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Área de PDI em Pesquisa, Desenvolvimento e Inovação em Leishmanioses 2013

Veja, abaixo, a relação de artigos científicos publicados pelo IOC, na referida Área Temática, organizados em ordem alfabética crescente:

Total: 0
Campos MCO, Castro-Pinto DB, Ribeiro GA, Berredo-Pinho MM, Gomes LHF, da Silva Bellieny MS, Goulart CM, Echevarria A and Leon LL (2013), "P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance.", Parasitol Res., Jun, 2013. Vol. 112(6), pp. 2341-2351.
Abstract: Drug resistance in protozoan parasites has been associated with the P-glycoprotein (Pgp), an energy-dependent efflux pump that transports substances across the membrane. Interestingly, the genes TcPGP1 and TcPGP2 have been described in Trypanosoma cruzi, although the function of these genes has not been fully elucidated. The main goal of this work was to investigate Pgp efflux pump activity and expression in T. cruzi lines submitted to in vitro induced resistance to the compounds 4-N-(2-methoxy styryl)-thiosemicarbazone (2-Meotio) and benznidazole (Bz) and to verify the stability of the resistant phenotypes during the parasite life cycle. We observed that the EC50 values for the treatment of epimastigotes with 2-Meotio or Bz were increased at least 4.7-fold in resistant lines, and this phenotype was maintained in metacyclic trypomastigotes, cell-derived trypomastigotes, and intracellular amastigotes. However, in epimastigotes, 2-Meotio resistance is reversible, but Bz resistance is irreversible. When compared with the parental line, the resistant lines exhibited higher Pgp efflux activity, reversion of the resistant phenotypes in the presence of Pgp inhibitors, cross-resistance with Pgp modulators, higher basal Pgp ATPase activity, and overexpression of the genes TcPGP1 and TcPGP2. In conclusion, the resistance induced in T. cruzi by the compounds 2-Meotio and Bz is maintained during the entire parasite life cycle. Furthermore, our data suggest the participation of the Pgp efflux pump in T. cruzi drug resistance.
BibTeX:
 @article{Campos2013, author = {Campos, Mônica Caroline Oliveira and Castro-Pinto, Denise Barçante and Ribeiro, Grazielle Alves and Berredo-Pinho, Márcia Moreira and Gomes, Leonardo Henrique Ferreira and da Silva Bellieny, Myrtes Santos and Goulart, Carla Marins and Echevarria, Aurea and Leon, Leonor Laura}, title = {P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance.}, journal = {Parasitol Res}, year = {2013}, volume = {112}, number = {6}, pages = {2341--2351}, url = {http://dx.doi.org/10.1007/s00436-013-3398-z}, doi = {10.1007/s00436-013-3398-z} } 
Carrara VD, Cunha EF, Torres-Santos EC, Correa AG, Monteiro L, Demarchi IG, Lonardoni MVC and Cortez DAG (2013), "Antileishmanial activity of amides from Piper amalago and synthetic analogs", Revista Brasileira De Farmacognosia-brazilian Journal of Pharmacognosy., May, 2013. Vol. 23(3), pp. 447-454. Soc Brasileira Farmacognosia.
Abstract: Two natural amides isolated from the chloroform extract of Piper amalago L., Piperaceae, leaves, a hydrogenated derivative and seven synthetic analogs were tested against the promastigote and intracellular amastigote forms of Leishmania amazonensis. The antileishmanial activity was evaluated in terms of growth inhibitory concentration for 50% of protozoa (IC50). The cytotoxicity toward the J774A1 macrophages was evaluated in terms of the cytotoxic concentrations for 50% of macrophages (CC50). The ability to induce nitric oxide production was also investigated for all compounds. The saturated amide 7-(1,3-benzodioxol-5-yl)-1-(1-pyrrolidinyl)-1-heptanone was obtained by hydrogenation of the natural compound N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl]pyrrolidine. Synthetic amides were prepared by addition of the appropriate amine to the corresponding acyl chloride. The natural compound, N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine, was the most active of all tested compounds against the promastigote and intracellular amastigote forms with IC50 values of 15 mu M and 14.5 mu M, respectively. None of the compounds modulated the production of nitric oxide.
BibTeX:
 @article{Carrara2013, author = {Carrara, V. D. and Cunha, E. F. and Torres-Santos, E. C. and Correa, A. G. and Monteiro, L. and Demarchi, I. G. and Lonardoni, M. V. C. and Cortez, D. A. G.}, title = {Antileishmanial activity of amides from Piper amalago and synthetic analogs}, journal = {Revista Brasileira De Farmacognosia-brazilian Journal of Pharmacognosy}, publisher = {Soc Brasileira Farmacognosia}, year = {2013}, volume = {23}, number = {3}, pages = {447--454}, doi = {10.1590/S0102-695X2013005000022} } 
Charret KS, Lagrota-Candido J, Carvalho-Pinto CE, Hottz CF, Lira MLF, Rodrigues RF, Gomes AO, Bernardino AM, Canto-Cavalheiro MM, Leon LL and Amaral VF (2013), "The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives", Experimental Parasitology., February, 2013. Vol. 133(2), pp. 201-210. Academic Press Inc Elsevier Science.
