Effect of Acarbose on the Increased Plasma Concentration of Uric Acid Induced by Sucrose Ingestion

Sucrose is converted fructose and glucose, which may increase plasma uric acid concentration (pUA) through increased purine degradation and/or decreased uric acid (UA) excretion. To investigate effects of acarbose, an inhibitor of alpha-glucosidase, on the increased pUA from sucrose administration, we measured pUA and urinary UA excretion in 6 healthy subjects before and after administering sucrose, with and without co-administration of acarbose. Sucrose raised pUA by 10% (p < 0.01). However, excretion and fractional clearance of UA were unchanged. Sucrose and acarbose coadministration also increased pUA, but less than did sucrose alone (sucrose: 4.9 to 5.4 mg/dl; sucrose + acarbose, 4.7 to 4.9 mg/dl, p < 0.05) without changes in urinary excretion and fractional clearance of UA. Acarbose appears to attenuate the rise in pUA by sucrose ingestion by inhibiting sucrose absorption.     

The comparison of insulin and uric acid levels in adolescents with and without metabolic syndrome

Background and Aim

The prevalence of metabolic syndrome (MS) increased in recent years in both adolescents and children groups. The aim of the study is evaluating the relationship between insulin and uric acid (UA) level in MS in adolescents

Materials and Methods

we studied 120 adolescence aged 10 to 19 in two groups: control group without metabolic syndrome and case group with metabolic syndrome. The Criteria of ATP III was considered as a diagnosis factor for metabolic syndrome.

Discussion

Various studies have been conducted in various populations to evaluate the relationship between UA level and MS in adolescents. Abdominal obesity, low HDL, hypertriglyceridemia and hypertension are associated with high UA level. In their analysis, the MS OR in UA level?4.9, 4.9-5.8 and ?5.8 mg/dl was 1, 2.53 and 9.03, respectively, which were higher than our findings in current study. Hyperinsulinemia caused by insulin resistance is one of the complications associated with MS, which puts individuals at risk of diabetes and cardiovascular events.

Results

Uric acid level in the Case group was significantly higher than the control group (p = 0.0001, 43.8±1.4 vs. 4.1±1 mg/dl, respectively). Insulin level was significantly higher in the case group in compare to the control group (p = 0.008, 9.8± 5.3 vs. 12.2±6 μU/ml, respectively).

Conclusion

The findings of this case-control study showed that adolescents with metabolic syndrome have a higher uric acid and insulin level in compare to normal subjects. We hypothesis that increase in serum insulin and uric acid level can be a risk factor in the development of metabolic syndrome.

     

Effects of long-term beer ingestion on plasma concentrations and urinary excretion of purine bases.

To investigate the long-term effects of beer ingestion on plasma concentrations of purine bases (hypoxanthine, xanthine, and uric acid), ten healthy males ingested beer (15 ml/kg body weight) every evening for three months. Blood and 24-hour urine samples were collected in the morning on one day before and one, two, and three months after starting the experiment to determine the plasma concentrations and urinary excretion of uric acid, hypoxanthine, and xanthine. Plasma concentrations and urinary excretion of uric acid, hypoxanthine, and xanthine in five of the participants that did not regularly ingest beer at a quantity of more than 15 ml/kg body weight in a single day prior to the experiment were not increased during the experimental period. In contrast, plasma concentrations and urinary excretion of uric acid were increased in five participants who regularly ingested more than 15 ml/kg body weight of beer in a single day prior to the experiment, although hypoxanthine and xanthine levels were not significantly increased during the experimental period. In both groups, uric acid clearance and purine ingestion were not significantly different throughout the study. Our results suggest that the production of uric acid caused by ethanol ingestion from beer is a significant contributor to the increase in plasma uric acid concentration in patients that regularly consume more than 15 ml/kg body weight of beer each day. Therefore, patients with gout should be encouraged to refrain from drinking large amounts of beer on a daily basis.     

Effects of profuse sweating induced by exercise on urinary uric acid excretion in a hot environment

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.     

