Protective immunity of single and multi-antigen DNA vaccines against schistosomiasis

We evaluated the usefulness of the combination of three plasmids encoding tegumental (pECL and pSM14) and muscular (pIRV5) antigens of the Schistosoma mansoni on improving the protective immunity over the use of a single antigen as DNA vaccines. Female BALB/c mice were inoculated twice with 25 µg DNA plasmid within two weeks interval. The challenge was performed with 80 cercarias of a regional isolate of S. mansoni (SLM) one week after the last immunization. Six weeks after challenge, all mice were perfused for worm load determination. The following groups were analyzed: saline; empty vector; monovalent formulations of pECL; pSM14 and pIRV5 and also double combinations of pECL/pIRV5 and pIRV5/pSM14 and a triple combination of pECL/pIRV5/pSM14. The protection was expressed as a percentage of worm loads in each group compared with the saline group. The results obtained were 41% (p < 0.05); 52% (p < 0.05); 51% (p < 0.05); 48% (p < 0.05); 55% (p < 0.05); 45% (p < 0.05); 65% (p < 0.05) for each group respectively.

Evolution of ascariasis in humans and pigs: a multi-disciplinary approach

The nematode parasite Ascaris lumbricoides infects the digestive tracts of over 1.4 billion people worldwide, and its sister species, Ascaris suum, has infected a countless number of domesticated and feral pigs. It is generally thought that the putative ancestor to these worms infected either humans or pigs, but with the advent of domestication, they had ample opportunity to jump to a new host and subsequently specialize and evolve into a new species. While nuclear DNA markers decisively separate the two populations, mitochondrial sequences reveal that three major haplotypes are found in A. suum and in A. lumbricoides, indicating either occasional hybridization, causing introgression of gene trees, or retention of polymorphism dating back to the original ancestral species. This article provides an illustration of the combined contribution of parasitology, archaeoparasitology, genetics and paleogenetics to the history of ascariasis. We specifically investigate the molecular history of ascariasis in humans by sequencing DNA from the eggs of Ascaris found among ancient archeological remains. The findings of this paleogenetic survey will explain whether the three mitochondrial haplotypes result from recent hybridization and introgression, due to intensive human-pig interaction, or whether their co-occurrence predates pig husbandry, perhaps dating back to the common ancestor. We hope to show how human-pig interaction has shaped the recent evolutionary history of this disease, perhaps revealing the identity of the ancestral host.

Application of control measures for infections caused by multi-resistant gram-negative bacteria in intensive care unit patients

Multi-resistant gram-negative rods are important pathogens in intensive care units (ICU), cause high rates of mortality, and need infection control measures to avoid spread to another patients. This study was undertaken prospectively with all of the patients hospitalized at ICU, Anesthesiology of the Hospital São Paulo, using the ICU component of the National Nosocomial Infection Surveillance System (NNIS) methodology, between March 1, 1997 and June 30, 1998. Hospital infections occurring during the first three months after the establishment of prevention and control measures (3/1/97 to 5/31/97) were compared to those of the last three months (3/1/98 to 5/31/98). In this period, 933 NNIS patients were studied, with 139 during the first period and 211 in the second period. The overall rates of infection by multi-resistant microorganisms in the first and second periods were, respectively, urinary tract infection: 3.28/1000 patients/day; 2.5/1000 patients/day; pneumonia: 2.10/1000 patients/day; 5.0/1000 patients/day; bloodstream infection: 1.09/1000 patients/day; 2.5/1000 patients/day. A comparison between overall infection rates of both periods (Wilcoxon test) showed no statistical significance (p = 0.067). The use of intervention measures effectively decreased the hospital bloodstream infection rate (p < 0.001), which shows that control measures in ICU can contribute to preventing hospital infections.

Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs

The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs), sum of FICs (ΣFICs) and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis.

