What's new for 'Trypanosomatids' in PubMed

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Sent on Wednesday, 2010 Jul 07
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 - 7 of 7

1.	J Cell Biol. 2010 Jul 5. [Epub ahead of print] The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation. Kuang Z, Lewis RS, Curtis JM, Zhan Y, Saunders BM, Babon JJ, Kolesnik TB, Low A, Masters SL, Willson TA, Kedzierski L, Yao S, Handman E, Norton RS, Nicholson SE. The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia. Abstract Inducible nitric oxide (NO) synthase (iNOS; NOS2) produces NO and related reactive nitrogen species, which are critical effectors of the innate host response and are required for the intracellular killing of pathogens such as Mycobacterium tuberculosis and Leishmania major. We have identified SPRY domain-containing SOCS (suppressor of cytokine signaling) box protein 2 (SPSB2) as a novel negative regulator that recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in its proteasomal degradation. SPSB2 interacts with the N-terminal region of iNOS via a binding interface on SPSB2 that has been mapped by nuclear magnetic resonance spectroscopy and mutational analyses. SPSB2-deficient macrophages showed prolonged iNOS expression, resulting in a corresponding increase in NO production and enhanced killing of L. major parasites. These results lay the foundation for the development of small molecule inhibitors that could disrupt the SPSB-iNOS interaction and thus prolong the intracellular lifetime of iNOS, which may be beneficial in chronic and persistent infections.
	PMID: 20603330 [PubMed - as supplied by publisher]
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2.	Exp Parasitol. 2010 Jul 2. [Epub ahead of print] Leishmania major: Secreted antigens of Leishmania major promastigotes shift the immune response of the C57BL/6 mice toward Th2 in vitro. Tabatabaee PA, Abolhassani M, Mahdavi M, Nahrevanian H, Azadmanesh K. Dept. of Immunology, Hybridoma Lab.,Pasteur Institute of Iran, Tehran, Iran. Abstract BALB/c mice are sensitive to Leishmaniamajor infection, while C57BL/6 mice are resistant and able to mount an effective immune response against the parasite. Since the secreted antigens of L. major suppress the proliferation of BALB/c mice lymphocytes in vitro, we analyzed their effects on the immune system of resistant C57BL/6 mice. Secreted antigens were semi-purified and two fractions with immunosuppressive activity were isolated. Fifteen mug/ml of fraction could suppress 60% of lymphocyte proliferation and prevent the stimulated lymphocytes entering from G1 phase into the S phase of the cell cycle. These fractions decreased the production of IFN-gamma, increased IL-4 level in the lymphocyte culture and down-regulated the nitric oxide production by activated macrophages. These results may suggest that L. major parasite by secreting immunosuppressive factors could down-regulate the immune system of both sensitive and resistant mice for own survival advantage. Copyright © 2010 Elsevier Inc. All rights reserved.
	PMID: 20603118 [PubMed - as supplied by publisher]
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3.	Parasitology. 2010 Aug;137(9):1357-92. Lipidomic analysis of bloodstream and procyclic form Trypanosoma brucei. Richmond GS, Gibellini F, Young SA, Major L, Denton H, Lilley A, Smith TK. Centre for Biomolecular Sciences, The North Haugh, The University, St. Andrews, KY16 9ST, Scotland, U.K. Abstract SUMMARYThe biological membranes of Trypanosoma brucei contain a complex array of phospholipids that are synthesized de novo from precursors obtained either directly from the host, or as catabolised endocytosed lipids. This paper describes the use of nanoflow electrospray tandem mass spectrometry and high resolution mass spectrometry in both positive and negative ion modes, allowing the identification of ~500 individual molecular phospholipids species from total lipid extracts of cultured bloodstream and procyclic form T. brucei. Various molecular species of all of the major subclasses of glycerophospholipids were identified including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol as well as phosphatidic acid, phosphatidylglycerol and cardolipin, and the sphingolipids sphingomyelin, inositol phosphoceramide and ethanolamine phosphoceramide. The lipidomic data obtained in this study will aid future biochemical phenotyping of either genetically or chemically manipulated commonly used bloodstream and procyclic strains of Trypanosoma brucei. Hopefully this will allow a greater understanding of the bizarre world of lipids in this important human pathogen.
