What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2010 Jun 15
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 10 of 11

1.	PLoS Negl Trop Dis. 2010 Jun 8;4(6):e705. Visceral leishmaniasis relapse in southern Sudan (1999-2007): a retrospective study of risk factors and trends. Gorski S, Collin SM, Ritmeijer K, Keus K, Gatluak F, Mueller M, Davidson RN. Médecins Sans Frontières, Amsterdam, The Netherlands. Abstract BACKGROUND: Risk factors associated with L. donovani visceral leishmaniasis (VL; kala azar) relapse are poorly characterized. METHODS: We investigated patient characteristics and drug regimens associated with VL relapse using data from Médecins Sans Frontières - Holland (MSF) treatment centres in Southern Sudan. We used MSF operational data to investigate trends in VL relapse and associated risk factors. RESULTS: We obtained data for 8,800 primary VL and 621 relapse VL patients treated between 1999 and 2007. Records of previous treatment for 166 VL relapse patients (26.7%) were compared with 7,924 primary VL patients who had no record of subsequent relapse. Primary VL patients who relapsed had larger spleens on admission (Hackett grade >/=3 vs0, odds ratio (OR) for relapse = 3.62 (95% CI 1.08, 12.12)) and on discharge (Hackett grade >/=3 vs 0, OR = 5.50 (1.84, 16.49)). Age, sex, malnutrition, mobility, and complications of treatment were not associated with risk of relapse, nor was there any trend over time. Treatment with 17-day sodium stibogluconate/paromomycin (SSG/PM) combination therapy vs 30-day SSG monotherapy was associated with increased risk of relapse (OR = 2.08 (1.21, 3.58)) but reduced risk of death (OR = 0.27 (0.20, 0.37)), although these estimates are likely to be residually confounded. MSF operational data showed a crude upward trend in the proportion of VL relapse patients (annual percentage change (APC) = 11.4% (-3.4%, 28.5%)) and a downward trend in deaths (APC = -18.1% (-22.5%, -13.4%)). CONCLUSIONS: Splenomegaly and 17-day SSG/PM vs 30-day SSG were associated with increased risk of VL relapse. The crude upward trend in VL relapses in Southern Sudan may be attributable to improved access to treatment and reduced mortality due to SSG/PM combination therapy.
	PMID: 20544032 [PubMed - in process]
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2.	PLoS Negl Trop Dis. 2010 Jun 8;4(6):e704. Screening of Tryp anosoma brucei gambiense in Domestic Livestock and Tsetse Flies from an Insular Endemic Focus (Luba, Equatorial Guinea). Cordon-Obras C, García-Estébanez C, Ndong-Mabale N, Abaga S, Ndongo-Asumu P, Benito A, Cano J. National Centre of Tropical Medicine (Institute of Health Carlos III), Madrid, Spain. Abstract BACKGROUND: Sleeping sickness is spread over 36 Sub-Saharan African countries. In West and Central Africa, the disease is caused by Trypanosoma brucei gambiense, which produces a chronic clinical manifestation. The Luba focus (Bioko Island, Equatorial Guinea) has not reported autochthonous sleeping sickness cases since 1995, but given the complexity of the epidemiological cycle, the elimination of the parasite in the environment is difficult to categorically ensure. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work is to assess, by a molecular approach (Polymerase Chain Reaction, PCR), the possible permanence of T. b. gambiense in the vector (Glossina spp.) and domestic fauna in order to improve our understanding of the epidemiological situation of the disease in an isolated focus considered to be under control. The results obtained show the absence of the parasite in peridomestic livestock but its presence, although at very low rate, in the vector. On the other hand, interesting entomological data highlight that an elevated concentration of tsetse flies was observed in two out of the ten villages considered to be in the focus. CONCLUSIONS: These findings demonstrate that even in conditions of apparent control, a complete parasite clearance is difficult to achieve. Further investigations must be focused on animal reservoirs which could allow the parasites to persist without leading to human cases. In Luba, where domestic livestock are scarcer than other foci in mainland Equatorial Guinea, the epidemiological significance of wild fauna should be assessed to establish their role in the maintenance of the infection.
