Photobiomodulation therapy modulates epigenetic events and NF-κB expression in oral epithelial wound healing.

The aim of this study was to evaluate the effect of photobiomodulation therapy (PBMT) on histone 3 acetylation (acH3) and NF-κB expression during oral ulcer healing. A total of 48 male Wistar rats were divided into control group (CG) and PBMT group (n = 24 each). Traumatic ulcers were created in the dorsum of the rats' tongue with a punch tool. Irradiation with InGaAlP laser, 660 nm, 40 mW, 0.04 cm2 spot size, 4 J/cm2, 4 s, and 0.16 J per spot was performed once a day in close contact for 10 consecutive days. CG received only daily handling. Rats were euthanized on days 3, 5, and 10 (n = 8) and were monitored daily to assess wound status. Immunohistochemical analysis for acH3 and NF-κB detection was performed. One thousand epithelial cells were counted, and mean acH3- and NF-κB-positive cells were calculated and compared between the groups. PBMT accelerated the repair of oral ulcers. On day 3, PBMT showed significantly higher means for acH3- and NF-κB-positive cells than CG. On day 5, no difference was observed between the groups concerning both markers. On day 10, PBMT presented lower acH3 and NF-κB means than the control group. We concluded that PBMT stimulates keratinocyte migration in the early stage of oral wound healing and keratinocyte differentiation at the final stage by modulating histone acetylation and NF-κB expression.

Copaiba oil-resin (Copaifera reticulata Ducke) modulates the inflammation in a model of injury to rats' tongues.

BACKGROUND: The regeneration of integrity and tissue homeostasis after injury is a fundamental property and involves complex biological processes fully dynamic and interconnected. Although there are medications prescribed to accelerate the process of wound healing by reducing the exaggerated inflammatory response, comes the need to search for different compounds of Amazonian biodiversity that can contribute to the acceleration of the healing process. Among these products, the copaiba oil-resin is one of the most prominent feature in this scenario, as they have been reported its medicinal properties. METHODS: Aiming to evaluate the anti-inflammatory and healing effect of copaiba oil-resin (Copaifera reticulata Ducke) in transfixing injury of rats' tongues first proceeded up the copaiba oil-resin oral toxicity test in 5 male mice to stipulate the therapeutic dose which was established at 200 mg/kg/day. Then it was induced transfixing injury in a total of 15 Wistar rats. The animals were randomly divided into three groups based on the treatment: control group, dexamethasone group and copaiba oil-resin group. After 7 days of treatment, histological slides stained with hematoxylin and eosin was prepared. Immunohistochemistry for CD68 (macrophage marker) was performed and analyzed by the cell counter Image J. RESULTS: The acute toxicity test showed that the oil-resin copal has low toxicity. Furthermore, copaiba oil-resin therapy modulates the inflammatory response by decreasing the chronic inflammatory infiltrate, edema and specifically the number of macrophages. CONCLUSIONS: The results indicate the potential of the Amazon region and showed up relevant because therapy with this extract modulates the inflammatory process.

Effects of Copaiba Oil Topical Administration on Oral Wound Healing.

The effects of topical copaiba oil extract and topical corticosteroid were assessed on oral wound healing in an in vivo model using 96 male Wistar rats. Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The animals were divided into: Control; Corticosteroid; Placebo and Copaiba oil Group. The animals received two daily applications of the products. The control group received only daily handling. Six rats in each group were euthanized at days 3, 5, 10 and 14. The animals were monitored daily to determine wound status. The weigh was assessed at day 0 and euthanasia day. The percentage of repair was calculated, and histopathological aspects were analyzed. The Kruskal-Wallis test was used to compare the results between groups and times of evaluation. Closing time was assessed through the log-rank test. The corticosteroid group lost more weight at days 10 and 14 than the control group (p < 0.05). Moreover, the healing time of corticosteroid group was longer than the control group (p = 0.007). No differences were observed between the copaiba oil group and the control group. We concluded that topical copaiba oil, in spite of being safe, did not accelerate the process of oral wound healing. Copyright © 2017 John Wiley & Sons, Ltd.

Photobiomodulation regulates cytokine release and new blood vessel formation during oral wound healing in rats.

