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Sent on Thursday, 2011 Nov 24Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results |
1. | Int J Biol Sci. 2011;7(9):1382-90. Epub 2011 Nov 1.Role of Co-stimulation in Leishmaniasis.Tuladhar R, Natarajan G, Satoskar AR.Source1. Department of Microbiology, The Ohio State University, Columbus, Ohio 43221, USA. AbstractLeishmania are obligate intracellular parasites that cause a wide spectrum of diseases ranging from cutaneous, mucocutaneous and the visceral kind. Persistence or resolution of leishmaniasis is governed by host immune response. Co-stimulation is an important secondary signal that governs the extent, strength and direction of the immune response that follows. Co-stimulation by CD40, B7 and OX40 family has been shown to influence the outcome following Leishmania infection and manipulation of these pathways has shown promise for use in immune therapy of leishmaniasis. In this review, we discuss the roles of CD40, B7 and OX40 co-stimulatory pathways in regulating immunity to Leishmania and their implications in the treatment of this disease. |
2. | Int J Biol Sci. 2011;7(9):1334-44. Epub 2011 Nov 1.Paratransgenic control of vector borne diseases.Hurwitz I, Fieck A, Read A, Hillesland H, Klein N, Kang A, Durvasula R.SourceCenter for Global Health, Department of Internal Medicine, University of New Mexico and New Mexico VA Health Care System, Albuquerque, New Mexico, USA. AbstractConventional methodologies to control vector borne diseases with chemical pesticides are often associated with environmental toxicity, adverse effects on human health and the emergence of insect resistance. In the paratransgenic strategy, symbiotic or commensal microbes of host insects are transformed to express gene products that interfere with pathogen transmission. These genetically altered microbes are re-introduced back to the insect where expression of the engineered molecules decreases the host's ability to transmit the pathogen. We have successfully utilized this strategy to reduce carriage rates of Trypanosoma cruzi, the causative agent of Chagas disease, in the triatomine bug, Rhodnius prolixus, and are currently developing this methodology to control the transmission of Leishmania donovani by the sand fly Phlebotomus argentipes. Several effector molecules, including antimicrobial peptides and highly specific single chain antibodies, are currently being explored for their anti-parasite activities in these two systems. In preparation for eventual field use, we are actively engaged in risk assessment studies addressing the issue of horizontal gene transfer from the modified bacteria to environmental microbes. |
3. | Int J Biol Sci. 2011;7(9):1220-9. Epub 2011 Oct 25.Deletion of the Aryl Hydrocarbon Receptor Enhances the Inflammatory Response to Leishmania major Infection.Elizondo G, Rodríguez-Sosa M, Estrada-Muñiz E, Gonzalez FJ, Vega L.Source1. Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional. Departamento de Biología Celular. Av. IPN 2508. San Pedro Zacatenco. C. P. 07360, México D. F., México. AbstractThe aryl hydrocarbon receptor (AhR) is a ligand-activated receptor that mediates the toxicity of environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recently, it has been shown that the AhR plays a role in immune and inflammatory regulation. However, most of these studies are based on the activation of AhR by exogenous ligands. Therefore, in the present study, we addressed the role of this transcription factor, in the absent of exogenous ligand, on the immune response to Leishmania major infection. Our results indicate that inactivation of the AhR results in an alteration of the levels of several cytokines. Lymph node cells from infected Ahr-null animals displayed an increase in IFNγ and IL-12 levels, together with a decrease in IL-4 and IL-10 levels compared to wild-type (wt) mice. Ahr-null mice also presented higher serum levels of the pro-inflammatory cytokine TNF-α prior to parasite inoculation and during infection compared to wt mice. Moreover, a 30% decrease in the population of T(reg) cells was observed in Ahr-null mice. This decrease was associated with a reduction in Foxp3 mRNA levels. Finally, the alteration in the cytokine profile results in a better resolution of the L. major infection. |
