Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide
| Ano de defesa: | 2025 |
|---|---|
| Autor(a) principal: | |
| Orientador(a): | |
| Banca de defesa: | , , , , |
| Tipo de documento: | Tese |
| Tipo de acesso: | Acesso aberto |
| Idioma: | por |
| Instituição de defesa: |
Universidade Nove de Julho
|
| Programa de Pós-Graduação: |
Programa de Pós-Graduação em Medicina – Biofotônica
|
| Departamento: |
Saúde
|
| País: |
Brasil
|
| Palavras-chave em Português: | |
| Palavras-chave em Inglês: | |
| Área do conhecimento CNPq: | |
| Link de acesso: | http://bibliotecatede.uninove.br/handle/tede/3784 |
Resumo: | Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, and progressive disease that causes irreversible joint damage. The conventional treatment is pharmacological, typically involving anti-inflammatory drugs, though these are often associated with adverse effects. Photobiomodulation therapy (PBM) has been linked to the modulation of inflammation and pain and represents a potential therapeutic alternative for RA. This study aimed to evaluate the effects of PBM on pain modulation—through mechanical allodynia—tissue repair, assessed by collagen proportion, and functional recovery, evaluated via biomechanical analysis of cartilage, in an experimental model of RA induced in rats. Methodology: Male Wistar rats were divided into five groups: healthy controls without RA (CTL), RA-induced without treatment (NT), RA treated with PBM applied locally to the knee (PBM), RA treated with dexamethasone (DEX), and RA treated with a combination of PBM and dexamethasone (PBM+DEX). RA was induced using injections of type II collagen and Freund’s adjuvant. Treatments were administered three times per week for one month: PBM (808 nm; 4 J; 100 mW) applied locally or intraperitoneal dexamethasone. Mechanical allodynia was assessed weekly. At the end of the treatment, animals were euthanized, and cartilage was harvested for biomechanical and histological analyses. Results: All RA groups showed a significant reduction in resistance and deformation capacity compared to the CTL group (p < 0.001). Only the PBM group exhibited a significant improvement in deformation capacity compared to the NT group. All treated groups showed an increased proportion of total collagen compared to the NT group (p < 0.05). The PBM group was the only one to show consistent improvement in mechanical allodynia across all time points compared to the other RA groups (p < 0.01). Conclusion: Local PBM irradiation promotes the maintenance of collagen proportion and improves the tissue’s deformation capacity. While combined PBM+DEX therapy maintained the collagen proportion, it did not provide additional benefits regarding mechanical properties or pain sensitivity as assessed by the mechanical allodynia test. |
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Marcos, Rodrigo Labhttps://orcid.org/0000-0002-9750-6491http://lattes.cnpq.br/2964112163504080Marcos, Rodrigo Labathttps://orcid.org/0000-0002-9750-6491http://lattes.cnpq.br/2964112163504080Cecatto, Rebeca Bolteshttps://orcid.org/0000-0001-5675-6665http://lattes.cnpq.br/0228531403374909Cury, Diego Pulzattohttps://orcid.org/0000-0002-8571-7144http://lattes.cnpq.br/1524485838237057Prates, Renato Araujohttps://orcid.org/0000-0002-8115-9237http://lattes.cnpq.br/7664790931310514Ramos, Henrique Romanhttps://orcid.org/0000-0002-4327-842Xhttp://lattes.cnpq.br/1842119906977271http://lattes.cnpq.br/2258319861959044Romano Neto, Orlando2025-09-01T15:25:05Z2025-06-26Romano Neto, Orlando. Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide. 2025. 