Vespa et al., 1994;Biron and Gazzinelli, 1995 Aliberti et al., 1996;Fearon and Locksley, 1996; Trinchieri and Scott, 1996). In addition, the early Seder et al., 1993; Abbas et al., 1996; Fearon macrophage proinflammatory cytokines by Trypanoand Locksley, 1996). During infection with T.cruzi, the soma cruzi is considered to be important in controlling induction of parasite-specific CMI is likely to be involved the infection and the outcome of Chagas' disease. Here in at least two aspects of Chagas' disease pathophysiology we show that the potent tumour necrosis factor-α-, (Vespa et al., 1994;Fearon and Locksley, 1996; Brener interleukin-12-and nitric oxide-inducing activities of and Gazzinelli, 1997). The first is the control of parasite T.cruzi trypomastigote mucins were recovered quantireplication and its spread in the vertebrate host tissues. tatively in a highly purified and characterized glycosyl-The second is the inflammatory reaction observed in the phosphatidylinositol (GPI) anchor fraction of this infected host tissues, which is likely to be a major cause material. The bioactive trypomastigote GPI fraction of cardiac tissue damage during the acute and chronic was compared with a relatively inactive GPI fraction phases of the disease. prepared from T.cruzi epimastigote mucins. The trypoRelatively little is known about the protozoan parasite mastigote GPI structures were found to contain addimolecules that initiate the synthesis of pro-inflammatory tional galactose residues and unsaturated, instead of cytokines and nitric oxide (NO) by macrophages. Recent saturated, fatty acids in the sn-2 position of the alkylstudies have suggested a role for glycosylphosphatidylacylglycerolipid component. The latter feature is esseninositol (GPI) anchors from Plasmodium falciparum tial for the extreme potency of the trypomastigote (Schofield and Hackett, 1993;Schofield et al., 1996; GPI fraction, which is at least as active as bacterial Tachado et al., 1996Tachado et al., , 1997 and Trypanosoma brucei endotoxin and Mycoplasma lipopeptide and, therefore, (Magez et al., 1998) in this process. However, no evidence one of the most potent microbial proinflammatory of the biochemical purity of the P.falciparum GPIs was agents known.provided, making estimates of their concentrations dubiKeywords: Chagas' disease/cytokines/glycosylphosphaous. Furthermore, the possibility of Mycoplasma lipopeptidylinositol/inflammation/nitric oxide tide (Mühlradt et al., 1997) contamination (that has confounded other studies into proinflammatory factors) cannot be formally excluded. In the case of the T.brucei GPI work, highly purified and structurally characterized

Exosome-like vesicles containing virulence factors, enzymes, and antigens have recently been characterized in fungal pathogens, such as Cryptococcus neoformans and Histoplasma capsulatum. Here, we describe extracellular vesicles carrying highly immunogenic ␣-linked galactopyranosyl (␣-Gal) epitopes in Paracoccidioides brasiliensis. P. brasiliensis is a dimorphic fungus that causes human paracoccidioidomycosis (PCM). For vesicle preparations, cell-free supernatant fluids from yeast cells cultivated in Ham's defined medium-glucose were concentrated in an Amicon ultrafiltration system and ultracentrifuged at 100,000 ؋ g. P. brasiliensis antigens were present in preparations from phylogenetically distinct isolates Pb18 and Pb3, as observed in immunoblots revealed with sera from PCM patients. In an enzyme-linked immunosorbent assay (ELISA), vesicle components containing ␣-Gal epitopes reacted strongly with anti-␣-Gal antibodies isolated from both Chagas' disease and PCM patients, with Marasmius oreades agglutinin (MOA) (a lectin that recognizes terminal ␣-Gal), but only faintly with natural anti-␣-Gal. Reactivity was inhibited after treatment with ␣-galactosidase. Vesicle preparations analyzed by electron microscopy showed vesicular structures of 20 to 200 nm that were labeled both on the surface and in the lumen with MOA. In P. brasiliensis cells, components carrying ␣-Gal epitopes were found distributed on the cell wall, following a punctuated confocal pattern, and inside large intracellular vacuoles. Lipid-free vesicle fractions reacted with anti-␣-Gal in ELISA only when not digested with ␣-galactosidase, while reactivity with glycoproteins was reduced after ␤-elimination, which is indicative of partial O-linked chain localization. Our findings open new areas to explore in terms of host-parasite relationships in PCM and the role played in vivo by vesicle components and ␣-galactosyl epitopes.

