What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2012 May 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 - 6 of 6

1.	ScientificWorldJournal. 2012;2012:963658. Epub 2012 Apr 1. Footprinting of Inhibitor Interactions of In Silico Identified Inhibitors of Trypanothione Reductase of Leishmania Parasite. Venkatesan SK, Dubey VK. Source Department of Biotechnology, Indian Institute of Technology Guwahati, Assam 781039, India. Abstract Structure-based virtual screening of NCI Diversity set II compounds was performed to indentify novel inhibitor scaffolds of trypanothione reductase (TR) from Leishmania infantum. The top 50 ranked hits were clustered using the AuPoSOM tool. Majority of the top-ranked compounds were Tricyclic. Clustering of hits yielded four major clusters each comprising varying number of subclusters differing in their mode of binding and orientation in the active site. Moreover, for the first time, we report selected alkaloids and dibenzothiazepines as inhibitors of Leishmania infantum TR. The mode of binding observed among the clusters also potentiates the probable in vitro inhibition kinetics and aids in defining key interaction which might contribute to the inhibition of enzymatic reduction of T[S] 2. The method provides scope for automation and integration into the virtual screening process employing docking softwares, for clustering the small molecule inhibitors based upon protein-ligand interactions.
	PMID: 22550471 [PubMed - as supplied by publisher]

2.	Int J Parasitol. 2012 Apr 24. [Epub ahead of print] Trypanosoma brucei: Chemical evidence that cathepsin L is essential for survival and a relevant drug target. Steverding D, Sexton DW, Wang X, Gehrke SS, Wagner GK, Caffrey CR. Source Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK. Abstract The protozoan parasite causing human African trypanosomiasis, Trypanosoma brucei, displays cysteine peptidase activity, the chemical inhibition of which is lethal to the parasite. This activity comprises a cathepsin B (TbCATB) and a cathepsin L (TbCATL). Previous RNA interference (RNAi) data suggest that TbCATB rather than TbCATL is essential to survival even though silencing of the latter was incomplete. Also, chemical evidence supporting the essentiality of either enzyme which would facilitate a target-based drug development programme is lacking. Using specific peptidyl inhibitors and substrates, we quantified the contributions of TbCATB and TbCATL to the survival of T. brucei. At 100μM, the minimal inhibitory concentration that kills all parasites in culture, the non-specific cathepsin inhibitors, benzyloxycarbonyl-phenylalanyl-arginyl-diazomethyl ketone (Z-FA-diazomethyl ketone) and (l-3-trans-propylcarbamoyloxirane-2-carbonyl)-l-isoleucyl-l-proline methyl ester (CA-074Me) inhibited TbCATL and TbCATB by >99%. The cathepsin L (CATL)-specific inhibitor, ((2S,3S)-oxirane-2,3-dicarboxylic acid 2-[((S)-1-benzylcarbamoyl-2-phenyl-ethyl)-amide] 3-{[2-(4-hydroxy-phenyl)-ethyl]-amide}) (CAA0225), killed parasites with >99% inhibition of TbCATL but only 70% inhibition of TbCATB. Conversely, the cathepsin B (CATB)-specific inhibitor, (l-3-trans-propylcarbamoyloxirane-2-carbonyl)-l-isoleucyl-l-proline (CA-074), did not affect survival even though TbCATB inhibition at >95% was statistically indistinguishable from the complete inhibition by Z-FA-diazomethyl ketone and CA-074Me. The observed inhibition of TbCATL by CA-074 and CA-074Me was shown to be facilitated by the reducing intracellular environment. All inhibitors, except the CATB-specific inhibitor, CA-074, blockaded lysosomal hydrolysis prior to death. The results suggest that TbCATL, rather than TbCATB, is essential to the survival of T. brucei and an appropriate drug target. Copyright © 2012. Published by Elsevier Ltd.
	PMID: 22549023 [PubMed - as supplied by publisher]

