Wednesday, June 23, 2010

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 17

1. Infect Immun. 2010 Jun 21. [Epub ahead of print]

Leishmania donovani amastigotes impair IFN-{gamma}-induced STAT1{alpha} nuclear translocation by blocking the interaction between STAT1{alpha} and importin-{alpha}5.

Matte C, Descoteaux A.

INRS-Institut Armand-Frappier and Centre for host-parasite interactions, Laval, QC, Canada H7V 1B7.

Abstract

The protozoan parasite Leishmania donovani, the etiological agent of visceral leishmaniasis, is renowned for its capacity to sabotage macrophage functions and signaling pathways stimulated by activators such as interferon (IFN)-gamma. Our knowledge of the strategies utilized by L. donovani to impair macrophage responsiveness to IFN-gamma remains fragmentary. In the present study, we investigated the impact of an infection by the amastigote stage of L. donovani on IFN-gamma responses and signaling via the Janus kinase (JAK)-Signal transducer and activator of transcription (STAT) pathway, in mouse bone marrow-derived macrophages. IFN-gamma-induced expression of MHC II and inducible nitric oxide synthase (iNOS) was strongly reduced in L. donovani amastigote-infected macrophages. As the expression of those genes is mediated by the transcription factors STAT1alpha and IFN regulatory factor (IRF)-1, we investigated their activation in amastigote-infected macrophages treated with IFN-gamma. We found that whereas STAT1alpha protein levels and phosphorylation on Tyr701 and Ser727 were normal, IRF-1 expression was inhibited in infected macrophages. This inhibition of IRF-1 expression correlated with a defective nuclear translocation of STAT1alpha, and further analyses revealed that IFN-gamma-induced STAT1alpha association with the nuclear transport adaptor importin-alpha5 was compromised in L. donovani amastigote-infected macrophages. Taken together, our results provide evidence for a novel mechanism used by L. donovani amastigotes to interfere with IFN-gamma-activated macrophage functions and provides a better understanding of the strategies deployed by this parasite to ensure its intracellular survival.

PMID: 20566692 [PubMed - as supplied by publisher]
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2. Exp Parasitol. 2010 Jun 8. [Epub ahead of print]

Effects of HIV aspar tyl-proteinase inhibitors on Leishmania sp.

Valdivieso E, Rangel A, Moreno J, Saugar JM, Cañavate C, Alvar J, Dagger F.

Laboratorio de Biología Celular de Parásitos, Instituto de Biología Experimental, Universidad Central de Venezuela, Caracas 1041-A, Venezuela.

Abstract

In this work, we have found an antiproliferative effect on Leishmania sp. promastigotes and axenic amastigotes by the human immunodeficiency virus (HIV) aspartyl-proteinase inhibitors, Ac-Leu-Val-Phenylalaninal, Saquinavir mesylate and Nelfinavir, the latter two being used as part of antiretroviral therapy. This effect appears to be the result of cell division blockage. In addition, these drugs induced in culture a decrease in the percentage of co-infected HIV/Leishmania monocytes and amastigotes of Leishmania per macrophage. The finding of a dose-dependent inhibition of Leishmania promastigotes aspartyl-proteinase activity by these drugs allows us to propose this activity as the drug parasite target. A direct action of these HIV aspartyl-proteinase inhibitors on the parasite, would be correlated with the effect that highly active antiretroviral therapy have had in the decrease of HIV/Leishmania coinfection, opening an interesting perspective for new drugs research development based on this novel parasite proteinase family. Copyright © 2010. Published by Elsevier Inc.

PMID: 20566367 [PubMed - as supplied by publisher]
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3. Exp Parasitol. 2010 Jun 8. [Epub ahead of print]

Leishmania species: Detection and identification by nested PCR assay from skin samples of rodent reservoirs.

Akhavan AA, Mirhendi H, Khamesipour A, Alimohammadian MH, Rassi Y, Bates P, Kamhawi S, Valenzuela JG, Arandian MH, Abdoli H, Jalali-Zand N, Jafari R, Shareghi N, Ghanei M, Yaghoobi-Ershadi MR.

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

Abstract

Many rodent species act as reservoir hosts of zoonotic cutaneous leishmaniasis in endemic areas. In the present study a simple and reliable assay based on nested PCR was developed for the detection and identification of Leishmania parasites from rodent skin samples. We designed Leishmania-specific primers that successfully amplified ITS regions of Leishmania major, Leishmania gerbilli and Leishmania turanica using nested PCR. Out of 95 field collected Rhombomys opimus, 21 were positive by microscopic examination and 48 by nested PCR. The percentage of gerbils infected with L. major, L. gerbilli and L. turanica was 3.2%, 1.1% and 27.4%, respectively. In 15.8% of the rodents, we found mixed natural infections by L. major and L. turanica, 1.1% by L. major and L. gerbilli, and 2.1% by the three species. We concluded that this method is simple and reliable for detecting and identifying Leishmania species circulating in rodent populations. Copyright © 2010. Published by Elsevier Inc.

