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Sent on Wednesday, 2009 Dec 30Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | J Comput Aided Mol Des. 2009 Dec 29. [Epub ahead of print]Characterization of dipeptidylcarboxypeptidase of Leishmania donovani: a molecular model for structure based design of antileishmanials.Baig MS, Kumar A, Siddiqi MI, Goyal N.Division of Biochemistry, Central Drug Research Institute, Lucknow, 226001, India. Leishmania donovani dipeptidylcarboxypeptidsae (LdDCP), an angiotensin converting enzyme (ACE) related metallopeptidase has been identified and characterized as a putative drug target for antileishmanial chemotherapy. The kinetic parameters for LdDCP with substrate, Hip-His-Leu were determined as, Km, 4 mM and Vmax, 1.173 mumole/ml/min. Inhibition studies revealed that known ACE inhibitors (captopril and bradykinin potentiating peptide; BPP1) were weak inhibitors for LdDCP as compared to human testicular ACE (htACE) with Ki values of 35.8 nM and 3.9 muM, respectively. Three dimensional model of LdDCP was generated based on crystal structure of Escherichia coli DCP (EcDCP) by means of comparative modeling and assessed using PROSAII, PROCHECK and WHATIF. Captopril docking with htACE, LdDCP and EcDCP and analysis of molecular electrostatic potentials (MEP) suggested that the active site domain of three enzymes has several minor but potentially important structural differences. These differences could be exploited for designing selective inhibitor of LdDCP thereby antileishmanial compounds either by denovo drug design or virtual screening of small molecule databases. |
| PMID: 20039100 [PubMed - as supplied by publisher] | |
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| 2. | Antimicrob Agents Chemother. 2009 Dec 28. [Epub ahead of print]Early curative applications of aminoglycosides (WR279396) on experimental Leishmania major-loaded cutaneous site do not impair the acquisition of immunity.Lecoeur H, Buffet PA, Milon G, Lang T.Département de Parasitologie et Mycologie, Unité d'Immunophysiologie et Parasitisme Intracellulaire, Unité de Mycologie Médicale, Institut Pasteur & Service de Parasitologie Mycologie, INSERM UMR 945 CHU Hôpital Pitié Salpêtrière, 47-83 Boulevard de l'Hôpital 75651 PARIS CEDEX 13. Topical therapy is an attractive approach for the treatment of L. major cutaneous leishmaniasis (CL). WR279396, a third-generation aminoglycoside ointment, is now in Phase 3 trials. Because applying a cream is easier than performing injections of pentavalent antimony, many patients with CL will likely be treated with WR279396 soon after lesion onset. However, this new therapeutic approach may impair the acquisition of immunity. We evaluated the impact of early topical therapy on acquired immunity in an optimized mouse model of L. major-induced CL, the latter having allowed establishing the WR279396 ointment efficacy. Acquired immunity was defined as the absence of lesions upon re-inoculation of the same parasite isolate at a different skin site. Bioluminescence-based follow-up of luciferase-expressing L. major loads was also performed. In this model, the control of L. major loads at the initial inoculation site and the acquisition of immunity were simultaneous (day 22 post-inoculation). The clinical and parasitological efficacy of WR279396 applied as early as day 11 post-inoculation, i.e., during the L. major multiplying phase, did not impair the acquisition of immunity to a second L. major challenge. This is reassuring in the perspective of the wide deployment of WR279396-based therapy in L. major-endemic foci. |
| PMID: 20038619 [PubMed - as supplied by publisher] | |
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| 3. | Biochem Biophys Res Commun. 2009 Dec 18;390(3):541-6. Epub 2009 Oct 7.Heme-induced Trypanosoma cruzi proliferation is mediated by CaM kinase II.Souza CF, Carneiro AB, Silveira AB, Laranja GA, Silva-Neto MA, Costa SC, Paes MC.Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fiocruz, Brazil. Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted through triatomine vectors during their blood-meal on vertebrate hosts. These hematophagous insects usually ingest approximately 10mM of heme bound to hemoglobin in a single meal. Blood forms of the parasite are transformed into epimastigotes in the crop which initiates a few hours after parasite ingestion. In a previous work, we investigated the role of heme in parasite cell proliferation and showed that the addition of heme significantly increased parasite proliferation in a dose-dependent manner [1]. To investigate whether the heme effect is mediated by protein kinase signalling pathways, parasite proliferation was evaluated in the presence of several protein kinase (PK) inhibitors. We found that only KN-93, a classical inhibitor of calcium-calmodulin-dependent kinases (CaMKs), blocked heme-induced cell proliferation. KN-92, an inactive analogue of KN-93, was not able to block this effect. A T. cruzi CaMKII homologue is most likely the main enzyme involved in this process since parasite proliferation was also blocked when Myr-AIP, an inhibitory peptide for mammalian CaMKII, was included in the cell proliferation assay. Moreover, CaMK activity increased in parasite cells with the addition of heme as shown by immunological and biochemical assays. In conclusion, the present results are the first strong indications that CaMKII is involved in the heme-induced cell signalling pathway that mediates parasite proliferation. |
| PMID: 19818332 [PubMed - indexed for MEDLINE] | |
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| 4. | Vet Parasitol. 2009 Nov 12;165(3-4):241-7. Epub 2009 Jul 15.Comparison of two immunochromatographic assays and the indirect immunoflu orescence antibody test for diagnosis of Trypanosoma cruzi infection in dogs in south central Louisiana.Nieto PD, Boughton R, Dorn PL, Steurer F, Raychaudhuri S, Esfandiari J, Gonçalves E, Diaz J, Malone JB.Louisiana State University, School of Veterinary Medicine, South Stadium Road, Baton Rouge, LA 70803, USA. pnieto@lsuhsc.edu Two rapid tests evaluated in dogs considered to be of high risk of infection with the Chagas parasite Trypanosoma cruzi using two immunochromatographic assays: Trypanosoma Detect for canine, InBios, Seattle, WA and CHAGAS STAT-PAK assay, Chembio Diagnostic Systems, Medford, NY, in south central Louisiana. For this purpose a serological survey was carried out in a total of 122 dogs and a serum bank was created. These 122 animals were first tested by IFAT that was used as the standard test. From the serum bank 50 samples were tested using the two rapid Chagas assays and results compared to the standard test IFAT. The serological survey using IFAT showed a prevalence of T. cruzi infection in 22.1% of the tested dogs. In the immunochromatographic assays, 13 and 11 animals were positive on rapid assay: Trypanosoma Detect for canine, InBios and CHAGAS STAT-PAK, Chembio Diagnostic Systems, respectively compared to 11 positive by IFAT. These two immunochromatographic tests have shown high susceptibility and specificity compared to our standard method IFAT. The rapid, easy and accurate screening assays used in conjunction with confirmatory tests, would be an excellent tool for veterinarians to diagnose T. cruzi infection. Early detection of T. cruzi infection may prevent complications through an effective treatment. Greater awareness by veterinarians of the risk, clinical findings, history along with diagnostic methods will contribute greatly to an understanding of the true prevalence of Chagas disease in dogs in Louisiana. |
| PMID: 19647943 [PubMed - indexed for MEDLINE] | |
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