Área de PDI em Pesquisa, Desenvolvimento e Inovação em Doença de Chagas 2013
Veja, abaixo, a relação de artigos científicos publicados pelo IOC, na referida Área Temática, organizados em ordem alfabética crescente:
| Batista VSP, Fernandes FA, Cordeiro-Estrela P, Sarquis O and Lima MM (2013), "Ecotope effect in Triatoma brasiliensis (Hemiptera: Reduviidae) suggests phenotypic plasticity rather than adaptation", Medical and Veterinary Entomology., September, 2013. Vol. 27(3), pp. 247-254. Wiley-blackwell. [DOI] |
| Abstract: Triatoma brasiliensis (Hemiptera: Reduviidae) is an important vector of Chagas' disease in both sylvatic and peridomestic ecotopes. Discriminating between these populations of Triatominae has been proposed as a means of investigating re-infestation rates of human dwellings. Geometric morphometrics have been widely applied in the study of Triatominae polymorphisms at species and population levels. This study characterizes morphometric differences between sylvatic and peridomestic populations, as well as between sexes in T. brasiliensis specimens from Jaguaruana, Ceara, in northeastern Brazil. No differences in either the shape or size of the cephalic capsule were apparent between sexes or ecotopes. However, the wings showed differentiation in shape and size. Sexual dimorphism was detected, with females presenting significantly higher values and conformations. Size differentiation was also evident, with sylvatic specimens being generally larger than peridomestic examples. These results indicate that differences in the wings of T. brasiliensis may be related to the existence of phenotypic plasticity, and variations in size and shape may be associated with different ecotopes, possibly as a result of conditions in each micro-habitat, such as temperature, relative humidity, food supply and density. |
BibTeX:@article{Batista2013, author = {Batista, V. S. P. and Fernandes, F. A. and Cordeiro-Estrela, P. and Sarquis, O. and Lima, M. M.}, title = {Ecotope effect in Triatoma brasiliensis (Hemiptera: Reduviidae) suggests phenotypic plasticity rather than adaptation}, journal = {Medical and Veterinary Entomology}, publisher = {Wiley-blackwell}, year = {2013}, volume = {27}, number = {3}, pages = {247--254}, doi = {10.1111/j.1365-2915.2012.01043.x}} |
| Choy JW, Bryant C, Calvet CM, Doyle PS, Gunatilleke SS, Leung SSF, Ang KKH, Chen S, Gut J, Oses-Prieto JA, Johnston JB, Arkin MR, Burlingame AL, Taunton J, Jacobson MP, McKerrow JM, Podust LM and Renslo AR (2013), "Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target", Beilstein Journal of Organic Chemistry., January, 2013. Vol. 9, pp. 15-25. Beilstein-institut. [DOI] |
| Abstract: Inhibition of the Trypanosoma cruzi cysteine protease cruzain has been proposed as a therapeutic approach for the treatment of Chagas' disease. Among the best-studied cruzain inhibitors to date is the vinylsulfone K777 (1), which has proven effective in animal models of Chagas' disease. Recent structure-activity studies aimed at addressing potential liabilities of 1 have now produced analogues such as N-[(2S)-1-[[(E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]amino]-3-(4-methylphenyl)-1-oxopropan-2-yl]pyridine-4-carboxamide (4), which is trypanocidal at ten-fold lower concentrations than for 1. We now find that the trypanocidal activity of 4 derives primarily from the inhibition of T. cruzi 14-alpha-demethylase (TcCYP51), a cytochrome P450 enzyme involved in the biosynthesis of ergosterol in the parasite. Compound 4 also inhibits mammalian CYP isoforms but is trypanocidal at concentrations below those required to significantly inhibit mammalian CYPs in vitro. A chemical-proteomics approach employing an activity-based probe derived from 1 was used to identify mammalian cathepsin B as a potentially important off-target of 1 and 4. Computational docking studies and the evaluation of truncated analogues of 4 reveal structural determinants for TcCYP51 binding, information that will be useful in further optimization of this new class of inhibitors. |
BibTeX:@article{Choy2013, author = {Choy, J. W. and Bryant, C. and Calvet, C. M. and Doyle, P. S. and Gunatilleke, S. S. and Leung, S. S. F. and Ang, K. K. H. and Chen, S. and Gut, J. and Oses-Prieto, J. A. and Johnston, J. B. and Arkin, M. R. and Burlingame, A. L. and Taunton, J. and Jacobson, M. P. and McKerrow, J. M. and Podust, L. M. and Renslo, A. R.}, title = {Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target}, journal = {Beilstein Journal of Organic Chemistry}, publisher = {Beilstein-institut}, year = {2013}, volume = {9}, pages = {15--25}, doi = {10.3762/bjoc.9.3}} |
| Correia N, Almeida CE, Lima-Neiva V, Gumiel M, Dornak LL, Lima MM, Medeiros LMO, Mendonca VJ, da Rosa JA and Costa J (2013), "Cross-mating experiments detect reproductive compatibility between Triatoma sherlocki and other members of the Triatorna brasiliensis species complex", Acta Tropica., October, 2013. Vol. 128(1), pp. 162-167. Elsevier Science Bv. [DOI] |
| Abstract: Phylogenetic approaches based on mitochondrial DNA variation (fragments of Cyt B and 16S ribosomal RNA) have revealed Triatoma sherlocki as the most recent species addition to the Triatoma brasiliensis species complex; a monophyletic group which includes T. brasiliensis, Triatoma melanica, and Triatoma juazeirensis. T. sherlocki is the most differentiated among all species of this complex: it is unable to fly, possesses longer legs than the other members, and has reddish tonality in some parts of its exochorion. We question whether these species are reproductively compatible because of this pronounced morphological differentiation, and therefore, we present a series of cross breeding experiments that test compatibility between T. sherlocki and other members of the T. brasiliensis complex. We extended our analyses to include crosses between T. sherlocki and Triatoma lend, because the latter has been suggested as a possible member of this complex. T. sherlocki male x T. lend female pairs failed to produce hybrids. All other crosses of T. sherlocki and members of T. brasiliensis species complex, as well as backcrosses, produced viable offspring through the third generation. This study stresses the importance of searching for the features that may isolate members of the T. brasiliensis species complex. (C) 2013 Elsevier B.V. All rights reserved. |
BibTeX:@article{Correia2013, author = {Correia, N. and Almeida, C. E. and Lima-Neiva, V. and Gumiel, M. and Dornak, L. L. and Lima, M. M. and Medeiros, L. M. O. and Mendonca, V. J. and da Rosa, J. A. and Costa, J.}, title = {Cross-mating experiments detect reproductive compatibility between Triatoma sherlocki and other members of the Triatorna brasiliensis species complex}, journal = {Acta Tropica}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {128}, number = {1}, pages = {162--167}, doi = {10.1016/j.actatropica.2013.06.019}} |
| Coura JR (2013), "The discovery of Chagas disease (1908-1909): great successes and certain misunderstandings and challenges", Revista Da Sociedade Brasileira De Medicina Tropical., July, 2013. Vol. 46(4), pp. 389-390. Soc Brasileira Medicina Tropical. [DOI] |
BibTeX:@article{Coura2013, author = {Coura, J. R.}, title = {The discovery of Chagas disease (1908-1909): great successes and certain misunderstandings and challenges}, journal = {Revista Da Sociedade Brasileira De Medicina Tropical}, publisher = {Soc Brasileira Medicina Tropical}, year = {2013}, volume = {46}, number = {4}, pages = {389--390}, doi = {10.1590/0037-8682-0143-2013}} |
