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Sent on Tuesday, 2010 Mar 02Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Eukaryot Cell. 2010 Feb 26. [Epub ahead of print]A Trk/HKT-type K+ transporter from Trypanosoma brucei.Mosimann M, Goshima S, Wenzler T, Lüscher A, Uozumi N, Mäser P.Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland; Department of Biomolecular Engineering, Tohoku University, Sendai 980-8579, Japan; Swiss Tropical Institute, 4002 Basel, Switzerland. The molecular mechanisms of K(+) homeostasis are only poorly understood for protozoan parasites. Trypanosoma brucei ssp., the causative agents of human sleeping sickness and nagana, are strictly extracellular and need to actively concentrate K(+) from their hosts' body fluids. The T. brucei genome contains two putative K(+) channel genes, yet the trypanosomes are insensitive to K(+) antagonists and K(+) channel-blocking agents, and they do not spontaneously depolarize in response to high extracellular K(+) concentrations. However, the trypanosomes are extremely sensitive to K(+) ionophores such as valinomycin. Surprisingly, T. brucei possess a member of the Trk/HKT superfamily of monovalent cation permeases which were so far only known from bacteria, archaea, fungi and plants. The protein was named TbHKT and functions as a Na(+)-independent K(+) transporter when expressed in Escherichia coli, Saccharomyces cerevisiae, or in Xenopus laevis oocytes. In trypanosomes, TbHKT1 is expressed in both the mammalian bloodstream stage and the Tsetse fly midgut stage; however, RNAi-mediated silencing of TbHKT1 expression did not produce a growth phenotype in either stage. The presence of HKT genes in trypanosomatids adds a further piece to the enigmatic phylogeny of the Trk/HKT superfamily of K(+) transporters. Parsimonial analysis suggests that the transporters were present in the first eukaryotes but subsequently lost in several of the major eukaryotic lineages, in at least four independent events. |
| PMID: 20190075 [PubMed - as supplied by publisher] | |
| 2. | Vet Parasitol. 2010 Jan 25. [Epub ahead of print]Relationship of Leishmania-specific IgG levels and IgG avidity with parasite density and clinical signs in canine leishmaniasis.Neto RG, Giunchetti RC, Carneiro CM, Vitor RW, Coura-Vital W, Quaresma PF, Ker HG, Melo LA, Gontijo CM, Reis AB.Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil; Laboratório de Leishmanioses, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil. The clinical status and tissue parasite burden of the skin and spleen of 40 dogs naturally infected with Leishmania chagasi (syn. Leishmania infantum), together with 5 uninfected control dogs, were assessed. On the basis of the clinical evaluation, infected dogs were classified as asymptomatic (AD) or symptomatic (SD). Infected animals were also grouped according to their parasite load as exhibiting low (LP), medium (MP) and high (HP) parasitism. The results indicated a high parasite load in the skin samples of SD animals in relation to the AD group. The serum immunoglobin isotype profiles of the studied animals revealed increased levels of IgG(1) in the AD and LP dogs, whereas high levels of IgG(2) were correlated with SD and HP dogs. The avidity index (AI) of IgG(total) in the SD group was high in comparison of that of the AD group. Moreover, animals with a larger parasite burden either in the spleen or skin showed higher AI values than animals with lower parasitism. Based on these findings, it is suggested that CVL commences with an asymptomatic clinical form with low parasitism, high production of IgG(1) and low affinity of IgG(total) molecules, and evolves into a symptomatic clinical form with higher parasitism intensity, higher IgG(2) levels, and high affinity of IgG(total). Copyright © 2010 Elsevier B.V. All rights reserved. |
| PMID: 20188477 [PubMed - as supplied by publisher] | |
