Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. Inst., 2002. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Southern California, 1999. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.Med.Sc.)--University of Hong Kong, 2004. / Also available in print.

Thesis (Ph. D.)--University of Southern California, 1999. / Includes bibliographical references.

Submitted by Aline Cardoso Pereira (aline.cardosopereira@hotmail.com) on 2018-08-02T22:27:37Z No. of bitstreams: 1 DISSERTAÇÃO DE MESTRADO - ALINE C. PEREIRA.pdf: 2161021 bytes, checksum: 07880c29666b475277e0461208a4bf5a (MD5) / Approved for entry into archive by Isabel Pereira de Matos (isabel@fmva.unesp.br) on 2018-08-03T18:51:33Z (GMT) No. of bitstreams: 1 pereira_ac_me_araca_int.pdf: 2161021 bytes, checksum: 07880c29666b475277e0461208a4bf5a (MD5) / Made available in DSpace on 2018-08-03T18:51:33Z (GMT). No. of bitstreams: 1 pereira_ac_me_araca_int.pdf: 2161021 bytes, checksum: 07880c29666b475277e0461208a4bf5a (MD5) Previous issue date: 2018-06-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / As ceratites ulcerativas são comuns na rotina do médico veterinário de pequenos animais, visto que a córnea é uma estrutura vulnerável devido sua exposição ao meio externo. Por compreender uma das estruturas responsáveis pela refração luminosa e participante do mecanismo de formação da imagem, é de extrema importância a integridade da anatomia e transparência da córnea para esta continuar desempenhando suas funções. Estudos ainda são realizados com o intuito de viabilizar opções terapêuticas cirúrgicas para o tratamento de úlceras de córnea complicadas, tentando alcançar uma cicatrização com um menor dano à estrutura corneal e menor opacidade cicatricial, devolvendo a transparência da córnea. Visto que os polímeros biodegradáveis tem se mostrado alvo de pesquisas atuais para aplicações médicas, com este estudo objetivou-se avaliar originalmente a biocompatibilidade da membrana do polímero poli(butileno adipato-co-tereftalato) (PBAT) na córnea e posterior aplicação clínica deste material nas ceratites ulcerativas profundas. Para tal, foi realizada avaliação clínica experimental e histopatológica após enxertia interlamelar do PBAT em córnea de coelhos, ao longo de 60 dias, e acompanhamento da evolução clínica do emprego da membrana de PBAT no tratamento de ceratites ulcerativas complicadas em cães, comparando ao uso do enxerto conjuntival, ao longo de 90 dias. Devido aos baixos sinais de inflamação corneal clínicos e histopatológicos nos coelhos e a cicatrização corneal em todos os cães, sem ocorrência de déficit visual, com o presente estudo acreditamos ter viabilizado mais uma opção terapêutica para as ceratites ulcerativas na medicina veterinária. / Ulcerative keratitis are common in the routine of a small animals veterinary doctor, given that the cornea is a vulnerable structure due to its exposure to external environment. For containing one of the structures responsible for light refraction and participant in the mechanism of formation of images, it is of extreme importance the integrity and transparency of the cornea in order for it to continue to develop its functions. Studies are still performed with the intent of making feasible surgical therapeutic options for the treatment of complicated corneal ulcers, trying to reach cicatrization with less damage to the corneal structure and less scar opacity, seeking corneal transparency. Given that biodegradable polymers have been target of current research for medical applications, the objective of this study was to evaluate originally the biocompatibility of the poly (butylene adipate-co-terephthalate) polymer (PBAT) in the cornea and posterior clinical application of this material in deep ulcerative keratitis. It was performed clinical and histopathological evaluation after interlamellar grafting of PBAT in the cornea of rabbits, over 60 days, and follow-up of the clinical evolution of PBAT membrane in the treatment of complicated ulcerative keratitis in dogs, comparing to the use of conjunctival graft, over 90 days. Due to low levels of clinical and histopathological corneal inflammation found in rabbits and corneal cicatrization in all dogs, without occurence of visual deficit, with this study we believe it was made feasible another therapeutic option for ulcerative keratitis in veterinary medicine.

