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Using logistic regression analysh, we investigated whether or not excessive alcohol intake and increased BMI, both of which are known causes of lipid metabolism abnormality, are associated with increased serum triglyceride, apolipoprotein B concentrations and decreased high-density lipoprotein cholesterol (HDL-C), high-density lipoprotein 2 cholesterol (HDL-C) levels in patients with gout. Serum triglyceride levels were significantly higher in patients with gout than in normal subjects In contrast, serum levels of HDL-C and HD-C were significantly lower in patients with gout than in normal subjects. These results were further analysed using stepwise logistic regression. This analysis demonstrated that both serum triglyceride levels and alcohol consumption discriminated subjects with gout from controls but BMI, HDL-C and HDL-C did not, suggesting that increased serum triglyceride levels exist intrinsically in gout, while decreased concentrations of HDL-C and HDL-C may be attributed to hypertriglyceridaemia. [ABSTRACT FROM PUBLISHER]

We reviewed lifestyle factors that influence serum uric acid levels and risk of gout flare, and how to improve their deleterious effects. Since obesity increases uric acid and weight gain increases gout risk, weight reduction by daily exercise and limiting intake of excess calories is recommended. However, strenuous exercise, which causes adenine nucleotide degradation; starvation, which decreases uric acid excretion; and dehydration may raise the level of uric acid in serum and trigger gout. Increased intake of purine-rich foods, such as meat and seafood, raise the level of uric acid in serum and is associated with increased risk of gout, whereas dairy products, especially low-fat types, are associated with a lower risk of gout. Also, heavy alcohol drinking raises the uric acid level and increases the risk of gout through adenine nucleotide degradation and lactate production. Sweet fruits and soft drinks containing fructose should be moderated, since fructose may raise uric acid and increase gout risk through uric acid production and/or decreased excretion. On the other hand, the Mediterranean diet is recommended for gout patients, since it may also help prevent hyperuricemia. Furthermore, coffee and vitamin C supplementation could be considered as preventive measures, as those can lower serum uric acid levels as well as the risk of gout., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The effects of tofisopam, a GABA-receptor agonist, following oral administration (300mg) with and without allopurinol pretreatment on the plasma concentration and renal transport of uric acid and oxypurinol were investigated in 5 healthy subjects. Fractional and urinary excretions of uric acid were both significantly increased at 2-3 hours after tofisopam administration (559% and 459%, respectively), while plasma uric acid concentration was significantly decreased (36%) at 2.5 hours, suggesting that tofisopam affects uric acid metabolism via the tubular transport system. The hypouricemic effect of tofisopam was comparable to or greater than that of losartan and/or fenofibrate, which also have uric acid-lowering activity. In addition, with prior administration of allopurinol, the fractional and urinary excretions of oxypurinol were increased at 2-3 hours after tofisopam administration (51% and 33%, respectively), while the plasma oxypurinol concentration was significantly decreased at 1.5 and 2.5 hours (15% and 21%, respectively). Accordingly, tofisopam may be an attractive compound for treatment of hyperuricemia and/or gout, especially in patients complicated with autonomic dysfunction symptoms, though it is possible that the uric acid-lowering effect of oxypurinol is attenuated by tofisopam., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Although hyperuricemia is suggested to increase allantoin production in both pro- and antioxidant manners, it remains undetermined whether it increases the serum concentration of allantoin. In addition, since uric acid has both pro- and antioxidant actions, a decrease in the serum concentration of uric acid may have an effect on the pro-oxidant-antioxidant balance., Methods: To examine whether serum allantoin is correlated with serum urate, we measured those levels as well as other parameters in 63 healthy subjects. In addition, to determine whether serum allantoin is correlated with reactive oxygen species (ROS) biomarkers, we measured 8-hydroxy deoxyguanosine and 15-F2t-isoprostane, markers of ROS, in urine samples from 30 gout patients before and 1 year after benzbromarone treatment (50 mg/d)., Results: The serum concentration of allantoin was correlated with that of urate in healthy subjects (R = 0.27, p < 0.05). Benzbromarone treatment in the patients decreased the concentrations of allantoin and urate in serum by 17% (p < 0.05) and 49% (p < 0.05), respectively, and the benzbromarone-induced change in serum allantoin was correlated with that in serum urate (R = 0.39, p < 0.05). However, benzbromarone treatment did not change the ratios of 8-hydroxydeoxyguanosine/creatinine or 15-F2t-isoprostane/creatinine in urine., Conclusions: Our findings suggest that hyperuricemia contributes to an increase in serum concentration of allantoin, though they do not indicate that hyperuricemia is a major factor for controlling oxidative stress in vivo.

