Development of protocol for osteoradionecrosis induction in rats and evaluation of meloxicam as radioprotector

Orientadores: Lourenço Correr Sobrinho, Matheus Lima de OliveiraTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: O objetivo neste estudo foi desenvolver um novo protocolo de indução de osteorradionecrose mandibular em ratos e avaliar o comportamento do meloxicam como possível substância radioprotetora. Para isso, dois estudos foram desenvolvidos. No primeiro estudo, um total de 45 ratos Wistar machos foram utilizados nas diferentes partes desse estudo. Inicialmente, 25 ratos foram divididos aleatoriamente em 5 grupos (n = 5) de acordo com o protocolo da dose de radiação: sem irradiação e irradiados com 15 Gy, 20 Gy, 25 Gy e 30 Gy utilizando-se um acelerador linear. Posteriormente, outros 15 ratos foram divididos aleatoriamente em 3 grupos (n = 5) de acordo com o momento da exodontia dos três molares inferiores do lado direito: 7, 10 ou 14 dias após a irradiação com 20 Gy. Por fim, as exodontias foram realizadas em outros 5 ratos sem irradiação (C-E10) para comparação com os do grupo das exodontias 10 dias após a irradiação (I-E10). As mandíbulas dos grupos C-E10 e I-E10 foram submetidas à avaliação macroscópica e análise por meio de micro-CT. Os animais irradiados sobreviveram durante todo o período do estudo apenas com doses únicas de 15 Gy e 20 Gy. O tempo adequado para as exodontias após a irradiação a fim de induzir osteoradionecrose mandibular foi definido como 10 dias. A avaliação macroscópica das hemimandíbulas do lado direito mostrou presença de osteorradionecrose no grupo I-E10 e cicatrização gengival completa no grupo C-E10. A análise por meio de micro-CT da reparação do alvéolo indicou um atraso significativo na reparação no grupo I-E10 quando comparado ao grupo C-E10. No segundo estudo, um total de 60 ratos Wistar machos foram divididos aleatoriamente em 6 grupos (n = 10) de acordo com os procedimentos de administração do meloxicam e irradiação: controle, irradiado, uma dose de meloxicam, uma dose de meloxicam e irradiado, três doses de meloxicam e três doses de meloxicam e irradiado. A administração do meloxicam (20 mg/kg por dose) iniciou-se 1 h antes da irradiação (dose única de 20 Gy) com as doses subsequentes a cada 24 h para os grupos com três doses, sendo os animais submetidos à exodontia dos três molares inferiores do lado direito 10 dias após a irradiação. As mandíbulas foram submetidas à avaliação macroscópica e análise por meio de micro-CT. A avaliação macroscópica das hemimandíbulas do lado direito mostrou presença de osteorradionecrose em todos os grupos irradiados e cicatrização gengival completa em todos os grupos não irradiados. A análise por meio de micro-CT da reparação do alvéolo indicou um atraso significativo na reparação em todos os grupos irradiados quando comparado a todos os grupos não irradiados. Concluiu-se que a dose única de radiação de 20 Gy restrita à região de cabeça e pescoço combinada à exodontia dos três molares inferiores 10 dias após a irradiação constitui um protocolo viável de indução de osteorradionecrose mandibular em ratos com fonte externa de radiação. Além disso, concluiu-se que o meloxicam é pouco eficaz como substância radioprotetora do desenvolvimento da osteorradionecrose mandibular quando há exodontias.Abstract: The aim in this study was to develop a novel protocol for mandibular osteoradionecrosis induction in rats and to evaluate meloxicam as radioprotector candidate. For this, two studies were developed. In the first study, a total of 45 male Wistar rats were used in different parts of this study. Firstly, 25 rats were randomly divided into 5 groups (n = 5) according to the radiation dose protocol: without irradiation, and irradiated with 15 Gy, 20 Gy, 25 Gy or 30 Gy using a linear accelerator. Secondly, 15 other rats were randomly divided into 3 groups (n = 5) according to the time of extraction of the three right mandibular molars: 7, 10 or 14 days after irradiation of 20 Gy. Lastly, dental extractions were performed in 5 other rats without irradiation (C-E10) for comparison with those of the group of dental extractions 10 days after irradiation (I-E10). The mandibles of C-E10 and I-E10 groups were assessed by macroscopic evaluation and micro-CT analysis. The irradiated animals survived throughout the study period only at single doses of 15 Gy and 20 Gy. The suitable time for dental extractions after irradiation to induce mandibular osteoradionecrosis was defined as 10 days. Macroscopic evaluation of the right hemimandibles showed presence of osteoradionecrosis in I-E10 group and complete gingival healing in C-E10 group. Micro-CT analysis of the alveolar socket healing indicated a significant delay in healing in I-E10 group when compared to C-E10 group. In the second study, a total of 60 male Wistar rats were randomly divided into 6 groups (n = 10) according to the procedures of meloxicam administration and irradiation: control, irradiated, one dose of meloxicam, one dose of meloxicam irradiated, three doses of meloxicam, and three doses of meloxicam irradiated. Meloxicam administration (20 mg/kg per dose) started 1 h before irradiation (single dose of 20 Gy) with the subsequent doses after every 24 h for the groups with three doses, and the animals underwent extraction of the three right mandibular molars 10 days after. The mandibles were assessed by macroscopic evaluation and micro-CT analysis. Macroscopic evaluation of the right hemimandibles showed osteoradionecrosis in all the irradiated groups and complete gingival healing in all the non-irradiated groups. Micro-CT analysis of the alveolar socket healing indicated a significant delay in healing in all the irradiated groups when compared to all the non-irradiated groups. In conclusion, a single radiation dose of 20 Gy focused on head and neck region combined with the extraction of the three mandibular molars 10 days after irradiation constitutes a feasible protocol of mandibular osteoradionecrosis induction in rats with external beam radiation therapy. In addition, meloxicam is poorly effective as radioprotector to prevent mandibular osteoradionecrosis in the presence of dental extractions.DoutoradoRadiologia OdontológicaDoutora em Radiologia Odontológica001CAPE

