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Sent on Friday, 2010 Apr 02Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Parasitol Res. 2010 Apr 1. [Epub ahead of print]Screening of antileishmanial activity from marine sponge extracts collected off the Tunisian coast.Ben Kahla-Nakbi A, Haouas N, El Ouaer A, Guerbej H, Mustapha KB, Babba H.Laboratoire de Biodiversité et Biotechnologie Marine, Institut National des Sciences et Technologies de la Mer (annexe Monastir), Annexe Monastir, BP 59 Monastir, 5000, Tunisia, Nakbi_amel@yahoo.fr. The present study reports on the in vitro antileishmanial activity of two Ircinidae (Dictyoceratida, Demospongiae, Porifera) Ircinia spinosula and Sarcotragus sp. Sampled from the east coast of Tunisia. The ethyl acetate, dichloromethane, and aqueous extracts were tested against Leishmania major promastigotes. The anti-proliferative activity was checked using different extracts concentration during 72 h. We found that the IC50 (sub-inhibitory concentration) values ranged from 1.39 to 264.67 mug/ml. The most active extract was that from sarcotragus sp dichloromethane extract. Microscopic observations showed that the extracts promoted cellular alterations and induce enlargement of the nucleus and modification of the parasite shape. These promising results in relation with in vitro antileishmanial activity open the way for complementary investigation in order to purify and identify active molecules. |
| PMID: 20358229 [PubMed - as supplied by publisher] | |
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| 2. | Proc Biol Sci. 2010 Mar 31. [Epub ahead of print]Nutrient provisioning facilitates homeostasis between tsetse fly (Diptera: Glossinidae) symbionts.Snyder AK, Deberry JW, Runyen-Janecky L, Rio RV.Department of Biology, West Virginia University, , 53 Campus Drive 5106 LSB, Morgantown, WV 26506, USA. Host-associated microbial interactions may involve genome complementation, driving-enhanced communal efficiency and stability. The tsetse fly (Diptera: Glossinidae), the obligate vector of African trypanosomes (Trypanosoma brucei subspp.), harbours two enteric Gammaproteobacteria symbionts: Wigglesworthia glossinidia and Sodalis glossinidius. Host coevolution has streamlined the Wigglesworthia genome to complement the exclusively sanguivorous tsetse lifestyle. Comparative genomics reveal that the Sodalis genome contains the majority of Wigglesworthia genes. This significant genomic overlap calls into question why tsetse maintains the coresidence of both symbionts and, furthermore, how symbiont homeostasis is maintained. One of the few distinctions between the Wigglesworthia and Sodalis genomes lies in thiamine biosynthesis. While Wigglesworthia can synthesize thiamine, Sodalis lacks this capability but retains a thiamine ABC transporter (tbpAthiPQ) believed to salvage thiamine. This genetic complementation may represent the early convergence of metabolic pathways that may act to retain Wigglesworthia and evade species antagonism. We show that thiamine monophosphate, the specific thiamine derivative putatively synthesized by Wigglesworthia, impacts Sodalis thiamine transporter expression, proliferation and intracellular localization. A greater understanding of tsetse symbiont interactions may generate alternative control strategies for this significant medical and agricultural pest, while also providing insight into the evolution of microbial associations within hosts. |
| PMID: 20356887 [PubMed - as supplied by publisher] | |
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| 3. | Bioorg Med Chem. 2010 Mar 12. [Epub ahead of print]Trypanoside, anti-tuberculosis, leishmanicidal, and cytotoxic activities of tetrahydrobenzothienopyrimidines.Aponte JC, Vaisberg AJ, Castillo D, Gonzalez G, Estevez Y, Arevalo J, Quiliano M, Zimic M, Verástegui M, Málaga E, Gilman RH, Bustamante JM, Tarleton RL, Wang Y, Franzblau SG, Pauli GF, Sauvain M, Hammond GB.Department of Chemistry, University of Louisville, Louisville, KY 40292, USA. The synthesis of 2-(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)hydrazone-derivatives (BTPs) and their in vitro evaluation against Trypanosoma cruzi trypomastigotes, Mycobacterium tuberculosis, Leishmania amazonensis axenic amastigotes, and six human cancer cell lines is described. The in vivo activity of the most active and least toxic compounds against T. cruzi and L. amazonensis was also studied. BTPs constitute a new family of drug leads with potential activity against infectious diseases. Due to their drug-like properties, this series of compounds can potentially serve as templates for future drug-optimization and drug-development efforts for use as therapeutic agents in developing countries. Copyright © 2010 Elsevier Ltd. All rights reserved. |
