Differential expression of Cadherins switch and Caveolin-2 during stages of oral carcinogenesis.

Background: Oral squamous cell carcinoma (OSCC) accounts for 90% of oral malignancies, which may be preceded by oral potentially malignant disorders (OPMDs). Cancer progression involves the downregulation of epithelial markers (E-cadherin) and the upregulation of mesenchymal markers (N-cadherin), which together characterise the epithelial-mesenchymal transition (EMT). Furthermore, caveolin can act on cell adhesion and migration events that regulate the expression of the E-cadherin/α-ß-catenin complex, thus favouring aggressive biological behaviour. This study aimed to analyse the immunoexpression of E-cadherin, N-cadherin and caveolin-2 at different stages of oral carcinogenesis to identify reliable biomarkers to predict malignant potential. Methods: Expressions of E-cadherin and N-cadherin in 14 normal oral mucosae (NOM), 14 OPMD and 33 OSCC specimens were evaluated using immunohistochemistry. Clinicopathological parameters were also assessed. Results: E-cadherin immunoexpression was significantly reduced during the progression of oral carcinogenesis (P = 0.0018). N-cadherin immunoexpression did not show any statistical differences between these groups. However, a representative number of N-cadherin-positive OSCC cases did not express E-cadherin. The expression of caveolin-2 increased significantly with the progression of the disease, from NOM to OSCC (P value: 0.0028). Conclusion: These findings indicate that cadherin switch and caveolin-2 immunoexpression may be regulatory events in oral carcinogenesis.

Association between alcohol dependence and both periodontal disease and tooth loss: a cross-sectional study.

The impact of alcohol consumption on periodontal disease and tooth loss is still under debate. The aim of this cross-sectional study was to evaluate the association between alcohol dependence and both periodontal diseases and tooth loss in Brazilian native Indians. Full mouth periodontal examination was performed and tooth loss was clinically evaluated in a representative sample of 225 Indians (≥ 19 years). Sociodemographic, oral health-related data, and alcohol dependence were evaluated using structured questionnaires. The subjects were categorized as either alcohol-dependent or non-dependent according to the Alcohol Use Disorders Identification Test results. Severe periodontal disease was defined in individuals with ≥ 2 proximal sites with a clinical attachment level ≥ 6 mm, not on the same tooth, and ≥ 1 proximal site with a probing depth ≥ 5 mm. Tooth loss was categorized as one or more missing teeth, or no missing teeth. Bivariate models followed by logistic regression were used to assess the association between alcohol dependence and both periodontal disease and tooth loss. Prevalence ratio (PR) was calculated using Mantel-Haenszel analysis. Alcohol dependence increased 2.5 times the risk for tooth loss (prevalence ratio [PR] =2.49, 95% confidence interval [CI] = 1.01-9.04, p = 0.05). Severe periodontal disease was not associated with alcohol dependence (OR = 0.54, 95% CI = 0.22-1.31, p = 0.23). In conclusion, alcohol dependence was associated with tooth loss in the present population, but severe periodontal disease was not. Questions on alcohol dependence should be included in dental anamnesis questionnaires, and patients diagnosed with alcohol dependence should be referred for dental evaluation.

Immunohistochemical Characterization of Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma.

Myofibroblasts are differentiated contractile cells that can secrete extracellular matrix components, cytokines, proteases, and proangiogenic factors. In neoplastic processes such as oral squamous cell carcinoma (OSCC), myofibroblasts are recognized as cancer-associated fibroblasts (CAFs) and actively participate in tumor progression. As the presence of myofibroblasts in the stroma may be an important parameter of invasion and proliferation, the aim of this study was to evaluate the presence of CAFs in OSCC by immunophenotyping and their association with histologic classification and clinicopathologic parameters. A total of 34 formalin-fixed, paraffin-embedded samples of OSCC were analyzed for CAF histology and immunophenotype established on the basis of the simultaneous immunohistochemical expression of α-SMA, fibronectin, FSP1, HHF35, and vimentin. According to the histologic classification of CAFs, 16 (47%) cases were classified as the mature subtype and 18 (53%) as the immature subtype. CAF immunophenotype was detected in 19 (56%) cases, and the immunophenotype was variable in 15 (44%) cases. The CAFs immunophenotype was significantly associated with the immature histologic subtype. Immunohistochemical expression of α-SMA, fibronectin, FSP1, HHF35, and vimentin represents a suitable CAF immunophenotype in OSCC. The CAF immunophenotype is associated with the immature histologic subtype. The characterization of CAFs may identify tumors with a distinct biological profile in OSCC. Studies extending the investigation of CAFs to OSCC are needed to determine the actual role of this cell population as a possible prognostic marker.

