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Sent on Saturday, 2010 Feb 20Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | Rev Salud Publica (Bogota). 2009 Aug;11(4):641-52.[Western blot, ELISA and indirect immunofluorescence test evaluation of Leishmania (Leishmania) infantum-infected dogs.][Article in Spanish] Vargas-Duarte JJ, López-Páez MC, Escovar-Castro JE, Fernández-Manrique J.Instituto de Genética, Universidad Nacional de Colombia. Objective Evaluating canine visceral leishmaniasis diagnostic test performance in Colombia and adapting the Western blot test in naturally and experimentally infected dogs. Methods Sera were obtained from 10 experimentally L. Infantum-infected dogs, 5 naturally infected dogs, 16 healthy dogs, 26 Babesia canis, Erhlichia canis, Dirofilaria immitis, Trypanosoma cruzi and Leishmania (Viannia) spp infected dogs, 40 dogs from non-endemic areas and 150 from endemic areas. Sera were tested for L. infantum infection using immunofluorescent antibody (IFAT), ELISA and Western blot (WB) tests. Results Positives results were obtained for 73 % of known infected dogs by the IFAT test and false positives were obtained for 2.5 % of non-infected dogs using WB. ELISA was not efficient for diagnosis. 24 antigenic fractions were recognised in tested sera using WB; however, 29, 34, 50, 69, 75, 86, 99 and 123 kDa bands were recognised in sera from dogs from non-endemic areas, healthy dogs and Trypanosoma cruzi, Erhlichia canis, Dirofilaria immitis and Babesia canis infected dogs. The 13 kDa fraction proved potentially useful for diagnosing canine visceral leishmaniasis. ConclusionsThe separate use of parasitological and serological test could lead to misdiagnosis of Leishmania infection; using both kinds of technique simultaneously is thus highly recommended. |
PMID: 20169220 [PubMed - in process] | |
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2. | J Biomed Biotechnol. 2010;2010:525241. Epub 2010 Feb 11.Gene expression in trypanosomatid parasites.Martínez-Calvillo S, Vizuet-de-Rueda JC, Florencio-Martínez LE, Manning-Cela RG, Figueroa-Angulo EE.Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Col. Los Reyes Iztacala, Tlalnepantla, Edo. de México, CP 54090, Mexico. The parasites Leishmania spp., Trypanosoma brucei, and Trypanosoma cruzi are the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids. In silico analyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa. |
PMID: 20169133 [PubMed - in process] | |
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3. | PLoS One. 2010 Feb 16;5(2):e9211.Cerebral and Peripheral Changes Occurring in Nitric Oxide (NO) Synthesis in a Rat Model of Sleeping Sickness: Identification of Brain iNOS Expressing Cells.Amrouni D, Gautier-Sauvigné S, Meiller A, Vincendeau P, Bouteille B, Buguet A, Cespuglio R.University of Lyon, Faculty of Medicine, EA 4170 Laboratory of Free Radicals, Energy Substrates and Cerebral Physiopathology, & Neurochem platform, Lyon, France. BACKGROUND: The implication of nitric oxide (NO) in the development of human African trypanosomiasis (HAT) using an animal model, was examined. The manner by which the trypanocidal activity of NO is impaired in the periphery and in the brain of rats infected with Trypanosoma brucei brucei (T. b. brucei) was analyzed through: (i) the changes occurring in NO concentration in both peripheral (blood) and cerebral compartments; (ii) the activity of nNOS and iNOS enzymes; (iii) identification of the brain cell types in which the NO-pathways are particularly active during the time-course of the infection. METHODOLOGY/PRINCIPAL FINDINGS: NO concentration (direct measures by voltammetry) was determined in central (brain) and peripheral (blood) compartments in healthy and infected animals at various days post-infection: D5, D10, D16 and D22. Opposite changes were observed in the two compartments. NO production increased in the brain (hypothalamus) from D10 (+32%) to D16 (+71%), but decreased in the blood from D10 (-22%) to D16 (-46%) and D22 (-60%). In parallel with NO measures, cerebral iNOS activity increased and peaked significantly at D16 (up to +700%). However, nNOS activity did not vary. Immunohistochemical staining confirmed iNOS activation in several brain regions, particularly in the hypothalamus. In peritoneal macrophages, iNOS activity decreased from D10 (-83%) to D16 (-65%) and D22 (-74%) similarly to circulating NO. CONCLUSION/SIGNIFICANCE: The NO changes observed in our rat model were dependent on iNOS activity in both peripheral and central compartments. In the periphery, the NO production decrease may reflect an arginase-mediated synthesis of polyamines necessary to trypanosome growth. In the brain, the increased NO concentration may result from an enhanced activity of iNOS present in neurons and glial cells. It may be regarded as a marker of deleterious inflammatory reactions. |
PMID: 20169057 [PubMed - in process] | |
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4. | Bioorg Med Chem Lett. 2010 Jan 25. [Epub ahead of print]Design and evaluation of Trypanosoma brucei metacaspase inhibitors.Berg M, Veken PV, Joossens J, Muthusamy V, Breugelmans M, Moss CX, Rudolf J, Cos P, Coombs GH, Maes L, Haemers A, Mottram JC, Augustyns K.Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. Metacaspase (MCA) is an important enzyme in Trypanosoma brucei, absent from humans and differing significantly from the orthologous human caspases. Therefore MCA constitutes a new attractive drug target for antiparasitic chemotherapeutics, which needs further characterization to support the discovery of innovative drug candidates. A first series of inhibitors has been prepared on the basis of known substrate specificity and the predicted catalytic mechanism of the enzyme. In this Letter we present the first inhibitors of TbMCA2 with low micromolar enzymatic and antiparasitic activity in vitro combined with low cytotoxicity. Copyright © 2010 Elsevier Ltd. All rights reserved. |
PMID: 20167486 [PubMed - as supplied by publisher] | |
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5. | Curr Med Chem. 2010 Feb 18. [Epub ahead of print]Trypanosomatid Parasites Causing Neglected Diseases.Nu Szlig Baum K, Honek J, van Curtlandt Cadmus CM, Efferth T.Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany. efferth@uni-mainz.de. Parasitic diseases such as Kala azar (visceral leishmaniasis), Chagas disease (American trypanosomiasis) and African sleeping sickness (African trypanosomiasis) are affecting more than 27 million people worldwide. They are categorized amongst the most important neglected diseases causing approximately 150,000 deaths annually. As no vaccination is available, treatment is solely dependent on chemotherapeutic drugs. This review provides a comprehensive insight into the treatment of Kala azar, Chagas disease and African sleeping sickness. In addition to established drugs, novel smallmolecule- based therapeutic approaches are discussed. Drugs currently used for the treatment of Kala azar include pentavalent antimonials, Amphotericin B, Miltefosine, and Paromomycin. Liposomal formulations such as AmBisome(R) provide promising alternatives. Furthermore, antiproliferative compounds might open new avenues in Kala azar treatment. Regarding Chagas disease, chemotherapy is based on two drugs, Nifurtimox and Benznidazole. However, sequencing of T. cruzi genome in the year 2005 raises a hope for new drug targets. Proteases, sterols and sialic acids are potential promising drug targets. Suramin, Penamidine, Melarsporol and Eflornithine are well-established drugs to treat African sleeping sickness. New treatment options include combination therapy of Eflornithine and Nifurtimox, a Chagas disease therapeutic.. However, all approved chemotherapeutic compounds for trypanosomatid diseases suffer from high toxicity. Further, increasing resistance limits their efficacy and compliance. |
PMID: 20166934 [PubMed - as supplied by publisher] | |
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