| 3. | Microbes Infect. 2010 Feb 23. [Epub ahead of print]Prolyl Oligopeptidase of Trypanosoma brucei hydrolyzes native collagen, peptide hormones and is active in the plasma of infected mice.Bastos IM, Motta FN, Charneau S, Santana JM, Dubost L, Augustyns K, Grellier P.Laboratório de Interação Parasito-Hospedeiro, Faculdade de Medicina, Universidade de Brasília, 70910-900-DF, Brazil; Faculdade Ceilândia, Universidade de Brasília, 72220-240-DF, Brazil. Proteases play important roles in many biological processes of parasites, including their host interactions. In sleeping sickness, Trypanosoma brucei proteases released into the host bloodstream could hydrolyze host factors, such as hormones, contributing to the development of the disease's symptoms. In this study, we present the identification of the Trypanosoma brucei prolyl oligopeptidase gene (poptb) and the characterization of its corresponding enzyme, POP Tb. Secondary structure predictions of POP Tb show a structural composition highly similar to other POPs. Recombinant POP Tb produced in E. coli was active and highly sensitive to inhibitors of T. cruzi POP Tc80. These inhibitors, which prevent T. cruzi entry into non-phagocytic cells, arrested growth of the T. brucei bloodstream form in a dose-dependent manner. POP Tb hydrolyzes peptide hormones containing Pro or Ala at the P1 position at a slightly alkaline pH, and also cleaves type I collagen in vitro and native collagen present in rat mesentery. Furthermore, POP Tb is released into the bloodstream of T. brucei infected mice where it remains active. These data suggest that POP Tb might contribute to the pathogenesis of sleeping sickness. Copyright © 2010. Published by Elsevier SAS. |
| PMID: 20188209 [PubMed - as supplied by publisher] | |
| 4. | J Biomed Biotechnol. 2010;2010:341783. Epub 2009 Dec 21.Immunological and therapeutic strategies against salmonid cryptobiosis.Woo PT.Department of Integrative Biology, University of Guelph, Guelph, ON, Canada. Salmonid cryptobiosis is caused by the haemoflagellate, Cryptobia salmositica. Clinical signs of the disease in salmon (Oncorhynchus spp.) include exophthalmia, general oedema, abdominal distension with ascites, anaemia, and anorexia. The disease-causing factor is a metalloprotease and the monoclonal antibody (mAb-001) against it is therapeutic. MAb-001 does not fix complement but agglutinates the parasite. Some brook charr, Salvelinus fontinalis cannot be infected (Cryptobia-resistant); this resistance is controlled by a dominant Mendelian locus and is inherited. In Cryptobia-resistant charr the pathogen is lysed via the Alternative Pathway of Complement Activation. However, some charr can be infected and they have high parasitaemias with no disease (Cryptobia-tolerant). In infected Cryptobia-tolerant charr the metalloprotease is neutralized by a natural antiprotease, alpha2 macroglobulin. Two vaccines have been developed. A single dose of the attenuated vaccine protects 100% of salmonids (juveniles and adults) for at least 24 months. Complement fixing antibody production and cell-mediated response in vaccinated fish rise significantly after challenge. Fish injected with the DNA vaccine initially have slight anaemias but they recover and have agglutinating antibodies. On challenge, DNA-vaccinated fish have lower parasitaemias, delayed peak parasitaemias and faster recoveries. Isometamidium chloride is therapeutic against the pathogen and its effectiveness is increased after conjugation to antibodies. PMCID: PMC2801003 |
| PMID: 20052385 [PubMed - indexed for MEDLINE] | |
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| 5. | Eur J Immunol. 2010 Feb;40(2):417-25.Apoptotic lymphocytes treated with IgG from Trypanosoma cruzi infection increase TNF-alpha secretion and reduce parasite replication in macrophages.Montalvão F, Almeida GM, Silva EM, Borges VM, Vasconcellos R, Takiya CM, Lopes MF, Nunes MP, DosReis GA.Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Phagocytic removal of apoptotic lymphocytes exacerbates replication of Trypanosoma cruzi in macrophages. We investigated the presence of Ab against apoptotic lymphocytes in T. cruzi infection and the role of these Ab in parasite replication. Both control and chagasic serum contained IgG Ab that opsonized apoptotic lymphocytes. Treatment of apoptotic lymphocytes with purified IgG from chagasic, but not control serum, reduced T. cruzi replication in macrophages. The protective effect of chagasic IgG depended on Fcgamma receptors, as demonstrated by the requirement for the intact Fc portion of IgG, and the effect could be abrogated by treating macrophages with an anti-CD16/CD32 Fab fragment. Chagasic IgG displayed increased reactivity against a subset of apoptotic cell Ag, as measured by flow cytometry and immunoblot analyses. Apoptotic lymphocytes treated with chagasic IgG, but not control IgG, increased production of TNF-alpha, while decreasing production of TGF-beta1 by infected macrophages. Increased control of parasite replication required TNF-alpha production. Previous immunization with apoptotic cells or injection of apoptotic cells opsonized with chagasic IgG reduced parasitemia in infected mice. These results indicate that Ab raised against apoptotic cells could play a protective role in control of T. cruzi replication by macrophages. |
