The objective is to assess the effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats. Male Wistar rats, 8-week-old, were categorized into four groups, which were the control (n = 9), diabetes (n = 9), infliximab-treated diabetes (n = 10), and FR167653-treated diabetes (n = 9) groups. Diabetes was induced by intraperitoneal injection of STZ (40 mg/kg). Thereafter, infliximab was injected intraperitoneally once a month (5.5 mg/kg) and FR167653 was administered orally by mixing with the rat chow (0.08%). The effects of infliximab and FR167653 on urinary albumin excretion were observed for 12 weeks. Body weight, blood sugar, 24-h urinary TNF-alpha, and 24-h urinary albumin/creatinine ratio (Ualb/Ucr) levels were determined at 1, 4, 8, and 12 weeks after the STZ-injection. Treatment of rats with STZ caused a significant loss of body weight, as well as polyuria and hyperglycemia within 1 week, while the urinary excretions of albumin and TNF-alpha were increased. Neither infliximab nor FR167653 affected body weight or blood sugar levels, whereas both decreased urinary albumin excretion, together with a modest decrease in the urinary excretion of TNF-alpha. These results suggest a role of TNF-alpha in the pathogenesis of diabetic nephropathy and show that TNF-alpha inhibition is a potential therapeutic strategy.
Objective: To assess the effect of a combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism in hypertriglyceridaemic and/or hypertensive patients with gout. Methods: Twenty seven patients with gout were included in a fenofibrate plus anti-hyperuricaemic agents combination study, and 25 in a losartan plus anti-hyperuricaemic agents combination study. Serum uric acid concentration, uric acid clearance, and 24 hour urinary uric acid excretion were measured before and two months after the addition of fenofibrate (300 mg once daily) or losartan (50 mg once daily) to anti-hyperuricaemic agents. Results: Combination therapy of fenofibrate or losartan with anti-hyperuricaemic agents, which included benzbromarone (50 mg once daily) or allopurinol (200 mg twice a day), significantly reduced serum uric acid concentrations in accordance with increased uric acid excretion. Conclusion: A combination of fenofibrate or losartan with anti-hyperuricaemic agents is a good option for the treatment of gout patients with hypertriglyceridaemia and/or hypertension, though the additional hypouricaemic effect may be modest. P atients with gout often have complications of visceral fat obesity, hypertension, hyperlipidaemia, and impaired glucose tolerance.
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