Wednesday, June 20, 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 - 10 of 11

1. Korean J Parasitol. 2012 Jun;50(2):133-6. Epub 2012 May 24.

Visceral leishmaniasis mimicking autoimmune hepatitis, primary biliary cirrhosis, and systemic lupus erythematosus overlap.

Tunccan OG, Tufan A, Telli G, Akyürek N, Pamukçuoğlu M, Yılmaz G, Hızel K.

Source

Department of Clinical Microbiology and Infectious Diseases, Gazi University Hospital Besevler, 06500, Ankara, Turkey.

Abstract

Visceral leishmaniasis (VL) is a life-threatening infection caused by Leishmania species. In addition to typical clinical findings as fever, hepatosplenomegaly, and cachexia, VL is associated with autoimmune phenomena. To date, VL mimicking or exacerbating various autoimmune diseases have been described, including systemic lupus erythematosus (SLE), rheumatoid arthritis, and autoimmune hepatitis (AIH). Herein, we presented a patient with VL who had overlapping clinical features with SLE, AIH, as well as antimitochondrial antibody (AMA-M2) positive primary biliary cirrhosis.

PMID: 22711924 [PubMed - in process]
2. Planta. 2012 Jun 19. [Epub ahead of print]

Kinetic and phylogenetic analysis of plant polyamine uptake transporters.

Mulangi V, Chibucos MC, Phuntumart V, Morris PF.

Source

Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, 43403, USA.

Abstract

The rice gene POLYAMINE UPTAKE TRANSPORTER1 (PUT1) was originally identified based on its homology to the polyamine uptake transporters LmPOT1 and TcPAT12 in Leishmania major and Trypanosoma cruzi, respectively. Here we show that five additional transporters from rice and Arabidopsis that cluster in the same clade as PUT1 all function as high affinity spermidine uptake transporters. Yeast expression assays of these genes confirmed that uptake of spermidine was minimally affected by 166 fold or greater concentrations of amino acids. Characterized polyamine transporters from both Arabidopsis thaliana and Oryza sativa along with the two polyamine transporters from L. major and T. cruzi were aligned and used to generate a hidden Markov model. This model was used to identify significant matches to proteins in other angiosperms, bryophytes, chlorophyta, discicristates, excavates, stramenopiles and amoebozoa. No significant matches were identified in fungal or metazoan genomes. Phylogenic analysis showed that some sequences from the haptophyte, Emiliania huxleyi, as well as sequences from oomycetes and diatoms clustered closer to sequences from plant genomes than from a homologous sequence in the red algal genome Galdieria sulphuraria, consistent with the hypothesis that these polyamine transporters were acquired by horizontal transfer from green algae. Leishmania and Trypansosoma formed a separate cluster with genes from other Discicristates and two Entamoeba species. We surmise that the genes in Entamoeba species were acquired by phagotrophy of Discicristates. In summary, phylogenetic and functional analysis has identified two clades of genes that are predictive of polyamine transport activity.

PMID: 22711282 [PubMed - as supplied by publisher]
3. Org Biomol Chem. 2012 Jun 19. [Epub ahead of print]

New parasite inhibitors encompassing novel conformationally-locked 5'-acyl sulfamoyl adenosines.

Dixit SS, Upadhayaya RS, Chattopadhyaya J.

Source

Program of Chemical Biology, Institute of Cell and Molecular Biology, Biomedical Centre, Uppsala University, SE-75123 Uppsala, Sweden. jyoti@boc.uu.se.