| PMID: 19950177 [PubMed - indexed for MEDLINE] | |
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| 6. | Exp Parasitol. 2010 Mar;124(3):319-24. Epub 2009 Nov 26.Neolignans from plants in northeastern Brazil (Lauraceae) with activity against Trypanosoma cruzi.Cabral MM, Barbosa-Filho JM, Maia GL, Chaves MC, Braga MV, De Souza W, Soares RO.Laboratório de Diptera, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365, 21045-900 Rio de Janeiro, RJ, Brazil. mmaleck@ioc.fiocruz.br Trypanosoma cruzi is the ethiological agent for Chagas disease in Latin America. This study aimed to test the trypanocidal effect of licarin A and burchellin isolated from plants in northeastern Brazil. These neolignans were tested on T. cruzi and on peritoneal macrophages, to evaluate drug toxicity. Epimastigote growth was inhibited in 45% with licarin A and 20% with burchellin with an IC(50)/96 h of 462.7 microM and 756 microM, respectively. Epimastigotes treated with licarin A presented swollen mitochondria and disorganized mitochondrial cristae, kDNA and Golgi complex. When treated with burchellin, they presented enormous autophagosomes and chromatin disorganization. Licarin A and burchellin were able to induce trypomastigote death with IC(50)/24 h of 960 microM and 520 microM, respectively. Although licarin A presented an IC(50) for trypomastigotes higher than for epimastigotes, both substances acted as therapeutic trypanocidal agents, because they were able to kill parasites without affecting macrophages. Due to our results, burchellin and licarin A need to be further analysed to observe if they may be used as alternative blood additive prophylaxis against Chagas disease, since it has been established that blood transfusion is an important mechanism in the transmission process. Copyright 2009 Elsevier Inc. All rights reserved. |
| PMID: 19944690 [PubMed - indexed for MEDLINE] | |
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| 7. | Exp Parasitol. 2010 Mar;124(3):301-5. Epub 2009 Dec 16.Trypanosoma evansi: Effect of experimental infection on the osmotic fragility, lipid peroxidation and calcium-ATPase activity of rat red blood cells.Mijares A, Vivas J, Abad C, Betancourt M, Piñero S, Proverbio F, Marín R, Portillo R.Laboratorio de Fisiología de Parásitos, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, A.P. 21827, Caracas 1020A, Venezuela. Trypanosoma evansi is the causative agent of equine trypanosomoses. The disease is characterized by fever, anemia, and cachexia. Peroxidative damage of the red blood cells caused by the parasite, may contribute to the pathogenesis of the anemia seen in trypanosomoses. Consequently, we evaluated the hematocrit, the osmotic fragility of the red blood cells, the level of lipid peroxidation and the activity of the Ca-ATPase of red blood cell ghosts from rats experimentally infected with T. evansi. After 72 h inoculation, the hematocrit decreased from 49.5% to 33%; the osmotic fragility of the red blood cells was approximately 40% higher as compared to the healthy animals; and the red blood cell ghosts showed a higher level of lipid peroxidation and a lower Ca-ATPase activity than the red cell ghosts from the healthy animals. In vitro incubations of red blood cells from healthy animals with T. evansi, produced also a significant increase of the osmotic fragility of the red blood cells. Copyright 2009 Elsevier Inc. All rights reserved. |
| PMID: 19931529 [PubMed - indexed for MEDLINE] | |
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| 8. | Mem Inst Oswaldo Cruz. 2009 Jul;104 Suppl 1:311-8.Ergosterol biosynthesis and drug development for Chagas disease.Urbina JA.Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela. jurbina@mac.com This article presents an overview of the currently available drugs nifurtimox (NFX) and benznidazole (BZN) used against Trypanosoma cruzi, the aetiological agent of Chagas disease; herein we discuss their limitations along with potential alternatives with a focus on ergosterol biosynthesis inhibitors (EBI). These compounds are currently the most advanced candidates for new anti-T. cruzi agents given that they block de novo production of 24-alkyl-sterols, which are essential for parasite survival and cannot be replaced by a host's own cholesterol. Among these compounds, new triazole derivatives that inhibit the parasite's C14alpha sterol demethylase are the most promising, as they have