What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2010 Sep 21
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 - 10 of 14

1.	Mol Biochem Parasitol. 2010 Sep 13. [Epub ahead of print] Genome-wide RNAi screens in bloodstream form trypanosomes identify drug transporters. Burkard GS, Jutzi P, Roditi I. Institute of Cell Biology, University of Bern, Bern, Switzerland. Abstract An inducible RNA interference (RNAi) library, consisting of a pool of independent stable transformants with 9-fold genome coverage, was constructed in bloodstream form Trypanosoma brucei using an improved transfection protocol. RNAi induction and selection of resistant parasites was performed in the presence of melarsoprol or eflornithine. The former led to the isolation of the adenosine transporter TbAT1, which is known to be involved in melarsoprol uptake, while the latter identified an amino acid transporter, AAT6. Knockdown of AAT6 reduced mRNA levels to 30-35% in independent clones and increased resistance to eflornithine >5-fold. Genome-wide screens with this library allow an unbiased approach to gene discovery, are extremely rapid and do not exclude essential genes.
	PMID: 20851719 [PubMed - as supplied by publisher]
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2.	Vet Parasitol. 2010 Aug 24. [Epub ahead of print] Low seroprevalence of Leishmania infantum infection in cats from northern Portugal based on DAT and ELISA. Cardoso L, Lopes AP, Sherry K, Schallig H, Solano-Gallego L. Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro, P.O. Box 1013, 5001-801 Vila Real, Portugal; Parasite Disease Group, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Portugal. Abstract Cats have been considered playing a role in the epidemiology of leishmaniosis caused by Leishmania infantum, an endemic zoonosis in countries of the Mediterranean basin. The present study assessed the prevalence of antibodies to L. infantum in 316 domestic cats from northern Portugal, by means of the direct agglutination test (DAT) and an enzyme-linked immunosorbent assay (ELISA). Seroreactivity to DAT was found in six cats, and nine cats were positive in the ELISA, including the six DAT-positive animals. The overall seroprevalence of Leishmania infection was 2.8%, based on ELISA and DAT. A substantial agreement (99%; κ value=0.80) was found between DAT and ELISA results. The difference between seroprevalence values in females (0.7%) and males (4.7%) was statistically significant (p=0.045). The age of seropositive cats ranged from 31 to 84 months. Cats with 5-6 years (60-71 months) and 6-7 years (72-83 months) presented the highest level of seropositivity (15.4% and 33.3%, respectively). A significant difference was found comparing the seroprevalences in cats aged less than 24 months (0.0%) and in those with 24 months or more (7.3%) (p=0.022). Seroprevalences in cats living in a rural environment (10.5%) or in urban areas (0.0%) were also found to be significantly different (p<0.001). No significant differences were detected between serological status to Leishmania in pure non-European and European or mixed breeds (p=0.442), cats that lived totally indoors and those that had access to outdoors (p=0.412), cats seropositive and seronegative to Toxoplasma gondii (p=0.276), or apparently healthy animals and those with clinical illness (p=0.271). This study is the largest epidemiological investigation performed on feline Leishmania infection in Portugal. The seroprevalence of Leishmania infection was low in cats living in northern Portugal, a region where canine leishmaniosis is endemic. Nevertheless, Leishmania infection must not be underestimated and leishmaniosis may be included in the differential diagnosis of cutaneous or systemic clinical signs in cats.
	PMID: 20851524 [PubMed - as supplied by publisher]
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3.	J Inorg Biochem. 2010 Aug 19. [Epub ahead of print] Anti-Leishmanial activity of homo- and heteroleptic bismuth(III) carboxylates. Andrews PC, Frank R, Junk PC, Kedzierski L, Kumar I, Maclellan JG. School of Chemistry, Monash University, Clayton, Melbourne, Vic. 3800, Australia. Abstract Bismuth(III) complexes of NSAIDs (Non-Steroidal Anti Inflammatory Drugs) and substituted benzoic acids (o-methoxybenzoic acid, m-methoxybenzoic acid, o-nitrobenzoic acid, 3,5-diacetamidobenzoic acid, and 5-[(R/S)-2,3-dihydroxypropyl carbamoyl]-2-pyridine carboxylic acid) have been synthesised and fully characterised. Two new bis-carboxylato bismuth complexes have been characterised by single crystal X-ray diffraction, namely [PhBi(o-MeOC(6)H(4)CO(2))(2)(bipy)]·0.5EtOH (bipy=2,2'-bipyridine) and [PhBi(C(9)H(11)N(2)O(3)CO(2))(2)(H(2)O)]·6H(2)O. All compounds were tested against the parasite Leishmania major promastigotes for their anti-Leishmanial activity and were further assessed for their toxicity to mammalian cells. The NSAID free acids and their bismuth derivatives show negligible anti-Leishmanial activity at concentrations 1.95 to 250μg/mL against the promastigotes of L. major whereas in the case of mammalian cells only bismuth complexes of naproxen and mefenamic acid have significant effect at concentration≥250μg/mL. The bismuth(III) complexes of substituted benzoic acids show significant anti-Leishmanial activity against the promastigotes of L. major V121 at very low concentrations while their respective free carboxylic acids show no effective activity. However, the bismuth compounds inhibit the growth of the mammalian cells at all concentrations studied (1.95 to 500μg/mL) following 48h incubation. The comparatively low toxicity of BiCl(3) and Bi(NO(3))(3), suggests that overall toxicity of bismuth complexes towards the parasite is both ligand and metal dependent.
