanthine/hypoxanthine (per SD of 321) (sβ 0.08; CI, 0.02-0.17) were associated with higher DBP z-scores, but not with SBP z-scores. In school-age children, uric acid and the ratios of uric acid/xanthine and xanthine/hypoxanthine were significantly associated with DBP z-scores. Suggesting that, both uric acid concentration and increased XO activity are associated with BP.
Hernandez-Divers, S J; Martinez-Jimenez, D; Bush, S; Latimer, K S; Zwart, P; Kroeze, E J B Veldhuis
A two-phase cross-over therapeutic study was performed with 19 green iguanas (Iguana iguana) maintained within a preferred optimum temperature range of 26 to 37 degrees C. During phase 1, they were fed a normal vegetarian diet and medicated orally with either allopurinol or a placebo control once a day for seven days. Uric acid concentrations, total protein, packed-cell volumes (pcv) and bodyweights were recorded from each lizard before and after treatment to determine the effects of allopurinol. In phase 2, after a 10-day washout period, the iguanas were fed a high protein diet to induce hyperuricaemia. Normo- and hyperuricaemic iguanas that received 24.2 (3.2) mg/kg allopurinol had significantly lower mean (sd) uric acid concentrations (100.3 [53.1] micromol/l) than the controls (159.3 [100.3] micromol/l). There were no detectable interactions between the doses of allopurinol or placebo, and the iguanas' diet, weight, pcv or total protein. The allopurinol was well tolerated, and there was no significant clinical, gross or histological evidence of hepatic or renal toxicity in the iguanas that received the drug. However, in the kidneys of the hyperuricaemic iguanas that did not receive allopurinol there were proliferative changes in the glomeruli and degeneration of tubular epithelia. Allopurinol given orally at 25 mg/kg daily is able to reduce plasma uric acid levels by 41 to 45 per cent, and is therefore recommended for the treatment of hyperuricaemia in the green iguana.
Juraschek, Stephen P; McAdams-Demarco, Mara; Gelber, Allan C; Sacks, Frank M.; Appel, Lawrence J; White, Karen; Miller, Edgar R
Objective The effects of carbohydrates on plasma uric acid levels are controversial. We determined the individual and combined effects of carbohydrate quality (glycemic index, GI) and quantity (proportion of total daily energy, %carb) on uric acid. Methods We conducted a randomized, crossover feeding trial in overweight or obese adults without cardiovascular disease (N=163). Participants were fed each of four diets over 5-week periods separated by 2-week washout periods. Body weight was kept constant. The four diets were: high GI (GI ≥65) with high %carb (58% kcal), low GI (GI ≤45) with low %carb (40% kcal), low GI with high %carb; and high GI with low %carb. Plasma uric acid was measured at baseline and after each feeding period for comparison between the 4 diets. Results Study participants were 52% women and 50% non-Hispanic black with a mean age of 52.6 years and a mean uric acid of 4.7 (SD, 1.2) mg/dL. Reducing GI lowered uric acid when the %carb was low (−0.24 mg/dL; P <0.001) or high (−0.17 mg/dL; P <0.001). Reducing the %carb marginally increased uric acid only when GI was high (P = 0.05). The combined effect of lowering GI and increasing the %carb was −0.27 mg/dL (P <0.001). This effect was observed even after adjustment for concurrent changes in kidney function, insulin sensitivity, and products of glycolysis. Conclusions Reducing GI lowers uric acid. Future studies should examine whether reducing GI can prevent gout onset or flares. TRIAL REGISTRATION clinicaltrials.gov, Identifier: NCT00608049 PMID:26636424
Simoyi, Melvin F; Van Dyke, Knox; Klandorf, Hillar
Birds have high metabolic rates, body temperatures, and plasma glucose concentrations yet physiologically age at a rate slower than comparably sized mammals. These studies were designed to test the hypothesis that the antioxidant uric acid protects birds against oxidative stress. Mixed sex broiler chicks (3 wk old) were fed diets supplemented or not with purines (0.6 mol hypoxanthine or inosine). Study 1 consisted of 18 female Cobb x Cobb broilers that were fed purines for 7 days, whereas study 2 consisted of 12 males in a 21-day trial. Study 3 involved 30 mixed sex broilers that were fed 40 or 50 mg allopurinol/kg body mass (BM) for 21 days, a drug that lowers plasma uric acid (PUA). PUA and leukocyte oxidative activity (LOA) were determined weekly for all studies. For study 2, pectoralis major shear force, relative kidney and liver sizes (RKS and RLS), and plasma glucose concentrations were also determined. In study 1, PUA concentration was increased three- and twofold (P < 0.001) in birds fed inosine or hypoxanthine, respectively, compared with control birds. LOA of birds supplemented with inosine was lower (P < 0.05) than that of control or hypoxanthine birds. In study 2, PUA concentrations were increased fivefold (P < 0.001) in birds fed inosine and twofold (P < 0.001) in birds fed hypoxanthine compared with control birds at day 21. RKS (g/kg BM) was greater (P < 0.001) for chicks fed purine diets compared with control chicks. Muscle shear value was lower (P < 0.05) in chicks fed purine diets. PUA concentration was decreased (P < 0.001) in birds consuming allopurinol diets, whereas LOA was increased (P < 0.01) in study 3. These studies show that PUA concentrations can be related to oxidative stress in birds, which can be linked to tissue aging.
Meadows, J; Smith, R C
Uric acid effectively reduced hemolysis and methemoglobin formation in bovine and swine erythrocytes bubbled with ozone in vitro. In bovine erythrocytes, formation of thiobarbituric acid-reactive material was inhibited by uric acid, but there was little immediate protection for the swine cells. Antioxidant protection was due to preferential degradation of the uric acid by ozone. These results provide evidence to support the hypothesis that in plasma, uric acid can provide antioxidant protection for erythrocytes.
Saunders, J P; Donner, T W; Sadler, J H; Levin, G V; Makris, N G
D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal
Simoyi, M F; Klandorf, H
Previous studies have shown that addition of fructose to the diet of broilers raises plasma uric acid (PUA) concentration and improves productive performance. The purpose of this experiment was to establish the effect of feeding fructose on turkey PUA concentration and productive performance. Turkey poults (n = 64) were weighed and randomly assigned to diets containing 0 (control), 5, 10, and 15% fructose with four replicates of four poults each per treatment. All diets were isocaloric and isonitrogenous. Feed and water were offered ad libitum for 14 wk. Body weights were measured biweekly throughout the study, and blood samples were drawn from wk 8 to 10 for determination of PUA concentration, leukocyte oxidative activity (LOA), and differential leukocyte counts. Relative liver size (g/kg BW) was also determined. The heaviest body weights were recorded from turkeys fed 10% fructose diet (P < 0.05). Supplemental fructose had no effect on the feed to gain ratio, relative liver size, or PUA concentrations. LOA increased in poults fed the 15% fructose diet. Turkeys fed 10 and 15% fructose diets had higher monocyte and lower polymorphonuclear lymphocyte counts (P < 0.05) compared to those fed control and 5% fructose diets. Feeding fructose to turkeys at 10% of the diet improved productive performance. However, dietary fructose had no effect on PUA or, consequently, LOA.
Jung, Dong-Hyuk; Lee, Yong-Jae; Lee, Hye-Ree; Lee, Jung-Hyun
Several studies have reported that hyperuricemia is associated with the development of hypertension and cardiovascular disease. Increasing evidences also suggest that hyperuricemia may have a pathogenic role in the progression of renal disease. Paradoxically, uric acid is also widely accepted to have antioxidant activity in experimental studies. We aimed to investigate the association between glomerular filtration rate (GFR) and uric acid in healthy individuals with a normal serum level of uric acid. We examined renal function determined by GFR and uric acid in 3,376 subjects (1,896 men; 1,480 women; aged 20-80 yr) who underwent medical examinations at Gangnam Severance Hospital from November 2006 to June 2007. Determinants for renal function and uric acid levels were also investigated. In both men and women, GFR was negatively correlated with systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, uric acid, log transformed C reactive protein, and log transformed triglycerides. In multivariate regression analysis, total uric acid was found to be an independent factor associated with estimated GFR in both men and women. This result suggests that uric acid appears to contribute to renal impairment in subjects with normal serum level of uric acid. PMID:21165292
Lytvyn, Y; Škrtić, M; Yang, G K; Lai, V; Scholey, J W; Yip, P M; Perkins, B A; Cherney, D Z I
Increased plasma uric acid (PUA) levels are associated with impaired renal function in patients with Type 1 diabetes, but the mechanisms are not well understood. Our aim was to evaluate whether higher PUA levels are associated with increased afferent arteriolar resistance in patients with Type 1 diabetes vs. healthy controls, thereby influencing renal function. PUA, GFR (inulin) and effective renal plasma flow (ERPF; para-aminohippurate) were measured in 70 otherwise healthy patients with Type 1 diabetes and 60 healthy controls. Gomez's equations were used to estimate afferent (RA ) and efferent (RE ) arteriolar resistances, glomerular hydrostatic pressure (PGLO ) and filtration pressure (ΔPF ). The relationships between PUA and glomerular haemodynamic parameters were evaluated by univariable linear regression correlation coefficients. In patients with Type 1 diabetes, higher PUA correlated with lower PGLO (P = 0.002) and ΔPF (P = 0.0007), with higher RA (P = 0.001), but not with RE (P = 0.55). These associations were accompanied by correlations between higher PUA with lower GFR (P = 0.0007), ERPF (P = 0.008), RBF (P = 0.047) and higher RVR (P = 0.021). There were no significant correlations between PUA and renal haemodynamic parameters in the healthy controls. The association between higher PUA with lower GFR and lower ERPF in patients with Type 1 diabetes is driven by alterations in the estimated RA . PUA-mediated RA may be caused by increased tone or thickening of the afferent renal arteriole, which might potentiate renal injury by causing ischaemia to the renal microcirculation. © 2015 Diabetes UK.
Drewa, Tomasz; Wolski, Zbigniew; Gruszka, Marzena; Misterek, Bartosz; Lysik, Joanna
It was a chance discovery that ambroxol parenteral administration led to urinary bladder stone formation in rats. This study was undertaken to examine the serum uric acid levels and urine pH in rats after ambroxol parenteral treatment. Ambroxol influence on the uric acid level was measured in 5 rats (Rattus sp.) treated with 60 mg/kg (dissolved in injection water, sc, daily) during 2 weeks. Ambroxol influence on urine pH was examined on 45 rats divided into 3 groups. Rats from the 1st and 2nd group received 30 and 60 mg/kg/24h ambroxol, respectively. Urine was collected once daily and measured with strip kit. All values were presented as the means with standard deviations. The Student t test was used to compare the means, p < 0.05 was considered as significant. Dynamics of pH changes was measured in 4 rats treated with 60 mg/kg/24h of ambroxol. Controls received 1 mL of injection water sc. Serum uric acid level increased up to 8.7 +/- 1.0 mg/dL vs. 5.7 +/- 1.0 mg/dL in control (p < 0.002). In the 1st and 2nd group urine pH increased up to 7.5 +/- 0.5 and 7.6 +/- 0.5 vs. 6.7 +/- 0.4 (p < 0.05). Ambroxol withdrawal resulted in sequential urine pH decrease. 11 days after interruption of ambroxol therapy pH reached the starting value. Urine pH changes and possible disturbances in uric acid metabolic pathway may influence on the stone formation in rats after ambroxol parenteral treatment. The influence of ambroxol on urinary tract GAG layer and the balance between xanthine and CaOx in the urine should be checked.
Fabbrini, Elisa; Serafini, Mauro; Colic Baric, Irena; Hazen, Stanley L.; Klein, Samuel
Oxidative stress is purported to be involved in the pathogenesis of obesity-associated insulin resistance. We evaluated whether alterations in levels of circulating uric acid (UA), a systemic antioxidant, affects the following: 1) systemic (plasma and saliva) nonenzymatic antioxidant capacity (NEAC); 2) markers of systemic (urinary 8-iso-prostaglandin-F2α) and muscle (carbonylated protein content) oxidative stress; and 3) whole-body insulin sensitivity (percentage increase in glucose uptake during a hyperinsulinemic-euglycemic clamp procedure). Thirty-one obese subjects (BMI 37.1 ± 0.7 kg/m2) with either high serum UA (HUA; 7.1 ± 0.4 mg/dL; n = 15) or normal serum UA (NUA; 4.5 ± 0.2 mg/dL; n = 16) levels were studied; 13 subjects with HUA levels were studied again after reduction of serum UA levels to 0 by infusing a recombinant urate oxidase. HUA subjects had 20–90% greater NEAC, but lower insulin sensitivity (40%) and levels of markers of oxidative stress (30%) than subjects in the NUA group (all P < 0.05). Acute UA reduction caused a 45–95% decrease in NEAC and a 25–40% increase in levels of systemic and muscle markers of oxidative stress (all P < 0.05), but did not affect insulin sensitivity (from 168 ± 25% to 156 ± 17%, P = NS). These results demonstrate that circulating UA is a major antioxidant and might help protect against free-radical oxidative damage. However, oxidative stress is not a major determinant of insulin action in vivo. PMID:24353177
Mita-Mendoza, Neida K; van de Hoef, Diana L; Lopera-Mesa, Tatiana M; Doumbia, Saibou; Konate, Drissa; Doumbouya, Mory; Gu, Wenjuan; Anderson, Jennifer M; Santos-Argumedo, Leopoldo; Rodriguez, Ana; Fay, Michael P; Diakite, Mahamadou; Long, Carole A; Fairhurst, Rick M
Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA) was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria. We measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-Selectin), thrombomodulin (sTM), tissue factor (sTF) and vascular endothelial growth factor (VEGF) in the plasma of Malian children aged 0.5-17 years with uncomplicated malaria (UM, n = 487) and non-cerebral severe malaria (NCSM, n = 68). In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season). We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001). Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043), sICAM-1 (r = 0.255, p<0.0001) and sTM (r = 0.175, p = 0.0001) levels. After adjusting for parasite density, UA levels predict sTM levels. Elevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of endothelial TM may represent a novel mechanism of malaria pathogenesis, in
Barros, Marcelo P; Ganini, Douglas; Lorenço-Lima, Leandro; Soares, Chrislaine O; Pereira, Benedito; Bechara, Etelvino Jh; Silveira, Leonardo R; Curi, Rui; Souza-Junior, Tacito P
Dietary creatine has been largely used as an ergogenic aid to improve strength and athletic performance, especially in short-term and high energy-demanding anaerobic exercise. Recent findings have also suggested a possible antioxidant role for creatine in muscle tissues during exercise. Here we evaluate the effects of a 1-week regimen of 20 g/day creatine supplementation on the plasma antioxidant capacity, free and heme iron content, and uric acid and lipid peroxidation levels of young subjects (23.1 ± 5.8 years old) immediately before and 5 and 60 min after the exhaustive Wingate test. Maximum anaerobic power was improved by acute creatine supplementation (10.5 %), but it was accompanied by a 2.4-fold increase in pro-oxidant free iron ions in the plasma. However, potential iron-driven oxidative insult was adequately counterbalanced by proportional increases in antioxidant ferric-reducing activity in plasma (FRAP), leading to unaltered lipid peroxidation levels. Interestingly, the FRAP index, found to be highly dependent on uric acid levels in the placebo group, also had an additional contribution from other circulating metabolites in creatine-fed subjects. Our data suggest that acute creatine supplementation improved the anaerobic performance of athletes and limited short-term oxidative insults, since creatine-induced iron overload was efficiently circumvented by acquired FRAP capacity attributed to: overproduction of uric acid in energy-depleted muscles (as an end-product of purine metabolism and a powerful iron chelating agent) and inherent antioxidant activity of creatine.
Machín, M; Simoyi, M F; Blemings, K P; Klandorf, H
Uric acid is an important antioxidant and methods to elevate its plasma concentration may be important in animal health. In a first study, the effect of dietary protein on plasma uric acid (PUA) and glucose concentrations were determined in 3-week-old chicks. Twenty-four broiler chicks were randomly assigned to four diets: a commercial control diet (C, 20% crude protein), low protein (LP) containing 10% casein, medium protein (MP) containing 20% casein or high protein (HP) containing 45% casein for a 3-week experiment. PUA concentration increased (P<0.05) in chicks fed HP diet and declined (P<0.05) in chicks fed LP while plasma glucose concentrations were lower (P<0.05) in chicks fed the LP diet at the end of the study. In a second study, PUA and leukocyte oxidative activity (LOA) were determined in broilers fed C, LP, MP or HP diets for 4 weeks. As in the first study, dietary protein directly affected PUA concentrations. In birds consuming HP diets, PUA was negatively correlated (P=0.06) with lowered LOA. These data support the view that increases in dietary protein can increase PUA concentrations, which can ameliorate oxidative stress.
Cameron, J Stewart
The interrelationship between uric acid and renal disease is reviewed in a historical context. Four phases can be distinguished--the descriptions of uric acid stones and gravel in the eighteenth century, of chronically scarred kidneys containing urate crystals in the nineteenth, the appearance of the syndrome of acute urate nephropathy following tumour lysis in the mid twentieth century, and finally the realization that soluble urate affects both systemic and glomerular blood vessels, and may play a role in both hypertension and chronic renal damage.
Huda, Nazmul; Hossain, Shakhawoat; Rahman, Mashiur; Karim, Md Rezaul; Islam, Khairul; Mamun, Abdullah Al; Hossain, Md Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled
Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p<0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose-response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. Copyright © 2014 Elsevier Inc. All rights reserved.
Ding, Xiao-Han; Wang, Xiaona; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei; Ye, Ping
Abstract Hyperuricemia has been demonstrated to be a risk factor for cardiovascular diseases. Though the association between uric acid (UA) and arterial stiffness has been investigated previously in patients with basic diseases, the predictive value of baseline UA level for arterial stiffness has not been conducted. We aimed at identifying the predictive role of UA for arterial stiffness prospectively. A longitudinal follow-up study in a routine health check-up population was performed with an average follow-up of 4.8 years. The demographic information, baseline and follow-up anthropometric parameters, arterial stiffness (pulse-wave velocity, PWV), and biomarker variables including UA have been measured and analyzed. A total of 1447 valid follow-ups were available for the final analysis. Both of the baseline and follow-up UA levels were significantly higher in the arterial stiffness groups than that in the nonarterial stiffness groups (all P values <0.001). The follow-up carotid-femoral PWV [(cf-PWV), r = 0.161, P < 0.001] was strongly correlated with baseline UA. At the follow-up cross-section, cf-PWV was also closely associated with UA (r = 0.101, P < 0.001). Logistic regressions revealed that a higher baseline UA level was an independent predictor of follow-up arterial stiffness assessed by cf-PWV [odds ratio (OR): 1.824; P = 0.046]. A higher baseline level of UA is closely related to arterial stiffness and is an independent predictor of arterial stiffening. PMID:28178136
Bjornstad, Petter; Lanaspa, Miguel A.; Ishimoto, Takuji; Kosugi, Tomoki; Kume, Shinji; Jalal, Diana; Maahs, David M.; Snell-Bergeon, Janet K.; Johnson, Richard J.
Clinical studies have reported associations between serum uric acid levels and the development of diabetic nephropathy, but the underlying mechanisms remain elusive. There is evidence from animal studies that blocking uric acid production protects the kidney from tubulointerstitial injury, which may suggest a causal role for uric acid in the development of diabetic tubular injury. In turn, when fructose, which is endogenously produced in diabetes via the polyol pathway, is metabolised, uric acid is generated from a side-chain reaction driven by ATP depletion and purine nucleotide turnover. For this reason, uric acid derived from endogenous fructose could cause tubulointerstitial injury in diabetes. Accordingly, our research group recently demonstrated that blocking fructose metabolism in a diabetic mouse model mitigated the development of tubulointerstitial injury by lowering tubular uric acid production. In this review we discuss the relationship between uric acid and fructose as a novel mechanism for the development of diabetic tubular injury. PMID:26049401
El Ridi, Rashika; Tallima, Hatem
Uric acid is synthesized mainly in the liver, intestines and the vascular endothelium as the end product of an exogenous pool of purines, and endogenously from damaged, dying and dead cells, whereby nucleic acids, adenine and guanine, are degraded into uric acid. Mentioning uric acid generates dread because it is the established etiological agent of the severe, acute and chronic inflammatory arthritis, gout and is implicated in the initiation and progress of the metabolic syndrome. Yet, uric acid is the predominant anti-oxidant molecule in plasma and is necessary and sufficient for induction of type 2 immune responses. These properties may explain its protective potential in neurological and infectious diseases, mainly schistosomiasis. The pivotal protective potential of uric acid against blood-borne pathogens and neurological and autoimmune diseases is yet to be established.
Godycki-Cwirko, Maciek; Krol, Maciej; Krol, Bogusław; Zwolinska, Anna; Kolodziejczyk, Krzysztof; Kasielski, Marek; Padula, Gianluca; Grebowski, Jacek; Grębocki, Jacek; Kazmierska, Paulina; Kazimierska, Paulina; Miatkowski, Marcin; Markowski, Jarosław; Nowak, Dariusz
To determine whether (1) rapid consumption of 1 L of apple juice increases blood antioxidant capacity, measured as ferric-reducing ability of plasma (FRAP) and serum 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, and (2) apple polyphenols or fructose-induced elevation of plasma uric acid contributes to post-juice increase of blood antioxidant activity. The study involved 12 (mean age 32 ± 5 years, mean body weight 73 ± 7 kg) healthy nonsmoking subjects. Tested subjects consumed 1 L of clear apple juice and then FRAP; serum DPPH-scavenging activity, serum uric acid, and total plasma phenolics and quercetin levels were measured just before juice ingestion and 1, 2.5, and 4 hours after ingestion. This was repeated 3 times with 4-day intervals, but volunteers drank either 1 L of clear apple juice without polyphenols (placebo), or 1 L of cloudy apple juice (positive control), or 1 L of water (negative control) at the time. All juices had similar content of sugars (i.e., saccharose, glucose, and fructose) and precisely defined composition of phenolics and antioxidant activity. Consumption of all 3 juices transiently increased FRAP and serum DPPH-scavenging activity, with peak values at 1 hour post-juice ingestion. This was paralleled by the rise of serum uric acid, but no significant changes in plasma total phenolics and quercetin levels were observed after all dietary interventions. At the same time, no substantial differences were found between juices (especially between clear apple juice and clear apple juice without polyphenols) concerning the measured variables. A strong significant correlation was noted instead between serum uric acid and plasma antioxidant activity at all analyzed time points, before and after juice ingestion. Plasma total phenolics and quercetin levels were not associated with FRAP and serum DPPH radical-scavenging activity. We have demonstrated that rapid consumption of apple juice increased plasma antioxidant activity in
Huda, Nazmul; Hossain, Shakhawoat; Rahman, Mashiur; Karim, Md. Rezaul; Islam, Khairul; Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled
Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with
Prebis, J W; Gruskin, A B; Polinsky, M S; Baluarte, H J
Serum uric acid concentrations and the fractional excretion of uric acid were determined in 31 children from 3 1/2 to 18 years of age with essential hypertension. While on an unrestricted sodium intake, elevated serum values of uric acid were found in 13 of 31 (42%) of the children. After ingesting a low-sodium diet (200 mg/day) for three days, mean serum uric acid values increased by 0.7 mg/dl (P less than 0.001). There was a significant inverse correlation between the serum uric acid concentrations and fractional excretion of uric acid during the normal and low-sodium diet. This study indicates that the major factor leading to hyperuricemia in our hypertensive patients was a decrease in urate clearance. Insofar as hyperuricemia may represent a cardiovascular risk factor, this abnormality already exists in a significant fraction of hypertensive children and adolescents.
Plasma and uric acid levels were measured in 132 men with calcium-containing renal stones and in 24 healthy men of similar ages. Fasting resulted in a significant fall in the mean plasma uric acid level of normal subjects. Intermittent hyperuricaemia was observed in 7% of fasting patients. Intermittent hyperuricosuria was found in 17% of non-fasting patients but in only 2 to 6% of fasting subjects. Most of the uric acid abnormalities in patients with calcium stones therefore appear to be due to diet and may be prevented by reducing the consumption of purine-rich foods. A direct relationship was observed between uric acid excretion and urine flow at normal flow rates. It is suggested that the apparent increase in stone incidence, which occurs with rising living standards, may be due partly to increased consumption of purine-rich foods.
Poffers, J; Lumeij, J T; Timmermans-Sprang, E P M; Redig, P T
The present paper reports the effects of allopurinol in a raptor hyperuricaemic model. The study was performed as a follow-up to previous experiments wherein allopurinol was used in doses of 100 and 50 mg/kg, and was proved to be toxic at these higher dose rates. To investigate whether 25 mg/kg (semel in die) s.i.d. allopurinol is a safe and effective dose in Red-tailed Hawks (Buteo jamaicensis) to reduce plasma uric acid concentrations, experimental studies were performed using the physiologically occurring postprandial hyperuricaemia. Preprandial and postprandial plasma concentrations of xanthine, hypoxanthine, allopurinol, oxypurinol and uric acid were established by high-performance liquid chromatography at various time intervals after receiving allopurinol (25 mg/kg SID) or placebo. No significant differences were observed between the experimental and the control group. These results indicate that this dose is safe to administer; however, this dose failed to cause a significant effect on plasma uric acid concentrations. Because of the low therapeutic ratio of allopurinol in Red-tailed Hawks, follow-up studies have concentrated on an alternative for the treatment of hyperuricaemia, namely urate oxidase.
Wang, Haidong; Li, Xi; Zhang, Wenting; Liu, Yao; Wang, Shijun; Liu, Xiaoquan; He, Hua
1. Salvianolic acid A (SalA) was found to attenuate plasma uric acid (UA) concentration and xanthine oxidase (XO) activity in acute myocardial infraction (AMI) rats, which was characterized with developed mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model. 2. AMI was induced in rats by coronary artery ligation. Surviving AMI rats received a single intravenous dose of 5 mg/kg of SalA and normal saline. The plasma SalA concentrations were determined by HPLC-MS/MS method. The plasma UA concentrations were determined by HPLC method and plasma XO activity were measured spectrophotometrically. An integrated mathematical model characterized the relationship between plasma UA and SalA. 3. Pharmacokinetics was described using two-compartment model for SalA with linear metabolic process. In post-AMI rats, XO activity and UA concentrations were increased, while SalA dosing palliated this increase. These effects were well captured by using two series of transduction models, simulating the delay of inhibition on XO driven by SalA and UA elevation resulted from the multiple factors, respectively. 4. The effect was well described by the developed PK-PD model, indicating that SalA can exert cardiovascular protective effects by decreasing elevated plasma UA levels induced by AMI.
Maalouf, Naim M.
Type 2 diabetes is associated with an increased propensity for uric acid nephrolithiasis. In individuals with diabetes, this increased risk is due to a lower urine pH that results from obesity, dietary factors, and impaired renal ammoniagenesis. The epidemiology and pathogenesis of uric acid stone disease in patients with diabetes are hereby reviewed, and potential molecular mechanisms are proposed.
Laughon, S.K.; Catov, J.; Powers, R.W.; Roberts, J.M.; Gandley, R.E.
BACKGROUND The association of elevated serum uric acid with the development of hypertension is established outside of pregnancy. We investigated whether first trimester uric acid was associated with the development of the following: gestational hypertension or preeclampsia, these outcomes stratified by presence of hyperuricemia at delivery since this denotes more severe disease, preterm birth or small for gestational age (SGA). METHODS Uric acid was measured in 1541 banked maternal plasma samples from a prior prospective cohort study that were collected at a mean gestational age of 9.0 (± 2.5) weeks. Polytomous regressions were performed and adjusted for parity and pre-pregnancy body mass index. RESULTS First trimester uric acid in the highest quartile (>3.56 mg/dL) compared to lowest three quartiles was associated with an increased risk of developing preeclampsia (adjusted OR = 1.82; 95% CI, 1.03–3.21) but not gestational hypertension. In women with hypertensive disease complicated by hyperuricemia at delivery, high first trimester uric acid was associated with a 3.22-fold increased risk of hyperuricemic gestational hypertension and a 3.65-fold increased risk of hyperuricemic preeclampsia. High first trimester uric acid was not associated with gestational hypertension or preeclampsia without hyperuricemia at delivery, preterm birth, or SGA. In women who developed hypertensive disease, elevated uric acid at delivery was only partly explained by elevated uric acid in the first trimester (r2 = .23). CONCLUSIONS First trimester elevated uric acid was associated with later preeclampsia and more strongly with preeclampsia and gestational hypertension with hyperuricemia. PMID:21252861
Simultaneous determination of plasma creatinine, uric acid, kynurenine and tryptophan by high-performance liquid chromatography: method validation and in application to the assessment of renal function.
A high-performance liquid chromatography with ultraviolet detection method has been developed for the simultaneous determination of a set of reliable markers of renal function, including creatinine, uric acid, kynurenine and tryptophan in plasma. Separation was achieved by an Agilent HC-C18 (2) analytical column. Gradient elution and programmed wavelength detection allowed the method to be used to analyze these compounds by just one injection. The total run time was 25 min with all peaks of interest being eluted within 13 min. Good linear responses were found with correlation coefficient >0.999 for all analytes within the concentration range of the relevant levels. The recovery was: creatinine, 101 ± 1%; uric acid, 94.9 ± 3.7%; kynurenine, 100 ± 2%; and tryptophan, 92.6 ± 2.9%. Coefficients of variation within-run and between-run of all analytes were ≤2.4%. The limit of detection of the method was: creatinine, 0.1 µmol/L; uric acid, 0.05 µmol/L; kynurenine, 0.02 µmol/L; and tryptophan, 1 µmol/L. The developed method could be employed as a useful tool for the detection of chronic kidney disease, even at an early stage. Copyright © 2014 John Wiley & Sons, Ltd.
Scheepers, Lieke E J M; Boonen, Annelies; Dagnelie, Pieter C; Schram, Miranda T; van der Kallen, Carla J H; Henry, Ronald M A; Kroon, Abraham A; Stehouwer, Coen D A; Arts, Ilja C W
Accumulation of reactive oxygen species by increased uric acid production has been suggested as a possible underlying mechanism for the association between uric acid and high blood pressure (BP). We, therefore, investigated the association between serum uric acid concentration and 24-h urinary uric acid excretion, as proxy for uric acid production, with ambulatory 24-h blood pressure and hypertension. Cross-sectional analyses were conducted among 2555 individuals [52% men, mean age 60.0 ± 8.2 years; 27% type 2 diabetes (by design)] from The Maastricht Study. Multivariable regression analyses were performed to investigate the association of serum uric acid and 24-h urinary uric acid excretion with 24-h pulse pressure, 24-h mean arterial pressure (MAP), and hypertension. After adjustment for traditional hypertension risk factors, serum uric acid concentration (per SD of 81 μmol/l) was associated with higher 24-h MAP [β 0.63 mmHg; confidence interval (CI) 0.27-1.00] and positively associated with hypertension (odds ratio 1.43; CI 1.27-1.61). Urinary uric acid excretion (per SD of 140 mg/day/1.73 m) was associated with higher 24-h MAP (β 0.79 mmHg; CI 0.46-1.12) and with hypertension (odds ratio 1.13; CI 1.02-1.25). There was no significant association between serum and 24-h urinary uric acid excretion with 24-h pulse pressure. There was no interaction with sex or age for the aforementioned associations. Higher serum and urinary uric acid concentrations were associated with higher 24-h MAP and hypertension. These results suggest that serum and 24-urinary uric acid concentrations, the latter as proxy for uric acid production are, independent of each other, associated with BP and hypertension.
Kennedy, A C; Boddy, K; King, P C; Brennan, J; Anderson, J A; Buchanan, W W
The serum uric acid concentration in normal healthy subjects has been studied in relation to sex, height, weight, lean body mass measured from total body potassium and predicted from the Hume-Weyers formula (1971), total body potassium, plasma potassium and urea, and packed cell volume. The strongest correlation was found with sex, but height, weight, total body potassium, lean body mass (measured and predicted) also correlated significantly with serum uric acid concentration. However, when the sex variable was removed, the other factors lost their significant correlation. Finally, total red blood cell and plasma volumes were predicted (Hume and Goldberg, 1964) and from these an estimate of total plasma uric acid, total plasma potassium, and total red blood cell potassium obtained. Measured total body potassium was found to correlate well with total plasma potassium and total red blood cell potassium independent of sex. Total plasma uric acid correlated well with measured total body potassium when both sexes were considered and when separated into male and female groups the males retained a significant correlation as did the female group. PMID:686865
Flament, A; Delleur, V; Poulipoulis, A; Marlier, D
1. Corticosterone, cortisol, triglycerides, aspartate aminotransferase (AST) and uric acid (UA) plasma concentration were measured at 8 (7 days after group housing), 12 (after 7 days of force feeding) and 13 weeks of age (at slaughter after 12 days of force feeding), and 45 min after an adrenocorticotrophic hormone (ACTH) stimulation test at 8 weeks of age in 12 male mule ducks in an on-farm experiment. 2. No significant increase of corticosterone was found during the force-feeding period compared with the concentration after housing. 3. Comparison of corticosterone and cortisol values indicates that cortisol can be considered as a reliable acute stress indicator in future routine examinations. 4. Plasma concentrations of triglycerides and aspartate aminotransferase increased progressively from pre-force feeding period to slaughtering. 5. Plasma concentrations of uric acid increased from the start at 8 weeks of age to the mid-force feeding period but no difference was noticed between the mid-force feeding period and slaughtering. 6. It is concluded that acute stress induced by force-feeding is similar at the beginning and end of the commercial production of foie gras.
Volterrani, Maurizio; Iellamo, Ferdinando; Sposato, Barbara; Romeo, Franco
Recent evidence would indicate that high serum uric acid (SUA) levels can be a significant and independent risk factor for hypertension and cardiovascular diseases, such as ischemic heart disease and heart failure. In the last few years an independent risk relationship between hyperuricemia, cardiovascular disease and mortality has also been reported. Hyperuricemia has been shown as an independent risk factor for acute myocardial infarction and an independent and conjoint association of either gout and SUA with total and cardiovascular mortality has been reported, with mortality impact in gout patients increasing with rising SUA concentrations, even for SUA levels in the normal to high range. These findings prompted a growing research interest on the possible benefits of uric acid lowering drugs in cardiovascular diseases. Indeed, clinical studies have reported on the beneficial effects of uric acid lowering drugs, in particular of xanthine oxidase inhibitors, in hypertension, ischemic heart disease and heart failure. Two main mechanisms have been claimed to explain the dangerous effects of hyperuricemia and, as a consequence, the benefits of uric acid lowering therapy: endothelial dysfunction and systemic inflammation. This brief review aims to summarize current evidence from human studies on the role of acid uric lowering therapy in cardiovascular diseases for practical and clinical purposes. The possible mechanisms underlying the benefits of acid uric lowering therapy are also addressed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Jin, Ming; Yang, Fan; Yang, Irene; Yin, Ying; Luo, Jin Jun; Wang, Hong; Yang, Xiao-Feng
Uric acid is the product of purine metabolism. It is known that hyperuricemia, defined as high levels of blood uric acid, is the major etiological factor of gout. A number of epidemiological reports have increasingly linked hyperuricemia with cardiovascular and neurological diseases. Studies highlighting the pathogenic mechanisms of uric acid point to an inflammatory response as the primary mechanism for inducing gout and possibly contributing to uric acid's vascular effects. Monosodium urate (MSU) crystals induce an inflammatory reaction, which are recognized by Toll-like receptors (TLRs). These TLRs then activate NALP3 inflammasome. MSU also triggers neutrophil activation and further produces immune mediators, which lead to a proinflammatory response. In addition, soluble uric acid can also mediate the generation of free radicals and function as a pro-oxidant. This review summarizes the epidemiological studies of hyperuricemia and cardiovascular disease, takes a brief look at hyperuricemia and its role in neurological diseases, and highlights the studies of the advanced pathological mechanisms of uric acid and inflammation. PMID:22201767
Vásquez-Vivar, J; Santos, A M; Junqueira, V B; Augusto, O
Formation of peroxynitrite by the fast reaction between nitric oxide and superoxide anion may represent a critical control point in cells producing both species, leading to either down-regulation of the physiological effects of superoxide anion and nitric oxide by forming an inert product, nitrate, or to potentiation of their toxic effects by oxidation of nearby molecules by peroxynitrite. (The term peroxynitrite is used to refer to the sum of all possible forms of peroxynitrite anion and peroxynitrous acid unless otherwise specified.) In this report we demonstrate that, in spite of all the antioxidant defences present in human plasma, its interaction with peroxynitrite leads to generation of free radical intermediates such as (i) the ascorbyl radical, detected by direct EPR, (ii) the albumin-thiyl radical, detected by spin-trapping experiments with both N-tert-butyl-alpha-phenylnitrone and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and (iii) a uric acid-derived free radical, detected as the DMPO radical adduct in plasma whose thiol groups were previously blocked with 5,5-dithiobis-(2-nitrobenzoic acid). The identity of the latter adduct was confirmed by parallel experiments demonstrating that it is not detectable in plasma pretreated with uricase, whereas it is formed in incubations of peroxynitrite with uric acid. Peroxynitrite-mediated oxidations were also followed by oxygen consumption and ascorbate and plasma-thiol depletion. Our results support the view that peroxynitrite-mediated one-electron oxidation of biomolecules may be an important event in its cytotoxic mechanism. In addition, the data have methodological implications by providing support for the use of EPR methodologies for monitoring both free radical reactions and ascorbate concentrations in biological fluids. PMID:8615782
Grases, F; Ramis, M; Villacampa, A I; Costa-Bauzá, A
An in vitro study of the inhibitory effects that some substances occasionally present in urine can provoke on the crystallization of uric acid has been performed. The most remarkable crystallization inhibitory effects were produced by mucine at concentrations of >0.5 mg/l. Pentosan polysulfate and chondroitin sulfate also clearly increased the uric acid crystallization times at concentrations of >100 mg/l. Saponins, such as escin and glycyrrhizic acid, also produced a notable delay in uric acid crystallization times at concentrations of >10 mg/l. Similar effects were observed in the presence of a surfactant substance, lauryl sulfate. N-Acetyl-L-cysteine caused crystallization perturbations only when it was present at concentrations of >50 mg/l. Citric acid and phytic acid caused no effects on uric acid crystallization even at the highest concentrations assayed (1,000 and 5 mg/l, respectively). From the results obtained it can be deduced that mainly glycoproteins, glycosaminoglycans and surfactant substances can exert protective effects against uric acid crystallization.
Maiuolo, Jessica; Oppedisano, Francesca; Gratteri, Santo; Muscoli, Carolina; Mollace, Vincenzo
Purines perform many important functions in the cell, being the formation of the monomeric precursors of nucleic acids DNA and RNA the most relevant one. Purines which also contribute to modulate energy metabolism and signal transduction, are structural components of some coenzymes and have been shown to play important roles in the physiology of platelets, muscles and neurotransmission. All cells require a balanced quantity of purines for growth, proliferation and survival. Under physiological conditions the enzymes involved in the purine metabolism maintain in the cell a balanced ratio between their synthesis and degradation. In humans the final compound of purines catabolism is uric acid. All other mammals possess the enzyme uricase that converts uric acid to allantoin that is easily eliminated through urine. Overproduction of uric acid, generated from the metabolism of purines, has been proven to play emerging roles in human disease. In fact the increase of serum uric acid is inversely associated with disease severity and especially with cardiovascular disease states. This review describes the enzymatic pathways involved in the degradation of purines, getting into their structure and biochemistry until the uric acid formation. Copyright © 2015. Published by Elsevier Ireland Ltd.
Moe, Orson W.
Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form. PMID:25045326
Souza-Junior, TP; Lorenço-Lima, L; Ganini, D; Vardaris, CV; Polotow, TG
Reactive oxygen species are produced during anaerobic exercise mostly by Fe ions released into plasma and endothelial/muscle xanthine oxidase activation that generates uric acid (UA) as the endpoint metabolite. Paradoxically, UA is considered a major antioxidant by virtue of being able to chelate pro-oxidative iron ions. This work aimed to evaluate the relationship between UA and plasma markers of oxidative stress following the exhaustive Wingate test. Plasma samples of 17 male undergraduate students were collected before, 5 and 60 min after maximal anaerobic effort for the measurement of total iron, haem iron, UA, ferric-reducing antioxidant activity in plasma (FRAP), and malondialdehyde (MDA, biomarker of lipoperoxidation). Iron and FRAP showed similar kinetics in plasma, demonstrating an adequate pro-/antioxidant balance immediately after exercise and during the recovery period (5–60 min). Slight variations of haem iron concentrations did not support a relevant contribution of rhabdomyolysis or haemolysis for iron overload following exercise. UA concentration did not vary immediately after exercise but rather increased 29% during the recovery period. Unaltered MDA levels were concomitantly measured. We propose that delayed UA accumulation in plasma is an auxiliary antioxidant response to post-exercise (iron-mediated) oxidative stress, and the high correlation between total UA and FRAP in plasma (R-Square = 0.636; p = 0.00582) supports this hypothesis. PMID:25435669
Souza-Junior, Tp; Lorenço-Lima, L; Ganini, D; Vardaris, Cv; Polotow, Tg; Barros, Mp
Reactive oxygen species are produced during anaerobic exercise mostly by Fe ions released into plasma and endothelial/muscle xanthine oxidase activation that generates uric acid (UA) as the endpoint metabolite. Paradoxically, UA is considered a major antioxidant by virtue of being able to chelate pro-oxidative iron ions. This work aimed to evaluate the relationship between UA and plasma markers of oxidative stress following the exhaustive Wingate test. Plasma samples of 17 male undergraduate students were collected before, 5 and 60 min after maximal anaerobic effort for the measurement of total iron, haem iron, UA, ferric-reducing antioxidant activity in plasma (FRAP), and malondialdehyde (MDA, biomarker of lipoperoxidation). Iron and FRAP showed similar kinetics in plasma, demonstrating an adequate pro-/antioxidant balance immediately after exercise and during the recovery period (5-60 min). Slight variations of haem iron concentrations did not support a relevant contribution of rhabdomyolysis or haemolysis for iron overload following exercise. UA concentration did not vary immediately after exercise but rather increased 29% during the recovery period. Unaltered MDA levels were concomitantly measured. We propose that delayed UA accumulation in plasma is an auxiliary antioxidant response to post-exercise (iron-mediated) oxidative stress, and the high correlation between total UA and FRAP in plasma (R-Square = 0.636; p = 0.00582) supports this hypothesis.
Background Increase in the incidence of hyperuricemia associated with gout as well as hypertension, renal diseases and cardiovascular diseases has been a public health concern. We examined the possibility of facilitated excretion of uric acid by change in urine pH by managing food materials. Methods Within the framework of the Japanese government's health promotion program, we made recipes which consist of protein-rich and less vegetable-fruit food materials for H+-load (acid diet) and others composed of less protein but vegetable-fruit rich food materials (alkali diet). Healthy female students were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl-,SO42-,PO4-) necessary for the estimation of acid-base balance were measured. Results Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42-] +organic acid-gut alkai) were linearly related with those of the excretion of acid (titratable acidity+ [NH4+] - [HCO3-]), indicating that H+ in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, where uric acid excretion increased from 302 mg/day at pH 5.9 to 413 mg/day at pH 6.5, despite the fact that the alkali diet contained a smaller purine load than the acid diet. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed food is effective for removing uric acid from the body. PMID:20955624
Clode, Peta L; Saunders, Martin; Maker, Garth; Ludwig, Martha; Atkins, Craig A
The symbiosis between cnidarians and dinoflagellate algae is not understood at the cell or molecular level, yet this relationship is responsible for the formation of thousands of square kilometres of coral reefs. We have investigated the nature of crystalline material prominent within marine algal symbionts of Aiptasia sp. anemones. This material, which has historically been considered to be calcium oxalate, is shown to be uric acid. We demonstrate that these abundant uric acid stores can be mobilized rapidly, thereby allowing the algal symbionts to flourish in an otherwise N-poor environment. This is the first report of uric acid accumulation by symbiotic marine algae. These data provide new insight and considerations for understanding the physiological basis of algal symbioses, and represent a new and previously unconsidered aspect of N metabolism in cnidarian, and a variety of other, marine symbioses.
Johnson, Richard J.; Nakagawa, Takahiko; Jalal, Diana; Sánchez-Lozada, Laura Gabriela; Kang, Duk-Hee; Ritz, Eberhard
Serum uric acid is commonly elevated in subjects with chronic kidney disease (CKD), but was historically viewed as an issue of limited interest. Recently, uric acid has been resurrected as a potential contributory risk factor in the development and progression of CKD. Most studies documented that an elevated serum uric acid level independently predicts the development of CKD. Raising the uric acid level in rats can induce glomerular hypertension and renal disease as noted by the development of arteriolosclerosis, glomerular injury and tubulointerstitial fibrosis. Pilot studies suggest that lowering plasma uric acid concentrations may slow the progression of renal disease in subjects with CKD. While further clinical trials are necessary, uric acid is emerging as a potentially modifiable risk factor for CKD. Gout was considered a cause of CKD in the mid-nineteenth century , and, prior to the availability of therapies to lower the uric acid level, the development of end-stage renal disease was common in gouty patients. In their large series of gouty subjects Talbott and Terplan found that nearly 100% had variable degrees of CKD at autopsy (arteriolosclerosis, glomerulosclerosis and interstitial fibrosis) . Additional studies showed that during life impaired renal function occurred in half of these subjects . As many of these subjects had urate crystals in their tubules and interstitium, especially in the outer renal medulla, the disease became known as gouty nephropathy. The identity of this condition fell in question as the presence of these crystals may occur in subjects without renal disease; furthermore, the focal location of the crystals could not explain the diffuse renal scarring present. In addition, many subjects with gout also had coexistent conditions such as hypertension and vascular disease, leading some experts to suggest that the renal injury in gout was secondary to these latter conditions rather than to uric acid per se . Indeed, gout was
Wu, Audrey H; Gladden, James D; Ahmed, Mustafa; Ahmed, Ali; Filippatos, Gerasimos
This review summarizes recent published literature on the association between serum uric acid and cardiovascular disease, a relationship which is complex and not fully elucidated. Uric acid may be a marker for risk, a causative agent in cardiovascular disease, or both. Various biologic factors can influence serum uric acid levels, and serum uric acid level itself is closely related to conditions such as hypertension, dyslipidemia, obesity, and impaired glucose metabolism, that contribute to cardiovascular disease pathophysiology. Serum uric acid levels have been found to be associated with adverse outcomes, including mortality, in the general population. In addition, serum uric acid is associated with increased risk for incident coronary heart disease, heart failure, and atrial fibrillation. In the setting of established systolic heart failure, serum uric acid is positively associated with disease severity and mortality risk. Whether targeting treatment based on uric acid levels might affect clinical outcomes is still being studied. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Uric acid test system. 862.1775 Section 862.1775...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1775 Uric acid test system. (a) Identification. A uric acid test system is a device intended to...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Uric acid test system. 862.1775 Section 862.1775...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1775 Uric acid test system. (a) Identification. A uric acid test system is a device intended to...
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Uric acid test system. 862.1775 Section 862.1775...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1775 Uric acid test system. (a) Identification. A uric acid test system is a device intended to...
Gallego-Delgado, Julio; Ty, Maureen; Orengo, Jamie M; van de Hoef, Diana; Rodriguez, Ana
Malaria, which is caused by Plasmodium parasite erythrocyte infection, is a highly inflammatory disease with characteristic periodic fevers caused by the synchronous rupture of infected erythrocytes to release daughter parasites. Despite the importance of inflammation in the pathology and mortality induced by malaria, the parasite-derived factors inducing the inflammatory response are still not well characterized. Uric acid is emerging as a central inflammatory molecule in malaria. Not only is uric acid found in the precipitated form in infected erythrocytes, but high concentrations of hypoxanthine, a precursor for uric acid, also accumulate in infected erythrocytes. Both are released upon infected erythrocyte rupture into the circulation where hypoxanthine would be converted into uric acid and precipitated uric acid would encounter immune cells. Uric acid is an important contributor to inflammatory cytokine secretion, dendritic cell and T cell responses induced by Plasmodium, suggesting uric acid as a novel molecular target for anti-inflammatory therapies in malaria.
Hosomi, Atsushi; Nakanishi, Takeo; Fujita, Takuya; Tamai, Ikumi
Urinary excretion accounts for two-thirds of total elimination of uric acid and the remainder is excreted in feces. However, the mechanism of extra-renal elimination is poorly understood. In the present study, we aimed to clarify the mechanism and the extent of elimination of uric acid through liver and intestine using oxonate-treated rats and Caco-2 cells as a model of human intestinal epithelium. In oxonate-treated rats, significant amounts of externally administered and endogenous uric acid were recovered in the intestinal lumen, while biliary excretion was minimal. Accordingly, direct intestinal secretion was thought to be a substantial contributor to extra-renal elimination of uric acid. Since human efflux transporter BCRP/ABCG2 accepts uric acid as a substrate and genetic polymorphism causing a decrease of BCRP activity is known to be associated with hyperuricemia and gout, the contribution of rBcrp to intestinal secretion was examined. rBcrp was confirmed to transport uric acid in a membrane vesicle study, and intestinal regional differences of expression of rBcrp mRNA were well correlated with uric acid secretory activity into the intestinal lumen. Bcrp1 knockout mice exhibited significantly decreased intestinal secretion and an increased plasma concentration of uric acid. Furthermore, a Bcrp inhibitor, elacridar, caused a decrease of intestinal secretion of uric acid. In Caco-2 cells, uric acid showed a polarized flux from the basolateral to apical side, and this flux was almost abolished in the presence of elacridar. These results demonstrate that BCRP contributes at least in part to the intestinal excretion of uric acid as extra-renal elimination pathway in humans and rats. PMID:22348008
Lee, I. Russel; Yang, Liting; Sebetso, Gaseene; Allen, Rebecca; Doan, Thi H. N.; Blundell, Ross; Lui, Edmund Y. L.; Morrow, Carl A.; Fraser, James A.
Degradation of purines to uric acid is generally conserved among organisms, however, the end product of uric acid degradation varies from species to species depending on the presence of active catabolic enzymes. In humans, most higher primates and birds, the urate oxidase gene is non-functional and hence uric acid is not further broken down. Uric acid in human blood plasma serves as an antioxidant and an immune enhancer; conversely, excessive amounts cause the common affliction gout. In contrast, uric acid is completely degraded to ammonia in most fungi. Currently, relatively little is known about uric acid catabolism in the fungal pathogen Cryptococcus neoformans even though this yeast is commonly isolated from uric acid-rich pigeon guano. In addition, uric acid utilization enhances the production of the cryptococcal virulence factors capsule and urease, and may potentially modulate the host immune response during infection. Based on these important observations, we employed both Agrobacterium-mediated insertional mutagenesis and bioinformatics to predict all the uric acid catabolic enzyme-encoding genes in the H99 genome. The candidate C. neoformans uric acid catabolic genes identified were named: URO1 (urate oxidase), URO2 (HIU hydrolase), URO3 (OHCU decarboxylase), DAL1 (allantoinase), DAL2,3,3 (allantoicase-ureidoglycolate hydrolase fusion protein), and URE1 (urease). All six ORFs were then deleted via homologous recombination; assaying of the deletion mutants' ability to assimilate uric acid and its pathway intermediates as the sole nitrogen source validated their enzymatic functions. While Uro1, Uro2, Uro3, Dal1 and Dal2,3,3 were demonstrated to be dispensable for virulence, the significance of using a modified animal model system of cryptococcosis for improved mimicking of human pathogenicity is discussed. PMID:23667704
Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro
Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681
Cameron, Mary Ann; Maalouf, Naim M.; Poindexter, John; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W.
Many biologic functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary acid-base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and uric acid stones are typical of excessively low urine pH. Here we placed 9 healthy volunteers and 10 uric acid stone formers on fixed metabolic diets to study the diurnal pattern of urinary acidification. All showed clear diurnal trends in urinary acidification but none of the patterns were affected by inhibitors of the gastric proton pump. Uric acid stone formers had similar patterns of change through the day but their urine pH was always lower compared to healthy volunteers. Uric acid stone formers excreted more acid (normalized to acid ingestion) with the excess excreted primarily as titratable acid rather than ammonium. Urine base excretion was also lower in uric acid stone formers (normalized to base ingestion) along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of un-dissociated uric acid throughout the day and consequently an increased risk of uric acid stones. PMID:22297671
Mrug, Sylvie; Mrug, Michal
Elevated levels of uric acid have been linked with impulsive and disinhibited behavior in clinical and community populations of adults, but no studies have examined uric acid in relation to adolescent aggression. This study examined the prospective role of uric acid in aggressive behavior among urban, low income adolescents, and whether this relationship varies by gender. A total of 84 adolescents (M age 13.36years; 50% male; 95% African American) self-reported on their physical aggression at baseline and 1.5years later. At baseline, the youth also completed a 12-h (overnight) urine collection at home which was used to measure uric acid excretion. After adjusting for baseline aggression and age, greater uric acid excretion predicted more frequent aggressive behavior at follow up, with no significant gender differences. The results suggest that lowering uric acid levels may help reduce youth aggression. Copyright © 2016 Elsevier Inc. All rights reserved.
Chekin, Fereshteh; Boukherroub, Rabah; Szunerits, Sabine
A hybrid nanocomposite of MoS2 nanosheets and reduced graphene oxide (rGO) was fabricated by a facile and effective method. The morphology and structure of the nanocomposite (MoS2-rGO) were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, electrochemical impedance spectroscopy and cyclic voltammetry. The MoS2 nanosheets were uniformly anchored on the rGO framework with strong adhesion. A glassy carbon electrode modified by drop-casting with MoS2-rGO was used for the electrochemical oxidation of cysteamine (CA) in the presence of uric acid (UA). Under optimum conditions, the anodic peak current of CA shows a linear relation with the CA concentration between 0.01 and 20μM with a detection limit of 7nM. The proposed electrochemical sensor was used for determination of CA in human plasma. Copyright © 2016 Elsevier B.V. All rights reserved.
of the excreta of adult Tribolium used in this study for natural infestation, accumulates in infested products providing a quantitative measure of past...by Adult Tribolium 8 4 FLUOROMETRIC METHOD FOR DETERMINATION OF URIC ACID IN FLOUR Introduction Chemical and microanalytical techniques have been...determining uric acid content.’ Approximately 18% of the total excreta from Tribolium confusum is uric acid.2 Various investigators have established
Cardona, Fernando; Rojo-Martínez, Gemma; de la Cruz Almaraz, María; Soriguer, Federico; García-Fuentes, Eduardo; Tinahones, Francisco José
Abnormal uric acid levels are considered by some to be a risk factor for metabolic disorders, whereas others consider it to be just a marker. We therefore examined the association between plasma uric acid concentrations and the risk of type 2 diabetes mellitus. We undertook a prospective, 8-year study of 411 persons from the general population with no carbohydrate metabolism disorder at the start of the study evaluated by oral glucose overload. The following variables were measured at the beginning and end of the study: uric acid, triglycerides, cholesterol, high-density lipoprotein cholesterol, glucose and insulin in plasma, body mass index and waist-to-hip ratio. The participants were classified according to their plasma uric acid concentration, with a cut-off at the 33rd percentile (men, 291.45 and women, 208.18 micromol/l). Participants with plasma uric acid concentrations above the 33rd percentile at the start of the study had worse lipid and anthropometric profiles. These persons were at greater risk for carbohydrate disorder at the end of the 8- year follow-up study (relative risk, 1.73; 95% confidence interval, 1.04-2.8). No significant differences were found in age or in the remaining variables studied between these two groups. Increased uric acid levels in response to a possible chronic increase in oxidative stress may predict future disorders or complications such as type 2 diabetes in otherwise healthy persons.
KROLL, KEITH; BUKOWSKI, THOMAS R.; SCHWARTZ, LISA M.; KNOEPFLER, DAVID; BASSINGTHWAIGHTE, JAMES B.
Much of the adenosine formed in the heart is degraded by endothelial enzymes to uric acid, which is exported across the coronary capillary endothelial cell membrane before renal excretion. Because previous experiments suggested that cell permeability for uric acid is either very high (similar to water) or very low, multiple indicator-dilution experiments were carried out to distinguish between the two possibilities. An intravascular reference tracer, l31I-labeled albumin, and an extracellular reference tracer, l-[3H]glucose, were injected together with [14C]uric acid as a bolus into the coronary inflow, while fractionating the venous outflow for 90 s. Recovery of injected uric acid averaged 99.0 ± 2.9% (mean ± SD, n = 12) that of l-glucose. Peak capillary extraction of Multiple tracer dilution estimates of l-glucose and uric acid averaged 0.38 ± 0.032 and 0.42 ± 0.035 (P < 0.005) compared with albumin. Except at the peaks, the dilution curves for [14C]-uric acid and l-[3H]glucose coincided closely, indicating that little uric acid was transported into cells. The dilution curves were analyzed using an axially distributed, multipathway, four region mathematical model, to estimate membrane permeability-surface area (PS) products. Since the endothelial cell PS for uric acid was low (0.12 ± 0.09 ml·g−1·min−1), ~3% of the PS reported for adenosine, the possibility of flow-limited exchange for uric acid is ruled out. To estimate steady-state endothelial concentrations of uric acid in vivo, equations were developed describing electrochemical potential gradients for dissociated and undissociated forms of a weak acid. Despite endothelial production, intracellular concentrations that are lower than outside are expected because the negative membrane potential and lower cellular pH assist uric acid efflux. PMID:1539702
Wang, Zhongchao; Lin, Yanlin; Liu, Yuxiu; Chen, Ying; Wang, Bin; Li, Changgui; Yan, Shengli; Wang, Yangang; Zhao, Wenjuan
Previous studies assessing the association between serum uric acid levels and neurological outcome after acute ischemic stroke reported conflicting results. A systematic review and meta-analysis were conducted to assess the impact of serum uric acid levels on outcome after acute ischemic stroke. Pubmed, Embase, Web of Science, and Google scholar were searched through September 26, 2014 to identify eligible published or unpublished studies on the association between serum uric acid levels and outcome after acute ischemic stroke. Hazard ratio (HR) for poor outcome or mean differences of serum uric acid levels with 95% confidence intervals (95% CIs) were pooled using meta-analysis. The primary outcome was occurrence of poor outcomes, while the secondary outcome was the mean differences of serum uric acid levels in patients with good or poor outcomes. Ten eligible studies with a total of 8131 acute ischemic stroke patients were included into the meta-analysis. Compared with low serum uric acid level, high serum uric acid level was associated better outcome after acute ischemic stroke (HR = 0.77, 95% CI 0.68-0.88, P = 0.0001). Sensitivity analysis further identified the prognostic role of serum uric acid levels on outcome after acute ischemic stroke. Patients with good outcomes had a higher serum uric acid level compared with those with poor outcome (mean difference = 30.61 μmol/L, 95% CI 20.13-41.08, P < 0.00001). There was no obvious risk of publication bias in the meta-analysis. This meta-analysis supports that serum uric acid level has a protective effect on neurological outcome after acute ischemic stroke. High uric acid level at the onset is a biomarker of better prognosis in patients with acute ischemic stroke.