62 f. Tese( Programa de Pós-Graduação em Medicina – Biofotônica) - Universidade Nove de Julho, São Paulo.http://bibliotecatede.uninove.br/handle/tede/3784Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, and progressive disease that causes irreversible joint damage. The conventional treatment is pharmacological, typically involving anti-inflammatory drugs, though these are often associated with adverse effects. Photobiomodulation therapy (PBM) has been linked to the modulation of inflammation and pain and represents a potential therapeutic alternative for RA. This study aimed to evaluate the effects of PBM on pain modulation—through mechanical allodynia—tissue repair, assessed by collagen proportion, and functional recovery, evaluated via biomechanical analysis of cartilage, in an experimental model of RA induced in rats. Methodology: Male Wistar rats were divided into five groups: healthy controls without RA (CTL), RA-induced without treatment (NT), RA treated with PBM applied locally to the knee (PBM), RA treated with dexamethasone (DEX), and RA treated with a combination of PBM and dexamethasone (PBM+DEX). RA was induced using injections of type II collagen and Freund’s adjuvant. Treatments were administered three times per week for one month: PBM (808 nm; 4 J; 100 mW) applied locally or intraperitoneal dexamethasone. Mechanical allodynia was assessed weekly. At the end of the treatment, animals were euthanized, and cartilage was harvested for biomechanical and histological analyses. Results: All RA groups showed a significant reduction in resistance and deformation capacity compared to the CTL group (p < 0.001). Only the PBM group exhibited a significant improvement in deformation capacity compared to the NT group. All treated groups showed an increased proportion of total collagen compared to the NT group (p < 0.05). The PBM group was the only one to show consistent improvement in mechanical allodynia across all time points compared to the other RA groups (p < 0.01). Conclusion: Local PBM irradiation promotes the maintenance of collagen proportion and improves the tissue’s deformation capacity. While combined PBM+DEX therapy maintained the collagen proportion, it did not provide additional benefits regarding mechanical properties or pain sensitivity as assessed by the mechanical allodynia test.A artrite reumatoide (AR) é uma doença crônica, autoimune, sistêmica e progressiva, que causa danos irreversíveis às articulações. O tratamento tradicional é farmacológico, com uso de anti-inflamatórios, porém efeitos adversos são observados. A terapia por fotobiomodulação (PBM) está associada ao controle do processo inflamatório e doloroso, sendo uma opção para o tratamento da AR. O objetivo deste trabalho foi estudar o efeito da PBM no processo doloroso, a partir da alodinia mecânica, no controle do reparo tecidual, observando aspectos histológicos pela proporção de colágeno, e funcionais, pela avaliação biomecânica da cartilagem, em modelo experimental de AR induzida em ratos. Metodologia: Ratos Wistar machos foram distribuídos em 5 grupos: sem AR (CTL) ou com AR, sem tratamento (NT) ou tratados com Fotobiomodulação com aplicação local no joelho (PBM), tratados com Dexametasona (DEX) ou com terapia associada (PBM+DEX). Depois de anestesiados, os animais foram induzidos a AR com injeções de Colágeno Tipo II e adjuvante de Freund. Os animais foram tratados 3 vezes por semana durante 1 mês com PBM (808nm; 4J; 100mW) ou Dexametasona intraperitoneal. O teste de alodinia mecânica foi realizado 1 vez por semana. No final do tratamento, os animais foram eutanasiados e a cartilagem recuperada e armazenada para análises biomecânicas e morfológicas. Resultados: Todos os grupos com AR demonstraram redução da resistência e da capacidade de deformação (p<0,001) comparados ao CTL. Somente o grupo PBM apresentou melhora na capacidade de deformação comparado ao grupo NT. Todos os grupos tratados apresentaram aumento na proporção de colágeno total comparado ao grupo NT (p<0,05). O grupo PBM apresentou melhora na alodinia mecânica na 3ª semana, comparado