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Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.

Background: Gingival pigmentation is a discoloration of the gingiva due to a variety of lesions and conditions associated with several endogenous and exogenous etiologic features., Objective: The purpose of this study is to describe a report of gingival pigmentation in a patient who used doxycycline., Case Report: A 21-year-old Caucasian female was under dermatological treatment and antibiotic therapy with doxycycline 100 mg (one time a day) for 90 days. She presented brown pigmentation at the gingival margin on the facial surfaces of the upper and lower anterior incisors and premolars. The patient was evaluated by immunohistochemical (S-100, Melan-A, and HMB-45) and histopathologic analyses, and clinical history. Blood levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were analyzed by UV/Vis spectroscopy. The adrenaline, noradrenaline, and dopamine in blood were analyzed by high-performance liquid chromatography (HPLC); dehidroepiandrosterone (DHEA) in serum by radioimmunoassay; and luteinizing hormone (LH) and 25-Hydroxyvitamin D by chemiluminescence. Hematoxylin-eosin stained sections revealed keratinocytes with pigment compatible with melanin. The Fontana-Masson staining was positive in melanophages and in some basal keratinocytes. S-100, Melan A and HMB-45 were confirmed as positive markers of melanocytic differentiation in gingival tissue. We observed a significant increase in malondialdehyde (p˂0.05) and a decrease in superoxide dismutase levels (p˂0.05). The dopamine value was found to be 15 pg/ml (reference value ≤ 10 pg/ml)., Conclusion: The use of doxycycline is associated with an increase in oxidative stress and of dopamine with melanin pigments in the gingival tissue. This case report showed a cause-effect relationship between exposure to doxycycline and pigmentation of the marginal gingiva., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To evaluate the antimicrobial activity, mechanical properties, and fluoride release capacity of glass ionomer cement (GIC) used for cementing orthodontic bands and modified by ethanolic extract of red propolis (EERP) in different concentrations., Materials and Methods: Two orthodontic GICs containing EERP at 10%, 25%, and 50%, were used. The following assays were carried out: cell viability tests against Streptococcus mutans and Candida albicans, diametral tensile strength, compressive strength, shear bond strength, microhardness, and fluoride release capacity. The statistical analyses of the antimicrobial tests, fluoride release, diametral tensile strength, compressive strength, and microhardness were performed using two-way analysis of variance and Tukey test (P < .05). Shear bond strength data were analyzed using one-way analysis of variance followed by Tukey test (P < .05)., Results: At the concentrations of 25% and 50%, EERP was shown to be a promising antimicrobial agent incorporated into GICs against C albicans (P < .001) and S mutans (P < .001). The fluoride release capacity of the GICs was not affected, and the EERP concentration of 25% was the one that least affected the mechanical properties of the cements (P > .05)., Conclusions: The GICs containing EERP at 25% showed a significant increase in their antimicrobial activity against S mutans and C albicans, while mechanical properties and fluoride release remained without significant changes., (© 2021 by The EH Angle Education and Research Foundation, Inc.)

Purpose: To evaluate the biocompatibility in rat subcutaneous tissue of conventional orthodontic cements, Riva (R) and Meron (M), modified by the addition of ethanolic extract of red propolis (EERP), at different concentrations and time intervals., Materials and Methods: One hundred eight male adult Wistar rats were used, distributed in nine groups of cements with added EERP at the concentrations used (C-control, MC, M10, M25, M50, RC, R10, R25, and R50). The rats were sacrificed after 3 time intervals (7, 15, and 30 days). Histological and immunohistochemical analyses were performed. The findings were statistically analyzed using the Kruskal-Wallis test followed by Dunn's test (p < 0.05)., Results: The highest concentrations led to a higher level of inflammation at the initial times (p < 0.05), but without differences after 30 days. In terms of collagen, there was less collagenization at the initial times in comparison with the control group C. However, over time, the addition of propolis resulted in healing compatible with that of group C. The level of CD68 immunostaining was statistically significantly higher in the groups with the highest concentrations (R50 and M50) (p = 0.001)., Conclusion: Orthodontic cements with the addition of EERP were found to be biocompatible in rat subcutaneous tissue. Riva cement with the addition of 50% EERP showed the highest tissue inflammation, but with satisfactory tissue repair.