| PMID: 20356752 [PubMed - as supplied by publisher] | |
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| 4. | J Med Entomol. 2010 Jan;47(1):80-8.Micr odistribution of sylvatic triatomine populations in central-coastal Ecuador.Suarez-Davalos V, Dangles O, Villacis AG, Grijalva MJ.Center for Infectious Disease Research, Pontifical Catholic University of Ecuador, Quito, Ecuador. Chagas disease is a serious public health problem in Ecuador, where nearly 230,000 individuals show Trypanosoma cruzi infection. Sylvatic T. cruzi transmission is a threat to current control strategies. This is because of the possibility of house reinfestation by sylvatic triatomines after insecticide treatment. This work quantified the spatial distribution of triatomines in sylvatic habitats and its relationship with nearby human dwellings. A simple random sampling design using live-baited traps and manual searches for triatomines was used in areas near human communities in Manabi province, Ecuador, during June and July 2007. We identified risk factors associated with triatomine density using generalized linear models, and developed predictive maps for triatomine density interpolation. There were 345 triatomines belonging to the species Rhodnius ecuadoriensis and Panstrongylus howardi collected in sylvatic areas. Spatial analyses revealed an aggregated distribution pattern of the sylvatic triatomine populations (clustered mostly at a distance smaller than 100 m). Generalized linear models showed that the distance from the nearest house, nest type, and height from ground level were the main factors explaining triatomine densities. Squirrel nests (Sciurus stramineus), located in plants other than palms, above 5 m and close to the domicile presented higher infestation. Interpolation maps of triatomine microdistribution are presented as potential tools to predict triatomine occurrence. The presence of sylvatic populations and the synanthropic tendency of the vectors highlight the need for continuous active and passive entomological surveillance for the long-term control of Chagas disease. |
| PMID: 20180312 [PubMed - indexed for MEDLINE] | |
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| 5. | Am Fam Physician. 2010 Feb 15;81(4):407; author reply 407.Chagas disease as secondary cause of cardiomyopathy.Junnila JL.Comment on: |
| PMID: 20148493 [PubMed - indexed for MEDLINE] | |
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| 6. | J Med Chem. 2010 Mar 11;53(5):1951-63.Michael acceptor based antiplasmodial and antitrypanosomal cysteine protease inhibitors with unusual amino acids.Breuning A, Degel B, Schulz F, Büchold C, Stempka M, Machon U, Heppner S, Gelhaus C, Leippe M, Leyh M, Kisker C, Rath J, Stich A, Gut J, Rosenthal PJ, Schmuck C, Schirmeister T.Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, Germany. New peptidic Michael acceptor based cysteine protease inhibitors displaying antiparasitic activity were identified by testing a broad series of 45 compounds in total, containing Asn, Gln, or Phe. As target enzymes, falcipain-2 and -3 from P. falciparum and rhodesain from T. b. rhodesiense were used. In the case of the Asn/Gln containing compounds, the trityl-protected, diastereomeric E-configured vinylogous dipeptide esters 16 (Boc-(S)-Phg-(R/S)-vGln(Trt)-OEt) were discovered as most active inhibitors concerning both protease inhibition and antiparasitic acitivity, with inhibition constants in the submicromolar range. The compounds were shown to display time-dependent and competitive inhibition. In the case of the Phe containing compounds, the maleic acid derivatives 42 and 43 (BnO-Phe<--Mal-Phe-OBn, BnO-Phe<--Mal-Phe-Ala-OBn, Mal = maleic acid) displayed good inhibition of rhodesain as well as good antitrypanosomal activity, while the fumaric acid derived E-analogue 14 (BnO-Phe<--Fum-Phe-OBn) only displayed inhibition of the target enzymes but no antiparasitic activity. Inhibition by these Phe derivatives was shown to be time-independent and competitive. |
