Corticosterone evaluation in Wistar rats infected with the Y strain of Trypanosoma cruzi during the chronic phase

Understanding the mechanisms responsible for mediating the effects of stress on Trypanosoma cruzi infection is crucial for determining the full impact of stress on Chagas` disease and for devising effective interventions. Dehydroepiandrosterone (DHEA), a steroid hormone synthesized from pregnenolone, is secreted by the adrenal cortex in response to stress. Although its physiologic role has not been fully defined, DHEA has been shown to modulate immune function. In the present study, we evaluated the levels of corticosterone and the ability of T. cruzi infection to modulate the expression of Th2 cytokines in Wistar rats with chronic Chagas` disease submitted to repetitive stress. The animals submitted to stress displayed enhanced levels of corticosterone as compared to control counterparts. Stress and infection triggered the most elevated concentrations of corticosterone. DHEA significantly reduced corticosterone levels for infected and stressed animals with DHEA. The infected animals displayed enhanced levels of IL-10 and IL-4 as compared to control ones. Stress combined with infection triggered the higher levels of IL-10 and IL-4. DHEA alone and combined with infection and stress significantly increased IL-10 and IL-4 levels. Then, this study might provide additional clues about factors that regulate some of the immunoregulatory aspects of T. cruzi infection and might offer new opportunities for therapeutic interventions. (C) 2010 Elsevier Inc. All rights reserved.

Effects of dehydroepiandrosterone-sulfate (DHEA-S) and benznidazole treatments during acute infection of two different Trypanosoma cruzi strains

A significant role for hormones in regulating the balance of Th1- and Th2-associated cytokines with a role in modulating diseases has been accumulating. Previously, we reported that dehydroepiandrosterone (DHEA), the most abundant steroid hormone synthesized by the adrenal cortex, markedly reduced the blood and tissue parasites in experimentally Trypanosoma cruzi-infected rats. Based on these findings, the main purpose of this study was to investigate the effect of dehydroepiandrosterone-sulfate ester (DHEA-S) therapy alone or in combination with benznidazole (BNZ) (recommended in Brazil for the treatment of T. cruzi infection) will be effective during the acute phase of two different lineages of T. cruzi strains: type I (Y strain) and type II (Bolivia strain) of T. cruzi. Administration of either DHEA-S or BNZ alone or in combination significantly reduced the Y strain parasite load as compared with untreated. Furthermore treatment with DHEA-S resulted in Bolivia strain clearance. This protective effect of DHEA-S was associated with the host`s immune response, as evidence by enhanced levels of interferon-gamma and interleukin-2. DHEA-S treatment also increased peritoneal macrophages levels and nitrite production. DHEA-S treatment was effective in reducing the mortality rate as compared to BNZ alone or to combiner DHEA-S+BNZ treatment of T. cruzi Bolivia strain infected animals. These findings suggest that hormonal therapy may have a protective effect in the treatment of T. cruzi infection. (C) 2009 Elsevier GmbH. All rights reserved.

Enhanced protection by melatonin and meloxicam combination in experimental infection by Trypanosoma cruzi

P>The aim of this study was to evaluate a possible synergism between melatonin and meloxicam in up-regulating the immune response in male Wistar rats infected with Trypanosoma cruzi during immunosuppression phenomenon, which characterizes the acute phase of the Chagas` disease. Male Wistar rats were infected with the Y strain of T. cruzi. Experiments were performed on 7, 14 and 21 days post-infection. Several immunological parameters were evaluated including gamma-interferon (IFN-gamma), interleukin-2 (IL-2), nitric oxide (NO) and prostaglandin E(2) (PGE(2)). The combined treatment with melatonin and meloxicam significantly enhanced the release of IL-2 and INF-gamma into animals` serum, when compared with the infected control groups during the course of infection. Furthermore, the blockade of PGE(2) synthesis and the increased release of NO by macrophage cells from T. cruzi-infected animals contributed to regulate the production of Th1 subset cytokines significantly reducing the parasitaemia in animals treated with the combination of both substances. Therefore, our results suggest that the association of melatonin and meloxicam was more effective in protecting animals against the harmful actions of T. cruzi infection as compared with the treatments of meloxicam or melatonin alone.