| Da Silva RB, Loback VB, Salomao K, de Castro SL, Wardell JL, Wardell SMSV, Costa TEMM, Penido C, Henriques MDMD, Carvalho SA, da Silva EF and Fraga CAM (2013), "Synthesis and Trypanocidal Activity of Novel 2,4,5-Triaryl-N-Hydroxylimidazole Derivatives", Molecules., March, 2013. Vol. 18(3), pp. 3445-3457. Mdpi Ag. [DOI] |
| Abstract: Herein, we report the design, synthesis and trypanocidal activity of some novel trisubstituted imidazole derivatives. These heterocyclic derivatives were structurally planned by exploring the concept of molecular hybridisation between two arylhydrazones derived from megazol, which has potent trypanocidal activity. The trypanocidal activity of these triarylimidazole derivatives was evaluated against infective trypomastigote forms of T. cruzi and the derivative 2'-(4-bromophenyl)-1-methyl-5'-phenyl-1H,3'H-2,4'-biimidazol-3'-ol showed moderate biological activity (IC50 = 23.9 mu M) when compared to benznidazole, a standard trypanocidal drug. These compounds did not present cytotoxic effects at concentrations near the trypanocidal IC50, being considered a good starting point for the development of new anti-Chagas drug candidates. |
BibTeX:@article{, author = {Da Silva, R. B. and Loback, V. B. and Salomao, K. and de Castro, S. L. and Wardell, J. L. and Wardell, S. M. S. V. and Costa, T. E. M. M. and Penido, C. and Henriques, M. D. M. D. and Carvalho, S. A. and da Silva, E. F. and Fraga, C. A. M.}, title = {Synthesis and Trypanocidal Activity of Novel 2,4,5-Triaryl-N-Hydroxylimidazole Derivatives}, journal = {Molecules}, publisher = {Mdpi Ag}, year = {2013}, volume = {18}, number = {3}, pages = {3445--3457}, doi = {10.3390/molecules18033445}} |
| De Araujo VAL, Boite MC, Cupolillo E, Jansen AM and Roque ALR (2013), "Mixed infection in the anteater Tamandua tetradactyla (Mammalia: Pilosa) from Para State, Brazil: Trypanosoma cruzi, T. rangeli and Leishmania infantum", Parasitology., April, 2013. Vol. 140(4), pp. 455-460. Cambridge Univ Press. [DOI] |
| Abstract: Some Trypanosoma and Leishmania species are multi-host parasites whose distribution overlaps in several parts of the Brazilian Amazon basin. Despite being a common trait among wild mammals, mixed infections and their consequences for the host's health and parasite transmission are still a poorly known phenomenon. Here we describe a triple mixed infection - Trypanosoma cruzi, T. rangeli and Leishmania infantum - in a bone marrow sample from an anteater Tamandua tetradactyla captured in a house backyard from the endemic Abaetetuba municipality in the Amazon basin. T. cruzi was also isolated from blood samples. The mini-exon multiplex PCR characterization detected the infection by T. rangeli and T. cruzi (TcI genotype), while L. infantum infection was confirmed by an ITS-PCR followed by amplicon sequencing. This is the first description of T. rangeli isolation from bone marrow and the first report of L. infantum infection in xenarthrans. The implications of this finding are discussed considering the influence of mixed infections in the role of this mammal species as a putative reservoir host of these 3 trypanosomatid species. |
BibTeX:@article{, author = {De Araujo, V. A. L. and Boite, M. C. and Cupolillo, E. and Jansen, A. M. and Roque, A. L. R.}, title = {Mixed infection in the anteater Tamandua tetradactyla (Mammalia: Pilosa) from Para State, Brazil: Trypanosoma cruzi, T. rangeli and Leishmania infantum}, journal = {Parasitology}, publisher = {Cambridge Univ Press}, year = {2013}, volume = {140}, number = {4}, pages = {455--460}, doi = {10.1017/S0031182012001886}} |
| de Meis J, Barreto de Albuquerque J, Silva Dos Santos D, Farias-de-Oliveira DA, Berbert LR, Cotta-de-Almeida V and Savino W (2013), "Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice.", Front Immunol. Vol. 4, pp. 216. [DOI] |
| Abstract: Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. |
BibTeX:@article{deMeis2013a, author = {de Meis, Juliana and Barreto de Albuquerque, Juliana and Silva Dos Santos, Danielle and Farias-de-Oliveira, Désio Aurélio and Berbert, Luiz Ricardo and Cotta-de-Almeida, Vinícius and Savino, Wilson}, title = {Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice.}, journal = {Front Immunol}, year = {2013}, volume = {4}, pages = {216}, url = {http://dx.doi.org/10.3389/fimmu.2013.00216}, doi = {10.3389/fimmu.2013.00216}} |
| De Souza-Lima RD, Barbosa MDV, Coura JR, Arcanjo ARL, Nascimento AD, Ferreira JMBB, Magalhaes LK, de Albuquerque BC, Araujo GAN and Guerra JAD (2013), "Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon", Revista Da Sociedade Brasileira De Medicina Tropical., July, 2013. Vol. 46(4), pp. 510-514. Soc Brasileira Medicina Tropical. [DOI] |
| Abstract: Introduction: Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. Methods: We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. Results: There were 15 males (average age, 31.3 years), all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. Conclusions: All patients had consumed acai products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil |
BibTeX:@article{Souza-Lima2013, author = {De Souza-Lima, R. D. and Barbosa, M. D. V. and Coura, J. R. and Arcanjo, A. R. L. and Nascimento, A. D. and Ferreira, J. M. B. B. and Magalhaes, L. K. and de Albuquerque, B. C. and Araujo, G. A. N. and Guerra, J. A. D.}, title = {Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon}, journal = {Revista Da Sociedade Brasileira De Medicina Tropical}, publisher = {Soc Brasileira Medicina Tropical}, year = {2013}, volume = {46}, number = {4}, pages = {510--514}, doi = {10.1590/0037-8682-1367-2013}} |
| Diogo EBT, Dias GG, Rodrigues BL, Guimarães TT, Valença WO, Camara CA, de Oliveira RN, da Silva MG, Ferreira VF, de Paiva YG, Goulart MOF, Menna-Barreto RFS, de Castro SL and da Silva Júnior EN (2013), "Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: Electrochemical studies on the effects of the quinoidal moiety.", Bioorg Med Chem., Nov, 2013. Vol. 21(21), pp. 6337-6348. [DOI] |
| Abstract: In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17-24, 28-30 and 36-38 are described herein for the first time. Three of these novel compounds (28-30) were found to be more potent than the standard drug benznidazole, with IC50/24h values between 6.8 and 80.8μM. Analysis of the toxicity to heart muscle cells led to LC50/24h of <125, 63.1 and 281.6μM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. |
BibTeX:@article{Diogo2013, author = {Diogo, Emilay B T. and Dias, Gleiston G. and Rodrigues, Bernardo L. and Guimarães, Tiago T. and Valença, Wagner O. and Camara, Celso A. and de Oliveira, Ronaldo N. and da Silva, Mauro G. and Ferreira, Vitor F. and de Paiva, Yen Galdino and Goulart, Marilia O F. and Menna-Barreto, Rubem F S. and de Castro, Solange L. and da Silva Júnior, Eufrânio N.}, title = {Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: Electrochemical studies on the effects of the quinoidal moiety.}, journal = {Bioorg Med Chem}, year = {2013}, volume = {21}, number = {21}, pages = {6337--6348}, url = {http://dx.doi.org/10.1016/j.bmc.2013.08.055}, doi = {10.1016/j.bmc.2013.08.055}} |
| Farias-de-Oliveira DA, Villa-Verde DMS, Panzenhagen PHN, dos Santos DS, Berbert LR, Savino W and de Meis J (2013), "Caspase-8 and caspase-9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely infected mice", Journal of Leukocyte Biology., February, 2013. Vol. 93(2), pp. 227-234. Federation Amer Soc Exp Biol. [DOI] |
