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Sent on Tuesday, 2011 Nov 08Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Eukaryot Cell. 2011 Nov 4. [Epub ahead of print]A trypanosomal pentatricopeptide repeat protein stabilizes the mitochondrial mRNAs of cytochrome oxidase subunit 1 and 2.Pusnik M, Schneider A.SourceDepartment of Chemistry and Biochemistry, University of Bern, Freiestr. 3, CH-3012 Bern, Switzerland. AbstractThe pentatricopeptide repeat (PPR) protein family consists of organellar proteins predicted to bind to specific RNA sequences. Plants have hundreds of distinct PPR proteins, whereas other eukaryotes generally much fewer. The genome of the parasitic protozoa Trypanosoma brucei is predicted to encode more than 30 different PPR proteins which is an extraordinary high number for a non-plant organism. Here we report the characterization TbPPR9. Epitope tagging shows that the protein is exclusively mitochondrially localized. Interestingly, while in induced RNAi cell lines TbPPR9 is efficiently downregulated the level of its mRNA is not affected. Ablation of TbPPR9 selectively abolishes oxidative but not mitochondrial substrate level phosphorylation. The molecular basis of this phenotype is the fact that TbPPR9 is required for the stability of the cytochrome oxidase subunit 1 (COX1) and COX2 mRNAs. This is supported by the observation that ablation of TbPPR9 destabilizes the COX complex but not the cytochrome bc1 or the ATP synthase complex. Moreover, it was shown by blue native gel electrophoresis that TbPPR9 is present in a large complex of unknown composition. |
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| 2. | Lasers Surg Med. 2011 Sep;43(7):755-67. doi: 10.1002/lsm.21080.Photodynamic therapy for infections: Clinical applications.Kharkwal GB, Sharma SK, Huang YY, Dai T, Hamblin MR.SourceWellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Dermatology, Harvard Medical School, Boston, Massachusetts. AbstractBACKGROUND AND OBJECTIVE:Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT. STUDY DESIGN/MATERIALS AND METHODS:The published peer-reviewed literature was reviewed between 1960 and 2011. RESULTS:The basics of antimicrobial PDT are discussed. Clinical applications of antimicrobial PDT to localized viral infections caused by herpes and papilloma viruses, and nonviral dermatological infections such as acne and other yeast, fungal and bacterial skin infections are covered. PDT has been used to treat bacterial infections in brain abscesses and non-healing ulcers. PDT for dental infections including periodontitis and endodontics has been well studied. PDT has also been used for cutaneous Leishmaniasis. Clinical trials of PDT and blue light alone therapy for gastric Helicobacter pylori infection are also covered. CONCLUSION:As yet clinical PDT for infections has been mainly in the field of dermatology using 5-aminolevulanic acid and in dentistry using phenothiazinium dyes. We expect more to see applications of PDT to more challenging infections using advanced antimicrobial photosensitizers targeted to microbial cells in the years to come. Lasers Surg. Med. 43:755-767, 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc. |
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| 3. | Medicina (B Aires). 2011;71(5):420-8.[Role of three ELISA tests using promastigote homogenates of Leishmania braziliensis, L. amazonensis and L. guyanensis in the diagnosis of tegumentary leishmaniasis]. [Article in Spanish] Gil JF, Hoyos CL, Cimino RO, Krolewiecki AJ, López Quiroga I, Cajal SP, Juárez M, García Bustos MF, Mora MC, Marco JD, Nasser JR.SourceInstituto de Investigaciones en Enfermedades Tropicales (IIET), Sede Regional Orán. AbstractIt is important to know whether the variability of species of Leishmania parasites circulating in a region affects the performance of the ELISA test for the diagnosis of leishmaniasis. Therefore, the aim of this study was to analyze the reactivity of the ELISA using homogenates of promastigotes of Leishmania (V.) braziliensis (ELISAb), Leishmania (L) amazonensis (ELISAa) and Leishmania (V.) guyanensis (ELISAg) against different sera groups. Samples from individuals with cutaneous leishmaniasis (n = 37), mucocutaneous leishmaniasis (n = 8), healthy controls (n = 52), persons infected with Trypanosoma cruzi (n = 11) and mixed infections (n = 