ao grupo NT (p<0,01). Conclusão: A PBM irradiada de forma local promove manutenção da proporção de colágeno com melhora da capacidade de deformação tecidual. O tratamento associado PBM+DEX manteve melhora na proporção de colágeno, porém, sem efeito adicional nas propriedades mecânicas ou na sensibilidade à dor pelo teste de alodinia mecânica.Submitted by Nadir Basilio (nadirsb@uninove.br) on 2025-09-01T15:25:05Z No. of bitstreams: 1 Orlando Romano Neto.pdf: 1479692 bytes, checksum: f288558e6320f3a1624ecb4792ab3c08 (MD5)Made available in DSpace on 2025-09-01T15:25:05Z (GMT). No. of bitstreams: 1 Orlando Romano Neto.pdf: 1479692 bytes, checksum: f288558e6320f3a1624ecb4792ab3c08 (MD5) Previous issue date: 2025-06-26application/pdfporUniversidade Nove de JulhoPrograma de Pós-Graduação em Medicina – BiofotônicaUNINOVEBrasilSaúdefotobiomodulaçãoartrite reumatoidecartilagemcolágenopropriedades mecânicasphotobiomodulationrheumatoid arthritiscartilagecollagenmechanical propertiesCIENCIAS DA SAUDEEfeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoideEffect of combined photobiomodulation and dexamethasone on pain sensitivity and mechanical strength of knee cartilage in an experimental model of rheumatoid arthritisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis8765449414823306929600info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da Uninoveinstname:Universidade Nove de Julho (UNINOVE)instacron:UNINOVEORIGINALOrlando Romano Neto.pdfOrlando Romano Neto.pdfapplication/pdf1479692http://localhost:8080/tede/bitstream/tede/3784/2/Orlando+Romano+Neto.pdff288558e6320f3a1624ecb4792ab3c08MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://localhost:8080/tede/bitstream/tede/3784/1/license.txtbd3efa91386c1718a7f26a329fdcb468MD51tede/37842025-11-10 11:50:10.797oai:localhost:tede/3784Tk9UQTogQ09MT1FVRSBBUVVJIEEgU1VBIFBSw5NQUklBIExJQ0VOw4dBCkVzdGEgbGljZW7Dp2EgZGUgZXhlbXBsbyDDqSBmb3JuZWNpZGEgYXBlbmFzIHBhcmEgZmlucyBpbmZvcm1hdGl2b3MuCgpMSUNFTsOHQSBERSBESVNUUklCVUnDh8ODTyBOw4NPLUVYQ0xVU0lWQQoKQ29tIGEgYXByZXNlbnRhw6fDo28gZGVzdGEgbGljZW7Dp2EsIHZvY8OqIChvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSDDoCBVbml2ZXJzaWRhZGUgClhYWCAoU2lnbGEgZGEgVW5pdmVyc2lkYWRlKSBvIGRpcmVpdG8gbsOjby1leGNsdXNpdm8gZGUgcmVwcm9kdXppciwgIHRyYWR1emlyIChjb25mb3JtZSBkZWZpbmlkbyBhYmFpeG8pLCBlL291IApkaXN0cmlidWlyIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0csO0bmljbyBlIAplbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mgw6F1ZGlvIG91IHbDrWRlby4KClZvY8OqIGNvbmNvcmRhIHF1ZSBhIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSBwb2RlLCBzZW0gYWx0ZXJhciBvIGNvbnRlw7pkbywgdHJhbnNwb3IgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIApwYXJhIHF1YWxxdWVyIG1laW8gb3UgZm9ybWF0byBwYXJhIGZpbnMgZGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIHRhbWLDqW0gY29uY29yZGEgcXVlIGEgU2lnbGEgZGUgVW5pdmVyc2lkYWRlIHBvZGUgbWFudGVyIG1haXMgZGUgdW1hIGPDs3BpYSBhIHN1YSB0ZXNlIG91IApkaXNzZXJ0YcOnw6NvIHBhcmEgZmlucyBkZSBzZWd1cmFuw6dhLCBiYWNrLXVwIGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIGRlY2xhcmEgcXVlIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyDDqSBvcmlnaW5hbCBlIHF1ZSB2b2PDqiB0ZW0gbyBwb2RlciBkZSBjb25jZWRlciBvcyBkaXJlaXRvcyBjb250aWRvcyAKbmVzdGEgbGljZW7Dp2EuIFZvY8OqIHRhbWLDqW0gZGVjbGFyYSBxdWUgbyBkZXDDs3NpdG8gZGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBuw6NvLCBxdWUgc2VqYSBkZSBzZXUgCmNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3XDqW0uCgpDYXNvIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiAKZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzc8OjbyBpcnJlc3RyaXRhIGRvIGRldGVudG9yIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBwYXJhIGNvbmNlZGVyIMOgIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSAKb3MgZGlyZWl0b3MgYXByZXNlbnRhZG9zIG5lc3RhIGxpY2Vuw6dhLCBlIHF1ZSBlc3NlIG1hdGVyaWFsIGRlIHByb3ByaWVkYWRlIGRlIHRlcmNlaXJvcyBlc3TDoSBjbGFyYW1lbnRlIAppZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBubyBjb250ZcO6ZG8gZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIG9yYSBkZXBvc2l0YWRhLgoKQ0FTTyBBIFRFU0UgT1UgRElTU0VSVEHDh8ODTyBPUkEgREVQT1NJVEFEQSBURU5IQSBTSURPIFJFU1VMVEFETyBERSBVTSBQQVRST0PDjU5JTyBPVSAKQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PIFFVRSBOw4NPIFNFSkEgQSBTSUdMQSBERSAKVU5JVkVSU0lEQURFLCBWT0PDiiBERUNMQVJBIFFVRSBSRVNQRUlUT1UgVE9ET1MgRSBRVUFJU1FVRVIgRElSRUlUT1MgREUgUkVWSVPDg08gQ09NTyAKVEFNQsOJTSBBUyBERU1BSVMgT0JSSUdBw4fDlUVTIEVYSUdJREFTIFBPUiBDT05UUkFUTyBPVSBBQ09SRE8uCgpBIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lIChzKSBvdSBvKHMpIG5vbWUocykgZG8ocykgCmRldGVudG9yKGVzKSBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvLCBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIGFsw6ltIGRhcXVlbGFzIApjb25jZWRpZGFzIHBvciBlc3RhIGxpY2Vuw6dhLgo=Biblioteca Digital de Teses e Dissertaçõeshttp://bibliotecatede.uninove.br/PRIhttp://bibliotecatede.uninove.br/oai/requestbibliotecatede@uninove.br||bibliotecatede@uninove.bropendoar:2025-11-10T14:50:10Biblioteca Digital de Teses e Dissertações da Uninove - Universidade Nove de Julho (UNINOVE)false |
| dc.title.por.fl_str_mv |
Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide |
| dc.title.alternative.eng.fl_str_mv |
Effect of combined photobiomodulation and dexamethasone on pain sensitivity and mechanical strength of knee cartilage in an experimental model of rheumatoid arthritis |
| title |
Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide |
| spellingShingle |
Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide Romano Neto, Orlando fotobiomodulação artrite reumatoide cartilagem colágeno propriedades mecânicas photobiomodulation rheumatoid arthritis cartilage collagen mechanical properties CIENCIAS DA SAUDE |
| title_short |
Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide |
| title_full |
Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide |
| title_fullStr |
Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide |
| title_full_unstemmed |
Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide |
| title_sort |
Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide |
| author |
Romano Neto, Orlando |
| author_facet |
Romano Neto, Orlando |
| author_role |
author |
| dc.contributor.advisor1.fl_str_mv |
Marcos, Rodrigo Lab |
| dc.contributor.advisor1ID.fl_str_mv |
https://orcid.org/0000-0002-9750-6491 |
| dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2964112163504080 |
| dc.contributor.referee1.fl_str_mv |
Marcos, Rodrigo Labat |
| dc.contributor.referee1ID.fl_str_mv |
https://orcid.org/0000-0002-9750-6491 |
| dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/2964112163504080 |
| dc.contributor.referee2.fl_str_mv |
Cecatto, Rebeca Boltes |
| dc.contributor.referee2ID.fl_str_mv |
https://orcid.org/0000-0001-5675-6665 |
| dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/0228531403374909 |
| dc.contributor.referee3.fl_str_mv |
Cury, Diego Pulzatto |
| dc.contributor.referee3ID.fl_str_mv |
https://orcid.org/0000-0002-8571-7144 |
| dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/1524485838237057 |
| dc.contributor.referee4.fl_str_mv |
Prates, Renato Araujo |
| dc.contributor.referee4ID.fl_str_mv |
https://orcid.org/0000-0002-8115-9237 |
| dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/7664790931310514 |
| dc.contributor.referee5.fl_str_mv |
Ramos, Henrique Roman |
| dc.contributor.referee5ID.fl_str_mv |
https://orcid.org/0000-0002-4327-842X |
| dc.contributor.referee5Lattes.fl_str_mv |
http://lattes.cnpq.br/1842119906977271 |
| dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2258319861959044 |
| dc.contributor.author.fl_str_mv |
Romano Neto, Orlando |
| contributor_str_mv |
Marcos, Rodrigo Lab Marcos, Rodrigo Labat Cecatto, Rebeca Boltes Cury, Diego Pulzatto Prates, Renato Araujo Ramos, Henrique Roman |
| dc.subject.por.fl_str_mv |