Association of dental infections with systemic diseases in Brazilian Native Indigenous: a cross-sectional study.

The aim of this cross-sectional study was to evaluate the association between dental infections and systemic diseases in the Indigenous population of Brazil. A representative sample of 225 Indigenous (≥19 years) was assessed. The T-test and bivariate and logistic models were used to assess the associations of diabetes, hypertension, and obesity with dental caries and destructive periodontal disease. After adjustments for covariates, dental caries were associated with hypertension (odds ratio = 1.95; 95% confidence interval: 1.03-3.66; P = .04). Individuals with destructive periodontal disease had a higher systolic blood pressure (124 ± 20.34 mm Hg) than those without destructive periodontal disease (117.52 ± 16.54 mm Hg; P = .01). In conclusion, dental infections were found to be associated with hypertension in the present population. Thus, patients diagnosed with hypertension should be referred for dental evaluation and vice versa.

Risk indicators for tooth loss in Kiriri Adult Indians: a cross-sectional study.

BACKGROUND: The aim of this cross-sectional study was to evaluate the risk indicators of tooth loss in adult Kiriri Indians from Brazil. METHODS: A representative sample of 225 Indians (≥ 19 years of age) was assessed. Interviews using a structured written questionnaire were performed to collect data on demographics and socio-economic status, and health-related data. Probing depth, the distance between the cement-enamel junction and the free gingival margin, and decayed, missing or filled teeth were evaluated. Bivariate and logistic models were used to assess associations between tooth loss and age, sex, income, education, diabetic status, smoking habits, dental caries, severe periodontitis, plaque index and previous dental visit. RESULTS: Eighty per cent of subjects had lost one tooth or more, and 20% had lost eight teeth or more. Mean (± standard deviation) tooth loss was 5.09 (± 5.83) teeth. After adjustment for covariates, loss of one tooth or more was associated with older age [≥ 35 years; odds ratio (OR) = 4.06, 95% confidence interval (95% CI): 1.38-11.94, P = 0.01], severe periodontitis (OR = 3.35, 95% CI: 0.99-11.24, P = 0.05), higher dental caries (OR = 3.24, 95% CI: 1.35-7.78, P = 0.01) and previous dental visit (OR = 23.32, 95% CI: 5.75-94.63, P < 0.001). CONCLUSION: Tooth loss is highly prevalent in Kiriri Indians. Older age, severe periodontitis, higher caries index and previous dental visit were associated with tooth loss. Prevention and treatment programmes, targeting high-risk groups, are required to promote the oral health of the population.

Effect of laser phototherapy on the hyalinization following orthodontic tooth movement in rats.

OBJECTIVE: We aimed to assess histologic changes after the use of laser phototherapy (LPT) during induced tooth movement with 40 g/F on young adult male rats. BACKGROUND DATA: Hyalinization is a sterile necrosis at the pressure zone of the periodontal ligament observed during the initial stages of the orthodontic movement, and extensive hyaline areas might cause an important delay in the tooth movement. The use of LPT is considered an enhancement factor for bone repair, as it stimulates microcirculation as well as the cellular metabolism. MATERIALS AND METHODS: Thirty animals were divided into two groups (n=15), named according to the time of animal death (7, 13, and 19 days). Half of the animals in each group were subjected to irradiation with infrared (IR) laser (λ790 nm, round shaped beam, 40 mW, continuous wave (CW), diameter=2 mm (0.0314 cm(2)), 1.273 W/cm(2), time=2×112 sec+1×275 sec (total time 499 sec), 2×142.6/4.48 J+1×350/11 J, 635.2 J/cm(2)/20 J/ session), during orthodontic movement, the other half were used as nonirradiated controls. After animal death, specimens were sectioned, processed, and stained with hematoxylin and eosin (HE) and Sirius Red, and were used for semi-quantitative histologic analysis by light microscopy. Data were statistically analyzed. RESULTS: We demonstrated that LPT positively affected an important aspect of dental movement; the hyalinization. In the present study, we found a significant reduced expression of hyalinization after 19 days. On irradiated subjects, hyalinization was increased at day 7 with significant reduction at day 13. CONCLUSIONS: It is possible to conclude that the use of laser light caused histologic alterations during the orthodontic movement characterized by increased formation of areas of hyalinization at early stages, and late reduction when compared to nonirradiated animals.