Urinary excretion of uric acid,allantoin, and 8-OH-Deoxyguanosine in uricase-knockout mice

ABSTRACT

Although uricase-knockout (Uox KO) mice are reported to develop uric acid (UA) nephropathy, those that mature without severe nephropathy could be useful for research into purine metabolism in humans. In this study, we measured the urinary excretion of creatinine, UA, allantoin, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) collected from Uox KO mice housed in metabolic cages. UA and allantoin were determined using liquid chromatography–mass spectrometry and creatinine and 8-OHdG were measured with a commercial kit. Uox KO mice excreted significantly higher levels of UA than wild-type mice (C57BL/6), while the excretion of allantoin was significantly lower. Urinary allantoin was detected in Uox KO mice despite a lack of uricase, which is the same as in humans. In contrast to the elevated levels of UA, the daily excretion of 8-OHdG, an oxidative stress marker, was lower in Uox KO mice. UA is thought to act as an anti-oxidizing agent in humans; thus, these results show that Uox KO mice are potential animal models for research into human purine metabolism.     

Effect of purine-free low-malt liquor (happo-shu) on the plasma concentrations and urinary excretion of purine bases and uridine--comparison between purine-free and regular happo-shu.

To determine whether purine-free and regular low-malt liquor beverages (happo-shu) increase the plasma concentration and urinary excretion of purine bases (hypoxanthine, xanthine, uric acid) and uridine, 6 healthy males were given regular (10 ml/kg of body weight) and purine-free happo-shu (10 ml/kg of body weight). Plasma concentration-time curves were plotted, and the areas under the curves for uric acid and total purine bases (the sum of hypoxanthine, xanthine, and uric acid) were greater in the regular than in the purine-free happo-shu ingestion experiment (both p < 0.05). In addition, the total urinary excretion of xanthine, total purine bases, and uridine was greater in the regular than in the purine-free happo-shu ingestion experiment (p < 0.05 in all cases), although the total urinary excretion of hypoxanthine and uric acid was no different between the regular and the purine-free happo-shu ingestion experiments. These results suggest that uridine contained in regular happo-shu might contribute to an increase in the urinary excretion of uridine along with ethanol, and that the purines contained in regular happo-shu may contribute to the increase in plasma concentration of uric acid due to purine degradation.     

Acute effect of hydrochlorothiazide on renal calcium and magnesium handling in postmenopausal women

A single 50 mg dose of hydrochlorothiazide (HCTZ) decreases the urinary excretion of calcium (U(Ca)V), clearance (C(Ca)) and fractional excretion (FE(Ca)) of calcium. This is accompanied by an increase of total calcium and ionized calcium (Ca2+) concentrations in the serum. On the other hand, HCTZ increases fractional excretion of magnesium (FE(Mg)) and decreases serum Mg2+ concentrations. Moreover, HCTZ decreases markedly clearance of phosphate (C(Pi)) and fractional excretion of phosphate (FE(Pi)) and increases serum phosphate (Pi) concentrations in healthy postmenopausal women. It is concluded that intrinsic renal cellular control promptly uncouples calcium and magnesium tubular reabsorption even without K+ depletion.     

Metabolic Syndrome in Primary Gout

Background and Objectives. Primary gout has traditionally been associated with obesity, arterial hypertension, and abnormal lipid and glucose homeostasis, but we do not know the prevalence of these vascular risk factors in patients with primary gout from a Mediterranean country. Patients and Method. All patients with primary gout and 2 or more acute arthritis episodes documented by a physician were selected for the study. The diagnosis of MS required ≥3 criteria (ATP III). Patients were classified in two groups: decreased (underexcretors) and normal (normoexcretors) uric acid excretion related to serum urate levels. Results. One hundred and four patients (mean age, 59 years; 100 males) with primary gout were included in the study. MS was diagnosed in 38 subjects (37%). The most frequent triad defining MS was an increased waist circumference, blood pressure, and trygliceride levels. The prevalence of type 2 diabetes mellitus (T2D) was significantly higher in patients with the MS (21/38, 55%) as compared with subjects without the MS (3/66, 5%; p < 0.001). Mean serum urate level in patients with and without MS was identical (8.1 mg/dL), but mean 24-hour uric acid excretion was significantly lower in the former than in the latter (444 ± 110 mg/24-hour/1,73 m² versus 546 ± 221 mg/day/1,73 m²; p = 0.009). Conclusions. The condition of the MS occurs in about one-third of the patients with primary gout. Increased waist circumference, blood pressure, and triglycerides levels is the most frequent MS triad. Diminished urinary uric acid excretion is more severe in gout patients with the MS.     

