Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Atualmente, grande parte das investigaÃÃes sÃo dirigidas para a anÃlise de mediadores da resposta imuno-inflamatÃria local e sistÃmica apÃs a agressÃo tÃrmica. A Mitomicina-C (MMC), um antibiÃtico isolado do Streptomyces caespitosus, à utilizado clinicamente para diminuir o processo de cicatrizaÃÃo de feridas, devido a sua aÃÃo antiproliferativa em fibroblastos in vitro. Produziram-se queimaduras dÃrmicas em quarenta e oito camundongos Swiss albino utilizando-se um ferro de solda modificado, aplicado à pele por nove segundos. No primeiro dia (DO) a queimadura foi submetida a tratamento tÃpico, em dose Ãnica, com SF 0,9% (controle) ou Mitomicina-C (MMC). Avaliaram-se os efeitos da MMC na cicatrizaÃÃo de queimaduras utilizando-se mÃtodos macroscÃpicos, microscÃpicos e computacionais no 4 dia (D4), 7o (D7), 14o (D14) e 21o pÃs-queimadura (D21PQ). Na anÃlise macroscÃpica, utilizou-se escala visual analÃgica (EVA), e planimetria digital; nas microscÃpicas, as amostras de pele foram coradas pela picrosirius red (PR) analisadas à microscopia de luz polarizada, quantificando-se a densidade do colÃgeno tipo I e tipo III. Os parÃmetros biomÃtricos nÃo evidenciaram efeitos deletÃrios sobre o estado nutricional dos animais. A EVA demonstrou que as feridas do grupo MMC exibiram melhor aparÃncia significativa que as do grupo controle no D14PQ com p= 0,0002. A taxa mÃdia de migraÃÃo das margens das feridas (TMM) evidenciou menor valor no grupo MMC, sendo diferenÃa bastante significativa (p =0, 0033). A morfometria do processamento de imagem assistida por computador evidenciou que o colÃgeno tipo I teve um comportamento decrescente de deposiÃÃo no grupo controle; jà no grupo tratado com MMC, foi crescente entre D4 e D14, decrescendo entre D14 e D21. Da mesma forma constatou-se uma diferenÃa significante entre os grupos no D14 e bastante significante no D21 na quantidade de colÃgeno tipo III das feridas do grupo MMC, o que evidencia a capacidade da MMC de retardar a transformaÃÃo do colÃgeno imaturo (tipo III) em maturo (tipo I). A MMC foi eficaz em retardar a maturaÃÃo da ferida por queimadura tÃrmica, gerando menor quantidade de fibrose. / Many research works which are currently being carried out are driven towards the analysis of the mediators of the local and systematical immune inflammatory response after episodes of thermal aggression. Mitomycin-C (MMC), an insulated antibiotic of the Streptomyces caespitosus kind is used clinically in order to shorten the wound healing process due to its anti-proliferation action in fibroblasts in vitro. Dermal burns were produced on forty eight Swiss albine mice as a result of using an adapted iron-welding device which inflicted burns upon the back dorsum of the cavies for a lapse of time of nine seconds. On the first day the burns received topical treatment in a single dose with 0.9% sterile isotonic saline (control) or Mitomycin-C (MMC). The effects of MMC in the healing process of the burns were evaluated by using macroscopic, microscopic and computerized methods on the 4th day (PBD 4), 7th (PBD 7), 14th (PBD 14) and on the 21st post-burn day (PBD 21). For the macroscopic analysis an analogical visual scale (AVS) and a digital planimetry were used. On the microscopic analysis, the samples of the skin were colored by picrosirius red (PR) and analyzed at a microscope under a polarized light and the quantification of the collagen type I and III was carried out. The biometric parameters did not evidence any harmful effects over the nutritional conditions of the animals. The AVS evidenced that the wounds of the MMC group presented a significant better look than those of the control group in the PBD 14 (p= 0.0002). The wound edge migration rates (WEMR) evidenced a smaller rate in the MMC group than those of the control group, with significant difference (p =0.0033). The morphometry of the image processing, computer-assisted showed that the collagen type I presented a decreasing behavior in the process of healing in the control group, whereas in the group which was treated with MMC there was growth between PBD 4 and PBD 14 and a decrease between PBD 14 and PBD 21.Likewise, there was a significant difference among the groups on PBD 14 and a quite significant difference on PBD 21 in the amount of collagen type III on the wounds of the MMC, which evidences the capacity of MMC in slowing down the transformation of the immature collagen (type III) into a mature one (type I). MMC has proved to be efficacious in slowing the maturation of the wounds caused by thermal burns, thus generating a minor amount of fibrosis.

