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Sent on Wednesday, 2011 Aug 24Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Rev Soc Bras Med Trop. 2011 Aug 19. pii: S0037-86822011005000049. [Epub ahead of print]Evaluation of Leishmania (Leishmania) chagasi strains isolated from dogs originating from two visceral leishmaniasis-endemic areas in Brazil using multilocus enzyme electrophoresis.Coutinho CE, Santos DO, Baptista C, Figueiredo FB, Madeira MD.SourceLaboratório de Vigilância em Leishmaniose, Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ. AbstractINTRODUCTION:Domestic dogs are the most important reservoir in the peridomestic transmission cycle of Leishmania (Leishmania) chagasi. The genetic variability of subpopulations of this parasite circulating in dogs has not been thoroughly analyzed in Brazil, even though this knowledge has important implications in the clinical-epidemiological context. METHODS:The objective of this study was to evaluate and compare the phenotypic variability of 153 L. chagasi strains isolated from dogs originating from the municipalities of Rio de Janeiro (n = 57) and Belo Horizonte (n = 96), where the disease is endemic. Strains isolated only from intact skin were selected and analyzed by multilocus enzyme electrophoresis using nine enzyme systems (6PG, GPI, NH1 and NH2, G6P, PGM, MDH, ME, and IDHNADP). RESULTS:The electrophoretic profile was identical for all isolates analyzed and was the same as that of the L. chagasi reference strain (MHOM/BR/74/PP75). Phenetic analysis showed a similarity index of one for all strains, with the isolates sharing 100% of the characteristics analyzed. CONCLUSIONS:The results demonstrate that the L. chagasi populations circulating in dogs from Rio de Janeiro and Belo Horizonte belong to a single zymodeme. |
| 2. | Rev Soc Bras Med Trop. 2011 Aug;44(4):520-1.Immunophenotyping of circulating T cells in a mucosal leishmaniasis patient coinfected with HIV.Castellano LR, Llaguno M, Silva MV, Machado JR, Correia D, Silva-Vergara ML, Rodrigues V.SourceLaboratório de Imunologia, Departamento de Ciências Biológicas, Universidade Federal do Triângulo Mineiro, Uberaba, MG. AbstractHIV coinfection modifies the clinical course of leishmaniasis by promoting a Th2 pattern of cytokine production. However, little information is available regarding the lymphocytic response in untreated coinfected patients. This work presents the immunophenotyping of Leishmania-stimulated T cells from a treatment-naÏve HIV+ patient with ML. Leishmania braziliensis antigens induced CD69 expression on CD3+CD4+ and CD3+CD8+ cells. It also increased IL-4 intracellular staining on CD3+CD4+GATA3- population and decreased the percentage of CD3+CD4+IL-17+ cells. This suggests that modulations in the IL-4R/STAT6 pathway and the Th17 population may serve as parasitic evasion mechanisms in HIV/ML. Further studies are required to confirm these results. |
| 3. | Future Med Chem. 2011 Aug;3(10):1259-78.Benzoxaboroles: a new class of potential drugs for human African trypanosomiasis.Jacobs RT, Plattner JJ, Nare B, Wring SA, Chen D, Freund Y, Gaukel EG, Orr MD, Perales JB, Jenks M, Noe RA, Sligar JM, Zhang YK, Bacchi CJ, Yarlett N, Don R.SourceSCYNEXIS, Inc., PO Box 12878, Research Triangle Park, NC 27709-2878, USA. AbstractHuman African trypanosomiasis, caused by the kinetoplastid parasite Trypanosoma brucei, affects thousands of people across sub-Saharan Africa, and is fatal if left untreated. Treatment options for this disease, particularly stage 2 disease, which occurs after parasites have infected brain tissue, are limited due to inadequate efficacy, toxicity and the complexity of treatment regimens. We have discovered and optimized a series of benzoxaborole-6-carboxamides to provide trypanocidal compounds that are orally active in murine models of human African trypanosomiasis. A key feature of this series is the presence of a boron atom in the heterocyclic core structure, which is essential to the observed trypanocidal activity. We also report the in vivo pharmacokinetic properties of lead compounds from the series and selection of SCYX-7158 as a preclinical candidate. |
| 4. | Proc Natl Acad Sci U S A. 2011 May 31;108(22):9304-9. Epub 2011 May 18.Genetic and expression analysis of cattle identifies candidate genes in pathways responding to Trypanosoma congolense infection.Noyes H, Brass A, Obara I, Anderson S, Archibald AL, Bradley DG, Fisher P, Freeman A, Gibson J, Gicheru M, Hall L, Hanotte O, Hulme H, McKeever D, Murray C, Oh SJ, Tate C, Smith K, Tapio M, Wambugu J, Williams DJ, Agaba M, Kemp SJ.SourceSchool of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom. AbstractAfrican bovine trypanosomiasis caused by Trypanosoma sp., is a major constraint on cattle productivity in sub-Saharan Africa. Some African Bos taurus breeds are highly tolerant of infection, but the potentially more productive Bos indicus zebu breeds are much more susceptible. Zebu cattle are well adapted for plowing and haulage, and increasing their tolerance of trypanosomiasis could have a major impact on crop cultivation as well as dairy and beef production. We used three strategies to obtain short lists of candidate genes within QTL that were previously shown to regulate response to infection. We analyzed the transcriptomes of trypanotolerant N'Dama and susceptible Boran cattle after infection with Trypanosoma congolense. We sequenced EST libraries from these two breeds to identify polymorphisms that might underlie previously identified quantitative trait loci (QTL), and we assessed QTL regions and candidate loci for evidence of selective sweeps. The scan of the EST sequences identified a previously undescribed polymorphism in ARHGAP15 in the Bta2 trypanotolerance QTL. The polymorphism affects gene function in vitro and could contribute to the observed differences in expression of the MAPK pathway in vivo. The expression data showed that TLR and MAPK pathways responded to infection, and the former contained TICAM1, which is within a QTL on Bta7. Genetic analyses showed that selective sweeps had occurred at TICAM1 and ARHGAP15 loci in African taurine cattle, making them strong candidates for the genes underlying the QTL. Candidate QTL genes were identified in other QTL by their expression profile and the pathways in which they participate. |
