Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFC |
Texto Completo: | http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13034 |
Resumo: | Despite their popular use in breast augmentation and reconstruction surgeries, the limited biocompatibility of silicone implants can induce severe side effects, including adverse capsularcontracture (ACC), an excessive foreign body reaction that forms, by unknown reason, a tight and hard fibrous capsule around the implant. A non-surgical treatment for ACC will be desirable as revision surgery for capsulotomy or capsulectomy with implant exchange are associated with a high risk of recurrence and complications. Recently it has been shown that sympathetic denervation accelerates wound contraction and delays reepithelialization in rats. Another study demonstrated that beta-adrenoceptor blockade has antifibrotic effects in a murine model of nonsinusoidal liver fibrosis. This study examines the effects of using propranolol, a non-selective beta-adrenoceptor antangonist, to prevent capsular formation around texturized silicone prosthesis implanted in the dorsum of male guinea-pigs. Animals (n=36) were randomly distributed into two equal groups, untreated or orally treated with propranololol (10 mg/kg dissolved in daily water). Capsules and implants were removed and examined for inflammation, thickness, fibrosis progression, density of type I and III collagen and fractal dimension by histological scoring using hematoxilin-eosin stained samples, digital histometry for measuring capsular thickness, picrosirius-polarization and digital image analysis for type I and type III collagen density and fractal dimension calculation by box-counting after 7, 14 or 21 days.Propranolol significantly reduced inflammation scores in the capsular tissue as compared to untreated group. Also, the capsular content of type I and type III collagen showed a statistical difference among the groups at different time points (p< 0,0001, Kruskal-Wallis test). The type I collagen density observed at 1, 2 or 3 weeks decreased significantly compared with that found in the control group. Conversely, the density of type III collagen increased in propranolol-treated group along the time.The capsule thickness in propranolol-treated cavies was significantly thinner and exhibited higher collagen type III/type I ratios and more irregular collagen fiber alignments than control animals. The observed decrease in fractal dimension of collagen also supported the alleviation of capsular formation by propranolol usage. Taken together, these data show that propranolol efficiently delays formation (antiproliferative or citotoxity effects) and maturation (antifibrogenic effect) of capsule around textured implants. Therefore, the blockade of beta-adrenoceptors is a promising option to support future therapeutic strategies in the treatment/prevention of capsular contracture. |
id |
UFC_970c89d7c5cab5c7f8ba4d382c58ba10 |
---|---|
oai_identifier_str |
oai:www.teses.ufc.br:8804 |
network_acronym_str |
UFC |
network_name_str |
Biblioteca Digital de Teses e Dissertações da UFC |
spelling |
info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisFractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants DimensÃo fractal e histometria digital na avaliaÃÃo dos efeitos do propranolol sobre a reaÃÃo capsular ao implante de silicone2014-08-29Jose Alberto Dias Leite49292838768http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4794139Y6Lusmar Veras Rodrigues05910803387http://lattes.cnpq.br/8297021871089734AntÃnio Ribeiro da Silva Filho09338306372http://lattes.cnpq.br/7587254459420282Moacir Cymrot83155392800http://lattes.cnpq.br/6469119883564873 MAXIMILIANO AGUIAR PORTO6424904239135286504353Charles Jean Gomes de MesquitaUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em CirurgiaUFCBRCIRURGIADespite their popular use in breast augmentation and reconstruction surgeries, the limited biocompatibility of silicone implants can induce severe side effects, including adverse capsularcontracture (ACC), an excessive foreign body reaction that forms, by unknown reason, a tight and hard fibrous capsule around the implant. A non-surgical treatment for ACC will be desirable as revision surgery for capsulotomy or capsulectomy with implant exchange are associated with a high risk of recurrence and complications. Recently it has been shown