What's new for 'Trypanosomatids' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

Sender's message:

Sent on Wednesday, 2010 Dec 01
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
Click here to view complete results in PubMed. (Results may change over time.)
To unsubscribe from these e-mail updates click here.

PubMed Results

Items 1 - 10 of 11

1.	Antimicrob Agents Chemother. 2010 Nov 29. [Epub ahead of print] An in silico screening, structure-activity relationship and biologic evaluation of selective pteridine reductase inhibitors targeting visceral leishmaniasis. Kaur J, Kumar P, Tyagi S, Pathak R, Batra S, Singh P, Singh N. Drug Target Discovery & Development & Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattar Manzil Palace, P.O. Box No. 173, Lucknow-226001, CSIR, India; Connexious Life Sciences, Bangalore, India; Department of Chemistry, D.A.V. (P.G.) College, Dehradun-248001, India. Abstract In this study we have utilized the concept of rational drug design to identify novel compounds with optimal selectivity, efficacy and safety, which would bind to the target enzyme pteridine reductase (PTR1) in Leishmania parasites. Twelve compounds afforded from Baylis-Hillman chemistry were docked using QUANTUM program into the active site of Leishmania donovani PTR1 (LdPTR1) homology model. Biological activity for these compounds was estimated in green fluorescent protein (GFP) transfected L. donovani promastigotes and the most potential analogue was further investigated in intracellular amastigotes. Structure-activity relationship based on homology model drawn on our recombinant enzyme was substantiated by recombinant enzyme inhibition assay and growth of the cell culture. Flow cytometry results indicated that 7-(4-chlorobenzyl)-3-methyl-4-(4-trifluoromethyl-phenyl)-3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-one (7) was ten times more active on L. donovani amastigotes (IC50=3 μM) than on promastigotes (IC50=29 μM). The 7 exhibited Ki value of 0.72 μM in recombinant enzyme inhibition assay. We have discovered that novel pyrimido[1, 2-a]pyrimidin-2-one systems generated from the allyl amines afforded from the Baylis-Hillman acetates could have potential as a valuable pharmacological tool against the neglected disease visceral leishmaniasis (VL).
	PMID: 21115787 [PubMed - as supplied by publisher]

2.	Hum Exp Toxicol. 2010 Dec;29(12):980-1015. Resveratrol commonly displays hormesis: Occurrence and biomedical significance. Calabrese EJ, Mattson MP, Calabrese V. Department of Public Health, Environmental Health Sciences, University of Massachusetts, Amherst, MA, USA. edwardc@schoolph.umass.edu. Abstract Resveratrol induces hormetic dose responses in a wide range of biological models, affecting numerous endpoints of biomedical and therapeutic significance. These responses were reported for numerous human tumor cell lines affecting breast, prostate, colon, lung, uterine and leukemia. In such cases, low concentrations of resveratrol enhanced tumor cell proliferation whereas higher concentrations were inhibitory. Similar resveratrol-induced biphasic dose responses were seen with several parasitic diseases, including Leishmaniasis and trichinella. Hormetic effects were also reported in animal models for cardiovascular induced injury, gastric lesions, ischemic stroke, Alzheimer's disease and osteoporosis. In these cases, there was often a protective effect at low doses but an adverse effect at higher doses, exacerbating the disease process/incidence. This analysis indicates that many effects induced by resveratrol are dependent on dose and that opposite effects occur at low and high doses, being indicative of a hormetic dose response. Despite consistent occurrence of hormetic dose responses of resveratrol in a wide range of biomedical models, epidemiologic and clinical trials are needed to assess the nature of its dose-response in humans.
	PMID: 21115559 [PubMed - in process]

