Tuesday, July 28, 2009

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 16

1: Molecules. 2009 Jul 10;14(7):2491-500.

Leishmanicidal activity of aliphatic and aromatic lactones: correlation structure-activity.

Castaño M, Cardona W, Quiñones W, Robledo S, Echeverri F.

Grupo de Química Orgánica de Productos Naturales-SIU, Universidad de Antioquia, P.O. Box 1226, Medellín, Colombia.

Several aliphatic and aromatic lactones and two dimers were synthesized using the sequence: allylation - esterification - metathesis. These compounds were active in vitro against intracellular amastigotes of Leishmania panamensis. The structure-activity relationship showed the importance of the aliphatic side chain to enhance the biological activity and to obtain lower cytotoxicity. It was also observed that a decrease in the size of the lactone ring increases the selectivity index.

PMID: 19633618 [PubMed - in process]

2: Molecules. 2009 Jun 30;14(7):2317-36.

Pentavalent antimonials: new perspectives for old drugs.

Frézard F, Demicheli C, Ribeiro RR.

Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, 31270-901 Belo Horizonte, MG, Brazil. frezard@icb.ufmg.br

Pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate, have been used for more than half a century in the therapy of the parasitic disease leishmaniasis. Even though antimonials are still the first-line drugs, they exhibit several limitations, including severe side effects, the need for daily parenteral administration and drug resistance. The molecular structure of antimonials, their metabolism and mechanism of action are still being investigated. Some recent studies suggest that pentavalent antimony acts as a prodrug that is converted to active and more toxic trivalent antimony. Other works support the direct involvement of pentavalent antimony. Recent data suggest that the biomolecules, thiols and ribonucleosides, may mediate the actions of these drugs. This review will summarize the progress to date on the chemistry and biochemistry of pentavalent antimony. It will also present the most recent works being done to improve antimonial chemotherapy. These works include the development of simple synthetic methods for pentavalent antimonials, liposome-based formulations for targeting the Leishmania parasites responsible for visceral leishmaniasis and cyclodextrin-based formulations to promote the oral delivery of antimony.

PMID: 19633606 [PubMed - in process]

3: Pediatr Infect Dis J. 2009 Aug;28(8):753-4.

Visceral leishmaniasis associated hemophagocytic syndrome in patients with chronic granulomatous disease.

Martín A, Marques L, Soler-Palacín P, Caragol I, Hernandez M, Figueras C, Español T.

From the *Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d'Hebron Hospital, Barcelona, Spain; daggerPediatric Service, Hospital Maria Pia, Porto, Portugal; and double daggerImmunology Unit, Vall d'Hebron Hospital, Barcelona, Spain.

Visceral leishmaniasis is a severe form of infection caused by a parasite endemic along the Mediterranean coast. Complications such as infection-associated hemophagocytic syndrome can occur despite correct therapy. We report visceral leishmaniasis-associated infection-associated hemophagocytic syndrome in 3 patients with chronic granulomatous disease.

PMID: 19633526 [PubMed - in process]

4: Eukaryot Cell. 2009 Jul 24. [Epub ahead of print]Click here to read

The fate of GPI-less procyclin and characterisation of sialylated non-GPI anchored surface coat molecules of procyclic form Trypanosoma brucei.

Güther ML, Beattie K, Lamont DJ, James J, Prescott AR, Ferguson MA.

Division of Biological Chemistry and Drug Discovery, FingerPrints Proteomics Facility, Centre for High-Resolution Imaging and Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

