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1.
Mem. Inst. Oswaldo Cruz ; 99(7): 757-761, Nov. 2004. ilus, tab, graf
Article Dans Anglais | LILACS | ID: lil-391608

Résumé

The antileishmanial activity of lapachol, isolapachol, and dihydrolapachol, along with soluble derivatives (potassium salt) and acetate was obtained. All the compounds were assayed against metacyclic promastigotes of two different species of Leishmania associated to tegumentar leishmaniasis: L. amazonensis and L. braziliensis. All compounds presented significant activity, being isolapachol acetate the most active against promastigotes, with IC50/24h = 1.6 ± 0.0 µg/ml and 3.4 ± 0.5 µg/ml for, respectively, L. amazonensis and L. braziliensis. This compound was also assayed in vivo against L. amazonensis and showed to be active. Its toxicity in vitro was also established, and at concentration similar to the IC50, no toxicity was evidenced. In all experiments, pentamidine isethionate was used as a reference drug. The present results reinforce the potential use of substituted hydroxyquinones and derivatives as promising antileishmanial drugs and suggest a continuing study within this class of compounds.


Sujets)
Animaux , Souris , Antiprotozoaires , Leishmania brasiliensis , Macrophages péritonéaux , Tests de sensibilité parasitaire , Facteurs temps
2.
Mem. Inst. Oswaldo Cruz ; 99(3): 325-327, May 2004. ilus, graf
Article Dans Anglais | LILACS | ID: lil-362003

Résumé

Infections due to protozoa of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials (SbV), which present renal and cardiac toxicity. Besides, the precise chemical structure and mechanism of action of these drugs are unknown up to date. In order to find new drugs against leishmaniasis, we have been studying extracts of Brazilian trees. In the present study, we have evaluated the effectiveness of an alkaloid extract of Aspidosperma ramiflorum Muell. Arg. (Apocynaceae), against the extracellular forms promastigotes of L. (L.) amazonensis and L. (V.) braziliensis. The alkaloid extract of A. ramiflorum was much more effective against L. (L.) amazonensis (LD50 < 47 µg/ml) than L. (V.) braziliensis. Based on these in vitro results against L. (L.) amazonensis new studies should be made to find the compounds with anti-leishmanial activity.


Sujets)
Animaux , Alcaloïdes , Antiprotozoaires , Leishmania brasiliensis , Extraits de plantes , Alcaloïdes , Évaluation de médicament
3.
Rev. Soc. Bras. Med. Trop ; 36(2): 241-248, mar.-abr. 2003. ilus
Article Dans Anglais | LILACS | ID: lil-340903

Résumé

Philander frenata and Didelphis marsupialis harbor parasitism by Trypanosoma cruzi without developing any apparent disease and on the contrary to D. marsupialis, P. frenata maintains parasitism by T. cruzi II subpopulations. Here we compared the humoral immune response of the two didelphids naturally and experimentally infected with T. cruzi II group, employing SDS-PAGE/Western blot techniques and by an Indirect immunofluorescence assay. We also studied the histopathological pattern of naturally and experimentally infected P. frenata with T. cruzi. P. frenata sera recognized more antigens than D. marsupialis, and the recognition pattern did not show any change over the course of the follow up of both didelphid species. Polypeptides of 66 and 90kDa were the most prominent antigens recognized by both species in the soluble and enriched membrane fractions. P. frenata recognized intensely also a 45kDa antigen. Our findings indicate that: 1) there were no quantitative or qualitative differences in the patent or subpatent phases in the recognition pattern of P. frenata; 2) the significant differences in the recognition pattern of parasitic antigens by P. frenata and D. marsupialis sera suggest that they probably "learned" to live in harmony with T. cruzi by different strategies; 3) although P. frenata do not display apparent disease, tissular lesions tended to be more severe than has been described in D. marsupialis; and 4) Both didelphids probably acquired infection by T. cruzi after their evolutionary divergence


Sujets)
Animaux , Humains , Anticorps antiprotozoaires/biosynthèse , Maladie de Chagas/médecine vétérinaire , Opossum/parasitologie , Trypanosoma cruzi/physiologie , Anticorps antiprotozoaires/sang , Antigènes de protozoaire/immunologie , Technique de Western , Brésil , Maladie de Chagas/immunologie , Maladie de Chagas/anatomopathologie , Modèles animaux de maladie humaine , Réservoirs de maladies , Technique d'immunofluorescence indirecte , Interactions hôte-parasite , Trypanosoma cruzi/immunologie
4.
Mem. Inst. Oswaldo Cruz ; 94(6): 791-4, Nov.-Dec. 1999.
Article Dans Anglais | LILACS | ID: lil-251341

Résumé

In a previous work we demonstrated that diarylheptanoids extracted from Centrolobium sclerophyllum are very active against Leishmania amazonensis promastigotes. In order to continue our studies with these class of compounds, we decided to evaluate the activity of several diarylheptanoids derived from curcumin (diferuloyl methane) against the extracellular form (promastigotes) of L. amazonensis. Furthermore, an experiment against the intracellular form of the parasite (amastigotes) was carried out, comparing the most active compound among the curcumin derivatives (the methylcurcumin) with des-O-methylcentrolobine, the most active diarylheptanoid derived from C. sclerophyllum


Sujets)
Souris , Animaux , Anti-inflammatoires non stéroïdiens/pharmacologie , Curcumine/analogues et dérivés , Curcumine/pharmacologie , Leishmania/effets des médicaments et des substances chimiques , Souris de lignée BALB C
5.
Mem. Inst. Oswaldo Cruz ; 87(2): 229-34, abr.-jun. 1992. tab, ilus
Article Dans Anglais | LILACS | ID: lil-116310

Résumé

Immunoblot analysis was used to investigate antigenic differences among clinical isolates of Leishmania amazonensis and their role in the etiology of the diseases. Western blots of promastigote homogenates were analyzed with either monoclonal antibodies (MAbs) specific for the L. mexicana complex (M-4, M-6, M-9 and M-11) or polyclonal sera from L. amazonensis infected patients with the various forms of clinical disease. In the case of the MAbs, no significant variation was observed among the strains of L. amazonensis, isolated from cases of cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), diffuse cutaneous leishmaniasis (DCL), visceral leishmaniasis (VL) or post kala-azar dermal leishmaniasis (PKDL), in either the relative morbility (Mr) or the quantitative amount (intensity) of the antigenic determinats. In the case of the sera of the infected patients, the patterns of antigenic reactivity of these strains revealed that, despite showing the presence of shared antigens, differences were observed between some of the antigenic components of the various isolates of L. amazonensis that were recognized by a single serum. Differences were also demonstrated between the antigenic determinants of a single isolate of L. amazonensis that were recognized by the different patient's sera. No apparent association was consistently found, however, between the Mr components identified in these isolates and clinical form of the disease or the geographical area of isolation. In addition, the spectrum of antigens recognized by the sera from patients with the same clinical form were not identical; although in some instances, similar Mr antigens were shared. These results indicate that isolates of L. amazonensis are not antigenically identical (homogeneous) and that the immune responses (antibodies) observed among infected patients are heterogeneous


Sujets)
Animaux , Anticorps monoclonaux/analyse , Antigènes/analyse , Technique de Western , Leishmaniose/étiologie , Leishmania/isolement et purification , Brésil
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