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Concept: Uric acid

320

Background Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease. Methods We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization). Results In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis. Conclusions In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).

Concepts: Cardiovascular diseases, Low-density lipoprotein, Gout, Uric acid, Xanthine oxidase inhibitor, Cardiovascular disease, Atherosclerosis, Myocardial infarction

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The safe disposal of human excreta is of paramount importance for the health and welfare of populations living in low income countries as well as the prevention of pollution to the surrounding environment. On-site sanitation (OSS) systems are the most numerous means of treating excreta in low income countries, these facilities aim at treating human waste at source and can provide a hygienic and affordable method of waste disposal. However, current OSS systems need improvement and require further research and development. Development of OSS facilities that treat excreta at, or close to, its source require knowledge of the waste stream entering the system. Data regarding the generation rate and the chemical and physical composition of fresh feces and urine was collected from the medical literature as well as the treatability sector. The data were summarized and statistical analysis was used to quantify the major factors that were a significant cause of variability. The impact of this data on biological processes, thermal processes, physical separators, and chemical processes was then assessed. Results showed that the median fecal wet mass production was 128 g/cap/day, with a median dry mass of 29 g/cap/day. Fecal output in healthy individuals was 1.20 defecations per 24 hr period and the main factor affecting fecal mass was the fiber intake of the population. Fecal wet mass values were increased by a factor of 2 in low income countries (high fiber intakes) in comparison to values found in high income countries (low fiber intakes). Feces had a median pH of 6.64 and were composed of 74.6% water. Bacterial biomass is the major component (25-54% of dry solids) of the organic fraction of the feces. Undigested carbohydrate, fiber, protein, and fat comprise the remainder and the amounts depend on diet and diarrhea prevalence in the population. The inorganic component of the feces is primarily undigested dietary elements that also depend on dietary supply. Median urine generation rates were 1.42 L/cap/day with a dry solids content of 59 g/cap/day. Variation in the volume and composition of urine is caused by differences in physical exertion, environmental conditions, as well as water, salt, and high protein intakes. Urine has a pH 6.2 and contains the largest fractions of nitrogen, phosphorus, and potassium released from the body. The urinary excretion of nitrogen was significant (10.98 g/cap/day) with urea the most predominant constituent making up over 50% of total organic solids. The dietary intake of food and fluid is the major cause of variation in both the fecal and urine composition and these variables should always be considered if the generation rate, physical, and chemical composition of feces and urine is to be accurately predicted.

Concepts: Nitrogen, Uric acid, Organic compound, Defecation, Urine, Constipation, Nutrition, Protein

165

Kidney stones (nephrolithiasis) are a widespread disease. Thus, blocking stone formation and finding new therapeutic methods is an important area of study. Diosmin (a major component of the bile) is known to have antioxidant as well as renoprotective effects. The present investigation aimed to evaluate the effect of diosmin on renal tissue protection in rats with ethylene glycol-induced nephrolithiasis.

Concepts: Vitamin D, Vitamin C, Uric acid, Urinary bladder, Oxalate, Nephrology, Kidney, Kidney stone

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The association between serum uric acid (UA) levels and atrial fibrillation (AF) in the general population in Japan is not well known.Methods and Results:In total, 285,882 consecutive subjects (men, 130,897; women, 154,985; age, 58±15 years) not receiving treatment for hyperuricemia who underwent health checkups were enrolled. Subjects were stratified into deciles according to age, body mass index, estimated glomerular filtration rate, systolic blood pressure, and UA level. AF prevalence was calculated for each decile. The odds ratio that defined the decile with the lowest AF prevalence as reference was calculated in each sex. In men, the mean UA was 6.0±1.4 mg/dl; AF prevalence was 1.8% and was lowest in the decile with UA 4.4-4.9 mg/dl. Deciles with both high and low UA (5.4-5.6 mg/dl to >7.8 mg/dl and <4.3 mg/dl) were associated with significantly higher AF prevalence. In women, the mean UA was 4.5±1.1 mg/dl; AF prevalence was 0.7% and was lowest in the decile with UA 3.6-3.8 mg/dl. Deciles with highest UA (5.0-5.2 mg/dl to >5.9 mg/dl) were associated with significantly higher AF prevalence. The analysis adjusted for other clinical covariates demonstrated an independent association between UA and AF in both sexes.

Concepts: Atherosclerosis, Atrial fibrillation, Body mass index, Blood pressure, Blood, Stroke, Urea, Uric acid

147

To investigate the relationship between serum uric acid levels and cardiovascular disease in Asians.

