Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos

Bibliographic Details
Main Author: Ferreira Júnior, Antonio Ernando Carlos
Publication Date: 2016
Format: Master thesis
Language: por
Source: Repositório Institucional da Universidade Federal do Ceará (UFC)
dARK ID: ark:/83112/001300001ztn7
Download full: http://www.repositorio.ufc.br/handle/riufc/16315
Summary: Bone healing after tooth extraction depends on variables such as surgical technique, local and systemic factors and use of pharmacological substances. Anti-inflammatory drugs can alter the tissue repair, interfering with the inflammatory phase of healing. Infliximab is a chimeric monoclonal antibody, human-murine anti-Tumor Necrosis Factor alpha (TNF-α) which has been widely used to replace corticosteroids in rheumatology clinic because it has fewer side effects in the long term. However, TNF-α pathway acts directly on osteoclastogenesis, can change the physiological response of bone turnover and its inhibition may lead to immunosuppression, increasing the risk of local infection. It was aim of this study to evaluate the influence of infliximab in healing after dental extractions alveoli. For this purpose, 84 Wistar rats (n = 7) were randomized into two groups (infliximab EV 5 mg / kg or saline EV 1ml / kg, pre-treated with 4 weekly administrations prior to extraction, weekly maintained until the day of sacrifice) . The animals were sacrificed 1, 3, 7, 14, 21 and 28 days after surgery. The occurrence of root fractures, surgical time and the weight of extracted teeth were recorded. On the day of sacrifice the weight of animals and organs (liver, spleen, kidneys, stomach) were measured. After fixation in 10% formalin buffered and macroscopic analysis, jaw and fragments of these organs, followed for histological processing and microscopic study. The jaws were submitted to radiographic, histomorphometric (size of the deposition of scar tissue, percentage of area represented by bone tissue and number of polymorphonuclear neutrophils, mononuclear and osteoclasts), immunohistochemistry (Picrossirius Red) and immunohistochemistry (TNF-α) . There were no differences seen in determining the radiolucent area related to post-extraction site between the experimental groups (p = 0.646). However, the histomorphometric analysis was visualized lower completion by bone and a greater amount of tissue remaining in infllximabe group significantly on day 14 (p <0.001). Furthermore, a smaller number of polymorphonuclear neutrophils in 3 (p <0.01) and 7 days (p <0,001) mononuclear on the 7th day (p <0.01) and osteoclasts in the 7th and 14th days (p < 0.01 and p <0.001, respectively) were observed. It also observed lower TNF-α immunoreactivity in the post-extraction sites on days 7,14, 21 and 28 (p <0.01; p <0.05, p <0.05 and p <0.01 respectively). We conclude that TNF-α inhibitors may alter the bone repair capacity in post-extraction sites. These findings suggest the need for further precautions in gory dental procedures in patients undergoing systemic therapy of these drugs.
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spelling Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratosTherapy influence of evaluation by infliximab on bone healing after tooth extraction dental alveoli in ratsFator de Necrose Tumoral alfaInfliximabRemodelação ÓsseaBone healing after tooth extraction depends on variables such as surgical technique, local and systemic factors and use of pharmacological substances. Anti-inflammatory drugs can alter the tissue repair, interfering with the inflammatory phase of healing. Infliximab is a chimeric monoclonal antibody, human-murine anti-Tumor Necrosis Factor alpha (TNF-α) which has been widely used to replace corticosteroids in rheumatology clinic because it has fewer side effects in the long term. However, TNF-α pathway acts directly on osteoclastogenesis, can change the physiological response of bone turnover and its inhibition may lead to immunosuppression, increasing the risk of local infection. It was aim of this study to evaluate the influence of infliximab in healing after dental extractions alveoli. For this purpose, 84 Wistar rats (n = 7) were randomized into two groups (infliximab EV 5 mg / kg or saline EV 1ml / kg, pre-treated with 4 weekly administrations prior to extraction, weekly maintained until the day of sacrifice) . The animals were sacrificed 1, 3, 7, 14, 21 and 28 days after surgery. The occurrence of root fractures, surgical time and the weight of extracted teeth were recorded. On the day of sacrifice the weight of animals and organs (liver, spleen, kidneys, stomach) were measured. After fixation in 10% formalin buffered and macroscopic analysis, jaw and fragments of these organs, followed for histological processing and microscopic