3.	J Vector Ecol. 2012 Jun;37(1):148-153. doi: 10.1111/j.1948-7134.2012.00211.x. The role of Palmyra palm trees (Borassus flabellifer) and sand fly distribution in northeastern India. Poché RM, Garlapati R, Elnaiem DE, Perry D, Poché D. Source Genesis Laboratories, Inc., Wellington, CO 80549, U.S.A., richard@genesislabs.com Boring Canal Road, Patna, India University of Maryland Eastern Shore, Princess Anne, MD 21853, U.S.A. Abstract Visceral leishmaniasis (VL), known as Kala-azar in India, is a parasite transmitted by the bite of the sand fly vector Phlebotomus argentipes. Published information on the species indicates it is a poor flyer, mainly hopping and gliding. This study describes the vector as more arboreal than previously documented. Data collected indicate the ability of P. argentipes and Sergentomyia spp to attain vertical heights in Palmyra palm trees Borassus flabellifer up to 18.4 m above ground level. To determine if sand flies were either climbing the tree trunk to rest in the canopy or flying, sticky traps were set around the tree trunk and checked for captures overnight. CDC traps set in the palm tree canopy resulted in the capture of 5,067 sand flies, 3,990 of which were P. argentipes. Traps were set during daylight hours to determine if sand flies remained and rested in the canopy. A total of 128 sand flies were trapped over 29 trap days in the palm trees. With the CDC traps, 130 P. argentipes and no Sergentomyia spp were captured. The converse was true for the sticky traps set around tree trunks 3 m below the CDC traps. Of the 105 sand flies collected, only one was P. argentipes and 104 were Sergentomyia spp. As reported elsewhere, this indicates Sergentomyia spp tend to climb and hop, wheareas P. argentipes are capable of longer and more sustained flight. Data presented herein suggest that P. argentipes is more exophylic and exophagic than previously reported. These findings have implications for sand fly control. © 2012 The Society for Vector Ecology.
	PMID: 22548548 [PubMed - as supplied by publisher]

4.	J Vector Ecol. 2012 Jun;37(1):137-147. doi: 10.1111/j.1948-7134.2012.00210.x. Wing size and shape variation of Phlebotomus papatasi (Diptera: Psychodidae) populations from the south and north slopes of the Atlas Mountains in Morocco. Prudhomme J, Gunay F, Rahola N, Ouanaimi F, Guernaoui S, Boumezzough A, Bañuls AL, Sereno D, Alten B. Source UMR MIVEGEC (IRD 224-CNRS 5290-Universités Montpellier 1 et 2), Montpellier, F-34394, France Hacettepe University, Faculty of Science, Department of Biology, Ecology Section, ESRL Laboratories, 06800 Beytepe, Ankara, Turkey, kaynas@hacettepe.edu.tr Université Cadi Ayyad, Faculté des Sciences Semlalia, Equipe Ecologie Animale et Environnement-LabL2E (URAC 32), BP 2390-40080 Marrakech-Maroc. Abstract The wing shape and size morphology of populations of the medically important phlebotomine sand fly, Phlebotomus papatasi, were examined in two endemic (south of the Atlas Mountains) and nonendemic (north of the Atlas Mountains) foci of cutaneaous leishmaniasis by using geometric morphometrics in Morocco. Although it is present in all of Morocco, P. papatasi is the main vector of Leishmania major in only southern part of the Atlas Mountains. There are four major mountain ranges that serve as geographical barriers for species distribution in the study area and at least four gaps were recognized among these barriers. We found statistically significant differences in wing shape morphology between southern and northern populations. Analysis clearly recognized two main groups of populations on both sides of the mountains. The graphical depiction of Principal Component Analysis (PCA) and Canonical Variates Analysis (CVA) confirmed our morphometric study suggesting that the difference in wing morphology between the populations indicates that the population of P. papatasi shows phenotypic plasticity in the study area. According to centroid size analyses, which were used as measures of wing size differences among different sites, the north population of P. papatasi had relatively larger wings than the south population. © 2012 The Society for Vector Ecology.
	PMID: 22548547 [PubMed - as supplied by publisher]

