Prostaglandin E 2 and the suppression of phagocyte innate immune responses in different organs

The local and systemic production of prostaglandin E 2 (PGE 2 ) and its actions in phagocytes lead to immunosuppressive conditions. PGE 2 is produced at high levels during inflammation, and its suppressive effects are caused by the ligation of the E prostanoid receptors EP 2 and EP 4 , which results in the production of cyclic AMP. However, PGE 2 also exhibits immunostimulatory properties due to binding to EP 3 , which results in decreased cAMP levels. The various guanine nucleotide-binding proteins (G proteins) that are coupled to the different EP receptors account for the pleiotropic roles of PGE 2 in different disease states. Here, we discuss the production of PGE 2 and the actions of this prostanoid in phagocytes from different tissues, the relative contribution of PGE 2 to the modulation of innate immune responses, and the novel therapeutic opportunities that can be used to control inflammatory responses

Prostaglandin E and the Suppression of Phagocyte Innate Immune Responses in Different Organs

The local and systemic production of prostaglandin E2 (PGE2) and its actions in phagocytes lead to immunosuppressive conditions. PGE2 is produced at high levels during inflammation, and its suppressive effects are caused by the ligation of the E prostanoid receptors EP2 and EP4, which results in the production of cyclic AMP. However, PGE2 also exhibits immunostimulatory properties due to binding to EP3, which results in decreased cAMP levels. The various guanine nucleotide-binding proteins (G proteins) that are coupled to the different EP receptors account for the pleiotropic roles of PGE2 in different disease states. Here, we discuss the production of PGE2 and the actions of this prostanoid in phagocytes from different tissues, the relative contribution of PGE2 to the modulation of innate immune responses, and the novel therapeutic opportunities that can be used to control inflammatory responses

Preventive Effect of Commercial Desensitizing Toothpastes on Bovine Enamel Erosion in vitro

This study evaluated in vitro commercial desensitizing toothpastes with respect to the prevention of erosion and explored the effect of their agents alone or in combination with fluoride. Bovine enamel blocks were randomly allocated to five groups of 20 and exposed to: Sensodyne ProNamel (1,425 ppm F as NaF, 5% KNO(3)), Sensodyne Original (no fluoride, 10% SrCl(2)), Colgate Sensitive (1,450 ppm F as sodium monofluorophosphate, 5% K citrate), Crest (fluoride-only toothpaste, 1,100 ppm F as NaF) and water (negative control). A second experiment was conducted with experimental dentifrices containing fluoride (NaF, 1,100 ppm F), 10% SrCl(2), 5% KNO(3) or 5% K citrate alone or the latter three combined with F. The samples were submitted to four cycles, alternating demineralization (cola, 10 min) and remineralization (artificial saliva, 1 h). Before and between cyclic de- and remineralization, blocks were treated with slurries of the respective toothpastes or water (1 min). Erosive tissue loss was analyzed by profilometry. Data were analyzed by Kruskal-Wallis and Dunn`s tests (p < 0.05). The mean erosion depth (+/- SE, mu m) was significantly less for Colgate Sensitive (0.04 +/- 0.00), Sensodyne Original (0.06 +/- 0.01) and Crest (0.07 +/- 0.01) than for Sensodyne ProNamel (2.36 +/- 0.25) or water (2.92 +/- 0.24), which did not significantly differ from each other. Both F and the desensitizing agents alone reduced erosion, but no additive effect was found. In addition, the combination of F and KNO(3) did not reduce erosion. These in vitro results suggest that the presence of fluoride or desensitizing substances in toothpastes, alone or in combination, can reduce erosion of enamel, but this is not valid for all the formulations. Copyright (C) 2010 S. Karger AG, BaselFAPESP - Foundation for Support to the Research of the State of Sao Paulo[2008/00211-3

Effect of an iron mouthrinse on enamel and dentine erosion subjected or not to abrasion: An in situ/ex vivo study

Objectives: This in situ/ex vivo study evaluated whether a rinse with an iron solution could reduce wear and the percentage of microhardness change of human enamel and dentine submitted to erosion followed by brushing after 1 or 30 min.Design: During 2 experimental 5-day crossover phases (wash-out period of 10 days), 10 volunteers wore intraoral palatal devices, with 12 specimens (6 of enamel and 6 of dentine) arranged in 3 horizontal rows (4 specimens each). In one phase, the volunteers immersed the device for 5 min in 150 mL of cola drink, 4 times a day. Immediately after immersion, no treatment was performed in one row. The other row was brushed after 1 min using a fluoride dentifrice and the device was replaced into mouth. After 30 min, the remaining row was brushed. In the other phase, the procedures were repeated, but after immersion the volunteers rinsed for 1 min with 10 mL of a 10 mM ferrous sulphate solution. Changes in surface microhardness (%SMH) and wear (profilometry) of enamel and dentine were measured. Data were tested using ANOVA and Tukey's tests (p < 0.05).Results: the enamel presented more wear than dentine, under all experimental conditions. The iron solution caused a significant reduction on the %SMH in enamel, and a significant reduction on the wear in dentine, regardless the other conditions.Conclusions: Rinsing with an iron solution after an erosive attack, followed or not by an abrasive episode, may be a viable alternative to reduce the loss of dental structure. (c) 2006 Elsevier Ltd. All rights reserved