Rubio-Guerra, Alberto F; Morales-López, Herlinda; Garro-Almendaro, Ana K; Vargas-Ayala, German; Durán-Salgado, Montserrat B; Huerta-Ramírez, Saul; Lozano-Nuevo, Jose J
Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia.
Yildirim, Ali; Keles, Fatma; Kosger, Pelin; Ozdemir, Gokmen; Ucar, Birsen; Kilic, Zubeyir
This study evaluated uric acid concentrations in normotensive children of parents with hypertension. Eighty normotensive children from families with and without a history of essential hypertension were included. Concentrations of lipid parameters and uric acid were compared. Demographic and anthropometric characteristics were similar in the groups. Systolic and diastolic blood pressure were higher in the normotensive children of parents with hypertension without statistically significant difference (P > 0.05). Uric acid concentrations were higher in the normotensive children of parents with hypertension (4.61 versus 3.57 mg/dL, P < 0.01). Total cholesterol and triglyceride concentrations were similar in the two groups. Systolic and diastolic blood pressure were significantly higher in control children aged >10 years (P < 0.01). Uric acid levels were significantly higher in all children with more pronounced difference after age 10 of years (P < 0.001). Positive correlations were found between the level of serum uric acid and age, body weight, body mass index, and systolic and diastolic blood pressure in the normotensive children of parents. The higher uric acid levels in the normotensive children of hypertensive parents suggest that uric acid may be a predeterminant of hypertension. Monitoring of uric acid levels in these children may allow for prevention or earlier treatment of future hypertension. PMID:26464873
Grases, F; Villacampa, A I; Costa-Bauzá, A; Söhnel, O
The study of the composition and structure of 41 stones composed of uric acid was complemented by in vitro investigation of the crystallization of uric acid. Uric acid dihydrate (UAD) precipitates from synthetic urine under physiological conditions when the medium is supersaturated with respect to this compound, though uric acid anhydrous (UAA) represents the thermodynamically stable form. Solid UAD in contact with liquid transforms into UAA within 2 days. This transition is accompanied by development of hexagonal bulky crystals of UAA and appearance of cracks in the UAD crystals. Uric acid calculi can be classified into two groups, differing in outer appearance and inner structure. Type I includes stones with a little central core and a compact columnar UAA shell and stones with interior structured in alternating densely non-columnar layers developed around a central core; both of them are formed mainly by crystalline growth at low uric acid supersaturation. Type II includes porous stones without inner structure and stones formed by a well developed outermost layer with an inner central cavity; this type of stones is formed mainly by sedimentation of uric acid crystals generated at higher uric acid supersaturation.
Yilmaz, Emrah; Tamer, Emine; Artüz, Ferda; Külcü Çakmak, Seray; Köktürk, Fürüzan
Psoriasis has been accepted as a systemic disease and it is known to be associated with various disorders including metabolic syndrome. High serum uric acid levels are also associated with the components of metabolic syndrome. In this study, we aimed to determine serum uric acid levels in patients with psoriasis and the association of uric acid levels with disease activity by taking the presence of metabolic syndrome criteria into account, since it is one of the most important factors that affect serum uric acid levels. In this cross-sectional study, we evaluated 70 psoriasis patients and 70 healthy individuals who were matched with the patients according to the presence of metabolic syndrome. We evaluated the demographic features, levels of serum uric acid, Psoriasis Area Severity Index (PASI) scores, presence of psoriatic arthritis, nail involvement, and metabolic syndrome criteria of the patients. Serum uric acid levels of psoriasis patients were significantly higher than those of controls. There was a positive correlation between PASI scores and serum uric acid levels of the patients. As hyperuricemia had a close relationship with psoriasis and PASI scores, we suggest monitoring patients with psoriasis for serum uric acid levels during treatment and follow-up.
Cibičková, Ľ; Langová, K; Vaverková, H; Kubíčková, V; Karásek, D
Hyperuricemia has been described as associated with the risk of development metabolic syndrome; however the relationship between the uric acid level and particular parameters of metabolic syndrome remained unclear. We performed a cross-sectional study on a cohort of 833 dyslipidemic patients and correlated their levels of uric acid with parameters of insulin resistance, lipid metabolism, C-reactive protein, anthropometric parameters. We also defined patients with hypertriglyceridemic waist phenotype and compered their uric acid levels with those without this phenotype. We found that levels of uric acid are associated with parameters of metabolic syndrome. Specifically, dyslipidemia characteristic for metabolic syndrome (low HDL-cholesterol and high triglycerides) correlates better with uric acid levels than parameters of insulin resistance. Also waist circumference correlates better with uric acid levels than body mass index. Patients with hypertriglyceridemic waist phenotype had higher levels of uric acid when compared with patients without this phenotype. Serum uric acid levels are even in low levels linearly correlated with parameters of metabolic syndrome (better with typical lipid characteristics than with parameters of insulin resistance) and could be associated with higher cardiovascular risk.
Mehrpooya, Maryam; Larti, Farnoosh; Nozari, Younes; Sattarzadeh-Badkoobeh, Roya; Zand Parsa, Amir Farhang; Zebardast, Jayran; Tavoosi, Anahita; Shahbazi, Fatemeh
The present study aimed to compare the serum level of uric acid in patients with and without heart failure and also to determine the association between uric acid level and clinical status by Killip class in patients with STEMI. This case-control study was conducted on 50 consecutives as control group and 50 patients with acute heart failure, (20 patients had acute STEMI), who documented by both clinical conditions and echocardiography assessment. The mean plasma level of uric acid in the case group was 7.6±1.6 milligrams/deciliter (mg/dL) and in the control group was 4.5±1.5 respectively (P<0.001). These values in patients with STEMI was about 9.2±0.86, but in patients with acute heart failure in absence of STEMI was 6.5±1.04 (P<0.001). Moreover, there was significant difference among the level of uric acid and Killip classes (P<0.001). Also there was significant difference for uric acid level between HFrEF (HF with reduced EF) and severe LV systolic dysfunction (0.049). In STEMI patients with culprit LAD, mean uric acid was significantly higher than cases with culprit LCX [(9.7±0.98 versus 8.6±0.52 respectively) P=0.012]. Regarding treatment plan in patients with STEMI, mean level of uric acid in those considered for CABG was significantly higher than who were considered for PCI, 9.9±0.82 versus 8.9±0.76 respectively, P=0.029. In STEMI patients with higher killip class, higher level of uric acid was seen. Also, the severity of LV systolic dysfunction was associated with higher level of uric acid.
Trinchieri, Alberto; Montanari, Emanuele
The aim of this study was to estimate uric acid renal stone prevalence rates of adults in different countries of the world. PubMed was searched for papers dealing with "urinary calculi and prevalence or composition" for the period from January 1996 to June 2016. Alternative searches were made to collect further information on specific topics. The prevalence rate of uric acid stones was computed by the general renal stone prevalence rate and the frequency of uric acid stones in each country. After the initial search, 2180 papers were extracted. Out of them, 79 papers were selected after the reading of the titles and of the abstracts. For ten countries, papers relating to both the renal stone prevalence in the general population and the frequency of uric stones were available. Additional search produced 13 papers that completed information on 11 more countries in 5 continents. Estimated prevalence rate of uric acid stones was >0.75% in Thailand, Pakistan, Saudi Arabia, Iran, South Africa (white population), United States and Australia; ranged 0.50-0.75% in Turkey, Israel, Italy, India (Southern), Spain, Taiwan, Germany, Brazil; and <0.50% in Tunisia, China, Korea, Japan, Caribe, South Africa (blacks), India (Northern). Climate and diet are major determinants of uric acid stone formation. A hot and dry climate increases fluid losses reducing urinary volume and urinary pH. A diet rich in meat protein causes low urinary pH and increased uric acid excretion. On the other hand, uric acid stone formation is frequently associated with obesity, metabolic syndrome and diabetes type 2 that are linked to dietary energy excess mainly from carbohydrate and saturated fat and also present with low urine pH values. An epidemic of uric acid stone formation could be if current nutritional trends will be maintained both in developed countries and in developing countries and the areas of greater climatic risk for the formation of uric acid stones will enlarge as result of the "global
Maarman, Gerald J; Andrew, Brittany M; Blackhurst, Dee M; Ojuka, Edward O
Excess uric acid has been shown to induce oxidative stress, triglyceride accumulation, and mitochondrial dysfunction in the liver and is an independent predictor of type-2 diabetes. Skeletal muscle plays a dominant role in type 2 diabetes and presents a large surface area to plasma uric acid. However, the effects of uric acid on skeletal muscle are underinvestigated. Our aim was therefore to characterize the effects of excessive uric acid on oxidative stress, triglyceride content, and mitochondrial function in skeletal muscle C2C12 myotubes and assess how these are modulated by the antioxidant molecule melatonin. Differentiated C2C12 myotubes were exposed to 750 µM uric acid or uric acid + 10 nM melatonin for 72 h. Compared with control, uric acid increased triglyceride content by ~237%, oxidative stress by 32%, and antioxidant capacity by 135%. Uric acid also reduced endogenous ROUTINE respiration, complex II-linked oxidative phosphorylation, and electron transfer system capacities. Melatonin counteracted the effects of uric acid without further altering antioxidant capacity. Our data demonstrate that excess uric acid has adverse effects on skeletal muscle similar to those previously reported in hepatocytes and suggest that melatonin at a low physiological concentration of 10 nM may be a possible therapy against some adverse effects of excess uric acid.NEW & NOTEWORTHY Few studies have investigated the effects of uric acid on skeletal muscle. This study shows that hyperuricemia induces mitochondrial dysfunction and triglyceride accumulation in skeletal muscle. The findings may explain why hyperuricemia is an independent predictor of diabetes. Copyright © 2017 the American Physiological Society.
Sloop, Gregory D; Bialczak, Jessica K; Weidman, Joseph J; St Cyr, J A
Uric acid may be a risk factor for atherosclerotic cardiovascular disease, although the data conflict and the mechanism by which it may cause cardiovascular disease is uncertain. This study was performed to test the hypothesis that uric acid, an anion at physiologic pH, can cause erythrocyte aggregation, which itself is associated with cardiovascular disease. Normal erythrocytes and erythrocytes with a positive direct antiglobulin test for surface IgG were incubated for 15 minutes in 14.8 mg/dL uric acid. Erythrocytes without added uric acid were used as controls. Erythrocytes were then examined microscopically for aggregation. Aggregates of up to 30 erythrocytes were noted when normal erythrocytes were incubated in uric acid. Larger aggregates were noted when erythrocytes with surface IgG were incubated in uric acid. Aggregation was negligible in controls. These data show that uric acid causes erythrocyte aggregation. The most likely mechanism is decreased erythrocyte zeta potential. Erythrocyte aggregates will increase blood viscosity at low shear rates and increase the risk of atherothrombosis. In this manner, hyperuricemia and decreased zeta potential may be risk factors for atherosclerotic cardiovascular disease.
Brody, David M; Litvan, Irene; Warner, Steve; Riley, David E; Hall, Deborah A; Kluger, Benzi M; Shprecher, David R; Cunningham, Christopher R
The pathophysiology of both PD and PSP is characterized by a pro-oxidant state. Uric acid is an oxidative stress marker. High uric acid blood levels have been associated with a reduced risk of PD and a decreased rate of disease progression. We investigated whether a low serum concentration of uric acid is also associated with PSP. We measured serum uric acid concentrations in a subsample of the ENGENE PSP Cohort that included 75 cases and 75 frequency-matched-by-sex healthy controls (69 spouses, 6 in-laws) from four centers willing to participate (Case Western, Rush University, University of Utah, and University of Louisville). Case severity was characterized using the total PSP-Rating Scale, UPDRS, and Mattis Dementia Rating Scale. Unconditional logistic regression, Pearson's chi-squared test, and analysis of variance were used, as appropriate. The mean uric acid level among cases (4.0 mg/dL) was not significantly lower than that of controls (4.1 mg/dL). When controlling for sex, there were no between-group statistical differences in uric acid levels. Uric acid levels were not correlated with disease severity. The results of this study do not provide evidence of uric acid having a protective role in PSP, even if oxidative injury is important in the pathophysiology of this disorder. The lack of statistical significance suggests that there is no direct association between uric acid levels and PSP. However, a small inverse association cannot be excluded. © 2016 Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.
Uzun, K; Vural, H; Ozer, F; Imecik, O
Uric acid is known to be an end product of purine metabolism. Increases in uric acid may be found in clinical conditions associated with tissue hypoxia. We have investigated the value of uric acid to differentiate between a transudate and exudate. In this study, we measured uric acid in the pleural fluid and the serum of 110 patients, 30 women and 80 men with a mean age of 49.5+/-19 years. Light's criteria were used to differentiate between a transudate and exudate. Mean serum uric acid was 496.7+/-153.4 micromol/l in patients with transudates and 291.3+/-143.1 micromol/l in patients with exudates. Mean pleural fluid uric acid was 487.7+/-165 micromol/l in patients with transudates and 279.9+/-142.1 micromol/l in patients with exudates. These data showed that the levels of serum and pleural uric acid were higher in transudates than exudates (p<0.01). However, there was no significant difference between pleural fluid/serum uric acid ratio of the two patient groups (p>0.05). The specificity and sensitivity of pleural uric acid for diagnosis of transudate effusions were 73% and 80.6%, respectively. The specificity and sensitivity of pleural uric acid for diagnosis of transudate effusions from exudates without malignancy were 71.8% and 91.7%, respectively. The sensitivity and specificity of pleural lactate dehydrogenase for diagnosis of exudates were 82% and 89%; the sensitivity and specificity of pleural fluid/serum lactate dehydrogenase were 85% and 89%; the sensitivity and specificity of pleural fluid/serum protein were 91% and 89%, respectively. Using all three of Light's criteria together, the sensitivity was 91% and its specificity was 94%. Our findings indicate that determination of uric acid in pleural fluid may be of diagnostic value in differential diagnosis of transudates and exudates. The sensitivity of pleural uric acid measurement was higher for exudates without malignancy. However, Light's criteria remain the best means of separating transudates from
Li, Haibo; Zha, Xiaojuan; Zhu, Yu; Liu, Mengxue; Guo, Rui; Wen, Yufeng
Abstract There are some published studies focus on the invert U-shaped relationship between fasting plasma glucose (FPG) and serum uric acid (UA), while the threshold value and gender differences of this relationship were still obscure. We aimed to explore the dose–response relation between FPG level and serum UA concentration by conducted this epidemiological research in a large health check-up population in China. A total of 237,703 people were collected from January 2011 to July 2014 in our cross-sectional study; 100,348 subjects age 18 to 89 years and without known diabetes were included for the current analysis. One-way analysis of variance, generalized additive models, and 2-piecewise linear regression model were used. The mean concentration of UA with FPG of <6.1, 6.1 to 6.9, and ≥7.0 mmol/L was 240.9, 260.2, and 259.6 μmol/L in women and 349.0, 360.8, and 331.0 μmol/L in men. An invert U-shape with a threshold FPG of 7.5 (women)/6.5 (men) mmol/L was observed in the regression curve of FPG and UA, even after adjusting for potential confounders. The adjusted regression coefficients were 2.4 (95% confidence interval [CI]: 1.5 to 3.4, P < 0.001) for FPG < 7.5 mmol/L, −3.2 (95% CI: −5.0 to −1.3, P < 0.001) for FPG ≥ 7.5 mmol/L in women; while 0.8 (95% CI: −0.4 to 2.0, P = 0.19) for FPG < 6.5 mmol/L, −7.1 (95% CI: −8.0 to −6.1, P < 0.001) for FPG ≥ 6.5 mmol/L in men. Furthermore, the interaction between different FPG level and sex was significant (P < 0.05). An invert U-shape with a threshold of FPG was existed for serum UA level in Chinese adults age 18 to 89 years without known diabetes, and significant gender differences were found. Future researches should pay more attention to this relationship. PMID:27100447
Acute consumption of organic and conventional tropical grape juices (Vitis labrusca L.) increases antioxidants in plasma and erythrocytes, but not glucose and uric acid levels, in healthy individuals.
Toaldo, Isabela Maia; Cruz, Fernanda Alves; da Silva, Edson Luiz; Bordignon-Luiz, Marilde T
Bioactive polyphenols in grapes are influenced by grape variety and cultivation conditions. The Vitis labrusca L. varieties are cultivated in tropical regions and used for grape juice production. We hypothesized that polyphenols from tropical grape juices would beneficially affect redox homeostasis in humans. Therefore, the effects of acute consumption of organic and conventional grape juices from V labrusca L. on antioxidants biomarkers were investigated in healthy individuals. In a controlled, randomized, crossover, intervention trial, 24 individuals were assigned to drink 400 mL of conventional juice, organic juice, or water. Each intervention was followed by a 14-day washout period. Blood samples were obtained before and 1 hour after acute intake and analyzed for erythrocyte reduced glutathione, serum total antioxidant capacity, antioxidant enzymes in erythrocytes, and glucose and uric acid in serum. The ingestion of both grape juices resulted in elevated levels of reduced glutathione (P< .001) and serum total antioxidant capacity (P< .05) and increased activity of catalase (P< .001), superoxide dismutase (P< .001), and glutathione peroxidase (P< .05) compared with the control intervention, with no significant differences between grape juices (P< .05). The intake of juices did not affect significantly the concentrations of glucose or uric acid. Grape juice polyphenols were associated with increased antioxidants, and the chemical differences between organic and conventional juices were not predictive of the observed responses. The results suggest a bioactive potential of V labrusca L. juices to improve redox homeostasis, which is involved in defense against oxidative stress in humans.
Lombardo, F; Bonatti, M; Zamboni, G A; Avesani, G; Oberhofer, N; Bonelli, M; Pycha, A; Pozzi Mucelli, R; Bonatti, G
To differentiate uric acid from non-uric acid renal stones based on their spectral attenuation values. The present study was approved by the institutional review board and the need for informed consent was waived. Thirty-three consecutive patients (21 men, 12 women; mean age 55 years) with symptomatic urolithiasis underwent dual-energy computed tomography (DECT) using a second-generation dual-source CT system. Stone composition was assessed by means of chemical analysis after extraction or spontaneous expulsion. The composition of one stone was considered to represent all remaining stones in patients presenting with more than one stone. Image-domain virtual monoenergetic images were generated from the dual-energy datasets. One radiologist evaluated stone attenuation values from 40 to 190 keV; attenuation curves were created and 40/190 keV attenuation ratios calculated. Qualitative evaluation of the spectral attenuation curves was also performed. Imaging findings were compared with laboratory results. Sixty-two stones were considered in 33 patients (mean diameter 6.5 mm). Fifteen of the 62 stones were mainly composed of uric acid and 47/62 of cysteine or calcium oxalates/phosphates. Forty to 190 keV attenuation ratios were significantly lower for uric acid stones (mean 0.87±0.3) than for non-uric acid stones (mean 3.80±0.6; p<0.0001). Accuracy was 100% with a cut-off value of 1.76. Qualitative analysis of spectral attenuation curves showed unique shapes for uric acid and non-uric acid stones. Spectral CT quantitatively and qualitatively differentiates uric acid from non-uric acid stones. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Tugores, Antonio; Rodríguez-González, Fayna
Hyperuricemia is defined as serum uric acid level of more than 7 mg/dL and blood levels of uric acid are causally associated with gout, as implicated by evidence from randomized clinical trials using urate lowering therapies. Uric acid as a cardiovascular risk factor often accompanies metabolic syndrome, hypertension, diabetes, dyslipidemia, chronic renal disease, and obesity. Despite the association of hyperuricemia with cardiovascular risk factors, it has remained controversial as to whether uric acid is an independent predictor of cardiovascular disease. To settle this issue, and in the absence of large randomized controlled trials, Mendelian randomization analysis in which the exposure is defined based on the presence or absence of a specific allele that influences a risk factor of interest have tried to shed light on this. PMID:28066631
Kumari, Asha; Mittal, Pawan; Kumar, Rajender; Goel, Richa; Bansal, Piyush; Kumar, Himanshu Devender; Bhutani, Jaikrit
Introduction Nephrolithiasis is a complex disease affecting all age groups globally. As the causative factors for nephrolithiasis rises significantly, its incidence, prevalence and recurrence continues to baffle clinicians and patients. Aim To study the prevalence of different types of renal stones extracted by Percutaneous Nephrolithotomy (PCNL) and open surgical procedures. Materials and Methods Renal stones from 50 patients were retrieved by Percutaneous Nephrolithotomy (PCNL), Ureterorenoscopy (URS) and open surgical techniques for qualitative tests for detection of calcium, oxalate, uric acid, phosphate, ammonium ion, carbonate, cystine and xanthine. Results Three patients had stone removed by open surgery and rest had undergone PCNL. Nine of the stones were pure of calcium oxalate, 9 were of pure uric acid and 32 were mixed stones. Forty one stones had calcium. Among the mixed stones, oxalate was present in 25 samples (39 of total), uric acid was seen in 17 (25 of total stones), phosphate was present in 23 (23 of total) and carbonate was present in 4 stones (4 of total). Only 1 patient had triple phosphate stone. 12 were of staghorn appearance of which 6 were of struvite type, 6 were pure uric acid and remaining were mixed oxalate-phosphate stones. Conclusion Our study, though in a small number of hospital based patients, found much higher prevalence of uric acid stones and mixed stones than reported by previous hospital based studies in north India (oxalate stones~90%, uric acid~1% and mixed stones~3%). Biochemical analysis of renal stones is warranted in all cases. PMID:27630833
Olak-Białoń, Bogusława; Marcisz, Czesław; Jonderko, Gerard; Olak, Zygfryd; Szymszal, Jan; Orzeł, Arkadiusz
The drinking of coffee, a commonly used beverage, was a subject of many studies, mainly regarded to coffee influence on cardiovascular system. However, only one study indicates that coffee drinking in male adults may lead to decrease in serum uric acid level. Hyperuricaemia is a risk factor of many diseases. The aim of this study was to examine the influence of coffee drinking on serum uric acid concentration. 1955 working persons aged from 18 to 65 years were included into research. There were 571 women among them. We determined energy expenditure during professional work, blood pressure, body mass index, and measured serum levels of uric acid, glucose and creatinine. The amount of coffee and ethanol consumption was evaluated on the ground of an interview. It was showed that persons drinking coffee have lower serum uric acid concentration than non-drinkers, especially among women, who drank more coffee then men. Uricaemia was correlated negatively with number of cups of coffee consumed and positively with body mass index, ethanol consumption and diastolic blood pressure. The author conclude that: 1) among women drinking on an average 10 cups of coffee per week appeared a decrease in serum uric acid concentration and a lower risk of development of hyperuricaemia, 2) elevated serum uric acid concentration is accompanied by elevated blood pressure and increased body mass index.
Bronk, J R; Shaw, M I
The in vitro recirculation technique was used to study the uptake and transport of uric acid by the jejunum of mouse small intestine. Three components of the serosal secretions appeared to be endogenously derived nucleic acid derivatives; two of these were identified as uric acid and uracil. There was no detectable metabolism of uric acid by the intestine. Uric acid transported from the lumen appeared in the serosal fluid at a concentration higher than that in the lumen. The final serosal/luminal concentration ratio of about 1.18 for exogenous uric acid was found to be constant over the concentration range studied (0.01-0.1 mM). The presence of exogenous uric acid in the lumen did not affect the production of endogenous uric acid by the intestine and its release into the serosal secretions. Mucosal concentration of exogenous uric acid was below, but the total mucosal concentration (exogenous+endogenous) was above, that in the lumen. There was no evidence for the secretion of endogenous uric acid into the lumen. Oxypurinol significantly decreased the rate of serosal appearance of exogenous uric acid. Allopurinol did not affect the transport of exogenous uric acid from the lumen and there was negligible metabolism of allopurinol to oxypurinol by the tissue. Uracil did not affect the transport of exogenous uric acid from the lumen, or the serosal appearance of endogenous uric acid. Likewise uracil transport was unaffected by luminal uric acid. PMID:3795104
Pak, C Y; Tolentino, R; Stewart, A; Galosy, R A
The effect of thiazide (hydrochlorothiazide 100 mg per day orally in two divided doses for up to 3 years) on uric acid metabolism was examined in 21 patients with renal stones suffering from renal hypercalciuria or absorptive hypercalciuria. Serum concentration of uric acid increased during thiazide therapy in every patient. In 12 of 21 patients, there was a transient or persistent rise in urinary uric acid of more than 50 mg per day during treatment. The mean urinary uric acid produced by thiazide was positively correlated with the change in the renal clearance of uric acid. Thus, an increase in urinary uric acid was often associated with a rise in uric acid clearance. The results suggest that thiazide may either increase the production of uric acid or decrease the extrarenal disposal of uric acid, in some patients.
Doizi, Steeve; Rodgers, Kathy; Poindexter, John; Sakhaee, Khashayar; Maalouf, Naim M
We assessed decreased inhibitor activity or increased promoter activity in the urine of idiopathic uric acid stone formers compared to nonstone formers independent of urinary pH. A total of 30 idiopathic uric acid stone formers, and 9 obese and 12 lean nonstone formers collected 24-hour urine while on a metabolic diet. Three urine aliquots per subject were used to assess spontaneous nucleation (de novo crystal formation), crystal growth using a 0.1 mg/ml anhydrous uric acid seed and steady-state uric acid solubility (the maximum amount of uric acid dissolvable in urine) using a 5 mg/ml uric acid seed. All experiments were performed for 6 hours at a constant pH of 5.0. Uric acid concentration was measured in filtered aliquots at 0, 3 and 6 hours. At baseline 24-hour urinary pH was significantly lower and uric acid saturation was significantly higher in idiopathic uric acid stone formers. No significant spontaneous nucleation developed and similar uric acid steady-state solubility was reached in the 3 groups. Idiopathic uric acid stone formers and lean nonstone formers showed a similar decrease in uric acid concentration during crystal growth. Obese nonstone formers started with a higher uric acid concentration and consequently demonstrated a greater decrease in the uric acid concentration for crystal growth. This study suggests that there is no significant difference between idiopathic uric acid stone formers and nonstone formers in promoter or inhibitor activity in whole urine against uric acid stone formation when urine pH is maintained constant. The findings suggest that uric acid stone formation is dictated by high urinary saturation with respect to uric acid, which is driven primarily by low urine pH. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Ngo, Tin C; Assimos, Dean G
The prevalence of urolithiasis has been increasing for the past few decades in industrialized nations. Uric acid calculi account for a significant percentage of urinary stones. Certain risk factors may be involved in the pathogenesis of uric acid nephrolithiasis, including hyperuricosuria, low urinary volume, and persistently low urinary pH. Patients with medical conditions that promote profound hyperuricosuria are at high risk of developing uric acid calculi. These conditions include chronic diarrheal states; myeloproliferative disorders; insulin resistance, including diabetes mellitus; and monogenic metabolic disorders, such as Lesch-Nyhan syndrome. Computed tomography can provide a definitive diagnosis. Except in cases in which there is severe obstruction, progressive azotemia, serious infection, or unremitting pain, the initial treatment of patients with uric acid nephrolithiasis should be medical dissolution therapy because this approach is successful in the majority of cases. A thorough review of the epidemiology and pathophysiology of uric acid nephrolithiasis is crucial for the diagnosis, treatment, and prevention of stones in patients with this condition. PMID:17396168
Bobulescu, Ion Alexandru; Moe, Orson W.
In addition to its role as a metabolic waste product, uric acid has been proposed to be an important molecule with multiple functions in human physiology and pathophysiology and may be linked to human diseases beyond nephrolithiasis and gout. Uric acid homeostasis is determined by the balance between production, intestinal secretion, and renal excretion. The kidney is an important regulator of circulating uric acid levels, by reabsorbing around 90% of filtered urate, while being responsible for 60–70% of total body uric acid excretion. Defective renal handling of urate is a frequent pathophysiologic factor underpinning hyperuricemia and gout. In spite of tremendous advances over the past decade, the molecular mechanisms of renal urate transport are still incompletely understood. Many transport proteins are candidate participants in urate handling, with URAT1 and GLUT9 being the best characterized to date. Understanding these transporters is increasingly important for the practicing clinician as new research unveils their physiology, importance in drug action, and genetic association with uric acid levels in human populations. The future may see the introduction of new drugs that specifically act on individual renal urate transporters for the treatment of hyperuricemia and gout. PMID:23089270
Tasaki, Eisuke; Sakurai, Hiroki; Nitao, Masaru; Matsuura, Kenji; Iuchi, Yoshihito
Reactive oxygen species (ROS) are generated spontaneously in all organisms and cause oxidative damage to biomolecules when present in excess. Accumulated oxidative damage accelerates aging; enhanced antioxidant capacity may be a positive factor for longevity. Recently, numerous studies of aging and longevity have been performed using short-lived animals, however, longevity mechanisms remain unknown. Here we show that a termite Reticulitermes speratus that is thought to be long-lived eusocial insect than other solitary insects uses large quantities of uric acid as an antioxidant against ROS. We demonstrated that the accumulation of uric acid considerably increases the free radical-scavenging activity and resistance against ultraviolet-induced oxidative stress in laboratory-maintained termites. In addition, we found that externally administered uric acid aided termite survival under highly oxidative conditions. The present data demonstrates that in addition to nutritional and metabolic roles, uric acid is an essential antioxidant for survival and contributes significantly to longevity. Uric acid also plays important roles in primates but causes gout when present in excess in humans. Further longevity studies of long-lived organisms may provide important breakthroughs with human health applications. PMID:28609463
Gout is an arthritis characterized by elevated uric acid in the bloodstream. In this condition, crystals of uric acid are formed and accumulate in the synovial fluids. Crystal deposition leads to acute inflammation, which is associated with the spontaneous resolution of the disease. Recent studies have led to significant advances in the understanding of the basic biology of crystal-mediated inflammation. Uric acid has been identified as a danger signal that triggers a cytosolic sensor, the inflammasome. This signaling platform is required for the activation of interleukin-1, a cytokine that is critical to the initiation of acute inflammation in gout. Importantly, both molecular and pathological evidence support the notion that gout is a prototypical member of the growing family of autoinflammatory diseases. This review discusses the role of the inflammasome in gout and the emerging new therapeutic strategies aimed at controlling inflammation in crystal arthritis.
Torricelli, Fabio Cesar Miranda; Chueh, Shih-Chieh Jeff; Shen, Shujane
Abstract Background: Bladder urinary calculi occur in 3%–8% of men with bladder outlet obstruction, and although most of them are composed of calcium, in a few cases uric acid bladder stones are diagnosed. Case Presentation: We present clinical images and therapeutic management of a 65-year-old diabetic man with significant prostate enlargement and >30 bladder stones, the largest being 17 mm. Despite the large stone burden, the patient was managed by cystolithotripsy. Remarkably, stone composition analysis revealed 100% uric acid stone. Intraoperative and postoperative course were uneventfully. Conclusion: Uric acid bladder stone pathogenesis seems to be multifactorial with local and systemic factors contributing in different manners and even large stone burdens may be cystoscopically managed. PMID:28265592
Bird, Michael I; Tait, Elaine; Wurster, Christopher M; Furness, Robert W
We report results obtained using a new technique developed to measure the stable-isotope composition of uric acid isolated from bird excreta (guano). Results from a diet-switch feeding trial using zebra finches suggest that the delta(13)C of uric acid in the guano equilibrates with the diet of the bird within 3 days of a change in diet, while the equilibration time for delta(15)N may be longer. The average carbon isotope discrimination between uric acid and food before the diet switch was +0.34 +/- 1 per thousand (1sigma) while after the diet switch this increased slightly to +0.83 +/- 0.7 per thousand (1sigma). Nitrogen isotope discrimination was +1.3 +/- 0.3 per thousand (1sigma) and +0.3 +/- 0.3 per thousand (1sigma) before and after the diet switch; however, it is possible that the nitrogen isotope values did not fully equilibrate with diet switch over the course of the experiment. Analyses of other chemical fractions of the guano (organic residue after uric acid extraction and non-uric acid organics solubilised during extraction) suggest a total range of up to 3 per thousand for both delta(13)C and delta(15)N values in individual components of a single bulk guano sample. The analysis of natural samples from a range of terrestrial and marine species demonstrates that the technique yields isotopic compositions consistent with the known diets of the birds. The results from natural samples further demonstrate that multiple samples from the same species collected from the same location yield similar results, while different species from the same location exhibit a range of isotopic compositions indicative of different dietary preferences. Given that many samples of guano can be rapidly collected without any requirement to capture specimens for invasive sampling, the stable-isotope analysis of uric acid offers a new, simple and potentially powerful tool for studying avian ecology and metabolism.
Szczurek, Paulina; Mosiichuk, Nadia; Woliński, Jarosław; Yatsenko, Tetiana; Grujic, Danica; Lozinska, Liudmyla; Pieszka, Marek; Święch, Ewa; Pierzynowski, Stefan Grzegorz; Goncharova, Kateryna
An elevated level of serum uric acid-hyperuricemia, is strongly associated with the development of gout and chronic kidney disease (CKD) which is often accompanied by a significantly reduced glomerular filtration rate (GFR). In the present study, we investigated the extra-renal elimination of uric acid via the intestine in a healthy pig model and the effect of oral uricase therapy on plasma uric acid concentrations in pigs with induced hyperuricemia and CKD. The experiment was conducted on eleven, ten-week-old pigs (n = 11). The porcine model of CKD was developed by performing 9/10 nephrectomy surgery on eight pigs. A stable model of hyperuricemia was established in only five of the eight nephrectomized pigs by frequent injections of uric acid (UA) into the jugular vein. All pigs (three healthy pigs and five CKD pigs) were operated for implantation of jugular vein catheters and the three healthy pigs also had portal vein catheters inserted. Blood uric acid concentrations were measured spectrophotometrically, using the Uric Acid Assay Kit (BioAssay Systems, Hayward, USA). The piglets with CKD received orally administered uricase (treatment) and served as their own controls (without uricase supplementation). Oral uricase therapy significantly decreased plasma uric acid concentrations in pigs with CKD, whereas hyperuricemia was observed in the pigs whilst not being treated with uricase. Urinary uric acid excretion was similar during both the treatment and control periods during the first 8 h and 24 h after UA infusions in the CKD pigs. To demonstrate the elimination of UA via the intestine, the healthy pigs were infused with UA into the jugular vein. The blood collected from the jugular vein represents circulating UA concentrations and the blood collected from the portal vein represents the concentration of UA leaving the intestine. The final (after 2 h) concentration of UA was significantly lower in blood collected from the portal vein compared to that collected from
Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi
Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UE(UA)) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UE(UA), suggesting that SUA decreased as a result of the increase in the UE(UA). The increase in UE(UA) was correlated with an increase in urinary D-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UE(UA) is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and D-glucose. It was observed that the efflux of [(14) C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm D-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [(14) C]UA by oocytes was cis-inhibited by 100 mm D-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UE(UA) could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose.
Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi
Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127
Settle, T; Carro, M D; Falkenstein, E; Radke, W; Klandorf, H
The purpose of these studies was to determine the effects of uric acid (UA) and inosine administration on xanthine oxidoreductase activity in broilers. In experiment one, 25 broilers were assigned to 5 treatment groups: control, AL (25 mg of allopurinol/kg of body mass), AR (AL for 2 wk followed by allopurinol withdrawal over wk 3), UAF (AL plus 6.25 g of UA sodium salt/kg of feed), and UAI (AL plus 120 mg of UA sodium salt injected daily). The UA administration had no effect on plasma concentration of UA (P > 0.05), and all allopurinol-treated birds had lower (P < 0.05) UA levels than controls. The UA concentrations were restored in both plasma and kidney of AR birds at wk 3, but liver UA concentrations remained lower. Whereas xanthine oxidoreductase (XOR) activity in the liver (LXOR) was reduced (P < 0.05) by allopurinol treatment, XOR activity in the kidney (KXOR) was not affected (P = 0.05). In experiment two, 3 groups of 5 birds each were fed 0 (control), 0.6 M inosine/kg of feed (INO), or INO plus 50 mg of allopurinol/kg of body mass (INOAL). The INOAL birds showed lower total LXOR activity, but KXOR activity was not affected. Both INO and INOAL birds had higher plasma and kidney UA concentrations than controls. The results suggest that regulation of UA production is tissue dependent.
Chong, Hong-Heng; An, Geng
To study the percentage of uric acid calculus in uroliths and its metabolic character in Dongjiang River valley. To analyze the chemical composition of 290 urinary stones by infrared (IR) spectroscopy and study the ratio changes of uric acid calculus. Uric acid calculus patients and healthy people were studied. Personal characteristics, dietary habits were collected. Conditional logistic regression was used for data analysis and studied the dietary risk factors of uric acid calculus. Patients with uric acid calculus, calcium oxalate and those without urinary calculus were undergone metabolic evaluation analysis. The results of uric acid calculus patients compared to another two groups to analysis the relations between the formation of uric acid calculus and metabolism factors. Uric acid calculi were found in 53 cases (18.3%). The multiple logistic regression analysis suggested that low daily water intake, eating more salted and animal food, less vegetable were very closely associated with uric acid calculus. Comparing to calcium oxalate patients, the urine volume, the value of pH, urine calcium, urine oxalic acid were lower, but uric acid was higher than it. The value of pH, urine oxalic acid and citric acid were lower than them, but uric acid and urine calcium were higher than none urinary calculus peoples. Blood potassium and magnesium were lower than them. The percentage of uric acid stones had obvious advanced. Less daily water intake, eating salted food, eating more animal food, less vegetables and daily orange juice intake, eating sea food are the mainly dietary risk factors to the formation of uric acid calculus. Urine volume, the value of pH, citric acid, urine calcium, urine uric acid and the blood natrium, potassium, magnesium, calcium, uric acid have significant influence to the information of uric acid stones.
Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin
Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.
Shen, Zancong; Rowlings, Colin; Kerr, Brad; Hingorani, Vijay; Manhard, Kimberly; Quart, Barry; Yeh, Li-Tain; Storgard, Chris
Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32). Following single doses of lesinurad solution, absorption was rapid and exposure (maximum observed plasma concentration and area under the plasma concentration-time curve) increased in a dose-proportional manner. Following multiple qday doses, there was no apparent accumulation of lesinurad. Urinary excretion of unchanged lesinurad was generally between 30% and 40% of dose. Increases in urinary excretion of uric acid and reductions in serum uric acid correlated with dose. Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing. A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules. Lesinurad was generally safe and well tolerated.
Shen, Zancong; Rowlings, Colin; Kerr, Brad; Hingorani, Vijay; Manhard, Kimberly; Quart, Barry; Yeh, Li-Tain; Storgard, Chris
Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32). Following single doses of lesinurad solution, absorption was rapid and exposure (maximum observed plasma concentration and area under the plasma concentration–time curve) increased in a dose-proportional manner. Following multiple qday doses, there was no apparent accumulation of lesinurad. Urinary excretion of unchanged lesinurad was generally between 30% and 40% of dose. Increases in urinary excretion of uric acid and reductions in serum uric acid correlated with dose. Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing. A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules. Lesinurad was generally safe and well tolerated. PMID:26170627
Bruun, J M; Maersk, M; Belza, A; Astrup, A; Richelsen, B
Sucrose-sweetened soft drinks (SSSDs) are associated with the development of metabolic disorders. Fructose is a major component of SSSDs and is demonstrated to induce uric acid (UA) production and stimulate fat accumulation independent of excess caloric intake. UA induce insulin resistance and low-grade inflammation, suggesting that UA may have a causal role in the development of metabolic complications. The objective of this study is to investigate the long-term effects of consuming SSSDs on circulating levels of UA in overweight and obese subjects. Using a previously published study, circulating UA levels were assessed at baseline and after 6 months using chromogenic enzymatic absorptiometry. The study included 47 overweight and obese subjects without diabetes, randomised to consume 1 l daily of either SSSD (regular cola), isocaloric semi-skimmed milk, diet cola or water for 6 months. Circulating UA levels increased ~15% (P = 0.02) after the 6-month intervention in the SSSD group with no change in the other groups. In the SSSD group, circulating UA levels increased significantly after the intervention in both absolute (P = 0.005) and relative values (P = 0.004). The change in UA after the intervention correlated with changes in liver fat (P = 0.005), triglycerides (P = 0.02) and insulin (P = 0.002). In this secondary analysis daily intake of 1 l SSSD for 6 months was found to increase circulating UA levels compared with isocaloric milk, diet cola and water. Thus, a high daily intake of SSSDs in overweight and obese subjects without overt diabetes may increase the risk of developing metabolic complications through the elevation of UA. This trial is registered at ClinicalTrials.gov as NCT00777647.
Ren, Yanfeng; Ji, Linong; Mu, Yiming; Hong, Tianpei; Ji, Qiuhe; Guo, Lixin; Huang, Qin; Yang, Xilin
This study aimed to explore independent associations between serum uric acid and hypoglycaemia, and whether mildly increased serum uric acid exacerbated the association between mild decline in estimated glomerular filtration rate (eGFR) and hypoglycaemia. A cross-sectional survey of 6713 inpatients with type 2 diabetes and eGFR ≥60 mL/min/1.73 m(2) and admitted to 81 tertiary care hospitals in China was conducted. Self-reported asymptotic hypoglycaemia with plasma glucose ≤3.9 mmol/L, hypoglycaemia episodes with symptoms in 1 month or hypoglycaemia that needed assistance from other people in 3 months before hospitalization was used to define hypoglycaemia. Binary logistic regression was used to estimate odds ratios of serum uric acid for hypoglycaemia. Three measures, that is, relative excess risk due to interaction (RERI), attributable proportion due to interaction and synergy index (S) were used to estimate the effect of mildly decreased eGFR on the association of serum uric acid with hypoglycaemia. Serum uric acid was associated with hypoglycaemia in an ordinal manner (P for trend <0.01) with an odds ratio of top quartile versus the lowest quartile up to 3.03 (95% confidence interval: 2.13-4.32). The odds ratio of serum uric acid levels ≥ versus <283 µmol/L (i.e. the median) was 1.98 (95% confidence interval:1.58-2.48). Serum uric acid levels ≥ versus <283 µmol/L greatly enhanced the association between mild decline in eGFR (eGFR < 90 mL/min/1.73 m(2) ) and hypoglycaemia from 0.94 (0.36-2.43) to 3.90 (2.55-5.95), with a significant additive interaction (P < 0.05 for RERI, AP and S). Mildly increased serum uric acid was associated with increased risk of hypoglycaemia and enhanced the association between mildly decreased eGFR and hypoglycaemia in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Mueller, Ernst F.; French, John R. P., Jr.
In an investigation of the relationship of uric acid (a metabolic end product) to achievement, this study hypothesized that a person's serum urate level (a factor often associated with gout) is positively related to achievement need as well as indicators of actual achievement. (Speed of promotion and number of yearly publications were chosen as…
Wijnands, José M A; Houben, Alfons J H M; Muris, Dennis M J; Boonen, Annelies; Schram, Miranda T; Sep, Simone J S; van der Kallen, Carla J H; Henry, Ronald M A; Dagnelie, Pieter C; van der Linden, Sjef; Schaper, Nicolaas C; Arts, Ilja C W; Stehouwer, Coen D A
Microvascular dysfunction has been suggested as a possible underlying mechanism for the association between uric acid and various diseases, such as hypertension, renal disease and cardiomyopathies. We therefore analysed the association between serum uric acid and skin microvascular function, a model of generalized microvascular function. A cross-sectional study was performed in 610 individuals [51.8% men; mean age 58.7 ± 8.6 years; 23.6% with type 2 diabetes (by design)] from The Maastricht Study. We assessed skin capillary density (capillaries/mm) by capillaroscopy at baseline, after 4 min of arterial occlusion, and after 2 min of venous congestion. Capillary recruitment after arterial occlusion and during venous congestion was expressed as the absolute change in capillary density after recruitment and as the percentage change in capillary density from baseline. Crude linear regression analyses showed that serum uric acid [per +1 standard deviation (SD) of 74 μmol/l] was not associated with baseline capillary density [β = -0.21 (95% confidence interval, 95% CI -1.61 to 1.19) P = 0.765], while an inverse association was found between uric acid and absolute change in capillary density after arterial occlusion [β = -1.15 (95% CI -2.36 to 0.06) P = 0.062] and during venous congestion [β = -1.41 (95% CI -2.68 to -0.14) P = 0.029]. However, after adjustment for sex, age and glucose metabolism status, these associations were no longer statistically significant. In addition, we found no association between uric acid and percentage capillary recruitment after arterial occlusion [β = -1.66 (95% CI -3.97 to 0.65) P = 0.159] or during venous congestion [β = -2.02 (95% CI -4.46 to 0.42) P = 0.104] in unadjusted analyses; multivariable analyses gave similar results. These results do not support the hypothesis that generalized microvascular dysfunction (as estimated in skin microcirculation) is the underlying mechanism for
Khalil, M I; Islam, M J; Ullah, M A; Khan, R K; Munira, S; Haque, M A; Mamun, M A; Islam, M T; Khan, M H
The present study has examined the association between ischemic stroke and hyperuricemia in Bangladeshi population. This age and sex matched case control study was carried out in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh during the period of January 2007 to December 2008. A total of 120 subjects were included in this study, among them 60 were cases and another 60 were controls. Data were collected purposively. Multiple logistic regressions were done to identify the risk factors for ischemic stroke. In this study 68.3% were male and 31.7% were female in both the groups. Male and female ratio of stroke patients was 2.16:1. Mean±SD of serum uric acid level of case and control group was 4.94±1.76 and 3.72±1.09 respectively. Among the case group 76.7% had normal and 23.3% had abnormal serum uric acid level. On the other hand, 93.3% respondents of control group had normal and 6.7% had abnormal serum uric acid (SUA) level. Significant differences was found between case and control group in term of SUA level (p<0.05). Since SUA level is a quantitative numerical variable, an increase in 1mg/dl has a 47.0% (95% CI 1.0% to 2.16%) increase in odds ratio (OR) of having ischemic stroke. This 47.0% is obtained by taking OR for uric acid-1. Elevated serum uric acid level is not significant for ischemic stroke among the Bangladeshi population.
Todd, Alwyn S; Walker, Robert J; MacGinley, Robert J; Kelly, Jaimon; Merriman, Tony R; Major, Tanya J; Johnson, Richard J
Subjects with hypertension are frequently obese or insulin resistant, both conditions in which hyperuricemia is common. Obese and insulin-resistant subjects are also known to have blood pressure that is more sensitive to changes in dietary sodium intake. Whether hyperuricemia is a resulting consequence, moderating or contributing factor to the development of hypertension has not been fully evaluated and very few studies have reported interactions between sodium intake and serum uric acid. We performed further analysis of our randomized controlled clinical trials (Australian New Zealand Clinical Trials Registry #12609000161224 and #12609000292279) designed to assess the effects of modifying sodium intake on concentrations of serum markers, including uric acid. Uric acid and other variables (including blood pressure, renin, and aldosterone) were measured at baseline and 4 weeks following the commencement of low (60 mmol/day), moderate (150 mmol/day), and high (200-250 mmol/day) dietary sodium intake. The median aldosterone-to-renin ratio was 1.90 [pg/ml]/[pg/ml] (range 0.10-11.04). Serum uric acid fell significantly in both the moderate and high interventions compared to the low sodium intervention. This pattern of response occurred when all subjects were analyzed, and when normotensive or hypertensive subjects were analyzed alone. Although previously reported in hypertensive subjects, these data provide evidence in normotensive subjects of an interaction between dietary sodium intake and serum uric acid. As this interaction is present in the absence of hypertension, it is possible it could play a role in hypertension development, and will need to be considered in future trials of dietary sodium intake. The trials were registered with the Australian and New Zealand Clinical Trials Registry as ACTRN12609000161224 and ACTRN1260.
GÜLTEKİN, Bülent Kadri; KESEBİR, Sermin; KABAK, Sevgi Gül; ERGÜN, Ferzan Fikret; TATLIDİL YAYLACI, Elif
Introduction Purinergic system dysfunction has been shown both in patients with bipolar disorder (BD) and those with schizophrenia. The aim of this study was to evaluate whether uric acid levels in male BD patients with manic episode and schizophrenia patients with psychotic relapse differ from healthy male subjects. Secondly to assess whether uric acid levels in both patient groups correlate with episode severity and if a decrease in uric acid levels correlate with clinical improvement. Method A total of 55 BD patients with manic episode and 59 schizophrenic patients with psychotic relapse were evaluated at baseline and at weeks 1, 2, 3 using the Young Mania Rating Scale (YMRS) and the Positive and Negative Syndrome Scale (PANSS), and their plasma uric acid levels were measured. 60 age-matched healthy males without history of any previous or current psychiatric diagnosis and treatment constituted the control group. In order to determine plasma uric acid levels, blood samples were centrifuged at 3000 × g for 15 minutes, stored at −80°C and measured in milligrams per deciliter. Results Uric acid levels in both patient groups with manic episode and psychotic relapse were found higher than in healthy controls (f=6.122, p=.027). The difference between repeated measurements of uric acid levels in BD patient group was found to be between baseline and first week measurements (after Bonferroni correction) (p<.001). No correlation was found between YMRS and PANSS scores and uric acid levels at 4 assessment times. Conclusion Uric acid levels in male BD and schizophrenia patients with manic episode and psychotic relapse were similar with each other, and higher than in healthy males. No correlation was found between uric acid levels and episode severity in both groups. However, for patients with BD, a decrease in uric acid levels between baseline and first week seems to be correlated with clinical improvement.
Yamamoto, Tetsuya; Moriwaki, Yuji; Takahashi, Sumio
There are many factors that contribute to hyperuricemia, including obesity, insulin resistance, alcohol consumption, diuretic use, hypertension, renal insufficiency, genetic makeup, etc. Of these, alcohol (ethanol) is the most important. Ethanol enhances adenine nucleotide degradation and increases lactic acid level in blood, leading to hyperuricemia. In beer, purines also contribute to an increase in plasma uric acid. Although rare, dehydration and ketoacidosis (due to ethanol ingestion) are associated with the ethanol-induced increase in serum uric acid levels. Ethanol also increases the plasma concentrations and urinary excretion of hypoxanthine and xanthine via the acceleration of adenine nucleotide degradation and a possible weak inhibition of xanthine dehydrogenase activity. Since many factors such as the ALDH2*1 gene and ADH2*2 gene, daily drinking habits, exercise, and dehydration enhance the increase in plasma concentration of uric acid induced by ethanol, it is important to pay attention to these factors, as well as ingested ethanol volume, type of alcoholic beverage, and the administration of anti-hyperuricemic agents, to prevent and treat ethanol-induced hyperuricemia.
Yasutake, Yuichi; Tomita, Kengo; Higashiyama, Masaaki; Furuhashi, Hirotaka; Shirakabe, Kazuhiko; Takajo, Takeshi; Maruta, Koji; Sato, Hirokazu; Narimatsu, Kazuyuki; Yoshikawa, Kenichi; Okada, Yoshikiyo; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Nagao, Shigeaki; Matsuo, Hirotaka; Miura, Soichiro; Hokari, Ryota
Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. In this study, we aimed to determine whether uric acid could reduce endpoints associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. A mouse model of NSAID-induced enteropathy was generated by administering indomethacin intraperitoneally to 8-week-old male C57BL/6 mice, and then vehicle or uric acid was administered orally. A group of mice treated with indomethacin was also concurrently administered inosinic acid, a uric acid precursor, and potassium oxonate, an inhibitor of uric acid metabolism, intraperitoneally. For in vitro analysis, Caco-2 cells treated with indomethacin were incubated in the presence or absence of uric acid. Oral administration of uric acid ameliorated NSAID-induced enteropathy in mice even though serum uric acid levels did not increase. Intraperitoneal administration of inosinic acid and potassium oxonate significantly elevated serum uric acid levels and ameliorated NSAID-induced enteropathy in mice. Both oral uric acid treatment and intraperitoneal treatment with inosinic acid and potassium oxonate significantly decreased lipid peroxidation in the ileum of mice with NSAID-induced enteropathy. Treatment with uric acid protected Caco-2 cells from indomethacin-induced oxidative stress, lipid peroxidation, and cytotoxicity. Uric acid within the intestinal lumen and in serum had a protective effect against NSAID-induced enteropathy in mice, through its antioxidant activity. Uric acid could be a promising therapeutic target for NSAID-induced enteropathy. This article is protected by copyright. All rights reserved.
Romero, Freddy; Pérez, Mariela; Chávez, Maribel; Parra, Gustavo; Durante, Paula
In this work, we aimed to study the effect of uric acid on gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were assigned to one of six groups (six rats each) which received intraperitoneal injections for 9 days: (S) saline; (UA) Uric acid alone; (G) Gentamicin alone; (G + UA) Gentamicin + uric acid; (G rec) Gentamicin recovery and (G + UA rec) Gentamicin + uric acid recovery. In (G rec) and (G + UA rec), rats recovered for 7 days after the last injection. Urine and blood samples were taken on day 0 and at the end of every stage. Kidneys were harvested for histological scoring, determination of renal malondialdehyde (MDA), zymography and western blots for matrix metalloprotease (MMP)-2 and MMP-9. Uric acid alone did not provoke changes in biochemical and histological parameters when compared to controls. Gentamicin alone increased significantly plasma creatinine and blood urea nitrogen and caused a moderate histological damage. When combined with uric acid, these conditions worsened. MMP-9 activity and expression was decreased in rats from group G + UA as compared with rats from group G, while activity of MMP-2 was similarly increased in both groups when compared to controls. The increase in renal MDA induced by gentamicin was not altered when it was combined with uric acid. During the recovery stage, all biochemical parameters returned to normal levels, though a trend for delay of tubular damage recovery was observed in group G + UA rec when compared with group G rec. The results indicate that uric acid worsens gentamicin-induced nephrotoxicity. The mechanism is likely to implicate down-regulation of MMP-9.
Heimbach, Esther J.; Bowden, Rodney G.; Griggs, Jackson O.; Beaujean, A. Alexander; Doyle, Eva I.; Doyle, Robert D.
Background Researchers have reported an independent direct relationship between lipid levels and hyperuricemia with MetS. The purpose of this study was to determine the relationship between serum uric acid levels and lipids among patients on allopurinol. Methods A retrospective secondary data analysis was conducted on 66 adult patients from a family health clinic in Central Texas. Medical records used were recorded during a nine year period (2002 - 2010) ascertaining the relationship between uric acid and lipids. Results Spearman correlations revealed a weak correlation between uric acid and total cholesterol, a weak correlation between uric acid and triglycerides and LDL-C. A weak inverse correlation was discovered between uric acid and HDL-C. A moderate correlation was discovered when all lipid variables combined were compared to uric acid. Conclusions We discovered LDL-C and triglycerides to be significant predictors of uric acid with weak correlations. Additionally, weak correlations existed between uric acid and total cholesterol and HDL-C with an inverse relationship discovered with HDL-C. These findings support the literature suggesting that uric acid is more likely to be associated with total cholesterol and triglycerides. In addition, new discoveries serve as an indication that LDL-C may also be associated with uric acids levels. The mechanism by which uric acid may regulate lipids is elusive but suggestions have included suppression of lipid peroxidase and decreases in critical lipase activity.
Sanguinetti, Silvia M; Batthyány, Carlos; Trostchansky, Andrés; Botti, Horacio; López, Graciela I; Wikinski, Regina L W; Rubbo, Homero; Schreier, Laura E
Interactions between uric acid and physiologically relevant fluxes of nitric oxide ((?)NO) during copper-mediated low-density lipoprotein (LDL) oxidation were evaluated. In the absence of (?)NO, a dual pro- and antioxidant action of uric acid was evident: low concentrations of uric acid enhanced lipid oxidation and alpha-tocopherol consumption, while its protective role was observed at higher concentrations. The prooxidant effects of uric acid were mostly related to its copper-reducing ability to form Cu(+), an initiator of lipid oxidation processes. While the prooxidant action of uric acid was completely inhibited by (?)NO, the antioxidant action of (?)NO was slightly counterbalanced by uric acid. Enhancement of alpha-tocopherol consumption by uric acid was inhibited in the presence of (?)NO while additive antioxidant effects between (?)NO and uric acid were observed in conditions where uric acid spared alpha-tocopherol. Altogether, these results suggest that in the artery wall, the (?)NO/uric acid pair may exert antioxidant actions on LDL, even if increased amounts of redox active copper were available at conditions favoring prooxidant activities of uric acid.
Park, Bohyun; Lee, Hye Ah; Lee, Sung Hee; Park, Bo Mi; Park, Eun Ae; Kim, Hae Soon; Cho, Su Jin; Park, Hyesook
Recent studies suggest that high levels of serum uric acid of very early life are a result of the in-utero environment and may lead to elevated blood pressure (BP) in adulthood. However, serum uric acid levels can change throughout life. We investigated the effect of serum uric acid levels in childhood on the BP tracking and analysed BP according to changes in serum uric acid levels in early life. A total of 449 children from the Ewha Birth and Growth Cohort study underwent at least 2 follow-up examinations. Data were collected across 3 check-up cycles. Serum uric acid levels, BP, and anthropometric characteristics were assessed at 3, 5, and 7 years of age. Children with a serum uric acid level higher than the median values had significantly increased systolic BP (SBP) and diastolic BP at 3 years of age. Baseline serum uric acid levels measured at 3 years of age, significantly affected subsequent BP in the sex and body mass index adjusted longitudinal data analysis (P < 0.05). Considering the changing pattern of serum uric acid over time, subjects with high uric acid levels at both 3 and 5 years of age had the highest SBP at 7 years of age. These findings suggest the importance of maintaining an adequate level of serum uric acids from the early life. Appropriate monitoring and intervention of uric acid levels in a high-risk group can reduce the risk of a future increased BP.
