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Sent on Wednesday, 2011 Oct 05Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | Sultan Qaboos Univ Med J. 2011 May;11(2):269-72. Epub 2011 May 15.Visceral Leishmaniasis with an Unusual Presentation in an HIV Positive Patient.Jawhar NM.SourceDepartment of Pathology, Nineveh Medical College, University of Mosul, Iraq. AbstractVisceral leishmaniasis is a disease caused by a haemoflagellate protozoan of the genus Leishmania. It has a wide geographical spread. Classic cases are found primarily in children and present with typical features that include fever, anaemia, hepatosplenomegaly, hypergammaglobulinaemia, and pancytopenia. The diagnosis is usually achieved by bone marrow smears, culture and serology; however, it can manifest itself atypically, mostly in patients infected with HIV and geriatric immunocompetent patients. We report an unusual case of visceral leishmaniasis diagnosed in a 27 year-old HIV-infected male who presented with abdominal discomfort and diarrhoea of four weeks duration associated with nausea and vomiting, but with no typical symptoms or signs of visceral leishmaniasis. The diagnosis was established through the identification of the Leishmania organism in duodenal and colonic biopsies and confirmed by subsequent bone marrow smears. |
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2. | PLoS One. 2011;6(9):e24820. Epub 2011 Sep 28.Characterization of Leishmania donovani Aquapor ins Shows Presence of Subcellular Aquaporins Similar to Tonoplast Intrinsic Proteins of Plants.Biyani N, Mandal S, Seth C, Saint M, Natarajan K, Ghosh I, Madhubala R.SourceSchool of Life Sciences, Jawaharlal Nehru University, New Delhi, India. AbstractLeishmania donovani, a protozoan parasite, resides in the macrophages of the mammalian host. The aquaporin family of proteins form important components of the parasite-host interface. The parasite-host interface could be a potential target for chemotherapy. Analysis of L. major and L. infantum genomes showed the presence of five aquaporins (AQPs) annotated as AQP9 (230aa), AQP putative (294aa), AQP-like protein (279aa), AQP1 (314aa) and AQP-like protein (596aa). We report here the structural modeling, localization and functional characterization of the AQPs from L. donovani. LdAQP1, LdAQP9, LdAQP2860 and LdAQP2870 have the canonical NPA-NPA motifs, whereas LdAQP putative has a non-canonical NPM-NPA motif. In the carboxyl terminal to the second NPA box of all AQPs except AQP1, a valine/alanine residue was found instead of the arginine. In that respect these four AQPs are similar to tonoplast intrinsic proteins in plants, which are localized to intracellular organelles. Confocal microscopy of L. donovani expressing GFP-tagged AQPs showed an intracellular localization of LdAQP9 and LdAQP2870. Real-time PCR assays showed expression of all aquaporins except LdAQP2860, whose level was undetectable. Three-dimensional homology modeling of the AQPs showed that LdAQP1 structure bears greater topological similarity to the aquaglyceroporin than to aquaporin of E. coli. The pore of LdAQP1 was very different from the rest in shape and size. The cavity of LdAQP2860 was highly irregular and undefined in geometry. For functional characterization, four AQP proteins were heterologously expressed in yeast. In the fps1Δ yeast cells, which lacked the key aquaglyceroporin, LdAQP1 alone displayed an osmosensitive phenotype indicating glycerol transport activity. However, expression of LdAQP1 and LdAQP putative in a yeast gpd1Δ strain, deleted for glycerol production, conferred osmosensitive phenotype indicating water transport activity or aquaporin function. Our analysis for the first time shows the presence of subcellular aquaporins and provides structural and functional characterization of aquaporins in Leishmania donovani. |
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3. | Immunol Cell Biol. 2011 Oct 4. doi: 10.1038/icb.2011.80. [Epub ahead of print]TGF-β(1) re-programs TLR4 signaling in L. donovani infection: enhancement of SHP-1 and ubiquitin-editing enzyme A20.Das S, Pandey K, Kumar A, Sardar AH, Purkait B, Kumar M, Kumar S, Ravidas VN, Roy S, Singh D, Das P.SourceDepartments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan, Patna, India. AbstractVisceral leishmaniasis (VL), caused by Leishmania donovani, is a major health concern in India. It represents T-helper type 2 (Th2) bias of cytokines in active state and Th1 bias at cure. However, the role of the parasite in regulating Toll-like receptor (TLR)-mediated macrophage activation in VL patients remains elusive. In this report, we demonstrated that later stages of L. donovani infection rendered tolerance to macrophages, leading to incapability for the production of inflammatory cytokines like tumor necrosis factor (TNF)-α and interleukin (IL)-1β in response to TLR stimulation. Overexpression of transforming growth factor (TGF)-β(1), but not IL-10, resulted in suppressed lipopolysaccharide (LPS)-induced production of TNF-α and downregulation of TLR4 expression in L. donovani-infected macrophages. Recombinant human (rh)TGF-β(1) markedly enhanced tyrosine phosphatase (Src homology region 2 domain-containing phosphatase-1) activity, but inhibited IL-1 receptor-activated kinase (IRAK)-1 activation. Addition of neutralizing TGF-β(1) antibody reversed these effects, and thus suggesting the pivotal role of TGF-β(1) in promoting refractoriness for LPS in macrophages. Surprisingly, the use of a tyrosine phosphatase inhibitor (sodium orthovanadate, Na(3)VO(4)) promoted IRAK-1 activation, confirming the negative inhibitory role of tyrosine phosphatase in macrophage activation. Furthermore, rhTGF-β(1) induced tolerance in infected macrophages by reducing inhibitory protein (IκBα) degradation in a time-dependent manner. In addition, short interfering RNA studies proved that overexpression of A20 ubiquitin-editing protein complex induced inhibitory activity of TGF-β(1) on LPS-mediated nuclear factor-κB activation. Thus, these findings suggest that TGF-β(1) promotes overexpression of A20 through tyrosine phosphatase activity that ensures transient activation of inflammatory signaling pathways in macrophages in active L. donovani infection.Immunology and Cell Biology advance online publication, 4 October 2011; doi:10.1038/icb.2011.80. |