Abstract

We describe the design, synthesis and biological evaluation of conformationally-locked 5'-acyl sulfamoyl adenosine derivatives as new parasitic inhibitors against Trypanosoma and Leishmania. The conformationally-locked (3'-endo, North-type) nucleosides have been synthesized by covalently attaching a 4'-CH(2)-O-2' bridge () across C2'-C4' of adenosine in order to reduce the conformational flexibility of the pentose ring. This is designed to decrease the entropic penalty for complex formation with the target protein, which may improve free-energy of stabilization of the complex leading to improved potency. Conformationally-locked 5'-acyl sulfamoyl adenosine derivatives () were tested against parasitic protozoans for the first time in this work, and showed potent inhibition of Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma rhodesiense and Leishmania infantum with IC(50) = 0.25-0.51 μM. In particular, the potent 5'-pentanyl acyl sulfamoyl adenosine derivative (IC(50) = 0.25 μM) against intracellular L. infantum amastigotes and Trypanosoma subspecies is interesting in view of its almost insignificant cytotoxicity in murine macrophage host cells (CC(50) >4 μM) and in diploid human fibroblasts MRC-5 cell lines (CC(50) 4 μM). This work also suggests that variable alkyl chain length of the acyl group on the acylsulfamoyl side chain at 5' can modulate the toxicity of 5'-O-sulfamoylnucleoside analogues. This conformationally-locked sulfamoyl adenosine scaffold presents some interesting possibilities for further drug design and lead optimization.

PMID: 22710960 [PubMed - as supplied by publisher]
4. Mol Biochem Parasitol. 2012 Jun 15. [Epub ahead of print]

Theoretical and in vitro studies of a C-terminal peptide from PGKC of Leishmania mexicana mexicana.

Kaushik S, Krishnarjuna B, Raghothama S, Aggarwal S, Raghunathan V, Ganjiwale A.

Source

National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi - 110067.

Abstract

Trypanosomatids cause deadly diseases in humans. Of the various biochemical pathways in trypanosomatids, glycolysis, has received special attention because of being sequestered in peroxisome like organelles critical for the survival of the parasites. This study focuses on phosphoglycerate kinase (PGK) from Leishmania spp which, exists in two isoforms, the cytoplasmic PGKB and glycosomal PGKC differing in their biochemical properties. Computational analysis predicted the likelihood of a transmembrane helix only in the glycosomal isoform PGKC, of approximate length 20 residues in the 62-residue extension, ending at, arginine residues R471 and R472. From experimental studies using circular dichroism and NMR with deuterated sodium dodecyl sulphate, we find that the transmembrane helix spans residues 448±2 to 476 in L. mexicana PGKC. The significance of this observation is discussed in the context of glycosomal transport and substrate tunneling.

Copyright © 2012. Published by Elsevier B.V.

PMID: 22710389 [PubMed - as supplied by publisher]
5. Actas Dermosifiliogr. 2012 Jun 16. [Epub ahead of print]

Unsuspected Visceral Leishmaniasis Infiltrating a Squamous Cell Carcinoma.

Armengot-Carbó M, Carmena-Ramón R, Rodrigo-Nicolás B, Ferrando-Marco J.

Source

Servicio de Dermatología, Hospital Arnau de Vilanova, Valencia, Spain.

Abstract

Amastigotes of the genus Leishmania have been observed in biopsies of apparently unrelated lesions in patients with AIDS and visceral leishmaniasis. We describe the case of a 40-year-old man with human immunodeficiency virus infection and severe immunodepression in whom the presence of the parasite was detected as an incidental finding on histological study of a perianal squamous cell carcinoma. This finding led to the diagnosis and subsequent treatment of previously unsuspected visceral leishmaniasis. In a review of the literature we have found no previous examples of this association.

Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

PMID: 22709710 [PubMed - as supplied by publisher]
6. Parasit Vectors. 2012 Jun 18;5(1):121. [Epub ahead of print]

Genetic, serological and biochemical characterization of Leishmania tropica from foci in northern Palestine and discovery of zymodeme MON-307.

Azmi K, Schnur L, Schonian G, Nasereddin A, Pratlong F, El Baidouri F, Ravel C, Dedet JP, Ereqat S, Abdeen Z.

Abstract

ABSTRACT:

BACKGROUND:

Many cases of cutaneous leishmaniasis (CL) have been recorded in the Jenin District based on their clinical appearance. Here, their parasites have been characterized in depth.

METHODS:

Leishmanial parasites isolated from 12 human cases of CL from the Jenin District were cultured as promastigotes, whose DNA was extracted. The ITS1 sequence and the 7SL RNA gene were analysed as was the kinetoplast minicircle DNA (kDNA) sequence. Excreted factor (EF) serotyping and multilocus enzyme electrophoresis (MLEE) were also applied.

