Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chromatographic technique on anion exchange column was developed. It permets to determine unmetabolized pyrazinamide and three major metabolities: pyrazinoic acid, 5-hydroxypyrazinoic acid and an unidentified compound. In a xanthinuric patient only traces of 5-hydroxypyrazinoic acid were found 12 hours after 3 g pyrazinamide were given. These finding confirms that pyrazinoic acid is oxidised through the the action of xanthine oxidase. Both the clearances of hypoxanthine and of xanthine are as rapid as that of endogenous creatinine in a xanthinuric patient. But the effects of pyrazinamide are different on both purine bases. Urinary excretion of hypoxanthine is slightly but not significantly reduced while excretion of xanthine is decreased by about 75%. Evidence was demonstrated that pyrazinoic acid is likely the agent causing xanthine retention. These results suggest that the mechanisms of renal transport of xanthine and hypoxanthine are different.
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PMID:Study of urinary pyrazinamide metabolites and their action on the renal excretion of xanthine and hypoxanthine in a xanthinuric patient. 66 78

The hypouricemic effect of benzbromarone has been investigated in six subjects. Benzbromarone increased urate: creatinine by 371 per cent over control values at two to four hours after administration. Over a 24 hour period, the mean serum uric acid decreased from a control value of 7.8 +/- 0.8 to 4.3 +/- 0.6 mg/dl. This uricosuric effect was completely reversed by pyrazinamide, partially inhibited by acetylsalicyclic acid and sulfinpyrazone, and was not accompanied by an elevation of the creatinine clearance or an inhibition of urate binding to plasma protein. In vitro studies showed only 22 per cent inhibition of urate binding by benzbromarone five muM, a concentration which is transiently reached in man. Kinetic studies of human liver xanthine oxidase demonstrated non-competitive inhibition with variable hypoxanthine and a Ki slope of 8.5 muM. The Ki slopes for benzarone and allopurinol were 19.0 muM and 0.05 muM respectively. There was no elevation of the urinary oxypurines following benzbromarone ingestion. These observations suggest that only the renal tubular activity of benzbromarone is relevant to its hypouricemic effects in man. (J Rheumatol 2: 437-445, 1975).
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PMID:The pharmacology of hypouricemic effect of benzbromarone. 120 75

Xanthine oxidase catalyzes the biotransformation of many drugs, including the thiopurines and methyl-xanthines. We used a sensitive radiochemical assay to determine optimal conditions for the assay of human liver xanthine oxidase activity. We then used those assay conditions to study the nature and extent of individual variation of xanthine oxidase activity in 189 samples of hepatic tissue from patients undergoing clinically indicated partial hepatectomy or open liver biopsy. The average hepatic xanthine oxidase activity was 21% higher in samples from male patients than in those from female patients (1.27 +/- 0.43 [mean +/- SD, n = 92] versus 1.05 +/- 0.38 U/gm tissue [n = 97, p less than 0.0001], respectively). Seventy-nine of these tissue samples had been obtained from patients with normal liver function studies and normal serum creatinine values. Average xanthine oxidase activity in these 79 samples remained approximately 20% higher for men than for women (1.35 +/- 0.38 versus 1.12 +/- 0.33 U/gm tissue, respectively). Probit analysis of the data for samples from patients with normal liver function studies and normal creatinine values suggested the presence of a subgroup of samples with relatively low xanthine oxidase activity in 21% (9 of 42) of male patients and 27% (10 of 37) of female patients. These observations may have implications with regard to individual variation in the biotransformation of drugs metabolized by xanthine oxidase.
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PMID:Human liver xanthine oxidase: nature and extent of individual variation. 175 10

The molybdenum (Mo) levels in the plasma and urine of 30 premature and 15 full-term infants have been compared with the Mo intakes and urine uric acid excretion (uric acid/creatinine ratio) produced by the Mo enzyme xanthine oxidase. The Mo intakes of full-term infants were 41 +/- 14 nmol/kg/day (mean +/- SEM). In the premature group breast milk supplied significantly less Mo (4.3 +/- 0.4 nmol/kg/day) than infant formulas (101 +/- 31 nmol/kg/day) or premature formula (255 +/- 13 nmol/kg/day). When fed breast milk, the preterm infants displayed similar or higher plasma and urine Mo and urine uric acid levels than formula-fed infants. For the whole preterm group a significant correlation was determined for urine Mo levels and Mo intakes as well as for plasma Mo and uric acid excretion. The bioavailability of breast milk Mo seems to be higher than formula Mo according to the Mo levels and to their statistical link with uric acid excretion which could be proposed as a functional index of Mo status. These parameters displayed similar values in breast milk-fed prematures and control full-term infants. The Mo needs of formula-fed premature newborns remain to be defined using complete balance trials.
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PMID:Molybdenum in the premature infant. 207 21