study. The jaws were submitted to radiographic, histomorphometric (size of the deposition of scar tissue, percentage of area represented by bone tissue and number of polymorphonuclear neutrophils, mononuclear and osteoclasts), immunohistochemistry (Picrossirius Red) and immunohistochemistry (TNF-α) . There were no differences seen in determining the radiolucent area related to post-extraction site between the experimental groups (p = 0.646). However, the histomorphometric analysis was visualized lower completion by bone and a greater amount of tissue remaining in infllximabe group significantly on day 14 (p <0.001). Furthermore, a smaller number of polymorphonuclear neutrophils in 3 (p <0.01) and 7 days (p <0,001) mononuclear on the 7th day (p <0.01) and osteoclasts in the 7th and 14th days (p < 0.01 and p <0.001, respectively) were observed. It also observed lower TNF-α immunoreactivity in the post-extraction sites on days 7,14, 21 and 28 (p <0.01; p <0.05, p <0.05 and p <0.01 respectively). We conclude that TNF-α inhibitors may alter the bone repair capacity in post-extraction sites. These findings suggest the need for further precautions in gory dental procedures in patients undergoing systemic therapy of these drugs.A cicatrização óssea pós-exodontia depende de variáveis como técnica cirúrgica, fatores locais e sistêmicos e uso de substâncias farmacológicas. Os anti-inflamatórios podem alterar a reparação tecidual, interferindo na etapa inflamatória de cicatrização. O infliximabe é um anticorpo monoclonal quimérico, humano-murino, anti-Fator de Necrose Tumoral alfa (TNF-α) que tem sido amplamente utilizado em substituição aos corticosteroides na clínica reumatológica por possuir menos efeitos adversos em longo prazo. No entanto, a via TNF-α age diretamente na osteoclastogênese, podendo modificar a resposta fisiológica do turnover ósseo e sua inibição pode provocar imunossupressão, aumentando o risco de infecção local. Foi objetivo deste estudo avaliar a influência do infliximabe na cicatrização de alvéolos dentários pós-exodontias. Para tanto, 84 ratos Wistar (n=7) foram distribuídos aleatoriamente em dois grupos de estudo (infliximabe EV 5mg/kg ou salina EV 1ml/kg, pré tratados com 4 administrações semanais antes da exodontia, mantidas semanalmente até o dia do sacrifício). Os animais foram sacrificados 1, 3, 7, 14, 21 e 28 dias após o procedimento cirúrgico. A ocorrência de fraturas radiculares, o tempo cirúrgico e o peso dos dentes extraídos foram anotados. No dia do sacrifício o peso dos animais e dos órgãos (fígado, baço, rins, estômago) foram aferidos. Após fixação em formol 10% tamponado e análise macroscópica, a mandíbula e fragmentos desses órgãos, seguiram para processamento histológico e estudo microscópico. As mandíbulas foram submetidas à avaliação radiográfica, histomorfométrica (dimensão da deposição de tecido conjuntivo cicatricial, percentual da área representada por tecido ósseo e número de polimorfonucleares neutrófilos, mononucleares e osteoclastos), histoquímica (Picrossirius Red) e imuno-histoquímica (TNF-α). Não foram vistas diferenças na aferição da área radiolúcida referente ao sítio pós-exodontia entre os grupos experimentais (p=0,646). Entretanto, na análise histomorfométrica, foi visualizado menor preenchimento por tecido ósseo bem como maior quantidade de tecido conjuntivo remanescente no grupo infllximabe, de forma significante no 14º dia (p<0,001). Além disso, um menor número de polimorfonucleares neutrófilos no 3º (p< 0,01) e 7º dias (p<0,001), de mononucleares no 7º dia (p<0,01) e de osteoclastos no 7º e 14º dias (p<0,01 e p< 0,001, respectivamente) foi observado. Também foi verificada menor imunoexpressão de TNF-α nos sítios pós-exodontia nos dias 7,14, 21 e 28 (p<0,01; p<0,05, p<0,05 e p<0,01 respectivamente). Conclui-se que inibidores de TNF-α podem alterar a capacidade de reparo ósseo em sítios pós-exodontia. Estes achados sinalizam a necessidade de maiores precauções nos procedimentos odontológicos cruentos em pacientes sob terapia sistêmica desses fármacos.Alves, Ana Paula Negreiros NunesFerreira Júnior, Antonio Ernando Carlos2016-04-19T12:49:00Z2016-04-19T12:49:00Z2016-02-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfFERREIRA JÚNIOR, A. E.C. Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos. 2016. 83 f. Dissertação (Mestrado em Odontologia) - Faculdade Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2016.http://www.repositorio.ufc.br/handle/riufc/16315ark:/83112/001300001ztn7porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-01-31T18:48:20Zoai:repositorio.ufc.br:riufc/16315Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-01-31T18:48:20Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos
Therapy influence of evaluation by infliximab on bone healing after tooth extraction dental alveoli in rats
title Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos
spellingShingle Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos
Ferreira Júnior, Antonio Ernando Carlos
Fator de Necrose Tumoral alfa
Infliximab
Remodelação Óssea
title_short Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos
title_full Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos
title_fullStr Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos
title_full_unstemmed Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos
title_sort Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos
author Ferreira Júnior, Antonio Ernando Carlos
author_facet Ferreira Júnior, Antonio Ernando Carlos
author_role author
dc.contributor.none.fl_str_mv Alves, Ana Paula Negreiros Nunes
dc.contributor.author.fl_str_mv Ferreira Júnior, Antonio Ernando Carlos
dc.subject.por.fl_str_mv Fator de Necrose Tumoral alfa
Infliximab
Remodelação Óssea
topic Fator de Necrose Tumoral alfa
Infliximab
Remodelação Óssea
description Bone healing after tooth extraction depends on variables such as surgical technique, local and systemic factors and use of pharmacological substances. Anti-inflammatory drugs can alter the tissue repair, interfering with the inflammatory phase of healing. Infliximab is a chimeric monoclonal antibody, human-murine anti-Tumor Necrosis Factor alpha (TNF-α) which has been widely used to replace corticosteroids in rheumatology clinic because it has fewer side effects in the long term. However, TNF-α pathway acts directly on osteoclastogenesis, can change the physiological response of bone turnover and its inhibition may lead to immunosuppression, increasing the risk of local infection. It was aim of this study to evaluate the influence of infliximab in healing after dental extractions alveoli. For this purpose, 84 Wistar rats (n = 7) were randomized into two groups (infliximab EV 5 mg / kg or saline EV 1ml / kg, pre-treated with 4 weekly administrations prior to extraction, weekly maintained until the day of sacrifice) . The animals were sacrificed 1, 3, 7, 14, 21 and 28 days after surgery. The occurrence of root fractures, surgical time and the weight of extracted teeth were recorded. On the day of sacrifice the weight of animals and organs (liver, spleen, kidneys, stomach) were measured. After fixation in 10% formalin buffered and macroscopic analysis, jaw and fragments of these organs, followed for histological processing and microscopic study. The jaws were submitted to radiographic, histomorphometric (size of the deposition of scar tissue, percentage of area represented by bone tissue and number of polymorphonuclear neutrophils, mononuclear and osteoclasts), immunohistochemistry (Picrossirius Red) and immunohistochemistry (TNF-α) . There were no differences seen in determining the radiolucent area related to post-extraction site between the experimental groups (p = 0.646). However, the histomorphometric analysis was visualized lower completion by bone and a greater amount of tissue remaining in infllximabe group significantly on day 14 (p <0.001). Furthermore, a smaller number of polymorphonuclear neutrophils in 3 (p <0.01) and 7 days (p <0,001) mononuclear on the 7th day (p <0.01) and osteoclasts in the 7th and 14th days (p < 0.01 and p <0.001, respectively) were observed. It also observed lower TNF-α immunoreactivity in the post-extraction sites on days 7,14, 21 and 28 (p <0.01; p <0.05, p <0.05 and p <0.01 respectively). We conclude that TNF-α inhibitors may alter the bone repair capacity in post-extraction sites. These findings suggest the need for further precautions in gory dental procedures in patients undergoing systemic therapy of these drugs.
publishDate 2016
dc.date.none.fl_str_mv 2016-04-19T12:49:00Z
2016-04-19T12:49:00Z
2016-02-19
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv FERREIRA JÚNIOR, A. E.C. Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos. 2016. 83 f. Dissertação (Mestrado em Odontologia) - Faculdade Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2016.
http://www.repositorio.ufc.br/handle/riufc/16315
dc.identifier.dark.fl_str_mv ark:/83112/001300001ztn7
identifier_str_mv FERREIRA JÚNIOR, A. E.C. Avaliação da influência da terapia por infliximabe na cicatrização óssea de alvéolos dentários pós-exodontia em ratos. 2016. 83 f. Dissertação (Mestrado em Odontologia) - Faculdade Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2016.
ark:/83112/001300001ztn7
url http://www.repositorio.ufc.br/handle/riufc/16315
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reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
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repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
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