Lactobacillus gasseri PA-3 utilizes the purines GMP and guanosine and decreases their absorption in rats

Excessive intake of purine-rich foods elevates serum uric acid levels, making it a risk factor for hyperuricemia.

We hypothesized that lactic acid bacteria ingested with food might utilize purines and contribute to their decreased absorption in the intestines, thereby preventing hyperuricemia. We previously reported that Lactobacillus gasseri PA-3 (PA-3) incorporates adenosine/inosine and related purines and that oral ingestion of PA-3 reduced the absorption of these purines in rats. However, it is unclear whether PA-3 also decreases the absorption of other purines, such as guanosine 5′-monophosphate (GMP) and guanosine. This study investigated whether PA-3 incorporates GMP and guanosine and reduces their absorption in rats.

PA-3 incorporated both purines, with ¹⁴C-GMP uptake being greater than that of ¹⁴C-guanosine. Radioactivity in rat blood was significantly lower 30, 45, and 60 minutes after administration of ¹⁴C-GMP plus PA-3 than after administration of ¹⁴C-GMP alone and was significantly lower 15 minutes after administration of ¹⁴C-guanosine plus PA-3 than after administration of ¹⁴C-guanosine alone.

PA-3 incorporates GMP and guanosine in vitro. Oral administration of PA-3 with GMP and guanosine reduces the intestinal absorption of these purines in vivo. These findings, together with those of previous studies, indicate that PA-3 reduces the absorption of major purines contained in foods. PA-3 may also attenuate the excessive absorption of dietary purines in humans, protecting these individuals against hyperuricemia.     

Lactobacillus gasseri PA-3, but not L. gasseri OLL2996, reduces the absorption of purine nucleosides in rats

Lactobacillus gasseri PA-3 (PA-3) is a bacterial strain with a strong ability to degrade purine nucleosides. We previously showed that PA-3 incorporates purines in vitro and that oral administration of PA-3 and purines to rats attenuated their absorption of purines. It remains unclear whether these effects of PA-3 depend on bacterial strains. This study therefore compared the abilities of PA-3 and another bacterial strain of L. gasseri, OLL2996, which has shown decreased ability to degrade purine nucleosides in vitro, to incorporate purine nucleosides and to inhibit the absorption of purines fed to rats. Each bacterial strain was incubated in the presence of ¹⁴C-adenosine or ¹⁴C-inosine and the incorporation of each purine was evaluated by measuring their radioactivity. In vivo, rats were fed ¹⁴C-labeled purines along with PA-3 or OLL2996 and the absorption of these ¹⁴C-labeled purines was evaluated by analyzing radioactivity of blood samples. PA-3 incorporated about twice as much ¹⁴C-adenosine and ¹⁴C-inosine as OLL2996. The elevation of radioactivity levels in blood was 10–20% lower in rats treated with PA-3 than in control rats, after feeding with both ¹⁴C-adenosine and ¹⁴C-inosine as purines. In contrast, treatment with OLL2996 did not have statistically significant effects on radioactivity compared with the control group. These results indicate that the magnitude of bacterial inhibition of purine absorption is dependent on bacterial strain, correlating at least partly with the ability to incorporate and degrade purines.     

The association between serum ferritin and uric acid in humans

Objective: Urate forms a coordination complex with Fe³⁺ which does not support electron transport. The only enzymatic source of urate is xanthine oxidoreductase. If a major purpose of xanthine oxidoreductase is the production of urate to function as an iron chelator and antioxidant, a system for coupling the activity of this enzyme to the availability of catalytically-active metal would be required. We tested the hypothesis that there is an association between iron availability and urate production in healthy humans by correlating serum concentrations of ferritin with uric acid levels.

Materials and methods: The study population included 4932 females and 4794 males in the National Health and Nutrition Examination Survey III. They were 20 years of age or older and in good health.

Results: Serum concentrations of ferritin correlated positively with uric acid levels in healthy individuals (R²=0.41, p<0.001). This association was independent of an effect of gender, age, race/ethnic group, body mass, and alcohol consumption.

Conclusions: The relationship between serum ferritin and uric acid predicts hyperuricemia and gout in groups with iron accumulation. This elevation in the production of uric acid with increased concentrations of iron could possibly reflect a response of the host to diminish the oxidative stress presented by available metal as the uric acid assumes the empty or loosely bound coordination sites of the iron to diminish electron transport and subsequent oxidant generation.     

