Beyond the mouth: Uncovering non-secretory multiple myeloma through oral symptoms.

Non-secretory multiple myeloma (NSMM) is a rare cancer of plasma cells characterized by the absence of detectable monoclonal M protein in the blood or urine. A 57-year-old woman presented with mandibular pain but without intraoral swelling. Imaging studies revealed multiple osteolytic lesions in her mandible and pronounced root resorption of the left mandibular second molar. Biopsy results showed atypical plasmacytoid cells positive for anti-kappa, CD138, MUM1, and CD79a antibodies, but negative for anti-lambda and CD20. These results were indicative of a malignant plasma cell neoplasm. No abnormalities were revealed by free light chain assay or by serum or urine protein electrophoresis, leading to a diagnosis of NSMM. The patient began chemotherapy in conjunction with bisphosphonate therapy and achieved remission following treatment. This case underscores the critical role of dentists in the early detection and prevention of NSMM complications, as the disease can initially present in the oral cavity.

Tumor Budding and Poor Prognosis in Oral Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Tumor budding (TB) has been investigated in several types of solid tumors. In oral cancer, studies show its association with survival. However, for its implementation in routine histological analyses, results with a high certainty of evidence are needed. Therefore, the aim of this systematic review is to explore the association between tumor budding and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in oral cancer. METHODS: A search was performed in Embase, PubMed, Scopus, Livivo, Web of Science, and Google Scholar. We adopted the following inclusion criteria: studies that evaluate tumor budding in oral cancer, that investigate survival, and presenting cohort design. We excluded reviews and studies without hazard-ratio (HR) data. RESULTS: This systematic review included 22 studies and showed an association between TB and survival. High-grade TB is associated with a worse OS in univariate analysis (HR = 3.11; 95% CI: 2.06-4.69, p<0.01) and multivariate analysis (HR = 2.62; 95% CI: 1.64-4.20, p<0.01); with a poorer DSS in univariate (HR = 2.43; 95% CI: 1.94-3.03, p<0.01) and multivariate analysis (HR = 2.01; 95% CI: 1.43-2.83, p< 0.01); and with a worse DFS in univariate (HR = 1.94; 95% CI: 1.44-2.62, p<0.01) and multivariate analysis (HR = 2.15; 95% CI: 1.31-3.53, p< 0.01). Sensitivity analysis showed that the results are robust, and no significant publication bias was identified in univariate analysis for DFS (Egger's test: p = 0.94). The certainty of the evidence was graded as low or very low. CONCLUSION: Our findings indicate that TB is an independent prognostic factor of OS, DSS, and DFS in oral cancer. However, further studies are needed to increase the certainty of the evidence.

Oral carcinogenesis triggers a nociceptive behavior and c-Fos expression in rats' trigeminal pathway.

OBJECTIVE: To recognize changes that occur along the trigeminal pathway in oral cancer in order to establish an effective approach to pain control. METHODS: Wistar rats were divided into control and 4-NQO groups for 8, 12, 16, or 20 weeks. 4-NQO suspension was administered on the animals' tongues. Mechanical hyperalgesia, assessment of facial expressions, and an open-field test were performed. After euthanasia, the animals' tongues were removed for macro- and microscopic analysis. c-Fos expression was analyzed in the trigeminal pathway structures. RESULTS: 4-NQO induced time-dependent macroscopic lesions that were compatible with neoplastic tumors. Histopathological analysis confirmed oral squamous cell carcinoma in 50% of the animals on the 20th week. There was a significant nociceptive threshold reduction during the first two weeks, followed by a threshold return to the baseline levels, decreasing again from the 12th week. Facial nociceptive expression scores were observed on the 20th week, while increased grooming and exploratory activity were observed on the 8th week. Trigeminal ganglion showed an increased c-Fos immunoexpression on the 20th week, and in the trigeminal subnucleus caudalis, it occurred on the 16th and 20th. The long-term carcinogenic exposure caused changes in the nociceptive behavior and c-Fos expression in the rats' trigeminal pathway.