5.	J Vector Ecol. 2012 Jun;37(1):90-96. doi: 10.1111/j.1948-7134.2012.00204.x. Sand fly vectors (Diptera, Psychodidae) of American visceral leishmaniasis areas in the Atlantic Forest, State of Espírito Santo, southeastern Brazil. de Souza Pinto I, Ferreira AL, Valim V, Dos Santos Carvalho F, da Silva GM, Falcão AL, Dietze R, Falqueto A. Source Laboratório de Biologia Molecular de Insetos, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos, CEP 21040-360, Rio de Janeiro, RJ, Brazil, pintoisrael@gmail.com Unidade de Medicina Tropical, Departamento de Medicina Social, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, Maruípe, CEP 29043-900, Vitória, ES, Brazil Departamento de Clínica Médica, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, Maruípe, CEP 29043-900, Vitória, ES, Brazil Laboratório de Referência Nacional e Internacional para Flebotomíneos, Centro de Pesquisas René Rachou, Av. Augusto de Lima 1715, 30190-002, Belo Horizonte, MG, Brazil Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, Maruípe, CEP 29043-900, Vitória, ES, Brazil. Abstract The aim of this study was to evaluate the sand fly fauna of American visceral leishmaniasis (AVL) endemic areas within the Central Atlantic Forest Biodiversity Corridor, State of Espírito Santo, southeastern Brazil. The sand fly captures were performed between January, 1989 and December, 2003 in localities where autochthonous cases of AVL were recorded, as well as in their boundary areas. Sand flies were collected from surrounding houses and domestic animal shelters using two to five CDC automatic light traps, and manual captures were also performed using mouth aspirators in one illuminated Shannon trap during the first four hours of the night. We used cladistic analysis to determine the geographic relationships among the collected sand fly species as well as the index species for the occurrence of other sand flies. A total of 62,469 sand flies belonging to 17 species and eight genera was collected in 164 localities from nine municipalities with AVL records. The richness (S=17) and diversity (H=0.971) of sand flies were lower than in conservation areas and similar to modified environments in the Atlantic Forest of Espírito Santo. Lutzomyia longipalpis was identified in 79 localities. The cladistic analysis identified Evandromyia lenti as the index species for Lutzomyia longipalpis. The latter seems to be the main vector of AVL in the Central Atlantic Forest Biodiversity Corridor due to its high abundance and distribution matching the disease occurence. Therefore, Evandromyia lenti may be used as an index species for the occurrence of Lutzomyia longipalpis. © 2012 The Society for Vector Ecology.
	PMID: 22548541 [PubMed - as supplied by publisher]

6.	Med Mycol. 2012 May 2. [Epub ahead of print] Activity of compounds isolated from Baccharis dracunculifolia D.C. (Asteraceae) against Paracoccidioides brasiliensis. Johann S, Oliveira FB, Siqueira EP, Cisalpino PS, Rosa CA, Alves TM, Zani CL, Cota BB. Source * Laboratório de Química de Produtos Naturais, Centro de Pesquisas René Rachou , Belo Horizonte, Minas Gerais. Abstract Paracoccidioidomycosis is a prevalent systemic mycosis in Latin America which requires prolonged treatment with highly toxic antifungals. Baccharis dracunculifolia is a medicinal plant in Brazil that is a candidate in the search for new drugs. Fractions of the hexanic extracts were obtained using chromatographic procedures and assessed using an antifungal assay with Paracoccidioides brasiliensis (Pb18), tumor cell lines and amastigote forms of Leishmania, L. amazonensis. Four compounds were isolated, i.e., ursolic acid (1), methyl linolenate (2), caryophyllene oxide (3), and trans-nerolidol (4). Compounds 2, 3 and 4 displayed antifungal activity against four isolates of Paracocci dioides with MIC values ranging from 3.9-250 μg/ml. Only caryophyllene oxide showed differences in the MIC values against Pb18 when the medium was supplemented with ergosterol, which suggested that the compound interacts with ergosterol. Ursolic acid was active in the cytotoxic assays and showed leishmanicidal activity. Scanning electron microscopy demonstrated that compounds 2, 3 and 4 decreased the cell size and produced an irregular cell wall surface on P. brasiliensis cells. The present results showed the biological activities of the isolated compounds and revealed that these compounds may affect the cell surface and growth of P. brasiliensis isolates.
	PMID: 22548242 [PubMed - as supplied by publisher]