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation

BackgroundA 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.MethodsWe used male Wistar rats, which were orally administered fructose (5 g/kg). Those rats were used in each experiment at 12 h after administration.ResultsSingle 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.ConclusionsSingle 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.     

Serum Uric Acid Levels and Risk of Metabolic Syndrome in Healthy Adults

ObjectiveTo investigate the relationship between hyperuricemia and metabolic syndrome in a population of healthy subjects.MethodsWe studied 1,573 healthy adults (25 to 64 years old) in the population laboratory of the Tehran University of Medical Sciences. The study was designed according to the World Health Organization MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) project with use of the National Cholesterol Education Program Adult Treatment Panel III criteria for metabolic syndrome.ResultsThe crude prevalence of the metabolic syndrome was 29.9% (age-adjusted, 27.5%). The rate of metabolic syndrome significantly increased in higher quartiles of serum uric acid in both sexes but especially in women (P < .0001 versus P = .026). The bivariate correlation was significant between uric acid levels and age, total serum cholesterol, high-density lipoprotein cholesterol, triglycerides, body mass index, waist and hip circumferences, waist-to-hip ratio, and systolic and diastolic blood pressures; however, there was not a significant correlation between serum uric acid concentrations and fasting plasma glucose.ConclusionThese data indicate that an independent relationship exists between hyperuricemia and the metabolic syndrome. Moreover, hyperuricemia is significantly correlated with hypertriglyceridemia, hypertension, and visceral obesity. Early detection of hyperuricemia seems to be essential for prevention of the metabolic syndrome. (Endocr Pract. 2008;14:298-304)     

Allantoxanamide: A potent new uricase inhibitor in vivo

Allantoxanamide (2,4-dihydroxy-6-carboxamide-1,3,5-triazine) was studied as a uricase inhibitor in the rat. Uricase activity $\text{in vitro}$ was inhibited 50% by allantoxanamide at 9 × 10- M concentration. A single 250 mg/kg i.p. dose in the rat gave rise to a serum uric acid level of 14 mg/dl 6 hr after dosing; serum uric acid was still elevated (10 mg/dl) after 24 hr. At this dose level, deposition of uric acid in kidney tubules was observed. Studies with [8-¹⁴ C] uric acid indicated that the effect of allantoxanamide on serum uric acid was due to inhibition of uricase. The allantoxanamide-treated rat may serve as a useful animal model for the study of problems related to purine biosynthesis, drug-induced hyperuricemia and hyperuricosuria, and associated nephropathy.     

Hyperuricemia enhances intracellular urate accumulation via down-regulation of cell-surface BCRP/ABCG2 expression in vascular endothelial cells

Hyperuricemia has been recognized as an independent risk factor for cardiovascular disease. Urate stimulates NADPH oxidase and induces production of reactive oxygen species (ROS); consequently, intracellular urate accumulation can induce oxidative stress leading to endothelial dysfunction. Here, we studied the mechanism involved, using human umbilical vascular endothelial cells (HUVEC) as a model. Pretreatment with 15 mg/dL unlabeled uric acid (corresponding to hyperuricemia) resulted in increased uptake of [¹⁴C]uric acid at steady-state by HUVEC, whereas pretreatment with 5 mg/dL uric acid (in the normal serum concentration range) did not. However, the initial uptake rate of [¹⁴C]uric acid was not affected by uric acid at either concentration. These results suggest that efflux transport of uric acid is decreased under hyperuricemic conditions. We observed a concomitant decrease of phosphorylated endothelial nitric oxide synthase. Plasma membrane expression of breast cancer resistance protein (BCRP), a uric acid efflux transporter, was decreased under hyperuricemia, though the total cellular expression of BCRP remained constant. Uric acid did not affect expression of another uric acid efflux transporter, multidrug resistance associated protein 4 (MRP4). Moreover, phosphorylation of Akt, which regulates plasma membrane localization of BCRP, was decreased. These uric acid-induced changes of BCRP and Akt were reversed in the presence of the antioxidant N-acetylcysteine. These results suggest that in hyperuricemia, uric acid-induced ROS generation inhibits Akt phosphorylation, causing a decrease in plasma membrane localization of BCRP, and the resulting decrease of BCRP-mediated efflux leads to increased uric acid accumulation and dysregulation of endothelial function.     

