Wednesday, January 25, 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 - 8 of 8

1. PLoS Negl Trop Dis. 2012 Jan;6(1):e1467. Epub 2012 Jan 17.

Should I get screened for sleeping sickness? A qualitative study in kasai province, democratic republic of congo.

Mpanya A, Hendrickx D, Vuna M, Kanyinda A, Lumbala C, Tshilombo V, Mitashi P, Luboya O, Kande V, Boelaert M, Lefèvre P, Lutumba P.

Source

Programme National de Lutte contre la Trypanosomiase Humaine Africain (PNLTHA), Kinshasa, Democratic Republic of Congo.

Abstract

BACKGROUND:

Control of human African trypanosomiasis (sleeping sickness) in the Democratic Republic of Congo is based on mass population active screening by mobile teams. Although generally considered a successful strategy, the community participation rates in these screening activities and ensuing treatment remain low in the Kasai-Oriental province. A better understanding of the reasons behind this observation is necessary to improve regional control activities.

METHODS:

Thirteen focus group discussions were held in five health zones of the Kasai-Oriental province to gain insights in the regional perceptions regarding sleeping sickness and the national control programme's activities.

PRINCIPAL FINDINGS:

Sleeping sickness is well known among the population and is considered a serious and life-threatening disease. The disease is acknowledged to have severe implications for the individual (e.g., persistence of manic periods and trembling hands, even after treatment), at the family level (e.g., income loss, conflicts, separations) and for communities (e.g., disruption of community life and activities). Several important barriers to screening and treatment were identified. Fear of drug toxicity, lack of confidentiality during screening procedures, financial barriers and a lack of communication between the mobile teams and local communities were described. Additionally, a number of regionally accepted prohibitions related to sleeping sickness treatment were described that were found to be a strong impediment to disease screening and treatment. These prohibitions, which do not seem to have a rational basis, have far-reaching socio-economic repercussions and severely restrict the participation in day-to-day life.

CONCLUSIONS/SIGNIFICANCE:

A mobile screening calendar more adapted to the local conditions with more respect for privacy, the use of less toxic drugs, and a better understanding of the origin as well as better communication about the prohibitions related to treatment would facilitate higher participation rates among the Kasai-Oriental population in sleeping sickness screening and treatment activities organized by the national HAT control programme.

PMID:
22272367
[PubMed - in process]
2. PLoS Negl Trop Dis. 2012 Jan;6(1):e1463. Epub 2012 Jan 17.

Genetic Polymorphisms and Drug Susceptibility in Four Isolates of Leishmania tropica Obtained from Canadian Soldiers Returning from Afghanistan.

Plourde M, Coelho A, Keynan Y, Larios OE, Ndao M, Ruest A, Roy G, Rubinstein E, Ouellette M.

Source

Centre de Recherche en Infectiologie du Centre de Recherche du CHUQ and Département de Microbiologie, Immunologie et Infectiologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada.

Abstract

BACKGROUND:

Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease characterized by the presence of one or more lesions on the skin that usually heal spontaneously after a few months. Most cases of CL worldwide occur in Southwest Asia, Africa and South America, and a number of cases have been reported among troops deployed to Afghanistan. No vaccines are available against this disease, and its treatment relies on chemotherapy. The aim of this study was to characterize parasites isolated from Canadian soldiers at the molecular level and to determine their susceptibility profile against a panel of antileishmanials to identify appropriate therapies.

METHODOLOGY/PRINCIPAL FINDINGS:

Parasites were isolated from skin lesions and characterized as Leishmania tropica based on their pulsed field gel electrophoresis profiles and pteridine reductase 1 (PTR1) sequences. Unusually high allelic polymorphisms were observed at several genetic loci for the L. tropica isolates that were characterized. The drug susceptibility profile of intracellular amastigote parasites was determined using an established macrophage assay. All isolates were sensitive to miltefosine, amphotericin B, sodium stibogluconate (Pentostam) and paromomycin, but were not susceptible to fluconazole. Variable levels of susceptibility were observed for the antimalarial agent atovaquone/proguanil (Malarone). Three Canadian soldiers from this study were successfully treated with miltefosine.

