Systemic administration of propranolol reduces bone resorption and inflammation in apical periodontitis of chronically stressed rats.

AIM: To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats. METHODOLOGY: Twenty-four 70-day-old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal-Wallis followed by Dunn's test. Significance level was set at 5% (p < .05) for all assessed parameters. RESULTS: Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05). CONCLUSIONS: Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.

Side effects of different head and neck radiotherapy doses on wistar rat's behavior.

Radiotherapy (RT) is a common treatment for head and neck tumors. However, it causes several physical and behavioral side effects, and no study has assessed the emotional effects in rats. Therefore, the present study evaluated the influence of head and neck RT on the behavior and body weight gain in Wistar rats. Fifty-four male Wistar rats were allocated into six groups (n = 9) according to the irradiation dose, which was applied at the first day of the experiment: RT-7.5 (single dose of 7.5 Gy); RT-10 (single dose of 10 Gy); RT-15 (single dose of 15 Gy); RT-30 (single dose of 30 Gy); Control (without RT). The animals were irradiated in the region of the right face, and behavioral tests and weighing were performed on days one, seven, and 28. The open field and Y-maze tests were undertaken to analyze the animal's behavior. The dose of 30 Gy was lethal when applied to the head and neck region. The irradiated animals had less weight gain when compared to the control ones, but there was no statistical difference. In the open field and Y-maze tests, lower mobility of animals in the RT groups was observed both on day seven and at the end of the experiment (day 28) when compared to the control rats (p < 0.05). It was possible to conclude that the different doses of radiation induced depressive behavior in the animals, and that the weight gain tended to be lower in the irradiated groups, however, without statistical difference.

Efeito da sinvastatina e do propranolol no desenvolvimento da lesão periapical de ratos submetidos ao estresse / Effect of Simvastatin and Propranolol on the development of periapical lesions in rats subjected to stress

Uma vez que o estresse crônico pode estimular o sistema nervoso simpático, diminuindo a resposta imune, favorecendo a perda óssea frente a um processo inflamatório, os objetivos deste estudo foram: 1) Avaliar os efeitos de modelos de indução de estresse no desenvolvimento da periodontite apical (P.a) e avaliar o nível de estresse gerado pelos mesmos; 2) A partir do melhor protocolo de estresse obtido foi avaliado o perfil inflamatório da PA induzida em animais sob condições de estresse, utilizando sistemicamente a Sinvastatina, Propranolol e a Sinvastatina associada ao propranolol. Na primeira parte foram utilizados 32 ratos Wistar (N=8) divididos aleatoriamente em: SE: sem estresse, sem periodontite apical (P.a); SE+P.a: sem estresse, com P.A; EP+P.a: Estresse previsível + P.a; EI+P.a: estresse imprevisível + P.a. Os animais foram submetidos ao estresse crônico por 42 dias sendo que no dia 21 foi induzida a P.a. Para comprovação do estresse foram utilizadas análises de peso e comportamentais de campo aberto (CA) e labirinto em y (Y). Foram realizadas análises micro tomográfica e histológica para avaliar o efeito de ambas as metodologias sobre a progressão da P.a. Os dados foram avaliados estatisticamente. Observou-se que não houve diferença no ganho de peso entre os animais SE e SE+P.a. Em relação aos grupos estressados o grupo estresse imprevisível apresentou menor ganho de peso quando comparado ao grupo sem estresse. Nos testes comportamentais, Y e CA observou-se um mesmo padrão de comportamento nos animais do grupo SE e SE+P.a (p>0.05). Verificou-se diferenças entre os grupos SE+P.a e EI +P.a no volume da lesão periapical, mas não houve diferença entre os protocolos de estresse. A Análise histológica mostrou maior área de P.a nos animais do grupo EI+P.a o que também foi observado pela análise microtomográfica. Na segunda etapa foram utilizados 48 animais divididos em 5 grupos (N=8): SE+P.a: sem estresse e com P.a; E+SS: Estresse + Periodontite Apical + soro; E+SN: Estresse + Periodontite Apical + Sinvastatina; E+P: Estresse + Periodontite Apical + Propranolol e S+SN+P: Estresse + Periodontite Apical + Sinvastatina + Propranolol. O protocolo de estresse utilizado foi o estresse crônico imprevisível por 42 dias. Realizou-se análises de peso e comportamentais de labirinto em y e campo aberto. Após a eutanásia foram realizadas as análises microtomográfica e a análise histológica e histomorfométrica. Os valores obtidos foram analisados estatisticamente.Observouse que todos os grupos medicados apresentaram ganho de peso maior do que o grupo solução salina. No grupo Sinvastatina e no grupo Propranolol, os animais apresentaram maior atividade locomotora do que no grupo Solução salina. O volume da P.a foi significativamente menor nos grupos Sinvastatina e Propranolol quando comparado ao grupo solução salina. Na análise histológica observou-se que a área da lesão foi significativamente menor nos animais do grupo Sinvastatina quando comparado ao da solução salina, bem como menor intensidade e extensão do infiltrado inflamatório. Concluindo-se que o estresse crônico imprevisível aumenta a perda óssea periapical em animais com PA induzida. Além disso, concluiu-se que tanto a Sinvastatina quanto o Propranolol reduze o estresse crônico, reduzindo a perda óssea nestes animias (AU)