Evaluation of meloxicam as a radiation-protective agent on mandibles of irradiated rats

Orientador: Deborah Queiroz de Freitas FrançaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: O presente estudo teve como objetivo avaliar o possível efeito radioprotetor do anti-inflamatório não esteroide meloxicam na prevenção da osteorradionecrose, na reparação alveolar e na resistência óssea em mandíbulas de ratos irradiados. Para isso, 40 ratos Wistar machos foram divididos em 4 grupos (n=10): controle (GC), irradiado (GI), meloxicam (GM) e meloxicam irradiado (GMI). Aos 75 dias de vida, foi administrado dose única de 0,2 mg/kg de meloxicam nos animais dos grupos GM e GMI. Uma hora depois, realizou-se a irradiação dos animais dos grupos GI e GMI com dose única de 15 Gy de radiação X na região de mandíbula. Decorridos 40 dias, foi realizado a exodontia bilateral dos primeiros molares inferiores nos animais, os quais foram mortos após 15 dias (n=5) e 30 dias (n=5). Utilizou-se a microtomografia computadorizada para avaliação da reparação alveolar, por meio da análise dos parâmetros da microestrutura trabecular óssea, como: volume tecidual total, volume ósseo, fração de volume ósseo, espessura trabecular média, número trabecular médio e separação trabecular média; e o teste de flexão para a avaliação da resistência óssea. A Análise de Variância um fator, com teste post hoc de Tukey, demonstrou que, aos 15 dias, o volume ósseo, a fração de volume ósseo e a espessura trabecular média foram significativamente superiores nos grupos GC e GM comparados aos grupos GI e GMI; já a separação trabecular média teve resultado estatístico inferior no grupo GI em relação aos demais. Aos 30 dias, houve diferença significante apenas na separação trabecular média, cujo resultado estatístico foi inferior no grupo GI em comparação aos grupos GC e GM, não tendo o grupo GMI diferido estatisticamente dos demais. Quanto à resistência óssea, o grupo GI foi significativamente inferior em relação aos grupos GC e GM, não tendo o grupo GMI diferido estatisticamente dos demais. Concluiu-se, assim, que foi observado ausência de osteorradionecrose clínica e que o meloxicam, embora não tenha demonstrado evidente efeito radioprotetor, apresentou efeito positivo na separação trabecular média da microestrutura trabecular óssea da reparação alveolar e na resistência ósseaAbstract: The aim of this study was to evaluate the possible radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on the prevention of osteoradionecrosis, alveolar socket healing and bone strength in the mandibles of irradiated rats. Forty male Wistar rats were divided into 4 groups (n=10): control (CG), irradiated (IG), meloxicam (MG), and meloxicam irradiated (MIG). When the animals were 75 days old, a single dose of 0.2 mg/kg meloxicam was administered to the animals in the MG and MIG groups. One hour later, the animals in the IG and MIG groups were irradiated with a single 15 Gy dose of X-rays in the mandible region. Forty days later, the mandibular first molars were extracted bilaterally and the animals were killed after 15 days (n=5) or 30 days (n=5). Micro-computed tomography was used to evaluate healing in the alveolar socket; trabecular bone microarchitecture features such as total volume, bone volume, bone volume fraction, trabecular number, trabecular thickness and trabecular separation were assessed. A bending test was used to evaluate bone strength. At 15 days, the one-way analysis of variance, followed by post hoc comparisons with the Tukey test, demonstrated that bone volume, bone volume fraction and trabecular thickness were significantly higher in the CG and MG groups than in the IG and MIG groups; and trabecular separation had lower statistical result in the IG group in comparison with the other groups. At 30 days, there was a significant difference only in trabecular separation, which statistical result was lower in the IG group than in the CG and MG groups, and the MIG group did not differ statistically from the others. Bone strength was significantly lower in the IG group compared with the CG and MG groups, and the MIG group did not differ statistically from the others. Therefore, it was concluded that the absence of clinical osteoradionecrosis was observed and the meloxicam, even though it has not demonstrated a clear radioprotective effect, had a positive effect on the trabecular separation of trabecular bone microarchitecture in alveolar socket healing and the bone strengthMestradoRadiologia OdontologicaMestra em Radiologia Odontológic

Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats

<div><p>Abstract This study evaluated the action of ionizing radiation and the possible radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on the bone physiology of rat mandibles by assessing the alveolar socket healing and bone strength. Forty male Wistar rats were divided in 4 groups (n=10): control (CG), irradiated (IG), meloxicam (MG), meloxicam irradiated (MIG). A dose of 0.2 mg/kg meloxicam was administered to MG and MIG. After this, IG and MIG were irradiated with 15 Gy radiation dose in the mandible. Forty days after the above procedures, the mandibular first molars were extracted and the animals were killed after 15 or 30 days (n=5). Micro-computed tomography and bending test were used to evaluate alveolar socket healing and bone strength, respectively. At 15 days, bone volume, bone volume fraction and trabecular thickness were higher in the CG and MG than in the IG and MIG; and trabecular separation was higher in the IG compared with the others. At 30 days, there was a difference only in trabecular separation, which was higher in IG than in CG and MG, and MIG did not differ from the others. Bone strength was lower in IG compared with CG and MG, and MIG did not differ from the others. In conclusion, the ionizing radiation affected the bone physiology of rat mandibles, delaying the alveolar socket healing and reducing the bone strength. Moreover, the meloxicam had a positive effect on the trabecular separation in alveolar socket healing and on the bone strength.</p></div

Influence of vistascan image enhancement filters on diagnosis of simulated periapical lesions on intraoral radiographs

To evaluate whether image enhancement filters of VistaScan system improve the diagnostic accuracy of simulated periapical lesions. Methods: 10 sockets were prepared on bovine ribs to fit a bovine tooth. Bone defects were created and successively enlarged providing four groups (n = 10): Group 0, absence of lesions; Group 1, periapical lesions with 1.6 mm in diameter; Group 2, with 1.8 mm in diameter; and Group 3, with 2.1 mm in diameter. Periapical radiographs were taken using a photostimulable storage phosphor plate and DBSWIN software. VistaScan filters were applied and the images were allocated into seven groups: Nonfiltered, Fine, Caries 1, Caries 2, Endodontic, Periodontal and Noise Reduction. All the 280 images were assessed about the presence or absence of periapical lesions. Pixel intensities standard deviation were compared between nonfiltered and filtered images. Two-Way Analysis of Variance and the post hoc Tukey's test were used to compare area under the ROC curve, sensitivity and specificity. Results: VistaScan filters showed no significant difference for area under receiver operating characteristic curve (p = 0.124), sensitivity (p = 0.835) and specificity (p = 0.832). Area under receiver operating characteristic curve (p = 0.000) and sensitivity (p = 0.000) in 2.1 mm lesions size were significantly higher than in 1.6 mm and 1.8 mm lesions size. Pixel intensities standard deviation was significantly changed in the filtered images compared to nonfiltered ones (p 0.05). Conclusion: VistaScan enhancement filters do not influence the diagnostic accuracy of simulated periapical lesions. On the other hand, larger lesions were more frequently detected. The filters change the pixel intensities reducing or intensifying the differences between similar regions48CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQSem informaçã

Detection of fractured endodontic instruments in root canals: comparison between different digital radiography systems and cone-beam computed tomography