Induction of protective T-helper 1 immune responses against Echinococcus granulosus in mice by a multi-T-cell epitope antigen based on five proteins

In this study, we designed an experiment to predict a potential immunodominant T-cell epitope and evaluate the protectivity of this antigen in immunised mice. The T-cell epitopes of the candidate proteins (EgGST, EgA31, Eg95, EgTrp and P14-3-3) were detected using available web-based databases. The synthesised DNA was subcloned into the pET41a+ vector and expressed in Escherichia coli as a fusion to glutathione-S-transferase protein (GST). The resulting chimeric protein was then purified by affinity chromatography. Twenty female C57BL/6 mice were immunised with the antigen emulsified in Freund's adjuvant. Mouse splenocytes were then cultured in Dulbecco's Modified Eagle's Medium in the presence of the antigen. The production of interferon-γ was significantly higher in the immunised mice than in the control mice (> 1,300 pg/mL), but interleukin (IL)-10 and IL-4 production was not statistically different between the two groups. In a challenge study in which mice were infected with 500 live protoscolices, a high protectivity level (99.6%) was demonstrated in immunised BALB/C mice compared to the findings in the control groups [GST and adjuvant (Adj) ]. These results demonstrate the successful application of the predicted T-cell epitope in designing a vaccine against Echinococcus granulosus in a mouse model.

Antischistosomal activity of a calcium channel antagonist on schistosomula and adult Schistosoma mansoni worms

Current schistosomiasis control strategies are largely based on chemotherapeutic agents and a limited number of drugs are available today. Praziquantel (PZQ) is the only drug currently used in schistosomiasis control programs. Unfortunately, this drug shows poor efficacy in patients during the earliest infection phases. The effects of PZQ appear to operate on the voltage-operated Ca2+channels, which are located on the external Schistosoma mansoni membrane. Because some Ca2+channels have dihydropyridine drug class (a class that includes nifedipine) sensitivity, an in vitro analysis using a calcium channel antagonist (clinically used for cardiovascular hypertension) was performed to determine the antischistosomal effects of nifedipine on schistosomula and adult worm cultures. Nifedipine demonstrated antischistosomal activity against schistosomula and significantly reduced viability at all of the concentrations used alone or in combination with PZQ. In contrast, PZQ did not show significant efficacy when used alone. Adult worms were also affected by nifedipine after a 24 h incubation and exhibited impaired motility, several lesions on the tegument and intense contractility. These data support the idea of Ca2+channels subunits as drug targets and favour alternative therapeutic schemes when drug resistance has been reported. In this paper, strong arguments encouraging drug research are presented, with a focus on exploring schistosomal Ca2+channels.

The use of halloysite clay and carboxyl-functionalised multi-walled carbon nanotubes for recombinant LipL32 antigen delivery enhanced the IgG response

We studied the feasibility of using halloysite clay nanotubes (HNTs) and carboxyl-functionalised multi-walled carbon nanotubes (COOH-MWCNTs) as antigen carriers to improve immune responses against a recombinant LipL32 protein (rLipL32). Immunisation using the HNTs or COOH-MWCNTs significantly increased the rLipL32-specific IgG antibody titres (p < 0.05) of Golden Syrian hamsters. None of the vaccines tested conferred protection against a challenge using a virulent Leptospira interrogans strain. These results demonstrated that nanotubes can be used as antigen carriers for delivery in hosts and the induction of a humoral immune response against purified leptospiral antigens used in subunit vaccine preparations.

A three-pronged approach to social business: a Brazilian multi-case analysis

Social businesses present a new paradigm to capitalism, in which private companies, non-profit organizations and civil society create a new type of business with the main objective of solving social problems with financial sustainability and efficiency through market mechanisms. As any new phenomenon, different authors conceptualize social businesses with distinct views. This article aims to present and characterize three different perspectives of social business definitions: the European, the American and that of the emerging countries. Each one of these views was illustrated by a different Brazilian case. We conclude with the idea that all the cases have similar characteristics, but also relevant differences that are more than merely geographical. The perspectives analyzed in this paper provide an analytical framework for understanding the field of social businesses. Moreover, the cases demonstrate that in the Brazilian context the field of social business is under construction and that as such it draws on different conceptual influences to deal with a complex and challenging reality.

