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Serum uric acid.

Data from the 1977 College of American Pathologists (CAP) Comprehensive Chemistry Survey and other programs have been analyzed in an interlaboratory comparison of the measurements of serum uric acid. The majority of clinical laboratories utilize some form of phosphotungstic acid (PTA) oxidation-reduction technic for the measurement of uric acid. Methods based on uricase are most often performed on some automated device. In this Survey, in which specimens containing minimal potential interfering compounds were used, there are no significant differences in the results obtained by phosphotungstic acid and uricase methods.

Chemistry, Clinical↗

Serum albumin, creatinine, uric acid and hypertensive disorders of pregnancy.

BACKGROUND: Pre-eclampsia is a form of hypertensive disorder of pregnancy. It is a common cause of both maternal and perinatal morbidity and mortality in both developed and developing countries. OBJECTIVE: To evaluate the possibility of early prediction of hypertensive disorders of pregnancy using single estimation of serum protein, creatinine and uric in serum samples of healthy primigravidae with singleton pregnancy. SETTING: University College Hospital, Ibadan. SUBJECTS: Fifty nine normortensive primigravidae. METHODS: Fifty nine healthy normotensive primigravidae with singleton pregnancy who booked for antenal care and delivered at the University College Hospital, Ibadan had single estimations of their serum albumin, creatinine and uric acid levels at booking before the 20th week of pregnancy. The women were followed up longitudinally throughout pregnancy. RESULTS: Pre-eclampsia occurred in five of the patients (21.7%), two had pregnancy induced hypertension only (8.7%) while 16 remained normotensive (69.6%). The difference in the mean serum concentration of uric acid (0.162 +/- 0.02 mmol/L) and creatinine (93.70 +/- 10.08 micromol/L) respectively were not statistically significant (p>0.05). However, the difference in the mean serum albumin levels (4.06 +/- 0.06 versus 3.71 +/- 0.33 gm/dl) was significantly higher in the pre-eclampsia group (p<0.05). The predictive performance of these tests was generally low whether alone or in combination. CONCLUSION: Single estimation of serum uric acid and creatinine levels early in pregnancy are of little value in the prediction of pre-eclampsia. A large study is recommended to properly define the value of serum albumin levels in pregnancy in the prediction of pre-eclampsia in the light of the findings of this study.

Adult↗

[Malonyldialdehyde, uric acid and white cell count as markers of oxidative stress in acute myocardial infarction and acute coronary insufficiency].

UNLABELLED: Free radicals, produced in large amounts during myocardial ischemia and reperfusion, take part in the degradation of cellular and subcellular membrane structures. The source of oxygen radicals in the ischemic myocardium are neutrophils recruited into the necrotic region, as well as metabolic transformation of hypoxantine and xantine to uric acid. Subsequent reactions generate lipid peroxides and cytotoxic and-products of oxidation, among which is malondialdehyde (MDA). The aim of this study was to measure of MDA, uric acid and white cell count as markers of oxidative stress in patients with acute coronary insufficiency and acute myocardial infarction. We studied 75 participants (20 females and 55 males) aged 38-75, including 13 patients with acute myocardial insufficiency (group I: 6 females and 7 males, aged 40-66 years, mean 59.4 +/- 6.52), 40 patients with acute myocardial infarction (group II: 8 females and 32 males aged 38-72 years, mean 57.3 +/- 9.57) and 22 healthy volunteers (control group: 6 females and 16 males aged 39-75 years, mean 53.1 +/- 9.62). CONCLUSIONS: 1. Elevated levels of MDA in patients with acute myocardial infarction may reflect secondary disorders of cellular metabolism and late appearance of degradation products of lipid peroxides; 2. Uric acid may serve as an additional marker of free radical reactions in patients with acute myocardial infarction and acute coronary insufficiency.

Adult↗

Uric acid and the kidney: urate transport, stone disease and progressive renal failure.

In this brief review and update, we try to cover recent developments in our understanding of uric acid transport by the kidney, the contribution of uric acid to renal stone disease, its potential role in progressive renal failure and, most recently, the novel and as yet unexplained link between the urinary glycoprotein Tamm-Horsfall protein (uromodulin) and hyperuricaemia and two inherited forms of renal disease with chronic renal failure.

Animals↗

Serum leptin in formerly small-for-gestational-age children during adolescence: relationship to gender, puberty, body composition, insulin sensitivity, creatinine, and serum uric acid.