3.	FEBS Lett. 2010 Nov 26. [Epub ahead of print] Identification and functional characterization of a poly(A)-binding protein from Leishmania infantum (LiPABP). Guerra N, Vega-Sendino M, Pérez-Morgado MI, Ramos E, Soto M, Gonzalez VM, Elena Martín M. Servicio de Bioquímica-Investigación, Hospital Ramón y Cajal, IRyCIS, 28034 Madrid, Spain. Abstract Gene expression regulation in Leishmania has been related to post-transcriptional events involving mainly sequences present in the 5' and 3' UTRs. PABPs are high-affinity poly(A)-binding proteins that are implicated in the regulation of translation initiation, RNA stability and other important biological processes. We describe a poly(A)-binding protein from Leishmania infantum (LiPABP) that shows a very high homology with PABPs from other eukaryotic organisms, including mammals and other parasites. LiPABP conserves the main domains present in other PABPs, maintains poly(A)-binding properties and is phosphorylated by p38 MAPK. Using the sera from dogs infected with L. infantum, we demonstrate that LiPABP is expressed in L. infantum promastigotes. Copyright © 2010. Published by Elsevier B.V.
	PMID: 21115009 [PubMed - as supplied by publisher]

4.	Bioorg Med Chem. 2010 Nov 5. [Epub ahead of print] Synthesis and antitrypanosomal evaluation of derivatives of N-benzyl-1,2-dihydroquinolin-6-ols: Effect of core substitutions and salt formation. Reid CS, Patrick DA, He S, Fotie J, Premalatha K, Tidwell RR, Wang MZ, Liu Q, Gershkovich P, Wasan KM, Wenzler T, Brun R, Werbovetz KA. Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA. Abstract Analogs of the trypanocidal lead compound 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate were prepared to extend the structure-activity relationship in this series of molecules, improve the in vivo antitrypanosomal activity of the lead, and determine whether ester prodrugs are needed to overcome the instability of the dihydroquinolin-6-ols. Two of the most active compounds identified in this study were 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-(2-methoxy)benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride. These stable solids possessed low nanomolar IC(50) values against Trypanosoma brucei rhodesiense STIB900 in vitro and provided cures in an early treatment acute mouse model of African trypanosomiasis when given ip at 50mg/kg/day for four consecutive days. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 21112788 [PubMed - as supplied by publisher]
	Related citations

5.	Exp Parasitol. 2010 Nov 24. [Epub ahead of print] Leishmania chagasi: An ecto- 3'-nucleotidase activity modulated by inorganic phosphate and its possible involvement in parasite-macrophage interaction. Vieira DP, da Silva RP, Saraiva EM, Lopes AH, Meyer-Fernandes JR. Instituto de Microbiologia Prof. Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, UFRJ;Cidade Universitária, Ilha do Fundão, Rio de Janeiro, R.J. 21941-590, Brasil; Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, UFRJ;Cidade Universitária, Ilha do Fundão, Rio de Janeiro, R.J. 21941-590, Brasil. Abstract In this work we showed that living cells of Leishmania chagasi was able to hydrolyze 3'AMP ten times more than 5'AMP. When parasites were grown in a low phosphate concentration (2 mM) the cellular proliferation decreased by 50% compared to cells grown in the presence of a high phosphate concentration (80 mM). However, the ecto-3'nucleotidase activity was two-fold higher when L. chagasi was grown in a low phosphate concentration. This modulation observed on ecto-3'nucleotidase activity was not observed on ecto-5'nucleotidase activity. These results suggest that low concentration of Pi in the culture medium modulates ecto-3'nucleotidase activity that may lead to modulation of important processes for the cell. Interestingly, the macrophage-parasite interaction increased by 45% when Leishmania chagasi were grown at low phosphate concentration compared to the parasites grown in the presence of high phosphate source. Altogether, the results described here suggest that 3'nucleotidase activity modulated by external stimuli, Pi concentration, could be involved on parasite-macrophage interaction. Copyright © 2010 Elsevier Inc. All rights reserved.
	PMID: 21111737 [PubMed - as supplied by publisher]
	Related citations

6.	Biomed Pharmacother. 2010 Nov 5. [Epub ahead of print] Thiopurine derivatives containing triazole and steroid: Synthesis, antimalarial and antileishmanial activities. Corrales RC, de Souza NB, Pinheiro LS, Abramo C, Coimbra ES, Da Silva AD. Departamento de Química, ICE, Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900, Brazil. Abstract A series of novel 6-thiopurine derivates containing 1,2,3-triazole were synthesized and their in vivo antimalarial activity and in vitro antileishmanial activity were examined. The compounds 10, 11, 12 and 14 presented higher values of inhibition of parasite multiplication than chloroquine. For antileishmanial activity, the compound 14 showed activity against the three species of Leishmania tested. None of compounds showed cytotoxicity against mammalian cells. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
	PMID: 21111565 [PubMed - as supplied by publisher]
	Related citations