fotobiomodulação artrite reumatoide cartilagem colágeno propriedades mecânicas |
| topic |
fotobiomodulação artrite reumatoide cartilagem colágeno propriedades mecânicas photobiomodulation rheumatoid arthritis cartilage collagen mechanical properties CIENCIAS DA SAUDE |
| dc.subject.eng.fl_str_mv |
photobiomodulation rheumatoid arthritis cartilage collagen mechanical properties |
| dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE |
| description |
Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, and progressive disease that causes irreversible joint damage. The conventional treatment is pharmacological, typically involving anti-inflammatory drugs, though these are often associated with adverse effects. Photobiomodulation therapy (PBM) has been linked to the modulation of inflammation and pain and represents a potential therapeutic alternative for RA. This study aimed to evaluate the effects of PBM on pain modulation—through mechanical allodynia—tissue repair, assessed by collagen proportion, and functional recovery, evaluated via biomechanical analysis of cartilage, in an experimental model of RA induced in rats. Methodology: Male Wistar rats were divided into five groups: healthy controls without RA (CTL), RA-induced without treatment (NT), RA treated with PBM applied locally to the knee (PBM), RA treated with dexamethasone (DEX), and RA treated with a combination of PBM and dexamethasone (PBM+DEX). RA was induced using injections of type II collagen and Freund’s adjuvant. Treatments were administered three times per week for one month: PBM (808 nm; 4 J; 100 mW) applied locally or intraperitoneal dexamethasone. Mechanical allodynia was assessed weekly. At the end of the treatment, animals were euthanized, and cartilage was harvested for biomechanical and histological analyses. Results: All RA groups showed a significant reduction in resistance and deformation capacity compared to the CTL group (p < 0.001). Only the PBM group exhibited a significant improvement in deformation capacity compared to the NT group. All treated groups showed an increased proportion of total collagen compared to the NT group (p < 0.05). The PBM group was the only one to show consistent improvement in mechanical allodynia across all time points compared to the other RA groups (p < 0.01). Conclusion: Local PBM irradiation promotes the maintenance of collagen proportion and improves the tissue’s deformation capacity. While combined PBM+DEX therapy maintained the collagen proportion, it did not provide additional benefits regarding mechanical properties or pain sensitivity as assessed by the mechanical allodynia test. |
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2025 |
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2025-09-01T15:25:05Z |
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2025-06-26 |
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info:eu-repo/semantics/publishedVersion |
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Romano Neto, Orlando. Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide. 2025. 62 f. Tese( Programa de Pós-Graduação em Medicina – Biofotônica) - Universidade Nove de Julho, São Paulo. |
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http://bibliotecatede.uninove.br/handle/tede/3784 |
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Romano Neto, Orlando. Efeito da fotobiomodulação associada ao uso de dexametasona na sensibilidade e resistência mecânica da cartilagem do joelho, em modelo experimental de artrite reumatoide. 2025. 62 f. Tese( Programa de Pós-Graduação em Medicina – Biofotônica) - Universidade Nove de Julho, São Paulo. |
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Biblioteca Digital de Teses e Dissertações da Uninove - Universidade Nove de Julho (UNINOVE) |
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