Thursday, June 11, 2009

What's new for 'Trypanosomatids' in PubMed

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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 -4 of 4

1: J Ethnopharmacol. 2009 Jun 25;123(3):413-22.

Medicinal plants from the Yanesha (Peru): evaluation of the leishmanicidal and antimalarial activity of selected extracts.

Valadeau C, Pabon A, Deharo E, Albán-Castillo J, Estevez Y, Lores FA, Rojas R, Gamboa D, Sauvain M, Castillo D, Bourdy G.

IFEA UMIFRE 17 CNRS/MAEE, Casilla 18-1217, Lima, Peru.

AIM OF THE STUDY: Ninety-four ethanolic extracts of plants used medicinally by the Yanesha, an Amazonian Peruvian ethnic group, for affections related to leishmaniasis and malaria were screened in vitro against Leishmania amazonensis amastigotes and against a Plasmodium falciparum chloroquine resistant strain. MATERIALS AND METHODS: The viability of Leishmania amazonensis amastigote stages was assessed by the reduction of tetrazolium salt (MTT) while the impact on Plasmodium falciparum was determined by measuring the incorporation of radio-labelled hypoxanthine. RESULTS AND CONCLUSIONS: Six plant species displayed good activity against Plasmodium falciparum chloroquine resistant strain (IC(50) < 10 microg/ml): a Monimiaceae, Siparuna aspera (Ruiz & Pavon), A. DC., two Zingiberaceae, Renealmia thyrsoidea (Ruiz & Pavon) Poepp. & Endl. and Renealmia alpinia (Rottb.), two Piperaceae (Piper aduncum L. and Piper sp.) and the leaves of Jacaranda copaia (Aubl.) D. Don (Bignoniaceae). Eight species displayed interesting leishmanicidal activities (IC50 < 10 microg/ml): Carica papaya L. (Caricaceae), Piper dennisii Trel (Piperaceae), Hedychium coronarium J. König (Zingiberaceae), Cestrum racemosum Ruiz & Pav. (Solanaceae), Renealmia alpinia (Rottb.) Zingiberaceae, Lantana sp. (Verbenaceae), Hyptis lacustris A. St.-Hil. ex Benth. (Lamiaceae) and Calea montana Klat. (Asteraceae). Most of them are used against skin affections by Yanesha people. Results are discussed herein, according to the traditional use of the plants and compared with data obtained from the literature.

PMID: 19514108 [PubMed - in process]

2: PLoS Negl Trop Dis. 2009 Jun 9;3(6):e455.Click here to read

Gene Conversion Transfers the GAF-A Domain of Phosphodiesterase TbrPDEB1 to One Allele of TbrPDEB2 of Trypanosoma brucei.

Kunz S, Luginbuehl E, Seebeck T.

Institute of Cell Biology, University of Bern, Bern, Switzerland.

BACKGROUND: Chromosome 9 of Trypanosoma brucei contains two closely spaced, very similar open reading frames for cyclic nucleotide specific phosphodiesterases TbrPDEB1 and TbrPDEB2. They are separated by 2379 bp, and both code for phosphodiesterases with two GAF domains in their N-terminal moieties and a catalytic domain at the C-terminus. METHODS AND FINDINGS: The current study reveals that in the Lister427 strain of T. brucei, these two genes have undergone gene conversion, replacing the coding region for the GAF-A domain of TbrPDEB2 by the corresponding region of the upstream gene TbrPDEB1. As a consequence, these strains express two slightly different versions of TbrPDEB2. TbrPDEB2a represents the wild-type phosphodiesterase, while TbrPDEB2b represents the product of the converted gene. Earlier work on the subcellular localization of TbrPDEB1 and TbrPDEB2 had demonstrated that TbrPDEB1 is predominantly located in the flagellum, whereas TbrPDEB2 partially locates to the flagellum but largely remains in the cell body. The current findings raised the question of whether this dual localization of TbrPDEB2 may reflect the two alleles. To resolve this, TbrPDEB2 of strain STIB247 that is homozygous for TbrPDEB2a was tagged in situ, and its intracellular localization was analyzed. CONCLUSIONS: The results obtained were very similar to those found earlier with Lister427, indicating that the dual localization of TbrPDEB2 reflects its true function and is not simply due to the presence of the two different alleles. Notably, the gene conversion event is unique for the Lister427 strain and all its derivatives. Based on this finding, a convenient PCR test has been developed that allows the stringent discrimination between Lister-derived strains that are common in many laboratories and other isolates. The technique is likely very useful to resolve questions about potential mix-ups of precious field isolates with the ubiquitous Lister strain.