The aim of the present study was to evaluate the effects of photobiomodulation (PBM) on cytokine levels and angiogenesis during oral wound healing. Ulcers were made on the dorsum of the tongue in 48 Wistar rats. Irradiation with an indium-gallium-aluminum-phosphide (InGaAlP) laser (660 nm; output power, 40 mW; spot size, 0.04 cm(2)) was performed once a day on two points of the ulcer for 14 days. Two different energy densities were used: 4 J/cm(2) (energy per point 0.16 J, total energy 0.32 J) and 20 J/cm(2) (energy per point 0.8 J, total energy 1.6 J). Tissue levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were investigated by enzyme-linked immunosorbent assay (ELISA). Image analysis of CD31-immunostained sections was used to investigate microvessel density (MVD). PBM increased the tissue levels of IL-1ß at the early stage of oral wound healing (p < 0.01) and increased the tissue levels of TNF-α during all stages of oral wound healing (p < 0.05). PBM at a dose of 4 J/cm(2) produced more significant results regarding cytokine modulation and was associated with higher MVD at day 5. Collectively, these findings indicate that cytokine modulation and increased angiogenesis are among the basic mechanisms whereby PBM improves oral wound repair.

Interproximal implant thread exposure after initial bone remodeling as a risk indicator for peri-implantitis.

BACKGROUND: Due to the clinical challenges involved in successfully treating peri-implantitis, it is imperative to identify patient- and implant-level risk factors for its prevention. The main goal of this retrospective longitudinal radiographic and clinical study was to investigate whether interproximal radiographic implant thread exposure after physiological bone remodeling may be a risk factor for peri-implantitis. The secondary goal was to evaluate several other potential risk indicators. METHODS: Of 4325 active dental school patients having implants placed, 165 partially edentulous adults (77 men, 88 women) aged 30-91 with ≥2 years of follow-up upon implant restoration were included. Implants with ≥1 interproximal thread exposed (no bone-to-implant contact) (n = 98, 35%) constituted the test group and those without exposed threads (n = 182, 65%) the control group. Descriptive, binary, and multivariate regression analyses were evaluated for goodness of fit. Wald tests were used to evaluate for significance set at 0.05. RESULTS: Of the 280 implants (98 test, 182 control), 8 (2.9%) failed over a mean follow-up period of 7.67 (±2.63) years, and 27 implants (19 test, 8 control) developed peri-implantitis, with the exposed group having eight-fold (7.82 times) adjusted greater odds than the non-exposed. The risk increased four-fold (3.77 times) with each thread exposed. No other patient- or implant-related potentially confounding risk factors were identified. CONCLUSIONS: Exposed interproximal implant threads after physiologic bone remodeling may be an independent risk indicator for incident peri-implantitis. Hence, clinicians should closely monitor patients with implant threads that have no bone-to-implant contact for incident peri-implantitis.

The impact of photobiomodulation therapy on the biology and behavior of head and neck squamous cell carcinomas cell lines.

Photobiomodulation therapy (PBMT) is an emerging therapeutic modality designed to prevent and treat chemotherapy-driven oral mucositis (OM). However, the response of tumor cells to the effects of PBMT remains poorly understood. Our study explores the effects of PBMT in head and neck squamous cell carcinoma (HNSCC) based on cellular proliferation, migration, and survival of tumor cells and its population of cancer stem cells (CSC). We explored the behavior of two HNSCC cell lines (HN6 and HN13) under two distinct conditions, a physiological growing condition (10% FBS), and under stress growing condition (2% FBS) prior to irradiation using diode laser (InGaAlP; MM Optics, São Carlos, SP, Brazil). Diode laser (660 nm) was applied with a power of 100 mW delivering a total energy per point of 0.24 J. MTT and wound healing test (scratch assay) were performed to evaluate, respectively, proliferation and migration of tumor cells. Clonogenic and spheres formation assays were also performed to evaluate the survival and percentage of CSC upon irradiation. Overall, we observed that PBMT does not exacerbate the behavior of HNSCC. We could only observe a decrease in cellular proliferation of one cell line (HN6) when cultured under nutritional stress conditions (p < .05). There were no significant differences between the control and the PBMT groups regarding cell migration, survival and the percentage of CSC. Collectively, our results suggest that in vitro administration of PBMT to HNSCC does not modify the behavior of tumor cells.

Bryne's grading system predicts poor disease-specific survival of oral squamous cell carcinoma: a comparative study among different histologic grading systems.