A Trypanosoma brucei TbGPI12 null mutant that is unable to express cell-surface procyclins and free glycosylphosphatidylinositols revealed that these are not the only surface coat molecules of the procyclic lifecycle stage. Here, we show that non-GPI anchored procyclins are N-glycosylated, accumulate in the lysosome and appear as proteolytic fragments in the medium. We also show, using lectin agglutination and galactose-oxidase/NaB(3)H4 labelling, that the cell surface of the TbGPI12 null parasites contain glycoconjugates that terminate in sialic acid linked to galactose. Following desialylation, a high apparent molecular weight glycoconjugate fraction was purified by ricin affinity chromatography and gel-filtration and shown to contain mannose, galactose, N-acetylglucosamine and fucose. The latter has not been previously reported in T.brucei glycoproteins. Proteomic analysis of this fraction revealed a mixture of polytopic transmembrane proteins, including P-type ATPase and vacuolar proton translocating pyrophosphatase. Immunolocalisation studies showed that both could be labelled on the surface of wild type and TbGPI12 null cells. Neither galactose-oxidase/NaB(3)H4 labelling of the non-GPI anchored surface glycoconjugates nor immunogold labelling of the P-type ATPase was affected by the presence of procyclins in the wild type cells, suggesting that the procyclins do not, by themselves, form a macromolecular barrier.

PMID: 19633269 [PubMed - as supplied by publisher]

5: Trends Parasitol. 2009 Jul 23. [Epub ahead of print]Click here to read

What has DNA sequencing revealed about the VSG expression sites of African trypanosomes?

McCulloch R, Horn D.

University of Glasgow, Wellcome Centre for Molecular Parasitology and Division of Infection and Immunity, Glasgow Biomedical Research Centre, 120 University Place, Glasgow, G12 8TA, UK.

Antigenic variation is crucial for the survival of African trypanosomes in mammals and involves switches in expression of variant surface glycoprotein genes, which are co-transcribed with a number of expression-site-associated genes (ESAGs) from loci termed 'bloodstream expression sites' (BESs). Trypanosomes possess multiple BESs, although the reason for this (and why ESAGs are resident in these loci) has remained a subject of debate. The genome sequence of Trypanosoma brucei, released in 2005, did not include the BESs because of their telomeric disposition. This gap in our knowledge has now been bridged by two new studies, which we discuss here, asking what has been revealed about the biological significance of BES multiplicity and ESAG function and evolution.

PMID: 19632154 [PubMed - as supplied by publisher]

6: J Ethnopharmacol. 2009 Jul 22. [Epub ahead of print]Click here to read

Ta'ta', Huayani: perception of leishmaniasis and evaluation of medicinal plants used by the Chayahuita in Peru. Part II.

Odonne G, Bourdy G, Castillo D, Estevez Y, Lancha-Tangoa A, Alban-Castillo J, Deharo E, Rojas R, Stien D, Sauvain M.

UMR EcoFoG, Université des Antilles et de la Guyane - CNRS, 2091 Route de Baduel - BP792 - 97337 Cayenne cedex, France; Université de Toulouse; UPS; UMR 152 (Laboratoire de pharmacochimie des substances naturelles et pharmacophores redox), 118, rte de Narbonne, F-31062 Toulouse cedex 9, France; IRD; UMR-152; Mission IRD Casilla 18-1209 Lima, Peru.

A knowledge attitude and practice study centred on leishmaniasis and its treatment was performed among the Chayahuita, an Amazonian Peruvian ethnic group living in an endemic area. Ninety-three Chayahuita people were interviewed, following a semi-structured questionnaire focussed on disease knowledge and perception, personal attitude and healing practices. Simultaneously, a collection of plants was performed in different ecotopes, in order to make an extensive inventory of the pharmacopoeia. For the Chayahuita, cutaneous (CL) and muco-cutaneous leishmaniasis (MCL) are considered as diseases of their own, with specific names, aetiologies, mode of transmission. Regarding CL, Chayahuita people consider that the humid characteristic of the skin ulcer is a discriminative fact orienting the diagnostic for Ta'ta' (leishmaniasis). This observation helps to understand by analogy treatments and diet prohibitions. All together, 46 different species were designated useful against LC and /or MCL (29 species by the means of the questionnaire and 27 species when collecting in different ecotopes). Thirty-seven extracts corresponding to 31 species used medicinally were screened in vitro against Leishmania amazonensis axenic amastigotes, assessing their viability by the reduction of tetrazolium salt (MTT). Six species displayed a good activity (10mug/ml<IC(50)< 20mug/ml): an undetermined hemi-epiphytic Clusiaceae, Cybianthus anthuriophyllus Pipoly (Myrsinaceae), two Piper, P. sanguineispicum Trel., and P. loretoanum Trel., (Piperaceae), Desmodium axillare Sw. DC. (Fabaceae), and Clibadium sylvestre (Aubl.) Baill. (Asteraceae). Results are discussed according traditional Chayahuita plant's use and disease concepts.