| PMID: 20131843 [PubMed - indexed for MEDLINE] | |
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| 7. | Acta Trop. 2010 Feb;113(2):134-8. Epub 2009 Oct 23.Benznidazole alters the pattern of Cyclophosphamide-induced reactivation in experimental Trypanosoma cruzi-dependent lineage infection.Santos DM, Martins TA, Caldas IS, Diniz LF, Machado-Coelho GL, Carneiro CM, Oliveira Rde P, Talvani A, Lana M, Bahia MT.Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG 35400-000, Brazil. The factors involved in the reactivation of chronic Chagas disease infection are not clear enough and may be related to host immune unbalance and/or parasite genetic diversity. To evaluate the role of the Trypanosoma cruzi genetic background in the Chagas disease reactivation, we inoculated Cyclophosphamide-immunosupressed (CyI) Swiss mice with clonal stocks from T. cruzi I (Cuica cl1, P209 cl1, Gamba cl1, SP104 cl1), T. cruzi II (IVV cl4, MVB cl8) and T. cruzi (Bug2148 cl1, MN cl2) lineages. We used the parasitemia as the parameter for Chagas disease reactivation and observed that CyI animals infected with T. cruzi stocks showed no reactivation and those infected with T. cruzi II stocks showed only 5% of reactivation. In contrast, immunosuppressed mice infected with stocks from T. cruzi I lineage showed 77.5 and 51.25% reactivation of the infection when Cyclophosphamide treatment was performed 60 and 180 days after inoculation, respectively. Next, we evaluated the efficacy of the Benznidazole (Bz) pre-treatment in reducing or preventing the recurrence of the infection in these CyI animals. In general, the percentage of the parasite recurrence was not altered among the CyI mice that received the Bz pre-treatment during the acute phase of the infection. Interestingly, when pre-Bz treatment was performed during the chronic phase, we observed two different patterns of response: (i) an increased protection among the animals inoculated with the SP104 cl1 (genotype 19) and Cuica cl1 (genotype 20) stocks; (ii) an increased percentage of parasitemia reactivation among mice inoculated with Gamba cl1 (genotype 19) and P209 cl1 (genotype 20) T. cruzi stocks. Our results corroborate our hypothesis by showing that the T. cruzi genetic background in combination with specific Bz treatment has an important role in the Chagas disease reactivation in immunosuppressed animals. Copyright 2009 Elsevier B.V. All rights reserved. |
| PMID: 19854145 [PubMed - indexed for MEDLINE] | |
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| 8. | J Mol Graph Model. 2009 Nov;28(4):371-81. Epub 2009 Sep 23.Assaying phenothiazine derivatives as trypanothione reductase and glutathione reductase inhibitors by theoretical docking and molecular dynamics studies.Iribarne F, Paulino M, Aguilera S, Tapia O.Laboratorio de Bioinformática y BioModelado Molecular, Departamento de Experimentación y Teoría de la Estructura de la Materia y sus Aplicaciones, Facultad de Química, Universidad de la República, C.C. 1157, Montevideo, Uruguay. fede@fq.edu.uy A theoretical docking study, conducted on a sample of previously reported phenothiazine derivatives, at the binding sites of Trypanosoma cruzi trypanothione reductase (TR) and human erythrocyte glutathione reductase (GR), examines interaction energies (affinities) towards the parasite enzyme to check for selectivity with respect to the human counterpart. Phenothiazine compounds were previously shown to be TR inhibitors. The analysis of data collected from the docking procedure was undertaken both from the numeric and graphical standpoints, including the comparison of force field, energies, molecular contacts and spatial location of the different orientations that ligands acquired at the binding sites. Molecular Dynamics simulations were also carried out for derivatives with known quantitative inhibition kinetics (K(i)). The results indicate that (positively) charged phenothiazines attain larger interaction