What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2010 Aug 26
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 5 of 5

1.	Heredity. 2010 Aug 25. [Epub ahead of print] Multiple genetic divergences and population expansions of a Mediterranean sandfly, Phlebotomus ariasi, in Europe during the Pleistocene glacial cycles. Mahamdallie SS, Pesson B, Ready PD. Department of Entomology, Natural History Museum, London, UK. Abstract Phlebotomus ariasi is one of the two sandflies transmitting the causative agent of zoonotic leishmaniasis, Leishmania infantum, in France and Iberia, and provides a rare case study of the postglacial re-colonization of France by a Mediterranean species. Four DNA sequences were analysed-mitochondrial cytochrome b (cyt b), nuclear elongation factor-1alpha (EF-1alpha) and two anonymous nuclear loci-for 14-15 French populations and single populations from northeast Spain, northwest Spain, Portugal and Morocco. The presence of cryptic sibling species was not revealed by phylogenetic analyses and testing for reproductive isolation between sympatric populations defined by the two most divergent cyt b haplogroups. No locus was shown to be under positive directional or balancing selection and, therefore, molecular variation was explained demographically. Each nuclear locus showed shallow isolation by distance from Portugal to the French Pyrenees, but for both cyt b and EF-1alpha there was then a step change to the upland Massif Central, where leading-edge populations showed low diversity at all loci. Multiple genetic divergences and population expansions were detected by analyses of cyt b and dated to the Pleistocene. Endemicity of one cyt b sub-lineage suggested the presence of a refuge north of the Pyrenees during the last glacial period. Monopolization of the Massif Central by genetically differentiated populations of P. ariasi might possibly hinder the northwards spread of leishmaniasis.Heredity advance online publication, 25 August 2010; doi:10.1038/hdy.2010.111.
	PMID: 20736970 [PubMed - as supplied by publisher]

2.	Mol Microbiol. 2010 Aug 2. doi: 10.1111/j.1365-2958.2010.07328.x. [Epub ahead of print] Purine Restriction Induces Pronounced Translational Upregulation of the NT1 Adenosine/Pyrimidine Nucleoside Transporter in Leishmania major. Ortiz D, Valdés R, Sanchez MA, Hayenga J, Elya C, Detke S, Landfear SM. Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon 97239 Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota 58202. Abstract Leishmania and other parasitic protozoa are unable to synthesize purines de novo and are reliant upon purine nucleoside and nucleobase transporters to import preformed purines from their hosts. To study the roles of the four purine permeases NT1-NT4 in Leishmania major, null mutants in each transporter gene were prepared and the effect of each gene deletion on purine uptake was monitored. Deletion of the NT3 purine nucleobase transporter gene or both NT3 and the NT2 nucleoside transporter gene resulted in pronounced upregulation of adenosine and uridine uptake mediated by the NT1 permease and also induced up to a 200-fold enhancement in the level of the NT1 protein but not mRNA. A similar level of upregulation of NT1 was achieved in wild type promastigotes that were transferred to medium deficient in purines. Pulse labeling and treatment of cells with the translation inhibitor cycloheximide revealed that control of NT1 expression occurs primarily at the level of translation and not protein turnover. These observations imply the existence of a translational control mechanism that enhances the ability of Leishmania parasites to import essential purines when they are present at limiting concentrations.
	PMID: 20735779 [PubMed - as supplied by publisher]

3.	Curr Drug Targets. 2010 Aug 25. [Epub ahead of print] Targeting Trypanothione Metabolism in Trypanosomatid Human Parasites. Olin-Sandoval V, Moreno-Sánchez R, Saavedra E. Departamento de Bioquímica, Instituto Nacional de Cardiología, México D.F., 14080, México. emma_saavedra2002@yahoo.com. Abstract The diseases caused by the trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania are widely distributed throughout the world. Because of the toxic side-effects and the economically unviable cost of the currently used pharmaceutical treatments, the search for new drug targets continues. Since the antioxidant metabolism in these parasites relies on trypanothione [T(SH)(2)], a functional analog of glutathione, most of the pathway enzymes involved in its synthesis, utilization and reduction have been proposed as drug targets for therapeutic intervention. In the present review, the antioxidant metabolism and the phenotypic effects of inhibiting by genetic (RNA interference, knock-out) or chemical approaches, the T(SH)(2) and polyamine pathway enzymes in the parasites is analyzed. Although the genetic strategies are helpful in identifying essential genes for parasite survival/infectivity, they are less useful for drug-target validation. The effectiveness of targeting each pathway enzyme was evaluated by considering (i) the enzyme kinetic properties and antioxidant metabolite concentrations and (ii) the current knowledge and experimental approaches to the study of the control of fluxes and intermediary concentrations in metabolic pathways. The metabolic control analysis indicates that highly potent and specific inhibitors have to be designed for trypanothione reductase and the peroxide detoxification system, and hence other enzymes emerge (gamma-glutamylcysteine synthetase, trypanothione synthetase, ornithine decarboxylase, S-adenosylmethionine decarboxylase and polyamine transporters) as alternative more suitable and effective drug targets in the antioxidant metabolism of trypanosomatids.
	PMID: 20735352 [PubMed - as supplied by publisher]

