Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

Inequities in maternal postnatal visits among public and private patients: 2004 Pelotas cohort study

<p>Abstract</p> <p>Background</p> <p>The postnatal period is the ideal time to deliver interventions to improve the health of both the newborn and the mother. However, postnatal care shows low-level coverage in a large number of countries. The objectives of this study were to: 1) investigate inequities in maternal postnatal visits, 2) examine differences in postnatal care coverage between public and private providers and 3) explore the relationship between the absence of maternal postnatal visits and exclusive breastfeeding, use of contraceptive methods and maternal smoking three months after birth.</p> <p>Methods</p> <p>In the calendar year of 2004 a birth cohort study was started in the city of Pelotas, Brazil. Mothers were interviewed soon after delivery and at three months after birth. The absence of postnatal visits was defined as having no consultations between the time of hospital discharge and the third month post-partum. Logistic regression analysis was used to estimate the association between absence of postnatal visits and type of insurance scheme adjusting for potential confounding factors.</p> <p>Results</p> <p>Poorer women, black/mixed, those with lower level of education, single mothers, adolescents, multiparae, smokers, women who delivered vaginally and those who were not assisted by a physician were less likely to attend postnatal care. Postnatal visits were also less frequent among women who relied in the public sector than among private patients (72.4% vs 96% among public and private patients, respectively, <it>x</it>²p < 0.001) and this difference was not explained either by maternal characteristics or by health care utilization patterns. Women who attended postnatal visits were more likely to exclusively breastfeed their infants, to use contraceptive methods and to be non-smokers three months after birth.</p> <p>Conclusion</p> <p>Postpartum care is available for every woman free of charge in the Brazilian Publicly-funded health care system. However, low levels of postpartum care were seen in the study (77%). Efforts should be made to increase the percentage of women receiving postpartum care, particularly those in socially disadvantaged groups. This could include locally-adapted health education interventions that address women's beliefs and attitudes towards postpartum care. There is a need to monitor postpartum care and collected data should be used to guide policies for health care systems.</p