Uric acid, as the end-product of purine metabolism in humans, presents a clinical problem because of its relative insolubility, particularly in the acid environment of the distal nephron of the kidney. As a result, states of enhanced purine catabolism increase the urate load on the kidney, leading to intrarenal precipitation. Major causes of increased purine metabolism are malignancies with rapid cell turnover, such as leukemias and lymphomas, and the added acceleration of cell lysis that occurs with chemotherapy and radiation. Serum urate levels rise rapidly, and acute renal failure occurs as a consequence of tubular deposition of urate and uric acid. The keys to the diagnosis of acute uric acid nephropathy are the appropriate clinical setting of increased cell lysis, oliguria, marked hyperuricemia, and hyperuricosuria. A urinary uric acid-to-creatinine ratio greater than 1 helps to distinguish acute uric acid nephropathy from other catabolic forms of acute renal failure in which serum urate is elevated. Preventive treatment involves pharmacologic xanthine oxidase inhibition with allopurinol and alkaline diuresis. Occasionally, acute renal failure occurs despite allopurinol because of the tubular precipitation of the precursor metabolites, such as xanthine, which accumulate with xanthine oxidase inhibition. Dialysis therapy may be required both to correct azotemia and to reduce the body burden of urate. Hemodialysis is preferred because it can achieve greater clearance than other dialysis modes.
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PMID:Acute uric acid nephropathy. 219 58

Despite efficient revascularisation procedures for vascular disease, the limb can occasionally be lost following reperfusion. One contributing factor might be the formation of oxygen free radicals. This study attempts to describe the conditions necessary for oxy-radical formation from adenine nucleotide breakdown products and the role of plasma creatine content as a marker of cellular injury. Twelve patients undergoing aortic reconstructive surgery were studied. Only partial ischaemia of the lower limbs was induced by the aortic clamping, since varying degrees of collateral circulation existed. Radial arterial and external iliac venous blood was obtained simultaneously before, during and after cross-clamping of the aorta, and plasma levels of ATP, ADP, hypoxanthine, phosphocreatine, creatine, creatinine and lactate measured using luminescence and spectrophotometry. Venous creatine content increased during ischaemia and was doubled 30 min after recirculation. This increase was possibly due to leakage following cellular injury agreeing with a previously observed decrease in muscle tissue creatine content. The iliac arterio-venous difference of hypoxanthine and lactate markedly increased immediately post-ischaemia, while the phosphocreatine difference decreased. Plasma hypoxanthine was abundant in the leg on reoxygenation. The existence of a xanthine oxidase system in skeletal muscle could produce favourable conditions for oxy-radical formation through hypoxanthine degradation, which may contribute to the known muscle tissue injury.
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PMID:Plasma metabolic disturbances and reperfusion injury following partial limb ischaemia in man. 271 61

Methylguanidine (MG), a toxin reported in uremia, is thought to be a product of creatinine oxidation. This study is designed to demonstrate the role of active oxygen in the oxidation of creatinine under conditions compatible with those found in uremia. MG synthesis is moderately stimulated by the superoxide radical derived from 3 mM hypoxanthine and 0.015 units/ml xanthine oxidase and inhibited by the addition of superoxide dismutase. This is increased markedly by the addition of 0.05% hydrogen peroxide and augmented to about 56,000 times the control rate in the presence of hydroxyl radicals derived from the reaction of 10 mM FeSO4 and 0.05% hydrogen peroxide. In addition, MG synthesis is inhibited by the addition of sorbitol, lactulose or ethanol, the scavengers of hydroxyl radicals. These results indicate that creatinine can be oxidized to MG by various species of active oxygen and that one of the mechanisms of MG synthesis is such oxidation. MG, therefore, may be a useful indicator of peroxidation in vivo.
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PMID:Active oxygen in methylguanidine synthesis. 302 53

