Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

OBJECTIVE: To evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL). METHODOLOGY: Forty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of blood vessels, blood vessels/µm2, cells/µm2, total blood vessel area, and average blood vessel area) and immunohistochemistry (IL-17, TNF-α, IL-6, and TGF-ß). The Kruskal-Wallis/Dunn test was used for statistical analysis. RESULTS: PCG showed an increase in total blood vessel area (p=0.008) and average blood vessel area (p=0.014), and digoxin treatment reversed these changes. DG4 showed a reduction in blood vessels/µm2 (p<0.001). In PCG odontoblasts, there was an increase in IL-17 (p=0.002) and TNF-α (p=0.002) immunostaining, and in DG4, these changes were reversed. Odontoblasts in the digoxin-treated groups also showed an increase in IL-6 immunostaining (p<0.001) and a reduction in TGF-ß immunostaining (p=0.002), and all ZOL-treated groups showed an increase in IL-17 (p=0.011) and TNF-α (p=0.017) in non-odontoblasts cells. CONCLUSION: ZOL induces TNF-α- and IL-17-dependent vasodilation and ectasia, and the classical Th17 response activation pathway does not seem to participate in this process.

Oral rehabilitation after partial maxilectomy for removal of pleomorphic adenoma: case report / Reabilitação oral após maxilectomia parcial para remoção de adenoma pleomórfico: relato de caso

ABSTRACT Salivary gland tumors account for only 3%-5% of all tumors in the head and neck, 10%-15% of which originate from minor salivary glands. Pleomorphic adenoma is a benign lesion of the salivary gland, most commonly occurring in the region of the hard and soft palates. The treatment of choice for pleomorphic adenomas is with the partial or total function of the extension of the lesion, and placing palatal obturators are one method of reestablishing masticatory function and facial esthetics. This study aimed to rehabilitate a patient using a palatal implant following partial maxillectomy for the removal of a pleomorphic adenoma. A young patient with pleomorphic adenoma of the hard palate underwent a partial right-sided maxillectomy procedure which removed the hard palate and alveolar regions of the molars. Prior to surgery, the patient was assessed to make a surgical guide for resection of the tumor, as well as a provisional obturator plate using orthodontic wire clasps. After healing, the patient was rehabilitated using a palatal obturator which had been incorporated into a removable partial denture. The clinical sequence used to fabricate the final prosthesis was as follows: initial molding after surgery, prosthesis design, preparation of the mouth, work molding, structure testing and orientation planning, teeth testing and installation, and periodic maintenance. Thus, we can conclude that the palatal obturator is an excellent means of restoring a patient's oral function, facial esthetics, and overall quality of life.

RESUMO Os tumores de glândulas salivares representam apenas 3%-5% de todos os tumores em região de cabeça e pescoço, dentre eles 10%-15% se originam de glândulas salivares menores. O adenoma pleomórfico é uma lesão benigna de glândula salivar, tendo uma maior prevalência em região de palato. O tratamento dessas lesões se dá por método excisional ou maxilectomia dependendo da extensão da lesão e, uma das formas de reestabelecimento da estética e função do paciente é com um obturador palatino. O objetivo deste trabalho foi relatar uma reabilitação oral através da utilização de um obturador palatino em um paciente submetido a maxilectomia parcial para remoção de adenoma pleomórfico. Paciente de 22 anos, com adenoma pleomórfico em região de palato, foi submetido a maxilectomia parcial, removendo região de palato duro e região alveolar dos molares do lado direito. Foi realizada moldagem da maxila previamente a cirurgia para confecção de um guia cirúrgico, o guia foi utilizado na ressecção do tumor e, serviu também, para confecção de uma placa obturadora provisória associada a fios ortodônticos. Após cicatrização completa, foi acordado que a reabilitação do paciente seria com uma prótese parcial removível do tipo obturador palatino. A sequência clínica para a realização da prótese foi: moldagem inicial após a cirurgia, delineamento, preparo de boca, moldagem de trabalho, prova da infraestrutura e plano de orientação, prova dos dentes, instalação e manutenções periódicas. Com isso, podemos concluir que o obturador palatino é um excelente meio de reestabelecer função e estética do paciente, melhorando sua qualidade de vida.

Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?