Thesis (Ph. D.)--Ohio State University, 2006. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2007 Apr 14

Made available in DSpace on 2015-12-06T22:54:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2006 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Objetivo: Avaliar a efetividade da Mitomicina C (MMC) tópica na prevenção e retardo da formação de sinéquias e estenose após manipulações endoscópicas funcionais dos seios paranasais em humanos. Forma de Estudo: Randomizado controlado. Método: 14 pacientes portadores de Rinossinusite Crônica foram submetidos a cirurgias endoscópicas funcionais dos seios paranasais, ao final das quais era colocado cotonóide neurocirúrgico com 1 ml de Mitomicina C (1,0 mg/ml) em um dos meatos médios e outro com 1 ml de solução salina no meato médio contralateral, que servia de controle, ambos por 5 minutos, de forma randomizada, sem que o autor tivesse conhecimento dos lados. O seguimento foi realizado pelo autor, cego em relação aos lados. Foi avaliada a presença de sinéquias em meatos médios e estenoses nas antrostomias. Resultados: Um total de 12 sinéquias (42,86 %) foram identificadas em 10 dos 14 pacientes (p = 0,57). Oito pacientes tiveram sinéquias unilaterais e dois, bilaterais. Dentre as 8 sinéquias unilaterais, somente 1 ocorreu no lado com MMC contra 7 no lado controle (p = 0,07). Ao final de um ano, no grupo MMC, houve 3 (21,43 %) sinéquias contra 9 (64,29 %) no grupo controle (p = 0,054). No lado com MMC todas as 3 (21,43 %) sinéquias foram parciais, enquanto no grupo controle houve 4 (28,57 %) parciais e 5 (35,71 %) totais (p = 0,025). Não houve sinéquias totais no grupo MMC (p = 0,034). Em relação às antrostomias, 1 (7,14 %) ipsilateral à MMC teve estenose, enquanto no grupo controle foram 9 (64,29 %) (p = 0,004). No grupo com MMC a única ocorrência (7,14 %) foi da forma parcial, enquanto que no controle foram 4 (28,57 %) parciais e 5 (35,71 %) totais (p = 0,006). Não houve diferença em relação ao tempo médio de ocorrência de sinéquias entre os grupos (p= 0,055), somente para o tipo total (p = 0,034). O tempo médio para aparecimento de estenoses nas antrostomias foi maior no grupo MMC (p = 0,0015), assim como a média para aparecimento de estenose total (p = 0,016). Conclusão: A Mitomicina C não foi eficaz na prevenção e retardo da formação de sinéquias parciais, porém, preveniu e retardou a formação de sinéquias totais e estenoses nas antrostomias, no pós-operatório de cirurgia endoscópica funcional dos seios paranasais em humanos. Tendo em vista a facilidade de seu uso na forma tópica, em dose única intra-operatória, com poucos efeitos colaterais, somados ao benefício que ela pode trazer, nossos resultados apresentam uma nova perspectiva para a diminuição dos insucessos da cirurgia endoscópica funcional dos seios paranasais. / Purpose: To assess the efficacy of topical Mitomycin C (MMC) in the prevention and delay of synechiae and stenosis formation after functional endoscopic sinus surgery in humans. Method: At the end of functional endoscopic sinus surgery in 14 patients, a cotton pledget soaked in 1 mL of 1 mg/mL MMC was randomly placed into the middle meatus of one nasal cavity for 5 minutes and an identical saline-soaked pledget was placed in the contralateral side in each patient. The author was blinded for the side of the substances. Patients were followed postoperatively by a blinded observer for the presence of synechiae in the middle meatus and stenosis of the maxillary antrostomy. Synechiae were rated as partial when not totally closed, and total when completely closed. Stenosis were rated as partial when smaller than a diameter of 3 mm, and total when completely closed. Results: 12 synechiae (42,86 %) were identified in 10 of 14 patients (p = 0,057). They were unilateral in 8 patients and bilateral in 2. Unilateral synechiae were observed on only 1 side treated with MMC and 7 controls (p = 0,07). After a follow-up of 1 year, 3 sides (21,43 %) treated with MMC and 9 controls (64,29%) had synechiae (p = 0,054). On the MMC side all of them were partial, while on the control side 4 (28,57 %) were