Milk kefir therapy improves the skeletal response to resistance exercise in rats submitted to glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIO) has emerged as a challenge after long-term glucocorticoids (GCs) administration. Exercise has been an important non-pharmacological option, while medications modulate bone remodeling despite adverse effects. In this way, milk Kefir (MK) therapy stands out as a safe alternative to improve bone metabolism. Our study aimed to investigate the effect of MK associated to resistance exercise on bone loss in rats with GIO. For this, sixty male Wistar rats were divided into 2 groups: normal (N) and subjected to GIO, which was subdivided into 4 groups: control (C), milk kefir therapy (K), Exercise (Ex), and Exercise+K (ExK). GIO was induced by dexamethasone (7 mg/kg - i.m.; 1×/wk, 5 wk). MK was administered daily (1×/day; 0.7 ml/animal) and the climb exercise with load was performed 3×/wk; both for 16 wk. Femur was collected for assessment of bone microarchitecture, quality and metabolism. GIO markedly reduced trabecular bone volume density (BV/TV) (-35 %), trabecular thickness (Tb.Th) (-33 %), mineral content of femur (-26 %) as well as bone collagen content (-56 %). Bone strength and its biomechanical properties given by flexural strength (-81 %), fracture load (-80 %), and the number of osteocytes (-84 %) were lowered after GIO. GCs reduced osteoblast number and function while increased osteoclast number, altering bone remodeling (p < 0.05). On the other hand, ExK significantly improved bone microarchitecture and quality, marked by fractal dimension increase (+38 %), cortical volume (+34 %), BV/TV (+34 %), Tb.Th (+33 %), mineral content and collagen maturity, while reduced the space between trabecula (-34 %). The Ex and ExK increased the number of osteocytes (p < 0.05) and they were able to reverse the lower osteoblast number. Both treatments used alone significantly enhanced bone biomechanical properties, but the ExK showed a more significant improvement. ExK ameliorated bone strength and biomechanics (p < 0.05) and stimulated bone formation and modulated bone remodeling (p < 0.05). MK and exercise administered isolated or in association increased the percentage of collagen bone filling after GIO (p < 0.05), but only ExK improved collagen maturity. Our results showed that MK associated to resistance exercise enhanced bone microarchitecture, quality and metabolism, being therefore an interesting tool to improve skeletal response during GIO.

Analysis of the Immunoexpression of Opioid Receptors and their Correlation with Markers of Angiogenesis, Cell Proliferation and Apoptosis in Breast Cancer.

OBJECTIVE: Breast cancer is a disease of great concern. The prognosis of this tumor is related to its staging. Opioids are widely used to minimize pain in oncology clinics; however, the relationship between the administration of opioids and their effects on tumor cells has yet to be elucidated. Therefore, this study aimed to evaluate the immunoexpression of mu- (µ) and kappa- (κ) opioid receptors and their correlation with markers of angiogenesis, cell proliferation, and apoptosis in biopsies of breast tumors. METHODS: Demographic data, tumor characteristics, opioid use, and prognostic factors were collected from medical records. After the selection of the excisional biopsies, immunohistochemistry was performed for µ- and κ-opioid receptors, vascular endothelial growth factor (VEGF), Ki-67, and TUNEL. RESULTS: A significant predominance of Ki-67 and µ-opioid receptor immunoexpression in the lymph nodes was observed in patients administered opioid medications. The luminal A subtype showed higher apoptosis levels (TUNEL) compared to the luminal B subtype. Patients with T4 tumor who had recurrence demonstrated a reduced expression of κ-opioid receptors at the lymph node location. Correlation analyses between the µ and κ opioid markers, VEGF, Ki-67, and TUNEL showed that these findings are likely involved in the same mechanisms the cancer of T4 stage breast cancer. CONCLUSION: The κ-opioid receptor has a lower immunoexpression in nodal tumor metastasis with recurrence, whereas the µ-opioid receptor is directly related to expression of TUNEL-positive cells  in tumors and indirectly to Ki-67 in nodal metastasis. Neither of the two receptors was expressed in the primary tumor or nodal metastasis in relation to VEGF.

Do Protocadherins Show Prognostic Value in the Carcinogenesis of Human Malignant Neoplasms? Systematic Review and Meta-Analysis.