Since chronic stress can stimulate the sympathetic nervous system, decreasing the immune response, favoring bone loss in the face of an inflammatory process, the objectives of this study were: 1) To evaluate the effects of stress induction models on the development of apical periodontitis (P.a) and assess the level of stress generated by them; 2) Based on the best stress protocol obtained, the inflammatory profile of BP induced in animals under stress conditions was evaluated, systemically using Simvastatin, Propranolol and Simvastatin associated with propranolol. In the first part, 32 Wistar rats (N=8) were randomly divided into: SE: without stress, without apical periodontitis (P.a); SE+P.a: without stress, with P.A; EP+P.a: Predictable stress + P.a; EI+P.a: unpredictable stress + P.a. The animals were subjected to chronic stress for 42 days, and on the 21st, P.a. To prove the stress, weight and behavioral analyzes of open field (CA) and maze in y (Y) were used. Micro tomographic and histological analyzes were performed to evaluate the effect of both methodologies on the progression of P.a. Data were statistically evaluated. It was observed that there was no difference in weight gain between SE and SE+P.a animals. In relation to the stressed groups, the unpredictable stress group showed less weight gain when compared to the non-stress group. In the behavioral tests, Y and CA, the same pattern of behavior was observed in animals from the SE and SE+P.a groups (p>0.05). There were differences between groups SE+P.a and EI +P.a in the volume of the periapical lesion, but there was no difference between the stress protocols. The histological analysis showed a greater area of P.a in the animals from the EI+P.a group, which was also observed by the microtomographic analysis. In the second stage, 48 animals were divided into 5 groups (N=8): SE+P.a: without stress and with P.a; E+SS: Stress + Apical Periodontitis + serum; E+SN: Stress + Apical Periodontitis + Simvastatin; E+P: Stress + Apical Periodontitis + Propranolol and S+SN+P: Stress + Apical Periodontitis + Simvastatin + Propranolol. The stress protocol used was unpredictable chronic stress for 42 days. Weight and behavioral analyzes of y-maze and open field were performed. After euthanasia, microtomographic analysis and histological and histomorphometric analysis were performed. The values obtained were statistically analyzed. It was observed that all medicated groups had greater weight gain than the saline group. In the Simvastatin group and in the Propranolol group, the animals showed greater locomotor activity than in the Saline group. The BP volume was significantly lower in the Simvastatin and Propranolol groups when compared to the saline group. In the histological analysis, it was observed that the area of the lesion was significantly smaller in the animals of the Simvastatin group when compared to the saline solution, as well as lower intensity and extension of the inflammatory infiltrate. Concluding that unpredictable chronic stress increases periapical bone loss in animals with induced AP. In addition, it was concluded that both Simvastatin and Propranolol reduce chronic stress, reducing bone loss in these animals. (AU)

