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Sent on Saturday, 2011 Sep 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. | Biochem Res Int. 2012;2012:691363. Epub 2011 Sep 21.Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes.Ali HZ, Harding CR, Denny PW.SourceBiophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK. AbstractLeishmania species are the causative agents of the leishmaniases, a spectrum of neglected tropical diseases. Amastigote stage parasites exist within macrophages and scavenge host factors for survival, for example, Leishmania species utilise host sphingolipid for synthesis of complex sphingolipid. In this study L. mexicana endocytosis was shown to be significantly upregulated in amastigotes, indicating that sphingolipid scavenging may be enhanced. However, inhibition of host sphingolipid biosynthesis had no significant effect on amastigote proliferation within a macrophage cell line. In addition, infection itself did not directly influence host biosynthesis. Notably, in contrast to L. major, L. mexicana amastigotes are indicated to possess a complete biosynthetic pathway suggesting that scavenged sphingolipids may be nonessential for proliferation. This suggested that Old and New World species differ in their interactions with the macrophage host. This will need to be considered when targeting the Leishmania sphingolipid biosynthetic pathway with novel therapeutics. |
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| 2. | J Clin Microbiol. 2011 Sep 21. [Epub ahead of print]Serial quantitative PCR assay for detection, species-discrimination and quantification of Leishmania spp. in human samples.Weirather JL, Jeronimo SM, Gautam S, Sundar S, Kang M, Kurtz MA, Haque R, Schriefer A, Talhari S, Carvalho EM, Donelson JE, Wilson ME.SourceIowa City VA Medical Center. AbstractThe Leishmania species cause a variety of human disease syndromes. Methods for diagnosis and species differentiation are insensitive and many require invasive sampling. Although quantitative PCR (qPCR) methods are reported for leishmania detection, no systematic method to quantify parasites and determine the species in clinical specimens is established. We developed a serial qPCR strategy to identify and rapidly differentiate Leishmania species, and quantify parasites in clinical or environmental specimens. SYBR green qPCR is mainly employed, with corresponding Taqman assays for validation. Screening primers recognize kinetoplast minicircle DNA of all Leishmania species. Species identification employs further qPCR set(s) individualized for geographic regions, combining species discriminating probes with melt curve analysis. The assay was sufficient to detect, speciate and quantify Leishmania spp. in sera, cutaneous biopsies, or cultured isolates from subjects on Bangladesh or Brazil with different forms of leishmaniasis. The multicopy kDNA probes were the most sensitive and useful for quantification based on promastigote standard curves. To test their validity for quantification, kDNA copy numbers were compared between Leishmania species, isolates, and life stages using qPCR. Maxicircle and minicircle copy numbers differed up to 6 fold between Leishmania species, but differences were smaller between strains of the same species. Amastigote and promastigote leishmania life stages retained similar numbers of kDNA maxi- or minicircles. Thus, serial qPCR is useful for leishmania detection and speciation, and for absolute quantification when compared to a standard curve from the same Leishmania species. |
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| 3. | Eur J Med Chem. 2011 Sep 8. [Epub ahead of print]Synthesis and evaluation of the anti parasitic activity of aromatic nitro compounds.Lopes MS, de Souza Pietra RC, Borgati TF, Romeiro CF, Júnior PA, Romanha AJ, Alves RJ, Souza-Fagundes EM, Fernandes AP, de Oliveira RB.SourceDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos 6627, Belo Horizonte, MG 31.270-901, Brazil. AbstractA series of nitroaromatic compounds was synthesized and evaluated as potential antileishmanial and trypanocidal agents. Five compounds exerted significant anti-leishmanial activity in vitro against promastigotes forms of Leishmania (L.) amazonensis, with IC(50) in the range of 23-59 μmol L(-1), but none were active against amastigotes intracellular forms of Trypanosoma cruzi. In vitro cytotoxicity on the proliferation of human peripheral blood mononuclear cells (PBMC) stimulated with phytohemaglutinin (PHA) was also evaluated. Two compounds, 6 and 7, were found to present a promising anti-leishmanial activity with IC(50) values of 59.5 and 50.6 μM, respectively, without affecting the lymphocyte proliferation in PBMCs (selectivity index of 16.1 and 21.7, respectively), indicating low toxicity to human cells. Copyright © 2011 Elsevier Masson SAS. All rights reserved. |
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| 4. | Acta Trop. 2011 Sep 16. [Epub ahead of print]Lutzomyia (Pintomyia) fischeri (Diptera: Psychodidae: Phlebotominae), a probable vector of American Cutaneous Leishmaniasis: Detection of natural infection by Leishmania (Viannia) DNA in specimens from the municipality of Porto Alegre (RS), Brazil, using multiplex PCR assay.Pereira DD, Souza GD, Pereira TD, Zwetsch A, Britto C, Rangel EF.SourceLaboratório de Biologia Molecular e Doenças Endêmicas - IOC, Rio de Janeiro, RJ, Brazil. AbstractIn order to determine natural Leishmania (Viannia) infection in Lutzomyia (Pintomyia) fischeri, a multiplex PCR methodology coupled to non-isotopic hybridization was adopted for the analysis of sand fly samples collected by CDC light traps in an endemic area of American Cutaneous Leishmaniasis (ACL) in the periurban region of the municipality of Porto Alegre, Rio Grande do Sul State, Brazil. We analyzed by PCR methodology 560 specimens of Lutzomyia (Pintomyia) fischeri (520 females and 40 males). The wild sand flies were grouped into 56 pools (52 females and 4 males) of 10 each, and positive results were detected in 2 of the 52 female pools, representing a minimum infection rate of 0.38% based on the presence of at least 1 infected insect in the pool. This result associated with some local evidence such as anthopophily, spatial distribution in accordance with the transmission area and human case incidence, suggests that L. (P.)fischeri may be considered as a secondary vector of ACL in the studied locality. Copyright © 2011. Published by Elsevier B.V. |