BACKGROUND: Protocadherins (PCDHs) have been reported as tumor suppressor genes, implying that these genes may be involved in tumor suppression in a variety of cancers. However, a thorough understanding of the functions and mechanisms of PCDHs remains limited. Our aim was to investigate the methylation profile of PCDHs in human malignant neoplasms. METHODS: This systematic review has been recorded in PROSPERO (#42019117844) and conducted according to PRISMA's checklist; search was conducted in LILACS, PubMed, Science Direct, Scopus, and Web of Science databases, manually, with search queries and without date or language restrictions. RESULTS: We found 91 articles, of which 26 were used for this meta-analysis and categorized according to the origin of the neoplasia. In total, 3,377 cases were compiled, with PCDH10, PCDH17, and PCDH8 being the most studied; males were 2.22 times more affected than females. Studies have shown significant heterogeneity (p <0.001), with the odds ratio varying between cases and controls [2.20 (95% CI = 1.11- 4.35) to 209.05 (95% CI = 12.64- 2,457.18)], and the value of association between methylation and cancers studied was 26.08 (95% CI = 15.42-44.13). CONCLUSION: In this systematic review, we have demonstrated using meta-analysis that PCDHs could emerge as potential tumor suppressor genes and that a significant increase in methylation may be useful for early detection of different cancers. This work may help in the identification of new prognostic biomarkers in malignant neoplasms.

CD133 Role in Oral Carcinogenesis.

OBJECTIVE: to investigate CD133 immunoexpression, cancer stem cells marker, in oral epithelial dysplasias (OEDs) and oral squamous cells carcinomas (OSCCs) and understandits possible involvement in the malignant transformation process of these lesions and to better elucidate their biological behavior. MATERIAL AND METHODS: Tissue samples of 15 cases of OSCCs and 15 OEDs were subjected to CD133 antibody immunohistochemistry reactions. The analysis used quantitative parameters (number of immunostained cells regardless of immunostaining sublocations). RESULTS: All samples of OSCCs and OEDs showed positive immunostaining, with no significant difference between these groups (p = 0.283). We did not observe statistical difference between the degree of dysplasia and the amount of CD133+ cells (p = 0.899). CD133 immunoexpression showed no association with the OEDs and OSCCs sites. It was observed that nuclear and cytoplasmic immunostaining was more evident with the progression of the malignant process. CONCLUSION: It is suggested that the CD133 cellular localization together with the histopathological criteria of OEDs classification can contribute to provide more concrete indications about the oral carcinogenesis process.

Loss of heterozygosity and immunoexpression of PTEN in oral epithelial dysplasia and squamous cell carcinoma.

INTRODUCTION: Oral epithelial dysplasia (OED) is a risk factor for developing subsequent oral squamous cell carcinoma (OSCC). Loss of heterozygosity (LOH) profiles have been validated as risk predictors of malignant transformation of OED. It is still unclear if Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) allelic loss also occurs in initial stage malignant lesions and if the allelic loss is involved as one of the mechanisms of oral carcinogenesis. Thus, this study objective investigate LOH of PTEN gene and the immunohistochemical expression of the protein in OED and OSCC samples. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded samples of 19 OEDs and 16 OSCCs were included to immunohistochemistry and LOH analysis. Two polymorphic microsatellite markers (AFMA086WG9 and D10S1765) located in chromosome 10 were used in this study for LOH analysis. For immunohistochemical analysis, 5 random fields with 400× magnification were evaluated quantitatively and qualitatively in epithelial and neoplastic cells. RESULTS: AFMA086WG9 marker only demonstrated LOH in OEDs cases (10.5%). D10S1765 marker demonstrated LOH in 57.2% of OEDs and 50% of OSCCs. Higher nuclear immunostaining was detected in cases of OSCCs when compared to OEDs (p < .001) and there was strong cytoplasmic immunoexpression in OSCCs (p < .045). CONCLUSIONS: We provide evidence that the allelic loss of PTEN is present in premalignant oral lesions and OSCCs, however the LOH of PTEN does not seems to influence its protein expression.

Pharmacological Characterization and Raman Spectroscopy Evaluation of Oral and Maxillofacial Surgery-Related Carnoy´S Solution Modified by Different Viscosity Agents.