that sympathetic denervation accelerates wound contraction and delays reepithelialization in rats. Another study demonstrated that beta-adrenoceptor blockade has antifibrotic effects in a murine model of nonsinusoidal liver fibrosis. This study examines the effects of using propranolol, a non-selective beta-adrenoceptor antangonist, to prevent capsular formation around texturized silicone prosthesis implanted in the dorsum of male guinea-pigs. Animals (n=36) were randomly distributed into two equal groups, untreated or orally treated with propranololol (10 mg/kg dissolved in daily water). Capsules and implants were removed and examined for inflammation, thickness, fibrosis progression, density of type I and III collagen and fractal dimension by histological scoring using hematoxilin-eosin stained samples, digital histometry for measuring capsular thickness, picrosirius-polarization and digital image analysis for type I and type III collagen density and fractal dimension calculation by box-counting after 7, 14 or 21 days.Propranolol significantly reduced inflammation scores in the capsular tissue as compared to untreated group. Also, the capsular content of type I and type III collagen showed a statistical difference among the groups at different time points (p< 0,0001, Kruskal-Wallis test). The type I collagen density observed at 1, 2 or 3 weeks decreased significantly compared with that found in the control group. Conversely, the density of type III collagen increased in propranolol-treated group along the time.The capsule thickness in propranolol-treated cavies was significantly thinner and exhibited higher collagen type III/type I ratios and more irregular collagen fiber alignments than control animals. The observed decrease in fractal dimension of collagen also supported the alleviation of capsular formation by propranolol usage. Taken together, these data show that propranolol efficiently delays formation (antiproliferative or citotoxity effects) and maturation (antifibrogenic effect) of capsule around textured implants. Therefore, the blockade of beta-adrenoceptors is a promising option to support future therapeutic strategies in the treatment/prevention of capsular contracture.As mamoplastias com implante de silicone sÃo as cirurgias plÃsticas mais realizadas no mundo. O organismo reage a qualquer implante, encapsulando-o. Por razÃes desconhecidas, algumas cÃpsulas tornam-se patologicamente ativas gerando uma contratura capsular adversa (CCA), fibrose constritiva que deforma a mama reduzindo o resultado estÃtico. Esta afecÃÃo de difÃcil tratamento requer, em alguns casos, reintervenÃÃes cirÃrgicas que nÃo impedem a recidiva. Tratamentos adjuvantes com drogas e/ou mÃtodos fÃsicos apresentam respostas variÃveis e frequentemente insatisfatÃrias. O propranolol, antagonista nÃo seletivo de betadrenoceptores, vem sendo empregado em estudos prÃ-clÃnicos em que a resposta fibrÃtica à importante parÃmetro de avaliaÃÃo e prognÃstico. A demanda por mÃtodos quantitativos e a traduÃÃo dos dados de bancada à clÃnica à uma constante. MÃtodos tradicionais como a histo-morfometria e a picrosirius-polarizaÃÃo tem sua acurÃcia aumentada quando associados a tÃcnicas computacionais. A anÃlise da DimensÃo Fractal (DF), metodologia nÃo linear de mensuraÃÃo, tem se mostrado Ãtil na avaliaÃÃo de imagens biolÃgicas permitindo visualizaÃÃo e compreensÃo de detalhes imperceptÃveis ao olhar humano. O objetivo desse trabalho foi associar essas tecnologias (ferramentas computacionais e recursos matemÃticos) na avaliaÃÃo quantitativa dos efeitos do propranolol na formaÃÃo da cÃpsula fibrosa peri-implante. Foram implantadas no plano subcutÃneo 36 miniprÃteses texturizadas, preenchidas com gel de silicone (20 mL), no dorso de cobaias (Cavia porcellus). Os animais foram divididos aleatoriamente em dois grupos (n=18, cada) sendo tratados ou nÃo com propranolol (10 mg/Kg dissolvido na Ãgua de beber diÃria (150 mL)). Os animais foram acompanhados e sacrificados apÃs 7, 14 ou 21 dias. ApÃs a retirada em bloco e explantaÃÃo cuidadosa da prÃtese, a cÃpsula e o tecido do peri-implante foram preparados e corados pela hematoxilina-eosina (HE) ou picrosirius-red (PSR). A inflamaÃÃo foi quantificada por atribuiÃÃo de escores. Microfotografias digitais das amostras coradas pelo PSR foram obtidas sob polarizaÃÃo de forma padronizada para mensurar a espessura da