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Sent on Wednesday, 2011 Jul 27Search 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. 2011 Jul 26. [Epub ahead of print]Antitrypanosomal activity of some medicinal plants from Nigerian ethnomedicine.Abiodun OO, Gbotosho GO, Ajaiyeoba EO, Brun R, Oduola AM.SourceDepartment of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria, oyinoduola@yahoo.co.uk. AbstractHuman African trypanosomiasis is a neglected tropical disease with complex clinical presentation, diagnosis, and difficult treatment. The available drugs for the treatment of trypanosomiasis are old, expensive, and less effective, associated with severe adverse reactions and face the problem of drug resistance. This situation underlines the urgent need for the development of new, effective, cheap, and safe drugs for the treatment of trypanosomiasis. The search for new antitrypanosomal agents in this study is based on ethnomedicine. In vitro antitrypanosomal activity of 36 plant extracts from 10 plant species from Nigerian ethnomedicine was evaluated against bloodstream forms of Trypanosoma brucei rhodesiense STIB 900. Cytotoxic activity was determined against mammalian L6 cells. Alamar blue assay was used to measure the endpoint of both antitrypanosomal and toxicity assays. The ethyl acetate extract of leaves of Ocimum gratissimum Linn. (Labiatae) showed the highest antitrypanosomal activity (IC(50) of 2.08 ± 0.01 μg/ml) and a high selective index of 29. Furthermore, the hexane, ethyl acetate, or methanol extracts of Trema orientalis (L.) Blume (Ulmaceae), Pericopsis laxiflora (Benth. ex Baker) Meeuwen, Jatropha curcas Linn. (Euphorbiaceae), Terminalia catappa Linn. (Combretaceae), and Vitex doniana Sweet (Verbenaceae) displayed remarkable antitrypanosomal activity (IC(50) 2.1-17.2 μg/ml) with high selectivity indices (20-80) for trypanosomes. The antitrypanosomal activity of T. catappa and T. orientalis against T. brucei rhodesiense (STIB 900) is being reported for the first time in Nigerian ethnomedicine, and these plants could be a potential source of antitrypanosomal agents. |
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| 2. | Antimicrob Agents Chemother. 2011 Jul 25. [Epub ahead of print]Utility of carbaporphyrin ketals (dimethyl, diethyl) in the treatment of cutaneous leishmaniasis: Studies in vitro and in vivo.Taylor VM, Cedeño DL, Muñoz DL, Jones MA, Lash TD, Young AM, Constantino MH, Esposito N, Vélez ID, Robledo SM.SourcePECET, School of Medicine, Universidad de Antioquia, MedellÃn, Colombia. AbstractCarbaporphyrin ketals are porphyrinoid compounds in which a pyrrole ring of a typical porphyrin macrocycle has been replaced by a ketal-substituted indene ring. It was recently demonstrated that these compounds are effective in vitro against Leishmania tarentolae. Their in vitro effectiveness is increased when exposed to visible light, acting as photosensitizers capable of mediating the production of reactive oxygen species (ROS). Following on this evidence, the effectiveness and cytotoxicity of the dimethyl and diethyl carbaporphyrin ketals (CKOMe and CKOEt) were determined in vitro using pathogenic Leishmania species with and without exposure to visible light (2 and 4 hours). The effectiveness on various pathogenic Leishmania species was determined to be in a micromolar range. Additionally, the effect of encapsulating the carbaporphyrin ketals in liposome formulations was tested. Liposomal delivery diminished their toxicity while the effectiveness was enhanced upon exposure to visible light (photodynamic effect). The cytotoxicity in both human U937 cells and hamster peritoneal macrophages were in the ranges 0.3-9 μM and 7-330 μM respectively. When tested in vivo, using a hamster (Mesocricetus auratus) model of cutaneous leishmaniasis, CKOMe was active even in the dark suggesting that the compound once metabolized in the animal tissue produces an active ingredient that does not seem to be photosensitive. Reduction in lesion size, histopathologic analyses and smears confirmed the in vivo effectiveness of the compound since the parasitic load was diminished without noticeable toxic effects. |