BACKGROUND: There are several lesions of odontogenic and non-odontogenic origin in the oral cavity, such as odontogenic keratocyst, as well as many treatment options for such lesions. In order to reduce recurrence due to conservative treatments and less aesthetic and functional impairment of the patient (radical therapies), Carnoy's solution has been used as an adjuvant to surgery, showing satisfactory results. Its application is not standardized, presenting risks to adjacent tissues. Thus, we characterized the Carnoy's solution with different viscosity agents to enhance its applicability. MATERIAL AND METHODS: All solutions prepared (Carnoy with and without chloroform) were added with viscosity agent: ethyl cellulose, propylene glycol, and glycerol totaling eight solutions. The pharmacological characterization of the solutions was performed by determining the mass density and relative density (using a clean and dry pycnometer), pH (using pH meter), and concentration of Fe3+ (using ultraviolet/visible spectroscopy). The analyses of the inorganic components were determined by Raman micro spectrometry. Data were analyzed with statistical program BIOESTAT 5.3. RESULTS: Solutions with ethyl cellulose were discarded due to precipitate formation and suspension of the viscosity agent. In the other solutions, viscosity increase (propylene glycol solutions) and acidic pH were observed mainly in the glycerol group. The ferric chloride characterized as a hemostatic agent had its concentration increased with the use of thickening agents, theoretically favoring its action. CONCLUSION: The similarity of the propylene glycol and glycerol molecules justifies the Raman spectra of these substances to be similar and the difficulty in obtaining a "fingerprint".
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Immunoexpression of canonical Wnt and NF-κB signaling pathways in the temporomandibular joint of arthritic rats.

OBJECTIVE: To investigate the participation of canonical Wnt and NF-κB signaling pathways in an experimental model of chronic arthritis induced by methylated bovine serum albumin (mBSA) in rat temporomandibular joint (TMJ). MATERIALS AND METHODS: Wistar rats were sensitized by mBSA+Complete Freund Adjuvant (CFA)/Incomplete Freund Adjuvant (IFA) on the first 14 days (1 ×/week). Subsequently, they received 1, 2 or 3 mBSA or saline solution injections into the TMJ (1 ×/week). Hypernociceptive threshold was assessed during the whole experimental period. 24 h after the mBSA injections, the TMJs were removed for histopathological and immunohistochemical analyses for TNF-α, IL-1ß, NF-κB, RANKL, Wnt-10b, ß-catenin and DKK1. RESULTS: The nociceptive threshold was significantly reduced after mBSA injections. An inflammatory infiltrate and thickening of the synovial membrane were observed only after mBSA booster injections. Immunolabeling of TNF-α, IL-1ß and Wnt-10b was increased in the synovial membrane in arthritic groups. The immunoexpression of nuclear ß-catenin was significantly higher only in the group that received 2 booster TMJ injections. However, NF-κB, RANKL and DKK1 immunoexpression were increased only in animals with 3 mBSA intra-articular injections. CONCLUSION: Our results suggest that canonical Wnt and NF-κB signaling pathways participate in the hypernociception and inflammatory response in TMJ synovial membrane during the development of rheumatoid arthritis in rats.

Immunohistochemical Evaluation of GLUT-3 and GLUT-4 in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Objectives: To evaluate immunohistochemically the expression of GLUT-3 and GLUT-4 in oral epithelial dysplasia (OED) and the oral squamous cell carcinoma (OSCC) and assess possible involvement in the malignant transformation of oral lesions. Methods: Tissue samples of 15 cases of OSCC and 15 of OED were subjected to immunohistochemistry with anti-GLUT-3 and anti-GLUT-4 antibodies. Five fields of each case were analyzed, to provide percentages of positive cells at 400X magnification. Result: GLUT-3 and GLUT-4 were positive in 100% of the analyzed samples, the percentage immunolabeling for GLUT-3 ranging from 19% to 73% in the OED group and 10% to 89% in the OSCC group. Positive immunolabeling for GLUT-4 ranged from 15.2% to 79.9% in the OSCC group and 27.1% to 92.6% in the OED group. Statistical analysis with the Mann-Whitney test revealed that there was a higher expression of GLUT-4 in the OED group than in the OSCC group (p=0.04) without any significant difference in the GLUT-3 expression (p=0.852). Conclusion: GLUT-4 expression may indicate some role in oncogenic mechanisms which can determine a malignant phenotype. Thus, it is suggested that further studies on the role of GLUT-3 in oral carcinogenesis be conducted.