Ulcerative colitis (UC), a subset of inflammatory bowel disease (IBD), is a chronic uncontrolled inflammatory condition of the intestinal mucosa. As its etiology remains unclear, no specific effective treatment is available. Therefore, development of novel strategies for IBD treatment remains a major medical need. Qing-dai Powder (QDP), an ancient herbal medicinal formula, exerted potent therapeutic effect on intractable UC patients; however, evidence-based support is needed. The aims of this study are: i) to delineate the anti-colitis effect of QDP and its underlying mechanisms in murine colitis; 2) to explore the rationality of QDP formula; 3) to investigate the anti-colitis effects of major component(s) or/and active ingredient(s) of QDP and their underlying mechanisms in murine colitis. In the present study, the therapeutic effect of QDP on UC was investigated on dextran sulfate sodium (DSS)-induced acute murine colitis. Results showed that i) QDP dose-dependently attenuated disease activity index (DAI), colon shortening, histological damage and colonic myeloperoxidase (MPO) activity of DSS-treated mice; ii) QDP significantly decreased the infiltration of immune cells, particularly macrophages and CD4+ T cells, colonic levels of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, and plasma level of chemokine MCP-1. In RAW 264.7 cells, QDP significantly suppressed lipopolysaccharide (LPS)-induced the production of TNF-α and IL-6, and the expression levels of COX-2 and iNOS via inhibiting IкB-α degradation and p65 nuclear translocation; Also, in primary CD4+ T cells, QDP significantly suppressed the differentiation of Th1 and Th17 cells. These findings indicate that the anti-colitis effects of QDP might be associated with inhibition of inflammatory responses of colonic macrophages and CD4+ T cells. QDP is composed of Qing-dai and Ku-fan. The comparative study of anti-colitis of QDP, Qing-dai and Ku-fan revealed that QDP is a reasonable TCM formula, and Qing-dai is mainly responsible for the anti-colitis effect of QDP and Ku-fan exhibits a weak beneficial effect. Mechanistically, it was found that Qing-dai significantly suppressed Th1 and Th17 responses, characterized as i) suppressing mRNA expression of Th1 cytokine IFN-γ and Th17 cytokine IL-17A, inhibiting the production of Th1 and Th17-related cytokines IFN-γ, IL-17A/F and TNF-α in the colon of DSS-treated mice; ii) restraining the proportions of Th1 and Th17 cells in mesenteric lymph nodes of DSS-treated mice; iii) suppressing the differentiation of Th1 and Th17 cells in vitro. Indirubin is the principle active component of Qing-dai. It was found that indirubin significantly suppressed the generation of Th17 cells in DSS-treated mice, evidenced by i) suppressing the mRNA expression of IFN-γ, IL-17A, and RORγt, and inhibiting the production of IL-17A/F, TNF-α, IL-1β and IL-6 in the colon of DSS-treated mice; ii) reducing Th17 cells in mesenteric lymph nodes of DSS-treated mice through reducing GSK-3β activity and p-STAT3 expression; iii) suppressing the differentiation of Th17 cells through down-regulating the expression of GSK-3β and p-STAT3 in vitro. In summary, the present study provides evidence-based support for the clinical use of QDP in the management of UC, and indicates that indirubin is the main active compound of QDP responsible for its anti-colitis effect.