PMID: 20566364 [PubMed - as supplied by publisher]
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4. Phytother Res. 2010 Jun 17. [Epub ahead of print]

Antimycobacterial, antiprotozoal and cytotoxic potential of twenty-one brown algae (phaeophyceae) from British and Irish waters.

Spavieri J, Allmendinger A, Kaiser M, Casey R, Hingley-Wilson S, Lalvani A, Guiry MD, Blunden G, Tasdemir D.

Department of Pharmaceutical and Biological Chemistry, Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London, London WC1N 1AX, UK.

Abstract

In the continuation of our research on seaweeds, crude extracts of 21 brown algae collected from the south coast of England and the west coast of Ireland were screened for in vitro trypanocidal, leishmanicidal and antimycobacterial activities. Mammalian stages of a small set of parasitic protozoa; i.e. Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, and the tubercle bacillus Mycobacterium tuberculosis were used as test organisms. The extracts were also evaluated for selectivity by testing on a mammalian cell line (L6 cells). Only four extracts were moderately active against T. cruzi, whereas all algal extracts showed significant activity against T. brucei rhodesiense, with Halidrys siliquosa and Bifurcaria bifurcata (Sargassaceae) being the most potent (IC(50) values 1.2 and 1.9 mug/mL). All algal extracts also displayed leishmanicidal activity, with H. siliquosa and B. bifurcata again being the most active (IC(50)s 6.4 and 8.6 mug/mL). When tested against M. tuberculosis, only the B. bifurcata extract was found to have some antitubercular potential (MIC value 64.0 mug/mL). Only three seaweed extracts, i.e. H. siliquosa, B. bifurcata and Cystoseira tamariscifolia showed some cytotoxicity. To our knowledge, this is the first study on the antiprotozoal and antimycobacterial activity of brown algae from British and Irish waters. Copyright (c) 2010 John Wiley & Sons, Ltd.

PMID: 20564461 [PubMed - as supplied by publisher]
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5. ScientificWorldJournal. 2010 Jun 14;10:1067-72.

Synthesis and antileishmanial activity of lipophilic aroma tic aminoalcohols.

Reis Corrales RN, Pinheiro LS, Coimbra ES, Da Silva AD, Le Hyaric M.

Departamento de Química, I.C.E., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais, Brazil. robertacnr@bol.com.br

Abstract

In this work, we report on the preparation and evaluation of the in vitro antileishmanial activity of a series of lipophilic aromatic aminoalcohols. All compounds were assessed for their in vitro antiproliferative activity against promastigotes of three Leishmania species. The most lipophilic aminoalcohols bearing an aliphatic moiety with eight to 12 carbon atoms displayed a good activity against L. amazonensis and L. major, and two of them also showed antiproliferative activity against L. chagasi. The best results were obtained for the N-dodecanoyl ethylenediamine derivative and for N-decyl aminoalcohol (IC50=5.2 and 0.7 microM, respectively).

PMID: 20563528 [PubMed - in process]
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6. Rev Soc Bras Med Trop. 2010 Jun;43(3):333-5.

[Leishmania (Leishmania) infantum chagasi in wild canids kept in captivity i n the State of Mato Grosso]

[Article in Portuguese]

Souza NP, Almeida Ado B, Freitas TP, Paz RC, Dutra V, Nakazato L, Sousa VR.

Departamento de Clínica Médica Veterinária, Faculdade de Agronomia e Medicina Veterinária, Universidade Federal de Mato Grosso, Cuiabá, MT.

Abstract

INTRODUCTION: Visceral leishmaniasis is a zoonosis that affects many mammals, and domestic canids are the main reservoirs in urban environments. This note describes infection by Leishmania (Leishmania) infantum chagasi among wild canids kept in captivity in the State of Mato Grosso, Brazil. METHODS: Skin, bone marrow and lymph node samples were collected from six crab-eating foxes (Cerdocyon thous) and one bush dog (Spheotos venaticus), in order to detect and characterize Leishmania using the PCR-RFLP technique. RESULTS: All the animals studied were positive for Leishmania (L.) infantum chagasi. CONCLUSIONS: This study highlights the importance of adequate monitoring of these animals, as well as greater control of this disease, given that these animals are in a public recreation environment.

Free Article
PMID: 20563507 [PubMed - in process]
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7. Trop Biomed. 2010 Apr;27(1):89-102.

Immune response of BALB/c mice against an experimental vaccine of Alum pre cipitated autoclaved Leishmania major (Alum-ALM) mixed with BCG or Mycobacterium vaccae.

Nateghi Rostami M, Keshavarz H, Khamesipour A.

Medical Parasitology and Mycology Department, School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Immune response in BALB/c mice immunized 3 times with different doses (50 mug or 200 mug of protein) of Alum precipitated autoclaved Leishmania major (Alum-ALM) mixed with either BCG (1 x10(7); CFU) or different doses of killed Mycobacterium vaccae (1 x10(6), 1 x10(7)) was assessed. Mice immunized with low dose of Alum-ALM mixed with either BCG or low M. vaccae showed a significantly higher IFN-gamma production and a lower IL-4 level and a significantly lower parasite burden compared to the control PBS injected group. It seems that immunization with a low dose of Alum-ALM mixed with an adjuvant induces a Th1 type of immune response in susceptible BALB/c mice.

