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Acrylonitrile-acrylic acid copolymer membrane imprinted with uric acid for clinical uses.

The preparation of new polymeric membranes using molecular imprinting technology for application in blood filtration devices is described. Membranes, based on an acrylic acid-acrylonitrile copolymer, produced through phase inversion, were modified by introducing specific binding sites for uric acid into their structure. The materials prepared are intended for use to selectively remove uric acid from the blood in the case of increased serum uric acid values associated with different pathologies. The interactions at a molecular level between the membrane forming copolymer and the template were investigated by means of calorimetry, infrared spectroscopy and morphological analysis. The presence of interactions between the template and the copolymer, and a good thermal stability of the imprinted membranes were observed. In addition, the results of rebinding tests on the imprinted membranes indicated a good capacity of molecular recognition for the template and satisfactory selectivity properties towards compounds of similar structure such as theophylline. Membrane permeability values suggest their application as (ultra) haemofiltration devices. Poly(acrylonitrile-co-acrylic acid) membrane.

Acrylates↗

A rapid method for the diagnosis of acute uric acid nephropathy.

Acute uric acid nephropathy is a reversible type of renal failure that results from the deposition of uric acid crystals in the collecting tubules. The present study has compared a number of laboratory tests in 5 patients with a clinical diagnosis of this disorder and 27 patients with acute renal failure of other causes. Neither the serum creatinine, BUN, serum urate concentrations, nor the ratio of serum urate:BUN differentiated between these two groups of patients. However, the ratio of uric acid to creatinine concentration on a random urine specimen did differentiate between these two patient populations. All patients with uric acid nephropathy had a ratio greater than 1.0, while all patients with other types of acute renal failure had ratios of less than 1.0.

Acute Kidney Injury↗

Differential pulse voltammetry in vivo--evidence that uric acid contributes to the indole oxidation peak.

Previous studies using differential pulse voltammetry have shown that indoleamines contribute to the oxidation peak at +280-300 mV (peak 3) measured in the rat striatum in vivo using carbon fibre electrodes. In this study, using similar techniques, it is shown that 5-hydroxyindoleacetic acid and uric acid oxidize at a similar potential (+270-290 mV) in vitro. Additionally, by microinfusing uric acid or its metabolizing enzyme uricase, it is shown that uric acid oxidation contributes to about 30% of the height of peak 3 measured in the rat striatum in vivo. These results indicate that care needs to be taken in interpreting changes in the height of the in vivo peak 3 since it is not solely due to the oxidation of brain indoleamines.

Animals↗

Studies on the morphology of human uric acid stones.

Human uric acid acid renal stones are easily distinguished from other urinary calculi by their globular or spherical shape, their colour and their hardness. Investigations of uric acid crystals grown in the presence of a variety of pigments indicate that a disordered layer structure of the uric acid dihydrate is responsible for the colour of such crystals, caused by the inclusion of pigment molecules into the crystal lattice. This in turn may help to explain the other special properties of uric acid stones.

Crystallography↗

Lever pressing for food reward and in vivo voltammetry: evidence for increases in extracellular homovanillic acid, the dopamine metabolite, and uric acid in the rat caudate nucleus.

Linear sweep voltammetry at chronically implanted carbon paste electrodes was used to study extracellular levels of homovanillic acid, a metabolite of dopamine, in the caudate nucleus of freely moving rats. Local infusion of homovanillic acid close to the electrode confirmed that peak 3, at about 550 mV, could be used for this purpose. Thirty minutes of lever pressing for food reward was followed by an increase in homovanillic acid, maximal about 30 min later (+42%). An earlier and larger (+51%) increase in peak 2 (350-400 mV) was seen, highly correlated (r = 0.98) with the rate of lever pressing across individuals. A smaller decrease (-23%) in peak 1 (200 mV; ascorbic acid) was seen 75 min after the behavioural session. Administration of allopurinol, an inhibitor of uric acid production, selectively abolished peak 2. Allopurinol prior to lever pressing reduced the increase in peak 2 very substantially (by 77%), confirming that this too was mainly due to uric acid. These results indicate that linear sweep voltammetry can be used to study the time course of changes in dopamine metabolism, and in other neurochemicals, in individual freely moving rats in relation to behaviour under experimental control. More specifically, they demonstrate directly that rewarded lever pressing increases dopamine metabolism in the caudate, which had previously only been inferred from indirect approaches. The level of uric acid is also increased, and it is suggested that this may serve as an index of metabolic activity.

Allopurinol↗

Hypouricemic effects of acacetin and 4,5-o-dicaffeoylquinic acid methyl ester on serum uric acid levels in potassium oxonate-pretreated rats.

The effects of acacetin (1) and 4,5-O-dicaffeoylquinic acid methyl ester (2), compounds contained in the flowers of Chrysanthemum sinense SABINE, on the serum uric acid level were investigated using the rats pretreated with the uricase inhibitor potassium oxonate as an animal model for hyperuricemia. When administered per orally at doses of 20 and 50 mg/kg, 1 reduced the serum uric acid level by 49.9 and 63.9%, respectively and 2 reduced the level by 31.2 and 44.4%, respectively. On the other hand, when the same doses were given intraperitoneally, both of compounds also exhibited a dose-dependent and more marked reduction of the serum uric acid level (% reduction at 20 and 50 mg/kg were 63.0 and 95.1% in 1, respectively and 66.9 and 86.5% in 2, respectively). Furthermore, the compounds 1 and 2 inhibited the rat liver xanthine oxidase activity with IC(50) values of 2.22 muM and 5.27 muM, respectively. These results demonstrated the hypouricemic action of 1 and 2, which may be attributable to their xanthine oxidase inhibitory activity.

