What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2010 Sep 14
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 - 10 of 16

1.	Methods Mol Biol. 2010;673:231-8. A Functional Proteomic Study of the Trypanosoma brucei Nuclear Pore Complex: An Informatic Strategy. Degrasse JA, Devos D. U.S. Food and Drug Administration, College Park, MD, USA. Abstract The nuclear pore complex (NPC) is the sole mediator of transport between the nucleus and the cytoplasm. The NPC is composed of about 30 distinct proteins, termed nucleoporins or nups. The yeast (Rout et al., J Cell Biol 148:635-651, 2000) and mammalian (Cronshaw et al., J Cell Biol 158:915-927, 2002) NPC have been extensively studied. However, the two species are relatively closely related. Thus, to reveal details about NPC evolution, we chose to characterize the NPC of a distantly related organism, Trypanosoma brucei. We took a subcellular proteomic approach and used several complementary strategies to identify 865 proteins associated with the nuclear envelope. Over 50% of ∼8,100 open reading frames of T. brucei have little or no known function because T. brucei is distantly related to model metazoa and fungi (Berriman et al., Science 309:416-422, 2005). By sequence similarity alone, we could identify only five nucleoporins. This chapter outlines our strategy to identify 17 additional nucleoporins as well as contribute functional annotation data to the T. brucei genome database.
	PMID: 20835803 [PubMed - in process]

2.	Mem Inst Oswaldo Cruz. 2010 Aug;105(5):692-7. HIV/AIDS-associated visceral leishmaniasis in patients from an endemic area in Central-west Brazil. Alexandrino-de-Oliveira P, Santos-Oliveira JR, Dorval ME, Da-Costa FC, Pereira GR, Cunha RV, Paniago AM, Da-Cruz AM. Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil, 21045-900. Abstract An increase in morbidity associated with visceral leishmaniasis (VL) in human immunodeficiency virus (HIV)/AIDS patients has been described in Africa and the Mediterranean. Despite the high endemicity of VL and HIV-1/AIDS in Brazil, this association has not been thoroughly investigated. Our aim was to evaluate the epidemiologic and clinical characteristics of VL-HIV-1/AIDS cases from Central-west [Mato Grosso do Sul (MS)] Brazil. Medical records of 23 VL-HIV-1/AIDS patients were reviewed. Patients were predominantly adult males (87%) and 34.8% of the patients were intravenous drug users (IVDU). Leishmaniasis was the first opportunistic infection in 60% of the HIV-1 patients. Fever occurred in all patients, although splenomegaly and hepatomegaly were absent in 21.7% of the cases. CD4+ T-cell counts were below 200 cells/mm³ in 80% of the cases and the counts did not increase after clinical remission despite antiretroviral therapy. The first drug chosen to treat the cases was antimonial, but the therapeutic regimen was altered to amphotericin B in 12 of 17 cases due to side effects. Relapses were reported in 56.5% of the patients. IVDU may constitute an important risk factor for the transmission of both diseases in MS. VL-HIV-1/AIDS patients in MS share similar clinical characteristics as those from other endemic regions worldwide. Thus, these findings are critical for improving the surveillance of VL-HIV/AIDS patients.
	PMID: 20835619 [PubMed - in process]

3.	Braz J Infect Dis. 2010 Jun;14(3):297-8. Monoclonal gammopathy associated with visceral leishmaniasis. Sharma V, Agarwal MP, Giri S. Abstract Monoclonal gammopathy can accompany diverse conditions and is usually benign. It should be distinguished from monoclonal gammopathy of undetermined significance (MGUS) which can rarely turn malignant. Visceral leishmaniasis has only rarely been associated with monoclonal gammopathy. We describe the case of a 55-year-old male who had monoclonal gammopathy associated with visceral leishmanisais, which reversed with stibogluconate therapy.
	PMID: 20835517 [PubMed - in process]

4.	J Vector Borne Dis. 2010 Sep;47(3):168-74. The potential of the extracts of Tagetes minuta Linnaeus (Asteraceae),Acalypha fruticosa Forssk (Euphorbiaceae) and Tarchonanthuscamphoratus L. (Compositae) against Phlebotomus duboscqi Neveu Lemaire (Diptera: Psychodidae), the vector for Leishmania major Yakimoff and Schokhor. Ireri LN, Kongoro J, Ngure P, Mutai C, Langat B, Tonui W, Kimutai A, Mucheru O. Division of Vector Borne and Neglected Tropical Diseases, Embu. Abstract Background & objectives: Harmful effects of synthetic chemical insecticides including vector resistance, environmental pollution and health hazards have necessitated the current significance in the search for plant-based insecticide products that are environmentally safe and effective to leishmaniases control. The insecticidal activity of Tagetes minuta Linnaeus (Asteraceae), Acalypha fruticosa Forssk (Euphorbiaceae) and Tarchonanthus camphoratus L. (Compositae) extracts were investigated against Phlebotomus duboscqi Neveu Lemaire (Diptera: Psychodidae). Methods: The extracts were prepared from dried aerial parts soaked in methanol and ethyl acetate twice until the filtrates became clear, filtered and dried out by rotary evaporation at 30-35oC. The solid extracts obtained were later prepared into 2.5, 5 and 10 mg/ml. Two millilitres of the solutions were blotted on filter papers, which were dried overnight and placed into jars where adult sandflies were aspirated. Males and females were assayed separately. Results & conclusion: The extracts had significant mortality (p<0.05) in both males and females bioassays but were not significantly different between sexes. The extracts of Acalypha fruticosa and Tagetes minuta had significantly higher mortality rates than those of Tarchonanthus camphoratus and the different concentrations used showed significantly different mortality rates and 10 mg/ml was the most effective concentration. Cent percent mortality was obtained at 96 h of exposure to 5 and 10 mg/ml concentrations except for Tarchonanthus camphoratus which had a mortality of only 46.7% in 10 mg/ml bioassay. These extracts were found to be insecticidal to adult sandflies.
	PMID: 20834087 [PubMed - in process]

