[Application of the kinetics of elimination of drugs to metabolic substances experimental elimination of uric acid (Quevauviller method)].
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Humans↗
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Drinking and its relation to smoking, BP, blood lipids, and uric acid. The Framingham study.
Drinking habits and other characteristics were observed for 20 years in a cohort of 5,209 Framingham, Mass, men and women. During this period the average amount of alcohol consumed rose 63%. The percent increase was greater for women than men and greater for younger persons than older. Serum uric acid and phospholipid concentrations were higher at higher levels of alcohol consumption. Lipoprotein levels of 0 to 12 and 100 to 400 Svedberg units were positively associated with alcohol consumption in men but negatively associated with alcohol consumption in women. Blood pressure was higher in nondrinkers than light drinkers, but among drinkers BPs were higher at higher consumption levels. While cigarette smokers had lower BPs than nonsmokers, this seemed to be due to their lower weight. Persons who increased their alcohol consumption during follow-up had a small mean increase in serum phospholipid and uric acid levels, BP, and weight relative to the average changes for these variables.
Adult↗
Hypertension aggregates in families of kidney stone patients with high urinary excretion of uric acid.
OBJECTIVE: To determine whether kidney stone disease (KSD) and hypertension (HTN) share a common familial component that is determined by a specific urinary biochemical abnormality. DESIGN: Familial aggregation study. PATIENTS: Two hundred and twelve KSD patients, aged 18-50 years, collected a 24-h urine sample to measure the urinary excretion of uric acid, calcium, oxalate, magnesium and citrate, and were interviewed about the occurrence of HTN among first-degree relatives. OUTCOME: Positive family history (FHx) of HTN defined as two or more relatives with HTN, and HTN occurring in the fathers, mothers and siblings. RESULTS: Positive FHx of HTN was significantly associated with increasing urinary excretion of uric acid (P = 0.03) but not with the excretion of the other substances. When the patients were divided into those with and without hyperuricosuria, the adjusted odds ratio (OR) for positive FHx of HTN in a hyperuricosuric KSD patient was 3.8 (95% CI, 1.22-11.66). Separate analysis on the occurrence of HTN in the fathers, mothers and siblings of the probands indicated that hyperuricosuria is positively related to HTN occurring in the siblings of the patients (P < 0.001) but not in the fathers or in the mothers. The adjusted OR for HTN occurring in siblings of hyperuricosuric patients compared with siblings of non-hyperuricosuric patients was 3.8 (2.12-6.67). CONCLUSION: Siblings of KSD patients with hyperuricosuria had a significantly increased prevalence of HTN that could not be accounted for by age, family size, body-mass index and personal history of HTN of the probands. Additional studies need to be undertaken to determine whether this familial clustering has a genetic or environmental origin.
Adult↗
Warfarin and uric acid after myocardial infarction.
In order to assess the influence of warfarin on serum urate concentration, changes in serum urate were studied in 50 patients after myocardial infarction. The patients studied were part of a prospective, randomized placebo-controlled study of warfarin after myocardial infarction. Twenty-three of the patients were treated with warfarin and 27 received placebo. The mean uric acid level fell in both groups during an average of 10 months (range 6-20 months), the reduction being of the same order of magnitude in either group. This implies that warfarin, in contrast to some other oral anticoagulants, does not exert any uric acid lowering effect.
Adult↗
[Current status of prevention and therapy of urinary calculi and peroral chemo-litholysis with special attention to the relationship of increased excretion of uric acid in oxalate lithiasis].
A survey shall be given of the present state of prevention and therapy of urolithiasis as well as of the up to now much restricted possibilities of the chemolitholysis. Particular attention is paid to calcium on account of its participation in the development of oxalate and phosphate calculi which together might be 70--80% of all calculi as well as to the rather limited possibilities of the reduction of the oxalate secretion in the urine. The encouragement of the oxalate lithiasis by increased uric acid in the urine as well as the reduction of the frequency of relapses not only of the concrements of the uric acid but also of the oxalate concrements by the uricostatic Allopurinol (e.g. zyloric) is dealt with.
Calcium Oxalate↗
Network pharmacology combined with ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method to explore the mechanism of Shizhi Fang in treating uric acid nephropathy mice.
