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Sent on Saturday, 2012 January 14Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS One. 2012;7(1):e29103. Epub 2012 Jan 5.Low CXCL13 Expression, Splenic Lymphoid Tissue Atrophy and Germinal Center Disruption in Severe Canine Visceral Leishmaniasis.Silva JS, Andrade AC, Santana CC, Santos LQ, de Oliveira CI, Veras PS, Vassallo J, Dos-Santos WL.SourceFundação Oswaldo Cruz - Centro de Pesquisas Gonçalo Moniz, Salvador, Bahia, Brazil. AbstractVisceral leishmaniasis is associated with atrophy and histological disorganization of splenic compartments. In this paper, we compared organized and disorganized splenic lymphoid tissue from dogs naturally infected with Leishmania infantum assessing the size of the white pulp compartments, the distribution of T, B and S100(+) dendritic cells, using immunohistochemistry and morphometry and the expression of CCR7 and the cytokines, CXCL13, lymphotoxin (LT)-α, LT-β, CCL19, CCL21, TNF-α, IL-10, IFN-γ and TGF-β, using by real time RT-PCR. The lymphoid follicles and marginal zones were smaller (3.2 and 1.9 times, respectively; Mann-Whitney, P<0.02) in animals with disorganized splenic tissue in comparison to those with organized splenic lymphoid tissue. In spleens with disorganized lymphoid tissue, the numbers of T cells and S100(+) dendritic cells were decreased in the follicles, and the numbers of B cells were reduced in both the follicles and marginal zones. CXCL13 mRNA expression was lower in animals with disorganized lymphoid tissue (0.5±0.4) compared to those with organized lymphoid tissue (2.7±2.9, both relative to 18S expression, P = 0.01). These changes in the spleen were associated with higher frequency of severe disease (7/12) in the animals with disorganized than in animals with organized (2/13, Chi-square, P = 0.01) splenic lymphoid tissue. The data presented herein suggest that natural infection with Leishmania infantum is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis. Furthermore the fact that this work uses dogs naturally infected with Leishmania infantum emphasizes the relevance of the data presented herein for the knowledge on the canine and human visceral leishmaniasis. |
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| 2. | PLoS Pathog. 2012 Jan;8(1):e1002474. Epub 2012 Jan 5.Trypanosoma cruzi trans-Sialidase in Complex with a Neutralizing Antibody: Structure/Function Studies towards the Rational Design of Inhibitors.Buschiazzo A, Muiá R, Larrieux N, Pitcovsky T, Mucci J, Campetella O.SourceInstitut Pasteur de Montevideo, Unit of Protein Crystallography, Montevideo, Uruguay. AbstractTrans-sialidase (TS), a virulence factor from Trypanosoma cruzi, is an enzyme playing key roles in the biology of this protozoan parasite. Absent from the mammalian host, it constitutes a potential target for the development of novel chemotherapeutic drugs, an urgent need to combat Chagas' disease. TS is involved in host cell invasion and parasite survival in the bloodstream. However, TS is also actively shed by the parasite to the bloodstream, inducing systemic effects readily detected during the acute phase of the disease, in particular, hematological alterations and triggering of immune cells apoptosis, until specific neutralizing antibodies are elicited. These antibodies constitute the only known submicromolar inhibitor of TS's catalytic activity. We now report the identification and detailed characterization of a neutralizing mouse monoclonal antibody (mAb 13G9), recognizing T. cruzi TS with high specificity and subnanomolar affinity. This mAb displays undetectable association with the T. cruzi superfamily of TS-like proteins or yet with the TS-related enzymes from Trypanosoma brucei or Trypanosoma rangeli. In immunofluorescence assays, mAb 13G9 labeled 100% of the parasites from the infective trypomastigote stage. This mAb also reduces parasite invasion of cultured cells and strongly inhibits parasite surface sialylation. The crystal structure of the mAb 13G9 antigen-binding fragment in complex with the globular region of T. cruzi TS was determined, revealing detailed molecular insights of the inhibition mechanism. Not occluding the enzyme's catalytic site, the antibody performs a subtle action by inhibiting the movement of an assisting tyrosine (Y(119)), whose mobility is known to play a key role in the trans-glycosidase mechanism. As an example of enzymatic inhibition involving non-catalytic residues that occupy sites distal from the substrate-binding pocket, this first near atomic characterization of a high affinity inhibitory molecule for TS provides a rational framework for novel strategies in the design of chemotherapeutic compounds. |
