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Sent on Tuesday, 2011 May 17Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS One. 2011 May 10;6(5):e18873.Influence of Clinical Status and Parasite Load on Erythropoiesis and Leucopoiesis in Dogs Naturally Infected with Leishmania (Leishmania) chagasi.Trópia de Abreu R, Carvalho MG, Carneiro CM, Giunchetti RC, Teixeira-Carvalho A, Martins-Filho OA, Coura-Vital W, Corrêa-Oliveira R, Reis AB.SourceLaboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Departamento de Análises Clínicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. AbstractBACKGROUND:The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). METHODOLOGY/PRINCIPAL FINDINGS:The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. CONCLUSIONS:Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL. |
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| 2. | PLoS Negl Trop Dis. 2011 May 10;5(5):e1139.Seasonality and Prevalence of Leishmania major Infection in Phlebotomus duboscqi Neveu-Lemaire from Two Neighboring Villages in Central Mali.Anderson JM, Samake S, Jaramillo-Gutierrez G, Sissoko I, Coulibaly CA, Traoré B, Soucko C, Guindo B, Diarra D, Fay MP, Lawyer PG, Doumbia S, Valenzuela JG, Kamhawi S.SourceLaboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America. AbstractPhlebotomus duboscqi is the principle vector of Leishmania major, the causative agent of cutaneous leishmaniasis (CL), in West Africa and is the suspected vector in Mali. Although found throughout the country the seasonality and infection prevalence of P. duboscqi has not been established in Mali. We conducted a three year study in two neighboring villages, Kemena and Sougoula, in Central Mali, an area with a leishmanin skin test positivity of up to 45%. During the first year, we evaluated the overall diversity of sand flies. Of 18,595 flies collected, 12,952 (69%) belonged to 12 species of Sergentomyia and 5,643 (31%) to two species of the genus Phlebotomus, P. duboscqi and P. rodhaini. Of those, P. duboscqi was the most abundant, representing 99% of the collected Phlebotomus species. P. duboscqi was the primary sand fly collected inside dwellings, mostly by resting site collection. The seasonality and infection prevalence of P. duboscqi was monitored over two consecutive years. P. dubsocqi were collected throughout the year. Using a quasi-Poisson model we observed a significant annual (year 1 to year 2), seasonal (monthly) and village effect (Kemena versus Sougoula) on the number of collected P. duboscqi. The significant seasonal effect of the quasi-Poisson model reflects two seasonal collection peaks in May-July and October-November. The infection status of pooled P. duboscqi females was determined by PCR. The infection prevalence of pooled females, estimated using the maximum likelihood estimate of prevalence, was 2.7% in Kemena and Sougoula. Based on the PCR product size, L. major was identified as the only species found in flies from the two villages. This was confirmed by sequence alignment of a subset of PCR products from infected flies to known Leishmania species, incriminating P. duboscqi as the vector of CL in Mali. |
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| 3. | PLoS Negl Trop Dis. 2011 May 10;5(5):e1021.Comparative Gene Expression Analysis throughout the Life Cycle of Leishmania braziliensis: Diversity of Expression Profiles among Clinical Isolates.Adaui V, Castillo D, Zimic M, Gutierrez A, Decuypere S, Vanaerschot M, De Doncker S, Schnorbusch K, Maes I, Van der Auwera G, Maes L, Llanos-Cuentas A, Arevalo J, Dujardin JC.SourceInstituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. AbstractBACKGROUND:Most of the Leishmania genome is reported to be constitutively expressed during the life cycle of the parasite, with a few regulated genes. Inter-species comparative transcriptomics evidenced a low number of species-specific differences related to differentially distributed genes or the differential regulation of conserved genes. It is of uppermost importance to ensure that the observed differences are indeed species-specific and not simply specific of the strains selected for representing the species. The relevance of this concern is illustrated by current study. METHODOLOGY/PRINCIPAL FINDINGS:We selected 5 clinical isolates of L. braziliensis characterized by their diversity of clinical and in vitro phenotypes. Real-time quantitative PCR was performed on promastigote and amastigote life stages to assess gene expression profiles at seven time points covering the whole life cycle. We tested 12 genes encoding proteins with roles in transport, thiol-based redox metabolism, cellular reduction, RNA poly(A)-tail metabolism, cytoskeleton function and ribosomal function. The general trend of expression profiles showed that regulation of gene expression essentially occurs around the stationary phase of promastigotes. However, the genes involved in this phenomenon appeared to vary significantly among the isolates considered. CONCLUSION/SIGNIFICANCE:Our results clearly illustrate the unique character of each isolate in terms of gene expression dynamics. Results obtained on an individual strain are not necessarily representative of a given species. Therefore, extreme care should be taken when comparing the profiles of different species and extrapolating functional differences between them. |
