Differential expression of galectin-3, beta-catenin, and cyclin D1 in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma of salivary glands

Background: Galectin-3 has been implicated in tumor progression of some malignancies as thyroid, prostate, and salivary gland tumors. Recently, it has been suggested that this protein may be an important mediator of the beta-catenin/Wnt pathway. Moreover, nuclear galectin-3 expression has been implicated in cell proliferation, promoting cyclin D1 activation. Thus, the present study aimed to correlate galectin-3 expression with beta-catenin and cyclin D1 expressions in adenoid cystic carcinoma (ACC) and in polymorphous low-grade adenocarcinoma (PLGA). Methods: Fifteen formalin-fixed paraffin-embedded cases of each tumor were retrieved from the files of the Surgical Oral Pathology Service at the University of Sao Paulo and the proteins were analyzed by immunohistochemistry. Results: Adenoid cystic carcinoma showed galectin-3 immunostaining mainly in the nuclei, while PLGA revealed a positive mostly cytoplasmic reaction to galectin-3 in the largest part of tumor cells. Both tumors showed intense cytoplasmic/nuclear staining for beta-catenin in majority of cases. Cyclin D1 immunoreactivity was not detected in 14/15 PLGA and showed specific nuclear staining in 10/15 cases of ACC in more than 5% of the neoplastic cells. Cyclin D1 expression was correlated with cytoplasmic and nuclear galectin-3 expression in ACC (P < 0.05). Conclusions: These results suggest that in ACC galectin-3 may play a role in cellular proliferation through cyclin D1 activation. In addition, nuclear expression of galectin-3 in ACC may be related to a more aggressive behavior of this lesion. Although beta-catenin seems to play a role in carcinogenesis in both lesions, it seems that it does not bind to galectin-3 for cyclin D1 stimulation.

WNT-5A, but not matrix metalloproteinase 3 or beta-catenin protein, expression is related to early stages of lip carcinogenesis

Background: Oncogenic Wnt/beta-catenin signaling occurs in numerous types of cancers, but little is known about the role of the Wnt protein family member, WNT-5A, in lip carcinogenesis. The aim of this study was to investigate WNT-5A, beta-catenin, and matrix metalloproteinase (MMP)-3 protein expression in actinic cheilitis (AC), and lip squamous cell carcinoma (LSCC). Methods: Twenty-one cases of AC, and fifty-one cases of LSCC were analyzed, with normal lip mucosa used as a control. Qualitative and semi-quantitative analyses of WNT-5A, beta-catenin, and MMP-3 immunostaining pattern and cellular distribution were performed. Results: WNT-5A was observed in more than 50% of the cells, scattered in all layers of AC, in contrast to the absence of immunostaining in normal lip mucosa. AC presented a higher level of WNT-5A expression than LSCC (P = 0.0289, Fisher test), while MMP-3 immunoexpression was statistically more significant in LSCC than in AC (P = 0.0285, Fisher test). Immunolabeling of beta-catenin protein was differentially distributed between samples; the majority of AC cases (61.90%) demonstrated a membranous-cytoplasmic pattern, while a considerable number of LSCC cases (29.41%) revealed a cytoplasmic pattern, instead of the usual membranous pattern. Conclusions: The present results suggest that WNT-5A may be an important marker during initial events of AC malignant transformation, in which non-canonical and canonical Wnt/beta-catenin signaling pathways could be involved. Additionally, WNT-5A might recruit other events in LSCC, such as MMP-3 protein synthesis, as its presence is increased in established malignant processes without beta-catenin dependency.

Microstructural and Ultrastructural Assessment of Inferior Alveolar Nerve Damage Following Nerve Lateralization and Implant Placement: An Experimental Study in Rabbits

