Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2018-03-15T18:13:31Z No. of bitstreams: 1 MARIANA_KLEIN_DIS.pdf: 2818382 bytes, checksum: 8bd8dc12dea147fdea294b9c63661941 (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-03-28T11:55:01Z (GMT) No. of bitstreams: 1 MARIANA_KLEIN_DIS.pdf: 2818382 bytes, checksum: 8bd8dc12dea147fdea294b9c63661941 (MD5) / Made available in DSpace on 2018-03-28T11:59:45Z (GMT). No. of bitstreams: 1 MARIANA_KLEIN_DIS.pdf: 2818382 bytes, checksum: 8bd8dc12dea147fdea294b9c63661941 (MD5) Previous issue date: 2018-01-22 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Ulcerative lesions are some of the most common injuries of the oral mucosa. Damage to the epithelial barrier results in discomfort, which may interfere with oral hygiene, chewing, swallowing and speech. The management of these lesions basically aims to optimize and accelerate tissue repair, in addition to reducing its symptomatology. However, there is no option considered gold standard for the treatment of traumatic mouth ulcers. Cannabidiol (CBD) is the main non-psychomimetic component of Cannabis sativa. It exerts potent antiinflammatory, antioxidant and analgesic effects when tested in various pathological conditions. The present dissertation is structured in the form of 2 scientific papers. The first article consists of a literature review to evaluate the different mechanisms of action of CBD that may be involved in the repair of ulcerative lesions, suggesting that this drug is promising for the treatment of oral inflammatory disorders. The second article is a report of an experimental study conducted in an animal model, to assess the effect of 5 and 10 mg/kg CBD on the repair of an ulcerative lesion induced on the ventral tongue of 60 Wistar rats after 3 and 7 days. Treatment with CBD decreased inflammatory scores after 3 days (p < 0.05), but was unable to clinically influence the size of ulcerative lesions. Thus, it is concluded that CBD has an inflammation modulating effect and may represent a promising alternative in the management of oral wounds. / As les?es ulceradas correspondem ?s enfermidades mais frequentes da mucosa bucal. O dano ? barreira epitelial resulta em desconforto, podendo interferir na higiene oral, mastiga??o, degluti??o e fala. O manejo dessas les?es objetiva basicamente otimizar e acelerar o reparo tecidual, al?m de diminuir a sintomatologia dolorosa. No entanto, n?o est? dispon?vel atualmente uma alternativa considerada o padr?o-ouro para o tratamento das ?lceras traum?ticas bucais. O canabidiol (CBD) ? o principal componente n?o-psicomim?tico da Cannabis sativa e desempenha potentes efeitos anti-inflamat?rios, antioxidantes e analg?sicos em diversas condi??es patol?gicas. A presente disserta??o est? estruturada na forma de 2 artigos cient?ficos. O primeiro consiste em uma revis?o de literatura, cujo objetivo foi avaliar os diferentes mecanismos de a??o do CBD que possam estar envolvidos no reparo de les?es ulceradas traum?ticas, sugerindo o car?ter promissor desta droga na terapia de dist?rbios inflamat?rios orais. O segundo trata de um estudo experimental desenvolvido em modelo animal, com objetivo de avaliar cl?nica e histologicamente o efeito da administra??o intraperitoneal do CBD, nas doses de 5 e 10 mg/kg, por 3 e 7 dias, no reparo de les?o ulcerada induzida no ventre lingual de 60 ratos Wistar. O tratamento com CBD foi capaz de diminuir os escores inflamat?rios das les?es ap?s 3 dias (p < 0,05), contudo n?o foi suficiente para interferir no tempo de cicatriza??o das ?lceras. Dessa forma, concluiu-se que o CBD ? capaz de modular o processo inflamat?rio em les?es ulceradas orais, podendo representar uma alternativa promissora no manejo dessa condi??o.

Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2018-06-27T15:29:59Z No. of bitstreams: 1 JULIANE_DE_QUADROS_DE_BORTOLLI_DIS.pdf: 1560215 bytes, checksum: 631d814b124322abfc0f1aaf6c260aa3 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-07-04T13:31:02Z (GMT) No. of bitstreams: 1 JULIANE_DE_QUADROS_DE_BORTOLLI_DIS.pdf: 1560215 bytes, checksum: 631d814b124322abfc0f1aaf6c260aa3 (MD5) / Made available in DSpace on 2018-07-04T13:41:52Z (GMT). No. of bitstreams: 1 JULIANE_DE_QUADROS_DE_BORTOLLI_DIS.pdf: 1560215 bytes, checksum: 631d814b124322abfc0f1aaf6c260aa3 (MD5) Previous issue date: 2018-03-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The oral mucosa is a frequent site for traumatic ulcers, which can be caused by mechanical or chemical agents. There is no a gold standard treatment for the management of these lesions, which can be painful and have a negative impact on quality of life. Although studies suggest the use of chamomile and curcumin in the treatment of ulcerated lesions of the oral mucosa, there is no a consensus as to its efficacy in the management of these lesions. The literature has shown that both phytotherapics modulate the levels of inflammatory cytokines such as TNF-? and IL-1?. Therefore, in the first article of this dissertation, an integrative literature review was conducted investigating the efficacy of topical interventions with chamomile and curcumin in the management of pain and in the healing of ulcerated lesions of the oral mucosa. Few controlled clinical trials have been found and they suggest a beneficial effect of chamomile and curcumin in the healing process and in the reduction of symptoms in patients with oral mucositis, recurrent aphthous ulceration and oral lichen planus. Studies in animal demonstrated a reduction in the inflammatory wound healing phase, increased deposition of collagen fibers and epithelization. The second article of this dissertation presents an experimental study, which was carried out to evaluate the effect of the 10% chamomile extract and 2% curcumin in the repair of traumatic ulcers on tongue of rats. Thirty-nine Wistar rats were divided into three groups: control, chamomile extract and curcumin. A 5-mm-diameter excisional wound was made in the center of ventral tongue. The substances were applied as a gel twice daily for five days. The animals were euthanized 7 days after the lesions were made. In the macroscopic evaluation, there was no significant difference among chamomile, curcumin and control groups regarding to area of residual ulcer (P= 0.20). Histological analysis also showed no difference among the groups regarding newly formed epithelium area (P=0.97) or intensity of inflammatory infiltrate (P=0.72). Considering the experimental model, the findings of the present study showed that 10% chamomile extract and 2% curcumin did not accelerate the repair of traumatic oral ulcers or reduced the intensity of the inflammatory infiltrate, contradicting previous findings in the literature. / A mucosa bucal ? um s?tio frequente para a ocorr?ncia de ?lceras traum?ticas, as quais podem ser causadas por agentes mec?nicos ou qu?micos. At? o momento, n?o existe um tratamento padr?o-ouro para o manejo dessas les?es, as quais podem ser dolorosas e ter impacto negativo na qualidade de vida dos pacientes. Apesar de estudos sugerirem a utiliza??o da camomila e da curcumina no tratamento de les?es ulceradas da mucosa bucal, n?o h? consenso sobre a sua efic?cia no manejo dessas les?es. A literatura tem demonstrado que ambos os fitoter?picos modulam os n?veis de citocinas pr?-inflamat?rias como TNF-? e IL-1?. No primeiro artigo desta disserta??o foi realizada uma revis?o integrativa da literatura investigando a efic?cia das interven??es t?picas com camomila e curcumina no manejo da dor e na cicatriza??o de les?es ulceradas da mucosa bucal. Poucos ensaios cl?nicos controlados foram encontrados e estes sugerem um efeito ben?fico da camomila e da curcumina no processo cicatricial e na redu??o da sintomatologia em pacientes com mucosite oral, ulcera??o aftosa recorrente e l?quen plano oral. Estudos em modelos animais investigando os efeitos desses fitoter?picos em ?lceras traum?ticas bucais demonstraram redu??o da fase inflamat?ria do processo de cicatriza??o, maior deposi??o de fibras col?genas e epiteliza??o. O segundo artigo desta disserta??o apresenta um estudo experimental, que foi realizado com o objetivo de avaliar o efeito do extrato de camomila 10% e curcumina 2% no reparo de ?lceras traum?ticas em l?ngua de ratos. Trinta e nove ratos Wistar foram distribu?dos em tr?s grupos: controle, extrato de camomila e curcumina. Uma ?lcera de 5 mm de di?metro foi confeccionada no ventre lingual de cada animal. As subst?ncias foram aplicadas na forma de gel, duas vezes ao dia, durante cinco dias. Os animais foram eutanasiados sete dias ap?s a confec??o das les?es. Na avalia??o macrosc?pica, n?o houve diferen?a entre os grupos camomila, curcumina e controle quanto ? ?rea de ?lcera remanescente (P=0.20). A an?lise histol?gica tamb?m n?o demonstrou diferen?a entre os grupos quanto ? ?rea de tecido epitelial neoformado (P=0.97) ou intensidade do infiltrado inflamat?rio (P=0.72). Considerando o modelo experimental empregado, os achados do presente estudo demonstraram que extrato de camomila 10% e a curcumina 2% n?o aceleraram o reparo de ?lceras mecanicamente induzidas na mucosa bucal nem reduziram a intensidade do infiltrado inflamat?rio, contrariando achados pr?vios na literatura.