dc.contributor.advisor	Marques, Vera Linda Ribeiro
dc.contributor.advisor	Gil, José Pedro Planco Panades
dc.contributor.author	Cavaco, Isa da Conceição Lopes
dc.date.accessioned	2011-09-07T16:05:39Z
dc.date.available	2011-09-07T16:05:39Z
dc.date.issued	2007
dc.description	Tese dout., Bioquímica, Universidade do Algarve, 2007	por
dc.description.abstract	The overall aim of this thesis was the analysis of the genetic variability in genes coding for proteins important in drug metabolism. The analysis of the metabolism of antimalarial drugs, particularly amodiaquine, and the possible contribution of biotransformation for the susceptibility to the disease was also studied. The results obtained in the genotyping studies in the populations of Guinea- Bissau, Portugal, Sao Tome and Principe, Thailand and Zanzibar showed a high interethnic variability. A high variability in Africans was observed. The study of the effect of CYP2C8 genotype in the AQ treatment outcome revealed that none of the alleles analysed influence therapeutic efficacy. In the analysis of amodiaquine metabolism we focused particularly on the metabolite desethylamodiaquine. Using microsomes enriched with recombinant CYPs, a reduction in drug concentration was observed in the presence of CYP1A1. The posterior investigation of the genetic variation in CYP1A1 identified several SNPs, particularly in the Papua New Guinea population. However, this variability could not be associated with the extreme variability observed in pharmacokinetic parameters. The study on the influence of the GSTT1 null genotype in uncomplicated malaria revealed that the lack of this gene seems to be a protective factor in this disease	eng
dc.description.sponsorship	Fundação para a Ciência e Tecnologia (FCT)	por
dc.format	application/pdf	por
dc.identifier.other	576.3 CAV*Det Cave
dc.identifier.tid	101168551
dc.identifier.uri	http://hdl.handle.net/10400.1/818
dc.language.iso	eng	por
dc.relation	MOLECULAR DETERMINANTS IN RESPONSE TO MALARIA THERAPEUTICS
dc.subject	Teses	por
dc.subject	Biologia celular	por
dc.subject	Biologia molecular	por
dc.subject	Farmacologia	por
dc.subject	Genética	por
dc.title	Molecular determinants of the response to malaria therapeutics	por
dc.type	doctoral thesis
dspace.entity.type	Publication
oaire.awardTitle	MOLECULAR DETERMINANTS IN RESPONSE TO MALARIA THERAPEUTICS
oaire.awardURI	info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F8887%2F2002/PT
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.name	Fundação para a Ciência e a Tecnologia
rcaap.rights	openAccess	por
rcaap.type	doctoralThesis	por
relation.isProjectOfPublication	316988bf-c363-4d0d-b2f6-19700c3457da
relation.isProjectOfPublication.latestForDiscovery	316988bf-c363-4d0d-b2f6-19700c3457da
thesis.degree.grantor	Universidade do Algarve. Faculdade deCiências e Tecnologia	por
thesis.degree.level	Doutor	por
thesis.degree.name	Doutoramento em Bioquímica. Especialização em Biologia Celular e Molecular	por

Molecular determinants of the response to malaria therapeutics

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