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Sent on Thursday, 2010 Feb 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. | Acta Crystallogr D Biol Crystallogr. 2010 Mar;66(Pt 3):251-7. Epub 2010 Feb 12.Coiled-coil conformation of a pentamidine-DNA complex.Moreno T, Pous J, Subirana JA, Campos JL.Departament d'Enginyeria Química, Universitat Politècnica de Catalunya, E-08028 Barcelona, Spain. The coiled-coil structure formed by the complex of the DNA duplex d(ATATATATAT)(2) with pentamidine is presented. The duplex was found to have a mixed structure containing Watson-Crick and Hoogsteen base pairs. The drug stabilizes the coiled coil through the formation of cross-links between neighbouring duplexes. The central part of the drug is found in the minor groove as expected, whereas the charged terminal amidine groups protrude and interact with phosphates from neighbouring molecules. The formation of cross-links may be related to the biological effects of pentamidine, which is used as an antiprotozoal agent in trypanosomiasis, leishmaniasis and pneumonias associated with AIDS. The DNA sequence that was used is highly abundant in most eukaryotic genomes. However, very few data are available on DNA sequences which only contain A.T base pairs. |
| PMID: 20179336 [PubMed - in process] | |
| 2. | Int J Parasitol. 2010 Feb 20. [Epub ahead of print]LmxMPK4, an essential mitogen-activated protein kinase of Leishmania mexicana is phosphorylated and activated by the STE7-like protein kinase LmxMKK5.Freyend SJ, Rosenqvist H, Fink A, Melzer IM, Clos J, Jensen ON, Wiese M.Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK. The essential mitogen-activated protein kinase (MAP kinase), LmxMPK4, of Leishmania mexicana is minimally active when purified following recombinant expression in Escherichia coli and was therefore unsuitable for drug screening until now. Using an E. coli protein co-expression system we identified LmxMKK5, a STE7-like protein kinase from L. mexicana, which phosphorylates and activates recombinant LmxMPK4 in vitro. LmxMKK5 is comprised of 525 amino acids and has a calculated molecular mass of 55.9 kDa. The co-expressed, purified LmxMPK4 showed strong phosphotransferase activity in radiometric kinase assays and was confirmed by immunoblot and tandem mass spectrometry analyses to be phosphorylated on threonine 190 and tyrosine 192 of the typical TXY MAP kinase activation motif. The universal protein kinase inhibitor Staurosporine reduced the phosphotransferase activity of co-expressed and activated LmxMPK4 in a dose-dependent manner. To our knowledge this is the first time that an in vitro activator of an essential Leishmania MAP kinase was identified and our findings form the basis for the development of drug screening assays to identify small molecule inhibitors of LmxMPK4 in the search for new therapeutic drugs against leishmaniasis. Copyright © 2010. Published by Elsevier Ltd. |
| PMID: 20178803 [PubMed - as supplied by publisher] | |
| 3. | Vet Dermatol. 2009 Oct;20(5-6):471-89.Advances in the pathogenesis of canine leishmaniosis: epidemiologic and diagnostic implications.Saridomichelakis MN.< p class="aff">Clinic of Medicine, School of Veterinary Medicine, University of Thessaly, Karditsa, Greece.Canine leishmaniosis caused by Leishmania infantum (Syn. L. chagasi) is an important zoonosis with a complex pathogenesis. Parasite transmission occurs via female sandflies that inject promastigotes into the skin of the host. The interaction between the parasite and skin immune system is influenced by the repeated infectious bites and the simultaneous intradermal injection of sandfly saliva. Amastigotes are transported via infected macrophages to the regional lymph nodes and finally dissemination may occur. The outcome of the infection depends on host factors (genetic background, cell-mediated and humoral immune response, cytokine milieu, concurrent diseases) and parasite virulence. Resistance may be breed-associated; it is characterized by low to undetectable antibody production and effective cell-mediated immunity, and is orchestrated by cytokines such as interleukin-2, interferon-gamma and tumour necrosis factor-alpha. Susceptibility may be genetically determined or acquired (advanced age, concurrent diseases); in these dogs, parasite multiplication goes unrestricted and overproduction of specific and nonspecific antibodies occurs, leading to multiple organ pathology. Resistance or susceptibility is not an all-or-nothing phenomenon and many intermediate phenotypes may be found. From a diagnostic point of view, although clinical cases are readily identified using microscopy and serology, investigation should not stop at this point and an extensive search for underlying diseases is advised, especially in aged dogs. Conversely, microscopy and conventional serology are frequently negative in asymptomatic infected dogs; to identify such dogs, polymerase chain reaction, evaluation of cutaneous delayed-type hypersensitivity, in vitro lymphocyte proliferation test to Leishmania antigen, and Western blotting may be employed. |
| PMID: 20178485 [PubMed - in process] | |
| 4. | PLoS Negl Trop Dis. 2008;2(11):e336. Epub 2008 Nov 18.The costs of preventing and treating chagas disease in Colombia.Castillo-Riquelme M, Guhl F, Turriago B, Pinto N, Rosas F, Martínez MF, Fox-Rushby J, Davies C, Campbell-Lendrum D.Health Economic and Financing Programme, Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom. marianelacastillo@hotmail.com BACKGROUND: The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. METHODS: Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. FINDINGS: The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between $46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is $1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. CONCLUSION: Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare. PMCID: PMC2581604 |
| PMID: 19015725 [PubMed - indexed for MEDLINE] | |
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| 5. | PLoS Negl Trop Dis. 2008;2(9):e288. Epub 2008 Sep 3.HLA Class I-T cell epitopes from trans-sialidase proteins reveal functionally distinct subsets of CD 8+ T cells in chronic Chagas disease.Alvarez MG, Postan M, Weatherly DB, Albareda MC, Sidney J, Sette A, Olivera C, Armenti AH, Tarleton RL, Laucella SA.Hospital Interzonal General de Agudos "Eva Perón", San Martín, Provincia de Buenos Aires, Argentina. BACKGROUND: Previously, we identified a set of HLA-A020.1-restricted trans-sialidase peptides as targets of CD8+ T cell responses in HLA-A0201+ individuals chronically infected by T. cruzi. METHODS AND FINDINGS: Herein, we report the identification of peptides encoded by the same trans-sialidase gene family that bind alleles representative of the 6 most common class I HLA-supertypes. Based on a combination of bioinformatic predictions and HLA-supertype considerations, a total of 1001 epitopes predicted to bind to HLA A01, A02, A03, A24, B7 and B44 supertypes was selected. Ninety-six supertype-binder epitopes encoded by multiple trans-sialidase genes were tested for the ability to stimulate a recall CD8+ T cell response in the peripheral blood from subjects with chronic T. cruzi infection regardless the HLA haplotype. An overall hierarchy of antigenicity was apparent, with the A02 supertype peptides being the most frequently recognized in the Chagas disease population followed by the A03 and the A24 supertype epitopes. CD8+ T cell responses to promiscuous epitopes revealed that the CD8+ T cell compartment specific for T. cruzi displays a functional profile with T cells secreting interferon-gamma alone as the predominant pattern and very low prevalence of single IL-2-secreting or dual IFN-gamma/IL-2 secreting T cells denoting a lack of polyfunctional cytokine responses in chronic T. cruzi infection. CONCLUSIONS: This study identifies a set of T. cruzi peptides that should prove useful for monitoring immune competence and changes in infection and disease status in individuals with chronic Chagas disease. PMCID: PMC2565697 |
| PMID: 18846233 [PubMed - indexed for MEDLINE] | |
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