Uric Acid Metabolism in Patients with Primary Gout and the Metabolic Syndrome

Forty-four patients (40 males) with a mean age of 58 years were included in this pilot study. Mean serum urate concentration in patients with and without the metabolic syndrome (MS) was 8.8 mg/dL and 8.1 mg/dL, respectively. Urinary uric acid excretion was 543 mg/day/1.73m² in the former and 609 mg/day/1.73m² in the latter. Uric acid to creatinine ratio was 0.37 mg/mg in patients with the MS and 0.42 mg/mg in those without the MS. Mean serum urate increased from 8.6 mg/dL in subjects with three or more MS components to 10.3 mg/dL in those with five MS components. Serum urate was markedly lower in patients with mild MS (9 patients, 8.6 mg/dL) as compared to severe MS (10 patients, 9.2 mg/dL). In contrast, urinary uric acid to creatinine ratio was 0.42 mg/mg in patients with gout and mild MS and 0.33 mg/mg in gout patients with severe MS. Uric acid underexcretion appears to be more severe in gout patients with the MS. This disturbance appears to be related to the severity of the MS.     

Effect of Beer Ingestion on the Plasma Concentrations and Urinary Excretion of Purine Bases: One-Month Study

To investigate the effect of long-term beer ingestion on the plasma concentrations and urinary excretion of purine bases, 5 healthy males participated in the present study, during which they ingested beer every evening for 30 days. Blood and 24-hour urine samples were collected in the morning one day before and 14 and 30 days after the initiation of the beer ingestion. During the beer ingestion period, the plasma concentration and the urinary excretion of uric acid were increased significantly, while uric acid clearance was not decreased. Further, purine ingestion was not significantly different throughout the study. These results suggest that production of uric acid by ethanol ingestion was the main contributor to the increased plasma uric acid. Therefore, patients with gout should be encouraged to avoid drinking large amounts of beer on a daily basis.     

Effect of beer ingestion on the plasma concentrations and urinary excretion of purine bases: one-month study

To investigate the effect of long-term beer ingestion on the plasma concentrations and urinary excretion of purine bases, 5 healthy males participated in the present study, during which they ingested beer every evening for 30 days. Blood and 24-hour urine samples were collected in the morning one day before and 14 and 30 days after the initiation of the beer ingestion. During the beer ingestion period, the plasma concentration and the urinary excretion of uric acid were increased significantly, while uric acid clearance was not decreased. Further, purine ingestion was not significantly different throughout the study. These results suggest that production of uric acid by ethanol ingestion was the main contributor to the increased plasma uric acid. Therefore, patients with gout should be encouraged to avoid drinking large amounts of beer on a daily basis.     

Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia

During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.     

Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells

Elevated levels of serum uric acid (UA) are commonly associated with primary pulmonary hypertension but have generally not been thought to have any causal role. Recent experimental studies, however, have suggested that UA may affect various vasoactive mediators. We therefore tested the hypothesis that UA might alter nitric oxide (NO) levels in pulmonary arterial endothelial cells (PAEC). In isolated porcine pulmonary artery segments (PAS), UA (7.5 mg/dl) inhibits acetylcholine-induced vasodilation. The incubation of PAEC with UA caused a dose-dependent decrease in NO and cGMP production stimulated by bradykinin or Ca(2+)-ionophore A23187. We explored cellular mechanisms by which UA might cause reduced NO production focusing on the effects of UA on the l-arginine-endothelial NO synthase (eNOS) and l-arginine-arginase pathways. Incubation of PAEC with different concentrations of UA (2.5-15 mg/dl) for 24 h did not affect l-[(3)H]arginine uptake or activity/expression of eNOS. However, PAEC incubated with UA (7.5 mg/dl; 24 h) released more urea in culture media than control PAEC, suggesting that arginase activation might be involved in the UA effect. Kinetic analysis of arginase activity in PAEC lysates and rat liver and kidney homogenates demonstrated that UA activated arginase by increasing its affinity for l-arginine. An inhibitor of arginase (S)-(2-boronoethyl)-l-cysteine prevented UA-induced reduction of A23187-stimulated cGMP production by PAEC and abolished UA-induced inhibition of acetylcholine-stimulated vasodilation in PAS. We conclude that UA-induced arginase activation is a potential mechanism for reduction of NO production in PAEC.     