Serum leptin levels reflect body fat mass (FM), and have been described to be related to serum uric acid levels in adult type 2 diabetic and healthy subjects. We therefore aimed to evaluate the interrelationship between leptin and markers of the metabolic syndrome by studying serum leptin concentration, body mass index (BMI), percent body fat (Fat%), total fat mass (FM), sum of skinfolds (SS), triglycerides (TG), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, insulin, calculated insulin resistance (HOMA), creatinine (CR), and uric acid (UA) concentration in 50 former small-for-gestational-age (SGA) children and 21 infants born adequate for gestational age (AGA) at the time of mid-puberty. Our data confirm previous results showing a positive association between leptin and body fatness, and female gender. Twelve children with impaired glucose tolerance (IGT) had higher UA levels than subjects with normal glucose tolerance (NGT) (5.1 +/- 1.1 v 4.2 +/- 1.2 mg/dL, P <.05), and showed the strongest relation between serum leptin and UA (r =.76, P <.001). Multiple regression analyses demonstrated that gender, estimates of total body adiposity (Fat% and SS), birth weight (BW), gestational age (GA), stimulated glucose and insulin, and serum UA are independently associated with serum leptin concentration in former SGA children with dysglycemia (R(2) =.89, P <.001). A long-term effect of intrauterine growth restriction on body fatness, metabolic syndrome, and serum leptin levels is suggested.

Adolescent↗

Hypoxanthine, xanthine, and uric acid concentrations in the cerebrospinal fluid, plasma, and urine of hypoxemic pigs.

The concentrations of hypoxanthine, xanthine, and uric acid in plasma and cerebrospinal fluid (CSF), as well as the urinary output of hypoxanthine and xanthine, were measured in four groups of pigs (three groups with different degrees of hypoxemia and one control group). During hypoxemia with arterial O2 tension between 2.1 and 3.0 kPa [group 1, fractional inspired oxygen (FiO2) = 0.08], hypoxanthine increased in CSF from a mean basal value of 18.1 to 39.3 mumol/L at death (p less than 0.02), in plasma from 25.4 to 103.6 mumol/L (p less than 0.05), and in urine from 21.3 to 87.1 nmol/kg/min (p less than 0.02). Xanthine changed in a similar way: in CSF from 4.0 to 10.6 mumol/L (p less than 0.02), in plasma from 0.7 to 48.1 mumol/L (p less than 0.02), and in urine from 4.0 to 12.6 nmol/kg/min (p less than 0.05). Uric acid increased in CSF from 2.7 to 11.6 mumol/L (p less than 0.05), and in plasma from 15.4 to 125.0 mumol/L (p less than 0.02). During hypoxemia with arterial O2 tension between 3.0 and 4.0 kPa (group 2, FiO2 = 0.11), hypoxanthine increased in the CSF from 14.7 to 42.9 mumol/L (p less than 0.02). Plasma hypoxanthine increased from 20.3 to a maximum of 44.1 mumol/L (p less than 0.02), but decreased to initial values by the time of death. The urinary excretion of hypoxanthine increased from 13 to 54 nmol/kg/min (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Further studies on the use of allopurinol to reduce plasma uric acid concentrations in the Red-tailed Hawk (Buteo jamaicensis) hyperuricaemic model.

The present paper reports the effects of allopurinol in a raptor hyperuricaemic model. The study was performed as a follow-up to previous experiments wherein allopurinol was used in doses of 100 and 50 mg/kg, and was proved to be toxic at these higher dose rates. To investigate whether 25 mg/kg (semel in die) s.i.d. allopurinol is a safe and effective dose in Red-tailed Hawks (Buteo jamaicensis) to reduce plasma uric acid concentrations, experimental studies were performed using the physiologically occurring postprandial hyperuricaemia. Preprandial and postprandial plasma concentrations of xanthine, hypoxanthine, allopurinol, oxypurinol and uric acid were established by high-performance liquid chromatography at various time intervals after receiving allopurinol (25 mg/kg SID) or placebo. No significant differences were observed between the experimental and the control group. These results indicate that this dose is safe to administer; however, this dose failed to cause a significant effect on plasma uric acid concentrations. Because of the low therapeutic ratio of allopurinol in Red-tailed Hawks, follow-up studies have concentrated on an alternative for the treatment of hyperuricaemia, namely urate oxidase.

Allopurinol↗

Renal hypouricemia in school-aged children: screening of serum uric acid level before physical training.

