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Previous issue date: 2008-11-28 / A droga miltefosine é uma alquilfosfocolina de uso oral já usada na índia no tratamento da leishmaniose visceral. O objetivo do presente estudo foi avaliar a ação in vitro e in vivo da droga no tratamento da leishmaniose cutânea experimental. Nos testes in vitro promastigotas metacíclicas de leishmania (leishmania) amazonensis, leishmania (viannia) braziliensis e leishmania (viannia) guyanensis foram incubadas 48 horas na presença de diferentes concentrações de miltefosine (100 a 3,1?g/ml), n-metil glucamina (300 a 9,3?g/ml) e associação das duas drogas. A avaliação foi feita pelo método colorimétrico methyl thiazolyl blue. No teste in vivo, 80 camundongos, cepa c57bl/6 foram infectados com leishmania (leishmania) amazonensis e divididos em quatro grupos de tratamento (10 dias): miltefosine, n-metil glucamina, miltefosine+n-metil glucamina e controle sem tratamento. Doses: miltefosine via oral 20mg/kg/dia e n-metil glucamina intramuscular 400mg sb+5/kg/dia. Avaliação: medição da pata e parasitológico (culturas em meio novy-mcneal-nicolle, esfregaços para pesquisas de amastigotas e culturas em diluição limitante). Análises estatísticas: programa spss® versão 13.0. Resultados in vitro: a concentração inibitória capaz de destruir 50% (ic50) das promastigotas de leishmania (leishmania) amazonensis foi de 12,2?g/ml; para leishmania (viannia) braziliensis a ic50 foi de 22,9?g/ml e para leishmania (viannia) guyanensis a ic50 foi de 271,7?g/ml. Resultados in vivo: no grupo miltefosine as médias de diâmetro das patas caíram de 2,3 para 1,9 (p:0,004), no grupo controle as médias cresceram de 1,8 para 2,4 (p:0,001), nos grupos n-metil glucamina e miltefosine+n-metil glucamina não houve diferença estatística (p:0,407 e p:0,923). Nas culturas em meio novy-mcneal-nicolle e esfregaços para pesquisa de amastigotas os grupos miltefosine e miltefosine+n-metil glucamina tiveram as maiores porcentagens de exames negativos no pós-tratamento (p:0,017 e p:0,000). Nas culturas em diluição limitante não houve crescimento de formas promastigotas nos grupos miltefosine e miltefosine+n-metil glucamina. In vitro as promastigotas de leishmania (leishmania) amazonensis, leishmania (viannia) braziliensis e leishmania (viannia) guyanensis demonstraram sensibilidade ao miltefosine, sendo a leishmania (leishmania) amazonensis a mais sensível e a leishmania (viannia) guyanensis a menos sensível. In vivo a droga se mostrou eficaz no tratamento da leishmaniose cutânea experimental. Assim, conclui-se que a miltefosine parece ser uma droga potencial para o tratamento da leishmaniose cutânea no brasil. ______________________________________________________________________________________ ABSTRACT / Miltefosine is an oral hexadecylphosphocoline drug which has already been used for visceral
leishmaniasis treatment in India. The objective of this study was to evaluate in vitro and in
vivo drug action as a treatment on a cutaneous leishmaniasis trial. On in vitro tests metacyclic
promastigotes of Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis
and Leishmania (Viannia) guyanensis were incubated 48 hours into concentrations of
miltefosine (100 to 3.1ug/mL), N-methyl glucamine (300 to 9.3ug/mL) and a combination of
both drugs. The assessment was made by Methyl Thiazolyl Blue colorimetric method. On in
vivo tests 80 mice, C57BL/6 strain were infected with Leishmania (Leishmania) amazonensis
and divided into four treatment groups (10 days): miltefosine, N-methyl glucamine,
miltefosine + N-methyl glucamine and control with no treatment. Dosage: oral miltefosine
20mg/kg/day and intramuscular N-methyl glucamine 400mg Sb+5/Kg/day. Evaluation:
measurement of foot and parasitological (Novy-McNeal-Nicolle medium cultures, smears and
cultures in limiting dilution). Statistical analysis: SPSS® software version 13.0. In vitro
results: Leishmania (Leishmania) amazonensis IC50=12.2ug/mL; Leishmania (Viannia)
braziliensis IC50=22,9ug/ml and Leishmania (Viannia) guyanensis IC50=271,7ug/mL. In
vivo results: on miltefosine group the average diameter of the feet fell from 2.3 to 1.9 (p:
0.004), on control group the mean increased from 1.8 to 2.4 (p: 0.001), on the other two
groups there were no statistical difference (p: 0.407 and p: 0.923). In cultures and smears the
groups miltefosine and miltefosine + N-methyl glucamine had the highest percentages of
negative tests in post-treatment (p: 0.017 and p: 0,000). In limiting dilution the miltefosine
and miltefosine + N-methyl glucamine groups had no growth of promastigotes on crops after
treatment. Promastigotes forms of Leishmania (Leishmania) amazonensis, Leishmania
(Viannia) braziliensis and Leishmania (Viannia) guyanensis had in vitro sensitivity to
miltefosine (the first one had higher and the last one had lower sensitivity). The drug was
effective in vivo in the treatment of cutaneous leishmaniasis trial. It’s therefore concluded that
miltefosine can be considered as a potential treatment for cutaneous leishmaniasis in Brazil.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unb.br:10482/1725 |
| Date | 28 November 2008 |
| Creators | Campos, Jacksandra Farias de França |
| Contributors | Sampaio, Raimunda Nonata Ribeiro |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UnB, instname:Universidade de Brasília, instacron:UNB |
| Rights | info:eu-repo/semantics/openAccess |
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