14) were included in the study. We calculated sensitivities, specificities, cut offs, and predictive values for the three tests and compared them using ANOVA, kappa index, ROC curves comparison, and confidence intervals calculated by the bootstrap method. Significant differences were found when comparing the OD levels of sera from patients with cutaneous leishmaniasis against healthy controls, but there were no differences when comparing the different ELISAs. The sensitivities calculated for ELISAb and ELISAa were 84.6 and of 88.5% for ELISAg, while the value of specificity for the three tests was 96.2. The kappa index (0.87) and comparison of ROC curves showed similar performance for the three ELISAs (p = 0.225). The high reactivity obtained for these ELISAs in sera of patients with mucocutaneous leishmaniasis indicates this test as an important complement in the diagnosis of the disease. |
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| 4. | Bioorg Med Chem Lett. 2011 Oct 18. [Epub ahead of print]Synthesis and antileishmanial evaluation of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazole derivatives.Dos Santos MS, Oliveira ML, Bernardino AM, de Léo RM, Amaral VF, de Carvalho FT, Leon LL, Canto-Cavalheiro MM.SourceDepartamento de Física e Química, Instituto de Ciências Exatas, Universidade Federal de Itajubá, 37500-903 Itajubá, MG, Brazil. AbstractA series of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (4a-g) and 5-amino-1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (5a-g) were synthesized and evaluated in vitro against three Leishmania species: L. amazonensis, L. braziliensis and L. infantum (L. chagasi syn.). The cytotoxicity was assessed. Among the derivatives examined, six compounds emerged as the most active on promastigotes forms of L. amazonensis with IC(50) values ranging from 15 to 60μM. The reference drug pentamidine presented IC(50)=10μM. However, these new compounds were less cytotoxic than pentamidine. Based on these results, the more promising derivative 5d was tested further in vivo. This compound showed inhibition of the progression of cutaneous lesions in CBA mice infected with L. amazonensis relative to an untreated control. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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| 5. | Parasitology. 2011 Nov 7:1-9. [Epub ahead of print]In vitro and in vivo behaviour of sympatric Leishmania (V.) braziliensis, L. (V.) peruviana and their hybrids.Cortes S, Esteves C, Maurício I, Maia C, Cristovão JM, Miles M, Campino L.SourceUnidade de Parasitologia Médica, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira, 100, 1346-008 Lisboa, Portugal. AbstractSUMMARYLeishmania (Viannia) braziliensis is the main cause of highly disfiguring mucocutaneous leishmaniasis (MCL) in South America. The related species L. (V.) peruviana has only been identified in simple cutaneous lesions (CL). Hybrids between L. braziliensis and L. peruviana have been reported although genetic exchange in Leishmania is considered to be rare. Here we compared growth in vitro, adaptive capacity under thermal and oxidative stress and behaviour in a hamster model, of L. braziliensis, L. peruviana, and their putative hybrids. At 24°C, the optimal temperature for in vitro growth, L. braziliensis had the highest growth rate. In in vitro studies hybrid clones presented heterogeneous phenotypes, from slower growth rates, similar to L. peruviana, to higher growth rates, as observed in L. braziliensis. Hamsters infected with hybrid strains, presented the highest parasite densities and aggressive relapses at a later stage of infection. Hybrids generally presented higher plasticity and phenotypic diversity than the putative parental species, with potential eco-epidemiological implications, including an impact on the success of disease control. |
