Saturday, March 19, 2011

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 - 7 of 7

1. Afr Health Sci. 2010 Dec;10(4):341-8.

Entomological patterns in the human African trypanosomiasis focus of Komo Mondah, Gabon.

Kohagne T, M'eyi M, Mimpfoundi R, Louis J.

Programme sous régional de lutte contre la trypanosomiase humaine africaine, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC).

Abstract

BACKGROUND: The incidence of sleeping sickness is still considerable in the Komo Mondah focus, in spite of case-detection strategy. A combined strategy that associated both mass screening and vector control is effective for the control of the disease. In the perspective of a targeted vector control in main transmission sites, we have carried out an entomological survey in the epicentre of the focus.

OBJECTIVES: To determine tsetse flies distribution, human-fly contact point and eventually risk factors for acquisition of the disease.

METHODS: "Vavoua" traps were set for Glossina in four biotopes selected after an interview of HAT patients concerning their working places. Tsetse were captured and dissected. DNA from organs was analysed by PCR for trypanosome infections. The origin of blood meals was determined by ELISA.

RESULTS: The focus is infested by three species of Glossina: G. palpalis palpalis (1149: 91.85%) found in all biotopes; G. fuscipes fuscipes (85: 6.79%) and G. caliginea (17: 1.36%) found in water spots and landing stages. They are infected by three subgenera of trypanosomes and only G. palpalis palpalis is infected by human trypanosomes. G. fuscipes fuscipes is infected by T. brucei sl and G. caliginea is not infected. Flies are absent at the periphery of houses except in one village. Only 29.20% of blood meals were from humans. Landing stages built in swamp mangrove are presenting the higher index of epidemiological risk and populations are exposed to the disease when they go to the area for taking their fishing boats.

CONCLUSION: Swamp mangrove would be targeted in priority during a vector control campaign.

PMID: 21416035 [PubMed - in process]
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2. Nucleic Acids Res. 2011 Mar 16. [Epub ahead of print]

The structural basis for recognition of base J containing DNA by a novel DNA binding domain in JBP1.

Heidebrecht T, Christodoulou E, Chalmers MJ, Jan S, Ter Riet B, Grover RK, Joosten RP, Littler D, van Luenen H, Griffin PR, Wentworth P Jr, Borst P, Perrakis A.

Division of Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, Department of Molecular Therapeutics, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA, Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA and Department of Biochemistry, The University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.

Abstract

The J-binding protein 1 (JBP1) is essential for biosynthesis and maintenance of DNA base-J (β-d-glucosyl-hydroxymethyluracil). Base-J and JBP1 are confined to some pathogenic protozoa and are absent from higher eukaryotes, prokaryotes and viruses. We show that JBP1 recognizes J-containing DNA (J-DNA) through a 160-residue domain, DB-JBP1, with 10 000-fold preference over normal DNA. The crystal structure of DB-JBP1 revealed a helix-turn-helix variant fold, a 'helical bouquet' with a 'ribbon' helix encompassing the amino acids responsible for DNA binding. Mutation of a single residue (Asp525) in the ribbon helix abrogates specificity toward J-DNA. The same mutation renders JBP1 unable to rescue the targeted deletion of endogenous JBP1 genes in Leishmania and changes its distribution in the nucleus. Based on mutational analysis and hydrogen/deuterium-exchange mass-spectrometry data, a model of JBP1 bound to J-DNA was constructed and validated by small-angle X-ray scattering data. Our results open new possibilities for targeted prevention of J-DNA recognition as a therapeutic intervention for parasitic diseases.

PMID: 21415010 [PubMed - as supplied by publisher]
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3. Vaccine. 2011 Mar 14. [Epub ahead of print]

A clinical trial to evaluate the safety and immunoge nicity of the LEISH-F1+MPL-SE vaccine for use in the prevention of Visceral leishmaniasis.