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.     

The influence of endogenous mineralocorticoids on the composition of fetal urine

Experiments were carried out in 10 chronically catheterised fetal sheep aged 121-128 days. In 3 animals infusion of aldosterone (5 micrograms/h) caused a fall in fetal urinary Na/K ratio; an effect that was reversed by spironolactone 2.5 mg/kg followed by an infusion of 100 micrograms/h per kg. In 9 fetal sheep which had no previous treatment the same doses of spironolactone had no effect on fractional sodium excretion although the fractional excretion of potassium decreased (P less than 0.05) and the urinary sodium potassium (Na/K) ratio rose (P less than 0.05). Amiloride had a variable effect on sodium excretion but the fractional excretion of potassium decreased markedly (P less than 0.05). Thus in chronically catheterised fetal sheep, endogenous mineralocorticoid activity altered urinary potassium excretion and the urinary Na/K ratio. However this activity was low, as distal blockade with amiloride further decreased the fractional excretion of potassium and increased the urinary Na/K ratio.     

Behavior of plasma and urinary cAMP after intravenous fructose load

Increased excretion of uric acid and cAMP has been observed in many pathological conditions in man, but interrelation between behaviour of uric acid and cAMP is not well known. To investigate these aspects of purine metabolism the authors have studied behaviour of plasma and urinary cAMP in 8 subjects after intravenous rapid load of fructose (0.5 g/Kg b.w.) compared with the uric acid one. The results have shown that urinary excretion of cAMP after load of fructose is increased, but levels of plasma cAMP remain unchanged. These data confirm consensual relation between urinary uric acid and cAMP excretion, but the exact mechanism of this relation remains unexplained.     

Oxidative Stress in Young Zucker Rats with Impaired Glucose Tolerance is Diminished by Acarbose.

AIMS/HYPOTHESIS: There is evidence that acarbose reduces the risk for development of diabetes and cardiovascular complications. The mechanism underlying the vasculoprotective effect is however not known. We hypothesized that vasculoprotection observed by acarbose may be the consequence of a diminished generation of oxidative stress. METHODS: Lean and obese Zucker rats received a diet containing 10% sucrose for 7 days. A part of the rats was treated with acarbose (15 mg/kg/day in chow). Blood glucose, plasma insulin, lipid peroxides, and as a more specific marker of oxidative stress, 8-isoprostanes, were analyzed. As cellular markers of oxidative stress we determined the activities of mitochondrial aconitase and NADPH-oxidase in aorta, heart, and kidney. In addition, poly(ADP-ribose) polymerase activity (PARP) was measured in aorta. RESULTS: Sucrose feeding of obese Zucker rats resulted in increased blood glucose levels, plasma insulin, lipid peroxides and 8-isoprostanes. Mitochondrial aconitase was reduced; the activities of NAPDH-oxidase and PARP were enhanced. Treatment of obese Zucker rats with acarbose largely prevented these changes, whereas it had no effect in lean sucrose fed rats. CONCLUSION: Specifically in obese Zucker rats sucrose feeding is associated with an increased oxidative stress. The data provide IN VIVO evidence that mitochondria play a role in the generation of reactive oxygen species (ROS) in insulin resistant, hyperglycaemic states. Activation of PARP by ROS may be an important mediator of vascular dysfunction in insulin resistance. Treatment with acarbose is helpful to prevent the increase in oxidative stress and vascular dysfunction induced by hyperglycemia.     

