What's new for 'Trypanosomatids' in PubMed

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Sent on Sunday, 2010 Oct 03
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 - 9 of 9

1.	J Immunol. 2010 Sep 29. [Epub ahead of print] Leishmania Exosomes Modulate Innate and Adaptive Immune Responses through Effects on Monocytes and Dendritic Cells. Silverman JM, Clos J, Horakova E, Wang AY, Wiesgigl M, Kelly I, Lynn MA, McMaster WR, Foster LJ, Levings MK, Reiner NE. Division of Infectious Diseases, Department of Medicine. Abstract We investigated the properties of leishmania exosomes with respect to influencing innate and adaptive immune responses. Exosomes from Leishmania donovani modulated human monocyte cytokine responses to IFN-γ in a bimodal fashion by promoting IL-10 production and inhibiting that of TNF-α. Moreover, these vesicles were inhibitory with respect to cytokine responses (IL-12p70, TNF-α, and IL-10) by human monocyte-derived dendritic cells. Exosomes from wild-type (WT) L. donovani failed to prime monocyte-derived dendritic cells to drive the differentiation of naive CD4 T cells into IFN-γ-producing Th1 cells. In contrast, vesicles from heat shock protein (HSP)100(-/-) L. donovani showed a gain-of-function and proinflammatory phenotype and promoted the differentiation of naive CD4 lymphocytes into Th1 cells. Proteomic analysis showed that exosomes from WT and HSP100(-/-) leishmania had distinct protein cargo, suggesting that packaging of proteins into exosomes is dependent in part on HSP100. Treatment of C57BL/6 mice with WT L. donovani exosomes prior to challenge with WT organisms exacerbated infection and promoted IL-10 production in the spleen. In contrast, HSP100(-/-) exosomes promoted spleen cell production of IFN-γ and did not adversely affect hepatic parasite burdens. Furthermore, the proparasitic properties of WT exosomes were not species specific because BALB/c mice exposed to Leishmania major exosomes showed increased Th2 polarization and exacerbation of disease in response to infection with L. major. These findings demonstrate that leishmania exosomes are predominantly immunosuppressive. Moreover, to our knowledge, this is the first evidence to suggest that changes in the protein cargo of exosomes may influence the impact of these vesicles on myeloid cell function.
	PMID: 20881185 [PubMed - as supplied by publisher]
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2.	Arch Pediatr. 2010 Sep 27. [Epub ahead of print] [Treatment of severe hemophagocytic syndrome associate d with visceral leishmaniasis.] [Article in French] Bouguila J, Chabchoub I, Moncef Y, Mlika A, Saghrouni F, Boughamoura L, Essoussi AS. Service de pédiatrie, CHU Farhat Hached, avenue Ibn El Jazzar, 4000 Sousse, Tunisie. Abstract The association of hemophagocytic syndrome (HS) and visceral leishmaniasis is a frequent disorder during infancy in endemic areas such as Tunisia. The range of severity of HS secondary to visceral leishmaniasis includes both pure biological forms that resolve with antimicrobial therapy and life-threatening emergencies that require specific treatment. We describe 2 cases of severe HS secondary to visceral leishmaniasis. The diagnosis of HS was based on the HLH-2004 diagnostic criteria. Therapy involved pentavalent antimonial (Glucantime(®)) in both cases. The combination of corticosteroids with immunoglobulins, used in the 1st case, but introduced late, led to an unfavorable course and death. In the 2nd case, the specific treatment of HS was based on immunochemotherapy including etoposide and corticosteroids. Progression was favorable with a follow-up of 24 months. Etoposide containing therapeutic regimens can be proposed in severe forms of HS associated with visceral leishmaniasis.
	PMID: 20880678 [PubMed - as supplied by publisher]
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3.	Mol Microbiol. 2010 Aug 13. doi: 10.1111/j.1365-2958.2010.07350.x. [Epub ahead of print] The FACT subunit TbSpt16 is involved in cell cy cle specific control of VSG expression sites in Trypanosoma brucei. Denninger V, Fullbrook A, Bessat M, Ersfeld K, Rudenko G. Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College, South Kensington, London SW7 2AZ, UK. Department of Biological Sciences and Hull York Medical School, University of Hull, Cottingham Road, Hull HU6 7RX, UK. Abstract The African trypanosome Trypanosoma brucei monoallelically expresses one of more than 1000 Variant Surface Glycoprotein (VSG) genes. The active VSG is transcribed from one of about 15 telomeric VSG expression sites (ESs). It is unclear how monoallelic expression of VSG is controlled, and how inactive VSG ESs are silenced. Here, we show that blocking synthesis of the T. brucei FACT subunit TbSpt16 triggers a G2/early M phase cell cycle arrest in both bloodstream and insect form T. brucei. Segregation of T. brucei minichromosomes in these stalled cells is impaired, implicating FACT in maintenance of centromeres. Strikingly, knock-down of TbSpt16 results in 20- to 23-fold derepression of silent VSG ES promoters in bloodstream form T. brucei, with derepression specific to the G2/M cell cycle stage. In insect form T. brucei TbSpt16 knock-down results in 16- to 25-fold VSG ES derepression. Using chromatin immunoprecipitation (ChIP), TbSpt16 was found to be particularly enriched at the promoter region of silent but not active VSG ESs in bloodstream form T. brucei. The chromatin remodeler FACT is therefore implicated in maintenance of repressed chromatin present at silent VSG ES promoters, but is also essential for chromosome segregation presumably through maintenance of functional centromeres.