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4. | J Nat Prod. 2011 Oct 3. [Epub ahead of print]Triterpenoids with Rare Carbon Skeletons from Salvia hydrangea : Antiprotozoal Activity and Absolute Configurations.Moridi Farimani M, Bahadori MB, Taheri S, Ebrahimi SN, Zimmermann S, Brun R, Amin G, Hamburger M.SourceDepartment of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University , G. C., Evin, Tehran, Iran. AbstractSalvadione C (1) and perovskone B (2), two new triterpenoids with rare carbon skeletons, were isolated from an antiplasmodial n-hexane extract of Salvia hydrangea . The absolute configuration was determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. In vitro activity against Plasmodium falciparum K1 strain, Trypanosoma brucei rhodesiense STIB 900 strain, and cytotoxicity in rat myoblast (L6) cells were determined. Compounds 1 and 2 showed in vitro antiplasmodial activity, with IC(50) values of 1.43 and 0.18 μM and selectivity indices (SI) of 86.2 and 69.6, respectively. IC(50) values against T. brucei rhodesiense were found to be 4.33 and 15.92 μM, respectively. |
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5. | Am J Trop Med Hyg. 2011 Aug;85(2):221-4.Trypanosoma lewisi or T. lewisi-like infection in a 37-day-old Indian infant.Verma A, Manchanda S, Kumar N, Sharma A, Goel M, Banerjee PS, Garg R, Singh BP, Balharbi F, Lejon V, Deborggraeve S, Singh Rana UV, Puliyel J.SourceDepartment of Paediatrics, St. Stephens Hospital, Delhi, India. AbstractTrypanosomes were observed in the peripheral blood smear of a 37-day-old Indian infant admitted off feeds, with fever and convulsions. Trypanosoma (Herpetosoma) lewisi was identified in the blood. The species identification was confirmed by morphometry, polymerase chain reaction, and sequencing. Human infection with this organism is rare. Only seven cases of this infection have been reported previously in humans. The cases reported are reviewed to develop a composite picture of this disease. |
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6. | Clin Infect Dis. 2011 Jul 15;53(2):210; author reply 210-1.Bedbugs and transmission of Trypanosoma cruzi.Goddard J. |
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7. | Future Microbiol. 2011 Apr;6(4):459-74.Trans-splicing in trypanosomes: machinery and its impact on the parasite transcriptome.Michaeli S.SourceThe Mina & Everard Goodman Faculty of Life Sciences & Advanced Materials & Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel. michaes@mail.biu.ac.il AbstractIn trypanosomes, all RNAs are processed by the concerted action of trans-splicing and polyadenylation. In trans-splicing, a common spliced leader (SL) is donated to all mRNAs from a small RNA molecule, the SL RNA. This article summarizes recent findings in the field focusing on SL RNA transcription, cap modifications and pseudouridylation. The role(s) of these modifications for splicing and gene expression are discussed. The recruitment of SL RNA to the spliceosome depends on splicing factors and recent progress in identifying such factors is described. A recent major advance in understanding the role of trans-splicing in the trypanosome transcriptome was obtained by whole-genome mapping of the SL and polyadenylation sites, revealing surprising heterogeneity and suggesting that gene regulation, especially during cycling between the two hosts of the parasite, involves alternative trans-splicing. Finally, the SL silencing mechanism, which is harnessed by the parasite to control gene expression under stress, is discussed. |
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8. | Int J Cardiol. 2010 Nov 19;145(2):362-3.Chagas disease and mortality in old age as an emerging issue: 10 year follow-up of the Bambuí population-based cohort study (Brazil).Lima-Costa MF, Peixoto SV, Ribeiro AL.AbstractEarlier studies of the natural history of Chagas disease (ChD), which is caused by the protozoan Trypanosoma cruzi, had suggested that the consequences of the disease in the elderly are negligible. The objective of this study was to estimate long-term mortality in ChD in old age using data from a large population-based cohort study. The study was conducted in Bambui City (~15,000 inhabitants), Brazil. Participants were 1479 residents aged 60 years and over (84.9% from total), who were followed from 1997 to 2007. During a mean follow-up of 8.72 years, 567 participants died, resulting in a total of 12,896 person-years observation. The baseline prevalence of T. cruzi infection was 38.1%. T. cruzi infection was a strong predictor of mortality among cohort members, and this association remained largely significant after adjustments for age, sex, and conventional cardiovascular risk factors (hazard ratio [HR] = 1.56; 95% CI 1.32-1.85). Increased risks for mortality associated with T. cruzi infection were consistently observed in those aged 60-69 (HR= 1.79; 95%CI 1.37-1.85), 70-79 (HR=1.35; 95% CI 1.04-1.76) and 80 years and over (HR= 1.59; 95% CI 1.09-2.33). Overall, population attributable risk for mortality due to T. cruzi infection was 13.2% (95% CI 9.8-16.4). Our results indicate that ChD is a relevant individual and population health issue in old age, supporting the need for measures to reduce the burden of ChD in this growing segment of the population. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
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