Abstract: Because there is no vaccine in clinical use, control of Leishmaniasis relies almost exclusively on chemotherapy and the conventional treatments exhibit high toxicity for patients and emerging drug resistance. Recently, we showed that oral treatment with synthetic pyrazole carbohydrazide compounds induced lower parasite load in draining lymph nodes and reduced skin lesion size without causing any toxic effects in an experimental murine infection model with Leishmania amazonensis. In this study, CBA mice were infected in the footpad with L amazonensis and then orally treated with pyrazole carbohydrazides derivatives, such as BrNO2, NO2Cl and NO2Br and their histopathological and immunological effects were then investigated. Epidermis and dermis had lower levels of inflammatory infiltration compared to the infected untreated control mice. In the dermis of treated animals, the numbers of vacuolated macrophages containing intracellular parasites were far lower than in infected untreated animals. In addition to dermal macrophages, we also observed a mixed inflammatory infiltrate containing lymphocytes and granulocyte cells. Lower numbers of B cells (B220+) and T lymphocytes (CD3+) were identified in the lesions of treated mice compared with the untreated, infected mice. In draining lymph node cells, the number of T lymphocytes (CD3+) was decreased, and the numbers of B cells (CD19+) and CDS+ T cells were increased in infected mice, when compared with the non-infected control group. In additional, we have shown that infected treated and untreated lymph node cells had similar levels of TGF-beta and IFN-gamma mRNA expression, whereas IL-4 was expressed at a lower level in the treated group. Increased levels of the specific anti-Leishmania IgG2a or IgG3 antibody subclass were observed in NO2Cl or BrNO2-treated group, respectively. Overall, our experimental findings suggest that pyrazole carbohydrazides exert modulation of IL-4 expression and B cell levels; however, further evaluation is required to determine the optimal treatment regime. (C) 2012 Elsevier Inc. All rights reserved.
BibTeX:
 @article{Charret2013, author = {Charret, K. S. and Lagrota-Candido, J. and Carvalho-Pinto, C. E. and Hottz, C. F. and Lira, M. L. F. and Rodrigues, R. F. and Gomes, A. O. and Bernardino, A. M. and Canto-Cavalheiro, M. M. and Leon, L. L. and Amaral, V. F.}, title = {The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives}, journal = {Experimental Parasitology}, publisher = {Academic Press Inc Elsevier Science}, year = {2013}, volume = {133}, number = {2}, pages = {201--210}, doi = {10.1016/j.exppara.2012.11.022} } 
Covas CDF, Cardoso CC, Gomes-Silva A, Oliveira JRS, Da-Cruz AM and Moraes MO (2013), "Candidate gene case-control and functional study shows macrophage inhibitory factor (MIF) polymorphism is associated with cutaneous leishmaniasis", Cytokine., January, 2013. Vol. 61(1), pp. 168-172. Academic Press Ltd- Elsevier Science Ltd.
Abstract: American tegumentary leishmaniasis (ATL) is an infectious disease caused mostly by Leishmania (Viannia) braziliensis in Southeast Brazil. The clinical manifestations are vast, ranging from asymptomatic to severe mucosal leishmaniasis (ML). It has been suggested that variation of the pathogen does not fully explain the response spectrum and the variability of clinical manifestations. Previous data have shown that host genetics also play a role in disease outcome. Herein, we have tested the association of TNF, IL10, IL12 and MIF single nucleotide polymorphisms (SNPs) using a case-control study design including 110 cutaneous leishmaniasis (CL) patients and 682 healthy subjects. The genotype-phenotype correlation was also assessed using leishmania antigens to stimulate peripheral blood mononuclear cells obtained from cured CL patients. Results demonstrated that the MIF - 173C allele is associated with leishmaniasis outcome and also with lower levels of MIF in culture supernatants. Also, the TNF - 308AA genotype was statistically increased among leishmaniasis patients. The results showed here suggest that the lower levels of MIF produced by MIF - 173C carriers could influence the host-Leishmania interaction, favoring infection and disease progression. On the other hand, high TNF levels can contribute to tissue damage, consequently leading to skin lesions. (C) 2012 Elsevier Ltd. All rights reserved.
BibTeX:
 @article{Covas2013, author = {Covas, C. D. F. and Cardoso, C. C. and Gomes-Silva, A. and Oliveira, J. R. S. and Da-Cruz, A. M. and Moraes, M. O.}, title = {Candidate gene case-control and functional study shows macrophage inhibitory factor (MIF) polymorphism is associated with cutaneous leishmaniasis}, journal = {Cytokine}, publisher = {Academic Press Ltd- Elsevier Science Ltd}, year = {2013}, volume = {61}, number = {1}, pages = {168--172}, doi = {10.1016/j.cyto.2012.09.012} } 
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.
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{DeAraujo2013, 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 Oliveira EF, Silva EA, Casaril AE, Fernandes CES, Paranhos AC, Gamarra RM, Ribeiro AA, Brazil RP and Oliveira AG (2013), "Behavioral Aspects of Lutzomyia longipalpis (Diptera: Psychodidae) in Urban Area Endemic for Visceral Leishmaniasis", Journal of Medical Entomology., March, 2013. Vol. 50(2), pp. 277-284. Entomological Soc Amer.
Abstract: The study of some of the behavioral aspects of the main vector of Leishmania infantum chagasi Cunha & Chagas in the Americas, Lutzomyia longipalpis (Lutz & Neiva), such as dispersion, population size, and vector survival rates, is important for the elucidation of the mechanisms of visceral leishmaniasis transmission. These parameters were studied by means of capture-mark-release-recapture experiments in an urban area of Campo Grande municipality, an endemic area of visceral leishmaniasis, situated in Mato Grosso do Sul state, Brazil. Six capture-mark-release-recapture experiments were undertaken between November 2009 and November 2010 and once in January 2012 with a view to assessing the population size and survival rate of Lu. longipalpis. The insects were released in a peridomicile surrounded by 13 residences. The recaptures were undertaken with automatic light traps for four consecutive weeks after release in the surrounding area. In total, 3,354 sand flics were captured, marked, and released. The overall recapture rate during the capture-mark-release-recapture experiments was 4.23%, of which 92.45% were recaptured at the release site, indicating limited dispersal. The greatest distance recorded from the release site was 165 m for males and 241 m for females. The male daily survival rate, calculated on the basis of regressions from the numbers of marked recaptured insects during the 15 successive days after release was 0.897. The estimated male population size measured by the Lincoln Index was 10,947.127. Though Lu. longipalpis presented a limited dispersion the physical barriers typical of urban environments did not prevent the sand flies from flying long distances.