Effect of phytic acid on postprandial serum uric acid level in healthy volunteers: a randomized,double-blind,crossover study

Abstract

Phytic acid, a constituent of various plants, has been related to health benefits. Phytic acid has been shown to inhibit purine nucleotide metabolism in vitro and suppress elevation of plasma uric acid levels after purine administration in animal models. This study investigated the effect of phytic acid on postprandial serum uric acid (SUA) in humans. This randomized, double-blind, crossover design study included 48 healthy subjects with normal fasting SUA. Subjects consumed a control drink and a phytic acid drink with purine-rich food, and serum and urine uric acid levels were measured for 360?min after purine loading. Phytic acid lowered the incremental area under the curve (0–360?min) and incremental maximum concentration of SUA after purine loading (p?<?0.05); tended to lower cumulative urinary uric acid excretion (0–360?min) after purine loading (p?<?0.10); and suppressed postprandial SUA in this clinical study. Altogether, our findings suggest that phytic acid may play a beneficial role in controlling postprandial SUA.     

IgA肾病合并高尿酸血症患者的危险因素分析

摘要 目的：探讨IgA肾病合并高尿酸血症患者的危险因素。方法：回顾性分析2018年1月至2021年1月于我院进行治疗的IgA肾病患者149例的病理资料,根据高尿酸血症发生情况分为高尿酸血症组（n=65）,正常尿酸组（n=84）。比较两组病理特征,收集患者年龄、性别、BMI、性别、高血压、血肌酐、尿素氮、血白蛋白、血胆固醇、甘油三酯、24 h尿蛋白定量、IL-6、IL-1及胱抑素C及CRP等资料,分析高尿酸血症发生的危险因素。结果：两组患者年龄、BMI、CRP差异无统计学意义（P>0.05）;性别、高血压、血肌酐、尿素氮、血白蛋白、血胆固醇、甘油三酯、24 h尿蛋白定量、IL-6、IL-1及胱抑素C与IgA肾病患者发生高尿酸血症相关（P<0.05）;高尿酸组患者球性硬化、节段硬化、新月体形成、小管萎缩、间质炎性浸润及间质纤维化发生率均显著高于正常尿酸组,差异显著（P<0.05）;多因素非条件Logistic分析显示,性别、高血压、血肌酐、尿素氮、血白蛋白、血胆固醇、甘油三酯、24 h尿蛋白定量、IL-6、IL-1及胱抑素C均是IgA肾病患者发生高尿酸血症的独立危险因素（P<0.05）。结论：患者性别、高血压、血肌酐、尿素氮、血白蛋白、血胆固醇、甘油三酯、24 h尿蛋白定量、IL-6、IL-1及胱抑素C均是IgA肾病患者发生高尿酸血症的危险因素,临床上对于具有危险因素的患者引起重视,提高治疗效果。     

Anti-MJ/NXP-2 autoantibody specificity in a cohort of adult Italian patients with polymyositis/dermatomyositis

Introduction

Increased frequencies of hyperuricemia and gout have been associated with primary hyperparathyroidism, and recent clinical trials of parathyroid hormone (PTH) have reported hyperuricemic adverse events. We evaluated the potential population impact of PTH on serum uric acid (SUA) levels by using a nationally representative sample of United States adults.

Methods

By using data from 8,316 participants aged 18 years and older in the National Health and Nutrition Examination Survey 2003 to 2006, we examined the relation between serum PTH and SUA levels with weighted linear regression. Additionally, we examined the relation with hyperuricemia by using weighted logistic regression.

Results

SUA levels increased with increasing serum PTH concentration. After adjusting for age, sex, dietary factors, glomerular filtration rate (GFR), and other potentially related biomarkers (calcium, phosphorus, alkaline-phosphatase, 25-hydroxyvitamin D), the SUA level differences from the bottom (referent) to top quintiles of serum PTH levels were 0, 8, 13, 14, and 19 ??M (95% CI, 12 to 26; P for trend, < 0.001). These estimates were larger among renally impaired individuals (multivariate SUA difference between the extreme quintiles of PTH, 26 versus 15 ??M among those with GFR ?? 60 versus < 60 ml/min per 1.73 m², respectively) (P for interaction = 0.004). The odds of hyperuricemia by various definitions increased with increasing PTH levels as well (multivariate P values for trend, < 0.05).

Conclusions

These nationally representative data indicate that serum PTH levels are independently associated with serum uric acid levels and the frequency of hyperuricemia at the population level.     

