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Sent on Sunday, 2011 December 25Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS One. 2011;6(12):e29062. Epub 2011 Dec 14.Curative Effect of 18β-Glycyrrhetinic Acid in Experimental Visceral Leishmaniasis Depends on Phosphatase-Dependent Modulation of Cellular MAP Kinases.Ukil A, Kar S, Srivastav S, Ghosh K, Das PK.SourceDepartment of Biochemistry, Calcutta University, Kolkata, India. AbstractWe earlier showed that 18β-glycyrrhetinic acid (GRA), a pentacyclic triterpenoid from licorice root, could completely cure visceral leishmaniasis in BALB/c mouse model. This was associated with induction of nitric oxide and proinflammatory cytokine production through the up regulation of NF-κB. In the present study we tried to decipher the underlying cellular mechanisms of the curative effect of GRA. Analysis of MAP kinase pathways revealed that GRA caused strong activation of p38 and to a lesser extent, ERK in bone marrow-derived macrophages (BMDM). Almost complete abrogation of GRA-induced cytokine production in presence of specific inhibitors of p38 and ERK1/2 confirmed the involvement of these MAP kinases in GRA-mediated responses. GRA induced mitogen- and stress-activated protein kinase (MSK1) activity in a time-dependent manner suggested that GRA-mediated NF-κB transactivation is mediated by p38, ERK and MSK1 pathway. As kinase/phosphatase balance plays an important role in modulating infection, the effect of GRA on MAPK directed phosphatases (MKP) was studied. GRA markedly reduced the expression and activities of three phosphatases, MKP1, MKP3 and protein phosphatase 2A (PP2A) along with a substantial reduction of p38 and ERK dephosphorylation in infected BMDM. Similarly in the in vivo situation, GRA treatment of L. donovani-infected BALB/c mice caused marked reduction of spleen parasite burden associated with concomitant decrease of individual phosphatase levels. However, activation of kinases also played an important role as the protective effect of GRA was significantly abrogated by pharmacological inhibition of p38 and ERK pathway. Curative effect of GRA may, therefore, be associated with restoration of proper cellular kinase/phosphatase balance, rather than modulation of either kinases or phosphatases. |
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| 2. | Molecules. 2011 Dec 22;17(1):15-33.HPLC Analysis of Supercritical Carbon Dioxide and Compressed Propane Extracts from Piper amalago L. with Antileishmanial Activity.Carrara Vda S, Serra LZ, Cardozo-Filho L, Cunha-Júnior EF, Torres-Santos EC, Cortez DA.SourceDepartamento de Farmácia, Universidade Estadual de Maringá, 87020-900, Maringá, Paraná, Brazil. dagcortez@uem.br. AbstractPiper amalago L. leaves were extracted with supercritical carbon dioxide and compressed propane under different conditions, and with chloroform by the conventional maceration method. These methods were compared for the pyrrolidine alkaloid content. Supercritical carbon dioxide (SFE-CO(2)) at 313 K and 12.55 MPa showed the highest selectivity for the main compound (600.53 mg/g of extract). A gradient high-performance liquid chromatography (HPLC) method was developed and validated to quantify the alkaloid N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl]pyrrolidine (1) in the extracts. The HPLC method showed linearity, precision and accuracy, allowing the quantitative analysis of the alkaloid in all the samples. All the extracts were tested against the promastigote and intracellular amastigote forms of Leishmania amazonensis. The antileishmanial activity was evaluated in terms of inhibitory concentration for 50% of protozoa (IC(50)). The cytotoxicity was also evaluated against J774A1 macrophages, and the cytotoxic concentrations for 50% of macrophages were obtained (CC(50)). The SFE-CO(2) (313 K; 12.55 MPa) extract showed the highest antileishmanial activity with the following IC(50) values of 16 and 7 µg/mL against the promastigotes and intracellular amastigotes forms, respectively. The extract showed low cytotoxicity with a CC(50) value of 93 µg/mL. |
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| 3. | Trends Parasitol. 2011 Dec 20. [Epub ahead of print]Regulation and function of polyamines in African trypanosomes.Willert E, Phillips MA.SourceDepartment of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390-9041, USA. AbstractThe polyamine biosynthetic pathway is an important drug target for the treatment of human African trypanosomiasis (HAT), raising interest in understanding polyamine function and their mechanism of regulation. Polyamine levels are tightly controlled in mammalian cells, but similar regulatory mechanisms appear absent in trypanosomes. Instead trypanosomatid S-adenosylmethionine decarboxylase (AdoMetDC), which catalyzes a key step in the biosynthesis of the polyamine spermidine, is activated by dimerization with an inducible protein termed prozyme. Prozyme is an inactive paralog of the active AdoMetDC enzyme that evolved by gene duplication and is found only in the trypanosomatids. In Trypanosoma brucei, AdoMetDC activity appears to be controlled by regulation of prozyme protein levels, potentially at the translational level. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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| 4. | Future Microbiol. 