	PMID: 20851471 [PubMed - as supplied by publisher]
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4.	Vaccine. 2010 Sep 16. [Epub ahead of print] A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with sodium stibogluconate for the treatment of mucosal leish maniasis. Llanos-Cuentas A, Calderón W, Cruz M, Ashman JA, Alves FP, Coler RN, Bogatzki LY, Bertholet S, Laughlin EM, Kahn SJ, Beckmann AM, Cowgill KD, Reed SG, Piazza FM. Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. Abstract Adult patients with mucosal leishmaniasis (ML) were enrolled in a randomized, double-blind, placebo-controlled, dose-escalating clinical trial and were randomly assigned to receive three injections of either the LEISH-F1+MPL-SE vaccine (consisting of 5, 10, or 20μg recombinant Leishmania polyprotein LEISH-F1 antigen+25μg MPL(®)-SE adjuvant) (n=36) or saline placebo (n=12). The study injections were given subcutaneously on Days 0, 28, and 56, and the patients were followed through Day 336 for safety, immunological, and clinical evolution endpoints. All patients received standard chemotherapy with sodium stibogluconate starting on Day 0. The vaccine was safe and well tolerated, and induced both humoral and cell-mediated immune responses. Furthermore, intracellular cytokine staining showed an increase in the proportion of memory LEISH-F1-specific IL-2(+) CD4 T-cells after vaccination, which was associated with clinical cure. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in patients with ML.
	PMID: 20851080 [PubMed - as supplied by publisher]
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5.	Trans R Soc Trop Med Hyg. 2010 Sep 16. [Epub ahead of print] An amphotericin B-based drug for treating experimental Leishmania major infection. Corware KD, Rogers M, Teo I, Müller I, Shaunak S. Department of Infectious Diseases & Immunity, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. Abstract There is an urgent need for a non-toxic and low-cost treatment for cutaneous leishmaniasis. We synthesised and tested in vivo an amphotericin B-poly(methacrylic acid) drug (AmB-PMA) that had previously shown in-vitro activity against Leishmania major and L. donovani parasites. Efficacy was determined using L. major footpad infection in 30 non-healing BALB/c mice. Three subcutaneous injections of AmB-PMA at days 7, 14 and 21 post-infection resulted in a reduction of ∼80% in lesion size by day 35 post-infection in 18 treated mice compared with six untreated controls, and complete healing of lesions by day 50 with no lesion relapse seen at day 80 post-infection in six treated mice. Healing was associated with decreased IL-10 (P=0.002) and increased IFN-γ (P=0.005) in the footpad.
	PMID: 20850850 [PubMed - as supplied by publisher]
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6.	Bioorg Med Chem Lett. 2010 Sep 15. [Epub ahead of print] Synthesis and biological evaluation of indolyl glyoxyla mides as a new class of antileishmanial agents. Chauhan SS, Gupta L, Mittal M, Vishwakarma P, Gupta S, Chauhan PM. Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, Lucknow 226001, India. Abstract A series of indolylglyoxylamide derivatives have been synthesized and evaluated in vitro against amastigote form of Leishmania donovani. Compound 8c has been identified as the most active analog of the series with IC(50) value of 5.17μM and SI value of 31.48, and is several folds more potent than the standard drugs sodium stilbogluconate and pentamidine.