Effect of vitamin E therapy on serum uric acid in DOCA-salt-treated rats

Uric acid is considered as an antioxidant in the blood. Despite its proposed protective properties, elevated plasma uric acid has been associated with hypertension in a variety of disorders. The purpose of this study was to investigate the relationship between the increase of arterial blood pressure and the changes in serum uric acid, measured during the gradual development of experimental hypertension in deoxycorticosterone (DOCA)-salt-treated rats. Blood pressure was monitored by tail-cuff method, urinary and plasma uric acid was measured by autoanalyzer during the induction of hypertension in 1-, 2-, 3- and 4-week DOCA-salt-treated Sprague-Dawley rats. Vitamin E (200 mg/kg/day/gavage) was co-administered with DOCA-salt for 4 weeks. From the first week of DOCA-salt treatment, rats exhibited marked increases in blood pressure. DOCA-salt treatment also resulted in a significant increase in serum uric acid and a significant decrease in urinary uric acid at the end of the first week. These changes in serum and urinary uric acid remained until the 4th week of DOCA-salt treatment but blood pressure continued to increase throughout the study. Vitamin E treatment increased urinary excretion of uric acid and decreased blood pressure and serum uric acid in DOCA-salt-treated rats. These data suggest that enhanced serum uric acid may be a contributing factor to the onset of hypertension in DOCA-salt-treated rats. A uricosuric effect is suggested for vitamin E in the treatment of hypertension.     

Humoral hypercalcemia caused by a rat Leydig-cell tumor is associated with suppressed parathyroid hormone secretion and increased urinary cAMP excretion

We studied the effect of a transplantable Leydig-cell tumor (Rice H-500) on serum calcium, parathyroid hormone (PTH), and urinary cAMP in intact Fischer-344 rats. The tumor caused rapid and severe hypercalcemia (control = 10.5 +/- 0.1 mg/dl [mean +/- S.E.] vs. 14.6 +/- 0.9 at day 12 post tumor inoculation) without evidence of metastasis. Progressive renal impairment and death generally occurred within 15 days of tumor inoculation. Serum PTH declined from control values before hypercalcemia occurred and was significantly reduced in tumor-bearing hypercalcemic rats (mean = 60 +/- 8% of control values). Urinary cAMP excretion was increased in tumor-bearing rats (mean at day 12 post inoculation = 12.2 +/- 1.4 nmol/dl creatinine clearance vs. control = 6.2 +/- 0.2) and correlated positively with serum calcium. The Rice H-500 Leydig-cell tumor appears to secrete a humoral factor capable of causing hypercalcemia. This factor may also increase urinary cAMP excretion in a manner analogous to PTH, but it is not detected by PTH radioimmunoassay.     

Effects of varying doses of methionine sulfoximine on liver glutamine synthetase activity and time courses of blood and urinary nitrogenous compounds in the chicken (Gallus domesticus)

1. The activity of liver glutamine synthetase was inhibited to 7-12% of the control activity by an intracardiac injection with methionine sulfoximine (MSM) at dosages of 20, 50, 75 and 100 mg/kg body wt. 2. Plasma glutamine concentrations in all the MSM treatments decreased sharply, then reached steady-state levels within 0.5-2.5 hr, which were almost proportional to a dose of MSM. 3. Blood ammonia concentration sharply increased to a steady-state level attained at 4.5 hr, which was proportional to a dose of MSM. The excretion rate of urinary ammonia augmented linearly up to the dose dependent maximum rates within 2-5 hr. 4. Plasma uric acid concentration dropped linearly by about 6.4 mg/100 ml at doses of 50, 75 and 100 mg MSM and by 3.7 mg/100 ml at a dose of 20 mg MSM within 2.5 hr, then recovered a little. 5. The decreases in excretion rates of urinary uric acid for the first 4 hr were almost the same at doses of 50 mg and larger, being twice as large as that of the control chicken. 6. Any doses of MSM affected neither the time course of excretion rate of total urinary nitrogen nor its total amounts for 7 hr after MSM treatment.