Uridine is a pyrimidine nucleoside that plays a crucial role in synthesis of RNA, glycogen, and biomembrane. In humans, uridine is present in plasma in considerably higher quantities than other purine and pyrimidine nucleosides, thus it may be utilized for endogenous pyrimidine synthesis. Uridine has a number of biological effects on a variety of organs with or without disease, such as the reproductive organs, central and peripheral nervous systems, and liver. In addition, it is used in clinical situations as a rescue agent to protect against the adverse effects of 5-fluorouracil. Since the biological actions of uridine may be related to its plasma concentration, it is important to examine factors that have effects on that concentration. Factors associated with an increase in plasma concentration of uridine include enhanced ATP consumption, enhanced uridine diphosphate (UDP)-glucose consumption via glycogenesis, inhibited uridine uptake by cells via the nucleoside transport pathway, increased intestinal absorption, and increased 5-phosphribosyl-1-pyrophosphate and urea synthesis. In contrast, factors that decrease the plasma concentration of uridine are associated with accelerated uridine uptake by cells via the nucleoside transport pathway and decreased pyrimidine synthesis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We treated two patients with male infertility due to 21-hydroxylase deficiency. Endocrinologic examinations disclosed low levels of LH and FSH, with elevated ACTH and 17-OH-progesterone in both. In addition, a small testicular tumor was found in Case 1, which disappeared after adrenal replacement. Suppressed gonadotropin levels caused by increased androgen seemed to underlie the sperm dysfunction in these patients. Dexamethasone and then clomiphene were administered in Case 1, and dexamethasone in Case 2. Spermatogenesis was somewhat improved in both patients and pregnancy achieved in Case 2, though spontaneous abortion later occurred.

Objective: It has been demonstrated that uridine infusion induces insulin resistance in rats. Furthermore, it was recently reported that plasma uridine is correlated with homeostasis model assessment of insulin resistance (HOMA-R) in hypertensive patients. Therefore, we investigated whether plasma uridine was correlated with HOMA-R in patients with non-insulin-dependent diabetes mellitus (NIDDM)., Subjects and Methods: The subjects were 23 male patients with NIDDM (average age 63 years) and 18 healthy males (average age 60 years). Blood samples were drawn after an overnight fast, plasma uridine was then measured using high-performance liquid chromatography., Results: The average plasma uridine concentration in patients with NIDDM was higher than that in healthy subjects (P < 0.05). Furthermore, plasma uridine values were positively correlated with HOMA-R (r = 0.48, P < 0.05), serum insulin (r = 0.46, P < 0.05), and serum C-peptide radioimmunoreactivity (CPR) (r = 0.44, P < 0.05) values, whereas they were not significantly correlated with fasting blood glucose or hemoglobin A1c values., Conclusion: We found a positive relationship between plasma uridine value and HOMA-R, serum insulin, and CPR, suggesting that plasma uridine is a marker of insulin resistance in patients with NIDDM.

To investigate whether the concentration of uridine in plasma is related to the urinary excretion of urea, 45 healthy male subjects with normouricemia and normal blood pressure were studied after providing informed consent. Immediately after collection of 24-hour urine, blood samples were drawn after an overnight fast except for water. The contents of ingested foods during the 24-hour urine collection period were described by the subjects and analyzed by a dietician. Simple regression analysis showed that plasma uridine was correlated with the urinary excretions of urea (R = 0.41, P < .01), uric acid (R = 0.36, P < .05), and uridine (R = 0.30, P < .05), as well as uric acid clearance (R = 0.35, P < .05) and purine intake (R = 0.30, P < .05). In contrast, multiple regression analysis showed a positive relationship only between plasma uridine and urinary excretion of urea. These results suggest that an increase in de novo pyrimidine synthesis leads to an increased concentration of uridine in plasma via nitrogen catabolism in healthy subjects with normouricemia and normal blood pressure., ((c) 2010 Elsevier Inc. All rights reserved.)