Abstract. Data from a six-year follow-up of Trypanosoma cruzi−infected adolescents enrolled in a randomized, double-blind, clinical trial of benznidazole showed successful chemotherapy in 64.7% (95% confidence interval [CI] ‫ס‬ 50.2−78.7) and 84.7% (95% CI ‫ס‬ 66.8−92.9), respectively, by intention-to treat and by per protocol analysis measured by seronegativity in a chemiluminescent enzyme-linked immunosorbent assay with a purified trypomastigote mucin antigen. No incident case of cardiomyopathy was detected by electrocardiogram assessment in this cohort of adolescents who had been infected in childhood. The persistent and consistently long-term negative serologic reactions suggest the absence of the parasite in the treated patients and reinforces the recommendation of early benznidazole chemotherapy for T. cruzi-infected infants as a public health policy in endemic areas.While the elimination of Chagas disease has been considered a reasonable public health goal, 1 controversies remain about the efficiency of trypanocidal chemotherapy, especially in chronic asymptomatic individuals. Currently, there is a need to find appropriate drugs or therapeutic regimens with existing drugs that can be used in Trypanosoma cruzi−infected individuals to prevent development of severe clinical forms of Chagas disease. In a previous randomized, double-blind, clinical trial carried out among infants in Brazil, we showed that a 60 day-course of benznidazole in patients with early chronic infections with T. cruzi was safe and effective in 55.8% of the children, as shown by seronegative conversion of specific antibodies after a 38-month follow-up, when compared with the placebo group.2 In addition, a short-term effect of benznidazole on the prevention of cardiac damage was also observed. A similar efficacy (62%) for benznidazole was also observed in a study conducted in Argentinean children.

Palladacycle compounds obtained from N, N-dimethyl-1-phenethylamine (dmpa), phenyl-2-pyridinyl-acetylene and 1-phenyl-3-N, N-dimethylamine-propine, respectively, were complexed to 1, 2 ethanebis (diphenylphosphine) (dppe) ligand to synthesize antitumor cyclopalladated complexes that were tested in vitro and in vivo against syngeneic B16F10-Nex2 murine melanoma cells of low immunogenicity implanted subcutaneously in mice. Complexes were not toxic to mice injected 3 times i.p. with as much as 60 M/animal/ week. Of 3 cyclopalladated complexes that were inhibitory in vitro at low concentrations (<1.25 M), complex 7a was the most active in vivo, delaying tumor growth and prolonging animal survival. In vitro, binucleate complex 7a caused a collapse of respiratory activity with an abrupt decrease of extracellular acidification on short incubation (up to 100 min), followed by DNA degradation after 24 hr. The apoptosis-like reaction to this Pd-complex was not accompanied by increased levels of caspases 1 and 3. Complex 7a bound to a bacterial plasmid DNA, causing late conformational changes after 24 hr. Two other complexes with different C, N-cycles were also apoptotic and 2 binucleated ones were inactive. These results introduce the palladacycle-dppe complexes as promising antitumor drugs with exquisite structural specificities and for action in vivo and in vitro.

BackgroundIn most countries, the financial service sector has undergone great organizational changes in the past decades, with potential negative impact on bank workers' mental health. The aim of this paper is to estimate the prevalence of minor psychiatric disorders (MPD) among Brazilian bank workers and to investigate whether they are associated with an adverse psychosocial working environment.MethodsA cross-sectional study of a random sample of 2,500 workers in a Brazilian state bank in 2008. The presence of MPD was determined by the General Health Questionnaire.(GHQ). Psychosocial work conditions were assessed by means of the Effort-Reward Imbalance (ERI) and Job Content Questionnaire (JCQ). The presence and magnitude of the independent associations between MPD and adverse psychosocial working conditions were determined by Prevalence Ratios, obtained by Poisson regression.ResultsFrom 2,337 eligible workers, 88% participated. The prevalence of MPD was greater among women (45% vs. 41%; p > 0.05). In the multivariate analysis, the prevalence of MPD was twice as high among bank workers exposed to high psychological demand and low control at work and under high effort and low reward working conditions. The lack of social support at work and the presence of over-commitment were also associated with higher prevalence of MPD. A negative interaction effect was found between over-commitment and effort-reward imbalance.ConclusionThe prevalence of MPD is high among bank workers. The results reinforce the association between MPD and adverse psychosocial working conditions, assessed by the JCQ and ERI models. The direction of the interaction observed between over-commitment and ERI was contrary to what was expected.