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| 4. | Indian J Dermatol. 2011 Jan;56(1):37-9.Decreased effect of glucantime in cutaneous leishmaniasis complicated with secondary bacterial infection.Sadeghian G, Ziaei H, Bidabadi LS, Baghbaderani AZ.SourceSkin Disease and Leishmaniasis Research Center, Isfahan, Iran. AbstractBACKGROUND:Glucantime is regarded as the first-line treatment of cutaneous leishmaniasis (CL); however, failure to treatment is a problem in many cases. AIM:The aim was to evaluate the therapeutic effect of glucantime in CL complicated with secondary bacterial infection compared to uncomplicated lesions. METHODS:This experimental study was performed in Skin Diseases and Leishmaniasis Research Center, Isfahan, Iran. A total of 161 patients enrolled in the study had CL confirmed by positive smear of lesions. All the patients were treated with systemic glucantime for 3 weeks and followed for 2 months. Response to treatment was defined as loss of infiltration, reepithelization, and negative smear. Depending on the results of bacterial cultures, the lesions were divided into two groups and the efficacy of glucantime was compared. RESULTS:A total of 123 patients (76.4%) were negative, and 38 patients (23.6%) were positive for secondary bacterial infection. In groups with negative bacterial culture response to treatment was 65% (80 patients) and in the other positive group, it was 31.6% (12 patients), with a difference (χ(2) = 13.77, P < 0.01). CONCLUSION:Therapeutic effect of glucantime showed a decrease in CL lesions with secondary bacterial infection. Therefore, in the cases of unresponsiveness to treatment, the lesions should be evaluated for bacterial infection, before repeating the treatment. |
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| 5. | PLoS Negl Trop Dis. 2011 May 3;5(5):e1023.Mining a cathepsin inhibitor library for new antiparasitic drug leads.Ang KK, Ratnam J, Gut J, Legac J, Hansell E, Mackey ZB, Skrzypczynska KM, Debnath A, Engel JC, Rosenthal PJ, McKerrow JH, Arkin MR, Renslo AR.SourceThe Small Molecule Discovery Center, University of California San Francisco, San Francisco, California, United States of America. AbstractThe targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∼2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts. |
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| 6. | Eukaryot Cell. 2011 May 13. [Epub ahead of print]TbISWI regulates multiple Pol I transcribed loci and is present at Pol II transcription boundaries in Trypanosoma brucei.Stanne TM, Kushwaha M, Wand M, Taylor JE, Rudenko G.SourceThe Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, U.K. AbstractThe unicellular eukaryote Trypanosoma brucei is unusual in having very little transcriptional control. The bulk of the T. brucei genome is constitutively transcribed by RNA polymerase II (Pol II) as extensive polycistronic transcription units. Exceptions to this rule include several RNA polymerase I (Pol I) transcription units such as the VSG expression sites (ESs), which are mono-allelically expressed. TbISWI, a member of the SWI2/SNF2 related chromatin remodelling ATPases, plays a role in repression of Pol I-transcribed ESs in both bloodstream and procyclic form T. brucei. Here, we show that TbISWI binds both active and silent ESs, but is depleted from the ES promoters themselves. TbISWI knock-down results in an increase in VSG transcripts from the silent VSG ESs. In addition to its role in repression of the silent ESs, TbISWI also contributes to the downregulation of the Pol I-transcribed procyclin loci, as well as nontranscribed VSG Basic Copy arrays and mini-chromosomes. We also show that TbISWI is enriched at a number of strand switch regions which form the boundaries between Pol II transcription units. These strand switch regions are the presumed sites of Pol II transcription initiation and termination, and are enriched in modified histones and histone variants. Our results indicate that TbISWI is a versatile chromatin remodeler that regulates transcription at multiple Pol I loci, and which is particularly abundant at many Pol II transcription boundaries in T. brucei. |