	PMID: 20544031 [PubMed - in process]
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3.	PLoS Negl Trop Dis. 2010 Jun 8;4(6):e703. Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment. Donaghy L, Cabillic F, Corlu A, Rostan O, Toutirais O, Guguen-Guillouzo C, Guiguen C, Gangneux JP. Université de Rennes 1, Rennes, France. Abstract BACKGROUND: Recent advances demonstrated that liver dendritic cells (DCs) promote immunologic hyporesponsiveness that may contribute to hepatic tolerance. Although there has been significant work on the phenotypic and functional roles of such DCs, the impact of liver microenvironment on the immune properties of infected DC is still poorly explored, probably because of the limitations of modelization. METHODOLOGY/PRINCIPAL FINDINGS: Here, we hypothesized that DC tolerogenic properties have an impact on the antimicrobial response, particularly during the infection by the protozoan parasite Leishmania donovani. Indeed, a lymphocytic Th2 environment was reported to favour the growth and proliferation of L. donovani. We first modelized an adequate monocyte-differentiated DC model, either in rat liver epithelial cell- or in a human hepatic non-parenchymal cell-conditioned medium in order to infect them further. We established that DCs differentiated in a hepatic microenvironment displayed a CD14+/CD16+/CD123+ phenotype, secreted low IL-12p70 and had an impaired capacity to stimulate allogeneic T lymphocyte proliferation and IFNgamma secretion. We then infected DCs with L. donovani in the in vitro-defined hepatic microenvironment. The infection of hepatic DCs restored their capacity to stimulate allogeneic T-cell proliferation and to induce lymphocytic secretion of IFNgamma. Such characteristics were recently shown to favour granuloma formation in mice liver. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the specific immunostimulatory properties of infected hepatic DCs might amplify the granuloma maturation, which warrants the effective control of infection in the liver during visceral leishmaniasis.
	PMID: 20544029 [PubMed - in process]
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4.	PLoS Negl Trop Dis. 2010 Jun 8;4(6):e701. Crystal Structures of TbCatB and Rhodesain, Potential Chemotherapeutic Targets and Major Cysteine Proteases of Trypanosoma brucei. Kerr ID, Wu P, Marion-Tsukamaki R, Mackey ZB, Brinen LS. Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America. Abstract BACKGROUND: Trypanosoma brucei is the etiological agent of Human African Trypanosomiasis, an endemic parasitic disease of sub-Saharan Africa. TbCatB and rhodesain are the sole Clan CA papain-like cysteine proteases produced by the parasite during infection of the mammalian host and are implicated in the progression of disease. Of considerable interest is the exploration of these two enzymes as targets for cysteine protease inhibitors that are effective against T. brucei. METHODS AND FINDINGS: We have determined, by X-ray crystallography, the first reported structure of TbCatB in complex with the cathepsin B selective inhibitor CA074. In addition we report the structure of rhodesain in complex with the vinyl-sulfone K11002. CONCLUSIONS: The mature domain of our TbCat*CA074 structure contains unique features for a cathepsin B-like enzyme including an elongated N-terminus extending 16 residues past the predicted maturation cleavage site. N-terminal Edman sequencing reveals an even longer extension than is observed amongst the ordered portions of the crystal structure. The TbCat*CA074 structure confirms that the occluding loop, which is an essential part of the substrate-binding site, creates a larger prime side pocket in the active site cleft than is found in mammalian cathepsin B-small molecule structures. Our data further highlight enhanced flexibility in the occluding loop main chain and structural deviations from mammalian cathepsin B enzymes that may affect activity and inhibitor design. Comparisons with the rhodesain*K11002 structure highlight key differences that may impact the design of cysteine protease inhibitors as anti-trypanosomal drugs.
