O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico

Detalhes bibliográficos
Ano de defesa: 2019
Autor(a) principal: Coelho, Camila Carvalho de Oliveira
Orientador(a): Alves, Ana Paula Negreiros Nunes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/46038
Resumo: Bisphosphonates-Related Osteonecrosis of Jaw (BRONJ) has no defined pathophysiology, but it is believed that local infection may participates of it development. The aim of this study was to evaluate the role of microorganism in osteochemonecrosis of jaw induced by zoledronic acid (ZA). For this purpose, C57BL/6 wild type mice (WT), specific-pathogen-free (SPF) and conventionalized (CONV), that are SPF animals inoculated with microbiota from WT animals (n = 6) were subjected to ZA adminstrations (1 mg/kg, intraperitoneally) for three weeks. Four weeks later, second lower left molar was extracted, followed by a new administration ZA realized seven days after surgery. Other animals, WT, SPF and CONV (n = 6) received saline solution intraperitoneally (controls). Body weight gain was performed weekly and haematological analyzes on day 0 and 70. Oral biofilms were collected from animals on days 0 and 70 for qualitative cytological analysis. After euthanasia (day 70), jaws and organs were excised. With the jaws, microtomographies was made to measure suggestive hypodense area of necrosis and, after decalcification, histologic slides (hematoxylin-eosin) for histomorphometric analysis of the post-exodontia alveolus. Kidney, liver, spleen and stomach were analyzed histopathologically for toxicity parameters. Qualitative cytological analysis revealed success in the conventionalization, with permanence of the similar microbiota to the WT animals from day 0 to 70. The SPF-ZA group, which exhibited cocci on day 0, showed filamentous bacteria at the end of the experiment. Greater hypodense area was seen in the post-exodontia alveoli of ZA-treated animals compared to saline groups. Histomorphometrically, WT-ZA and CONVZA groups exhibited a greater number of inflammatory cells and total osteoclasts in the postextraction sites, compared to those treated with saline, in addition to more frequent bacterial colonies and bone sequestra. The administration of ZA was associated with the probable occurrence of anemic events, a tendency of reduction in the number of platelets and the vacuolization of tubular epithelium in the kidney. SPF animals exhibited delay in body weight gain. Thus, the presence of a pathogenic oral microbiota was related to the occurrence of BRONJ lesions in WT and CONV mice, while their absence revealed, only, temporal cicatricial delay, without classic signs of necrotic lesion.
id UFC-7_89bd3e37d31cf042ccff8c791afa5073
oai_identifier_str oai:repositorio.ufc.br:riufc/46038
network_acronym_str UFC-7
network_name_str Repositório Institucional da Universidade Federal do Ceará (UFC)
repository_id_str
spelling Coelho, Camila Carvalho de OliveiraAlves, Ana Paula Negreiros Nunes2019-09-24T13:13:47Z2019-09-24T13:13:47Z2019-04-29COELHO, C. C. O. O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico. 2019. 117 f. Tese (Doutorado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2019.http://www.repositorio.ufc.br/handle/riufc/46038Bisphosphonates-Related Osteonecrosis of Jaw (BRONJ) has no defined pathophysiology, but it is believed that local infection may participates of it development. The aim of this study was to evaluate the role of microorganism in osteochemonecrosis of jaw induced by zoledronic acid (ZA). For this purpose, C57BL/6 wild type mice (WT), specific-pathogen-free (SPF) and conventionalized (CONV), that are SPF animals inoculated with microbiota from WT animals (n = 6) were subjected to ZA adminstrations (1 mg/kg, intraperitoneally) for three weeks. Four weeks later, second lower left molar was extracted, followed by a new administration ZA realized seven days after surgery. Other animals, WT, SPF and CONV (n = 6) received saline solution intraperitoneally (controls). Body weight gain was performed weekly and haematological analyzes on day 0 and 70. Oral biofilms were collected from animals on days 0 and 70 for qualitative cytological analysis. After euthanasia (day 70), jaws and organs were excised. With the jaws, microtomographies was made to measure suggestive hypodense area of necrosis and, after decalcification, histologic slides (hematoxylin-eosin) for histomorphometric analysis of the post-exodontia alveolus. Kidney, liver, spleen and stomach were analyzed histopathologically for