Lee, Hyun Woo; Choi, Sun Mi; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Lee, Sang-Min
Uric acid acts as both a pathogenic inflammatory mediator and an antioxidative agent. Several studies have shown that uric acid level correlates with the incidence, severity, and prognosis of pulmonary diseases. However, the association between uric acid level and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how serum uric acid level is related with clinical prognosis of ARDS. A retrospective cohort study with propensity score matching was conducted at a medical intensive care unit of a tertiary teaching hospital. The medical records of patients diagnosed with ARDS admitted from 2005 through 2011 were reviewed. Two hundred thirty-seven patients with ARDS met the inclusion criteria. Patients with a serum uric acid level <3.0 mg/dL were classified into the low uric acid group, and those with a level ≥3 mg/dL were classified into the normal to high uric acid group. We selected 40 patients in each group using propensity score matching. A higher percentage of patients in the low uric acid group experienced clinical improvement in ARDS. More patients died from sepsis in the normal to high uric acid group. Kaplan-Meier analysis showed that a low serum uric acid level was significantly associated with better survival rate. In patients with ARDS, a low serum uric acid level may be a prognostic marker of a low risk of in-hospital mortality.
Ogryzlo, M. A.; Urowitz, M. B.; Weber, H. M.; Houpt, J. B.
Allopurinol (4-hydroxypyrazolo (3,4-d)-pyrimidine) is a potent xanthine oxidase inhibitor which inhibits the oxidation of naturally occurring oxypurines, thus decreasing uric acid formation. The clinical and metabolic effects of this agent were studied in 80 subjects with primary and secondary gout and other disorders of uric acid metabolism. Allopurinol has been universally successful in lowering the serum uric acid concentration and uric acid excretion to normal levels, while not significantly affecting the clearance of urate or other aspects of renal function. Oxypurine excretion increased concomitantly with the fall in urine uric acid. The agent is particularly valuable in the management of problems of gout with azotemia, acute uric acid nephropathy and uric acid urolithiasis. The minor side effects, clinical indications and theoretical complications are discussed. PMID:5923471
León-Carmona, Jorge Rafael; Galano, Annia
The reactions of uric and 1-methyluric acids in nonpolar environments, as well as those of the corresponding urate anions in aqueous solution, with (•)OH, (•)OCH(3), (•)OOH, and (•)OOCH(3) have been studied using the density functional theory. Different mechanisms of reactions have been taken into account, and their relative importance on the antiradical activity of these compounds is analyzed. Both uric and methyluric acids are better scavengers in aqueous solution than in nonpolar media, which indicates that the urate anions are the most active species. The free radical scavenging activity of the studied compounds was found to be excellent for (•)OH, and very good for (•)OCH(3). In addition, 1-methyluric acid is predicted to moderately protect against peroxyl oxidation, while the protective effects of uric acid against these particular species are not expected to be significant. In addition, 1-methyluric acid was found to be a better radical scavenger than its precursor, caffeine, suggesting that the antiradical activity of the latter might be explained by the action of its metabolites, rather than by its direct activity. © 2011 American Chemical Society
Wu, Sheng Hui; Shu, Xiao Ou; Milne, Ginger; Xiang, Yong-Bing; Zhang, Xianglan; Cai, Qiuyin; Fazio, Sergio; Linton, MacRae F; Chen, Honglei; Purdue, Mark; Rothman, Nathaniel; Gao, Yu-Tang; Zheng, Wei; Yang, Gong
Objective To evaluate the association of uric acid (UA) levels with a panel of markers of oxidative stress and inflammation. Methods Plasma UA levels, along with a panel of oxidative stress and inflammatory markers, were measured in 755 Chinese women. Results Plasma UA levels were inversely associated with urinary levels of the oxidative stress marker F2-isoprostanes and positively correlated to levels of inflammatory markers such as C-reactive protein and some proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) in blood as well as prostaglandin E2 metabolites in urine. Conclusions Plasma UA levels correlate to oxidation and inflammation biomarkers in opposite directions in women. PMID:26301880
Trinchieri, Alberto; Montanari, Emanuele
The aim of this study was to compare the clinical characteristics of "pure" uric acid renal stone formers (UA-RSFs) with that of mixed uric acid/calcium oxalate stone formers (UC-RSFs) and to identify which urinary and dietary risk factors predispose to their formation. A total of 136 UA-RSFs and 115 UC-RSFs were extracted from our database of renal stone formers. A control group of 60 subjects without history of renal stones was considered for comparison. Data from serum chemistries, 24-h urine collections and 24-h dietary recalls were considered. UA-RSFs had a significantly (p = 0.001) higher body mass index (26.3 ± 3.6 kg/m(2)) than UC-RSFs, whereas body mass index of UA-RSFs was higher but not significantly than in controls (24.6 ± 4.7) (p = 0.108). The mean urinary pH was significantly lower in UA-RSFs (5.57 ± 0.58) and UC-RSFs (5.71 ± 0.56) compared with controls (5.83 ± 0.29) (p = 0.007). No difference of daily urinary uric acid excretion was observed in the three groups (p = 0.902). Daily urinary calcium excretion was significantly (p = 0.018) higher in UC-RSFs (224 ± 149 mg/day) than UA-RSFs (179 ± 115) whereas no significant difference was observed with controls (181 ± 89). UA-RSFs tend to have a lower uric acid fractional excretion (0.083 ± 0.045% vs 0.107+/-0.165; p = 0.120) and had significantly higher serum uric acid (5.33 ± 1.66 vs 4.78 ± 1.44 mg/dl; p = 0.007) than UC-RSFs. The mean energy, carbohydrate and vitamin C intakes were higher in UA-SFs (1987 ± 683 kcal, 272 ± 91 g, 112 ± 72 mg) and UC-SFs (1836 ± 74 kcal, 265 ± 117, 140 ± 118) with respect to controls (1474 ± 601, 188 ± 84, 76 ± 53) (p = 0.000). UA-RSFs should be differentiated from UC-RSFs as they present lower urinary pH, lower uric acid fractional excretion and higher serum uric acid. On the contrary, patients with UC-RSFs show urinary risk factors
Amartey, N.A.A.; Mensah, F.O.
Introduction: Diabetes mellitus is one of the most common metabolic diseases worldwide. This metabolic disorder contributes greatly to the significant proportion of the burden of renal damage and dysfunction. The aim of the study was to investigate the renal function of the diabetic patients who visit the Clinical Analysis Laboratory (CAn-Lab) at the Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. Materials and Methods: Demographic data as well as medical history were obtained through the administration of a questionnaire. Anthro-pometric measurements were taken and blood samples were analysed for glucose, uric acid, urea and creatinine. Data collected were analysed using SPSS version 16.0. Results: A total of 34 diabetic patients, aged from 40-77 y were recruited, 22 (64.7%) of them were males with mean age of 57.40 ± 11.8 y (±SD), while 12 (35.3%) were females with mean age of 58.17 ± 7.47 y. There was a statistically significant difference between the mean duration of the disease, as the females had longer duration, 12.50 ± 6.95 y, as compared to 7.32 ± 4.48 y in males (p=0.033). The mean plasma creatinine level in the females was 84.17 ± 54.73 μmol/l. In the diabetic population, there was a positive correlation between age and plasma creatinine level, (r=0.375, p=0.029). In the female diabetics, there was a positive correlation between fasting blood sugar (FBS) and the measured metabolic end products (r>0.5, p<0.05), a positive correlation between body mass index (BMI) and uric acid (r=0.576, p=0.005) and a positive correlation between BMI and FBS (r= 0.625, p= 0.030). Conclusion: Our results on the parameters measured; show that the diabetic population was experiencing mild kidney dysfunction, compared to non-diabetic controls. PMID:25859443
Chen, Zhiqiang; Yao, Linfang; Ye, Zhangqun; Yang, Weimin
This study was designed to evaluate the efficacy of local litholytic irrigation (LLI) in the treatment of ureteral uric acid calculi. Fourteen cases of ureteral uric acid calculi were diagnosed by abdominal plain radiography (KUB), retrograde urography, ultrasonography (B-mode ultrasound), spiral computerized tomography(CT) and blood biochemical examinations. A ureteral catheter was passed retrogradely across ureteral calculi by cystoscopy. LLI with tromethamine-E (THAM-E) was performed via the ureteral catheter after the improvement of renal function and general situation and the control of urinary tract infection under the condition of intravenous application of antibiotics. The irrigation rate varied from 1000 to 1500 ml per day. Retrograde pyelography demonstrated complete dissolution of all the stones, 13 cases within 10 days and 1 within 12 days. Mild hematuria was observed in the majority of the cases and temporary aggravated lumbago in 1 case, with no other side effects. It is concluded that LLI is a practical and effective method in the treatment of ureteral uric acid calculi for its advantages of shorter duration,lower cost, less physical suffering and no severe complications.
Braga, Tarcio Teodoro; Forni, Maria Fernanda; Correa-Costa, Matheus; Ramos, Rodrigo Nalio; Barbuto, Jose Alexandre; Branco, Paola; Castoldi, Angela; Hiyane, Meire Ioshie; Davanso, Mariana Rodrigues; Latz, Eicke; Franklin, Bernardo S; Kowaltowski, Alicia J; Camara, Niels Olsen Saraiva
Uric acid is a damage-associated molecular pattern (DAMP), released from ischemic tissues and dying cells which, when crystalized, is able to activate the NLRP3 inflammasome. Soluble uric acid (sUA) is found in high concentrations in the serum of great apes, and even higher in some diseases, before the appearance of crystals. In the present study, we sought to investigate whether uric acid, in the soluble form, could also activate the NLRP3 inflammasome and induce the production of IL-1β. We monitored ROS, mitochondrial area and respiratory parameters from macrophages following sUA stimulus. We observed that sUA is released in a hypoxic environment and is able to induce IL-1β release. This process is followed by production of mitochondrial ROS, ASC speck formation and caspase-1 activation. Nlrp3(-/-) macrophages presented a protected redox state, increased maximum and reserve oxygen consumption ratio (OCR) and higher VDAC protein levels when compared to WT and Myd88(-/-) cells. Using a disease model characterized by increased sUA levels, we observed a correlation between sUA, inflammasome activation and fibrosis. These findings suggest sUA activates the NLRP3 inflammasome. We propose that future therapeutic strategies for renal fibrosis should include strategies that block sUA or inhibit its recognition by phagocytes.
Braga, Tarcio Teodoro; Forni, Maria Fernanda; Correa-Costa, Matheus; Ramos, Rodrigo Nalio; Barbuto, Jose Alexandre; Branco, Paola; Castoldi, Angela; Hiyane, Meire Ioshie; Davanso, Mariana Rodrigues; Latz, Eicke; Franklin, Bernardo S.; Kowaltowski, Alicia J.; Camara, Niels Olsen Saraiva
Uric acid is a damage-associated molecular pattern (DAMP), released from ischemic tissues and dying cells which, when crystalized, is able to activate the NLRP3 inflammasome. Soluble uric acid (sUA) is found in high concentrations in the serum of great apes, and even higher in some diseases, before the appearance of crystals. In the present study, we sought to investigate whether uric acid, in the soluble form, could also activate the NLRP3 inflammasome and induce the production of IL-1β. We monitored ROS, mitochondrial area and respiratory parameters from macrophages following sUA stimulus. We observed that sUA is released in a hypoxic environment and is able to induce IL-1β release. This process is followed by production of mitochondrial ROS, ASC speck formation and caspase-1 activation. Nlrp3−/− macrophages presented a protected redox state, increased maximum and reserve oxygen consumption ratio (OCR) and higher VDAC protein levels when compared to WT and Myd88−/− cells. Using a disease model characterized by increased sUA levels, we observed a correlation between sUA, inflammasome activation and fibrosis. These findings suggest sUA activates the NLRP3 inflammasome. We propose that future therapeutic strategies for renal fibrosis should include strategies that block sUA or inhibit its recognition by phagocytes. PMID:28084303
Hahn, Kai; Kanbay, Mehmet; Lanaspa, Miguel A; Johnson, Richard J; Ejaz, A Ahsan
Acute kidney injury causes great morbidity and mortality in both the community and hospital settings. Understanding the etiological factors and the pathophysiological principles resulting in acute kidney injury is essential in prompting appropriate therapies. Recently hyperuricemia has been recognized as a potentially modifiable risk factor for acute kidney injury, including that associated with cardiovascular surgery, radiocontrast administration, rhabdomyolysis, and associated with heat stress. This review discussed the evidence that repeated episodes of acute kidney injury from heat stress and dehydration may also underlie the pathogenesis of the chronic kidney disease epidemic that is occurring in Central America (Mesoamerican nephropathy). Potential mechanisms for how uric acid might contribute to acute kidney injury are also discussed, including systemic effects on renal microvasculature and hemodynamics, and local crystalline and noncrystalline effects on the renal tubules. Pilot clinical trials also show potential benefits of lowering uric acid on acute kidney injury associated with a variety of insults. In summary, there is mounting evidence that hyperuricemia may have a significant role in the development of acute kidney injury. Prospective, placebo controlled, randomized trials are needed to determine the potential benefit of uric acid lowering therapy on kidney and cardio-metabolic diseases.
Johnson, Richard J; Nakagawa, Takahiko; Sanchez-Lozada, L Gabriela; Shafiu, Mohamed; Sundaram, Shikha; Le, Myphuong; Ishimoto, Takuji; Sautin, Yuri Y; Lanaspa, Miguel A
The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that "a calorie is just a calorie" and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.
Bernardi, E; Bowden, D J; Brimblecombe, P; Kenneally, H; Morselli, L
Bird droppings are often quoted as a decay agent for outdoor goods, in particular buildings and statues. Undoubtedly, they represent one of the major causes of aesthetic damage on outdoor materials, but the real chemical damage they are able to induce, in particular on metals, is not so well studied. This work focused on the short term role of uric acid, the main constituent of bird urine, with respect to copper, which make such an important contribution to architectural elements of buildings and outdoor sculpture. Preliminary results of laboratory tests and analyses on real exposed samples showed that uric acid chemically affects copper and bronzes: the surface of the metal is modified and copper urates formed. Also natural patina, formed on statues and roof, react with uric acid, even if it seems to afford some protection toward bird droppings. In general, experimental results confirm that the potential chemical damage by bird droppings is significant when considering external cultural heritage such as statues, metal monuments and buildings with historic copper roofs.
Johnson, Richard J.; Nakagawa, Takahiko; Sanchez-Lozada, L. Gabriela; Shafiu, Mohamed; Sundaram, Shikha; Le, Myphuong; Ishimoto, Takuji; Sautin, Yuri Y.; Lanaspa, Miguel A.
The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease. PMID:24065788
Jalal, Diana I.; Chonchol, Michel; Chen, Wei; Targher, Giovanni
The prevalence of chronic kidney disease (CKD) has risen and will continue to rise in the United States and worldwide. This is alarming considering that CKD remains an irreversible condition and patients who progress to chronic kidney failure suffer reduced quality of life and high mortality rates. As such, it is imperative to identify modifiable risk factors to develop strategies to slow CKD progression. One such factor is hyperuricemia. Recent observational studies have associated hyperuricemia with kidney disease. In addition, hyperuricemia is largely prevalent in patients with CKD. Data from experimental studies have revealed several potential mechanisms by which hyperuricemia may contribute to the development and progression of CKD. In this manuscript we offer a critical review of the experimental evidence linking hyperuricemia to CKD, we highlight the gaps in our knowledge on the topic as it stands today, and we review the observational and interventional studies that have examined the potential nephro-protective effect of lowering uric acid in CKD patients . While uric acid may also be linked to cardiovascular disease and mortality in patients with CKD, this review will focus only on uric acid as a potential therapeutic target to prevent kidney disease onset and progression. PMID:23058478
Goodman, Adam M; Wheelock, Muriah D; Harnett, Nathaniel G; Mrug, Sylvie; Granger, Douglas A; Knight, David C
Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid's impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. Brain regions including the prefrontal cortex, amygdala, and hippocampus underlie stress reactivity and emotion regulation. Thus, uric acid may impact emotion by modifying the function of these brain regions. The present study used functional magnetic resonance imaging (fMRI) during a psychosocial stress task to investigate the relationship between baseline uric acid levels (in saliva) and brain function. Results demonstrate that activity within the bilateral hippocampal complex varied with uric acid concentrations. Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Wan, Xingyong; Xu, Chengfu; Lin, Yiming; Lu, Chao; Li, Dejian; Sang, Jianzhong; He, Haijian; Liu, Xiao; Li, Youming; Yu, Chaohui
Hyperuricemia significantly increases risk of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. However, the mechanisms responsible for this association are as yet unclear. This study aimed to investigate the effects and underlying mechanisms of uric acid on development of NAFLD and insulin resistance. We initially analyzed the impact of uric acid on the development of hepatic steatosis and insulin resistance in mice and in two cell models, HepG2 and L02. Subsequently, we studied the role of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in uric acid-induced fat accumulation and insulin signaling impairment. We found that uric acid directly induces hepatocyte fat accumulation, insulin resistance, and insulin signaling impairment both in vivo and in vitro. We also found that uric acid-induced NLRP3 inflammasome activation, whereas lowering uric acid by allopurinol inhibited NLRP3 inflammasome activation in a high fat diet mouse model of NAFLD. Moreover, knocking down NLRP3 expression significantly attenuated uric acid-induced fat accumulation both in HepG2 cells and L02 cells. Knocking down NLRP3 expression also rescued uric acid-induced insulin signaling impairment in both cell types. Uric acid regulates hepatic steatosis and insulin resistance through the NLRP3 inflammasome. Uric acid may be a new therapeutic target for NAFLD and insulin resistance. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Buemann, B; Toubro, S; Holst, J J; Rehfeld, J F; Bibby, B M; Astrup, A
D-Fructose has been found to increase uric acid production by accelerating the degradation of purine nucleotides, probably due to hepatocellular depletion of inorganic phosphate (Pi) by an accumulation of ketohexose-1-phosphate. The hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate is slower than the degradation of D-fructose-1-phosphate. We tested the effect of 30 g oral D-tagatose versus D-fructose on plasma uric acid and other metabolic parameters in 8 male subjects by a double-blind crossover design. Both the peak concentration and 4-hour area under the curve (AUC) of serum uric acid were significantly higher after D-tagatose compared with either 30 g D-fructose or plain water. The decline in serum Pi concentration was greater at 50 minutes after D-tagatose versus D-fructose. The thermogenic and lactacidemic responses to D-tagatose were blunted compared with D-fructose. D-Tagatose attenuated the glycemic and insulinemic responses to a meal that was consumed 255 minutes after its administration. Moreover, both fructose and D-tagatose increased plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The metabolic effects of D-tagatose occurred despite its putative poor absorption.
McMullan, Ciaran J; Borgi, Lea; Fisher, Naomi; Curhan, Gary; Forman, John
Higher serum uric acid levels, even within the reference range, are strongly associated with increased activity of the renin-angiotensin system (RAS) and risk of incident hypertension. However, the effect of lowering serum uric acid on RAS activity in humans is unknown, although the data that lowering serum uric acid can reduce BP are conflicting. In a double-blind placebo-controlled trial conducted from 2011 to 2015, we randomly assigned 149 overweight or obese adults with serum uric acid ≥5.0 mg/dl to uric acid lowering with either probenecid or allopurinol, or to placebo. The primary endpoints were kidney-specific and systemic RAS activity. Secondary endpoints included mean 24-hour systolic BP, mean awake and asleep BP, and nocturnal dipping. Allopurinol and probenecid markedly lowered serum uric acid after 4 and 8 weeks compared with placebo (mean serum uric acid in allopurinol, probenecid, and placebo at 8 weeks was 2.9, 3.5, and 5.6 mg/dl, respectively). The change in kidney-specific RAS activity, measured as change in the median (interquartile range) renal plasma flow response to captopril (in ml/min per 1.73 m(2)) from baseline to 8 weeks, was -4 (-25 to 32) in the probenecid group (P=0.83), -4 (-16 to 9) in the allopurinol group (P=0.32), and 1 (-21 to 17) in the placebo group (P=0.96), with no significant treatment effect (P=0.77). Similarly, plasma renin activity and plasma angiotensin II levels did not significantly change with treatment. The change in mean (±SD) 24-hour systolic BPs from baseline to 8 weeks was -1.6±10.1 with probenecid (P=0.43), -0.4±6.1 with allopurinol (P=0.76), and 0.5±6.0 with placebo (P=0.65); there was no significant treatment effect (P=0.58). Adverse events occurred in 9%, 12%, and 2% of those given probenecid, allopurinol, or placebo, respectively. In contrast to animal experiments and observational studies, this randomized, placebo-controlled trial found that uric acid lowering had no effect on kidney-specific or
Scheven, Lieneke; Joosten, Michel M.; de Jong, Paul E.; Bakker, Stephan J. L.; Gansevoort, Ron T.
Background Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. Methods and Results Included were 7688 participants of the PREVEND Study, an observational, general population‐based cohort study. Linear regression analyses were used to test associations of baseline albuminuria with baseline serum uric acid concentration and tubular uric acid reabsorption (calculated as [100−fractional uric acid excretion]%). Cox regression analyses were used to study the association of baseline serum uric acid and albuminuria with incident cardiovascular morbidity and mortality. In cross‐sectional analyses, albuminuria was associated positively with serum uric acid concentration, both crude and after adjustment for potential confounders (both P<0.001). Albuminuria was found to be associated positively with tubular uric acid reabsorption, again both crude and after adjustment for potential confounders (both P<0.001). In longitudinal analyses during a median follow‐up of 10.5 years, 702 cardiovascular events occurred. After adjusting for cardiovascular risk factors, both albuminuria and serum uric acid were associated with incident cardiovascular events (Hazard Ratios 1.09 [1.03 to 1.17], P=0.01 and 1.19 [1.09 to 1.30], P<0.001, respectively). A significant interaction between these variables was present (P<0.001), consistent with high serum uric acid being less predictive for cardiovascular morbidity and mortality in the presence of high albuminuria and vice versa. Conclusions Albuminuria is strongly associated with tubular uric acid reabsorption, and consequently with serum uric acid concentration. This phenomenon may explain in part why albuminuria is associated with cardiovascular outcome. PMID:24772520
Wang, Yang; Hu, Jia-Wen; Lv, Yong-Bo; Chu, Chao; Wang, Ke-Ke; Zheng, Wen-Ling; Cao, Yu-Meng; Yuan, Zu-Yi; Mu, Jian-Jun
Uric acid is the end product of purine metabolism. Metabolic disorders of uric acid are associated with many disease states. Substantial evidence suggests the possible role of uric acid as a mediator of high blood pressure. Elevated uric acid is closely associated with new onset essential hypertension in adolescents and prehypertension; and urate-lowering agents can significantly improve these early stages of hypertension. Uric acid also influences salt sensitivity of blood pressure through two phases. Local renin-angiotensin-aldosterone system activation initiates renal damage, arteriolopathy, and endothelium dysfunction, which is followed by the dysregulation of sodium homeostasis, thereby leading to increased salt sensitivity. In this review we summarize the available evidence to contribute to a better understanding of the casual relationship between uric acid and early or intermediate stages of hypertension. We hope our review can contribute to the prevention of hypertension or provide new insights into a treatment that would slow the progression of hypertension.
Wang, Yang; Hu, Jia-Wen; Lv, Yong-Bo; Chu, Chao; Wang, Ke-Ke; Zheng, Wen-Ling; Cao, Yu-Meng; Yuan, Zu-Yi; Mu, Jian-Jun
Uric acid is the end product of purine metabolism. Metabolic disorders of uric acid are associated with many disease states. Substantial evidence suggests the possible role of uric acid as a mediator of high blood pressure. Elevated uric acid is closely associated with new onset essential hypertension in adolescents and prehypertension; and urate-lowering agents can significantly improve these early stages of hypertension. Uric acid also influences salt sensitivity of blood pressure through two phases. Local renin-angiotensin-aldosterone system activation initiates renal damage, arteriolopathy, and endothelium dysfunction, which is followed by the dysregulation of sodium homeostasis, thereby leading to increased salt sensitivity. In this review we summarize the available evidence to contribute to a better understanding of the casual relationship between uric acid and early or intermediate stages of hypertension. We hope our review can contribute to the prevention of hypertension or provide new insights into a treatment that would slow the progression of hypertension. PMID:28190873
Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A.; Nakagawa, Takahiko; Johnson, Richard J.
Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. PMID:26703429
Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A; Nakagawa, Takahiko; Johnson, Richard J
Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. Copyright © 2015 European Federation of Internal Medicine. All rights reserved.
Nemati, Eghlim; Khosravi, Arezoo; Einollahi, Behzad; Meshkati, Mehdi; Taghipour, Mehrdad; Abbaszadeh, Shahin
Introduction: Uric acid is one of the most significant uremic toxins accumulating in chronic renal failure patients treated with standard dialysis. Its clearance has not any exact relation with urea and creatinine clearance. Objectives: The aim of this study was to investigate the relationship between adequacy of dialysis and serum level of uric acid in dialysis patients of some dialysis centers in Iran. Patients and Methods: In this study 1271 hemodialysis patients who have been treated for more than 3 months were evaluated. Their information and examinations from their files in all over the country were gathered and analyzed using SPSS versin18.0. Results: In this study, a significant relationship between dialysis duration and serum level of uric acid was not detected, however, a significant relationship between patients Kt/V and uric acid (R=0.43, P=0.029) was seen. Patients who had higher adequacy of dialysis had a higher level of plasma uric acid. Conclusion: For better controlling of plasma uric acid level of hemodialysis patients, increasing of the adequacy of dialysis or its duration is not effective. Other modalities of decreasing of serum uric acid like, changing diet or lifestyle or medical therapy may be necessary.
Jasinge, Eresha; Kularatnam, Grace Angeline Malarnangai; Dilanthi, Hewa Warawitage; Vidanapathirana, Dinesha Maduri; Jayasena, Kandana Liyanage Subhashinie Priyadarshika Kapilani Menike; Chandrasiri, Nambage Dona Priyani Dhammika; Indika, Neluwa Liyanage Ruwan; Ratnayake, Pyara Dilani; Gunasekara, Vindya Nandani; Fairbanks, Lynette Dianne; Stiburkova, Blanka
Uric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine. CASE 1: A one-and-half-year-old boy was investigated for haematuria and a calculus in the bladder. Xanthine crystals were seen in microscopic examination of urine sediment. Low uric acid concentrations in serum and low urinary fractional excretion of uric acid associated with high urinary excretion of xanthine and hypoxanthine were compatible with xanthine oxidase deficiency. CASE 2: An 8-month-old boy presented with intractable seizures, feeding difficulties, screaming episodes, microcephaly, facial dysmorphism and severe neuro developmental delay. Low uric acid level in serum, low fractional excretion of uric acid and radiological findings were consistent with possible molybdenum cofactor deficiency. Diagnosis was confirmed by elevated levels of xanthine, hypoxanthine and sulfocysteine levels in urine. CASE 3: A 3-year-10-month-old boy presented with global developmental delay, failure to thrive, dystonia and self-destructive behaviour. High uric acid levels in serum, increased fractional excretion of uric acid and absent hypoxanthine-guanine phosphoribosyltransferase enzyme level confirmed the diagnosis of Lesch-Nyhan syndrome. CASE 4: A 9-year-old boy was investigated for lower abdominal pain, gross haematuria and right renal calculus. Low uric acid level in serum and increased fractional excretion of uric acid pointed towards hereditary renal hypouricaemia which was confirmed by genetic studies. Abnormal uric acid level in blood and urine is a valuable tool in screening for clinical conditions related to derangement of the nucleic acid metabolic pathway.
Koren, Omry; Knezevic, Vishnia; Ron, Eliora Z; Rosenberg, Eugene
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.
Takeuchi, Y.; Miyashita, Y.; Mizukawa, Y.; Iwasaka, M.
The present study focuses on the magnetic behavior of uric acid crystals, which are responsible for gout. Under a sub-Tesla (T)-level magnetic field, rotational motion of the crystals, which were caused by diamagnetic torque, was observed. We used horizontal magnetic fields with a maximum magnitude of 500 mT generated by an electromagnet to observe the magnetic orientation of the uric acid microcrystals by a microscope. The uric acid crystals showed a perpendicular magnetic field orientation with a minimum threshold of 130 mT. We speculate that the distinct diamagnetic anisotropy in the uric acid crystals resulted in their rotational responses.
Sutin, Angelina R.; Cutler, Roy G.; Camandola, Simonetta; Uda, Manuela; Feldman, Neil H.; Cucca, Francesco; Zonderman, Alan B.; Mattson, Mark P.; Ferrucci, Luigi; Schlessinger, David; Terracciano, Antonio
Background The ability to control impulses varies greatly, and difficulty with impulse control can have severe consequences; in the extreme, it is the defining feature of many psychiatric disorders. Evidence from disparate lines of research suggests that uric acid is elevated in psychiatric disorders characterized by high impulsivity, such as ADHD and bipolar disorder. The present research tests the hypothesis that impulsivity is associated with higher uric acid in humans and mice. Methods Using two longitudinal, non-clinical community samples (total N=6883), we test whether there is an association between uric acid and normal variation in trait impulsivity measured with the Revised NEO Personality Inventory. We also examined the effect of uric acid on behavior by comparing wild-type mice (WT), which naturally have low levels of uric acid, to mice genetically modified (UOX) to accumulate high levels of uric acid. Results In both human samples, the emotional aspects of trait impulsivity, specifically Impulsiveness and Excitement-Seeking, were associated with higher levels of uric acid concurrently and when uric acid was measured 3–5 years later. Consistent with the human data, the UOX mice displayed significantly more exploratory and novelty-seeking behavior than the WT mice. Conclusion Higher uric acid was associated with impulsivity in both humans and mice. The identification of biological markers of impulsivity may lead to a better understanding of the physiological mechanisms involved in impulsivity, and may suggest potential targets for therapeutic intervention. PMID:23582268
Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min
Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017. Published by Elsevier B.V.
Crane, John K.; Mongiardo, Krystin M.
Uric acid can be generated in the gastrointestinal (GI) tract from the breakdown of nucleotides ingested in the diet or from purines released from host cells as a result of pathogen-induced cell damage. Xanthine oxidase (XO) is the enzyme that converts hypoxanthine or xanthine into uric acid, a reaction that also generates hydrogen peroxide. It has been assumed that the product of XO responsible for the pro-inflammatory effects of this enzyme is hydrogen peroxide. Recent literature on uric acid, however, has indicated that uric acid itself may have biological effects. We tested whether uric acid itself has detectable pro-inflammatory effects using an in vivo model using ligated rabbit intestinal segments (“loops”) as well as in vitro assays using cultured cells. Addition of exogenous uric acid increased the influx of heterophils into rabbit intestinal loops, as measured by myeloperoxidase activity. In addition, white blood cells adhered avidly to uric acid crystals, forming large aggregates of cells. Uric acid acts as a leukocyte chemoattractant in the GI tract. The role of uric acid in enteric infections and in non-infectious disorders of the GI tract deserves more attention. PMID:24377830
Meadows, J; Smith, R C; Reeves, J
Aqueous preparations of linolenic acid, bovine serum albumin, and bovine erythrocyte membrane fragments were bubbled with ozone in the presence or absence of uric acid. Ozonation of the membrane fragments or the bovine serum albumin did not result in protein degradation. After 15 min of ozonation, the absorbance of the thiobarbituric acid-reactive material increased by 0.34 in the linolenic acid preparation and by 0.08 in the suspension of membrane fragments. In the presence of uric acid, these changes in absorbance were reduced to 0.14 for the fatty acid and to 0.01 for the membrane fragments. This result indicates that uric acid protects lipids from ozone-induced oxidation.
Kanbara, Aya; Miura, Yoshisuke; Hyogo, Hideyuki; Chayama, Kazuaki; Seyama, Issei
The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Within the framework of the Japanese government's health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl-,SO42-,PO4-) necessary for the estimation of acid-base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42-] + organic acid - gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] - [HCO3-]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as
Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid
Shankar, Anoop; Xiao, Jie; Ducatman, Alan
Perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, are man-made chemicals that have been detected in the blood of over 98% of the US population. Serum uric acid is a novel biomarker, even mild elevations of which has been implicated in the development of hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. We examined the relationship of serum perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, and elevated uric acid levels in a representative sample of US adults. We examined 3883 participants from the 1999-2000 and 2003-2006 National Health and Nutritional Examination Surveys, a representative, multiethnic population-based survey of noninstitutionalized US adults. Serum perfluorooctanoic acid and perfluorooctane sulfonate were analyzed as quartiles. The main outcome was hyperuricemia. We found that serum levels of perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with hyperuricemia. This association appeared to be independent of confounders such as age, gender, race-ethnicity, body mass index, diabetes, hypertension, and serum cholesterol. Compared with subjects in quartile 1 (referent), the multivariate odds ratio for hyperuricemia among subjects in quartile 4 was 1.97 (95% confidence interval 1.44-2.70, P < 0.0001) for perfluorooctanoic acid and 1.48% (95% confidence interval 0.99-2.22, P = 0.0433) for perfluorooctane sulfonate. This observed association persisted in subgroup analysis by gender and body mass index. Our results demonstrate that elevated levels of perfluoroalkyl chemicals are associated with hyperuricemia even at low perfluoroalkyl chemical exposure levels as seen in the US general population.
Shankar, Anoop; Xiao, Jie; Ducatman, Alan
Background: Perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, are man-made chemicals that have been detected in the blood of over 98% of the US population. Serum uric acid is a novel biomarker, even mild elevations of which has been implicated in the development of hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. We examined the relationship of serum perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, and elevated uric acid levels in a representative sample of US adults. Methods: We examined 3883 participants from the 1999–2000 and 2003–2006 National Health and Nutritional Examination Surveys, a representative, multiethnic population-based survey of noninstitutionalized US adults. Serum perfluorooctanoic acid and perfluorooctane sulfonate were analyzed as quartiles. The main outcome was hyperuricemia. Results: We found that serum levels of perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with hyperuricemia. This association appeared to be independent of confounders such as age, gender, race-ethnicity, body mass index, diabetes, hypertension, and serum cholesterol. Compared with subjects in quartile 1 (referent), the multivariate odds ratio for hyperuricemia among subjects in quartile 4 was 1.97 (95% confidence interval 1.44–2.70, P < 0.0001) for perfluorooctanoic acid and 1.48% (95% confidence interval 0.99–2.22, P = 0.0433) for perfluorooctane sulfonate. This observed association persisted in subgroup analysis by gender and body mass index. Conclusion: Our results demonstrate that elevated levels of perfluoroalkyl chemicals are associated with hyperuricemia even at low perfluoroalkyl chemical exposure levels as seen in the US general population. PMID:22003309
Rule, Andrew D.; Fridley, Brooke L.; Hunt, Steven C.; Asmann, Yan; Boerwinkle, Eric; Pankow, James S.; Mosley, Thomas H.; Turner, Stephen T.
Background. Uric acid is heritable and associated with hypertension and insulin resistance. We sought to identify genomic regions influencing serum uric acid in families in which two or more siblings had hypertension. Methods. Uric acid levels and microsatellite markers were assayed in the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort (1075 whites and 1333 blacks) and the Hypertension Genetic Epidemiology Network (HyperGEN) cohort (1542 whites and 1627 blacks). Genome-wide linkage analyses of uric acid and bivariate linkage analyses of uric acid with an additional surrogate of insulin resistance were completed. Pathway analysis explored gene sets enriched at loci influencing uric acid. Results. In the GENOA white cohort, loci influencing uric acid were identified on chromosome 8 at 135 cM [multipoint logarithm of odds score (MLS) = 2.4], on chromosome 9 at 113 cM (MLS = 3.7) and on chromosome 16 at 93 cM (MLS = 2.3), but did not replicate in HyperGEN. At these loci, there was evidence of pleiotropy with other surrogates of insulin resistance and genes in the fructose and mannose metabolism pathway were enriched. In the HyperGEN-black cohort, there was some evidence of a locus for uric acid on chromosome 4 at 135 cM (MLS = 2.4) that had modest replication in GENOA (MLS = 1.2). Conclusions. Several novel loci linked to uric acid were identified but none showed clear replication. Widespread diuretic use, a medication that raises uric acid levels, was an important study limitation. Bivariate linkage analyses and pathway analysis were consistent with genes regulating insulin resistance and fructose metabolism contributing to the heritability of uric acid. PMID:19258383
Huff, Ryan D; Hsu, Alan C-Y; Nichol, Kristy S; Jones, Bernadette; Knight, Darryl A; Wark, Peter A B; Hansbro, Philip M; Hirota, Jeremy A
The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines.
Pasalic, Daria; Marinkovic, Natalija; Feher-Turkovic, Lana
With considering serum concentration of the uric acid in humans we are observing hyperuricemia and possible gout development. Many epidemiological studies have shown the relationship between the uric acid and different disorders such are obesity, metabolic syndrome, hypertension and coronary artery disease. Clinicians and investigators recognized serum uric acid concentration as very important diagnostic and prognostic factor of many multifactorial disorders. This review presented few clinical conditions which are not directly related to uric acid, but the concentrations of uric acid might have a great impact in observing, monitoring, prognosis and therapy of such disorders. Uric acid is recognized as a marker of oxidative stress. Production of the uric acid includes enzyme xanthine oxidase which is involved in producing of radical-oxigen species (ROS). As by-products ROS have a significant role in the increased vascular oxidative stress and might be involved in atherogenesis. Uric acid may inhibit endothelial function by inhibition of nitric oxide-function under conditions of oxidative stress. Down regulation of nitric oxide and induction of endothelial dysfunction might also be involved in pathogenesis of hypertension. The most important and well evidenced is possible predictive role of uric acid in predicting short-term outcome (mortality) in acute myocardial infarction (AMI) patients and stroke. Nephrolithiasis of uric acid origin is significantly more common among patients with the metabolic syndrome and obesity. On contrary to this, uric acid also acts is an “antioxidant”, a free radical scavenger and a chelator of transitional metal ions which are converted to poorly reactive forms. PMID:22384520
Gersch, Christine; Palii, Sergiu P.; Imaram, Witcha; Kim, Kyung Mee; Karumanchi, S. Ananth; Angerhofer, Alexander; Johnson, Richard J.; Henderson, George N.
Hyperuricemia is associated with hypertension, metabolic syndrome, preeclampsia, cardiovascular disease and renal disease, all conditions associated with oxidative stress. We hypothesized that uric acid, a known antioxidant, might become prooxidative following its reaction with oxidants; and, thereby contribute to the pathogenesis of these diseases. Uric acid and 1,3-15N2-uric acid were reacted with peroxynitrite in different buffers and in the presence of alcohols, antioxidants and in human plasma. The reaction products were identified using liquid chromatography-mass spectrometry (LC-MS) analyses. The reactions generate reactive intermediates that yielded triuret as their final product. We also found that the antioxidant, ascorbate, could partially prevent this reaction. Whereas triuret was preferentially generated by the reactions in aqueous buffers, when uric acid or 1,3-15N2-uric acid was reacted with peroxynitrite in the presence of alcohols, it yielded alkylated alcohols as the final product. By extension, this reaction can alkylate other biomolecules containing OH groups and others containing labile hydrogens. Triuret was also found to be elevated in the urine of subjects with preeclampsia, a pregnancy-specific hypertensive syndrome that is associated with oxidative stress, whereas very little triuret is produced in normal healthy volunteers. We conclude that under conditions of oxidative stress, uric acid can form reactive intermediates, including potential alkylating species, by reacting with peroxynitrite. These reactive intermediates could possibly explain how uric acid contributes to the pathogenesis of diseases such as the metabolic syndrome and hypertension. PMID:19219741
Kim, Jayoung; Imani, Somayeh; de Araujo, William R.; Warchall, Julian; Valdés-Ramírez, Gabriela; Paixão, Thiago R.L.C.; Mercier, Patrick P.; Wang, Joseph
This article demonstrates an instrumented mouthguard capable of non-invasively monitoring salivary uric acid (SUA) levels. The enzyme (uricase)-modified screen printed electrode system has been integrated onto a mouthguard platform along with anatomically-miniaturized instrumentation electronics featuring a potentiostat, microcontroller, and a Bluetooth Low Energy (BLE) transceiver. Unlike RFID-based biosensing systems, which require large proximal power sources, the developed platform enables real-time wireless transmission of the sensed information to standard smartphones, laptops, and other consumer electronics for on-demand processing, diagnostics, or storage. The mouthguard biosensor system offers high sensitivity, selectivity, and stability towards uric acid detection in human saliva, covering the concentration ranges for both healthy people and hyperuricemia patients. The new wireless mouthguard biosensor system is able to monitor SUA level in real-time and continuous fashion, and can be readily expanded to an array of sensors for different analytes to enable an attractive wearable monitoring system for diverse health and fitness applications. PMID:26276541
Kim, Jayoung; Imani, Somayeh; de Araujo, William R; Warchall, Julian; Valdés-Ramírez, Gabriela; Paixão, Thiago R L C; Mercier, Patrick P; Wang, Joseph
This article demonstrates an instrumented mouthguard capable of non-invasively monitoring salivary uric acid (SUA) levels. The enzyme (uricase)-modified screen printed electrode system has been integrated onto a mouthguard platform along with anatomically-miniaturized instrumentation electronics featuring a potentiostat, microcontroller, and a Bluetooth Low Energy (BLE) transceiver. Unlike RFID-based biosensing systems, which require large proximal power sources, the developed platform enables real-time wireless transmission of the sensed information to standard smartphones, laptops, and other consumer electronics for on-demand processing, diagnostics, or storage. The mouthguard biosensor system offers high sensitivity, selectivity, and stability towards uric acid detection in human saliva, covering the concentration ranges for both healthy people and hyperuricemia patients. The new wireless mouthguard biosensor system is able to monitor SUA level in real-time and continuous fashion, and can be readily expanded to an array of sensors for different analytes to enable an attractive wearable monitoring system for diverse health and fitness applications. Copyright © 2015 Elsevier B.V. All rights reserved.
Guan, Weihua; Reed, Mark A
An enzyme-free redox potential sensor using off-chip extended-gate field effect transistor (EGFET) with a ferrocenyl-alkanethiol modified gold electrode has been used to quantify uric acid concentration in human serum and urine. Hexacyanoferrate (II) and (III) ions are used as redox reagent. The potentiometric sensor measures the interface potential on the ferrocene immobilized gold electrode, which is modulated by the redox reaction between uric acid and hexacyanoferrate ions. The device shows a near Nernstian response to uric acid and is highly specific to uric acid in human serum and urine. The interference that comes from glucose, bilirubin, ascorbic acid, and hemoglobin is negligible in the normal concentration range of these interferents. The sensor also exhibits excellent long term reliability and is regenerative. This extended gate field effect transistor based sensor is promising for point-of-care detection of uric acid due to the small size, low cost, and low sample volume consumption.
Hafez, Rehab M; Abdel-Rahman, Tahany M; Naguib, Rasha M
Uric acid increased accumulation and/or reduced excretion in human bodies is closely related to pathogenesis of gout and hyperuricemia. It is highly affected by the high intake of food rich in purine. Uric acid is present in both higher plants and microorganisms with species dependent concentration. Urate-degrading enzymes are found both in plants and microorganisms but the mechanisms by which plant degrade uric acid was found to be different among them. Higher plants produce various metabolites which could inhibit xanthine oxidase and xanthine oxidoreductase, so prohibit the oxidation of hypoxanthine to xanthine then to uric acid in the purine metabolism. However, microorganisms produce group of degrading enzymes uricase, allantoinase, allantoicase and urease, which catalyze the degradation of uric acid to the ammonia. In humans, researchers found that several mutations caused a pseudogenization (silencing) of the uricase gene in ancestral apes which exist as an insoluble crystalloid in peroxisomes. This is in contrast to microorganisms in which uricases are soluble and exist either in cytoplasm or peroxisomes. Moreover, many recombinant uricases with higher activity than the wild type uricases could be induced successfully in many microorganisms. The present review deals with the occurrence of uric acid in plants and other organisms specially microorganisms in addition to the mechanisms by which plant extracts, metabolites and enzymes could reduce uric acid in blood. The genetic and genes encoding for uric acid in plants and microorganisms are also presented.
Xia, Xi; Luo, Qimei; Li, Bin; Lin, Zhenchuan; Yu, Xueqing; Huang, Fengxian
Studies have shown inconsistent results about the association between serum uric acid levels and mortality in patients with chronic kidney disease (CKD). A systematic literature search in MEDLINE, Web of Science and bibliographies of retrieved articles was performed to identify studies investigating the association between serum uric acid and mortality in patients with CKD. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were calculated using random-effects models. A total of 24 studies with 25,453 patients with CKD were included. By meta-analysis, patients with the highest serum uric acid level were associated with a significantly higher risk for mortality (14 studies; HR, 1.52; 95% CI, 1.33-1.73) compared with patients with the lowest serum uric acid level. For dose-response analysis, a linear relationship (8 studies; Pfor non-linearity=0.14) between serum uric acid levels and risk of mortality was found. Overall, an increase of 1mg/dl in serum uric acid level was associated with an 8% increased risk of mortality (21 studies; HR, 1.08; 95% CI, 1.04-1.11). Elevated serum uric acid levels are significantly associated with risk of mortality in patients with CKD. Further randomized controlled trials should attempt to determine whether it improves survival to target serum uric acid in patients with CKD. Copyright © 2016 Elsevier Inc. All rights reserved.
Oğuz, Nurgül; Kırça, Mustafa; Çetin, Arzu; Yeşilkaya, Akın
Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.
Ahmadieh, Hala; Azar, Sami
Hyperuricemia has been linked to metabolic syndrome, cardiovascular disease, and chronic kidney disease. Hyperuricemia and type 2 diabetes mellitus were inter-related, type 2 diabetes mellitus was more at risk of having a higher serum uric acid level, and also individuals with higher serum uric acid had higher risk of developing type 2 diabetes in the future. Insulin resistance seems to play an important role in the causal relationship between metabolic syndrome, type 2 diabetes, and hyperuricemia. Oral diabetic drugs that would have additional beneficial effects on reducing serum uric acid levels are of importance. Selective SGLT2 inhibitors were extensively studied in type 2 diabetes mellitus and were found to have improvement of glycemic control, in addition to their proven metabolic effects on weight and blood pressure. Additional beneficial effect of SGLT2 inhibitors on serum uric acid level reduction is investigated. Recently, data have been accumulating showing that they have additional beneficial effects on serum uric acid reduction. As for the postulated mechanism, serum uric acid decreased in SGLT2 inhibitor users as a result of the increase in the urinary excretion rate of uric acid, due to the inhibition of uric acid reabsorption mediated by the effect of the drug on the GLUT9 isoform 2, located at the collecting duct of the renal tubule.
We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects. PMID:27652270
Li, Hui-Zhang; Chen, Zhi; Hou, Cang-Long; Tang, Yi-Xing; Wang, Fei; Fu, Qing-Ge
To investigate the effect of uric acid on the osteogenic and adipogenic differentiation of human bone mesenchymal stem cells (hBMSCs). The hBMSCs were isolated from bone marrow of six healthy donors. Cell morphology was observed by microscopy and cell surface markers (CD44 and CD34) of hBMSCs were analyzed by immunofluorescence. Cell morphology and immunofluorescence analysis showed that hBMSCs were successfully isolated from bone marrow. The number of hBMSCs in uric acid groups was higher than that in the control group on day 3, 4, and 5. Alizarin red staining showed that number of calcium nodules in uric acid groups was more than that of the control group. Oil red-O staining showed that the number of red fat vacuoles decreased with the increased concentration of uric acid. In summary, uric acid could promote the proliferation and osteogenic differentiation of hBMSCs while inhibit adipogenic differentiation of hBMSCs.
Wang, Yu; Lin, Zhijian; Zhang, Bing; Nie, Anzheng; Bian, Meng
Excessive production and/or reduced excretion of uric acid could lead to hyperuricemia, which could be a major cause of disability. Hyperuricemia has received increasing attention in the last few decades due to its global prevalence. Cichorium intybus L., commonly known as chicory, is a perennial herb of the asteraceae family. It was previously shown to exert potent hypouricemic effects linked with decreasing uric acid formation in the liver by down-regulating the activity of xanthine oxidase, and increasing uric acid excretion by up-regulating the renal OAT3 mRNA expression. The present study aimed to evaluate its extra-renal excretion and possible molecular mechanism underlying the transporter responsible for intestinal uric acid excretion in vivo. Chicory was administered intragastrically to hyperuricemic rats induced by drinking 10% fructose water. The uricosuric effect was evaluated by determining the serum uric acid level as well as the intestinal uric acid excretion by HPLC. The location and expression levels of ATP-binding cassette transporter, sub-family G, member 2 (ABCG2) in jejunum and ileum were analyzed. The administration of chicory decreased the serum uric acid level significantly and increased the intestinal uric acid excretion obviously in hyperuricemic rats induced by 10% fructose drinking. Staining showed that ABCG2 was expressed in the apical membrane of the epithelium and glands of the jejunum and ileum in rats. Further examination showed that chicory enhanced the mRNA and protein expressions of ABCG2 markedly in a dose-dependent manner in jejunum and ileum. These findings indicate that chicory increases uric acid excretion by intestines, which may be related to the stimulation of intestinal uric acid excretion via down-regulating the mRNA and protein expressions of ABCG2.
Wang, Wen-Ling; Sheu, Shi-Yuan; Huang, Wen-Dar; Chuang, Ya-Ling; Tseng, Han-Chun; Hwang, Tzann-Shun; Fu, Yuan-Tsung; Kuo, Yueh-Hsiung; Yao, Chun-Hsu; Kuo, Tzong-Fu
Background: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time. Materials and Methods: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration. Results: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 μg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents. SUMMARY Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n-hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP
Kumagai, Takanori; Ota, Tatsuru; Tamura, Yoshifuru; Chang, Wen Xiu; Shibata, Shigeru; Uchida, Shunya
Uric acid (UA) remains a possible risk factor of chronic kidney disease (CKD) but its potential role should be elucidated given a fact that multidisciplinary treatments assure a sole strategy to inhibit the progression to end-stage renal disease (ESRD). In clinical setting, most observational studies showed that elevation of serum uric acid (SUA) independently predicts the incidence and the development of CKD. The meta-analysis showed that SUA-lowering therapy with allopurinol may retard the progression of CKD but did not reach conclusive results due to small-sized studies. Larger scale, randomized placebo-controlled trials to assess SUA-lowering therapy are needed. Our recent analysis by propensity score methods has shown that the threshold of SUA should be less than 6.5 mg/dL to abrogate ESRD. In animal models an increase in SUA by the administration of oxonic acid, uricase inhibitor, or nephrectomy can induce glomerular hypertension, arteriolosclerosis including afferent arteriolopathy and tubulointerstitial fibrosis. The ever-growing discoveries of urate transporters prompt us to learn UA metabolism in the kidney and intestine. One example is that the intestinal ABCG2 may play a compensatory role at face of decreased renal clearance of UA in nephrectomized rats, the trigger of which is not a uremic toxin but SUA itself. This review will summarize the recent knowledge on the relationship between SUA and the kidney and try to draw a conclusion when and how to treat asymptomatic hyperuricemia accompanied by CKD. Finally we will address a future perspective on UA study including a Mendelian randomization approach.
Chakraborti, Goutam; Biswas, Rabindranath; Chakraborti, Sandip; Sen, Pradyot Kumar
Background: Lichen planus (LP) is a common disorder whose etiopathogenesis is not clear. Recently, it has been suggested that increased reactive oxygen species (ROS) play important roles in the underlying mechanism of LP. Objectives: The principal aim of this study was to evaluate serum uric acid (UA) levels as a measure of the antioxidant defense status in LP patients. Methods: Serum UA levels were determined in 58 LP patients and 61 controls. Results: Serum UA levels were significantly decreased in patients with respect to controls. Moreover, serum UA level was decreased according to increasing duration of disease. Conclusions: The results of our study suggest that LP is associated with decrease of UA levels in serum. UA may be a potential, useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring. PMID:25484383
Sato, Masanobu; Wakayama, Tomohiko; Mamada, Hideaki; Shirasaka, Yoshiyuki; Nakanishi, Takeo; Tamai, Ikumi
Uric acid transporter URAT1 contributes significantly to reabsorption of uric acid in humans to maintain a constant serum uric acid (SUA) level. Since alteration of SUA level is associated with various diseases, it is important to clarify the mechanism of change in SUA. However, although expression of mRNA of an ortholog of URAT1 (rUrat1) in rats has been reported, functional analysis and localization have not been done. Therefore, rat rUrat1 was functionally analyzed using gene expression systems and isolated brush-border membrane vesicles (BBMVs) prepared from rat kidney, and its localization in kidney was examined immunohistochemically. Uric acid transport by rUrat1 was chloride (Cl-) susceptible with a Km of 1773μM. It was inhibited by benzbromarone and trans-stimulated by lactate and pyrazinecarboxylic acid (PZA). Cl- gradient-susceptible uric acid transport by BBMVs showed similar characteristics to those of uric acid transport by rUrat1. Moreover, rUrat1 was localized at the apical membrane in proximal tubular epithelial cells in rat kidney. Accordingly, rUrat1 is considered to be involved in uric acid reabsorption in rats in the same manner as URAT1 in humans. Therefore, rUrat1 may be a useful model to study issues related to the role of human URAT1.
Kono, Hajime; Chen, Chun-Jen; Ontiveros, Fernando; Rock, Kenneth L.
Necrosis stimulates inflammation, and this response is medically relevant because it contributes to the pathogenesis of a number of diseases. It is thought that necrosis stimulates inflammation because dying cells release proinflammatory molecules that are recognized by the immune system. However, relatively little is known about the molecular identity of these molecules and their contribution to responses in vivo. Here, we investigated the role of uric acid in the inflammatory response to necrotic cells in mice. We found that dead cells not only released intracellular stores of uric acid but also produced it in large amounts postmortem as nucleic acids were degraded. Using newly developed Tg mice that have reduced levels of uric acid either intracellularly and/or extracellularly, we found that uric acid depletion substantially reduces the cell death–induced inflammatory response. Similar results were obtained with pharmacological treatments that reduced uric acid levels either by blocking its synthesis or hydrolyzing it in the extracellular fluids. Importantly, uric acid depletion selectively inhibited the inflammatory response to dying cells but not to microbial molecules or sterile irritant particles. Collectively, our data identify uric acid as a proinflammatory molecule released from dying cells that contributes significantly to the cell death–induced inflammatory responses in vivo. PMID:20501947
Mujahid, Adnan; Khan, Aimen Idrees; Afzal, Adeel; Hussain, Tajamal; Raza, Muhammad Hamid; Shah, Asma Tufail; uz Zaman, Waheed
Molecularly imprinted titania nanoparticles are su ccessfully synthesized by sol-gel method for the selective recognition of uric acid. Atomic force microscopy is used to study the morphology of uric acid imprinted titania nanoparticles with diameter in the range of 100-150 nm. Scanning electron microscopy images of thick titania layer indicate the formation of fine network of titania nanoparticles with uniform distribution. Molecular imprinting of uric acid as well as its subsequent washing is confirmed by Fourier transformation infrared spectroscopy measurements. Uric acid rebinding studies reveal the recognition capability of imprinted particles in the range of 0.01-0.095 mmol, which is applicable in monitoring normal to elevated levels of uric acid in human blood. The optical shift (signal) of imprinted particles is six times higher in comparison with non-imprinted particles for the same concentration of uric acid. Imprinted titania particles have shown substantially reduced binding affinity toward interfering and structurally related substances, e.g. ascorbic acid and guanine. These results suggest the possible application of titania nanoparticles in uric acid recognition and quantification in blood serum.
Giraud-Billoud, Maximiliano; Abud, María A; Cueto, Juan A; Vega, Israel A; Castro-Vazquez, Alfredo
The physiological ability to estivate is relevant for the maintenance of population size in the invasive Pomacea canaliculata. However, tissue reoxygenation during arousal from estivation poses the problem of acute oxidative stress. Uric acid is a potent antioxidant in several systems and it is stored in specialized tissues of P. canaliculata. Changes in tissue concentration of thiobarbituric acid reactive substances (TBARS), uric acid and allantoin were measured during estivation and arousal in P. canaliculata. Both TBARS and uric acid increased two-fold during 45 days estivation, probably as a consequence of concomitant oxyradical production during uric acid synthesis by xanthine oxidase. However, after arousal was induced, uric acid and TBARS dropped to or near baseline levels within 20 min and remained low up to 24h after arousal induction, while the urate oxidation product allantoin continuously rose to a maximum at 24h after induction, indicating the participation of uric acid as an antioxidant during reoxygenation. Neither uric acid nor allantoin was detected in the excreta during this 24h period. Urate oxidase activity was also found in organs of active snails, but activity shut down during estivation and only a partial and sustained recovery was observed in the midgut gland.
Perna, Laura; Mons, Ute; Schöttker, Ben; Brenner, Hermann
Several studies reported an association between concentrations of serum uric acid and cognitive function, but the evidence is contradictory. It is known that uric acid is associated with cardiovascular diseases, especially among women. Stratifying by sex and history of cardiovascular disease may clarify whether uric acid is an independent risk factor for cognitive dysfunction. A population-based study was conducted in the German State of Saarland. A subgroup of participants aged ≥70years underwent a comprehensive assessment of cognitive function. Linear regression models and restricted cubic spline functions were used to assess association of uric acid with cognitive performance in 1144 study participants. High levels of uric acid were associated with worse cognitive performance among women (-0.57; 95% CI: -1.10 to -0.04) but not among men (-0.12; 95% CI: -0.64 to 0.39). The association was much stronger among the subgroup of women with cardiovascular diseases (-1.91; 95% CI: -3.15 to -0.67) and also revealed a dose-response relationship in this subgroup. Serum uric acid showed an inverse association with cognitive function among women and the association was amplified by the presence of cardiovascular disease. These results highlight the importance of stratifying by sex and cardiovascular disease in future studies on uric acid and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.