Trypanosoma cruzi: Do different sylvatic strains trigger distinct immune responses?

Strains of Trypanosoma cruzi are multiclonal populations that can be classified in groups or genotypes, differing in pathogenicity, virulence, and histotropism. In this experiment the distinct behavior of two strains of T. cruzi, MORC-1 and MORC-2, was documented. Blood parasitemia, spleen proliferation, nitric oxide, histopathology of the spleen and heart were used as tools to evaluate parasite persistence. Groups of male mice were separated and divided in three groups: Control (C), Infected (IM-1) and Infected (IM-2). The peak of parasitemia occurred on 10 days post infection for both strains. LPS stimulated animals, infected MORC-2 group displayed significant higher concentrations of NO when compared to infected MORC-1 group (P < 0.05). For ConA stimulated lymphoproliferation, infected MORC-1 group displayed higher proliferation index as compared to infected MORC-2 group. An opposite behavior for IL-4 and TNF-alpha was observed according to the strain. For MORC-1 enhanced concentrations of IL-4 were present with concomitant reduced levels of TNF-alpha, while for MORC-2 enhanced concentrations of TNF-alpha and reduced levels of IL-4 were found. The histopathology of heart and spleen showed important differences in which MORC-1 displayed statistically enhanced number of amastigote in the heart and spleen as compared to MORC-2. Concluding, each strain triggered a distinct immune response with enhanced cytokine TH-1 profile for MORC-2 and TH-2 for MORC-1. (C) 2009 Elsevier Inc. All rights reserved.

Melatonin and dehydroepiandrosterone combination: does this treatment exert a synergistic effect during experimental Trypanosoma cruzi infection?

Previous studies showed that melatonin or dehydroepiandrosterone (DHEA) enhances the immune response against parasitic pathogens. The present study investigated the in vitro activity of melatonin combined with DHEA in a period of 24 hr during the course of in vivo T. cruzi infection. The in vitro activity of melatonin or DHEA alone, as well as together, were tested for the trypomastigote forms (doses ranging from 0.5 to 128 mu m). In vitro, neither melatonin nor DHEA alone had any activity against trypomastigote forms, although when the highest concentration of combined melatonin and DHEA was used, it was active against the trypomastigote forms of the parasite. However, for this concentration, a quite toxicity on peritoneal macrophages was observed. For in vivo evaluation, male Wistar rats were infected with the Y strain of T. cruzi. They were orally treated with 10 mg/kg body weight/day of melatonin and subcutaneously with 40 mg/kg body weight/day of DHEA. Treatment with melatonin, DHEA and the association showed a significant reduction in the number of blood trypomastigotes during the acute phase of infection as compared to untreated animals (P < 0.05). A significant increase in the number of macrophages and nitric oxide (NO) concentrations were observed during the peak of parasitaemia with melatonin alone or combined with DHEA. However, with DHEA alone the highest concentration of NO was observed (P < 0.05). Moreover, DHEA treatment increased TNF-alpha levels during the infection (P < 0.05). These results show that melatonin, DHEA or the combination of both reduces parasitemia during the acute phase of infection. The combined action of both molecules did not exert a synergic action on the host`s ability to fight infection, and it seems that among all treatments DHEA induces a more efficient immune response.

Influence of melatonin therapy and orchiectomy on T cell subsets in male Wistar rats infected with Trypanosoma cruzi

Gonadal steroids exert an important influence on the host immune response during infection. Changes resulting from the absence or replacement of gonadal hormones may represent a distinct evolution of a particular parasite. Taking into account the greater susceptibility of males to parasites, the magnitude of the immune response seems to depend on the interaction of many hormones that will act synergistically with other immune cells. The aims of this research were to evaluate the effects of the luck of male sex hormones due to orchiectomy, and the influence of oral administration of melatonin on the immune response of male Wistar rats infected with the Y strain of Trypanosoma cruzi. The percentage of CD3(+) CD4(+) and CD3(+) CD8(+) lymphocyte T cell subsets were evaluated using flow cytometry and the measurement of IL-2 and IL-12. For all parameters examined, a synergistic action of melatonin and orchiectomy on the host`s immune response was observed, promoting an effective response against the parasite during the acute phase of infection. These results offer insight into other possibilities for possibly controlling T. cruzi proliferation through melatonin therapy and also the stimulatory effects on host`s immune response triggered by the absence of male gonadal steroids during the acute phase of infection.