This study compared the detection of fractured instruments in root canals with and without filling by periapical radiographs from 3 digital systems and cone-beam computed tomographic (CBCT) images with different resolutions. Methods: Thirty-one human molars (80 canals) were used. Root canals were divided into the following groups: the control group, without fillings; the fracture group, without fillings and with fractured files; the fill group, filled; and the fill/fracture group, filled and with fractured files. Digital radiographs in ortho-, mesio-, and distoradial directions were performed in 2 semidirect systems (VistaScan [Diirr Dental, Beitigheim-Bissinger, Germany] and Express [Instrumentarium Imaging, Tuusula, Finland]) and a direct system (SnapShot [Instrumentarium Imaging]). CBCT images were acquired with 0.085-mm and 0.2-mm voxel sizes. All images were assessed and reassessed by 4 observers for the presence or absence of fractured files on a 5-point scale. The sensitivity, specificity, and accuracy were calculated. Results: In the absence of filling, accuracy values were high, and there were no statistical differences among the radiographic techniques, different digital systems, or the different CBCT voxels sizes. In the presence of filling, the accuracy of periapical radiographs was significantly higher than CBCT images. In general, Snapshot showed higher accuracy than VistaScan and Express. Conclusions: Periapical radiographs in 1 incidence were accurate for the detection of fractured endodontic instruments inside the root canal in the absence or presence of filling, suggesting that this technique should be the first choice as well as the direct digital radiographic system. In the presence of filling, the decision to perform a CBCT examination must take into consideration its low accuracy.This study compared the detection of fractured instruments in root canals with and without filling by periapical radiographs from 3 digital systems and cone-beam computed tomographic (CBCT) images with different resolutions. Methods: Thirty-one human molars (80 canals) were used. Root canals were divided into the following groups: the control group, without fillings; the fracture group, without fillings and with fractured files; the fill group, filled; and the fill/fracture group, filled and with fractured files. Digital radiographs in ortho-, mesio-, and distoradial directions were performed in 2 semidirect systems (VistaScan [Diirr Dental, Beitigheim-Bissinger, Germany] and Express [Instrumentarium Imaging, Tuusula, Finland]) and a direct system (SnapShot [Instrumentarium Imaging]). CBCT images were acquired with 0.085-mm and 0.2-mm voxel sizes. All images were assessed and reassessed by 4 observers for the presence or absence of fractured files on a 5-point scale. The sensitivity, specificity, and accuracy were calculated. Results: In the absence of filling, accuracy values were high, and there were no statistical differences among the radiographic techniques, different digital systems, or the different CBCT voxels sizes. In the presence of filling, the accuracy of periapical radiographs was significantly higher than CBCT images. In general, Snapshot showed higher accuracy than VistaScan and Express. Conclusions: Periapical radiographs in 1 incidence were accurate for the detection of fractured endodontic instruments inside the root canal in the absence or presence of filling, suggesting that this technique should be the first choice as well as the direct digital radiographic system. In the presence of filling, the decision to perform a CBCT examination must take into consideration its low accuracy43454454

Development and validation of a formula based on maxillary sinus measurements as a tool for sex estimation: a cone beam computed tomography study

BackgroundAs sex estimation is an important step to delineate the biological profile, the development of tools employing anatomical structures which may maintain their integrity even after extreme events, such as the maxillary sinus, become useful for forensic identification. Thus, the aim in the present study was to develop and validate a formula for sex estimation through measurements in the maxillary sinuses in a Brazilian population, using cone beam computed tomography (CBCT) scans.Material and methodsLinear and volumetric measurements in the maxillary sinus were performed bilaterally in 94 CBCT scans from 45 males (mean age 25.20.79) and 49 females (mean age 23.70.50). The OnDemand 3D software was employed for linear measurements (height, length and width of, and the largest distance between the right and left maxillary sinuses), while the ITK-SNAP 3.0 segmentation software was used to acquire the volume. The data obtained was applied to a mathematical model for sex estimation. To validate the developed formula, another sample composed of 60 CBCT images of Brazilian individuals was tested.Results p id=Par3 Overall, maxillary sinuses' measurements were significantly higher in males, without statistically significant differences between the right and left sides within each group. The most dimorphic measurement was the height, with an accuracy of 77.7% regarding sex estimation. The formula created lead to a sex estimation of 87.8% for females and 80% for males, with an overall accuracy of 84%. When the formula validity was tested in another sample, it showed an accuracy of 82.4%.Conclusion The formula developed through measurements in the maxillary sinus using CBCT scans showed an accuracy of 84% for sex estimation and can be applied as a complementary method for human identification in the Brazilian population13341241124