Pictograph system for diagnosis making and data management in endodontics / Sistema de pictograma para elaboração de diagnóstico e gerenciamento de dados em endodontia

Objective: this questionnaire aimed to evaluate the approval of a new pictograph system for endodontic diagnosis by undergraduate and graduate students/endodontist instead of a conventional method. Methods: after a presentation to a total of 224 participants explaining the pictograph system, the participants (166 undergraduate students and 58 graduate students/endodontist) received a standardized questionnaire with three questions. The data were analyzed using the mult prop macro basing on Tukey's test for multiple comparison with (P ≤ 0.05). The first question was to define the education level of the participants; the second question about which diagnosis method is preferred; and the third question about the intention of using one of the methods in the future. The questionnaire was realized in May 2019. The response rate was 97.7%. Results: the first question showed that 74.10% and 25.90% were under graduate and graduate students/endodontist respectively. After statistical analysis there was no significant difference between the groups in the second and the third questions. In the second question (71.08% and 62.06%) of undergraduate and graduate student/endodontists respectively preferred the pictograph method over the conventional method. In the third question (60.24% and 51.72%) of undergraduate and graduate student/endodontists respectively showed interest in using the pictograph method in their professional career. Conclusion: the pictograph method in endodontic diagnosis is accepted by the majority of undergraduate and graduate students/endodontists. Training and experience affect the diagnosis making. (AU)

Objetivo: este questionário teve como objetivo avaliara aprovação de um novo sistema de imagem para diagnóstico endodôntico por estudantes de graduação e pós-graduação/endodontista, em vez de um método convencional. Métodos: após uma apresentação a um total de 224 participantes explicando o sistema de pictograma, os participantes (166 estudantes de graduação e 58 de pós graduação/endodontista) receberam um questionário padronizado com três perguntas. Os dados foram analisados usando a macro multi propósito baseada no teste de Tukey para comparação múltipla com (P ≤ 0,05). A primeira pergunta foi definir o nível de escolaridade dos participantes; a segunda pergunta sobre qual método de diagnóstico é preferido; e a terceira pergunta sobre a intenção de usar um dos métodos no futuro. O questionário foi realizado em maio de 2019. A taxa de resposta foi de 97,7%. Resultados: a primeira pergunta mostrou que 74,10% e 25,90% eram estudantes de graduação e pós-graduação / endodontista, respectivamente. Após análise estatística, não houve diferença significativa entre os grupos na segunda e na terceira questões. Na segunda questão (71,08% e 62,06%) dos estudantes de graduação e pós-graduação / endodontistas, respectivamente, preferiram o método de pictograma ao método convencional. Na terceira questão (60,24% e 51,72%) dos estudantes de graduação e pós-graduação /endodontistas, respectivamente, demonstraram interesse em utilizar o método de pictograma em sua carreira profissional. Conclusão: o método do pictograma no diagnóstico endodôntico é aceito pela maioria dos estudantes de graduação e pós-graduação / endodontistas. Treinamento e experiência afetam a elaboração do diagnóstico (AU)

Estimulação do eixo Hipotálamo-hipófise-adrenal pelo estresse crônico e seu efeito na progressão da lesão periapical / Hypothalamus-pituitary-adrenal axis stimulation by chronic stress and its effect in apical periodontitis progression