L-阿拉伯糖对尿酸的调节作用

转录因子是一类在生物生命活动过程中起到调控作用的重要因子,参与了各种信号转导和调控过程,可以直接或间接结合在顺式作用元件上,实现调控目标基因转录效率的抑制或增强,从而使植物在应对逆境胁迫下做出反应。 WRKY转录因子在大多数植物体内都有分布,是一类进化非常保守的转录因子家族,参与植物生长发育以及响应逆境胁迫的生理过程。众多研究表明,WRKY转录因子在植物中能够应答各种生物胁迫,如细菌、病毒和真菌等;多种非生物胁迫,包括高温、冷害、高光和高盐等;以及在各种植物激素,包括茉莉酸( JA)、水杨酸( SA)、脱落酸( ABA)和赤霉素( GA)等,在其信号传递途径中都起着重要作用。 WRKY转录因子家族蛋白至少含有一段60个氨基酸左右的高度保守序列,被称为WRKY结构域,其中WRKYGQK多肽序列是最为保守的,因此而得名。该转录因子的WRKY结构域能与目标基因启动子中的顺式作用元件W￣box( TTGAC序列)特异结合,从而调节目标基因的表达,其调控基因表达主要受病原菌、虫咬、机械损伤、外界胁迫压力和信号分子的诱导。该文介绍了植物WRKY转录因子在植物应对冷害、干旱、高盐等非生物胁迫与病菌、虫害等生物胁迫反应中的重要调控功能,并总结了WRKY转录因子在调控这些逆境胁迫反应过程中的主要生理机制。     

Serum Uric Acid and Chronic Kidney Disease: The Role of Hypertension

Background

There are inconsistent findings on the role of hyperuricemia as an independent risk factor for chronic kidney disease (CKD). Hypertension has been implicated as a factor influencing the association between serum uric acid and CKD. In this population-based study we investigated the association between serum uric acid and decline in renal function and tested whether hypertension moderates this association.

Methods

We included 2601 subjects aged 55 years and over from the Rotterdam Study. Serum uric acid and estimated glomerular filtration rate (eGFR) were assessed at baseline. After average 6.5 years of follow-up, second eGFR was assessed. CKD was defined as eGFR<60 ml/min/1.73 m². All associations were corrected for socio-demographic and cardiovascular factors.

Results

Each unit (mg/dL) increase in serum uric acid was associated with 0.19 ml/min per 1.73 m² faster annual decline in eGFR. While the association between serum uric acid and incidence of CKD was not significant in our study population (Hazard Ratio: 1.12, 95% confidence interval [CI]: 0.98–1.28), incorporating our results in a meta-analysis with eleven published studies revealed a significant association (Relative Risk: 1.18, 95%CI: 1.15–1.22). In the stratified analyses, we observed that the associations of serum uric acid with eGFR decline and incident CKD were stronger in hypertensive subjects (P for interaction = 0.046 and 0.024, respectively).

Conclusions

Our findings suggest that hyperuricemia is independently associated with a decline in renal function. Stronger association in hypertensive individuals may indicate that hypertension mediates the association between serum uric acid and CKD.     

The independent association between parathyroid hormone levels and hyperuricemia: a national population study

Introduction

Increased frequencies of hyperuricemia and gout have been associated with primary hyperparathyroidism, and recent clinical trials of parathyroid hormone (PTH) have reported hyperuricemic adverse events. We evaluated the potential population impact of PTH on serum uric acid (SUA) levels by using a nationally representative sample of United States adults.

Methods

By using data from 8,316 participants aged 18 years and older in the National Health and Nutrition Examination Survey 2003 to 2006, we examined the relation between serum PTH and SUA levels with weighted linear regression. Additionally, we examined the relation with hyperuricemia by using weighted logistic regression.

Results

SUA levels increased with increasing serum PTH concentration. After adjusting for age, sex, dietary factors, glomerular filtration rate (GFR), and other potentially related biomarkers (calcium, phosphorus, alkaline-phosphatase, 25-hydroxyvitamin D), the SUA level differences from the bottom (referent) to top quintiles of serum PTH levels were 0, 8, 13, 14, and 19 μM (95% CI, 12 to 26; P for trend, < 0.001). These estimates were larger among renally impaired individuals (multivariate SUA difference between the extreme quintiles of PTH, 26 versus 15 μM among those with GFR ≥ 60 versus < 60 ml/min per 1.73 m², respectively) (P for interaction = 0.004). The odds of hyperuricemia by various definitions increased with increasing PTH levels as well (multivariate P values for trend, < 0.05).

Conclusions

These nationally representative data indicate that serum PTH levels are independently associated with serum uric acid levels and the frequency of hyperuricemia at the population level.     