We present two cases of a 12-year-old Japanese boy and a 14-year-old Japanese girl who had exercise-induced acute renal failure (ARF). They experienced general fatigue, nausea/vomiting, and vague discomfort in the abdomen after physical exercise at school. In case of the boy, abdominal pain subsided, but renal dysfunction lasted 17 days, with peak levels of creatinine 9.4 mg/dl and uric acid 11.3 mg/dl. On the other hand, as the girl had suffered from hypouricemia before, she followed a doctor's guidance on prevention of ARF. Consequently, she was promptly diagnosed as having exercise-induced ARF associated with hypouricemia, and rapidly recovered from ARF within a week. The difference between their clinical courses suggested a possibility that previous laboratory evaluation of serum uric acid assisted in the management of exercise-induced ARF associated with hypouricemia. School-aged children, especially Japanese and Asian, may be advised to have their serum uric acid measured before starting physical training at school.

Acute Kidney Injury↗

Direct ultraviolet method for enzymatic determination of uric acid, with equilibrium and kinetic data-processing options.

We developed and evaluated a direct ultraviolet method for the enzymatic determination of uric acid in serum, plasma, or urine, without deproteinization of sera and plasma. Equilibrium and nonlinear curve-fitting kinetic options are evaluated and compared, and results of the proposed method are compared with those of a candidate Reference Method. All data-processing options yield a linear relation for absorbance and concentration of uric acid between 0.1 and 2 mmol/L; with the equilibrium option, results are linear to 5 mmol/L. For 100 plasma samples, results correlate well between the proposed method (y) and a reference method (x): y = 0.99x - 0.002 mmol/L. Between-run imprecision is about 2.3%, and interference by hemolyzed, icteric, or lipemic specimens or specimens containing high concentrations of xanthine or paraproteins is minimal. The kinetic option with a data-processing range of 100 s or longer yields results that correlate well with the equilibrium method: y = 1.006x + 0.002 mmol/L (n = 118). For 20 urine samples processed by the proposed (y) and a reference (x) methods, y = 1.04x + 0.038 mmol/L.

Buffers↗

Effect of urea and uric acid on influenza virus type C. Brief report.

The replication of influenza type C/1233 virus following inoculation into the amniotic sac of embryonated hen's eggs is significantly greater than that seen in the allantoic cavity. However, optimal growth condition for amniotically propagated C/1233 occur in the allantois of 8-day old embryos incubated post-inoculation at 32 degrees C. Differences in pH levels between the amniotic and allantoic cavities did not account for the variable growth ability of C/1233 virus, but in both in vitro and in ovo studies, levels of urea and uric acid, or urea-uric acid mixtures caused significant reductions in virus yield.

Animals↗

[Enzymatic determination of uric acid in serum with the trinder reaction (author's transl)].

We describe a direct colorimetric method for the enzymatic assay of uric acid. 50 microliters serum aliquots are incubated for 30 min with a diluted hexacyanoferrate solution, to remove interference by non-specific reducing agents. Uric acid is then oxidized to allantoin in the presence of uricase (Aspergillus flavus), with the simultaneous production of hydrogen peroxide; this is measured by a modified Emerson-Trinder reaction, in which phenol has been replaced by sulphonated 2,4-dichlorophenol, a more sensitive chromogen. The method gives linear results up to 20 mg of uric acid/100 ml.

Colorimetry↗

Dissolution of uric acid stones causing acute obstructing anuria in three consecutive infants.

We report on 3 infants with obstructive anuria due to bilateral uric acid stones. In all patients the precipitating cause of acute obstructive renal failure was choking of bilateral ureteropelvic junction with numerous small uric acid stones without cause pelvicaliceal dilatation. While the chemical dissolution therapy succeeded in dissolving the stones in 2 patients, unilateral percutaneous nephrostomy application associated with alkalization achieved dissolution of obstructing stones in the remaining 1 patient.

Acute Kidney Injury↗

Immobilized-enzyme nylon-tube reactor for routine determination of uric acid in serum.

We report here the preparation of an immobilized-enzyme nylon-tube reactor containing uricase (EC 1.7.3.3) and the assembly of a flow-through system (Technicon AutoAnalyzer II) for the routine determination of uric acid in serum. Results of these uric acid analyses by use of immobilized uricase, in conjunction with peroxidase (EC 1.11.1.7) and aminophenazone-dichlorophenol in solution, are compared with those obtained with the same enzyme in solution by use of the uricase-PAP (peroxidase, 4-aminophenazone, dichlorophenol) method. Clinical trials carried out routinely with the uricase reactor give reliable and reproducible results with high precision at an appreciably lower cost. The reactors are stable to continued or intermittent use for at least three months or for 4000 tests.

