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From control to eradication of malaria:the end of being stuck in second gear?

Asian Pacific Journal of Tropical Medicine 2010年第5期3卷 412-420页

作者： khadjavi amina Giribaldi Giuliana Prato Mauro Department of Genetics Biology and BiochemistryUniversity of Torino Medical School10126TorinoItaly

More than 2 billion people are at risk of malaria,which primarily affects poor populations in tropical and subtropical areas,including Southern *** malaria incidence has been reduced strongly in some parts of endemic regions by combinations of interventions,including artemisinin-based therapies and insecticide-treated bed nets,a new goal has been established recently by charity foundations which support research on malaria:the worldwide eradication of the *** away with control approaches which have been applied for the last 50 years and more focus on elimination objectives will deeply change priorities in the area of malaria treatment,chemoprevention,vector control,vaccine research and health system *** this review,actual knowledge on pathogenesis and pharmacology is discussed,and new drugs, vaccines and insecticides are described.

关键词： Malaria Plasmodium falciparum Anopheles mosquito Antimalarial drugs Vaccine Vector control Hemozoin Matrix metalloproteinases

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Malarial pigment enhances heat shock protein-27 in THP-1 cells:new perspectives for in vitro studies on monocyte apoptosis prevention

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Asian Pacific Journal of Tropical Medicine 2010年第12期3卷 934-938页

作者： Mauro Prato Valentina Gallo Elena Valente amina khadjavi Giorgia Mandili Giuliana Giribaldi Department of Genetics Biology and BiochemistryUniversity of Torino Medical SchoolTorinoItaly

Objective:To investigate the effect of malarial pigment(hemozoin,HZ) on expression of heat shock proteins(HSPs) and cell viability in human monocytes by using a stable cell line(THP-1 cells).Methods:THP-1 cells were fed with native HZ or treated with pro-apoptotic molecule gliotoxin for 9 ***,the protein expression of HSP-27 and HSP-70 was evaluated by western ***,HZ-fed cells were cultured up to 72 h and cell viability parameters(survival,apoptosis and necrosis rates) were measured by flow cytometric analysis. Results:HZ increased basal protein levels of HSP-27 without altering those of HSP-70 in THP-1 cells,and promoted long-term cell survival without inducing *** expected,gliotoxin inhibited HSP-27 protein expression and promoted long-term cell ***: Present data show that HZ prevents cell apoptosis and enhances the expression of anli-apoptotic HSP-27 in THP-1 cells,confirming the previous evidences obtained from HZ-fed immunopurified *** the use of a stable cell line is pivotal to perform HSP-27 silencing experiments, monocytic THP-1 cells could be a good candidate line for such an approach,which is heavily required to clarify the role of HSP-27 in survival of impaired HZ-fed monocytes during falciparum malaria.

关键词： Hemozoin Plasmodium falciparum Malaria Monocyte THP-1 cells Phagocytosis Apoptosis Heat shock protein-27

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Macrophage Inflammatory Protein-lalpha mediates Matrix Metalloproteinase-9 enhancement in human adherent monocytes fed with malarial pigment

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Asian Pacific Journal of Tropical Medicine 2011年第12期4卷 925-930页

作者： Giuliana Giribaldi Elena Valente amina khadjavi Manuela Polimeni Mauro Prato Dipartimento di Genetica Biologia e BiochimicaFacolta di Medicina e ChirurgiaUniversita degli studi di TorinoTorinoItaly Dipartimento di Genetica Biologia e BiochimicaFacolta di Medicina e ChirurgiaUniversita degli studi di TorinoTurinoItaly Corresponding author:Prof.Mauro Prato PhDDepartment of GeneticsBiology and BiochemistryUniversity of Torino Medical School10126TorinoItaly

Objective:To investigate the role of macrophage inflammatory protein-1alpha(MIP-1 alpha) in the detrimental enhancement of matrix mnetalloproteinase-9(MMP-9) expression,release and activity induced by phagocytosis of malarial pigment(haemozoin,HZ) in human monocytes. Methods:Human adherent monocytes were unfed/fed with native HZ for 2 *** 24 hours. MIP-1 alpha production was evaluated by ELISA in cell *** /fed monocytes were treated in presence/absence of anti-human MIP-1 alpha blocking antibodies or recombinant human MIP-lalpha for 15 h(RNA studies) or 24 h(protein studies): therefore,MMP-9 mRNA expression was evaluated in cell lysatcs by Real Time RT-PCR,whereas proMMP-9 and active MMP-9 protein release were measured in cell supernatants by Western blotting and gelatin ***:Phagocytosis of HZ by human monocytes increased production of MIP-1 *** expression of MMP-9 and protein release of proMMP-9 and active *** the HZ-enbancing effects on MMP-9 were abrogated by anti-human MIP- 1 alpha blocking antibodies and mimicked by recombinant human MIP-l ***: The present work suggests a role for MIP-lalpha in the HZ-dependent enhancement of MMP-9 expression,release and activity observed in human *** new detrimental effects of HZ-triggered proinflammatory response by phagocytic cells in falciparum malaria.

关键词： Plasmodium falciparum Malaria Monocyte Phagocytosis Haemozoin Matrix metalloproteinase-9 Macrophage inflammatory proteinlalpha

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