Orientador: Luiz Claudio Di Stasi / Banca: Célia Akiko Hiruma / Banca: Claudia Helena Pellizzon / Banca: Alessandra Gambero / Banca: Marcelo Aparecido da Silva / Resumo: As cumarinas representam uma importante classe de compostos fenólicos com inúmeras propriedades farmacológicas que incluem inibição da peroxidação lipídica, da geração de ânion superóxido dependente de neutrófilos, da citotoxicidade induzida por hidroperóxido de ácido linoleíco, da atividade de lipooxigenases e ciclooxigenases, além de agirem como agentes imunossupressores e antiinflamatórios. Todas estas propriedades são essenciais para que um produto seja potencialmente ativo para o tratamento das doenças inflamatórias intestinais (DII). A sulfassalazina (primeira opção terapêutica no tratamento das DII) possui vários efeitos colaterais, especialmente quando usada em altas doses ou em períodos longos de tratamento. O objetivo do presente trabalho foi avaliar se cumarina e 4-hidroxi-cumarina possuem efeitos preventivos e/ou curativos no modelo de colite induzida por ácido trinitrobenzenosulfônico (TNBS) em ratos e também se as associações de cumarina ou 4-hidroxi-cumarina com doses menores de sulfassalazina produzem efeitos antiinflamatórios com menor incidência de efeitos colaterais decorrentes da administração da sulfassalazina. Além disso, foram feitos estudos complementares para verificar se tais cumarinas modulam a produção de citocinas próinflamatórias em cultivos celulares in vitro e ex vivo. Este estudo testou a atividade antiinflamatória dos compostos-testes cumarina (2,5 a 50mg/Kg) e 4-hidroxicumarina (5 a 50mg/Kg) e das associações de cumarina com a sulfassalazina (C5+S5; C5+S15 e C5+S25) ou da 4-hidroxi-cumarina com a sulfassalazina (4-OHC25+S5, 4-OHC25+S15 e 4-OHC25+S25) em duas condições experimentais distintas: quando a mucosa colônica está intacta (efeito preventivo); quando a mucosa colônica está afetada por um processo inflamatório intestinal (efeito curativo) assim como preventivo da recidiva do processo inflamatório ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Coumarins comprise an important class of phenolic compounds with many pharmacological properties that includes inhibition of membrane lipid peroxidation, inhibition on neutrophil-dependent superoxide anion generation, inhibition on the linoleic acid hydroperoxide-induced cytotoxicity, and inhibition on cyclooxygenase and lipoxygenase activities, which could result in antiinflammatory and immunosuppressant effect. Those are some desired features for a candidate compound in the treatment of inflammatory bowel diseases (IBD). On the other hand, the IBD are life persisting diseases with unpredictable episodic reactivations and difficult treatment in severe cases. Sulfasalazine, the first choice drug in the treatment of mild to moderately active IBD cases, presents serious side effects when used in high doses or in long-term treatment. Thus, the aim of this study was to evaluate the effects of coumarin and 4-hydroxy-coumarin in rat experimental intestinal inflammation. Additionally, we evaluated the possibility of coumarins association to sulfasalazine in rat intestinal inflammatory conditions. For this purpose, the antiinflammatory activity of test compounds, coumarin (2.5 to 50mg/kg) and 4-hydroxy-coumarin (5 to 50mg/kg) and associations of coumarin with sulfasalazine (C5 plus S5, C5 plus S15, C5 plus S25) or 4-hydroxy-coumarin with sulfasalazine (4-OHC25 plus S5, 4-OHC25 plus S15 and 4-OHC25 plus S25) were tested in the model of trinitrobenzenesulphonic acid (TNBS) induced rat colitis in two different experimental conditions: when the colonic mucosa is intact (preventive effect), and when a previous inflammatory damage is caused to the colonic mucosa (curative effect), additionally to a reactivation of the inflammatory process (relapse prevention). The colonic damage was evaluated macroscopically, histologically and biochemically. For cell cultures evaluation of cytokine ... (Complete abstract click electronic access below) / Doutor