The generation and re-generation of social capital and enterprises in multi-stakeholders social cooperative enterprises: a system dynamic approach

Theories on social capital and on social entrepreneurship have mainly highlighted the attitude of social capital to generate enterprises and to foster good relations between third sector organizations and the public sector. This paper considers the social capital in a specific third sector enterprise; here, multi-stakeholder social cooperatives are seen, at the same time, as social capital results, creators and incubators. In the particular enterprises that identify themselves as community social enterprises, social capital, both as organizational and relational capital, is fundamental: SCEs arise from but also produce and disseminate social capital. This paper aims to improve the building of relational social capital and the refining of helpful relations drawn from other arenas, where they were created and from where they are sometimes transferred to other realities, where their role is carried on further (often working in non-profit, horizontally and vertically arranged groups, where they share resources and relations). To represent this perspective, we use a qualitative system dynamic approach in which social capital is measured using proxies. Cooperation of volunteers, customers, community leaders and third sector local organizations is fundamental to establish trust relations between public local authorities and cooperatives. These relations help the latter to maintain long-term contracts with local authorities as providers of social services and enable them to add innovation to their services, by developing experiences and management models and maintaining an interchange with civil servants regarding these matters. The long-term relations and the organizational relations linking SCEs and public organizations help to create and to renovate social capital. Thus, multi-stakeholder cooperatives originated via social capital developed in third sector organizations produce new social capital within the cooperatives themselves and between different cooperatives (entrepreneurial components of the third sector) and the public sector. In their entrepreneurial life, cooperatives have to contrast the "working drift," as a result of which only workers remain as members of the cooperative, while other stakeholders leave the organization. Those who are not workers in the cooperative are (stake)holders with "weak ties," who are nevertheless fundamental in making a worker's cooperative an authentic social multi-stakeholders cooperative. To maintain multi-stakeholder governance and the relations with third sector and civil society, social cooperatives have to reinforce participation and dialogue with civil society through ongoing efforts to include people that provide social proposals. We try to represent these processes in a system dynamic model applied to local cooperatives, measuring the social capital created by the social cooperative through proxies, such as number of volunteers and strong cooperation with public institutions. Using a reverse-engineering approach, we can individuate the determinants of the creation of social capital and thereby give support to governance that creates social capital.

Analysis of multi-scale systemic risk in Brazil's financial market

This work analyzes whether the relationship between risk and returns predicted by the Capital Asset Pricing Model (CAPM) is valid in the Brazilian stock market. The analysis is based on discrete wavelet decomposition on different time scales. This technique allows to analyze the relationship between different time horizons, since the short-term ones (2 to 4 days) up to the long-term ones (64 to 128 days). The results indicate that there is a negative or null relationship between systemic risk and returns for Brazil from 2004 to 2007. As the average excess return of a market portfolio in relation to a risk-free asset during that period was positive, it would be expected this relationship to be positive. That is, higher systematic risk should result in higher excess returns, which did not occur. Therefore, during that period, appropriate compensation for systemic risk was not observed in the Brazilian market. The scales that proved to be most significant to the risk-return relation were the first three, which corresponded to short-term time horizons. When treating differently, year-by-year, and consequently separating positive and negative premiums, some relevance is found, during some years, in the risk/return relation predicted by the CAPM. However, this pattern did not persist throughout the years. Therefore, there is not any evidence strong enough confirming that the asset pricing follows the model.

A didática na perspectiva multi/intercultural em ação: construindo uma proposta

Este trabalho se situa no contexto da pesquisa Ressignificando a Didática na Perspectiva Multi/Intercultural, realizada com o apoio do Conselho Nacional de Pesquisas Tecnológicas, no período de 2003 a 2006. Teve por principal objetivo construir e desenvolver, em caráter exploratório, um curso de Didática dirigido à licenciatura em Pedagogia, na perspectiva multi/intercultural, com abordagem metodológica inspirada na pesquisa-ação. A experiência desenvolveu-se durante um semestre letivo e foi realizada pela equipe do Grupo de Pesquisas sobre Cotidiano Escolar, Educação e Cultura(s), composta por dez integrantes. Apoiou-se em ampla literatura sobre a temática, que vem sendo explorada pelo grupo desde 1996. Após descrição e análise do desenvolvimento do curso, são levantados questionamentos, tensões e desafios para a incorporação da interculturalidade nas práticas educativas, em torno dos seguintes eixos: múltiplas narrativas, alteridade e estranhamento, e desconstrução e resistência. Conclui reafirmando a relevância da temática abordada e a complexidade da proposta em discussão.