Low-Level Fluoride Exposure Increases Insulin Sensitivity in Experimental Diabetes

The effect of chronic fluoride (F) exposure from the drinking water on parameters related to glucose homeostasis was investigated. Wistar rats were randomly distributed into 2 groups (diabetic [D] and nondiabetic [ND]; n = 54 each). In D, diabetes was induced with streptozotocin. Each group was further divided into 3 subgroups (0, 10, or 50 mgF/L in drinking water). After 22 days of treatment, plasma and liver samples were collected. No alterations in glycemia, insulinemia, K-ITT, and HOMA2-IR (homeostasis model assessment 2 of insulin resistance) were seen for ND. F-exposure of D rats led to significantly lower insulinemia, without alterations in glycemia (increased %S). Proteomic analysis detected 19, 39, and 16 proteins differentially expressed for the comparisons D0 vs. D10, D0 vs. D50, and D10 vs. D50, respectively. Gene Ontology with the most significant terms in the comparisons D0 vs. D10, D0 vs. D50, and D50 vs. D10 were organic acid metabolic process and carboxylic acid metabolic process, organic acid metabolic process, and cellular ketone metabolic process. Analysis of subnetworks revealed that proteins with fold changes interacted with GLUT4 in comparison D0 vs. D10. Among these proteins, ERj3p was present in D10. Upregulation of this protein in the presence of F might help to explain the higher %S found in these animals. These data suggest that fluoride might enhance glucose homeostasis in diabetes and identify specific biological mechanisms that merit future studies.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Supplementary Material for: Proteomics of Secretory-Stage and Maturation-Stage Enamel of Genetically Distinct Mice

<p>The mechanisms by which excessive ingestion of fluoride (F) during amelogenesis leads to dental fluorosis (DF) are still not precisely known. Inbred strains of mice vary in their susceptibility to develop DF, and therefore permit the investigation of underlying molecular events influencing DF severity. We employed a proteomic approach to characterize and evaluate changes in protein expression from secretory-stage and maturation-stage enamel in 2 strains of mice with different susceptibilities to DF (A/J, i.e. ‘susceptible' and 129P3/J, i.e. ‘resistant'). Weanling male and female susceptible and resistant mice fed a low-F diet were divided into 2 F-water treatment groups. They received water containing 0 (control) or 50 mg F/l for 6 weeks. Plasma and incisor enamel was analyzed for F content. For proteomic analysis, the enamel proteins extracted for each group were separated by 2-dimensional electrophoresis and subsequently characterized by liquid-chromatography electrospray-ionization quadrupole time-of-flight mass spectrometry. F data were analyzed by 2-way ANOVA and Bonferroni's test (p < 0.05). Resistant mice had significantly higher plasma and enamel F concentrations when compared with susceptible mice in the F-treated groups. The proteomic results for mice treated with 0 mg F/l revealed that during the secretory stage, resistant mice had a higher abundance of proteins than their susceptible counterparts, but this was reversed during the maturation stage. Treatment with F greatly increased the number of protein spots detected in both stages. Many proteins not previously described in enamel (e.g. type 1 collagen) as well as some uncharacterized proteins were identified. Our findings reveal new insights regarding amelogenesis and how genetic background and F affect this process.</p

Insights into preventive measures for dental erosion

Dental erosion is defined as the loss of tooth substance by acid exposure not involving bacteria. The etiology of erosion is related to different behavioral, biological and chemical factors. Based on an overview of the current literature, this paper presents a summary of the preventive strategies relevant for patients suffering from dental erosion. Behavioral factors, such as special drinking habits, unhealthy lifestyle factors or occupational acid exposure, might modify the extent of dental erosion. Thus, preventive strategies have to include measures to reduce the frequency and duration of acid exposure as well as adequate oral hygiene measures, as it is known that eroded surfaces are more susceptible to abrasion. Biological factors, such as saliva or acquired pellicle, act protectively against erosive demineralization. Therefore, the production of saliva should be enhanced, especially in patients with hyposalivation or xerostomia. With regard to chemical factors, the modification of acidic solutions with ions, especially calcium, was shown to reduce the demineralization, but the efficacy depends on the other chemical factors, such as the type of acid. To enhance the remineralization of eroded surfaces and to prevent further progression of dental wear, high-concentrated fluoride applications are recommended. Currently, little information is available about the efficacy of other preventive strategies, such as calcium and laser application, as well as the use of matrix metalloproteinase inhibitors. Further studies considering these factors are required. In conclusion, preventive strategies for patients suffering from erosion are mainly obtained from in vitro and in situ studies and include dietary counseling, stimulation of salivary flow, optimization of fluoride regimens, modification of erosive beverages and adequate oral hygiene measures