cÃpsula, densidade do colÃgeno tipo I e tipo III, Ãndice de fibrose (densidade do colÃgeno/espessura capsular) e cÃlculo da dimensÃo fractal pelo mÃtodo de contagem de caixas. Foi utilizada anÃlise estatÃstica paramÃtrica ou nÃo paramÃtrica conforme a natureza dos dados, considerando um nÃvel de significÃncia P < 0,05. NÃo ocorreram casos de infecÃÃo, seroma, hematoma ou deslocamento do implante. Todos os animais, independentemente do grupo e do momento do sacrifÃcio exibiam uma cÃpsula fibrosa. As cÃpsulas dos animais tratados com propranolol exibiam significantemente menor intensidade de inflamaÃÃo, cÃpsulas menos espessas, menor Ãndice fibrÃtico e menores valores de dimensÃo fractal do que as do grupo controle. A DF revelou correlaÃÃo inversa com esses parÃmetros. Em conjunto, estes achados sÃo condizentes com a inibiÃÃo da formaÃÃo da cÃpsula pelo betabloqueio sistÃmico nÃo seletivo, sugerindo aÃÃo anti-inflamatÃria e antifibrogÃnica do Propranolol.CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13034application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:26:18Zmail@mail.com - |
dc.title.en.fl_str_mv |
Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants |
dc.title.alternative.pt.fl_str_mv |
DimensÃo fractal e histometria digital na avaliaÃÃo dos efeitos do propranolol sobre a reaÃÃo capsular ao implante de silicone |
title |
Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants |
spellingShingle |
Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants Charles Jean Gomes de Mesquita CIRURGIA |
title_short |
Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants |
title_full |
Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants |
title_fullStr |
Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants |
title_full_unstemmed |
Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants |
title_sort |
Fractal dimension and digital histometry to analyze the effect of propranololol on capsular contracture formed around silicone implants |
author |
Charles Jean Gomes de Mesquita |
author_facet |
Charles Jean Gomes de Mesquita |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Jose Alberto Dias Leite |
dc.contributor.advisor1ID.fl_str_mv |
49292838768 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4794139Y6 |
dc.contributor.referee1.fl_str_mv |
Lusmar Veras Rodrigues |
dc.contributor.referee1ID.fl_str_mv |
05910803387 |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/8297021871089734 |
dc.contributor.referee2.fl_str_mv |
AntÃnio Ribeiro da Silva Filho |
dc.contributor.referee2ID.fl_str_mv |
09338306372 |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/7587254459420282 |
dc.contributor.referee3.fl_str_mv |
Moacir Cymrot |
dc.contributor.referee3ID.fl_str_mv |
83155392800 |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/6469119883564873 |
dc.contributor.referee4.fl_str_mv |
MAXIMILIANO AGUIAR PORTO |
dc.contributor.referee4ID.fl_str_mv |
64249042391 |
dc.contributor.authorID.fl_str_mv |
35286504353 |
dc.contributor.author.fl_str_mv |
Charles Jean Gomes de Mesquita |
contributor_str_mv |
Jose Alberto Dias Leite Lusmar Veras Rodrigues AntÃnio Ribeiro da Silva Filho Moacir Cymrot MAXIMILIANO AGUIAR PORTO |
dc.subject.cnpq.fl_str_mv |
CIRURGIA |
topic |
CIRURGIA |
dc.description.sponsorship.fl_txt_mv |
CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior |
dc.description.abstract.por.fl_txt_mv |
Despite their popular use in breast augmentation and reconstruction surgeries, the limited biocompatibility of silicone implants can induce severe side effects, including adverse capsularcontracture (ACC), an excessive foreign body reaction that forms, by unknown reason, a tight and hard fibrous capsule around the implant. A non-surgical treatment for ACC will be desirable as revision surgery for capsulotomy or capsulectomy with implant exchange are associated with a high risk of recurrence and complications. Recently it has been shown that sympathetic denervation accelerates wound contraction and delays reepithelialization in rats. Another study demonstrated that beta-adrenoceptor blockade has antifibrotic effects in a murine model of nonsinusoidal liver fibrosis. This study examines the effects of using propranolol, a non-selective beta-adrenoceptor antangonist, to prevent capsular formation around texturized silicone prosthesis implanted in the dorsum of male