OBJECTIVE: To elucidate the potential mechanisms of Shizhi Fang (SZF, ) in the treatment of uric acid nephropathy (UAN). METHODS: SZF-containing serum was prepared from six male rats and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was employed was integrated with UPLC-Q-TOF-MS to predict SZF targets for the treatment of UAN, which were subsequently validated through in vivo experiments. Sixty male Bagg Albino Laboratory-Bred Mouse, substrain c mice were randomly allocated into six groups: Normal, Model, Febuxostat, and three SZF dosage groups. Except for the Normal group, all mice were administered potassium oxonate (250 mg/kg) and adenine (50 mg/kg) via gavage to induce UAN. Four hours post-administration, the Febuxostat group received Febuxostat (6 mg/kg), while the SZF groups received low (0.234 g/kg), medium (0.468 g/kg), or high (0.936 g/kg) doses of SZF. The Normal and Model groups were given an equivalent volume of saline. All treatments were conducted over a period of four weeks. Urine and blood samples were collected for biochemical analysis, and kidney tissues were subjected to histopathological examination and Western blot analysis. RESULTS: Nine prototype compounds and 30 metabolites were identified in SZF serum. Network pharmacology analysis revealed 195 drug targets and 1608 disease targets, with 76 common drug-disease targets, including signal transducer and activator of transcription 3 (STAT3), proto-oncogene tyrosine-protein kinase Src (SRC), matrix metalloproteinase-9 (MMP9), Caspase 3, and toll-like receptor 4 (TLR4) as key targets. Gene Ontology analysis identified 325 biological processes, 48 cellular components, and 72 molecular functions, while Kyoto Encyclopedia of Genes and Genomes analysis identified 113 pathways. Molecular docking demonstrated strong binding affinities between active compounds and their targets. In the animal study, SZF treatment alleviated pathological damage and improved serum and urine biochemical markers compared to the Model group (P < 0.05, P < 0.01, P < 0.001). Western blot analysis showed a significant reduction in phosphorylated-STAT3, phosphorylated-SRC, MMP9, TLR4, and Caspase3 expression in renal tissues of SZF-treated mice (P < 0.001). CONCLUSION: SZF may exert therapeutic effects on UAN through multiple targets and pathways.
Animals↗
Oxidation products of uric acid and ascorbic acid in preterm infants with chronic lung disease.
Allantoin, the oxidation product of uric acid (UA), can be used as an in vivo marker of free radical generation. The aims of the present study were to evaluate the allantoin changes in plasma and bronchoalveolar lavage fluid (BALF) as well as to examine plasma levels of ascorbic acid (AA) and its oxidation product, dehydroascorbic acid (DHAA), in infants with or without chronic lung disease (CLD) during the first week of life. The study population was 20 infants of 24-30 weeks gestation, comprising 10 who subsequently developed CLD and 10 without CLD. In the CLD infants, the plasma allantoin/UA ratio showed a significant increase after day 1 and continued to increase gradually to reach a peak on day 6 (6.5 +/- 4.1% for CLD and 2.1 +/- 0.9% for non-CLD infants). The allantoin/UA ratio in BALF was also higher in CLD infants and the difference reached significance on days 4-6 (41.2 +/- 15.8% for CLD and 11.7 +/- 9.9% for non-CLD infants). In contrast to allantoin, the plasma DHAA/AA ratio did not differ between the 2 groups throughout the study period. Our findings that the allantoin/UA ratios were significantly higher in CLD than non-CLD infants not only in plasma but also in BALF, and that the intergroup differences of this ratio in both plasma and BALF was more prominent in the latter half of the first week of life further confirm our previous speculation that oxygen radicals are involved in the development of neonatal CLD.
Allantoin↗
Day and night work: changes in cholesterol, uric acid, glucose and potassium in serum and in circadian patterns of urinary catecholamine excretion. A longitudinal cross-over study of railway workers.
Two groups of railway workers (n = 16 and n = 17) have been followed on their place of work during a period of shifts between day and night work. Catecholamine excretion in the urine and blood levels of lipids, glucose, uric acid, potassium and calcium were followed during the different phases of shift work. Dramatic fluctuations were noted in the diurnal pattern of catecholamine excretion during and after night work. Significant elevations in the serum levels of cholesterol, glucose, uric acid and potassium were observed during the first week after a night shift, and these changes could not be explained on the basis of shifts in the diurnal pattern or changes in dietary or other habits.
Adult↗
Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch.
Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed for 5 wk each in a cross-over design a diet, similar to one currently consumed in the United States, with 20% of the kilocalories from either fructose or high-amylose cornstarch to determine the effects of the two diets on various blood metabolites considered to be risk factors associated with heart disease. In the hyperinsulinemic men the intake of fructose as compared with cornstarch significantly increased total triglycerides and their lipoprotein distribution; total and very-low-density lipoprotein cholesterol; apoproteins B-100, C-II, C-III; and uric acid. In the nonhyperinsulinemic men total triglycerides, total and low-density lipoprotein cholesterol and uric acid were significantly greater after the consumption of fructose than after cornstarch. The results indicate that in a diet high in saturated fatty acids and cholesterol, fructose increases the levels of risk factors associated with heart disease, especially in hyperinsulinemic men.