Does LED phototherapy influence the repair of bone defects grafted with MTA, bone morphogenetic proteins, and guided bone regeneration? A description of the repair process on rodents.

This work carried out a histological analysis on bone defects grafted (MTA) treated or not with LED, BMPs, and membrane (GBR). Benefits of their isolated or combined usage on bone repair were reported, but not their association. Ninety rats were divided into ten groups and each subdivided into three. Defects on G II and I were filled with the blood clot. G II was further LED irradiated. G III and IV were filled with MTA; G IV was further LED irradiated. In G V and VI, the defects were filled with MTA and covered with a membrane (GBR). G VI was further LED irradiated. In G VII and VIII, BMPs were added to the MTA and group VIII was further LED irradiated. In G IX and X, the MTA + BMP graft was covered with a membrane (GBR). G X was further LED irradiated. LED was applied over the defect at 48-h intervals and repeated for 15 days. Specimens were processed, cut, and stained with H&E and Sirius red and underwent histological analysis. The use of LED light alone dramatically reduced inflammation. However, its use on MTA associated with BMP and/or GBR increased the severity of the inflammatory reaction. Regarding bone reabsorption, the poorest result was seen when the LED light was associated with the MTA + BMP graft. In the groups Clot and MTA + GBR, no bone reabsorption was detectable. Increased collagen deposition was observed when the LED light was associated with the use of the MTA associated with BMP and/or GBR. Increased new bone formation was observed when the LED light was used alone or associated with the use of MTA + GBR, MTA + BMP, on association of MTA + BMP + GBR and when BMP was added to the MTA. Our results indicate that the use of LED light alone or in association with MTA, MTA + BMP, MTA + GBR, and MTA + BMP + GBR caused less inflammation, and an increase of both collagen deposition and bone deposition as seen on both histological and morphometric analysis.

Light microscopic description of the effects of laser phototherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration in a rodent model.

We carried out a histological analysis on bone defects grafted with mineral trioxide aggregate (MTA) treated or not with laser, bone morphogenetic protein (BMP), and guided bone regeneration (GBR). Benefits of the use of MTA, laser, BMPs, and GBR on bone repair are well known, but there is no report on their association with laser light. Ninety rats were divided into 10 groups each subdivided into 3. Defects on G II and I were filled with the blood clot. G II was further irradiated with LED. G III and IV were filled with MTA; G IV was further irradiated with laser. G V and VI, the defects filled with MTA and covered with a membrane (GBR). G VI was further irradiated with laser. G VII and VIII, BMPs were added to the MTA and group VIII further irradiated with laser. G IX and X, the MTA + BMP graft was covered with a membrane (GBR). G X was further irradiated with laser. Laser light (λ = 850 nm, 150 mW, 4 J/cm(2) ) was applied over the defect at 48-h intervals and repeated for 15 days. Specimens were processed, cut and stained with H&E and Sirius red and underwent histological analysis. Subjects on group X were irradiated. The results showed different tissue response on all groups during the experimental time. Major changes were seen on irradiated subjects and included marked deposition of new bone in advanced maturation. It is concluded that near infrared laser phototherapy improved the results of the use of the MTA on bone defects.

Laser-induced alveolar bone changes during orthodontic movement: a histological study on rodents.

OBJECTIVE: The aim of this study was to assess by light microscopy changes in alveolar bone during orthodontic movement in rats. BACKGROUND: Orthodontic movement causes both removal and deposition of bone tissue. The use of laser phototherapy (LPT) is considered an enhancement factor for bone repair. METHODS: Thirty Wistar rats were divided into two groups (n = 15) and subdivided according to animal death (7,13, and 19 days). Half of the animals in each group were treated with LPT during orthodontic movement. After animal death, specimens were processed and underwent histological and semi-quantitative analyses (HE and Sirius red). RESULTS: LPT-irradiated specimens showed significantly higher numbers of osteoclasts when compared with controls at both 7 (p = 0.015) and 19 (p = 0.007) days, as well as significant increases in the number of osteoblasts (p = 0.015) between days 7 and 13. The amount of collagen matrix was significantly reduced between days 7 and 13 at both pressure and tension sites in controls (p = 0.015) but not in LPT-treated animals. LPT-treated subjects showed significantly greater deposition of collagen matrix at the pressure site at both the thirteenth (p = 0.007) and nineteenth days (p = 0.001). At the tension site, a significant increase in the amount of collagen matrix was observed in non-irradiated specimens (p = 0.048) between days 7 and 19. CONCLUSIONS: LPT caused significant histological changes in the alveolar bone during induced tooth movement, including alterations in the number of both osteoclasts and osteoblasts and in collagen deposition in both pressure and tension areas.