Purpose: The present study assessed damage to the inferior alveolar nerve (IAN) following nerve lateralization and implant placement surgery through optical and transmission electron microscopy (TEM). Materials and Methods: IAN lateralization was performed in 16 adult female rabbits (Oryctolagus cuniculus). During the nerve lateralization procedure, one implant was placed through the mandibular canal, and the IAN was replaced in direct contact with the implant The implant was placed in the right mandible, and the left side was used as a control (no surgical procedure) After 8 weeks, the animals were sacrificed and samples were prepared for optical and TEM analysis of IAN structural damage Histomorphometric analysis was performed to determine the number and cross-sectional dimensions of nerve fascicles and myelin sheath thickness between experimental and control grouos. The different parameters were compared by one-way analysis of variance at the 95% significance level Results: Alterations in the perineural and endoneural regions of the IAN, with higher degrees of vascularization., were observed in the experimental group TEM showed that the majority of the myelinated nerve fibers were not affected in the experimental samples. No significant variation in the number of fascicles was observed, significantly larger fascicle height and width were observed in the control group, and significantly thicker myelin sheaths were observed in the experimental samples Conclusion: IAN lateralization resulted in substantial degrees of tissue disorganization at the microstructural level because of the presence of edema However, at the ultrastructural level, small amounts of fiber degeneration were observed. INT J ORAL MAXILLOFAC IMPLANTS 2009,24-859-865

Electrocardiographic Alterations During Endosseous Implant Placement Performed with Local Anesthetic Agents

Purpose: The purpose of this study was to analyze electrocardiographic alterations during dental implant surgeries when local anesthetic agents were used. Materials and Methods: Twenty implants were placed in 18 healthy patients. An electrocardiogram and Wincardio software were used to gather recordings from 12 static leads every 2 minutes, continuously record coronary artery (D2) derivations, and automatically measure the following electrocardiographic parameters: heart rate, duration and amplitude of the P wave, PR segment duration, ST segment deviation, QRS complex duration, and duration of the RR, QT, and corrected QT (QTc) intervals. Results: Analysis of variance of the values obtained at the different stages showed significant differences (P < .05) for the heart rate and for the duration of the RR and QT intervals. The heart rate increased during the anesthesia, incision, and bone drilling stages, reaching a peak during drilling. Duration of the RR and QT intervals decreased during the incision and drilling stages. Among the electrocardiographic parameters individually assessed, several altered values were found for the duration of the P wave, the QRS complex, and the QT and QTc intervals. Sinusal tachycardia and bradycardia, sinusal arrhythmia, supraventricular extrasystole, ventricular extrasystole, and T-wave inversion were detected. Conclusion: Dental implant placement surgery may induce electrocardiographic alterations. The most frequently found arrhythmias were extrasystole and sinusal tachycardia. The anesthesia, incision, and bone drilling stages exhibited the highest heart rate values and the shortest durations of the RR and QT intervals. INT J ORAL MAXILLOFAC IMPLANTS 2009;24:412-418

Alpha lipoic acid in burning mouth syndrome - a randomized double-blind placebo-controlled trial

The burning mouth syndrome (BMS) is a chronic condition characterized by oral burning pain in the absence of clinical abnormalities and without established therapy. The purpose of this study was to evaluate the effectiveness of alpha lipoic acid (ALA) in the management of BMS symptoms through a randomized double-blind placebo-controlled trial. Thirty-eight patients (34 women and four men, median age 62.9 years, range 36-78) were included and 31 completed the study. The patients were randomized into two cycles of treatment: one with alpha lipoic acid and one with placebo both administered in identical capsules. These cycles were separated by a washout period of 20 days. The oral symptoms and the treatment response were assessed using a 100-mm visual analog scale before and after each cycle and the global perceived effect score, using a 5-point scale after each treatment cycle. The level of reduction on burning was significant for both treatments (paired t-test: P < 0.05; rp = 0.011; ral < 0.001). Considering the two cycles together, 22 patients reported at least some improvement after ALA use and 23 patients after placebo. Comparison of the oral assessment scores of the two cycles failed to demonstrate the effectiveness of ALA over placebo (t-test: P > 0.05; r = 0.75).