肠道菌群与高尿酸血症及痛风的相关性研究

高尿酸血症以及痛风的发病率持续升高,已经成为一个重大的公共卫生问题。肠道菌群的结构改变或失调可引起机体代谢紊乱,肠道微生态尤其与代谢性疾病的发生发展关系密切。目前研究发现高尿酸血症、痛风患者存在肠道菌群失调,降尿酸治疗后肠道菌群可发生相应改变,并且益生菌制剂具有降尿酸作用。本文概述高尿酸血症及痛风患者的肠道菌群特点,从高嘌呤及高果糖饮食对肠道菌群的影响、肠道参与嘌呤和尿酸的代谢、代谢性内毒素血症以及痛风相关炎症因子等方面探讨肠道菌群与高尿酸血症及痛风的关系,并展望肠道菌群可能成为未来诊治高尿酸血症以及痛风的一种新方法。     

Utilization of organic compounds as the sole source of nitrogen by Thiobacillus thiooxidans

Thiobacillus thiooxidans DSM 504 was shown to grow with adenine, hypoxanthine, xanthine and uric acid as sole sources of nitrogen. Growth with these compounds was observed after lag periods of varying lengths, unless the cells had been previously grown with the same purine base. The disappearance of adenine was accompanied by a temporary accumulation of hypoxanthine in the medium. The utilization of purines was inhibited by ammonia (1 mM). Guanine, pyrimidines and some other organic compounds were not utilized.Non-standard abbreviation U-¹⁴C uniformly labeled by ¹⁴C     

Uric Acid Level Has a U-Shaped Association with Loss of Kidney Function in Healthy People: A Prospective Cohort Study

BackgroundThe relationship between hyperuricemia and chronic kidney disease (CKD) has been found in various observational studies. Although hypouricemia is associated with cardiovascular events, it has not been established as a risk factor for CKD. We investigated the relationship between serum uric acid level and the loss of kidney function and incident CKD in healthy people.ResultsThe following data was obtained: mean±SD age, male, 39.6±10.4 years, female 38.4±10.8 years; eGFR, male, 81.9±16.4 ml/min/1.73m2, female, 82.1±17.5 ml/min/1.73m2; serum uric acid level, male, 5.8±1.2 mg/dl, female, 4.1±0.9 mg/dl. Both low and high serum uric acid levels were associated with the outcome and eGFR decline in males (multivariate logistic additional additive models, linear p = 0.0001, spline p = 0.043; generalized additive models, linear p = 0.0001, spline p = 0.012). In subjects with low serum uric acid levels (male, <5 mg/dl; female, <3.6 mg/dl), multivariate linear mixed models showed that low serum uric acid levels were associated with eGFR decline in a time-dependent manner (male, p = 0.0001; female, p = 0.045).ConclusionThis study showed that low as well as high levels of uric acid are associated with the loss of kidney function. Hypouricemia is a candidate predictor of kidney function decline in healthy people.     

Comprehensive analysis of mechanism underlying hypouricemic effect of glucosyl hesperidin

Hyperuricemia is caused by hepatic overproduction of uric acid and/or underexcretion of urate from the kidneys and small intestine. Although increased intake of citrus fruits, a fructose-rich food, is associated with increased risk of gout in humans, hesperidin, a flavonoid naturally present in citrus fruits, reportedly reduces serum uric acid (SUA) levels by inhibiting xanthine oxidase (XOD) activity in rats. However, the effects of hesperidin on renal and intestinal urate excretion were previously unknown. In this study, we used glucosyl hesperidin (GH), which has greater bioavailability than hesperidin, to clarify comprehensive mechanisms underlying the hypouricemic effects of hesperidin in vivo. GH dose-dependently decreased SUA levels in mice with hyperuricemia induced by potassium oxonate and a fructose-rich diet, and inhibited XOD activity in the liver. GH decreased renal urate excretion without changes in kidney URAT1, ABCG2 or GLUT9 expressions, suggesting that reducing uric acid pool size by inhibiting XOD decreased renal urate excretion. We also found that GH had no effect on intestinal urate excretion or protein expression of ABCG2. Therefore, we concluded that GH exhibits a hypouricemic effect by inhibiting XOD activity in the liver without increasing renal or intestinal urate excretion. Of note, this is the first study to elucidate the effect of a flavonoid on intestinal urate excretion using a mice model, whose findings should prove useful in future food science research in the area of urate metabolism. Taking these findings together, GH may be useful for preventing hyperuricemia, especially in people with the overproduction type.     