Abstract Objective To evaluate the influence of RORγT inhibition by digoxin on inflammatory changes related to interleukin-17 (IL-17) in the pulp of rats treated with zoledronate (ZOL). Methodology Forty male Wistar rats were divided into a negative control group (NCG) treated with saline solution, a positive control group (PCG) treated with ZOL (0.20 mg/kg), and three groups treated with ZOL and co-treated with digoxin 1, 2, or 4 mg/kg (DG1, 2, and 4). After four intravenous administrations of ZOL or saline solution in a 70-day protocol, the right molars were evaluated by histomorphometry (number of blood vessels, blood vessels/µm2, cells/µm2, total blood vessel area, and average blood vessel area) and immunohistochemistry (IL-17, TNF-α, IL-6, and TGF-β). The Kruskal-Wallis/Dunn test was used for statistical analysis. Results PCG showed an increase in total blood vessel area (p=0.008) and average blood vessel area (p=0.014), and digoxin treatment reversed these changes. DG4 showed a reduction in blood vessels/µm2 (p<0.001). In PCG odontoblasts, there was an increase in IL-17 (p=0.002) and TNF-α (p=0.002) immunostaining, and in DG4, these changes were reversed. Odontoblasts in the digoxin-treated groups also showed an increase in IL-6 immunostaining (p<0.001) and a reduction in TGF-β immunostaining (p=0.002), and all ZOL-treated groups showed an increase in IL-17 (p=0.011) and TNF-α (p=0.017) in non-odontoblasts cells. Conclusion ZOL induces TNF-α- and IL-17-dependent vasodilation and ectasia, and the classical Th17 response activation pathway does not seem to participate in this process.

Development and professional validation of an App to support Oral Cancer Screening.

The objective of this study was to develop and validate an App for identifying risk factors for oral cancer. To this end, we developed an App (OCS: Oral Cancer Screening) with predictors of Oral Cancer (OC) and algorithm assembly to estimate the risk of its development. METHODOLOGY: Simulated clinical cases were designed so that 40 professionals with expertise in oral diagnostics could validate the algorithm and test its usability (SUS: System Usability Score) and acceptability (TAM: Technology Acceptance Model). Cronbach's alpha coefficient, Friedman/Dunn tests, and Spearman correlation evaluated the SUS and TAM scales. ROC curve was plotted to estimate the cutoff point of the algorithm in suggesting a high risk for OCS of the simulated cases. Chi-square and Fisher's exact tests were additionally used (p<0.05, SPSS v20.0). RESULTS: Professionals with expertise in oral diagnosis had usability of 84.63±10.66 and acceptability of 84.75±10.62, which correlated positively (p<0.001, r=0.647). Acting in clinical areas of dentistry (p=0.034) and history of performing OC risk factor orientation (p=0.048) increased acceptability while acting in higher education increased usability (p=0.011). The cutoff point suggested by the App after validation of the simulated clinical cases showed high sensitivity of 84.8% and lower specificity of 58.4%. CONCLUSION: The OCS was effective and with adequate sensitivity, usability, and acceptability and may contribute to the detection of early oral lesions.

Development and professional validation of an App to support Oral Cancer Screening

Abstract The objective of this study was to develop and validate an App for identifying risk factors for oral cancer. To this end, we developed an App (OCS: Oral Cancer Screening) with predictors of Oral Cancer (OC) and algorithm assembly to estimate the risk of its development. Methodology: Simulated clinical cases were designed so that 40 professionals with expertise in oral diagnostics could validate the algorithm and test its usability (SUS: System Usability Score) and acceptability (TAM: Technology Acceptance Model). Cronbach's alpha coefficient, Friedman/Dunn tests, and Spearman correlation evaluated the SUS and TAM scales. ROC curve was plotted to estimate the cutoff point of the algorithm in suggesting a high risk for OCS of the simulated cases. Chi-square and Fisher's exact tests were additionally used (p<0.05, SPSS v20.0). Results: Professionals with expertise in oral diagnosis had usability of 84.63±10.66 and acceptability of 84.75±10.62, which correlated positively (p<0.001, r=0.647). Acting in clinical areas of dentistry (p=0.034) and history of performing OC risk factor orientation (p=0.048) increased acceptability while acting in higher education increased usability (p=0.011). The cutoff point suggested by the App after validation of the simulated clinical cases showed high sensitivity of 84.8% and lower specificity of 58.4%. Conclusion: The OCS was effective and with adequate sensitivity, usability, and acceptability and may contribute to the detection of early oral lesions.