Precise Insertion of Orthodontic Miniscrews with a Stereolithographic Surgical Guide Based on Cone Beam Computed Tomography Data: A Pilot Study

Purpose: Orthodontic miniscrews are commonly used to achieve absolute anchorage during tooth movement. One of the most frequent complications is screw loss as a result of root contact. Increased precision during the process of miniscrew insertion would help prevent screw loss and potential root damage, improving treatment outcomes. Stereo lithographic surgical guides have been commonly used for prosthetic implants to increase the precision of insertion. The objective of this paper was to describe the use of a stereolithographic surgical guide suitable for one-component orthodontic miniscrews based on cone beam computed tomography (CBCT) data and to evaluate implant placement accuracy. Materials and Methods: Acrylic splints were adapted to the dental arches of four patients, and six radiopaque reference points were filled with gutta-percha. The patients were submitted to CBCT while they wore the occlusal splint. Another series of images was captured with the splint alone. After superimposition and segmentation, miniscrew insertion was simulated using planning software that allowed the user to check the implant position in all planes and in three dimensions. In a rapid-prototyping machine, a stereolithographic guide was fabricated with metallic sleeves located at the insertion points to allow for three-dimensional control of the pilot bur. The surgical guide was worn during surgery. After implant insertion, each patient was submitted to CBCT a second time to verify the implant position and the accuracy of the placement of the miniscrews. Results: The average differences between the planned and inserted positions for the ten miniscrews were 0.86 mm at the coronal end, 0.71 mm at the center, and 0.87 mm at the apical tip. The average angular discrepancy was 1.76 degrees. Conclusions: The use of stereolithographic surgical guides based on CBCT data allows for accurate orthodontic mini screw insertion without damaging neighboring anatomic structures. INT J ORAL MAXILLOFAC IMPLANTS 2011;26:860-865

Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts

Background and Objective: Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts. Materials and Methods: Fibroblasts were stimulated for 48 h with 10(-4) or 10(-9) m Substance P; untreated fibroblasts served as controls. The expression of MMP-1, -2, -3, -7 and -11 and of TIMP-1 and -2 was evaluated using real-time polymerase chain reaction and western blotting. Resulsts: There was a significant, concentration-dependent stimulatory effect of Substance P on MMP-1, -2, -3 and -7 and TIMP-2 gene expression (p < 0.05), and a probable effect on MMP-11 (p = 0.06). At the higher concentration (10(-4) m Substance P), MMP-1, -2, -3, -7 and -11 and TIMP-2 showed the greatest up-regulation; at the lower concentration (10(-9) (M) Substance P), MMP-1, -3 and -7 and TIMP-2 exhibited diminished up-regulation, with MMP-2 and -11 showing down-regulation (p < 0.05). Expression of TIMP-1 was not affected by Substance P (p > 0.05). Western blotting confirmed that Substance P up-regulated MMP-1, -2, -3 and -11 and TIMP-2. MMP-1, -3 and -11 and TIMP-2 showed greater up-regulation at the higher Substance P concentration and diminished up-regulation at the lower concentration. MMP-2 was up-regulated to a similar degree at both Substance P concentrations. Conclusion: In gingival fibroblast cells, Substance P at the higher concentration (10(-4) m) induced greater up-regulation of MMP-1, -3 and -11 and TIMP-2 expression, but at the lower concentration (10(-9) (M)) induced diminished up-regulation, which may represent a mechanism for modulating periodontal breakdown.

Scanning Electron Microscopy In Vitro Study on the Effect of Carisolv Application on Periodontally Diseased Root Surfaces

The purpose of this study was to evaluate the characteristics of diseased root surfaces treated by the association of scaling and the application of Carisolv. Twenty-four uniradicular periodontally involved teeth were used in this study The teeth were divided randomly into three groups: eight teeth were scaled and root planed until there was a complete visible removal of calculus (group 1), Carisolv was applied on the root surfaces of eight teeth twice for 30 seconds before scaling with a sharp curette (group 2), and eight teeth received the same treatment as in group 2 but with a blunt curette (group 3). Specimens were examined using scanning electron microscopy The superficial aspect of the roots from group 1 presented scratches that mirrored the curette cutting edge, and the smear layer completely covered the surface. Root surfaces from groups 2 and 3 also presented a smear layer that covered the surface completely but it was somewhat smoother than group 1. The use of Carisolv as an adjunct to scaling and root planing presented no advantage for smear layer removal over scaling alone, suggesting that no benefit is obtained by the use of Carisolv during periodontal mechanical treatment. (Int J Periodontics Restorative Dent 2011;31:91-95.)