7.	Mol Biochem Parasitol. 2010 Nov 23. [Epub ahead of print] The Four Trypanosomatid eIF4E Homologues Fall into Two Separate Groups; with D istinct Features in Primary Sequence and Biological Properties. Freire ER, Dhalia R, Moura DM, Lima TD, Lima RP, Reis CR, Hughes K, Figueiredo RC, Standart N, Carrington M, Neto OP. Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Av. Moraes Rego s/n, Campus UFPE, Recife PE 50670-420. Abstract Translation initiation in eukaryotes requires eIF4E, the cap binding protein, which mediates its function through an interaction with the scaffolding protein eIF4G, as part of the eIF4F complex. In trypanosomatids, four eIF4E homologues have been described but the specific function of each is not well characterized. Here, we report a study of these proteins in Trypanosoma brucei (TbEIF4E1 through 4). At the sequence level, they can be assigned to two groups; TbEIF4E1 and 2, similar in size to metazoan eIF4E1; and TbEIF4E3 and 4, with long N-terminal extensions. All are constitutively expressed, but whilst TbEIF4E1 and 2 localise to both the nucleus and cytoplasm, TbEIF4E3 and 4 are strictly cytoplasmic and are also more abundant. After knockdown through RNAi, TbEIF4E3 was the only homologue confirmed to be essential for viability of the insect procyclic form. In contrast, TbEIF4E1, 3 and 4 were all essential for the mammalian bloodstream form. Simultaneous RNAi knockdown of TbEIF4E1 and 2 caused cessation of growth and death in procyclics, but with a delayed impact on translation, whilst knockdown of TbEIF4E3 alone or a combined TbEIF4E1 and 4 knockdown led to substantial translation inhibition which preceded cellular death by several days, at least. Only TbEIF4E3 and 4 were found to interact with T. brucei eIF4G homologues; TbEIF4E3 bound both TbEIF4G3 and 4 whilst TbEIF4E4 bound only to TbEIF4G3. These results are consistent with TbEIF4E3 and 4 having distinct but relevant roles in initiation of protein synthesis. Copyright © 2010. Published by Elsevier B.V.
	PMID: 21111007 [PubMed - as supplied by publisher]
	Related citations

8.	Exp Parasitol. 2010 Nov 23. [Epub ahead of print] Leishmania chagasi: effect of the iron deficiency on the infection in BALB/c mice. Malafaia G, de Nadai Marcon L, de Fátima Pereira L, Pedrosa ML, Rezende SA. Laboratório de Ciências Ambientais, Departamento de Ciências Biológicas, Instituto Federal de Educação, Ciência e Tecnologia Goiano - Campus Urutaí (IF Goiano), Núcleo de Pesquisa em Ciências Ambientais e Biológicas (NPCAB). Abstract Iron deficiency and visceral leishmaniasis are serious problems of public health. The aim of this study was to evaluate the effect of iron deficiency, induced by the iron chelator desferrioxamine, on the course of the infection by Leishmania chagasi in BALB/c mice. Our data show that the iron chelator caused significant reduction in hemoglobin concentration of treated mice and reduction in parasite load in spleen and liver. Significant differences were not observed in the production of IFN-gamma and IL-4 among the experimental groups. In conclusion, the data reported in this paper suggest that iron deficiency may favor the host. If there is not enough iron available to the parasite, its multiplication may be reduced and infection attenuated. Copyright © 2010. Published by Elsevier Inc.
	PMID: 21110973 [PubMed - as supplied by publisher]
	Related citations

