Friday, December 24, 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 14

1. PLoS Negl Trop Dis. 2010 Dec 14;4(12):e915.

Sex, Subdivision, and Domestic Dispersal of Trypanosoma cruzi Lineage I in Southern Ecuador.

Ocaña-Mayorga S, Llewellyn MS, Costales JA, Miles MA, Grijalva MJ.

Centro de Investigación en Enfermedades Infecciosas, Pontificia Universidad Católica del Ecuador, Quito, Ecuador.

Abstract

BACKGROUND: Molecular epidemiology at the community level has an important guiding role in zoonotic disease control programmes where genetic markers are suitably variable to unravel the dynamics of local transmission. We evaluated the molecular diversity of Trypanosoma cruzi, the etiological agent of Chagas disease, in southern Ecuador (Loja Province). This kinetoplastid parasite has traditionally been a paradigm for clonal population structure in pathogenic organisms. However, the presence of naturally occurring hybrids, mitochondrial introgression, and evidence of genetic exchange in the laboratory question this dogma.

METHODOLOGY/PRINCIPAL FINDINGS: Eighty-one parasite isolates from domiciliary, peridomiciliary, and sylvatic triatomines and mammals were genotyped across 10 variable microsatellite loci. Two discrete parasite populations were defined: one predominantly composed of isolates from domestic and peridomestic foci, and another predominantly composed of isolates from sylvatic foci. Spatial genetic variation was absent from the former, suggesting rapid parasite dispersal across our study area. Furthermore, linkage equilibrium between loci, Hardy-Weinberg allele frequencies at individual loci, and a lack of repeated genotypes are indicative of frequent genetic exchange among individuals in the domestic/peridomestic population.

CONCLUSIONS/SIGNIFICANCE: These data represent novel population-level evidence of an extant capacity for sex among natural cycles of T. cruzi transmission. As such they have dramatic implications for our understanding of the fundamental genetics of this parasite. Our data also elucidate local disease transmission, whereby passive anthropogenic domestic mammal and triatomine dispersal across our study area is likely to account for the rapid domestic/peridomestic spread of the parasite. Finally we discuss how this, and the observed subdivision between sympatric sylvatic and domestic/peridomestic foci, can inform efforts at Chagas disease control in Ecuador.

PMID: 21179502 [PubMed - as supplied by publisher]
2. PLoS One. 2010 Dec 17;5(12):e15263.

A Method for Generation of Bone Marrow-Derived Macrophages from Cryopreserved Mouse Bone Marrow Cells.

Marim FM, Silveira TN, Lima DS, Zamboni DS.

Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo (FMRP/USP), Ribeirão Preto, Brazil.

Abstract

The broad use of transgenic and gene-targeted mice has established bone marrow-derived macrophages (BMDM) as important mammalian host cells for investigation of the macrophages biology. Over the last decade, extensive research has been done to determine how to freeze and store viable hematopoietic human cells; however, there is no information regarding generation of BMDM from frozen murine bone marrow (BM) cells. Here, we establish a highly efficient protocol to freeze murine BM cells and further generate BMDM. Cryopreserved murine BM cells maintain their potential for BMDM differentiation for more than 6 years. We compared BMDM obtained from fresh and frozen BM cells and found that both are similarly able to trigger the expression of CD80 and CD86 in response to LPS or infection with the intracellular bacteria Legionella pneumophila. Additionally, BMDM obtained from fresh or frozen BM cells equally restrict or support the intracellular multiplication of pathogens such as L. pneumophila and the protozoan parasite Leishmania (L.) amazonensis. Although further investigation are required to support the use of the method for generation of dendritic cells, preliminary experiments indicate that bone marrow-derived dendritic cells can also be generated from cryopreserved BM cells. Overall, the method described and validated herein represents a technical advance as it allows ready and easy generation of BMDM from a stock of frozen BM cells.

PMID: 21179419 [PubMed - as supplied by publisher]
3. Virulence. 2010 Oct 27;1(4):314-318.