CONCLUSIONS/SIGNIFICANCE:

This study shows high heterogeneity between the two L. tropica allelic versions of a gene but despite this, L. tropica isolated from Afghanistan are susceptible to several of the antileishmanial drugs available.

PMID:
22272366
[PubMed - in process]
3. PLoS Negl Trop Dis. 2012 Jan;6(1):e1430. Epub 2012 Jan 17.

Identification of Proteins in Promastigote and Amastigote-like Leishmania Using an Immunoproteomic Approach.

Coelho VT, Oliveira JS, Valadares DG, Chávez-Fumagalli MA, Duarte MC, Lage PS, Soto M, Santoro MM, Tavares CA, Fernandes AP, Coelho EA.

Source

Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Abstract

BACKGROUND:

The present study aims to identify antigens in protein extracts of promastigote and amastigote-like Leishmania (Leishmania) chagasi syn. L. (L.) infantum recognized by antibodies present in the sera of dogs with asymptomatic and symptomatic visceral leishmaniasis (VL).

METHODOLOGY/PRINCIPAL FINDINGS:

Proteins recognized by sera samples were separated by two-dimensional electrophoresis (2DE) and identified by mass spectrometry. A total of 550 spots were observed in the 2DE gels, and approximately 104 proteins were identified. Several stage-specific proteins could be identified by either or both classes of sera, including, as expected, previously known proteins identified as diagnosis, virulence factors, drug targets, or vaccine candidates. Three, seven, and five hypothetical proteins could be identified in promastigote antigenic extracts; while two, eleven, and three hypothetical proteins could be identified in amastigote-like antigenic extracts by asymptomatic and symptomatic sera, as well as a combination of both, respectively.

CONCLUSIONS/SIGNIFICANCE:

The present study represents a significant contribution not only in identifying stage-specific L. infantum molecules, but also in revealing the expression of a large number of hypothetical proteins. Moreover, when combined, the identified proteins constitute a significant source of information for the improvement of diagnostic tools and/or vaccine development to VL.

PMID:
22272364
[PubMed - in process]
4. Int J Otolaryngol. 2012;2012:809056. Epub 2012 Jan 4.

Epistaxis in visceral leishmaniasis with hematological correlation.

Sigdel B, Bhandary S, Rijal S.

Source

Department of Otorhinolaryngology and Head and Neck Surgery, Gandaki Medical College, Pokhara, Nepal.

Abstract

Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Results. Epistaxis was found in the age group of 7-66 years. Epistaxis was observed in 19 (23.8%) cases. One patient died because of epistaxis and neck hematoma. Conclusion. Epistaxis is a common ENT finding in endemic area of visceral leishmaniasis like our case.

PMID:
22272206
[PubMed - in process]
5. J Immunol. 2012 Jan 23. [Epub ahead of print]

Reciprocal Regulation of Protein Kinase C Isoforms Results in Differential Cellular Responsiveness.

Sudan R, Srivastava N, Pandey SP, Majumdar S, Saha B.

Source

National Centre for Cell Science, Ganeshkhind, Pune 411 007, India.

