Safety and immunogenicity of recombinant rabies virus (ERAGS) in mice and raccoon dogs.

PURPOSE: The development of a genetically modified live rabies vaccine applicable to wild raccoon dogs is necessary for the eradication of rabies in Korea. Thus, we constructed a recombinant rabies virus (RABV) called the ERAGS strain, using a reverse genetic system and evaluated its safety and efficacy in mice and its safety and immunogenicity in raccoon dogs. MATERIALS AND METHODS: ERAGS, which has Asn194Ser and Arg333Glu substitutions in the glycoprotein, was constructed using site-directed mutagenesis. Mice were inoculated with the ERAGS strain (either 10(5.0) or 10(7.0) FAID50/mL) via intramuscular (IM) or intracranial injections and then challenged with a virulent RABV. Raccoon dogs were administered the ERAGS strain (10(8.0) FAID50/mL) either orally or via the IM route and the immunogenicity of the strain was evaluated using fluorescent antibody virus neutralization tests. RESULTS: The ERAGS strain inoculated into murine neuroblastoma cells reached 10(7.8) FAID50/mL at 96-hour post-inoculation. The virus was not pathogenic and induced complete protection from virulent RABV in immunized 4- and 6-week-old mice. Korean raccoon dogs immunized with the ERAGS strain via IM or oral route were also safe from the virus and developed high titer levels (26.4-32.8 IU/mL) of virus-neutralizing antibody (VNA) at 4 weeks post-inoculation. CONCLUSION: The ERAGS RABV strain was effectively protective against rabies in mice and produced a high VNA titer in raccoon dogs.

Biocompatibility and strength retention of biodegradable Mg-Ca-Zn alloy bone implants.

The biocompatibility and strength retention of a Mg-Ca-Zn alloy were studied to evaluate its efficacy for osteosynthesis applications. Mg-Ca-Zn alloy and self-reinforced poly l-lactide (SR-PLLA) bone screws were implanted into New Zealand rabbits for radiography analysis, micro computed tomography analysis, histomorphometry, hematology, serum biochemistry, histopathology, and inductively coupled plasma mass spectrometry analysis. Bending and torsion tests were performed on intact specimens to find the initial mechanical strength of these Mg-Ca-Zn alloy bone screws. Strength retention of the Mg-Ca-Zn alloy implants were calculated from in vivo degradation rates and initial mechanical strength. Based on the animal study, Mg-Ca-Zn alloy bone screw showed absence of subcutaneous gas pockets, characteristic surface erosion properties, faster degradation rate than SR-PLLA bone screw, normal reference range of hematology and serum biochemistry, better histopathological response than SR-PLLA bone screw, and stable concentrations of each constituent element in soft tissues surrounding the implants. The initial strength and strength retention of Mg-Ca-Zn alloy were compared with those of various biomaterials. The initial strength of Mg-Ca-Zn alloy was higher than those of biostable and biodegradable polymers. The strength retention of Mg-Ca-Zn alloy bone screws was similar to those of biodegradable polymer. Therefore, this Mg-Ca-Zn alloy represents an excellent biodegradable biomaterial candidate for osteosynthesis applications.

Relationship between DNA ploidy and proliferative cell nuclear antigen index in canine hemangiopericytoma.

The mitotic index is reported to be correlated with recurrence, mean patient survival, and metastasis of canine hemangiopericytoma (CHP). However, to the authors' knowledge, studies investigating the parameters that can predict recurrence or metastasis of CHP with low mitotic index have not been done. To evaluate growth kinetics of CHP with low mitotic index, a retrospective analysis of the proliferative activity by antiproliferative cell nuclear antigen monoclonal antibody and DNA contents by flow cytometry (FCM) was performed with 21 formalin-fixed and paraffin-embedded CHP samples. Of the 21 tumors evaluated by FCM, 6 (26.6%) were aneuploid tumors, and 15 (71.4%) were diploid tumors. There was significant correlation between the PCNA index and ploidy pattern. The diploid group had 39.1 +/- 9.2 PCNA index, whereas the aneuploid group's proliferative cell nuclear antigen (PCNA) index was 63.1 +/- 8.2. The diploid group had mean mitotic index value of 1.140 +/- 0.855, and the aneuploid group had a mean value of 1.067 +/- 0.767. From these results, the CHP samples with low mitotic index were classified into either the aneuploid group with higher PCNA index or the diploid group with lower PCNA index, suggesting that DNA ploidy and proliferative activity may give an indication about malignancy of CHPs with a low mitotic index.