| Abstract: Trypanosoma cruzi acute infection leads to thymic atrophy, largely as a result of death of immature DP T cells. In a second vein, the glucocorticoid hormone imbalance promotes DP T cell apoptosis in infected mice. Herein, we assessed the involvement of caspase signaling in thymocyte death during T. cruzi acute infection. BALB/c mice were infected i.p. with 10(2) trypomastigote forms of T. cruzi and analyzed from 7 to 19 dpi. Thymocyte apoptosis was observed in early stages of infection, increasing along with time postinfection. Immature DN and DP as well as CD4(+) and CD8(+) thymocytes from infected mice showed increased activation of caspase-8, -9, and -3. In vitro treatment of thymocytes from infected mice with a general caspase inhibitor or the combination of caspase-8- and caspase-9-specific inhibitors increased the number of living thymocytes. Intrathymic injection of the general caspase inhibitor, but not caspase-8 or -9 inhibitors individually, prevented thymic atrophy and thymocyte depletion in infected mice. Moreover, blockade of glucocorticoid receptor activity with RU486 prevented DP thymocyte apoptosis, together with caspase-8 and -9 activation. These findings indicate that DP T cell apoptosis following experimental T. cruzi acute infection is dependent on glucocorticoid stimulation, promoting caspase-8 and -9 activation. J. Leukoc. Biol. 93: 227-234; 2013. |
BibTeX:@article{Farias-de-Oliveira2013, author = {Farias-de-Oliveira, D. A. and Villa-Verde, D. M. S. and Panzenhagen, P. H. N. and dos Santos, D. S. and Berbert, L. R. and Savino, W. and de Meis, J.}, title = {Caspase-8 and caspase-9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely infected mice}, journal = {Journal of Leukocyte Biology}, publisher = {Federation Amer Soc Exp Biol}, year = {2013}, volume = {93}, number = {2}, pages = {227--234}, doi = {10.1189/jlb.1211589}} |
| Giarola NLL, de Almeida-Amaral EE, Collopy I, Fonseca-de-Souza AL, Majerowicz D, Paes LS, Gondim KC and Meyer-Fernandes JR (2013), "Trypanosoma cruzi: Effects of heat shock on ecto-ATPase activity", Experimental Parasitology., April, 2013. Vol. 133(4), pp. 434-441. Academic Press Inc Elsevier Science. [DOI] |
| Abstract: In this work, we demonstrate that Dypanosoma cruzi Y strain epimastigotes exhibit Mg2+-dependent ecto-ATPase activity that is stimulated by heat shock. When the epimastigotes were incubated at 37 degrees C for 2 h, the ecto-ATPase activity of the cells was 43.95 +/- 0.97 nmol Pi/h x 10(7) cells, whereas the ecto-ATPase activity of cells that were not exposed to heat shock stress was 16.97 +/- 0.30 nmol Pi/h x 10(7) cells. The ecto-ATPase activities of cells, that were exposed or not exposed to heat shock stress had approximately the same K-m values (2.25 +/- 0.26 mM ATP and 1.55 +/- 0.23 mM ATP, respectively) and different V-max values. The heat-shocked cells had higher V-max values (54.38 +/- 3.07 nmol Pi/h x 10(7) cells) than the cells that were not exposed to heat shock (19.38 +/- 1.76 nmol Pi/h x 10(7) cells). We also observed that the ectophosphatase and ecto-5'nucleotidase activities of cells that had been incubated at 28 degrees C or 37 degrees C were the same. Interestingly, cycloheximide, an inhibitor of protein synthesis, suppressed the heat shock effect of ecto-ATPase activity on T. cruzi. The Mg2+-dependent ecto-ATPase activity from the Y strain (high virulence) was approximately 2-fold higher than that of Dm28c (a clone with low virulence). In addition, these two strains presented different responses to heat shock with regard to their ecto-ATPase activities; Y strain epimastigotes had a stimulation of 2.52-fold while the Dm28c strain had a 1.71-fold stimulation. In this context, the virulent trypomastigote form of T. cruzi, Dm28c, had an ecto-ATPase activity that was more than 7-fold higher (66.67 +/- 5.98 nmol Pi/h x 10(7) cells) than that of the insect epimastigote forms (8.91 +/- 0.76 nmol Pi/h x 10(7) cells). This difference increased to approximately 10-fold when both forms were subjected to heat shock stress (181.14 +/- 16.48 nmol Pi/h x 10(7) cells for trypomastigotes and 16.71 +/- 1.17 nmol Pi/h x 10(7) cells for epimastigotes at 37 degrees C). The ecto-ATPase activity of a plasma membrane-enriched fraction obtained from T. cruzi epimastigotes was not increased by heat treatment, which suggested that cytoplasmic components had an influence on enzyme activation by heat shock stress. (C) 2012 Elsevier Inc. All rights reserved. |
BibTeX:@article{, author = {Giarola, N. L. L. and de Almeida-Amaral, E. E. and Collopy, I. and Fonseca-de-Souza, A. L. and Majerowicz, D. and Paes, L. S. and Gondim, K. C. and Meyer-Fernandes, J. R.}, title = {Trypanosoma cruzi: Effects of heat shock on ecto-ATPase activity}, journal = {Experimental Parasitology}, publisher = {Academic Press Inc Elsevier Science}, year = {2013}, volume = {133}, number = {4}, pages = {434--441}, doi = {10.1016/j.exppara.2012.12.014}} |
| Gomes TF, Freitas FSS, Bezerra CM, Lima MM and Carvalho-Costa FA (2013), "Reasons for persistence of dwelling vulnerability to Chagas disease (American trypanosomiasis): a qualitative study in northeastern Brazil.", World Health Popul. Vol. 14(3), pp. 14-21. |
| Abstract: Interaction between Chagas disease vectors and man is continuous in vulnerable dwellings, in which the vectors feed on man and find conditions for reproduction. This study explores factors that affect the choice of home construction methods in a rural community in Brazil, emphasizing the rationale for the persistence of dwelling vulnerability. Information on local resident perspectives regarding safety and home construction methods was gathered through domiciliary interviews with open questionnaires. The study revealed a large proportion of vulnerable mud huts, with others under construction. Insecurity over land tenure inhibits the construction of definitive houses. Mud homes are associated with greater structural stability. Cultural and economic factors have clearly been linked to the choice of method for home construction. The economic evolution of family conflicts with traditional aspects as well as the relative increased cost of the materials needed for mud house construction has not completely inhibited building with mud. |
BibTeX:@article{Gomes2013, author = {Gomes, Taís F. and Freitas, Francisca Samya S. and Bezerra, Claudia M. and Lima, Marli M. and Carvalho-Costa, Filipe A.}, title = {Reasons for persistence of dwelling vulnerability to Chagas disease (American trypanosomiasis): a qualitative study in northeastern Brazil.}, journal = {World Health Popul}, year = {2013}, volume = {14}, number = {3}, pages = {14--21}} |
| Grieco MAB, Cavalcante JJV, Cardoso AM, Vieira RP, Machado EA, Clementino MM, Medeiros MN, Albano RM, Garcia ES, de Souza W, Constantino R and Martins OB (2013), "Microbial Community Diversity in the Gut of the South American Termite Cornitermes cumulans (Isoptera: Termitidae)", Microbial Ecology., January, 2013. Vol. 65(1), pp. 197-204. Springer. [DOI] |
