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Trypanosoma cruzi cruzipain (Cz) bears a C-terminal domain (C-T) that contains sulfated epitopes “sulfotopes” (GlcNAc6S) on its unique N-glycosylation site. The effects of in vivo exposure to GlcNAc6S on heart tissue ultrastructure, immune responses, and along the outcome of infection by T. cruzi, were evaluated in a murine experimental model, BALB/c, using three independent strategies. First, mice were pre-exposed to C-T by immunization. C-T-immunized mice (C-TIM) showed IgG2a/IgG1

Chagas disease is a neglected parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi) that affects more than 6 million people, mainly in Latin America. Benznidazole is still the drug of choice in many countries to treat it in spite of its dosage regimen and adverse side effects such as such as allergic dermatitis, peripheral neuropathy and anorexia. Thus, novel, safer, and more efficacious treatments for such neglected infection are urgently required.In this study, the efficacy of orally administered low doses of benznidazole (BNZ) nanoparticles was evaluated during the acute phase in mice infected with T. cruzi Nicaragua (TcN) that were immunosuppressed during the chronic stage of the disease. Moreover, the production of T. cruzi-specific antibodies, cardiac tissue inflammation and reactive oxygen species generation by Vero cells treated with both BNZ nanoparticles (BNZ-nps) and raw BNZ (R-BNZ) were also evaluated.T. cruzi infected mice treated with 10, 25 or 50 mg/kg/day of BNZ-nps survived until euthanasia (92 days post infection (dpi)), while only 15% of infected untreated mice survived until the end of the experiment. PCR analysis of blood samples taken after induction of immunosuppression showed that a dosage of 25 mg/kg/day rendered 40% of the mice PCR-negative. The histological analysis of heart tissue showed a significant decrease in inflammation after treatments with 25 and 50 mg/kg/day, while a similar inflammatory damage was observed in both infected mice treated with R-BNZ (50 mg/kg/day) and untreated mice. In addition, only BNZ-nps treated mice led to lower levels of T. cruzi-specific antibodies to 50-100%. Finally, mammalian Vero cells treated with BNZ-nps or R-BNZ lead to a significant increase in ROS production.Based on these findings, this research highlights the in-vitro/in-vivo efficacy of nanoformulated BNZ against T. cruzi acute infections in immunosuppressed and non-immunosuppressed mice and provides further evidence for the optimization of dosage regimens to treat Chagas disease.

BackgroundAdults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells.Methodology/principal findingsTo test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4(+) T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4(+) T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4(+)TNF-α(+)-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4(+) T cells was evident in T. cruzi-infected children.Conclusions/significanceOur observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.

Two paradigms currently exist for information search. The first is the library paradigm, which has been largely automated and is the prevailing paradigm in today’s web search. The second is the village paradigm, and although it is older than the library paradigm, its automation has not been considered, yet certain elements of its key aspects have been automated, as in the cases of the Q&A communities or novel services such as Quora. The increasing popularity and availability of online social networks and question-answering communities have encouraged revisiting of the automation of the village paradigm owing to new helpful developments, primarily that people are more connected with their acquaintances on the internet and their contact lists are available. In this survey, we study how the village paradigm is today partially automated: we consider the selection of candidates for answering questions, answering questions automatically and helping candidates to decide what questions to answer. Other aspects are also considered, for example, the automation of a reward system. We conclude that a next step towards the automation of the village paradigm involves intelligent agents that can leverage a P2P (peer-to-peer) social network, which will create new and interesting issues deeply entwined with social networks in the form of information processing by agents in parallel and side by side with people. [ABSTRACT FROM PUBLISHER]

Recent studies have confirmed important regional differences in the prevalence of obesity, as well as a tendency for this prevalence to increase. Determination of the social factors involved in obesity may be very useful to design intervention and prevention strategies. This transverse study was undertaken in Pizarra (Malaga, Spain) from a random sample of the population between 18 and 65 years of age (n = 1226). All participants were interviewed and given a physical examination. Standardized anthropometrical measurements were made, and a baseline blood sample was taken after an oral glucose tolerance test. The overall prevalence of obesity (BMI > 30 kg/m2) was 28.8%. This figure increased continuously from 10% in the group aged 18–25 years to above 50% in the groups aged over 55 years. This prevalence is higher than that reported in most other studies in Spain. The obese persons ate differently, at least from a qualitative viewpoint, probably more saturated fats and fewer unsaturated fats, and had a different behaviour concerning alcohol and smoking. Marital status was related with the rate of obesity, and the close relation between the level of education and the risk of obesity was confirmed (OR = 3.8 for being obese and having no education compared to having university studies). The most important consequence of the study was that all these factors are potentially modifiable and preventable. An increased level of general education in the population may well contribute decisively to a reduction in the prevalence of obesity. [ABSTRACT FROM AUTHOR]