partial, and 5 (35,71 %) were total (p = 0,025). One side (7,14%) treated with MMC had stenosis, compared with 9 (64,29%) controls (p = 0,004). The time of occurrence of synechiae was not statistically different between the groups (0,055). However, the time of occurrence of the total type was longer in the MMC group (p = 0,034). The medium time of appearance of stenosis was statistically longer in the MMC group (p = 0,0015). All patients improved their symptoms at the end of our study. Moreover, none needed revision procedure or referred adverse effects. Conclusion: MMC was not efficient in the prevention and delay of synechiae formation. However, it was efficient in preventing and delaying total synechiae and stenosis formation after functional endoscopic sinus surgery in humans. Our results present a new perspective to achieve favorable success rates in functional endoscopic sinus surgery. / BV UNIFESP: Teses e dissertações

Orientador: Antônio José Maria Catâneo / Resumo: Objetivo: avaliar se a Mitomicina C (MMC) pode ampliar a taxa de sucesso da Dacriocistorrinostomia (DCR) externa ou endoscópica quando utilizada como tratamento adjuvante ao tratamento cirúrgico. Método: revisão sistemática de ensaios clínicos randomizados referentes a DCR externa ou endonasal, comparando as cirurgias realizadas com e sem MMC. Foram pesquisadas as bases de dados PubMed, Embase e Cochrane Central Register of Controlled Trials, de Janeiro de 1990 até Maio de 2018. A síntese dos resultados seguiu o programa RevMan 5.3 para a realização das meta-análises. Resultados: foram encontrados 937 estudos, dos quais 25 artigos foram considerados para a meta-análise. Subgrupo DCR externa (12 estudos, OR 2,69, IC 95% 1,36 a 5,32; I²= 38%), subgrupo DCR endoscópica (13 estudos, OR 1,70, IC 95% 1,21 a 2,39; I²= 0%). Observou-se que o uso da MMC aumenta a chance de sucesso da DCR nas duas técnicas (OR 2,03, IC 95% 1,44 a 2,88; I²= 16%) Conclusão: A MMC pode melhorar ligeiramente a taxa de sucesso na DCR externa e endoscópica. / Abstract: Objective: to evaluate the success rate of external or endoscopic dacryocystorhinostomy (DCR) with mitomycin C (MMC) as an adjuvant therapy. Method: a systematic review of randomized clinical trials (RCT) was done to analyze if the success rate of external or endoscopic DCR can be improve using MMC as adjuvant therapy. The following databases were searched: PubMed, Embase and Cochrane Central Register of Controlled Trials, ranging from January 1990 to May 2018. The results were obtained using the RevMan software (v5.3) to perform meta-analysis. Results: Nine hundred and thirthy-seven studies were found, of which 25 were considered for meta-analysis. The external DCR group had 12 studies (OR 2,69; 95% CI 1,36-5,32; I2= 38%), while the endoscopic DCR group had 13 studies (OR 1,70; 95% CI 1,12-2,39; I2= 0%). It was observed that the use of MMC can increases the success rate of DCR using both techniques (OR 2,03; 95% CI 1,44-2,88; I2= 16%). Conclusion: The use of MMC as adjuvant treatment in the external or endoscopic DCR can slightly improve the success rate of both techniques. / Mestre

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INTRODUÇÃO: É importante estudar a efetividade da trabeculectomia e estratégias para manter sua ação ao longo do tempo. Para melhorarmos o prognóstico das revisões cirúrgicas é imprescindível entendermos melhor a estrutura da bolha filtrante e suas possíveis causas de falência. Formas alternativas para se restabelecer a drenagem e o funcionamento da trabeculectomia não funcionante foram desenvolvidas, entre elas a Revisão Interna de Simmons. OBJETIVOS: Avaliar os efeitos da Revisão Interna de Simmons sobre a PIO; sobre o aspecto biomicroscópico da bolha no pós-operatório e sua correlação com achados biométricos obtidos pela biomicroscopia ultra-sônica. CASUÍSTICA E MÉTODOS: Foram incluídos e estudados de forma prospectiva por 6 meses, 29 pacientes portadores de glaucoma primário, submetidos a trabeculectomia prévia,há pelo menos três meses, que apresentavam PIO acima do esperado para o controle do glaucoma, apesar de medicação hipotensora