O Uso terapêutico de mediadores anti-inflamatórios da via do ácido araquidônico

Arachidonic acid (AA) a precursor in the formation of eicosanoids which are lipid mediators with a number of functions in human physiology and pathology. The most of the eicosanoids act as proinflammatory mediators and contribute to the development and proliferation of tumors. In this thesis we evaluated two mediators: 15-deoxy-Δ12,14-PGJ2 (15d- PGJ2) and epoxieicosatrienoic acids (EETs) both act with an opposite activity of most eicosanoids, with an anti-inflammatory and and anti-tumoral action these two distinct mediators from AA pathway were used in this thesis in two different projects. First: 15d- PGJ2, was described that to have an antiproliferative activity and to induce apoptosis in several types of tumor cells however, the effect of 15d- PGJ2 in thyroid cancer cells was unknown in this sense, we tested in vitro cultured thyroid tumor cells, here in TPC1 cells, and treated with different concentrations of 15d- PGJ2 (0 to 20 uM) the treated cells showed a decrease in proliferation and an increase in apoptosis and a decrease in IL-6 release and relative expression. These key results together demonstrate that 15d- PGJ2 can be used as a new therapy for thyroid cancer. Second: The EETs are converted to their diols by soluble epoxy hydrolase (sEH) to maintain the stability of EETs and their anti-inflammatory activity, an inhibitor (TPPU) against was used to sEH in a periodontitis model induced with Aggregatibacter actinomycetemcomitans. The oral treatment in mice with TPPU and sEH Knockout animals showed bone loss reduction accompanied by a decrease in the osteoclastogenic molecules, like RANK, RANKL and OPG, demonstrating that pharmacological inhibition of sEH may have therapeutic value in periodontitis and inflammatory diseases that involve bone resorption.

Avaliação comparativa da remodelação óssea periimplantar em implantes com junção cone-morse e hexágono externo: estudo clínico randomizado controlado, duplo cego, boca dividida

Background: Several theories, such as the biological width formation, the inflammatory reactions due to the implant-abutment microgap contamination, and the periimplant stress/strain concentration causing bone microdamage accumulation, have been suggested to explain early periimplant bone loss. However, it is yet not well understood to which extent the implant-abutment connection type may influence the remodeling process around dental implants. Aim: to evaluate clinical, bacteriological, and biomechanical parameters related to periimplant bone loss at the crestal region, comparing external hexagon (EH) and Morse-taper (MT) connections. Materials and methods: Twelve patients with totally edentulous mandibles received four custom made Ø 3.8 x 13 mm implants in the interforaminal region of the mandible, with the same design, but different prosthetic connections (two of them EH or MT, randomly placed based on a split-mouth design), and a immediate implant- supported prosthesis. Clinical parameters (periimplant probing pocket depth, modified gingival index and mucosal thickness) were evaluated at 6 sites around the implants, at a 12 month follow-up. The distance from the top of the implant to the first bone-to-implant contact – IT-FBIC was evaluated on standardized digital peri-apical radiographs acquired at 1, 3, 6 and 12 months follow-up. Samples of the subgingival microbiota were collected 1, 3 and 6 months after implant loading. DNA were extracted and used for the quantification of Tanerella forsythia, Porphyromonas gingivalis, Aggragatibacter actinomycetemcomitans, Prevotella intermedia and Fusobacterium nucleatum. Comparison among multiple periods of observation were performed using repeated-measures Analysis of Variance (ANOVA), followed by a Tukey post-hoc test, while two-period based comparisons were made using paired t- test. Further, 36 computer-tomographic based finite element (FE) models were accomplished, simulating each patient in 3 loading conditions. The results for the peak EQV strain in periimplant bone were interpreted by means of a general linear model (ANOVA). Results: The variation in periimplant bone loss assessed by means of radiographs was significantly different between the connection types (P<0.001). Mean IT-FBIC was 1.17±0.44 mm for EH, and 0.17±0.54 mm for MT, considering all evaluated time periods. All clinical parameters presented not significant differences. No significant microbiological differences could be observed between both connection types. Most of the collected samples had very few pathogens, meaning that these regions were healthy from a microbiological point of view. In FE analysis, a significantly higher peak of EQV strain (P=0.005) was found for EH (mean 3438.65 µ∑) compared to MT (mean 840.98 µ∑) connection. Conclusions: Varying implant-abutment connection type will result in diverse periimplant bone remodeling, regardless of clinical and microbiological conditions. This fact is more likely attributed to the singular loading transmission through different implant-abutment connections to the periimplant bone. The present findings suggest that Morse-taper connection is more efficient to prevent periimplant bone loss, compared to an external hexagon connection.