BibTeX:
 @article{DeOliveira2013, author = {De Oliveira, E. F. and Silva, E. A. and Casaril, A. E. and Fernandes, C. E. S. and Paranhos, A. C. and Gamarra, R. M. and Ribeiro, A. A. and Brazil, R. P. and Oliveira, A. G.}, title = {Behavioral Aspects of Lutzomyia longipalpis (Diptera: Psychodidae) in Urban Area Endemic for Visceral Leishmaniasis}, journal = {Journal of Medical Entomology}, publisher = {Entomological Soc Amer}, year = {2013}, volume = {50}, number = {2}, pages = {277--284}, doi = {10.1603/ME12082} } 
De Oliveira GM, Madeira MdF, Oliveira FS, Pires MQ and Pacheco RdS (2013), "Canine Cutaneous Leishmaniasis: Dissemination and Tissue Tropism of Genetically Distinct Leishmania (Viannia) braziliensis Populations.", Vet Med Int. Vol. 2013, pp. 982183.
Abstract: Little is known regarding the internal dissemination of initial cutaneous lesions and tissue tropism of Leishmania (Viannia) braziliensis populations in naturally infected dogs. The aim of this study was to investigate genetic polymorphisms of L. (V.) braziliensis populations in different anatomic sites of naturally infected dogs by using polymerase chain reaction (PCR) and low-stringency single specific primer-PCR (LSSP-PCR) techniques. The amplified products were analyzed by LSSP-PCR to investigate the genetic variability of the parasite populations present in different anatomical sites. Twenty-three out of the 52 samples gave PCR-positive results. The existence of L. (V.) braziliensis strains that remained restricted to cutaneous lesions and others showing characteristics of dissemination to internal organs and healthy skin was observed. LSSP-PCR and numerical analyses revealed that parasite populations that do not disseminate were genetically similar and belonged to a separate phenetic cluster. In contrast, populations that showed spreading to internal organs displayed a more polymorphic genetic profile. Despite the heterogeneity, L. (V.) braziliensis populations with identical genetic profiles were observed in popliteal and cervical lymph nodes of the same animal. Our results indicate that infection in dogs can be manifested by dissemination and tissue tropism of genetically distinct populations of L. (V.) braziliensis.
BibTeX:
 @article{deOliveira2013, author = {De Oliveira, Guilherme Marx and Madeira, Maria de Fátima and Oliveira, Fernanda Santos and Pires, Marize Quinhones and Pacheco, Raquel da Silva}, title = {Canine Cutaneous Leishmaniasis: Dissemination and Tissue Tropism of Genetically Distinct Leishmania (Viannia) braziliensis Populations.}, journal = {Vet Med Int}, year = {2013}, volume = {2013}, pages = {982183}, url = {http://dx.doi.org/10.1155/2013/982183}, doi = {10.1155/2013/982183} } 
Detoni ML, Fessel MR, Maia ACRG, Porcino GN, Quellis LR, Faria-Pinto P, Marques MJ, Juliano MA, Juliano L, Diniz VA, Corte-Real S, Goncalves-da-Costa SC, Souza CSF and Vasconcelos EG (2013), "An antigenic domain of the Leishmania amazonensis nucleoside triphosphate diphosphohydrolase (NTPDase 1) is associated with disease progression in susceptible infected mice", Parasitology Research., August, 2013. Vol. 112(8), pp. 2773-2782. Springer.
Abstract: An antigenic conserved B domain was previously identified within nucleoside triphosphate diphosphohydrolases (NTPDases) of plants and parasites. Now, the r-potDomain B, a 6x His-tag polypeptide belonging to the conserved B domain from the potato apyrase, and synthetic peptides LbB1LJ and LbB2LJ derived from the B domain from Leishmania NTPDase 1 were used as molecular tools for studies of the Leishmania amazonensis NTPDase 1. Widespread subcellular location of the specific NTPDase 1 was detected by Western blots of promastigote fractions and ultrastructural immunocytochemical microscopy using immune sera raised against these biomolecules. In addition, the L. amazonensis-infected BALB/c mice were evaluated at 12 to 120 days after infection, which progresses showing typical nodular lesion. High antibody reactivity with either r-potDomain B, LbB1LJ, or LbB2LJ was found in L. amazonensis-infected BALB/c mice indicating the antigenicity of the B domain from NTPDase 1 isoform. The IgG1 antibody reactivity significantly increased at 90-120 days postinfection, 18- to 24-fold when compared to the 12th day, and remained elevated even at 120th after infection, coinciding with the most active stage of the disease. In contrast, significantly higher IgG2a antibody reactivity with each biomolecule was observed at 40th day, about two- to fourfold higher than those found at 12th or 20th day, and decreased along 120-day period. Apparently, the conserved B domain is capable to induce IgG2a production in early disease stages. All together, these results suggest that r-potDomain B or synthetic peptides could be molecular starting points in experimental protocols of immunotherapy and/or vaccination for leishmaniasis.
BibTeX:
 @article{Detoni2013, author = {Detoni, M. L. and Fessel, M. R. and Maia, A. C. R. G. and Porcino, G. N. and Quellis, L. R. and Faria-Pinto, P. and Marques, M. J. and Juliano, M. A. and Juliano, L. and Diniz, V. A. and Corte-Real, S. and Goncalves-da-Costa, S. C. and Souza, C. S. F. and Vasconcelos, E. G.}, title = {An antigenic domain of the Leishmania amazonensis nucleoside triphosphate diphosphohydrolase (NTPDase 1) is associated with disease progression in susceptible infected mice}, journal = {Parasitology Research}, publisher = {Springer}, year = {2013}, volume = {112}, number = {8}, pages = {2773--2782}, doi = {10.1007/s00436-013-3445-9} } 
Faria JV, dos Santos MS, Bernardino AMR, Becker KM, Machado GMC, Rodrigues RF, Canto-Cavalheiro MM and Leon LL (2013), "Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp", Bioorganic & Medicinal Chemistry Letters., December, 2013. Vol. 23(23), pp. 6310-6312. Pergamon-elsevier Science Ltd.