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| 5. | J Am Chem Soc. 2011 Sep 22. [Epub ahead of print]Mechanism for Activation of Triosephosphate Isomerase by Phosphite Dianion: The Role of a Ligand-Driven Co nformational Change.Malabanan MM, Amyes TL, Richard JP.AbstractThe L232A mutation at triosephosphate isomerase (TIM) from <i>Trypanosoma brucei brucei</i> results in a small 6-fold decrease in <i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub> for the reversible enzyme-catalyzed isomerization of glyceraldehyde 3-phosphate to give dihydroxyacetone phosphate. By contrast, this mutation leads to a 17-fold increase in the second-order rate constant for the TIM-catalyzed proton transfer reaction of the truncated substrate piece [1-<sup>13</sup>C]-glycolaldehyde ([1-<sup>13</sup>C]-GA) in D<sub>2</sub>O; a 25-fold increase in the third-order rate constant for reaction of the substrate pieces GA + and phosphite dianion (HPO<sub>3</sub><sup>2-</sup>); and a 16-fold decrease in <i>K</i><sub>d</sub> for binding of HPO<sub>3</sub><sup>2-</sup> to the free enzyme. Most significantly, the mutation also results in an 11-fold decrease in the extent of activation of the enzyme towards turnover of GA by bound HPO<sub>3</sub><sup>2-</sup>. The data provide striking evidence that the L232A mutation leads to a ca. 1.7 kcal/mol stabilization of a catalytically active loop-closed form of TIM (E<sub>c</sub>) relative to an inactive open form (E<sub>o</sub>). We propose that this is due to the relief, at L232A mutant TIM, of unfavorable steric interactions between the bulky hydrophobic side chain of Leu-232 and the basic carboxylate side chain of Glu-167, the catalytic base, which destabilize E<sub>c</sub> relative to E<sub>o</sub>. |
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| 6. | Bioorg Med Chem Lett. 2011 Sep 1. [Epub ahead of print]Biological evaluation of glycosyl-isoindigo derivatives against the pathogenic agents of tropical diseases (malaria, Chagas disease, leishmaniasis and human African trypanosomiasis).Bouchikhi F, Anizon F, Brun R, Moreau P.SourceClermont Université, Université Blaise Pascal, SEESIB, BP 10448, F-63000 Clermont-Ferrand, France; CNRS, UMR 6504, SEESIB, F-63177 Aubière, France. AbstractThe biological activities of diversely substituted glycosyl-isoindigo derivatives against the causative agents of tropical diseases (malaria, Chagas disease, leishmaniasis and human African trypanosomiasis) are reported. Some of the compounds tested showed interesting activities with good selectivity indices, particularly against Trypanosoma brucei rhodesiense. These results suggested, for the first time, that glycosyl-isoindigo derivatives could be of interest for the discovery of new lead compounds to treat tropical diseases. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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| 7. | J Med Entomol. 2011 Sep;48(5):1091-4.High Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) prevalence in Triatoma sanguis uga (Hemiptera: Redviidae) in southeastern Louisiana.Cesa K, Caillouët KA, Dorn PL, Wesson DM.SourceDepartment of Tropical Medicine, Tulane University, New Orleans, LA 70112, USA. AbstractFrom May through November 2007, intensive weekly surveys at the site of a previously reported autochthonous human case of Chagas parasite infection resulted in the collection of 298 Triatoma sanguisuga (Leconte) specimens, of which 60.4% (180) were polymerase chain reaction positive for Trypanosoma cruzi Chagas. All were adults, in a ratio of approximately 1:1 female to male, indicating that the domicile was not colonized, but was a destination for these host-seeking adults. We report on seasonal activity pattern, T. cruzi prevalence in T. sanguisuga, and attempts at insect exclusion and control at the case residence. |
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| 8. | J Med Entomol. 2011 Sep;48(5):1016-22.Possible implication of the genetic composition of the Lutzomyia longipalpis (Diptera: Psychodidae) populations in the epidemiology of the visceral leishmaniasis.Rocha Lde S, Falqueto A, Dos Santos CB, Grimaldi GJ, Cupolillo E.SourceLaboratório de Pesquisas em Leishmanioses, Instituto Oswaldo Cruz, IOC/FIOCRUZ, Pavilhão Leônidas Deane-sala 509, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, Brazil 21045-900. lsr@ioc.fiocruz.br AbstractLutzomyia longipalpis (Diptera: Psychodidae) is the principal vector of American visceral leishmaniasis. Several studies have indicated that the Lu. longipalpis population structure is complex. It has been suggested that genetic divergence caused by genetic drift, selection, or both may affect the vectorial capacity of Lu. longipalpis. However, it remains unclear whether genetic differences among Lu. longipalpis populations are directly implicated in the transmission features of visceral leishmaniasis. We evaluated the genetic composition and the patterns of genetic differentiation among Lu. longipalpis populations collected from regions with different patterns of transmission of visceral leishmaniasis by analyzing the sequence variation in the mitochondrial cytochrome b gene. Furthermore, we investigated the temporal distribution of haplotypes and compared our results with those obtained in a previous study. Our data indicate that there are differences in the haplotype composition and that there has been significant differentiation between the analyzed populations. Our results reveal that measures used to control visceral leishmaniasis might have influenced the genetic composition of the vector population. This finding raises important questions concerning the epidemiology of visceral leishmaniasis, because these differences in the genetic structures among populations of Lu. longipalpis may have implications with respect to their efficiency as vectors for visceral leishmaniasis. |
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