No abstract

Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.

No abstract

Repeated transfusions for the treatment of thalassaemia major cause an insult to the patient's immune system and provoke post-transfusion purpura and haemolytic reactions that can be severe and life threatening. This study aims to investigate the presence of erythrocyte autoantibodies and CD59 expression on the surface of red blood cells (RBCs) in patients with beta-thalassaemia major, and any relationship to frequency of blood transfusion. The study looks at a total of 49 patients (both children and adults) with beta-thalassaemia major, divided into four groups according to the number of blood transfusions received and the presence or absence of the spleen. Glycosylated haemoglobin, Coombs' test (direct and indirect) and CD59 level on the RBC surface (by flow cytometry) are estimated in all patients studied. Glycosylated haemoglobin level was significantly lower in those who had received less than 10 units of blood (group III) than in those who had received more than 25 units of blood and had undergone splenectomy (group Ib), and was significantly lower in those who had received 10-25 units of blood (group II) than in those that comprised group Ib (F=3.598, P=0.0205). Considering CD59 expression, there was a marked difference between the groups. Expression was highest in group III and diminished progressively through groups II, Ia (polytransfused, non-splenectomised) and Ib (F=19.83, P=0.0000). No relationship was observed between CD59 expression and either blood group or gender. A significant negative correlation between CD59 expression and reticulocyte percentage (r=-0.538, P=0.000) and normoblast count (r=-0.5455, P=0.000) was found. A negative correlation between lymphocytosis and CD59 expression was also noted in groups III (r=-0.745, P=0.013), Ia (r=-0.5849, P=0.022) and Ib (r=-0.6711, P=0.009). Direct Coombs' test was positive in only one patient in group Ib, who also showed the lowest haemoglobin level. Thalassaemia patients exposed to multiple antigens through repeated blood transfusions showed lower CD59 expression than did those who had received fewer transfused units, which is a good method of detecting potential autoantibodies. Furthermore, a negative Coombs' test does not exclude autoimmunisation in such patients.

No abstract