Resumo O objetivo deste estudo foi desenvolver e validar um aplicativo para identificação de fatores de risco para câncer bucal. Para tanto, desenvolvemos um aplicativo (OCS: Oral Cancer Screening) com preditores de Câncer Oral (CO) e montagem de algoritmo para estimar o risco de seu desenvolvimento. Metodologia: Casos clínicos simulados foram projetados para que 40 profissionais com expertise em diagnóstico oral pudessem validar o algoritmo e testar sua usabilidade (SUS: System Usabilidade Score) e aceitabilidade (TAM: Technology Acceptance Model). O coeficiente alfa de Cronbach, os testes de Friedman/Dunn e a correlação de Spearman avaliaram as escalas SUS e TAM. A curva ROC foi traçada para estimar o ponto de corte do algoritmo ao sugerir um alto risco para OCS dos casos simulados. Os testes do qui-quadrado e exato de Fisher foram usados adicionalmente (p<0,05, SPSS v20.0). Resultados: Profissionais com expertise em diagnóstico oral tiveram usabilidade de 84,63±10,66 e aceitabilidade de 84,75±10,62, que se correlacionaram positivamente (p<0,001, r=0,647). Atuar em áreas clínicas da odontologia (p=0,034) e histórico de realização de CO orientação de fator de risco (p=0,048) aumentaram a aceitabilidade enquanto atuar no ensino superior aumentou a usabilidade (p=0,011). O ponto de corte sugerido pelo App após validação dos casos clínicos simulados apresentou alta sensibilidade de 84,8% e baixa especificidade de 58,4%. Conclusão: O OCS foi eficaz e com sensibilidade, usabilidade e aceitabilidade adequadas e pode contribuir para a detecção de lesões orais precoces.

Photodynamic therapy and photobiomodulation therapy in zoledronic acid-induced osteonecrosis in rats.

BACKGROUND: This study investigated the effect of antimicrobial photodynamic therapy (PDT), using methylene blue (MBO) and photobiomodulation therapy (PT), on the alveolar bone of rats submitted to bisphosphonate-induced osteonecrosis of the maxillaries (OMB) model using zoledronic acid (ZA). METHODS: Sixty rats divided into six groups were used: SALINE, PDT, ZA, ZA+PDT, ZA+PT, and ZA+MBO. Three weekly administrations (Days 0, 7, and 14) of ZA 0.20 mg/kg or saline solution were performed. After one month (Day 42), the exodontia of the left lower first molars were performed. An additional dose of ZA was administered at Day 49. PDT was performed on days 42, 45, 49, and 54. One month after exodontia (Day 70), the animals were euthanized to obtain samples for imaging and microscopic analysis. ANOVA/Bonferroni tests were used for statistical analysis. RESULTS: The ZA+PDT group showed a significantly lower percentage of apoptotic osteocytes than the ZA group (p < 0.001). The ZA+MBO, ZA+PT, and PDT groups significantly reduced the number of mononuclear cells compared to the ZA group (p < 0.001). The ZA+PT and ZA+PDT groups showed a significant reduction in the number of CD 68+ (p < 0.001) and CD3+ (p = 0.002) cells compared to the ZA group. The number of cells expressing INF-y had a significant reduction in the groups co-treated with PT and PDT compared to the ZA group (p < 0.001). CONCLUSIONS: We conclude that PDT and PT attenuated the severity of OMB and the inflammatory process due to a reduction of macrophages, T lymphocytes, and cytokines that stimulate the activity of these cells.

Radiographic evaluation of dental anomalies in patients with congenital Zika virus syndrome.

