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Sent on Friday, 2012 April 20Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Drug Test Anal. 2012 Apr 18. doi: 10.1002/dta.389. [Epub ahead of print]Paromomycin-loaded albumin microspheres: Efficacy and stability studies.Khan W, Kumar R, Singh S, Arora SK, Kumar N.SourceNational Institute of Pharmaceutical Education & Research (NIPER), Nagar, India. AbstractIn the present work, paromomycin-loaded albumin microspheres (PM-MS) have been formulated for passive targeting of paromomycin (PM) to macrophages, for the treatment of visceral leishmaniasis (VL). PM-MS were prepared by spray-drying method with a mean particle size of ≈ 3 µm. Thermal and chemical cross-linking methods were used for controlling drug release from the prepared microspheres (MS). PM-MS were then tested for efficacy and stability studies. In efficacy study, in vitro promastigote assay was carried out to assess the susceptibility of promastigote to PM in the concentration range of 5.0-150 µg/ml; cytotoxicity assay was performed to determine possible toxicity of PM for the host cells (peritoneal macrophages) and intracellular amastigote assay was carried out to determine the efficacy of free PM (PM solution) and encapsulated PM (PM-MS). Results obtained indicated a significant increase in efficacy of PM-MS in comparison to PM solution at equivalent concentration. Subsequently, stability studies of prepared formulation was carried out at various temperature and humidity conditions, these studies provided stability of formulation at all tested conditions including accelerated conditions. Thus, it can be concluded that present work provides an optimized formulation with stability and enhanced efficacy. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd. |
| PMID: 22514145 [PubMed - as supplied by publisher] | |
| 2. | J Chem Inf Model. 2012 Apr 19. [Epub ahead of print]Elements of Nucleotide Specificity in the Trypanosoma brucei Mitochondrial RNA Editing Enzyme RET2.Demir O, Amaro RE.AbstractThe causative agent of African sleeping sickness, Trypanosoma brucei, goes through an unusual mitochondrial RNA editing process that is essential for its survival. RNA editing terminal uridylyl transferase 2 of T. brucei (TbRET2) is an indispensable component of the editosome machinery that performs this editing. TbRET2 is required to maintain the vitality of both the insect and bloodstream forms of the parasite, and, with its high-resolution crystal structure, it poses as a promising pharmaceutical target. Neither the exclusive requirement of UTP for catalysis, nor the RNA primer preference of TbRET2 is well understood. Using all-atom explicitly solvated molecular dynamics (MD) simulations, we investigated the effect of UTP binding on TbRET2 structure and dynamics, as well as the determinants governing TbRET2's exclusive UTP preference. Through our investigations of various nucleoside triphosphate substrates (NTPs), we show that UTP pre-organizes the binding site through an extensive water-mediated H-bonding network, bringing Glu-424 and Arg-144 sidechains to an optimum position for RNA primer binding. In contrast, CTP and ATP cannot achieve this pre-organization and thus preclude productive RNA primer binding. Additionally, we have located ligand-binding "hot spots" of TbRET2 based on the MD conformational ensembles and computational fragment mapping. TbRET2 reveals different binding pockets in the apo and UTP-bound MD simulations, which could be targeted for inhibitor design. |
| PMID: 22512810 [PubMed - as supplied by publisher] | |
| 3. | PLoS Negl Trop Dis. 2011 Dec;5(12):e1454. Epub 2011 Dec 20.High prevalence of drug resistance in animal trypanosomes without a history of drug exposure.Chitanga S, Marcotty T, Namangala B, Van den Bossche P, Van Den Abbeele J, Delespaux V.SourceInstitute of Tropical Medicine Antwerp, Antwerp, Belgium. AbstractBACKGROUND:Trypanosomosis caused by Trypanosoma congolense is a major constraint to animal health in sub-Saharan Africa. Unfortunately, the treatment of the disease is impaired by the spread of drug resistance. Resistance to diminazene aceturate (DA) in T. congolense is linked to a mutation modifying the functioning of a P2-type purine-transporter responsible for the uptake of the drug. Our objective was to verify if the mutation was linked or not to drug pressure. METHODOLOGY/PRINCIPAL FINDINGS:Thirty-four T. congolense isolates sampled from tsetse or wildlife were screened for the DA-resistance linked mutation using DpnII-PCR-RFLP. The results showed 1 sensitive, 12 resistant and 21 mixed DpnII-PCR-RFLP profiles. This suggests that the mutation is present on at least one allele of each of the 33 isolates. For twelve of the isolates, a standard screening method in mice was used by (i) microscopic examination, (ii) trypanosome-specific 18S-PCR after 2 months of observation and (iii) weekly trypanosome-specific 18S-PCR for 8 weeks. The results showed that all mice remained microscopically trypanosome-positive after treatment with 5 mg/kg DA. With 10 and 20 mg/kg, 8.3% (n = 72) and 0% (n = 72) of the mice became parasitologically positive after treatment. However, in these latter groups the trypanosome-specific 18S-PCR indicated a higher degree of trypanosome-positivity, i.e., with a unique test, 51.4% (n = 72) and 38.9% (n = 72) and with the weekly tests 79.2% (n = 24) and 66.7% (n = 24) for 10 and 20 mg/kg respectively. CONCLUSION/SIGNIFICANCE:The widespread presence of the DA-resistance linked mutation in T. congolense isolated from wildlife suggests that this mutation is favourable to parasite survival and/or its dissemination in the host population independent from the presence of drug. After treatment with DA, those T. congolense isolates cause persisting low parasitaemias even after complete elimination of the drug and with little impact on the host's health. |