Effects of laser photobiomodulation on cutaneous wounds treated with mitomycin C: a histomorphometric and histological study in a rodent model.

AIM: The aim of the present study was to assess histologically the effect of Laser Photobiomodulation (LPBM) on skin wounds treated with Mitomycin C (MMC). BACKGROUND DATA: Wound healing occurs because of a competitive mechanism between the synthesis and lyses of collagen. Therefore, any factor that increases the lyses or reduces the synthesis of collagen may result in changes in the healing process. MMC is an antineoplastic drug that inhibits fibroblast proliferation, collagen synthesis, and neoangiogenesis. LPBM has been shown to stimulate wound healing, increasing the production of collagen, fibroblastic proliferation, and angiogenesis. MATERIALS AND METHODS: Forty-eight Wistar rats were randomly distributed into 4 main groups (n = 12): G1--control (G1a--7 d and G1b--14 d); G2--MMC (G2a--7 d and G2b--14 d); G3--MMC + lambda660 nm laser (G3a--7 d and G3b--14 d); and G4--MMC + lambda790 nm laser (G4a--7 d and G4b--14 d). Under general anesthesia, one excisional wound was created on the dorsum of each animal. Two ml of MMC solution was applied to the wound 4 h after surgery for 5 min. LPBM was performed on groups G3 (lambda690 nm; 20 J/cm(2); 30 mW; Phi = 2 mm) and G4 (lambda790 nm; 20 J/cm(2); 40 mW; Phi = 2 mm), starting immediately after the application of the MMC and repeated every other day during the experimental period. Laser light was applied transcutaneously at 4 equidistant points on the wound margin (4 x 5 J/cm(2), 20 J/cm(2)/session). The specimens were routinely cut and processed to wax. The slides were stained with HE and Sirius red. Computerized hystomorphometry was performed. RESULTS: LPBM resulted in reduced inflammation and an increase in both fibroblast proliferation and collagen deposition. CONCLUSION: The use of LPBM improves wound healing in subjects treated with MMC.

Dose and wavelength of laser light have influence on the repair of cutaneous wounds.

OBJECTIVE: The objective of the present study was to compare histologically the effect of GaAlAs (lambda 830 nm, phi approximately 2 mm(2), 35 mW) and InGaAlP (lambda 685 nm, phi approximately 2 mm(2), 35 mW) lasers, alone or in association with doses of 20 or 50 J/cm(2) on cutaneous wounds in the dorsum of the Wistar rat. BACKGROUND DATA: The healing time of surgical wounds is of extreme importance and it is usually associated with a post-operative period free of infection and with less pain and inflammation. MATERIALS AND METHODS: Sixty Wistar rats were divided into seven groups: Group I - control (non-irradiated); Group II - lambda 685 nm, 20 J/cm(2); Group III - lambda 830 nm, 20 J/cm(2); Group IV - lambda 685 nm and lambda 830 nm, 20 J/cm(2); Group V - lambda 685 nm, 50 J/cm(2)); Group VI - lambda 830 nm, 50 J/cm(2); and Group VII - lambda 685 nm and 830 nm, 50 J/cm(2). The animals were sacrificed 3, 5, and 7 days after surgery. RESULTS: Light microscopic analysis using H&E and Picrosírius stains showed that, at the end of the experimental period, irradiated subjects showed increased collagen production and organization when compared to non-irradiated controls. Inflammation was still present in all groups at this time. CONCLUSION: Group IV (lambda 830 nm and lambda 685 nm, 20 J/cm(2)) presented better results at the end of the experimental period. It is concluded that low-level light therapy (LLLT) can have a positive biomodulatory effect on the repair of cutaneous wounds.