RESULTS:

This extensive characterization identified the strains as Leishmania tropica of two very distinct sub-types that parallel the two sub-groups discerned by multilocus microsatellite typing (MLMT) done previously. A high degree of congruity was displayed among the results generated by the different analytical methods that had examined various cellular components and exposed intra-specific heterogeneity among the 12 strains. Three of the ten strains subjected to MLEE constituted a new zymodeme, zymodeme MON- 307, and seven belonged to the known zymodeme MON-137. Ten of the 15 enzymes in the profile of zymodeme MON-307 displayed different electrophoretic mobilities compared with the enzyme profile of the zymodeme MON-137. The closest profile to that of zymodeme MON-307 was that of the zymodeme MON-76 known from Syria. Strains of the zymodeme MON-307 were EF sub-serotype A2 and those of the zymodeme MON-137 were either A9 or A9B4. The sub-serotype B4 component appears, so far, to be unique to some strains of L. tropica of zymodeme MON-137. Strains of the zymodeme MON-137 displayed a distinctive fragment of 417 bp that was absent in those of zymodeme MON-307 when their kDNA was digested with the endonuclease RsaI. kDNA-RFLP after digestion with the endonuclease MboI facilitated a further level of differentiation that partially coincided with the geographical distribution of the human cases from which the strains came.

CONCLUSIONS:

The Palestinian strains that were assigned to different genetic groups differed in their MLEE profiles and their EF types. A new zymodeme, zymodeme MON-307 was discovered that seems to be unique to the northern part of the Palestinian West Bank. What seemed to be a straight forward classical situation of L. tropica causing anthroponotic CL in the Jenin District might be a more complex situation, owing to the presence of two separate sub-types of L. tropica that, possibly, indicates two separate transmission cycles involving two separate types of phlebotomine sand fly vector.

PMID: 22709680 [PubMed - as supplied by publisher]
7. Nat Prod Res. 2012 Jun 18. [Epub ahead of print]

An antileishmanial prenyloxy-naphthoquinone from roots of Plumbago zeylanica.

Mishra BB, Gour JK, Kishore N, Singh RK, Tripathi V, Tiwari VK.

Source

a Department of Chemistry , Centre of Advanced Study, Banaras Hindu University , Varanasi 221005 , Uttar Pradesh , India.

Abstract

Leishmania donovani, an obligate intracellular parasite of genus Leishmania causes visceral leishmaniasis that affects millions of people worldwide, especially in the Indian subcontinent and East Africa. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness but the growing incidence of their resistance has seriously hampered their use. This study discloses strong in vitro antileishmanial activity of 2-methyl-5 -(3'-methyl-but-2'-enyloxy)-[1,4]naphthoquinone (1), a prenyloxy-naphthoquinone isolated and characterised from roots of the plant Plumbago zeylanica (family - Plumbaginaceae). The observed EC(50) for the compound 1 against promastigote and amastigote forms of L. donovani was significantly (p < 0.001) lower than miltefosine, a reference drug. In context to limited treatment options and growing resistance for available drugs, compound 1 offers a greater prospect towards antileishmanial drug discovery and development.

PMID: 22708724 [PubMed - as supplied by publisher]
8. Mini Rev Med Chem. 2012 Mar;12(3):227-35.

Ru(II)-based antimicrobials: looking beyond organic drugs.

Ramos AI, Braga TM, Braga SS.

Source

Department of Chemistry and CICECO, University of Aveiro, 3810-193 Aveiro, Portugal.

