Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Involvement of free radicals and their scavenging enzymes in mice pulmonary thromboembolism, induced by intravenous infusion of collagen and adrenaline, has been studied. Malonaldehyde (MDA) and activities of xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) were estimated in platelets, heart and lung homogenates. MDA increased in all the tissues sharply, while animals showed 70-80% thrombocytopenia. Xanthine oxidase activity in these animals increase significantly in heart. However, increased SOD activity and decreased catalase activity was observed in platelets. Intravenous administration of superoxide dismutase (5 mg/kg), catalase (5 mg/kg) and mannitol (200 mg/kg) protected the mice against pulmonary thromboembolism. The importance of free radicals in mice pulmonary thromboembolism has been demonstrated.
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PMID:Role of free radicals in pulmonary thromboembolism in mice. 251 Mar 58

Azathioprine, a cytostatic and immunosuppressive drug in use for some 30 years, can give rise to life-threatening neutropenia and thrombocytopenia. This may be caused by unexpectedly high concentrations of cytotoxic metabolites due to abnormally slow inactivation of 6-mercaptopurine (6-MP) by thiopurine S-methyltransferase (TPMT) and/or xanthine oxidase. Low TPMT activity may be due to genetic polymorphism or interaction with drugs such as salicylic acid derivatives, while xanthine oxidase may be inhibited by allopurinol. High TPMT activity, on the other hand, may hamper cytostatic treatment. Safer and more effective treatment with azathioprine and its metabolite 6-MP becomes possible with new laboratory methods for pharmacotherapy monitoring.
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PMID:[Bone marrow depression after azathioprine. New discoveries on an old drug]. 1082 62

Atypical hemolytic-uremic syndrome (HUS) is a rare life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic injury to organs, especially the kidneys. Microvascular injury and thrombosis are the dominant histologic findings. Complement activation through the alternative pathway plays a critical role in the pathogenesis of atypical HUS. Genetic abnormalities involving complement regulatory proteins and complement components form the molecular basis for complement activation. Endothelial cell dysfunction, probably because of the effects of complement activation, is an intermediate stage in the pathophysiologic cascade. Atypical HUS has a grave prognosis. Although mortality approaches 25% during the acute phase, end-stage renal disease develops in nearly half of patients within a year. Atypical HUS has a high recurrence rate after renal transplantation, and recurrent disease often leads to graft loss. Plasma therapy in the form of plasma exchange or infusion has remained the standard treatment for atypical HUS. However, many patients do not respond to plasma therapy and some require prolonged treatment. Approved by the Food and Drug Administration in the treatment of atypical HUS, eculizumab is a humanized monoclonal antibody that blocks cleavage of complement C5 into biologically active mediators of inflammation and cytolysis. Although case reports have shown the efficacy of eculizumab, randomized clinical trials are lacking. Therapeutic strategies targeting endothelial cells have demonstrated promising results in experimental settings. Therefore, inhibitors of angiotensin-converting enzyme, HMG-CoA reductase, and xanthine oxidase as well as antioxidants, such as ascorbic acid, may have salutary effects in patients with atypical HUS.
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PMID:Atypical Hemolytic-Uremic Syndrome: A Clinical Review. 2468 22

When severe gout with tophi persists despite treatment with allopurinol, a xanthine oxidase inhibitor, the hypouricaemic drug of choice is probenecid, a uricosuric agent, in the absence of a better alternative. Pegloticase is a pegylated recombinant uricase. This enzyme catabolises uric acid into allantoin, a water-soluble substance that is excreted by the kidneys. Pegloticase has been granted EU marketing authorisation in patients who continue to have severe gout attacks despite treatment with a xanthine oxidase inhibitor such as allopurinol. Pegloticase has not been compared with probenecid nor has it been evaluated in patients who have no other treatment options. Two double-blind, randomised, placebo-controlled trials have been conducted. They lasted only 6 months and involved 212 patients in whom allopurino/therapy had failed, usually because of serious adverse effects. Pegloticase lowered uric acid levels but increased the frequency of gout flares early during treatment. At best, it had only a minor symptomatic effect on pain and disability. Its long-term effects are unknown. About 10% of patients had a serious adverse effect attributed to pegloticase, including reactions during the infusion, anaphylactic reactions, and skin infections. Thrombocytopenia and severe cardiac adverse effects are other probable adverse effects. About 90% of patients treated with pegloticase developed anti-pegloticase antibodies. Given the limited short-term symptomatic efficacy and the absence of comparative long-term evaluation, patients should not be exposed to the potentially serious adverse effects of pegloticase. Probenecid is a better choice when allopurinol is ineffective or poorly tolerated. Currently, patients with no remaining therapeutic options should simply continue to receive symptomatic treatment of gout attacks.
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PMID:Pegloticase. An excessively dangerous and inadequately evaluated hypouricaemic drug. 2516 87

Allopurinol is a xanthine oxidase inhibitor used in management of chronic gout. It acts by reducing the amount of uric acid by inhibiting purine metabolism. A middle-aged hypertensive female who was on allopurinol for 7 months presented with generalized weakness and exertional dyspnea. Investigations revealed pancytopenia: normocytic normochromic anemia (Hb-3.2g/dL, TLC-3400/mm3) and severe thrombocytopenia (Platelets-1000/mm3) with mild hepatosplenomegaly and grade 2 medico renal disease with normal cardiac status. Nutritional, hemolytic and infective causes were ruled out. She was transfused with fresh whole blood, platelets, administered empirical antibiotics and started on steroids. Initially, she responded to treatment but later developed an episode of convulsions with anuria and succumbed to leukopenic sepsis secondary to hypo/aplastic anemia probably due to allopurinol. Allopurinol is used extensively in the management of chronic gout and is well tolerated due to its safety profile. But we here report a case of allopurinol induced aplastic anemia leading to the demise of a patient. Allopurinol though safe needs careful monitoring.
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PMID:Allopurinol: Sorrow to the marrow. 3275 32