utilizada. Foram fatores de inclusão a conjuntiva livre e o óstio interno da trabeculectomia patente à gonioscopia. O critério de sucesso foi: abaixamento da PIO, igual ou maior que 30% da PIO em relação à PIO pré-operatória e/ou pressão final menor ou igual a 15mmHg, com ou sem medicação antiglaucomatosa associada. RESULTADOS: Houve uma queda estatisticamente significante da PIO e do número de medicações utilizadas após a cirurgia. A PIO média antes da operação era de 23,72 ± 4,10 mmHg e ao término do estudo, de 15,04 ± 4,00 mmHg (p=0,000016). A média das pressões da curva tonométrica antes da cirurgia era de 22,36 ± 3,91mmHg, caindo para 15,01 ± 3,95mmHg no PO180d (p=0,0000001). Antes da cirurgia, a média do número de medicações usadas era de 2,1 ± 0,77 e ao término do estudo, 1,22 ± 1,01 (p=0,001117). Houve um aumento do tamanho da bolha filtrante, avaliado pela biomicroscopia. As bolhas apresentaram altura média de 0,28 ± 0,65 e terminaram o estudo com altura de 0,78 ± 0,85 (p=0,000016). Não houve diferença na altura da bolha, medida pela biomicroscopia ultra-sônica após a cirurgia. A pressão intra-ocular apresentou relação inversamente proporcional à dimensão da bolha filtrante, com significância estatística. As complicações mais encontradas foram: descolamento da membrana de Descemet, no local da incisão principal em 5 doentes (17,2%), abertura inadvertida da conjuntiva em 4 (13,8%), e descolamento de coróide, em 3 (10,3%). CONCLUSÕES: A Revisão Interna de Simmons proporcionou diminuição de 30% da PIO em 52% dos pacientes e redução do número de medicações antiglaucomatosas associadas, quando utilizadas. As bolhas se mostraram-se estatisticamente maiores após o procedimento. Houve uma correlação perfeita entre a classificação da altura da bolha entre a medida biomicroscópica baseada na escala de Indiana e a biométrica obtida pela biomicroscopia ultra-sônica. Não houve aplanamento da curva tonométrica apesar desta ter diminuído 32%. Não foi observada mudança significativa no vício de refração ou na acuidade visual após a operação. A biomicroscopia ultra-sônica demonstrou uma associação inversa entre um maior número de complicações pós-operatórias e o tamanho menor do óstio interno da trabeculectomia. / INTRODUCTION: It is important to study the trabeculectomy effectiveness and strategies to keep its action within long time. To improve the prognostic presented on glaucoma surgical reviews it is essential to understand better the bleb structure and its possible cause of failing. Alternative ways of restoring the drainage and the good performance of trabeculectomy have been studied, among them the Internal Revision of Simmons. PURPOSE: Evaluate the surgery effects on the IOP; on the biomicroscopic aspect of the bleb and its co-relation with biometric founding gotten through UBM. METHODS: For six months, 29 patients with open angle glaucoma who had been submitted to trabeculectomy before, for at least three months, with IOP above the expected to the control of glaucoma, despite the medication used, were included and studied in a prospective way. These patients should present the conjunctive tissue not too scarry and internal ostio of trabeculectomy present on the gonioscopia. The success criterion was: lowering the IOP, equal or above 30% on pre-operatory IOP and/or final pressure below 15 mmHg, with or without eye drops. RESULTS: There was a statistically fall of IOP and amount of medication used after the surgery. The average of IOP before surgery was 23.27 ± 4.10 mmHg and at the end of study was 15.04 ± 4.00 mmHg (p=0.000016). The average of the IOP curve pressure before surgery was 22.36 ± 3.91mmHg, dropped to 15.01 ± 4.0 mmHg at PO180d (p=0.0000001). Before the surgery the average of medication used was 2.1 ± 0.77 and at the end of the study it was 1.22 ± 1.01 (p=0.001117). There was an increase of the filtering bleb size clinically measured. The blebs had an average height of 0.28 ± 0.65 and at the end of the study their height was 0.78 ± 0.85 (p=0.000016). The UBM didn?t show any difference in the bleb size. The intra-ocular pressure presented an inversely