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| 6. | Antioxid Redox Signal. 2011 Nov 5. [Epub ahead of print]Low Molecular Mass Antioxidants in Parasites.Krauth-Siegel L, Leroux AE.SourceUniversität Heidelberg, Biochemie-Zentrum, Heidelberg, Germany; luise.krauth-siegel@bzh.uni-heidelberg.de. AbstractSignificance: Parasitic infections continue to be a major problem for global human health. Vaccines are practically not available and chemotherapy is highly unsatisfactory. One approach towards a novel antiparasitic drug development is to unravel pathways that may be suited as future targets. Parasitic organisms show a remarkable diversity with respect to the nature and functions of their main low molecular mass antioxidants and many of them developed pathways that do not have a counterpart in their mammalian hosts. Recent Advances: Work of the last years disclosed the individual antioxidants employed by parasites and their distinct pathways. Entamoeba, Trichomonas and Giardia directly use cysteine as main low molecular mass thiol but have divergent cysteine metabolisms. Malarial parasites rely exclusively on cysteine uptake and generate glutathione as main free thiol as do metazoan parasites. Trypanosomes and Leishmania have a unique trypanothione-based thiol metabolism but employ individual mechanisms for their cysteine supply. In addition, some trypanosomatids synthesize ovothiol A and/or ascorbate. Various essential parasite enzymes such as trypanothione synthetase and trypanothione reductase in Trypanosomatids and the Schistosoma thioredoxin glutathione reductase are currently intensively explored as drug target molecules. Critical Issues: Essentiality is a prerequisite but not a sufficient property of an enzyme to become a suited drug target. The availability of an appropriate in vivo screening system and many other factors are equally important. Future Directions: The current organism-wide RNA-interference and proteome analyses are supposed to reveal many more interesting candidates for future drug development approaches directed against the parasite antioxidant defense systems. |
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| 7. | Parasitology. 2011 Nov 7:1-8. [Epub ahead of print]Leishmania (Viannia) braziliensis: insights on subcellular distribution and biochemical properties of heparin-binding proteins.DE Castro Côrtes LM, DE Souza Pereira MC, DE Oliveira FO, Corte-Real S, DA Silva FS, Pereira BA, DE Fátima Madeira M, DE Moraes MT, Brazil RP, Alves CR.SourceLaboratório de Biologia Molecular e Doenças Endêmicas, IOC - FIOCRUZ, Av. Brasil 4365, Rio de Janeiro, CEP 21040-360, Brasil. AbstractSUMMARYLeishmaniasis is a vector-borne disease and an important public health issue. Glycosaminoglycan ligands in Leishmania parasites are potential targets for new strategies to control this disease. We report the subcellular distribution of heparin-binding proteins (HBPs) in Leishmania (Viannia) braziliensis and specific biochemical characteristics of L. (V.) braziliensis HBPs. Promastigotes were fractionated, and flagella and membrane samples were applied to HiTrap Heparin affinity chromatography columns. Heparin-bound fractions from flagella and membrane samples were designated HBP Ff and HBP Mf, respectively. Fraction HBP Ff presented a higher concentration of HBPs relative to HBP Mf, and SDS-PAGE analyses showed 2 major protein bands in both fractions (65 and 55 kDa). The 65 kDa band showed gelatinolytic activity and was sensitive to inhibition by 1,10-phenanthroline. The localization of HBPs on the promastigote surfaces was confirmed using surface plasmon resonance (SPR) biosensor analysis by binding the parasites to a heparin-coated sensor chip; that was inhibited in a dose-dependent manner by pre-incubating the parasites with variable concentrations of heparin, thus indicating distinct heparin-binding capacities for the two fractions. In conclusion, protein fractions isolated from either the flagella or membranes of L. (V.) braziliensis promastigotes have characteristics of metallo-proteinases and are able to bind to glycosaminoglycans. |
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| 8. | PLoS One. 2011;6(6):e21027. Epub 2011 Jun 17.Analysis of proteasomal proteolysis during the in vitro metacyclogenesis of Trypanosoma cruzi.Cardoso J, Lima Cde P, Leal T, Gradia DF, Fragoso SP, Goldenberg S, De Sá RG, Krieger MA.SourceInstituto Carlos Chagas/FIOCRUZ, Curitiba, Parana, Brazil. AbstractProteasomes are large protein complexes, whose main function is to degrade unnecessary or damaged proteins. The inhibition of proteasome activity in Trypanosoma cruzi blocks parasite replication and cellular differentiation. We demonstrate that proteasome-dependent proteolysis occurs during the cellular differentiation of T. cruzi from replicative non-infectious epimastigotes to non-replicative and infectious