Numerous studies have reported abnormalities in the development of oral structures in congenital infections that also involve microcephaly. In this context, it is necessary to identify possible dental anomalies of shape and/or number in patients with Zika virus syndrome using radiography. The study population consisted of 35 children born with congenital ZIKV who underwent intraoral radiographic examinations for 24 consecutive months. A modified periapical technique was performed in an occlusal position for the maxilla and mandible. Categorical data were expressed as absolute and percentage frequencies and compared using Pearson's Chi-square test, with a 95% confidence interval. Of the entire sample, eight children (22.8%) had dental anomalies of shape and/or number, and four children (11.4%) presented with both anomalies, with agenesis of the upper and lower deciduous/permanent incisors and dental form modifications, such as microdontia and anomalous cusps. When we considered age and sex, there was no statistically significant difference between patients who presented with agenesis and those who presented with modifications. Children with congenital Zika virus syndrome were more likely to have dental modifications in the number and shape of their teeth, and it is essential to implement medium- to long-term monitoring to diagnose other possible alterations throughout the development of the mixed and permanent dentition, favoring their treatment.

Prognostic factors on surgically and non-surgically treated oral squamous cell carcinoma: Advances in survival in fifteen years of follow up.

BACKGROUND: Retrospectively to evaluate the influence of radiochemotherapy (RCT) in the treatment of surgically and non-surgically treated Oral Squamous Cell Carcinoma (OSCC). MATERIAL AND METHODS: We analysed 934 patients treated in Hospital Haroldo Juaçaba (2000-2014; 15 years of study) by extraction of data type of cancer, localization of tumour, sex, age, race, education level, risk factors (smoking and alcohol use), year of diagnosis, TNM stage, therapeutic approach, health system used (public or private) and overall survival (OS). Surgically and non-surgically treated OSCC were compared by chi-square and Fisher's exact tests, and their prognostic factors were analysed by log-rank Mantel-Cox plus Cox regression tests (SPSS 20.0, p<0.05). RESULTS: Non-surgically treated OSCC patients had a lower OS than surgically treated OSCC patients (p<0.001), but an increase in OS was shown in both groups. Although the 2010-2014 period (p=0.003), education level (p=0.032), tongue/mouth floor/palate localization (p=0.023) and TNM stage (p<0.05) were important in non-surgically treated OSCC OS, the major prognostic factors were node metastasis (p=0.003) and non-use of RCT (p=0.039) (multivariate analysis). In surgically treated OSCC patients, higher OS was shown in the 2010-2014 period (p<0.001), females (p=0.012), non-drinkers (p=0.011), non-smokers (p=0.009) and those with lower TNM stage (p<0.05), but the major prognostic factor was the 2010-2014 period (p=0.004) (multivariate analysis), which was directly associated with an increase in RCT indication (p<0.001). CONCLUSIONS: The increase in RCT improved the OS in this large cohort of surgically and non-surgically treated OSCC patients. Key words:Mouth neoplasms, neck, radiotherapy, drug therapy, combination.

Radiographic evaluation of dental anomalies in patients with congenital Zika virus syndrome

Abstract: Numerous studies have reported abnormalities in the development of oral structures in congenital infections that also involve microcephaly. In this context, it is necessary to identify possible dental anomalies of shape and/or number in patients with Zika virus syndrome using radiography. The study population consisted of 35 children born with congenital ZIKV who underwent intraoral radiographic examinations for 24 consecutive months. A modified periapical technique was performed in an occlusal position for the maxilla and mandible. Categorical data were expressed as absolute and percentage frequencies and compared using Pearson's Chi-square test, with a 95% confidence interval. Of the entire sample, eight children (22.8%) had dental anomalies of shape and/or number, and four children (11.4%) presented with both anomalies, with agenesis of the upper and lower deciduous/permanent incisors and dental form modifications, such as microdontia and anomalous cusps. When we considered age and sex, there was no statistically significant difference between patients who presented with agenesis and those who presented with modifications. Children with congenital Zika virus syndrome were more likely to have dental modifications in the number and shape of their teeth, and it is essential to implement medium- to long-term monitoring to diagnose other possible alterations throughout the development of the mixed and permanent dentition, favoring their treatment.

Evaluation of a collagen matrix in a mandible defect in rats submitted to the use of bisphosphonates.

