Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2006. / Submitted by Larissa Ferreira dos Angelos (ferreirangelos@gmail.com) on 2009-10-22T16:43:08Z No. of bitstreams: 1 Dissertacao Ada Amalia Ayala Urdapilleta.pdf: 1206521 bytes, checksum: d4b01a13486ebae64d1139c28f407682 (MD5) / Approved for entry into archive by Gomes Neide(nagomes2005@gmail.com) on 2010-07-06T17:19:08Z (GMT) No. of bitstreams: 1 Dissertacao Ada Amalia Ayala Urdapilleta.pdf: 1206521 bytes, checksum: d4b01a13486ebae64d1139c28f407682 (MD5) / Made available in DSpace on 2010-07-06T17:19:08Z (GMT). No. of bitstreams: 1 Dissertacao Ada Amalia Ayala Urdapilleta.pdf: 1206521 bytes, checksum: d4b01a13486ebae64d1139c28f407682 (MD5) Previous issue date: 2006 / Leishmaniose é uma infecção parasitária e endêmica causada pelo protozoário do gênero Leishmania. Cerca de 1,5 milhões de pessoas são acometidas pela leishmaniose cutânea que atinge 88 países e tem notificação compulsória em apenas 30 deles. Apresenta-se em todo Continente Americano e o Brasil é o país que têm a maior prevalência de casos. Este estudo foi realizado com dezenove substâncias liquênicas. Foram testadas in vitro para avaliar a atividade leishmanicida em formas promastigotas de Leishmania (L.) amazonensis e Leishmania (V.) braziliensis. A atividade anti-leishmania foi comparada com a ação do fármaco Miltefosina. Substâncias de seis espécies testadas (Parmotrema tinctorum, Parmotrema dilatatum, Cladonia verticillaris, Cladina confusa, Ramalina peranceps e Parmotrema lichexanthonicum) mostraram atividade no intervalo de concentrações de 100 a 12,5 μg/mL. Dentre as substâncias liquênicas testadas, o orselinato de n-pentila mostrou a maior atividade, apresentou-se ativo até a concentração de 12,5 μg/mL frente as formas promastigotas de Leishmania (V.) braziliensis e na concentração de 50 μg/mL frente as formas promastigotas de Leishmania (L.) amazonensis. Os resultados obtidos são promissores e as substâncias liquênicas ativas podem ser fonte de susbtânicas contra Leishmania ssp. _______________________________________________________________________________________ ABSTRACT / Leishmaniasis is a parasitary and endemic infection caused by Leishmania parasites. About 1,5 million people are attacked for cutaneous leishmaniasis, reaching 88 countries, being of obligatory notification in only 30 of them. Presented in all American continent and has Brazil the country with the biggest prevalence of cases. This study it was carried through with nineteen extracted substances of lichens. It was tested in vitro to evaluate the leishmanicida action on forms promastigote of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis.The anti-leishmania activity was compared with the activity of Miltefosine drug. Substances of liches from six species tested (Parmotrema tinctorum, Parmotrema dilatatum, Cladonia verticillaris, confused Cladina, Ramalina peranceps and Parmotrema lichexanthonicum) showed activity in concentrations ranging from 100 to 12,5 μg/mL. Among the tested substances of liches, the orselinato of n-pentila showed the best activity up to the concentrations of 12,5 μg/mL for Leishmania (Viannia) braziliensis and the concentrations of 50 μg/mL for Leishmania (Leishmania) amazonensis. The results obtained are promissing and the substances of lichens may represents a source of active substances against Lesihmnia ssp.

Thèse (Ph. D.)--Université Laval, 2003. / Bibliogr.: f. 218-245. Publié aussi en version électronique.

No description available.

No description available.

Glycosomes are subcellular organelles that are evolutionarily related to the peroxisomes of higher eukaryotes. The Leishmania glycosome performs various metabolic processes that are essential for the survival of these parasites, such as the glycolytic process. Proteins that are destined for import into the glycosome interact selectively with specific cytosolic receptors peroxin 5(PEX5) or PEX7. The PEX5-protein complex migrates toward the glycosomal membrane where it interacts with PEX14, a vital step for protein important into the glycosome. / This project investigated the interaction mechanism of Leishmania donovani PEX14 with the glycosomal membrane. The regions responsible for PEX14 interaction with the glycosomal membrane are established in higher eukaryotes. LdPEX14 is poorly conserved with respect to the other PEX14 homologues. In Leishmania the interaction of LdPEX14 with the glycsomal membrane has been shown to be unique in terms of its lack of insertion in the glycosomal membrane. Using LdPEX14 mutants it was determined that the first 63 amino acids are important for the interaction of LdPEX14 with the glycosomal membrane. Results further suggest that LdPEX14 is a homopolymer forming a complex of 20S in size which is vital for the proper functioning of the glycosome.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Thèse (Ph. D.)--Université Laval, 2009. / Texte en anglais avec résumés en français et en anglais. Bibliogr. Publié aussi en version électronique dans la Collection Mémoires et thèses électroniques.

Hannover, University, Diss., 2005.

Thèse (M.Sc.) -- Université Laval, 1997. / Bibliogr.: f. 65-77. Publié aussi en version électronique.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2008. / Submitted by wesley oliveira leite (leite.wesley@yahoo.com.br) on 2009-09-11T20:00:51Z No. of bitstreams: 1 2008_JacksandraFariasFrancaCampos.pdf: 1569774 bytes, checksum: 8166369e43a9689cdd652bf76794766f (MD5) / Approved for entry into archive by Luis Felipe Souza Silva(luis@bce.unb.br) on 2009-09-21T17:23:38Z (GMT) No. of bitstreams: 1 2008_JacksandraFariasFrancaCampos.pdf: 1569774 bytes, checksum: 8166369e43a9689cdd652bf76794766f (MD5) / Made available in DSpace on 2009-09-21T17:23:38Z (GMT). No. of bitstreams: 1 2008_JacksandraFariasFrancaCampos.pdf: 1569774 bytes, checksum: 8166369e43a9689cdd652bf76794766f (MD5) 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.