Proteases and phosphatases during leishmania-macrophage interaction: Paving the road for pathogenesis.

Gómez MA, Olivier M.

Centro Internacional de Entrenamiento e Investigaciones Médicas; CIDEIM; Cali, Colombia.

Abstract

The outcome of Leishmania infection depends both on host and pathogen factors. Macrophages, the specialized host cells for uptake and intracellular development of Leishmania, play a central role in the control of infection. Leishmania has evolved strategies to downregulate host cell functions, largely mediated by the parasite-induced activation of macrophage protein tyrosine phosphatases (PTPs). We have recently identified PTP1B and TCPTP as two additional PTPs engaged upon Leishmania infection and have unraveled an intimate interaction between the Leishmania surface protease GP63 and host PTPs, which mediates a mechanism of cleavage-dependent PTP activation. Here we discuss new perspectives for GP63-mediated parasite virulence and propose putative mechanisms of GP63 internalization into host macrophages and access to intracellular substrates.

PMID: 21178462 [PubMed - as supplied by publisher]
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4. J Vector Borne Dis. 2010 Dec;47(4):204-210.

Complete conservation of an immu nogenic gene (lcr1) in Leishmania infantum and Leishmania chagasi isolated from Iran, Spain and Brazi.

Mahmoudzadeh-Niknam H, Abrishami F, Doroudia M, Moradi M, Alimohammadian MH, Parviz P.

Department of Immunology, Iran.

Abstract

Background & objectives: Kala-azar is the visceral and most severe form of leishmaniasis that leads to death if untreated. The causative agents of visceral leishmaniasis (VL) are members of Leishmania (L.) donovani complex which includes L. chagasi and L. infantum. Genome sequences have raised the question whether L. chagasi and L. infantum are synonymous or different. This question has important implications for clinical and epidemiological studies, evaluation of vaccines and drugs, and disease control. LCR1 is an immunogenic molecule discovered from L. chagasi with potential as a component of a Leishmania subunit vaccine. If this protein has potentials for being used in a vaccine or diagnostic testing, there should be little variability in this molecule between L. infantum isolates from diverse geographic regions. The aim of this study was to determine whether lcr1 of an Iranian strain of L. infantum was identical to lcr1 of both L. infantum strain from a different geographic region (Spain) and that of an L. chagasi isolate from Brazil. Methods: L. infantum isolated from an Iranian kala-azar patient was studied. Lcr1 from this isolate was PCR amplified, cloned, and studied by restriction digest analysis and sequencing. Results: The sequences of lcr1 of the Iranian L. infantum were completely identical at nucleotide level to lcr1 sequences of both the Spanish L. infantum and the Brazilian L. chagasi strains. Conclusion: Complete conservation of the DNA sequence encoding for LCR1 molecule between geographically distinct Leishmania species adds credibility to the potential for LCR1 as a component of a subunit vaccine and diagnostic test for kala-azar.

PMID: 21178212 [PubMed - as supplied by publisher]
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5. J Clin Microbiol. 2010 Dec 22. [Epub ahead of print]

Diagnostic Performance of Filter Paper Lesion Impression PCR in Secondarily Infected Ulcers and Non-ulcerative Lesions of Cutaneous Leishmaniasis.

Boggild AK, Pilar Ramos A, Valencia BM, Veland N, Calderon F, Arevalo J, Low DE, Llanos-Cuentas A.

Tropical Disease Unit, Division of Infectious Diseases, UHN-Toronto General Hospital, Toronto, Canada; Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Canada; Dept. of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru.

Abstract

We compared traditional diagnostic methods to filter paper lesion impression (FPLI) PCR in secondarily infected ulcers, and in non-ulcerative lesions. Sensitivity and specificity of FPLI PCR in secondarily infected lesions (N=8) were 100%. In primarily non-ulcerative lesions (N=15), sensitivity of FPLI PCR was inferior to pooled invasive specimen PCR (72.7% versus 100%) (p=0.10). FPLI PCR is sensitive, specific, and unlike invasive procedures, can be used in secondarily infected ulcers. Invasive specimen collection is superior in non-ulcerative lesions.