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| 3. | Vaccine. 2011 Jul 22. [Epub ahead of print]Natural products and the search for novel vaccine adjuvants.Rey-Ladino J, Ross AG, Cripps AW, McManus DP, Quinn R.SourceGriffith Health Institute, School of Public Health, Griffith University, Logan Campus, Meadowbrook, Queensland 4131, Australia. AbstractVaccines that protect against intracellular infections such as malaria, Leishmania and Chlamydia require strong cellular responses based on CD4(+) T cells and CD8(+) T cells in addition to antibodies. Such cell-mediated responses can be potentiated with adjuvants. However, very few adjuvants have been licensed for use in humans; thus there is an urgent need for the discovery of new non-toxic adjuvants in order to produce more efficacious vaccines. Until recently, the mechanisms of how adjuvants worked remained largely unknown, but, it is becoming clearer that many function via host germline-encoded pattern recognition receptors (PRRs) expressed by most immune and non-immune cells. Most PRRs sense infection and transmit a series of signals that ultimately lead to the development of immunity. PRR mediated signalling can be harnessed to search for new vaccine adjuvants. Dendritic cells (DCs) express many PRRs and are remarkably effective at directing T cell immunity. Natural products (NPs) have been the basis of many drugs and are a rich source of immune activators and/or regulators of the immune response. Here we review PRRs in the context of NPs and propose the use of DCs as biological probes to help identify novel immune type molecules and adjuvants within collections of NPs. Copyright © 2011. Published by Elsevier Ltd. |
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| 4. | Int J Parasitol. 2011 Jul 13. [Epub ahead of print]Early activated Th-1 type and dominantly diverse natural killer T (CD3(+)CD161(+)Vα24(-)) cells in bone marrow among visceral leishmaniasis patients.Rai AK, Thakur CP, Seth T, Mitra DK.SourceDepartment of Transplant Immunology and Immunogenetics, All India Institutes of Medical Sciences, Ansari Nagar, New Delhi 110029, India. AbstractLipid antigens of Leishmania donovani-like lipophosphoglycans (LPG) are demonstrated to be a potent ligand for natural killer T (NKT) cell activation. Little is known about the phenotype or function of these cells and their trafficking pattern to the bone marrow (BM) of visceral leishmaniasis (VL) patients. Their precise role in humans still requires pathological validation. The study included 42 parasitologically confirmed patients (mean age 24.80±16.26years; range 3-70years; 25 males and 17 females), 33 healthy contact subjects (family/non-family members) and normal BM specimens (NBM; n=9). Enumeration of NKT cells and quantification of parasites (before and after therapy) were performed for the recruited patients. Results established that non-CD1d restricted, diverse cells are the dominant population among resident but not enriched NKT (CD3(+)CD161(+)) cells at the disease site (BM). Expression profiles for various markers are indicative of their early activated (CD69(+), CD62L(low), CD11a(high)) CCR5(+) phenotype at the BM. Functionally, BM-derived NKT cells were dominantly producing IFN-γ in response to L. donovani antigen in vitro. Given these observations, these data indicate that CD3(+)CD161(+) diverse NKT cells are heterogeneous in function and of the dominant Th-1 phenotype at the disease site. Copyright © 2011. Published by Elsevier Ltd. |
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| 5. | Genome Biol. 2011 Jul 25;12(7):R66. [Epub ahead of print]The minimal kinome of Giardia lamblia illuminates earl y kinase evolution and unique parasite biology.Manning G, Reiner DS, Lauwaet T, Dacre M, Smith A, Zhai Y, Svard S, Gillin FD.AbstractABSTRACT: BACKGROUND:The major human intestinal pathogen, Giardia lamblia is a very early-branching eukaryote with a minimal genome of broad evolutionary and biological interest. RESULTS:To explore early kinase evolution and regulation of Giardia biology, we cataloged the kinomes of three sequenced strains. Comparison with published kinomes and those of the excavates Trichomonas vaginalis and Leishmania major shows that Giardia's 80 core kinases constitute the smallest known core kinome of any eukaryote that can be grown in pure culture, reflecting both its early origin and secondary gene loss. Kinase losses in DNA repair, mitochondrial function, transcription, splicing, and stress response reflect this reduced genome, while the presence of other kinases helps define the kinome of the last