allopurinol and Gastroesophageal-Reflux

Necrotic cell death in vivo induces a robust neutrophilic inflammatory response and the resulting inflammation can cause further tissue damage and disease. Dying cells induce this inflammation by releasing pro-inflammatory intracellular components, one of which is uric acid. Cells contain high levels of intracellular uric acid, which is produced when purines are oxidized by the enzyme xanthine oxidase. Here we test whether a non-nucleoside xanthine oxidase inhibitor, Febuxostat (FBX), can reduce intracellular uric acid levels and inhibit cell death-induced inflammation in two different murine tissue injury models; acid-induced acute lung injury and acetaminophen liver injury. Infiltration of inflammatory cells induced by acid injection into lungs or peritoneal administration of acetaminophen was evaluated by quantification with flow cytometry and tissue myeloperoxidase activity in the presence or absence of FBX treatment. Uric acid levels in serum and tissue were measured before giving the stimuli and during inflammation. The impact of FBX treatment on the peritoneal inflammation caused by the microbial stimulus, zymosan, was also analyzed to see whether FBX had a broad anti-inflammatory effect. We found that FBX reduced uric acid levels in acid-injured lung tissue and inhibited acute pulmonary inflammation triggered by lung injury. Similarly, FBX reduced uric acid levels in the liver and inhibited inflammation in response to acetaminophen-induced hepatic injury. In contrast, FBX did not reduce inflammation to zymosan, and therefore is not acting as a general anti-inflammatory agent. These results point to the potential of using agents like FBX to treat cell death-induced inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Death; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Enzyme Inhibitors; Febuxostat; Gastroesophageal Reflux; Gout Suppressants; Liver; Lung; Lung Injury; Male; Mice, Inbred C57BL; Necrosis; Neutrophil Infiltration; Peritoneum; Peritonitis; Thiazoles; Uric Acid; Xanthine Oxidase

Patients with gout have comorbidities, but the impact of these comorbidities on treatment has not been studied.. A total of 575 patients with gout were stratified according to certainty of diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification code alone (cohort I), American College of Radiology criteria (cohort II), and crystal diagnosis (cohort III). Comorbid conditions were defined according to International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified as either moderate or severe. Drug contraindications were defined as moderate or strong, based on Food and Drug Administration criteria and severity of disease.. The most common comorbidity was hypertension (prevalence 0.89). The presence of comorbidities resulted in a high frequency of contraindications to approved gout medications. More than 90% of patients had at least 1 contraindication to nonsteroidal anti-inflammatory drugs. Many patients demonstrated multiple contraindications to 1 or more gout medications. Frequently, patients were prescribed medications to which they harbored contraindications. The prevalence of patients prescribed colchicine despite having at least 1 strong contraindication was 30% (cohort I), 37% (cohort II), and 39.6% (cohort III).. Patients with gout typically harbor multiple comorbidities that result in contraindications to many of the medications available to treat gout. Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications.

Topics: Aged; Aged, 80 and over; Allopurinol; Colchicine; Comorbidity; Contraindications; Diabetes Mellitus; Drug Prescriptions; Female; Gastroesophageal Reflux; Glucocorticoids; Gout; Gout Suppressants; Hepatitis, Chronic; Humans; Hypertension; Male; Middle Aged; Prevalence; Probenecid; Renal Insufficiency, Chronic; Severity of Illness Index; Uricosuric Agents

The aetiology of idiopathic pulmonary fibrosis remains poorly understood, but recent studies have suggested that diabetes mellitus and gastro-oesophageal reflux may be risk factors.. To test possible associations between diabetes mellitus and gastro-oesophageal reflux with idiopathic pulmonary fibrosis in the general population.. We designed a case-control study in the setting of UK general practices contributing data to The Health Improvement Network primary care database (THIN). We selected patients over 40 years of age with a first diagnosis of idiopathic pulmonary fibrosis, and up to 4 controls per case matched by age, gender, and general practice. We estimated odds ratios for exposure to gastro-oesophageal reflux, gout, hypercholesterolaemia and diabetes mellitus using conditional logistic regression. We explored the role of confounding by smoking habit, socio-economic status, and medication with prednisolone.. Amongst our 920 cases we found increased risks of use of insulin (odds ratio (OR) 2.36; 95% confidence interval (CI) 1.46-3.83) and use of ulcer drugs (OR 2.20; 95% CI 1.88-2.58). These were almost unchanged when we excluded cases and controls who had been prescribed prednisolone. We found no association with hypercholesterolaemia or gout, nor with smoking status or socio-economic status.. The study provides further evidence of an association between idiopathic pulmonary fibrosis and both diabetes mellitus and gastro-oesophageal reflux.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Antacids; Anti-Inflammatory Agents; Diabetes Complications; Diabetes Mellitus; Epidemiologic Methods; Family Practice; Female; Gastroesophageal Reflux; Humans; Hypoglycemic Agents; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Prednisolone; Smoking; United Kingdom