Postischemic renal failure is a severe problem following cadaveric renal transplantation, especially if the kidney has been harvested from a non-heartbeating donor, and thereby subjected to periods of both warm and cold ischemia. It is well established that a substantial component of postischemic injury is produced by oxygen-derived free radicals generated from xanthine oxidase at reperfusion. However, the clinical potential of free radical ablative therapy is dependent upon the proportion of the total injury caused by this reperfusion mechanism, compared with the proportion resulting from ischemic injury per se. Therefore, we quantitatively evaluated these proportions in porcine kidneys subjected to various periods of warm (renal artery occlusion in situ), cold (harvest, cold preservation, and allotransplantation), and combined warm and cold ischemia. Experiments were paired, one kidney treated with either superoxide dismutase (SOD) or allopurinol for free radical ablation, the contralateral kidney serving as a control. Creatinine clearance (Ccr) was measured separately for each kidney 48 hr after reperfusion. After 1 and 2 hr of warm ischemia, Ccr dropped to 50% and 36% of normal, respectively. This was improved to 110% and 55% when SOD was given into the renal artery at reperfusion. Similarly, after 24 and 48 hr of cold ischemia, kidney function was significantly improved from 30% and 18% to 72% and 47% of normal, respectively, when allopurinol was added to the preservation solution. SOD used at harvest and again at reperfusion was particularly effective following combined warm and cold ischemia, in a situation mimicking the harvest of cadaver kidneys from a non-heartbeating donor. These findings suggest that the ablation of free radical-mediated reperfusion injury may improve posttransplant renal function sufficiently to allow expansion of the cadaveric donor pool to include non-heartbeating donors.
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PMID:Ablation of free radical-mediated reperfusion injury for the salvage of kidneys taken from non-heartbeating donors. A quantitative evaluation of the proportion of injury caused by reperfusion following periods of warm, cold, and combined warm and cold ischemia. 327 16

In order to elucidate toxic and protective mechanisms responsible for allopurinol-induced nephrotoxicity in rats, we investigated changes in plasma creatinine concentration, renal lipid peroxidation, and renal activities of xanthine oxidase, superoxide dismutase and catalase, as enzymatic factors in producing and scavenging oxygen radicals. The rats received subcutaneous injections of allopurinol in a dose of 100 mg/kg body weight, once a day for 3 days. In comparison to the control rats, the following changes were observed in the allopurinol-administered rats: an increase in plasma creatinine concentration, increases in renal contents of malonaldehyde, hypoxanthine and xanthine, and an increase of renal activity of xanthine oxidase, and decreases in renal activities of superoxide dismutase and catalase. Peaks in these changes were observed coincidentally on the third day after the administration of the drug was started. Afterwards, these parameters all returned to the control levels. These results strongly suggested that the allopurinol nephrotoxicity was attributed to the increase of lipid peroxidation which had been caused both by an increase in the ability of producing the oxygen radicals and by a decrease in the ability of scavenging the radicals.
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PMID:Possible mechanism responsible for allopurinol-nephrotoxicity: lipid peroxidation and systems of producing- and scavenging oxygen radicals. 343 94

Because of the incomplete absorption of acyclovir (ACV) when given orally in humans, efforts have been made to develop a prodrug of ACV that would be better absorbed from the gastrointestinal tract and then converted in vivo to ACV. One such compound, desciclovir (DCV), is converted to acyclovir in vivo by xanthine oxidase. We gave each of 13 healthy volunteers 250 mg (about 3.25 mg/kg of body weight) of DCV orally thrice daily for 10 days, collected serial plasma and urine specimens, and measured DCV and ACV concentrations. The absorption of DCV was at least 75%, and almost two-thirds of the administered oral dose was recovered in the urine as ACV. Peak ACV levels in plasma were about 5 micrograms/ml and were reached in less than 1 h. The levels of ACV achieved in plasma were of the same magnitude as those reported for subjects given intravenous ACV at a dose of 2.5 mg/kg and approximately 10-fold higher than levels attained after administration of 200 mg of oral ACV every 4 h as measured in previous studies. The half-life of DCV was 0.85 +/- 0.16 h, compared with 2.6 +/- 0.5 h for ACV, indicating rapid conversion of DCV to ACV. There was no substantial increase in ACV levels in plasma on day 11 compared with day 2. No serious or consistent adverse effects were noted. In particular, the creatinine level in serum did not significantly rise in any subject and remained within the normal range in all.
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PMID:Pharmacokinetics and tolerance of desciclovir, a prodrug of acyclovir, in healthy human volunteers. 367 44


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