allopurinol and Metabolic-Diseases

Xanthine (3,7-dihydro-purine-2,6-dione) is generated from guanine by guanine deaminase and hypoxanthine by xanthine oxidase (XOD). The determination of xanthine in meat indicates its freshness, while its level in serum/urine provides valuable information about diagnosis and medical management of certain metabolic disorders such as xanthinuria, hyperurecemia, gout and renal failure. Although chromatographic methods such a HPLC, capillary electrophoresis and mass spectrometry are available for quantification of xanthine in biological materials, these suffer from certain limitations such as complexity, time consuming sample preparation and requirement of expensive apparatus and trained persons to operate. Immobilized XOD based biosensors have emerged as simple, rapid, sensitive and economic tools for determination of xanthine in food industries and clinical diagnosis. This review article describes the various immobilization methods of XOD and different matrices used for construction of xanthine biosensors, their classification, analytical performance and applications along with their merits and demerits. The future perspectives for improvement of present xanthine biosensors are also discussed.

Topics: Biosensing Techniques; Clinical Chemistry Tests; Enzymes, Immobilized; Food Analysis; Humans; Metabolic Diseases; Xanthine; Xanthine Oxidase

Topics: Acidosis; Acute Kidney Injury; Allopurinol; Aluminum Hydroxide; Burkitt Lymphoma; Child; Humans; Hypercalcemia; Hyperlipidemias; Hypertension, Renal; Hypoglycemia; Lymphoma; Male; Mannitol; Metabolic Diseases; Phosphorus Metabolism Disorders; Uric Acid; Xanthines

Topics: Adenosine Triphosphate; Allopurinol; Animals; Carbohydrate Metabolism, Inborn Errors; Fructose; Humans; Metabolic Diseases; Metabolism, Inborn Errors; Myocardial Infarction; Oxidation-Reduction; Purine Nucleotides; Ribonucleotides; Shock, Hemorrhagic; Uric Acid

Topics: Adenine; Allopurinol; Carbon Radioisotopes; Erythrocytes; Fibroblasts; Glucosephosphate Dehydrogenase; Glutamine; Glutathione Reductase; Gout; Guanine; Humans; Hypoxanthines; Lesch-Nyhan Syndrome; Liver; Metabolic Diseases; Molecular Weight; Orotic Acid; Pentosyltransferases; Purines; Uric Acid; Xanthine Oxidase

Topics: Allopurinol; Anemia, Pernicious; Animals; Azauridine; Carboxy-Lyases; Fatty Liver; Female; Humans; Infant, Newborn; Jaundice, Neonatal; Lipids; Metabolic Diseases; Metabolism, Inborn Errors; Milk; Myocardial Infarction; Ornithine Carbamoyltransferase; Orotic Acid; Pentosyltransferases; Pregnancy; Uric Acid

Topics: Alcoholism; Australia; Bloodletting; Gastric Juice; Hemochromatosis; Humans; Intestinal Absorption; Intestinal Mucosa; Iron; Liver Cirrhosis; Metabolic Diseases; Prognosis; Xanthine Oxidase

Topics: Allopurinol; Chondrocalcinosis; Colchicine; Diagnosis, Differential; Diet Therapy; Gout; Humans; Inosine Nucleotides; Joint Diseases; Metabolic Diseases; Orotic Acid; Purines; Urate Oxidase; Uric Acid; Uricosuric Agents

To compare the characteristics of female versus male gout patients and assess urate-lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout.. This was a retrospective analysis of 4,101 hyperuricemic (serum urate [sUA] level ≥8.0 mg/dl) gout subjects enrolled in 3 phase III comparative trials and randomized to receive placebo, febuxostat (40 mg, 80 mg, 120 mg, or 240 mg daily), or allopurinol (100 mg, 200 mg, or 300 mg daily, based on renal function). Baseline demographics and characteristics were summarized and compared between female and male subjects. Urate-lowering efficacy, which was defined as the proportion of subjects with sUA levels <6.0 mg/dl at final visit, was assessed for all subjects and, among women, according to baseline renal function.. Female gout subjects (n = 226) were older with significantly higher rates of obesity and metabolic and cardiovascular comorbidities than their male counterparts. The percentage of female subjects with sUA levels <6.0 mg/dl at final visit was 0% in the placebo group, 54.3%, 85.1%, 81.0%, and 100.0% in the febuxostat 40 mg, 80 mg, 120 mg, and 240 mg groups, respectively, and 45.9% in the allopurinol group. Similar patterns of urate-lowering efficacy rates were observed when stratified by renal function. Among all the female subjects, febuxostat 80 mg was significantly more efficacious than allopurinol (P < 0.001). Rates of adverse events (AEs) were low. The most frequently reported AEs were upper respiratory tract infections, musculoskeletal/connective tissue disorders, and diarrhea.. These data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Cardiovascular Diseases; Comorbidity; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Illinois; Male; Metabolic Diseases; Middle Aged; Obesity; Retrospective Studies; Sex Factors; Thiazoles; Treatment Outcome; Uric Acid; Young Adult