Raeisi, A; Ostovar, A; Vahdat, K; Rezaei, P; Darabi, H; Moshtaghi, D; Nabipour, I
To explore the independent correlation between serum uric acid and low-grade inflammation (measured by high-sensitivity C-reactive protein, hs-CRP) in postmenopausal women. A total of 378 healthy Iranian postmenopausal women were randomly selected in a population-based study. Circulating hs-CRP levels were measured by highly specific enzyme-linked immunosorbent assay method and an enzymatic calorimetric method was used to measure serum levels of uric acid. Pearson correlation coefficient, multiple linear regression and logistic regression models were used to analyze the association between uric acid and hs-CRP levels. A statistically significant correlation was seen between serum levels of uric acid and log-transformed circulating hs-CRP (r = 0.25, p < 0.001). After adjustment for age and cardiovascular risk factors (according to NCEP ATP III criteria), circulating hs-CRP levels were significantly associated with serum uric acid levels (β = 0.20, p < 0.001). After adjustment for age and cardiovascular risk factors, hs-CRP levels ≥3 mg/l were significantly associated with higher uric acid levels (odds ratio =1.52, 95% confidence interval 1.18-1.96). Higher serum uric acid levels were positively and independently associated with circulating hs-CRP in healthy postmenopausal women.
Bartoli, Francesco; Crocamo, Cristina; Gennaro, Giulia Maria; Castagna, Gloria; Trotta, Giulia; Clerici, Massimo; Carrà, Giuseppe
Recent evidence shows that bipolar disorder might be associated with a purinergic system dysfunction. This study aimed at (i) testing the association between bipolar disorder and uric acid serum levels, and (ii) clarifying whether this relationship is mediated by metabolic syndrome and other relevant metabolic parameters. Patients consecutively admitted to a Mental Health Inpatient Unit, with a diagnosis of bipolar disorder or other severe mental disorders, and an appropriate healthy control sample, were included in this cross-sectional, exploratory study. We performed linear regression analyses, to explore factors associated with uric acid levels, and formal tests of mediation to assess mediating effect of candidate variables. 176 individuals with mental disorders and 89 healthy controls met inclusion criteria. Bipolar disorder was the only diagnostic subgroup significantly associated with increased uric acid levels. Furthermore, male gender, metabolic syndrome, as well as abdominal circumference and triglycerides levels, had a significant effect on uric acid. Relevant mediation analyses showed that the estimated effect between bipolar disorder and uric acid levels was only partially mediated by metabolic abnormalities. This study suggests a direct association between bipolar disorder and uric acid levels, only partially mediated by metabolic abnormalities. It seems consistent with results of previous studies highlighting a purinergic dysfunction in bipolar disorder and the role that purinergic modulators, lowering uric acid levels, could have in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.
Broome, Jacqueline E.; Lis, Agnieszka
In previous work, we identified xanthine oxidase (XO) as an important enzyme in the interaction between the host and enteropathogenic Escherichia coli (EPEC) and Shiga-toxigenic E. coli (STEC). Many of the biological effects of XO were due to the hydrogen peroxide produced by the enzyme. We wondered, however, if uric acid generated by XO also had biological effects in the gastrointestinal tract. Uric acid triggered inflammatory responses in the gut, including increased submucosal edema and release of extracellular DNA from host cells. While uric acid alone was unable to trigger a chloride secretory response in intestinal monolayers, it did potentiate the secretory response to cyclic AMP agonists. Uric acid crystals were formed in vivo in the lumen of the gut in response to EPEC and STEC infections. While trying to visualize uric acid crystals formed during EPEC and STEC infections, we noticed that uric acid crystals became enmeshed in the neutrophilic extracellular traps (NETs) produced from host cells in response to bacteria in cultured cell systems and in the intestine in vivo. Uric acid levels in the gut lumen increased in response to exogenous DNA, and these increases were enhanced by the actions of DNase I. Interestingly, addition of DNase I reduced the numbers of EPEC bacteria recovered after a 20-h infection and protected against EPEC-induced histologic damage. PMID:26787720
Chen, X B; Calder, A G; Prasitkusol, P; Kyle, D J; Jayasuriya, M C
A method for the determination of 15N enrichment and concentration of allantoin and uric acid simultaneously in urine using gas chromatography/mass spectrometry (GC/MS) is described. The urine samples contained [1,3-15N2] uric acid and its oxidation product allantoin. The uric acid and allantoin were isolated using an AG1-X8 (Cl-form) anion-exchange column and heated with a mixture containing 1:1 dimethylformamide and N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA). The tert-butyldimethylsilyl (TBDMS) derivatives of allantoin and uric acid formed were injected into a gas chromatograph interfaced with a mass spectrometer operated under electron impact ionization conditions. Isotope ratio measurements were made from the abundance of the M-57 ions at m/z 398, 399 and 400 for allantoin and at m/z 567 and 569 for uric acid. 15N2 allantoin (99 at.%) was produced from [1,3-15N2] uric acid by treatment with uricase and used as a standard. Quantitation of allantoin and uric acid was based on isotopic dilution by spiking the urine sample with known quantities of 99 at.% [15N] uric acid and allantoin internal standards. The observed isotope ratio measurements from the prepared standards matched the theoretical values. Coefficients of variation in measurements of isotope ratio and concentration were 0.2 and 0.5%, respectively. The method was applied in a study to measure the urinary recovery of [1,3-15N2] uric acid continuously infused for 8-10 h into the blood of four sheep each on two occasions. Within 24 h, 65.9 +/- 9.1% of the tracer was excreted in the urine unchanged. Little was converted into allantoin (approximately 7% of the dose). The total recovery (5 days) of the infused tracer averaged 69.5 +/- 7.6% as uric acid and 76.8 +/- 9.3% as the sum of uric acid and allantoin. Uricase activities in plasma, liver and kidney of sheep were also measured using [1,3-15N2] uric acid as a substrate. Uricase activity was estimated to be 0.6 mU g-1 wet tissue in
Ryu, Wi-Sun; Kim, Chi Kyung; Kim, Beom Joon; Lee, Seung-Hoon
Unlike experimental studies indicating a neuroprotective property of uric acid, clinical studies have shown that elevated levels of uric acid are associated with a risk of ischemic stroke. However, the association of uric acid with cerebral hemorrhage has seldom been tested. We aimed to elucidate the association between uric acid and cerebral microbleeds (CMBs), a hemorrhage-prone cerebral microangiopathy. Seven hundred twenty-four patients with ischemic stroke who were consecutively admitted to our hospital were included in this study. We collected demographic, clinical, and laboratory data, including uric acid level, and examined the presence of CMBs using T2*-weighted gradient-echo MRI. We used logistic regression analysis to examine an independent association between uric acid and CMBs. Two-hundred twenty-six patients had CMBs (31.2%). After adjusting for possible confounders, elevated uric acid was independently associated with the presence of CMBs (the highest quartile vs. lowest quartile, adjusted odd ratio [OR], 1.98; 95% confidence interval [CI], 1.16–3.39). This association retained in patients with deep or infratentorial CMBs (with or without lobar CMBs) but not among those with lobar CMBs. In addition, this association was robust among patients with hypertension (the highest quartile vs. lowest quartile, adjusted OR, 2.74; 95% CI, 1.43–5.24). In contrast, we did not find the association in patients without hypertension. We demonstrated that serum uric acid is independently associated with the presence of CMBs. In particular, the relation between uric acid and CMBs was robust in hypertensive patients. PMID:23372838
Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja
Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p <2 × 10(-6)) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10(-7). We observed a strong association (p < 8 × 10(-8)) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10(-6), MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.
Nuccio, Eugene; McFann, Kim; Madero, Magdalena; Sarnak, Mark J.; Jalal, Diana
BACKGROUND Uric acid is associated with increased risk of cardiovascular disease and arterial stiffness in patients with hypertension or stroke. It remains unknown if uric acid is associated with arterial stiffness in the general population. METHODS We analyzed the association between serum uric acid levels and measures of arterial stiffness such as carotid-femoral pulse wave velocity (CF PWV), carotid-radial pulse wave velocity (CR PWV) and augmentation index (AI) in 4,140 participants from the Generation 3 Framingham cohort using linear regression. RESULTS Mean (SD) age was 40.0 (8.8) years and mean (SD) serum uric acid levels were 5.3 (1.5) mg/dl. Mean (SD) CF PWV was 7.0 (1.4) m/s. Individuals in the highest quartile of uric acid were more likely to be male, have a higher prevalence of hypertension, higher BMI, fasting glucose and insulin, and lower estimated glomerular filtration rate (eGFR). Multivariate adjusted means of CF PWV were 6.90, 6.94, 7.06, and 7.15 m/s for uric acid quartile 1, 2, 3, and 4 respectively. In unadjusted analysis each 1mg/dl increase in uric acid was associated with higher CF-PWV (β = 0.27; 95% CI = 0.25, 0.29; P < 0.0001). This was attenuated but remained significant after adjusting for age, sex, smoking, hypertension, BMI, fasting glucose, insulin, animal protein intake, and eGFR (β= 0.06; 95% CI = 0.02, 0.09; P < 0.0007). There was no association between serum uric acid levels and AI upon adjustment for cardiovascular risk factors. CONCLUSIONS Serum uric acid levels are significantly associated with CF PWV and CR PWV in a younger Caucasian population. PMID:25552515
Rahimian, Reza; Fakhfouri, Gohar; Daneshmand, Ali; Mohammadi, Hamed; Bahremand, Arash; Rasouli, Mohammad Reza; Mousavizadeh, Kazem; Dehpour, Ahmad Reza
Inflammatory bowel disease comprises chronic recurrent inflammation of gastrointestinal tract. This study was conducted to investigate inosine, a potent immunomodulator, in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced chronic model of experimental colitis, and contribution of adenosine A(2A) receptors and the metabolite uric acid as possible underlying mechanisms. Experimental colitis was rendered in rats by a single colonic administration of 10 mg of TNBS. Inosine, potassium oxonate (a hepatic uricase inhibitor), SCH-442416 (a selective adenosine A(2A) receptor antagonist), inosine+potassium oxonate, or inosine+SCH-442416 were given twice daily for 7 successive days. At the end of experiment, macroscopic and histopathologic scores, colonic malondialdehyde (MDA), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-1beta (IL-1β) levels, and myeloperoxidase (MPO) activity were assessed. Plasma uric acid level was measured throughout the experiment. Both macroscopic and histological features of colonic injury were markedly ameliorated by either inosine, oxonate or inosine+oxonate. Likewise, the elevated amounts of MPO and MDA abated as well as those of TNF-α and IL-1β (P<0.05). SCH-442416 partially reversed the effect of inosine on theses markers, while inosine+oxonate showed a higher degree of protection than each treatment alone (P<.0.05). No significant difference was observed between TNBS and SCH-442416 groups. Uric acid levels were significantly higher in inosine or oxonate groups compared to control. Inosine+oxonate resulted in an even more elvelated uric acid level than each treatment alone (P<0.05). Inosine elicits notable anti-inflammatory effects on TNBS-induced colitis in rats. Uric acid and adenosine A(2A) receptors contribute to these salutary properties.
Towiwat, Patapong; Li, Zhan-Guo
About 2500 years ago, gout was observed by Hippocrates and many people suffered severe pain and deformity. Lifestyle and diet play a significant role in gout and serum uric acid levels. Epidemiological and research studies have supported this evidence. Many recommendations and guidelines from different parts of the world mention the impact of diet on gout. Recently, new research has shown associations between vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and the risk of gout. Our review summarizes recently published research regarding dietary impact on the risk of gout and serum uric acid levels. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
Kesebir, Sermin; Tatlıdil Yaylacı, Elif; Süner, Ozgür; Gültekin, Bülent Kadri
The aim of this study was to investigate whether uric acid levels are different between patients with remission period of bipolar disorder type I (BD) and patients with remission period of major depressive disorder (MDD). For this aim 41 patients diagnosed with BD and 30 patients diagnosed with recurrent MDD according to DSM-IV who were in remission period for at least 8 weeks were evaluated consecutively. The median age and gender distribution of the two groups were similar. Subjects with comorbid psychiatric diagnosis and/or severe medical illnesses were excluded. Affective temperament was evaluated with TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire). Plasma uric acid levels were recorded in mg/dl. The uric acid levels of BD patients were found higher than patients with MDD and healthy controls. Additionally uric acid levels of MDD patients were lower than patients with BD and healthy subjects (F=4.183, p=0.039). A moderate correlation between hyperthymic and irritable temperament scores and uric acid levels was detected in both patient groups and in healthy controls. A negative correlation was observed between depressive temperament and uric acid levels only in MDD group. The measurements of temperament were estimated depending on the patient׳s statement. The medications that patients used were not controlled. There is a purinergic dysfunction not only in BD but also in MDD patients. High uric acid levels are associated with hyperthymic and irritable temperament scores whereas low uric acid levels are associated with depressive temperament scores. Copyright © 2014 Elsevier B.V. All rights reserved.
Kanbara, A; Seyama, I
A potential utilization of dietary intervention for reducing hyperuricemia was tested by managing food materials. Within the framework of the Japanese Government's health promotion program, we made recipes that consisted of more protein-rich and less vegetable/fruit-rich materials for the acidic diet and others composed of less protein-rich and more vegetable/fruit-rich materials for the alkaline diet. We have shown that urine alkalization facilitates uric acid excretion. In this study, it has been clarified with simultaneous measurements of both serum and urine uric acid concentration that acidic diets increase serum uric acid together with a decrease of uric acid excretion. The ratio (R) of uric acid clearance/creatinine clearance was calculated. On the third experimental day, the relative R, referring to that of the first day for the acidic diet, became smaller than that for the alkaline diet, indicating that in acidic urine, uric acid excretion is limited by more active reabsorption, compared with that in alkaline urine. Taken together, we tentatively conclude that dietary intervention may well be the safest and the most economical way for the prevention of hyperuricemia.
Khasanah, Miratul; Widati, Alfa Akustia; Fitri, Sarita Aulia
Imprinted zeolite modified carbon paste electrode (carbon paste-IZ) has been developed and applied to determine uric acid by potentiometry. The imprinted zeolite (IZ) was synthesized by the mole ratio of uric acid/Si of 0.0306. The modified electrode was manufactured by mass ratio of carbon, IZ and solid paraffin was 40:25:35. The modified electrode had shown the measurement range of 10-5 M to 10-2 M with Nernst factor of 28.6 mV/decade, the detection limit of 5.86 × 10-6 M and the accuracy of 95.3 - 105.0%. Response time of the electrode for uric acid 10-5 M - 10-2 M was 25 - 44 s. The developed electrode showed the high selectivity toward uric acid in the urea matrix. Life time of the carbon paste-IZ electrode was 10 weeks.
Purnima, Samudrala; El-Aal, Bahiga Galal Abd
A substantial body of epidemiological and experimental evidence suggests the significance of serum uric acid as an important and independent risk factor of cardio vascular and renal diseases especially in patients with diabetes mellitus, hypertension. Hyperuricemia is a risk factor of coronary heart disease. Several studies showed positive association between hyperuricemia and CHD risk factors. To analyze the serum uric acid levels in patients with diabetes and hypertension, which helps in understanding its role as prognostic marker of coronary heart disease. The study was conducted in population of Wadi-Al Dawasir (K.S.A.) aged 20-80 years through random sampling from October 2012 to June 2013. It included 250 samples and the cases were categorized into diabetic and hypertensive. In the cases, purely hypertensive were 52, diabetic were 57 and mixed group included both diabetic and hypertensive patients 65. Fasting blood was collected to analyze lipid profile which included (total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein) and serum uric acid in association with age and heredity was also studied. Patient demographics were recorded. The study revealed significant association of serum uric acid (p<0.014*) and total cholesterol (p<0.007**) triglycerides (p<0.009**) low density lipoprotein (p<0.044*) in hypertensive group. Serum uric acid levels in the mixed group patients with diabetes and hypertension reported serum uric acid (p<0.0037), total cholesterol (p<0.089+) proved to have increased risk of coronary heart disease. When compared to controls (non-diabetic p<0.529) and (non-hypertensive p<0.021*) with respect to serum uric acid levels show the magnitude of risk to coronary heart disease. With progressing age the association of lipid profile and serum uric acid reported (p<0.001**) in diabetics. Significant correlations were found between serum uric acid and risk factors for CHD. This is first study of its kind in this region
Dutta, Ambarish; Henley, William; Pilling, Luke C; Wallace, Robert B; Melzer, David
To estimate the association between uric acid and cardiovascular mortality in older adults, independent of traditional risk factors, and to estimate the risk prediction gain by adding uric acid measurements to the Framingham Cardiovascular Risk Score (FCRS). Longitudinal observational study of two population-based cohorts. The Established Populations for Epidemiologic Studies of the Elderly, Iowa (Iowa-EPESE) and the Third National Health and Nutritional Examination Survey (NHANES III). One thousand twenty-eight Iowa-EPESE participants and 1,316 NHANES III participants. Selected participants were aged 70 and older without overt cardiovascular disease, renal dysfunction, or diuretic use who lived for 3 years or longer after baseline. Outcome was age at cardiovascular death during follow-up (12–20 years). Uric acid and cardiovascular risk factors such as smoking, systolic blood pressure, diabetes mellitus, obesity, serum cholesterol, and high-density lipoprotein cholesterol were measured at baseline. High serum uric acid (>7.0 mg/dL) was associated with male sex, obesity, lipid levels, and estimated glomerular filtration rate at baseline. Fully adjusted hazard ratios (HRs) for cardiovascular death with high uric acid versus normal were 1.36 (95% confidence interval (CI) = 1.10–1.69) in Iowa-EPESE and 1.43 (95% CI = 1.04–1.99) in NHANES III; pooled HR was 1.38 (95% CI = 1.16–1.61). The net reclassification improvement achieved by adding uric acid measurement to the FCRS was 9% to 20%. In individuals aged 70 and older without overt CVD, renal dysfunction, or diuretic use, serum uric acid greater than 7.0 mg/dL was associated with greater CVD mortality independent of classic CVD risk factors. Adding uric acid measurement to the FCRS would improve prediction in older adults.
Kunikullaya, K U; Purushottam, N; Prakash, V; Mohan, S; Chinnaswamy, R
Autonomic dysfunction with dominant sympathetic tone is a common finding among hypertensives and prehypertensives. Uric acid is one of the independent predictors of hypertension. There are very few studies which have shown a relationship between the autonomic tone and uric acid generation pathway among prehypertensives and hypertensives. Aim of the study was to estimate and correlate serum uric acid levels with autonomic function as measured by heart rate variability (HRV) among prehypertensives and hypertensives. Cross-sectional study of three groups, prehypertensives, hypertensives and normotensives, classified according to Joint National Committee VII criteria, with 35 subjects in each group were included in this study. Serum uric acid levels were estimated by using colorimetric assay kit. HRV was analyzed after recording lead II Electrocardiogram using RMS Vagus HRV software (RMS, India). One-way ANOVA and Pearson's correlation was done using SPSS 18.0 software. Mean uric acid levels were 5.62±2.21mg/dL in normal subjects, 7.06±2.87mg/dL in prehypertensives and 9.77±2.04mg/dL in hypertensives. There was statistically significant negative correlation between uric acid and time domain parameters of HRV in the whole sample and among prehypertensives and positive correlation with low frequency power (LF) in ms(2) and n.u. Serum uric acid levels were high in prehypertensives and hypertensives as compared to normal subjects. Further, there was statistically significant correlation seen between uric acid levels and sympathetic domain parameters particularly among prehypertensives. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.
Sedaghat, Sanaz; Pazoki, Raha; Uitterlinden, Andre G; Hofman, Albert; Stricker, Bruno H Ch; Ikram, M Arfan; Franco, Oscar H; Dehghan, Abbas
High levels of serum uric acid are associated with hypertension in observational studies. The aim of this study was to investigate the association of uric acid gene variants with blood pressure. We studied 5791 participants aged ≥55 years from the Rotterdam Study. Thirty gene variants identified for serum uric acid level were used to compile genetic risk score (GRS). We used linear regression models to investigate the association of the uric acid GRS with systolic and diastolic blood pressure in the whole study population and separately in participants with and without comorbidities and medication use. In the age- and sex-adjusted model, each SD increase in uric acid GRS was associated with 0.75 mm Hg lower systolic blood pressure (95% confidence interval, -1.31 to -0.19) and 0.42 mm Hg lower diastolic blood pressure (95% confidence interval, -0.72 to -0.13). The association did not attenuate after further adjustment for antihypertensive medication use and conventional cardiovascular risk factors. In subgroup analysis, the association of uric acid GRS with systolic blood pressure was significantly stronger in participants (n=885) on diuretic treatment (P for interaction, 0.007). In conclusion, we found that higher uric acid GRS is associated with lower systolic and diastolic blood pressure. Diuretics treatment may modify the association of uric acid genetic risk score and systolic blood pressure. Our study suggests that genome wide association study's findings can be associated with an intermediate factor or have a pleiotropic role and, therefore, should be applied for Mendelian Randomization with caution. © 2014 American Heart Association, Inc.
Oya, H; Nagaya, N; Satoh, T; Sakamaki, F; Kyotani, S; Fujita, M; Nakanishi, N; Miyatake, K
OBJECTIVE—To assess haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome. DESIGN—Retrospective observational study. SETTING—Tertiary referral centre. PATIENTS—94 adult patients with Eisenmenger syndrome who were diagnosed between September 1982 and July 1998. MAIN OUTCOME MEASURES—Serum uric acid was measured in all patients, together with clinical and haemodynamic variables related to mortality. RESULTS—Serum uric acid was raised in patients with Eisenmenger syndrome compared with age and sex matched control subjects (7.0 v 4.7 mg/dl, p < 0.0001) and increased in proportion to the severity of New York Heart Association functional class. Serum uric acid was positively correlated with mean pulmonary arterial pressure (r = 0.30, p = 0.0052) and total pulmonary resistance index (r = 0.55, p < 0.0001), and negatively correlated with cardiac index (r = −0.50, p < 0.0001). During a mean follow up period of 97 months, 38 patients died of cardiopulmonary causes. Among various clinical, echocardiographic, and laboratory variables, serum uric acid remained predictive in multivariate analysis. Kaplan-Meier survival curves based on median serum uric acid showed that patients with high values had a significantly worse survival rate than those with low values (log-lank test: p = 0.0014 in male patients, p = 0.0034 in female patients). CONCLUSIONS—Serum uric acid increases in proportion to haemodynamic severity in adult patients with Eisenmenger syndrome and is independently associated with long term mortality. Keywords: Eisenmenger syndrome; prognosis; uric acid; haemodynamics PMID:10862589
Solak, Yalcin; Akilli, Hakan; Kayrak, Mehmet; Aribas, Alpay; Gaipov, Abduzhappar; Turk, Suleyman; Perez-Pozo, Santos E.; Covic, Adrian; McFann, Kim; Johnson, Richard J.; Kanbay, Mehmet
Introduction Erectile dysfunction (ED) is a frequent complaint of elderly subjects, and is closely associated with endothelial dysfunction and cardiovascular disease. Uric acid is also associated with endothelial dysfunction, oxidative stress and cardiovascular disease, raising the hypothesis that an increased serum uric acid might predict erectile dysfunction in patients who are at risk for coronary artery disease. Aim To evaluate the association of serum uric acid levels with presence and severity of ED in patients presenting with chest pain of presumed cardiac origin. Methods This is a cross-sectional study of 312 adult male patients with suspected coronary artery disease who underwent exercise stress test (EST) for workup of chest pain and completed a sexual health inventory for men (SHIM) survey form to determine the presence and severity of ED. Routine serum biochemistry (and uric acid levels) were measured. Logistic regression analysis was used to assess risk factors for ED. Main Outcome Measures The short version of the international index of erectile function (IIEF-5) questionnaire diagnosed ED (cutoff score ≤21). Serum Uric acid levels were determined. Patients with chest pain of suspected cardiac origin underwent an exercise stress test. Results 149 of 312 (47.7%) male subjects had ED by survey criteria. Patients with ED were older and had more frequent CAD, hypertension, diabetes, and impaired renal function, and also had significantly higher levels of uric acid, fibrinogen, glucose, CRP, triglycerides compared with patients without ED. Uric acid levels were associated with ED by univariate analysis (OR = 1.36, p = 0.002); however, this association was not observed in multivariate analysis adjusted for eGFR. Conclusion Subjects presenting with chest pain of presumed cardiac origin are more likely to have ED if they have elevated uric acid levels. PMID:24433559
Jia, Guanghong; Habibi, Javad; Bostick, Brian P; Ma, Lixin; DeMarco, Vincent G; Aroor, Annayya R; Hayden, Melvin R; Whaley-Connell, Adam T; Sowers, James R
The rising obesity rates parallel increased consumption of a Western diet, high in fat and fructose, which is associated with increased uric acid. Population-based data support that elevated serum uric acids are associated with left ventricular hypertrophy and diastolic dysfunction. However, the mechanism by which excess uric acid promotes these maladaptive cardiac effects has not been explored. In assessing the role of Western diet-induced increases in uric acid, we hypothesized that reductions in uric acid would prevent Western diet-induced development of cardiomyocyte hypertrophy, cardiac stiffness, and impaired diastolic relaxation by reducing growth and profibrotic signaling pathways. Four-weeks-old C57BL6/J male mice were fed excess fat (46%) and fructose (17.5%) with or without allopurinol (125 mg/L), a xanthine oxidase inhibitor, for 16 weeks. The Western diet-induced increases in serum uric acid along with increases in cardiac tissue xanthine oxidase activity temporally related to increases in body weight, fat mass, and insulin resistance without changes in blood pressure. The Western diet induced cardiomyocte hypertrophy, myocardial oxidative stress, interstitial fibrosis, and impaired diastolic relaxation. Further, the Western diet enhanced activation of the S6 kinase-1 growth pathway and the profibrotic transforming growth factor-β1/Smad2/3 signaling pathway and macrophage proinflammatory polarization. All results improved with allopurinol treatment, which lowered cardiac xanthine oxidase as well as serum uric acid levels. These findings support the notion that increased production of uric acid with intake of a Western diet promotes cardiomyocyte hypertrophy, inflammation, and oxidative stress that lead to myocardial fibrosis and associated impaired diastolic relaxation. © 2014 American Heart Association, Inc.
Bassols, J; Martínez-Calcerrada, J M; Prats-Puig, A; Carreras-Badosa, G; Díaz-Roldán, F; Osiniri, I; Riera-Pérez, E; de Zegher, F; Ibáñez, L; López-Bermejo, A
Increased uric acid is an independent biomarker for cardiovascular disease in obese adolescents and adults. We investigated whether uric acid relates to carotid intima-media thickness (cIMT) in prepubertal children, and whether body mass index (BMI) and preperitoneal fat modulate this association. 359 asymptomatic prepubertal Caucasian children were stratified according to BMI categories (171 with BMI-SDS < 0; 188 with BMI-SDS ≥ 0) and according to preperitoneal fat levels (180 with preperitoneal fat <50th centile; 179 with preperitoneal fat >50th centile). Uric acid levels, insulin resistance (homeostasis model assessment insulin resistance; HOMA-IR), C-reactive protein (CRP), triacylglycerol (TG), systolic blood pressure (SBP), abdominal fat and cIMT (both by ultrasound) were assessed. Uric acid was associated with several cardiovascular risk factors, namely higher HOMA-IR, CRP, TG, BMI, waist, SBP, preperitoneal fat and cIMT (all P < 0.001 to P < 0.0001). Significant BMI and preperitoneal fat interactions were documented in the relationship between uric acid and cIMT (both P < 0.05), as uric acid was preferentially related to cIMT in heavier children (β = 0.247, P < 0.001, r(2) = 9.1%) and in children with more preperitoneal fat (β = 0.263, P < 0.0001, r(2) = 11.9%). Serum uric acid is associated with cIMT in asymptomatic prepubertal children. Both higher BMI and preperitoneal fat aggravate the potential risk of atherosclerotic disease imposed by higher concentrations of uric acid. © 2015 World Obesity.
Crişan, Tania O; Cleophas, Maartje C P; Novakovic, Boris; Erler, Kathrin; van de Veerdonk, Frank L; Stunnenberg, Hendrik G; Netea, Mihai G; Dinarello, Charles A; Joosten, Leo A B
Metabolic triggers are important inducers of the inflammatory processes in gout. Whereas the high serum urate levels observed in patients with gout predispose them to the formation of monosodium urate (MSU) crystals, soluble urate also primes for inflammatory signals in cells responding to gout-related stimuli, but also in other common metabolic diseases. In this study, we investigated the mechanisms through which uric acid selectively lowers human blood monocyte production of the natural inhibitor IL-1 receptor antagonist (IL-1Ra) and shifts production toward the highly inflammatory IL-1β. Monocytes from healthy volunteers were first primed with uric acid for 24 h and then subjected to stimulation with lipopolysaccharide (LPS) in the presence or absence of MSU. Transcriptomic analysis revealed broad inflammatory pathways associated with uric acid priming, with NF-κB and mammalian target of rapamycin (mTOR) signaling strongly increased. Functional validation did not identify NF-κB or AMP-activated protein kinase phosphorylation, but uric acid priming induced phosphorylation of AKT and proline-rich AKT substrate 40 kDa (PRAS 40), which in turn activated mTOR. Subsequently, Western blot for the autophagic structure LC3-I and LC3-II (microtubule-associated protein 1A/1B-light chain 3) fractions, as well as fluorescence microscopy of LC3-GFP-overexpressing HeLa cells, revealed lower autophagic activity in cells exposed to uric acid compared with control conditions. Interestingly, reactive oxygen species production was diminished by uric acid priming. Thus, the Akt-PRAS40 pathway is activated by uric acid, which inhibits autophagy and recapitulates the uric acid-induced proinflammatory cytokine phenotype.
Goh, King-Siang; Sheu, Hwo-Shuenn; Hua, Tzu-En; Kang, Mei-Hua; Li, Chia-Wei
Background In firefly light organs, reflector layer is a specialized tissue which is believed to play a key role for increasing the bioluminescence intensity through reflection. However, the nature of this unique tissue remains elusive. In this report, we investigated the role, fine structure and nature of the reflector layer in the light organ of adult Luciola cerata. Principal Findings Our results indicated that the reflector layer is capable of reflecting bioluminescence, and contains abundant uric acid. Electron microscopy (EM) demonstrated that the cytosol of the reflector layer's cells is filled with densely packed spherical granules, which should be the uric acid granules. These granules are highly regular in size (∼700 nm in diameter), and exhibit a radial internal structure. X-ray diffraction (XRD) analyses revealed that an intense single peak pattern with a d-spacing value of 0.320 nm is specifically detected in the light organ, and is highly similar to the diffraction peak pattern and d-spacing value of needle-formed crystals of monosodium urate monohydrate. However, the molar ratio evaluation of uric acid to various cations (K+, Na+, Ca2+ and Mg2+) in the light organ deduced that only a few uric acid molecules were in the form of urate salts. Thus, non-salt uric acid should be the source of the diffraction signal detected in the light organ. Conclusions In the light organ, the intense single peak diffraction signal might come from a unique needle-like uric acid form, which is different from other known structures of non-salt uric acid form. The finding of a radial structure in the granules of reflector layer implies that the spherical uric acid granules might be formed by the radial arrangement of needle-formed packing matter. PMID:23441187
Grossman, Chagai; Shemesh, Joseph; Koren-Morag, Nira; Bornstein, Gil; Ben-Zvi, Ilan; Grossman, Ehud
Uric acid (UA) is associated with atherosclerosis, and coronary artery calcium (CAC) is a marker of atherosclerosis. The authors studied the association between UA and CAC. A total of 663 asymptomatic patients (564 men; mean age, 55±7 years) were evaluated for the presence of CAC. The study population was divided into three tertiles according to their UA levels, and the prevalence of CAC was compared between the tertiles. CAC was detected in 349 (53%) patients. Levels of UA were significantly higher in those with CAC than in those without CAC (5.6+1.2 vs 5.3+1.3; P=.003). The odds ratio for the presence of CAC in the highest vs lowest UA tertile was 1.72 (95% confidence interval, 1.17-2.51). The highest UA tertile remained associated with the presence of CAC after adjustment for known cardiovascular risk factors. The results show that high serum UA levels are associated with the presence of CAC.
Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun
In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage.
Zou, Huiqing; Xiang, Mingfeng; Ye, Xinming; Xiong, Yuanzhen; Xie, Baogang; Shao, Jianghua
Serum uric acid (UA) concentration is positively associated with proteinuria. However, the relationship between proteinuria and urinary metabolites of purine metabolism remains unknown. This study developed a hydrophilic interaction chromatography (HILIC)-based HPLC method with ultraviolet detection (UV) to quantify creatinine (Cr), UA, xanthine, and hypoxanthine in human urine simultaneously. The urinary concentrations of UA and Cr obtained by our method are consistent with those measured by an autoanalyzer. The HPLC-HILIC-UV method was validated as selective and robust with simple sample preparation for measuring UA, xanthine, hypoxanthine and Cr, which is suitable for large clinical studies. The UA/Cr ratios in random urine samples were 5.5 times lower in proteinuria patients (0.077±0.008) than in healthy individuals (0.424±0.037). Moreover, the UA/hypoxanthine ratio in proteinuria patients was approximately 10 times lower than that in healthy individuals. Our findings revealed a reduced urinary UA excretion, which is one of the factors leading to increased serum UA in proteinuria patients. Copyright © 2015 Elsevier B.V. All rights reserved.
Vassalle, Cristina; Mazzone, Annamaria; Sabatino, Laura; Carpeggiani, Clara
Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this biomarker behaves like other antioxidants, which can shift from the physiological antioxidant action to a pro-oxidizing effect according to their level and to microenvironment conditions. However, data on patients (general population or CAD cohorts) are controversial, so the debate on the role of hyperuricemia as a causative factor for CVD is still ongoing. Increasing evidence indicates UA as more meaningful to assess CVD in women, even though this aspect needs deeper investigation. It will be important to identify thresholds responsible for UA "biological shift" from protective to harmful effects in different pathological conditions, and according to possible gender-related differences. In any case, UA is a low-tech and inexpensive biomarker, generally performed at patient's hospitalization and, therefore, easily accessible information for clinicians. For these reasons, UA might represent a useful additive tool as much as a CV risk marker. Thus, in view of available evidence, progressive UA elevation with levels higher than 6 mg/dL could be considered an "alarm" for increased CV risk.
Vassalle, Cristina; Mazzone, Annamaria; Sabatino, Laura; Carpeggiani, Clara
Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this biomarker behaves like other antioxidants, which can shift from the physiological antioxidant action to a pro-oxidizing effect according to their level and to microenvironment conditions. However, data on patients (general population or CAD cohorts) are controversial, so the debate on the role of hyperuricemia as a causative factor for CVD is still ongoing. Increasing evidence indicates UA as more meaningful to assess CVD in women, even though this aspect needs deeper investigation. It will be important to identify thresholds responsible for UA “biological shift” from protective to harmful effects in different pathological conditions, and according to possible gender-related differences. In any case, UA is a low-tech and inexpensive biomarker, generally performed at patient’s hospitalization and, therefore, easily accessible information for clinicians. For these reasons, UA might represent a useful additive tool as much as a CV risk marker. Thus, in view of available evidence, progressive UA elevation with levels higher than 6 mg/dL could be considered an “alarm” for increased CV risk. PMID:28933392
Ghaemi-Oskouie, Faranak; Shi, Yan
Gout is an ancient disease that still plagues us. Its pathogenic culprit, uric acid crystal deposition in tissues, is a strong inflammatory stimulant. In recent years, the mechanisms through which uric acid crystals promote inflammation have been a subject of increasing interest among rheumatologists and immunologists. Uric acid has been identified as an endogenous adjuvant that drives immune responses in the absence of microbial stimulation. Because uric acid is a ubiquitous metabolite that is produced in high quantities upon cellular injury, the ramifications of its effects may be considerable in health and in disease. Uric acid crystals also have been shown to trigger interleukin-1β-mediated inflammation via activation of the NOD-like receptor protein (NLRP)3 inflammasome, a multimolecular complex whose activation appears to be central to many pathological inflammatory conditions. In this article, we review the possible mechanisms of uric acid-mediated inflammation and offer some historical perspectives on what has been learned about the complex effects of a relatively simple substance.
Kioko, Bridgit; Ogundolie, Taiwo; Adebiyi, Morenike; Ettinoffe, Yehnara; Rhodes, Caleb; Gordon, Brittney; Thompson, Nishone; Mohammed, Muzaffer; Abel, Biebele; Aslan, Kadir
In this study, we demonstrated a unique application of our Metal-Assisted and Microwave-Accelerated Evaporative Crystallization (MA-MAEC) technique for the de-crystallization of uric acid crystals, which causes gout in humans when monosodium urate crystals accumulate in the synovial fluid found in the joints of bones. Given the shortcomings of the existing treatments for gout, we investigated whether the MA-MAEC technique can offer an alternative solution to the treatment of gout. Our technique is based on the use of metal nanoparticles (i.e., gold colloids) with low microwave heating to accelerate the de-crystallization process. In this regard, we employed a two-step process; (i) crystallization of uric acid on glass slides, which act as a solid platform to mimic a bone, (ii) de-crystallization of uric acid crystals on glass slides with the addition of gold colloids and low power microwave heating, which act as "nano-bullets" when microwave heated in a solution. We observed that the size and number of the uric acid crystals were reduced by >60% within 10 minutes of low power microwave heating. In addition, the use of gold colloids without microwave heating (i.e. control experiment) did not result in the de-crystallization of the uric acid crystals, which proves the utility of our MA-MAEC technique in the de-crystallization of uric acid.
Teng, F; Zhu, R; Zou, C; Xue, Y; Yang, M; Song, H; Liang, J
The aim of this study was to examine the independent relationship between serum uric acid (SUA) and blood pressure, and to assess their joint effects on obesity, fasting glucose and lipids. The study samples were from a community-based health examination survey in Xuzhou, Jiangsu province of China (2009). Blood pressure, body mass index, fasting glucose, lipids and SUA were measured. After excluding individuals with fasting glucose greater than 7 mmol l(-1), a total of 8415 subjects with biomarkers available were included in the present study. Blood pressure increased with elevated SUA levels, after adjusting for age and sex. Further adjustment for fasting glucose, lipids and alcohol consumption did not change the increasing trend. The associations between uric acid and hypertension were most evident in those with highest quintiles of high-density lipoprotein cholesterol (HDL-C). In addition, the associations were significant in both men and women, and we found significant interactions between uric acid status and age on hypertension. When the joint effects were examined, we found an additive effect of triglycerides and uric acid levels on diastolic blood pressure (DBP). There was significant association between SUA and hypertension, independent of other metabolic risk factors. HDL-C levels may modify the associations between uric acid and hypertension. The effects of triglycerides and uric acid levels on DBP were additive.
Cete, Servet; Yaşar, Ahmet; Arslan, Fatma
In order to prepare a biosensor for the determination of uric acid, electropolymerization of pyrrole on Pt surface was carried out with an electrochemical cell containing pyrrole, ferrocene (as a electron mediator) and tetrabutylammonium tetrafluoroborat in acetonitrile by cyclic voltammetry between 0.0 and 1.0 V (vs. Ag/AgCl) at a scan rate of 50 mV/s upon Pt electrode. Uricase was immobilized by a glutaraldehyde/gelatine croslinking procedure on to polypyrrole film after the electropolymerization processes. The response of the biosensor against uric acid was measured after 330 seconds following the application of a constant potential of +0.7 V (vs. Ag/AgCl). The resulting biosensor exhibits excellent electrocatalysis for the uric acid. The amperometric determination is based on the electrochemical detection of H2O2, which is generated in enzymatic reaction of uric acid. The sensor responds to uric acid with a detection limit of 5.0 x 10(-7) M. The sensor remains relatively stable for 5 weeks. Interference effect were investigated on the amperometric response of the biosensor. Determination of uric acid was carried out in the biological fluids by biosensor.
Davies, M J; Trujillo, A; Vijapurkar, U; Damaraju, C V; Meininger, G
Hyperuricaemia is associated with an increased risk of gout, kidney stones and cardiovascular disease. The present post hoc analysis of pooled data from four placebo-controlled phase III studies assessed the effect of canagliflozin, a sodium-glucose co-transporter 2 inhibitor, on serum uric acid levels in patients with type 2 diabetes mellitus (T2DM) and in a subset of patients with hyperuricaemia [defined as baseline serum uric acid ≥475 µmol/l (∼8 mg/dl)]. At week 26, canagliflozin 100 and 300 mg were associated with a ∼13% reduction in serum uric acid compared with placebo. In the subset of patients with hyperuricaemia, placebo-subtracted percent reductions in serum uric acid were similar to those in the overall cohort. More patients in the hyperuricaemic group achieved a serum uric acid level of <360 µmol/l (∼6 mg/dl) with both canagliflozin 100 mg (23.5%) and 300 mg (32.4%) compared with placebo (3.1%). Incidences of gout and kidney stones were low and similar across groups. In conclusion, canagliflozin treatment decreased serum uric acid in patients with T2DM, including those with baseline hyperuricaemia. © 2015 John Wiley & Sons Ltd.
Iswantini, Dyah; Rachmatia, Rescy; Diana, Novita Rose; Nurhidayat, Novik; Akhiruddin; Saprudin, Deden
Research of uric acid biosensor used a Lactobacillus plantarum was successfully conducted. Lactobacillus plantarum could produce uricase that could be used as uric acid biosensor. Therefore, lifetime of bacteria were quite short that caused the bacteria could not detect uric acid for a long time. To avoid this problem, development of biofilm for uric acid biosensor is important. Biofilms is a structured community of bacterial cells, stick together and are able to maintain a bacteria in an extreme environments. The purpose of present study was to determine and compare the activity of uricase produced by L. plantarum, deposited whithin biofilm and planktonic bacteria on glassy carbon electrode (GCEb & GCE), also to determine the stability of biofilm. The optimization process was conducted by using temperature, pH, and substrate concentration as the parameters. It showed that the activity of uricase within biofilm was able to increase the oxidation current. GCEb and GCE yielded the oxidation current in the amount of 47.24 μA and 23.04 μA, respectively, under the same condition. Results indicated that the optimum condition for uric acid biosensor using biofilm were pH 10, temperature of 40 oC, and uric acid concentration of 5 mM. The stability of GCEb decreased after 10 hours used, with decreasing percentage over 86.33%. This low stability probably caused by the unprotected active site of the enzyme that the enzyme is easier to experience the denaturation.
Darmokoesoemo, Handoko; Khasanah, Miratul; Widayanti, Nesti; Kadmi, Yassine; Elmsellem, Hicham; Kusuma, Heri Septya
The development of carbon paste electrodes modified by molecularly imprinted polymer (MIP) for the potentiometric analysis of uric acid was carried out in this study. The aim of the study was to determine the optimum composition of the electrode constituent material, the optimum pH of the uric acid solution, and the performance of the electrode, which was measured by its response time, measurement range, Nernst factor, detection limits, selectivity coefficient, precision, accuracy, and life time. MIP was made from methyl methacrylate as the monomer, ethylene glycol dimethacrylate as the cross-linker, and uric acid as the template. Electrodes that give optimum performance were produced from carbon, MIP, and paraffin with a ratio of 40:25:35 (% w/w). The obtained results show that the measurement of uric acid solution gives optimum results at pH 5, Nernst factor of 30.19 mV/decade, and a measurement range of 10-6-10-3 M. The minimum detection limit of this method was 3.03.10-6 M, and the precision and accuracy toward uric acid with concentration of 10-6-10-3 M ranged between 1.36-2.03% and 63.9-166%. The selectivity coefficient value was less than 1, which indicated that the electrode was selective against uric acid and not interfered with by urea. This electrode has a response time of less than 2 min; its life time is 8 weeks with 104 usage times.
Chaudhary, Kunal; Malhotra, Kunal; Sowers, James; Aroor, Annayya
Elevated serum uric acid levels are a frequent finding in persons with obesity, hypertension, cardiovascular and kidney disease as well as in those with the cardiorenal metabolic syndrome (CRS). The increased consumption of a fructose-rich Western diet has contributed to the increasing incidence of the CRS, obesity and diabetes especially in industrialized populations. There is also increasing evidence that supports a causal role of high dietary fructose driving elevations in uric acid in association with the CRS. Animal and epidemiological studies support the notion that elevated serum uric acid levels play an important role in promoting insulin resistance and hypertension and suggest potential pathophysiological mechanisms that contribute to the development of the CRS and associated cardiovascular disease and chronic kidney disease. To this point, elevated serum levels of uric acid appear to contribute to impaired nitric oxide production/endothelial dysfunction, increased vascular stiffness, inappropriate activation of the renin-angiotensin-aldosterone system, enhanced oxidative stress, and maladaptive immune and inflammatory responses. These abnormalities, in turn, promote vascular, cardiac and renal fibrosis as well as associated functional abnormalities. Small clinical trials have suggested that uric acid-lowering therapies may be beneficial in such patients; however, a consensus on the treatment of asymptomatic hyperuricemia is lacking. Larger randomized controlled trials need to be performed in order to critically evaluate the beneficial effect of lowering serum uric acid in patients with the CRS and those with diabetes and/or hypertension. PMID:24454316
Darmawan, Guntur; Hamijoyo, Laniyati; Hasan, Irsan
non-alcoholic fatty liver disease (NAFLD) is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD. a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). All data were analyzed using REVIEW MANAGER 5.3. eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; p<0.00001). Subgroup analyses were done based on study design, gender, non-diabetic subjects, non-obese subjects. All subgroup analyses showed statistically significant adjusted OR and most of which having low to moderate heterogeneity. Two studies revealed relationship between increased serum uric acid levels and severity of NAFLD. No publication bias was observed. our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.
van de Hoef, Diana L.; Coppens, Isabelle; Holowka, Thomas; Ben Mamoun, Choukri; Branch, OraLee; Rodriguez, Ana
Malaria is characterized by cyclical fevers and high levels of inflammation, and while an early inflammatory response contributes to parasite clearance, excessive and persistent inflammation can lead to severe forms of the disease. Here, we show that Plasmodium falciparum-infected erythrocytes contain uric acid precipitates in the cytoplasm of the parasitophorous vacuole, which are released when erythrocytes rupture. Uric acid precipitates are highly inflammatory molecules that are considered a danger signal for innate immunity and are the causative agent in gout. We determined that P. falciparum-derived uric acid precipitates induce maturation of human dendritic cells, increasing the expression of cell surface co-stimulatory molecules such as CD80 and CD86, while decreasing human leukocyte antigen-DR expression. In accordance with this, uric acid accounts for a significant proportion of the total stimulatory activity induced by parasite-infected erythrocytes. Moreover, the identification of uric acid precipitates in P. falciparum- and P. vivax-infected erythrocytes obtained directly from malaria patients underscores the in vivo and clinical relevance of our findings. Altogether, our data implicate uric acid precipitates as a potentially important contributor to the innate immune response to Plasmodium infection and may provide a novel target for adjunct therapies. PMID:23405174
Afsar, Baris; Elsurer, Rengin; Covic, Adrian; Johnson, Richard J.; Kanbay, Mehmet
Background Elevated serum uric acid has been associated with cognitive dysfunction and vascular cognitive impairment in the elderly. Serum uric acid is also commonly elevated in chronic kidney disease (CKD), but its relationship with cognitive function in these patients has not been addressed. Methods Subjects with CKD (defined as eGFR <60/ml/min/1.73 m2) were evaluated for cognitive dysfunction using the validated Standardized Mini-Mental State Examination (SMMSE). Individuals with dementia, depression or other psychiatric disorders were excluded, as were subjects on uric acid-lowering therapy or with serious illnesses such as severe anemia or active or ongoing cardiovascular or cerebrovascular disease. Results 247 subjects were enrolled. SMMSE scores showed stepwise deterioration with increasing quartile of serum uric acid (26.4; 26.1; 25.5; 25.3, score range 20–30, p = 0.019). Post-hoc analysis demonstrated that there was no linear trend and only groups 1 and 4 were different with respect to SMMSE scores (p = 0.025). Stepwise multivariate linear regression revealed that age, educational status, presence of cerebrovascular disease, and serum uric acid were independently related to SMMSE scores. Conclusion Serum uric acid levels are independently and inversely associated with mild cognitive dysfunction in subjects with CKD. PMID:21659739
Jung, Jae H; Song, Gwan G; Lee, Young H; Kim, Jae-Hoon; Hyun, Myung H; Choi, Sung J
Serum uric acid levels increase in postmenopausal women, but decrease when hormone therapy (HT) is administered. No study has, however, evaluated the effects of different types of HT on serum uric acid levels. We therefore examined whether estrogen therapy (ET), estrogen plus progestogen therapy (EPT), and tibolone use affected serum uric acid levels in this population. We performed a retrospective cohort study of postmenopausal women. From 2005 to 2015, postmenopausal women who had undergone blood uric acid-level testing at least twice were enrolled. Participants were grouped according to HT regimen: ET, EPT, or tibolone. The nonhormone therapy group did not receive HT. Differences in serum uric acid levels were examined in each group. Our analysis was adjusted to accommodate different follow-up intervals for individual participants. Multiple variables were adjusted using the Tukey-Kramer method. Age, body mass index, hypertension, diabetes mellitus, dyslipidemia, estimated glomerular filtration rate, alcohol consumption, smoking status, and comedications were also adjusted. After adjusting for multiple variables, the serum uric acid level increased to 0.87 ± 0.27 mg/dL (least squares mean ± standard error) in the nonhormone therapy group, and serum uric levels in the EPT group were found to be significantly lower (-0.38 ± 0.29 mg/dL, P < 0.001). The serum uric acid levels in the ET and tibolone groups did not, however, differ significantly from the nonhormone therapy group level. We attribute our findings to the effects of progestogen, rather than estrogen.
Gout is an ancient disease that still plagues us. Its pathogenic culprit, uric acid crystal deposition in tissues, is a strong inflammatory stimulant. In recent years, the mechanisms through which uric acid crystals promote inflammation have been a subject of increasing interest among rheumatologists and immunologists. Uric acid has been identified as an endogenous adjuvant that drives immune responses in the absence of microbial stimulation. Because uric acid is a ubiquitous metabolite that is produced in high quantities upon cellular injury, the ramifications of its effects may be considerable in health and in disease. Uric acid crystals also have been shown to trigger interleukin-1β–mediated inflammation via activation of the NOD-like receptor protein (NLRP)3 inflammasome, a multimolecular complex whose activation appears to be central to many pathological inflammatory conditions. In this article, we review the possible mechanisms of uric acid–mediated inflammation and offer some historical perspectives on what has been learned about the complex effects of a relatively simple substance. PMID:21234729
Background A link between uric acid (UA) levels and cardiovascular diseases has been previously reported. However, its importance as a risk factor is still controversial. This study sought to determine whether elevated serum uric acid levels are associated with cardiovascular disease (CVD) in middle-aged and elderly Chinese individuals. Methods We conducted a population-based cross-sectional study in Shanghai, with a total of 8510 participants aged ≥40 years. The CVD included diagnosed coronary heart disease (CHD) and stroke. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Results Uric acid levels were positively associated with BMI, waist circumference, triglycerides, systolic blood pressure, diastolic blood pressure, glycohemoglobin, fasting plasma glucose, postprandial 2-hour plasma glucose (all P < 0.05), and negatively associated with HDL-cholesterol (P < 0.001). The prevalence of CVD significantly increased with increasing quartiles of UA in those without MetS group (p trend < 0.001), but not necessarily increased in those with MetS. After adjustment for metabolic syndrome and other cardiovascular risk factors, multivariate logistic regression analysis showed that odds ratios (OR) for CHD, stroke, and CVD in those in the fourth quartiles were 2.34 (95% confidence interval [CI] 1.73 to 3.45), 2.18 (95% CI 1.86 to 3.28), and 2.16 (95% CI 1.80 to 3.29), respectively, compared with those in the first quartile of UA. Conclusions Elevated serum uric acid level was associated with CVD, independent of conventional cardiovascular disease risk factors and metabolic syndrome. PMID:24568132
Shen, Zancong; Gillen, Michael; Miner, Jeffrey N; Bucci, Gail; Wilson, David M; Hall, Jesse W
Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in healthy adult males. This was a Phase I, randomized, double-blind, placebo-controlled, single and multiple ascending dose study. Panels of eight male subjects received a single oral dose of verinurad or placebo in either a fasted or fed state; panels of 10-12 male subjects received ascending doses of once-daily verinurad or placebo in a fasted state for 10 days. Serial blood and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse event (AE) reports, laboratory tests, vital signs, and electrocardiograms (ECGs). A total of 81 adult males completed the study. Following single doses of verinurad, maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in a dose-proportional manner; Cmax occurred at 0.5-0.75 hours and 1.25 hours in the fasted and fed states, respectively. Food decreased AUC by 23% and Cmax by 37%-53%. There was a modest accumulation of verinurad following multiple daily doses. Verinurad reduced serum urate levels by up to 62% (40 mg, single dose) and 61% (10 mg, multiple dose). The increase in urinary excretion of uric acid was greatest in the first 6 hours after dosing and was still evident ≥24 hours for verinurad doses ≥2 mg. Verinurad was well tolerated at all doses. No serious AEs, severe AEs, discontinuations due to AEs, or clinically significant laboratory or ECG abnormalities were reported. Single and multiple doses of verinurad were well tolerated, absorption was rapid, and exposure was dose proportional. Verinurad increased urinary uric acid elimination and resulted in sustained reductions in serum urate. These data support further clinical evaluation of once-daily verinurad as a treatment for
Numnuam, Apon; Thavarungkul, Panote; Kanatharana, Proespichaya
A novel amperometric uric acid biosensor was fabricated by immobilizing uricase on an electrospun nanocomposite of chitosan-carbon nanotubes nanofiber (Chi-CNTsNF) covering an electrodeposited layer of silver nanoparticles (AgNPs) on a gold electrode (uricase/Chi-CNTsNF/AgNPs/Au). The uric acid response was determined at an optimum applied potential of -0.35 V vs Ag/AgCl in a flow-injection system based on the change of the reduction current for dissolved oxygen during oxidation of uric acid by the immobilized uricase. The response was directly proportional to the uric acid concentration. Under the optimum conditions, the fabricated uric acid biosensor had a very wide linear range, 1.0-400 μmol L(-1), with a very low limit of detection of 1.0 μmol L(-1) (s/n = 3). The operational stability of the uricase/Chi-CNTsNF/AgNPs/Au biosensor (up to 205 injections) was excellent and the storage life was more than six weeks. A low Michaelis-Menten constant of 0.21 mmol L(-1) indicated that the immobilized uricase had high affinity for uric acid. The presence of potential common interfering substances, for example ascorbic acid, glucose, and lactic acid, had negligible effects on the performance of the biosensor. When used for analysis of uric acid in serum samples, the results agreed well with those obtained by use of the standard enzymatic colorimetric method (P > 0.05).
Lytvyn, Yuliya; Škrtić, Marko; Yang, Gary K; Yip, Paul M; Perkins, Bruce A; Cherney, David Z I
Plasma uric acid (PUA) is associated with metabolic, cardiovascular, and renal abnormalities in patients with type 2 diabetes but is less well understood in type 1 diabetes (T1D). Our aim was to compare PUA levels and fractional uric acid excretion (FEUA) in patients with T1D vs. healthy controls (HC) during euglycemia and hyperglycemia. PUA, FEUA, blood pressure (BP), glomerular filtration rate (GFR-inulin), and effective renal plasma flow (ERPF-paraaminohippurate) were evaluated in patients with T1D (n = 66) during clamped euglycemia (glucose 4-6 mmol/l) and hyperglycemia (9-11 mmol/l), and in HC (n = 41) during euglycemia. To separate the effects of hyperglycemia vs. increased glycosuria, parameters were evaluated during clamped euglycemia in a subset of T1D patients before and after sodium glucose cotransporter 2 (SGLT2) inhibition for 8 wk. PUA was lower in T1D vs. HC (228 ± 62 vs. 305 ± 75 μmol/l, P < 0.0001). In T1D, hyperglycemia further decreased PUA (228 ± 62 to 199 ± 65 μmol/l, P < 0.0001), which was accompanied by an increase in FEUA (7.3 ± 3.8 to 11.6 ± 6.7, P < 0.0001). In T1D, PUA levels correlated positively with SBP (P = 0.029) and negatively with ERPF (P = 0.031) and GFR (P = 0.028). After induction of glycosuria with SGLT2 inhibition while maintaining clamped euglycemia, PUA decreased (P < 0.0001) and FEUA increased (P < 0.0001). PUA is lower in T1D vs. HC and positively correlates with SBP and negatively with GFR and ERPF in T1D. Glycosuria rather than hyperglycemia increases uricosuria in T1D. Future studies examining the effect of uric acid-lowering therapies should account for the impact of ambient glycemia, which causes an important uricosuric effect. Copyright © 2015 the American Physiological Society.
Wang, J.; Qu, M.; Leng, S.; McCollough, C. H.
In this study, the feasibility of differentiating uric acid from non-uric acid kidney stones in the presence of iodinated contrast material was evaluated using dual-energy CT (DECT). Iodine subtraction was accomplished with a commercial three material decomposition algorithm to create a virtual non-contrast (VNC) image set. VNC images were then used to segment stone regions from tissue background. The DE ratio of each stone was calculated using the CT images acquired at two different energies with DECT using the stone map generated from the VNC images. The performance of DE ratio-based stone differentiation was evaluated at five different iodine concentrations (21, 42, 63, 84 and 105 mg/ml). The DE ratio of stones in iodine solution was found larger than those obtained in non-iodine cases. This is mainly caused by the partial volume effect around the boundary between the stone and iodine solution. The overestimation of the DE ratio leads to substantial overlap between different stone types. To address the partial volume effect, an expectation-maximization (EM) approach was implemented to estimate the contribution of iodine and stone within each image pixel in their mixture area. The DE ratio of each stone was corrected to maximally remove the influence of iodine solutions. The separation of uric-acid and non-uric-acid stone was improved in the presence of iodine solution.