common eukaryotic ancestor. Immunofluorescence analysis shows abundant phospho-staining in trophozoites, with phosphotyrosine abundant in the nuclei and phosphothreonine and phosphoserine in distinct cytoskeletal organelles. The Nek kinase family has been massively expanded, accounting for 198 of the 278 protein kinases in Giardia. Most Neks are catalytically inactive, have very divergent sequences and undergo extensive duplication and loss between strains. Many Neks are highly induced during development. We localized four catalytically active Neks to distinct parts of the cytoskeleton and one inactive Nek to the cytoplasm. CONCLUSION:The reduced kinome of Giardia sheds new light on early kinase evolution, and its highly divergent sequences add to the definition of individual kinase families as well as offering specific drug targets. Giardia's massive Nek expansion may reflect its distinctive lifestyle, biphasic life cycle and complex cytoskeleton. |
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| 6. | Biochem Soc Trans. 2011 Aug 1;39(4):966-70.An expanded family of proteins with BPI/LBP/PLUNC-like domains in trypanosome parasites: an association with pathogenicity?Gluenz E< /a>, Barker AR, Gull K.SourceSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, U.K. AbstractTrypanosomatids are protozoan parasites that cause human and animal disease. Trypanosoma brucei telomeric ESs (expression sites) contain genes that are critical for parasite survival in the bloodstream, including the VSG (variant surface glycoprotein) genes, used for antigenic variation, and the SRA (serum-resistance-associated) gene, which confers resistance to lysis by human serum. In addition, ESs contain ESAGs (expression-site-associated genes), whose functions, with few exceptions, have remained elusive. A bioinformatic analysis of the ESAG5 gene of T. brucei showed that it encodes a protein with two BPI (bactericidal/permeability-increasing protein)/LBP (lipopolysaccharide-binding protein)/PLUNC (palate, lung and nasal epithelium clone)-like domains and that it belongs to a multigene family termed (GR)ESAG5 (gene related to ESAG5). Members of this family are found with various copy number in different members of the Trypanosomatidae family. T. brucei has an expanded repertoire, with multiple ESAG5 copies and at least five GRESAG5 genes. In contrast, the parasites of the genus Leishmania, which are intracellular parasites, have only a single GRESAG5 gene. Although the amino acid sequence identity between the (GR)ESAG5 gene products between species is as low as 15-25%, the BPI/LBP/PLUNC-like domain organization and the length of the proteins are highly conserved, and the proteins are predicted to be membrane-anchored or secreted. Current work focuses on the elucidation of possible roles for this gene family in infection. This is likely to provide novel insights into the evolution of the BPI/LBP/PLUNC-like domains. |
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| 7. | J Agric Food Chem. 2011 Jul 25. [Epub ahead of print]Antiplasmodial and Antitrypanosomal Activity of Pyrethrins and Pyrethroids.Hata Y, Zimmermann S, Quitschau M, Kaiser M, Hamburger M, Adams M.AbstractIn a screen of 1800 plant and fungal extracts for antiplasmodial, antitrypanosomal and leishmanicidal activity, the n-hexane extract of Chrysanthemum cinerariifolium (Trevir.) Vis. flowers showed strong activity against Plasmodium falciparum. We isolated the five pyrethrins pyrethrin II (1), jasmolin II (2), cinerin II (3), pyrethrin I (4), and jasmolin I (5), which together constitute a large part of this extract and tested them alongside 15 synthetic pyrethroids for their activity against P. falciparum and T. brucei rhodesiense, and for cytotoxicity in rat myoblast L6 cells. The pyrethrins showed antiplasmodial activity with IC50s between 4 and 12 µM, and antitrypanosomal activity with IC50s from 7 to 31 µM. The pyrethroids exhibited weaker antiplasmodial and antitrypanosomal activity than the pyrethrins. Both pyrethrins and pyrethroids showed moderate cytotoxicity against L6 cells. Pyrethrin II (1) was the most selective antiplasmodial compound, with a selectivity index of 24. |