guinea-pigs. Animals (n=36) were randomly distributed into two equal groups, untreated or orally treated with propranololol (10 mg/kg dissolved in daily water). Capsules and implants were removed and examined for inflammation, thickness, fibrosis progression, density of type I and III collagen and fractal dimension by histological scoring using hematoxilin-eosin stained samples, digital histometry for measuring capsular thickness, picrosirius-polarization and digital image analysis for type I and type III collagen density and fractal dimension calculation by box-counting after 7, 14 or 21 days.Propranolol significantly reduced inflammation scores in the capsular tissue as compared to untreated group. Also, the capsular content of type I and type III collagen showed a statistical difference among the groups at different time points (p< 0,0001, Kruskal-Wallis test). The type I collagen density observed at 1, 2 or 3 weeks decreased significantly compared with that found in the control group. Conversely, the density of type III collagen increased in propranolol-treated group along the time.The capsule thickness in propranolol-treated cavies was significantly thinner and exhibited higher collagen type III/type I ratios and more irregular collagen fiber alignments than control animals. The observed decrease in fractal dimension of collagen also supported the alleviation of capsular formation by propranolol usage. Taken together, these data show that propranolol efficiently delays formation (antiproliferative or citotoxity effects) and maturation (antifibrogenic effect) of capsule around textured implants. Therefore, the blockade of beta-adrenoceptors is a promising option to support future therapeutic strategies in the treatment/prevention of capsular contracture. As mamoplastias com implante de silicone sÃo as cirurgias plÃsticas mais realizadas no mundo. O organismo reage a qualquer implante, encapsulando-o. Por razÃes desconhecidas, algumas cÃpsulas tornam-se patologicamente ativas gerando uma contratura capsular adversa (CCA), fibrose constritiva que deforma a mama reduzindo o resultado estÃtico. Esta afecÃÃo de difÃcil tratamento requer, em alguns casos, reintervenÃÃes cirÃrgicas que nÃo impedem a recidiva. Tratamentos adjuvantes com drogas e/ou mÃtodos fÃsicos apresentam respostas variÃveis e frequentemente insatisfatÃrias. O propranolol, antagonista nÃo seletivo de betadrenoceptores, vem sendo empregado em estudos prÃ-clÃnicos em que a resposta fibrÃtica à importante parÃmetro de avaliaÃÃo e prognÃstico. A demanda por mÃtodos quantitativos e a traduÃÃo dos dados de bancada à clÃnica à uma constante. MÃtodos tradicionais como a histo-morfometria e a picrosirius-polarizaÃÃo tem sua acurÃcia aumentada quando associados a tÃcnicas computacionais. A anÃlise da DimensÃo Fractal (DF), metodologia nÃo linear de mensuraÃÃo, tem se mostrado Ãtil na avaliaÃÃo de imagens biolÃgicas permitindo visualizaÃÃo e compreensÃo de detalhes imperceptÃveis ao olhar humano. O objetivo desse trabalho foi associar essas tecnologias (ferramentas computacionais e recursos matemÃticos) na avaliaÃÃo quantitativa dos efeitos do propranolol na formaÃÃo da cÃpsula fibrosa peri-implante. Foram implantadas no plano subcutÃneo 36 miniprÃteses texturizadas, preenchidas com gel de silicone (20 mL), no dorso de cobaias (Cavia porcellus). Os animais foram divididos aleatoriamente em dois grupos (n=18, cada) sendo tratados ou nÃo com propranolol (10 mg/Kg dissolvido na Ãgua de beber diÃria (150 mL)). Os animais foram acompanhados e sacrificados apÃs 7, 14 ou 21 dias. ApÃs a retirada em bloco e explantaÃÃo cuidadosa da prÃtese, a cÃpsula e o tecido do peri-implante foram preparados e corados pela hematoxilina-eosina (HE) ou picrosirius-red (PSR). A inflamaÃÃo foi quantificada por atribuiÃÃo de escores. Microfotografias digitais das amostras coradas pelo PSR foram obtidas sob polarizaÃÃo de forma padronizada para mensurar a espessura da cÃpsula, densidade do colÃgeno tipo I e tipo III, Ãndice de fibrose (densidade do colÃgeno/espessura capsular) e cÃlculo da dimensÃo fractal pelo mÃtodo de contagem de caixas. Foi utilizada anÃlise estatÃstica paramÃtrica ou nÃo paramÃtrica conforme a natureza dos dados, considerando um nÃvel de significÃncia P < 0,05. NÃo ocorreram casos de infecÃÃo, seroma, hematoma ou deslocamento do implante. Todos os animais, independentemente do grupo e do momento do sacrifÃcio exibiam uma cÃpsula fibrosa. As cÃpsulas dos animais tratados com propranolol exibiam significantemente menor intensidade de inflamaÃÃo, cÃpsulas menos espessas, menor Ãndice fibrÃtico e menores valores de dimensÃo fractal do que as do grupo controle. A DF revelou correlaÃÃo inversa com esses parÃmetros. Em conjunto, estes achados sÃo condizentes com a inibiÃÃo da formaÃÃo da cÃpsula pelo betabloqueio sistÃmico nÃo seletivo, sugerindo aÃÃo anti-inflamatÃria e antifibrogÃnica do Propranolol. |