Measuring Bond Strength Between Fiber Post and Root Dentin: A Comparison of Different Tests

Purpose The aim of this study was to evaluate the ability of bond strength tests to accurately measure the bond strength of fiber posts luted into root canals Materials and Methods The test methods studied were hourglass microtensile (HM), push-out (PS), modified push out (MP) and pull out (PL) The evaluated parameters were bond strength values, reliability (using Weibull analysis), failure mode (using confocal microscopy), and stress distribution (using finite element analysis) Forty human intact single rooted and endodontically treated teeth were divided into four groups Each group was assigned one of the test methods The samples in the HM and PS groups were 1 0 +/- 0 1 mm thick, the HM samples were hourglass shaped and the PS samples were disk shaped For the PL and MP groups, each 1 mm dentin slice was luted with a fiber post piece Three dimensional models of each group were made and stress was analyzed based on Von Mises criteria Results PL provided the highest values of bond strength followed by MP both of which also had greater amounts of adhesive failures PS showed the highest frequency of cohesive failures MP showed a more homogeneous stress distribution and a higher Weibull modulus Conclusion The specimen design directly influences the biomechanical behavior of bond strength tests

Microshear Bond Strength of Self-etching Systems Associated with a Hydrophobic Resin Layer

Purpose: To evaluate in vitro the microshear bond strength of adhesive systems applied to dentin according to manufacturers` instructions, associated or not with a hydrophobic layer of unfilled resin. Materials and Methods: Six self-etching adhesives (Clearfil SE Bond, Kuraray Medical; AdheSE, lvoclar Vivadent; Xeno III, Dentsply; I Bond, Heraeus-Kulzer; Bond Force, Tokuyama; Futurabond DC, Voco) were tested. The labial dentin of sixty bovine incisors was exposed, and the teeth were divided into two groups according to the application or not of an extra hydrophobic resin layer (Scotchbond Multi Purpose Plus, bottle 3). Six composite cylinders (Filtek Z250, 3M ESPE) were built up on each treated surface. Specimens were stored in distilled water at 37 C for 24 h and then subjected to the microshear bond strength test in a universal testing machine at a crosshead speed of 0.5 mm/min. Microshear bond strength values were analyzed by 2-way ANOVA and Tukey`s post-hoc test. Failure mode was determined using a stereomicroscope under 20X magnification. Results: The application of the hydrophobic resin layer did not affect bond strength, except for AdheSE. However, the bond strengths with the hydrophobic layer were similar among the six tested systems (Clearfil: 17.1 +/- 7.9; AdheSE: 14.5 +/- 7.1; Xeno III: 12.8 +/- 7.7; I Bond: 9.5 +/- 5.8; Bond Force: 17.5 +/- 4.1; Futurabond: 7.7 +/- 2.3). When used as recommended by the manufacturers, Bond Force presented statistically higher bond strength than AdheSE and I Bond (p < 0.05) (Clearfil 10.4 +/- 4.9; AdheSE 1.6 +/- 1.6; Xeno III: 9.0 +/- 3.8; I Bond: 3.0 +/- 1.5; Bond Force: 14 +/- 3.9; Futurabond: 8.8 +/- 3.8). Failure mode was predominantly adhesive. Conclusion: The bond strength of the self-etching systems tested was not significantly affected by the application of a hydrophobic layer, but a significant improvement was observed in AdheSE.

Influence of BisGMA, TEGDMA, and BisEMA contents on viscosity, conversion, and flexural strength of experimental resins and composites

Different monomer structures lead to different physical and mechanical properties for both the monomers and the polymers. The objective of this study was to determine the influence of the bisphenylglycidyl dimethacrylate (BisGMA) concentration (33, 50 or 66 mol%) and the co-monomer content [triethylene glycol dimethacrylate (TEGDMA), ethoxylated bisphenol-A dimethacrylate (BisEMA), or both in equal parts] on viscosity (eta), degree of conversion (DC), and flexural strength (FS). eta was measured using a viscometer, DC was obtained by Fourier transfer Raman (FT-Raman) spectroscopy, and FS was determined by three-point bending. At 50 and 66% BisGMA, increases in eta were observed following the partial and total substitution of TEGDMA by BisEMA. For 33% BisGMA, eta increased significantly only when no TEGDMA was present. The DC was influenced by BisGMA content and co-monomer type. Mixtures containing 66% BisGMA showed a lower DC compared with mixtures containing other concentrations of BisGMA. The BisEMA mixtures had a lower DC compared with the TEGDMA mixtures. The FS was influenced by co-monomer content only. BisEMA mixtures presented a statistically lower FS, followed by TEGDMA + BisEMA mixtures, and then by TEGDMA mixtures. Partial or total replacement of TEGDMA by BisEMA increased eta, which was associated with the observed decreases in DC and FS. Although the BisGMA content influenced the DC, it did not affect the FS results.