Adult↗
[Serum uric acid in type 2 diabetic patients complicated by stroke].
OBJECTIVE: To investigate the association of hyperuricemia with the incidence of stroke in type 2 diabetic patients. METHODS: Sixty type 2 diabetic patients with stroke, 75 patients with simple stoke and 67 simple type 2 diabetic patients were randomly selected from the hospitalized patients. The serum levels of uric acid (UA), total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol(LDL), very-low-density lipoproteincholesterol (VLDL) and high-density lipoprotein- cholesterol (HDL) of all the patients were determined and comparison between the groups performed. RESULTS: Male type 2 diabetic patients with stroke had significantly higher mean levels of serum uric acid than simple diabetic patients, but such patients of both genders all had lower HDL levels. CONCLUSION: The decreased serum HDL level poses as an important risk factor for stroke in all type 2 diabetic patients, among whom the male patients in particular have hyperuricemia as another important risk factor for stroke.
Cholesterol, HDL↗
[Effect of halofenate on triglyceride and uric acid levels, coagulation and platelet behaviour in patients with hyperlipoproteinemia type IV and hyperuricemia (author's transl)].
From experimental work, an influence of a drug with hypolipidemic and hypouricemic acition on blood coagulability and platelet function may be expected. Consequently, if these effects were demonstrable in man the drug could be assumed to reduce the tendency to develop thrombosis and atherosclerosis in patients with hyperlipidemia and hyperuricemia. In the study reported, the effect of 2-acetamidoethyl-(p-chlorophenyl)-(m-trifluoro-methylphenoxy)-acetate (halofenate) was investigated in 14 patients suffering from hyperlipoproteinemia type IV and hyperuricemia. Platelet aggregation and adhesiveness, plasma levels of triglycerides, cholesterol, uric acid, and clotting factors were regularly examined during a three-month double blind trial. While uric acid and triglyceride levels decreased, no influence of the drug treatment could be observed on platelet function and blood coagulability by the laboratory methods used.
Adult↗
Interaction of allopurinol and hydrochlorothiazide during prolonged oral administration of both drugs in normal subjects. I. Uric acid kinetics.
The interaction of allopurinol (300 mg/day) and hydrochlorothiazide (50 mg/day) was studied in seven healthy male volunteers during prolonged coadministration of the two drugs using defined dietary conditions. A formula diet was administered with the allopurinol throughout the 24-day study, while hydrochlorothiazide was added during days 11-21. After the addition of hydrochlorothiazide both plasma uric acid and plasma oxipurinol rose for 6 days--24% and 30%, respectively, compared to steady-state levels during allopurinol alone (P < 0.01 each). In neither substance were variations in renal excretion significant. By the end of combined treatment (day 21), the changes induced by hydrochlorothiazide had already been reversed to a considerable extent. It is concluded that both in normal individuals and in patients with normal renal clearance of uric acid the effect of hydrochlorothiazide on the plasma concentration and renal excretion of oxipurinol is small. When taking both drugs, there is no increased risk during long-term treatment, and a risk is even questionable during the first days.
Administration, Oral↗
Familial hypouricaemia associated with renal tubular uricosuria and uric acid calculi: case report.
We describe a patient with the rare combination of uric acid calculi, familial hypouricaemia, and increased renal urate clearance.
Adult↗
Effects of daily corticosterone injections upon plasma glucose, insulin, uric acid and electrolytes and food intake pattern in the chicken.
The effect of daily injections of corticosterone (about 0.85 or 4.3 mg/day) on corticosterone-insulin interactions were investigated in ad libitum-fed chickens. The short term (0-5 hr after the injection) hyperglycaemic effect of corticosterone was accompanied by an increase in plasma uric acid levels but was not associated with consistent changes of alpha-amino non protein nitrogen, potassium, sodium or insulin. On the 8th and 15th days of experiment and after an overnight fast (i.e. about 20 hrs after an injection of corticosterone), the responses to a test-meal were measured and glucose tolerance was estimated. Birds receiving 4.3 mg corticosterone showed increased plasma glucose levels when fasting and just after (15 min) the test-meal and the glucose load. Glucose tolerance was slightly improved in birds injected with 0.85 mg corticosterone. In both tests, plasma levels of alpha-amino non protein nitrogen and possibly, uric acid (initial post-stimulation stages in birds treated with 4.3 mg corticosterone) were increased by corticosterone treatment, suggesting catabolism of amino acids. Additionally, in both tests, plasma insulin levels were increased in corticosterone-treated animals. Fasting plasma potassium levels were only decreased by the 4.3 mg dose of corticosterone. Plasma sodium levels were decreased 45-90 min following the test-meal, in all animals including controls. This effect remains unexplained. Following both the test-meal and the glucose tolerance test, plasma potassium levels decreased transiently. This effect may be compared to the hypokalaemic effect of exogenous insulin in mammals.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Voltammetric carbon paste electrodes monitor uric acid and not 5-HIAA at the 5-hydroxyindole potential in the rat brain.