4.	Clin Infect Dis. 2010 Aug 24. [Epub ahead of print] Iatrogenic Transmission of Human T Cell Lymphotropic Virus Type 1 and Hepatitis C Virus through Parenteral Treatment and Chemoprophylaxis of Sleeping Sickness in Colonial Equatorial Africa. Pépin J, Labbé AC, Mamadou-Yaya F, Mbélesso P, Mbadingaï S, Deslandes S, Locas MC, Frost E. Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, and 2Department of Microbiology and Immunology, Université de Montréal, Montreal, Quebec, Canada; 3Ministry of Public Health and 4Faculty of Health Sciences, University of Bangui, Bangui, Central African Republic. Abstract Background. The simultaneous emergence of human immunodeficiency virus (HIV)-1 group M and HIV-2 into human populations, circa 1921-1940, is attributed to urbanization and changes in sexual behavior. We hypothesized that the initial dissemination of HIV-1, before sexual transmission predominated, was facilitated by the administration, via reusable syringes and needles, of parenteral drugs against tropical diseases. As proxies for highly lethal HIV-1, we investigated risk factors for hepatitis C virus (HCV) and human T cell lymphotropic virus 1 (HTLV-1) infections, blood-borne viruses compatible with prolonged survival, in an area known in 1936-1950 as the most virulent focus of African trypanosomiasis. Methods. Cross-sectional survey of individuals 55 years and older in Mbimou land and Nola, Central African Republic. Dried blood spots were used for HCV and HTLV-1 serologic testing and nucleic acid detection. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were measured by logistic regression. Results. The only risk factor for HCV genotype 4 infection was treatment of trypanosomiasis before 1951 (OR, 3.13; 95% CI, 1.38-7.09). HTLV-1 infection was associated with having received 2 injections of pentamidine for trypanosomiasis chemoprophylaxis (adjusted OR, 2.03; 95% CI, 1.01-4.06) and with transfusions (adjusted OR, 2.82; 95% CI, 1.04-7.67). From historical data, we predicted that 59% of Mbimous 65 years and older would report treatment for trypanosomiasis before 1951; only 11% did so. Conclusions. Treatment of trypanosomiasis before 1951 may have caused iatrogenic HCV transmission. Population-wide half-yearly intramuscular pentamidine for trypanosomiasis chemoprophylaxis in 1947-1953 may have caused iatrogenic HTLV-1 transmission. These and other interventions against tropical diseases could have iatrogenically transmitted SIV(cpz), jump-starting the HIV-1 epidemic. The excess mortality among patients with trypanosomiasis treated before 1951 supports this hypothesis.
	PMID: 20735238 [PubMed - as supplied by publisher]

5.	Tanzan J Health Res. 2009 Oct;11(4):226-34. Antiplasmodial, anti-trypanosomal, anti-leishmanial and cytotoxicity activity of selected Tanzanian medicinal plants. Malebo HM, Tanja W, Cal M, Swaleh SA, Omolo MO, Hassanali A, Séquin U, Hamburger M, Brun R, Ndiege IO. National Institute for Medical Research, P.O. Box 9653, Dar es Salaam, Tanzania. Abstract The antiplasmodial, anti-trypanosomal and anti-leishmanial activity of 25 plant extracts obtained from seven Tanzanian medicinal plants: Annickia (Enantia) kummeriae (Annonaceae), Artemisia annua (Asteraceae), Pseudospondias microcarpa (Anacardiaceae), Drypetes natalensis (Euphorbiaceae), Acridocarpus chloropterus (Malpighiaceae), Maytenus senegalensis (Celastraceae) and Neurautanenia mitis (Papilonaceae), were evaluated in vitro against Plasmodium falciparum K1, Trypanosoma brucei rhodesiense STIB 900 and axenic Leishmania donovani MHOM-ET-67/82. Out of the 25 extracts tested, 17 showed good antiplasmodial activity (IC50 0.04-5.0 microg/ml), 7 exhibited moderate anti-trypanosomal activity (IC50 2.3-2.8 microg/ml), while 5 displayed mild anti-leishmanial activity (IC50 8.8-9.79 microg/ml). A. kummeriae, A. annua, P. microcarpa, D. natalensis, M. senegalensis and N. mitis extracts had good antiplasmodial activity (IC50 0.04-2.1 microg/ml) and selectivity indices (29.2-2,250 microg/ml). The high antiplasmodial, moderate anti-trypanosomal and mild anti-leishmanial activity make these plants good candidates for bioassay-guided isolation of anti-protozoal compounds which could serve as new lead structures for drug development.
	PMID: 20734703 [PubMed - in process]