Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis.

Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL(-1) concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0.05 mg mL(-1). The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.

B-cell epitopes of antigenic proteins in Leishmania infantum: an in silico analysis.

Serodiagnosis of visceral leishmaniasis is often hindered by cross-reactions to other parasitic diseases. Identifying specific B-cell epitopes in proteins is therefore important for immunodiagnostics, as well as for disease control by vaccines. This study aimed to identify linear and conformational B-cell epitopes and to evaluate the secondary structure of antigen proteins in Leishmania infantum using in silico analysis. Linear epitopes were predicted using the Immune Epitope Database and Analysis Resource (IEDB), BepiPred and BcePred programs. The conformational B-cell epitopes were identified using the CBTOPE server. The combination of the predictions using IEDB, BepiPred and BcePred generated 148 linear epitopes from the calpain-like cysteine peptidase (CP), thiol-dependent reductase 1 (TDR1) and HSP70 proteins. In total, 164 conformational epitopes were predicted, mostly located in the linear epitope region. The predicted epitopes are located in α helix and random coil regions in the thiol-dependent reductase 1 and HSP70 proteins. New linear and conformational B-cell epitopes of L. infantum proteins were identified in silico, and the prediction using various programs ensures greater accuracy of the results, as suggested by confirmation of previously identified HSP70 epitopes.

Relevance of developmental testing of exposure to methamidophos during gestation to its toxicology evaluation.

The organophosphate insecticide (OP) are known to be able to promote cholinergic toxicity related to neurobehavioral findings. The measures of cholinesterase activity are the most common index of its action. The influence was evaluated, of the OP methamidophos (1.0 mg/kg), by oral exposure during gestational organogenesis of rats, on maturational and behavioral aspects of offspring development. This dose did not promote evidence of maternal toxicity. The pesticide did not affect body weight gain of the dams and offspring, but interfered with the offspring's physical and maturational development landmarks according to age. The behavioral performance of the offspring with or without a pharmacological challenge was tested at different postnatal days (pnd 14, 21 and 40) in an open-field apparatus. The results showed a large standard deviation that prejudiced the conclusions. There were no observed alterations in the swimming behavior tested also at pnd 7, 14 and 21. As long as the obtained results showed some subtle effects on rat development, the data, as possible additional effect biomarkers for risk analysis, will aid further studies of the embryo-feto-toxic potential of OP exposure.

Biological monitoring of embrio-fetal exposure to methamidophos or chlorothalonil on rat development.

Maternal exposure to pesticides during the pre-implantation and very early post-implantation periods of pregnancy is correlated with numerous adverse effects on the offspring and in reproductive parameters like an increase in resorption, a decrease in fetal survival and weight, and teratogenic effects. Although the epidemiological evidence is inconclusive as regards the risk of the adverse outcome of pregnancy and developmental toxicity events, the use of biomarkers in exposure assessment may contribute to recognizing a potential health impairment. The present study evaluated the influence of prenatal oral exposure to an insecticide (1.0 mg methamidophos/kg) or a fungicide (200.0 mg chlorothalonil/kg) during gestation days 1 to 6 on maturational and behavioral aspects of offspring development of rats. The pesticides did not affect the body weight gain of dams and offspring, nor did the exposure affect the weight of gravid uterus, fetus, placenta and ovary. There were no observed alterations in the swimming behavior tested at postnatal days 7, 14 and 21, but the pesticides interfered with physical and maturational development landmarks of offspring according to age, showing subtle effects on behavioral and physical development. These findings show the importance of categorizing developmental effects, establishing the relationship between age and important performances, to recognize potential impacts on human populations.