allopurinol and Central-Nervous-System-Diseases

Hereditary xanthinuria is a rare autosomal recessive disorder, with xanthine oxidase deficiency. Patients often display renal symptoms because they excrete a large amounts of xanthine in urine. An high-fluid-intake, alow-purine-food, and alkalinization of urine are effective in the patients. Molybdenum cofactor is essential for xanthine oxidase, sulfite oxidase and aldehyde oxidase. Patients with molybdenum cofactor deficiency display severe neurological symptoms, such as severe convulsions. The patients increase urinary excretions of xanthine and sulfite. Treatments are ineffective for neurological symptoms.

Topics: Central Nervous System Diseases; Coenzymes; Diagnosis, Differential; Diet Therapy; Humans; Infant, Newborn; Metalloproteins; Molybdenum Cofactors; Pteridines; Purine-Pyrimidine Metabolism, Inborn Errors; Seizures; Uric Acid; Xanthine; Xanthine Oxidase; Xanthines

: Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative.. : A multicenter study with randomized, placebo-controlled, double-blind, parallel-group comparison was carried out to evaluate the efficacy and safety of febuxostat in 103 patients with hyperuricemia (including patients with gout) in Japan.. : Subjects were treated with febuxostat (20 or 40 mg/d) or a placebo for 8 weeks. The variables evaluated were the percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 8 weeks.. : The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 91.2% in the febuxostat 40-mg/d group, 45.7% in the 20-mg/d group, and 0.0% in the placebo group. The percent changes in serum uric acid levels after 8 weeks were -44.9% in the febuxostat 40-mg/d group, -28.9% in the 20-mg/d group, and -0.6% to -0.5% in the placebo group. No severe or medically significant adverse reaction attributable to febuxostat was noted, and there was no event that could pose a clinical problem. The efficacy did not differ depending on the presence/absence of gout history.. : These results suggest that febuxostat (20 or 40 mg/d) is useful as a new means of treating hyperuricemia and is capable of reducing serum uric acid levels to 6.0 mg/dL or less (goal of treatment) with high safety regardless of the presence/absence of gout history.

Topics: Adult; Central Nervous System Diseases; Dental Enamel; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Febuxostat; Female; Follow-Up Studies; Gout; Gout Suppressants; Humans; Japan; Kidney Diseases, Cystic; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid; Xanthine Oxidase

The objective of the present study was to investigate the possible neuroprotective effect of resveratrol against streptozotocin-induced hyperglycaemia in the rat brain and medulla spinalis. Thirty adult male Wistar rats were divided into three groups as follows: control group, streptozotocin-induced diabetic-untreated group, and streptozotocin-induced diabetic resveratrol-treated group. Diabetes was induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). Three days after streptozotocin injection, resveratrol (10 mg/kg) was injected intraperiteonally daily over 6 weeks to the rats in the treatment group. Six weeks later, seven rats from each group were killed and the brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical studies (lipid peroxidation measuring malondialdehyde [MDA], xanthine oxidase [XO], nitric oxide [NO] and glutathione). MDA, XO and NO levels in hippocampus, cortex, cerebellum, brain stem and spinal cord in the streptozotocin-induced diabetic-untreated group increased significantly. Treatment with resveratrol significantly reduced MDA, XO and NO production and increased glutathione levels when compared to the streptozotocin-induced diabetic-untreated group. This study demonstrates that resveratrol is a potent neuroprotective agent against diabetic oxidative damage.

Topics: Animals; Central Nervous System Diseases; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Free Radical Scavengers; Glutathione; Hyperglycemia; Lipid Peroxidation; Male; Malondialdehyde; Medulla Oblongata; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Resveratrol; Spinal Cord; Stilbenes; Vasodilator Agents; Xanthine Oxidase

Topics: Adolescent; Allopurinol; Aminohydrolases; Athetosis; Brain; Central Nervous System Diseases; Cerebral Palsy; Chorea; Erythrocytes; Fibroblasts; Glucosyltransferases; Humans; Hypoxanthines; Intellectual Disability; Liver; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Self Mutilation; Spasm; Xanthines