When treating gout patients, we have incidentally found elevated serum levels of adiponectin in some after administration of benzbromarone. In the present study, we determined whether benzbromarone increases the serum level of adiponectin in gout patients and investigated the mechanism involved. Sixty-nine patients with gout were separated into two groups, and then treated for 1 year with uric acid-lowering therapy using benzbromarone or allopurinol. After overnight fasting, blood samples were drawn before and at 1 year after beginning of treatment. In an in vitro study, 3T3L1 cells were incubated in medium containing benzbromarone, allopurinol, pioglitazone, or uric acid, after which real time PCR assays were performed for messenger RNA of adiponectin, aP2, and CD36. Furthermore, 3T3L1 cells were incubated in medium containing GW9662 (PPARgamma antagonist) together with benzbromarone or pioglitazone, after which real-time PCR assays were performed for messenger RNA of adiponectin. In the in vivo study, benzbromarone increased the serum concentration of adiponectin in the subjects, whereas allopurinol did not. In vitro, benzbromarone and pioglitazone each increased the levels of messenger RNA of adiponectin, aP2, and CD36 in 3T3 cells, whereas allopurinol and uric acid did not. Also, GW9662 suppressed the increase in adiponectin mRNA induced by benzbromarone as well as that by pioglitazone. Together, our results suggest that benzbromarone enhances the production of adiponectin via activation of PPARgamma, which is a weak agonist for PPARgamma.

We performed mutational analyses of a woman patient with congenital nephrogenic diabetes insipidus referred to us during pregnancy. The diagnosis was made during the neonatal period, after which she was treated with spironolactone and hydrochlorothiazide. Our examination showed the patient to be apparently in good health without definite evidence of dehydration. Serum and urine osmolality were 220 mOsm/L and 50 mOsm/L, respectively, and the serum concentration of AVP was 2.7 pg/mL. Results of a water-deprivation test performed after delivery were compatible with nephrogenic diabetes insipidus. Mutational analyses showed that the patient was a compound heterozygote with point mutations at nucleotide position 298 (G to A; G100R) in exon 1 and nucleotide position 374 (C to T; T125M) in exon 2 of the aquaporin 2 gene, which have been previously described.

We investigated the effects of allopurinol on beer-induced changes in the plasma concentration and urinary excretion of purine bases. Five healthy subjects underwent three studies: ingestion of beer after taking 300 mg allopurinol (combination study); ingestion of beer alone; ingestion of allopurinol alone. Increased plasma concentrations and urinary excretion of hypoxanthine were greater in the combination study than the beer alone study. However, increases in total plasma purine base concentrations were greater in the beer alone study, even though increases in plasma uridine concentrations did not differ. Beer-induced increases in plasma concentrations of purine bases appear partially offset by increased urinary excretion of hypoxanthine after allopurinol, which also controls increases in plasma uric acid levels caused by alcoholic beverage ingestion.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Image duplication has been observed within Figure 3. The corresponding author has been asked to provide an acceptable explanation for this duplication but has not been able to do so, neither have the original source files been supplied.

