We hypothesized that the six-monthly application of silver diamine fluoride (SDF) can arrest the development of caries in the deciduous dentition of six-year-old schoolchildren and prevent caries in their first permanent molars. A prospective controlled clinical trial was conducted on the efficacy of a 38% SDF solution for caries reduction. Four hundred and twenty-five six-year-old children were divided into two groups: One group received SDF solution in primary canines and molars and first permanent molars every 6 mos for 36 mos. The second group served as controls. The 36-month follow-up was completed by 373 children. The mean number of new decayed surfaces appearing in primary teeth during the study was 0.29 in the SDF group vs. 1.43 in controls. The mean of new decayed surfaces in first permanent molars was 0.37 in the SDF group vs. 1.06 in controls. The SDF solution was found to be effective for caries reduction in primary teeth and first permanent molars in schoolchildren.
BACKGROUND AND PURPOSEActivation of the intrarenal renin-angiotensin system (RAS) and increased renal medullary hydrogen peroxide (H2O2) contribute to hypertension. We examined whether H2O2 mediated hypertension and intrarenal RAS activation induced by angiotensin II (Ang II). ) was given to Ang II-treated rats, from day 7 to day 14. Systolic blood pressure was measured throughout the study. H2O2, angiotensin AT1 receptor and Nox4 expression and nuclear factor-kB (NF-kB) activation were evaluated in the kidney. Plasma and urinary H2O2 and angiotensinogen were also measured.
EXPERIMENTAL APPROACH
KEY RESULTSAng II increased H2O2, AT1 receptor and Nox4 expression and NF-kB activation in the renal medulla, but not in the cortex. Ang II raised plasma and urinary H2O2 levels, increased urinary angiotensinogen but reduced plasma angiotensinogen. PEG-catalase had a short-term antihypertensive effect and transiently suppressed urinary angiotensinogen. PEG-catalase decreased renal medullary expression of AT1 receptors and Nox4 in Ang II-infused rats. Renal medullary NF-kB activation was correlated with local H2O2 levels and urinary angiotensinogen excretion. Loss of antihypertensive efficacy was associated with an eightfold increase of plasma angiotensinogen.
CONCLUSIONS AND IMPLICATIONSThe renal medulla is a major target for Ang II-induced redox dysfunction. H2O2 appears to be the key mediator enhancing intrarenal RAS activation and decreasing systemic RAS activity. The specific control of renal medullary H2O2 levels may provide future grounds for the treatment of hypertension.
AbbreviationsAng II, angiotensin II; DPI, diphenylene iodonium; EMSA, electrophoretic mobility shift assay; fEMSA, fluorescent electrophoretic mobility shift assay; GPx, glutathione peroxidase; L-NAME, nitro-L-arginine methylester; MPO, myeloperoxidase; PEG, polyethylene glycol; RAS, renin-angiotensin system; RFU, relative fluorescence units; ROS, reactive oxygen species; SBP, systolic blood pressure; SHR, spontaneously hypertensive rats; SOD, superoxide dismutase BJP British Journal of Pharmacology
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