PMID: 21177908 [PubMed - as supplied by publisher]
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6. Ann Rheum Dis. 2010 Dec 21. [Epub ahead of print]

Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.Salmon-Ceron D, Tubach F, Lortholary O, Chosidow O, Bretagne S, Nicolas N, Cuillerier E, Fautrel B, Michelet C, Morel J, Puéchal X, Wendling D, Lemann M, Ravaud P, Mariette X; for the RATIO group.

1Université Paris Descartes Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin Broca Hôtel Dieu, Unité de Maladies Infectieuses, Pôle de médecine, Paris, France.

Abstract

BACKGROUND: /st> Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs).

OBJECTIVE: /st> To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors.

METHODS: /st> A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease.

RESULTS: /st> 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002).

CONCLUSION: /st> Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.

PMID: 21177290 [PubMed - as supplied by publisher]
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7. Exp Parasitol. 2010 Dec 18. [Epub ahead of print]

Influence of long term treatment with pravastatin on the survival, evolution of cutaneous lesion and weight of animals infected by Leishmania (L.) amazonensis.

Kückelhaus CS, Kückelhaus SA, Muniz-Junqueira MI.

Laboratory of Cellular Immunology, Pathology, Faculty of Medicine, University of Brasilia, Brasilia, DF, Brazil, 70.910-900; Nucleus of Tropical Medicine, Faculty of Medicine, University of Brasilia, Brasilia, DF, Brazil, 70.910-900.

Abstract

The high toxicity of current drugs for treatment of leishmaniasis is a major hindrance for controlling the disease. Pravastatin is a well-known drug with anti-inflammatory and immunomodulatory properties that may modulate host defense mechanisms against Leishmania. We evaluated the influence of prolonged pravastatin treatment on the survival of Leishmania amazonensis-infected animals (BALB/c, C5BL6 mice and Syrian hamsters), including weekly measurement of cutaneous lesions (footpad thickness) and weight. Pravastatin improved survival of Leishmania-infected BALB/c mice but not of infected C57BL6 mice or hamsters. On the 50(th) week of follow-up, 71% of pravastatin-treated Leishmania-infected BALB/c mice were alive against 29% of control group (p<0.01). Low footpad thickness was found on BALB/c pravastatin treated mice from the 14(th) week (p<0.05), and 20(th) week onward for C57BL6 treated mice. Pravastatin treatment decreased weight loss in Leishmania-infected C57BL6 mice and Syrian hamsters, but not infected BALB/c mice. Our results points to beneficial effects of pravastatin on the evolution of the disease in the murine leishmaniasis model.

Copyright © 2010. Published by Elsevier Inc.
PMID: 21176775 [PubMed - as supplied by publisher]
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8. J Vector Ecol. 2010 Dec;35(2):325-332. doi: 10.1111/j.1948-7134.2010.00090.x.

Richness and diversity of sand flies (Diptera, Psychodidae) in an Atlantic rainforest reserve in southeastern Brazil.

Pinto IS, Dos Santos CB, Ferreira AL, Falqueto A.

Laboratório de Parasitologia, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, 29043-900 Vitória, Espírito Santo, Brazil.

Abstract

Our objective was to study and evaluate the richness and diversity of Phlebotominae fauna in the Duas Bocas Biological Reserve (DBBR) in the state of Espírito Santo, in southeastern Brazil. Sand fly collections were carried out during four consecutive nights each month between August 2007 and July 2008 at DBBR by using CDC automatic light traps and an illuminated Shannon trap. Specific richness (S) and Shannon diversity index (H) was calculated for each trap. We collected 18,868 sand flies belonging to 29 species and 13 genera. Nyssomyia yuilli yuilli was the most abundant species followed by Psychodopygus ayrozai, Ps. hirsutus, Psathyromyia pascalei, and Ps. matosi. We recorded Brumptomyia cardosoi, Br. troglodytes, and Ps. geniculatus for the first time in the state of Espírito Santo. We discuss the differences in diversity and richness of the sand flies in both traps and in relation to other Brazilian localities and biomes. We also discuss the possibility of wild transmission of Leishmania in the DBBR and the influence of the sand fly species in leishmaniasis transmission to the adjacent areas of the reserve.