5.	J Vector Borne Dis. 2010 Sep;47(3):160-7. Experimental chemotherapy with Allium sativum (Liliaceae)methanolic extract in rodents infected with Leishmania major and Leishmania donovani. Adedotun BW, Anjili CO, Ngeiywa MM, Ngure PK, Kigondu EM, Ingonga J, Makwali J. Mombasa Technical Training Institute, Department of Applied Sciences, Mombasa; Abstract Background & objectives: Several plant products have been tested and found to possess antileishmanial activity. The present study was undertaken to establish whether methanolic extract of Allium sativum Linn has antileishmanial activity in comparison to standard drugs. Methods: Methanolic extract of A. sativum bulbs was screened for in vitro and in vivo antileishmanial activity against Leishmania major strain (NLB 145) and L. donovani strain (NLB 065). Pentostam and Amphotericin B were used as standard drugs. BALB/c mice and golden hamsters (Mesocricetus auratus) were used in in vivo studies on L. major and L. donovani respectively. Results: The extract exhibited very low cytotoxicity (IC50 >450 μg/ml) against Vero cells. The extract had significantly better (p <0.001) leishmanicidal activity against both species (IC50 34.22 μg/ml to L. major, 37.41 μg/ml to L. donovani) than Pentostam. However, the activity was significantly lower (p <0.001) than that of Amphotericin B against both the species. At a concentration of 250 μg/ml, the extract induced the production of 60 μM of nitric oxide, a ten-fold up-regulation in activated macrophages. The multiplication indices for L. major amastigotes treated in 100 μg/ml were significantly different (p <0.05). Treatment with the extract, daily for 28 days led to a significant reduction (p <0.05) in footpad swelling in BALB/c mice; similar activity noticed in the treatment with standard drugs. The Leishman-Donovan Units (LDU) for the extract treated animals were significantly higher (p <0.05) than those of standard drugs, but lower compared to the negative control. Interpretation & conclusion: Since the mechanism of action for the methanolic extract is apparently immunomodulatory, garlic compounds could be purified and tried as complementary medicine in the management of leishmaniases.
	PMID: 20834086 [PubMed - in process]

6.	J Vector Borne Dis. 2010 Sep;47(3):127-39. A cost benefit analysis of elimination of kala-azar in Indian subcontinent: an example of Nepal. Adhikari SR, Supakankunti S. Faculty of Economics, Centre for Health Economics, Chulalongkorn University, Thailand. Abstract Background & objectives: Visceral leishmaniasis, locally known as kala-azar (KA) has been considered as a major public health problem in Bangladesh, India and Nepal that affects 100,000 people per year with 147 million people at risk. Elimination of infectious disease is an ultimate goal of the public health system, therefore, the efforts have recently gained momentum from various organizations and governments to expand KA interventions in the endemic countries. The paper aims to estimate discounted net benefits and internal rate of return (IRR) to evaluate the economic feasibility for elimination of KA by utilizing available secondary information. Methods: Cross-sectional data were collected from different sources to estimate societal costs of and benefits from KA interventions with a 13-year project period. Total costs are estimated based on the unit cost of inputs used for interventions. The benefits are derived from productivity change and resources saved due to reduction of KA incidence. Net benefits and IRRs are estimated based on standard procedures used in the field of economics, subsequently the sensitivity analysis is conducted. Results: A total discounted net benefit of KA intervention is Nepalese Rupees (NRs) 65,287 million with 35% IRR. The result suggests that for every rupee invested in KA intervention at present will yield NRs 71 in future. The regional benefits from the interventions will be greater than the sum of benefits gained by the individual country due to its nature of public goods. Conclusion: Elimination of KA is a good investment opportunity for the Government and international partners involved in the health sector.
	PMID: 20834081 [PubMed - in process]