| Abstract: Termites inhabit tropical and subtropical areas where they contribute to structure and composition of soils by efficiently degrading biomass with aid of resident gut microbiota. In this study, culture-independent molecular analysis was performed based on bacterial and archaeal 16S rRNA clone libraries to describe the gut microbial communities within Cornitermes cumulans, a South American litter-feeding termite. Our data reveal extensive bacterial diversity, mainly composed of organisms from the phyla Spirochaetes, Bacteroidetes, Firmicutes, Actinobacteria, and Fibrobacteres. In contrast, a low diversity of archaeal 16S rRNA sequences was found, comprising mainly members of the Crenarchaeota phylum. The diversity of archaeal methanogens was further analyzed by sequencing clones from a library for the mcrA gene, which encodes the enzyme methyl coenzyme reductase, responsible for catalyzing the last step in methane production, methane being an important greenhouse gas. The mcrA sequences were diverse and divided phylogenetically into three clades related to uncultured environmental archaea and methanogens found in different termite species. C. cumulans is a litter-feeding, mound-building termite considered a keystone species in natural ecosystems and also a pest in agriculture. Here, we describe the archaeal and bacterial communities within this termite, revealing for the first time its intriguing microbiota. |
BibTeX:@article{Grieco2013, author = {Grieco, M. A. B. and Cavalcante, J. J. V. and Cardoso, A. M. and Vieira, R. P. and Machado, E. A. and Clementino, M. M. and Medeiros, M. N. and Albano, R. M. and Garcia, E. S. and de Souza, W. and Constantino, R. and Martins, O. B.}, title = {Microbial Community Diversity in the Gut of the South American Termite Cornitermes cumulans (Isoptera: Termitidae)}, journal = {Microbial Ecology}, publisher = {Springer}, year = {2013}, volume = {65}, number = {1}, pages = {197--204}, doi = {10.1007/s00248-012-0119-6}} |
| Moreira OC, Ramirez JD, Velazquez E, Melo MFAD, Lima-Ferreira C, Guhl F, Sosa-Estani S, Marin-Neto JA, Morillo CA and Britto C (2013), "Towards the establishment of a consensus real-time qPCR to monitor Trypanosoma cruzi parasitemia in patients with chronic Chagas disease cardiomyopathy: A substudy from the BENEFIT trial", Acta Tropica., January, 2013. Vol. 125(1), pp. 23-31. Elsevier Science Bv. [DOI] |
| Abstract: Quantitative real-time PCR (qPCR) is an accurate method to quantify Trypanosoma cruzi DNA and can be used to follow-up parasitemia in Chagas disease (CD) patients undergoing chemotherapy. The Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) study is an international, multicenter, randomized, double-blinded and placebo-controlled clinical trial to evaluate the efficacy of benznidazole (BZ) treatment in patients with chronic Chagas cardiomyopathy (CCC). One important question to be addressed concerns the effectiveness of BZ in reducing overall parasite load in CCC patients, even in the absence of parasitological cure. This report describes the evaluation of multiple procedures for DNA extraction and qPCR-based protocols aiming to establish a standardized methodology for the absolute quantification of T. cruzi DNA in Guanidine-EDTA blood (GEB) samples. A panel of five primer sets directed to the T. cruzi nuclear satellite DNA repeats (Sat-DNA) and to the minicircle DNA conserved regions (kDNA) was compared in either SYBR Green or TaqMan systems. Standard curve parameters such as, amplification efficiency, coefficient of determination and intercept were evaluated, as well as different procedures to generate standard samples containing pre-established T. cruzi DNA concentration. Initially, each primer set was assayed in a SYBR Green qPCR to estimate parasite load in GEB samples from chronic Chagas disease patients. The results achieved from Bayesian transmutability analysis elected the primer sets Cruzi1/Cruzi2 (p = 0.0031) and Diaz7/Diaz8 (p = 0.0023) coupled to the QIAamp DNA Kit extraction protocol (silica gel column), as the most suitable for monitoring parasitemia in these patients. Comparison between the parasite burden of 150 GEB samples of BENEFIT patients from Argentina, Brazil and Colombia, prior to drug/placebo administration, was performed using Cruzi1/Cruzi2 primers in a SYBR Green approach. The median parasitemia found in patients from Argentina and Colombia (1.93 and 2.31 parasite equivalents/mL, respectively) was around 20 times higher than the one estimated for the Brazilian patients (0.1 parasite equivalents/mL). This difference could be in part due to the complexity of T. cruzi genetic diversity, which is a factor possibly implicated in different clinical presentations of the disease and/or influencing parasitemia levels in infected individuals from different regions of Latin America. The results of SYBR Green qPCR assays herein presented prove this methodology to be more cost efficient than the alternative use of internal fluorogenic probes. In addition, its sensitivity and reproducibility are shown to be adequate to detect low parasitemia burden in patients with chronic Chagas disease. (C) 2012 Elsevier B.V. All rights reserved. |
BibTeX:@article{, author = {Moreira, O. C. and Ramirez, J. D. and Velazquez, E. and Melo, M. F. A. D. and Lima-Ferreira, C. and Guhl, F. and Sosa-Estani, S. and Marin-Neto, J. A. and Morillo, C. A. and Britto, C.}, title = {Towards the establishment of a consensus real-time qPCR to monitor Trypanosoma cruzi parasitemia in patients with chronic Chagas disease cardiomyopathy: A substudy from the BENEFIT trial}, journal = {Acta Tropica}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {125}, number = {1}, pages = {23--31}, doi = {10.1016/j.actatropica.2012.08.020}} |
| Nardy AFFR, da Silva JL, Perez AR, de Meis J, Farias-de-Oliveira DA, Penha L, Oliveira ID, Dias WB, Todeschini AR, Freire-De-Lima CG, Bellio M, Caruso-Neves C, Pinheiro AA, Takiya CM, Bottasso O, Savino W and Morrot A (2013), "Trans-sialidase from Trypanosoma cruzi enhances the adhesion properties and fibronectin-driven migration of thymocytes", Microbes and Infection., May, 2013. Vol. 15(5), pp. 365-374. Elsevier Science Bv. [DOI] |
| Abstract: In experimental Trypanosoma cruzi infections, severe thymic atrophy leads to release of activated CD4(+)CD8(+) double-positive (DP) T cells to the periphery. In humans, activated DP T cells are found in the blood in association with severe cardiac forms of human chronic Chagas disease. The mechanisms underlying the premature thymocyte release during the chagasic thymic atrophy remain elusive. We tested whether the migratory properties of intrathymic thymocytes are modulated by the parasite trans-sialidase (TS). We found that TS affected the dynamics of thymocytes undergoing intrathymic maturation, and these changes were accompanied by an increase in the number of recent DP thymic emigrants in the peripheral lymphoid organs. We demonstrated that increased percentages of blood DP T cell subsets were associated with augmented antibody titers against TS in chagasic patients with chronic cardiomyopathy. In vitro studies showed that TS was able to activate the MAPK pathway and actin filament mobilization in thymocytes. These effects were correlated with its ability to modulate the adhesion of thymocytes to thymic epithelial cells and their migration toward extracellular matrix. These findings point to effects of TS that could influence the escape of immature thymocytes in Chagas disease. (C) 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. |
BibTeX:@article{Nardy2013, author = {Nardy, A. F. F. R. and da Silva, J. L. and Perez, A. R. and de Meis, J. and Farias-de-Oliveira, D. A. and Penha, L. and Oliveira, I. D. and Dias, W. B. and Todeschini, A. R. and Freire-De-Lima, C. G. and Bellio, M. and Caruso-Neves, C. and Pinheiro, A. A. and Takiya, C. M. and Bottasso, O. and Savino, W. and Morrot, A.}, title = {Trans-sialidase from Trypanosoma cruzi enhances the adhesion properties and fibronectin-driven migration of thymocytes}, journal = {Microbes and Infection}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {15}, number = {5}, pages = {365--374}, doi = {10.1016/j.micinf.2013.02.003}} |