Drug Stability↗

Measurement of uric acid, ascorbic acid, and related metabolites in biological fluids.

A rapid and quantitative method for the simultaneous measurement of uric acid, ascorbic acid, and related metabolites in biological fluids is described. This method makes use of anion-exchange extraction columns to isolate the desired compounds from a wide range of biological fluids, and anion-exchange HPLC with ultraviolet detection for their separation and measurement. By this procedure the contents of uric and ascorbic acids in human serum and urine were estimated. Furthermore, the oxidation of uric acid to allantoin and ascorbic acid to dehydroascorbic acid could be readily monitored.

Allantoin↗

Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone.

Benzbromarone has been reported to increase the renal clearance of oxypurinol, an active metabolite of allopurinol. We examined the renal transport of oxypurinol to determine whether such a change in renal clearance could be explained by altered transporter-mediated reabsorption. Since the first step of reabsorption takes place at the renal epithelial apical membrane, we focused on membrane transporters. Benzbromarone is an inhibitor of reabsorption of uric acid mediated by the uric acid transporter (URAT) URAT1 (SLC22A12), which is expressed at the apical membrane of proximal tubular cells in humans. Uptake of oxypurinol by Xenopus oocytes injected with complementary RNA of URAT1 was significantly higher than that by water-injected oocytes, and the uptake was saturable, with a K(m) of about 800 microM. Moreover, benzbromarone inhibited the oxypurinol uptake by URAT1 at concentrations as low as 0.01 microM. The uptake of oxypurinol by another organic anion transporter (OAT), OAT4 (SLC22A11), which is also expressed at the apical membrane of proximal tubular epithelial cells, was negligible, whereas the uptake of [3H]estrone-3-sulfate by OAT4 was significantly inhibited by oxypurinol. Furthermore, neither the transport activity of organic cation/carnitine transporter (OCTN) 1 nor OCTN2 was affected by oxypurinol or benzbromarone. These results indicate that URAT1 is involved in renal reabsorption of oxypurinol, and the increment of renal clearance of oxypurinol upon concomitant administration of benzbromarone could be due to drug interaction at URAT1.

Animals↗

Growth of Candida famata and Trichosporon cutaneum on uric acid as the sole source of carbon and energy, a hitherto unknown property of yeasts.

Yeast strains capable of utilizing uric acid as the sole source of carbon and energy were isolated from soil by the enrichment culture method. The strains were identified as Candida famata (Harrison) Meyer et Yarrow and Trichosporon cutaneum (De Beurm., Gougerot et Vaucher) Ota. On the subcellular level growth of yeasts on uric acid was accompanied with the development of a number of large microbodies in the cells.

Candida↗

[Donnan equilibrium and kinetics of uric acid transport across human erythrocyte membrane].

The study of the effects of varying pH and ionic composition of external solution on the uric acid ratio (see article) for human erythrocytes at equilibrium and on its permeability constant shows that the distribution of uric acid agrees with the laws of the Gibbs-Donnan equilibrium and its passage across the human erythrocyte membrane with the law of ionic diffusion.

Benzoates↗

Uric acid in hypertension and cardiovascular disease.

Cardiovascular disease, and particularly coronary artery disease, remains the leading cause of mortality worldwide, despite recent substantial declines. Hypertension, long recognized as a risk factor for both stroke and myocardial infarction, is an important target for preventive intervention. However, effective hypotensive therapy produces incomplete cardioprotection, and most events that would have occurred in the natural state continue to occur among controlled hypertensive patients. Further progress in reducing the burden of cardiac disease will depend on early identification of risk in successfully treated hypertensive subjects and the development of preventive interventions that go beyond simple reduction of blood pressure. Recently, elevation of uric acid has been found to be associated with subsequent morbidity and mortality in the general population among patients with congestive heart failure, diabetes and hypertension. A prospective study in a large cohort of well controlled hypertensive subjects has revealed a strong, specific, stepwise, independent association of increasing serum uric acid and cardiac morbidity and mortality. Unanswered, however, is the question of whether uric acid is simply an associated phenomenon, or actually contributes to the occurrence of cardiac events.

Angiotensin Receptor Antagonists↗