7.	Eukaryot Cell. 2010 Sep 10. [Epub ahead of print] A novel protein kinase localized to lipid droplets is required for droplet biogenesis in trypanosomes. Flaspohler JA, Jensen BC, Saveria T, Kifer CT, Parsons M. Seattle Biomedical Research Institute, 307 Westlake Ave. N., Seattle, WA 98109 USA; Dept. of Biology, Concordia College, 901 8th St. South Moorhead, MN 56562; Dept. of Global Health, University of Washington, Seattle, WA, 98195, USA. Abstract Ubiquitous amongst eukaryotes, lipid droplets are organelles which function to coordinate intracellular lipid homeostasis. Their morphology and abundance is affected by numerous genes, many of which are involved in lipid metabolism. In this report we identify a Trypanosoma brucei protein kinase, LDK, and demonstrate its localization to the periphery of lipid droplets. Association with lipid droplets was abrogated when the hydrophobic domain of LDK was deleted, supporting a model in which the hydrophobic domain is associated with or inserted into the membrane monolayer of the organelle. RNAi knockdown of LDK modestly affected growth of mammalian bloodstream stage parasites but did not affect growth of insect (procyclic) stage parasites. However, the abundance of lipid droplets dramatically decreased in both cases. This loss was dominant over treatment with myriocin or growth in delipidated serum, both of which induce lipid body biogenesis. Growth in delipidated serum also increased LDK autophosphorylation activity. Thus LDK is required for the biogenesis or maintenance of lipid droplets, and is one of the few protein kinases specifically and predominantly associated with an intracellular organelle.
	PMID: 20833891 [PubMed - as supplied by publisher]

8.	Lancet. 2010 Sep 11;376(9744):922-7. Introduction of European priority review vouchers to encourage development of new medicines for neglected diseases. Ridley DB, Sánchez AC. Fuqua School of Business, Duke University, Durham, NC, USA; Center for European Studies, Duke University, Durham, NC, USA. Abstract Every year 1 billion people worldwide are affected by traditionally neglected diseases, such as malaria, tuberculosis, leishmaniasis, and lymphatic filariasis, which impose tremendous public health burdens. Governments, foundations, and drug manufacturers have, however, started to support development of new treatments. European Union Member States have been leaders in implementing so-called push mechanisms (payment for drug development) and pull funding (reward for output), such as the advance market commitment, which creates a market for vaccines by guaranteeing prices. We propose an additional step that could be taken to encourage development of medicines for neglected diseases. A priority review voucher scheme, as is already in place in the USA, would reward a manufacturer that developed a new medicine for neglected diseases with a voucher that could be redeemed for priority review of a future medicine, probably a potential blockbuster drug. Unlike the US system a European voucher would also accelerate pricing and reimbursement decisions. This scheme would be likely to provide substantial benefits to voucher holders, society, and public health organisations.
	PMID: 20833303 [PubMed - in process]

9.	Bioorg Med Chem. 2010 Jul 11. [Epub ahead of print] Synthesis and evaluation of original amidoximes as antileishmanial agents. Bouhlel A, Curti C, Dumètre A, Laget M, Crozet MD, Azas N, Vanelle P. Laboratoire de Pharmaco-Chimie Radicalaire (LPCR), Faculté de Pharmacie, Universités d'Aix-Marseille I, II, et III-CNRS, UMR 6264: Laboratoire Chimie Provence, 27 Boulevard Jean Moulin, 13385 Marseille cedex 05, France. Abstract An original series of amidoxime derivatives was synthesized using manganese(III) acetate, Buchwald-Hartwig and Heck reactions. Two amidoximes (39 and 52) showed interesting in vitro activities toward Leishmania donovani promastigotes, exhibiting 8.3 and 8.8μM IC(50) values. Moreover, the cytotoxicity of these compounds was evaluated on human THP1 cells, giving access to the corresponding selectivity index. Among the 25 tested compounds, amidoximes 38 and 39 and diamidoximes 50 and 52 exhibited a better selectivity index than pentamidine used as a drug compound reference.
	PMID: 20833057 [PubMed - as supplied by publisher]

10.	Vet Parasitol. 2010 Aug 17. [Epub ahead of print] First report of infection of Lutzomyia longipalpis by Leishmania (Leishmania) infantum from a naturally infected cat of Brazil. da Silva SM, Rabelo PF, Gontijo ND, Ribeiro RR, Melo MN, Ribeiro VM, Michalick MS. Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 Pampulha, 31270-901 Belo Horizonte, MG, Brazil. Abstract In recent years, cases of feline visceral leishmaniasis (FVL) have been described in different countries. In urban areas, domestic cats are suggested as possible alternative reservoirs of Leishmania (L.) infantum, the causal agent of visceral leishmaniasis (VL). This paper reports the first case of infection of Lutzomyia longipalpis by L. infantum of a naturally infected cat from Brazil through xenodiagnosis. The presence of a cat with FVL and its infectivity to the natural vector in Belo Horizonte city, an endemic area of VL in Brazil, suggests the need for further studies to determine the rate of occurrence of FVL among domestic cats and the infectivity ratio of L. longipalpis in endemic areas, and what is the role of these animals in the epidemiology of the disease.
	PMID: 20832944 [PubMed - as supplied by publisher]