OBJECTIVES: The aim of this study was to access the prognostic value of 4 histopathologic grading systems of oral squamous cell carcinoma (OSCC): The World Health Organization (WHO), Anneroth, Bryne (1989), and Bryne (1992). STUDY DESIGN: Eighty-five cases of OSCC diagnosed between 1996 and 2010 at the Clinics Hospital of Porto Alegre (Porto Alegre, Brazil) were included. Slides stained with hematoxylin and eosin were obtained, and a histologic grade was assigned on the basis of the consensus of 3 expert oral pathologists, who were blinded to the clinicopathologic factors. Each system was correlated with proliferative labeling index, accessed through Ki67 immunostaining, clinicopathologic factors, patient outcome (alive or deceased), and survival time. RESULTS: The increase in Bryne (1992) histologic grades was accompanied by an increase in proliferative labeling index. Moreover, this system was the only one associated with patient outcome (P = .01) and survival. Bryne (1992) grading system grade III tumors were associated with poor disease-specific survival according to univariate and multivariate cox regression analyses and the log-rank test (P < .05). The other systems evaluated presented no association with patients' outcome or survival. CONCLUSIONS: The Bryne (1992) grading system is more effective in predicting survival in OSCC compared with the systems proposed by the WHO, Anneroth, or Bryne (1989).

Overexpression of MutSα Complex Proteins Predicts Poor Prognosis in Oral Squamous Cell Carcinoma.

The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC).The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC.All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ±â€Š15.21 and 31.46 ±â€Š22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02).This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC.

Cowden syndrome--a case report emphasizing the role of the dental surgeon in diagnosis.

Cowden syndrome or multiple hamartoma syndrome, is a rare genetic condition inherited in an autosomal dominant pattern characterized by cutaneous manifestations, polyps, thyroid gland neoplasias, and macrocephaly. This report presents the case of a 36-year-old patient who looked for dental treatment for a gingival nodule. Current and past medical history and oral and facial manifestations led to the diagnosis of Cowden syndrome. This case report emphasizes the role of the dental surgeon in the diagnosis of this systemic disease, based on the analysis of medical history and manifestations in the oral cavity.

Effects of a mucoadhesive formulation containing Curcuma longa L. on oral wound healing

Introduction: The aim of this study was to investigate the effects of a topical mucoadhesive formulation with Curcuma longa L. extract (MFC) on oral wound healing. Methods: Seventy-two Wistar rats were randomly assigned to 3 groups: Control, Vehicle, and MFC. Traumatic ulcers were made on the dorsum of the tongue with a 3-mm diameter punch. Vehicle and MFC groups received application of the products twice a day, while animals in the control group were cared for in identical conditions but received no product application. Six rats in each group were euthanized at days 3, 5, 10, and 14. Percentage of repair was calculated based on wound area. HE-stained histological sections were obtained for semi-quantitative analysis of re-epithelization and inflammation. Results: Clinical findings revealed that at days 3 and 5, animals from the MFC group exhibited a significantly higher percentage of wound repair. At day 5, animals from this group also demonstrated a significant increase in the degree of re-epithelization and inflammation. Conclusions: MFC is capable of accelerating oral wound repair in an in vivo model by modulating the inflammatory process and stimulating epithelial proliferation. (AU)

Disseminated paracoccidioidomycosis diagnosis based on oral lesions.

Paracoccidioidomycosis (PCM) is a deep mycosis with primary lung manifestations that may present cutaneous and oral lesions. Oral lesions mimic other infectious diseases or even squamous cell carcinoma, clinically and microscopically. Sometimes, the dentist is the first to detect the disease, because lung lesions are asymptomatic, or even misdiagnosed. An unusual case of PCM with 5 months of evolution presenting pulmonary, oral, and cutaneous lesions that was diagnosed by the dentist based on oral lesions is presented and discussed.

TGF-ß1 and its association with clinicopathological features, proliferative activity and prognosis in oral squamous cell carcinoma: an immunohistochemical study

Introduction: The prognostic value of transforming growth factor beta-1 (TGF-ß1) in oral cancer remains unclear. Therefore, the aim of this study was to evaluate TGF-ß1 expression in oral squamous cell carcinoma (OSCC) samples and its association with clinicopathological data, tumor proliferative activity, and patients' prognosis. Methods: A total of 68 patients with histopathological diagnosis of OSCC were included, as well as 9 cases of normal oral mucosa for comparison purposes. The OSCC sample was categorized according to patients' outcomes in favorable prognosis (n=30) or unfavorable prognosis (n=38). Immunohistochemical staining for TGF-ß1 and Ki-67 were performed. The slides were semi-quantitatively and quantitatively evaluated for TGF-ß1 and Ki-67, respectively. Results: TGF-ß1 was significantly increased in OSCC compared to normal oral mucosa (<0.01). An inverse correlation was found between TGF-ß1 and Ki67 staining in OSCC (p=0.01). No association was found between TGF-ß1 expression and OSCC clinicopathological features, prognosis or survival. Conclusions: TGF-ß1 had no prognostic value and appears to maintain its suppressive role concerning cell proliferation. (AU)