Single-dose intranasal administration with mDEF201 (adenovirus vectored mouse interferon-alpha) confers protection from mortality in a lethal SARS-CoV BALB/c mouse model.

Interferons (IFNs) are a first line of defense against viral infection. Herein we describe the use of an adenovirus vectored mouse IFN alpha gene (mDEF201) as a prophylactic and treatment countermeasure in a SARS-CoV-infected BALB/c mouse model. Complete survival protection was observed in mice given a single dose of mDEF201 administered intranasally 1, 3, 5, 7, or 14 days prior to lethal SARS-CoV challenge (p<0.001), and body weights of these treated mice were unaffected by the challenge. In addition, low doses of mDEF201 protected lungs in a dose dependent manner as measured by a reduction in gross pathology. Intranasal treatment with mDEF201 ranging from 10(6) to 10(8)PFU significantly protected mice against a lethal SARS-CoV infection in a dose dependent manner up to 12h post infection (p<0.001). The data suggest that mDEF201 is a new class of antiviral agent further development as treatment for SARS-CoV infections.

Induction of interferon-gamma-inducible protein 10 by SARS-CoV infection, interferon alfacon 1 and interferon inducer in human bronchial epithelial Calu-3 cells and BALB/c mice.

BACKGROUND: The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is poorly understood. Several mechanisms involving both direct effects on target cells and indirect effects via the immune system might exist. SARS-CoV has been shown in vitro to induce changes of cytokines and chemokines in various human and animal cells. We previously reported that interferon (IFN) alfacon-1 was more active against SARS-CoV infection in human bronchial epithelial Calu-3 cells than in African green monkey kidney epithelial cells on day 3 post-infection. METHODS: In the current study, we first evaluated the efficacy of IFN-alfacon 1 in Calu-3 cells during the first 7 days of virus infection. We then used the two-antibody sandwich ELISA method to detect IFN-gamma-inducible protein 10 (IP-10). We further evaluated the efficacy of antivirals directed against SARS-CoV infection in BALB/c mice. RESULTS: A potent, prolonged inhibition of SARS-CoV replication in Calu-3 cells with IFN-alfacon 1 was observed. Furthermore, IP-10, an IFN-inducible leukocyte chemoattractant, was detected in Calu-3 cells after SARS-CoV infection. Interestingly, IP-10 expression was shown to be significantly increased when SARS-CoV-infected Calu-3 cells were treated with IFN alfacon-1. IP-10 expression was detected in the lungs of SARS-CoV-infected BALB/c mice. Significantly high levels of mouse IP-10 in BALB/c mice was also detected when SARS-CoV-infected mice were treated with the interferon inducer, polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine and carboxymethyl cellulose (poly IC:LC). Treatment with poly IC:LC by intranasal route were effective in protecting mice against a lethal infection with mouse-adapted SARS-CoV and reduced the viral lung titres. CONCLUSIONS: Our data might provide an important insight into the mechanism of pathogenesis of SARS-CoV and these properties might be therapeutically advantageous.

Nursing home executive directors' perception of oral care in long-term care facilities.

Oral health in long-term care (LTC) facilities has been repeatedly documented as less than ideal. The complex nature of this environment has made it difficult to understand and improve the oral health status of residents through education and training. The purpose of the study was to investigate how the executive directors (EDs) of LTC facilities value oral health and to determine facility variables, which may influence how oral care is delivered. A mail survey of the EDs of all LTC facilities in Ohio (n = 1018) was conducted with 338 responses received after secondary follow-up (33.2% response rate). The 30-item survey included information concerning the nursing facility, the EDs, the EDs' perception of the level of oral health care, and value statements rated on a Likert-like scale. The results of the survey showed that more than two-thirds of the EDs were female and that most facilities were proprietary (70.3%). ED gender was not statistically associated with any of the oral health variables. Fifty-three percent of the EDs rated their residents' oral health as fair or poor but were still satisfied with the oral care provided at their facilities. The apparent discontinuity between perceived levels of oral health and satisfaction with oral care suggests that EDs are distanced from the oral care of their residents or they do not acknowledge oral health care needs. While the survey results revealed important facility characteristics and administrators' perceptions about oral health, the most important aspect of this project was the low response rate despite secondary follow-up. That, coupled with the negativity expressed upon follow-up, suggests a larger issue that may affect oral health in nursing facilities: oral health continues to have a low priority in this setting. Continuing efforts to improve oral health and educate LTC professionals about oral health's influence on general health is critical for managing the oral health of future generations of aging adults.