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| 7. | Eukaryot Cell. 2011 May 13. [Epub ahead of print]Ubiquitylation and Developmental Regulation of Invariant Surface Protein Expression in Trypanosomes.Leung KF, Riley FS, Carrington M, Field MC.SourceDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. AbstractThe cell surface of Trypanosoma brucei is dominated by the GPI-anchored variant surface glycoprotein (VSG), which is essential for immune evasion. VSG biosynthesis, trafficking and turnover are well documented but trans-membrane domain (TMD) proteins, including the invariant surface glycoproteins (ISGs), are less well characterized. Internalization and degradation of ISG65 depends on ubiquitylation of conserved cytoplasmic lysines. Using epitope-tagged ISG75 and reporter chimeric proteins bearing the cytoplasmic and trans-membrane regions of ISG75, together with multiple lysine-to-arginine mutants, we demonstrate that the cytoplasmic tail of ISG75 is both sufficient and necessary for endosomal targeting and degradation. The ISG75 chimeric reporter protein localized to endocytic organelles while lysine null versions were significantly stabilized at the cell surface. Importantly, ISG75 cytoplasmic lysines are modified by extensive oligoubiquitin chains and ubiquitylation is abolished in the lysine null. Furthermore, we find evidence for differential modes of turnover of ISG65 and ISG75. Full-length lysine null ISG65 localization and protein turnover is significantly perturbed but not ISG75, while ubiquitin-conjugates can be detected for full-length lysine null ISG75 but not ISG65. We find that ISG75 ectodomain has a predicted coiled-coil suggesting that ISG75 could be part of a complex while ISG65 behaves independently. We also demonstrate a developmental stage-specific mechanism for exclusion of surface ISG expression in insect-stage cells, by a ubiquitin-independent mechanism. We suggest that ubiquitylation may be a general mechanism for regulating trans-membrane domain surface proteins in trypanosomes. |
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| 8. | Endocrinol Nutr. 2011 May 13. [Epub ahead of print]Visceral leishmaniasis in a type 1 diabetic patient with isolated pancreas transplant.< /h1> |
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| 9. | Eur J Med Chem. 2011 Apr 28. [Epub ahead of print]Selenocyanates and diselenides: A new class of potent antileishmanial agents.Plano D, Baquedano Y, Moreno-Mateos D, Font M, Jiménez-Ruiz A, Palop JA, Sanmartín C.SourceSección de Síntesis, Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain. AbstractThirty five selenocyanate and diselenide compounds were subjected to in vitro screening against Leishmania infantum promastigotes and the most active ones were also tested in an axenic amastigote model. In order to establish the selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1 cell lines. Thirteen derivatives exhibit better IC(50) values than miltefosine and edelfosine. Bis(4-aminophenyl)diselenide exhibits the best activity when assayed in infected macrophages and one of the lowest cytotoxic activities against the human cell lines tested, with SI values of 32 and 24 against Jurkat and THP-1 cells, respectively. This compound thus represents a new lead for further studies aimed at establishing its mechanism of action. Copyright © 2011 Elsevier Masson SAS. All rights reserved. |
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| 10. | Trends Parasitol. 2011 May 12. [Epub ahead of print]Can domestic cats be considered reservoir hosts of zoonotic leishman iasis?Maia C, Campino L.SourceUnidade de Parasitologia Médica, Centro de Malária e Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal; Department of Parasitology, Faculty of Sciences, Charles University, Vinicna 7, Prague 2, 128 44 Czech Republic. AbstractCanine and human zoonotic leishmaniasis caused by Leishmania infantum, which is transmitted by the bite of infected phlebotomine sand flies, is a serious public health problem in the Mediterranean basin and Latin America. Among reports on newly identified mammalian hosts recurrently found infected with L. infantum, those regarding domestic cats deserve attention for the potential implications to public health. It has been shown that these animals cohabiting with humans can be infected (although only a few cases develop disease) and harbor parasites in an available way for transmission to competent vectors. Nonetheless, their role as reservoir hosts is still controversial. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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