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Sent on Wednesday, 2011 Aug 31Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results |
1. | Int Immunopharmacol. 2011 Aug 26. [Epub ahead of print]Immunomodulation by chemotherapeutic agents against Leishmaniasis.Saha P, Mukhopadhyay D, Chatterjee M.AbstractLeishmaniasis is caused by protozoan parasites of the genus Leishmania and causes a wide spectrum of clinical manifestations ranging from self-healing cutaneous lesions to the fatal visceral form. The use of pentavalent antimony, the mainstay of therapy of Leishmaniasis is now limited by its toxicity and alarming increase in unresponsiveness, especially in the Indian subcontinent. Furthermore, other anti-leishmanial drugs are unaffordable in many affected countries and as vaccination based approaches have not yet proved to be effective, chemotherapy remains the only alternative, emphasizing the need for identifying novel drug targets. In this review, we have described the different host immune signaling pathways that could be considered as potential drug targets for Leishmania chemotherapy. Copyright © 2011. Published by Elsevier B.V. |
2. | Acta Trop. 2011 Aug 22. [Epub ahead of print]DNA vaccination with KMP11 and Lutzomyia longipalpis salivary protein protects hamsters against visceral leishmaniasis.da Silva RA, Tavares NM, Costa D, Pitombo M, Barbosa L, Fukutani K, Miranda JC, de Oliveira CI, Valenzuela JG, Barral A, Soto M, Barral-Netto M, Brodskyn C.SourceCentro de Pesquisas Gonçalo Moniz (CPqGM), FIOCRUZ, Salvador, Bahia, Brazil; Universidade Federal da Bahia - UFBA (Instituto Multidisciplinar em Saúde, Vitória da Conquista, Bahia, Brazil; Instituto de Ciências da Saúde e Faculdade de Medicina, Brazil. AbstractIt was recently shown that immunization of hamsters with DNA plasmids coding LJM19, a sand fly salivary protein, partially protected against a challenge with Leishmania chagasi, whereas immunization with KMP11 DNA plasmid, a Leishmania antigen, induced protection against L. donovani infection. In the present study, we evaluated the protective effect of immunization with both LJM19 and KMP11 DNA plasmid together. Concerning the protection against an infection by L. chagasi, immunization with DNA plasmids coding LJM19 or KMP11, as well as with both plasmids combined, induced IFN-γ production in draining lymph nodes at 7, 14 and 21 days post-immunization. Immunized hamsters challenged with L. chagasi plus Salivary Gland Sonicate (SGS) from Lutzomyia longipalpis showed an enhancement of IFN-γ/IL-10 and IFN-γ/TGF-β in draining lymph nodes after 7 and 14 days of infection. Two and five months after challenge, immunized animals showed reduced parasite load in the liver and spleen, as well as increased IFN-γ/IL-10 and IFN-γ/TGF-β ratios in the spleen. Furthermore, immunized animals remained with a normal hematological profile even five months after the challenge, whereas L. chagasi in unimmunized hamsters lead to a significant anemia. The protection observed with LJM19 or KMP11 DNA plasmids used alone was very similar to the protection obtained by the combination of both plasmids. Copyright © 2011. Published by Elsevier B.V. |
3. | Science. 2011 Aug 19;333(6045):934.Infectious diseases. A tropical disease hits the road.Leslie M. |
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4. | Science. 2011 Aug 19;333(6045):933-5.Infectious diseases. Drug developers finally take aim at a neglected diseas e.Leslie M. |
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5. | Rev Argent Microbiol. 2011 Apr-May;43(2):79-80.[The death of Dr. Mariano J. Levin]. [ Article in Spanish] Cataldi AA. Free Article |
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6. | PLoS One. 2011 Apr 18;6(4):e18791.Identification of amino acids that account for long-range interactions in two triosephosphate isomerases from pathogenic trypanosomes.García-Torres I, Cabrera N, Torres-Larios A, Rodríguez-Bolaños M, Díaz-Mazariegos S, Gómez-Puyou A, Perez-Montfort R.SourceDepartamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, México DF, Mexico. AbstractFor a better comprehension of the structure-function relationship in proteins it is necessary to identify the amino acids that are relevant for measurable protein functions. Because of the numerous contacts that amino acids establish within proteins and the cooperative nature of their interactions, it is difficult to achieve this goal. Thus, the study of protein-ligand interactions is usually focused on local environmental structural differences. Here, using a pair of triosephosphate isomerase enzymes with extremely high homology from two different organisms, we demonstrate that the control of a seventy-fold difference in reactivity of the interface cysteine is located in several amino acids from two structurally unrelated regions that do not contact the cysteine sensitive to the sulfhydryl reagent methylmethane sulfonate, nor the residues in its immediate vicinity. The change in reactivity is due to an increase in the apparent pKa of the interface cysteine produced by the mutated residues. Our work, which involved grafting systematically portions of one protein into the other protein, revealed unsuspected and multisite long-range interactions that modulate the properties of the interface cysteines and has general implications for future studies on protein structure-function relationships. |