Abstract

Immunological homeostasis is often maintained by counteractive functions of two different cell types or two different receptors signaling through different intermediates in the same cell. One of these signaling intermediates is protein kinase C (PKC). Ten differentially regulated PKC isoforms are integral to receptor-triggered responses in different cells. So far, eight PKC isoforms are reported to be expressed in macrophages. Whether a single receptor differentially uses PKC isoforms to regulate counteractive effector functions has never been addressed. As CD40 is the only receptor characterized to trigger counteractive functions, we examined the relative role of PKC isoforms in the CD40-induced macrophage functions. We report that in BALB/c mouse macrophages, higher doses of CD40 stimulation induce optimum phosphorylation and translocation of PKCα, βI, βII, and ε whereas lower doses of CD40 stimulation activates PKCδ, ζ, and λ. Infection of macrophages with the protozoan parasite Leishmania major impairs PKCα, βI, βII, and ε isoforms but enhances PKCδ, ζ, and λ isoforms, suggesting a reciprocity among these PKC isoforms. Indeed, PKCα, βI, βII, and ε isoforms mediate CD40-induced p38MAPK phosphorylation, IL-12 expression, and Leishmania killing; PKCδ and ζ/λ mediate ERK1/2 phosphorylation, IL-10 production, and parasite growth. Treatment of the susceptible BALB/c mice with the lentivirally expressed PKCδ- or ζ-specific short hairpin RNA significantly reduces the infection and reinstates host-protective IFN-γ-dominated T cell response, defining the differential roles for PKC isoforms in immune homeostasis and novel PKC-targeted immunotherapeutic and parasite-derived immune evasion strategies.

PMID:
22271653
[PubMed - as supplied by publisher]
6. Vet Parasitol. 2012 Jan 5. [Epub ahead of print]

Leishmania tropica experimental infection in the rat using luciferase-transfected parasites.

Talmi-Frank D, Jaffe CL, Nasereddin A, Baneth G.

Source

School of Veterinary Medicine, Hebrew University, P.O. Box 12, Rehovot 76100, Israel.

Abstract

Leishmania tropica is the causative agent of zoonotic cutaneous leishmaniasis in different parts of the Old World. Although it is a common cause of disease in some areas of the world, there is insufficient knowledge on the pathogenicity of this parasite in mammalian hosts and animal models. L. tropica luciferase-transfected metacyclic-stage promastigotes were inoculated into the footpad or ear of Sprague Dawley (SD) rats. Parasite DNA was detected by kDNA real time PCR in the blood at varying levels from 2days to 5weeks post infection (PI) in the absence of clinical signs. Parasite DNA was found in the spleen of all rats at the end of the study, and the parasitic load was up to 40 times higher in the spleen when compared with inoculation sites. Parasites were cultured from the spleen, and skin inoculation sites 5weeks PI. Bioluminescent parasites were observed by in vivo imaging at one day PI, but the technique was not sufficiently sensitive to follow parasite spread after this time. This study provides new evidence for the viscerotropic spread of L. tropica in the rat and demonstrates that the rat can serve as a model for persistent visceralizing infection with this parasite.

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

PMID:
22270032
[PubMed - as supplied by publisher]
7. J Leukoc Biol. 2011 Dec;90(6):1079-87. Epub 2011 Sep 13.

Tregs and infections: on the potential value of modifying their function.

Sehrawat S, Rouse BT.

Source

Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. ss1@wi.mit.edu

Abstract

CD4(+) T cells, which express a master transcription factor, Foxp3, have been recognized as bona fide Tregs. These cells are essential to maintain immune homeostasis in healthy as well as infected mice and humans. Extensive investigations in the last decade have provided ways to manipulate the Foxp3(+) Treg response therapeutically so the role of such cells in microbe-induced inflammatory reactions can be evaluated. This review focuses on our current understanding of the mechanisms required for the generation and sustenance of Tregs in vivo and the potential value of modulating Tregs to control microbe-induced immunopathological responses.

PMCID: PMC3236550
[Available on 2012/12/1]
PMID:
21914856
[PubMed - indexed for MEDLINE]
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8. Eur J Pharm Biopharm. 2011 Aug;78(3):377-84. Epub 2011 Mar 17.

Benznidazole microcrystal preparation by solvent ch ange precipitation and in vivo evaluation in the treatment of Chagas disease.

Maximiano FP, de Paula LM, Figueiredo VP, de Andrade IM, Talvani A, Sá-Barreto LC, Bahia MT, Cunha-Filho MS.

Source

Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto-MG, Brazil.

Abstract

Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results.

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

PMID:
21397015
[PubMed - indexed for MEDLINE]
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