description |
Despite their popular use in breast augmentation and reconstruction surgeries, the limited biocompatibility of silicone implants can induce severe side effects, including adverse capsularcontracture (ACC), an excessive foreign body reaction that forms, by unknown reason, a tight and hard fibrous capsule around the implant. A non-surgical treatment for ACC will be desirable as revision surgery for capsulotomy or capsulectomy with implant exchange are associated with a high risk of recurrence and complications. Recently it has been shown that sympathetic denervation accelerates wound contraction and delays reepithelialization in rats. Another study demonstrated that beta-adrenoceptor blockade has antifibrotic effects in a murine model of nonsinusoidal liver fibrosis. This study examines the effects of using propranolol, a non-selective beta-adrenoceptor antangonist, to prevent capsular formation around texturized silicone prosthesis implanted in the dorsum of male guinea-pigs. Animals (n=36) were randomly distributed into two equal groups, untreated or orally treated with propranololol (10 mg/kg dissolved in daily water). Capsules and implants were removed and examined for inflammation, thickness, fibrosis progression, density of type I and III collagen and fractal dimension by histological scoring using hematoxilin-eosin stained samples, digital histometry for measuring capsular thickness, picrosirius-polarization and digital image analysis for type I and type III collagen density and fractal dimension calculation by box-counting after 7, 14 or 21 days.Propranolol significantly reduced inflammation scores in the capsular tissue as compared to untreated group. Also, the capsular content of type I and type III collagen showed a statistical difference among the groups at different time points (p< 0,0001, Kruskal-Wallis test). The type I collagen density observed at 1, 2 or 3 weeks decreased significantly compared with that found in the control group. Conversely, the density of type III collagen increased in propranolol-treated group along the time.The capsule thickness in propranolol-treated cavies was significantly thinner and exhibited higher collagen type III/type I ratios and more irregular collagen fiber alignments than control animals. The observed decrease in fractal dimension of collagen also supported the alleviation of capsular formation by propranolol usage. Taken together, these data show that propranolol efficiently delays formation (antiproliferative or citotoxity effects) and maturation (antifibrogenic effect) of capsule around textured implants. Therefore, the blockade of beta-adrenoceptors is a promising option to support future therapeutic strategies in the treatment/prevention of capsular contracture. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-08-29 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
status_str |
publishedVersion |
format |
doctoralThesis |
dc.identifier.uri.fl_str_mv |
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13034 |
url |
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13034 |
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.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal do Cearà |
dc.publisher.program.fl_str_mv |
Programa de PÃs-GraduaÃÃo em Cirurgia |
dc.publisher.initials.fl_str_mv |
UFC |
dc.publisher.country.fl_str_mv |
BR |
publisher.none.fl_str_mv |
Universidade Federal do Cearà |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFC instname:Universidade Federal do Ceará instacron:UFC |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFC |
collection |
Biblioteca Digital de Teses e Dissertações da UFC |
instname_str |
Universidade Federal do Ceará |
instacron_str |
UFC |
institution |
UFC |
repository.name.fl_str_mv |
-
|
repository.mail.fl_str_mv |
mail@mail.com |
_version_ |
1643295196543188992 |