Leung, James; Karachaliou, Mayia; Alves, Claudia; Diallinas, George; Byrne, Bernadette
The Nucleobase-Ascorbate Transporters (NATs) family includes carriers with fundamental functions in uptake of key cellular metabolites, such as uric acid or vitamin C. The best studied example of a NAT transporter is the uric acid-xanthine permease (UapA) from the model ascomycete Aspergillus nidulans. Detailed genetic and biochemical analyses have revealed much about the mechanism of action of this protein; however, the difficulties associated with handling eukaryotic membrane proteins have limited efforts to elucidate the precise structure-function relationships of UapA by structural analysis. In this manuscript, we describe the heterologous overexpression of functional UapA as a fusion with GFP in different strains of Saccharomyces cerevisiae. The UapA-GFP construct expressed to 2.3 mg/L in a pep4Delta deletion strain lacking a key vacuolar endopeptidase and 3.8 mg/L in an npi1-1 mutant strain with defective Rsp5 ubiquitin ligase activity. Epifluorescence microscopy revealed that the UapA-GFP was predominately localized to the plasma membrane in both strains, although a higher intensity of fluorescence was observed for the npi1-1 mutant strain plasma membrane. In agreement with these observations, the npi1-1 mutant strain demonstrated a approximately 5-fold increase in uptake of [(3)H]-xanthine compared to the pep4Delta deletion strain. Despite yielding the best results for functional expression, in-gel fluorescence of the UapA-GFP expressed in the npi1-1 mutant strain revealed that the protein was subject to significant proteolytic degradation. Large scale expression of the protein using the pep4Delta deletion strain followed by purification produced mg quantities of pure, monodispersed protein suitable for further structural and functional studies. In addition, this work has generated a yeast cell based system for performing reverse genetics and other targeted approaches, in order to further understand the mechanism of action of this important model protein.
Huang, Li-Ling; Huang, Chien-Tsai; Chen, Mei-Lien; Mao, I-Fang
In order to determine whether exercise-induced profuse sweating could reduce urinary uric acid excretion, we simulated badminton players training and measured their uric acid in urine, sweat and blood during the training period. Thirteen male volunteers who were well-trained badminton players were recruited in this study. On the first 2 days and the last 2 days of the study period none of the subjects engaged in any intense exercise- or activity-inducing profuse sweat, but they accepted routine training 2 h per day during the middle 3 days. The results show that mean serum urate levels of thirteen volunteers rose significantly on day 4, when the concentrations increased by 18.2% over day 2 (P < 0.05). The mean ten-hour urinary uric acid excretion of seven volunteers on the 3 training days was significantly less at 178.5 micromol/day and 118.3 micromol/day than those on the preceding and subsequent days of the training days, respectively (P < 0.05). Furthermore, for six volunteers, the mean ratio of clearance of uric acid to creatinine was 6.6% on day 2, which significantly decreased to 5.4% on day 4 (P < 0.05). It is concluded profuse sweating exercise results in a decrease of urinary uric acid excretion amounts and leads to increased serum uric acid after the exercise. We suggest that persons who take vigorous exercise or are exposed to hot environments need drinking enough fluids to prevent dehydration and maintain adequate urinary output. People with profuse sweat after rigorous exercise are recommended taking sports drinks containing abundant sodium in order to decrease serum uric acid.
García-Esquinas, Esther; Guallar-Castillón, Pilar; Carnicero, José Antonio; Buño, Antonio; García-García, Francisco José; Rodríguez-Mañas, Leocadio; Rodríguez-Artalejo, Fernando
To evaluate for the first time the longitudinal relationship between serum uric acid concentrations and risk of frailty. Prospective cohort study of 2198 non-institutionalized individuals aged ≥60years recruited in 2008-2010. At baseline, information was obtained on socio-demographic factors, health behaviors and morbidity, while serum uric acid was determined in 12-h fasting blood samples. Study participants were followed-up through 2012 to assess incident frailty, defined as ≥2 of the following 4 Fried criteria: exhaustion, muscle weakness, low physical activity, and slow walking speed. During a mean 3.5-year follow-up, 256 cases of incident frailty were identified. After multivariate adjustment, the odds ratios (95% confidence interval) of frailty comparing the second and third tertiles of uric acid to the lowest tertile were, respectively: 1.18 (0.83-1.68) and 1.57 (1.11-2.22); p-linear trend=0.01. The corresponding result for a 1mg/dL increase in serum uric acid concentration was 1.12 (1.00-1.24). Similar associations were observed across subgroups defined by sex, age, body mass index, and physical activity. As regards each frailty component, the odds ratios (95% confidence interval) per 1mg/dL increase in serum uric acid were 1.10 (0.99-1.23) for low physical activity, 1.08 (0.95-1.23) for low walking speed, 1.08 (0.67-1.73) for exhaustion and 0.91 (0.81-1.02) for weakness. Serum uric acid concentrations are positively associated with the risk of frailty in older adults. Further studies are needed to evaluate whether specific dietary recommendations or pharmacological strategies aimed at lowering serum uric acid would be beneficial to prevent the development of this syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.
Spettel, Sara; Shah, Paras; Sekhar, Kiran; Herr, Allen; White, Mark D
To determine the in vivo ability to predict uric acid stone composition by Hounsfield units (HU) with the addition of urine parameters. We reviewed all consecutive stones sent for analysis during a 4-year period from our institution for patients with an in-house computed tomography (CT) scan within the prior 6 months and urinalysis within the prior week. CT scans were independently reviewed by a radiologist blinded to stone composition. Of the 507 patients with stones sent for analysis, 235 met the criteria for inclusion. Analysis showed 212 stones were predominantly calcium-based, and 22 were predominantly uric acid in composition. There was a significant difference between calcium stones and uric acid stones in mean HU (890 ± 20 vs 484 ± 44; P <.01) and urine pH (6.4 ± 0.8 vs 5.1 ± 0.2; P <.01). Receiver operating characteristic curve evaluation gave optimal predictive values of HU ≤494 (rounded to 500) and pH of ≤5.5 to predict uric acid stones. The combination of HU and pH criteria resulted in a sensitivity of 86% and a specificity of 98%, with a positive predictive value of 80%, which increased to 90% if we limited to stones >4 mm. Uric acid stones show a significant difference in HU and urine pH from calcium stones, and the use of both criteria is superior to either separately. For a stone >4 mm, a HU ≤500 and pH ≤5.5 has a positive predictive value of 90% for uric acid composition. Our prediction model gives a straightforward tool that can be easily measured to predict a uric acid stone. Copyright © 2013 Elsevier Inc. All rights reserved.
Mrug, Sylvie; Mrug, Michal; Morris, Anjana Madan; Reynolds, Nina; Patel, Anita; Hill, Danielle C; Feig, Daniel I
Hyperuricemia predicts the incidence of hypertension in adults and its treatment has blood pressure (BP)-lowering effects in adolescents. To date, no studies have examined the predictive usage of hyperuricemia or urinary uric acid excretion on BP changes in adolescents. Mechanistic models suggest that uric acid impairs both endothelial function and vascular compliance, which would potentially exacerbate a myriad of hypertensive mechanisms, yet little is known about interaction of uric acid and other hypertension risk factors. The primary study was aimed at the effects of stress on BP in adolescents. A community sample of 84 low-income, urban adolescents (50% male, 95% African American, mean age = 13.36 ± 1 years) was recruited from public schools. Youth completed a 12-hour (overnight) urine collection at home and their BP was measured during rest and in response to acute psychosocial stress. Seventy-six of the adolescents participated in a follow-up visit at 1.5 years when their resting BP was reassessed. In this substudy, we assessed the relationship of renal urate excretion and BP reactivity. After adjusting for resting BP levels at baseline and other covariates, higher levels of uric acid excretion predicted greater BP reactivity to acute psychosocial stress and higher resting BP at 18 months. Urinary excretion of uric acid can serve as an alternative, noninvasive measure of serum uric acid levels that are predictive of BP changes. As hyperuricemia-associated hypertension is treatable, urban adolescents may benefit from routine screening for hyperuricemia or high uric acid excretion. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
C, Rasika; Ghose, Seetesh
Background: Early intervention and appropriate treatment in patients with GDM will help in preventing the adverse maternal and fetal outcome and protect them from long term complications. Several studies have shown the association of hyperuricemia with GDM. This study was undertaken to find out the association of elevated first trimester uric acid with development of GDM. Materials and Methods: This prospective observational study was conducted in Mahatma Gandhi Medical Collage and Research Institute, Pondicherry, India, between November 2010 and May 2012. A total of 70 pregnant women were included and parameters like age, parity, BMI, history of DM, serum uric acid at <15 weeks and at 24 to 28 weeks and one step test at 24 to 28 weeks were noted and compared. Results: There was no significant correlation between the demographic variables and GDM, but a moderate significance noted between the family history of DM and one step test (p=0.048). Though there is a proportional increase in the serum uric acid with increase in the BMI, it was not statistically significant. A significant correlation was seen between BMI and risk of development of GDM (p= 0.001). Though there is a significant correlation between serum uric acid at <15 weeks and at 24 to 28 weeks, serum uric acid at <15 weeks of gestation is a better predictor of GGI and GDM (Pearson’s correlation = 0.735). Conclusion: There is increase in the risk of development of GDM with increased levels of serum uric acid in the first trimester. Uric acid levels at <15 weeks of gestation is more significantly associated with risk of development of GDM than it’s levels at 24 to 28 weeks of gestation. PMID:25653992
C, Rasika; Samal, Sunita; Ghose, Seetesh
Early intervention and appropriate treatment in patients with GDM will help in preventing the adverse maternal and fetal outcome and protect them from long term complications. Several studies have shown the association of hyperuricemia with GDM. This study was undertaken to find out the association of elevated first trimester uric acid with development of GDM. This prospective observational study was conducted in Mahatma Gandhi Medical Collage and Research Institute, Pondicherry, India, between November 2010 and May 2012. A total of 70 pregnant women were included and parameters like age, parity, BMI, history of DM, serum uric acid at <15 weeks and at 24 to 28 weeks and one step test at 24 to 28 weeks were noted and compared. There was no significant correlation between the demographic variables and GDM, but a moderate significance noted between the family history of DM and one step test (p=0.048). Though there is a proportional increase in the serum uric acid with increase in the BMI, it was not statistically significant. A significant correlation was seen between BMI and risk of development of GDM (p= 0.001). Though there is a significant correlation between serum uric acid at <15 weeks and at 24 to 28 weeks, serum uric acid at <15 weeks of gestation is a better predictor of GGI and GDM (Pearson's correlation = 0.735). There is increase in the risk of development of GDM with increased levels of serum uric acid in the first trimester. Uric acid levels at <15 weeks of gestation is more significantly associated with risk of development of GDM than it's levels at 24 to 28 weeks of gestation.
Juraschek, Stephen P; McAdams-Demarco, Mara; Miller, Edgar R; Gelber, Allan C; Maynard, Janet W; Pankow, James S; Young, Hunter; Coresh, Josef; Selvin, Elizabeth
Some observational studies have identified elevated uric acid concentration as a risk factor for diabetes, while others have found an inverse relationship. We examined both the association of uric acid level with incident diabetes and the change in uric acid concentration after a diabetes diagnosis. We analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study and quantified the independent association between uric acid level and incident diabetes via Cox proportional hazards models. The association between duration of diabetes and change in uric acid level was examined via linear regression. Among 11,134 participants without diagnosed diabetes at baseline (1987-1989), there were 1,294 incident cases of diabetes during a median of 9 years of follow-up (1987-1998). Uric acid level was associated with diabetes even after adjustment for risk factors (per 1 mg/dL, hazard ratio = 1.18, 95% confidence interval: 1.13, 1.23), and the association remained significant after adjustment for fasting glucose and insulin levels. Among participants with diabetes (n = 1,510), every additional 5 years' duration of diabetes was associated with a 0.10-mg/dL (95% confidence interval: 0.04, 0.15) lower uric acid level after adjustment. We conclude that uric acid concentration rises prior to diagnosis of diabetes and then declines with diabetes duration. Future studies investigating uric acid as a risk factor for cardiovascular disease should adequately account for the impact and timing of diabetes development.
Mohandas, Rajesh; Sautina, Laura; Beem, Elaine; Schuler, Anna; Chan, Wai-Yan; Domsic, John; McKenna, Robert; Johnson, Richard J.; Segal, Mark S.
Uric acid affects endothelial and adipose cell function and has been linked to diseases such as hypertension, metabolic syndrome, and cardiovascular disease. Interestingly uric acid has been shown to increase endothelial progenitor cell (EPC) mobilization, a potential mechanism to repair endothelial injury. Since EPC mobilization is dependent on activity of the enzyme CD26/dipeptidyl peptidase (DPP)IV, we examined the effect uric acid has on CD26/DPPIV activity. Uric acid inhibited the CD26/DPPIV associated with human umbilical vein endothelial cells but not human recombinant (hr)CD26/DPPIV. However, triuret, a product of uric acid and peroxynitrite, could inhibit cell associated and hrCD26/DPPIV. Increasing or decreasing intracellular peroxynitrite levels enhanced or decreased the ability of uric acid to inhibit cell associated CD26/DPPIV respectively. Last, protein modeling demonstrates how triuret can act as a small molecule inhibitor of CD26/DPPIV activity. This is the first time that uric acid or a uric acid reaction product has been shown to affect enzymatic activity and suggests a novel avenue of research in the role of uric acid in the development of clinically important diseases. PMID:24925478
Juraschek, Stephen P.; McAdams-Demarco, Mara; Miller, Edgar R.; Gelber, Allan C.; Maynard, Janet W.; Pankow, James S.; Young, Hunter; Coresh, Josef; Selvin, Elizabeth
Some observational studies have identified elevated uric acid concentration as a risk factor for diabetes, while others have found an inverse relationship. We examined both the association of uric acid level with incident diabetes and the change in uric acid concentration after a diabetes diagnosis. We analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study and quantified the independent association between uric acid level and incident diabetes via Cox proportional hazards models. The association between duration of diabetes and change in uric acid level was examined via linear regression. Among 11,134 participants without diagnosed diabetes at baseline (1987–1989), there were 1,294 incident cases of diabetes during a median of 9 years of follow-up (1987–1998). Uric acid level was associated with diabetes even after adjustment for risk factors (per 1 mg/dL, hazard ratio = 1.18, 95% confidence interval: 1.13, 1.23), and the association remained significant after adjustment for fasting glucose and insulin levels. Among participants with diabetes (n = 1,510), every additional 5 years’ duration of diabetes was associated with a 0.10-mg/dL (95% confidence interval: 0.04, 0.15) lower uric acid level after adjustment. We conclude that uric acid concentration rises prior to diagnosis of diabetes and then declines with diabetes duration. Future studies investigating uric acid as a risk factor for cardiovascular disease should adequately account for the impact and timing of diabetes development. PMID:24418684
Mohandas, Rajesh; Sautina, Laura; Beem, Elaine; Schuler, Anna; Chan, Wai-Yan; Domsic, John; McKenna, Robert; Johnson, Richard J; Segal, Mark S
Uric acid affects endothelial and adipose cell function and has been linked to diseases such as hypertension, metabolic syndrome, and cardiovascular disease. Interestingly uric acid has been shown to increase endothelial progenitor cell (EPC) mobilization, a potential mechanism to repair endothelial injury. Since EPC mobilization is dependent on activity of the enzyme CD26/dipeptidyl peptidase (DPP)IV, we examined the effect uric acid will have on CD26/DPPIV activity. Uric acid inhibited the CD26/DPPIV associated with human umbilical vein endothelial cells but not human recombinant (hr) CD26/DPPIV. However, triuret, a product of uric acid and peroxynitrite, could inhibit cell associated and hrCD26/DPPIV. Increasing or decreasing intracellular peroxynitrite levels enhanced or decreased the ability of uric acid to inhibit cell associated CD26/DPPIV, respectively. Finally, protein modeling demonstrates how triuret can act as a small molecule inhibitor of CD26/DPPIV activity. This is the first time that uric acid or a uric acid reaction product has been shown to affect enzymatic activity and suggests a novel avenue of research in the role of uric acid in the development of clinically important diseases. Published by Elsevier Inc.
Asghar, Zeenat A.; Thompson, Alysha; Chi, Maggie; Cusumano, Andrew; Scheaffer, Suzanne; Al-Hammadi, Noor; Saben, Jessica L.; Moley, Kelle H.
Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans. PMID:27125896
Lindeman, Neal I; Melanson, Stacy E F; McDonnell, Anne; DeAngelo, Daniel J; Jarolim, Petr
Rasburicase, used for hyperuricemia of tumor lysis syndrome, retains activity at room temperature (RT) in in vitro studies. Cold-temperature handling is recommended for uric acid measurements in patients receiving rasburicase: collection in prechilled tubes, transportation on ice, and 4°C centrifugation. We performed a prospective study of these requirements. A total of 65 pairs of blood samples were collected from 34 patients, 12-24 h after receiving rasburicase. The effect of temperature on uric acid concentration was tested on paired samples handled either at RT or when cold: centrifugation (18 sample pairs), collection tube (14 pairs), transportation (24 pairs), and nine pairs were retested after 1 h at RT. No significant temperature effect was seen on the uric acid measurements for any of the cold-handling steps: proportional, absolute biases were -1.4%, -0.06 mg/dL (centrifugation), -1.5%, +0.02 mg/dL (tube temperature), and -2.2%, -0.01 mg/dL (transportation). A 20% negative bias was seen in samples retested after 1 h at RT. Cold handling (prechilled tubes, iced transportation, 4°C centrifugation) was equivalent to RT for immediate measurement. An additional 1 h delay at RT led to a 20% decrease in uric acid. The cold handling measures required by the manufacturer are not necessary for uric acid testing of patients receiving rasburicase treatment, if testing is performed without delay.
de Miranda, Josiane Aparecida; Almeida, Guilherme Gomide; Martins, Raissa Isabelle Leão; Cunha, Mariana Botrel; Belo, Vanessa Almeida; dos Santos, José Eduardo Tanus; Mourão-Júnior, Carlos Alberto; Lanna, Carla Márcia Moreira
To investigate the association between serum uric acid levels and insulin resistance in children and adolescents with obesity. Cross-sectional study with 245 children and adolescents (134 obese and 111 controls), aged 8 to 18 years. The anthropometric variables (weight, height and waist circumference), blood pressure and biochemical parameters were collected. The clinical characteristics of the groups were analyzed by t-test or chi-square test. To evaluate the association between uric acid levels and insulin resistance the Pearson's test and logistic regression were applied. The prevalence of insulin resistance was 26.9%. The anthropometric variables, systolic and diastolic blood pressure and biochemical variables were significantly higher in the obese group (p<0.001), except for the high-density-lipoprotein cholesterol. There was a positive and significant correlation between anthropometric variables and uric acid with HOMA-IR in the obese and in the control groups, which was higher in the obese group and in the total sample. The logistic regression model that included age, gender and obesity, showed an odds ratio of uric acid as a variable associated with insulin resistance of 1.91 (95%CI 1.40 to 2.62; p<-0.001). The increase in serum uric acid showed a positive statistical correlation with insulin resistance and it is associated with and increased risk of insulin resistance in obese children and adolescents. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.
Takir, Mumtaz; Kostek, Osman; Ozkok, Abdullah; Elcioglu, Omer Celal; Bakan, Ali; Erek, Aybala; Mutlu, Hasan Huseyin; Telci, Ozge; Semerci, Aysun; Odabas, Ali Riza; Afsar, Baris; Smits, Gerard; ALanaspa, Miguel; Sharma, Shailendra; Johnson, Richard J; Kanbay, Mehmet
Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes, but whether it has a causal role in insulin resistance remains controversial. Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Subjects with asymptomatic hyperuricemia (n = 73) were prospectively placed on allopurinol (n = 40) or control (n = 33) for 3 months. An additional control group consisted of 48 normouricemic subjects. Serum uric acid, fasting glucose, fasting insulin, HOMA-IR (homeostatic model assessment of insulin resistance), and high-sensitivity C-reactive protein were measured at baseline and at 3 months. Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose, fasting insulin, and HOMA-IR index, as well as a reduction in serum high-sensitivity C-reactive protein. The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline (n = 8 [20%] vs n = 30 [75%], 3 months vs baseline, P < 0.001). In the hyperuricemic control group, only glucose decreased significantly and, in the normouricemic control, no end point changed. Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes.
de Miranda, Josiane Aparecida; Almeida, Guilherme Gomide; Martins, Raissa Isabelle Leão; Cunha, Mariana Botrel; Belo, Vanessa Almeida; dos Santos, José Eduardo Tanus; Mourão-Júnior, Carlos Alberto; Lanna, Carla Márcia Moreira
Objective: To investigate the association between serum uric acid levels and insulin resistance in children and adolescents with obesity. Methods: Cross-sectional study with 245 children and adolescents (134 obese and 111 controls), aged 8-18 years. The anthropometric variables (weight, height and waist circumference), blood pressure and biochemical parameters were collected. The clinical characteristics of the groups were analyzed by t-test or chi-square test. To evaluate the association between uric acid levels and insulin resistance the Pearson's test and logistic regression were applied. Results: The prevalence of insulin resistance was 26.9%. The anthropometric variables, systolic and diastolic blood pressure and biochemical variables were significantly higher in the obese group (p<0.001), except for the high-density-lipoprotein cholesterol. There was a positive and significant correlation between anthropometric variables and uric acid with HOMA-IR in the obese and in the control groups, which was higher in the obese group and in the total sample. The logistic regression model that included age, gender and obesity, showed an odds ratio of uric acid as a variable associated with insulin resistance of 1.91 (95%CI 1.40-2.62; p<−0.001). Conclusions: The increase in serum uric acid showed a positive statistical correlation with insulin resistance and it is associated with and increased risk of insulin resistance in obese children and adolescents. PMID:26300523
da Silva, Hellen Abreu; Carraro, Júlia Cristina Cardoso; Bressan, Josefina; Hermsdorff, Helen Hermana Miranda
Objective To identify possible relations between serum uric acid levels and metabolic syndrome and its components in a population with cardiometabolic risk. Methods This cross-sectional study included 80 subjects (46 women), with mean age of 48±16 years, seen at the Cardiovascular Health Program. Results The prevalence of hyperuricemia and metabolic syndrome was 6.3% and 47.1%, respectively. Uric acid level was significantly higher in individuals with metabolic syndrome (5.1±1.6mg/dL), as compared to those with no syndrome or with pre-syndrome (3.9±1.2 and 4.1±1.3mg/dL, respectively; p<0.05). The uric acid levels were significantly higher in men presenting abdominal obesity, and among women with abdominal obesity, lower HDL-c levels and higher blood pressure (p<0.05). Conclusion Uric acid concentrations were positively related to the occurrence of metabolic syndrome and its components, and there were differences between genders. Our results indicate serum uric acid as a potential biomarker for patients with cardiometabolic risk. PMID:26018145
Orengo, Jamie Marie; Leliwa-Sytek, Aleksandra; Evans, James E.; Evans, Barbara; van de Hoef, Diana; Nyako, Marian; Day, Karen; Rodriguez, Ana
Background Malaria triggers a high inflammatory response in the host that mediates most of the associated pathologies and contributes to death. The identification of pro-inflammatory molecules derived from Plasmodium is essential to understand the mechanisms of pathogenesis and to develop targeted interventions. Uric acid derived from hypoxanthine accumulated in infected erythrocytes has been recently proposed as a mediator of inflammation in rodent malaria. Methods and Findings We found that human erythrocytes infected with Plasmodium falciparum gradually accumulate hypoxanthine in their late stages of development. To analyze the role of hypoxanthine-derived uric acid induced by P. falciparum on the inflammatory cytokine response from human blood mononuclear cells, cultures were treated with allopurinol, to inhibit uric acid formation from hypoxanthine, or with uricase, to degrade uric acid. Both treatments significantly reduce the secretion of TNF, IL-6, IL-1β and IL-10 from human cells. Conclusions and Significance Uric acid is a major contributor of the inflammatory response triggered by P. falciparum in human peripheral blood mononuclear cells. Since the inflammatory reaction induced by P. falciparum is considered a major cause of malaria pathogenesis, identifying the mechanisms used by the parasite to induce the host inflammatory response is essential to develop urgently needed therapies against this disease. PMID:19381275
Lanaspa, Miguel A.; Sanchez-Lozada, Laura G.; Cicerchi, Christina; Li, Nanxing; Roncal-Jimenez, Carlos A.; Ishimoto, Takuji; Le, Myphuong; Garcia, Gabriela E.; Thomas, Jeffrey B.; Rivard, Christopher J.; Andres-Hernando, Ana; Hunter, Brandi; Schreiner, George; Rodriguez-Iturbe, Bernardo; Sautin, Yuri Y.; Johnson, Richard J.
Excessive dietary fructose intake may have an important role in the current epidemics of fatty liver, obesity and diabetes as its intake parallels the development of these syndromes and because it can induce features of metabolic syndrome. The effects of fructose to induce fatty liver, hypertriglyceridemia and insulin resistance, however, vary dramatically among individuals. The first step in fructose metabolism is mediated by fructokinase (KHK), which phosphorylates fructose to fructose-1-phosphate; intracellular uric acid is also generated as a consequence of the transient ATP depletion that occurs during this reaction. Here we show in human hepatocytes that uric acid up-regulates KHK expression thus leading to the amplification of the lipogenic effects of fructose. Inhibition of uric acid production markedly blocked fructose-induced triglyceride accumulation in hepatocytes in vitro and in vivo. The mechanism whereby uric acid stimulates KHK expression involves the activation of the transcription factor ChREBP, which, in turn, results in the transcriptional activation of KHK by binding to a specific sequence within its promoter. Since subjects sensitive to fructose often develop phenotypes associated with hyperuricemia, uric acid may be an underlying factor in sensitizing hepatocytes to fructose metabolism during the development of fatty liver. PMID:23112875
Zhao, Shulin; Lan, Xuehua; Liu, Yi-Ming
A sensitive method based on gold nanoparticle-enhanced capillary electrophoresis-chemiluminescence detection was developed for quantifying uric acid in serum. In this work, gold nanoparticles were added into the running buffer of capillary electrophoresis to catalyze the post-column chemiluminescence reaction between luminol and hydrogen peroxide, achieving highly efficient chemiluminescence emission. Negative peaks were produced due to the inhibitory effects on chemiluminescence emission from uric acid eluted from the electrophoretic capillary. The decrease in chemiluminescence intensity was proportional to the concentration of uric acid in the range of 2.5 × 10−7 ~ 1.0 × 10−5 M. Detection limit was 4.6 × 10−8 M uric acid. Ten human serum samples were analyzed by the presented method. Serum level of uric acid was found to be in the range from 204 to 324 μM for healthy subjects (n=5), and from 464 to 497 μM for diabetic patients (n=5). The two groups were significantly different (p < 0.05). The results suggested a potential application of the proposed assay in rapid primary diagnosis of diseases such as diabetes. PMID:19650050
Chauhan, Nidhi; Pundir, Chandra Shekhar
An amperometric uric acid biosensor was fabricated by immobilizing uricase (EC 18.104.22.168) onto gold nanoparticle (AuNP)/multiwalled carbon nanotube (MWCNT) layer deposited on Au electrode via carbodiimide linkage. Determination of uric acid was performed by oxidation of enzymically generated H(2)O(2) at 0.4V. The sensor showed optimal response within 7s at 40°C in 50mM Tris-HCl buffer (pH 7.5). The linear working range of the biosensor was 0.01-0.8mM. The limit of detection (LOD) was 0.01mM. The sensor measured uric acid levels in serum of healthy individuals and persons suffering from gout. The analytical recoveries of the added uric acid, 10 and 20mgL(-1), were 98.0% and 96.5%, respectively. Within- and between-batch coefficients of variation were less than 5.6% and less than 4.7%, respectively. A good correlation (r=0.998) was obtained between serum uric acid values by the standard enzymic colorimetric method and the current method. A number of serum substances had practically no interference. The sensor was used in more than 200 assays and had a storage life of 120 days at 4°C. Copyright © 2011 Elsevier Inc. All rights reserved.
Ballesta-Claver, J; Díaz Ortega, I F; Valencia-Mirón, M C; Capitán-Vallvey, L F
A new electrochemiluminescent (ECL) disposable biosensor for uric acid was manufactured by immobilization in a double-layer design of luminol as a copolymer with 3,3',5,5'-tetramethylbenzidine (TMB) and the enzyme uricase in chitosan on gold screen-printed cells. The good mechanical and improved electroluminescent characteristics of the new copolymer poly(luminol-TMB) make it possible to determine uric acid by measuring the growing ECL emission with the analyte concentration. The combination of enzymatic selectivity with ECL sensitivity results in a disposable analytical device with a linear range for uric acid from 1.5×10(-6) to 1.0×10(-4) M, a limit of detection of 4.4×10(-7) M and a precision of 13.1% (1.0×10(-5) M, n=10) as relative standard deviation. Satisfactory results were obtained for uric acid determination in 24h-urine samples compared to a reference procedure. This uric acid biosensor can be used as a low-cost alternative to conventional methods.
Lanaspa, Miguel A; Sanchez-Lozada, Laura G; Cicerchi, Christina; Li, Nanxing; Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Le, Myphuong; Garcia, Gabriela E; Thomas, Jeffrey B; Rivard, Christopher J; Andres-Hernando, Ana; Hunter, Brandi; Schreiner, George; Rodriguez-Iturbe, Bernardo; Sautin, Yuri Y; Johnson, Richard J
Excessive dietary fructose intake may have an important role in the current epidemics of fatty liver, obesity and diabetes as its intake parallels the development of these syndromes and because it can induce features of metabolic syndrome. The effects of fructose to induce fatty liver, hypertriglyceridemia and insulin resistance, however, vary dramatically among individuals. The first step in fructose metabolism is mediated by fructokinase (KHK), which phosphorylates fructose to fructose-1-phosphate; intracellular uric acid is also generated as a consequence of the transient ATP depletion that occurs during this reaction. Here we show in human hepatocytes that uric acid up-regulates KHK expression thus leading to the amplification of the lipogenic effects of fructose. Inhibition of uric acid production markedly blocked fructose-induced triglyceride accumulation in hepatocytes in vitro and in vivo. The mechanism whereby uric acid stimulates KHK expression involves the activation of the transcription factor ChREBP, which, in turn, results in the transcriptional activation of KHK by binding to a specific sequence within its promoter. Since subjects sensitive to fructose often develop phenotypes associated with hyperuricemia, uric acid may be an underlying factor in sensitizing hepatocytes to fructose metabolism during the development of fatty liver.
Du, Na; Xu, Donghua; Hou, Xu; Song, Xuejia; Liu, Cancan; Chen, Ying; Wang, Yangang; Li, Xin
The association between Alzheimer's disease and uric acid levels had gained great interest in recent years, but there was still lack of definite evidence. A systematic review and meta-analysis of relevant studies was performed to comprehensively estimate the association. Relevant studies published before October 26, 2014, were searched in PubMed, Embase, and China Biology Medicine (CBM) databases. Study-specific data were combined using random-effects or fixed-effects models of meta-analysis according to between-study heterogeneity. Twenty-four studies (21 case-control and 3 cohort studies) were finally included into the meta-analysis. Those 21 case-control studies included a total of 1128 cases of Alzheimer's disease and 2498 controls without Alzheimer's disease. Those 3 cohort studies included a total of 7327 participants. Meta-analysis showed that patients with Alzheimer's disease had lower levels of uric acid than healthy controls (weighted mean difference (WMD) = -0.77 mg/dl, 95% CI -2.28 to -0.36, P = 0.0002). High serum uric acid levels were significantly associated with decreased risk of Alzheimer's disease (risk ratio (RR) = 0.66, 95% CI 0.52-0.85, P = 0.001). There was low risk of publication bias in the meta-analysis. There is an inverse association between serum uric acid levels and Alzheimer's disease. High serum uric acid level is a protective factor of Alzheimer's disease.
Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei
Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883
Kanchana, P; Sekar, C
Hydroxyapatite nanoparticles have been synthesized using EDTA as organic modifier by a simple microwave irradiation method and its application for the selective determination of uric acid (UA) has been demonstrated. Electrochemical behavior of uric acid at HA nanoparticle modified glassy carbon electrode (E-HA/GCE) has been investigated by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), linear sweep voltammetry (LSV) and amperometry. The E-HA modified electrode exhibits efficient electrochemical activity towards uric acid sensing without requiring enzyme or electron mediator. Amperometry studies revealed that the fabricated electrode has excellent sensitivity for uric acid with the lowest detection limit of 142 nM over a wide concentration range from 1 × 10(-7) to 3 × 10(-5)M. Moreover, the studied E-HA modified GC electrode exhibits a good reproducibility and long-term stability and an admirable selectivity towards the determination of UA even in the presence of potential interferents. The analytical performance of this sensor was evaluated for the detection of uric acid in human urine and blood serum samples. Copyright © 2014. Published by Elsevier B.V.
Ding, Xiang; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Zhang, Yi; Xiong, Yi-Lin; Gao, Shu-Guang; Li, Yu-Sheng; Lei, Guang-Hua
To examine the cross-sectional associations of the serum uric acid level and hyperuricemia (HU) with the radiographic features of osteoarthritis (OA), including osteophytes (OST) and joint space narrowing (JSN), a total of 4685 subjects were included in this study. Blood samples were drawn from all subjects. Serum uric acid and some other indexes were detected. OST and JSN were assessed for each subject according to the Osteoarthritis Research Society International (OARSI) atlas. A multivariable logistic analysis model was applied to test the target associations after adjusting a number of potential confounding factors. The prevalence of OST was increased in the highest tertile of uric acid compared to the lowest in female subjects (OR 1.46, 95 % CI 1.07-1.99, P for trend = 0.02). Meanwhile, a positive association between OST and HU was observed in female subjects (OR 1.43, 95 % CI 1.01-2.03, P = 0.05). However, serum uric acid and HU were not significantly associated with JSN in male subjects. The findings of this study indicated that the serum uric acid concentration and prevalence of HU are positively associated with OST of the knee in the female population. Level of evidence Cross-sectional study, Level III.
Asghar, Zeenat A; Thompson, Alysha; Chi, Maggie; Cusumano, Andrew; Scheaffer, Suzanne; Al-Hammadi, Noor; Saben, Jessica L; Moley, Kelle H
Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans.
Mohamed, Amr Ali; Matijević, Egon
Uric acid, the major component in many kinds of kidney stones, as well as its sodium, ammonium, calcium, and barium salts were successfully prepared as uniform dispersions by precipitation in basic aqueous solutions. The effects of the reactant concentrations, pH, and the stabilizers were evaluated in detail. Except for the platelets of the pure acid, all prepared compounds appeared as needles or their aggregates. The electron micrographs showed that kidney stones consisted of such aggregates although less regular in size and morphology. All prepared urate salts had a 1:1 cation/uric acid ratio, regardless of the valence of the cation. The electrokinetic measurements showed all these particles to have negative ζ-potentials over the pH range 3-9. The precipitated salt particles were chemically and morphologically unstable at low pH values by decomposing into ill-defined aggregates of the pure uric acid.
Bae, Eunjin; Cho, Hyun-Jeong; Shin, Nara; Kim, Sun Moon; Yang, Seung Hee; Kim, Dong Ki; Kim, Yong-Lim; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam Ho; Kim, Yon Su; Lee, Hajeong
Abstract We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007–2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis. PMID:27310949
Alves-Junior, Eduardo R.; Arruda, Talita A.; Lopes, Jose C.; Fontes, Cor J.F.
Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18–69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with
Nogi, Shinpei; Fujita, Shu-Ichi; Okamoto, Yusuke; Kizawa, Shun; Morita, Hideaki; Ito, Takahide; Sakane, Kazushi; Sohmiya, Koichi; Hoshiga, Masaaki; Ishizaka, Nobukazu
Serum uric acid (SUA) is associated with the severity and prognosis of systolic heart failure. We investigated the potential association between SUA and cardiac diastolic dysfunction among total of 744 cardiac patients (202 women and 542 men) who had preserved left ventricular ejection fraction. Presence of diastolic dysfunction was assessed by echocardiographic data, plasma B-type natriuretic peptide concentration, and left ventricular hypertrophy. Univariate analysis showed that the prevalence of diastolic dysfunction increased with increasing SUA value in women, but not in men. When sex-nonspecific SUA quartiles were used, multivariate logistic regression analysis, among female patients who were not taking uric acid lowering medication, showed that the third (SUA, 5.7-6.4 mg) and the fourth (SUA, ≥6.5 mg/dl) SUA quartiles were associated with diastolic dysfunction with an odds ratio of 3.25 (P < 0.05) and 8.06 (P < 0.001), respectively, when compared with the first SUA quartile (≤4.7 mg/dl). When sex-specific SUA quartiles were used among these population, multivariate logistic regression analysis showed that the fourth SUA quartile (≥5.7 mg/dl) was associated with diastolic dysfunction with an odds ratio of 5.34 (P < 0.05) when compared with the first SUA quartile (≤4.1 mg/dl). By contrast, the relationship between SUA and diastolic dysfunction was not significant in men, irrespective of which of the sex-nonspecific or sex-specific SUA quartiles were used. These data indicated that among cardiac patients with preserved ejection fraction, SUA was significantly associated with diastolic dysfunction in women but not in men.
Pormsila, Worapan; Krähenbühl, Stephan; Hauser, Peter C
The suitability of capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C(4)D) for the direct determination of uric acid in human plasma and urine was investigated. It was found that a careful optimization of the buffer composition and pH was necessary to achieve selective determination in the complex sample matrices. An electrolyte solution consisting of 10mM 2-morpholinoethanesulfonic acid (MES), 10mM histidine and 0.1mM hexadecyltrimethylammonium bromide (CTAB), pH 6.0, was finally found suitable for use as running buffer for both sample matrices. The limit of detection (3 S/N) was determined as 3.3 microM. The linearity of the response was tested for the range between 10 and 500 microM and a correlation coefficient of 0.9996 was obtained. Intra- and inter-day variabilities were <10%. Quantitative analysis of urine and plasma samples showed a good correlation with the routine enzymatic method currently used at the University Hospital of Basel.
Simental-Mendía, Esteban; Simental-Mendía, Luis E; Guerrero-Romero, Fernando
It has been reported that patients with multiple sclerosis (MS) exhibit lower serum uric acid levels; however, the association between uric acid concentrations and benign MS (BMS) has not been assessed. Hence, the objective of the present study was to determine whether the serum concentrations of uric acid are associated with the presence of BMS. Men and non-pregnant women over 16 years of age with diagnosis of MS were enrolled in a cross-sectional study. Expanded Disability Status Scale score < 3, progression of disease ≤10 years, diabetes, renal or hepatic diseases, gout, malignancy, alcohol intake, and treatment with thiazide diuretics and/or acetylsalicylic acid were exclusion criteria. According to subtype of disease, the eligible patients were allocated into groups with BMS and other varieties of MS. A logistic regression analysis was conducted in order to evaluate the association between serum concentrations of uric acid and BMS. A total of 106 patients were included, 39 in the group with BMS and 67 in the group with other varieties of MS. The logistic regression analysis adjusted by age, sex, and disease duration showed that increased concentrations of uric acid, indeed within the physiological levels, are significantly associated with the presence of BMS (OR = 2.60; 95% CI: 1.55-4.38, p < 0.001). The results of the present study suggest that elevated concentrations of uric acid, indeed within the physiological range, are likely linked to the presence of BMS.
Wakuda, Hirokazu; Uchida, Shinya; Ikeda, Masahiko; Tabuchi, Masaki; Akahoshi, Yasumitsu; Shinozuka, Kazumasa; Yamada, Shizuo
Although hyperlipidemia, high blood pressure, and diabetes increase the risk of arteriosclerosis, it is not clear whether hyperuricemia increases the risk of arteriosclerosis or not. We examined the effects of uric acid and curative drugs for hyperuricemia on atherosclerosis-susceptible C57BL/6J apolipoprotein E-deficient (apoE(-/-)) mice. Male apoE(-/-) mice (age: 6 weeks) were fed a normal diet (normal diet group) or a uric acid-enriched diet. Mice fed the uric acid-enriched diet were divided into three groups and administered a drinking vehicle (high uric acid diet group), allopurinol (20 mg·kg(-1)·d(-1)), or benzbromarone (20 mg·kg(-1)·d(-1)) for 10 weeks. Serum uric acid concentrations were higher in the high uric acid diet group than in the normal diet group, and concentrations in the allopurinol and benzbromarone groups were lower than in the high uric acid diet group. Serum total cholesterol and triglyceride levels were lower in the allopurinol group than in the high uric acid diet group. Oxidative stress was lower in the benzbromarone group than in the high uric acid diet group. Atherosclerotic lesion areas were smaller in the allopurinol and benzbromarone groups than in the high uric acid diet group. Thus, hyperuricemia may not be an independent risk factor for arteriosclerosis; however, the administration of allopurinol and benzbromarone prevented the development of atherosclerosis in apoE(-/-) mice fed a uric acid-enriched diet. The anti-atherosclerotic effect was in part due to lower total cholesterol and oxidative stress in the serum. Other possible mechanisms underlying this effect should be investigated.
Zhang, Bin; Yang, Ning; Lin, Shao-Peng; Zhang, Feng
Cerebral infarction (CI) is a common clinical cerebrovascular disease, and to explore the pathophysiological mechanisms and seek effective treatment means are the hotspot and difficult point in medical research nowadays. Numerous studies have confirmed that uric acid plays an important role in CI, but the mechanism has not yet been clarified. When treating HT22 and BV-2 cells with different concentrations of uric acid, uric acid below 450 μM does not have significant effect on cell viability, but uric acid more than 500 μM can significantly inhibit cell viability. After establishing models of OGD (oxygen-glucose deprivation) with HT22 and BV-2 cells, uric acid at a low concentration (50 μM) cannot improve cell viability and apoptosis, and Reactive oxygen species (ROS) levels during OGD/reoxygenation; a suitable concentration (300 μM) of uric acid can significantly improve cell viability and apoptosis, and reduce ROS production during OGD/reoxygenation; but a high concentration (1000 μM) of uric acid can further reduce cell viability and enhance ROS production. After establishing middle cerebral artery occlusion of male rats with suture method, damage and increase of ROS production in brain tissue could be seen, and after adding suitable concentration of uric acid, the degree of brain damage and ROS production was reduced. Therefore, different concentrations of uric acid should have different effect, and suitable concentrations of uric acid have neuroprotective effect, and this finding may provide guidance for study on the clinical curative effect of uric acid.
The binding interaction between human hemoglobin and uric acid has been studied for the first time, by UV-vis absorption and steady-state, synchronous and three-dimensional fluorescence techniques. Characteristic effects observed for human hemoglobin intrinsic fluorescence during interaction with uric acid at neutral pH point at the formation of stacking non-covalent and non-fluorescent complexes. All the calculated parameters, the binding, fluorescence quenching and bimolecular quenching rate constants, as well as Förster resonance energy transfer parameters confirm the existence of static quenching. The results of synchronous fluorescence measurements indicate that the fluorescence quenching of human hemoglobin originates both from Trp and Tyr residues and that the addition of uric acid could significantly hinder the physiological functions of human hemoglobin.
The binding interaction between human hemoglobin and uric acid has been studied for the first time, by UV-vis absorption and steady-state, synchronous and three-dimensional fluorescence techniques. Characteristic effects observed for human hemoglobin intrinsic fluorescence during interaction with uric acid at neutral pH point at the formation of stacking non-covalent and non-fluorescent complexes. All the calculated parameters, the binding, fluorescence quenching and bimolecular quenching rate constants, as well as Förster resonance energy transfer parameters confirm the existence of static quenching. The results of synchronous fluorescence measurements indicate that the fluorescence quenching of human hemoglobin originates both from Trp and Tyr residues and that the addition of uric acid could significantly hinder the physiological functions of human hemoglobin.
Miyaoka, Tokiko; Mochizuki, Toshio; Takei, Takashi; Tsuchiya, Ken; Nitta, Kosaku
Hyperuricemia is common in chronic kidney disease (CKD), but data regarding the relationship between serum uric acid levels and the long-term outcomes of CKD patients have been limited. The present study evaluated the associations between baseline serum uric acid levels with mortality and end-stage renal disease (ESRD). The subjects of this study were 551 stage 2-4 CKD patients. Cox proportional hazards models were used to evaluate the relationship between serum uric acid tertiles and all-cause mortality, cardiovascular disease (CVD) mortality, 50 % reduction in estimated glomerular filtration rate (eGFR), and development of ESRD, initially without adjustment, and then after adjusting for several groups of covariates. The mean age of the study subjects was 58.5 years, 59.3 % were men, and 10.0 % had diabetes. The mean eGFR was 42.02 ± 18.52 ml/min/1.73 m(2). In all subjects, the mean serum uric acid level was 6.57 ± 1.35 mg/dl, and 52.2 % of study subjects were on hypouricemic therapy (allopurinol; 48.3 %) at baseline. Thirty-one patients (6.1 %) died during a follow-up period of approximately 6 years. There was no significant association between serum uric acid level and all-cause mortality, CVD mortality, development of ESRD and 50 % reduction in eGFR in the unadjusted Cox models. In the adjusted models, hyperuricemia was found to be associated with all-cause mortality and CVD mortality after adjustment with CVD risk factors, kidney disease factors, and allopurinol, but not associated with development of ESRD and 50 % reduction in eGFR. The results of this study showed that hyperuricemia but not serum uric acid levels were associated with all-cause mortality, CVD mortality after adjustments with CVD risk factors, kidney disease factors, and allopurinol in stage 2-4 CKD patients.
Al-Meshaweh, Ahoud F; Jafar, Yaqoub; Asem, Mohammad; Akanji, Abayomi O
The objective of this study was to explore the relationships between circulating uric acid and lipid levels and components of the metabolic syndrome (MetS) in Arab dyslipidemic patients, a group already at high coronary artery disease risk. The medical records of 1,229 subjects (632 men, 597 women) referred for treatment of dyslipidemia and followed up for at least 12 months were reviewed. Serum levels of uric acid and lipids (total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein) and other variables in the National Cholesterol Education Program ATP III criteria definition of MetS were assessed at initial presentation and every 4- 6 months, under specific lipid-lowering treatment (statins and/or fibrates), in each of the subjects. Their respective associations were explored by appropriate logistic regression techniques with control for confounding risk factors, including age, gender and body mass index. 306 subjects (24.9%) of the study population were hyperuricemic; they were more likely to be men, obese and diabetic. Also the serum uric acid level (mean ± SD) was greater in men with MetS compared with men without (377.0 ± 98.0 vs. 361.6 ± 83.1 μmol/l, p < 0.05), an observation not reproduced in women. Uric acid levels had significant associations with the presence of fasting hyperglycemia, hypertension and large waist circumference (WC) in men, but only with large WC in women. With statin treatment, uric acid levels decreased by 10% within 1 year of treatment; with fibrates, uric acid levels remained unchanged or slightly increased. The data showed that hyperuricemia is common in dyslipidemic patients in Kuwait, where its important determinants are male sex, obesity, diabetes and statin treatment. Copyright © 2011 S. Karger AG, Basel.
Ahmad, Mousa N.; Haddad, Fares H.; Azzeh, Firas S.
BACKGROUND/OBJECTIVES Metabolic syndrome (MetS) is a set of interrelated metabolic risk factors that increase the risk of cardiovascular morbidity and mortality. Studies regarding the specificity and sensitivity of serum levels of leptin and uric acid as predictors of MetS are limited. The aim of this study was to evaluate the serum levels of leptin and uric acid in terms of their specificity and sensitivity as predictors of MetS in the studied Jordanian group. SUBJECTS/METHODS In this cross sectional study, 630 adult subjects (308 men and 322 women) were recruited from the King Hussein Medical Center (Amman, Jordan). The diagnosis of MetS was made according to the 2005 International Diabetes Federation criteria. Receiver operating characteristic curves were used to determine the efficacy of serum levels of leptin and uric acid as predictors of MetS in the studied Jordanian group. RESULTS Study results showed that for identification of subjects with MetS risk, area under the curve (AUC) for leptin was 0.721 and 0.683 in men and women, respectively. Serum uric acid levels in men showed no significant association with any MetS risk factors and no significant AUC, while uric acid AUC was 0.706 in women. CONCLUSION Serum leptin levels can be useful biomarkers for evaluation of the risk of MetS independent of baseline obesity in both men and women. On the other hand, serum uric acid levels predicted the risk of MetS only in women. PMID:27478548
Bartoli, Francesco; Crocamo, Cristina; Mazza, Mario Gennaro; Clerici, Massimo; Carrà, Giuseppe
Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I(2) index. Relevant sensitivity and meta-regression analyses were conducted. We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p < 0.001, I(2) = 82.9%) and those with major depression (SMD = 0.46, p < 0.001; I(2) = 68.7%). However, meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I(2) = 58.8%), a sensitivity analysis did not confirm the association. In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research. Copyright © 2016 Elsevier Ltd. All rights reserved.
Ji, Chunpeng; Li, Yanping; Cui, Liufu; Cai, Jianfang; Shi, Jihong; Cheng, Feon W; Li, Yuqing; Curhan, Gary C; Wu, Shouling; Gao, Xiang
To test whether prenatal exposure to earthquake (as a surrogate for acute prenatal stress) could have unfavorable effects on uric acid levels later in life. We included 536 individuals who had been prenatally exposed to the Tangshan earthquake in 1976, and 536 sex- and age-matched individuals without that exposure. Serum uric acid concentrations were measured based on fasting blood samples, which were repeatedly collected in 2006, 2008, and 2010. Mean uric acid concentrations in 2010 and the increasing rate from 2006 to 2010 were compared between the 2 groups, after adjustment for age, sex, body mass index, serum concentrations of glucose, triglycerides, C-reactive protein level, estimated glomerular filtration rate, and other potential confounders. We also used multiple logistic regression to estimate the risk of hyperuricemia (>416 μmole/liter in men or >357 μmole/liter in women) in 2010 by calculating the odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjustment for the previously mentioned covariates. Participants with prenatal exposure to the earthquake had higher concentrations of serum uric acid (adjusted means 315 μmole/liter versus 296 μmole/liter; P = 0.001) and a higher likelihood of having hyperuricemia (multivariate adjusted OR 1.70 [95% CI 1.09-2.66]) in 2010 relative to those without the exposure. Prenatal exposure to the earthquake was consistently significantly associated with a faster increase in uric acid concentration from 2006 to 2010 (P < 0.001). Prenatal exposure to the earthquake was associated with higher serum uric acid and higher odds of hyperuricemia in early adulthood. © 2016, American College of Rheumatology.
Prasad, A K; Czekalowski, J W; Jennings, R
The replication of influenza type C/1233 virus following inoculation into the amniotic sac of embryonated hen's eggs is significantly greater than that seen in the allantoic cavity. However, optimal growth condition for amniotically propagated C/1233 occur in the allantois of 8-day old embryos incubated post-inoculation at 32 degrees C. Differences in pH levels between the amniotic and allantoic cavities did not account for the variable growth ability of C/1233 virus, but in both in vitro and in ovo studies, levels of urea and uric acid, or urea-uric acid mixtures caused significant reductions in virus yield.
Kubomura, Daiki; Yamada, Masanori; Masui, Ayano
Long-term reduction of serum urate levels is vital in the treatment of gout. However, it is difficult to convince gout-free individuals of the necessity of treatment as few appropriate over-the-counter remedies and dietary supplements are available. Therefore, the present study aimed to investigate the antihyperuricemic efficacy and safety of a tuna extract containing the imidazole compounds to evaluate its potential as a functional food ingredient. A randomized, 4-week, double-blind, placebo-controlled study was conducted. A total of 48 male gout-free subjects with insignificantly high serum uric acid were randomly assigned to low- and high-dose tuna extract groups or a placebo group. The efficacy of the extract was assessed by measuring serum uric acid levels. Furthermore, a safety assessment was performed by physical parameters, hematology, blood biochemistry and urinalysis. The results indicated that the uric acid level was decreased at week 4 during the intervention in the tuna extract groups (low and high dose, −0.23 and −0.34 mg/dl, respectively) compared to the placebo group (−0.07 mg/dl). At week 4 after the intervention, a significant reduction in uric acid levels (−0.41 mg/dl; P<0.05) was observed in the high-dose tuna extract group compared with the placebo group (+0.11 mg/dl). No dose-related adverse events were observed during and following the intervention. Therefore, the present results suggest that oral administration of tuna extract containing the imidazole compounds has hypouricemic activity with no undesirable side effects. PMID:27446553
Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it...
Selcukbiricik, F; Kanbay, M; Solak, Y; Bilici, A; Kanıtez, M; Balık, E; Mandel, N M
Bevacizumab is a monoclonal antibody which is a vascular endothelial growth factor inhibitor. It obscures vascularization of tumor tissue and damages intratumoral microcirculation. The damaged intratumoral microcirculation leads to tissue hypoxia and results in increase of uric acid level. The main aim of our study was to investigate the relationship between uric acid change and response to bevacizumab therapy. This study included a total of 158 patients with metastatic colorectal cancer who had received bevacizumab therapy. The number of male patients was 100 (63.3 %) while female patients number was 58 (37.7 %). The median age was 61 (29-83). There was relationship between increase of uric acid level of third month uric acid level and stable disease (p < 0.001). There was a significant overall survival increased in the group with increased uric acid level (p < 0.001). The decline of CEA level was related to uric acid level (p < 0.022). In conclusion, this study is the first showing significant increases of serum uric acid in patients with metastatic colorectal cancer who favorably responded to chemotherapy with bevacizumab. But further studies are justified to test whether monitoring uric acid levels might predict clinical outcomes of patients with metastatic colorectal cancer.
Desideri, Giovambattista; Gentile, Roberta; Antonosante, Andrea; Benedetti, Elisabetta; Grassi, Davide; Cristiano, Loredana; Manocchio, Antonello; Selli, Sara; Ippoliti, Rodolfo; Ferri, Claudio; Borghi, Claudio; Giordano, Antonio; Cimini, Annamaria
There is still a considerable debate concerning whether uric acid is neuroprotective or neurotoxic agent. To clarify this topic, we tested the effects of uric acid on neuronal cells biology by using differentiated SHSY5Y neuroblastoma cells incubated with amyloid β to reproduce an in vitro model of Alzheimer's disease. The incubation of cells with uric acid at the dose of 40 µM or higher significantly reduced cell viability and potentiated the proapoptotic effect of amyloid β. Finally, uric acid enhanced the generation of 4-hydroxynonenal and the expression of PPARβ/δ promoted by amyloid β, indicating a prooxidant effects. In conclusion, uric acid could exert a detrimental influence on neuronal biology being this influence further potentiated by the concomitant exposure to neurotoxic stimuli. This effect is evident for uric acid concentrations close to those achievable in cerebrospinal fluid in presence of mild hyperuricemia thus suggesting a potential role of uric acid in pathophysiology of cognitive dysfunction. These effects are influenced by the concentrations of uric acid and by the presence of favoring conditions that commonly occur in neurodegenerative disorders and well as in the aging brain, including increased oxidative stress and exposure to amyloid β. J. Cell. Physiol. 232: 1069-1078, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Siener, Roswitha; Hesse, Albrecht
About 10-15% of all urinary stones are composed of uric acid. A high urinary uric acid excretion, a low urine volume and an acidic urinary pH value are suggested to be the most important risk factors for uric acid stone formation. The effect of a vegetarian diet and different omnivorous diets on the risk of uric acid crystallization was investigated. Ten healthy male subjects ingested a self-selected meat-containing diet (SD) for two weeks, and three different standardized diets for a period of 5 days each. The Westerntype diet (WD) was representative of the usual dietary habits,whereas the balanced omnivorous diet (OD) and the ovo-lacto-vegetarian diet (VD) were calculated according to the requirements. The risk of uric acid crystallization was highest on the ingestion of diets SD and WD, due to the high urinary uric acid excretion and the acidic urinary pH. The relative supersaturation with uric acid declined significantly by 85% on the intake of diet OD, consequent to the decrease in uric acid excretion and concentration and the increase in urinary pH value. The ingestion of the vegetarian diet VD led to a further significant reduction in the risk of uric acid crystallization by 93% compared to diet WD. The results indicate that the intake of a balanced vegetarian diet with a moderate animal protein and purine content, an adequate fluid intake and a high alkali-load with fruits and vegetables results in the lowest risk of uric acid crystallization compared to the omnivorous diets.
Bates, Anne L.; Orem, William H.; Newman, Susan; Gawlik, Dale E.; Lerch, Harry E.; Corum, Margo D.; Van Winkle, Monica
Concentrations of organic biomarkers and concentrations of phosphorus in soil cores can potentially be used as proxies for historic population densities of wading birds on tree islands in the Florida Everglades. This report focuses on establishing a link between the organic biomarker uric acid found in wading bird guano and the high phosphorus concentrations in tree island soils in the Florida Everglades. Uric acid was determined in soil core sections, in surface samples, and in bird guano by using a method of high-performance liquid chromatography-mass spectrometry (HPLC-MS) developed for this purpose. Preliminary results show an overall correlation between uric acid and total phosphorus in three soil cores, with a general trend of decreasing concentrations of both uric acid and phosphorus with depth. However, we have also found no uric acid in a soil core having high concentrations of phosphorus. We believe that this result may be explained by different geochemical circumstances at that site.
Fannelli, G M; Weiner, I M
The effects of salicylate, probenecid (Benemid) and pyrazinoate on uric acid excretion were determined in clearance experiments in the chimpanzee and Cebus monkey (C. albifrons and C. apella). The results were correlated with data from these species in the literature and where possible to analogous data in man. With salicylate, the rank order of responsiveness in terms of uricosuric action was chimpanzee greater than man greater than C. albifrons = C. apella. This was true when comparisons were made on the bases of drug concentration in plasma or the rate of drug excretion per milliliter of glomerular filtrate. A similar rank order was obtained with probenecid except that C. albifrons was slightly more responsive than C. apella. The latter comparisons were on the basis of plasma concentration of drug. The chimpanzee is more susceptible to the uricosuric action of pyrazinoate than is C. apella. With salicylate and pyrazinoate, there was urate retention at levels lower than those required for a uricosuric effect. The results suggest that in comparison with man, the chimpanzee is a hyperresponder to uricosuric drugs and Cebus monkeys are hyporesponders. Therefore, these findings limit extensions of quantitative results from one species to another.