Exuberante granuloma piogênico em localização incomum: relato de caso / An exuberant presentation of pyogenic granuloma: case report

O granuloma piogênico é definido como um processo proliferativo reacional não neoplásico, composto por tecido de granulação com extensa vascularização, provavelmente decorrente da irritação crônica de baixa intensidade, como raízes residuais, cálculos subgengivais e restaurações com excesso em faces proximais. Apresenta predileção pelo sexo feminino da 2ª à 4ª década de vida, sendo a gengiva o sítio preferencial de acometimento. Em cerca de 80% dos casos, as lesões extragengivais são consideradas raras na literatura e, quando presentes, diagnósticos tardios podem ser experimentados. O objetivo do presente trabalho é relatar o caso de um paciente do sexo masculino, de 14 anos de idade, apresentando um exuberante granuloma piogênico em mucosa labial inferior anterior bem como realizar uma revisão de literatura sobre os aspectos clínicos e sobre o tratamento do granuloma piogênico. Para tanto, foi realizada uma busca nas bases de dados pubmed e bireme, das quais foram selecionados artigos científicos entre 2006 e 2016, nos idiomas português e inglês, utilizando-se os descritores: "granuloma piogênico", "doenças da gengiva" e "mucosa bucal". O tratamento realizado foi a excisão cirúrgica simples da lesão. Atualmente, 11 meses após o procedimento cirúrgico, não há recidiva da lesão... (AU)

Pyogenic Granuloma is defined as a non-neoplastic proliferative process, composed by granulation tissue with large vascularization, probably caused by a cronic reaction with low intensity like residual roots, subgingival, dental calculus and restaurations with proximal excess of material . Presents some predilection for female patients on second and fourth decades of life and gums as preferencial site of involvement in almost 80% of cases. Extra- gingival pathologies are considerated rares in literature and when present, a late diagnosis can be done. The objective of present study is describe a case of male patient, 14 years old, prespyogenic granuloma. For this porpoise was realized a search in databasis PubMed and Bireme, which selected scientific articles between 2006- 2016, in Portuguese and English languages, using the descriptors "pyogenic granuloma", "gingival diseases" and "mouth mucosa". The performed treatment for the case was surgical and simple excision of lesion. Actually, eleven months after the surgical procedure, there is no recurrence of lesion... (AU)

Lesão periférica de células gigantes em região palatina anterior: excisão cirúrgica e acompanhamento de um ano

A lesão periférica de células gigantes (LPCG) é consideradaum processo proliferativo não neoplásico.Acredita-se que seu fator etiológico esteja associado aofator reacional, como o trauma ou a irritação local. Tallesão pode se desenvolver em região anterior e regiãoposterior de gengiva ou em rebordo alveolar, sendo amandíbula mais afetada do que a maxila. Objetivo: esteestudo relata o caso clínico de uma paciente do sexofeminino, 38 anos de idade, que possuía um crescimentoexofítico em região anterior de palato duro. Relatode caso: esse crescimento apresentava formato nodular,de superfície lobulada com áreas ulceradas, medindo20 mm, localizado na região de papila incisiva. Combase nas características clínicas, o tratamento realizadofoi a biópsia excisional, seguido de raspagem e alisamentoradicular. No exame histopatológico, foram evidenciadasáreas de proliferação de células gigantes ediscreta pigmentação por hemossiderina, confirmandoa hipótese diagnóstica de LPCG. Considerações finais:o acompanhamento pós-operatório evidenciou um ótimoprocesso de cicatrização sem recidiva após um anodesde o início do tratamento.

DNA methylation profiles of 22 apoptosis-related genes in odontogenic keratocysts before and after marsupialization.