4. | Geospat Health. 2011 Nov;6(1):33-40.Ecological study and risk mapping of leishmaniasis in an endemic area of Brazil based on a geographical information systems approach.Machado da Silva AV, Magalhães MD, Peçanha Brazil R, Carreira JC.SourceLaboratório de Bioquímica de Proteínas e Peptídeos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. AbstractVisceral leishmaniasis is a vector-borne disease highly influenced by eco-epidemiological factors. Geographical information systems (GIS) have proved to be a suitable approach for the analysis of environmental components that affect the spatial distribution of diseases. Exploiting this methodology, a model was developed for the mapping of the distribution and incidence of canine leishmaniasis in an endemic area of Brazil. Local variations were observed with respect to infection incidence and distribution of serological titers, i.e. high titers were noted close to areas with preserved vegetation, while low titers were more frequent in areas where people kept chickens. Based on these results, we conclude that the environment plays an important role in generating relatively protected areas within larger endemic regions, but that it can also contribute to the creation of hotspots with clusters of comparatively high serological titers indicating a high level of transmission compared with neighbouring areas. |
5. | Planta Med. 2011 Nov 22. [Epub ahead of print]9β-Hydroxyparthenolide Esters from Inula montbretiana and Their Antiprotozoal Activity.Gökbulut A, Kaiser M, Brun R, Sarer E, Schmidt TJ.SourceAnkara University, Faculty of Pharmacy, Department of Pharmacognosy, Ankara, Turkey. AbstractIn continuation of ongoing studies on the potential of natural products as antiprotozoal leads or drugs, it was found that the CH (2)Cl (2) extract obtained from the flowering aerial parts of INULA MONTBRETIANA DC. (Asteraceae, tribe Inuleae) displays antiprotozoal activity, especially against TRYPANOSOMA BRUCEI RHODESIENSE (IC (50): 3.38 µg/mL). Isolation of the possible active constituents led to the identification of six sesquiterpene lactones, all esters of 9 β-hydroxyparthenolide. Two isolates, namely, 9 β-(3',4'-epoxy-3'-methylpentanoyloxy)-parthenolide and 9 β-(3'-oxo-2'-methylbutanoyloxy)-parthenolide, represented diastereomeric mixtures differing only in the configuration within the acyl moieties. According to IN VITRO test results, the mixture of esters with diastereomeric 3,4-epoxy-3-methylpentanoic acid was the most active constituent against TRYPANOSOMA BRUCEI RHODESIENSE (IC (50): 0.26 µg/mL) and was less cytotoxic against rat skeletal myoblasts (L6 cell line) with a selectivity index of about 9. The mixture of diastereomeric 2-methyl-3-oxobutyric acid esters was the most potent against PLASMODIUM FALCIPARUM (IC (50): 1.48 µg/mL) and displayed a selectivity index of about 35. © Georg Thieme Verlag KG Stuttgart · New York. |
6. | Mol Biochem Parasitol. 2011 Nov 15. [Epub ahead of print]The crystal structure of Leishmania major N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclohydrolase and assessment of a potential drug target.Eadsforth TC, Cameron S, Hunter WN.SourceDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK. AbstractThree enzyme activities in the protozoan Leishmania major, namely N(5),N(10)-methylenetetrahydrofolate dehydrogenase/N(5),N(10)-methenyltetrahydrofolate cyclohydrolase (DHCH) and N(10)-formyltetrahydrofolate ligase (FTL) produce the essential intermediate N(10)-formyltetrahydrofolate. Although trypanosomatids possess at least one functional DHCH, the same is not true for FTL, which is absent in Trypanosoma brucei. Here, we present the 2.7Å resolution crystal structure of the bifunctional apo-DHCH from L. major, which is a potential drug target. Sequence alignments show that the cytosolic enzymes found in trypanosomatids share a high level of identity of approximately 60%. Additionally, residues that interact and participate in catalysis in the human homologue are conserved amongst trypanosomatid sequences and this may complicate attempts to derive potent, parasite specific DHCH inhibitors. Copyright © 2011. Published by Elsevier B.V. |
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