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| 3. | Glycobiology. 2012 Jan 12. [Epub ahead of print]The lipid linked oligosaccharide donor specificities of Trypanosoma brucei oligosaccharyltransferases.Izquierdo L, Mehlert A, Ferguson MA.SourceDivision of Biological Chemistry and Drug Discovery, The College of Life Sciences, University of Dundee, Dundee, UK. AbstractWe recently presented a model for site-specific protein N-glycosylation in Trypanosoma brucei whereby the TbSTT3A oligosaccharyltransferase first selectively transfers biantennary Man(5)GlcNAc(2) from the lipid linked oligosaccharide donor Man(5)GlcNAc(2)-PP-Dol to N-glycosylation sequons in acidic to neutral peptide sequences and TbSTT3B selectively transfers triantennary Man(9)GlcNAc(2) to any remaining sequons. In this paper, we investigate the specificities of the two oligosaccharyltransferases for their preferred lipid linked oligosaccharide donors by glycotyping the variant surface glycoprotein synthesized by bloodstream form T.brucei TbALG12 null mutants. The TbALG12 gene encodes the α1-6 mannosyltransferase that converts Man(7)GlcNAc(2)-PP-Dol to Man(8)GlcNAc(2)-PP-Dol. The variant surface glycoprotein synthesized by the TbALG12 null mutant in the presence and absence of α-mannosidase inhibitors was characterized by electrospray mass spectrometry both intact and as Pronase glycopetides. The results show that TbSTT3A is able to transfer Man(7)GlcNAc(2) as well as Man(5)GlcNAc(2) to its preferred acidic glycosylation site at Asn263 and that, in the absence of Man(9)GlcNAc(2)-PP-Dol, TbSTT3B transfers both Man(7)GlcNAc(2) and Man(5)GlcNAc(2) to the remaining site at Asn428, albeit with low efficiency. These data suggests that the preferences of TbSTT3A and TbSTT3B for their lipid linked oligosaccharide donors are based on the c-branch of the Man(9)GlcNAc(2) oligosaccharide, such that the presence of the c-branch prevents recognition and/or transfer by TbSTT3A, whereas the presence of the c-branch enhances recognition and/or transfer by TbSTT3B. |
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| 4. | Mem Inst Oswaldo Cruz. 2011 Dec;106(8):1049-51.Report of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) in a cutaneous-leishmaniasis-endemic area of Panama.Valderrama A, Tavares MG, Andrade Filho JD.SourceDepartamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, MG, Brasil. AbstractLutzomyia longipalpis is the primary vector of the parasite responsible for visceral leishmaniasis in the Americas. In the present study, Lu. longipalpis was found in a domiciliary area in Limón, a district in Capira, a region in which cutaneous leishmaniasis is endemic in Panama. Previously, this species has been found in a humid forest in this same region. Finding Lu. longipalpis in domiciliary areas indicates that this species may be adapting to new habitats and that it may play a role in the transmission of leishmaniasis in Panama. |
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| 5. | Mem Inst Oswaldo Cruz. 2011 Dec;106(8):1039-44.Distribution of phlebotomine fauna (Diptera: Psychodidae) across an urban-rural gradient in an area of endemic visceral leishmaniasis in northern Brazil.Oliveira DM, Saraiva EM, Ishikawa EA, Sousa AA, Silva EO, Silva IM.SourceLaboratório de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. AbstractThe number of visceral leishmaniasis (VL) cases has increased over the past 10 years in Brazil, especially in the North and Northeast regions of the country. The aim of this study was to evaluate the urbanisation of VL vectors in Barcarena, Pará, an area in northern Brazil where VL is endemic. Sandflies were captured using Centers for Disease Control (CDC) light traps along an urban-rural gradient. The CDC traps were installed inside hen houses at a height of 150 cm. A total of 5,089 sandflies were collected and 11 species were identified. The predominant species was Lutzomyia longipalpis (rate of 95.15%), which suggests its participation in the transmission of VL. A total of 1,451 Lu. longipalpis females were dissected and no Leishmania infections were detected. Most of the sandflies were captured at the border of a forest (88.25%) and no flies were captured in the urban area, which suggests that transmission is still restricted to rural sites. However, the fact that a specimen was collected in an intermediate area indicates that urbanisation is a real possibility and that vector monitoring is important. |