proportional relation to the dimension of the filtering bleb, with statistic significance. The most frequently problems found were: detachment of Descemet membrane where the main incision was performed, in 5 (17.28%) patients; hole in the conjuntiva in 4 (13.88%), detachment of the choroid in 3 (10.38%). CONCLUSIONS: The surgery was effective, for provided 30% decrease of initial IOP in 52% without or with eye drops statistically in small number than in presurgery. The blebs have appeared, statistically, bigger after the procedure. There was a perfect correlation between the bleb height classification, within the clinical measurement, based on the Indian scale, and the biometric one, gotten by UBM. There was no flattening of the IOP curve pressure despite this one had been 32% lower than the initial one. No significant change has occurred in the vicious of refraction or in the visual accuracy after the surgery. The UBM demonstrated an association between a larger number of complications post-surgery and the internal size of the trabeculectomy ostio.

Made available in DSpace on 2014-12-17T14:13:40Z (GMT). No. of bitstreams: 1 FranciscoIP_TESE_PARCIAL.pdf: 210737 bytes, checksum: 77c1b45b267230f3fe0cd598e41eee0c (MD5) Previous issue date: 2011-07-01 / The topical corneal application of antimitotic mitomycin-C (MMC) during refractive surgery is still characterized by a lack of standardization and considerable empirism. For this reason the creation of a system capable of reliable drug delivery represents a beneficial innovation for patients submitted to these procedures. Objective: Elaborate a new MMC delivery system during the transoperatory period of photorefractive keratectomy (PRK) followed by patent application. Methods: The project consists of an in vitro experimental study to create an MMC (0.02%) release system. The drug was impregnated in sterile Whatman? 41 paper filter discs with a diameter of 8 mm. After drying, the discs were applied to antibiogram plates seeded with Staphylococcus epidermidis (American Type Culture Collection ATCC 12228), followed by the addition of a drop of sterile water. At the end of 1 minute, the discs were removed and the plates incubated for 48 hours at 35oC. Mean drop volume in the collyrium flasks was measured using analytical balance weighing. The inhibition halo (mm) was correlated with the MMC impregnated into the disc. After completion of the invention design a patent application was lodged at the National Institute of Industrial Property. Results: The correspondence between MMC-produced inhibition halos indicated that a dose of 16?g was ideal for impregnating into the discs. The mean drop volume obtained from the collyrium flasks was 37.7 ?L. A minute after the application of one drop of balanced saline solution, the system released an adequate concentration for PRK surgery. Conclusion: A new MMC delivery system was created for transoperatory application in photorefractive keratectomy (PRK). Publication of the patent application (number PI 0704739-8) gives the authors exclusive intellectual property rights. The study was sponsored by Ophthalmos Ind?stria e Com?rcio de Produtos Farmac?uticos S.A. (S?o Paulo-SP, Brazil) and received the indispensable scientific contribution of researchers from the fields of Pharmacy, Medicine, Biology, Statistics and Law, characterizing the work as multidisciplinary, in accordance with norms established by the Postgraduate Health Sciences Program of the Federal University of Rio Grande do Norte (UFRN) / A aplica??o t?pica corneana do antimit?tico mitomicina C (MMC) durante as cirurgias refrativas ainda ? caracterizada por uma falta de padroniza??o e grande empirismo. Por isso, a cria??o de um sistema capaz de disponibilizar a droga de forma padronizada representa uma inova??o que vem beneficiar os pacientes submetidos ?queles procedimentos. Objetivo: Elaborar um novo sistema de aplica??o da MMC durante o per?odo transoperat?rio da cirurgia de ceratectomia fotorrefrativa (Photorefractive keratectomy- PRK) com posterior dep?sito do Pedido de Patente. M?todos: O projeto representou um estudo experimental in vitro para cria??o de um sistema de libera??o de MMC a 0,02%. A droga foi impregnada em discos est?reis de papel filtro do tipo Whatman? 