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Sent on Wednesday, 2009 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: Bioinformation. 2008;3(3):114-8. Epub 2008 Nov 2.
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Insights from the analysis of a predicted model of gp63 in Leishmania donovani.
Leishmaniasis is a protozoal disease of human that occurs in most parts of the world. By considering the progress of bioinformatics in molecular modeling, major surface glycoprotein of Leishmania donovani (gp63) structure was modeled using homology modeling with high accuracy based on the X-ray crystal structure of the Leishmania major gp63 as a template, and then analyzed 3D structure of gp63 which can reveal exact facts about its structure and interaction. The objective of this study was to find folding and three dimensional structure of the gp63 as potent antigen for human. In this project, we applied the theory of evolution method, including comparative modeling and threading. This study presented a simple protocol for rapid and precise finding 3D structure of gp63 and investigation of its structural properties. The translated amino acid sequence showed that Leishmania donovani gp63 contains 590 amino acids precursor protein consisting of an NH(2)-terminal signal peptide of 39 amino acids for membrane targeting, a pro region of 48 amino acids, the mature protein of 478 amino acids containing glycosylation and putative catalytic sites, and a COOH-terminal signal peptide of 25 amino acids for GPI attachment. Based on our model, the protein consists of three domains: the N-terminal, central and C-terminal domains. Additionally, these results could guide future structure-function analyses of gp63 protein.
PMID: 19238247 [PubMed - in process]
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- Molecular cloning of the major surface antigen of leishmania. [J Exp Med. 1988]
- Heterogeneity of the genes encoding the major surface glycoprotein of Leishmania donovani. [Mol Biochem Parasitol. 1991]
- Differentially expressed Leishmania major gp63 genes encode cell surface leishmanolysin with distinct signals for glycosylphosphatidylinositol attachment. [Mol Biochem Parasitol. 1998]
- ReviewMutational and functional analysis of the Leishmania surface metalloproteinase GP63: similarities to matrix metalloproteinases. [Parasitology. 1994]
- ReviewBridging the gap between structural bioinformatics and receptor research: the membrane-embedded, ligand-gated, P2X glycoprotein receptor. [Curr Top Med Chem. 2004]
- 2: PLoS Negl Trop Dis. 2009;3(2):e384. Epub 2009 Feb 24.
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Identification of Three Classes of Heteroaromatic Compounds with Activity against Intracellular Trypanosoma cruzi by Chemical Library Screening.
Department of Medical Parasitology, New York University School of Medicine, New York, New York, United States of America.
The development of new drugs against Chagas disease is a priority since the currently available medicines have toxic effects, partial efficacy and are targeted against the acute phase of disease. At present, there is no drug to treat the chronic stage. In this study, we have optimized a whole cell-based assay for high throughput screening of compounds that inhibit infection of mammalian cells by Trypanosoma cruzi trypomastigotes. A 2000-compound chemical library was screened using a recombinant T. cruzi (Tulahuen strain) expressing beta-galactosidase. Three hits were selected for their high activity against T. cruzi and low toxicity to host cells in vitro: PCH1, NT1 and CX1 (IC(50): 54, 190 and 23 nM, respectively). Each of these three compounds presents a different mechanism of action on intracellular proliferation of T. cruzi amastigotes. CX1 shows strong trypanocidal activity, an essential characteristic for the development of drugs against the chronic stage of Chagas disease where parasites are found intracellular in a quiescent stage. NT1 has a trypanostatic effect, while PCH1 affects parasite division. The three compounds also show high activity against intracellular T. cruzi from the Y strain and against the related kinetoplastid species Leishmania major and L. amazonensis. Characterization of the anti-T. cruzi activity of molecules chemically related to the three library hits allowed the selection of two compounds with IC(50) values of 2 nM (PCH6 and CX2). These values are approximately 100 times lower than those of the medicines used in patients against T. cruzi. These results provide new candidate molecules for the development of treatments against Chagas disease and leishmaniasis.
PMID: 19238193 [PubMed - in process]
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Related Articles
- Phenyl substitution of furamidine markedly potentiates its anti-parasitic activity against Trypanosoma cruzi and Leishmania amazonensis. [Biochem Pharmacol. 2004]
- Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase. [Antimicrob Agents Chemother. 1996]
- Activity of "reversed" diamidines against Trypanosoma cruzi "in vitro". [Biochem Pharmacol. 2007]
- ReviewChemotherapy of Chagas disease. [Curr Pharm Des. 2002]
- ReviewMolecular mimicry between Trypanosoma cruzi and host nervous tissues. [Acta Cient Venez. 1992]
- 3: Infect Immun. 2009 Feb 23. [Epub ahead of print]
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Immunological determinants of clinical outcome in Peruvian patients with tegumentary leishmaniasis treated by pentavalent antimonials.
