No abstract

Leishmaniasis is a zoonotic disease caused by the species of the genus Leishmania, flagellated protozoa that multiply inside mammalian macrophages and are transmitted by the bite of the sandfly. The disease is widespread and due to the lack of fully effective treatment and vaccination the search for new drugs and immune targets is needed. Proteomics seems to be a suitable strategy because the annotated sequenced genome of L. major is available. Here, we present a high-resolution proteome for L. infantum promastigotes comprising of around 700 spots. Western blot with rabbit hyperimmune serum raised against L. infantum promastiogote extracts and further analysis by MALDI-TOF and MALDI-TOF/TOF MS allowed the identification of various relevant functional antigenic proteins. Major antigenic proteins were identified as propionil carboxilasa, ATPase beta subunit, transketolase, proteasome subunit, succinyl-diaminopimelate desuccinylase, a probable tubulin alpha chain, the full-size heat shock protein 70, and several proteins of unknown function. In addition, one enzyme from the ergosterol biosynthesis pathway (adrenodoxin reductase) and the structural paraflagellar rod protein 3 (PAR3) were found among non-antigenic proteins. This study corroborates the usefulness of proteomics in identifying new proteins with crucial biological functions in Leishmania parasites.

To establish suitable immunobiological parameters for in vivo testing of new antileishmanial compounds in the golden hamster model of visceral leishmaniasis, two groups of 8 animals were infected each with 10(5) or 10(7) stationary promastigotes by the intracardiac route and the clinical and immunoparasitological features were monitored up to day 155 after infection. All animals became infected at both doses, although significant differences were observed between parasite burdens in liver and spleen. The mean number of parasites in animals infected with 10(7) promastigotes increased by 9.5 times in liver and by 43.1 times in spleen compared with those infected with 10(5) promastigotes. In animals given the higher dose, the outcome of the disease occurred between days 75 and 90 after infection, whereas no signs of disease were apparent in those given the lower infecting dose. Positive antibody (IgG) responses were detected earlier (week 5-7 after infection) in animals infected with the higher dose than in those infected with the lower dose (week 8-10 after infection), but these responses did not correlate with individual parasitological loads in liver and spleen. An inverse correlation was observed between infecting doses and in vitro spleen lymphocyte proliferation against mitogens (ConA). The proportion of CD4(+) and CD19(+) spleen cell increased in animals given the higher infection, whereas it decreased in those given the lower infection compared to naive controls.

No abstract

The antiparasitic activity of racemic albendazole-sulphoxide (Ricobendazole = racRBZ) and its (+) and (-) enantiomers was tested in an ex vivo murine model for Trichinella spiralis infection. Larvae were isolated from the muscle of infected mice and exposed to concentrations between 0.01 and 1 microg/ml of the racemic mixture or to each of its enantiomers. The activity of each compound was then assayed by measuring the ability of the treated larvae to infect naive mice (larval viability). At a concentration of 0.5 microg/ml, all 3 compounds were highly effective in reducing the viability of the larvae, achieving reductions of 91.26% (racRBZ), 96.7% (+), and 89.2% (-), when compared with untreated controls. At lower concentrations (0.1 microg/ml), only treatment with (+)RBZ rendered a significant reduction in larval viability in comparison with controls (84.3%; P < 0.01), whereas at 0.01 microg/ml, none of the compounds altered larval viability (P > 0.05).