been shown to have curative activity in murine models of acute and chronic Chagas disease and are active against NFX and BZN-resistant T. cruzi strains; among this class of compounds, posaconazole (Schering-Plough Research Institute) and ravuconazole (Eisai Company) are poised for clinical trials in Chagas disease patients in the short term. Other T. cruzi-specific EBI, with in vitro and in vivo potency, include squalene synthase, lanosterol synthase and squalene epoxidase-inhibitors as well as compounds with dual mechanisms of action (ergosterol biosynthesis inhibition and free radical generation), but they are less advanced in their development process. The main putative advantages of EBI over currently available therapies include their higher potency and selectivity in both acute and chronic infections, activity against NFX and BZN-resistant T. cruzi strains, and much better tolerability and safety profiles. Limitations may include complexity and cost of manufacture of the new compounds. As for any new drug, such compounds will require extensive clinical testing before being introduced for clinical use, and the complexity of such studies, particularly in chronic patients, will be compounded by the current limitations in the verification of true parasitological cures for T. cruzi infections. |
| PMID: 19753490 [PubMed - indexed for MEDLINE] | |
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| 9. | Mem Inst Oswaldo Cruz. 2009 Jul;104 Suppl 1:301-10.Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies.Soeiro Mde N, Dantas AP, Daliry A, Silva CF, Batista DG, de Souza EM, Oliveira GM, Salomão K, Batista MM, Pacheco MG, Silva PB, Santa-Rita RM, Barreto RF, Boykin DW, Castro SL.Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brasil. Chagas disease, which is caused by the intracellular parasite Trypanosoma cruzi, is a neglected illness with 12-14 million reported cases in endemic geographic regions of Latin America. While the disease still represents an important public health problem in these affected areas, the available therapy, which was introduced more than four decades ago, is far from ideal due to its substantial toxicity, its limited effects on different parasite stocks, and its poor activity during the chronic phase of the disease. For the past 15 years, our group, in collaboration with research groups focused on medicinal chemistry, has been working on experimental chemotherapies for Chagas disease, investigating the biological activity, toxicity, selectivity and cellular targets of different classes of compounds on T. cruzi. In this report, we present an overview of these in vitro and in vivo studies, focusing on the most promising classes of compounds with the aim of contributing to the current knowledge of the treatment of Chagas disease and aiding in the development of a new arsenal of candidates with anti-T. cruzi efficacy. |
| PMID: 19753489 [PubMed - indexed for MEDLINE] | |
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| 10. | Mem Inst Oswaldo Cruz. 2009 Jul;104 Suppl 1:295-300.Proline racemas es: insights into Trypanosoma cruzi peptides containing D-proline.Coatnoan N, Berneman A, Chamond N, Minoprio P.Département d'Immunologie, Laboratoire d'Immunobiologie des Infections à Trypanosoma, Institut Pasteur, Paris, France. Trypanosoma cruzi proline racemases (TcPRAC) are homodimeric enzymes that interconvert the L and D-enantiomers of proline. At least two paralogous copies of proline racemase (PR) genes are present per parasite haploid genome and they are differentially expressed during T. cruzi development. Non-infective epimastigote forms that overexpress PR genes differentiate more readily into metacyclic infective forms that are more invasive to host cells, indicating that PR participates in mechanisms of virulence acquisition. Using a combination of biochemical and enzymatic methods, we show here that, in addition to free D-amino acids, non-infective epimastigote and infective metacyclic parasite extracts possess peptides composed notably of D-proline. The relative contribution of TcPRAC to D-proline availability and its further assembly into peptides was estimated through the use of wild-type parasites and parasites over-expressing TcPRAC genes. Our data suggest that D-proline-bearing peptides, similarly to the mucopeptide layer of bacterial cell walls, may be of benefit to T. cruzi by providing resistance against host proteolytic mechanisms. |
| PMID: 19753488 [PubMed - indexed for MEDLINE] | |
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