Travel and Migration Medicine Unit, University Hospital and School of Medicine, Geneva, Switzerland; Immunology and Allergy, University Hospital and School of Medicine, Geneva, Switzerland; Molecular Parasitology & Epidemiology Units, Institute of Tropical Medicine, Antwerp, Belgium; Laboratory of Molecular Parasitology, Instituto de Medicina Tropical "Alexander von Humboldt", Lima, Peru.
The mechanisms linking the immune response to cutaneous (CL) and mucosal (ML) Leishmania lesions and response to treatment are incompletely understood. Our aim was to prospectively assess by reverse transcribed, quantitative polymerase chain reaction the levels of mRNA for IFN-gamma, TNF-alpha, IL-10, IL-4, IL-13, as well as the presence of T cells (CD2) and macrophages (CD68) in CL and ML lesions and to follow their changes in response to treatment with pentavalent antimonials (SbV). The Leishmanin Skin Test (LST) was performed in all CL and ML patients before treatment. Patient population included individuals living in endemic areas of Peru, 129 with CL and 43 with ML. When compared to CL, the LST size was larger, the levels of all cytokine mRNA but IL-10 were higher, T cell mRNA similar and macrophage mRNA lower in ML. The proportion of CL patients with a LST size larger than 8 mm was higher among responders to treatment. In CL the pre-treatment levels of cytokines mRNA did not discriminate between responders and non-responders, however treatment was accompanied by a reduction in the levels of T cell and cytokine mRNA more in responders than in non-responders. Furthermore, the production of cytokines per T cell and macrophages decreased with treatment but IL-10 production remained high in non-responders. Overall these findings point to a complex relationship between New World Leishmania parasites, skin and mucosal immune response, and treatment outcome. The persistence of high levels of IL-10 in CL is characteristically associated with poor response to treatment.
PMID: 19237520 [PubMed - as supplied by publisher]
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Related Articles
- Parasitological and immunological follow-up of American tegumentary leishmaniasis patients. [Trans R Soc Trop Med Hyg. 2002]
- Dichotomy of protective cellular immune responses to human visceral leishmaniasis. [Clin Exp Immunol. 2005]
- T-cell-mediated immune responses in patients with cutaneous or mucosal leishmaniasis: long-term evaluation after therapy. [Clin Diagn Lab Immunol. 2002]
- Review[Immunopathology of American tegumentary leishmaniasis] [Acta Cient Venez. 1998]
- ReviewLeishmaniasis: recognition and management with a focus on the immunocompromised patient. [Am J Clin Dermatol. 2002]
- 4: Trans R Soc Trop Med Hyg. 2009 Feb 21. [Epub ahead of print]
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Presence of antibodies against Leishmania chagasi in haemodialysed patients.
Department of Infectious Diseases, UFRN, Natal, Rio Grande do Norte - RN, Brazil.
In the last decades there has been an increase in cases of visceral leishmaniasis complicating the post-transplant phase, mainly following kidney transplantation. The aim of this study was to evaluate the reactivity of haemodialysed patients using IFAT. Blood samples of 310 individuals from Natal, RN, Brazil, were collected and analysed. Data regarding blood transfusion, cause of end-stage renal disease and duration of haemodialysis were also analysed. In total, 69 patients (22.3%) were positive by IFAT. This study suggests that antibody detection should be performed in this group of patients since they are possible candidates for kidney transplantation.
PMID: 19237180 [PubMed - as supplied by publisher]
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- Immunofluorescent antibody test in American visceral leishmaniasis: sensitivity and specificity of different morphological forms of two Leishmania species. [Am J Trop Med Hyg. 1983]
- Long-lasting protection against canine visceral leishmaniasis using the LiESAp-MDP vaccine in endemic areas of France: double-blind randomised efficacy field trial. [Vaccine. 2007]
- Cross-reactivity between antibodies in the sera of individuals with leishmaniasis, toxoplasmosis, and Chagas' disease and antigens of the blood-stage forms of Plasmodium falciparum determined by indirect immunofluorescence. [Am J Trop Med Hyg. 1995]
- Review[Feline leishmaniasis: what's the epidemiological role of the cat?] [Parassitologia. 2004]
- ReviewClinical use of polymerase chain reaction performed on peripheral blood and bone marrow samples for the diagnosis and monitoring of visceral leishmaniasis in HIV-infected and HIV-uninfected patients: a single-center, 8-year experience in Italy and review of the literature. [Clin Infect Dis. 2007]
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