Abstract: A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity of these compounds was evaluated on the RAW 264.7 cell line. The results showed that among the assayed compounds the substituted 3-chlorophenyl (4a) (IC50/24 h = 15 +/- 0.14 lM) and 3,4-dichlorophenyl tetrazoles (4d) (IC50/24 h = 26 +/- 0.09 lM) were the most potent against L. braziliensis promastigotes, as compared the reference drug pentamidine, which presented IC50 = 13 +/- 0.04 lM. In addition, 4a and 4d derivatives were less cytotoxic than pentamidine. However, these tetrazole derivatives (4) and pyrazole-4-carbonitriles precursors (3) differ against each of the tested species and were more effective against L. braziliensis than on L. amazonensis. (C) 2013 Elsevier Ltd. All rights reserved.
BibTeX:
 @article{Faria2013, author = {Faria, J. V. and dos Santos, M. S. and Bernardino, A. M. R. and Becker, K. M. and Machado, G. M. C. and Rodrigues, R. F. and Canto-Cavalheiro, M. M. and Leon, L. L.}, title = {Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp}, journal = {Bioorganic & Medicinal Chemistry Letters}, publisher = {Pergamon-elsevier Science Ltd}, year = {2013}, volume = {23}, number = {23}, pages = {6310--6312}, doi = {10.1016/j.bmcl.2013.09.062} } 
Fonseca-Silva F, Inacio JDF, Canto-Cavalheiro MM and Almeida-Amaral EE (2013), "Reactive Oxygen Species Production by Quercetin Causes the Death of Leishmania amazonensis Intracellular Amastigotes.", J Nat Prod., Aug, 2013. Vol. 76(8), pp. 1505-1508.
Abstract: The present study reports the mechanism of the antileishmanial activity of quercetin (1) against the intracellular amastigote form of Leishmania amazonensis. Treatment with 1 reduced the infection index in L. amazonensis-infected macrophages in a dose-dependent manner, with an IC50 value of 3.4 μM and a selectivity index of 16.8, and additionally increased ROS generation also in a dose-dependent manner. Quercetin (1) has been described as a pro-oxidant that induces the production of reactive oxygen species, which can cause cell death. Taken together, these results suggest that ROS production plays a role in the mechanism of action of 1 in the control of intracellular amastigotes of L. amazonensis.
BibTeX:
 @article{Fonseca-Silva2013, author = {Fonseca-Silva, Fernanda and Inacio, Job D F. and Canto-Cavalheiro, Marilene M. and Almeida-Amaral, Elmo E.}, title = {Reactive Oxygen Species Production by Quercetin Causes the Death of Leishmania amazonensis Intracellular Amastigotes.}, journal = {J Nat Prod}, year = {2013}, volume = {76}, number = {8}, pages = {1505--1508}, url = {http://dx.doi.org/10.1021/np400193m}, doi = {10.1021/np400193m} } 
Gomes-Silva A, Valverde JG, Ribeiro-Romao RP, Placido-Pereira RM and Da-Cruz AM (2013), "Golden hamster (Mesocricetus auratus) as an experimental model for Leishmania (Viannia) braziliensis infection", Parasitology., May, 2013. Vol. 140(6), pp. 771-779. Cambridge Univ Press.
Abstract: The lack of an adequate model for Leishmania (Viannia) braziliensis infection is a limiting factor for studying American tegumentary leishmaniasis (ATL). The golden hamster (Mesocricetus auratus) is a promising model because besides being highly susceptible to dermotropic Leishmania infection, the lesions are very similar to cutaneous leishmaniasis (CL) in humans. However, different Leishmania isolates or species and/or protocols have resulted in different outcomes, whereas no study has evaluated the reproducibility of L. braziliensis infection in this model. The natural history of L. braziliensis infection in 34 hamsters was evaluated by using a single parasite isolate in 8 independent experiments under similar experimental conditions. Clinical, histological and immunological analyses were performed. The hamsters presented skin ulcers similar to those observed in ATL. The intra-experiment lesion increment tended to show an intermediary variance. Histological analysis of infected skins showed granulomatous reaction, scarce amastigotes, and Schaumann's bodies. Blood lymphocytes proliferated in response to leishmanial antigens. The severity of the infection was positively correlated to spleen weight, and the titres of anti-Leishmania IgG antibodies. Our findings indicate that the hamster is an appropriate model for immunopathogenesis studies of CL caused by L. braziliensis, supporting its use in clinical, vaccine and chemotherapy experimental protocols.
BibTeX:
 @article{Gomes-Silva2013, author = {Gomes-Silva, A. and Valverde, J. G. and Ribeiro-Romao, R. P. and Placido-Pereira, R. M. and Da-Cruz, A. M.}, title = {Golden hamster (Mesocricetus auratus) as an experimental model for Leishmania (Viannia) braziliensis infection}, journal = {Parasitology}, publisher = {Cambridge Univ Press}, year = {2013}, volume = {140}, number = {6}, pages = {771--779}, doi = {10.1017/S0031182012002156} } 
Gonzalez-Caballero N, Valenzuela JG, Mc Ribeiro J, Cuervo P and Brazil RP (), "Transcriptome exploration of the sex pheromone gland of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae)", Parasites & Vectors.
