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Previous issue date: 2014-08-29 / Introduction : Injuries in peripheral nerves are common in clinical practice being responsible for serious problems and often permanent as loss of motor, sensitive functions, acute and chronic pain. Although surgical, physiotherapy and diagnostic techniques have evolved in recent decades, the clinical outcomes of nerve recovery still unsatisfactory, which encourages many researchers to seek drugs and devices that may help regeneration (NOBLE et al, 1998; OLIVEIRA et al, 2004). Various trophic factors, also known as growth factors (GF) are used and tested in vitro and in vivo in an attempt to assist the regeneration of peripheral nerves. These proteins act directly on the proliferation and differentiation of various cell types, being able to promote tissue repair and functional recovery (BOYD AND GORDON, 2003). Among them, we highlight the FK506 (Tacrolimus), a ligand for immunophilins with strong immunosuppressive effect that has potential neurotrophic and neuroprotective actions. Studies have shown that FK506 increases the rate of axonal regeneration and also the level of necessary reinnervation after peripheral nerve injury, besides enhancing recovery from nerve damage. Objective : Evaluating in vivo the availability and effect of FK 506 on the repair of injury of rat sciatic nerve. Material and Methods : Thirty-six male adult Wistar rats were randomized into three groups (I - control, II - Systemic FK506 III - FK506 site;). To evaluate the effect of different treatments, the sciatic nerve of animals was transected, creating a defect of 10 mm and then tubulized with the silicone chamber. In the control group, no additional treatment was performed. In systemic group, FK506 (dose 0.1 mg/kg/day) was administered systemically via osmotic minipump ALZET while in the local group the administration also occurred through the ALZET osmotic minipump, but adapted to release into the silicone chamber the same dose. The performed treatment lasted 90 days. Results : Data from the present study suggest that the immunosuppressive drug FK506 has a positive effect on the nervous functional improvement and the use of osmotic minipumps is effective in continuous dispensing of the drug. The most important finding of this research is that the degree of functional recovery, measured by the rate of sciatic function after injury with loss of substance and repair through tubing, it is better when FK506 is administered locally whether compared to systemic administration in animal models. No other studies have used local application of the drug with constant release rate for comparison were found. / Introdu??o : Les?es em nervos perif?ricos s?o frequentes na pr?tica cl?nica sendo respons?veis por problemas graves e muitas vezes permanentes como perda de fun??es motoras, sensitivas, dor aguda e cr?nica. Embora as t?cnicas cir?rgicas, fisioter?picas e de diagn?stico tenham evolu?do nas ?ltimas d?cadas, os desfechos cl?nicos de recupera??o nervosa continuam insatisfat?rios, o que estimula diversos pesquisadores a buscarem drogas e dispositivos que possam auxiliar na regenera??o (NOBLE et al, 1998; OLIVEIRA et al, 2004). Diversos fatores tr?ficos, tamb?m conhecidos como fatores de crescimento (FC), s?o utilizados e testados in vitro e in vivo como uma tentativa de auxiliar a regenera??o de nervos perif?ricos.Essas prote?nas atuam diretamente na prolifera??o e diferencia??o de diversos tipos celulares, sendo capazes de promover reparo tecidual e recupera??o funcional (BOYD E GORDON, 2003). Dentre eles, destaca-se o FK506 (Tacrolimus), um ligante de imunofilinas com forte efeito imunossupressor que apresenta potenciais a??es neurotr?ficas e neuroprotetoras. Estudos t?m mostrado que o FK506 aumenta a taxa de regenera??o axonal e tamb?m o n?vel de reinerva??o necess?ria ap?s les?o do nervo perif?rico, al?m de melhorar a recupera??o ap?s les?es no nervo. Objetivo : Avaliar in vivo a viabilidade e efeito do FK 506 sobre o reparo de les?o de nervo ci?tico de ratos Material e M?todos : Trinta e seis ratos Wistar, machos, adultos foram randomicamente distribu?dos em tr?s grupos (I controle; II FK506 sist?mico; III FK506 local;). Para avaliar o efeito dos diferentes tratamentos, o nervo ci?tico dos animais foi transeccionado criando um defeito de 10mm e, em seguida, tubulizado com c?mara de silicone. No grupo controle, nenhum tratamento adicional foi realizado. No grupo sist?mico, o FK506 (dose 0,1mg/kg/dia) foi administrado sistemicamente via minibomba osm?tica ALZET enquanto que no grupo local a administra??o tamb?m ocorreu atrav?s da minibomba osm?tica ALZET, mas adaptada para libera??o dentro da c?mara de silicone na mesma dose. O tratamento empregado teve dura??o de 90 dias. Resultados : Os dados do presente estudo sugerem que a droga imunossupressora FK506 possui efeito positivo na melhora funcional nervosa e o uso de minibombas osm?ticas ? eficaz na dispensa??o cont?nua da droga. O dado mais importante dessa pesquisa ? que o grau de recupera??o funcional, medido atrav?s do ?ndice de fun??o ci?tica ap?s les?o com perda de subst?ncia e reparo atrav?s de tubuliza??o, ? melhor quando o FK506 ? administrado localmente se comparado ? administra??o sist?mica em modelos animais. N?o foram encontrados outros trabalhos que tenham usado aplica??o local da droga com taxa de libera??o constante para efeitos de compara??o.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/1792 |
| Date | 29 August 2014 |
| Creators | Goldani, Eduardo |
| Contributors | Silva, Jefferson Luis Braga da |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, BR, Faculdade de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7620745074616285884, 500, 600, -8624664729441623247 |
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