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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Efeito do Imiquimode na CicatrizaÃÃo de Queimadura em Ratos / Efeitos do imiquimode na cicatrizaÃÃo de queimaduras em ratos

Charles Jean Gomes de Mesquita 07 April 2008 (has links)
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Queimaduras podem causar substancial morbidade e contraturas devido à hiperproliferaÃÃo fibroblÃstica. O imiquimode, imunomodulador utilizado em doenÃas virais e neoplasias cutÃneas, promove resposta imune inata e adaptativa, interagindo com Toll-Like Receptors, permitindo reconhecer antÃgenos e cÃlulas invasoras, ativando cÃlulas de Langerhans e citocinas endÃgenas capazes de suprimir a hiperproliferaÃÃo fibroblÃstica, mostrando-se Ãtil no tratamento de cicatrizes hipertrÃficas e quelÃides. Inexistiam trabalhos sobre o imiquimode em queimaduras cutÃneas. Avaliou-se os efeitos do imiquimode na cicatrizaÃÃo de queimaduras utilizando-se mÃtodos macroscÃpicos, microscÃpicos e computacionais. Produziram-se queimaduras dÃrmicas profundas de cada lado da linha mÃdia dorsal em 32 ratos Wistar utilizando um ferro-de-solda modificado aplicado a pele por 9s. Instituiram-se tratamentos 3X/semana a partir do segundo dia pÃs-queimadura (D2PQ). No lado direito (controle) utilizou-se soluÃÃo salina isotÃnica (SAL). à esquerda utilizou-se imiquimode (IMQ) tÃpico 5%. Oito animais foram eutanasiados nos D4, D7, D14 e D21PQ, obtendo-se fotografias digitais e amostras teciduais. Na anÃlise macroscÃpica utilizou-se escala visual analÃgica (EVA), escala de exame clÃnico (EEC) e planimetria digital. Para anÃlises microscÃpicas utilizaram-se amostras coradas pela hematoxilina-eosina (HE) ou picrosirius-red (PR). Nas amostras HE, sob microscopia Ãtica, quantificou-se o tipo e a intensidade da reaÃÃo inflamatÃria e a involuÃÃo temporal do dano tecidual pela atribuiÃÃo de escores. Amostras PR foram analisadas à microscopia de luz polarizada, quantificando-se a densidade do colÃgeno tipo I e tipo III e razÃo colÃgeno I: colÃgeno III (RazÃo I:III). NÃo houve mortes, infecÃÃo nem autocanibalismo. Os parÃmetros biomÃtricos nÃo evidenciaram efeitos deletÃrios sobre o estado nutricional. A EVA favoreceu discretamente o grupo SAL (P=0,0491). A EEC nÃo mostrou diferenÃas significativas. A planimetria digital evidenciou menor velocidade de reparaÃÃo nas feridas do grupo IMQ (P<0,05). A quantificaÃÃo da Ãrea de lesÃo mostrou involuÃÃo similar, exceto no D14PQ onde a Ãrea de necrose era maior no grupo IMQ (P<0,05). A anÃlise histolÃgica qualitativa mostrou um processo reparatÃrio mais lentificado no grupo IMQ em todos os tempos. No D7PQ, a intensidade da reaÃÃo inflamatÃria foi classificada como discreta em 50% das feridas do grupo SAL e intensa ou moderada em 75% do grupo IMQ (P<0,005). No D21PQ a inflamaÃÃo foi mais extensa no grupo IMQ (P<0,005). Observou-se que 50% das feridas do grupo SAL exibiam reaÃÃo inflamatÃria subaguda e 37,5% crÃnica, enquanto nenhuma ferida do grupo IMQ mostrava inflamaÃÃo crÃnica no D7PQ (P<0,005). No D21PQ a inflamaÃÃo no grupo IMQ era subaguda (68,75%) e no grupo SAL 56,25% era crÃnica (P<0,05). A morfometria do colÃgeno evidenciou aumento do colÃgeno tipo I e diminuiÃÃo do colÃgeno tipo III nos dois grupos. A razÃo colÃgeno I: colÃgeno III foi menor no grupo IMQ em D4 e D21PQ (P<0,05). O modelo reproduziu queimaduras dÃrmicas, preservando anexos essenciais à reepitelizaÃÃo. A picrossirius-polarizaÃÃo foi eficaz no reconhecimento do colÃgeno e os mÃtodos computacionais foram eficientes, identificando diferenÃas mÃnimas no processo lesÃo-reparaÃÃo. O imiquimode foi eficaz em promover o processo inflamatÃrio e retardar a maturaÃÃo, gerando menor quantidade de fibrose / Burns can result in substantial morbidity because of fibroblastic hyperproliferation and contracture. Imiquimod is a immunomodifier -TLR-7 agonist used in viral diseases and in neoplastic conditions like actinic keratosis, melanoma, and non-melanoma skin cancer. It acts by promoting endogenous cytokines known to suppress fibroblast proliferation. A new recent use is in treating keloids and hypertrophic scars to reduce scarring. No study of the effect of imiquimod on cutaneous burns has been performed. This study examined burn healing in the presence of topical imiquimod by evaluation of wound appearance, computer-aided image analysis, and histology in a rat model. Standardized partial-thickness burns were produced on the dorsum of thirty-two Wistar rats. Right-sided wounds received therapy with isotonic saline (sham). Left-sided wounds were treated with imiquimod cream at 5% (IMQ). This was repeated 3 times/week after injury. Euthanasia was performed at 4th, 7th, 14th and 21st Postburn days (PBD). Wounds were harvested for histological analysis. Evaluation of wound appearance was performed using clinical assessment scale (CAS) and a visual analogue scale (VAS). Scars area and perimeter were measured using digital planimetry to assess wound edge migration by Gilmanâs modified Equation. Inflammation type and intensity was graded by histological scale. Collagen type was identified by picrosirius-polarization and morphometric analysis was performed. VAS scores showed discretally improved appearance in the imiquimod-treated wounds versus the saline-treated control at PBD21 (P=0.0491). There was no difference in CAS scores. Wound edge migration was significantly slowest in imiquimod-treated wounds (p<0.05). Histological evidence of partial thickness dermal injury with sparing of dermal appendage epithelial cells was seen in all wounds. Histologic characteristics of gradually diminished injured area between groups were similar except in imiquimod-treated wounds at PBD14 (p<0.05). Inflamattory state was bigger in imiquimod-treated wounds at PBD7 and PBD21 (p<0.005). At PBD7 there was no chronic-type of inflammatory reaction in imiquimod-treated group, although in saline-treated group chronic plus sub-acute type was present in 87.5% (p<0.005). At PBD21 68.75% of imiquimod-treated group showed acute plus subacute inflammatory state, and saline-treated group displayed chronic-type in 56.25% of the wounds. The total amount of collagen increased in both groups throughout all time points. Morphometry showed an inversed ratio type I to type III collagen. Ratios of type I collagen to type III collagen was much lower in imiquimod-treated wounds at PBD4 and PBD21. Topical treatment with Imiquimod 5% cream for partial-thickness burn wounds 3 times/week courses do not improve clinical appearance and scarring during late healing. There is no difference in histology during the short-term healing process. Computer-aided image proccessing was efficient to evaluate burned-wound healing. Wound healing and fibrosis was impaired in imiquimod- treated wound group

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