Abstract: Background: Molecules involved in pheromone biosynthesis may represent alternative targets for insect population control. This may be particularly useful in managing the reproduction of Lutzomyia longipalpis, the main vector of the protozoan parasite Leishmania infantum in Latin America. Besides the chemical identity of the major components of the L. longipalpis sex pheromone, there is no information regarding the molecular biology behind its production. To understand this process, obtaining information on which genes are expressed in the pheromone gland is essential. Methods: In this study we used a transcriptomic approach to explore the pheromone gland and adjacent abdominal tergites in order to obtain substantial general sequence information. We used a laboratory-reared L. longipalpis (one spot, 9-Methyl GermacreneB) population, captured in Lapinha Cave, state of Minas Gerais, Brazil for this analysis. Results: From a total of 3,547 cDNA clones, 2,502 high quality sequences from the pheromone gland and adjacent tissues were obtained and assembled into 1,387 contigs. Through blast searches of public databases, a group of transcripts encoding proteins potentially involved in the production of terpenoid precursors were identified in the 4th abdominal tergite, the segment containing the pheromone gland. Among them, protein-coding transcripts for four enzymes of the mevalonate pathway such as 3-hydroxyl-3-methyl glutaryl CoA reductase, phosphomevalonate kinase, diphosphomevalonate descarboxylase, and isopentenyl pyrophosphate isomerase were identified. Moreover, transcripts coding for farnesyl diphosphate synthase and NADP+ dependent farnesol dehydrogenase were also found in the same tergite. Additionally, genes potentially involved in pheromone transportation were identified from the three abdominal tergites analyzed. Conclusion: This study constitutes the first transcriptomic analysis exploring the repertoire of genes expressed in the tissue containing the L. longipalpis pheromone gland as well as the flanking tissues. Using a comparative approach, a set of molecules potentially present in the mevalonate pathway emerge as interesting subjects for further study regarding their association to pheromone biosynthesis. The sequences presented here may be used as a reference set for future research on pheromone production or other characteristics of pheromone communication in this insect. Moreover, some matches for transcripts of unknown function may provide fertile ground of an in-depth study of pheromone-gland specific molecules.
BibTeX:
 @article{Gonzalez-Caballero, author = {Gonzalez-Caballero, N. and Valenzuela, J. G. and Mc Ribeiro, J. and Cuervo, P. and Brazil, R. P.}, title = {Transcriptome exploration of the sex pheromone gland of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae)}, journal = {Parasites & Vectors}, doi = {10.1186/1756-3305-6-56} } 
Inacio JDF, Canto-Cavalheiro MM and Almeida-Amaral EE (2013), "In Vitro and in Vivo Effects of (-)-Epigallocatechin 3-O-gallate on Leishmania amazonensis", Journal of Natural Products., October, 2013. Vol. 76(10), pp. 1993-1996. Amer Chemical Soc.
Abstract: (-)-Epigallocatechin 3-O-gallate (1), the most abundant flavanol in green tea, has been reported to have antiproliferative effects on Trypanosoma cruzi. The present study reports the effects in vitro and in vivo of 1 on Leishmania amazonensis. L. amazonensis-infected macrophages treated with 1 exhibited a significant reduction of the infection index in a dose-dependent manner, with an IC50 value of 1.6 mu M. Oral administration of 1 on L. amazonensis-infected BALB/c mice (30 mg/kg/day) resulted in a decrease in the lesion size and parasite burden, without altering serological markers of toxicity. These data demonstrate the in vitro and in vivo leishmanicidal effects of compound 1.
BibTeX:
 @article{Inacio2013, author = {Inacio, J. D. F. and Canto-Cavalheiro, M. M. and Almeida-Amaral, E. E.}, title = {In Vitro and in Vivo Effects of (-)-Epigallocatechin 3-O-gallate on Leishmania amazonensis}, journal = {Journal of Natural Products}, publisher = {Amer Chemical Soc}, year = {2013}, volume = {76}, number = {10}, pages = {1993--1996}, doi = {10.1021/np400624d} } 
Oliveira FS, Valete-Rosalino CM, Pacheco SJB, Costa FAC, Schubach AO and Pacheco RS (2013), "American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis: assessment of parasite genetic variability at intra- and inter-patient levels.", Parasit Vectors. Vol. 6, pp. 189.
Abstract: The genetic variability of Leishmania (Viannia) braziliensis was assessed at intra and interpatient levels of individuals with different clinical manifestations of American tegumentary leishmaniasis (ATL).Fifty-two samples, of which 13 originated from cutaneous lesions and 39 from mucosal lesions, provided by 35 patients, were examined by low-stringency single-specific-primer PCR (LSSP-PCR) and phenetic analysis. Genetic variability of L. (V.) braziliensis, in kinetoplast DNA (kDNA) signatures, was compared both from different patients and from different lesions of the same patient. Phenetic analysis was performed to evaluate the degree of heterogeneity of the kDNA minicircles. In order to evaluate inter and intrapatient L. (V.) braziliensis genetic variability, the percentage of shared bands and analysis of the coefficients of similarity were analyzed.Different genetic profiles, representing kDNA signatures of the parasite, were obtained by LSSP-PCR analysis of each sample. Phenetic analysis grouped genetic profiles of different levels of differentiation from more similar to most divergent. The percentage of shared bands at the inter and intrapatient levels was 77% and 89 respectively. Comparison of the average inter and intrapatient coefficients of similarity and their standard deviations were statistically significant (p < 0.001).Genetic variability at the intrapatient level was less pronounced than that between different patients. A conceptual model was proposed to better understand the complexity at both levels.