The results of animal experiments and clinical observations concerning the pathological role of hyperuricaemia and the effect of allopurinol treatment in acute metabolic disturbances and critically ill patients is reported. In uricase enzyme blocked rats treated by oxonic acid, urate nephropathy could be elicited by endogenous purine catabolism in shock. Hyperuricaemia aggravated the shock, while allopurinol increased the survival time. In shock resistant rats hyperuricaemia did not develop when shock was elicited. Allopurinol prevented hyperuricaemia and increased the physical performance of swimming rats, while in experimental DIC allopurinol reduced markedly the hyperuricaemia and the kidney damage. In clinical studies a close correlation was observed between the degree of hyperuricaemia and the severity of illness. Serum uric acid values were lowered in cases treated by peritoneal dialysis. In randomized control studies of newborns with IRDS the survival rate was improved by allopurinol treatment. In critically ill patients with various illnesses allopurinol prevented the progression of the pathological process and improved the clinical condition. The effect of allopurinol in acute clinical metabolic disturbances may be due to its protection against the renal damage by hyperuricaemia and against purine loss by inhibition of xanthine oxidase during the hypoxic stress and the enhancement of hypoxanthine salvage by HGPRT. Allopurinol reduced the production of superoxide radicals and thus the effect of injury may also be moderated by xanthine oxidase blockade.

Topics: Acute Disease; Age Factors; Allopurinol; Animals; Child; Clinical Trials as Topic; Humans; Infant; Infant, Newborn; Kidney; Metabolic Diseases; Rats; Respiratory Distress Syndrome, Newborn; Uric Acid

A series of 1-phenylpyrazoles was evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds prepared, 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (Y-700) had the most potent enzyme inhibition and displayed longer-lasting hypouricemic action than did allopurinol in a rat model of hyperuricemia induced by the uricase inhibitor potassium oxonate.

Topics: Allopurinol; Animals; Area Under Curve; Gout; Gout Suppressants; Male; Metabolic Diseases; Models, Animal; Pyrazoles; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Urate Oxidase; Uric Acid; Xanthine Oxidase

Thirty-three children ranging from 2 weeks to 12 years of age were selected for allopurinol loading, 16 on the basis of an increased urinary ourotate excretion detected by routine organic acid analysis (group A), and 17 for clinical reasons suggesting a urea cycle defect (group B). The allopurinol load test proved positive in 13 of 16 patients from group A, mean peak orotate 64.0 mumol/mmol creatinine (upper limit of reference range, 13.2) and 11 of 17 patients from group B, mean peak orotate 41.0 mumol/mmol creatinine (upper limit of reference range, 13.2). Thorough investigation of these patients including urinary and plasma amino acid analysis and, in 17 cases, liver biopsy for histology and measurement of ornithine carbamyltransferase (OCT) and carbamyl-phosphate synthetase (CPS) activity failed to identify any evidence of a urea cycle disorder. However, muscle biopsies performed in 11 patients showed some evidence of mitochondrial disease in four cases, two defined on the basis of reduced respiratory chain enzyme activity and two on the basis of mtDNA abnormalities. These findings indicate that an increased excretion of orotate in sick children may not be uncommon and that a positive allopurinol load test result may not indicate a specific inherited urea cycle defect. In addition, these results raise the interesting possibility that defective ureagenesis may be a feature of mitochondrial disease in some individuals.