Carro, M D; Falkenstein, E; Radke, W J; Klandorf, H
The purpose of this study was to determine the effects of allopurinol (AL) on xanthine oxidoreductase (XOR) activity and uric acid (UA) levels in chickens. Thirty 5-week-old broilers were divided into three groups and fed 0 (control), 25 (AL25) or 50 (AL50) mg AL per kg of body mass for 5 weeks. Chicks were weighed twice weekly and leukocyte oxidative activity (LOA) and plasma purine levels were determined weekly in five birds per group. Chicks were sacrificed after 2 or 5 weeks, and samples from tissues were taken for analysis of XOR activity. Plasma UA concentrations were lower (P<0.001) and xanthine and hypoxanthine concentrations were greater (P<0.001) in AL25 and AL50 birds compared to controls, whereas no differences (P=0.904) were detected in allantoin concentrations. By week 5, body mass was reduced (P<0.001) to 84.0 and 65.1% of that in controls for AL25 and AL50 broilers, respectively, and LOA was 4.1 times greater (P<0.05) in AL25 compared to control birds. Liver XOR activity was increased by 1.1 and 1.2 times in AL25 and AL50 birds, but there was no change (P>0.05) in XOR activity in the pancreas and intestine. These results suggest that AL effect on XOR activity is tissue dependent.
Norton, D.R.; Plunkett, M.A.; Richards, F.A.
The present study was initiated in order to develop a rapid and accurate method for the determination of uric acid in fresh, brackish, and sea water. It was found that the spectrophotometric determination of uric acid based upon its reaction with arsenophosphotungstic acid reagent in the presence of cyanide ion meets this objective. The absorbancy of the blue complex was measured at 890 m??. Slight variations from Beer's law were generally found. The results show the effects of pH, reaction time, concentration of reagents, and temperature upon color development and precipitate formation. Disodium dihydrogen ethylenediamine tetraacetate (Versene) was used as a buffering and complexirig agent. The results are significant in that they give the absorption spectrum of the blue complex and the effects of variables upon its absorbancy. Studies were made with the method to determine the stability of reagents and standard solutions and to determine the rate of bacterial decomposition of uric acid. Measurements of the solubility of uric acid are reported.
Ahola, Aila J; Sandholm, Niina; Forsblom, Carol; Harjutsalo, Valma; Dahlström, Emma; Groop, Per-Henrik
Previous studies have shown a relationship between uric acid concentration and progression of renal disease. Here we studied causality between the serum uric acid concentration and progression of diabetic nephropathy in 3895 individuals with type 1 diabetes in the FinnDiane Study. The renal status was assessed with the urinary albumin excretion rate and estimated glomerular filtration rate (eGFR) at baseline and at the end of the follow-up. Based on previous genomewide association studies on serum uric acid concentration, 23 single nucleotide polymorphisms (SNPs) with good imputation quality were selected for the SNP score. This score was used to assess the causality between serum uric acid and renal complications using a Mendelian randomization approach. At baseline, the serum uric acid concentration was higher with worsening renal status. In multivariable Cox regression analyses, baseline serum uric acid concentration was not independently associated with progression of diabetic nephropathy over a mean follow-up of 7 years. However, over the same period, baseline serum uric acid was independently associated with the decline in eGFR. In the cross-sectional logistic regression analyses, the SNP score was associated with the serum uric acid concentration. Nevertheless, the Mendelian randomization showed no causality between uric acid and diabetic nephropathy, eGFR categories, or eGFR as a continuous variable. Thus, our results suggest that the serum uric acid concentration is not causally related to diabetic nephropathy but is a downstream marker of kidney damage. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Ye, B S; Lee, W W; Ham, J H; Lee, J J; Lee, P H; Sohn, Y H
The association of serum uric acid, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and longitudinal cognitive decline was evaluated using the AD Neuroimaging Initiative database. In 271 healthy subjects, 596 mild cognitive impairment patients and 197 AD patients, serum uric acid and CSF AD biomarkers were measured at baseline, and Mini-Mental State Examination and AD Assessment Scale - Cognitive Subscale (ADAS-cog) were assessed serially (mean duration, 2.9 years). The effect of uric acid on longitudinal cognitive decline was evaluated using linear mixed effect models for Mini-Mental State Examination and ADAS-cog scores in female and male subjects separately, with possible confounders controlled (model 1). To determine the effects of uric acid independent of CSF biomarker (Aβ1-42 or tau) and to test whether the detrimental effects of CSF biomarker differ according to uric acid, CSF biomarker and its interaction with uric acid were further included in model 1 (model 2). Higher levels of uric acid were associated with slower cognitive decline, particularly in the mild cognitive impairment and dementia subgroups, and more prominently in female subjects. Model 2 with CSF Aβ1-42 showed that higher levels of uric acid were associated with a slower cognitive decline and alleviated the detrimental effect of Aβ1-42 on cognitive decline. Model 2 with CSF tau showed that higher levels of uric acid alleviated the detrimental effect of tau on cognitive decline in female subjects but not in male subjects. Higher levels of uric acid had protective effects on longitudinal cognitive decline independent of and interactively with CSF AD biomarkers. © 2016 EAN.
Wu, Hongliang; Jia, Qian; Liu, Gaifen; Liu, Liping; Pu, Yuehua; Zhao, Xingquan; Wang, Chunxue; Wang, Yilong; Wang, Yongjun
The relationship between uric acid and stroke prognosis is ambiguous. Some studies have explored this relationship in acute stroke but have different results. In this study, we explored the relationship between uric acid levels and 1-year outcomes and vascular events of acute ischemic stroke patients and cerebral hemorrhage patients. In all, 1452 continued first, acute ischemic stroke patients and 380 continued cerebral hemorrhage patients were admitted to our hospitals. Serum uric acid concentrations were measured in 1351 ischemic stroke patients and 380 cerebral hemorrhage patients at admission. We evaluated the relationship between uric acid levels and outcomes (modified Rankin scale [mRS] > 2, all-cause death, vascular events, stroke recurrent) at 14 days, 90 days, and 1 year after stroke onset. The median uric acid concentration was 303.0 μmol/L in ischemic stroke patients and 269 μmol/L in cerebral hemorrhage patients. In univariate analysis, uric acid levels were not correlated with outcomes in cerebral hemorrhage patients. We used multiple logistic regression analysis to show that lower serum uric acid levels independently predicted poor functional outcomes (mRS >2) at 1 year after ischemic stroke onset (odds ratio [OR] = .335, 95% confidence interval [CI]: .164-.684, P = .003). Also, lower serum uric acid levels were independently correlated with vascular events in the first year in ischemic stroke patients. By multiple cox proportional hazards analysis, we obtained data which reveal that serum uric acid levels were not correlated with all-cause death (OR = .992, 95% CI: .683-1.443, P = .969) in ischemic stroke patients. Serum uric acid may be neuroprotective in acute ischemic stroke patients. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
It is tried to explain physico-chemically or crystallo-chemically the so-called "salting out effect", i.e. the influence of the Ca-oxalate precipitation by uric often discussed in urolith research which, indeed, is regarded as real by several researchers and by other investigators refused with emphasis, in order to understand better the connections between hyperuricosuria and oxalate lithiasis which obtrude themselves from the observation material. However, this phenomenon of the facilitated oxalate precipitation at increased uric acid level in the urine further needs directed research.
Lin, Jin-Ding; Lin, Pei-Ying; Lin, Lan-Ping; Hsu, Shang-Wei; Yen, Chia-Feng; Fang, Wen-Hui; Wu, Sheng-Ru; Chien, Wu-Chien; Loh, Ching-Hui; Chu, Cordia M.
The aims of the preset study were to describe the profile of serum uric acid, the prevalence of hyperuricemia and its risk factors among children and adolescents with intellectual disabilities. We conducted a cross-sectional study of 941 children and adolescents with intellectual disabilities (aged 4-18 years) who participated in annual health…
Feng, Ying; Sun, Fang; Gao, Yongchao; Yang, Jiancheng; Wu, Gaofeng; Lin, Shumei; Hu, Jianmin
Hyperuricemia can lead to direct kidney damage. Taurine participates in several renal physiological processes and has been shown as a renoprotective agent. It has been reported that taurine could reduce uric acid levels in diabetic rats, but to date there was no research on the effects of taurine on hyperuricemic rats with kidney injury. In present study, hyperuricemic rat models were induced by intragastric administration of adenine and ethambutol hydrochloride for 10 days, and taurine (1% or 2%) were added in the drinking water 7 days in advance for consecutively 17 days. The results showed that taurine alleviated renal morphological and pathological changes as well as kidney dysfunction in hyperuricemic rats. Taurine could efficiently decrease the elevated xanthine oxidase activities in hyperuricemic rats, indicating its effect on the regulation of uric acid formation. The reabsorption and secretion of uric acid are dependent on a number of urate transporters. Expressions of three urate transporters were significantly down-regulated in hyperuricemic rats, while taurine prevented the decrease of mRNA and protein expression levels of these urate transporters. The results indicate that taurine might play a role in the regulation of renal uric acid excretion. Therefore, taurine could be a promising agent for the treatment of hyperuricemia. Copyright © 2017 Elsevier Inc. All rights reserved.
Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic...
Lin, Jin-Ding; Lin, Pei-Ying; Lin, Lan-Ping; Hsu, Shang-Wei; Yen, Chia-Feng; Fang, Wen-Hui; Wu, Sheng-Ru; Chien, Wu-Chien; Loh, Ching-Hui; Chu, Cordia M.
The aims of the preset study were to describe the profile of serum uric acid, the prevalence of hyperuricemia and its risk factors among children and adolescents with intellectual disabilities. We conducted a cross-sectional study of 941 children and adolescents with intellectual disabilities (aged 4-18 years) who participated in annual health…
Fu, Yuan-Qing; Yang, Hong; Zheng, Ju-Sheng; Zeng, Xiao-Yun; Zeng, Wen; Fan, Zhi-Fen; Chen, Min; Wang, Ling; Li, Duo
The objective was to determine whether serum uric acid concentrations were associated with metabolic syndrome in a population from Wuhan. 5,628 subjects (2,838 men, 2,790 women) aged 18-80 years were recruited in Wuhan, China. Biochemical parameters of venous blood were measured by standard methods and metabolic syndrome was defined by Chinese Diabetes Society criteria. Association analysis was performed by logistic regression. 8.2% of the included subjects were confirmed as having metabolic syndrome and 14.4% were confirmed as having hyperuricemia. After multivariable adjustment, logistic regression showed the odds ratios of metabolic syndrome for subjects in the highest quartile of serum uric acid concentration was 2.84 (95% CI: 2.09-3.86) compared with those in the lowest quartile and no gender difference was found. For each component of metabolic syndrome, subjects in the highest quartile of serum uric acid concentrations had increased multivariable odds ratios for high BMI (OR: 3.29, 95% CI: 2.71-3.98), for hypertension (OR: 3.54, 95% CI: 2.93-3.86), for dyslipidemia (OR: 2.49, 95% CI: 1.98-3.14), but not for hyperglycemia (OR: 1.21, 95% CI: 0.87-1.67). Odd ratio of metabolic syndrome was significantly positively associated with serum uric acid concentration among the present sample of 5,628 subjects in Wuhan.
Kirschvink, Nathalie; Fiévez, Laurence; Bureau, Fabrice; Degand, Guy; Maghuin-Rogister, Guy; Smith, Nicola; Art, Tatiana; Lekeux, Pierre
The phenomenon of ozone tolerance is described, but the underlying mechanisms remain unknown. We tested whether adaptation to multiday ozone exposure was related to an upregulated pulmonary antioxidant defence. Six calves were exposed to 0.75 ppm ozone, 12 h day(-1) for seven consecutive days. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed before, after the first (D1), third (D3) and seventh (D7) exposure. Differential cell count, total proteins, 8-epi-PGF2alpha, glutathione and uric acid were determined in BAL. Dynamic lung compliance and arterial oxygen tension were significantly decreased and lung oedema impaired pulmonary function on D1. By repeating ozone exposures, progressive functional adaptation occurred. Ozone induced a significant increase of BAL neutrophil percentage on D1. On D3 and D7, neutrophil percentage was progressively decreased, but remained significantly elevated. BAL total proteins were significantly increased on D1 and decreased progressively until D7. 8-Epi-PGF2alpha was significantly increased on D1 and was returned to baseline on D3 and D7, whilst glutathione significantly increased on D3 and returned to baseline on D7. Uric acid was increased ten-fold on D1. On D3, uric acid was increased six-fold and was persistently elevated at D7. This study suggests that ozone adaptation of functional and inflammatory variables is accompanied with sustained BAL uric acid elevation.
Lian, Lushi; E, Yue; Li, Jing; Blatchley, Ernest R
Cyanogen chloride (CNCl) and trichloramine (NCl3) are important disinfection byproducts in chlorinated swimming pools. However, some unknowns exist regarding the precursors of their formation. In this study, uric acid is shown to be an efficient precursor to formation of CNCl and NCl3. The molar yields of CNCl and NCl3 were observed to be as high as 44% (pH = 6.0, chlorine/precursor molar ratio [Cl/P] = 6.4) and 108% (pH = 7.0, Cl/P = 30), respectively, both being strong functions of Cl/P, pH, and temperature. Analysis of swimming pool water samples, combined with the results of experiments involving chlorination of uric acid, and chlorination of body fluid analog mixtures, indicated that uric acid chlorination may account for a large fraction of CNCl formation in swimming pools. Moreover, given that uric acid introduction to pools is attributable to urination, a voluntary action for most swimmers, these findings indicate important benefits to pool water and air chemistry that could result from improved hygiene habits on the part of swimmers.
Eleftheriadis, Theodoros; Pissas, Georgios; Sounidaki, Maria; Antoniadi, Georgia; Antoniadis, Nikolaos; Liakopoulos, Vassilios; Stefanidis, Ioannis
Hyperuricemia is common among kidney transplant recipients and has been associated with worse graft outcome. Since episodes of acute cellular rejection and chronic humoral rejection contribute to decreased graft survival, in this study the effect of uric acid on cellular and humoral alloimmunity was evaluated. Cellular alloimmunity was assessed by cell proliferation in two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC). For assessing humoral alloimmunity we developed a method in which humoral alloimmunity was induced in one-way MLR. Then the de novo production of alloantibodies was measured with an antibody-mediated complement-dependent cytotoxicity assay, in which supernatants from the above MRLs were used against resting PBMC similar to the stimulator cells of the above MLRs. Uric acid at a concentration above its crystallization threshold increased cellular proliferation in two-way MLRs. Supernatants from one-way MLRs performed in the presence of uric acid were more cytotoxic against PBMC from individuals that had conferred the stimulator cells for the above MLRs. Uric acid increases both cellular and humoral alloimmunity in human PBMC. These results offer a possible pathogenetic mechanism for the observed relation between hyperuricemia and worse kidney allograft survival. This article is protected by copyright. All rights reserved.
Zhang, Feifei; Tang, Jie; Wang, Zonghua; Qin, Lu-Chang
Graphene and single-walled carbon nanotube (SWNT) composite aerogel has been prepared by hydrothermal synthesis. The restacking of graphene is effectively reduced by SWNTs inserted in between graphene layers in order to make available more active sites and reactive surface area. Electrochemical experiments show that the graphene-SWNT composite electrode has superior catalytic performance in selective detection of uric acid (UA).
Bobridge, K S; Haines, G L; Mori, T A; Beilin, L J; Oddy, W H; Sherriff, J; O'Sullivan, T A
Evidence that fructose intake may modify blood pressure is generally limited to adult populations. This study examined cross-sectional associations between dietary intake of fructose, serum uric acid and blood pressure in 814 adolescents aged 13-15 years participating in the Western Australian Pregnancy Cohort (Raine) Study. Energy-adjusted fructose intake was derived from 3-day food records, serum uric acid concentration was assessed using fasting blood and resting blood pressure was determined using repeated oscillometric readings. In multivariate linear regression models, we did not see a significant association between fructose and blood pressure in boys or girls. In boys, fructose intake was independently associated with serum uric acid (P<0.01), and serum uric acid was independently associated with systolic blood pressure (P<0.01) and mean arterial pressure (P<0.001). Although there are independent associations, there is no direct relationship between fructose intake and blood pressure. Our data suggest that gender may influence these relationships in adolescence, with significant associations observed more frequently in boys than girls.
Johnson, L M; Harrison, J H; Riley, R E
Data were collected from six experiments using duodenally cannulated Holstein dairy cows (88 combinations of cow and period) to evaluate the relationship between urinary purine metabolites and microbial N flow. Experiments evaluated the effects of dietary factors on microbial N production, which included 1) varying concentrations of ruminally degradable protein and nonstructural carbohydrates, 2) supplemental sources of protected amino acids, 3) grass silage treated with fibrolytic enzymes, 4) bacterial inoculation of corn silage, and 5) ruminal starch availability as affected by corn silages of varying maturity. The coefficient of determination for individual experiments that measured the relationship between microbial N flow and allantoin or uric acid excretion in urine ranged from 0.01 to 0.68 and 0.02 to 0.82, respectively. Across all experiments, the coefficients of determination between microbial N flow and allantoin or uric acid excretion in urine were r2 = 0.002 and 0.11, respectively. Removal of data from one experiment improved the overall coefficient of determination between microbial N flow and urinary uric acid to r2 = 0.32. Urinary allantoin excretion across experiments was negatively correlated with microbial N flow, but urinary allantoin excretion within experiments was positively correlated with microbial N flow. Uric acid excretion in urine was positively correlated with microbial N flow across and within experiments, except for one experiment. Our data demonstrate that uric acid excretion in urine can be used to predict microbial N production, except in early lactation, and that urinary allantoin excretion cannot be used to predict microbial N production accurately among cows at different stages of lactation.
Yang, Haibin; Zhang, Jialing; Liu, Guiying; Zhang, Ping
To determinate adenine, guanine, hypoxanthine, xanthine and uric acid simultaneously in meat, a reversed-phase high performance liquid chromatography (HPLC) was developed. The meat were hydrolyzed with perchloric acid 10% (v/v) in boiling water for 60 mm. After the hydrolysate was adjusted to pH 4, centrifuge , and filtrated with a 0.45 mirom membrane, the supernatants were separated on an Agilent ZORBAX Eclipse XDB-C18 column (250 mm x 4.6 mm i.d., 5 microm) at 25 degrees C with a mobile phase of 7 x 10(-3) mol/L KH2PO4-H3P04(pH 4.0) ,a flow rate of 1.0 ml/ mm, and UV detection at 254 nm. Each component in the corresponding concentration range showed a good linear relation with its peak area, correlation coefficient r > 0.9999, recovery was 90.0%-107. 5%, RSD was 1.7%-13.3%. In addition to containing four kinds of purines, there was quite amount of uric acid (about 133.7 -86.2 pug/g) in the mentioned meat. The ratio of uric acid to total purine and uric acid was about 7%. The content of total purine in chicken was (1759.3 +/- 64.6) microg/g higher than in rabbit, mutton, pork and beef (1440-1000 microg/g). The validated method is simple, rapid, accurate and reliable to the determination of purines and uric acid in meat.
Mumford, Sunni L.; Dasharathy, Sonya S.; Pollack, Anna Z.; Perkins, Neil J.; Mattison, Donald R.; Cole, Stephen R.; Wactawski-Wende, Jean; Schisterman, Enrique F.
STUDY QUESTION Do uric acid levels across the menstrual cycle show associations with endogenous estradiol (E2) and reproductive hormone concentrations in regularly menstruating women? SUMMARY ANSWER Mean uric acid concentrations were highest during the follicular phase, and were inversely associated with E2 and progesterone, and positively associated with FSH. WHAT IS KNOWN ALREADY E2 may decrease serum levels of uric acid in post-menopausal women; however, the interplay between endogenous reproductive hormones and uric acid levels among regularly menstruating women has not been elucidated. STUDY DESIGN, SIZE, DURATION The BioCycle study was a prospective cohort study conducted at the University at Buffalo research centre from 2005 to 2007, which followed healthy women for one (n = 9) or 2 (n = 250) menstrual cycle(s). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were healthy women aged 18–44 years. Hormones and uric acid were measured in serum eight times each cycle for up to two cycles. Marginal structural models with inverse probability of exposure weights were used to evaluate the associations between endogenous hormones and uric acid concentrations. MAIN RESULTS AND THE ROLE OF CHANCE Uric acid levels were observed to vary across the menstrual cycle, with the lowest levels observed during the luteal phase. Every log-unit increase in E2 was associated with a decrease in uric acid of 1.1% (β = −0.011; 95% confidence interval (CI): −0.019, −0.004; persistent-effects model), and for every log-unit increase in progesterone, uric acid decreased by ∼0.8% (β = −0.008; 95% CI: −0.012, −0.004; persistent-effects model). FSH was positively associated with uric acid concentrations, such that each log-unit increase was associated with a 1.6% increase in uric acid (β = 0.016; 95% CI: 0.005, 0.026; persistent-effects model). Progesterone and FSH were also associated with uric acid levels in acute-effects models. Of 509 cycles, 42 were anovulatory
Xu, D Q; Du, J; Zheng, Z; Tang, Y; Zou, L; Zhang, Y H; Zhang, H T
Objective: To evaluate whether early postoperative serum uric acid level can predict postoperative acute renal injury (AKI) among patients undergoing coronary artery bypass grafting (CABG). Methods: The study retrospectively enrolled 1 306 patients undergoing CABG in Fuwai Hospital between September 2012 and December 2013. The patients were divided into 5 groups by the concentrations of serum uric acid measured on the morning of the first postoperative day, and uric acid categories were as follow: less than 195 μmol/L (Q1 group, 262 cases), 195-236 μmol/L (Q2 group, 263 cases), 237-280 μmol/L (Q3 group, 260 cases), 281-336 μmol/L (Q4 group, 261 cases), more than 336 μmol/L (Q5 group, 260 cases). The primary end points were AKI (RIFLE criteria), severe AKI (AKI≥stage Ⅰ), postoperative continuous renal replacement therapy (CRRT) requirement, in-hospital death, length of stay in hospital and intensive care unit(ICU). The area under the receiver-operating characteristic (ROC) curve (AUC) was used to determine the ability of the early postoperative serum uric acid level as a risk factor for postoperative AKI prediction. Results: Among the 1 306 patients enrolled in the study, AKI was found in 335 patients (25.65%). After adjusting for variables that were different between the 5 groups, the Q5 group had significantly higher risk of AKI, AKI≥ stage Ⅰ and the requirement of CRRT (P<0.01). The ROC for the outcome of postoperative AKI had an AUC of 0.648 (95% CI: 0.612-0.683) when serum creatinine levels alone were used and 0.722 (95% CI: 0.688-0.755) when serum uric acid levels alone were used (both P<0.001). Early postoperative serum uric acid was a better predictor than serum creatinine(P<0.001). Conclusion: The serum uric acid concentration within 12 hours after operation is an independent predictor of postoperative AKI in patients undergoing CABG, which could be used to identify patients at high risk for AKI.
Aslanoglu, Mehmet; Kutluay, Aysegul; Abbasoglu, Sultan; Karabulut, Serpil
A reliable and reproducible method for the determination of uric acid in urine samples has been developed. The method is based on the modification of a glassy carbon electrode by 3-acetylthiophene using cyclic voltammetry. The poly(3-acetylthiophene) modified glassy carbon electrode showed an excellent electrocatalytic effect towards the oxidation of uric acid in 0.1 m phosphate buffer solution (PBS) at pH 7.2. Compared with a bare glassy carbon electrode (GCE), an obvious shift of the oxidation peak potential in the cathodic direction and a marked enhancement of the anodic current response for uric acid were observed. The poly(3-acetylthiophene)/GCE was used for the determination of uric acid using square wave voltammetry. The peak current increased linearly with the concentration of uric acid in the range of 1.25 x 10(-5)-1.75 x 10(-4) M. The detection limit was 5.27 x 10(-7) M by square wave voltammetry. The poly(3-acetylthiophene)/GCE was also effective to determine uric acid and ascorbic acid in a mixture and resolved the overlapping anodic peaks of these two species into two well-defined voltammetric peaks in cyclic voltammetry at 0.030 V and 0.320 V (vs. Ag/AgCl) for ascorbic acid and uric acid, respectively. The modified electrode exhibited stable and sensitive current responses toward uric acid and ascorbic acid. The method has successfully been applied for determination of uric acid in urine samples.
Iswantini, Dyah; Nurhidayat, Novik; Trivadila; Widiyatmoko, Okik
Determination of uric acid concentration in human urine and blood is needed to diagnose several diseases, especially the occurrence of kidney disease in gout patients. Therefore, it is needed to develop a simple and inexpensive method for uric acid detection. The purpose of the research was to observe the use of Indonesian microbe that was immobilized on natural zeolite as a source of uricase for uric acid biosensor. Selection of mediators and determination of optimum condition measurement, the stability and kinetic properties of L. plantarum uricase were performed using carbon paste electrode. Cyclic voltammetry was employed to investigate the catalytic behavior of the biosensor. The result indicated that the best mediator for measurement of L. plantarum uricase activity was Qo (2,3-dimethoxy-5-methyl-1,4 benzoquinone). Optimum conditions for immobilization of L. plantarum uricase on zeolite were obtained at pH 7.6, with temperature of 28 degrees C, using uric acid concentration of 0.015 mM and zeolite mass at 135 mg K(M) and V(Max) of L. plantarum uricase obtained from Lineweaver-burk equation for the immobilization uricase on zeolite were 8.6728 x 10(-4) mM and 6.3052 mM, respectively. K(M) value of L. plantarum uricase directly immobilized onto the electrode surface was smaller than K(M) value of L. plantarum uricase immobilized on zeolite. The smaller K(M) value shows the higher affinity toward the substrate. The Electrode when kept at 10 degrees C was stable until 6 days, however the immobilized electrode on zeolite was stable until 18 days. Therefore, Indonesian L. plantarum could be used as a uric acid biosensor.
Ather, Jennifer L.; Burgess, Edward J.; Hoyt, Laura R.; Randall, Matthew J.; Mandal, Mridul K.; Matthews, Dwight E.; Boyson, Jonathan E.; Poynter, Matthew E.
Nitrogen dioxide (NO2) is an environmental air pollutant and endogenously-generated oxidant that contributes to the exacerbation of respiratory disease and can function as an adjuvant to allergically sensitize to an innocuous inhaled antigen. Since uric acid has been implicated as a mediator of adjuvant activity, we sought to determine whether uric acid was elevated and participated in a mouse model of NO2-promoted allergic sensitization. We found that uric acid was increased in the airways of mice exposed to NO2 and that administration of uricase inhibited the development of ovalbumin (OVA)-driven allergic airway disease subsequent to OVA challenge as well as the generation of OVA-specific antibodies. However, uricase was itself immunogenic, inducing a uricase-specific adaptive immune response that occurred even when the enzymatic activity of uricase had been inactivated. Inhibition of the OVA-specific response was not due to the capacity of uricase to inhibit OVA uptake or processing and presentation by dendritic cells, but at a later step that inhibited OVA-specific CD4+ T cell proliferation and cytokine production. Whereas blocking uric acid formation by allopurinol did not affect outcomes, administration of ultra-clean human serum albumin at protein concentrations equivalent to that of uricase inhibited NO2-promoted allergic airway disease. These results implicate that whereas uric acid levels are elevated in the airways of NO2-exposed mice, the powerful inhibitory effect of uricase administration on allergic sensitization is mediated more through antigen-specific immune deviation than on suppression of allergic sensitization, a mechanism to be considered in the interpretation of results from other experimental systems. PMID:27465529
Huang, He; Huang, Baotao; Li, Yulin; Huang, Yan; Li, Jing; Yao, Hongmei; Jing, Xianchao; Chen, Jianrong; Wang, Ji
We aimed to perform a systematic review and meta-analysis to assess the association between serum uric acid and incident heart failure (HF)/prognosis of HF patients. A systematic electronic literature search was conducted in Embase (Ovid SP, from 1974 to May 2013), Medline (Ovid SP, from 1946 to May 2013), and the Chinese Biomedical Literature Database (CBM, from 1978 to May 2013) to identify studies reporting on the association between serum uric acid and HF. Either a random effects model or a fixed effects model was used for pooling data. Five studies reporting on incident HF and 28 studies reporting on the adverse outcomes of HF patients were included. The results showed that hyperuricaemia was associated with an increased risk of incident HF [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.41-1.94], and the risk of all-cause mortality (HR 2.15, 95% CI 1.64-2.83), cardiovascular mortality (HR 1.45, 95% CI 1.18-1.78), and the composite of death or cardiac events (HR 1.39, 95% CI 1.18-1.63) in HF patients. For every 1 mg/dL increase in serum uric acid, the odds of development of HF increased by 19% (HR 1.19, 95% CI 1.17-1.21), and the risk of all-cause mortality and the composite endpoint in HF patients increased by 4% (HR 1.04, 95% CI 1.02-1.06) and 28% (HR 1.28, 95% CI 0.97-1.70), respectively. Subgroup analyses supported the positive association between serum uric acid and HF. Elevated serum uric acid is associated with an increased risk of incident HF and adverse outcomes in HF patients. First published online by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.
Matsumura, Kiyoshi; Arima, Hisatomi; Tominaga, Mitsuhiro; Ohtsubo, Toshio; Sasaguri, Toshiyuki; Fujii, Koji; Fukuhara, Masayo; Uezono, Keiko; Morinaga, Yuki; Ohta, Yuko; Otonari, Takatoshi; Kawasaki, Junya; Kato, Isao; Tsuchihashi, Takuya
It has been shown that losartan, an angiotensin II receptor blocker (ARB), reduces serum uric acid levels. However, the effects of losartan on serum uric acid levels in the patients treated with a thiazide diuretic have not been fully elucidated. We have investigated the effects of losartan compared with other ARBs on blood variables and blood pressure control in hypertensive patients treated with a thiazide diuretic using data from the COMFORT study. The present analysis included a total of 118 hypertensive subjects on combination treatment with ARBs except for losartan and a diuretic who were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or to continuation of two pills, an ARB except for losartan and a diuretic. Blood pressures were evaluated at 1, 3, and 6 months after randomization and changes in blood variables including serum uric acid were evaluated during 6 months treatment period. Mean follow-up blood pressure levels were not different between the combination pill (losartan treatment) group and the control (ARBs except for losartan) group. On the other hand, serum uric acid significantly decreased in the combination pill group compared with the control group (-0.44 versus + 0.10 mg/dl; p = 0.01), although hematocrit, serum creatinine, sodium and potassium were not different between the groups. These results suggest that the treatment regimen switched from a combination therapy of ARBs except for losartan and a diuretic to a combination pill (losartan/ hydrochlorothiazide) decreases serum uric acid without affecting blood pressure control.
Kamei, Keita; Konta, Tsuneo; Ichikawa, Kazunobu; Sato, Hiroko; Suzuki, Natsuko; Kabasawa, Asami; Suzuki, Kazuko; Hirayama, Atsushi; Shibata, Yoko; Watanabe, Tetsu; Kato, Takeo; Ueno, Yoshiyuki; Kayama, Takamasa; Kubota, Isao
Serum uric acid level is regulated by gender, dietary habit, genetic predisposition, and renal function, and is associated with the development of renal and cardiovascular diseases. This study prospectively investigated the association between serum uric acid levels and mortality in a community-based population. Three thousand four hundred and eighty-seven subjects regardless of the antihyperuricemic medication (45 % male; mean age 62 years old) from the Takahata town in Japan participated in this study and were followed up for 8 years (median 7.5 years). We examined the association between serum uric acid levels at baseline and the all-cause and cardiovascular mortality, respectively, in this population. One hundred seventy-nine subjects died during the follow-up period, with 49 deaths attributed to cardiovascular causes. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher along with the increase in serum uric acid levels at baseline among female (Log-rank P < 0.01), but not male subjects (P = 0.97). Cox-proportional hazard model analysis with adjustment for possible confounders including age, renal function, and comorbidities revealed that hyperuricemia (uric acid ≥7.0 mg/dL) was an independent risk factor for all-cause and cardiovascular mortality, respectively, in female [hazard ratio (HR) 5.92, 95 % confidence interval (CI) 2.10-14.6 for all-cause mortality, and HR 10.7, 95 % CI 1.76-50.2 for cardiovascular mortality], but not male subjects. Hyperuricemia was an independent risk for all-cause and cardiovascular mortality in female, but not among the male subjects in a community-based population.
Reátegui-Sokolova, C; Ugarte-Gil, Manuel F; Gamboa-Cárdenas, Rocío V; Zevallos, Francisco; Cucho-Venegas, Jorge M; Alfaro-Lozano, José L; Medina, Mariela; Rodriguez-Bellido, Zoila; Pastor-Asurza, Cesar A; Alarcón, Graciela S; Perich-Campos, Risto A
This study aims to determine whether uric acid levels contribute to new renal damage in systemic lupus erythematosus (SLE) patients. This prospective study was conducted in consecutive patients seen since 2012. Patients had a baseline visit and follow-up visits every 6 months. Patients with ≥2 visits were included; those with end-stage renal disease (regardless of dialysis or transplantation) were excluded. Renal damage was ascertained using the SLICC/ACR damage index (SDI). Univariable and multivariable Cox-regression models were performed to determine the risk of new renal damage. Uric acid was included as a continuous and dichotomous (per receiving operating characteristic curve) variable. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, serum creatinine, baseline use of prednisone, antimalarials, and immunosuppressive drugs. One hundred and eighty-six patients were evaluated; their mean (SD) age at diagnosis was 36.8 (13.7) years; nearly all patients were mestizo. Disease duration was 7.7 (6.8) years. Follow-up time was 2.3 (1.1) years. The SLEDAI was 5.2 (4.3) and the SDI 0.8 (1.1). Uric acid levels were 4.5 (1.3) mg/dl. During follow-up, 16 (8.6%) patients developed at least one new point in the renal domain of the SDI. In multivariable analyses, uric acid levels (continuous and dichotomous) at baseline predicted the development of new renal damage (HR 3.21 (1.39-7.42), p 0.006; HR 18.28 (2.80-119.48), p 0.002; respectively). Higher uric acid levels contribute to the development of new renal damage in SLE patients independent of other well-known risk factors for such occurrence.
Yoshikawa, Hideto; Yamazaki, Sawako; Abe, Tokinari
The previous study showed that both valproic acid (VPA) and a bedridden state decreased the serum uric acid level, and VPA-induced renal tubular dysfunction was suspected to be one cause of hypouricemia in severely disabled children. However, it was uncertain what factor of bedridden state influences the uric acid level in severely disabled children. Among many factors of a bedridden state that might influence the uric acid level, we examined the influence of elemental nutrition on the serum uric acid level in severely disabled children because many severely disabled children with marked hypouricemia receive elemental nutrition. Thirty-one severely disabled children were included in this study, who were divided into two groups-group A: 11 patients with elemental nutrition; group B: 20 patients with non-elemental nutrition. The laboratory data in both groups were analyzed statistically, using the t-test. The uric acid level was significantly decreased in group A compared with group B (p < 0.01) without elevation of urinary excretion of uric acid. Other laboratory data, except phosphate and potassium, did not differ between the two groups significantly. An elemental diet may be one factor that decreases the uric acid level in severely disabled children.
Trautwein-Schult, Anke; Jankowska, Dagmara; Cordes, Arno; Hoferichter, Petra; Klein, Christina; Matros, Andrea; Mock, Hans-Peter; Baronian, Keith; Bode, Rüdiger; Kunze, Gotthard
Hyperuricemia and its symptoms are becoming increasingly common worldwide. Elevated serum uric acid levels are caused by increased uric acid synthesis from food constituents and reduced renal excretion. Treatment in most cases involves reducing alcohol intake and consumption of meat and fish or treatment with pharmaceuticals. Another approach could be to reduce uric acid level in food, either during production or consumption. This work reports the production of recombinant urate oxidase by Arxula adeninivorans and its application to reduce uric acid in a food product. The A. adeninivorans urate oxidase amino acid sequence was found to be similar to urate oxidases from other fungi (61-65% identity). In media supplemented with adenine, hypoxanthine or uric acid, induction of the urate oxidase (AUOX) gene and intracellular accumulation of urate oxidase (Auoxp) was observed. The enzyme characteristics were analyzed from isolates of the wild-type strain A. adeninivorans LS3, as well as from those of transgenic strains expressing the AUOX gene under control of the strong constitutive TEF1 promoter or the inducible AYNI1 promoter. The enzyme showed high substrate specificity for uric acid, a broad temperature and pH range, high thermostability and the ability to reduce uric acid content in food. © 2013 S. Karger AG, Basel.
Shen, Zancong; Gillen, Michael; Miner, Jeffrey N; Bucci, Gail; Wilson, David M; Hall, Jesse W
Purpose Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in healthy adult males. Subjects and methods This was a Phase I, randomized, double-blind, placebo-controlled, single and multiple ascending dose study. Panels of eight male subjects received a single oral dose of verinurad or placebo in either a fasted or fed state; panels of 10–12 male subjects received ascending doses of once-daily verinurad or placebo in a fasted state for 10 days. Serial blood and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse event (AE) reports, laboratory tests, vital signs, and electrocardiograms (ECGs). Results A total of 81 adult males completed the study. Following single doses of verinurad, maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) increased in a dose-proportional manner; Cmax occurred at 0.5–0.75 hours and 1.25 hours in the fasted and fed states, respectively. Food decreased AUC by 23% and Cmax by 37%−53%. There was a modest accumulation of verinurad following multiple daily doses. Verinurad reduced serum urate levels by up to 62% (40 mg, single dose) and 61% (10 mg, multiple dose). The increase in urinary excretion of uric acid was greatest in the first 6 hours after dosing and was still evident ≥24 hours for verinurad doses ≥2 mg. Verinurad was well tolerated at all doses. No serious AEs, severe AEs, discontinuations due to AEs, or clinically significant laboratory or ECG abnormalities were reported. Conclusion Single and multiple doses of verinurad were well tolerated, absorption was rapid, and exposure was dose proportional. Verinurad increased urinary uric acid elimination and resulted in sustained reductions in serum urate. These data support further
Iracheta-Vellve, Arvin; Petrasek, Jan; Satishchandran, Abhishek; Gyongyosi, Benedek; Saha, Banishree; Kodys, Karen; Fitzgerald, Katherine A.; Kurt-Jones, Evelyn A.; Szabo, Gyongyi
Background & Aims The inflammasome is a well-characterized inducer of inflammation in ASH. Inflammasome activation requires two signals for mature interleukin (IL)-1β production. Here we asked whether metabolic danger signals trigger inflammasome activation in ASH. Methods Wild-type mice, ATP receptor 2×7 (P2rx7)-KO mice, or mice overexpressing uricase were fed Lieber-DeCarli ethanol or control diet. We also implemented a pharmacological approach in which mice were treated with probenecid or allopurinol. Results The sterile danger signals, ATP and uric acid, were increased in the serum and liver of alcohol-fed mice. Depletion of uric acid or ATP, or lack of ATP signaling attenuated ASH and prevented inflammasome activation and its major downstream cytokine, IL-1β. Pharmacological depletion of uric acid with allopurinol provided significant protection from alcohol-induced inflammatory response, steatosis and liver damage, and additional protection was achieved in mice treated with probenecid, which depletes uric acid and blocks ATP-induced P2rx7 signaling. We found that alcohol-damaged hepatocytes released uric acid and ATP in vivo and in vitro and that these sterile danger signals activated the inflammasome in LPS-exposed liver mononuclear cells. Conclusions Our data indicate that the second signal in inflammasome activation and IL-1β production in ASH results from the endogenous danger signals, uric acid and ATP. Inhibition of signaling triggered by uric acid and ATP may have therapeutic implications in ASH. PMID:26100496
Costa, A; Igualá, I; Bedini, J; Quintó, L; Conget, I
High uric acid concentration is a common finding in subjects with risk factors for cardiovascular disease (CVD), including some characteristics of the metabolic syndrome. However, its exact role in this setting and in the progression to type 2 diabetes mellitus (DM) is not well understood and could be affected by confounding factors such as hypertriglyceridemia. Our study aimed to establish the relationship between uric acid (avoiding the interference of high triglyceride levels), insulin sensitivity, and components of the metabolic syndrome in a group of subjects at high risk of developing DM. Among 201 subjects included in the study, 111 (55.2%) showed an abnormal oral glucose tolerance and uric acid levels higher than those measured in subjects with normal glucose tolerance. Body mass index (BMI), triglycerides, diastolic blood pressure (DBP), and 2-hour glycemia in the oral glucose tolerance test (OGTT) contributed independently to uric acid concentration (R2 =.59). However, uric acid did not affect either insulin sensitivity or glucose tolerance. The recovery tests revealed that a triglyceride concentration > or = 3 mmol/L interfered with the measurement of uric acid level when a colorimetric method was used, but not when a dry-chemistry method was used. In conclusion, uric acid concentration is higher in subjects at high risk of DM with abnormal glucose tolerance and is independently determined by various components of the metabolic syndrome.
Gertler, Christoph; Bargiela, Rafael; Mapelli, Francesca; Han, Xifang; Chen, Jianwei; Hai, Tran; Amer, Ranya A; Mahjoubi, Mouna; Malkawi, Hanan; Magagnini, Mirko; Cherif, Ameur; Abdel-Fattah, Yasser R; Kalogerakis, Nicolas; Daffonchio, Daniele; Ferrer, Manuel; Golyshin, Peter N
Uric acid is a promising hydrophobic nitrogen source for biostimulation of microbial activities in oil-impacted marine environments. This study investigated metabolic processes and microbial community changes in a series of microcosms using sediment from the Mediterranean and the Red Sea amended with ammonium and uric acid. Respiration, emulsification, ammonium and protein concentration measurements suggested a rapid production of ammonium from uric acid accompanied by the development of microbial communities containing hydrocarbonoclastic bacteria after 3 weeks of incubation. About 80 % of uric acid was converted to ammonium within the first few days of the experiment. Microbial population dynamics were investigated by Ribosomal Intergenic Spacer Analysis and Illumina sequencing as well as by culture-based techniques. Resulting data indicated that strains related to Halomonas spp. converted uric acid into ammonium, which stimulated growth of microbial consortia dominated by Alcanivorax spp. and Pseudomonas spp. Several strains of Halomonas spp. were isolated on uric acid as the sole carbon source showed location specificity. These results point towards a possible role of halomonads in the conversion of uric acid to ammonium utilized by hydrocarbonoclastic bacteria.
Liu, L; Gu, Y; Li, C; Zhang, Q; Meng, G; Wu, H; Du, H; Shi, H; Xia, Y; Guo, X; Liu, X; Bao, X; Su, Q; Fang, L; Yu, F; Yang, H; Yu, B; Sun, S; Wang, X; Zhou, M; Jia, Q; Guo, Q; Song, K; Huang, G; Wang, G; Niu, K
Although the prevalence of prehypertension is rapidly increasing in China, the medical community has paid little attention to its prevention. Prior studies have demonstrated that uric acid directly contributes to vascular remodelling and endothelial dysfunction. However, few prospective studies have assessed the relationship between serum uric acid and prehypertension. We therefore designed a larger-scale cohort study to examine whether uric acid level is a predictive factor for developing prehypertension in adults. Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. A prospective assessment (n=15 143) was performed. Participants without a history of hypertension or prehypertension were followed up for 2 to 6 years with a median follow-up duration of 2.8 years. Serum uric acid levels and blood pressure were assessed yearly during the follow-up. Adjusted Cox proportional hazards regression models were used to assess relationships between the quintiles of uric acid levels and the incidence of prehypertension. The incidence of prehypertension was 191 per 1000 person-years. In the final multivariate models, the hazard ratios (95% confidence interval) for prehypertension across uric acid quintiles were 1.00 (reference), 0.98 (0.90-1.07), 1.01 (0.93-1.10), 1.09 (1.001-1.20) and 1.17 (1.06-1.29) (P for trend <0.001), respectively. This population-based prospective cohort study has demonstrated that uric acid level is an independent predictor for developing prehypertension.
Sodhi, Komal; Hilgefort, Jordan; Banks, George; Gilliam, Chelsea; Stevens, Sarah; Ansinelli, Hayden A.; Getty, Morghan; Abraham, Nader G.; Shapiro, Joseph I.
Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) levels. We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs) in the presence and absence of cobalt protoporphyrin (CoPP), an HO-1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels. PMID:26681956
Stinefelt, Beth; Leonard, Stephen S; Blemings, Kenneth P; Shi, Xianglin; Klandorf, Hillar
Uric acid (UA) has been proposed to be the dominant antioxidant in birds. The objective of this study was to investigate the quenching effect of varying concentrations of UA, including those found in avian plasma, on specific reactive oxygen species (ROS) and to determine the ability of UA to protect DNA and cellular membranes from ROS-mediated damage. Hydroxyl (OH) and superoxide (O2-) radicals were detected by electron spin resonance (ESR) and their presence was reduced following addition of UA (p <0.05) in a concentration-dependent manner. UA inhibited hydroxyl-mediated DNA damage, indicated by the presence of more precise, dense bands of lambda Hind III DNA after agarose gel electrophoresis and ethidium bromide staining (p <0.05). Lipid peroxidation of silica-exposed RAW 264.7 cell membranes was diminished (p <0.02) after addition of UA to the cell incubation mixture. These studies demonstrate that UA scavenges hydroxyl and superoxide radicals and protects against DNA damage and lipid peroxidation. These results indicate specific antioxidant protection that UA may afford birds against ROS-mediated damage.
de Andrade, Mariza; Matsumoto, Martha; Mosley, Tom H.; Kardia, Sharon; Turner, Stephen T.
Objectives. SLC2A9 gene variants associate with serum uric acid in white populations, but little is known about African American populations. Since SLC2A9 is a transporter, gene variants may be expected to associate more closely with the fractional excretion of urate, a measure of renal tubular transport, than with serum uric acid, which is influenced by production and extrarenal clearance. Methods. Genotypes of single nucleotide polymorphisms (SNPs) distributed across the SLC2A9 gene were obtained in the Genetic Epidemiology Network of Arteriopathy cohorts. The associations of SNPs with serum uric acid, fractional excretion of urate and urine urate-to-creatinine ratio were assessed with adjustments for age, sex, diuretic use, BMI, homocysteine and triglycerides. Results. We identified SLC2A9 gene variants that were associated with serum uric acid in 1155 African American subjects (53 SNPs) and 1132 white subjects (63 SNPs). The most statistically significant SNPs in African American subjects (rs13113918) and white subjects (rs11723439) were in the latter half of the gene and explained 2.7 and 2.8% of the variation in serum uric acid, respectively. After adjustment for this SNP in African Americans, 0.9% of the variation in serum uric acid was explained by an SNP (rs1568318) in the first half of the gene. Unexpectedly, SLC2A9 gene variants had stronger associations with serum uric acid than with fractional excretion of urate. Conclusions. These findings support two different loci by which SLC2A9 variants affect uric acid levels in African Americans and suggest SLC2A9 variants affect serum uric acid level via renal and extrarenal clearance. PMID:21186168
Konstantinova, O V; Yanenko, E K
154 patients with urolithiasis were under outpatient observation for 2-8 years. Among them there were 76 women and 78 men aged 21-66 years, of which 46 patients with uric acid urolithiasis, and 88--with calcium oxalate urolithiasis. Treatment of patients was carried out systematically, depending on their condition. Indications for the application of Blemaren® included the presence of uric acid stones, uric acid and/or oxalate crystalluria. The duration of treatment was 6.1 months. The dosage of the drug varied from 6 to 18 g per day and was selected individually, depending on the purpose of the appointment of Blemaren®. Reduction of the urine pH to 6.2- 6.8-7.2 was the criterion for properly selected dose. To dissolve uric acid stones in the presence of hyperuricemia and/or hyperuricuria, Blemaren® was administered in combination with allopurinol at a dose of 0.1 g 3-4 times a day. Besides pharmacotherapy, treatment included diet therapy. It was found that the morning urine pH in urate urolithiasis is sustainable and has a range of 5.0-6.0, in 80.4% of cases--range of 5.0-5.5. In calcium oxalate urolithiasis this parameter is also stable and has a range of 5.0-6.7, in 82.9% of cases--range of 5.5-6.0. Optimal urine pH to eliminate uric acid and oxalate crystalluria in patients with uric acid and calcium oxalate urolithiasis is the interval of 6.2-6.4. It was shown that Blemaren® is a highly effective agent for treatment and prevention of uric acid and calcium oxalate crystalluria in calcium oxalate and uric acid urolithiasis. Further, its effectiveness in dissolving of uric acid stones in the absence of an infectious inflammatory process is 82.3%.
Yan, Dandan; Wang, Jie; Jiang, Feng; Zhang, Rong; Wang, Tao; Wang, Shiyun; Peng, Danfeng; He, Zhen; Chen, Haibing; Bao, Yuqian; Hu, Cheng; Jia, Weiping
As the association between uric acid and macrovascular disease has been heavily debated, we aimed to confirm whether there is a causal relationship between uric acid and diabetic macrovascular disease through Mendelian randomization analysis. In 3207 type 2 diabetes patients, seventeen SNPs (single nucleotide polymorphisms) related to uric acid were genotyped. A weighted GRS (genetic risk score) was calculated using selected SNPs and the strength of their effects on uric acid levels. Diabetic macrovascular disease was diagnosed through vascular ultrasound, magnetic resonance imaging or other clinical evidence. Associations of diabetic macrovascular disease with uric acid and weighted GRS were evaluated separately. In total participants and among females, the prevalence of diabetic macrovascular disease was significantly higher in hyperuricemic group than in normouricemic group, and uric acid was associated with diabetic macrovascular disease (OR=1.068, p=0.0349; OR=1.122, p=0.0158). The prevalence of diabetic macrovascular disease increased with the weighted GRS in a J-shaped manner for the females. The weighted GRS was positively correlated with uric acid in total population, male patients and female patients (β=0.203, p<0.0001; β=0.255, p<0.0001; β=0.142, p<0.0001, respectively). The weighted GRS was significantly associated with diabetic macrovascular disease in female patients (OR=1.184, p=0.0039). Among females, the observed association between weighted GRS and diabetic macrovascular disease was greater than predicted. Using the uric acid-related weighted GRS as an instrumental variable for Mendelian randomization analysis, our study provided an evidence for causal relationship between uric acid and diabetic macrovascular disease in Chinese females with type 2 diabetes mellitus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Norvik, Jon V; Schirmer, Henrik; Ytrehus, Kirsti; Storhaug, Hilde M; Jenssen, Trond G; Eriksen, Bjørn O; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Wilsgaard, Tom; Solbu, Marit D
To investigate whether serum uric acid predicts adverse outcomes in persons with indices of diastolic dysfunction in a general population. We performed a prospective cohort study among 1460 women and 1480 men from 1994 to 2013. Endpoints were all-cause mortality, incident myocardial infarction, and incident ischaemic stroke. We stratified the analyses by echocardiographic markers of diastolic dysfunction, and uric acid was the independent variable of interest. Hazard ratios (HR) were estimated per 59 μmol/L increase in baseline uric acid. Multivariable adjusted Cox proportional hazards models showed that uric acid predicted all-cause mortality in subjects with E/A ratio <0.75 (HR 1.12, 95% confidence interval [CI] 1.00-1.25) or E/A ratio >1.5 (HR 1.51, 95% CI 1.09-2.09, P for interaction between E/A ratio category and uric acid = 0.02). Elevated uric acid increased mortality risk in persons with E-wave deceleration time <140 ms or >220 ms (HR 1.46, 95% CI 1.01-2.12 and HR 1.13, 95% CI 1.02-1.26, respectively; P for interaction = 0.04). Furthermore, in participants with isovolumetric relaxation time ≤60 ms, mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02-12.26, P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03-2.53, P for interaction = 0.047). Increased uric acid was associated with higher all-cause mortality risk in subjects with echocardiographic indices of diastolic dysfunction, and with higher ischaemic stroke risk in persons with severely enlarged left atria.
Yiu, Andrew; Van Hemelrijck, Mieke; Garmo, Hans; Holmberg, Lars; Malmström, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Jungner, Ingmar; Wulaningsih, Wahyu
Serum uric acid has been suggested to be associated with cancer risk. We aimed to study the association between serum uric acid and cancer incidence in a large Swedish cohort. A positive association was found between uric acid levels and overall cancer risk, and results were similar with adjustment for glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05-1.11) in men and 1.12 (1.09 - 1.16) in women. Site-specific analysis showed a positive association between uric acid and risk of colorectal, hepatobiliary, kidney, non-melanoma skin, and other cancers in men and of head and neck and other cancers in women. An inverse association was observed for pulmonary and central nervous system (CNS) cancers in men and breast, lymphatic and haematological, and CNS malignancies in women. We included 493,281 persons aged 20 years and older who had a measurement of serum uric acid and were cancer-free at baseline in the AMORIS study. Multivariable Cox proportional hazards regression was used to investigate sex-specific quartiles of serum uric acid in relation to cancer risk in men and women. Analysis was further adjusted for serum glucose, triglycerides and, where available, BMI. Site-specific analysis was performed for major cancers. Altered uric acid levels were associated with risk of overall and some specific cancers, further indicating the potential role of uric acid metabolism in carcinogenesis.
Yiu, Andrew; Van Hemelrijck, Mieke; Garmo, Hans; Holmberg, Lars; Malmström, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Jungner, Ingmar; Wulaningsih, Wahyu
Objectives Serum uric acid has been suggested to be associated with cancer risk. We aimed to study the association between serum uric acid and cancer incidence in a large Swedish cohort. Results A positive association was found between uric acid levels and overall cancer risk, and results were similar with adjustment for glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05–1.11) in men and 1.12 (1.09 – 1.16) in women. Site-specific analysis showed a positive association between uric acid and risk of colorectal, hepatobiliary, kidney, non-melanoma skin, and other cancers in men and of head and neck and other cancers in women. An inverse association was observed for pulmonary and central nervous system (CNS) cancers in men and breast, lymphatic and haematological, and CNS malignancies in women. Materials and Methods We included 493,281 persons aged 20 years and older who had a measurement of serum uric acid and were cancer-free at baseline in the AMORIS study. Multivariable Cox proportional hazards regression was used to investigate sex-specific quartiles of serum uric acid in relation to cancer risk in men and women. Analysis was further adjusted for serum glucose, triglycerides and, where available, BMI. Site-specific analysis was performed for major cancers. Conclusions Altered uric acid levels were associated with risk of overall and some specific cancers, further indicating the potential role of uric acid metabolism in carcinogenesis. PMID:28418841
de Oliveira, Erick Prado; Moreto, Fernando; Silveira, Liciana Vaz de Arruda; Burini, Roberto Carlos
High plasma uric acid (UA) is a prerequisite for gout and is also associated with the metabolic syndrome and its components and consequently risk factors for cardiovascular diseases. Hence, the management of UA serum concentrations would be essential for the treatment and/or prevention of human diseases and, to that end, it is necessary to know what the main factors that control the uricemia increase. The aim of this study was to evaluate the main factors associated with higher uricemia values analyzing diet, body composition and biochemical markers. 415 both gender individuals aged 21 to 82 years who participated in a lifestyle modification project were studied. Anthropometric evaluation consisted of weight and height measurements with later BMI estimation. Waist circumference was also measured. The muscle mass (Muscle Mass Index - MMI) and fat percentage were measured by bioimpedance. Dietary intake was estimated by 24-hour recalls with later quantification of the servings on the Brazilian food pyramid and the Healthy Eating Index. Uric acid, glucose, triglycerides (TG), total cholesterol, urea, creatinine, gamma-GT, albumin and calcium and HDL-c were quantified in serum by the dry-chemistry method. LDL-c was estimated by the Friedewald equation and ultrasensitive C-reactive protein (CRP) by the immunochemiluminiscence method. Statistical analysis was performed by the SAS software package, version 9.1. Linear regression (odds ratio) was performed with a 95% confidence interval (CI) in order to observe the odds ratio for presenting UA above the last quartile (♂UA > 6.5 mg/dL and ♀ UA > 5 mg/dL). The level of significance adopted was lower than 5%. Individuals with BMI ≥ 25 kg/m2 OR = 2.28(1.13-4.6) and lower MMI OR = 13.4 (5.21-34.56) showed greater chances of high UA levels even after all adjustments (gender, age, CRP, gamma-gt, LDL, creatinine, urea, albumin, HDL-c, TG, arterial hypertension and glucose). As regards biochemical markers, higher
Jayashankar, C A; Andrews, Henley Punnen; Vijayasarathi; Pinnelli, Venkata BharatKumar; Shashidharan, Basappaji; Nithin Kumar, H N; Vemulapalli, Swaapnika
We aimed to identify the predictors of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (type 2 DM). About fifty Asian Indian patients with type 2 DM patients aged >40 years and fifty sex- and age-matched nondiabetic controls were enrolled for this study. Following complete medical history and baseline clinical data, laboratory investigations were performed to assess fasting and postprandial plasma glucose levels, lipid profile, blood urea, serum creatinine, and serum uric acid levels. Body mass index (BMI), waist-to-hip ratio, serum uric acid, serum total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, very LDL cholesterol were significantly higher among diabetic patients compared to controls. On univariate analysis, serum LDL cholesterol (odds ratio [OR]: 29.67, P < 0.001), serum uric acid (OR: 25.65, P < 0.001), low high-density lipoprotein (HDL) cholesterol (OR: 21.12, P < 0.001), hypertension (OR: 17.06, P < 0.001), family history of cardiovascular disease (CVD) (OR: 9.43, P = 0.002), and duration of diabetes (OR: 4.65, P = 0.03) were identified as predictors of CVD among diabetic patients. On multivariate regression, only LDL cholesterol (OR: 1.51, P = 0.002) and serum uric acid (OR: 1.21, P = 0.01) were the independent predictors of CAD among diabetic patients. Significant positive correlation of serum uric acid with duration of diabetes (r = 0.38, P = 0.006), BMI (r = 0.35, P = 0.01), triglycerides (r = 0.356, P = 0.01), LDL cholesterol (r = 0.38, P = 0.007), HDL cholesterol (r = -0.514, P < 0.001), and hypertension (r = 0.524, P < 0.001) was observed. Serum LDL cholesterol and hyperuricemia may serve as independent predictors of CAD among Asian Indian subjects with type 2 DM.