BibTeX:
 @article{Oliveira2013, author = {Oliveira, Fernanda S. and Valete-Rosalino, Cláudia M. and Pacheco, Sandro J B. and Costa, Filipe A Carvalho and Schubach, Armando O. and Pacheco, Raquel S.}, title = {American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis: assessment of parasite genetic variability at intra- and inter-patient levels.}, journal = {Parasit Vectors}, year = {2013}, volume = {6}, pages = {189}, url = {http://dx.doi.org/10.1186/1756-3305-6-189}, doi = {10.1186/1756-3305-6-189} } 
Pereira LdOR, Maretti-Mira AC, Rodrigues KM, Lima RB, de Oliveira-Neto MP, Cupolillo E, Pirmez C and de Oliveira MP (2013), "Severity of tegumentary leishmaniasis is not exclusively associated with Leishmania RNA virus 1 infection in Brazil.", Mem Inst Oswaldo Cruz., Aug, 2013. Vol. 108(5), pp. 665-667.
Abstract: Leishmania RNA virus (LRV) has been shown to be a symbiotic component of Leishmania parasites in South America. Nested retro-transcription polymerase chain reaction was employed to investigate LRV1 presence in leishmaniasis lesions from Brazil. In endemic areas of Rio de Janeiro (RJ), no LRV1 infection was observed even with mucosal involvement. LRV1 was only detected in Leishmania (V.) guyanensis cutaneous lesions from the northern region, which were obtained from patients presenting with disease reactivation after clinical cure of their primary lesions. Our results indicated that the severity of leishmaniasis in some areas of RJ, where Leishmania (V.) brazi-liensis is the primary etiological agent, was not associated with Leishmania LRV1 infection.
BibTeX:
 @article{Pereira2013, author = {Pereira, Luiza de Oliveira Ramos and Maretti-Mira, Ana Cláudia and Rodrigues, Káris Maria and Lima, Rosimar Baptista and de Oliveira-Neto, Manoel Paes and Cupolillo, Elisa and Pirmez, Claude and de Oliveira, Márcia Pereira}, title = {Severity of tegumentary leishmaniasis is not exclusively associated with Leishmania RNA virus 1 infection in Brazil.}, journal = {Mem Inst Oswaldo Cruz}, year = {2013}, volume = {108}, number = {5}, pages = {665--667}, doi = {10.1590/0074-0276108052013021} } 
Ribeiro GA, Cunha EF, Pinheiro RO, Da-Silva SAG, Canto-Cavalheiro MM, da Silva AJM, Costa PRR, Netto CD, Melo RCN, Almeida-Amaral EE and Torres-Santos EC (2013), "LQB-118, an orally active pterocarpanquinone, induces selective oxidative stress and apoptosis in Leishmania amazonensis", Journal of Antimicrobial Chemotherapy., April, 2013. Vol. 68(4), pp. 789-799. Oxford Univ Press.
Abstract: Objectives: The pterocarpanquinone LQB-118, previously demonstrated to be effective in vivo via oral delivery, was investigated for its mechanism in selective parasite killing. Methods: Oxidative stress in Leishmania amazonensis was analysed by evaluating reactive oxygen species (ROS) production (2',7'-dichlorodihydrofluorescein diacetate) and the loss of mitochondrial membrane potential (Delta Psi(m)) using rhodamine, JC-1 and MitoCapture. Ultrastructural analysis was performed using transmission electron microscopy (TEM). DNA fragmentation was evaluated using terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). Results: Treatment with LQB-118 induced ROS production in the promastigotes of L. amazonensis in a concentration-dependent manner for the first 4 h and was sustained for 24 h. TEM analysis revealed several alterations typical of apoptosis. Promastigotes presented a reduction of Delta Psi(m), after 24 h of incubation with 2.5 mu M (18.7%), 5 mu M (63.7%) or 10 mu M (70.7%) LQB-118. A sub-G(0)/G(1) cell cycle phenotype was observed in 21%-83% of the promastigotes incubated with 1.25-10 mu M LQB-118. Concentration-dependent DNA fragmentation was observed in promastigotes treated with 2.5-10 mu M LQB-118, and selective DNA fragmentation was observed in intracellular amastigotes after 72 h with 2.5 mu M treatment. Conclusions: Our results suggest that LQB-118 selectively induces ROS-triggered and mitochondria-dependent apoptosis in this parasite.
BibTeX:
 @article{Ribeiro2013, author = {Ribeiro, G. A. and Cunha, E. F. and Pinheiro, R. O. and Da-Silva, S. A. G. and Canto-Cavalheiro, M. M. and da Silva, A. J. M. and Costa, P. R. R. and Netto, C. D. and Melo, R. C. N. and Almeida-Amaral, E. E. and Torres-Santos, E. C.}, title = {LQB-118, an orally active pterocarpanquinone, induces selective oxidative stress and apoptosis in Leishmania amazonensis}, journal = {Journal of Antimicrobial Chemotherapy}, publisher = {Oxford Univ Press}, year = {2013}, volume = {68}, number = {4}, pages = {789--799}, doi = {10.1093/jac/dks498} } 
Rodrigues EHG, Soares FCD, Werkhauser RP, de Brito MEF, Fernandes O, Abath FGC and Brandao A (2013), "The compositional landscape of minicircle sequences isolated from active lesions and scars of American cutaneous leishmaniasis", Parasites & Vectors., August, 2013. Vol. 6, pp. 228. Biomed Central Ltd.
Abstract: Background: American cutaneous leishmaniasis (ACL) is characterized by cutaneous lesions that heal spontaneously or after specific treatment. This paper reports on the analysis of kDNA minicircle sequences from clinical samples (typical lesions and scars) that were PCR-amplified with specific primers for Leishmania species of the subgenus Viannia. Methods: From 56 clinical isolates we obtained a single amplified fragment (ca. 790 bp), which after cloning and sequencing resulted in 290 minicircle sequences from both active lesions and scars. We aimed to get a compositional profile of these sequences in clinical samples and evaluate the corresponding compositional changes. Sequences were analyzed with the compseq and wordcount (Emboss package) to get the composition of di-, tri-, tetra-, penta- and hexanucleotides. Additionally, we built a nucleotide dictionary with words of 7, 8, 9 and 10 nucleotides. Results: This compositional analysis showed that minicircles amplified from active cutaneous lesions and scars have a distinct compositional profile as viewed by nucleotide composition of words up to 10mer. With regard to the most frequent nucleotide words above length 6, there is also a distinct pattern for 7, 8, 9 and 10mer. Conclusion: These results indicate that minicircle sequences can be monitored upon direct exposure to a selection/stressing environment (e.g. chemical action) by evaluating their nucleotide compositional profile. It might be useful as a molecular tool in research concerning the evolution of infecting Leishmania in both vector and vertebrate hosts.
