Influence of Ecto-Nucleoside Triphosphate Diphosphohydrolase Activity on Trypanosoma cruzi Infectivity and Virulence

The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, an endemic zoonosis present in some countries of South and Central Americas. The World Health Organization estimates that 100 million people are at risk of acquiring this disease. The infection affects mainly muscle tissues in the heart and digestive tract. There are no vaccines or effective treatment, especially in the chronic phase when most patients are diagnosed, which makes a strong case for the development of new drugs to treat the disease. In this work we evaluate a family of proteins called Ecto-Nucleoside-Triphosphate-Diphosphohydrolase (Ecto-NTPDase) as new chemotherapy target to block T. cruzi infection in mammalian cells and in mice. We have used inhibitors and antibodies against this protein and demonstrated that T. cruzi Ecto-NTPDases act as facilitators of infection in mammalian cells and virulence factors in mice model. Two of the drugs used in this study (Suramin and Gadolinium) are currently used for other diseases in humans, supporting the possibility of their use in the treatment of Chagas disease

Estrutura da assembléia de chironomidae em relação ao enriquecimento orgânico de um ambiente aquático

In this study we determined the taxonomic diversity of larval Chironomidae upstream and downstream to discharges of the sewage treatment plant (STP) from Agro-industrial District of Anápolis, State of Goiás, Brazil. Additionally, we evaluated the use of the lognormal distribution as a measure of biotic integrity of this system. The Chironomidae communities were sampled in three sites, upstream and downstream of the discharge of the sewage treatment plant (STP). We fitted the truncate lognormal distribution based on a nonlinear regression of the datasets using least squares as loss function in an iterative quasi-Newton procedure. The total of 21,498 individuals were sampled, from 24 Chironomidae genera, Chironomus, Polypedilum, Rheotanytarsus e Thienemanniella, with 73.9%, 14.4%, 7.1% and 4.5%, respectively, of all analyzed community; they are generally considered resistant to organic pollution. The assemblage of the site upstream was described for a truncate lognormal distribution. The extreme increase in abundance of some genera in the first site downstream produced a distribution not fitted to lognormal. The second site downstream however, permits a good fit to lognormal, probably due to the decrease in abundance of the dominant groups. These data substantiate the hypothesis that Chironomidae community is not suitably characterized by lognormal distribution at disturbed environments. Consequently, these aquatic communities were ecological disordered by organic pollution which caused the lost of sensible species and the dominance of those tolerants to this sort of impact. Additionally, the study highlighted the distribution lognormal approach as a valuable method to assess environmental impacts.A diversidade taxonômica da comunidade de Chironomidae em ambientes aquáticos poluídos e não-poluídos foi estudada na área de influência do Distrito Agroindustrial de Anápolis, Anápolis, GO, avaliando-se a distribuição lognormal como indicador da integridade biótica desses sistemas. Larvas de Chironomidae foram coletadas em três pontos a montante e jusante do lançamento do efluente da estação de tratamento de esgoto desse distrito industrial. O ajuste do modelo de distribuição foi realizado utilizando-se o modelo de regressão não-linear, adotando procedimento iterativo quasi-Newton. Foram amostrados 21.498 indivíduos de 24 gêneros de Chironomidae. Chironomus, Polypedilum, Rheotanytarsus e Thienemanniella foram os mais abundantes, visto que são geralmente considerados resistentes à poluição orgânica. A assembléia do ponto a montante do lançamento foi bem descrita pelo modelo de distribuição lognormal truncada. O grande aumento da abundância de alguns gêneros no primeiro ponto a jusante impossibilitou o ajuste da distribuição lognormal truncada. O segundo a jusante, no entanto, possibilitou bom ajuste, possivelmente devido à diminuição na abundância dos grupos dominantes. Esses dados corroboram a hipótese de que as assembléias de chironomideos em ambientes não alterados são bem descritas por uma distribuição lognormal, o que não pode ser observado em ambientes degradados. Desta forma, evidenciou-se que a poluição orgânica causa desestruturação das comunidades aquáticas desse sistema, com perda das espécies sensíveis e dominância das tolerantes a esse tipo de impacto. Além disso, fica evidente que a distribuição lognormal pode ser considerada uma valiosa abordagem para avaliação de impactos ambientais.CNP

Detection of IgG1 and IgG4 subtypes reactive against potato apyrase in schistosomiasis patients

In this paper, we showed for the first time that the conserved domains within Schistosoma mansoni ATP diphosphohydrolase isoforms, shared with potato apyrase, possess epitopes for the IgG1 and IgG4 subtypes, as 24 (80%) of the 30 schistosomiasis patients were seropositive for this vegetable protein. The analyses for each patient cured (n = 14) after treatment (AT) with praziquantel revealed variable IgG1 and IgG4 reactivity against potato apyrase. Different antigenic epitopes shared between the vegetable and parasite proteins could be involved in susceptibility or resistance to S. mansoni AT with praziquantel and these possibilities should be explored

Immunostimulatory property of a synthetic peptide belonging to the soluble ATP diphosphohydro-lase isoform (SmATPDase 2) and immunolocalisation of this protein in the Schistosoma mansoni egg

A peptide (SmB2LJ; r175-194) that belongs to a conserved domain from Schistosoma mansoni SmATPDase 2 and is shared with potato apyrase, as predicted by in silico analysis as antigenic, was synthesised and its immunostimulatory property was analysed. When inoculated in BALB/c mice, this peptide induced high levels of SmB2LJ-specific IgG1 and IgG2a subtypes, as detected by enzyme linked immunosorbent assay. In addition, dot blots were found to be positive for immune sera against potato apyrase and SmB2LJ. These results suggest that the conserved domain r175-194 from the S. mansoni SmATPDase 2 is antigenic. Western blots were performed and the anti-SmB2LJ antibody recognised in adult worm (soluble worm antigen preparation) or soluble egg antigen antigenic preparations two bands of approximately 63 and 55 kDa, molecular masses similar to those predicted for adult worm SmATPDase 2. This finding strongly suggests the expression of this same isoform in S. mansoni eggs. To assess localisation of SmATPDase 2, confocal fluorescence microscopy was performed using cryostat sections of infected mouse liver and polyclonal antiserum against SmB2LJ. Positive reactions were identified on the external surface from the miracidium in von Lichtenberg's envelope and, in the outer side of the egg-shell, showing that this soluble isoform is secreted from the S. mansoni eggs