Otero, J A; Miguel, V; González-Lobato, L; García-Villalba, R; Espín, J C; Prieto, J G; Merino, G; Álvarez, A I
The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and milk secretion of endogenous and exogenous compounds, actively affecting milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the secretion into milk of compounds implicated in milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases milk secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and milk secretion of compounds such as riboflavin (vitamin B2), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo. Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into milk with a two-fold increase in the milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid
Lytvyn, Yuliya; Har, Ronnie; Locke, Amy; Lai, Vesta; Fong, Derek; Advani, Andrew; Perkins, Bruce A; Cherney, David Z I
Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients (n = 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions (n = 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (RE), and glomerular hydrostatic pressure (PGLO). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg, P = 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in RE, PGLO, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal RE responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D. © 2017 by the American Diabetes Association.
Iwanaga, Takashi; Sato, Masanobu; Maeda, Tomoji; Ogihara, Toshio; Tamai, Ikumi
Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular disease. It has been reported that an angiotensin II receptor blocker (ARB), losartan, decreases SUA level, whereas other ARBs, such as candesartan, have no lowering effect. Because the renal uric acid transporter (URAT1) is an important factor controlling the SUA level, we examined the involvement of URAT1 in those differential effects of various ARBs on SUA level at clinically relevant concentrations. This study was done by using URAT1-expressing Xenopus oocytes. Losartan, pratosartan, and telmisartan exhibited cis-inhibitory effects on the uptake of uric acid by URAT1, whereas at higher concentrations, only telmisartan did, and these ARBs reduced the uptake in competitive inhibition kinetics. On the other hand, candesartan, EXP3174 [2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yI)methyl]imidazole-5-carboxylic acid] (a major metabolite of losartan), olmesartan, and valsartan were not inhibitory. Preloading of those ARBs in the oocytes enhanced the URAT1-mediated uric acid uptake, showing a trans-stimulatory effect. The present study is a first demonstration of the differential effects of ARBs on URAT1 that some ARBs are both cis-inhibitory and trans-stimulatory, depending on concentration, whereas others exhibit either a trans-stimulatory or cis-inhibitory effect alone, which could explain the clinically observed differential effects of ARBs on SUA level. Furthermore, it was found that such differential effects of ARBs on URAT1 could be predicted from the partial chemical structures of ARBs, which will be useful information for the appropriate use and development of ARBs without an increase of SUA.
Yamashita, Hiroshi; Kobiyama, Atsushi; Koike, Kazuhiko
The symbiosis between zooxanthellae (dinoflagellate genus Symbiodinium) and corals is a fundamental basis of tropical marine ecosystems. However the physiological interactions of the hosts and symbionts are poorly understood. Recently, intracellular crystalline deposits in Symbiodinium were revealed to be uric acid functioning for nutrient storage. This is the first exploration of these enigmatic crystalline materials that had previously been misidentified as oxalic acid, providing new insights into the nutritional strategies of Symbiodinium in oligotrophic tropical waters. However, we believe these deposits also function as eye-spots on the basis of light and electron microscopic observations of motile cells of cultured Symbiodinium. The cells possessed crystalline deposit clusters in rows with each row 100–150 nm thick corresponding to 1/4 the wavelength of light and making them suitable for maximum wave interference and reflection of light. Crystalline clusters in cells observed with a light microscope strongly refracted and polarized light, and reflected or absorbed short wavelength light. The facts that purines, including uric acid, have been identified as the main constituents of light reflectors in many organisms, and that the photoreceptor protein, opsin, was detected in our Symbiodinium strain, support the idea that uric acid deposits in Symbiodinium motile cells may function as a component of an eye-spot. PMID:19609449
Barbieri, L; Verdoia, M; Pergolini, P; Nardin, M; Rolla, R; Marino, P; Bellomo, G; Suryapranata, H; De Luca, G
High residual platelet reactivity (HRPR) is still an important challenge, despite the advent of new potent ADP-antagonists. Therefore it is of extreme importance to identify factors that can influence platelet activation. Serum uric acid (SUA) has been largely addressed in the past as a possible risk factor for coronary artery disease, with a possible association with platelets hyperreactivity. So far no studies have assessed the role of serum uric acid on the response to dual antiplatelet therapy. Therefore, the aim of our study was to evaluate the impact of uric acid levels on platelet function in patients treated with dual antiplatelet therapy (DAPT) with clopidogrel or ticagrelor. We scheduled for platelet function assessment at 30-90 days post-discharge patients treated with DAPT (ASA + clopidogrel or ticagrelor) for an ACS or elective percutaneous coronary intervention (PCI). Platelet function was assessed by whole blood impedance aggregometry (Multiplate(®)-Roche Diagnostics AG), HRPR was considered for ASPI test >862 AU(∗)min (for ASA) and ADP test values ≥417 AU* min (for ADP-antagonists). We included a total of 493 patients (262 were on ASA and clopidogrel and 231 on ASA and ticagrelor). Patients were divided according to quartiles of serum uric acid levels measured at the time of platelet aggregation assessment (Group 1 <4.6 mg/dL, n = 114; Group 2, 4.7-5.8 mg/dL, n = 133; Group 3, 5.9-6.8 mg/dL, n = 124; Group 4, >6.9, n = 122). Patients with higher uric acid levels were older, more often smokers, with history of hypertension and previous coronary artery bypass surgery and renal failure and were more often on therapy with diuretics at admission. Patients with higher SUA had higher triglycerides and fibrinogen. Uric acid levels did not influence ASPI, COL, TRAP and ADP tests. High residual platelet reactivity (HRPR) was observed in 1.5% of patients treated with ASA, with no difference according to SUA quartiles (p = 0.60), confirmed at multivariate
Westley, Chloe; Xu, Yun; Thilaganathan, Baskaran; Carnell, Andrew J; Turner, Nicholas J; Goodacre, Royston
High levels of uric acid in urine and serum can be indicative of hypertension and the pregnancy related condition, preeclampsia. We have developed a simple, cost-effective, portable surface enhanced Raman scattering (SERS) approach for the routine analysis of uric acid at clinically relevant levels in urine patient samples. This approach, combined with the standard addition method (SAM), allows for the absolute quantification of uric acid directly in a complex matrix such as that from human urine. Results are highly comparable and in very good agreement with HPLC results, with an average <9% difference in predictions between the two analytical approaches across all samples analyzed, with SERS demonstrating a 60-fold reduction in acquisition time compared with HPLC. For the first time, clinical prepreeclampsia patient samples have been used for quantitative uric acid detection using a simple, rapid colloidal SERS approach without the need for complex data analysis.
Steenland, Kyle; Tinker, Sarah; Shankar, Anoop; Ducatman, Alan
Background Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are compounds that do not occur in nature, have been widely used since World War II, and persist indefinitely in most environments. Median serum levels in the United States are 4 ng/mL for PFOA and 21 ng/mL for PFOS. PFOA has been associated with elevated uric acid in two studies of chemical workers. Uric acid is a risk factor for hypertension and possibly other cardiovascular outcomes. Methods We conducted a cross-sectional study of PFOA and PFOS and uric acid among 54,951 adult community residents in Ohio and West Virginia, who lived or worked in six water districts contaminated with PFOA from a chemical plant. Analyses were conducted by linear and logistic regression, adjusted for confounders. Results Both PFOA and PFOS were significantly associated with uric acid. An increase of 0.2–0.3 mg/dL uric acid was associated with an increase from the lowest to highest decile of either PFOA or PFOS. Hyperuricemia risk increased modestly with increasing PFOA; the odds ratios by quintile of PFOA were 1.00, 1.33 [95% confidence interval (CI), 1.24–1.43], 1.35 (95% CI, 1.26–1.45), 1.47 (95% CI, 1.37–1.58), and 1.47 (95% CI, 1.37–1.58; test for trend, p < 0.0001). We saw a less steep trend for PFOS. Inclusion of both correlated fluorocarbons in the model indicated PFOA was a more important predictor than was PFOS. Conclusion Higher serum levels of PFOA were associated with a higher prevalence of hyperuricemia, but the limitations of cross-sectional data and the possibility of noncausal mechanisms prohibit conclusions regarding causality. PMID:20123605
Justicia, Carles; Salas-Perdomo, Angélica; Pérez-de-Puig, Isabel; Deddens, Lisette H; van Tilborg, Geralda A F; Castellví, Clara; Dijkhuizen, Rick M; Chamorro, Ángel; Planas, Anna M
Hyperglycemia at stroke onset is associated with poor long-term clinical outcome in numerous studies. Hyperglycemia induces intracellular acidosis, lipid peroxidation, and peroxynitrite production resulting in the generation of oxidative and nitrosative stress in the ischemic tissue. Here, we studied the effects of acute hyperglycemia on in vivo intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil recruitment, and brain damage after ischemia/reperfusion in mice and tested whether the natural antioxidant uric acid was protective. Hyperglycemia was induced by i.p. administration of dextrose 45 min before transient occlusion of the middle cerebral artery. Magnetic resonance imaging (MRI) was performed at 24 h to measure lesion volume. A group of normoglycemic and hyperglycemic mice received an i.v. injection of micron-sized particles of iron oxide (MPIOs), conjugated with either anti-ICAM-1 antibody or control IgG, followed by T2*w MRI. Neutrophil infiltration was studied by immunofluorescence and flow cytometry. A group of hyperglycemic mice received an i.v. infusion of uric acid (16 mg/kg) or the vehicle starting after 45 min of reperfusion. ICAM-1-targeted MPIOs induced significantly larger MRI contrast-enhancing effects in the ischemic brain of hyperglycemic mice, which also showed more infiltrating neutrophils and larger lesions than normoglycemic mice. Uric acid reduced infarct volume in hyperglycemic mice but it did not prevent vascular ICAM-1 upregulation and did not significantly reduce the number of neutrophils in the ischemic brain tissue. In conclusion, hyperglycemia enhances stroke-induced vascular ICAM-1 and neutrophil infiltration and exacerbates the brain lesion. Uric acid reduces the lesion size after ischemia/reperfusion in hyperglycemic mice.
Sousa, Moisés S.S.R.; Saavedra, Francisco J.F.; Neto, Gabriel R.; Novaes, Giovanni S.; Souza, Antonio C. R.; Salerno, Verônica P.; Novaes, Jefferson S.
Resistance training (RT) can provide several benefits for individuals with Type 2 diabetes. The aim of this study was to investigate the effects of resistance training on the strength levels and uric acid (UA) concentration in individuals with Type 2 diabetes. The study included 68 patients (57.7±9.0 years) that participated in an organized program of RT for 12 weeks. The volunteers were divided into two groups: an experimental group (EG; n=34) that performed the resistance training program consisting of seven exercises executed in an alternating order based on segments; and a control group (CG; n=34) that maintained their normal daily life activities. Muscle strength and uric acid were measured both pre- and post-experiment. The results showed a significant increase in strength of the subjects in the EG for all exercises included in the study (p<0.001). Comparing the strength levels of the post-test, intergroup differences were found in supine sitting (p<0.001), leg extension (p<0.001), shoulder press (p<0.001), leg curl (p=0.001), seated row (p<0.001), leg press (p=0.001) and high pulley (p<0.001). The measured uric acid was significantly increased in both experimental and control groups (p<0.001 and p=0.001, respectively). The intergroup comparison showed a significant increase for the EG (p=0.024). We conclude that the training program was effective for strength gains despite an increase in uric acid in Type 2 diabetics. PMID:25713640
Choi, Hansol; Kim, Hyeon Chang; Song, Bo Mi; Park, Ji Hye; Lee, Ju-Mi; Yoon, Da-Lim; Yoon, Young Mi; Rhee, Yumie; Youm, Yousik; Kim, Chang Oh
Epidemiologic studies have demonstrated that elevated serum uric acid concentration is an independent risk factor for metabolic syndrome. However, few studies have focused on elderly populations. Thus, we investigated the association of serum uric acid concentration with metabolic syndrome in community-dwelling elderly Koreans. This cross-sectional analysis included 2940 participants (986 men and 1954 women) aged 65 years or older who participated in a baseline health assessment for the Korean Urban Rural Elderly cohort study from 2012 to 2014. Serum uric acid concentration was analyzed using both continuous and dichotomous variables. Hyperuricemia was defined as a uric acid concentration ≥7.0 mg/dL in men and ≥6.0 mg/dL in women. Metabolic syndrome was defined according to the 2009 harmonizing definition. Multiple logistic regression models were used to investigate independent association between serum uric acid and metabolic syndrome, after adjusting for age, body mass index, LDL cholesterol, glycated hemoglobin, blood urea nitrogen, estimated glomerular filtration rate health behaviors, and medications. Prevalence of metabolic syndrome and its components increased significantly according to uric acid concentration in both sexes. The adjusted odds ratios for having metabolic syndrome per 1.0mg/dL higher uric acid concentration were 1.16 (95% CI: 1.03-1.31) in men and 1.27 (95% CI: 1.13-1.42) in women. Hyperuricemia was also associated with metabolic syndrome, with adjusted odds ratios of 1.71 (95% CI: 1.11-2.63) in men and 1.55 (95% CI: 1.05-2.29) in women. Elevated serum uric acid concentration was independently associated with an increased prevalence of metabolic syndrome in community-dwelling elderly Koreans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Voruganti, V Saroja; Laston, Sandra; Haack, Karin; Mehta, Nitesh R; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G
Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children. The aim was to investigate whether variation in serum uric acid is under genetic influence and whether the association with SLC2A9 polymorphisms generalizes to Hispanic children of the Viva La Familia Study. We conducted a genomewide association study with 1.1 million genetic markers in 815 children. We found serum uric acid to be significantly heritable [h(2) ± SD = 0.45 ± 0.08, P = 5.8 × 10(-11)] and associated with SLC2A9 variants (P values between 10(-16) and 10(-7)). Several of the significantly associated polymorphisms were previously identified in studies in adults. We also found positive genetic correlations between serum uric acid and BMI z score (ρG = 0.45, P = 0.002), percentage of body fat (ρG = 0.28, P = 0.04), fat mass (ρG = 0.34, P = 0.02), waist circumference (ρG = 0.42, P = 0.003), and waist-to-height ratio (ρG = 0.46, P = 0.001). Our results show that variation in serum uric acid in Hispanic children is under considerable genetic influence and is associated with obesity-related phenotypes. As in adults, genetic variation in SLC2A9 is associated with serum uric acid concentrations, an important biomarker of renal and cardiovascular disease risk, in Hispanic children. © 2015 American Society for Nutrition.
Voruganti, V Saroja; Laston, Sandra; Haack, Karin; Mehta, Nitesh R; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G
Background: Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children. Objective: The aim was to investigate whether variation in serum uric acid is under genetic influence and whether the association with SLC2A9 polymorphisms generalizes to Hispanic children of the Viva La Familia Study. Design: We conducted a genomewide association study with 1.1 million genetic markers in 815 children. Results: We found serum uric acid to be significantly heritable [h2 ± SD = 0.45 ± 0.08, P = 5.8 × 10−11] and associated with SLC2A9 variants (P values between 10−16 and 10−7). Several of the significantly associated polymorphisms were previously identified in studies in adults. We also found positive genetic correlations between serum uric acid and BMI z score (ρG = 0.45, P = 0.002), percentage of body fat (ρG = 0.28, P = 0.04), fat mass (ρG = 0.34, P = 0.02), waist circumference (ρG = 0.42, P = 0.003), and waist-to-height ratio (ρG = 0.46, P = 0.001). Conclusions: Our results show that variation in serum uric acid in Hispanic children is under considerable genetic influence and is associated with obesity-related phenotypes. As in adults, genetic variation in SLC2A9 is associated with serum uric acid concentrations, an important biomarker of renal and cardiovascular disease risk, in Hispanic children. PMID:25833971
Sotoda, Yoko; Hirooka, Shigeki; Orita, Hiroyuki
Aim: We investigated the relationships of serum uric acid levels with the progression of atherosclerosis in patients with peripheral arterial disease (PAD) after treatment. Methods: Subjects were male patients diagnosed with PAD. Atherosclerosis at the common carotid artery was evaluated based on its intima-media thickness (IMT). Leg arterial flow was evaluated by measuring ankle-brachial index (ABI) and exercise-induced decrease in ABI. Results: Among various risk factors including age, blood pressure, adiposity, estimated glomerular filtration rate, and blood lipid, blood glucose, uric acid, fibrinogen and C-reactive protein levels, only uric acid levels showed significant correlations with ABI [Pearson's correlation coefficient, −0.292 (p < 0.01)] and leg exercise-induced decrease in ABI [Pearson's correlation coefficient, 0.236 (p < 0.05)]. However, there was no significant correlation between uric acid levels and maximum or mean IMT. Odds ratios of subjects with the 3rd tertile versus subjects with the 1st tertile for uric acid levels were significantly higher than the reference level of 1.00 for low ABI [4.44 (95% confidence interval, 1.45–13.65, p < 0.01)] and for high % decrease in ABI after exercise [4.31 (95% confidence interval, 1.34–13.82, p < 0.05)]. The associations of uric acid levels with the indicators of leg ischemia were also found after adjustment for age, history of revascularization therapy, diabetes, smoking, alcohol consumption, body mass index, triglyceride levels, and renal function. Conclusion: Uric acid levels are associated with the degree of leg ischemia in patients with PAD. Further interventional studies are needed to determine whether the correction of uric acid levels is effective in preventing the progression of PAD. PMID:28202852
Sotoda, Yoko; Hirooka, Shigeki; Orita, Hiroyuki; Wakabayashi, Ichiro
We investigated the relationships of serum uric acid levels with the progression of atherosclerosis in patients with peripheral arterial disease (PAD) after treatment. Subjects were male patients diagnosed with PAD. Atherosclerosis at the common carotid artery was evaluated based on its intima-media thickness (IMT). Leg arterial flow was evaluated by measuring ankle-brachial index (ABI) and exercise-induced decrease in ABI. Among various risk factors including age, blood pressure, adiposity, estimated glomerular filtration rate, and blood lipid, blood glucose, uric acid, fibrinogen and C-reactive protein levels, only uric acid levels showed significant correlations with ABI [Pearson's correlation coefficient, -0.292 (p＜0.01)] and leg exercise-induced decrease in ABI [Pearson's correlation coefficient, 0.236 (p＜ 0.05)]. However, there was no significant correlation between uric acid levels and maximum or mean IMT. Odds ratios of subjects with the 3rd tertile versus subjects with the 1st tertile for uric acid levels were significantly higher than the reference level of 1.00 for low ABI [4.44 (95% confidence interval, 1.45-13.65, p＜0.01)] and for high % decrease in ABI after exercise [4.31 (95% confidence interval, 1.34-13.82, p＜0.05)]. The associations of uric acid levels with the indicators of leg ischemia were also found after adjustment for age, history of revascularization therapy, diabetes, smoking, alcohol consumption, body mass index, triglyceride levels, and renal function. Uric acid levels are associated with the degree of leg ischemia in patients with PAD. Further interventional studies are needed to determine whether the correction of uric acid levels is effective in preventing the progression of PAD.
Gwag, Hye Bin; Yang, Jeong Hoon; Park, Taek Kyu; Song, Young Bin; Hahn, Joo Yong; Choi, Jin Ho; Lee, Sang Hoon; Gwon, Hyeon Cheol; Choi, Seung Hyuk
No data are available on the association of serum uric acid and vasospastic angina (VSA) which has endothelial dysfunction as a possible pathophysiologic mechanism. Low uric acid level might cause adverse outcomes in VSA in connection with endothelial dysfunction. We enrolled 818 VSA patients whose uric acid level was measured at admission. Patients were categorized according to tertiles of uric acid level: group I, ≤ 4.8 mg/dL; group II, 4.9-5.9 mg/dL; and group III, ≥ 6.0 mg/dL. Primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, acute myocardial infarction (MI), ischemic stroke, coronary revascularization, and rehospitalization for angina. Median follow-up duration was 49.2 months. Median uric acid values were 4.1 mg/dL for group I, 5.4 mg/dL for group II, and 6.7 mg/dL for group III. In the overall population, group II had a significantly lower incidence of MACE compared to group I (47 [17.1%] vs. 66 [24.6%]; hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.02-2.26; P = 0.040) and a tendency of lower incidence of MACEs compared to Group III (47 [17.1%] vs. 62 [22.5%]; HR, 1.44; 95% CI, 0.98-2.13; P = 0.067). Among group I patients, those who received nitrates had a higher incidence of MACEs than those without nitrate therapy (P < 0.001). Low uric acid level was associated with adverse clinical outcomes, while high uric acid level had a trend toward an increase in it. Use of nitrate in patients with low uric acid level might have adverse effects on clinical outcomes of VSA. © 2017 The Korean Academy of Medical Sciences.
Miland, E; Miranda Ordieres, A J; Tuñón Blanco, P; Smyth, M R; Fágáin, C O
A reagentless uric acid selective biosensor constructed by immobilising uricase and horseradish peroxidase (HRP) in carbon paste without the addition of an electron transfer mediator is described. The response of the electrode is based on the enzymatic reduction of hydrogen peroxide in the presence of uric acid. Uricase and HRP were dispersed in the carbon paste and the optimum paste mixture was determined. Poly(o-aminophenol) was electropolymerised at the working surface area of the electrode acting as a conducting polymer layer. Cyclic voltammetry was used to characterise the permselective characteristics of the polymer layer. At an applied potential of 50 mV vs. Ag/AgCl, a linear response was obtained up to 1 x 10(-4) M, with a limit of detection of 3 x 10(-6) M. The sensor had a response time of 37 s. a calibration precision of 2.2% (n = 4) and an estimated sample frequency of 20 h(-1). Responses to the analyte of interest were pH dependent. The sensor was incorporated into a flow injection system for the qualification of uric acid in human serum. Results compared favourably with a standard spectrophotometric method.
Joo, Kowoon; Kwon, Seong-Ryul; Lim, Mie-Jin; Jung, Kyong-Hee; Joo, Hoyeon; Park, Won
The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA≥6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.
Niegawa, Tomomi; Takitani, Kimitaka; Takaya, Ryuzo; Ishiro, Manabu; Kuroyanagi, Yuichi; Okasora, Keisuke; Minami, Yukako; Matsuda, Takuya; Tamai, Hiroshi
Down syndrome, caused by trisomy 21, is characterized by congenital abnormalities as well as mental retardation. From the neonatal stage through adolescence, patients with Down syndrome often have several complications. Thus, it is important to attain knowledge of the prevalence of these comorbidities in children with Down syndrome. We, therefore, evaluated the biochemical data, thyroid function, and anthropometric parameters, and analyzed the association among them in Japanese children and early adolescents with Down syndrome. There was no difference in the prevalence of obesity and overweight between boys and girls. The level of uric acid was higher in boys than in girls. Moreover, the prevalence of hyperuricemia was also higher in boys than in girls (approximately 32% and 10%, respectively). The prevalence of subclinical hypothyroidism in children with Down syndrome was approximately 20%, with no significant sex differences. The levels of uric acid and dehydroepiandrosterone-sulfate were positively associated with age, while the levels of thyroid-stimulating hormone and free thyroxine had a negative association with age. Overall, children with Down syndrome, exhibit a higher incidence of hyperuricemia. Therefore, uric acid levels, as well as thyroid function, from childhood to early adulthood should be monitored in this patient cohort. PMID:28955133
Niegawa, Tomomi; Takitani, Kimitaka; Takaya, Ryuzo; Ishiro, Manabu; Kuroyanagi, Yuichi; Okasora, Keisuke; Minami, Yukako; Matsuda, Takuya; Tamai, Hiroshi
Down syndrome, caused by trisomy 21, is characterized by congenital abnormalities as well as mental retardation. From the neonatal stage through adolescence, patients with Down syndrome often have several complications. Thus, it is important to attain knowledge of the prevalence of these comorbidities in children with Down syndrome. We, therefore, evaluated the biochemical data, thyroid function, and anthropometric parameters, and analyzed the association among them in Japanese children and early adolescents with Down syndrome. There was no difference in the prevalence of obesity and overweight between boys and girls. The level of uric acid was higher in boys than in girls. Moreover, the prevalence of hyperuricemia was also higher in boys than in girls (approximately 32% and 10%, respectively). The prevalence of subclinical hypothyroidism in children with Down syndrome was approximately 20%, with no significant sex differences. The levels of uric acid and dehydroepiandrosterone-sulfate were positively associated with age, while the levels of thyroid-stimulating hormone and free thyroxine had a negative association with age. Overall, children with Down syndrome, exhibit a higher incidence of hyperuricemia. Therefore, uric acid levels, as well as thyroid function, from childhood to early adulthood should be monitored in this patient cohort.
Huang, Wei; Cao, Yang; Chen, Yong; Zhou, Yang; Huang, Qingyou
3-D periodic mesoporous nickel oxide (NiO) particles with crystalline walls have been synthesized through the microwave-assisted hard template route toward the KIT-6 silica. It was investigated as a nonenzymatic amperometric sensor for the detection of uric acid. 3-D periodic nickel oxide matrix has been obtained by the hard template route from the KIT-6 silica template. The crystalline nickel oxide belonged to the Ia3d space group, and its structure was characterized by X-ray diffraction (XRD), N2 adsorption-desorption, and transmission electron microscopy (TEM). The analysis results showed that the microwave-assisted mesoporous NiO materials were more appropriate to be electrochemical sensors than the traditional mesoporous NiO. Cyclic voltammetry (CV) revealed that 3-D periodic NiO exhibited a direct electrocatalytic activity for the oxidation of uric acid in sodium hydroxide solution. The enzyme-less amperometric sensor used in the detection of uric acid with detection limit of 0.005 μM (S/N = 3) over wide linear detection ranges up to 0.374 mM and with a high sensitivity of 756.26 μA mM-1 cm-2, and a possible mechanism was also given in the paper.
Cai, Wen; Song, Jiang-mei; Zhang, Bei; Sun, Yu-ping; Yao, Hua; Zhang, Yue-xin
Objective. To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of serum uric acid level with NAFLD in Uygur people, Xinjiang. Methods. A total of 2241 Uyghur persons (1214 males and 1027 females) were interviewed for physical checkups from 2011 to 2012. The clinical data of questionnaire survey, body mass index (BMI), abdominal circumference, blood pressure, blood sugar, blood lipid, and serum uric acid level were collected for analysis. Results. The prevalence rates of NAFLD determined by abdominal ultrasound examination and hyperuricemia were 43.9% and 8.4%, respectively. The persons with NAFLD had significantly higher serum uric acid levels than those without NAFLD (320 ± 88 versus 254 ± 80 μmol/L; P < 0.001). The prevalence rate of NAFLD was significantly higher in subjects with hyperuricemia than that in those without hyperuricemia (78.19% versus 40.83%; P < 0.001), and the prevalence rate increased with progressively higher serum uric acid levels (P < 0.001). Multiple regression analysis showed that hyperuricemia was associated with an increased risk of NAFLD (odds ratio (OR): 2.628, 95% confidence interval (CI): 1.608–4.294, and P < 0.001). Conclusion. Serum uric acid level was significantly associated with NAFLD, and the prevalence rate of NAFLD increased with progressively higher serum uric acid levels. PMID:24516367
Du, Lei; Ma, Jianhua; Zhang, Xiaoning
Higher levels of serum uric acid tend to increase the diabetes-related complications. We performed a meta-analysis to investigate whether the higher serum uric acid levels were associated with cerebral infarction in type 2 diabetes patients. We searched for relevant studies in the PubMed, Embase, China National Knowledge Infrastructure, China BioMedicine, and VIP database until August 2015. All observational studies comparing serum uric acid levels in type 2 diabetic patients with and without cerebral infarction were included. We calculated the ratio of means (RoM) of serum uric acid by mean cerebral infarction/mean diabetic control from the individual studies and then pooled RoM and its 95 % confidence intervals (CI). A total of 23 eligible studies were identified. Pooled estimates indicated that type 2 diabetes patients with cerebral infarction were associated with 29 % (RoM 1.29; 95 % CI 1.26-1.31) higher serum uric acid levels than those without cerebral infarction in a random effect model. Subgroup analyses based on gender indicated that RoM was 1.23 (95 % CI 1.09-1.38) for men and 1.12 (95 % CI 0.98-1.27) for women. This meta-analysis suggests that higher serum uric acid levels may contribute to cerebral infarction in patients with type 2 diabetes.
Liang, Ching-Chao; Lin, Pi-Chen; Lee, Mei-Yueh; Chen, Szu-Chia; Shin, Shyi-Jang; Hsiao, Pi-Jung; Lin, Kun-Der; Hsu, Wei-Hao
Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015-1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084-1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.
Oliveira, Sayonara Rangel; Kallaur, Ana Paula; Lopes, Josiane; Colado Simão, Andrea Name; Vissoci Reiche, Edna Maria; de Almeida, Elaine Regina Delicato; Morimoto, Helena Kaminami; de Carvalho Jennings de Pereira, Wildea Lice; Alfieri, Daniela Frizon; Flauzino, Tamires; de Meleck Proença, Caio; Gomes, Anna Maria; Kaimen-Maciel, Damacio Ramón; Maes, Michael
Depression is accompanied by metabolic disorders in iron metabolism, lipoproteins, and insulin resistance. We measured plasma levels of ferritin, iron, lipids, insulin, and glucose and computed the homeostasis model assessment (HOMA2IR) and atherogenic index of plasma (AIP) in MS patients with and without depression and healthy controls. Explanatory variables were serum uric acid, interleukin (IL)-6, lipid hydroperoxides (CL-LOOH), albumin, and C-reactive protein (CRP). Depression was assessed using the Hospital Anxiety and Depression Scale (HADS), neurological disability using the Expanded Disability Status Scale (EDSS), and disease progression using ∆EDSS over five years earlier. HOMA2IR and insulin were predicted by diagnosis (increased in MS), age and body mass index (BMI); AIP by diagnosis, sex, BMI, CRP, and uric acid; triglycerides by diagnosis (higher in MS without depression), age, BMI and uric acid; ferritin by diagnosis (higher in MS), sex, CRP, and albumin; and iron by albumin. The HADS score was significantly predicted by ∆EDSS, gastro-intestinal symptoms, iron (inverse), and age. MS is characterized by significantly increased insulin resistance, which is determined by increased insulin levels; and increased ferritin, a biomarker of inflammation. Depression in MS is not associated with increased insulin resistance and atherogenicity but with lowered iron.
Bare, L. N.; Wiseman, R. F.; Abbott, O. J.
Bare, L. N. (University of Kentucky, Lexington), R. F. Wiseman, and O. J. Abbott. Effect of dietary antibiotics upon coliform bacteria and lactobacilli in the intestinal tract of uric acid-fed chicks. J. Bacteriol. 87:329–331. 1964.—Male chicks (1-day-old; Vantress X Arbor Acre) were fed a basal glucose-soybean oil meal diet, a 2% uric acid-containing diet with and without 5 mg/lb of zinc bacitracin and 20 mg/lb of procaine penicillin G, and one supplemented with the antibiotics only. After 4 weeks, the chicks receiving the uric acid without antibiotics showed a weight depression. The presence of antibiotics in the ration with the uric acid reversed this growth depression. Bacteriological and chemical analyses of the contents of the small intestine revealed an increase in numbers of uricolytic Aerobacter spp. and an increased degradation of uric acid in the tract of the “uric-antibiotic”-fed chicks. The counts of lactobacilli were always lowest in this group of chicks PMID:14151052
Du, Jiao; Yue, Ruirui; Ren, Fangfang; Yao, Zhangquan; Jiang, Fengxing; Yang, Ping; Du, Yukou
A novel and sensitive carbon fiber electrode (CFE) modified by graphene flowers was prepared and used to simultaneously determine ascorbic acid (AA), dopamine (DA) and uric acid (UA). SEM images showed that beautiful and layer-petal graphene flowers homogeneously bloomed on the surface of CFE. Moreover, sharp and obvious oxidation peaks were found at the obtained electrode when compared with CFE and glassy carbon electrode (GCE) for the oxidation of AA, DA and UA. Also, the linear calibration plots for AA, DA and UA were observed, respectively, in the ranges of 45.4-1489.23 μM, 0.7-45.21 μM and 3.78-183.87 μM in the individual detection of each component. By simultaneously changing the concentrations of AA, DA and UA, their oxidation peaks appeared at -0.05 V, 0.16 V and 2.6 V, and the good linear responses ranges were 73.52-2305.53 μM, 1.36-125.69 μM and 3.98-371.49 μM, respectively. In addition, the obtained electrode showed satisfactory results when applied to the determination of AA, DA and UA in urine and serum samples.
Johnson, Richard J.; Gaucher, Eric A.; Sautin, Yuri Y.; Henderson, George N.; Angerhofer, Alex J.; Benner, Steven A.
Humans have relatively low plasma ascorbate levels and high serum uric acid levels compared to most mammals due to the presence of genetic mutations in L-gulonolactone oxidase and uricase, respectively. We review the major hypotheses for why these mutations may have occurred. In particular, we suggest that both mutations may have provided a survival advantage to early primates by helping maintain blood pressure during periods of dietary change and environmental stress. We further propose that these mutations have the inadvertent disadvantage of increasing our risk for hypertension and cardiovascular disease in today’s society characterized by Western diet and increasing physical inactivity. Finally, we suggest that a “planetary biology” approach in which genetic changes are analyzed in relation to their biologic action and historical context may provide the ideal approach towards understanding the biology of the past, present and future. PMID:18331782
Johnson, Richard J; Gaucher, Eric A; Sautin, Yuri Y; Henderson, George N; Angerhofer, Alex J; Benner, Steven A
Humans have relatively low plasma ascorbate levels and high serum uric acid levels compared to most mammals due to the presence of genetic mutations in l-gulonolactone oxidase and uricase, respectively. We review the major hypotheses for why these mutations may have occurred. In particular, we suggest that both mutations may have provided a survival advantage to early primates by helping maintain blood pressure during periods of dietary change and environmental stress. We further propose that these mutations have the inadvertent disadvantage of increasing our risk for hypertension and cardiovascular disease in today's society characterized by Western diet and increasing physical inactivity. Finally, we suggest that a "planetary biology" approach in which genetic changes are analyzed in relation to their biological action and historical context may provide the ideal approach towards understanding the biology of the past, present and future.
Wei, Fengjiang; Chang, Baocheng; Yang, Xilin; Wang, Yaogang; Chen, Liming; Li, Wei-Dong
The aim of the study was to decipher the relationship between serum uric acid (SUA) and glycated hemoglobin A1c (HbA1c) or fasting plasma glucose (FPG) in both type 2 diabetes mellitus (T2DM) patients and normal subjects. A total of 2,250 unrelated T2DM patients and 4,420 Han Chinese subjects from a physical examination population were recruited for this study. In T2DM patients SUA levels were negatively correlated with HbA1c (rs = ‑0.109, P = 0.000) and 2 h plasma glucose levels (rs = ‑0.178, P = 0.000). In the physical examination population, SUA levels were inversely correlated with HbA1c (rs = ‑0.175, P = 0.000) and FPG (rs = ‑0.131, P = 0.009) in T2DM patients but positively correlated with HbA1c (rs = 0.040, P = 0.012) and FPG (rs = 0.084, P = 0.000) in normal-glucose subjects. Multivariate analyses showed that HbA1c was significantly negatively associated with HUA both in T2DM patients (OR = 0.872, 95% CI: 0.790~0.963) and in the physical examination T2DM patients (OR = 0.722, 95% CI: 0.539~0.968). Genetic association studies in T2DM patients showed that alleles of two glucose-uric acid transporter genes, ABCG2 and SLC2A9 were significantly associated with SUA levels (P < 0.05). SUA level is inversely correlated with HbA1c in T2DM patients but positively correlated with HbA1c in normal-glucose subjects. The reverse transporting of uric acid and glucose in renal tubules might be accounted for these associations.
Lin, Liqing; Chen, Jinghua; Yao, Hong; Chen, Yuanzhong; Zheng, Yanjie; Lin, Xinhua
A sensitive and selective electrochemical method for the determination of dopamine using an Evans Blue polymer film modified on glassy carbon electrode was developed. The Evans blue polymer film modified electrode shows excellent electrocatalytic activity toward the oxidation of dopamine in phosphate buffer solution (pH 4.5). The linear range of 1.0 x 10(-6)-3.0 x 10(-5) M and detection limit of 2.5 x 10(-7) M were observed in pH 4.5 phosphate buffer solutions. The interference studies showed that the modified electrode exhibits excellent selectivity in the presence of large excess of ascorbic acid and uric acid. The separation of the oxidation peak potentials for dopamine-ascorbic acid and dopamine-uric acid were about 182 mV and 180 mV, respectively. The differences are large enough to determine AA, DA and UA individually and simultaneously. This work provides a simple and easy approach to selectively detect dopamine in the presence of ascorbic acid and uric acid in physiological samples.
Tang, Shanshan; Zhang, Rong; Jiang, Feng; Wang, Jie; Chen, Miao; Peng, Danfeng; Yan, Jing; Wang, Shiyun; Bao, Yuqian; Hu, Cheng; Jia, Weiping
Irisin is a novel hormone secreted by skeletal muscle after exercise, which may ameliorate insulin resistance. In this study, we aimed to explore the relationship between circulating irisin levels and type 2 diabetes (T2DM) as well as related metabolic traits in a Chinese population. A total of 203 subjects were recruited. Of these, 68 subjects with NGT, 63 subjects with IGR and 72 subjects with new-onset T2DM. Circulating irisin levels were measured by ELISA. Detailed clinical investigations and biochemistry measurements were carried out in all of the subjects. Multivariate linear regression analysis was performed to assess the association between irisin levels and related metabolic characteristics. All subjects were classified into normal weight and overweight/obese subgroups according to body mass index (BMI). No significant differences in circulating irisin levels were identified among the three groups (p=0.9741). After adjusting for covariates, multiple linear regression analysis revealed that serum irisin level was independently and significantly associated with total cholesterol (p=0.0005), low-density lipoprotein cholesterol (p=0.0014), fasting fatty acids (p=0.0402) and uric acid (p=0.0062). By dividing the serum irisin levels into three tertile group, the values of total cholesterol, low-density lipoprotein cholesterol, fasting fatty acids and uric acid were all increased significantly with the increase of irisin (p<0.05) . Moreover, serum irisin levels remain closely related to total cholesterol in both normal weight and overweight/obese subgroups. Our study suggests that circulating irisin concentrations are significantly associated with lipid and uric acid metabolism in a Chinese population. This article is protected by copyright. All rights reserved.
Goldfarb, David S; MacDonald, Patricia A; Gunawardhana, Lhanoo; Chefo, Solomon; McLean, Lachy
Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation. Febuxostat, a xanthine oxidoreductase inhibitor, is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout. This work studied whether febuxostat, compared with allopurinol and placebo, would reduce 24-hour urinary uric acid excretion and prevent stone growth or new stone formation. In this 6-month, double-blind, multicenter, randomized controlled trial, hyperuricosuric participants with a recent history of calcium stones and one or more radio-opaque calcium stone ≥ 3 mm (as seen by multidetector computed tomography) received daily febuxostat at 80 mg, allopurinol at 300 mg, or placebo. The primary end point was percent change from baseline to month 6 in 24-hour urinary uric acid. Secondary end points included percent change from baseline to month 6 in size of index stone and change from baseline in the mean number of stones and 24-hour creatinine clearance. Of 99 enrolled participants, 86 participants completed the study. Febuxostat led to significantly greater reduction in 24-hour urinary uric acid (-58.6%) than either allopurinol (-36.4%; P=0.003) or placebo (-12.7%; P<0.001). Percent change from baseline in the size of the largest calcium stone was not different with febuxostat compared with allopurinol or placebo. There was no change in stone size, stone number, or renal function. No new safety concerns were noted for either drug. Febuxostat (80 mg) lowered 24-hour urinary uric acid significantly more than allopurinol (300 mg) in stone formers with higher urinary uric acid excretion after 6 months of treatment. There was no change in stone size or number over the 6-month period.
MacDonald, Patricia A.; Gunawardhana, Lhanoo; Chefo, Solomon; McLean, Lachy
Summary Background and objectives Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation. Febuxostat, a xanthine oxidoreductase inhibitor, is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout. This work studied whether febuxostat, compared with allopurinol and placebo, would reduce 24-hour urinary uric acid excretion and prevent stone growth or new stone formation. Design, setting, participants, & measurements In this 6-month, double-blind, multicenter, randomized controlled trial, hyperuricosuric participants with a recent history of calcium stones and one or more radio-opaque calcium stone ≥3 mm (as seen by multidetector computed tomography) received daily febuxostat at 80 mg, allopurinol at 300 mg, or placebo. The primary end point was percent change from baseline to month 6 in 24-hour urinary uric acid. Secondary end points included percent change from baseline to month 6 in size of index stone and change from baseline in the mean number of stones and 24-hour creatinine clearance. Results Of 99 enrolled participants, 86 participants completed the study. Febuxostat led to significantly greater reduction in 24-hour urinary uric acid (−58.6%) than either allopurinol (−36.4%; P=0.003) or placebo (−12.7%; P<0.001). Percent change from baseline in the size of the largest calcium stone was not different with febuxostat compared with allopurinol or placebo. There was no change in stone size, stone number, or renal function. No new safety concerns were noted for either drug. Conclusions Febuxostat (80 mg) lowered 24-hour urinary uric acid significantly more than allopurinol (300 mg) in stone formers with higher urinary uric acid excretion after 6 months of treatment. There was no change in stone size or number over the 6-month period. PMID:23929928
Chamorro, Ángel; Amaro, Sergio; Castellanos, Mar; Gomis, Meritxell; Urra, Xabier; Blasco, Jordi; Arenillas, Juan F; Román, Luis S; Muñoz, Roberto; Macho, Juan; Cánovas, David; Marti-Fabregas, Joan; Leira, Enrique C; Planas, Anna M
Background Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0-2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results The rate of successful revascularization was >80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08-34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06-226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent.
Kanbay, Mehmet; Afsar, Baris; Siriopol, Dimitrie; Unal, Hilmi Umut; Karaman, Murat; Saglam, Mutlu; Eyileten, Tayfun; Gezer, Mustafa; Verim, Samet; Oguz, Yusuf; Vural, Abdulgaffar; Ortiz, Alberto; Johnson, Richard J; Covic, Adrian; Yilmaz, Mahmut Ilker
Both elevated serum uric acid and serum asymmetric dimethylarginine (ADMA) are risk factors for cardiovascular disease. We hypothesized that combined elevation of uric acid and ADMA amplifies the risk of all-cause mortality and/or cardiovascular events (CVE) in patients with chronic kidney disease (CKD). A total of 259 patients with CKD stages 1-5 were followed up in a time-to-event analysis for all-cause mortality and fatal and non-fatal CVE (including death, stroke, and myocardial infarction). Baseline measurements included serum uric acid and ADMA and endothelial function [ultrasound determined flow-mediated dilatation (FMD)]. As a measure of endothelial function, log FMD value was positively associated with log eGFR, but negatively associated with log ADMA and log uric acid levels. During follow-up (median 38 months), 24 (9.3 %) deaths, 90 (34.7 %) CVE, and 95 (36.7 %) deaths and CVE (composite outcome) occurred. In the univariate Cox analysis, patients with both serum uric acid and ADMA levels above the median had an increased risk of all-cause mortality, CVE, and the composite outcome (HR 5.06, 95 % CI 2.01-12.76; HR 4.75, 95 % CI 2.98-7.59; and HR 4.13, 95 % CI 2.66-6.43, respectively). However, after adjustment for renal-specific risk factors (glomerular filtration rate, proteinuria, and hsCRP), this association was maintained only for CVE and the composite outcome. The addition of both biomarkers into a model with traditional and renal-specific risk factors did not increase the prediction abilities of the model for none of the three outcomes. Elevated serum uric acid and ADMA levels are associated with an increased cardiovascular risk, but their combination does not improve risk prediction. The effects are not additive, possibly because uric acid may lie in the causal pathway by which ADMA acts.
Yan, Dandan; Wang, Jie; Jiang, Feng; Zhang, Rong; Sun, Xue; Wang, Tao; Wang, Shiyun; Peng, Danfeng; He, Zhen; Bao, Yuqian; Hu, Cheng; Jia, Weiping
We aimed to investigate the association between uric acid related genetic loci and DKD susceptibility in type 2 diabetes patients. Seventeen single nucleotide polymorphisms (SNPs) from thirteen loci related to serum uric acid were genotyped in 2,892 type 2 diabetes patients. Associations between SNPs and uric acid, SNPs and quantitative traits related to DKD or its susceptibility were evaluated. In this study, uric acid showed a strong association with DKD (OR=1.006, p<0.0001). GCKR rs780094, SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142, SLC22A12 rs505802 and NRXN2 rs506338 were positively associated with serum uric acid (p=3.79E-05, 0.0002, 2.04E-10, 2.23E-09, 0.0018 and 0.0015, respectively). SLC2A9 rs11722228 and SF1 rs606458 were significantly associated with DKD (OR=0.864, p=0.0440; OR=1.223, p=0.0038). SLC2A9 rs3775948 and ABCG2 rs2231142 were associated with DKD marginally (OR=0.878, p=0.0506; OR=0.879, p=0.0698). SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 and SF1 rs606458 were significantly associated with the estimated glomerular filtration rate (p=0.0005, 0.0006, 0.0003, and 0.0424, respectively). Our study indicated that the uric acid related alleles of SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 might affect DKD susceptibility and possibly through non-uric acid pathway in the Chinese people with type 2 diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.
Gu, Liubao; Huang, Liji; Wu, Haidi; Lou, Qinglin; Bian, Rongwen
Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m(2) and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.
Timmermans, S J; Johnson, L M; Harrison, J H; Davidson, D
Data were collected from 10 experiments with duodenally cannulated Holstein dairy cows (271 combinations of cow and period) to evaluate the relationship between milk purine metabolites and microbial nitrogen flow. Experiments evaluated the effects of dietary factors on microbial N production and included: 1) supplemental sources of ruminally protected amino acids; 2) grass silage treated with fibrolytic enzymes; 3) bacterial inoculation of corn silage; 4) a comparison of corn and barley grain; 5) ruminal starch availability as affected by corn silages of varying maturity; and, 6) ruminal starch availability as affected by corn silages harvested at varying chop length and with or without mechanical processing. The coefficient of determination for individual experiments for the relationship between microbial nitrogen flow and allantoin or uric acid excretion in milk ranged from -0.01 to 0.77 and -0.06 to 0.22 respectively. Across all experiments, the coefficients of determination between microbial nitrogen flow and allantoin or uric acid excretion in milk were r2 = 0.09 and 0.01 respectively. Milk allantoin output was used to develop a prediction equation estimating microbial nitrogen flow to the duodenum. The greatest predictive value (r2 = 0.25) relationship was observed across non-bST experiments and included the factors of allantoin excretion, milk yield, dry matter intake, and days in milk. When milk yield was included in the model, the predictive value improved (r2 = 0.44). Based on these data, milk uric acid excretion alone cannot be used to predict microbial N production accurately [corrected].
Seyed-Sadjadi, Neda; Berg, Jade; Bilgin, Ayse A; Grant, Ross
Uric acid (UA) has been suggested as a novel risk factor for diabetes. However, its definite role in this prevalent disease is still the subject of much discussion because it is always accompanied with other major risk factors such as obesity and high visceral adiposity. In order to clarify the role of UA in diabetes, this study aimed to investigate the associations between plasma UA and fasting plasma glucose, HbA1c, lipid profile and inflammatory markers after accounting for the contribution of other diabetes risk factors such as BMI and VAT fat mass. In the present cross-sectional study, 100 non-diabetic middle-aged males (n = 48) and females (n = 52) were recruited. Central fat distribution measures including android to gynoid fat ratio, VAT and subcutaneous adipose tissue (SAT) fat mass were determined using dual-energy X-ray absorptiometry (DXA). Biochemical analysis was done using methods well established for clinical and research laboratories. Multiple linear regression analysis was performed to analyse the association between plasma UA and the biochemical and central fat distribution measures. UA was positivly associated with body mass index (BMI) (r (98) = 0.42, P ≤ 0.001), android to gynoid fat ratio (r (98) = 0.62, P ≤ 0.001) and VAT fat mass (r (96) = 0.55, P ≤ 0.001). UA was also positively associated with plasma glucose (r (98) = 0.33, P ≤ 0.001), hemoglobin A1c (r (93) = 0.25, P = 0.014), plasma triglyceride (r s (95) = 0.40, P ≤ 0.001), HDL cholesterol (r (98) = - 0.61, P ≤ 0.001) and CRP (r s (98) = 0.23, P = 0.026). However, these associations were no longer significant after accounting for BMI or/and VAT fat mass. No significant association was observed between UA and SAT fat mass (r (97) = 0.02, P ≥ 0.05), Total cholesterol (r (98) = 0.03, P ≥ 0.05), LDL cholesterol (r (98) = 0.13, P ≥ 0.05), TNF-α (r (97) = 0.12, P ≥ 0.05) and IL-6 (r (96) = -0.02, P ≥ 0
Adhikari, S.; Joshi, R.; Gopinathan, C.
The pulse radiolytic and spectrophotometric study of uric acid in presence of bovine serum albumin (BSA) has been carried out. In the spectrophotometric study there is no evidence for ground state interaction between BSA and uric acid. The oxidation reactions of uric acid in presence and absence of BSA employing CCl 3OO and Br radicals have been carried out. In a composition of equal concentration of uric acid and BSA, the CCl 3OO and Br radicals produce a transient absorption spectrum which show two peaks at 330 and 360 nm. The peak at 360 nm is ascribed due to weak complex formation between semioxidised BSA and uric acid radicals. The rate constant of CCl 3OO . radical with uric acid increases with the increase in BSA concentration which is explained as protection of BSA by uric acid from radical attack. The Br radical attacks uric acid and BSA in a manner similar to CCl 3OO radical. The bimolecular rate constants for the reaction of Br radical with BSA and uric acid have been found as 2.9 × 10 10 dm 3 mol -1 s -1 and 6.33 × 10 9 dm 3 mol -1 s -, respectively.
Tanaka, Toshiko; Milaneschi, Yuri; Zhang, Yongqing; Becker, Kevin G; Zukley, Linda; Ferrucci, Luigi
Uric acid has been linked with increased risk of chronic disease such as cardiovascular disease and this association has been attributed to a pro-inflammatory effect. Indeed, observational studies have shown that high uric acid is associated with high level of pro-inflammatory cytokines in the blood. However, whether high uric acid directly affects inflammation or rather represents a parallel defensive antioxidant mechanism in response to pathology that causes inflammation is unknown. To determine whether acute increase or decrease uric acid levels affects inflammation in healthy individuals, a randomized, placebo-controlled, double blind clinical study of uric acid or rasburicase with 20 healthy volunteers in each treatment-placebo group was conducted at the National Institute on Aging (NIA) Clinical Research Unit (CRU) at Harbor Hospital in Baltimore, MD. Change in inflammatory response was assessed by administering an oral lipid tolerance before and after the treatment of uric acid, rasburicase and placebo. Following uric acid administration, there was an accentuated increase in IL-6 during the oral lipid tolerance test (P<0.001). No significant differences were observed after lowering of uric acid with rasburicase. No side effects were reported throughout the trial. In health individuals, acute increase in uric acid results in an increased IL-6 response when challenged with lipid load. Such effect of amplification of inflammatory response may explain the higher risk of chronic diseases observed in subclinical hyperuricemia in observational studies. ClinicalTrials.gov NCT01323335.
Milaneschi, Yuri; Zhang, Yongqing; Becker, Kevin G.; Zukley, Linda; Ferrucci, Luigi
Uric acid has been linked with increased risk of chronic disease such as cardiovascular disease and this association has been attributed to a pro-inflammatory effect. Indeed, observational studies have shown that high uric acid is associated with high level of pro-inflammatory cytokines in the blood. However, whether high uric acid directly affects inflammation or rather represents a parallel defensive antioxidant mechanism in response to pathology that causes inflammation is unknown. To determine whether acute increase or decrease uric acid levels affects inflammation in healthy individuals, a randomized, placebo-controlled, double blind clinical study of uric acid or rasburicase with 20 healthy volunteers in each treatment-placebo group was conducted at the National Institute on Aging (NIA) Clinical Research Unit (CRU) at Harbor Hospital in Baltimore, MD. Change in inflammatory response was assessed by administering an oral lipid tolerance before and after the treatment of uric acid, rasburicase and placebo. Following uric acid administration, there was an accentuated increase in IL-6 during the oral lipid tolerance test (P<0.001). No significant differences were observed after lowering of uric acid with rasburicase. No side effects were reported throughout the trial. In health individuals, acute increase in uric acid results in an increased IL-6 response when challenged with lipid load. Such effect of amplification of inflammatory response may explain the higher risk of chronic diseases observed in subclinical hyperuricemia in observational studies. Trial Registration: ClinicalTrials.gov NCT01323335 PMID:28786993
Kaneko, Chihiro; Ogura, Jiro; Sasaki, Shunichi; Okamoto, Keisuke; Kobayashi, Masaki; Kuwayama, Kaori; Narumi, Katsuya; Iseki, Ken
A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia. Copyright © 2016 Elsevier B.V. All rights reserved.
Papakostas, Konstantinos; Frillingos, Stathis
The ubiquitous nucleobase-ascorbate transporter (NAT/NCS2) family includes more than 2,000 members, but only 15 have been characterized experimentally. Escherichia coli has 10 members, of which the uracil permease UraA and the xanthine permeases XanQ and XanP are functionally known. Of the remaining members, YgfU is closely related in sequence and genomic locus with XanQ. We analyzed YgfU and showed that it is a proton-gradient dependent, low-affinity (Km 0.5 mm), and high-capacity transporter for uric acid. It also shows a low capacity for transport of xanthine at 37 °C but not at 25 °C. Based on the set of positions delineated as important from our previous Cys-scanning analysis of permease XanQ, we subjected YgfU to rationally designed site-directed mutagenesis. The results show that the conserved His-37 (TM1), Glu-270 (TM8), Asp-298 (TM9), and Gln-318 and Asn-319 (TM10) are functionally irreplaceable, and Thr-100 (TM3) is essential for the uric acid selectivity because its replacement with Ala allows efficient uptake of xanthine. The key role of these residues is corroborated by the conservation pattern and homology modeling on the recently described x-ray structure of permease UraA. In addition, site-specific replacements at TM8 (S271A, M274D, V282S) impair expression in the membrane, and V320N (TM10) inactivates the permease, whereas R327G (TM10) or S426N (TM14) reduces the affinity for uric acid (4-fold increased Km). Our study shows that comprehensive analysis of structure-function relationships in a newly characterized transporter can be accomplished with relatively few site-directed replacements, based on the knowledge available from Cys-scanning mutagenesis of a prototypic homolog. PMID:22437829
Huang, Ya; Chen, Yuanxiang; Yang, Xiaolan; Zhao, Hua; Hu, Xiaolei; Pu, Jun; Liao, Juan; Long, Gaobo; Liao, Fei
A new formulation of the bireagent kit for serum uric acid assay was developed based on the effects of pH on enzyme stability. At 4 °C, half-lives of uricases from Bacillus fastidious and Arthrobacter globiforms were longer than 15 months at pH 9.2, but became shorter at pH below 8.0; half-lives of ascorbate oxidase and peroxidase were comparable at pH 6.5 and 7.0, but became much shorter at pH higher than 7.4. In the new formulation of the bireagent kit, Reagent A contained peroxidase, 4-aminoantipyrine, and ascorbate oxidase in 50 mM phosphate buffer at pH 6.5; Reagent B contained B. fastidious or A. globiforms uricase in 50 mM sodium borate buffer at pH 9.2; Reagents A and B were mixed at 4:1 to produce a final pH from 7.2 to 7.6 for developing a stable color. The new bireagent kit consumed smaller quantities of three enzymes for the same shelf life. With the new bireagent kit, there were linear responses of absorbance at 546 nm to uric acid up to 34 mM in reaction mixtures and a good correlation of uric acid levels in clinical sera with those by a commercial kit, but stronger resistance to ascorbate. Therefore, the new formulation was advantageous. © 2014 International Union of Biochemistry and Molecular Biology, Inc.
Khucharoenphaisan, K; Sinma, K
The strain PNR11 was isolated from gut of termite during the screening for uric acid degrading actinomyces. This strain was able to produce an intracellular uricase when cultured in fermentation medium containing uric acid as nitrogen source. Base on its morphological characters and 16S rDNA sequence analysis, this strain belong to the genus Saccharopolyspora. This is the first report ofuricase produced from the genus Saccharopolyspora. The aim of this study was to investigate the effects of different factors on uricase production by new source of Saccharopolyspora. Saccharopolyspora sp. PNR11 was cultured in production medium in order to determine the best cultivation period. The result showed that the time period required for maximum enzyme production was 24 h on a rotary shaker operating at 180 rpm. Optimized composition of the production medium consisted of 1% yeast extract, 1% maltose, 0.1% K2HPO4, 0.05% MgSO4 7H2O, 0.05% NaCl and 1% uric acid. The optimum pH and temperature for uricase production in the optimized medium were pH 7.0 and 30 degrees C, respectively. When the strain was cultured at optimized condition, the uricase activity reached to 216 mU mL(-1) in confidential level of 95%. The crude enzyme had an optimum temperature of uricase was 37 degrees C and it was stable up to 30 degrees C at pH 8.5. The optimum pH ofuricase was 8.5 and was stable in range of pH 7.0-10.0 at 4 degrees C. This strain might be considered as a candidate source for uricase production in the further studies. Present finding could be fulfill the information ofuricase produce from actinomycetes.
