63925 Sidwell
نویسندگان
چکیده
evaluating potential influenza virus inhibitors. However, the viral strains traditionally used in these models are fairly old and do not represent currently circulating viruses in nature. We developed two new lethal infection models in mice using mouse-adapted influenza A/New Caledonia/ 20/99 (H1N1) and influenza B/Sichuan/379/99 viruses. Both virus infections were used to study oral treatment with oseltamivir and ribavirin, both alone and in combination. Oral treatments were given twice daily for 5 days starting 4 h before infection in initial studies. Against influenza A, oseltamivir was active at 10, 20, and 40 mg/kg/day, protected 80–100% of mice from death and reduced lung consolidation – ribavirin was similarly effective at 20, 40, and 80 mg/kg/day. When treatments were initiated after virus challenge, delaying treatment with oseltamivir even 1 day caused it to be ineffective. Ribavirin prevented mortality by 50–80% when treatments were delayed 1–4 days after infection. The combination of the two drugs (oseltamivir at 20 mg/kg/day and ribavirin at 40 mg/kg/day) was no better than ribavirin alone. In contrast to what we observed with influenza A virus infections, oseltamivir and ribavirin showed similar doserelated antiviral activities against influenza B virus infections. The compounds both significantly increased survival when treatments started up to 4 days after infection, but ribavirin was more active than oseltamivir (50–80% survival compared to 30–40% survival, respectively, when starting treatments on days 2–4 after infection). By varying the doses of each drug that were used in combination (oseltamivir at 1.25, 2.5 and 5 mg/kg/day; ribavirin at 5, 10 and 20 mg/kg/day) certain dosage combinations were superior to either compound used alone as assessed by decreased mortality, lung virus titre, lung score and lung weight parameters. These activities differed from published results with older, more established virus strains as oseltamivir was less effective and ribavirin was more active than previously reported.
منابع مشابه
Utilization of alpha-1-acid glycoprotein levels in the serum as a parameter for in vivoassay of influenza virus inhibitors. Antivir Chem Chemother
متن کامل
Failure of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) to stimllate interferon.
In cultured cells, Virazole failed to stimulate either interferon or a cellular resistance which continued in its absence. Serum from Virazole-treated mice likewise contained no demonstrable interferon.
متن کاملHccc Reference 09/1695 Tom Sidwell March 1, 2010 To: Ms Leanne Evans Investigation Officer Health Care Complaints Commission Re: Meryl Dorey and the Avn Response to Hccc Complaint
It should be noted that Ms Dorey’s claim that “Dr Wakefieldʼs study was only the first of many to indicate a very strong and, in some cases clinically verifiable connection between vaccination and the development of ASDs [autism spectrum disorders]” is incorrect; the Wakefield paper itself does not come to that conclusion. The discussion of the Wakefield paper clearly states “We did not prove a...
متن کامل