Counterregulation of Th2 immunity by interleukin 12 reduces host defenses against Strongyloides venezuelensis infection

The aim of this study was to investigate the role of interleukin 12 (IL-12) during Strongyloides venezuelensis infection. IL-12(-/-) and wildtype C57BL/6 mice were subcutaneously infected with 1500 larvae of S. venezuelensis. On days 7, 14, and 21 post-infection, we determined eosinophil and mononuclear cell numbers in the blood and broncoalveolar lavage fluid (BALF), Th2 cytokine secretion in the lung parenchyma, and serum antibody levels. The numbers of eggs in the feces and worm parasites in the duodena were also quantified. The eosinophil and mononuclear cell counts and the concentrations of IL-3, IL-5, IL-10, IL-13, and IgG1 and IgE antibodies increased significantly in infected IL-12(-/-) and wild-type mice as compared with uninfected controls. However, the number of eosinophils and mononuclear cells in the blood and BALF and the Th2 cytokine levels in the lungs of infected IL-12-/- mice were greater than in infected wild-type C57BL/6 mice. In addition, serum IgE and IgG1 levels were also significantly enhanced in the infected mice lacking IL-12. Meanwhile, parasite burden and fecal egg counts were significantly decreased in infected IL-12-/- mice. Together, our results showed that the absence of IL-12 upregulates the Th2 immune response, which is important for control of S. venezuelensis infection. (C) 2009 Elsevier Masson SAS. All rights reserved.

A new thrombospondin-related anonymous protein homologue in Neospora caninum (NcMIC2-like1)

Neospora caninum is an Apicomplexan protozoan that has the dog as a definitive host and cattle (among other animals) as intermediate hosts. It causes encephalopathy in dogs and abortion in cows, with significant loss in worldwide livestock. As any Apicomplexan, the parasite invades the cells using proteins contained in the phylum-specific organelles, like the micronemes, rhoptries and dense granules. The aim of this study was the characterization of a homologue (denominated NcMIC2-like1) of N. caninum thrombospondin-related anonymous protein (NcMIC2), a micronemal protein previously shown to be involved in the attachment and connection with the intracellular motor responsible for the active process of invasion. A polyclonal antiserum raised against the recombinant NcMIC2-like1 functional core (thrombospondin and integrin domains) recognized the native form of NcMIC2-like1, inhibited the in vitro invasion process and localized NcMIC2-like1 at the apical complex of the parasite by confocal immunofluorescence, indicating its micronemal localization. The new molecule, NcMIC2-like1, has features that differentiates it from NcMIC2 in a substantial way to be considered a homologue dagger.

The predicate marker li in Mauritian Creole

There is a morpheme 'li' in Mauritian Creole (MC), which is homophonous with the 3sg pronoun, and which, in the early creole, occurs frequently between the subject and the predicate in affirmative, present tense clauses. I propose that that 'li' may have originated as a resumptive pronoun, co-referential with the subject, but following the grammaticalization of new determiner elements to mark the semantic contrasts of [±definite] and singular vs. plural, 'li' has now grammaticalized into a predicate marker. Its presence is sensitive to both the nature of the predicate, and to the definiteness and specificity features of the subject NP. My analysis is within the framework of Truth Conditional Semantics, where indefinite NPs are analyzed as variables that get introduced into the discourse, and must be bound by an operator to yield a closed proposition, with a truth value. Drawing on a comparison with a cognative morpheme 'i' in Seychellois Creole, I claim that its path to grammaticalization is linked to that of the specificity marking 'la'.