| Nascimento MSL, Albuquerque TDR, Do-Valle-Matta MA, Caldas IS, Diniz LF, Talvani A, Bahia MT, Andrade CM, Galvao LMC, Camara ACJ and Guedes PMM (2013), "Naturally Leishmania infantum-infected dogs display an overall impairment of chemokine and chemokine receptor expression during visceral leishmaniasis", Veterinary Immunology and Immunopathology., June, 2013. Vol. 154(3-4), pp. 202-208. Elsevier Science Bv. [DOI] |
| Abstract: Dogs are the primary reservoir for Leishmania parasites. The immune response induced by Leishmania infantum infection in these animals has not been completely elucidated, and few studies have investigated the relationship between the expression levels of chemokines and chemokine receptors and the clinical status of dogs with canine visceral leishmaniasis (CVL). The aim of this study was to correlate the clinical status of naturally L. infantum-infected dogs (from rural areas of Mossoro city, State of Rio Grande do Norte, Brazil) with the expression levels of chemokines (ccl1, ccl2, ccl3, ccl4, ccl5, ccl17, ccl20, ccl24, ccl26, cxcl9, cxcl10) and chemokine receptors (cxcr3, ccr3, ccr4, ccr5, ccr6, ccr8) in the liver and spleen determined using real-time PCR. Twenty-one dogs were clinically evaluated and classified as asymptomatic (n = 11) or symptomatic (n = 10). Splenomegaly, weight loss and onychogryphosis were the most pronounced symptoms. In the liver, the mRNA expression levels of ccl1, ccl17, ccl26, ccr3, ccr4, ccr5, ccr6, and ccr8 were lower in symptomatic animals than in asymptomatic animals. Compared with uninfected animals, symptomatic dogs had lower expression levels of almost all molecules analyzed. Moreover, high clinical scores were negatively correlated with ccr5 and ccr6 expression and positively correlated with cxcl10 expression. We conclude that the impairment of the expression of chemokines and chemokine receptors results in deficient leukocyte migration and hampers the immune response, leading to the development of disease. (C) 2013 Elsevier B.V. All rights reserved. |
BibTeX:@article{Nascimento2013, author = {Nascimento, M. S. L. and Albuquerque, T. D. R. and Do-Valle-Matta, M. A. and Caldas, I. S. and Diniz, L. F. and Talvani, A. and Bahia, M. T. and Andrade, C. M. and Galvao, L. M. C. and Camara, A. C. J. and Guedes, P. M. M.}, title = {Naturally Leishmania infantum-infected dogs display an overall impairment of chemokine and chemokine receptor expression during visceral leishmaniasis}, journal = {Veterinary Immunology and Immunopathology}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {154}, number = {3-4}, pages = {202--208}, doi = {10.1016/j.vetimm.2013.02.015}} |
| Nogueira NPD, Morgado-Diaz JA, Menna-Barreto RFS, Paes MC and da Silva-Lopez RE (2013), "Effects of a marine serine protease inhibitor on viability and morphology of Trypanosoma cruzi, the agent of Chagas disease", Acta Tropica., October, 2013. Vol. 128(1), pp. 27-35. Elsevier Science Bv. [DOI] |
| Abstract: It has been reported that serine peptidase activities of Trypanosoma cruzi play crucial roles in parasite dissemination and host cell invasion and therefore their inhibition could affect the progress of Chagas disease. The present study investigates the interference of the Stichodactyla helianthus Kunitz-type serine protease inhibitor (ShPI-I), a 55-amino acid peptide, in T. cruzi serine peptidase activities, parasite viability, and parasite morphology. The effect of this peptide was also studied in Leishmania amazonensis promastigotes and it was proved to be a powerful inhibitor of serine proteases activities and the parasite viability. The ultrastructural alterations caused by ShPI-I included vesiculation of the flagellar pocket membrane and the appearance of a cytoplasmic vesicle that resembles an autophagic vacuole. ShPI-I, which showed itself to be an important T. cruzi serine peptidase inhibitor, reduced the parasite viability, in a dose and time dependent manner. The maximum effect of peptide on T. cruzi viability was observed when ShPI-I at 1 x 10(-5) M was incubated for 24 and 48 h which killed completely both metacyclic trypomastigote and epimastigote forms. At 1 x 10(-6) M ShPI-I, in the same periods of time, reduced parasite viability about 91-95% respectively. Ultrastructural analysis demonstrated the formation of concentric membranar structures especially in the cytosol, involving organelles and small vesicles. Prales of endoplasmic reticulum were also detected, surrounding cytosolic vesicles that resembled autophagic vacuoles. These results suggest that serine peptidases are important in T. cruzi physiology since the inhibition of their activity killed parasites in vitro as well as inducing important morphological alterations. Protease inhibitors thus appear to have a potential role as anti-trypanosomatidal agents. (C) 2013 Elsevier B.V. All rights reserved. |
BibTeX:@article{Nogueira2013a, author = {Nogueira, N. P. D. and Morgado-Diaz, J. A. and Menna-Barreto, R. F. S. and Paes, M. C. and da Silva-Lopez, R. E.}, title = {Effects of a marine serine protease inhibitor on viability and morphology of Trypanosoma cruzi, the agent of Chagas disease}, journal = {Acta Tropica}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {128}, number = {1}, pages = {27--35}, doi = {10.1016/j.actatropica.2013.05.013}} |
| Nogueira RT, Nogueira AR, Pereira MCS, Rodrigues MM, Neves PCD, Galler R and Bonaldo MC (2013), "Recombinant Yellow Fever Viruses Elicit CD8(+) T Cell Responses and Protective Immunity against Trypanosoma cruzi", Plos One., March, 2013. Vol. 8(3), pp. e59347. Public Library Science. [DOI] |
| Abstract: Chagas' disease is a major public health problem affecting nearly 10 million in Latin America. Despite several experimental vaccines have shown to be immunogenic and protective in mouse models, there is not a current vaccine being licensed for humans or in clinical trial against T. cruzi infection. Towards this goal, we used the backbone of Yellow Fever (YF) 17D virus, one of the most effective and well-established human vaccines, to express an immunogenic fragment derived from T. cruzi Amastigote Surface Protein 2 (ASP-2). The cDNA sequence of an ASP-2 fragment was inserted between E and NS1 genes of YF 17D virus through the construction of a recombinant heterologous cassette. The replication ability and genetic stability of recombinant YF virus (YF17D/ENS1/Tc) was confirmed for at least six passages in Vero cells. Immunogenicity studies showed that YF17D/ENS1/Tc virus elicited neutralizing antibodies and gamma interferon (IFN-gamma) producing-cells against the YF virus. Also, it was able to prime a CD8(+) T cell directed against the transgenic T. cruzi epitope (TEWETGQI) which expanded significantly as measured by T cell-specific production of IFN-gamma before and after T. cruzi challenge. However, most important for the purposes of vaccine development was the fact that a more efficient protective response could be seen in mice challenged after vaccination with the YF viral formulation consisting of YF17D/ENS1/Tc and a YF17D recombinant virus expressing the TEWETGQI epitope at the NS2B-3 junction. The superior protective immunity observed might be due to an earlier priming of epitope-specific IFN-gamma-producing T CD8(+) cells induced by vaccination with this viral formulation. Our results suggest that the use of viral formulations consisting of a mixture of recombinant YF 17D viruses may be a promising strategy to elicit protective immune responses against pathogens, in general. |
