Made available in DSpace on 2014-06-11T19:31:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-28Bitstream added on 2014-06-13T20:21:58Z : No. of bitstreams: 1 mamede_fv_dr_jabo.pdf: 467286 bytes, checksum: f692f69fc0d5d4f1a73028aaad9d672a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Fundação para o Desenvolvimento da UNESP (FUNDUNESP) / 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. / 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.

The one-way mixed lymphocyte culture (MLC) is used to assess histocompatibility between donor and recipient. First introduced in 1966, this method involves the co-culture of lymphocytes from the peripheral blood of the donor and the recipient for a period of 6 to 7 days: antigen disparities, primarily in the HLA-DR region, stimulate proliferation of the responding cells, which is detected by addition of 3H-labelled thymidine and subsequent measurement of radioactivity. The lymphocytes of either the donor, used to predict graft-versus-host disease (GVHD) or recipient, used to predict host-versus-graft disease (HVGD)/graft rejection, are inactivated by exposure to radiation or mitomycin C, so that the observed proliferation is that of the other set of lymphocytes, hence the name “one-way” MLC. The amount of measured radioactivity is directly proportional to the amount of DNA synthesized, which is a reflection of the number of disparities at the major histocompatibility complex (MHC).Previous studies have established that inactivation of the lymphocytes by radiation and mitomycin C, has a negative effect on the structure/expression of HLA-DR molecules on the cell surface, which provides the primary stimulus for the MLC reaction. The laboratory research presented in this dissertation was designed i) to compare the viabilities and HLA-DR levels on stimulator cells exposed to cyclosporin A, mitomycin C and ionizing irradiation , in order to determine whether cyclosporin A can be used as an alternative to mitomycin C or radiation as inactivator of the stimulator cells in the one-way MLC; ii) to improve sensitivity and accelerate the MLC reaction by addition of IL-2; iii) establish a flow cytometric mixed lymphocyte assay using the fluorochrome 5,6 carboxyfluorescein diacetate succinimidyl ester (CFSE). Cyclosporin A showed striking similarities to mitomycin C and ionizing radiation in its effect on viability and reduction/structural changes in HLA-DR molecules of the stimulator cells. Exposure of the stimulator cells to 20ìM cyclosporin A, demonstrated a significant loss of both cell viability and HLA-DR molecule cell surface expression. Thus, in evaluating these three methods of inactivation of the stimulator cells in the one-way MLC, it was concluded that a one-way MLC may not in fact be an accurate and qualitative reflection of the histocompatibility between donor and recipient. Instead the two-way MLC , in which neither the donor’s nor recipient’s cells are inactivated, may be a more reliable alternative. The only limitation associated with a two-way MLC is the inability to distinguish between a host-versus-graft-rejection and a graft-versus-host reaction in the observed allogeneic response Addition of 5 and 10 IU/ml IL-2 to the MLC showed the opposite effect to that intended, inhibiting proliferation in the MLC. Previous studies have shown that an excess of IL-2 results in the production of suppressor T cells. The amount of IL-2 produced during the MLC depends on the number of disparities in the MLC between donor and recipient, which will be different for each MLC reaction. Since the number of allogeneic T cells involved in the MLC reaction is not known, the amount of IL-2 produced during the allogeneic immune response in the MLC can not be predicted and addition of exogenous IL-2 may result in production of suppressor T cells and an inhibition of proliferation. The two-way MLC was modified by staining one of the participating set of lymphocytes (donors or recipients) with CFSE and tracking proliferation in this population, using flow cytometry. The two-way CFSE-based MLC analyzed in this study were counterstained with CD25 (IL-2R). An increase in CD25 expression on the cell surface is an indicator of cell activation and proliferation. Proliferation, as indicated by a progressive loss of CFSE fluorescence correlated well with the corresponding increase in CD25 expression and accumulated daughter cells. In addition, by loading only one of the participating donors in the two-way MLC, the responder/stimulator interaction, observed in the one-way MLC, is re-established. Thus the modified, CFSE-based two-way MLC can be used to predict GVHD. To conclude, the use of CFSE labeling and flow-cytometry to measure proliferation in a two-way MLC, together with CD25 counterstaining provides an alternative, reliable and probably superior method to 3H thymidine uptake. / Dissertation (MSc)--University of Pretoria, 2009. / Immunology / unrestricted

No / The indolequinone EO9 demonstrated good preclinical activity but failed to show clinical efficacy against a range of tumours following intravenous drug administration. A significant factor in EO9's failure in the clinic has been attributed to its rapid pharmacokinetic elimination resulting in poor drug delivery to tumours. Intravesical administration of EO9 would circumvent the problem of drug delivery to tumours and the principal objective of this study is to determine whether or not bladder tumours have elevated levels of the enzyme NQO1 (NAD(P)H:quinone oxidoreductase) which plays a key role in activating EO9 under aerobic conditions. Elevated NQO1 levels in human bladder tumour tissue exist in a subset of patients as measured by both immunohistochemical and enzymatic assays. In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. Administration of EO9 in an acidic vehicle could be employed to reduce possible systemic toxicity as any drug absorbed into the blood stream would become relatively inactive due to an increase in pH.

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

Submitted by Tamata Tarcila Soares De Sousa (tamata_sousa@hotmail.com) on 2018-09-01T00:31:43Z No. of bitstreams: 1 Dissertação Tâmata.pdf: 1077586 bytes, checksum: f048570585d2618ecb085c9fbdd9efb2 (MD5) / Rejected by Sulamita Selma C Colnago null (sulamita@btu.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: Problema 1: A capa do seu trabalho não está de acordo com as normas do Programa de Pós-Graduação. Assim que efetuar essa correção, submeta o arquivo em PDF novamente. Agradecemos a compreensão. on 2018-09-03T14:26:12Z (GMT) / Submitted by Tamata Tarcila Soares De Sousa (tamata_sousa@hotmail.com) on 2018-09-05T21:45:36Z No. of bitstreams: 1 Dissertação Tâmata 2.pdf: 1080658 bytes, checksum: fd0c5cb8b997028c8f406d0cbcc0ed27 (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-09-10T19:56:21Z (GMT) No. of bitstreams: 1 sousa_tts_me_bot.pdf: 1080658 bytes, checksum: fd0c5cb8b997028c8f406d0cbcc0ed27 (MD5) / Made available in DSpace on 2018-09-10T19:56:21Z (GMT). No. of bitstreams: 1 sousa_tts_me_bot.pdf: 1080658 bytes, checksum: fd0c5cb8b997028c8f406d0cbcc0ed27 (MD5) Previous issue date: 2018-07-31 / 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. / 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.

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