Made available in DSpace on 2014-06-11T19:30:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-20Bitstream added on 2014-06-13T18:40:04Z : No. of bitstreams: 1 perches_cs_me_botfmvz_parcial.pdf: 57363 bytes, checksum: 7194bc6e69ce3bcd9c7d95014e54cd86 (MD5) Bitstreams deleted on 2015-06-25T13:01:27Z: perches_cs_me_botfmvz_parcial.pdf,. Added 1 bitstream(s) on 2015-06-25T13:03:36Z : No. of bitstreams: 1 000692053_20160720.pdf: 57206 bytes, checksum: d761ff391f9b209a38f7349c5ee3c1f1 (MD5) Bitstreams deleted on 2016-07-25T13:17:34Z: 000692053_20160720.pdf,. Added 1 bitstream(s) on 2016-07-25T13:18:43Z : No. of bitstreams: 1 000692053.pdf: 7043915 bytes, checksum: fa994284baa896bbc842afa959d5378b (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo do presente estudo foi avaliar e comparar por meio de exames oftalmológicos, histopatológicos e imuno-histoquímica para PCNA, o processo de reparação corneal de úlceras superficiais induzidas em coelhos, frente à utilização de colírios de óleo essencial de Citrus lemon, produto até então não utilizado em oftalmologia. Foram utilizadas 50 fêmeas da espécie leporina, todas submetidas à indução da úlcera superficial, constituindo-se 5 grupos experimentais de 10 animais cada. Em três grupos foram instilados colírios à base de óleo essencial de Citrus lemon, em diferentes concentrações, sendo 1,5% (GL1,5), 3% (GL3) e 5% (GL5). O grupo controle (GC) recebeu substituto da lágrima, e o grupo Tween 80 8% (GT) foi tratado com o diluente utilizado na produção dos colírios de citrus. Todos os protocolos foram realizados quatro vezes ao dia. Os grupos foram divididos, aleatoriamente, em dois subgrupos, de acordo com o período final de avaliação, sendo M1, coelhos avaliados após 24 horas, e M5, após 5 dias. Não houve diferença entre os tratamentos utilizados quanto aos sinais clínicos secreção ocular, hiperemia conjuntival, quemose e opacidade corneal. O grupo tratado com colírio de óleo essencial de Citrus lemon na concentração 1,5%, no período final de avaliação, apresentou maior sensibilidade ocular em relação ao GC, além de aumento da celularidade corneal, representada principalmente por células inflamatórias. Nas comparações entre os momentos iniciais e finais, os grupos tratados com substituto da lágrima, Tween 80 8% e colírio à base de óleo essencial de Citrus lemon 5% promoveram aumento na espessura epitelial na periferia da córnea e maior percentual de proliferação celular, na avaliação final. Quanto à úlcera de córnea, houve redução significativa da extensão total para leve... / The purpose of this study was to evaluate and compare through ophthalmic exams, histopathology and immunohistochemistry for PCNA, the repair process in superficial corneal ulcers induced in rabbits using eyedrops of Citrus lemon essential oil, a product not used in ophthalmology yet. Fifty female rabbits were submitted to induction of the corneal ulcer and then divided into 5 experimental groups of 10 animals each. Were instilled into three groups eyedrops of Citrus lemon essential oil, in different concentrations, being 1.5% (GL1, 5), 3% (GL3) and 5% (GL5). The control group (CG) received a tear substitute, and the Tween 80 8% group (GT) was treated with the diluent used in the production of eyedrops of citrus. All protocols were performed four times a day. The groups were divided randomly into two subgroups, according to the final period of evaluation, in the M1 rabbits were evaluated after 24 hours, and in the M5 after 5 days. There was no difference between treatments for clinical signs: ocular discharge, conjunctival hyperemia, chemosis and corneal opacity. In the final period of evaluation, the group treated with eyedrops of Citrus lemon essential oil in the concentration 1.5% showed a higher ocular sensitivity compared to the GC, and increased of corneal cellularity, represented mainly by inflammatory cells. In the comparison between the initial and final moments, the groups treated with tear substitute, Tween 80 8% and eyedrops of Citrus lemon essential oil 5% led to an increase in epithelial thickness at the periphery of the cornea and a higher percentage of cell proliferation, in the final evaluation. In the clinical evaluation of corneal ulcer, there was significant reduction in total length for mild or absent at the time of final evaluation in all groups; the exception was GL 3%, that showed a lower... (Complete abstract click electronic access below)