	PMID: 20602846 [PubMed - in process]
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4.	J Heart Lung Transplant. 2010 Mar;29(3):286-90. Epub 2009 Sep 26. Infections in heart transplant recipients in Brazil: the challenge of Chagas' disease. Godoy HL, Guerra CM, Viegas RF, Dinis RZ, Branco JN, Neto VA, Almeida DR. Division of Cardiology, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil. godoy.henrique@gmail.com Abstract BACKGROUND: Despite the high incidence of infections after heart transplantation, there is limited information about its epidemiology in patients from countries where Chagas' disease is endemic. METHODS: We analyzed the occurrence of infections in 126 patients aged older than 18 years who underwent transplantation from 1986 through 2007 at a Brazilian University Hospital and who survived at least 48 hours. RESULTS: Heart failure diagnoses before transplantation were idiopathic dilated cardiomyopathy (38.6%), Chagas' disease (34.9%), coronary artery disease (19.8%), and others (6.3%). The respiratory tract was the most common site of infections (40.9%), followed by surgical wound site (18.1%). Trypanosoma cruzi reactivations occurred in 38.8% of Chagas' disease patients: 47.0% had myocarditis, 23.5% had skin lesions, and 29.4% had both. New-onset ventricular dysfunction was observed in 47.0%, with complete response after specific treatment, and 41.0% were asymptomatic cases, diagnosed by routine endomyocardial biopsies. No patient died from such events. No differences in survival were found after 5 years of follow-up between recipients with and without Chagas' disease (p = 0.231). CONCLUSIONS: In a heart transplant population from a developing country, infectious complications occurred at a high rate. Tropical illnesses were uncommon, except for the high rate of Chagas' disease reactivations. Despite that, the overall outcome of these patients was similar to that of recipients with other cardiomyopathies.
	PMID: 19783174 [PubMed - indexed for MEDLINE]
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5.	Bioorg Med Chem Lett. 2009 Feb 1;19(3):589-96. Epub 2008 Dec 24. Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase fro m in silico screening. Neres J, Brewer ML, Ratier L, Botti H, Buschiazzo A, Edwards PN, Mortenson PN, Charlton MH, Alzari PM, Frasch AC, Bryce RA, Douglas KT. School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PT, UK. jneres@hotmail.com Abstract trans-Sialidase from Trypanosoma cruzi (TcTS) has emerged as a potential drug target for treatment of Chagas disease. Here, we report the results of virtual screening for the discovery of novel TcTS inhibitors, which targeted both the sialic acid and sialic acid acceptor sites of this enzyme. A library prepared from the Evotec database of commercially available compounds was screened using the molecular docking program GOLD, following the application of drug-likeness filters. Twenty-three compounds selected from the top-scoring ligands were purchased and assayed using a fluorimetric assay. Novel inhibitor scaffolds, with IC(50) values in the submillimolar range were discovered. The 3-benzothiazol-2-yl-4-phenyl-but-3-enoic acid scaffold was studied in more detail, and TcTS inhibition was confirmed by an alternative sialic acid transfer assay. Attempts to obtain crystal structures of these compounds with TcTS proved unsuccessful but provided evidence of ligand binding at the active site.
	PMID: 19144516 [PubMed - indexed for MEDLINE]
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6.	Bioorg Med Chem Lett. 2009 Feb 1;19(3):718-23. Epub 2008 Dec 14. Oxidosqualene cyclase from Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana expressed in yeast: a model for the development of novel antiparasitic agents. Balliano G, Dehmlow H, Oliaro-Bosso S, Scaldaferri M, Taramino S, Viola F, Caron G, Aebi J, Ackermann J. Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, via P. Giuria 9, 10125 Torino, Italy. gianni.balliano@unito.it Abstract A series of 25 compounds, some of which previously were described as inhibitors of human liver microsomal oxidosqualene cyclase (OSC), were tested as inhibitors of Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana OSCs expressed in an OSC-defective strain of S. cerevisiae. The screening identified three derivatives particularly promising for the development of novel anti-Trypanosoma agents and eight derivatives for the development of novel anti-Pneumocystis agents.
	PMID: 19119009 [PubMed - indexed for MEDLINE]
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7.	Bioorg Med Chem Lett. 2009 Feb 1;19(3):986-9. Epub 2008 Nov 24. Synthesis, in vitro antitrypanosomal and antibacterial activity of phenoxy, phenylthio or benzyloxy substituted quinolones. Ma X, Zhou W, Brun R. State Key Lab of New Drug & Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan Road, Shanghai 200437, PR China. chemx@nus.edu.sg Abstract Chagas' disease, caused by Trypanosoma cruzi(T. cruzi), is one of the most serious parasitic diseases in Latin America. The currently available chemotherapy, based on nifurtimox or benznidazole, is unsatisfactory due to the limited efficacy in the prevalent chronic stage of the disease and toxic side effects. In order to address these deficiencies, a series of quinolones based novel molecules have been synthesized and evaluated as potential antitrypanosomal agents. The most active analogue 10 inhibited T. cruzi with an IC(50) of 1.3 microg/mL. The results of this study have implications in the development of novel quinolone's antitrypanosomal agents.
	PMID: 19095449 [PubMed - indexed for MEDLINE]
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