Evaluation of two mineral trioxide aggregate compounds as pulp-capping agents in human teeth

The present randomized, controlled prospective study evaluated the histomorphological response of human dental pulps capped with two grey mineral trioxide aggregate (MTA) compounds. Pulp exposures were performed on the occlusal floor of 40 human permanent pre-molars. The pulp was capped either with ProRoot (Dentsply) or MTA-Angelus (Angelus) and restored with zinc oxide eugenol cement. After 30 and 60 days, teeth were extracted and processed for histological examination and the effects on the pulp were scored. The data were subjected to Kruskal-Wallis and Conover tests (alpha = 0.05). In five out of the 40 teeth bacteria were present in pulp tissue. No significant difference was observed between the two materials (P > 0.05) in terms of overall histological features (hard tissue bridge, inflammatory response, giant cells and particles of capping materials). Overall, 94% and 88% of the specimens capped with MTA-Angelus and ProRoot, respectively, showed either total or partial hard tissue bridge formation (P > 0.05). Both commercial materials ProRoot (Dentsply) and MTA-Angelus (Angelus) produced similar responses in the pulp when used for pulp capping in intact, caries-free teeth.

Impact of PI and NNRTI HAART-based therapy on oral lesions of Brazilian HIV-infected patients

Background: The incidence of oral lesions related to human immunodeficiency virus (HIV) infection have been investigated after treatment with highly active antiretroviral therapy (HAART) including protease inhibitors (PI) but no data are available on the effect of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy on incidence of acquired immunodeficiency syndrome (AIDS) oral manifestations or impact of HAART on oral manifestations of HIV infection in Brazil. The aim of this study was to describe the effects of anti-HIV therapy on the incidence of oral lesions during 17 years of AIDS epidemics in a Brazilian population. Methods: From 1989 to 2006, we collected data from 1595 consecutive HIV patients at the Special Care Dentistry Center, Sao Paulo, Brazil. We compared the effect of PI- and NNRTI-based antiretroviral therapy (ARVT) on the annual incidence of Kaposi sarcoma (KS), oral candidiasis (OC) and hairy leukoplakia (HL). The chi-squared test was used to test the association between oral lesions and therapeutic regimen (P < 0.05). Results: None of patients on ARVT presented with KS. Patients who used (nucleoside reverse transcriptase inhibitors) NRTI + PI were 0.9 times as likely to present with HL as those who used NRTI + NNRTI. This finding, however, was not statistically significant (P = 0.5). The relative risk for OC was 0.8 in patients with PI-based HAART. The increased risk among those on PIs was statistically significant (P = 0.004). Conclusions: The superiority of NNRTI regimens in decreasing OC incidence is consistent with current therapeutic guidelines which recommend NNRTI-based therapy as the treatment of choice for initial ARVT.

Effect of diabetes on orthodontic tooth movement in a mouse model

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading. Type 1 diabetes results in bone remodeling, suggesting that this disease might affect orthodontic tooth movement. The present study investigated the effects of the diabetic state on orthodontic tooth movement. An orthodontic appliance was placed in normoglycemic (NG), streptozotocin-induced diabetes (DB), and insulin-treated DB (IT) C57BL6/J mice. Histomorphometric analysis and quantitative PCR of periodontium were performed. The DB mice exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphate (TRAP) -positive osteoclasts than NG mice. This was associated with increased expression of factors involved in osteoclast activity and recruitment (Rankl, Csf1, Ccl2, Ccl5, and Tnfa) in DB mice. The expression of osteoblastic markers (Runx2, Ocn, Col1, and Alp) was decreased in DB mice. Reversal of the diabetic state by insulin treatment resulted in morphological findings similar to those of NG mice. These results suggest that the diabetic state up-regulates osteoclast migration and activity and down-regulates osteoblast differentiation, resulting in greater orthodontic tooth movement.