PMID: 19513125 [PubMed - in process]

3: Molecules. 2009 Jun 8;14(6):2062-76.

Quantitative structure--antiprotozoal activity relationships of sesquiterpene lactones.

Schmidt TJ, Nour AM, Khalid SA, Kaiser M, Brun R.

Westfälische Wilhelms-Universität Münster, Institut für Pharmazeutische Biologie und Phytochemie, Hittorfstrasse 56, D-48149 Münster, Germany. thomschm@uni-muenster.de

Prompted by results of our previous studies where we found high activity of some sesquiterpene lactones (STLs) against Trypanosoma brucei rhodesiense (which causes East African sleeping sickness), we have now conducted a structure-(in-vitro)-activity study on a set of 40 STLs against T. brucei rhodesiense, T. cruzi, Leishmania donovani and Plasmodium falciparum. Furthermore, cytotoxic activity against L6 rat skeletal myoblast cells was assessed. Some of the compounds possess high activity, especially against T. brucei (e.g. helenalin and some of its esters with IC(50)-values of 0.05-0.1 microM, which is about 10 times lower than their cytotoxic activity). It was found that all investigated antiprotozoal activities are significantly correlated with cytotoxicity and the major determinants for activity are a,b-unsaturated structural elements, also known to be essential for other biological activities of STLs. It was observed, however, that certain compounds are considerably more toxic against protozoa than against mammalian cells while others are more cytotoxic than active against the protozoa. A comparative QSAR analysis was therefore undertaken, in order to discern the antiparasitic activity of STLs against T. brucei and cytotoxicity. Both activities were found to depend to a large extent on the same structural elements and molecular properties. The observed variance in the biological data can be explained in terms of subtle variations in the relative influences of various molecular descriptors.

PMID: 19513006 [PubMed - in process]

4: Ann Trop Med Parasitol. 2009 Jun;103(4):297-306.

Antileishmanial activity in Israeli plants.

El-On J, Ozer L, Gopas J, Sneir R, Enav H, Luft N, Davidov G, Golan-Goldhirsh A.

The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel; Laboratory of Parasitology, Soroka University Medical Center, Beer Sheva 84101, Israel.

Leishmaniasis is a vector-borne disease caused by flagellated protozoan parasites of the genus Leishmania, which affects both humans and other mammals. Most of the available drugs against the disease are toxic and parasite resistance to some of the drugs has already developed. In the present study, the leishmanicidal activities of methanolic extracts of some Israeli plants have been evaluated in vitro, against the free-living promastigotes and intracellular amastigotes of Leishmania major. Of the 41 extracts examined, those of two plants (Nuphar lutea>Withania somnifera) were highly effective (with a maximum inhibitory effect of >50%), those of three other species (Pteris vittata>Smyrnium olusatrum>Trifolium clypeatum) were moderately effective (25%-50%) and another four extracts (Erodium malacoides>Hyparrhenia hirta>Thymelaea hirsuta>Pulicaria crispa) showed a marginal effect (15%-22%) against the parasites. Extracts of nine plant species therefore showed antileishmanial activity but only the extract of N. lutea, used at 1.25 mug/ml, eliminated all the intracellular parasites within 3 days of treatment, with no detectable toxicity to the host macrophages. The mean (S.D.) values recorded for the median inhibitory concentrations of this extract (IC(50)) against the promastigotes [2.0 (0.12) mug/ml] and amastigotes [0.65 (0.023) mug/ml] and the median lethal concentration (LD(50)) against macrophages [2.1 (0.096) mug/ml] were encouraging, giving a therapeutic selectivity index [LD(50)/IC(50) for amastigotes)] of 3.23. The extract of N. lutea was, in fact, generally as effective as the paromomycin that was used as the 'gold standard' drug. These results indicate that N. lutea and probably also Withania somnifera might be potential sources of clinically useful, antileishmanial compounds.

PMID: 19508747 [PubMed - in process]

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