Choi, Hyon K; Curhan, Gary
Coffee is one of the most widely consumed beverages in the world and may affect serum uric acid levels and risk of gout via various mechanisms. Our objective was to evaluate the relationship between coffee, tea, and caffeine intake and serum uric acid level in a nationally representative sample of men and women. Using data from 14,758 participants ages >/=20 years in the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between coffee, tea, and caffeine intake and serum uric acid level using linear regression. Additionally, we examined the relationship with hyperuricemia (serum uric acid >7.0 mg/dl among men and >5.7 mg/dl among women) using logistic regression. Intake was assessed by a food frequency questionnaire. Serum uric acid level decreased with increasing coffee intake. After adjusting for age and sex, serum uric acid level associated with coffee intake of 4 to 5 and >/=6 cups daily was lower than that associated with no intake by 0.26 mg/dl (95% confidence interval [95% CI] 0.11, 0.41) and 0.43 mg/dl (95% CI 0.23, 0.65; P for trend < 0.001), respectively. After adjusting for other covariates, the differences remained significant (P for trend < 0.001). Similarly, there was a modest inverse association between decaffeinated coffee intake and serum uric acid levels (multivariate P for trend 0.035). Total caffeine from coffee and other beverages and tea intake were not associated with serum uric acid levels (multivariate P for trend 0.15). The multivariate odds ratio for hyperuricemia in individuals with coffee intake >/=6 cups daily compared with those with no coffee use was 0.57 (95% CI 0.35, 0.94; P for trend 0.001). These findings from a nationally representative sample of US adults suggest that coffee consumption is associated with lower serum uric acid level and hyperuricemia frequency, but tea consumption is not. The inverse association with coffee appears to be via components of coffee other than caffeine.
Vinuthinee-Naidu, Munisamy-Naidu; Zunaina, Embong; Azreen-Redzal, Anuar; Nyi-Nyi, Naing
Uric acid is a final breakdown product of purine catabolism in humans. It's a potent antioxidant and can also act as a pro-oxidant that induces oxidative stress on the vascular endothelial cells, thus mediating progression of diabetic related diseases. Various epidemiological and experimental evidence suggest that uric acid has a role in the etiology of type 2 diabetes mellitus. We conducted a cross-sectional study to evaluate the correlation of retinal nerve fibre layer (RNFL) and macular thickness with serum uric acid in type 2 diabetic patients. A cross-sectional study was conducted in the Eye Clinic, Hospital Universiti Sains Malaysia, Kelantan between the period of August 2013 till July 2015 involving type 2 diabetes mellitus patients with no diabetic retinopathy and with non-proliferative diabetic retinopathy (NPDR). An evaluation for RNFL and macular thickness was measured using Spectralis Heidelberg optical coherence tomography. Six ml of venous blood was taken for the measurement of serum uric acid and glycosylated haemoglobin (HbA1C). A total of 180 diabetic patients were recruited (90 patients with no diabetic retinopathy and 90 patients with NPDR) into the study. The mean level of serum uric acid for both the groups was within normal range and there was no significance difference between the two groups. Based on gender, both male and female gender showed significantly higher level of mean serum uric acid in no diabetic retinopathy group (p = 0.004 respectively). The mean serum uric acid was significantly higher in patient with HbA1C < 6.5% (p < 0.031). Patients with NPDR have thicker RNFL and macular thickness compared to patients with no diabetic retinopathy. However, only the RNFL thickness of the temporal quadrant and the macular thickness of the superior outer, inferior outer and temporal outer subfields were statistically significant (p = 0.038, p = 0.004, 0.033 and <0.001 respectively). There was poor correlation between RNFL and macular
Luo, D L; Zhang, C J; Huang, Y G; Huang, T; Li, H Z
Objective: The growing body of literature showed a link between uric acid and pulmonary hypertension (PH), but the impact of hyperuremia on outcome of patients with PH has not been well defined. Therefore, the present study was performed to analyze the impact of uric acid on outcome of PH patients. Methods: One hundred seventy-three PH patients (112 females, mean age 38 years old), who were hospitalized in our department between January 2010 and December 2015, were included in our study, the PH diagnosis was made based on right heart catheterization examination result (mean pulmonary artery pressure≥25 mmHg(1 mmHg=0.133 kPa)). PH patients were divided into mild to moderate PH group (Rp/Rs≤0.6, n=97) and severe PH group (Rp/Rs>0.6, n=76). Fifty-one patients (33 females, mean age 45 years old) without PH based on right heart catheterization were included as control subjects. All participants were followed up for a median of 24 months(6-71 months). Clinical endpoints were defined as cardiogenic death or heart-and-lung transplantation. Results: Uric acid was positively correlated with pulmonary vascular resistance(r=0.398, P<0.01), systemic vascular resistance(r=0.244, P<0.01) and mean right atrial pressure (r=0.26, P<0.01), and was negatively correlated with cardiac index(r=-0.278, P<0.01)and mixed venous oxygen saturation (r=-0.322, P<0.01)in PH patients. Serum uric acid level was significantly higher in patients with severe PH than in patients with mild-to-moderate PH and the control subjects (both P<0.05). According to the receiver operating characteristic curve (ROC), 425.5 μmol/L was found to be the best cut-off value of serum uric acid level to predict the outcome of PH patients (sensitivity 50%, specificity 72%). During follow-up, patients with higher level of uric acid (>425.5 μmol/L) were linked with poorer clinical outcome compared to patients with uric acid <425.5 μmol/L(P=0.027). Conclusion: Our findings suggests that uric acid is associated with
Johnson, Richard J; Sautin, Yuri Y; Oliver, William J; Roncal, Carlos; Mu, Wei; Gabriela Sanchez-Lozada, L; Rodriguez-Iturbe, Bernardo; Nakagawa, Takahiko; Benner, Steven A
Uric acid has historically been viewed as a purine metabolic waste product excreted by the kidney and gut that is relatively unimportant other than its penchant to crystallize in joints to cause the disease gout. In recent years, however, there has been the realization that uric acid is not biologically inert but may have a wide range of actions, including being both a pro- and anti-oxidant, a neurostimulant, and an inducer of inflammation and activator of the innate immune response. In this paper, we present the hypothesis that uric acid has a key role in the foraging response associated with starvation and fasting. We further suggest that there is a complex interplay between fructose, uric acid and vitamin C, with fructose and uric acid stimulating the foraging response and vitamin C countering this response. Finally, we suggest that the mutations in ascorbate synthesis and uricase that characterized early primate evolution were likely in response to the need to stimulate the foraging "survival" response and might have inadvertently had a role in accelerating the development of bipedal locomotion and intellectual development. Unfortunately, due to marked changes in the diet, resulting in dramatic increases in fructose- and purine-rich foods, these identical genotypic changes may be largely responsible for the epidemic of obesity, diabetes and cardiovascular disease in today's society.
Salvador, R; Luque, M P; Ciudin, A; Paño, B; Buñesch, L; Sebastia, C; Nicolau, C
To prospectively evaluate the usefulness of dual-energy computed tomography (DECT) with and without dedicated software in identifying uric acid kidney stones in vivo. We studied 65 kidney stones in 63 patients. All stones were analyzed in vivo by DECT and ex vivo by spectrophotometry. We evaluated the diagnostic performance in identifying uric acid stones with DECT by analyzing the radiologic densities with dedicated software and without using it (through manual measurements) as well as by analyzing the attenuation ratios of the stones in both energies with and without the dedicated software. The six uric acid stones included were correctly identified by evaluating the attenuation ratios with a cutoff of 1.21, both with the dedicated software and without it, yielding perfect diagnostic performance without false positives or false negatives. The study of the attenuations of the stones obtained the following values on the receiver operating characteristic curves in the classification of the uric acid stones: 0.92 for the measurements done with the software and 0.89 for the manual measurements; a cutoff of 538 HU yielded 84% (42/50) diagnostic accuracy for the software and 83.1% (54/65) for the manual measurements. DECT enabled the uric acid stones to be identified correctly through the calculation of the ratio of the attenuations in the two energies. The results obtained with the dedicated software were similar to those obtained manually. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.
Mertz, D P
The daily administration of 25 mg effervescent granules is about equipotent with a daily dose of 200 mg allopurinol, giving due attention to the caution necessary for uricosuric therapy. The daily administration of 50 mg benzbromarone effervescent granules has a slight but significantly greater uric acid-lowering effect than treatment with 300 mg allopurinol per day. The tolerance of benzbromarone in the active form named was good in all cases. Side effects were not observed. Since benzbromarone as effervescent granules is taken with plenty of fluid this takes care of an increased fluid intake and introduces a motivation for doing so.
Kumar, Anand; Hens, Abhiram; Arun, Ravi Kumar; Chatterjee, Monosree; Mahato, Kuldeep; Layek, Keya; Chanda, Nripen
A paper based microfluidic device is fabricated that can rapidly detect very low concentrations of uric acid (UA) using 3,5,3',5'-tetramethyl benzidine (TMB), H2O2 and positively charged gold nanoparticles ((+)AuNPs). In the presence of (+)AuNPs, H2O2 reacts with TMB to produce a bluish-green colour which becomes colourless on reaction with UA. This colorimetric method can detect as low as 8.1 ppm of UA within <20 minutes on white filter paper. This technique provides an alternative way for UA detection.
Musso, Carlos Guido; Álvarez Gregori, Joaquín; Jauregui, José Ricardo; Macías Núñez, Juan Florencio
Renal physiology in the healthy oldest old has the following characteristics, in comparison with the renal physiology in the young: a reduced creatinine clearance, tubular pattern of creatinine back-filtration, preserved proximal tubule sodium reabsorption and uric acid secretion, reduced sodium reabsorption in the thick ascending loop of Henle, reduced free water clearance, increased urea excretion, presence of medulla hypotonicity, reduced urinary dilution and concentration capabilities, and finally a reduced collecting tubules response to furosemide which expresses a reduced potassium excretion in this segment due to a sort of aldosterone resistance. All physiological changes of the aged kidney are the same in both genders. PMID:24175249
Cruz-Domínguez, María Pilar; Cortés, Daniel H Montes; Zarate, Arturo; Tapia-González, María de los Ángeles; Álvarez-Acosta, Sandra; Damasio, Leticia; Manuel-Apolinar, Leticia
We compared and examined factors associated with ghrelin and uric acid in obese subjects (OB), obese plus type 2 diabetes mellitus (OBDM) and healthy controls (C). Methods. We analyzed blood count, renal function, liver enzymes, lipids, resistin, leptin, IL-6, uric acid and ghrelin in OB, OBDM and C. We included 76 subjects with different body mass index (BMI): 36 C (24 ± 3), 11 OB<40 (30-39.9), 20 OB>40 (40-60), and 9 OBDM (45.9 ± 9). Results. Metabolic profile was as follows: HOMA-IR 4.7 ± 3 and 5 ± 3 vs 2 ± 1 (p < 0.01), resistin 8.7 ± 2 and 9.4 ± 2 vs 5.4 ± 2 ng/mL (p < 0.001), leptin 6.2 ± 3.9 and 5.3 ± 2 vs 3.6 ± 1.8 ng/mL (p = 0.001) and IL-6 197.5 ± 78.9 and 223.6 ± 115 vs 7.4 ± 8.3 pg/mL (p = 0.001) in OB and OBDM vs C, respectively. Ghrelin was higher in OB<40 compared to C (1780 ± 197 vs 1465 ± 12 pg/mL, p < 0.05), and lower in OBDM (987.4 ± 114 pg/mL, p < 0.05). BMI showed a positive correlation with resistin (p < 0.001); leptin (p = 0.004), IL-6 (p = 0.001), uric acid (p = 0.0005) and negative with ghrelin (r = -0.431, p = 0.028). Resistin was directly correlated with leptin (p < 0.001) and inversely correlated with renal function (p = 0.03). Conclusion. Severe obesity and obesity-associated diabetes affected ghrelin and uric acid levels. This may well be associated with proinflammatory adipocytokines, insulin resistance, liver enzymes or renal function. PMID:24995108
Cruz-Domínguez, María Pilar; Cortés, Daniel H Montes; Zarate, Arturo; Tapia-González, María de Los Ángeles; Alvarez-Acosta, Sandra; Damasio, Leticia; Manuel-Apolinar, Leticia
We compared and examined factors associated with ghrelin and uric acid in obese subjects (OB), obese plus type 2 diabetes mellitus (OBDM) and healthy controls (C). Methods. We analyzed blood count, renal function, liver enzymes, lipids, resistin, leptin, IL-6, uric acid and ghrelin in OB, OBDM and C. We included 76 subjects with different body mass index (BMI): 36 C (24 ± 3), 11 OB<40 (30-39.9), 20 OB>40 (40-60), and 9 OBDM (45.9 ± 9). Results. Metabolic profile was as follows: HOMA-IR 4.7 ± 3 and 5 ± 3 vs 2 ± 1 (p < 0.01), resistin 8.7 ± 2 and 9.4 ± 2 vs 5.4 ± 2 ng/mL (p < 0.001), leptin 6.2 ± 3.9 and 5.3 ± 2 vs 3.6 ± 1.8 ng/mL (p = 0.001) and IL-6 197.5 ± 78.9 and 223.6 ± 115 vs 7.4 ± 8.3 pg/mL (p = 0.001) in OB and OBDM vs C, respectively. Ghrelin was higher in OB<40 compared to C (1780 ± 197 vs 1465 ± 12 pg/mL, p < 0.05), and lower in OBDM (987.4 ± 114 pg/mL, p < 0.05). BMI showed a positive correlation with resistin (p < 0.001); leptin (p = 0.004), IL-6 (p = 0.001), uric acid (p = 0.0005) and negative with ghrelin (r = -0.431, p = 0.028). Resistin was directly correlated with leptin (p < 0.001) and inversely correlated with renal function (p = 0.03). Conclusion. Severe obesity and obesity-associated diabetes affected ghrelin and uric acid levels. This may well be associated with proinflammatory adipocytokines, insulin resistance, liver enzymes or renal function.
Weaver, Virginia M; Schwartz, Brian S; Jaar, Bernard G; Ahn, Kyu-Dong; Todd, Andrew C; Lee, Sung-Soo; Kelsey, Karl T; Silbergeld, Ellen K; Lustberg, Mark E; Parsons, Patrick J; Wen, Jiayu; Lee, Byung-Kook
Recent research suggests that uric acid may be nephrotoxic at lower levels than previously recognized and that it may be one mechanism for lead-related nephrotoxicity. Therefore, in understanding mechanisms for lead-related nephrotoxicity, it would be of value to determine whether genetic polymorphisms that are associated with renal outcomes in lead workers and/or modify associations between lead dose and renal function are also associated with uric acid and/or modify associations between lead dose and uric acid. We analyzed data on three such genetic polymorphisms: delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR). Mean (+/- SD) tibia, blood, and dimercaptosuccinic acid-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0+/- 15.0 g/dL, and 0.77+/- 0.86 microg/mg creatinine, respectively, in 798 current and former lead workers. Participants with the eNOSAsp allele had lower mean serum uric acid compared with those with the Glu/Glu genotype. Among older workers (age > or = median of 40.6 years), ALAD genotype modified associations between lead dose and uric acid levels. Higher lead dose was significantly associated with higher uric acid in workers with the ALAD1-1 genotype; associations were in the opposite direction in participants with the variant ALAD1-2 genotype. In contrast, higher tibia lead was associated with higher uric acid in those with the variant VDRB allele; however, modification was dependent on participants with the bb genotype and high tibia lead levels. We conclude that genetic polymorphisms may modify uric acid mediation of lead-related adverse renal effects.
Muthukoori, Shanthini; Narayanan, Naagarajan; Chandra, Manuguri Sesha Sarath; Sethuraman, Swaminathan; Krishnan, Uma Maheswari
Gout is an abnormality in the body resulting in the accumulation of uric acid mainly in joints. Dissolution of uric acid crystals into soluble allantoin by the enzyme uricase might provide a better alternative for the treatment of gout. This work aims to investigate the feasibility of a transdermal patch loaded with uricase for better patient compliance. Mesoporous silica (SBA-15) was chosen as the matrix for immobilisation of uricase. Highly oriented mesoporous SBA-15 was synthesized, characterized and uricase was physisorbed in the mesoporous material. The percentage adsorption and release of enzyme in borate buffer was monitored. The release followed linear kinetics and greater than 80% enzyme activity was retained indicating the potential of this system as an effective enzyme immobilization matrix. The enzyme permeability was studied with Wistar rat skin and human cadaver skin. It was found that in case of untreated rat skin 10% of enzyme permeated through skin in 100 h. The permeation increased by adding permeation enhancer (combination of oleic acid in propylene glycol (OA in PG)). The permeation enhancement was studied under two concentrations of OA in PG (1%, 5%) in both rat and human cadaver skin and it was found that 1% OA in PG showed better result in rat skin and 5% OA in PG showed good results in human cadaver skin.
Mahshid, Sara; Luo, Shenglian; Yang, Lixia; Mahshid, Sahar Sadat; Askari, Masoud; Dolati, Abolghasem; Cai, Qingyun
The present work describes sensing application of modified TiO2 nanotubes having carbon-Pt nanoparticles for simultaneous detection of dopamine and uric acid. The TiO2 nanotubes electrode was prepared using anodizing method, followed by electrodeposition of Pt nanoparticles onto the tubes. Carbon was deposited by decomposition of polyethylene glycol in a tube furnace to improve the conductivity. The C-Pt-TiO2 nanotubes modified electrode was characterized by cyclic voltammetry and differential pulse voltammetry methods. The modified electrode displayed high sensitivity towards the oxidation of dopamine and uric acid in a phosphate buffer solution (pH 7.00). The electro-oxidation currents of dopamine and uric acid were linearly related to the concentration over a wide range of 3.5 x 10(-8) M to 1 x 10(-5) M and 1 x 10(-7) M to 3 x 10(-5) M respectively. The limit of detection was determined as 2 x 10(-10) M for dopamine at signal-to-noise ratio of 3. The interference of uric acid was also investigated. Electro-oxidation currents of dopamine in the presence of fix amount of uric acid represented a linear behaviour towards successive addition of dopamine in range of 1 x 10(-7) M to 1 x 10(-5) M. Furthermore, in a solution containing dopamine, uric acid and ascorbic acid the overlapped oxidation peaks of dopamine and ascorbic acid could be easily separated by using C-Pt-TiO2 nanotubes modified electrode.
Chen, Y.; Pietrzyk, R. A.; Whitson, P. A.
A high-performance liquid chromatographic method was developed as an alternative to automated enzymatic analysis of uric acid in human urine preserved with thymol and/or thimerosal. Uric acid (tR = 10 min) and creatinine (tR = 5 min) were separated and quantified during isocratic elution (0.025 M acetate buffer, pH 4.5) from a mu Bondapak C18 column. The uric-acid peak was identified chemically by incubating urine samples with uricase. The thymol/thimerosal peak appeared at 31 min during the washing step and did not interfere with the analysis. We validated the high-performance liquid chromatographic method for linearity, precision and accuracy, and the results were found to be excellent.
Chen, Y.; Pietrzyk, R. A.; Whitson, P. A.
A high-performance liquid chromatographic method was developed as an alternative to automated enzymatic analysis of uric acid in human urine preserved with thymol and/or thimerosal. Uric acid (tR = 10 min) and creatinine (tR = 5 min) were separated and quantified during isocratic elution (0.025 M acetate buffer, pH 4.5) from a mu Bondapak C18 column. The uric-acid peak was identified chemically by incubating urine samples with uricase. The thymol/thimerosal peak appeared at 31 min during the washing step and did not interfere with the analysis. We validated the high-performance liquid chromatographic method for linearity, precision and accuracy, and the results were found to be excellent.
Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans
Background Prospective studies in humans examining the effects of fructose consumption on biological markers associated with the development of metabolic syndrome are lacking. Therefore we investigated the relative effects of 10 wks of fructose or glucose consumption on plasma uric acid and RBP-4 concentrations, as well as liver enzyme (AST, ALT, and GGT) activities in men and women. Methods As part of a parallel arm study, older (age 40–72), overweight and obese male and female subjects (BMI 25–35 kg/m2) consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 wks. Fasting and 24-h blood collections were performed at baseline and following 10 wks of intervention and plasma concentrations of uric acid, RBP-4 and liver enzyme activities were measured. Results Consumption of fructose, but not glucose, led to significant increases of 24-h uric acid profiles (P < 0.0001) and RBP-4 concentrations (P = 0.012), as well as plasma GGT activity (P = 0.04). Fasting plasma uric acid concentrations increased in both groups; however, the response was significantly greater in subjects consuming fructose (P = 0.002 for effect of sugar). Within the fructose group male subjects exhibited larger increases of RBP-4 levels than women (P = 0.024). Conclusions These findings suggest that consumption of fructose at 25% of energy requirements for 10 wks, compared with isocaloric consumption of glucose, may contribute to the development of components of the metabolic syndrome by increasing circulating uric acid, GGT activity, suggesting alteration of hepatic function, and the production of RBP-4. PMID:22828276
A study was conducted to evaluate the effects of nitrocompounds on the growth of uric acid-utilizing microorganisms, nitrogen retention, and microbial community in laying hen manure. There were three treatments: control, 100 mM nitropropanol (NPL), and 100 mM nitropropionic acid (NPC). The mixed la...
Grove, Robert A.; Bildfell, Rob; Henny, Charles J.; Buhler, D.R.
We report the first case of uric acid nephrolithiasis in a free-ranging river otter (Lontra canadensis). A 7 yr old male river otter collected from the Skagit River of western Washington (USA) had bilateral nephrolithiasis and severely enlarged ureters (one of 305 examined [0.33%]). The uroliths were 97% uric acid and 3% protein. Microscopic changes in the kidney were confined to expansion of renal calyces, minor loss of medullary tissue, and multifocal atrophy of the cortical tubules. No inflammation was observed in either kidney or the ureters. The ureters were enlarged due to marked hypertrophy of smooth muscle plus dilation of the lumen. Fusion of the major calyces into a single ureteral lumen was several cm distal to that of two adult male otters used as histopathologic control specimens. This case report is part of a large contaminant study of river otters collected from Oregon and Washington. It is important to understand diseases and lesions of the otter as part of our overall evaluation of this population.
Lee, Yong Suk; Yang, Jeong Hoon; Choi, Jung Chul; Eun, Hee Chul
We had proposed the usefulness of cutaneous microdialysis for the study of antioxidants in the skin. We designed a study analyzing the level of uric acid in the skin, one of the major antioxidants, for an age-dependent change. 16 healthy male volunteers were divided into two groups according to age. Eleven subjects were in their 3rd decade, under 30 years of age (young group) and the others were their 8th decade (old group), over 70 years of age. Dialysate samples were analyzed using high-performance liquid chromatography analysis. In the young group the mean level of uric acid was 31.9+/-16.1 microg/ml, while in old group it was 13.4+/-5.2 microg/ml. This result demonstrated an in vivo state of antioxidant level in the human skin and the age-dependent difference was concordant with other in vitro or ex vivo studies; therefore, cutaneous microdialysis could be used in analysis and monitoring studies including human antioxidants and anti-aging. Copyright (c) 2005 S. Karger AG, Basel.
Bowden, Rodney G.; Shelmadine, Brian D.; Moreillon, Jennifer J.; Deike, Erika; Griggs, Jackson O.; Wilson, Ronald L.
Background Few studies have been conducted that compared lipid levels and uric acid in CKD or End-Stage Renal Disease (ESRD) patients with most using animal models. The purpose of the study was to explore effects on lipids while controlling uric acid levels in CKD patients. Methods Twenty-four CKD patients (N = 24) volunteered to participate in this study. The study was conducted using a double-blind, randomized, placebo controlled experimental protocol. The experimental group was prescribed 300 mg of allopurinol PO daily by their treating physician and followed prospectively for 8-weeks. The control group consumed a similar pill once a day for 8-weeks. Results ANCOVA revealed significant differences in total cholesterol (P = 0.009) and Apo B (P = 0.006) with lower levels in the allopurinol group. A trend emerged with LDL (P = 0.052) with lower levels in the allopurinol group. No significant differences were discovered in triglycerides (P = 0.403), HDL (P = 0.762) and total Cholesterol/HDL Ratio (P = 0.455). Conclusions After statistically controlling for compliance and inflammation significant differences between groups were observed for total cholesterol and Apo B. In both instances the allopurinol group had lower concentrations than the placebo group. Similarly, a trend was observed in LDL with the allopurinol group having lower concentrations than the placebo group.
Sinha, Tapan; Karan, S C; Kotwal, Atul
Many studies have been done to determine the risk factors associated with urolithiasis so that preventive measures can be undertaken to prevent stone formation. However the exact aetiology of urinary stones still remains elusive. A prospective control study of epidemiological factors that influence urinary stone formation was done to determine the aetiology of urinary stones. Patients with stone disease had a significantly higher body mass index. 24-h urine excretion of uric acid and phosphate was found to be significantly higher in stone patients as compared to controls. The intake of non-vegetarian food was significantly higher amongst stone formers. Stone patients had a significantly higher consumption of curd and cheese as compared to controls. There was a significant correlation noted between stone formation and a positive family and past history of stone disease. The results indicate that obese patients, especially those with a family history of stone disease, should be counselled on weight loss. Individuals with a past history of stone disease should be advised to reduce their dietary intake of foods rich in uric acid (meat, liver and beans).
Rock, Kenneth L.; Kataoka, Hiroshi; Lai, Jiann-Jyh
Uric acid is a waste product of purine catabolism. This molecule comes to clinical attention when it nucleates to form crystals of monosodium urate (MSU) in joints or other tissues and thereby causes the inflammatory disease of gout. Patients with gout also frequently suffer from a number of co-morbid conditions including hypertension, diabetes mellitus and cardiovascular disease. Why MSU crystals trigger inflammation and are associated with comorbidities of gout has been unclear, but recent studies provide new insights these issues. Rather than simply being a waste product, uric acid could serve a pathophysiological role as a local alarm signal that alerts the immune system to cell injury and helps to trigger both innate and adaptive immune responses. The inflammatory component of these immune responses is caused when urate crystals trigger both inflammasome-dependent and independent pathways to generate the proinflammatory cytokine IL-1. The resulting bioactive IL-1 stimulates the inflammation of gout and might contribute to the development of other comorbidities. Surprisingly, the same mechanisms underlie the inflammatory response to a number of irritant particles, many of which also cause disease. These new insights help to explain the pathogenesis of gout and point to potential new therapeutic targets for this and other sterile inflammatory diseases. PMID:22945591
Chan, Sic L.; Arumugam, Thiruma V.; Baharani, Akanksha; Tang, Sung-Chun; Yu, Qian-Sheng; Holloway, Harold W.; Wheeler, Ross; Poosala, Suresh; Greig, Nigel H.; Mattson, Mark P.
Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions. PMID:20386608
Johnson, Richard J.; Perez-Pozo, Santos E.; Sautin, Yuri Y.; Manitius, Jacek; Sanchez-Lozada, Laura Gabriela; Feig, Daniel I.; Shafiu, Mohamed; Segal, Mark; Glassock, Richard J.; Shimada, Michiko; Roncal, Carlos; Nakagawa, Takahiko
We propose that excessive fructose intake (>50 g/d) may be one of the underlying etiologies of metabolic syndrome and type 2 diabetes. The primary sources of fructose are sugar (sucrose) and high fructose corn syrup. First, fructose intake correlates closely with the rate of diabetes worldwide. Second, unlike other sugars, the ingestion of excessive fructose induces features of metabolic syndrome in both laboratory animals and humans. Third, fructose appears to mediate the metabolic syndrome in part by raising uric acid, and there are now extensive experimental and clinical data supporting uric acid in the pathogenesis of metabolic syndrome. Fourth, environmental and genetic considerations provide a potential explanation of why certain groups might be more susceptible to developing diabetes. Finally, we discuss the counterarguments associated with the hypothesis and a potential explanation for these findings. If diabetes might result from excessive intake of fructose, then simple public health measures could have a major impact on improving the overall health of our populace. PMID:19151107
Das, Arijit; Kumar, Prakash; Kumari, Abha; Chandra, Satish; Gari, Manju; Singh, Nidhi; Dey, Debleena
Background The relation between hypertension and hyperuricemia has been established by epidemiological studies. Calcium channel blockers are one of the first-line drugs for newly diagnosed patients with essential hypertension. Cilnidipine is a new calcium channel blocker acting by blocking both L- and N-type calcium channels. The aim of this study was to compare the effectiveness of amlodipine and cilnidipine in patients with essential hypertension and their effects on heart rate and serum uric acid levels. Methods Out of 100 enrolled patients, 92 completed the study. They were randomly assigned to amlodipine (N = 47) and cilnidipine (N = 45) groups. Cilnidipine was started at 10 mg/day and then adjusted to 5 - 20 mg/day, and amlodipine was started at 5 mg/day and then adjusted to 2.5 - 10 mg/day. Results After 24 weeks of study, patients in cilnidipine groups showed significant reduction in heart rate and serum uric acid levels from baseline (P = 0.00). Conclusion In clinical setting where both hypertension and hyperuricemia exist, cilnidipine can be a promising drug of choice. PMID:28197287
Zhang, Dihua; Bobulescu, I. Alexandru; Maalouf, Naim M.; Adams-Huet, Beverley; Poindexter, John; Park, Sun; Wei, Fuxin; Chen, Christopher; Moe, Orson W.; Sakhaee, Khashayar
Higher serum uric acid concentrations have been associated with higher bone mineral density in observational studies of older men and peri- or postmenopausal women, prompting speculation of a potential protective effect of uric acid on bone. Whether this relationship is present in the general population has not been examined and there is no data to support causality. We conducted a cross-sectional analysis of a probability sample of the US population. Demographic data, dietary intake, lifestyle risk factors and physical activity assessment data, serum biochemistry including serum uric acid, and bone mineral density were obtained from 6,759 National Health and Nutrition Examination Survey (NHANES; 2005-2010) participants over 30 years of age. In unadjusted analyses, higher serum uric acid levels were associated with higher bone mineral density at the femoral neck, total hip and lumbar spine in men, pre-menopausal women, and post-menopausal women not treated with estrogen. However, these associations were no longer statistically significant after adjustment for potential confounders, including age, body mass index, black race, alcohol consumption, estimated glomerular filtration rate (eGFR), serum alkaline phosphatase, and C-reactive protein (CRP). This is in contradistinction to some prevailing conclusions in the literature. To further examine the causal effect of higher serum uric acid on skeletal health, including biomechanical properties that are not measurable in humans, we used an established rat model of inducible mild hyperuricemia. There were no differences in bone mineral density, volume density, and biomechanical properties between hyperuricemic rats and normouricemic control animals. Taken together, our data do not support the hypothesis that higher serum uric acid has protective effects on bone health. This article is protected by copyright. All rights reserved PMID:25491196
Shoji, Tatsuya; Shinzawa, Maki; Hasuike, Yukiko; Nagatoya, Katsuyuki; Yamauchi, Atsushi; Hayashi, Terumasa; Kuragano, Takayuki; Moriyama, Toshiki; Isaka, Yoshitaka; Nakanishi, Takeshi
Background Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. Study Design Multicenter retrospective cohort study. Setting & Participants 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. Predictor Uric acid levels at renal biopsy. Outcomes The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". Measurements The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. Results An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. Limitations A cohort analyzed retorospectively. Conclusions This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients. PMID:27560997
Shin, Hyun-Sik; Lee, Hye-Ree; Lee, Duk-Chul; Shim, Jae-Yong; Cho, Kyung-Hee; Suh, Sang-Yeon
The aim of this prospective cohort study was to determine whether serum uric acid level is useful as a predictor of survival in terminally ill cancer patients. One hundred eighteen terminally ill cancer patients, including 63 (53.4%) males, were categorized into four groups by serum uric acid levels and followed up until death or to the end of the study. Cox's proportional hazard model was adopted to evaluate the joint effect of some clinicobiological variables on survival. From an initial model containing 51 variables, a final parsimonious model was obtained by means of a stepwise method. Repetitive dispersion analysis was performed for serum uric acid level in 39 subjects for 3 weeks until death. During the study period, 113 (95.76%) subjects expired, and the median survival time was 14 days. In univariate analysis, survival time of the fourth highest group (> or =7.2mg/dL) was significantly shorter than that of the others (hazard ratio (HR)=2.784, P<0.001). After adjustment for low performance status, moderate to severe pain, prolonged prothrombin time, hypocholesterolemia, and high lactate dehydrogenase (LDH) level, high serum uric acid level (> or =7.2mg/dL) was significantly and independently associated with short survival time (HR=2.637, P=0.001). Serum uric acid levels were also significantly increased between the first and the second week before death. These findings suggest that serum uric acid level can be useful in predicting life expectancy in terminally ill cancer patients.
Deng, Siyun; Deng, Qifei; Hu, Die; Li, Jun; Zhu, Xiaoyan; Guo, Huan; Wu, Tangchun
To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and serum uric acid levels in coke oven workers and to provide new clues to the pathogenic mechanism of PAHs. A total of 1302 coke oven workers were divided into four groups, namely control group and low-, intermediate-, and high-dose exposure groups. The concentrations of ambient PAHs at each workplace were determined by high-performance liquid chromatography. The detailed information on the occupational history and health of workers was collected by questionnaire survey and physical examination, and so were their blood and urine samples. Serum uric acid and creatinine levels were measured using a Hitachi 7020 automatic biochemical analyzer. Ten urinary PAH metabolites were detected by gas chromatography-mass spectrometry. Serum uric acid levels were the highest in the high-dose exposure group, followed by the intermediate- and low-dose exposure groups, and were the lowest in the control group. There were significant correlations between serum uric acid levels and the quartiles of 1-hydroxynaphthalene and 1-hydroxyphenanthrene (P < 0.05). After adjustment for PAH metabolite-related relationship, only urinary 1-hydroxyphenanthrene was significantly correlated with serum uric acid levels (P = 0.001). After adjustment for confounding factors and using the 1st quartile of 1-hydroxyphenanthrene as a reference, the odds ratio for hyperuricemia in subjects with the 2nd, 3rd, and 4th quartiles of 1-hydroxyphenanthrene were 1.55, 1.57, and 2.35, respectively. Urinary 1-hydroxyphenanthrene is associated with a dose-response increase in serum uric acid levels in coke oven workers, and exposure to phenanthrene in PAHs may be a risk factor for hyperuricemia.
Rubio-Guerra, Alberto F; Garro-Almendaro, Ana K; Elizalde-Barrera, Cesar I; Suarez-Cuenca, Juan A; Duran-Salgado, Montserrat B
Hyperuricemia leads to endothelial dysfunction and insulin resistance, and has been associated with diseases such as hypertension. Antihypertensive drugs modify serum uric acid levels, however, few data are available about their combinations on uricemia. In this study we evaluate the effect of two combinations of losartan, with amlodipine or with hydrochlorothiazide, on serum uric acid levels in hypertensive patients. A total of 60 hypertensive patients were randomized in two groups; group LA received losartan/amlodipine (100/5 mg) once a day, whereas LH group received losartan hydrochlorothiazide (100/12.5 mg) once a day for 3 months. In both groups serum uric acid levels were measured at the beginning and end of the study. Patients were evaluated monthly for blood pressure (BP) and adverse events. Statistical analysis was performed with a two-way analysis of variance (ANOVA) for repeated measures. All patients experienced a significant reduction of BP to the same extent (LA 155/94 to 123/79, LH 157/92 to 124/78 mmHg, p > 0.05). In the LA group, serum uric acid decreased from 6.5 ± 1.6 to 4.6 ± 1.3 mg/ml ( p = 0.0001), whereas in the LH group there was a nonsignificant increase from 5.82 ± 1.4 to 5.85 ± 1.5 mg/ml, ( p = 0.936). When both groups were compared, we found a significant reduction ( p < 0.00013) on serum uric acid levels in the LA group. Both combinations decrease BP values to the same extent, however, LA combination showed a reduction on serum uric acid levels, which may contribute to a reduction in the metabolic risk in hypertensive patients.
Viazzi, Francesca; Rebora, Paola; Giussani, Marco; Orlando, Antonina; Stella, Andrea; Antolini, Laura; Valsecchi, Maria Grazia; Pontremoli, Roberto; Genovesi, Simonetta
Primary hypertension is a growing concern in children because of the obesity epidemic largely attributable to western lifestyles. Serum uric acid is known to be influenced by dietary habits, correlates with obesity, and could represent a risk factor for hypertension. Preliminary studies in children highlighted uric acid as a potentially modifiable risk factor for the prevention and treatment of hypertension. The effect of lifestyle changes (increase of physical activity and dietary modifications) on blood pressure values, weight status, and serum uric acid levels in a cohort of 248 children referred for cardiovascular risk assessment were evaluated over a mean 1.5-year follow-up. At baseline, 48% of children were obese and 50% showed blood pressure values >90th percentile. At follow-up, a significant improvement in weight class (24% obese;P<0.0001) and blood pressure category (22% >90th percentile;P<0.0001) was found. Systolic blood pressure z-score (P<0.0001), uric acid value (P=0.0056), and puberty at baseline (P=0.0048) were independently associated with higher systolic blood pressure z-score at follow-up, whereas a negative association was observed with body mass index z-score decrease during follow-up (P=0.0033). The risk of hypertension at follow-up was associated with body mass index (P=0.0025) and systolic blood pressure (P<0.0001) z-score at baseline and inversely related to delta body mass index (P=0.0002), whereas the risk of showing hypertension ≥99th percentile was more than doubled for each baseline 1 mg/dL increase of serum uric acid (P=0.0130). Uric acid is a powerful determinant of blood pressure over time, independent of lifestyle modifications. © 2016 American Heart Association, Inc.
Kamei, Keita; Konta, Tsuneo; Hirayama, Atsushi; Ichikawa, Kazunobu; Kubota, Isao; Fujimoto, Shouichi; Iseki, Kunitoshi; Moriyama, Toshiki; Yamagata, Kunihiro; Tsuruya, Kazuhiko; Narita, Ichiei; Kondo, Masahide; Shibagaki, Yugo; Kasahara, Masato; Asahi, Koichi; Watanabe, Tsuyoshi
Hyperuricemia is an established risk factor for cardiovascular events and mortality. This study investigated the association between serum uric acid and the incidence of nonfatal stroke in a Japanese community-based population. We used a nationwide database of 155,322 subjects (aged 40-73, male 39 %) who participated in the annual "Specific Health Check and Guidance in Japan" checkup from 2008 to 2010. We examined the relationship between the quintiles of serum uric acid levels at baseline and the incidence of nonfatal stroke during a 2-year study period using self-reported data. The crude incidence of nonfatal stroke was significantly associated with serum uric acid levels at baseline, showing the lowest values in subjects with the 3rd quintile (Q3: men, 5.0-5.6; women, 3.8-4.3) of uric acid levels (mg/dL) and the highest values in subjects with the highest quintile (Q5: men ≥7.1, women ≥5.5) both in men and women (P < 0.05). In multivariate-adjusted logistic regression analysis, the odds ratio (OR) of the Q5 group was significantly higher than for the Q3 group in both men and women [men: OR 1.26, 95 % confidence interval (CI) 1.04-1.54, women: OR 1.24, 95 % CI 1.00-1.48]. In the subgroup analysis, the OR of the Q5 group of uric acid levels for incident stroke was high, irrespective of characteristics such as age, sex, and renal function. This study has shown that serum uric acid is independently associated with the incidence of nonfatal stroke in the general Japanese population.
Jindal, Kajal; Tomar, Monika; Gupta, Vinay
A third generation uric acid biosensor has been developed by exploiting the electrocatalytic functionality of nitrogen (N) doped zinc oxide (ZnO:N) thin film matrix deposited using pulsed laser deposition technique. The electrochemistry of ZnO:N thin film based electrode is investigated by using electrochemical impedance spectroscopy and cyclic voltammetry. The obtained results demonstrate that nitrogen doping in ZnO matrix offers a striking electrocatalytic activity to the immobilized uricase towards the oxidation of analyte (uric acid) and promotes the direct transfer of electrons from active sites of enzyme onto the electrode without any mediator. In contrast to pure ZnO, ZnO:N (8% N) thin film based uric acid biosensor gives a high sensitivity of about 1.38 mA/mM in the absence of mediator. Moreover, ZnO:N derived bio-electrode exhibits excellent selectivity and outstanding analytical stability and reproducibility, which enables a reliable and sensitive determination of uric acid in the serum. The ZnO:N thin film based biosensor exhibits a linear sensing response in the range from 0 to 1.0mM of uric acid concentration and the apparent Michaelis-Menten kinetic parameter (Km) is estimated to be about 0.13 mM which indicates the high affinity of the prepared bio-electrode towards uric acid. The obtained results are encouraging and indicate that the ZnO:N thin film matrix offers a new and promising platform for the development of novel third generation biosensors without using any mediator. © 2013 Published by Elsevier B.V.
Zhu, Chun-Sheng; Zhang, Bing; Lin, Zhi-Jian; Wang, Xue-Jie; Zhou, Yue; Sun, Xiao-Xia; Xiao, Ming-Liang
This study aimed to explore the spectrum-effect relationships between high-performance liquid chromatography fingerprints and the uric acid-lowering activities of chicory. Chemical fingerprints of chicory samples from ten different sources were determined by high-performance liquid chromatography, and then investigated by similarity analysis and hierarchical clustering analysis. Pharmacodynamics experiments were conducted in animals to obtain the uric acid-lowering activity information of each chicory sample. The spectrum-effect relationships between chemical fingerprints and the uric acid-lowering activities of chicory were established by canonical correlation analysis. The structures of potential effective peaks were identified by liquid chromatography with tandem mass spectrometry. The results showed that a close correlation existed between the spectrum and effect of chicory. Aesculin, chlorogenic acid, chicoric acid, isochlorogenic acid A/B/C and 13,14-seco-stigma5(6),14(15)-diene-3α-ol might be the main effective constituents. This work provides a general model of the combination of high-performance liquid chromatography and uric acid-lowering activities to study the spectrum-effect relationships of chicory, which can be used to discover the principle components responsible for the bioactivity.
Taurino, Irene; Van Hoof, Viviane; Magrez, Arnaud; Forró, László; De Micheli, Giovanni; Carrara, Sandro
We report a novel electrochemical sensor based on nanographite grown on platinum microelectrodes for the determination of bilirubin in the presence of normal concentrations of albumin. The albumin is a protein with an intrinsic ability to bind the bilirubin therefore reducing the concentration of the free electroactive metabolite in human fluids. In addition, the proposed device permits the discrimination of free bilirubin from two interferents, uric acid and ascorbic acid, by the separation of their oxidation peaks in voltammetry. Preliminary measurements in human serum prove that the proposed nanostructured platform can be used to detect bilirubin.
Uchida, Shunya; Takahashi, Masato; Sugawara, Masahiro; Saito, Tomoaki; Nakai, Kazuhiko; Fujita, Masami; Mochizuki, Koichi; Shin, Isu; Morita, Takashi; Hikita, Tomoyuki; Itakura, Hironao; Takahashi, Yuko; Mizuno, Shigeki; Ohno, Yasumi; Ito, Kageki; Ito, Takafumi; Soma, Masayoshi
This study assessed the urinary albumin/creatinine ratio (ACR) and uric acid metabolism in 70 hypertensive patients with chronic kidney disease in whom urinary ACR had remained ≥30 mg/g under the treatment of the L-type calcium channel blocker amlodipine. Three months after switching to the N/L-type calcium channel blocker cilnidipine, blood pressure (BP) did not change; however, urinary ACR significantly decreased with cilnidipine. Serum uric acid levels showed no significant change. In cases where uric acid production had been high (urinary uric acid/creatinine ratio ≥0.5), the urinary uric acid/creatinine ratio decreased significantly after cilnidipine treatment, suggesting that cilnidipine can suppress excessive uric acid formation. These results suggest that switching from amlodipine to cilnidipine results in a significant reduction in urinary ACR as well as significant reduction in uric acid production. Thus, cilnidipine is more useful than amlodipine in improving albuminuria and uric acid metabolism in hypertensive patients with chronic kidney disease.
Cai, Nan; Tan, Lu; Li, Yan; Xia, Tingting; Hu, Tianyu; Su, Xingguang
In this paper, a label-free biosensing platform for fluorescence detection of uric acid was designed on the peroxidase-mimicking activities of G-quadruplex/hemin DNAzyme and the introduction of caffeic acid. Uric acid could be decomposed by uricase and then produced hydrogen peroxide and allantoin. We thus successfully achieved the indirect detection of uric acid by monitoring the concentration of hydrogen peroxide. The G-quadruplex/hemin DNAzyme could act as peroxidase and decompose the hydrogen peroxide into hydroxyl radicals at room temperature. Due to the strong oxidizing of hydroxyl radicals, caffeic acid was converted to corresponding quinone, thus leading to fluorescence quenching of GQDs. Under the optimized experimental conditions, the quenched fluorescence intensity was linearly relative to the concentration of uric acid, ranging from 2 μM to 300 μM with a detection limit of 500 nM. The applicability of proposed method was further proved with satisfactory results in human serum and urine samples.
Cuevas-Ramos, Daniel; Almeda-Valdes, Paloma; Gómez-Pérez, Francisco J; Meza-Arana, Clara Elena; Cruz-Bautista, Ivette; Arellano-Campos, Olimpia; Navarrete-López, Mariana; Aguilar-Salinas, Carlos A
Fibroblast growth factor 21 (FGF21) levels have been linked with beneficial effects on glucose and lipid metabolism in animals. It is elevated in humans with the metabolic syndrome. This study investigates independent factors associated with serum FGF21 levels. Cross-sectional study done in healthy blue-collar workers. A medical history was taken, and FGF21 (measured using an ELISA commercial kit), glucose, uric acid, plasma lipids, total/high-molecular weight (HMW) adiponectin, and retinal-binding protein 4 (RBP4) were measured in 210 individuals with (n=81) and without (n=129) metabolic syndrome. The median of serum FGF21 levels were higher in subjects with metabolic syndrome (339.5 vs 276.4 ng/l, P=0.01). Serum FGF21 levels correlated positively with body mass index (BMI; r=0.23, P=0.001) and age (r=0.17, P=0.01). After adjusting for age and BMI, a significant positive correlation persisted for fasting glucose, uric acid, and physical activity in both males (r=0.21, r=0.11, and r=0.19, all P<0.05) and females (r=0.20, r=0.19, and r=0.14, all P<0.05). In addition, FGF21 also correlates negatively with RBP4 (r=-0.27, P=0.02), total (r=-0.26, P=0.03), and HMW adiponectin (r=-0.30, P=0.01) in women. A multiple linear regression model analysis identified that BMI (standardized beta (SB)=0.247; P=0.008), glucose (SB=0.226; P=0.003), uric acid (SB=0.191; P=0.04), and physical activity (SB=0.223; P=0.004) are independent factors influencing serum FGF21 levels (F=10.05, r(2)=0.19, P<0.001). In addition, fasting hyperglycemia > or =100 mg/dl, excess body weight with BMI > or =25 kg/m(2), and uric acid > or =5.5 mg/dl predicted higher serum FGF21 levels. Serum FGF21 levels are influenced by BMI, fasting glycemia, uric acid, and physical activity.
Background Hypertension can be generated by a great number of mechanisms including elevated uric acid (UA) that contribute to the anion superoxide production. However, physical exercise is recommended to prevent and/or control high blood pressure (BP). The purpose of this study was to investigate the relationship between BP and UA and whether this relationship may be mediated by the functional fitness index. Methods All participants (n = 123) performed the following tests: indirect maximal oxygen uptake (VO2max), AAHPERD Functional Fitness Battery Test to determine the general fitness functional index (GFFI), systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI) and blood sample collection to evaluate the total-cholesterol (CHOL), LDL-cholesterol (LDL-c), HDL-cholesterol (HDL-c), triglycerides (TG), uric acid (UA), nitrite (NO2) and thiobarbituric acid reactive substances (T-BARS). After the physical, hemodynamic and metabolic evaluations, all participants were allocated into three groups according to their GFFI: G1 (regular), G2 (good) and G3 (very good). Results Baseline blood pressure was higher in G1 when compared to G3 (+12% and +11%, for SBP and DBP, respectively, p<0.05) and the subjects who had higher values of BP also presented higher values of UA. Although UA was not different among GFFI groups, it presented a significant correlation with GFFI and VO2max. Also, nitrite concentration was elevated in G3 compared to G1 (140±29 μM vs 111± 29 μM, for G3 and G1, respectively, p<0.0001). As far as the lipid profile, participants in G3 presented better values of CHOL and TG when compared to those in G1. Conclusions Taking together the findings that subjects with higher BP had elevated values of UA and lower values of nitrite, it can be suggested that the relationship between blood pressure and the oxidative stress produced by acid uric may be mediated by training status. PMID:23799981
Patiño-Navarrete, Rafael; Piulachs, Maria-Dolors; Belles, Xavier; Moya, Andrés; Latorre, Amparo; Peretó, Juli
Uric acid stored in the fat body of cockroaches is a nitrogen reservoir mobilized in times of scarcity. The discovery of urease in Blattabacterium cuenoti, the primary endosymbiont of cockroaches, suggests that the endosymbiont may participate in cockroach nitrogen economy. However, bacterial urease may only be one piece in the entire nitrogen recycling process from insect uric acid. Thus, in addition to the uricolytic pathway to urea, there must be glutamine synthetase assimilating the released ammonia by the urease reaction to enable the stored nitrogen to be metabolically usable. None of the Blattabacterium genomes sequenced to date possess genes encoding for those enzymes. To test the host's contribution to the process, we have sequenced and analysed Blattella germanica transcriptomes from the fat body. We identified transcripts corresponding to all genes necessary for the synthesis of uric acid and its catabolism to urea, as well as for the synthesis of glutamine, asparagine, proline and glycine, i.e. the amino acids required by the endosymbiont. We also explored the changes in gene expression with different dietary protein levels. It appears that the ability to use uric acid as a nitrogen reservoir emerged in cockroaches after its age-old symbiotic association with bacteria.
Wen, Min; Zhou, Bo; Chen, Yun-Hua; Ma, Zhao-Lei; Gou, Yun; Zhang, Chun-Lin; Yu, Wen-Feng; Jiao, Ling
Background Lower serum uric acid (UA) levels have been reported as a risk factor in Parkinson’s disease (PD). However, the results have been inconsistent so far. Objectives The aim of the present study was to clarify the potential relationship of uric acid with PD. Methods Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger’s regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0. Results Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = −0.65, 95% CI [−0.84, −0.46], Z = 6.75, p <0.001; Non-Asia: SMD = −0.25, 95% CI [−0.43, −0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = −0.53, 95% CI [−0.70, −0.35], z = 5.98, p <0.001; men: SMD = −0.66, 95% CI [−0.87, −0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001). Conclusions Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the
Butler, Ryan; Inzunza, Jose; Suzuki, Hitoshi; Fujii-Kuriyama, Yoshiaki; Warner, Margaret; Gustafsson, Jan-Åke
The aryl hydrocarbon receptor (AhR) knockout mice raised in the laboratory of Fujii-Kuriyama have been under investigation for several years because of the presence in their urinary bladder of large, yellowish stones. The stones are composed of uric acid and become apparent in the bladders as tiny stones when mice are 10 wk of age. By the time the mice are 6 mo of age, there are usually two or three stones with diameters of 3–4 mm. The urate concentration in the serum was normal but in the urine the concentration was 40–50 mg/dL, which is 10 times higher than that in the WT littermates. There were no apparent histological pathologies in the kidney or joints and the levels of enzymes involved in elimination of purines were normal. The source of the uric acid was therefore judged to be from degradation of nucleic acids due to a high turnover of cells in the bladder itself. The bladder was fibrotic and the luminal side of the bladder epithelium was filled with eosinophilic granules. There was loss of E-cadherin between some epithelial cells, with an enlarged submucosal area filled with immune cells and sometimes invading epithelial cells. We hypothesize that in the absence of AhR there is loss of detoxifying enzymes, which leads to accumulation of unconjugated cytotoxins and carcinogens in the bladder. The presence of bladder toxins may have led to the increased apoptosis and inflammation as well as invasion of epithelial cells in the bladders of older mice. PMID:22232670
Butler, Ryan; Inzunza, Jose; Suzuki, Hitoshi; Fujii-Kuriyama, Yoshiaki; Warner, Margaret; Gustafsson, Jan-Åke
The aryl hydrocarbon receptor (AhR) knockout mice raised in the laboratory of Fujii-Kuriyama have been under investigation for several years because of the presence in their urinary bladder of large, yellowish stones. The stones are composed of uric acid and become apparent in the bladders as tiny stones when mice are 10 wk of age. By the time the mice are 6 mo of age, there are usually two or three stones with diameters of 3-4 mm. The urate concentration in the serum was normal but in the urine the concentration was 40-50 mg/dL, which is 10 times higher than that in the WT littermates. There were no apparent histological pathologies in the kidney or joints and the levels of enzymes involved in elimination of purines were normal. The source of the uric acid was therefore judged to be from degradation of nucleic acids due to a high turnover of cells in the bladder itself. The bladder was fibrotic and the luminal side of the bladder epithelium was filled with eosinophilic granules. There was loss of E-cadherin between some epithelial cells, with an enlarged submucosal area filled with immune cells and sometimes invading epithelial cells. We hypothesize that in the absence of AhR there is loss of detoxifying enzymes, which leads to accumulation of unconjugated cytotoxins and carcinogens in the bladder. The presence of bladder toxins may have led to the increased apoptosis and inflammation as well as invasion of epithelial cells in the bladders of older mice.
Li, Shasha; Zhao, Fei; Cheng, Shaoli; Wang, Xinyang; Hao, Yaning
The aim of this study was to explore the contribution and the mechanism of uric acid (UA) to phenotypic change in rat glomerular mesangial cells. Rat glomerular mesangial cells (HBZY-1) were exposed to UA (0.05 mmol/L to 0.4 mmol/L) for 24 h to 48 h. Subsequently, 4-phenyl butyric acid (4-PBA) (5 mg/dL) was added and 48 h incubation was performed. HBZY-1 cells exposed to UA (0.4 mmol/L) were incubated for 48 h. After incubation, the cells were examined under an inverted microscope and transmission electron microscope to observe their morphologies and the expressions of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), fibronectin (FN), glucose regulated protein 78 (GRP78), and the protein disulfide isomerase (PDI) proteins and mRNA in the HBZY-1 cells were measured by Western blot and reversed transcription-polymerase chain reaction. HBZY-1 cultured in UA showed evident morphological changes under transmission electron microscopy. The soluble UA stimulated the upregulation of the α-SMA, TGF-β1 and FN mRNA and proteins in a concentration- and time-dependent manner. UA-induced endoplasmic reticulum (ER) stress, as evidenced by the upregulation of the mRNA and protein expressions of GRP78 and PDI. However, the upregulation was reverted by 4-PBA, an inhibitor of ER stress. Uric acid induces phenotypic change in HBZY-1 cells. ER stress plays a central role in UA-induced phenotypic transformation in vitro. 4-PBA may be beneficial in attenuating UA-induced glomerular injury. © 2013 The Authors. Nephrology © 2013 Asian Pacific Society of Nephrology.
Kasl, Stanislav V.
This review examines the available evidence in support of the argument that serum uric acid (SUA) possesses considerable promise as an indicator of one type of biochemical influence on achievement behavior. The evidence arguing for further research into the role of serum cholesterol in achievement behavior is also examined. (Author/JR)
Zhuang, Quan-Quan; Lin, Zhi-Hang; Jiang, Yan-Cheng; Deng, Hao-Hua; He, Shao-Bin; Su, Li-Ting; Shi, Xiao-Qiong; Chen, Wei
Dendrite-like cobalt selenide nanostructures were synthesized from cobalt and selenium powder precursors by a solvothermal method in anhydrous ethylenediamine. The as-prepared nanocrystalline cobalt selenide was found to possess peroxidase-like activity that could catalyze the reaction of peroxidase substrates in the presence of H2O2. A spectrophotometric method for uric acid (UA) determination was developed based on the nanocrystalline cobalt selenide-catalyzed coupling reaction between N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt and 4-aminoantipyrine (4-AAP) in the presence of H2O2. Under optimum conditions, the absorbance was proportional to the concentration of UA over the range of 2.0-40 μM with a detection limit of 0.5 μM. The applicability of the proposed method has been validated by determination of UA in human serum samples with satisfactory results.
Sanna, Serena; Teumer, Alexander; Vitart, Veronique; Perola, Markus; Mangino, Massimo; Albrecht, Eva; Wallace, Chris; Farrall, Martin; Johansson, Åsa; Nyholt, Dale R.; Aulchenko, Yurii; Beckmann, Jacques S.; Bergmann, Sven; Bochud, Murielle; Brown, Morris; Campbell, Harry; Connell, John; Dominiczak, Anna; Homuth, Georg; Lamina, Claudia; McCarthy, Mark I.; Meitinger, Thomas; Mooser, Vincent; Munroe, Patricia; Nauck, Matthias; Peden, John; Prokisch, Holger; Salo, Perttu; Salomaa, Veikko; Samani, Nilesh J.; Schlessinger, David; Uda, Manuela; Völker, Uwe; Waeber, Gérard; Waterworth, Dawn; Wang-Sattler, Rui; Wright, Alan F.; Adamski, Jerzy; Whitfield, John B.; Gyllensten, Ulf; Wilson, James F.; Rudan, Igor; Pramstaller, Peter; Watkins, Hugh; Doering, Angela; Wichmann, H.-Erich; Spector, Tim D.; Peltonen, Leena; Völzke, Henry; Nagaraja, Ramaiah; Vollenweider, Peter; Caulfield, Mark; Illig, Thomas; Gieger, Christian
Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2×10−201), ABCG2 (p = 3.1×10−26), SLC17A1 (p = 3.0×10−14), SLC22A11 (p = 6.7×10−14), SLC22A12 (p = 2.0×10−9), SLC16A9 (p = 1.1×10−8), GCKR (p = 1.4×10−9), LRRC16A (p = 8.5×10−9), and near PDZK1 (p = 2.7×10−9). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0×10−26) and propionyl-L-carnitine (p = 5.0×10−8) concentrations, which in turn were associated with serum UA levels (p = 1.4×10−57 and p = 8.1×10−54, respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels. PMID:19503597
Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P
Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m(2) and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.
Khichar, Satyendra; Choudhary, Shyama; Singh, Veer Bahadur; Tater, Priyanka; Arvinda, R V; Ujjawal, Vivek
To determine whether elevations of uric acid levels are associated with the cluster of disorders described in metabolic syndrome and to evaluate whethe