OBJECTIVE: Odontogenic keratocysts (OKCs) are cystic lesions of the jaw and tend to recur after treatment. Marsupialization is an effective preliminary treatment for large OKCs. This procedure induces epithelial lining changes in association with reduction of Bcl-2 protein expression, but the underlying mechanisms remain unknown. The purpose of our study was to compare the methylation profile of the apoptosis-related genes of OKCs before and after marsupialization. STUDY DESIGN: We assessed the methylation percentages of the promoter region of 22 apoptosis-related genes in 13 OKCs, both marsupialized and nonmarsupialized lesions, by using methylation quantitative polymerase chain reaction array. We validated the expression of genes that showed the greatest differences in methylation percentages between the 2 groups. RESULTS: LTBR and BCLAF1 showed higher DNA methylation percentages in the marsupialized OKCs, but this difference did not affect gene expression (P > .05). The other 20 genes showed similar DNA methylation in both OKC groups. CONCLUSIONS: OKCs show a distinct methylation profile after marsupialization, but this is not followed by gene expression alterations.

Prospective Evaluation of Quality of Life in Patients Undergoing Primary Surgery for Oral Cancer: Preoperative and Postoperative Analysis

Background: The purpose of the present study was to compare the preoperative and postoperative health related quality of life (HRQoL) of a sample of patients undergoing primary surgery for oral cancer in 2012-13. Materials and Methods: A cross-sectional, prospective study of 54 patients in a Brazilian population was performed. HRQoL was measured preoperatively (after histopathological diagnosis) and postoperatively (2 months after surgery) using the University of Washington Quality of Life Questionnaire (UW-QOL). Clinicopathological, sociodemographic and lifestyle data were collected. Results: Surgery had a negative impact on most HRQoL domains, but pain, mood and anxiety scores were significantly improved. Most patients rated their health-related and overall postoperative HRQoL as good or very good. Conclusions: The UW-QOL was efficient at measuring HRQoL in our sample of patients with oral cancer. Surgery had a negative impact on HRQoL, especially due to sequelae affecting the stomatognathic system, yet patients classified their postoperative health-related and overall QoL as positive. Qualitative studies are necessary for confirmation of our results and further exploration.

Anti-inflammatory and anti-nociceptive effects of strontium ranelate on the zymosan-induced temporomandibular joint inflammatory hypernociception in rats depend on TNF-α inhibition.

BACKGROUND: Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Strontium ranelate has previously shown anti-inflammatory and antinociceptive effects on other experimental inflammatory pain models. Thus, we aim to investigate the strontium ranelate efficacy in reducing the zymosan-induced inflammatory hypernociception in the TMJ of rats by evaluating the TNF-α, IL-1ß, and hemeoxygenase-1 (HO-1) involvement. METHODS: Wistar rats were treated with strontium ranelate (0.5, 5 or 50 mg/kg, per os) 1 h before zymosan injection (iart). Mechanical threshold was assessed by Von Frey test and synovial lavage was collected for leukocyte counting and myeloperoxidase measurement, joint tissue and trigeminal ganglion were excised for histopathological analysis (H&E) and TNF-α/IL-1ß levels dosage (ELISA). Moreover, rats were pre-treated with ZnPP-IX (3 mg/kg, sc), a specific HO-1 inhibitor, before strontium ranelate administration (0.5 mg/kg, per os), and Evans Blue (5 mg/kg, iv) was administered to assess plasma extravasation. Pre-treatment with indomethacin (5 mg/kg, sc) was used as positive control while the sham group received 0.9% sterile saline (per os and iart). RESULTS: Strontium ranelate did not reduce leukocyte counting, myeloperoxidase activity, Evans Blue extravasation, IL-1ß levels, and TNF-α/IL-1ß immunolabeling; but it increased the nociceptive threshold and reduced TNF-α levels. Additionally, HO-1 inhibition did not change the strontium ranelate effects. CONCLUSION: Strontium ranelate may achieve its antinociceptive effects through the reduction of TNF-α levels in the trigeminal ganglion, but not suppressing IL-1ß expression nor inducing the HO-1 pathway.

Lectin from Abelmoschus esculentus reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats via heme oxygenase-1 pathway integrity and tnf-α and il-1ß suppression.

Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, having it shown anti-inflammatory activity. We evaluated A. esculentus lectin (AEL) efficacy in reducing zymosan-induced temporomandibular joint inflammatory hypernociception in rats along with the mechanism of action through which it exerts anti-inflammatory activity. Animals were pre-treated with AEL (0.01, 0.1 or 1mg/kg) before zymosan (Zy) injection in the TMJ to determine anti-inflammatory activity. To analyse the possible effect of the hemeoxygenase-1 (HO-1) and the nitric oxide (NO) pathways on AEL efficacy, animals were pre-treated with ZnPP-IX (3mg/kg), a specific HO-1 inhibitor, or aminoguanidine (30mg/kg), a selective iNOS inhibitor, before AEL administration. Von Frey test evaluated inflammatory hypernociception, synovial fluid collection was performed to determine leukocyte counting and myeloperoxidase (MPO) activity 6h after Zy injection, and Evans Blue extravasation determined vascular permeability. TMJ tissue was collected for histopathological analysis (H&E) and immunohistochemistry (TNF-α, IL-1ß, HO-1). In addition, TMJ tissue and trigeminal ganglion collection was performed for TNF-α and IL-1ß dosage (ELISA). AEL increased inflammatory nociceptive threshold, reduced leukocyte influx along with MPO activity, leukocyte influx into the synovial membrane, and Evans Blue extravasation. It promoted HO-1 overexpression whilst decreased TNF-α and IL-1ß expression in the TMJ tissue. AEL reduced TNF-α and IL-1ß levels in TMJ tissue and trigeminal ganglion. AEL effects, however, were not observed in the presence of ZnPP-IX. These findings suggest that AEL efficacy depends on TNF-α/IL-1ß inhibition and HO-1 pathway integrity.

Educational Utilization of Microsoft Powerpoint for Oral and Maxillofacial Cancer Presentations.

Electronic presentations have become useful tools for surgeons, other clinicians and patients, facilitating medical and legal support and scientific research. Microsoft® PowerPoint is by far and away the most commonly used computer-based presentation package. Setting up surgical clinical cases with PowerPoint makes it easy to register and follow patients for the purpose of discussion of treatment plan or scientific presentations. It facilitates communication between professionals, supervising clinical cases and teaching. It is often useful to create a template to standardize the presentation, offered by the software through the slide master. The purpose of this paper was to show a simple and practical method for creating a Microsoft® PowerPoint template for use in presentations concerning oral and maxillofacial cancer.

BRAFV600E mutation in the diagnosis of unicystic ameloblastoma.

BACKGROUND: Unicystic ameloblastoma, an odontogenic neoplasm, presents clinical and radiographic similarities with dentigerous and radicular cysts, non-neoplastic lesions. It is not always possible to reach a final diagnosis with the incisional biopsy, leading to inappropriate treatment. The BRAFV600E activating mutation has been reported in a high proportion of ameloblastomas. The purpose of the study was to assess the utility of the detection of the BRAFV600E mutation in the differential diagnosis of unicystic ameloblastoma with dentigerous and radicular cysts. METHODS: Twenty-six archival samples were included, comprising eight unicystic ameloblastomas (UAs), nine dentigerous and nine radicular cysts. The mutation was assessed in all samples by anti-BRAFV600E (clone VE1) immunohistochemistry (IHC) and by TaqMan mutation detection qPCR assay. Sanger sequencing was further carried out when samples showed conflicting results in the IHC and qPCR. RESULTS: Although all UAs (8/8) showed positive uniform BRAFV600E staining along the epithelial lining length, the mutation was not confirmed by qPCR and Sanger sequencing in three samples. Positive staining for the BRAFV600E protein was observed in one dentigerous cyst, but it was not confirmed by the molecular methods. Furthermore, 2/9 dentigerous cysts and 2/9 radicular cysts showed non-specific immunostaining of the epithelium or plasma cells. None of the dentigerous or radicular cysts cases presented the BRAFV600E mutation in the qPCR assay. CONCLUSIONS: The BRAFV600E antibody (clone VE1) IHC may show non-specific staining, but molecular assays may be useful for the diagnosis of unicystic ameloblastoma, in conjunction with clinical, radiological and histopathological features.