Sun F, Li X, Yang C, Lv P, Li G, Xu H, Li X, Yang C, Lv P, Li G, Xu H. A role for PERK in the mechanism underlying fluoride-induced bone turnover. Toxicology. 2014 Aug 14. pii: S0300-483X(14)00139-5. doi: 10.1016/j.tox.2014.07.006.
While it has been well-documented that excessive fluoride exposure caused the skeletal disease and osteoblasts played a critical role in the advanced skeletal fluorosis. The underlying mechanism mediated these effects remain poorly understand. The present study was undertaken to examine the effect of fluoride on bone of rats and MC3T3-E1 cells in vitro. Herein we found pathological features of high bone turnover in fluoride-treated rats, which was supported by increase of osteogenic and osteoclastogenic genes expression in different stages of fluoride exposure. The skeletal toxicity of fluoride was accompanied by activation of endoplasmic reticulum (ER) stress and subsequent unfolded protein response (UPR). A novel finding of this study was that expression of PKR-like endoplasmic reticulum kinase (PERK) was the same trend with receptor activator for nuclear factor-κ B ligand (RANKL), and NF-E2 p45-related factor 2 (Nrf2) was same trend with Runt-related transcription factor 2 (Runx2) in bones of rats exposed to varied fluoride condition. Based on these data, we hypothesized that up-regulation of PERK probably played role in mediating bone turnover induced by fluoride. Action of fluoride on MC3T3-E1 cells differentiation was demonstrated through analysis of alkaline phosphatase (ALP) activity and mineralized nodules formation. Meantime, an increase of binding immunoglobulin protein (BiP) expression indicated the active ER stress in cells exposed to various dose of fluoride. Blocking PERK expression using siRNA showed the obvious decrease of osteogenic and osteoclastogenic factors expression in MC3T3-E1 cells exposed to certain dose of fluoride that could positive stimulate osteoblastic viability. In conclusion these findings underscore the importance of PERK in modulating fluoride induced bone formation and bone resorption. Understanding the link between PERK and bone turnover could probe into the mechanism underlying different bone lesion of skeletal fluorosis.
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From here it looks as though the UN Human Rights Council does not have much to do with human rights. Just an observation….
“Iraqi Christian and Yazidi representatives will gather in Geneva on Tuesday to urge the U.N.’s top human rights body to hold an urgent meeting to discuss the plight of their imperiled communities. The Human Rights Council has largely ignored the issue up until now.” click here
Tuvalu should be much more concerned about a tsunami or storm surge. In any case, this population is not sustaining itself and will not be around long enough to see a 3 foot rise in sea level whatever the cause. (click here)
“Tuvalu, a scattering of nine coral atolls that is home to about 11,000 people, is one of several Pacific nations threatened by rising seas blamed on global warming.”
“Many are barely one meter (three feet) above sea level and scientists warn that nations such as Tuvalu, Kiribati and Tokelau could disappear beneath the waves if climate change continues unabated.”
“Sounds dire. But a pesky thing called observable science keeps getting in the way of the the island nations actually sinking.” click here
Posted in Climate
Agouropoulos A, Twetman S, Pandis N, Kavvadia K, Papagiannoulis. Caries-preventive effectiveness of fluoride varnish as adjunct to oral health promotion and supervised tooth brushing in preschool children: a double-blind randomized controlled trial. J Dent. 2014 Aug 11. pii: S0300-5712(14)00234-6. doi: 10.1016/j.jdent.2014.07.020.
AIM: To evaluate the effect of biannual fluoride varnish applications in preschool children as an adjunct to school-based oral health promotion and supervised tooth brushing with 1,000ppm fluoride toothpaste.
MATERIAL AND METHODS: 424 preschool children, 2-5 year of age, from 10 different schools in Athens were invited to this double-blind randomized controlled trial and 328 children completed the 2-year program. All children received oral health education with hygiene instructions twice yearly and attended supervised tooth brushing once daily. The test group was treated with fluoride varnish (0.9% diflurosilane) biannually while the control group had placebo applications. The primary endpoints were caries prevalence and increment; secondary outcomes were gingival health, mutans streptococci growth and salivary buffer capacity.
RESULTS: The groups were balanced at baseline and no significant differences in caries prevalence or increment were displayed between the groups after one and two years, respectively. There was a reduced number of new pre-cavitated enamel lesions during the second year of the study (p=0.05) but the decrease was not statistically significant in the intention-to-treat analysis. The secondary endpoints were unaffected by the varnish treatments.
CONCLUSION: Under the present conditions, biannual fluoride varnish applications in preschool children did not show significant caries-preventive benefits when provided as an adjunct to school-based supervised tooth brushing with 1,000ppm fluoride toothpaste. Clinical significance: In community based, caries prevention programs, for high caries risk preschool children, a fluoride varnish may add little to caries prevention, when fluoride toothpaste is used daily.