BibTeX:@article{Nogueira2013, author = {Nogueira, R. T. and Nogueira, A. R. and Pereira, M. C. S. and Rodrigues, M. M. and Neves, P. C. D. and Galler, R. and Bonaldo, M. C.}, title = {Recombinant Yellow Fever Viruses Elicit CD8(+) T Cell Responses and Protective Immunity against Trypanosoma cruzi}, journal = {Plos One}, publisher = {Public Library Science}, year = {2013}, volume = {8}, number = {3}, pages = {e59347}, doi = {10.1371/journal.pone.0059347}} |
| Oliveira FOR, Alves CR, Silva FS, Cortes LMC, Toma L, Boucas RI, Aguilar T, Nader HB and Pereira MCS (2013), "Trypanosoma cruzi heparin-binding proteins present a flagellar membrane localization and serine proteinase activity", Parasitology., February, 2013. Vol. 140(2), pp. 171-180. Cambridge Univ Press. [DOI] |
| Abstract: Heparin-binding proteins (HBPs) play a key role in Trypanosoma cruzi-host cell interactions. HBPs recognize heparan sulfate (HS) at the host cell surface and are able to induce the cytoadherence and invasion of this parasite. Herein, we analysed the biochemical properties of the HBPs and also evaluated the expression and subcellular localization of HBPs in T. cruzi trypomastigotes. A flow cytometry analysis revealed that HBPs are highly expressed at the surface of trypomastigotes, and their peculiar localization mainly at the flagellar membrane, which is known as an important signalling domain, may enhance their binding to HS and elicit the parasite invasion. The plasmon surface resonance results demonstrated the stability of HBPs and their affinity to HS and heparin. Additionally, gelatinolytic activities of 70 kDa, 65.8 kDa and 59 kDa HBPs over a broad pH range (5.5-8.0) were revealed using a zymography assay. These proteolytic activities were sensitive to serine proteinase inhibitors, such as aprotinin and phenylmethylsulfonyl fluoride, suggesting that HBPs have the properties of trypsin-like proteinases. |
BibTeX:@article{Oliveira2013, author = {Oliveira, F. O. R. and Alves, C. R. and Silva, F. S. and Cortes, L. M. C. and Toma, L. and Boucas, R. I. and Aguilar, T. and Nader, H. B. and Pereira, M. C. S.}, title = {Trypanosoma cruzi heparin-binding proteins present a flagellar membrane localization and serine proteinase activity}, journal = {Parasitology}, publisher = {Cambridge Univ Press}, year = {2013}, volume = {140}, number = {2}, pages = {171--180}, doi = {10.1017/S0031182012001448}} |
| Pinto AYD, Valente VD, Coura JR, Valente SAD, Junqueira ACV, Santos LC, Ferreira AG and de Macedo RC (2013), "Clinical Follow-Up of Responses to Treatment with Benznidazol in Amazon: A Cohort Study of Acute Chagas Disease", Plos One., May, 2013. Vol. 8(5), pp. e64450. Public Library Science. [DOI] |
| Abstract: A total of 179 individuals with acute Chagas disease mainly transmitted by oral source, from Para and Amapa State, Amazonian, Brazil were included during the period from 1988 to 2005. Blood samples were used to survey peripheral blood for T. cruzi hemoparasites by quantitative buffy coat (QBC), indirect xenodiagnosis, blood culture and serology to detection of total IgM and anti-T. cruzi IgG antibodies by indirect immunofluorescence assay (IFA) and indirect hemagglutination assay (HA). All assays were performed pre-treatment (0 days) and repeated 35 (+/- 7) and 68 (+/- 6) days after the initiation of treatment with benznidazol and every 6 months while remained seropositive. The endpoint of collection was performed in 2005. Total medium period of follow-up per person was 5.6 years. Also, a blood sample was collected from 72 randomly chosen treated patients to perform polimerase chain reaction (PCR) method. Proportions of subjects with negative or positive serology according to the number of years after treatment were compared. In the endpoint of follow-up we found 47 patients (26.7%) serologically negative, therefore considered cured and 5 (2.7%) exhibited mild cardiac Chagas disease. Other 132 patients had persistent positive serologic tests. The PCR carried out in 72 individuals was positive in 9.8%. Added, there was evidence of therapeutic failure immediately following treatment, as demonstrated by xenodiagnosis and blood culture methods in 2.3% and 3.5% of cases, respectively. There was a strong evidence of antibody clearing in the fourth year after treatment and continuous decrease of antibody titers. Authors suggest that control programs should apply operational researches with new drug interventions four years after the acute phase for those treated patients with persistently positive serology. |
BibTeX:@article{Pinto2013, author = {Pinto, A. Y. D. and Valente, V. D. and Coura, J. R. and Valente, S. A. D. and Junqueira, A. C. V. and Santos, L. C. and Ferreira, A. G. and de Macedo, R. C.}, title = {Clinical Follow-Up of Responses to Treatment with Benznidazol in Amazon: A Cohort Study of Acute Chagas Disease}, journal = {Plos One}, publisher = {Public Library Science}, year = {2013}, volume = {8}, number = {5}, pages = {e64450}, doi = {10.1371/journal.pone.0064450}} |
| Rebello KM, Menna-Barreto RFS, Chagas-Moutinho VA, Mota EM, Perales J, Neves-Ferreira AGC, Oliveira-Menezes A and Lenzi H (2013), "Morphological aspects of Angiostrongylus costaricensis by light and scanning electron microscopy", Acta Tropica., September, 2013. Vol. 127(3), pp. 191-198. Elsevier Science Bv. [DOI] |
| Abstract: Angiostrongylus costaricensis is a parasitic nematode that can cause severe gastrointestinal disease, known as abdominal angiostrongiliasis, in humans. This paper presents the characterization of first- and third-stage larvae and male and female adult worms of A. costaricensis by scanning electron and light microscopy. Several novel anatomical structures were identified by scanning electron microscopy, including details of the cuticular striations of the spicules in male worms and a protective flap of the cuticle covering the vulvar aperture in female worms. Other taxonomic features revealed by light microscopy include the gubernaculum and the esophageal-intestinal valve. The use of two microscopy techniques allowed a detailed characterization of the morphology of this nematode. A number of previously identified taxonomic features, such as the striated nature of the spicules and the lateral alae were confirmed; however, the use of scanning electron microscopy resulted in a reassessment of the correct number of papillae distributed around the oral opening and behind the cloacal opening. These observations, in combination with light microscopy-based characterization of the gubernaculum and esophageal valves, have allowed a more detailed description of this nematode taxonomy. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved. |
BibTeX:@article{Rebello2013, author = {Rebello, K. M. and Menna-Barreto, R. F. S. and Chagas-Moutinho, V. A. and Mota, E. M. and Perales, J. and Neves-Ferreira, A. G. C. and Oliveira-Menezes, A. and Lenzi, H.}, title = {Morphological aspects of Angiostrongylus costaricensis by light and scanning electron microscopy}, journal = {Acta Tropica}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {127}, number = {3}, pages = {191--198}, doi = {10.1016/j.actatropica.2013.05.002}} |
| Rocha FL, Roque ALR, Arrais RC, Santos JP, Lima VD, Xavier SCD, Cordeir-Estrela P, D'Andrea PS and Jansen AM (2013), "Trypanosoma cruzi TcI and TcII transmission among wild carnivores, small mammals and dogs in a conservation unit and surrounding areas, Brazil", Parasitology., February, 2013. Vol. 140(2), pp. 160-170. Cambridge Univ Press. [DOI] |