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| 8. | Biochem Biophys Res Commun. 2011 May 13;408(3):427-31. Epub 2011 Apr 13.Biochemical characterization of a protein tyrosine phosphatase from Trypanosoma cruzi involved in metacyclogenesis and cell invasion.Gallo G, Ramos TC, Tavares F, Rocha AA, Machi E, Schenkman S, Bahia D, Pesquero JB, Würtele M.SourceDepartamento de BiofÃsica, Universidade Federal de São Paulo, Rua Botucatu 862, 04023-062 São Paulo, Brazil. AbstractProtein tyrosine phosphatases (PTPs) form a large family of enzymes involved in the regulation of numerous cellular functions in eukaryotes. Several protein tyrosine phosphatases have been recently identified in trypanosomatides. Here we report the purification and biochemical characterization of TcPTP1, a protein tyrosine phosphatase from Trypanosoma cruzi, the causing agent of Chagas' disease. The enzyme was cloned and expressed recombinantly in Escherichia coli and purified by Ni-affinity chromatography. Biochemical characterization of recombinant TcPTP1 with the PTP pseudo-substrate pNPP allowed the estimation of a Michaelis-Menten constant K(m) of 4.5mM and a k(cat) of 2.8s(-1). We were able to demonstrate inhibition of the enzyme by the PTP1b inhibitor BZ3, which on its turn was able to accelerate the differentiation of epimastigotes into metacyclic forms of T. cruzi induced by nutritional stress. Additionally, this compound was able to inhibit by 50% the infectivity of T. cruzi trypomastigotes in a separate cellular assay. In conclusion our results indicate that TcPTP1 is of importance for cellular differentiation and invasivity of this parasite and thus is a valid target for the rational drug design of potential antibiotics directed against T. cruzi. Copyright © 2011 Elsevier Inc. All rights reserved. |
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| 9. | Parasitology. 2011 Apr;138(5):593-601. Epub 2011 Jan 27.Involvement of host cell heparan sulfate proteoglycan in Trypanosoma cruzi ama stigote attachment and invasion.Bambino-Medeiros R, Oliveira FO, Calvet CM, Vicente D, Toma L, Krieger MA, Meirelles MN, Pereira MC.SourceLaboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz/FIOCRUZ, Av Brasil 4365, Manguinhos, Rio de Janeiro 21045-900, Brazil. mirian@ioc.fiocruz.br AbstractCell surface glycosaminoglycans (GAGs) play an important role in the attachment and invasion process of a variety of intracellular pathogens. We have previously demonstrated that heparan sulfate proteoglycans (HSPG) mediate the invasion of trypomastigote forms of Trypanosoma cruzi in cardiomyocytes. Herein, we analysed whether GAGs are also implicated in amastigote invasion. Competition assays with soluble GAGs revealed that treatment of T. cruzi amastigotes with heparin and heparan sulfate leads to a reduction in the infection ratio, achieving 82% and 65% inhibition of invasion, respectively. Other sulfated GAGs, such as chondroitin sulfate, dermatan sulfate and keratan sulfate, had no effect on the invasion process. In addition, a significant decrease in infection occurred after interaction of amastigotes with GAG-deficient Chinese Hamster Ovary (CHO) cells, decreasing from 20% and 28% in wild-type CHO cells to 5% and 9% in the mutant cells after 2 h and 4 h of infection, respectively. These findings suggest that amastigote invasion also involves host cell surface heparan sulfate proteoglycans. The knowledge of the mechanism triggered by heparan sulfate-binding T. cruzi proteins may provide new potential candidates for Chagas disease therapy. |
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| 10. | Top Curr Chem. 2011;301:31-68.A survey of Ley's reactivity tuning in oligosaccharide synthesis.Gómez AM.SourceInstituto de QuÃmica Orgánica General (CSIC), Juan de la Cierva 3, 28006, Madrid, Spain. anagomez@iqog.csic.es AbstractThis chapter summarizes the concepts and chemistry developed by Ley's group in relation to the relevance of reactivity tuning in oligosaccharide coupling reactions. The recognition that protecting groups affect the reactivity of glycosyl donors allowed Ley's group to make imaginative use of their 1,2-diacetal protecting groups. The combination of 1,2-diacetals with the presence of different anomeric leaving groups provides up to four different levels of reactivity. The exploitation of these reactivity levels in chemoselective glycosylation processes (reactivity tuning) has allowed the development of highly simplified routes to several complex oligosaccharides in step-wise or one-pot procedures. |
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