Topics: Allopurinol; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Metabolic Diseases; Mitochondria; Muscles; Orotic Acid; Predictive Value of Tests; Sensitivity and Specificity; Urea; Uridine

With this rapid (20 min), sensitive (0.1 mumol/L), and reproducible reversed-phase "high-performance" liquid-chromatographic (HPLC) method hypoxanthine, xanthine, uric acid, allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine), and oxypurinol(4,6-dihydroxypyrazolo[3,4-d]pyrimidine) concentrations can be determined simultaneously in de-proteinized serum. We use an Amicon MPS-1 centrifugal ultrafiltration device, then inject the de-proteinized ultrafiltrate into a Toyosoda ODS-120A HPLC column and elute with a mobile phase consisting of potassium phosphate buffer (40 mmol/L, pH 2.2) containing 20 mL of methanol per liter. We used this method to investigate purine metabolism in 10 cases of hypouricemia (uric acid concentration in serum less than 60 mumol/L).

Topics: Adult; Aged; Allopurinol; Chromatography, High Pressure Liquid; Colorimetry; Female; Humans; Hypoxanthine; Hypoxanthines; Male; Metabolic Diseases; Middle Aged; Oxypurinol; Purines; Uric Acid; Xanthine; Xanthines

Topics: Amidophosphoribosyltransferase; Diet; Gout; Humans; Hypoxanthine Phosphoribosyltransferase; Kidney; Kidney Failure, Chronic; Metabolic Diseases; Uric Acid; Uricosuric Agents; Xanthine Oxidase

In 35 patients with uricopathy (arthritis urica, essential hyperuricaemia) the serum uric acid values, consumption of alcohol, overweight, hypertension and liver enzyma under dietary and medicamentous therapy (allopurinol) were investigated. Here during an observation lasting 12--48 months allopurinol proved as a well tolerable uricostatic drug which was sufficiently effective also with a considerable exogenic purine application. We only insufficiently succeeded in influencing overweight and alcohol consumption as well as hypertension by rheumatic dispensary care and family doctor.

Topics: Adult; Aged; Alcohol Drinking; Allopurinol; Ambulatory Care; Female; Humans; Male; Metabolic Diseases; Middle Aged; Obesity; Uric Acid

Two hundred two recurrent calcium oxalate stone-forming patients with idiopathic hypercalciuria or hyperuricosuria, or both, were treated for an average of 2.91 years (1 to 7 years) with thiazide or allopurinol, or both. The frequency of new stone formation was drastically reduced. During the treatment period of 625 patient years, 220.0 new stones should have occurred, whereas 22 were actually formed (chi-square=178, P less than 0.001). Thirty-four patients without discernible metabolic disturbances and treated only with increased fluid intake and dietary advice formed 29 new stones compared to a predicted 33.2 stones (87.3%). Thirty similar patients treated with thiazide and allopurinol formed six stones compared to a predicted 31.8, P less than 0.001. Chronic reversal of idiopathic hypercalciuria and hyperuricosuria with thiazide and allopurinol is an effective way to prevent recurrent calcium oxalate stones. Conservative measures are only of marginal effectiveness in treating metabolically normal stone forming patients; however, thiazide and allopurinol appear to decrease new stone formation.

Topics: Allopurinol; Calcium; Cystoscopy; Female; Hospitalization; Humans; Kidney Calculi; Male; Metabolic Diseases; Oxalates; Recurrence; Trichlormethiazide; Uric Acid

De novo purine biosynthesis has been investigated in circulating blood lymphocytes in vitro. N-formyl-glycinamide ribonucleotide (FGAR) has been mesured using 14C-formate incorporation in the presence of azaserine, a metabolic inhibitor blocking the metabolical pathway at the level of FGAR synthesis. Such a synthesis was measured in 20 healthy controls, 24 patients with primary gout (11 on allopurinol therapy) and 26 patients with chronic renal failure and secondary hyperuricemia (8 on allopurinol therapy). Among gouty patients without allopurinol therapy, FGAR synthesis was normal in 5 and increased in the others. FGAR synthesis was decreased in patients with renal failure whatever the therapy. However, FGAR synthesis remained increased in patients with a primary gout complicated with renal insufficiency. The test we propose for de novo purine biosynthesis measurement is simple and of value to analyse the patho-physiology of hyperuricemia and its therapy. The test allows an acurate discrimination between primary and secondary hyperuricemia in the presence of renal insufficiency.