	PMID: 20544024 [PubMed - in process]
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5.	Exp Parasitol. 2010 Jun 10. [Epub ahead of print] Leishmania infantum chagasi: A genome-based approach to identification of excreted/secreted proteins. Debroy S, Keenan AB, Ueno N, Jeronimo SM, Donelson JE, Wilson ME. Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. Abstract The parasitic protozoan, Leishmania, survives in harsh environments within its mammalian and sand fly hosts. Secreted proteins likely play critical roles in the parasite's interactions with its environment. As a preliminary identification of the spectrum of potential excreted/secreted (ES) proteins of Leishmania infantum chagasi (Lic), a causative agent of visceral leishmaniasis, we used standard algorithms to screen the annotated L. infantum genome for genes whose predicted protein products have an N-terminal signal peptide and lack transmembrane domains and membrane anchors. A suite of 181 candidate ES proteins were identified. These included several that were documented in the literature to be released by other Leishmania spp. Six candidate ES proteins were selected for further validation of their expression and release by different parasite stages. We found both amastigote-specific and promastigote-specific released proteins. The ES proteins of Lic are candidates for future studies of parasite virulence determinants and host protective immunity. Copyright © 2010. Published by Elsevier Inc.
	PMID: 20542033 [PubMed - as supplied by publisher]
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6.	Curr Opin Microbiol. 2010 Jun 10. [Epub ahead of print] Flagellum assembly and function during the Leishmania life cycle. Gluenz E, Ginger ML, McKean PG. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Abstract During a complex digenetic life cycle flagellated Leishmania parasites alternate between promastigote and amastigote forms which differ significantly in cellular morphology and flagellum length. Recent studies have provided important new insights into mechanisms by which Leishmania regulate expression of genes required for flagellum assembly, and mechanisms used to modify flagellum length. While the critical role of the promastigote flagellum in parasite biology has long been appreciated, the importance of the amastigote flagellum has often been disregarded. However, recent work suggests that the 'rudimentary' amastigote flagellum may serve indispensable roles in cellular organisation, and/or sensory perception, which are critical for intracellular survival of Leishmania within host macrophages. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 20541962 [PubMed - as supplied by publisher]
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7.	Mol Biochem Parasitol. 2010 Jun 9. [Epub ahead of print] Biochemical characterization of serine acetyltransferase and cysteine desulfhydrase from Leishmania major. Marciano D, Santana M, Mantilla BS, Silber AM, Marino-Buslje C, Nowicki C. Instituto de Química y Fisicoquímica Biológica IQUIFIB-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina. Abstract Cysteine metabolism exhibits atypical features in Leishmania parasites. The nucleotide sequence annotated as LmjF32.2640 encodes a cysteine desulfhydrase, which specifically catalyzes the breakdown of cysteine into pyruvate, NH3 and H2S Like in other pathogens, this capacity might be associated with regulatory mechanisms to control the intracellular level of cysteine, a highly toxic albeit essential amino acid, in addition to generate pyruvate for energy production. Besides, our results provide the first insight into the biochemical properties of L. major serine acetyltransferase (SAT), which is likely involved in the two routes for de novo synthesis of cysteine in this pathogen. When compared with other members of SAT family, the N-terminal region of L. major homologue is uniquely extended, and seems to be essential for proper protein folding. Furthermore, unlike plant and bacterial enzymes, the carboxy-terminal-C10 sequence stretch of L. major SAT appears not to be implicated in forming a tight bi-enzyme complex with cysteine synthase. Copyright © 2010. Published by Elsevier B.V.
