Wednesday, April 4, 2012

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. PLoS One. 2012;7(3):e33161. Epub 2012 Mar 21.

Induction of Protective CD4(+) T Cell-Mediated Immunity by a Leishmania Peptide Delivered in Recombinant Influenza Viruses.

Kedzierska K, Curtis JM, Valkenburg SA, Hatton LA, Kiu H, Doherty PC, Kedzierski L.

Source

Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.

Abstract

The available evidence suggests that protective immunity to Leishmania is achieved by priming the CD4(+) Th1 response. Therefore, we utilised a reverse genetics strategy to generate influenza A viruses to deliver an immunogenic Leishmania peptide. The single, immunodominant Leishmania-specific LACK(158-173) CD4(+) peptide was engineered into the neuraminidase stalk of H1N1 and H3N2 influenza A viruses. These recombinant viruses were used to vaccinate susceptible BALB/c mice to determine whether the resultant LACK(158-173)-specific CD4(+) T cell responses protected against live L. major infection. We show that vaccination with influenza-LACK(158-173) triggers LACK(158-173)-specific Th1-biased CD4(+) T cell responses within an appropriate cytokine milieu (IFN-γ, IL-12), essential for the magnitude and quality of the Th1 response. A single intraperitoneal exposure (non-replicative route of immunisation) to recombinant influenza delivers immunogenic peptides, leading to a marked reduction (2-4 log) in parasite burden, albeit without reduction in lesion size. This correlated with increased numbers of IFN-γ-producing CD4(+) T cells in vaccinated mice compared to controls. Importantly, the subsequent prime-boost approach with a serologically distinct strain of influenza (H1N1->H3N2) expressing LACK(158-173) led to a marked reduction in both lesion size and parasite burdens in vaccination trials. This protection correlated with high levels of IFN-γ producing cells in the spleen, which were maintained for 6 weeks post-challenge indicating the longevity of this protective effector response. Thus, these experiments show that Leishmania-derived peptides delivered in the context of recombinant influenza viruses are immunogenic in vivo, and warrant investigation of similar vaccine strategies to generate parasite-specific immunity.

PMID: 22470440 [PubMed - in process]
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2. Indian J Dermatol. 2012 Jan;57(1):55-7.

Unusual presentation of cutaneous leishmaniasis.

Sindhu PS, Ramesh V.

Source

Department of Dermatology and STD, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi, India.

Abstract

Two patients with mini-volcano type of skin lesions which showed histopathologic features of cutaneous leishmaniasis (CL) have been described. It was localised and linear in one case while widespread in the other. Both responded to sodium stibogluconate. The importance of recognising new emerging foci of CL is emphasised.

PMID: 22470213 [PubMed - in process]
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3. Emerg Infect Dis. 2012 Apr;18(4):704-6. doi: 10.3201/eid1804.110841.

Leishmania resistance to miltefosine associated with genetic marker.

Cojean S, Houzé S, Haouchine D, Huteau F, Lariven S, Hubert V, Michard F, Bories C, Pratlong F, Le Bras J, Loiseau PM, Matheron S.

Abstract

TO THE EDITOR: During 2000-2010, serial Leishmania isolates obtained from an HIV-infected patient who was not responding to treatment showed a gradual decrease in in vitro miltefosine susceptibility. We performed L. donovani miltefosine transporter (Ldmt) gene analysis to identify an association between miltefosine resistance of reference L. donovani lines and variability in miltefosine response of L. infantum isolates. A new single-nucleotide polymorphism (SNP), L832F, was identified, which might be a marker of miltefosine resistance in leishmaniasis.

PMID: 22469394 [PubMed - in process]
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4. Pharm Biol. 2012 Apr 3. [Epub ahead of print]

Terpenoidal constituents of Eucalyptus loxophleba ssp. lissophloia.

Sidana J, Singh S, Arora SK, Foley WJ, Singh IP.

Source

Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER) , Sector 67, S.A.S. Nagar, Punjab , India.

Abstract

Context: Eucalyptus has been a source of a number of biologically active compounds. The anti-leishmanial activity of terpenoids from Eucalyptus loxophleba (Benth.) ssp. lissophloia (Myrtaceae) has not yet been investigated. Objective: Isolation of the terpenoidal constituents for evaluation of in vitro anti-leishmanial activity against the Leishmania donovani (Dd8 strain) promastigotes. Materials and methods: The chloroform-methanol (8:2) extract of dried leaves of Eucalyptus loxophleba was used to isolate terpenoidal constituents employing solvent partitioning, column chromatography and preparative high performance liquid chromatography and characterized from spectral data. The anti-leishmanial activity of the isolated compounds was tested in vitro using an Alamar blue assay against a culture of L. donovani (Dd8 strain) promastigotes. Results: Two new naturally occurring triterpenes, named loxanic acid and 3-acetyl loxanic acid together with four known ursane triterpenoids and one bis-monoterpene glycoside, cuniloside B isolated from the leaves showed anti-leishmanial activity (IC(50) 133 to 235 μM) against the promastigotes of the tested strain. Conclusion: The terpenes isolated from the leaves of E. loxophleba showed moderate anti-leishmanial activity.