PMID: 20562818 [PubMed - in process]
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8. J Ethnopharmacol. 2010 May 31. [Epub ahead of print]

In vitro antiprotozoal, antimicrobial and antitumor activity of Pavetta crassipes K. Schum leaf extracts.

Baldé ES, Megalizzi V, Traoré MS, Cos P, Maes L, Decaestecker C, Pieters L, Baldé AM.

Département de Pharmacie, Faculté de Médecine, Pharmacie et Odontostomatologie, Université de Conakry, BP 6411 Conakry, Guinea; Laboratory of Toxicology, Institute of Pharmacy, Université Libre de Bruxelles (ULB), Boulevard du Triomphe, B-1050 Brussels, Belgium.

Abstract

AIM OF THE STUDY: To study the potential benefit of the traditional medicinal plant Pavetta crassipes K. Schum (Rubiaceae), which is widely distributed throughout West Africa, the methanol and dichloromethane extracts were isolated from the plant leaves to determine if they exhibited antiprotozoal, antibacterial, antifungal or antitumor activity in vitro. MATERIALS AND METHODS: The methanol and dichloromethane extracts and their specific fractions were obtained using bioassay-guided fractionation and investigated for antiproliferative activity in vitro in microorganisms (Staphylococcus aureus, Escherichia coli and Candida albicans), protozoans (Trypanosoma cruzi, Trypanosoma brucei, Leishmania infantum and Plasmodium falciparum), and cancer (U373, PC3, MXT and A549) and normal cell lines (NHDF and MRC-5). RESULTS: Most of the alkaloid fractions investigated exhibited antiproliferative activity in all the cancer cell lines, microorganisms and protozoans studied. CONCLUSIONS: The benefit of Pavetta crassipes as a traditional medicinal remedy was confirmed using antiprotozoal and cytotoxicity assays in vitro. These analyses revealed that the components present in the alkaloid extract of Pavetta crassipes are responsible for its antiprotozoal and cytotoxic efficacy. Copyright © 2010. Published by Elsevier Ireland Ltd.

PMID: 20561931 [PubMed - as supplied by publisher]
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9. Trends Parasitol. 2010 Jun 17. [Epub ahead of print]

Trypanosoma brucei: two steps to spread out from Africa.

Lun ZR, Lai DH, Li FJ, Lukeš J, Ayala FJ.

Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences, Key Laboratory of Tropical Diseases Control of the Ministry of Education, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou 510275, P.R. China.

Abstract

Trypanosoma brucei equiperdum and Trypanosoma brucei evansi are typically considered separate species, although a recent study suggested that these organisms can be classified as subspecies of Trypanosoma brucei, which we also favor. Here we present a scenario that attempts to explain the continuing evolution of the dyskinetoplastic and akinetoplastic strains, as a consequence of loss of selective pressure(s) leading to the loss of kinetoplast DNA. Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID: 20561822 [PubMed - as supplied by publisher]
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10. Int J Biochem Cell Biol. 2010 Jun 15. [Epub ahead of print]

A plate-based assay system for analyses and screening of the Leishmania m ajor inositol phosphorylceramide synthase.

Mina JG, Mosely JA, Ali HZ, Shams-Eldin H, Schwarz RT, Steel PG, Denny PW.

Biophysical Sciences Institute, School of Biological and Biomedical Sciences and Department of Chemistry, University Science Laboratories, South Road, Durham, DH1 3LE, UK; School of Medicine and Health, Durham University, Queen's Campus, Stockton-on-Tees, TS17 6BH, UK.

Abstract

Sphingolipids are key components of eukaryotic membranes, particularly the plasma membrane. The biosynthetic pathway for the formation of these lipid species is largely conserved. However, in contrast to mammals, which produce sphingomyelin, organisms such as the pathogenic fungi and protozoa synthesize inositol phosphorylceramide (IPC) as the primary phosphosphingolipid. The key step involves the reaction of ceramide and phosphatidylinositol catalysed by IPC synthase, an essential enzyme with no mammalian equivalent encoded by the AUR1 gene in yeast and recently identified functional orthologues in the pathogenic kinetoplastid protozoa. As such this enzyme represents a promising target for novel anti-fungal and anti-protozoal drugs. Given the paucity of effective treatments for kinetoplastid diseases such as leishmaniasis, there is a need to characterize the protozoan enzyme. To this end a fluorescent-based cell-free assay protocol in a 96-well plate format has been established for the Leishmania major IPC synthase. Using this system the kinetic parameters of the enzyme have been determined as obeying the double displacement model with apparent V(max)=2.31 pmol.min(-1).U(-1). Furthermore, inhibitory substrate analogues have been identified. Importantly this assay is amenable to development for use in high-throughput screening applications for lead inhibitors and as such may prove to be a pivotal tool in drug discovery. Copyright © 2010. Published by Elsevier Ltd.

PMID: 20561598 [PubMed - as supplied by publisher]
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