toxicity parameters. Qualitative cytological analysis revealed success in the conventionalization, with permanence of the similar microbiota to the WT animals from day 0 to 70. The SPF-ZA group, which exhibited cocci on day 0, showed filamentous bacteria at the end of the experiment. Greater hypodense area was seen in the post-exodontia alveoli of ZA-treated animals compared to saline groups. Histomorphometrically, WT-ZA and CONVZA groups exhibited a greater number of inflammatory cells and total osteoclasts in the postextraction sites, compared to those treated with saline, in addition to more frequent bacterial colonies and bone sequestra. The administration of ZA was associated with the probable occurrence of anemic events, a tendency of reduction in the number of platelets and the vacuolization of tubular epithelium in the kidney. SPF animals exhibited delay in body weight gain. Thus, the presence of a pathogenic oral microbiota was related to the occurrence of BRONJ lesions in WT and CONV mice, while their absence revealed, only, temporal cicatricial delay, without classic signs of necrotic lesion.A Osteonecrose dos Maxilares induzida por Bisfosfonatos (OMB) não possui fisiopatologia definida, mas se acredita que a infecção local possa participar do seu desenvolvimento. O objetivo desse estudo foi avaliar o papel do micro-organismo na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico (AZ). Para isso, camundongos C57BL/6 selvagens (SELV), Specific-Patogen-Free (SPF) e Convencionalizados (CONV), isto é, SPF inoculados com microbiota de animais SELV (n=6), foram submetidos às administrações de AZ (1 mg/kg, via intraperitoneal) por três semanas. Quatro semanas depois, realizou-se exodontia do segundo molar inferior esquerdo, seguida de nova administração de AZ, 7 dias após o procedimento cirúrgico. Outros animais, SELV, SPF e CONV (n=6), receberam solução salina via intraperitoneal (controles). Foram realizadas análises do ganho de massa corpórea semanalmente e hematológica no dia 0 e 70. Biofilmes orais foram colhidos dos animais nos dias 0 e 70 para análise citológica qualitativa. Após eutanásia (dia 70), mandíbulas e órgãos foram excisados. Com as mandíbulas, realizaram-se microtomografias para mensuração da área hipodensa sugestiva de necrose e, após descalcificação, lâminas histológicas (hematoxilinaeosina) para análise histomorfométrica do alvéolo pós-exodontia. Rim, fígado, baço e estômago foram analisados histopatologicamente para parâmetros de toxicidade. Análise citológica qualitativa revelou sucesso na convencionalização, com permanência de microbiota semelhante aos animais SELV do dia 0 ao 70. O grupo SPF-AZ, que exibiu cocos no dia 0, passou a evidenciar bactérias filamentosas ao final do experimento. Maior área hipodensa foi vista nos alvéolos pós-exodontia de animais tratados com AZ em relação aos grupos tratados com salina. Histomorfometricamente, grupos SELV-AZ e CONV-AZ exibiram maior número de células inflamatórias e osteoclastos totais nos sítios pós-exodontia, comparados aos tratados com salina, além de colônias bacterianas e sequestros ósseos mais frequentes. O número de osteoclastos apoptóticos foi maior nos animais tratados com AZ, independente do grupo. A administração de AZ esteve associada à provável ocorrência de eventos anêmicos, tendência à redução no número de plaquetas e à vacuolização de epitélio tubular no rim. Animais livres de patógenos específicos exibiram retardo no ganho de massa corpórea. Assim, a presença de uma microbiota oral patogênica esteve relacionada à ocorrência de lesões de OMB em camundongos SELV e CONV, enquanto sua ausência revelou, somente, atraso cicatricial temporal sem sinais clássicos de lesão necrótica.Osteonecrose da Arcada Osseodentária Associada a DifosfonatosBactériasVida Livre de GermesO papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônicoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/46038/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52ORIGINAL2019_tese_ccocoelho.pdf2019_tese_ccocoelho.pdfapplication/pdf16812935http://repositorio.ufc.br/bitstream/riufc/46038/1/2019_tese_ccocoelho.pdf53afd1eea417e6935d58f2c5789599b3MD51riufc/460382019-09-24 10:13:47.669oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-09-24T13:13:47Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico
title O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico
spellingShingle O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico
Coelho, Camila Carvalho de Oliveira