PMID: 19631728 [PubMed - as supplied by publisher]

7: Exp Parasitol. 2009 Jul 21. [Epub ahead of print]Click here to read

Phlebotomus perfiliewi transcaucasicus is circulating both Leishmania donovani and L. infantum in northwest Iran.

Oshaghi MA, Ravasan NM, Hide M, Javadian EA, Rassi Y, Sadraei J, Mohebali M, Hajjaran H, Zarei Z, Mohtarami F.

Department of Medical Entomology and Vector Control, School of Public Health and Institute of Health Research, Tehran University of Medical Sciences, Tehran, Iran.

Leishmania infantum is the causative agent of infantile visceral leishmaniasis (IVL) in the Mediterranean Basin and, based on isoenzyme typing of the parasite isolated from dogs; this parasite was considered to predominate in the all foci of IVL in Iran. However, based on PCR detection and sequencing of parasite Cystein Protease B (CPB), only one out of seven sandfly infections in Phlebotomus perfiliewi transcaucasicus was found to be L. infantum in the current investigation. The six other infections were haplotypes of L. donovani, the causative agent of anthroponotic visceral leishmaniasis (AVL) in West Africa and India. The deduced amino acid of the L. donovani haplotype was found to be novel and the shortest CPB protein reported within the Leishmania spp. Circulation of both L. donovani and L. infantum by P. perfiliewi transcaucasicus, in addition to previous data indicating its ability to circulate L. tropica, suggests that this species, like other vectors of VL, is a permissive vector. Finding L. donovani infecting P. perfiliewi transcaucasicus in the area demands extensive and intensive typing of natural Leishmania infections in epidemiological investigations in Iran and the Mediterranean Basin in general.

PMID: 19631209 [PubMed - as supplied by publisher]

8: Acta Trop. 2009 Jul 21. [Epub ahead of print]Click here to read

Genetic diversity of ribosomal RNA internal transcribed spacer sequences in Lutzomyia species from areas endemic for New World cutaneous leishmaniasis.

Kuwahara K, Kato H, Gomez EA, Uezato H, Mimori T, Yamamoto YI, Calvopiña M, Cáceres AG, Iwata H, Hashiguchi Y.

Department of Veterinary Hygiene, Faculty of Agriculture, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan.

In this study, each of 60 rRNA internal transcribed spacer (ITS) 1 and ITS2 sequences was determined from 44 individuals of 14 morphologically identified New World sand fly Lutzomyia species in Ecuador, and their inter- and intrapecies genetic diversity was compared. Distinguishing between related species based on the ITS1 sequence was difficult because of variability, while the genetic diversity of ITS2 was distinct even among closely-related species. Further, an assessment of intraspecies ITS sequence diversity in the subgenus Helcocyrtomyia revealed no correlation between sequence variation and geographic distribution. The results strongly suggested ITS2 to be a more suitable marker than ITS1 for the taxonomic analysis of Lutzomyia species including closely-related species. Moreover, neither ITS sequence may be useful for the analysis of population structures in Lutzomyia species.

PMID: 19631188 [PubMed - as supplied by publisher]

9: Acta Trop. 2009 Jul 21. [Epub ahead of print]Click here to read

Alterations in phenotypic profiles of peripheral blood cells from patients with human American cutaneous leishmaniasis following treatment with an antimonial drug and a vaccine.

Botelho AC, Mayrink W, Oliveira RC.

Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, FIOCRUZ, 30190-002, Belo Horizonte, MG, Brazil; Departamento de Fisiopatologia, Universidade Estadual de Montes Claros (UNIMONTES), 39401-001, Montes Claros, MG, Brazil.

The susceptibility or resistance of a vertebrate host to leishmaniasis is related to the specie of Leishmania and to the host immune response of the host. In the present study, the phenotypic profiles of the peripheral blood cells of patients with American cutaneous leishmaniasis (ACL) were evaluated before and after receiving three different therapeutic regimens. The study population comprised 24 patients, living in an ACL-endemic area of Caratinga (MG, Brazil), who had been diagnosed as ACL-positive on the basis of characteristic lesions, the Montenegro skin reactivity test, and/or positive parasitology. Subjects were divided into three groups and received treatment regimens based on (i) the pentavalent antimonial (SbV) N-methyl meglumine antimoniate (Glucantime((R))), (ii) the vaccine Leishvacin((R)), or (iii) SbV in association with the vaccine. Comparative analyses of peripheral mononuclear cells prior to and after treatment revealed that the therapeutic regimens induced no significant differences in the percentages of CD3+ and CD4+ T lymphocytes, CD19+ B lymphocytes, or CD16+ and CD56+ natural killer cells. Additionally, the CD4/CD8 and CD3/CD19 ratios remained unaltered by any of the treatments applied. Most previous studies in the field have focused on the analysis of peripheral blood from ACL patients following in vitro stimulation with either Leishmania antigens or mitogens. The ex vivo cellular immune phenotypic profiles determined in the present study, however, revealed that different ACL treatments did not significantly alter either the immune response exhibited by a patient prior to therapy or the expected cure rate.

PMID: 19631187 [PubMed - as supplied by publisher]

10: Parasitology. 2009 Jul 27:1-13. [Epub ahead of print]Click here to read

Dissimilar peptidase production by avirulent and virulent promastigotes of Leishmania braziliensis: inference on the parasite proliferation and interaction with macrophages.

Lima AK, Elias CG, Souza JE, Santos AL, Dutra PM.

Disciplina de Parasitologia, Departamento de Microbiologia, Imunologia e Parasitologia (DMIP), Faculdade de Ciências Médicas (FCM), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.

SUMMARYIn the present paper, we have analysed the cellular and extracellular proteolytic activity profiles in 2 distinct Leishmania braziliensis strains: a recently isolated (virulent) and a laboratory-adapted (avirulent) strain. Quantitative and qualitative differences on the peptidase expression were observed in both strains. For instance, low-molecular mass acidic cysteine peptidase activities were detected exclusively in the virulent strain. Similarly, metallopeptidase activities were mainly produced by L. braziliensis virulent promastigotes. Interestingly, metallo- and cysteine peptidase activities were drastically reduced after several in vitro passages of the virulent strain. Western blotting, flow cytometry and fluorescence microscopy analyses were performed to detect homologous of the major leishmania metallopeptidase (gp63) and cysteine peptidase (cpb) in virulent and avirulent strains of L. braziliensis. Our results revealed that the virulent strain produced higher amounts of gp63 and cpb molecules, detected both in the surface and cytoplasm regions, than the avirulent counterpart. Metallo- (1,10-phenanthroline and EGTA) and cysteine peptidase (E-64) inhibitors arrested the growth of L. braziliensis virulent strain in a dose-dependent manner, as well as the association index with peritoneal murine macrophages. Conversely, these peptidase inhibitors did not affect either the proliferation or the cellular interaction of the avirulent strain. Corroborating these findings, the pre-treatment of the virulent strain with both anti-peptidase antibodies promoted a prominent reduction in the interaction with macrophages, while the association index of the avirulent strain to macrophage was only slightly diminished. Moreover, the spent culture medium from virulent strain significantly enhanced the association index between avirulent strain and macrophages, and this effect was reversed by 1,10-phenanthroline. Collectively, the results presented herein suggest that peptidases participate in several crucial processes of L. braziliensis.

PMID: 19631015 [PubMed - as supplied by publisher]

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