Changes in the height of peak 2 obtained using linear sweep voltammetry and carbon paste electrodes chronically implanted in discrete brain regions of the unrestrained rat were measured under a variety of conditions; in the past this peak has been attributed to the oxidation of 5-hydroxyindoleacetic acid (5-HIAA). Unilateral 5,7-dihydroxytryptamine (5,7-DHT) lesions of the medial forebrain bundle reduced the 5-HIAA content of the striatum and hippocampus to 10% of the unlesioned side, but did not alter the height of peak 2 recorded in these regions. In contrast, microinfusion of uricase beside striatial electrodes reduced the height of peak 2 by 96%; systemic amphetamine-induced increases in the height of the peak were also prevented by this enzyme. These results indicate that uric acid, and not 5-HIAA, is mainly responsible for peak 2, and that changes in the height of this peak reflect changes in the extracellular concentration of uric acid.
Animals↗
Comparison of serum creatinine, uric acid, albumin and glucose in male professional endurance athletes compared with healthy controls.
Owing to considerable physical, endocrinological and metabolic adaptations, the analysis of biochemical data in elite and top-class athletes requires caution. With the aim to identify metabolic and biochemical adaptations to particular lifestyle conditions, such as regular and strenuous physical exercise, we measured the concentration of serum albumin, creatinine, uric acid and glucose in 80 male professional cyclists, 37 male members of the Italian national cross-country ski team and 60 male healthy sedentary controls at rest. At variance with earlier investigations, endurance athletes showed significantly decreased concentrations of serum creatinine (controls: 83.1+/-11.0 micromol/l; skiers: 78.0+/-8.4 micromol/l; p<0.05; cyclists: 73.8+/-10.4 micromol/l; p<0.01), uric acid (controls: 362+/-69 micromol/l; skiers: 331 +/-70 micromol/l; p<0.05; cyclists: 312+/-61 micromol/l; p<0.01) and glucose (controls: 5.35+/-0.54 mmol/l; skiers: 4.94+/-0.41 mmol/l; p<0.01; cyclists: 4.94+/-0.42 mmol/l; p<0.01). The concentration of serum albumin was also decreased in athletes, but the difference did not reach statistical significance (controls: 4.76+/-0.26 g/l; skiers: 4.71+/-0.22 g/l; p=0.384; cyclists: 4.68+/-0.22 g/l; p=0.393). Results of the present investigation demonstrate that values of laboratory testing lying outside conventional reference limits calculated on sedentary populations might express physiological adaptations to regular and demanding physical aerobic activity, emphasizing the need for the estimation of reliable reference limits in elite and professional athletes, to avoid equivocal interpretation of results within clinical and anti-doping contests.
Adaptation, Physiological↗
Reduction of serum uric acid by hormone replacement therapy in postmenopausal women with hyperuricaemia.
Reduction of serum uric acid by hormone replacement therapy in postmenopausal women with hyperuricaemia is one of the cardiovascular protective mechanisms by which hormone replacement therapy reduces the risk of cardiovascular disease.
Cardiovascular Diseases↗
[Serum concentration of uric acid, a diagnostic 'must' in patients with hyponatremia].
The renal handling of urate involves complete glomerular filtration followed by reabsorption and secretion mainly in the proximal renal tubule. The amount of urate excreted depends on the extracellular fluid volume. Expansion of extracellular fluid volume increases and contraction of extracellular fluid volume decreases the clearance of urate. In the syndrome of inappropriate secretion of antidiuretic hormone, there is volume expansion associated with low uric acid. A comparable situation is observed whenever exaggerated amounts of free water are consumed. Similarly, hypouricaemia and a tendency to low serum sodium concentrations are observed in normal pregnancy, a state with volume expansion, a physiological situation reversed when eclampsia occurs. On the other hand, when hyponatraemia is associated with contraction of extracellular fluid volume as it is often the case when thiazides or loop-diuretics are administered, hyponatraemia is paralleled by increased serum uric acid concentrations.
Blood Volume↗