© 2010 The Society for Vector Ecology.
PMID: 21175939 [PubMed - as supplied by publisher]
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9. Crit Rev Ther Drug Carrier Syst. 2010;27(6):461-507.

Emerging Role of Vesicular Carriers for Therapy of Visceral Leishmaniasis: Conventional versus Novel.

Kumar N, Gupta S, Dube A, Vyas S.

Nanomedicine Research Center, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga.

Abstract

Visceral leishmaniasis (VL) is a systemic protozoan infection that infects a million people living in subtropical and tropical areas. Drugs are the major treatment available against this fatal infection. Conventional chemotherapy of VL involves treatment with pen- tavalent antimonials, pentamidine, paromomycin, miltefosine, etc., but this treatment is challenging because of the failure of drugs to penetrate macrophages where the parasite hides, toxic side effects, and drug resistance due to incomplete treatment schedules. The newer therapeutic approach of combination therapy employing multi-drug combinations provides improved treatment of VL because the combination reduces length of treatment, relapse, and risk of toxicity and increases the therapeutic index. Although considerable success has been attained using combination therapies, none has yet achieved commercial status. Therefore, there is an urgent need of designing novel, site-specific leishmanicidal drug carriers for safe and effective management of VL. Colloidal carriers such as liposomes, niosomes, emulsomes, and their engineered versions offer superior therapeutic efficacy over the conventional treatment in terms of site-specific drug delivery related to absolute treatment of disease with reduced side effects and toxicity. The control over spatial and sequential distribution of drug molecules after systemic or localized administration represents the major dispute in drug-delivery systems, and this can be resolved by the use of these colloidal carriers. The present review describes current conventional and combination drug therapies with special consideration given to the emerging role of novel vesicular colloidal carriers designed against VL. Colloidal carriers employing drugs in combination could lead to reductions in the duration of conventional treatment, better patient compliance, and the prevention of anti-leishmanial drug resistance or toxicity.

PMID: 21175419 [PubMed - as supplied by publisher]
10. J Med Chem. 2010 Dec 22. [Epub ahead of print]

Synthesis and Antiprotozoal Activity of N-Alkoxy Analogues of the Trypanocidal Lead Compound 4,4'-Bis(imidazolinylamino)diphenylamine with Improved Human Blood-Brain Barrier Permeability.

Nieto L, Mascaraque A, Miller F, Glacial F, Ríos Martínez C, Kaiser M, Brun R, Dardonville C.

Instituto de Química Médica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain.

Abstract

To improve the blood-brain barrier permeability of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine (1), five N-alkoxy analogues were synthesized from bis(4-isothiocyanatophenyl)amine and N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides following successive chemical reactions in just one reactor ("one-pot procedure"). This involved: (a) formation of a thiourea intermediate, (b) removal of the amine protecting groups, and (c) intramolecular cyclization. The blood-brain barrier permeability of the compounds determined in vitro by transport assays through the hCMEC/D3 human cell line, a well-known and characterized human cellular blood-brain barrier model, showed that the N-hydroxy analogue 16 had enhanced blood-brain barrier permeability compared with the unsubstituted lead compound. Moreover, this compound displayed low micromolar IC(50) against Trypanosoma brucei rhodesiense and Plasmodium falciparum and moderate activity by intraperitoneal administration in the STIB900 murine model of acute sleeping sickness.

PMID: 21175162 [PubMed - as supplied by publisher]
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