2012 Jan;7:149-64.Iron-saturated lactoferrin and pathogenic protozoa: could this protein be an iron source for their parasitic style of life?Ortíz-Estrada G, Luna-Castro S, Piña-Vázquez C, Samaniego-Barrón L, León-Sicairos N, Serrano-Luna J, de la Garza M.SourceDepartamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. 14-740, México DF 07000, México. AbstractIron is an essential nutrient for the survival of pathogens inside a host. As a general strategy against microbes, mammals have evolved complex iron-withholding systems for efficiently decreasing the iron accessible to invaders. Pathogens that inhabit the respiratory, intestinal and genitourinary tracts encounter an iron-deficient environment on the mucosal surface, where ferric iron is chelated by lactoferrin, an extracellular glycoprotein of the innate immune system. However, parasitic protozoa have developed several mechanisms to obtain iron from host holo-lactoferrin. Tritrichomonas fetus, Trichomonas vaginalis, Toxoplasma gondii and Entamoeba histolytica express lactoferrin-binding proteins and use holo-lactoferrin as an iron source for growth in vitro; in some species, these binding proteins are immunogenic and, therefore, may serve as potential vaccine targets. Another mechanism to acquire lactoferrin iron has been reported in Leishmania spp. promastigotes, which use a surface reductase to recognize and reduce ferric iron to the accessible ferrous form. Cysteine proteases that cleave lactoferrin have been reported in E. histolytica. This review summarizes the available information on how parasites uptake and use the iron from lactoferrin to survive in hostile host environments. |
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| 5. | Berl Munch Tierarztl Wochenschr. 2011 Nov-Dec;124(11-12):434-42.The importance of canine leishmaniosis in non-endemic areas, with special emphasis on the situation in Germany.Mencke N.SourceBayer Animal Health GmbH, Leverkusen, Germany. norbert.mencke@bayer.com AbstractThis review article summarizes the situation of canine leishmaniosis in Germany. Published case studies on infections with Leishmania (L.) infantum in either humans or dogs are analyzed. Diagnosed cases of infections by Leishmania spp. in humans and animals are not a notifiable disease in Germany or other European countries. Taking this into consideration one may assume that there might be a significant gap between the analyzed and reported cases and the infectious status within the country. The reported case studies and results from surveys indicate that the majority of all L. infantum infections are acquired during travelling in endemic regions, predominantly the Mediterranean region. However there are cases reported from human infections and growing number of cases in dogs, where the case history may indicate an autochthonous infection within Germany, a country within a non-endemic region. The current data from entomological field studies proved the presence of two phlebotomine sand fly species. Phlebotomus (P.) mascittii, an anthropophilic sand fly species and P. perniciosus a proven vector of L. infantum. The impact from a growing leishmania-positive dog population within Germany, the distribution of at least two sand fly species, one with vector potential in the light of climate change and other non-vectorial transmissions are summarized. |
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| 6. | Res Microbiol. 2011 Jul-Aug;162(6):619-25. Epub 2011 May 18.The Trypanosoma cruzi genome; conserved core genes and extremely variable surface molecule families.Andersson B.SourceDepartment of Cell and Molecular Biology, Science for Life Laboratory, Karolinska Institutet, Berzelius väg 35, 171 77 Stockholm, Sweden. bjorn.andersson@ki.se AbstractThe protozoan parasite Trypanosoma cruzi is an important but neglected pathogen that causes chagas disease, which affects millions of people, mainly in latin America. The population structure and epidemiology of the parasite are complex, with much variability among strains. The genome sequence of a reference strain, CL Brener, was published in 2005, and the availability of this sequence has both revealed the complexity of the parasite genome and greatly facilitated research into parasite biology and pathogenesis, by making the sequences of more than 8000 core genes available. The T. cruzi genome is highly repetitive, which has resulted in inaccuracies in the genome sequence, and attempts have been made to provide a deeper analysis of repeated genes as a complement to the genome sequence. The genome was found to be organized in stable core regions containing housekeeping and other genes, surrounded by highly repetitive, often sub-telomeric highly variable regions containing multiple members of large families of surface molecule genes. Comparative sequencing of T. cruzi strains has been initiated and the results show that the core gene content of the parasite is highly conserved, but that much sequence variability, 3-4% difference at the DNA level on average between strains in coding regions, is present. The additional genomes will improve the understanding of parasite biology and epidemiology. Copyright © 2011 Institut Pasteur. Published by Elsevier SAS. All rights reserved. |
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