Administration, Oral↗

Concentration-dependent mode of interaction of angiotensin II receptor blockers with uric acid transporter.

Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular disease. It has been reported that an angiotensin II receptor blocker (ARB), losartan, decreases SUA level, whereas other ARBs, such as candesartan, have no lowering effect. Because the renal uric acid transporter (URAT1) is an important factor controlling the SUA level, we examined the involvement of URAT1 in those differential effects of various ARBs on SUA level at clinically relevant concentrations. This study was done by using URAT1-expressing Xenopus oocytes. Losartan, pratosartan, and telmisartan exhibited cis-inhibitory effects on the uptake of uric acid by URAT1, whereas at higher concentrations, only telmisartan did, and these ARBs reduced the uptake in competitive inhibition kinetics. On the other hand, candesartan, EXP3174 [2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yI)methyl]imidazole-5-carboxylic acid] (a major metabolite of losartan), olmesartan, and valsartan were not inhibitory. Preloading of those ARBs in the oocytes enhanced the URAT1-mediated uric acid uptake, showing a trans-stimulatory effect. The present study is a first demonstration of the differential effects of ARBs on URAT1 that some ARBs are both cis-inhibitory and trans-stimulatory, depending on concentration, whereas others exhibit either a trans-stimulatory or cis-inhibitory effect alone, which could explain the clinically observed differential effects of ARBs on SUA level. Furthermore, it was found that such differential effects of ARBs on URAT1 could be predicted from the partial chemical structures of ARBs, which will be useful information for the appropriate use and development of ARBs without an increase of SUA.

Angiotensin II Type 1 Receptor Blockers↗

Utility of oral dissolution therapy in the management of referred patients with secondarily treated uric acid stones.

OBJECTIVES: Uric acid stones are best managed by chemolysis. Some patients with acutely symptomatic stones opt for endourologic therapies. The radiolucent nature of these stones makes secondary interventions difficult to plan. Computed tomography becomes the modality of choice to identify stone locations and size in these patients. We analyzed patients with uric acid stones referred to our stone center after primary treatment had failed to establish the efficacy of oral alkalinization therapy. METHODS: Eleven patients presented after one or more failed attempts to intervene for uric acid stones. Charts were reviewed for age, sex, time with stone before referral, medical therapies undertaken, number of antecedent urologic interventions, number of radiographic studies performed, subsequent procedures performed, and outcomes with a minimal follow-up of 6 months. RESULTS: Eight patients were men and four presented with bilateral stone disease (overall, 15 involved upper tracts). Sixty-seven percent of patients had right-sided solitary calculi. All patients at presentation filled out urinary pH diaries. Of the 11 patients, 4 stated they had been prescribed oral alkaline therapy but were found to be noncompliant, 4 were never prescribed this therapy, and 3 took the medication sporadically. All patients were counseled on self-dosing to maintain their urinary pH between 6.0 and 6.5 and to continue the diaries. Computed tomography scans were done in 9 patients, and intravenous urography and ultrasonography in the other 2 patients confirmed the stone burden. Only 3 patients (27%) required subsequent interventions (ureteroscopic laser lithotripsy). CONCLUSIONS: Secondarily referred patients with uric acid stones are best treated with medical therapy. These findings suggest that the initial medical regimens had failed because of noncompliance or lack of effective follow-up by the primary urologist. Seventy-three percent of these patients had dissolution of the stones, requiring no further endourologic intervention.

Administration, Oral↗

Effect of visceral fat accumulation on uric acid metabolism in male obese subjects: visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity.

We investigated the relationship between uric acid (UA) metabolism and fat distribution in 36 obese men with a mean +/- SD age of 38 +/- 16 years and mean body-mass index (BMI) of 34 +/- 4 kg/m2. Subjects were divided into two groups: subcutaneous fat obesity (SFO) and visceral fat obesity (VFO), according to their abdominal fat distribution based on the results of computed tomography (CT). SFO was defined as having a ratio of visceral fat area (VFA) to subcutaneous fat area (V/S) of less than 0.4, and VFO was defined as having a V/S ratio > or = 0.4. The levels of serum total cholesterol (T-Chol), triglyceride (TG), and fasting plasma glucose (FPG), and the diastolic blood pressure (dBP) were significantly higher in the VFO group than in the SFO group. Serum UA levels were much higher in both the SFO and VFO groups than in the non-obese control group (492 +/- 107 and 474 +/- 90 v 309 +/- 48 micromol/L, respectively). The 24-hour urinary urate excretion (u-UA24h) and the UA clearance (Cua) to creatinine clearance (Ccr) ratio were significantly higher in the VFO group than in the SFO group (3.75 +/- 1.43 v 2.69 +/- 1.12 mmol/d, P < .05; and 5.9% +/- 2.0% v 3.6% +/- 1.7%, P < .001, respectively). The frequency of hyperuricemia was markedly higher in both the SFO and VFO groups compared with the control group (71% and 73% v 0%, respectively). Although the high serum UA level seemed to be related to low u-UA24h in 80% of SFO subjects with hyperuricemia, this was the case in only 10% of VFO subjects. While 44% of VFO subjects with hyperuricemia were designated as an overproduction type. These results suggest that the mechanism of hyperuricemia in obesity may be affected by the difference in body fat distribution and that the assessment of body fat distribution and types of hyperuricemia is crucial for the treatment of obese patients with hyperuricemia.

Adipose Tissue↗