Ketoconazole Inhibition of Intracellular Multiplication of Trypanosoma cruzi and Protection of Mice Against Lethal Infection with the Organism
Identifieur interne : 003570 ( Main/Exploration ); précédent : 003569; suivant : 003571Ketoconazole Inhibition of Intracellular Multiplication of Trypanosoma cruzi and Protection of Mice Against Lethal Infection with the Organism
Auteurs : Robert E. Mccabe [États-Unis] ; Jack S. Remington [États-Unis] ; Fausto G. Araujo [États-Unis]Source :
- Journal of Infectious Diseases [ 0022-1899 ] ; 1984.
Abstract
The effects of ketoconazole against infection with Trypanosoma cruzi both in vivo and in vitro were examined. In vivo, ketoconazole significantly protected mice infected with lethal inocula of the Y strain of T. cruzi even when treatment was initiated seven days after infection; protection was also demonstrated for three other strains. Although mice had demonstrable parasitemia after completion of therapy, tissue sections of treated mice revealed a complete absence of organisms. Concentrations of ketoconazole as low as 0.001 µg/ml inhibited in vitro replication of intracellular organisms, whereas concentrations of ketoconazole that prevented replication of intracellular amastigotes had no effect on extracellular organisms. This finding and the observation that inhibition of replication of amastigotes occurred in macrophages exposed to ketoconazole before infection suggests that the inhibitory effect depends on interaction of the drug with host cells. Thus ketoconazole should be tested as a therapeutic agent for Chagas' disease in humans.
Url:
DOI: 10.1093/infdis/150.4.594
Affiliations:
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Mccabe</name><affiliation wicri:level="2"><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, Stanford</wicri:cityArea></affiliation></author><author><name sortKey="Remington, Jack S" sort="Remington, Jack S" uniqKey="Remington J" first="Jack S." last="Remington">Jack S. Remington</name><affiliation wicri:level="2"><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, Stanford</wicri:cityArea></affiliation></author><author><name sortKey="Araujo, Fausto G" sort="Araujo, Fausto G" uniqKey="Araujo F" first="Fausto G." last="Araujo">Fausto G. Araujo</name><affiliation wicri:level="2"><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, Stanford</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Infectious Diseases</title><title level="j" type="abbrev">J Infect Dis.</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date when="1984-10">1984</date><biblScope unit="vol">150</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="594">594</biblScope><biblScope unit="page" to="601">601</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">The effects of ketoconazole against infection with Trypanosoma cruzi both in vivo and in vitro were examined. In vivo, ketoconazole significantly protected mice infected with lethal inocula of the Y strain of T. cruzi even when treatment was initiated seven days after infection; protection was also demonstrated for three other strains. Although mice had demonstrable parasitemia after completion of therapy, tissue sections of treated mice revealed a complete absence of organisms. Concentrations of ketoconazole as low as 0.001 µg/ml inhibited in vitro replication of intracellular organisms, whereas concentrations of ketoconazole that prevented replication of intracellular amastigotes had no effect on extracellular organisms. This finding and the observation that inhibition of replication of amastigotes occurred in macrophages exposed to ketoconazole before infection suggests that the inhibitory effect depends on interaction of the drug with host cells. Thus ketoconazole should be tested as a therapeutic agent for Chagas' disease in humans.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Mccabe, Robert E" sort="Mccabe, Robert E" uniqKey="Mccabe R" first="Robert E." last="Mccabe">Robert E. Mccabe</name></region><name sortKey="Araujo, Fausto G" sort="Araujo, Fausto G" uniqKey="Araujo F" first="Fausto G." last="Araujo">Fausto G. Araujo</name><name sortKey="Remington, Jack S" sort="Remington, Jack S" uniqKey="Remington J" first="Jack S." last="Remington">Jack S. Remington</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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