9.	Acta Trop. 2010 Nov 23. [Epub ahead of print] Phlebotominae fauna (Diptera: Psychodidae) in an urban district of Belo Horizonte; Brazil; endemic for visceral leishmaniasis: characterization of favored locations as determined by spatial analysis. Saraiva L, Filho JD, Falcão AL, Carvalho DA, Margonari C, Freitas CR, Gomes CR, Moreno EC, Melo MN. Departamento de Parasitologia, Instituto de Ciências Biológicas- Universidade Federal de Minas Gerais CP 486, 31270-907, Belo Horizonte, MG. Abstract Belo Horizonte, the capital of the southeastern state of Minas Gerais, Brazil, and the fourth-largest city in the country, has the highest incidence of human visceral leishmaniasis (VL) together with a high prevalence of canine VL. The Northeast Sanitary District (NSD) of Belo Horizonte has the largest historical average of human VL cases in the metropolitan region, and is classified as a priority area for epidemiological and entomological monitoring of the disease. The objectives of the present study were to determine the seasonal variation in phlebotomine fauna and to describe the environmental situations in the NSD through characterization of peri-domiciles and application of geographical information system analysis. Entomological captures were performed every two weeks during the period July 2006 to June 2007 using HP light traps placed at 16 locations where cases of human VL had been reported in 2005. The environmental characterization of these locations was accomplished using forms and photographic images. Spatial analyses was used to determine the influence of vegetation, hydrography, altitude and pockets of poverty on the occurrence of cases of human and canine VL, and of phlebotomine vectors. A total of 633 phlebotomines belonging to the subtribes Psychodopygina and Lutzomyina were captured and, of these, 75% were identified as Nyssomyia whitmani and 11% as Lutzomyia longipalpis. The majority of the studied peri-domiciles presented inadequate hygienic conditions that would favor the development of phlebotomines. No significant correlations could be established between biogeographical aspects and either the incidence of human and canine VL or the occurrence of phlebotomines. The proximity of areas with vegetation, villages, slums and open watercourses exerted little influence on the incidence of VL. These findings reinforce the urbanization of the VL profile since the disease occurred in locations where conditions that have been classically related to its prevalence were not present. The results reported herein will be important for implementing measures against VL in the study area. Copyright © 2010. Published by Elsevier B.V.
	PMID: 21110938 [PubMed - as supplied by publisher]
	Related citations

10.	Acta Trop. 2010 Nov 23. [Epub ahead of print] Survey on bovine trypanosomosis and its vector in Metekel and Awi zones of Northwest Ethi opia. Mekuria S, Gadissa F. Hawassa University Department of Veterinary Medicine P.O.Box 05 Hawassa Ethiopia. Abstract A cross-sectional study was conducted between November 2009 and December 2009 in the riverbank of Abay river tributaries, located in three districts of Awi and Metekel zones, North West Ethiopia. The prevalence of bovine trypanosomosis, associated risk factors and distribution as well as vector identification in the study area were considered. Blood samples were collected from 540 randomly selected local (zebu) breed of cattle in nine peasant associations of three districts and the assumed risk factors were recorded. The collected samples were examined using hematological and parasitological techniques. In this study, sixty-seven animals (12.42%) were infected with different species of trypanosomes. Most of the infections were due to T. congolense (77.6%) followed by T. vivax (14.9%), T.brucei (6.0%) and mixed infection of T.congolense and T.vivax (1.5%). There was no statistical significance (P>0.05) between sex, age and coat color of skin, but significant difference were observed in body condition, altitude and districts (p<0.05). Mean PCV value of infected (19.42%) and non-infected (24.13%) group of animals had significant variation; and mean PCV value of poor body condition were significantly difference (P<0.001) than good body condition. A total of 3072 tsetse flies of riverine species or palpalis group (Glossina tachinoides) and biting flies were caught, of these2792(90.9%) were tsetse flies and the remaining was Stomoxys and Tabanus. The overall apparent densities of tsetse and biting flies were 6.49 and 0.65 flies/trap/day, respectively and the difference was significant (P<0.05). The study revealed that bovine trypanosomosis is more prevalence in lowland and in poor body condition animals in the study area. Tsetse distribution also coincides with altitude, where there was high tsetse catch in lowland, but none in mid land. Therefore, prompt control strategy has to be designed and implemented in the area to minimize the distribution of tsetse as well as trypanosomosis prevalence. Copyright © 2010. Published by Elsevier B.V.
	PMID: 21110937 [PubMed - as supplied by publisher]
	Related citations