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| 6. | Mem Inst Oswaldo Cruz. 2011 Dec;106(8):1032-8.Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs.Reimão JQ, Tempone AG.SourceDepartamento de Parasitologia, Instituto Adolfo Lutz, São Paulo, SP, Brasil, 01246-000. AbstractThe need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs), sum of FICs (ΣFICs) and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis. |
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| 7. | Mem Inst Oswaldo Cruz. 2011 Dec;106(8):1024-31.Anthropogenic influence on the distribution, abundance and diversity of sandfly species (Diptera: Phlebotominae: Psychodidae), vectors of cutaneous leishmaniasis in Panama.Valderrama A, Tavares MG, Andrade Filho JD.SourceDepartamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, MG, Brasil, 36570-000. AbstractIn Panama, species of the genus Lutzomyia are vectors of American cutaneous leishmaniasis (ACL). There is no recent ecological information that may be used to develop tools for the control of this disease. Thus, the goal of this study was to determine the composition, distribution and diversity of Lutzomyia species that serve as vectors of ACL. Sandfly sampling was conducted in forests, fragmented forests and rural environments, in locations with records of ACL. Lutzomyia gomezi, Lutzomyia panamensis and Lutzomyia trapidoi were the most widely distributed and prevalent species. Analysis of each sampling point showed that the species abundance and diversity were greatest at points located in the fragmented forest landscape. However, when the samples were grouped according to the landscape characteristics of the locations, there was a greater diversity of species in the rural environment locations. The Kruskal Wallis analysis of species abundance found that Lu. gomezi and Lu. trapidoi were associated with fragmented environments, while Lu. panamensis, Lutzomyia olmeca bicolor and Lutzomyia ylephiletor were associated with forested environments. Therefore, we suggest that human activity influences the distribution, composition and diversity of the vector species responsible for leishmaniasis in Panama. |
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| 8. | Parasit Vectors. 2012 Jan 12;5(1):15. [Epub ahead of print]SYBR Green-based Real-Time PCR targeting kinetoplast DNA can be used to discriminate between the main etiologic agents of Brazilian cutaneous and visceral leishmaniases.Pita-Pereira D, Lins R, Oliveira MP, Lima RB, Pereira BA, Moreira OC, Brazil RP, Britto C.AbstractABSTRACT: BACKGROUND:Leishmaniases control has been hampered by the unavailability of rapid detection methods and the lack of suitable therapeutic and prophylactic measures. Accurate diagnosis, which can distinguish between Leishmania isolates, is essential for conducting appropriate prognosis, therapy and epidemiology. Molecular methods are currently being employed to detect Leishmania infection and categorize the parasites up to genus, complex or species level. Real-time PCR offers several advantages over traditional PCR, including faster processing time, higher sensitivity and decreased contamination risk. RESULTS:A SYBR Green real-time PCR targeting the conserved region of kinetoplast DNA minicircles was able to differentiate between Leishmania subgenera. A panel of reference strains representing subgenera Leishmania and Viannia was evaluated by the derivative dissociation curve analyses of the amplified fragment. Distinct values for the average melting temperature were observed, being 78.95 degreesC +/- 0.01 and 77.36 degreesC +/- 0.02 for Leishmania and Viannia, respectively (p<0.05). Using the Neighbor-Joining method and Kimura 2-parameters, the alignment of 12 sequences from the amplified conserved minicircles segment grouped together L. (V.) braziliensis and L. (V.) shawii with a bootstrap value of 100%; while for L. (L.) infantum and L. (L.) amazonensis, two groups were formed with bootstrap values of 100% and 62%, respectively. The lower dissociation temperature observed for the subgenus Viannia amplicons could be due to a lower proportion of guanine/cytosine sites (43.6%) when compared to species from subgenus Leishmania (average of 48.4%). The method was validated with 30 clinical specimens from visceral or cutaneous leishmaniases patients living in Brazil and also with DNA samples from naturally infected Lutzomyia spp. captured in two Brazilian localities. CONCLUSIONS:For all tested samples, a characteristic amplicon melting profile was evidenced for each Leishmania subgenus, corroborating the data from reference strains. Therefore, the analysis of thermal dissociation curves targeting the conserved kinetoplast DNA minicircles region is able to provide a rapid and reliable method to identify the main etiologic agents of cutaneous and visceral leishmaniases in endemic regions of Brazil. |