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| 5. | Biochim Biophys Acta. 2011 Sep;1814(9):1154-61. Epub 2011 Apr 30.Crystal structure of an enzymatically inactive trans-sialidase-like lectin from Trypanosoma cruzi: the carbohydrate binding mechanism involves residual sialidase activity.Oppezzo P, Obal G, Baraibar MA, Pritsch O, Alzari PM, Buschiazzo A.SourceInstitut Pasteur, Unité de Biochimie Structurale, Paris 75015, France. AbstractTrans-sialidases are surface-located proteins in Trypanosoma cruzi that participate in key parasite-host interactions and parasite virulence. These proteins are encoded by a large multigenic family, with tandem-repeated and individual genes dispersed throughout the genome. While a large number of genes encode for catalytically active enzyme isoforms, many others display mutations that involve catalytic residues. The latter ultimately code for catalytically inactive proteins with very high similarity to their active paralogs. These inactive members have been shown to be lectins, able to bind sialic acid and galactose in vitro, although their cellular functions are yet to be fully established. We now report structural and biochemical evidence extending the current molecular understanding of these lectins. We have solved the crystal structure of one such catalytically inactive trans-sialidase-like protein, after soaking with a specific carbohydrate ligand, sialyl-α2,3-lactose. Instead of the expected trisaccharide, the binding pocket was observed occupied by α-lactose, strongly suggesting that the protein retains residual hydrolytic activity. This hypothesis was validated by enzyme kinetics assays, in comparison to fully active wild-type trans-sialidase. Surface plasmon resonance also confirmed that these trans-sialidase-like lectins are not only able to bind small oligosaccharides, but also sialylated glycoproteins, which is relevant in the physiologic scenario of parasite infection. Inactive trans-sialidase proteins appear thus to be β-methyl-galactosyl-specific lectins, evolved within an exo-sialidase scaffold, thus explaining why their lectin activity is triggered by the presence of terminal sialic acid. Copyright © 2011 Elsevier B.V. All rights reserved. |
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| 6. | J Antimicrob Chemother. 2011 Jun;66(6):1295-7. Epub 2011 Apr 8.In vitro trypanocidal activity of DB745B and other novel arylimidamides against Trypanosoma cruzi.Da Silva CF, Junqueira A, Lima MM, Romanha AJ, Sales Junior PA, Stephens CE, Som P, Boykin DW, Soeiro Mde N.SourceLaboratório de Biologia Celular do Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. AbstractOBJECTIVES:As part of a search for new therapeutic opportunities to treat chagasic patients, in vitro efficacy studies were performed to characterize the activity of five novel arylimidamides (AIAs) against Trypanosoma cruzi. METHODS:The trypanocidal effect against T. cruzi was evaluated by light microscopy through the determination of IC₅₀ values. Cytotoxicity was determined by MTT assays against mouse cardiomyocytes. RESULTS:Our data demonstrated the trypanocidal efficacy of these new compounds against bloodstream trypomastigotes and intracellular amastigotes, exhibiting IC₅₀ values ranging from 0.015 to 2.5 and 0.02 to0.2 μM, respectively. One of the compounds, DB745B, was also highly active against a broad panel of isolates, including those naturally resistant to benznidazole. DB745B showed higher in vitro efficacy than the reference drugs used to treat patients (benznidazole IC₅₀= 12.94 μM) and to prevent blood bank infection (gentian violet IC₅₀= 30.6 μM). CONCLUSIONS:AIAs represent promising new chemical entities against T. cruzi and are also potential trypanocidal agents to prevent transfusion-associated Chagas' disease. |
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| 7. | Placenta. 2011 May;32(5):356-61. doi: 10.1016/j.placenta.2011.02.005. Epub 2011 Mar 21.Trypanosoma cruzi induces apoptosis in ex vivo infected human chorionic villi.Duaso J, Rojo G, Jaña F, Galanti N, Cabrera G, Bosco C, López-Muñoz R, Maya JD, Ferreira J, Kemmerling U.SourcePrograma de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago. AbstractChagas' disease, produced by the haemoflagellated protozoan Trypanosoma cruzi (T. cruzi), is one of the most frequent endemic diseases in Latin America. In spite that in the past few years T. cruzi congenital transmission has become of epidemiological importance, studies about this mechanism of infection are scarce. The placental tissue undergoes apoptosis throughout gestation, as part of its normal turnover. On the other hand, it is known that T. cruzi induces, delays or inhibits apoptosis in other mammalian tissues. In order to determine the effect of parasite invasion on normal apoptosis in the placenta, explants of human chorionic villi were incubated with 105 trypomastigotes for 24 h. Effective infection was tested by visualizing T. cruzi antigens in histological preparations and by PCR. Upon infection, apoptotic cell death was determined by light and transmission electron microscopy, TUNEL analysis, measurement of caspase-3 like activity and immunohistochemical detection of caspase 3 cleaved cytokeratin 18. Our results clearly show that T. cruzi induces apoptosis in the chorionic villi and suggest that this is one of mechanisms used by the parasite to insure infection and invasion of human placenta and fetus. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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