Chakravarty J, Kumar S, Trivedi S, Rai VK, Singh A, Ashman JA, Laughlin EM, Coler RN, Kahn SJ, Beckmann AM, Cowgill KD, Reed SG, Sundar S, Piazza FM.

Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Abstract

Healthy Indian adult volunteers, with or without a history of leishmaniasis, were evaluated for evidence of previous infection with Leishmania donovani based on the direct agglutination test (DAT). Three cohorts of 6 DAT-negative and 6 DAT-positive subjects were enrolled in an open-label, dose-escalating, uncontrolled clinical trial and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 5μg, 10μg, or 20μg recombinant Leishmania polyprotein LEISH-F1 antigen+25μg MPL(®)-SE adjuvant). The study injections were given subcutaneously on days 0, 28, and 56, and the subjects were followed through day 168 for safety and immunological endpoints. The vaccine was safe and well-tolerated in DAT-negative and DAT-positive subjects and induced T-cell production of IFN-γ and other cytokines in response to stimulation with the LEISH-F1 antigen. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without history of previous infection with Leishmania donovani.

Copyright © 2011. Published by Elsevier Ltd.
PMID: 21414377 [PubMed - as supplied by publisher]
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4. J Am Chem Soc. 2011 Mar 17. [Epub ahead of print]

Generation of Anti-trypanosomal Agents through Concise Synthesis and Structural Diversification of Sesquiterpene Analogues.

Oguri H, Hiruma T, Yamagishi Y, Oikawa H, Ishiyama A, Otoguro K, Yamada H, O̅mura S.

Division of Chemistry, Graduate School of Science and §Division of Innovative Research, Creative Research Institution, Hokkaido University , North 21, West 10, Kita-ku, Sapporo 001-0021, Japan.

Abstract

To access high-quality small-molecule libraries to screen lead candidates for neglected diseases exemplified by human African trypanosomiasis, we sought to develop a synthetic process that would produce collections of cyclic scaffolds relevant to an assortment of natural products exhibiting desirable biological activities. By extracting the common structural features among several sesquiterpenes, including artemisinin, anthecularin, and transtaganolides, we designed six types of scaffolds with systematic structural variations consisting of three types of stereochemical relationships on the sp(3) ring-junctions and two distinct arrays of tricyclic frameworks. A modular and stereodivergent assembly of dienynes exploiting a versatile manifold produced a series of cyclization precursors. Divergent cyclizations of the dienynes employing tandem ring-closing metathesis reactions overrode variant reactivities of the cyclization precursors, leading to the six canonical sets of the tricyclic scaffolds incorporating a diene group. Screenings of trypanosomal activities of the canonical sets, as well as regio- and stereoisomers of the tricyclic dienes, allowed generation of several anti-trypanosomal agents defining the three-dimensional shape of the pharmacophore. The candidate tricyclic dienes were selected by primary screenings and further subjected to installation of a peroxide bridge, which generated artemisinin analogues that exhibited potent in vitro anti-trypanosomal activities comparable or even superior to those of artemisinin and the approved drugs, suramin and eflornithine.

PMID: 21413715 [PubMed - as supplied by publisher]
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5. Am J Trop Med Hyg. 2011 Feb;84(2):344-50.

Magnetic resonance imaging to assess blood-brain barrier damage in murine trypanosomiasis.

Rodgers J, McCabe C, Gettinby G, Bradley B, Condon B, Kennedy PG.

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. Jean.Rodgers@glasgow.ac.uk

Abstract

The ability of trypanosomes to invade the brain and induce an inflammatory reaction is well-recognized. This study uses magnetic resonance imaging (MRI) in conjunction with a murine model of central nervous system (CNS) stage trypanosomiasis to investigate this phenomenon at the level of the blood-brain barrier (BBB). Mice were scanned before and after administration of the contrast agent. Signal enhancement maps were generated, and the percentage signal change was calculated. The severity of the neuroinflammation was also assessed. Statistical analysis of the signal change data revealed a significantly (P = 0.028) higher signal enhancement in mice at 28 days post-infection (least squares mean = 26.709) compared with uninfected animals (6.298), indicating the presence of BBB impairment. Leukocytes were found in the meninges and perivascular space of some blood vessels in the infected mice. This study shows that the integrity of the BBB is compromised during CNS stage trypanosomiasis and that the impairment does not correlate with inflammatory cell infiltration.