	PMID: 20541568 [PubMed - as supplied by publisher]
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8.	Acta Trop. 2010 Jun 9. [Epub ahead of print] Tsetse fly blood meal modification and trypanosome identification in two sleeping sickness foci in the forest of southern Cameroon. Farikou O, Njiokou F, Simo G, Asonganyi T, Cuny G, Geiger A. University of Yaoundé I, Faculty of Science, P.O. Box 812, Yaoundé, Cameroon; UMR 177, IRD-CIRAD, CIRAD TA A-17/G, Campus International de Baillarguet, 34398 Montpellier Cedex 5, France. Abstract The blood meal origins of 222 tsetse flies (213 Glossina palpalis palpalis, 7 Glossina pallicera pallicera, one Glossina nigrofusca and one Glossina caliginea) caught in 2008 in two Human African trypanosomiasis foci (Bipindi and Campo) of south Cameroon was investigated. 88.7% of tsetse flies blood meals were identified using the heteroduplex method and the origin of the remaining blood meals (11.3%) was identified by sequencing the Cytochrome B gene. Most of the meals were from humans (45.9%) and pigs (37.4%), 16.7% from wild animals. Interestingly, new tsetse fly hosts including turtle (Trionyx and Kinixys) and snake (Python sebae) were identified. Significant differences were recorded between Bipindi where the blood meals from pigs were predominant (66.7% vs 23.5% from humans) and Campo where blood meals from humans were predominant (62.9% vs 22.7% from pigs). Comparison with the data recorded in 2004 in the same foci (and with the same molecular approach) demonstrated significant modifications of the feeding patterns: increase in blood meals from pigs in Bipindi (66.7% in 2008 vs 44.8% in 2004) and in Campo (20.5% in 2008 vs 6.8% in 2004), decrease in that from human (significant in Bipindi only). 12.6%, 8.1% and 2.7% of the flies were, respectively, Trypanosoma congolense forest type, Trypanosoma congolense savannah type and Trypanosoma brucei gambiense infected. These results demonstrate that tsetse fly feeding patterns can be specific of a given area and can evolve rapidly with time. They show an active circulation of a variety of trypanosomes in sleeping sickness foci of southern Cameroon. Copyright © 2010. Published by Elsevier B.V.
	PMID: 20541513 [PubMed - as supplied by publisher]
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9.	Curr Opin Microbiol. 2010 Jun 9. [Epub ahead of print] Assembly of the flagellum and its role in cell morphogenesis in Trypanosoma brucei. Vaughan S. School of Life Sciences, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK. Abstract Eukaryotic flagella are microtubule-based structures required for a variety of functions including cell motility and sensory perception. Most eukaryotic flagella grow out from a cell into the surrounding medium, but when the flagellum of the protozoan parasite Trypanosoma brucei exits the cell via the flagellar pocket, it is attached along the length of the cell body by a cytoskeletal structure called the flagellum attachment zone (FAZ). The exact reasons for flagellum attachment have remained elusive, but evidence is emerging that the attached flagellum plays a major role in cell morphogenesis in this organism. In this review we discuss evidence published in the past four years that is unravelling the role of the flagellum in organelle segregation, inheritance of cell shape and cytokinesis. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 20541452 [PubMed - as supplied by publisher]
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10.	Exp Parasitol. 2010 Jun 8. [Epub ahead of print] Flow Cytometric Screening for Anti-Leishmanials in a Human Macrophage Cell Line. Mehta SR, Zhang XQ, Badaro R, Spina C, Day J, Chang KP, Schooley RT. Division of Infectious Diseases, University of California, San Diego, California, USA. Abstract High-throughput drug screening methods against the intracellular stage of Leishmania have been facilitated by the development of in vitro models of infection. The use of cell lines rather than primary cells facilitates these methods. Peripheral blood mononuclear cell (PBMC) derived macrophages and THP-1 cells were infected with stationary phase egfp transfected Leishmania amazonensis parasites and then treated with anti-leishmanial compounds. Drug activity was measured using a flow cytometric approach, and toxicity was assessed using either the MTT assay or trypan blue dye exclusion. Calculated EC(50)'s for amphotericin B, sodium stibogluconate, and miltefosine were 0.1445+/-0.0005 mug/ml, 0.1203+/- 0.018 mg/ml, and 26.71 muM using THP-1 cells, and 0.179+/-0.035 mug/ml 0.1948+/-0.0364 mg/ml, and 13.77+/-10.74 muM using PBMC derived macrophages, respectively. We conclude that a flow cytometric approach using egfp transfected Leishmania spp. can be used to evaluate anti-leishmanial compounds against the amastigote stage of the parasite in THP-1 cells with excellent concordance to human PBMC derived macrophages. Copyright © 2010 Elsevier Inc. All rights reserved.
	PMID: 20540940 [PubMed - as supplied by publisher]
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