Background: Since grape juice contains considerable amounts of fructose, which may increase the plasma concentration of urate, the combination of exercise and grape juice may increase the plasma concentration of urate to a greater degree than grape juice or exercise alone., Methods: We performed 3 experiments with 6 healthy male Japanese. The first was exercise alone (exercise alone experiment), the second was grape juice ingestion alone (grape juice alone experiment), and the third was a combination of exercise and grape juice ingestion (combination experiment)., Results: In the exercise alone experiment, the concentrations of purine bases and uridine in plasma, and lactate in blood, as well as the urinary excretion of oxypurines were increased, whereas the urinary excretion of uric acid and fractional excretion of purine bases were decreased. In the grape juice alone experiment, the concentrations of purine bases and uridine, as well as lactate in blood were increased, whereas the fractional excretion of uric acid was decreased. In the combination experiment, the concentrations of purine bases and uridine in plasma, and lactate in blood, as well as the urinary excretion of oxypurines were increased, whereas the urinary excretion of uric acid and fractional excretion of hypoxanthine, xanthine, and uric acid were decreased. The increase in plasma concentration of urate by the combination of exercise and grape juice was greater than that by each alone, though it was not significantly different from the sum of increases in those 2 experiments., Conclusion: Increases in adenine nucleotide degradation and lactic acid production caused by both exercise and grape juice ingestion play an important role in the increase in plasma concentration of urate, while those in combination have an additive effect on that concentration.

The objective is to assess the effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats. Male Wistar rats, 8-week-old, were categorized into four groups, which were the control (n = 9), diabetes (n = 9), infliximab-treated diabetes (n = 10), and FR167653-treated diabetes (n = 9) groups. Diabetes was induced by intraperitoneal injection of STZ (40 mg/kg). Thereafter, infliximab was injected intraperitoneally once a month (5.5 mg/kg) and FR167653 was administered orally by mixing with the rat chow (0.08%). The effects of infliximab and FR167653 on urinary albumin excretion were observed for 12 weeks. Body weight, blood sugar, 24-h urinary TNF-alpha, and 24-h urinary albumin/creatinine ratio (Ualb/Ucr) levels were determined at 1, 4, 8, and 12 weeks after the STZ-injection. Treatment of rats with STZ caused a significant loss of body weight, as well as polyuria and hyperglycemia within 1 week, while the urinary excretions of albumin and TNF-alpha were increased. Neither infliximab nor FR167653 affected body weight or blood sugar levels, whereas both decreased urinary albumin excretion, together with a modest decrease in the urinary excretion of TNF-alpha. These results suggest a role of TNF-alpha in the pathogenesis of diabetic nephropathy and show that TNF-alpha inhibition is a potential therapeutic strategy.

To determine whether an increase in the plasma concentration of uric acid by sucrose intake is ascribable to enhanced purine degradation and/or decreased urinary excretion of uric acid, we measured the plasma concentrations of purine bases (uric acid, hypoxanthine, and xanthine) and uridine, as well as the urinary excretion of purine bases in 7 healthy subjects before and after administering sucrose at 1.5 g/kg of body weight in 2 related experiments, with and without an administration of 300 mg of allopurinol. In addition, in the control experiment without an administration of sugar and with an administration of 300 mg of allopurinol, we measured the same parameters in those 7 subjects. Without added allopurinol, sucrose increased the plasma concentration of uric acid by 11% (P<.01) as well as that of uridine, although it did not significantly increase the plasma concentrations of hypoxanthine and xanthine or the urinary excretion of uric acid. On the other hand, the plasma concentration and urinary excretion of hypoxanthine were increased by 2.4-fold (P<.05) and 3.42-fold (P<.05), respectively, and the plasma concentration of xanthine was increased by 1.2-fold (P<.05) together with an increase in the plasma concentration of uridine in the experiment with allopurinol administration. In contrast, the plasma concentration and urinary excretion of uric acid and the urinary excretion of xanthine were not increased. In addition, in the control experiment, all parameters did not change significantly. These results indicate that purine degradation enhanced by sucrose plays a major role in the increased plasma concentration of uric acid.

A 35-year-old woman was referred to our institution for additional examinations to evaluate bilateral suprarenal masses incidentally found on abdominal ultrasonographic images obtained during an annual medical health checkup. Our computed tomographic scans showed bilateral and well-circumscribed low-density suprarenal masses, while MRI revealed the tumors to be heterogeneous with low intensity on T1-weighted images and high intensity on T2-weighted images. A laparoscopic adrenalectomy was performed under the suspicion of a malignant tumor, such as a malignant fibrous histiocytoma. Pathologic findings indicated a retroperitoneal ancient schwannoma of two histologic types: Antoni A and Antoni B. We considered that elucidation of the characteristic features of a schwannoma would provide helpful preoperative information for diagnosis.