PMCID: PMC3029195 Free PMC Article
PMID: 21292912 [PubMed - indexed for MEDLINE]
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6. Am J Trop Med Hyg. 2011 Feb;84(2):325-31.

Low doses of simvastatin therapy ameliorate cardiac inflammatory remodeling in Trypanosoma cruzi-infected dogs.

Melo L, Caldas IS, Azevedo MA, Gonçalves KR, da Silva do Nascimento AF, Figueiredo VP, de Figueiredo Diniz L, de Lima WG, Torres RM, Bahia MT, Talvani A.

Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil. lilianmel@yahoo.com.br

Abstract

Chagas cardiomyopathy remodeling is based on the presence of Trypanosoma cruzi in heart tissue and on the complex inflammatory response leading to a myocardium fibrosis and alterations in conductive and functional heart parameters. This study aims to evaluate Simvastatin on the inflammatory response and heart functionality using dogs infected with Y strain of T. cruzi. Animals were treated daily with Simvastatin (20 mg) for 6 months and submitted to clinical and immunopathological evaluations. Simvastatin reduced heart expression and serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) but not interleukin-10 (IL-10), possibly favoring blood parasitism but reducing inflammation and fibrosis in the left ventricle and right atrium. Simvastatin also ameliorated ejection fraction, diastolic diameter, and mass index of the left ventricle 6 months after infection. This study suggests that more investigation should be performed on the use of statins as a prophylactic therapy against cardiac remodeling because of their effects on modifying immune response and benefiting functional parameters in dogs with T. cruzi-induced ventricular dysfunctions.

PMCID: PMC3029192 [Available on 2012/2/4]
PMID: 21292909 [PubMed - indexed for MEDLINE]
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7. Infect Genet Evol. 2010 Dec;10(8):1278-81. Epub 2010 Jul 7.

Tamandua tetradactyla Linnaeus, 1758 (Myrmecophagidae) and Rhodnius robustus Larrousse, 1927 (Triatominae) infection focus by Trypanosoma rangeli Tejera, 1920 (Trypanosomatidae) in Attalea phalerata Mart. ex Spreng (Arecaceae) palm tree in the Brazilian Amazon.

Dias FB, Quartier M, Romaña CA, Diotaiuti L, Harry M.

Laboratório de Triatomíneos e Epidemiologia da Doença de Chagas, Centro de Pesquisa René Rachou, Av Augusto de Lima, 1715 Barro Preto, Belo Horizonte, MG, Brazil.

Abstract

A sylvatic infection focus of Trypanosoma rangeli, whose cycle involves the anteater Tamandua tetradactyla and triatomine insect Rhodnius robustus was observed in a pasture-dominated landscape of the rural riparian community of São Tomé located along the Tapajós river in the municipal district of Aveiro (State of Pará, Brazil), the Brazilian Amazon region. During a field work campaign with the objective of Chagas disease diagnosis in the Tapajós region, an anteater and 31 triatomines were found inhabiting in the same Attalea phalerata palm tree crown. Collected triatomines were identified as R. robustus with morphological and molecular procedures. The analysis of infection by T. rangeli using the repetitive ARN nucleolar Cl1 (sno-RNA-Cl1) gene showed that 25 triatomines of all stages were infected by T. rangeli (total infection rate of 80.6%). Infection by Trypanosoma cruzi using mini-exon markers was not identified. Examination of the digestive content of the triatomines demonstrated that the only feeding source found was the anteater. These results demonstrate that T. tetradactyla can be an important reservoir for T. rangeli and a good vehicle of the parasite within the Brazilian Amazon region.

Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.
PMID: 20619359 [PubMed - indexed for MEDLINE]
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