PMID: 22468852 [PubMed - as supplied by publisher]
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5. Ann Rheum Dis. 2012 Apr;71 Suppl 2:i60-i66.

Leishmaniasis in rheumatology, haematology and oncology: epidemiological, immunological and clinical aspects and caveats.

Bogdan C.

Source

Correspondence to Professor Dr Christian Bogdan, Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Wasserturmstraße 3/5, D-91054 Erlangen, Germany; christian.bogdan@uk-erlangen.de.

Abstract

Leishmaniasis is an intracellular protozoan infection that can lead to cutaneous, mucocutaneous, visceral or systemic manifestations depending on the parasite species and virulence and on the host immune response. It is endemic in countries of Europe (Mediterranean basin), Asia, Africa, Central and South America, but autochthonous cases begin to emerge outside classical disease areas. CD4+ T helper cells, interferon γ, dendritic cells and macrophages are the key components of antileishmanial defence. Leishmaniasis is an important differential diagnosis in patients with chronic lesions of the skin or mucous membranes or with fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, histocytosis, haemophagocytic syndrome or glomerulonephritis. Organ transplant recipients and patients with autoimmune syndromes are at particular risk of developing visceral leishmaniasis following immunosuppressive therapy (eg, with steroids, methotrexate, ciclosporin or tumour necrosis factor-neutralising biological agents). Diagnosis and adequate treatment of leishmaniasis requires the combined use of culture, microscopic and nucleic acid amplication methods and species identification by sequencing and other molecular techniques. Standard regimens for the treatment of visceral leishmaniasis are intravenous liposomal amphotericin B (3 mg/kg body weight for 10 days) or oral miltefosine (150 mg/day for 28 days).

PMID: 22460140 [PubMed - in process]
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6. Rev Peru Med Exp Salud Publica. 2011 Jul-Sep;28(3):560-3.

[Tegumentary leishmaniosis, a look at a neglected tropical disease].

[Article in Spanish]
Aidé S, Minaya G.

Source

Laboratorio de Leishmaniosis y Chagas, Instituto Nacional de Salud, Lima, Perú. asandoval@ins.gob.pe

Free Article
PMID: 22086642 [PubMed - indexed for MEDLINE]
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7. Mol Cell Proteomics. 2011 Dec;10(12):M110.007369. Epub 2011 Aug 10.

SUMOylation pathway in Trypanosoma cruzi: functional characterization and proteomic analysis of target proteins.

Bayona JC, Nakayasu ES, Laverrière M, Aguilar C, Sobreira TJ, Choi H, Nesvizhskii AI, Almeida IC, Cazzulo JJ, Alvarez VE.

Source

IIB-INTECH, Buenos Aires, Argentina.

Abstract

SUMOylation is a relevant protein post-translational modification in eukaryotes. The C terminus of proteolytically activated small ubiquitin-like modifier (SUMO) is covalently linked to a lysine residue of the target protein by an isopeptide bond, through a mechanism that includes an E1-activating enzyme, an E2-conjugating enzyme, and transfer to the target, sometimes with the assistance of a ligase. The modification is reversed by a protease, also responsible for SUMO maturation. A number of proteins have been identified as SUMO targets, participating in the regulation of cell cycle progression, transcription, translation, ubiquitination, and DNA repair. In this study, we report that orthologous genes corresponding to the SUMOylation pathway are present in the etiological agent of Chagas disease, Trypanosoma cruzi. Furthermore, the SUMOylation system is functionally active in this protozoan parasite, having the requirements for SUMO maturation and conjugation. Immunofluorescence analysis showed that T. cruzi SUMO (TcSUMO) is predominantly found in the nucleus. To identify SUMOylation targets and get an insight into their physiological roles we generated transfectant T. cruzi epimastigote lines expressing a double-tagged T. cruzi SUMO, and SUMOylated proteins were enriched by tandem affinity chromatography. By two-dimensional liquid chromatography-mass spectrometry a total of 236 proteins with diverse biological functions were identified as potential T. cruzi SUMO targets. Of these, metacaspase-3 was biochemically validated as a bona fide SUMOylation substrate. Proteomic studies in other organisms have reported that orthologs of putative T. cruzi SUMOylated proteins are similarly modified, indicating conserved functions for protein SUMOylation in this early divergent eukaryote.

PMCID: PMC3237068 [Available on 2012/12/1]
PMID: 21832256 [PubMed - indexed for MEDLINE]
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