41 com 8 mm de di?metro. Ap?s o processo de secagem, os discos foram aplicados em placas de antibiograma semeadas com Staphylococcus epidermidis (American Type Culture Collection ATCC 12228), recebendo em seguida uma gota de ?gua est?ril. Decorrido o per?odo de 1 minuto, os discos foram removidos e as placas incubadas por 48 horas a 35oC. O volume m?dio das gotas de frascos de col?rio foi medido pelo m?todo de pesagem em balan?a anal?tica. O halo de inibi??o, em mil?metros, foi correlacionado com a dose da MMC impregnada no disco. Com o delineamento da inven??o, procedeu-se o Dep?sito do Pedido de Patente no Instituto Nacional da Propriedade Industrial. Resultados: A correspond?ncia entre os halos de inibi??o produzidos pela MMC indicou a dose de 16?g como a ideal para ser impregnada nos discos. O volume m?dio de uma gota obtida dos frascos de col?rio foi 37,7 ?L. Com a aplica??o de uma gota de solu??o salina balanceada e ap?s o per?odo de um minuto, o sistema liberou uma concentra??o considerada adequada para a cirurgia de PRK. Conclus?o: Um novo sistema de aplica??o de MMC foi criado para sua aplica??o transoperat?ria na ceratectomia fotorrefrativa (PRK). A publica??o do Pedido de Patente sob o n?mero PI 0704739-8 outorga aos autores a prioridade exclusiva de sua Propriedade Intelectual. A pesquisa teve o patroc?nio da Ophthalmos Ind?stria e Com?rcio de Produtos Farmac?uticos S.A. (S?o Paulo-SP, Brasil) e a indispens?vel contribui??o cient?fica de pesquisadores das ?reas de Farm?cia, Medicina, Biologia, Estat?stica e Direito, revestindo o trabalho de um car?ter multidisciplinar, requisito inerente ?s exig?ncias do Programa de P?s-Gradua??o de Ci?ncias da Sa?de da Universidade Federal do Rio Grande do Norte (UFRN)

Orientador: José Luiz Laus / Banca: Geórgia Nadalini Rodrigues / Banca: Aline Adriana Bolzan / Banca: Cintia Lúcia Maniscalco / Banca: Julio Carlos Canola / Resumo: Mioplastias extra-oculares podem ensejar aderências entre o músculo operado e os tecidos adjacentes, produzindo, não raro, estrabismos cicatriciais. Com intuito de se minimizar a ocorrência de aderências, investigaram-se os efeitos da mitomicina C (MMC), um antifibrótico, em concentrações ascendentes de 0,008, 0,02 e 0,04%, aplicada no per-operatório de mioplastias do reto dorsal do bulbo do olho de coelhos. Para tal, foram operados 56 animais, os quais foram divididos em sete grupos. Para o pós-operatório, instituíram-se limpeza com solução fisiológica das áreas operadas, profilaxia antimicrobiana e antiinflamatória, na forma de colírio. Procederam-se avaliações clínica, histológica, morfométrica e quanto à imunoistoquímica, em que se estudou o Fator de Crescimento Fibroblástico-básico (FGF-2). Encontraram-se, clinicamente, mais aderências nos olhos controle, comparativamente aos tratados, no entanto, sem significação estatística (p>5%). À histologia, verificou-se que a MMC ensejou retardo da cicatrização junto às áreas das mioplastias, notadamente no grupo que a recebeu, à concentração de 0,02%. A imunoistoquímica revelou marcação do FGF-2 em fibroblastos e macrófagos, indistintamente, entre os grupos. Com base nos resultados, permite-se admitir que a MMC, nas concentrações em que fora empregada, foi capaz de retardar a cicatrização e, por conseguinte, o estrabismo secundário, sem ensejar efeitos colaterais. / Abstract: Extraocular myoplasties may cause adhesions to adjacent tissues, resulting cicatricial strabismus. With the purpose of reducing to a minimum the occurrence of adhesion, we studied the effects of mitomycin C (MMC), an antifibrotic, in concentrations of 0,008%, 0,02%, and 0,04% applied during intraoperative of myoplasties of the superior rectus muscle of laboratory albine rabbits. Fifty six animals were operated on and were divided in seven groups. During the postoperative the operated areas were cleaned with physiological solution. Eyedrop instillation to prevent inflammation and bacterial infection were used. The method to analyze the results