Concepts: Cardiovascular disease, Organic acids, Ammonia, Atherosclerosis, Uric acid

105

Objective To prospectively examine the relation between the Dietary Approaches to Stop Hypertension (DASH) and Western diets and risk of gout (ie, the clinical endpoint of hyperuricemia) in men.Design Prospective cohort study.Setting The Health Professionals Follow-up Study.Participants 44 444 men with no history of gout at baseline. Using validated food frequency questionnaires, each participant was assigned a DASH dietary pattern score (based on high intake of fruits, vegetables, nuts and legumes, low fat dairy products, and whole grains, and low intake of sodium, sweetened beverages, and red and processed meats) and a Western dietary pattern score (based on high intake of red and processed meats, French fries, refined grains, sweets, and desserts).Main outcome measure Risk of incident gout meeting the preliminary American College of Rheumatology survey criteria for gout, adjusting for potential confounders, including age, body mass index, hypertension, diuretic use, and alcohol intake.Results During 26 years of follow-up, 1731 confirmed cases of incident gout were documented. A higher DASH dietary pattern score was associated with a lower risk for gout (adjusted relative risk for extreme fifths 0.68, 95% confidence interval 0.57 to 0.80, P value for trend <0.001). In contrast, a higher Western dietary pattern score was associated with an increased risk for gout (1.42, 1.16 to 1.74, P=0.005).Conclusion The DASH diet is associated with a lower risk of gout, suggesting that its effect of lowering uric acid levels in individuals with hyperuricemia translates to a lower risk of gout. Conversely, the Western diet is associated with a higher risk of gout. The DASH diet may provide an attractive preventive dietary approach for men at risk of gout.

Concepts: Metabolic syndrome, Fast food, Gout, Hyperuricemia, Diuretic, Nutrition, Uric acid, Diets

49

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.

Concepts: Triglyceride, Fructose, Hyperuricemia, Xanthine oxidase, Metabolism, Enzyme, Gout, Uric acid

30

Gout is a consequence of an innate immune reaction to monosodium urate crystals deposited in joints. Acute gout attacks can be triggered by dietary factors that are themselves associated with serum urate levels. Tomato consumption is an anecdotal trigger of gout flares. This study aimed to measure the frequency of tomato consumption as a self-reported trigger of gout attacks in a large New Zealand sample set, and to test the hypothesis that tomato consumption is associated with serum urate levels.

Concepts: Trigger pad, Real number, Sample, Sample size, Immune system, Innate immune system, Uric acid, Gout

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PURPOSE: Few studies have focused on the metabolic changes induced by creatine supplementation. This study investigated the effects of creatine supplementation on plasma and urinary metabolite changes of athletes after endurance and sprint running. METHODS: Twelve male athletes (20.3 ± 1.4 y) performed two identical (65-70 % maximum heart rate reserved) 60 min running exercises (endurance trial) before and after creatine supplementation (12 g creatine monohydrate/day for 15 days), followed by a 5-day washout period. Subsequently, they performed two identical 100 m sprint running exercises (power trial) before and after 15 days of creatine supplementation in accordance with the supplementary protocol of the endurance trial. Body composition measurements were performed during the entire study. Plasma samples were examined for the concentrations of glucose, lactate, branched-chain amino acids (BCAAs), free-tryptophan (f-TRP), glutamine, alanine, hypoxanthine, and uric acid. Urinary samples were examined for the concentrations of hydroxyproline, 3-methylhistidine, urea nitrogen, and creatinine. RESULTS: Creatine supplementation significantly increased body weights of the athletes of endurance trial. Plasma lactate concentration and ratio of f-TRP/BCAAs after recovery from endurance running were significantly decreased with creatine supplementation. Plasma purine metabolites (the sum of hypoxanthine and uric acid), glutamine, urinary 3-methylhistidine, and urea nitrogen concentrations tended to decrease before running in trials with creatine supplements. After running, urinary hydroxyproline concentration significantly increased in the power trial with creatine supplements. CONCLUSIONS: The findings suggest that creatine supplementation tended to decrease muscle glycogen and protein degradation, especially after endurance exercise. However, creatine supplementation might induce collagen proteolysis in athletes after sprint running.

Concepts: Urea, Urine, Protein, Uric acid, Nitrogen, Ammonia, Amino acid, Metabolism

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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.

Concepts: Nitrogen, Uric acid, Kidney stone, Sodium, Water, PH, Ammonia, Chemistry