Uma vez que o estresse crônico pode estimular excessivamente o sistema nervoso simpático, levando a uma diminuição da resposta imune, favorecendo a perda óssea frente a um processo inflamatório, o objetivo deste estudo foi avaliar o efeito do estresse crônico na progressão da lesão periapical induzida e o melhor tempo para avaliação da progressão desta lesão. Quarenta e oito ratos Wistar foram submetidos à modelo animal de indução da lesão periapical através da exposição da cavidade pulpar dos primeiros molares inferiores direito e esquerdo ao meio bucal. Os animais foram divididos em 2 grupos: com estresse (E) e sem estresse (SE), que foram subdivididos em 3 subgrupos de acordo com o período de avaliação da progressão da lesão periapical (n=8): grupo estresse em 14 dias de formação de lesão periapical (E14); estresse e 21 dias de formação de lesão periapical (E21); estresse e 28 dias de formação de lesão periapical; sem estresse e 14 dias de formação de lesão periapical (SE14); sem estresse e 21 dias de formação de lesão periapical (SE28); sem estresse e 28 dias de formação de lesão periapical (SE28). Os grupos de estresse (E) começaram a ser submetidos ao estresse crônico 21 dias antes de iniciar a indução da lesão periapical e foram mantidos nesta condição de estresse durante todo o experimento.Foram realizadas as seguintes análises: a) peso dos animais no início e ao final do experimento; b) nível de corticosterona sanguínea para confirmação do estresse; c) microtomografia para avaliação da progressão da lesão; d) Análise histológica e histomorfométrica; d) Imunoistoquímica para avaliar expressão de RANKL e OPG . Os dados foram avaliados pelo software Graphpad prism 6 utilizando o teste Two Way Anova. A partir dos resultados obtidos observouse um menor ganho de peso nos grupos estressados em relação aos não estressados. A lesão mostrou-se significativamente maior no grupo estressado com 21 dias de lesão periapical. Nenhuma diferença estatística foi observada em relação ao infiltrado inflamatório, uma vez que todos os grupos apresentaram infiltrado inflamatório moderado. Em relação a extensão da lesão por meio da avaliação histomorfométrica, observou-se que a lesão era significativamente maior nos animais estressados do que nos não estressados no período de 21 dias. Através da imunohistoquímica não foi observado diferença significativa na expressão de RANKL e OPG (p<0.05). Conclui-se que o estresse crônico influencia na formação da lesão periapical em ratos Wistar, aumentando a perda óssea e que o melhor período para esta análise é de 21 dias de progressão da lesão periapical induzida em ratos(AU)

Since chronic stress may excessively stimulate the sympathetic nervous system, leading to a decreased immune response, favoring bone loss in the face of an inflammatory process, the aim of this study was to evaluate the effect of chronic stress on the progression of induced periapical injury and the best time to evaluate the progression of this lesion. Forty-eight Wistar rats were submitted to an animal model of induction of periapical lesion by exposing the right and left lower first molar pulp cavity to the oral environment. The animals were divided into 2 groups: with stress (E) and without stress (SE), which were subdivided into 3 subgroups according to the period of evaluation of periapical lesion progression (n = 8): stress and 14 days of periapical lesion formation (E14); stress and 21 days of periapical lesion formation (E21); stress and 28 days of periapical lesion formation; without stress and 14 days of periapical lesion formation (SE14); without stress and 21 days of periapical lesion formation (SE28); without stress and 28 days of periapical lesion formation (SE28). Stress groups (E) began to undergo chronic stress 21 days before the induction of periapical lesion began and were maintained in this stress condition throughout the experiment. The following analyzes were performed: a) weight of the animals at the beginning and end of the experiment; b) blood corticosterone level for stress confirmation; c) microtomography to evaluate the progression of the lesion; d) Histological and histomorphometric analysis; d) Immunohistochemistry to evaluate RANKL and OPG expression. Data were evaluated by Graphpad prism 6 software using the Two Way Anova test. From the results obtained it was observed a smaller weight gain in the stressed groups in relation to the non stressed ones. The lesion was significantly higher in the stressed group with 21 days of periapical lesion. No statistical difference was observed in relation to the inflammatory infiltrate, since all groups presented moderate inflammatory infiltrate. Regarding the extension of the lesion through histomorphometric evaluation, it was observed that the lesion was significantly larger in stressed animals than in non-stressed animals in the 21-day period. Through immunohistochemistry no significant difference was observed in the expression of RANKL and OPG (p <0.05). It is concluded that chronic stress influences the formation of periapical lesion in Wistar rats, increasing bone loss and that the best period for this analysis is 21 days of progression of induced periapical lesion in rats(AU)