	PMID: 20879999 [PubMed - as supplied by publisher]
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4.	Pediatr Ann. 2010 Jun;39(6):326-7. doi: 10.3928/00904481-20100521-01. Making a practice an academic office. Shulman ST.
	PMID: 20669884 [PubMed - indexed for MEDLINE]
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5.	J Chemother. 2010 Jun;22(3):169-74. Evaluation of the trypanocidal, cytotoxic and genotoxic activity of styrylquinoline analogs. García P, Genes C, Molano P, Torres O, Saez J, Triana O. Grupo Biologia y Control de Enfermedades Infecciosas, Universidad de Antioquia, Medellin, Colombia. Abstract Styrylquinolines isolated from Galipea longiflora have shown leishmanicidal, trypanocidal, nematocidal and antimalarial activity. Here, we propose to use analogs of these styrylquinolines to enhance the activity against Trypanosoma cruzi. Three compounds in a reduced and oxidized state were synthesized, and the activity against epimastigotes and trypomastigotes was evaluated. in addition, the cytotoxic activity and genotoxic effect were also determined. The results indicated that epimastigotes from different T. cruzi I stocks were highly sensitive to the three compounds. The PQM4 compound presented promising activity against trypomastigotes and low cytotoxic and genotoxic effects. Finally, we observed that the doublebond reduction of the lateral chain of the three carbons made on these compounds improved the activity and substantially diminished the toxicity of the compounds.
	PMID: 20566421 [PubMed - indexed for MEDLINE]
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6.	Vet Parasitol. 2010 Jul 15;171(1-2):22-31. Epub 2010 Mar 18. PCR-based diagnosis of surra-targeting VSG g ene: experimental studies in small laboratory rodents and buffalo. Sengupta PP, Balumahendiran M, Suryanaryana VV, Raghavendra AG, Shome BR, Gajendragad MR, Prabhudas K. Project Directorate on Animal Disease Monitoring and Surveillance, Hebbal, Bangalore 560024, Karnataka, India. pinakiprasad_s@rediffmail.com Abstract Trypanosoma evansi, the causative organism of 'surra' expresses its variable surface glycoprotein (VSG) at early, middle and late stages of infection in animals. The variable antigenic nature of VSG caused by switching its expression type favours evasion from the host immune response and leads to chronic and persistent infection. Developing a polymerase chain reaction (PCR)-based diagnostic tool targeting the VSG gene is expected to be highly specific and sensitive for diagnosis of surra. Hence, in the present study, we have designed EXP3F/4R primer pair and amplified the 1.4 kb of VSG gene of T. evansi and studied the phylogenetic relationship by in silico analysis. The PCR method was standardised using another set of primer, DITRYF/R, and 400 bp was amplified from blood and tissue samples of experimentally infected animals. Applying the PCR method, we were able to detect as low as 0.15 trypanosomeml(-1). Considering the number of parasite-to-DNA concentration, the PCR method has a sensitivity of 0.015 pg ml(-1). The PCR could detect the presence of the parasite as early as 24h post-infection (p.i.) and 72 h p.i., respectively, in experimentally infected rats and buffalo. No amplification was observed with DNA of Babesia bigemina and Theileria annulata, indicating the primers are specific for T. evansi. The PCR method could detect the dog, lion and leopard isolates of T. evansi. Similarly, amplifying the DNA from the experimentally infected tissues was also found to be sensitive. Thus, the findings of this study favour the application of PCR over the parasitological methods for the detection of the early and/or chronic stage of surra in domestic and wild animals.
	PMID: 20388585 [PubMed - indexed for MEDLINE]
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7.	Vet Parasitol. 2010 Jul 15;171(1-2):48-52. Epub 2010 Mar 3. Biochemical changes in cats infected with Trypanosoma evansi. Da Silva AS, Wolkmer P, Costa MM, Tonin AA, Eilers TL, Gressler LT, Otto MA, Zanette RA, Santurio JM, Lopes ST, Monteiro SG. Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria-RS, Brazil. aleksandro_ss@yahoo.com.br Abstract This study aimed at evaluating biochemical changes of cats (Felis catus) experimentally infected with Trypanosoma evansi. Seven animals were infected with 10(8) blood trypomastigotes per animal and six were used as controls. Blood smears were performed daily for 56 days and the hepatic, renal and muscular parameters in blood serum were evaluated at days 0, 7, 21, 35 and 49. The protozoan was found in the bloodstream 24-48 h post-inoculation (PI) and irregular peaks of parasitemia were observed throughout the experiment. Muscular enzymatic activities (aspartate aminotransferase and creatine kinase) were increased in infected cats compared to controls. Increased concentrations of total proteins and globulins and decreased levels of albumin and albumin/globulin ratio were observed in infected group versus the controls values (P<0.05). No alteration in serum activity of alanine aminotransferase, gamma-glutamyltransferase, creatinine and urea was observed in both groups.