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos
Bactérias
Vida Livre de Germes
title_short O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico
title_full O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico
title_fullStr O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico
title_full_unstemmed O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico
title_sort O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico
author Coelho, Camila Carvalho de Oliveira
author_facet Coelho, Camila Carvalho de Oliveira
author_role author
dc.contributor.author.fl_str_mv Coelho, Camila Carvalho de Oliveira
dc.contributor.advisor1.fl_str_mv Alves, Ana Paula Negreiros Nunes
contributor_str_mv Alves, Ana Paula Negreiros Nunes
dc.subject.por.fl_str_mv Osteonecrose da Arcada Osseodentária Associada a Difosfonatos
Bactérias
Vida Livre de Germes
topic Osteonecrose da Arcada Osseodentária Associada a Difosfonatos
Bactérias
Vida Livre de Germes
description Bisphosphonates-Related Osteonecrosis of Jaw (BRONJ) has no defined pathophysiology, but it is believed that local infection may participates of it development. The aim of this study was to evaluate the role of microorganism in osteochemonecrosis of jaw induced by zoledronic acid (ZA). For this purpose, C57BL/6 wild type mice (WT), specific-pathogen-free (SPF) and conventionalized (CONV), that are SPF animals inoculated with microbiota from WT animals (n = 6) were subjected to ZA adminstrations (1 mg/kg, intraperitoneally) for three weeks. Four weeks later, second lower left molar was extracted, followed by a new administration ZA realized seven days after surgery. Other animals, WT, SPF and CONV (n = 6) received saline solution intraperitoneally (controls). Body weight gain was performed weekly and haematological analyzes on day 0 and 70. Oral biofilms were collected from animals on days 0 and 70 for qualitative cytological analysis. After euthanasia (day 70), jaws and organs were excised. With the jaws, microtomographies was made to measure suggestive hypodense area of necrosis and, after decalcification, histologic slides (hematoxylin-eosin) for histomorphometric analysis of the post-exodontia alveolus. Kidney, liver, spleen and stomach were analyzed histopathologically for toxicity parameters. Qualitative cytological analysis revealed success in the conventionalization, with permanence of the similar microbiota to the WT animals from day 0 to 70. The SPF-ZA group, which exhibited cocci on day 0, showed filamentous bacteria at the end of the experiment. Greater hypodense area was seen in the post-exodontia alveoli of ZA-treated animals compared to saline groups. Histomorphometrically, WT-ZA and CONVZA groups exhibited a greater number of inflammatory cells and total osteoclasts in the postextraction sites, compared to those treated with saline, in addition to more frequent bacterial colonies and bone sequestra. The administration of ZA was associated with the probable occurrence of anemic events, a tendency of reduction in the number of platelets and the vacuolization of tubular epithelium in the kidney. SPF animals exhibited delay in body weight gain. Thus, the presence of a pathogenic oral microbiota was related to the occurrence of BRONJ lesions in WT and CONV mice, while their absence revealed, only, temporal cicatricial delay, without classic signs of necrotic lesion.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-09-24T13:13:47Z
dc.date.available.fl_str_mv 2019-09-24T13:13:47Z
dc.date.issued.fl_str_mv 2019-04-29
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv COELHO, C. C. O. O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico. 2019. 117 f. Tese (Doutorado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2019.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/46038
identifier_str_mv COELHO, C. C. O. O papel de biofilmes microbianos na osteoquimionecrose do osso mandibular induzida por ácido zoledrônico. 2019. 117 f. Tese (Doutorado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2019.
url http://www.repositorio.ufc.br/handle/riufc/46038
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
instacron_str UFC
institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
bitstream.url.fl_str_mv http://repositorio.ufc.br/bitstream/riufc/46038/2/license.txt
http://repositorio.ufc.br/bitstream/riufc/46038/1/2019_tese_ccocoelho.pdf
bitstream.checksum.fl_str_mv 8a4605be74aa9ea9d79846c1fba20a33
53afd1eea417e6935d58f2c5789599b3
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
_version_ 1847792994428649472