BibTeX:
 @article{Rodrigues2013, author = {Rodrigues, E. H. G. and Soares, F. C. D. and Werkhauser, R. P. and de Brito, M. E. F. and Fernandes, O. and Abath, F. G. C. and Brandao, A.}, title = {The compositional landscape of minicircle sequences isolated from active lesions and scars of American cutaneous leishmaniasis}, journal = {Parasites & Vectors}, publisher = {Biomed Central Ltd}, year = {2013}, volume = {6}, pages = {228}, doi = {10.1186/1756-3305-6-228} } 
Santos-Oliveira JR, Regis EG, Giacoia-Gripp CBW, Valverde JG, Alexandrino-de-Oliveira P, Lindoso JAL, Goto H, Oliveira-Neto MP, Guerra JO, Grinsztejn B, Jeronimo SB, Morgado MG and Da-Cruz AM (2013), "Microbial Translocation Induces an Intense Proinflammatory Response in PatientsWith Visceral Leishmaniasis and HIV Type 1 Coinfection", Journal of Infectious Diseases., July, 2013. Vol. 208(1), pp. 57-66. Oxford Univ Press Inc.
Abstract: Background. Leishmania infection is a cofactor in the heightened cellular activation observed in patients with American visceral leishmaniasis and human immunodeficiency virus type 1 (HIV) infection, with or without progression to AIDS (AVL/HIV). Thus, the persistence of a high parasite load despite antileishmanial therapy could be responsible for the continued immune stimulation. Methods. CD8(+) T cells expressing CD38, parasite load, lipopolysaccharide (LPS), soluble CD14, macrophage migration inhibitory factor (MIF), intestinal fatty acid-binding protein (IFABP), and proinflammatory cytokines (interleukin 1 beta, interleukin 6, interleukin 8, interleukin 17, interferon gamma, and tumor necrosis factor) were measured in 17 patients with AVL/HIV, 16 with HIV, and 14 healthy subjects (HS). Results. Lower Leishmania parasitemia was observed after antileishmanial and antiretroviral therapies. However, higher levels of CD38(+) on CD8(+) T cells were observed in both clinical phases of leishmaniasis, compared with HIV cases. AVL/HIV and HIV patients showed higher levels of LPS and IFABP than HS. Proinflammatory cytokine levels were significantly augmented in patients with active coinfection, as well as those with remission of Leishmania infection. LPS levels and Leishmania infection were positively correlated with CD38 expression on CD8(+) T cells and with IL-6 and IL-8 levels. Conclusions. LPS levels along with the immune consequences of Leishmania infection were associated with elevated cellular activation in coinfected patients. As a consequence, secondary chemoprophylaxis for leishmaniasis or even the use of antiinflammatory drugs or antibiotics may be considered for improving the prognosis of AVL/HIV.
BibTeX:
 @article{Santos-Oliveira2013, author = {Santos-Oliveira, J. R. and Regis, E. G. and Giacoia-Gripp, C. B. W. and Valverde, J. G. and Alexandrino-de-Oliveira, P. and Lindoso, J. A. L. and Goto, H. and Oliveira-Neto, M. P. and Guerra, J. O. and Grinsztejn, B. and Jeronimo, S. B. and Morgado, M. G. and Da-Cruz, A. M.}, title = {Microbial Translocation Induces an Intense Proinflammatory Response in PatientsWith Visceral Leishmaniasis and HIV Type 1 Coinfection}, journal = {Journal of Infectious Diseases}, publisher = {Oxford Univ Press Inc}, year = {2013}, volume = {208}, number = {1}, pages = {57--66}, doi = {10.1093/infdis/jit135} } 
Spiegel CN, Bretas JAC, Peixoto AA, Vigoder FM, Bruno RV and Soares MJ (2013), "Fine Structure of the Male Reproductive System and Reproductive Behavior of Lutzomyia longipalpis Sandflies (Diptera: Psychodidae: Phlebotominae)", Plos One., September, 2013. Vol. 8(9) Public Library Science.
Abstract: Background: The male reproductive system of insects can have several tissues responsible for the secretion of seminal fluid proteins (SFPs), such as testes, accessory glands, seminal vesicles, ejaculatory duct and ejaculatory bulb. The SFPs are transferred during mating and can induce several physiological and behavioral changes in females, such as increase in oviposition and decrease in sexual receptivity after copulation. The phlebotomine Lutzomyia longipalpis is the main vector of visceral leishmaniasis. Despite its medical importance, little is known about its reproductive biology. Here we present morphological aspects of the male L. longipalpis reproductive system by light, scanning and transmission electron microscopy, and compare the mating frequency of both virgin and previously mated females. Results: The male L. longipalpis reproductive system is comprised by a pair of oval-shaped testes linked to a seminal vesicle by vasa deferentia. It follows an ejaculatory duct with an ejaculatory pump (a large bulb enveloped by muscles and associated to tracheas). The terminal endings of the vasa deferentia are inserted into the seminal vesicle by invaginations of the seminal vesicle wall, which is composed by a single layer of gland cells, with well-developed endoplasmic reticulum profiles and secretion granules. Our data suggest that the seminal vesicle acts both as a spermatozoa reservoir and as an accessory gland. Mating experiments support this hypothesis, revealing a decrease in mating frequency after copulation that indicates the effect of putative SFPs. Conclusion: Ultrastructural features of the L. longipalpis male seminal vesicle indicated its possible role as an accessory gland. Behavioral observations revealed a reduction in mating frequency of copulated females. Together with transcriptome analyses from male sandfly reproductive organs identifying ESTs encoding orthologs of SFPs, these data indicate the presence of putative L. longipalpis SFPs reducing sexual mating frequency of copulated females.