consisted of clinical and histological evaluation and statistical analyzes. We also evaluated at the same time the amount of basic fibroblast growth factor (FGF-2) by immunohistochemical study. Clinically we found more adhesions in the eyes of the control group than in the groups of treated eyes. However there was no significant statistics difference between the two groups (p>5%). Histologically we found that MMC caused a delayed cicatrization in the mioplastic areas, specially in the group who received the 0,02% concentration. The immunohistochemical showed FGF-2 marking in fibroblasts and macrophages, but between the groups there wasn't no difference. Based on those results we conclude that MMC in the utilized concentrations was capable of delaying the cicatrization and consequently avoid the secondary strabismus without undesirable side effects. / Doutor

Background Evaluating potential genotoxicity of pharmaceutical drug candidates is important during drug development. A method that can be used for this purpose is the micronucleus assay (MN- assay) which can identify agents that induce chromosomal damage. One of the most commonly used cell lines in an in vitro MN-assay is Chinese Hamster Ovarian K1 (CHO-K1) cells. Propolis, a natural substance produced by honeybees from exudates of different types of plant, is used in folk medicine to improve health and prevent diseases and was the evaluated substance in this study. Aim The major aim of this thesis project was to evaluate the potential cytotoxic and genotoxic effects of propolis in CHO-K1 cells by in vitro MN-assay. Method Two solutions of propolis were prepared in different ways and CHO-K1 cells were cultured. The two different ethanolic extracts of propolis were evaluated with the cytochalasin B protocol of the MN-assay, using mitomycin C as a positive control. Results Ethanolic extract number 1 had a statistically significant increase of genotoxicity at 50 μg/ml and 100 μg/ml. It was also found to induce a statistically significant increase of cytotoxicity at all concentrations tested (5-100 μg/ml). Ethanolic extract number 2 had a statistically significant increase of genotoxicity at 50 μg/ml but no statistically significant increase of cytotoxicity. General conclusion Rather surprisingly, the present study showed that propolis induced chromosomal damage in CHO-K1 cells, and one of the extracts tested was also found to be cytotoxic using the cytochalasin B version of the in vitro MN-assay.

A central theme within the concept of enzyme-directed bioreductive drug development is the potential to predict tumour response based on the profiling of enzymes involved in the bioreductive activation process. Mitomycin C (MMC) is the prototypical bioreductive drug that is reduced to active intermediates by several reductases including NAD(P)H:quinone oxidoreductase (NQO1) and NADPH cytochrome P450 reductase (P450R). The purpose of our study was to determine whether NQO1 and P450R protein expression in a panel of low-grade, human superficial bladder tumours correlates with clinical response to MMC. A retrospective clinical study was conducted in which the response to MMC of 92 bladder cancer patients was compared to the immunohistochemical expression of NQO1 and P450R protein in archived paraffin-embedded bladder tumour specimens. A broad spectrum of NQO1 protein levels exists in bladder tumours between individual patients, ranging from intense to no immunohistochemical staining. In contrast, levels of P450R were similar with most tumours having moderate to high levels. All patients were chemotherapy naïve prior to receiving MMC and clinical response was defined as the time to first recurrence. A poor correlation exists between clinical response and NQO1, P450R or the expression patterns of various combinations of the 2 proteins. The results of our study demonstrate that the clinical response of superficial bladder cancers to MMC cannot be predicted on the basis of NQO1 and/or P450R protein expression and suggest that other factors (other reductases or post DNA damage events) have a significant bearing on tumour response.