Thermal effects in the evolution of initially layered mantle material

A simplified model for anisotropic mantle convection based on a novel class of rheologies, originally developed for folding instabilities in multilayered rock (MUHLHAUS et al., 2002), is extended ¨ through the introduction of a thermal anisotropy dependent on the local layering. To examine the effect of the thermal anisotropy on the evolution of mantle material, a parallel implementation of this model was undertaken using the Escript modelling toolkit and the Finley finite-element computational kernel (DAVIES et al., 2004). For the cases studied, there appears too little if any effect. For comparative purposes, the effects of anisotropic shear viscosity and the introduced thermal anisotropy are also presented. These results contribute to the characterization of viscous anisotropic mantle convection subject to variation in thermal conductivities and shear viscosities.

Fault-tolerant quantum computation with cluster states

The one-way quantum computing model introduced by Raussendorf and Briegel [Phys. Rev. Lett. 86, 5188 (2001)] shows that it is possible to quantum compute using only a fixed entangled resource known as a cluster state, and adaptive single-qubit measurements. This model is the basis for several practical proposals for quantum computation, including a promising proposal for optical quantum computation based on cluster states [M. A. Nielsen, Phys. Rev. Lett. (to be published), quant-ph/0402005]. A significant open question is whether such proposals are scalable in the presence of physically realistic noise. In this paper we prove two threshold theorems which show that scalable fault-tolerant quantum computation may be achieved in implementations based on cluster states, provided the noise in the implementations is below some constant threshold value. Our first threshold theorem applies to a class of implementations in which entangling gates are applied deterministically, but with a small amount of noise. We expect this threshold to be applicable in a wide variety of physical systems. Our second threshold theorem is specifically adapted to proposals such as the optical cluster-state proposal, in which nondeterministic entangling gates are used. A critical technical component of our proofs is two powerful theorems which relate the properties of noisy unitary operations restricted to act on a subspace of state space to extensions of those operations acting on the entire state space. We expect these theorems to have a variety of applications in other areas of quantum-information science.

Wolbachia: Invasion biology in South Pacific butterflies

Wolbachia ensdosymbionts are well known for their ability to manipulate the population biology and development of their hosts. One of the less studied outcomes of Wolbachia infection with this symbiont is the selective killing of male embryos. Recent work on butterflies living on different South Pacific islands is beginning to help us understand the complexity of the co-evolutionary interactions between these partners.

Wolbachia genomes: insights into an intracellular lifestyle

The genome sequence of the Wolbachia endosymbiont that infects the nematode Brugia malayi has recently been determined together with three partial Wolbachia genomes from different Drosophila species. These data along with the previously published Wolbachia genome from Drosophila melanogaster provide new insights into how this endosymbiont has managed to become so successful.

The potential of virulent Wolbachia to modulate disease transmission by insects

A virulent strain of Wolbachia has recently been identified in Drosophila that drastically reduces adult lifespan. It has been proposed that this phenotype might be introduced into insect disease vector populations to reduce pathogen transmission. Here we model the requirements for spread of such an agent and the associated reduction in disease transmission. First, a simulation of mosquito population age structure was used to describe the age distribution of mosquitoes transmitting dengue virus. Second, given varying levels of cytoplasmic incompatibility and fecundity effect, the maximum possible longevity reduction that would allow Wolbachia to invade was obtained. Finally, the two models were combined to estimate the reduction in disease transmission according to different introduction frequencies. With strong CI and limited effect of fecundity, an introduction of Wolbachia with an initial frequency of 0.4 could result in a 60–80% reduction of transmitting mosquitoes. Greater reductions are possible at higher initial release rates.

Wolbachia infections of tephritid fruit flies: molecular evidence for five distinct strains in a single host species

Endosymbiotic bacteria of the genus Wolbachia are widespread among arthropods and can induce cytoplasmic incompatibility, thelytokous parthenogenesis, male-killing or feminization in their hosts. Here, we report phylogenetic relationships of Wolbachia in tephritid fruit flies based on wsp gene sequences. We also report, for the first time, five distinct strains of Wolbachia in Bactrocera ascita sp. B. Four of the five Wolbachia strains found in this species were in the same groups as those found in other tephritid fruit flies, suggesting possible horizontal transmission of Wolbachia from other fruit flies into B. ascita sp. B. The unreliability of wsp-specific group primers demonstrated in this study suggests that these primers might be useful only for preliminary identification of Wolbachia. Final determination of group affiliation needs to be verified with wsp sequence data.