Document Detail


The Anti-Trypanosoma cruzi activity of posaconazole in a murine model of acute Chagas' disease is less dependent on gamma interferon than that of benznidazole.
MedLine Citation:
PMID:  17220408     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have investigated the influences of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) on the efficacy of posaconazole (POS) treatment of acute experimental infections with Trypanosoma cruzi; the standard drug, benznidazole (BZ), was used as a positive control. Wild-type (WT) mice infected with T. cruzi and treated with POS or BZ had no parasitemia, 100% survival, and cure rates of 86 to 89%. IFN-gamma-knockout (KO) mice infected with T. cruzi and treated with BZ controlled the infection during treatment but relapsed after the drug pressure ceased and had 0% survival, while those receiving POS better controlled the infection after the end of treatment and had 70% survival (P<0.0001 compared to the results for both untreated and BZ-treated animals). IL-12-KO mice infected and treated with POS or BZ had intermediate results, displaying enhanced parasitemia, decreased survival (77 to 83%), and reduced cure rates (35 to 39%) compared with those of the WT animals. Our results demonstrate that either IFN-gamma or IL-12 deficiency reduces the efficacy of POS or BZ in this experimental model but also indicate that the anti-T. cruzi activity of POS is much less dependent on the activity of IFN-gamma than that of BZ is.
Authors:
Marcela L Ferraz; Ricardo T Gazzinelli; Rosana O Alves; Julio A Urbina; Alvaro J Romanha
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-12
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  51     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-26     Completed Date:  2007-08-01     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1359-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Chagas Disease / drug therapy*
Interferon-gamma / pharmacology,  therapeutic use*
Interleukin-12 / biosynthesis,  pharmacology
Mice
Mice, Inbred C57BL
Nitroimidazoles / pharmacology,  therapeutic use*
Triazoles / pharmacology,  therapeutic use*
Trypanocidal Agents / therapeutic use*
Trypanosoma cruzi / drug effects*
Chemical
Reg. No./Substance:
0/Nitroimidazoles; 0/Triazoles; 0/Trypanocidal Agents; 187348-17-0/Interleukin-12; 22994-85-0/benzonidazole; 6TK1G07BHZ/posaconazole; 82115-62-6/Interferon-gamma
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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