nÃo hà / Muitas pesquisas evidenciaram o comprometimento do sistema nervoso perifÃrico na doenÃa inflamatÃria intestinal (DII). AtravÃs do teste de quantificaÃÃo sensitiva (QST) para pesquisa de limiares de sensibilidade a vibraÃÃo ( fibras nervosas grossas) e frio (fibras nervosas finas), (protocolo I) avaliamos 29 pacientes portadores de retocolite ulcerativa (RCU), 30 pacientes portadores de doenÃa de Crohn (DC) e 28 pacientes-controle. Foram aplicados questionÃrios de queixas sensitivas (protocolo II) em 27 pacientes portadores de RCU, 24 pacientes portadores de DC e 25 pacientes-controle. Esses mesmos pacientes realizaram o teste de enrugamento cutÃneo a Ãgua (TEC) (protocolo III), o qual avalia fibras finas do sistema nervoso autÃnomo. O teste de Fisher e teste de hipÃtese qui-quadrado comparando os 3 grupos (RCU, DC e Controle), utilizado na anÃlise do QST revelou maior propensÃo a neuropatia perifÃrica ou alteraÃÃo sensitiva em pacientes RCU e portadores de DII (RCU e DC) quando avaliados respectivamente sensibilidade vibratÃria e tÃrmica ao frio. Resultado de eletroneuromiografia (ENMG) foi anormal em 39,1% dos pacientes RCU e 38,4% pacientes DC. O questionÃrio de queixas sensitivas (protocolo II) revelou prevalÃncia de 51,8 % de queixas sensitivas em pacientes RCU e 50% em pacientes DC. Houve vÃrios tipos de queixas, sendo a mais comum, dormÃncia em mÃos e pÃs. TrÃs pacientes (2 RCU e 1 DC) apresentaram sintomas sugestivos da âsÃndrome das pernas inquietasâ e seis pacientes tinham relatos de tonturas (disfunÃÃo autonÃmica). Dos 14 pacientes RCU e 12 pacientes DC com queixas sensitivas, 57,1% e 25% respectivamente tinham alteraÃÃo em TEC. Dos pacientes RCU e DC que realizaram TEC (protocolo III), 48,1% e 41,7% respectivamente tinham resultado anormal, enquanto a ENMG foi anormal em 30% e 41,2% respectivamente. Podemos enfatizar que o QST e TEC parecem melhores que ENMG para diagnÃstico de alteraÃÃes sensitivas em pacientes com DII, visto que muitas destas alteraÃÃes podem corresponder a neuropatia de fibras finas. / Many studies have demonstrated the involvement of the peripheral nervous system in inflammatory bowel disease (IBD). By quantitative sensation testing (QST) to search for the vibration and cold sensitive thresholds (evaluates thick and small fibres respectively) (protocol I) we assessed 29 patients with ulcerative colitis (UC), 30 patients with Crohnâs disease (CD) and 28 control patients. Questionnaires were applied to sensory complaints (protocol II) in 27 patients with CD, 24 patients with UC and 25 control patients. The same patients underwent stimulated skin wrinkling induced by water (SSW) (protocol III), which evaluates small fibre of the autonomic nervous system. The Fisher test and hypothesis test chi-square comparing the three groups (UC, CD and control) used in analysis of QST revealed more prone to peripheral neuropathy or sensory changes in patients suffering from UC and IBD (UC and CD) when evaluated respectively vibration and cold thermal sensitivity. Results of electromyography (EMG) was abnormal in 39,1% of UC and 38,4% CD patients. The questionnaire of sensory complaints (protocol II) showed prevalence of sensory complaints in 51,8% UC and 50% CD patients. There were several types of complaints, the most common, numbness in hands and feet. Three patients (two UC and one CD) presented with symptoms suggestive of ârestless leg syndromeâ and six patients had reported dizziness (autonomic dysfunction). Of the 14 UC and 12 CD patients with sensory complaints, 57,1% and 25% respectively had change in SSW. Of UC and CD patients who underwent SSW (protoco III), 48,1% and 41,7% had abnormal results, while the EMG was abnormal in 30% and 41,2 % respectively. We emphasize that TEC and QST seem better than EMG for diagnosis of sensory changes in patients with IBD, as many of these changes may correspond to small fibre neuropathy.