PURPOSE: To assess the effect of a collagen matrix (Mucograft®) on the inflammatory process in a semi-critical experimental defect model in rats treated with bisphosphonates. METHODS: Eighteen Wistar rats were randomly divided into three groups: saline (CG), alendronate (ALD) 5mg/kg (AG) or zoledronic acid (ZA) 0.2mg/kg (ZG). ALD was administered orally for 10 weeks and ZA was administered intravascularly on days 0, 7 and 14 and 49. On day 42, a 2mm defect was created and filled with Mucograft® collagen matrix. The contralateral side was filled with a clot (control side). The animals were euthanized 70 days after the beginning of the experiment and the hemimandibles were radiographically and histologically (counting of empty osteocyte lacunae (%), apoptotic (%) and total osteoclasts, neutrophil and mononuclear inflammatory cells) analyzed. The variables were submitted to ANOVA/Bonferroni and t test (parametric data) (p <0.05, GraphPad Prism 5.0). RESULTS: Significant bone repair occurred in the groups treated with Mucograft®. High number of total inflammatory cells and neutrophils cells were showed in AG (p=0.026 and p=0.035) and AZ groups (p=0.005, p=0.034) on the control sides associated with delayed bone repair and the presence of devitalized bone tissue in AG and ZG on the Mucograft® side. CONCLUSION: Mucograft® collagen matrix attenuated the inflammatory process in a mandible defect in rats submitted to the use of bisphosphonates (AG and ZG).

Influence of the degree of conversion and Bis-GMA residues of bulk fill resins on tissue toxicity in an subcutaneous model in rats.

AIM: To analyse the influence of the degree of conversion (DC) and light curing residues of different bulk fills (BFs) composites on the inflammatory profile in the subcutaneous tissue of rats. MATERIALS AND METHODS: Resin disks of BF-resins and their active conventional resins (CR; 3M®, Ivoclar®, and Kerr®) were light-cured at 2 mm (BF-superficial) and 4 mm (BF-deep) thicknesses and analyzed by infrared spectroscopy (FTIR; n = 3/group; DC and light curing residues). Then, the disks were implanted in four quadrants in the subcutaneous tissue of Wistar rats (sham, CR, BF-superficial and RF-deep), and after 7, 14, and 28 days, the animals (n = 6/day) were euthanized for histological analysis of the intensity of the inflammatory process (scores 0-3). Kruskal-Wallis/Dunn and ANOVA/Bonferroni tests were used (p < 0.05, Graph Pad Prism 5.0). RESULTS: The DC of CR 3M® did not differ significantly compared to BF-superficial and BF-deep resins (p = 0.235). The Ivoclar® and Kerr® resins showed a higher DC with CR and BF-superficial compared to the BF-deep (p = 0.005 and p = 0.011, rctively). Kerr® resins showed a higher Bis-GMA/UDMA ratio, especially in BF-deep resin (p < 0.05). 3M® and Ivoclar resins did not show high inflammation scores, but for Kerr® BF resins (superficial and deep), the inflammatory process was significantly higher than that in the CR and sham quadrants (p = 0.031). CONCLUSION: The tissue inflammatory response after resin inoculation depends on the DC and light curing residues of Bis-GMA.

Evaluation of a collagen matrix in a mandible defect in rats submitted to the use of bisphosphonates

Abstract Purpose: To assess the effect of a collagen matrix (Mucograft®) on the inflammatory process in a semi-critical experimental defect model in rats treated with bisphosphonates. Methods: Eighteen Wistar rats were randomly divided into three groups: saline (CG), alendronate (ALD) 5mg/kg (AG) or zoledronic acid (ZA) 0.2mg/kg (ZG). ALD was administered orally for 10 weeks and ZA was administered intravascularly on days 0, 7 and 14 and 49. On day 42, a 2mm defect was created and filled with Mucograft® collagen matrix. The contralateral side was filled with a clot (control side). The animals were euthanized 70 days after the beginning of the experiment and the hemimandibles were radiographically and histologically (counting of empty osteocyte lacunae (%), apoptotic (%) and total osteoclasts, neutrophil and mononuclear inflammatory cells) analyzed. The variables were submitted to ANOVA/Bonferroni and t test (parametric data) (p <0.05, GraphPad Prism 5.0). Results: Significant bone repair occurred in the groups treated with Mucograft®. High number of total inflammatory cells and neutrophils cells were showed in AG (p=0.026 and p=0.035) and AZ groups (p=0.005, p=0.034) on the control sides associated with delayed bone repair and the presence of devitalized bone tissue in AG and ZG on the Mucograft® side. Conclusion: Mucograft® collagen matrix attenuated the inflammatory process in a mandible defect in rats submitted to the use of bisphosphonates (AG and ZG).