成人原发肾病综合征患者血尿酸与血脂代谢的关系

目的:研究成人原发肾病综合征(PNS)患者高尿酸血症的患病率及其与血脂代谢的关系。方法:将109例成人PNS患者根据其尿酸水平分为高尿酸血症组与血尿酸正常组,检测患者的血脂、血清脂蛋白、ALB及24小时尿蛋白定量,分析成人PNS患者高尿酸血症的患病率,比较高尿酸血症组与血尿酸正常组PNS患者的一般情况及血脂水平,并分析PNS患者血尿酸水平的相关因素。结果:成人PNS患者高尿酸血症的发病率为24.77%;高尿酸血症组患者TG及24小时尿蛋白定量水平明显高于血尿酸正常组(P0.01),两组患者TC、LDL-C、HDL-C、Apo AI及Apo B比较差异无统计学意义(P0.05);成人PNS患者血尿酸水平与TG及24小时尿蛋白定量水平呈正相关(r=0.350,P=0.001;r=0.533,P=0.014),与TC、LDL-C、HDL-C及ALB无明显相关性(P0.05)。结论:成人PNS患者高尿酸血症的发生率较高,高尿酸血症患者具有更高的TG及尿蛋白水平,且成人PNS患者血尿酸水平与TG及24小时尿蛋白定量具有相关性,应高度重视成人PNS患者的血尿酸水平。     

Hyperferritinemia and Hyperuricemia May Be Associated with Liver Function Abnormality in Obese Adolescents

Background

The iron status in human body and its association with liver function in adolescents was rarely studied. The objective was to investigate the association among the levels of serum ferritin, uric acid and alanine aminotransferase (ALT) in adolescents.

Methods and Results

A total of 2090 adolescents negative for hepatitis B surface antigen from one junior high school (786, 12–13 years), three senior high schools (973, 15–16 years) and one college (331, 18–19 years) participated in this survey. Anthropometric and biochemical measurements, including complete blood count, ALT, serum ferritin and uric acid were performed. An ALT>42 U/L was defined as elevated, a ferritin level >200 µg/L was defined as hyperferritinemia. A uric acid level >460 µmol/L in males and >340 µmol/L in females was defined as hyperuricemia. The chi-squared test, linear regression and multivariate logistic regression were used for the data analysis. Elevated ALT levels were detected in 76 (3.6%) students and were more prevalent in males than females (6.4% vs. 2.0%, p<0.001). The univariate analysis found gender, age group, body mass index, ferritin level, uric acid level and white blood cell count all to be significantly associated with elevated ALT. Linear regression showed a positive correlation among log(ferritin), uric acid level and ALT level. Elevated ALT occurred more frequently at ferritin level >100 µg/L. The logistic regression analysis found that body mass index, hyperferritinemia and hyperuricemia were significant factors associated with the ALT elevation, but gender, age, and white blood cell count were not.

Conclusions

Hyperferritinemia and hyperuricemia are two independently significant factors associated with ALT elevation among obese adolescents. More studies are needed to corroborate any hypothesis related to these phenomena.     

Evaluation of cellular purine transport and metabolism in the Caco-2 cell using comprehensive high-performance liquid chromatography method for analysis of purines

ABSTRACT

Using Caco-2 cells and our previously developed high-performance liquid chromatography method for quantification of purine bases, nucleosides, and nucleotides, we evaluated cellular purine transport and uptake. The analytes were separated using YMC-Triart C18 column with gradient elution. We used Caco-2 cells as intestinal model cells and monitored purine transport across a monolayer for 2 h. The degree of change of purine concentrations in the permeate was very slight; however, it was possible to simultaneously determine these parameters for all purines because of our method's high sensitivity. In the present study, the purine bases (adenine, guanine, hypoxanthine, and xanthine) showed a relatively high permeability as compared with the nucleosides (adenosine, guanosine, inosine, and xanthosine). Increased concentration of metabolites in the permeate was also observed following the addition of purines. In a cell uptake assay, both the cell culture medium (extracellular) and the cells extracted from Caco-2 with acetonitrile:water (7:3) (intracellular) were measured. The additional nucleoside did not increase significantly within the cells. On the other hand, we observed that nucleotide, such as ATP, increased in the cell in a time-dependent manner following the addition of nucleoside. The additional nucleosides were considered to be rather recycled via the salvage pathway than metabolized to purine bases and/or uric acid in the cell. Such differences might have affected the increase in the serum uric acid levels depending on purine form.