	PMID: 20850302 [PubMed - as supplied by publisher]
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7.	Rev Med Interne. 2010 Sep 15. [Epub ahead of print] [Visceral leishmaniasis: An update.] [Article in French] Faucher B, Piarroux R. Laboratoire de parasitologie et mycologie, centre hospitalo-universitaire de La-Timone, université de la Méditerranée, 264, rue Saint-Pierre, 13385 Marseille cedex 05, France. Abstract During the last decade, visceral leishmaniasis has been reconsidered in its epidemiology and strategies for diagnosis, treatment and prevention. This vectorial disease, responsible for more than 50,000 deaths each year across India, East Africa, South America, the Mediterranean area, Central Asia and China, is currently spreading over new territories. This formerly rural disease has even reached cities in South America. This spreading is caused by environmental changes due to global warming or human activity, and by the movement of workers and refugees. As a consequence, the burden of HIV/Leishmania coinfection is increasing in many developing countries even though effective antiretroviral therapy has led to a marked decrease in its incidence in Europe. The disease is now handled differently than it was 10 years ago: PCR has become the most accurate tool for diagnosis and follow-up in developed countries, and field diagnostic tools have been developed (antigenuria, rK39 dipstick). While resistance to antimoniate has appeared in India and Europe, new therapies have been evaluated such as miltefosine, the first oral therapy, or short treatment with liposomal amphotericin B. In France, liposomal amphotericin B has supplanted antimoniate meglumine because of better tolerance and shorter hospitalization duration. Protecting dogs through immunization or collars impregnated with deltamethrin proved effective to prevent zoonotic leishmaniasis due to Leishmania infantum.
	PMID: 20850210 [PubMed - as supplied by publisher]
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8.	Exp Parasitol. 2010 Nov;126(3):283-91. Epub 2010 Jun 18. Molecular mechanisms of host cell invasion by Trypanosoma cruzi. Epting CL, Coates BM, Engman DM. Department of Pediatrics, Northwestern University, Chicago, IL 60611, USA. c-epting@northwestern.edu Abstract The protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, is an obligate intracellular protozoan pathogen. Overlapping mechanisms ensure successful infection, yet the relationship between these cellular events and clinical disease remains obscure. This review explores the process of cell invasion from the perspective of cell surface interactions, intracellular signaling, modulation of the host cytoskeleton and endosomal compartment, and the intracellular innate immune response to infection.
	PMID: 20599990 [PubMed - indexed for MEDLINE]
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9.	Exp Parasitol. 2010 Nov;126(3):332-6. Epub 2010 Apr 28. Cellular analysis of host cell infection by different developmental stages of T rypanosoma cruzi. Florencio-Martínez L, Márquez-Dueñas C, Ballesteros-Rodea G, Martínez-Calvillo S, Manning-Cela R. Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México D.F., Mexico. Abstract Trypanosoma cruzi is an obligate intracellular parasite that infects phagocytic and non-phagocytic mammalian cells by a complex process that appears to involve several discrete steps. Even though the infection process was described many years ago, the molecular mechanisms involved remain poorly understood. As fluorescent proteins have proven to be excellent tools for live-cell imaging, we used EGFP- and DsRed1-1-transfected trypomastigotes, amastigotes and epimastigotes to study the infection process in living cells. Contrary to what has been reported, our results showed that epimastigotes are as infective as trypomastigotes and amastigotes. Besides, differences in replication, differentiation and parasite release times were observed among the stages. Our results suggest that the different developmental stages use distinct attachment and invasion mechanisms. We propose that fluorescent-based plasmid expression systems are good models for studying the infection process of intracellular microorganisms and could offers insights about the molecular mechanisms involved.
	PMID: 20433833 [PubMed - indexed for MEDLINE]
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10.	Acta Trop. 2010 Sep;115(3):205-11. Epub 2010 Mar 19. Genetic analyses of Trypanosoma cruzi isolates from naturally infected triatomine s and humans in northeastern Brazil. Câmara AC, Varela-Freire AA, Valadares HM, Macedo AM, D'Avila DA, Machado CR, Lages-Silva E, Chiari E, Galvão LM. Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Parasitologia, Brazil. Abstract Trypanosoma cruzi genetic diversity was investigated in 25 isolates (vectors and humans) from the semiarid zone of the State of Rio Grande do Norte, Brazil. Molecular markers (3' region of the 24Salpha rRNA; mitochondrial cytochrome oxidase subunit 2 (COII) gene; spliced leader intergenic region (SL-IR) gene; allelic size microsatellite polymorphism) identified 56% TcIII (100% Panstrongyluslutzi; 50% Triatomabrasiliensis); 40% TcII (91.7% humans; 50% T. brasiliensis) and 4% TcI (human). Microsatellite analysis revealed monoclonal and heterozygous patterns on one or more microsatellite loci in 64% of T. cruzi isolates (92.3% triatomines; 33.3% humans) and 36% putative polyclonal populations (66.7% humans; 7.7% triatomines) by loci SCLE10, SCLE11, TcTAT20, TcAAAT6, all belonging to TcII. Identical T. cruzi polyclonal profiles (88.9%) were detected, mostly from humans. The adaptative natural plasticity of TcII and TcIII and their potential for maintaining human infection in T. brasiliensis were confirmed. Intraspecific and phylogenetic T. cruzi diversity in the sylvatic and domestic transmission cycles in this specific region will provide exclusive control strategies.
	PMID: 20303924 [PubMed - indexed for MEDLINE]
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