Abstract

This review deals with the bactericidal, anti-fungal and even anti-parasitary properties of ruthenium complexes, both inorganic and organometallic, establishing comparisons between these and the available commercial drugs. The description is mostly composed of results found in the literature of the past two decades, complemented with relevant results from our group's research on antimicrobial ruthenium complexes. The complexes are divided into five groups according to the kind of ligands, geometry and chemical nature. The first group comprises ruthenium octahedral complexes with Schiff bases, the most well explored kind of ruthenium antimicrobials. The second group comprises complexes with planar ligands and an overall more flattened geometry, designed for DNA intercalation. In the following two groups, ruthenium complexes feature a particular functionality, which is, in one case, the presence of the PTA ligand for higher solubility in water, and, in the second, the mimicry of an active organic drug. Finally, a small section presents the most recent results on supramolecular antimicrobials comprising ruthenium, in particular a polymer and a cyclodextrin adduct.

© 2012 Bentham Science Publishers

PMID: 22356193 [PubMed - indexed for MEDLINE]
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9. Infect Genet Evol. 2012 Mar;12(2):240-53. Epub 2011 Dec 27.

The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications.

Zingales B, Miles MA, Campbell DA, Tibayrenc M, Macedo AM, Teixeira MM, Schijman AG, Llewellyn MS, Lages-Silva E, Machado CR, Andrade SG, Sturm NR.

Source

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Avenida Professor Lineu Prestes 748, 05508-000 São Paulo, SP, Brazil. zingales@iq.usp.br

Abstract

The protozoan Trypanosoma cruzi, its mammalian reservoirs, and vectors have existed in nature for millions of years. The human infection, named Chagas disease, is a major public health problem for Latin America. T. cruzi is genetically highly diverse and the understanding of the population structure of this parasite is critical because of the links to transmission cycles and disease. At present, T. cruzi is partitioned into six discrete typing units (DTUs), TcI-TcVI. Here we focus on the current status of taxonomy-related areas such as population structure, phylogeographical and eco-epidemiological features, and the correlation of DTU with natural and experimental infection. We also summarize methods for DTU genotyping, available for widespread use in endemic areas. For the immediate future multilocus sequence typing is likely to be the gold standard for population studies. We conclude that greater advances in our knowledge on pathogenic and epidemiological features of these parasites are expected in the coming decade through the comparative analysis of the genomes from isolates of various DTUs.

Copyright © 2012 Elsevier B.V. All rights reserved.

PMID: 22226704 [PubMed - indexed for MEDLINE]
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10. Infect Genet Evol. 2012 Mar;12(2):350-8. Epub 2011 Dec 22.

Candidate targets for Multilocus Sequence Typing of Trypanosoma cruzi: validation using parasite stocks from the Chaco Region and a set of reference strains.

Lauthier JJ, Tomasini N, Barnabé C, Rumi MM, D'Amato AM, Ragone PG, Yeo M, Lewis MD, Llewellyn MS, Basombrío MA, Miles MA, Tibayrenc M, Diosque P.

Source

Unidad de Epidemiología Molecular, Instituto de Patología Experimental, Universidad Nacional de Salta-CONICET, Av. Bolivia 5150, CP4400, Salta, Argentina.

Abstract

A Multilocus Sequence Typing (MLST) scheme was designed and applied to a set of 20 Trypanosoma cruzi stocks belonging to three main discrete typing units (T. cruzi I, V and VI) from a geographically restricted Chagas disease endemic area in Argentina, 12 reference strains comprising two from each of the six main discrete typing units of the parasite (T. cruzi I-VI), and one T. cruzi marinkellei strain. DNA fragments (≅400-bp) from 10 housekeeping genes were sequenced. A total of 4178 bp were analyzed for each stock. In all, 154 polymorphic sites were identified. Ninety-five sites were heterozygous in at least one analyzed stock. Seventeen diploid sequence types were identified from 32 studied T. cruzi stocks (including the reference strains). All stocks were correctly assigned to their corresponding discrete typing units. We propose this MLST scheme as provisional, with scope for improvement by studying new gene targets on a more diverse sample of stocks, in order to define an optimized MLST scheme for T. cruzi. This approach is an excellent candidate to become the gold standard for T. cruzi genetic typing. We suggest that MLST will have a strong impact on molecular epidemiological studies of Chagas disease and the phylogenetics of its causative agent.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID: 22210092 [PubMed - indexed for MEDLINE]
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