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Sent on Thursday, 2011 Jul 14Search 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 Negl Trop Dis. 2011 Jul;5(7):e1233. Epub 2011 Jul 5.Accuracy of five algorithms to diagnose gambiense human african trypanosomiasis.Checchi F, Chappuis F, Karunakara U, Priotto G, Chandramohan D.SourceFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. AbstractBACKGROUND:Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda. METHODOLOGY AND PRINCIPAL FINDINGS:The sequence of tests in each algorithm was programmed into a probabilistic model, informed by distributions of the sensitivity, specificity and staging accuracy of each test, constructed based on a literature review. The accuracy of algorithms was estimated in a baseline scenario and in a worst-case scenario introducing various near worst-case assumptions. In the baseline scenario, sensitivity was estimated as 85-90% in all but one algorithm, with specificity above 99.9% except for the Republic of Congo, where CATT serology was used as independent confirmation test: here, positive predictive value (PPV) was estimated at <50% in realistic active screening prevalence scenarios. Furthermore, most algorithms misclassified about one third of true stage 1 cases as stage 2, and about 10% of true stage 2 cases as stage 1. In the worst-case scenario, sensitivity was 75-90% and PPV no more than 75% at 1% prevalence, with about half of stage 1 cases misclassified as stage 2. CONCLUSIONS:Published evidence on the accuracy of widely used tests is scanty. Algorithms should carefully weigh the use of serology alone for confirmation, and could enhance sensitivity through serological suspect follow-up and repeat parasitology. Better evidence on the frequency of low-parasitaemia infections is needed. Simulation studies should guide the tailoring of algorithms to specific scenarios of HAT prevalence and availability of control tools. |
| 2. | Mol Pharmacol. 2011 Jul 12. [Epub ahead of print]Novel Betulin Derivatives as Antileishmanial Agents with Mode of Action Targeting Type IB DNA Topoisomerase.Chowdhury S, Mukherjee T, Sengupta S, Chowdhury SR, Mukhopadhyay S, Majumder HK.SourceIndian Institute of Chemical Biology. AbstractTowards developing antileishmanial agents with mode of action targeted to DNA topoisomerases of Leishmania donovani, we have synthesized a large number of derivatives of betulin. The compound, a natural triterpene isolated from the cork layer of Betula plants exhibits several pharmacological properties. Three compounds viz. disuccinyl betulin, diglutaryl dihydrobetulin and disuccinyl dihydrobetulin inhibit growth of the parasite as well as relaxation activity of the enzyme type IB topoisomerase (LdTOP1LS) of the parasite. Mechanistic studies suggest that these compounds interact with the enzyme in a reversible manner. The stoichiometry of these compounds binding to LdTOP1LS is 1:1 (mole : mole) with a dissociation constant of the order of ~10-(6)M. Unlike CPT, these compounds do not stabilize the cleavage complex, rather they abrogate the covalent complex formation. In processive mode of relaxation assay condition, these compounds slow down the strand rotation event which ultimately affect the relaxation of supercoiled DNA. Interestingly, these compounds reduce the intracellular parasite burden in macrophages infected with wild type Leishmania as well as with sodium antimony gluconate resistant parasite (GE1). Taken together, our data suggest that these betulin derivatives can be exploited as potential drug candidates against threatening drug resistant leishmaniasis. |
| 3. | Virol J. 2011 Mar 18;8:127.Biological and immunological characterization of recombinant Yellow Fever 17D viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8+ T cell epitope at two distinct regions of the genome.Nogueira RT, Nogueira AR, Pereira MC, Rodrigues MM, Galler R, Bonaldo MC.SourceFundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular de FlavivÃrus, Rio de Janeiro, Fundação Oswaldo Cruz, Avenida Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21045-900, Brazil. AbstractBACKGROUND:The attenuated Yellow fever (YF) 17D vaccine virus is one of the safest and most effective viral vaccines administered to humans, in which it elicits a polyvalent immune response. Herein, we used the YF 17D backbone to express a Trypanosoma cruzi CD8+ T cell epitope from the Amastigote Surface Protein 2 (ASP-2) to provide further evidence for the potential of this virus to express foreign epitopes. The TEWETGQI CD8+ T cell epitope was cloned and expressed based on two different genomic insertion sites: in the fg loop of the viral Envelope protein and the protease cleavage site between the NS2B and NS3. We investigated whether the site of expression had any influence on immunogenicity of this model epitope. RESULTS:Recombinant viruses replicated similarly to vaccine virus YF 17D in cell culture and remained genetically stable after several serial passages in Vero cells. Immunogenicity studies revealed that both recombinant viruses elicited neutralizing antibodies to the YF virus as well as generated an antigen-specific gamma interferon mediated T-cell response in immunized mice. The recombinant viruses displayed a more attenuated phenotype than the YF 17DD vaccine counterpart in mice. Vaccination of a mouse lineage highly susceptible to infection by T. cruzi with a homologous prime-boost regimen of recombinant YF viruses elicited TEWETGQI specific CD8+ T cells which might be correlated with a delay in mouse mortality after a challenge with a lethal dose of T. cruzi. CONCLUSIONS:We conclude that the YF 17D platform is useful to express T. cruzi (Protozoan) antigens at different functional regions of its genome with minimal reduction of vector fitness. In addition, the model T. cruzi epitope expressed at different regions of the YF 17D genome elicited a similar T cell-based immune response, suggesting that both expression sites are useful. However, the epitope as such is not protective and it remains to be seen whether expression of larger domains of ASP-2, which include the TEWETGQI epitope, will elicit better T-CD8+ responses to the latter. It is likely that additional antigens and recombinant virus formulations will be necessary to generate a protective response. |
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