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7. | Transfus Clin Biol. 2011 Apr;18(2):286-91. Epub 2011 Mar 26.[Chagas disease and blood transfusion: an emerging issue in non-endemic countries]. [Article in French] Assal A, Corbi C.SourceÉtablissement français du sang (EFS), 20, avenue du Stade-de-France, 93218 La Plaine Saint-Denis, France. azzedine.assal@efs.sante.fr AbstractChagas disease or American human trypanosomiasis, is a parasitic disease due to Trypanosoma cruzi, which is endemic in Latin America. The parasite is transmitted by haematophagous vectors from reduviidae family. In some patients, the parasite is responsible for severe complications such as cardiac manifestations, gastrointestinal involvement and neurologic disease. Imported Chagas disease by immigration in non-endemic countries poses the threat of the infection transmission by blood transfusion. In order to prevent this risk, the French Blood Services (EFS) introduced systematic screening of at-risk blood donors for anti-T. cruzi antibodies, in May 2007. The concerned donors are people originating from an endemic area, donors with mothers originating from such an area and individuals who had lived in or travelled to endemic areas. Donors were screened with two different Elisas simultaneously: one Elisa using purified parasite lysate antigens and the second one composed of recombinant antigens. Positive results and discrepant results were further assayed with an immunofluorescence assay. A seroprevalence assay was performed in the 17 French blood centres after an 18-month testing period from May 2007 to December 2008. During this period 4,637,479 million donations were collected. Out of these 163,740 donations were tested (3.5%). The prevalence of anti-T. cruzi antibodies was one in 32,800 donations. Five positive donors were identified. All of them were originating from endemic areas. A rate of 0.85% indeterminate results was found. Screening strategy revision was decided to reduce the number of donors unnecessarily deferred. Copyright © 2011 Elsevier Masson SAS. All rights reserved. |
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8. | Mem Inst Oswaldo Cruz. 2010 Nov;105(7):945-8.The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice.Miguel DC, Ferraz ML, Alves Rde O, Yokoyama-Yasunaka JK, Torrecilhas AC, Romanha AJ, Uliana SR.SourceDepartamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil. AbstractThe activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice. |
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9. | Mem Inst Oswaldo Cruz. 2010 Nov;105(7):918-24.Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease.Moreno M, D'ávila DA, Silva MN, Galvão LM, Macedo AM, Chiari E, Gontijo ED, Zingales B.SourceDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brasil. AbstractTherapeutic failure of benznidazole (BZ) is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years. A protocol for early screening of the drug resistance of infective strains would be valuable for orienting physicians towards alternative therapies, with a combination of existing drugs or new anti-T. cruzi agents. We developed a procedure that couples the isolation of parasites by haemoculture with quantification of BZ susceptibility in the resultant epimastigote forms. BZ activity was standardized with reference strains, which showed IC₅₀ to BZ between 7.6-32 µM. The assay was then applied to isolates from seven chronic patients prior to administration of BZ therapy. The IC₅₀ of the strains varied from 15.6 ± 3-51.4 ± 1 µM. Comparison of BZ susceptibility of the pre-treatment isolates of patients considered cured by several criteria and of non-cured patients indicates that the assay does not predict therapeutic outcome. A two-fold increase in BZ resistance in the post-treatment isolates of two patients was verified. Based on the profile of nine microsatellite loci, sub-population selection in non-cured patients was ruled out. |
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