trypomastigotes (metacyclogenesis). No peaks of ubiquitin-mediated degradation were observed and the profile of ubiquitinated conjugates was similar at all stages of differentiation. However, an analysis of carbonylated proteins showed significant variation in oxidized protein levels at the various stages of differentiation and the proteasome inhibition also increased oxidized protein levels. Our data suggest that different proteasome complexes coexist during metacyclogenesis. The 20S proteasome may be free or linked to regulatory particles (PA700, PA26 and PA200), at specific cell sites and the coordinated action of these complexes would make it possible for proteolysis of ubiquitin-tagged proteins and oxidized proteins, to coexist in the cell. |
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| 9. | PLoS One. 2011;6(6):e20836. Epub 2011 Jun 17.Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model.Gillingwater K, Gutierrez C, Bridges A, Wu H, Deborggraeve S, Ekangu RA, Kumar A, Ismail M, Boykin D, Brun R.SourceDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. AbstractThree diamidines (DB 75, DB 867 and DB 1192) were selected and their ability to cure T. evansi experimentally infected goats was investigated. A toxicity assessment and pharmacokinetic analysis of these compounds were additionally carried out. Goats demonstrated no signs of acute toxicity, when treated with four doses of 1 mg/kg/day (total dose 4 mg/kg). Complete curative efficacy of experimentally infected goats was seen in the positive control group treated with diminazene at 5 mg/kg and in the DB 75 and DB 867 groups treated at 2.5 mg/kg. Drug treatment was administered once every second day for a total of seven days. Complete cure was also seen in the group of goats treated with DB 75 at 1.25 mg/kg. DB 1192 was incapable of curing goats at either four-times 2.5 mg/kg or 1.25 mg/kg. Pharmacokinetic analysis clearly demonstrated that the treatment failures of DB 1192 were due to sub-therapeutic compound levels in goat plasma, whilst compound levels for DB 75 and DB 867 remained well within the therapeutic window. In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection. |
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| 10. | Parasitol Res. 2011 Aug;109(2):431-40. Epub 2011 Feb 18.Trypanosoma cruzi strains in the Calomys callosus: parasitemia and reaction of intracellular forms with stage-specific antibodies in the acute and chronic phase of infection and after immunosuppression.T aniwaki NN, Gonçalves VM, Romero JK, da Silva CV, da Silva S, Mortara RA.SourceElectron Microscopy Unit, Adolfo Lutz Institute, Av Dr Arnaldo 355, 01246-902 São Paulo, Brazil. ntaniwak@hotmail.com AbstractAn experimental model for chronic Chagas disease was developed to investigate whether reactivation is influenced by the genetic origin of Trypanosoma cruzi isolates. In addition, we examined whether the distribution of T. cruzi stage-specific epitopes, as defined by monoclonal antibodies (Mab), raised against mammalian-stage parasite forms, exhibited comparable distribution patterns in Calomys callosus myocardium during the acute phase and after reactivation of the infection. Animals were infected with parasites of the G (T. cruzi I), Y (T.cruzi II) or CL strains (T. cruzi VI). Heart sections were labelled with the Mabs 2C2, 1D9, 2B7, 3B9 and 4B9, which react with carbohydrate epitopes on Ssp-4, a major amastigote surface glycoprotein. Mab 1D9 and 2B7 showed polymorphic distributions over amastigotes among animals infected with the G, Y or CL strains. Mab 3B2, which recognises a non-carbohydrate epitope in flagellated forms, showed an active state of parasite dissemination in the myocardium of C. callosus that were infected with Y or CL strains and then immunosuppressed after 6 or 12 months. C. callosus infected with the G strain (T. cruzi I) displayed absence of amastigote nests in the heart after immunosuppression. Our results permit us to suggest that parasites of the G strain may be more sensitive to the immune response, since we could not find either evidence of parasitemia or amastigote nests. Conversely, parasites from the Y and CL strains appeared able to escape the immune response, as evidenced by an inflammatory infiltrate and disseminated infection after immunosuppression. |
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