دورية
Efficacy of Pyrvinium Pamoate against Cryptosporidium parvumInfection In Vitro and in a Neonatal Mouse Model
| العنوان: | Efficacy of Pyrvinium Pamoate against Cryptosporidium parvumInfection In Vitro and in a Neonatal Mouse Model |
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| المؤلفون: | Downey, Autumn S., Chong, Curtis R., Graczyk, Thaddeus K., Sullivan, David J. |
| المصدر: | Antimicrobial Agents and Chemotherapy; September 2008, Vol. 52 Issue: 9 p3106-3112, 7p |
| مستخلص: | ABSTRACTNo effective approved drug therapy exists for Cryptosporidiuminfection of immunocompromised patients. Here we investigated the nonabsorbed anthelmintic drug pyrvinium pamoate for inhibition of the growth of the intestinal protozoan parasite Cryptosporidium parvum. The concentration of pyrvinium that effected 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was 354 nM. For comparison, in the same assay, 50% growth inhibition was obtained with 711 μM paromomycin or 27 μM chloroquine. We used a neonatal mouse model to measure the anti-Cryptosporidiumactivity of pyrvinium pamoate in vivo. Beginning 3 days after infection, pyrvinium at 5 or 12.5 mg/kg of body weight/day was administered to the treatment group mice for 4 or 6 consecutive days. Nine days after infection, the mice were sacrificed, and drug efficacy was determined by comparing the numbers of oocysts in the fecal smears of treated versus untreated mice. The intensities of trophozoite infection in the ileocecal intestinal regions were also compared using hematoxylin-and-eosin-stained histological slides. We observed a >90% reduction in infection intensity in pyrvinium-treated mice relative to that in untreated controls, along with a substantial reduction in tissue pathology. Based on these results, pyrvinium pamoate is a potential drug candidate for the treatment of cryptosporidiosis in both immunocompetent and immunocompromised individuals. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 00664804 10986596 |
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| DOI: | 10.1128/AAC.00207-08 |