ABSTRACT
PURPOSE: The phosphodiesterases (PDEs) are critical components in the cyclic AMP/protein kinase A and the cyclic GMP/phosphokinase G signaling pathways. The cAMP and cGMP pathways are regulated by activation and dissolution of PDEs. Benfotiamine, a lipophilic derivation of thiamine is known an activator of transketolase, is reported to prevent diabetic nephropathy by decreasing proteinuria and reducing oxidative stress. We did this study to investigate the effect of benfotiamine in type 2 diabetic rat kidneys. MATERIALS AND METHODS: We prepared 10 male Long-Evans Tokushima Fatty (LETO: control) and 20 male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which developed non-insulin-dependent diabetes mellitus (NIDDM) naturally. An oral glucose tolerance test confirmed diabetic development in the OLETF rats at 26 weeks. We classified 10 of the OLETF rats into Group I, the no treatment group and the other 10 into Group II, the treatment group. Group II received 100 mg/kg benfotiamine after developing DM. At 44 weeks, we checked kidney weight, serum glucose, free testosterone, insulin, total cholesterol, and triglyceride before sacrifice. We designed the primers for rat PDE5, PDE5A1, and PDE5A2 genes were carried out semiquantitive multiplex RT-PCR. Immunohistochemical staining was performed for monoclonal mouse anti-cGB-PDE5 and mouse monoclonal anti-smooth muscle alpha-actin. RESULTS: For the Control Group, Group I, and Group II, kidney weight was 2.13+/-0.23, 2.08+/-0.22, and 1.94+/-0.44 g; serum glucose was 279.50+/-56.79, 338.00+/-55.00, and 314.71+/-139.1 mg/dl; free testosterone was 1.46+/-1.08, 1.05+/- 0.42, and 0.72+/-0.56 pg/dl; insulin was 1.03+/-0.43, 1.09+/-0.83, and 1.15+/-1.08 ng/ml; total cholesterol was 86.83+/-4.79, 132.00+/-7.69, and 118.14+/-30.93 mg/dl; and triglyceride was 78.83+/-16.47, 177.83+/-75.62, and 194.57+/-92.57 mg/dl, respectively. All three groups expressed PDE5, PDE5A1, PDE5A2 mRNA, but Group I PDE5 mRNA expression was lower than that of Group C, II. However, the expression of PDE5A1 and PDE5A2 mRNA was not significantly different among the three groups. CONCLUSIONS: Serum cholesterol, triglyceride, and glucose were significantly higher in OLETF than in LETO rats. The PDEs were lower in diabetic rat (OLETF) kidneys and PDEs may play a significant role in the development of diabetic renal complications. Benfotiamine is suggested to increase expression of PDE5 mRNA in the type 2 diabetes rat kidney, but the difference in expression levels between PDE5A1 and PDE5A2 was not significant. These findings suggest that benfotiamine may play a specific role in diabetic changes of the rat kidney via a PDE5-related pathway, but it is not clear whether subtype PDE5A1 and PDE5A2 genes play a specific role.
Subject(s)
Animals , Humans , Male , Mice , Rats , Actins , Cholesterol , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Diethylstilbestrol , Glucose , Glucose Tolerance Test , Insulin , Kidney , Muscles , Oxidative Stress , Phosphoric Diester Hydrolases , Phosphotransferases , Protein Isoforms , Proteinuria , Rats, Inbred OLETF , RNA, Messenger , Testosterone , Thiamine , TransketolaseABSTRACT
PURPOSE: It is well known that nocturia is a bothersome symptom that affects the quality of life (QoL). However, it is not known how much of a decrease in nocturnal frequency is needed to improve the QoL. We determined the minimal change in nocturnal frequency affecting the QoL of patients with nocturia. MATERIALS AND METHODS: A total of 87 patients with BPH and nocturia were treated with alpha-blocker and desmopressin for 8 weeks. Considering that the minimal clinically important change (MCIC) is different according to the baseline value, we divided the patients into two groups (group I, II). Group I had mild to moderate nocturia with voiding or =4 times per night. Voiding diaries and King's Health Questionnaires (KHQs) were evaluated before and after treatment. To determine the minimal change in nocturia affecting the QoL, statistical analysis was performed by Student's t-test and ANOVA test with the change in KHQ score according to decreased numbers of nocturnal frequency. RESULTS: Groups I and II had 35 and 52 patients, respectively. The minimal decrease in nocturnal frequency associated with a statistically significant decrease in sleep/energy domain scores was 1 time in Group I and 2 times in Group II. CONCLUSIONS: These data show that decreases in nocturia of at least 1 time in patients with mild to moderate nocturia ( or =4 times/night) are needed to improve the QoL.