| PMID: 22206039 [PubMed - indexed for MEDLINE] | |
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| 4. | Int J Parasitol. 2012 Jan;42(1):1-20. Epub 2011 Nov 22.When, how and why glycolysis became compartmentalised in the Kinetoplastea. A new look at an ancient organelle.Gualdrón-López M, Brennand A, Hannaert V, Quiñones W, Cáceres AJ, Bringaud F, Concepción JL, Michels PA.SourceResearch Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Université catholique de Louvain, Avenue Hippocrate 74, Postal Box B1.74.01, B-1200 Brussels, Belgium. AbstractA characteristic, well-studied feature of the pathogenic protists belonging to the family Trypanosomatidae is the compartmentalisation of the major part of the glycolytic pathway in peroxisome-like organelles, hence designated glycosomes. Such organelles containing glycolytic enzymes appear to be present in all members of the Kinetoplastea studied, and have recently also been detected in a representative of the Diplonemida, but they are absent from the Euglenida. Glycosomes therefore probably originated in a free-living, common ancestor of the Kinetoplastea and Diplonemida. The initial sequestering of glycolytic enzymes inside peroxisomes may have been the result of a minor mistargeting of proteins, as generally observed in eukaryotic cells, followed by preservation and its further expansion due to the selective advantage of this specific form of metabolic compartmentalisation. This selective advantage may have been a largely increased metabolic flexibility, allowing the organisms to adapt more readily and efficiently to different environmental conditions. Further evolution of glycosomes involved, in different taxonomic lineages, the acquisition of additional enzymes and pathways - often participating in core metabolic processes - as well as the loss of others. The acquisitions may have been promoted by the sharing of cofactors and crucial metabolites between different pathways, thus coupling different redox processes and catabolic and anabolic pathways within the organelle. A notable loss from the Trypanosomatidae concerned a major part of the typical peroxisomal H(2)O(2)-linked metabolism. We propose that the compartmentalisation of major parts of the enzyme repertoire involved in energy, carbohydrate and lipid metabolism has contributed to the multiple development of parasitism, and its elaboration to complicated life cycles involving consecutive different hosts, in the protists of the Kinetoplastea clade. Copyright © 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. |
| PMID: 22142562 [PubMed - indexed for MEDLINE] | |
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| 5. | Int J Parasitol. 2012 Jan;42(1):33-7. Epub 2011 Nov 22.A method for rapid regulation of protein expression in Trypanosoma cruzi.Ma YF, Weiss LM, Huang H.SourceDepartment of Pathology, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, 1300 Morris Park Avenue, Bronx, NY 10461, USA. AbstractAnalysis of gene function in Trypanosoma cruzi is limited due to the absence of rapid, simple and reversible genetic tools to regulate gene and corresponding protein expression. We have designed a modified pTREX vector which uses an N-terminal fusion of a ligand-controlled destabilisation domain (ddFKBP) to a gene/protein of interest. This vector allows rapid and reversible protein expression and efficient functional analysis of proteins in different T. cruzi life cycle stages. Copyright © 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. |
| PMID: 22138018 [PubMed - indexed for MEDLINE] | |
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| 6. | Heart Fail Rev. 2012 Jan;17(1):45-64.Chronic Chagas' heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine.Muñoz-Saravia SG, Haberland A, Wallukat G, Schimke I.SourceSanta Barbara Hospital Sucre, Sucre, Bolivia. AbstractChagas' disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America. Nearly 30% of infected patients develop life-threatening complications, and with a latency of 10-30 years, mostly Chagas' heart disease which is currently the major cause of morbidity and mortality in Latin America, enormously burdening economic resources and dramatically affecting patients' social and labor situations. Because of increasing migration, international tourism and parasite transfer by blood contact, intrauterine transfer and organ transplantation, Chagas' heart disease could potentially become a worldwide problem. To raise awareness of this problem, we reflect on the epidemiology and etiopathology of Chagas' disease, particularly Chagas' heart disease. To counteract Chagas' heart disease, in addition to the general interruption of the infection cycle and chemotherapeutic elimination of the infection agent, early and effective causal or symptomatic therapies would be indispensable. Prerequisites for this are improved knowledge of the pathogenesis and optimized patient management. From economic and logistics viewpoints, this last prerequisite should be performed using laboratory medicine tools. Consequently, we first summarize the mechanisms that have been suggested as driving Chagas' heart disease, mainly those associated with the presence of autoantibodies against G-protein-coupled receptors; secondly, we indicate new treatment strategies involving autoantibody apheresis and in vivo autoantibody neutralization; thirdly, we present laboratory medicine tools such as autoantibody estimation and heart marker measurement, proposed for diagnosis, risk assessment and patient guidance and lastly, we critically reflect upon the increase in inflammation and oxidative stress markers in Chagas' heart disease. |
| PMID: 21165698 [PubMed - indexed for MEDLINE] | |
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