Combined administration of resolvin E1 and lipoxin A4 resolves inflammation in a murine model of Alzheimer's disease.

Dysfunction in the resolution of inflammation may play a key role in Alzheimer's disease (AD). In this study, we found that the levels of specialized pro-resolving lipid mediators (SPMs) in the hippocampus of 5xFAD mice are significantly lower than in non-transgenic littermates. We, therefore, tested the hypothesis that treatment with resolvin E1 (RvE1) and lipoxin A4 (LXA4) alone or in combination will reverse the neuroinflammatory process and decrease Aß pathology. 5xFAD mice were treated intraperitoneally starting at 1month of age with RvE1 or LXA4 alone or in combination at a dose of 1.5 µg/kg, 3 times a week until 3months of age. We found that treatment with RvE1 or LXA4 alone or in combination increased the concentration of RvE1, LXA4, and RvD2 in the hippocampus as measured by ELISA. Combination treatment of RvE1 and LXA4 had a more potent effect on the activation of microglia and astrocytes than either treatment alone, measured by immunohistochemistry with Iba1 and GFAP antibodies, respectively. The concentrations of Aß40 and Aß42 were measured by ELISA and the percentage of Aß plaques were analyzed by immunohistochemistry. All treatments single and in combination, decreased the measures of Aß pathology and restored the homeostasis reversing the inflammatory process for inflammatory cytokines and chemokines (GM-CSF, IFN-γ, IL-1ß, IL-6, IL-10, TNF-α, MCP-1, MIP-1α, MIP-1ß, and RANTES) as measured by multiplex immunoassay. Overall, the study showed that the levels of SPMs in the hippocampus of 5xFAD mice were significantly lower than in wild-type mice; that treatment with RvE1 and LXA4 restored the level of these compounds, reversed the inflammatory process, and decreased the neuroinflammation associated with Aß pathology in 5xFAD mice.

Influence of placement depth and abutment connection pattern on bone remodeling around 1-stage implants: a prospective randomized controlled clinical trial.

OBJECTIVES: The aim of this study is to evaluate peri-implant marginal bone level changes in relation to crestal or subcrestal implant placement and type of fixture/abutment connection 3 months after implant placement. MATERIALS AND METHODS: The duration of the study was 3 months. A total of 105 implants were placed in 81 subjects following a one-stage surgical procedure and assigned into four groups. In the first and second groups, implants with a screwed tapered internal connection were placed subcrestally and crestally, respectively, while in the third and fourth groups, implants with an internal conical seal connection were similarly placed. Clinical recordings and standardized periapical digital radiographs were taken the day of implantation and 3 months later, before placement of the final prosthetic restoration. The modified plaque index (mPLI), modified gingival index (mGI), and probing depths (PD) were recorded at four sites around each implant, and the vertical distance between fixture/abutment junction and alveolar crest at the mesial and distal sites of each implant utilizing subtractive radiography were all measured on placement and at 3 months. RESULTS: There was no statistically significant difference between the four groups for PD. The highest values of mPLI and mGI were recorded for Group 2. The mean (±SE) peri-implant bone loss was recorded as follows: Group 1: 0.68 ± 0.07 mm, Group 2: 0.79 ± 0.06 mm, Group 3: 0.49 ± 0.06 mm, and Group 4: 0.40 ± 0.07 mm. The statistical analysis revealed significant differences in bone resorption between groups with different abutment connections. CONCLUSIONS: The connection between fixture/abutment rather than vertical implant placement in relation to alveolar bone level seems to affect peri-implant marginal bone resorption.

Trigeminal nerve stimulation triggers oral mast cell activation and vascular permeability.

BACKGROUND: The nervous system contributes to the pathophysiology of allergic and inflammatory diseases, including oral inflammation. Mast cells (MCs) are involved in their pathogenesis through proinflammatory mediator release. OBJECTIVE: To investigate the effect of trigeminal nerve (TN) stimulation compared with sham operation on MC activation and oral vascular permeability in the gingiva, palate, buccal mucosa, and tongue of the rat and to examine the possible role of substance P using rats treated with capsaicin as neonates to deplete substance P. METHODS: Six male Sprague-Dawley rats (250 g) were anesthetized and injected intravenously with Evans Blue (EB). Six other rats were injected neonatally with capsaicin (n = 3) or solvent (n = 3) and then injected with EB when they reached 250 g. The mandibular branch of the TN was stimulated for 1 minute (n = 3), and the remaining rats (n = 3) were subjected to sham operation. The ipsilateral and contralateral sides of the mouth were examined for EB extravasation, and tissue sections were removed for light and electron microscopy. RESULTS: TN stimulation resulted in EB extravasation in the ipsilateral side compared with the contralateral side or the ipsilateral side of sham-operated rats. Significant degranulation of MCs also was evident only on the ipsilateral side (P < .0001). There was no difference in MC degranulation between the vehicle- and capsaicin-treated rats, implying that neuropeptides other than substance P may be involved. CONCLUSION: This is the first time that TN stimulation has been shown to result in MC activation and oral vascular permeability, suggesting that MC inhibitors may be used for the treatment of oral inflammatory diseases.

Use of polyphenols in periodontal inflammation.

Periodontitis is an oral inflammatory disease of polymicrobial origin that causes the destruction of gingival connective tissue and the alveolar bone supporting the teeth. Host immune and inflammatory responses due to specific periodontopathogens and their metabolic products mediate local tissue destruction. Periodontal disease affects as many as 30% of adults and it is one of the most common chronic human diseases. However, traditional therapeutic modalities for periodontitis, including non-surgical or surgical periodontal therapy and occasional adjunctive antimicrobial therapy, have been only partially successful. Moreover, the widespread development of antibiotic resistance in pathogenic bacteria and unwanted effects on the gut flora necessitates new strategies to better control periodontal inflammation. Recently, natural compounds capable of modulating the host inflammatory response have received considerable attention. Here we review (Pubmed 1997 to 2013) the orally-related anti-bacterial and anti-inflammatory actions of polyphenols, naturally occurring molecules, capable of modulating the host inflammatory response. Of these, certain flavonoids appear to stand out because of their beneficial profile and clinical evidence. Unique formulations of novel flavonoids may be useful for further development as possible therapeutic agents for periodontal inflammation.