energies at TR active site, in line with previous experimental information. Suitable molecular size and shape is also needed to complement the electrostatic effect, as clearly evidenced by graphical analysis of output docked conformations. Docking energies values are reasonably well correlated with those obtained by Molecular Dynamics as well as with the experimental K(i) values, confirming once again the validity of this type of scoring methods to rapidly assess ligand-receptor affinities. Alongside newly discovered classes of TR inhibitors, the promazine (N-alkylaminopropylphenothiazine) nucleus should still be considered when good candidates are sought as leaders for selective TR inhibition. |
| PMID: 19801198 [PubMed - indexed for MEDLINE] | |
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| 9. | J Mol Graph Model. 2009 Nov;28(4):330-5. Epub 2009 Aug 31.Molecular docking of a series of peptidomimetics in the trypanothione binding site of T. cruzi trypanothione reductase.da Rocha Pita SS, Cirino JJ, de Alencastro RB, Castro HC, Rodrigues CR, Albuquerque MG.Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Química, Laboratório de Modelagem Molecular (LabMMol), Cidade Universitária, Ilha do Fundão, Centro de Tecnologia, Bloco A, 6(o) Andar, Sala 619, Rio de Janeiro, CEP 21941-909, RJ, Brazil. samuelpita@iq.ufrj.br Chagas' disease (CD) has been responsible for many deaths and disabilities mainly in South America. Currently, 40 million people are at risk of acquiring this disease and, existing therapies are still unsatisfactory, presenting harsh side effects. Therefore, the development of new chemical entities to reverse this state is critical. A series of peptidomimetics, developed by Mc Kie et al. (2001) [11], showed a reversible and competitive inhibition against Trypanosoma cruzi Trypanothione Reductase (TR). These inhibitors may be used as basis of lead compounds in the design of new drug candidates for the treatment of CD. In this work, we have docked this series of peptidomimetics into the TR binding site, using the FlexX algorithm as implemented in the Sybyl program, in order to access the binding mode of this class of compounds in the target enzyme. |
| PMID: 19766515 [PubMed - indexed for MEDLINE] | |
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| 10. | Acta Trop. 2010 Feb;113(2):195-8. Epub 2009 Sep 16.Transmissibility, by Glossina morsitans morsitans, of Trypanosoma congolense strains during the acute and chronic phases of infection.Masumu J, Akoda K, Van den Bossche P.University of Pretoria, Department of Veterinary Tropical Diseases, Private Bag X04, Onderstepoort 0110, Gauteng, South Africa. In order to verify whether chronic trypanosomal infections can affect the transmissibility of Trypanosoma congolense by tsetse flies, batches of Glossina morsitans morsitans were fed on mice infected with the same level of parasitemia (10(8.1)trypanosomes/ml of blood) of two cloned low virulent T. congolense strains during the acute and the chronic phases of infection. Results showed that the proportions of procyclic infections in flies that were fed during the acute phase (32.6% and 45.4% for isolates 1 and 2, respectively) were significantly higher (chi(2)=4.7, P<0.05 and chi(2)=23.7, P<0.0001, respectively) compared to the proportions of procyclic infections of flies fed during the chronic phase of infection (18.8% and 14.9% for isolates 1 and 2, respectively). Similarly the proportions of metacyclic infections in flies fed during the acute phase (32.6% and 45.4% for isolates 1 and 2, respectively) were significantly higher (chi(2)=6.3, P<0.05 and chi(2)=23.7, P<0.0001, respectively) compared to the proportions of metacyclic infections in flies fed during the chronic phase of infection (16.8% and 14.9% for isolates 1 and 2, respectively). No significant difference was found in the maturation rate of both strains during the acute phase compared to the chronic phase of infection (P>0.05). The results of this study suggest that T. congolense loses part of its transmissiblity by tsetse flies during the chronic phase of infection. Copyright 2009. Published by Elsevier B.V. |
| PMID: 19765543 [PubMed - indexed for MEDLINE] | |
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