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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2020.tde-20072018-102257
Document
Author
Full name
Francielle Rodrigues Guimarães
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2017
Supervisor
Committee
Frade, Marco Andrey Cipriani (President)
Leite, Saulo Nani
Guirro, Elaine Caldeira de Oliveira
Mendonça, Adriana Clemente
Parizotto, Nivaldo Antonio
Title in Portuguese
Fototerapia combinada (LED 470 e LASER 660/808 nm) no controle da infecção e no tratamento de úlceras cutâneas experimentais
Keywords in Portuguese
Cicatrização
Estudo pré-clínico
Fototerapia
Infecção
Úlceras cutâneas
Abstract in Portuguese
A cicatrização cutânea é um processo fisiológico complexo e dinâmico. Infecções podem causar desequilíbrio neste processo, tornando-o crônico, aumentando as chances de óbitos, amputações ou prejudicando a qualidade de vida dos pacientes. Buscou-se avaliar a eficácia e segurança da fototerapia combinada (LED 470 e LASER 660/808nm) no controle da infecção e no tratamento de úlceras cutâneas experimentais. Foi realizado levantamento epidemiológico e microbiológico dos pacientes com úlceras cutâneas atendidos no Ambulatório de Úlceras Neurovasculares do Hospital das Clínicas de Ribeirão Preto-FMRP-USP (ADUN do HC da FMRP-USP) nos últimos 5 anos. No modelo in vitro, foram avaliadas a atividade antimicrobiana, a citotoxicidade e a atividade cicatrizante da fototerapia. No modelo in vivo, foram avaliados o índice de cicatrização das úlceras (ICU), o processo inflamatório e a fibrogênese durante o reparo tecidual. Por fim, a aplicação clínica foi avaliada por um estudo de caso. Os pacientes atendidos no ADUN apresentavam idades variando de 40 e 59 anos, cuja origem do estado de São Paulo em 95% e mais da metade residiam em outros municípios. As úlceras apresentavam simultaneamente bactérias Gram positivas e negativas em 56,75%, além de infecções multibacterianas resistentes. As bactérias mais frequentes foram S. aureus, P. aeruginosa e E.coli, respectivamente. A fototerapia por LED azul e combinada demonstraram intensa atividade antimicrobiana in vitro. A fototerapia por LED azul e combinada possuem citotoxicidade proporcional à dose para células da pele. A fototerapia, em especial a fototerapia combinada, demonstrou potencial para acelerar cicatrização nos modelos in vitro e in vivo. No modelo experimental, a fototerapia combinada demonstrou melhor controle do processo inflamatório; maior angiogênese, fibrogênese e matriz extracelular; além de favorecer a maturação do colágeno durante o reparo tecidual. A fototerapia combinada acelerou o processo de cicatrização das úlceras cutâneas do paciente com hanseníase virchowiana com Fenômeno de Lúcio, contribuindo para o controle da infecção nas úlceras e para o sucesso da enxertia, sem toxicidade e/ou outros efeito colaterais observados. Além disso, paciente relatou diminuição importante da dor ao movimento e do desconforto ao leito. Diante dos resultados, a fototerapia combinada (LED 470 e LASER 660/808nm) demonstrou-se segura, eficaz, não invasiva e indolor, com significante potencial terapêutico às úlceras cutâneas crônicas e infectadas na prática clínica.
Title in English
Combined phototherapy (LED 470 and laser 660 / 808nm) in the control of infection and healing of skin ulcers
Keywords in English
Infections
Phototherapy
Preclinical
Skin ulcer
Wound healing
Abstract in English
Wound healing is a complex and dynamic physiological process. The presence of infections might disrupt this process, turning it into a chronic stage, with high risk of death or amputations, and damaging the quality of life of patients. We aimed to assess efficiency and safety of combined phototherapy (LED 470 and LASER 660/808nm) in the control of infections and in the treatment of experimental skin ulcers. Epidemiological and microbiological study of the patients with skin ulcers who attended the Ambulatory of Neurosvascular Ulcers of the Clinics Hospital in Ribeirao Preto-FMRP-USP (ADUN at HC at FMRP-USP) in the last 5 years was conducted. In vitro model tested antibacterial activity, cytotoxicity and healing activity of phototherapy. In vivo model assessed the wound healing index (WHI), inflammatory process and fibrogenesis during tissue repair. Finally, clinical testing consisted on the conduction of a case study. Patients from ADUN group were aged between 40 and 59 years of age. Ninety-five percent (95%) of them came from the state of São Paulo; while more than half of the sample lived outside the city of Ribeirão Preto. Both Granpositive and Gram-negative bacteria were observed in 56.75% of the ulcers, such as resistant multibacterial infections. The most frequent bacterias were, in order, S. aureus, P. aeruginosa and E. coli. Blue-light LED and combined phototherapy have shown high antibacterial activity in vitro. Blue-light LED and combined phototherapy have demonstrated cytotoxicity that was proportional to the dose applied on the skin cells. Phototherapy, specially when combined, had a potential to improve wound healing both in vitro and in vivo models. Combined phototherapy in the experimental model has provided better control of the inflammatory process, higher angiogenesis, fibrillogenesis and extracellular matrix, it has also favored collagen maturation during tissue repair. Combined phototherapy has increased wound healing process of skin ulcers in a patient with lepromatous leprosy and Lucio's phenomenon; it also helped controlling the infection on the ulcers and it enhanced the grafting process without toxicity or adverse effects. Patient has reported an important reduction of the pain when moving and discomfort in a lying position in bed. Then, the combined phototherapy (LED 470 and LASER 660/808nm) is safe, effective, non-invasive and painless; it has therapeutic potential in order to treat chronic and infected skin ulcers in clinical practice.
 
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Publishing Date
2020-04-29
 
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