BibTeX:
 @article{Spiegel2013, author = {Spiegel, C. N. and Bretas, J. A. C. and Peixoto, A. A. and Vigoder, F. M. and Bruno, R. V. and Soares, M. J.}, title = {Fine Structure of the Male Reproductive System and Reproductive Behavior of Lutzomyia longipalpis Sandflies (Diptera: Psychodidae: Phlebotominae)}, journal = {Plos One}, publisher = {Public Library Science}, year = {2013}, volume = {8}, number = {9}, doi = {10.1371/journal.pone.0074898} } 
Telleria EL, Sant'Anna MRV, Alkurbi MO, Pitaluga AN, Dillon RJ and Traub-Csekö YM (2013), "Bacterial feeding, Leishmania infection and distinct infection routes induce differential defensin expression in Lutzomyia longipalpis.", Parasit Vectors. Vol. 6, pp. 12.
Abstract: Phlebotomine insects harbor bacterial, viral and parasitic pathogens that can cause diseases of public health importance. Lutzomyia longipalpis is the main vector of visceral leishmaniasis in the New World. Insects can mount a powerful innate immune response to pathogens. Defensin peptides take part in this response and are known to be active against Gram-positive and Gram-negative bacteria, and some parasites. We studied the expression of a defensin gene from Lutzomyia longipalpis to understand its role in sand fly immune response.We identified, sequenced and evaluated the expression of a L. longipalpis defensin gene by semi-quantitative RT-PCR. The gene sequence was compared to other vectors defensins and expression was determined along developmental stages and after exposure of adult female L. longipalpis to bacteria and Leishmania.Phylogenetic analysis showed that the L. longipalpis defensin is closely related to a defensin from the Old World sand fly Phlebotomus duboscqi. Expression was high in late L4 larvae and pupae in comparison to early larval stages and newly emerged flies. Defensin expression was modulated by oral infection with bacteria. The Gram-positive Micrococcus luteus induced early high defensin expression, whilst the Gram-negative entomopathogenic Serratia marcescens induced a later response. Bacterial injection also induced defensin expression in adult insects. Female sand flies infected orally with Leishmania mexicana showed no significant difference in defensin expression compared to blood fed insects apart from a lower defensin expression 5 days post Leishmania infection. When Leishmania was introduced into the hemolymph by injection there was no induction of defensin expression until 72 h later.Our results suggest that L. longipalpis modulates defensin expression upon bacterial and Leishmania infection, with patterns of expression that are distinct among bacterial species and routes of infection.
BibTeX:
 @article{Telleria2013, author = {Telleria, Erich L. and Sant'Anna, Maurício R Viana and Alkurbi, Mohammad O. and Pitaluga, André N. and Dillon, Rod J. and Traub-Csekö, Yara M.}, title = {Bacterial feeding, Leishmania infection and distinct infection routes induce differential defensin expression in Lutzomyia longipalpis.}, journal = {Parasit Vectors}, year = {2013}, volume = {6}, pages = {12}, url = {http://dx.doi.org/10.1186/1756-3305-6-12}, doi = {10.1186/1756-3305-6-12} } 
Torres DC, Ribeiro-Alves M, Romero GAS, Davila AMR and Cupolillo E (2013), "Assessment of drug resistance related genes as candidate markers for treatment outcome prediction of cutaneous leishmaniasis in Brazil", Acta Tropica., May, 2013. Vol. 126(2), pp. 132-141. Elsevier Science Bv.
Abstract: The great public health problem posed by leishmaniasis has substantially worsened in recent years by the emergence of clinical failure. In Brazil, the poor prognosis observed for patients infected by Leishmania braziliensis (Lb) or L. guyanensis (Lg) may be related to parasite drug resistance. In the present study, 19 Lb and 29 Lg isolates were obtained from infected patients with different treatment outcomes. Translated amino acid sequence polymorphisms from four described antimony resistance related genes (AQP1, hsp70, MRPA and TRYR) were tested as candidate markers for antimonial treatment failure prediction. Possibly due to the low intraspecific variability observed in Lg samples, none of the prediction models had good prognosis values. Most strikingly, one mutation (T579A) found in hsp70 of Lb samples could predict 75% of the antimonial treatment failure clinical cases. Moreover, a multiple logistic regression model showed that the change from adenine to guanine at position 1735 of the hsp70 gene, which is responsible for the T579A mutation, significantly increased the chance of Lb clinical isolates to be associated with treatment failure (OR = 7.29; CI 95% = [1.17,45.25]; p = 0.0331). The use of molecular markers to predict treatment outcome presents practical and economic advantages as it allows the development of rapid assays to monitor the emergence of drug resistant parasites that can be clinically applied to aid the prognosis of cutaneous leishmaniasis in Brazil. (C) 2013 Elsevier B.V. All rights reserved.
BibTeX:
 @article{Torres2013, author = {Torres, D. C. and Ribeiro-Alves, M. and Romero, G. A. S. and Davila, A. M. R. and Cupolillo, E.}, title = {Assessment of drug resistance related genes as candidate markers for treatment outcome prediction of cutaneous leishmaniasis in Brazil}, journal = {Acta Tropica}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {126}, number = {2}, pages = {132--141}, doi = {10.1016/j.actatropica.2013.02.002} } 

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