| Abstract: Aiming to better understand the ecological aspects of Trypanosoma cruzi transmission cycles, wild carnivores, small mammals and dogs were examined for T. cruzi infection in the Serra da Canastra National Park region, Brazil. Isolates were genotyped using mini-exon gene and PCR-RFLP (1f8 and H3) genomic targets. Trypanosoma cruzi transmission was well established in the area and occurred in both wild and peridomestic environments. Dog seroprevalence was 29.4% (63/214) and TcI and TcII genotypes, besides mixed infections were observed. Only TcI was detected in wild mammals. Marsupials displayed lower relative abundance, but a high prevalence of positive haemocultures (4/22), whereas rodents displayed positive haemocultures (9/113) mainly in the abundant Akodon montensis and Cerradomys subflavus species. The felid Leopardus pardalis was the only carnivore to display positive haemoculture and was captured in the same region where the small mammal prevalence of T. cruzi infection was high. Two canid species, Chrysocyon brachyurus and Cerdocyon thous, were serologically positive for T. cruzi infection (4/8 and 8/39, respectively), probably related to their capacity to exploit different ecological niches. Herein, dog infection not only signals T. cruzi transmission but also the genotypes present. Distinct transmission strategies of the T. cruzi genotypes are discussed. |
BibTeX:@article{Rocha2013a, author = {Rocha, F. L. and Roque, A. L. R. and Arrais, R. C. and Santos, J. P. and Lima, V. D. and Xavier, S. C. D. and Cordeir-Estrela, P. and D'Andrea, P. S. and Jansen, A. M.}, title = {Trypanosoma cruzi TcI and TcII transmission among wild carnivores, small mammals and dogs in a conservation unit and surrounding areas, Brazil}, journal = {Parasitology}, publisher = {Cambridge Univ Press}, year = {2013}, volume = {140}, number = {2}, pages = {160--170}, doi = {10.1017/S0031182012001539}} |
| Rocha FL, Roque ALR, de Lima JS, Cheida CC, Lemos FG, de Azevedo FC, Arrais RC, Bilac D, Herrera HM, Mourão G and Jansen AM (2013), "Trypanosoma cruzi infection in neotropical wild carnivores (Mammalia: Carnivora): at the top of the T. cruzi transmission chain.", PLoS One. Vol. 8(7), pp. e67463. [DOI] |
| Abstract: Little is known on the role played by Neotropical wild carnivores in the Trypanosoma cruzi transmission cycles. We investigated T. cruzi infection in wild carnivores from three sites in Brazil through parasitological and serological tests. The seven carnivore species examined were infected by T. cruzi, but high parasitemias detectable by hemoculture were found only in two Procyonidae species. Genotyping by Mini-exon gene, PCR-RFLP (1f8/Akw21I) and kDNA genomic targets revealed that the raccoon (Procyon cancrivorus) harbored TcI and the coatis (Nasua nasua) harbored TcI, TcII, TcIII-IV and Trypanosoma rangeli, in single and mixed infections, besides four T. cruzi isolates that displayed odd band patterns in the Mini-exon assay. These findings corroborate the coati can be a bioaccumulator of T. cruzi Discrete Typing Units (DTU) and may act as a transmission hub, a connection point joining sylvatic transmission cycles within terrestrial and arboreal mammals and vectors. Also, the odd band patterns observed in coatis' isolates reinforce that T. cruzi diversity might be much higher than currently acknowledged. Additionally, we assembled our data with T. cruzi infection on Neotropical carnivores' literature records to provide a comprehensive analysis of the infection patterns among distinct carnivore species, especially considering their ecological traits and phylogeny. Altogether, fifteen Neotropical carnivore species were found naturally infected by T. cruzi. Species diet was associated with T. cruzi infection rates, supporting the hypothesis that predator-prey links are important mechanisms for T. cruzi maintenance and dispersion in the wild. Distinct T. cruzi infection patterns across carnivore species and study sites were notable. Musteloidea species consistently exhibit high parasitemias in different studies which indicate their high infectivity potential. Mesocarnivores that feed on both invertebrates and mammals, including the coati, a host that can be bioaccumulator of T. cruzi DTU's, seem to take place at the top of the T. cruzi transmission chain. |
BibTeX:@article{Rocha2013, author = {Rocha, Fabiana Lopes and Roque, André Luiz Rodrigues and de Lima, Juliane Saab and Cheida, Carolina Carvalho and Lemos, Frederico Gemesio and de Azevedo, Fernanda Cavalcanti and Arrais, Ricardo Corassa and Bilac, Daniele and Herrera, Heitor Miraglia and Mourão, Guilherme and Jansen, Ana Maria}, title = {Trypanosoma cruzi infection in neotropical wild carnivores (Mammalia: Carnivora): at the top of the T. cruzi transmission chain.}, journal = {PLoS One}, year = {2013}, volume = {8}, number = {7}, pages = {e67463}, url = {http://dx.doi.org/10.1371/journal.pone.0067463}, doi = {10.1371/journal.pone.0067463}} |
| Roque ALR, Xavier SCC, Gerhardt M, Silva MFO, Lima VS, D'Andrea PS and Jansen AM (2013), "Trypanosoma cruzi among wild and domestic mammals in different areas of the Abaetetuba municipality (Para State, Brazil), an endemic Chagas disease transmission area", Veterinary Parasitology., March, 2013. Vol. 193(1-3), pp. 71-77. Elsevier Science Bv. [DOI] |
| Abstract: The presence of acute Chagas disease (ACD) due to oral transmission is growing and expanding in several South American countries. Within the Amazon basin, the Abaetetuba municipality has been a site of recurrent cases spanning across distinct landscapes. Because Chagas disease is primarily a zoonotic infection, we compared the enzootic Trypanosoma cruzi transmission cycles in three different environmental areas of Abaetetuba to better understand this new epidemiological situation. Philander opossum was the most abundant mammalian species collected (38% of the collected mammals) with a T. cruzi prevalence of 57%, as determined by hemocultures. Didelphis inarsupialis was abundant only in the area with the higher level of environmental disturbance (approximately 42%) and did not yield detectable parasitemia. Despite similarities observed in the composition of the small mammalian fauna and the prevalence of T. cruzi infection among the studied areas, the potential of these hosts to infect vectors differed significantly according to the degree of land use (with prevalences of 5%, 41%, and 64% in areas A3, A1 and A2, respectively). Domestic mammals were also found to be infected, and one canine T. cruzi isolate was obtained. Our data demonstrated that the transmission of T. cruzi in the Amazon basin is far more complex than had been previously taught and showed that the probability of humans and domestic mammals coming into contact with infected bugs can vary dramatically, even within the same municipality. The exposure of dogs to T. cruzi infection (indicated by positive serology) was the common feature among the studied localities, stressing the importance of selecting domestic mammals as sentinels in the identification of T. cruzi transmission hotspots. (C) 2012 Elsevier B.V. All rights reserved. |
BibTeX:@article{, author = {Roque, A. L. R. and Xavier, S. C. C. and Gerhardt, M. and Silva, M. F. O. and Lima, V. S. and D'Andrea, P. S. and Jansen, A. M.}, title = {Trypanosoma cruzi among wild and domestic mammals in different areas of the Abaetetuba municipality (Para State, Brazil), an endemic Chagas disease transmission area}, journal = {Veterinary Parasitology}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {193}, number = {1-3}, pages = {71--77}, doi = {10.1016/j.vetpar.2012.11.028}} |