	PMID: 20338691 [PubMed - indexed for MEDLINE]
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8.	PLoS One. 2010 Feb 12;5(2):e9181. Inheritance of DNA transferred from American trypanosomes to human hosts. Hecht MM, Nitz N, Araujo PF, Sousa AO, Rosa Ade C, Gomes DA, Leonardecz E, Teixeira AR. Chagas Disease Multidisciplinary Research Laboratory, Faculty of Medicine, University of Brasilia, Brasília, Federal District, Brazil. Abstract Interspecies DNA transfer is a major biological process leading to the accumulation of mutations inherited by sexual reproduction among eukaryotes. Lateral DNA transfer events and their inheritance has been challenging to document. In this study we modified a thermal asymmetric interlaced PCR by using additional targeted primers, along with Southern blots, fluorescence techniques, and bioinformatics, to identify lateral DNA transfer events from parasite to host. Instances of naturally occurring human infections by Trypanosoma cruzi are documented, where mitochondrial minicircles integrated mainly into retrotransposable LINE-1 of various chromosomes. The founders of five families show minicircle integrations that were transferred vertically to their progeny. Microhomology end-joining of 6 to 22 AC-rich nucleotide repeats in the minicircles and host DNA mediates foreign DNA integration. Heterogeneous minicircle sequences were distributed randomly among families, with diversity increasing due to subsequent rearrangement of inserted fragments. Mosaic recombination and hitchhiking on retrotransposition events to different loci were more prevalent in germ line as compared to somatic cells. Potential new genes, pseudogenes, and knockouts were identified. A pathway of minicircle integration and maintenance in the host genome is suggested. Thus, infection by T. cruzi has the unexpected consequence of increasing human genetic diversity, and Chagas disease may be a fortuitous share of negative selection. This demonstration of contemporary transfer of eukaryotic DNA to the human genome and its subsequent inheritance by descendants introduces a significant change in the scientific concept of evolutionary biology and medicine. PMCID: PMC2820539 Free PMC Article
	PMID: 20169193 [PubMed - indexed for MEDLINE]
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9.	PLoS One. 2010 Feb 16;5(2):e9252. Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. Maggini J, Mirkin G, Bognanni I, Holmberg J, Piazzón IM, Nepomnaschy I, Costa H, Cañones C, Raiden S, Vermeulen M, Geffner JR. Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina. Abstract In recent years it has become clear that the therapeutic properties of bone marrow-derived mesenchymal stromal cells (MSC) are related not only to their ability to differentiate into different lineages but also to their capacity to suppress the immune response. We here studied the influence of MSC on macrophage function. Using mouse thioglycolate-elicited peritoneal macrophages (M) stimulated with LPS, we found that MSC markedly suppressed the production of the inflammatory cytokines TNF-alpha, IL-6, IL-12p70 and interferon-gamma while increased the production of IL-10 and IL-12p40. Similar results were observed using supernatants from MSC suggesting that factor(s) constitutively released by MSC are involved. Supporting a role for PGE(2) we observed that acetylsalicylic acid impaired the ability of MSC to inhibit the production of inflammatory cytokines and to stimulate the production of IL-10 by LPS-stimulated M. Moreover, we found that MSC constitutively produce PGE2 at levels able to inhibit the production of TNF-alpha and IL-6 by activated M. MSC also inhibited the up-regulation of CD86 and MHC class II in LPS-stimulated M impairing their ability to activate antigen-specific T CD4+ cells. On the other hand, they stimulated the uptake of apoptotic thymocytes by M. Of note, MSC turned M into cells highly susceptible to infection with the parasite Trypanosoma cruzi increasing more than 5-fold the rate of M infection. Using a model of inflammation triggered by s.c. implantation of glass cylinders, we found that MSC stimulated the recruitment of macrophages which showed a low expression of CD86 and the MHC class II molecule Ia(b) and a high ability to produce IL-10 and IL-12p40, but not IL-12 p70. In summary, our results suggest that MSC switch M into a regulatory profile characterized by a low ability to produce inflammatory cytokines, a high ability to phagocyte apoptotic cells, and a marked increase in their susceptibility to infection by intracellular pathogens. PMCID: PMC2821929 Free PMC Article
	PMID: 20169081 [PubMed - indexed for MEDLINE]
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