Background/objective: The beneficial effects of sub-antimicrobial dose doxycycline (SDD) associated with nonsurgical periodontal therapy are well documented. Recently, the effects of SDD on metalloproteinases have been investigated in the treatment of hypertension. The aim of this study was to evaluate the effects of SDD on ligature-induced periodontitis in spontaneously hypertensive rats (SHR)., Methods: Fifty-four adult male rats were divided into three groups: SHR-C, SHR-L and SHR-L-DOX (C - Control; L - Ligature). In group SHR-L-DOX, animals were treated with daily 5 mg/kg SDD administration. In L groups, a ligature remained around mandibular first molars for the first 10 days. Each group was divided for euthanasia at 10 or 21 days. Microtomographic and histometric analyses were performed. Osteoclastogenesis was evaluated by tartrate-resistant acid phosphatase (TRAP) assay and gene expression of 84 inflammatory mediators by polymerase chain reaction (PCR) array., Results: Group SHR-L-DOX presented reduced systolic blood pressure when compared with group SHR-L at both 10 and 21 days (p < 0.05). Group SHR-L-DOX showed decreased bone and attachment loss in comparison with group SHR-L at both 10 and 21 days (p < 0.05). SDD treatment reduced the amount of TRAP-positive cells at 10 days (p < 0.05). Group SHR-L-DOX showed a downregulated inflammatory genes profile in comparison with SHR-L at 10 and 21 days., Conclusion: SDD therapy exerted systemic modulatory effect on inflammation with reduced periodontal tissue destruction in hypertensive rats., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Diabetes mellitus increases periodontitis and pathogenicity of the oral microbiome. To further understand mechanisms through which diabetes affects periodontitis, we examined its impact on periodontal ligament fibroblasts in vivo and in vitro. Periodontitis was induced by inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in normoglycemic and diabetic mice. Diabetes, induced by multiple low-dose injections of streptozotocin increased osteoclast numbers and recruitment of neutrophils to the periodontal ligament, which could be accounted for by increased CXC motif chemokine 2 (CXCL2) and receptor activator of nuclear factor kappa B ligand (RANKL) expression by these cells. Diabetes also stimulated a significant increase in nuclear factor kappa B (NF-κB) expression and activation in periodontal ligament (PDL) fibroblasts. Surprisingly, we found that PDL fibroblasts express a 2.3-kb regulatory unit of Col1α1 (collagen type 1, alpha 1) promoter typical of osteoblasts. Diabetes-enhanced CXCL2 and RANKL expression in PDL fibroblasts was rescued in transgenic mice with lineage-specific NF-κB inhibition controlled by this regulatory element. In vitro, high glucose increased NF-κB transcriptional activity, NF-κB nuclear localization, and RANKL expression in PDL fibroblasts, which was reduced by NF-κB inhibition. Thus, diabetes induces changes in PDL fibroblast gene expression that can enhance neutrophil recruitment and bone resorption, which may be explained by high glucose-induced NF-κB activation. Furthermore, PDL fibroblasts express a regulatory element in vivo that is typical of committed osteoblasts.

Diabetes is a risk factor for periodontitis, an inflammatory bone disorder and the greatest cause of tooth loss in adults. Diabetes has a significant impact on the gut microbiota; however, studies in the oral cavity have been inconclusive. By 16S rRNA sequencing, we show here that diabetes causes a shift in oral bacterial composition and, by transfer to germ-free mice, that the oral microbiota of diabetic mice is more pathogenic. Furthermore, treatment with IL-17 antibody decreases the pathogenicity of the oral microbiota in diabetic mice; when transferred to recipient germ-free mice, oral microbiota from IL-17-treated donors induced reduced neutrophil recruitment, reduced IL-6 and RANKL, and less bone resorption. Thus, diabetes-enhanced IL-17 alters the oral microbiota and renders it more pathogenic. Our findings provide a mechanistic basis to better understand how diabetes can increase the risk and severity of tooth loss., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To compare the effect of toothbrushing abrasion with hydrated silica-based whitening and regular toothpastes on root dentin using contact profilometry., Materials and Methods: Ninety dentin specimens (4 x 4 x 2 mm) were randomly divided into five experimental groups (n = 18) according to the toothpaste: three whitening (W1, W2 and W3) and two regular toothpastes (R1 and R2) produced by two different manufacturers. Using a brushing machine, each specimen was brushed with a constant load of 300 g for 2500 cycles (4.5 cycles/s). The toothpastes were diluted at a ratio of 1:3 w/w (dentifrice:distilled water). The brush diamond tip of the profilometer moved at a constant speed of 0.05 mm/s with a force of 0.7 mN., Results: The average value of brushing abrasion in μm (mean ± SD) was obtained from five consecutive measurements of each specimen: W1 = 8.86 ± 1.58, W2 = 7.59 ± 1.04, W3 = 8.27 ± 2.39, R1 = 2.89 ± 1.05 and R2= 2.94 ± 1.29. There was a significant difference between groups (ANOVA, p<0.0001). Post-hoc Tukey's test for multiple comparisons showed differences between all the whitening and regular toothpastes, but not among the whitening nor among the regular toothpastes., Conclusion: The whitening toothpastes tested can cause more dentin abrasion than the regular ones.