| Salomao K, De Santana NA, Molina MT, De Castro SL and Menna-Barreto RFS (2013), "Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues", Bmc Microbiology., September, 2013. Vol. 13, pp. 196. Biomed Central Ltd. [DOI] |
| Abstract: Background: Naphthoquinones (NQs) are privileged structures in medicinal chemistry due to the biological effects associated with the induction of oxidative stress. The present study evaluated the activities of sixteen NQs derivatives on Trypanosoma cruzi. Results: Fourteen NQs displayed higher activity against bloodstream trypomastigotes of T. cruzi than benznidazole. Further assays with NQ1, NQ8, NQ9 and NQ12 showed inhibition of the proliferation of axenic epimastigotes and intracelulluar amastigotes interiorized in macrophages and in heart muscle cells. NQ8 was the most active NQ against both proliferative forms of T. cruzi. In epimastigotes the four NQs induced mitochondrial swelling, vacuolization, and flagellar blebbing. The treatment with NQs also induced the appearance of large endoplasmic reticulum profiles surrounding different cellular structures and of myelin-like membranous contours, morphological characteristics of an autophagic process. At IC50 concentration, NQ8 totally disrupted the Delta psi m of about 20% of the parasites, suggesting the induction of a sub-population with metabolically inactive mitochondria. On the other hand, NQ1, NQ9 or NQ12 led only to a discrete decrease of TMRE + labeling at IC50 values. NQ8 led also to an increase in the percentage of parasites labeled with DHE, indicative of ROS production, possibly the cause of the observed mitochondrial swelling. The other three NQs behaved similarly to untreated controls. Conclusions: NQ1, NQ8, NQ9 and NQ12 induce an autophagic phenotype in T. cruzi epimastigoted, as already observed with others NQs. The absence of oxidative stress in NQ1-, NQ9- and NQ12-treated parasites could be due to the existence of more than one mechanism of action involved in their trypanocidal activity, leaving ROS generation suppressed by the detoxification system of the parasite. The strong redox effect of NQ8 could be associated to the presence of the acetyl group in its structure facilitating quinone reduction, as previously demonstrated by electrochemical analysis. Further experiments using biochemical and molecular approaches are needed to better characterize ROS participation in the mechanism of action of these NQs. |
BibTeX:@article{Salomao2013, author = {Salomao, K. and De Santana, N. A. and Molina, M. T. and De Castro, S. L. and Menna-Barreto, R. F. S.}, title = {Trypanosoma cruzi mitochondrial swelling and membrane potential collapse as primary evidence of the mode of action of naphthoquinone analogues}, journal = {Bmc Microbiology}, publisher = {Biomed Central Ltd}, year = {2013}, volume = {13}, pages = {196}, doi = {10.1186/1471-2180-13-196}} |
| Saraiva RM, Waghabi MC, Vilela MF, Madeira FS, da Silva GMS, Xavier SS, Feige JJ, Hasslocher-Moreno AM and Araujo-Jorge TC (2013), "Predictive value of transforming growth factor-1in Chagas disease: towards a biomarker surrogate of clinical outcome", Transactions of the Royal Society of Tropical Medicine and Hygiene., August, 2013. Vol. 107(8), pp. 518-525. Oxford Univ Press. [DOI] |
| Abstract: Transforming growth factor-1 (TGF-1) may be implicated in the development of Chagas heart disease. However, the clinical value of TGF-1 measurement is yet to be determined. We retrospectively analyzed the outcome of 54 Chagas disease patients without heart failure and with left ventricular (LV) ejection fraction 45 whose TGF-1 serum values were determined between January 1998 and December 1999. Primary end point was all-cause mortality and secondary end point was the combination of all-cause mortality or hospitalization due to worsening heart failure or cardiac arrhythmias. TGF-1 was independently associated with the occurrence of the primary and secondary end points. The optimal cutoff for TGF-1 to identify the primary end point was 12.9 ng/ml (area under the curve 0.82, p 0.004, sensitivity 100, and specificity 57) and to identify the secondary end point was 30.8 ng/ml (area under the curve 0.72, p 0.03, sensitivity 60, and specificity 86). LV ejection fraction and LV end-diastolic diameter were also independent predictors of the primary and secondary endpoints, respectively. The described association between TGF-1 and clinical outcome provides evidence towards the clinical value of TGF-1 in Chagas disease. |
BibTeX:@article{Saraiva2013, author = {Saraiva, R. M. and Waghabi, M. C. and Vilela, M. F. and Madeira, F. S. and da Silva, G. M. S. and Xavier, S. S. and Feige, J. J. and Hasslocher-Moreno, A. M. and Araujo-Jorge, T. C.}, title = {Predictive value of transforming growth factor-1in Chagas disease: towards a biomarker surrogate of clinical outcome}, journal = {Transactions of the Royal Society of Tropical Medicine and Hygiene}, publisher = {Oxford Univ Press}, year = {2013}, volume = {107}, number = {8}, pages = {518--525}, doi = {10.1093/trstmh/trt050}} |
| Villar SR, Ronco MT, Bussy RF, Roggero E, Lepletier A, Manarin R, Savino W, Perez AR and Bottasso O (2013), "Tumor Necrosis Factor-alpha Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1", Plos One., May, 2013. Vol. 8(5) Public Library Science. [DOI] |
| Abstract: Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-alpha is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R1(-/-)) mice have a dysregulated synthesis of glucocorticoids (GCs) during Trypanosoma cruzi acute infection. Since TNF-alpha may influence GCs production, not only through the hypothalamus-pituitary axis, but also at the adrenal level, we now investigated the role of this cytokine on the adrenal GCs production. Wild type (WT) and TNF-R1(-/-) mice undergoing acute infection (Tc-WT and Tc-TNF-R1(-/-) groups), displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R1(-/-) compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-alpha expression was increased within the adrenal gland from both infected mouse groups, with Tc-WT mice showing an augmented TNF-R1 expression. Tc-WT mice showed increased levels of P-p38 and P-ERK compared to uninfected WT animals, whereas Tc-TNF-R1(-/-) mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-kappa B and AP-1 activation during infection was blunted in Tc-TNF-R1(-/-) mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R1(-/-) mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-alpha emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-kappa B and AP-1 seem to play a role in the adrenal synthesis of pro-inflammatory cytokines and enzymes regulating GCs synthesis. These results suggest the existence of an intrinsic immune-adrenal interaction involved in the dysregulated synthesis of GCs during murine Chagas disease. |
BibTeX:@article{Villar2013, author = {Villar, S. R. and Ronco, M. T. and Bussy, R. F. and Roggero, E. and Lepletier, A. and Manarin, R. and Savino, W. and Perez, A. R. and Bottasso, O.}, title = {Tumor Necrosis Factor-alpha Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1}, journal = {Plos One}, publisher = {Public Library Science}, year = {2013}, volume = {8}, number = {5}, doi = {10.1371/journal.pone.0063814}} |
Instituto Oswaldo Cruz /IOC /FIOCRUZ - Av. Brasil, 4365 - Tel: (21) 2598-4220
| INTRANET IOC| EXPEDIENTE
Manguinhos - Rio de Janeiro - RJ - Brasil CEP: 21040-360
