What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2011 Oct 29
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

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1.	Planta Med. 2011 Oct 27. [Epub ahead of print] Trypanocidal Activity of β-Lactone-γ-Lactam Proteasome Inhibitors. Steverding D, Wang X, Potts BC, Palladino MA. Source BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, UK. Abstract Four β-lactone- γ-lactam proteasome inhibitors of natural origin were tested for their trypanocidal activities IN VITRO using culture-adapted bloodstream forms of TRYPANOSOMA BRUCEI. All four compounds displayed activities in the nanomolar range. The most trypanocidal compounds with 50 % growth inhibition (GI (50)) values of around 3 nM were the bromine and iodine analogues of salinosporamide A, a potent proteasome inhibitor produced by the marine actinomycete SALINISPORA TROPICA. In general, trypanosomes were more susceptible to the compounds than were human HL-60 cells. The data support the potential of β-lactone- γ-lactam proteasome inhibitors for rational anti-trypanosomal drug development. © Georg Thieme Verlag KG Stuttgart · New York.
	PMID: 22034066 [PubMed - as supplied by publisher]

2.	Mol Biochem Parasitol. 2011 Oct 20. [Epub ahead of print] Role of trypanosomatid's arginase in polyamine biosynthesis and pathogenesis. Balaña-Fouce R, Calvo-Álvarez E, Alvarez-Velilla R, Prada CF, Pérez-Pertejo Y, Reguera RM. Source Dpto. Ciencias Biomédicas, Universidad de León, Campus de Vegazana s/n, 24071 León, Spain. Abstract l-Arginine is one of the precursor amino acids of polyamine biosynthesis in most living organisms including Leishmania parasites. l-Arginine is enzymatically hydrolyzed by arginase producing l-ornithine and urea. In Leishmania spp. and other trypanosomatids a single gene encoding arginase has been described. The product of this gene is compartmentalized in glycosomes and is the main source of l-ornithine for polyamine synthesis in these parasites. l-Ornithine is substrate of ornithine decarboxylase (ODC) - one of the key enzymes of polyamine biosynthesis and a validated target for therapeutic intervention - producing putrescine, which in turn is converted to spermidine by condensing with an aminopropyl group from decarboxylated S-adenosylmethionine. Unlike trypanosomatids, mammalian hosts have two arginases (arginase I and II), which have close structural and kinetic resemblances, but localize in different subcellular organelles, respond to different stimuli and have different immunological reactivity. Arginase I is a cytosolic enzyme, mostly expressed in the liver as a pivotal component of the urea cycle, providing in addition l-ornithine for polyamine synthesis. In contrast, arginase II localizes inside mitochondria and is metabolically involved in l-proline and l-glutamine biosynthesis. More striking is the role played by l-arginine as substrate for nitric oxide synthase (NOS2) in macrophages, the main route of clearance of many infectious agents including Leishmania and Trypanosoma cruzi. In infected macrophages l-arginine is catalysed by NOS2 or arginase, contributing to host defense or parasite killing, respectively. A balance between NOS2 and arginase activities is a crucial factor in the progression of the Leishmania infection inside macrophages. In response to T-helper type 2 (Th2) cytokines, resident macrophages induce arginase I inhibiting NO production from l-arginine, thereby promoting parasite proliferation. Conversely, the response to T-helper type 1 (Th1) cytokines is linked to NOS2 induction and parasite death. Moreover, induction of any of these enzymes is accompanied by suppression of the other. Specifically, arginase reduces NO synthesis by substrate depletion, and N(ω)-hydroxy-l-arginine, one of the intermediates of NOS2 catalysis, competitively inhibits arginase activity. In spite of abundant data concerning arginases in mammals as well their involvement in parasite killing, there are very few papers regarding the actual role of arginase in the parasite itself. This review is an update on the recent progress in research on leishmanial arginase including the role played by this enzyme in the establishment of infection in macrophages and the immune response of the host. A comparative study of arginases from other kinetoplatids is also discussed. Copyright © 2011. Published by Elsevier B.V.
	PMID: 22033378 [PubMed - as supplied by publisher]

3.	Am J Pathol. 2011 Jul;179(1):281-8. Epub 2011 May 14. Cavia porcellus as a model for experimental infection by Trypanosoma cruzi. Castro-Sesquen YE, Gilman RH, Yauri V, Angulo N, Verastegui M, Velásquez DE, Sterling CR, Martin D, Bern C. Source Asociación Benéfica PRISMA, San Miguel, Lima, Peru. Abstract The guinea pig (Cavia porcellus) is a natural reservoir for Trypanosoma cruzi but has seldom been used as an experimental infection model. We developed a guinea pig infection model for acute and chronic Chagas disease. Seventy-two guinea pigs were inoculated intradermally with 10(4) trypomastigotes of T. cruzi strain Y (experimental group); 18 guinea pigs were used as control group. Eight animals from the experimental group and two from the control group were sacrificed 5, 15, 20, 25, 40, 55, 115, 165, and 365 days after inoculation. During the acute phase (15 to 55 days), we observed parasitemia (with a peak on day 20) and positive IgM and IgG Western blots with anti-shed acute-phase antigen bands. The cardiac tissue showed vasculitis, necrosis (on days 40 to 55), moderate to severe inflammation, and abundant amastigote nests. Smaller numbers of amastigote nests were also present in kidney, brain, and other organs. In the early chronic phase (115 to 165 days), parasitemia disappeared and anti-T. cruzi IgG antibodies were still detectable. In cardiac tissue, the number of amastigote nests and the grade of inflammation decreased. In the chronic phase (365 days), the cardiac tissue showed vasculitis and fibrosis; detectable parasite DNA was associated with higher grades of inflammation. The experimental T. cruzi infection model in guinea pigs shows kinetics and pathologic changes similar to those of the human disease. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. PMCID: PMC3123796 [Available on 2012/7/1]
	PMID: 21703410 [PubMed - indexed for MEDLINE]
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