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| 9. | J Med Entomol. 2011 Nov;48(6):1145-59.Evaluation of ULV application s against Old World sand fly (Diptera: Psychodidae) species in equatorial Kenya.Britch SC, Linthicum KJ, Walker TW, Farooq M, Gordon SW, Clark JW, Ngere F, Ngonga D, Chepchieng C.SourceUnited States Department of Agriculture, Agricultural Research Service, Center for Medical, Agricultural, and Veterinary Entomology, 1600 SW 23rd Dr., Gainesville, FL 32608, USA. seth.britch@ars.usda.gov AbstractReducing populations of phlebotomine sand flies in areas prevalent for human leishmaniases is of ongoing importance to United States military operations and civilian populations in endemic regions. However, not enough is known regarding the efficacy of Department of Defense-approved pesticides and equipment against sand flies; specifically, the potential for ultra-low volume (ULV) pesticide applications to control Old World sand fly vectors. In this study we examine two sprayers, the Terminator ULV and the Grizzly ULV, with UV-labeled Duet and Fyfanon in four combinations against caged Phlebotomus duboscqi (Neveu-Lemaire) and wild sand fly populations in a natural environment in western Kenya. All equipment and Fyfanon have United States military National Stock Numbers and both pesticides are registered with the United States Environmental Protection Agency. Caged sand flies were reared from local P. duboscqi and the area has long been studied because of high incidences of human cutaneous and visceral Leishmania. Patterns of mortality across grids of caged sand flies showed greater efficacy from the Grizzly ULV regardless of chemical. The Terminator ULV performed well with Duet but with a less uniform and overall lower rate of mortality across the spray grid. Sampling of wild populations before and after treatments suggested local population suppression from ULV treatments, as well as a possible repellent effect in nearby untreated areas. Surprisingly, ULV active ingredient deposition inferred from patterns of UV-labeled droplets captured on cotton ribbons adjacent to sand fly cages in spray plots did not match patterns of mortality. We discuss the implications of this study, the first of its kind, for future military preventive medicine activities, including relative performance costs and benefits of larger or smaller sprayers, and the relative stability of ULV-induced mortality patterns in varied or sub-optimal conditions. |
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| 10. | Int J Biol Sci. 2011;7(8):1093-100. Epub 2011 Sep 8.IL-10-IFN-γ double producers CD4+ T cells are induced by immunization with an amastigote stage specific derived recombinant protein of Trypanosoma cruzi.Flores-García Y, Rosales-Encina JL, Satoskar AR, Talamás-Rohana P.SourceDepartamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, DF. 07360, Mexico. AbstractDuring the acute phase of infection, T. cruzi replicates extensively and releases immunomodulatory molecules that delay parasite-specific responses mediated by effector T cells. This mechanism of evasion allows the parasite to spread in the host. Parasite molecules that regulate the host immune response during Chagas'disease have not been fully identified. GPI-anchored mucins, glycoinositolphospholipids, and glycoproteins comprise some of the most abundant T. cruzi surface molecules. IL-10 IFN-γ-secreting CD4+ T cells are activated during chronic infections and are responsible for prolonged persistence of parasite and for host protection against severe inflammatory responses. In this work we evaluated the role of rMBP::SSP4 protein of T. cruzi, a recombinant protein derived from a GPI anchored antigen, SSP4, as an immunomodulator molecule, finding that it was able to induce high concentrations of IL-10 and IFN-γ both in vivo and in vitro; during this last condition, both cytokines were produced by IL-10-IFN-γ-secreting CD4+ T cells. |
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