Topics: Adult; Allopurinol; Azaserine; Carbon Radioisotopes; Female; Formates; Gout; Humans; In Vitro Techniques; Kidney Failure, Chronic; Male; Metabolic Diseases; Methods; Middle Aged; Purines; Ribonucleotides; Uric Acid

Topics: Allopurinol; Humans; Metabolic Diseases; Probenecid; Sulfinpyrazone; Uric Acid

Topics: Adult; Allopurinol; Humans; Metabolic Diseases; Orotic Acid; Ribonucleotides

Topics: Allopurinol; Anti-Inflammatory Agents; Gout; Humans; Metabolic Diseases; Uric Acid

Topics: Adult; Allopurinol; Benzoates; Benzofurans; Bromine; Gout; Gout Suppressants; Humans; Male; Metabolic Diseases; Uric Acid

Topics: Acute Disease; Adult; Allopurinol; Anti-Bacterial Agents; Bacterial Infections; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Metabolic Diseases; Prednisone; Remission, Spontaneous; Thioguanine; Uric Acid; Vincristine

Topics: Allopurinol; Gout; Humans; Metabolic Diseases; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Alloxan; Feedback; Gout; Guanine; Humans; Hypoxanthines; Kidney; Male; Metabolic Diseases; Middle Aged; Pentosyltransferases; Purines; Uric Acid; Uricosuric Agents; Xanthines

Topics: Adult; Allopurinol; Calcium; Female; Follow-Up Studies; Humans; Kidney Calculi; Male; Metabolic Diseases; Middle Aged; Radiography; Uric Acid

Topics: Adrenergic beta-Antagonists; Allopurinol; Blood Pressure; Contraceptives, Oral; Diuretics; Family Practice; Female; Humans; Hypertension; Mass Screening; Metabolic Diseases; Methyldopa; Middle Aged; Physician-Patient Relations; Uric Acid; Urography

Topics: Allopurinol; Diabetes Mellitus; Diet Therapy; Gout; Humans; Kidney Diseases; Metabolic Diseases; Uric Acid; Uricosuric Agents; Vascular Diseases

Topics: Adolescent; Adrenocortical Hyperfunction; Adult; Aged; Allopurinol; Child; Diet Therapy; Female; Femur Head; Femur Head Necrosis; Hematologic Diseases; Humans; Hyperlipidemias; Lipids; Liver Diseases; Male; Metabolic Diseases; Middle Aged; Phospholipids; Uric Acid

Topics: Acute Disease; Allopurinol; Colchicine; Diagnosis, Differential; Female; Gout; Humans; Indomethacin; Male; Metabolic Diseases; Phenylbutazone; Uric Acid

Topics: Allopurinol; Gout; Humans; Kidney Calculi; Metabolic Diseases; Multiphasic Screening; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Calcium; Creatinine; Cystinuria; Diuresis; Humans; Kidney; Kidney Calculi; Magnesium; Metabolic Diseases; Methylene Blue; Oxalates; Penicillamine; Phosphates; Uric Acid; Urinary Tract Infections; Urine; Water-Electrolyte Balance

Topics: Acute Disease; Allopurinol; Chronic Disease; Colchicine; Gout; Humans; Indomethacin; Metabolic Diseases; Phenylbutazone; Salicylates; Uric Acid; Uricosuric Agents

Topics: Adolescent; Allopurinol; Blood Urea Nitrogen; Child; Child, Preschool; Female; Humans; Leukocyte Count; Male; Metabolic Diseases; Neoplasms; Purines; Uric Acid; Xanthine Oxidase

Topics: Adult; Aged; Allopurinol; Female; Gout; Humans; Hypoxanthines; Male; Metabolic Diseases; Middle Aged; Uric Acid; Uricosuric Agents; Urinary Calculi; Xanthine Oxidase; Xanthines

Topics: Adult; Allopurinol; Carboxy-Lyases; Creatinine; Cyanides; Female; Glycolates; Glyoxylates; Humans; Male; Metabolic Diseases; Oxalates

Topics: Adolescent; Allopurinol; Child; Dietary Proteins; Disulfiram; Enzyme Inhibitors; Female; Folic Acid; Humans; Male; Metabolic Diseases; Oxalates; Pyridoxine; Vitamin K