Anti-vascular endothelial growth factor antibody monotherapy causes destructive advanced periodontitis in rice rats (Oryzomys palustris).

OBJECTIVE: Angiogenesis inhibitors (AgI) are commonly used in combination chemotherapy protocols to treat cancer, and have been linked to osteonecrosis of the jaw (ONJ). However, it is unknown if AgI therapy alone is sufficient to induce ONJ. We have previously established an ONJ model in rice rats with localized periodontitis that receive zoledronic acid (ZOL). The purpose of this study was to use this model to determine the role of anti-vascular endothelial growth factor A (anti-VEGF) antibody treatment of rice rats with localized maxillary periodontitis. We hypothesized that rice rats with localized maxillary periodontitis given anti-VEGF monotherapy will develop oral lesions that resemble ONJ, defined by exposed, necrotic alveolar bone. METHODS: At age 4 weeks, 45 male rice rats were randomized into three groups (n = 15): 1) VEH (saline), 2) ZOL (80 µg/kg body weight, intravenously once monthly), and 3) anti-VEGF (5 mg B20-4.1.1/kg body weight, subcutaneously twice weekly). After 24 weeks, rats were euthanized, jaws were excised and a high-resolution photograph of each quadrant was taken to assign a severity grade based on gross appearance. Jaws were then fixed, scanned by MicroCT, decalcified and sectioned for histopathologic and immunohistochemical analyses. RESULTS: 40-80% of the rats in the three groups developed gross oral lesions. 50% of ZOL rats developed ONJ. In contrast, 80% of the anti-VEGF rats developed destructive advanced periodontitis that was characterized by extreme alveolar bone loss and fibrosis. Anti-VEGF rats never developed exposed, necrotic bone. Furthermore, only anti-VEGF rats developed mild to severe mandibular periodontitis. Compared to VEH rats, more T-cells were found in periodontal lesions of anti-VEGF rats and more cells of the monocyte lineage were found in ONJ lesions of ZOL rats. CONCLUSIONS: Anti-VEGF monotherapy administered to a validated rodent model of ONJ caused a destructive advanced form of periodontitis that differed significantly from ONJ.

Inhibition of topoisomerase II by liriodenine.

The cytotoxic oxoaporphine alkaloid liriodenine, isolated from Cananga odorata, was found to be a potent inhibitor of topoisomerase II (EC 5.99.1.3) both in vivo and in vitro. Liriodenine treatment of SV40 (simian virus 40)-infected CV-1 cells caused highly catenated SV40 daughter chromosomes, a signature of topoisomerase II inhibition. Strong catalytic inhibition of topoisomerase II by liriodenine was confirmed by in vitro assays with purified human topoisomerase II and kinetoplast DNA. Liriodenine also caused low-level protein-DNA cross-links to pulse-labeled SV40 chromosomes in vivo, suggesting that it may be a weak topoisomerase II poison. This was supported by the finding that liriodenine caused topoisomerase II-DNA cross-links in an in vitro assay for topoisomerase II poisons. Verapamil did not increase either liriodenine-induced protein-DNA cross-links or catalytic inhibition of topoisomerase II in SV40-infected cells. This indicates that liriodenine is not a substrate for the verapamil-sensitive drug efflux pump in CV-1 cells.

20/20 Analysis: taking a close look at the margins.

This article presents "20/20 Analysis" as an experimental, output-oriented, noncategorical alternative to traditional approaches to identification of students for special education. 20/20 Analysis identifies students showing least (below 20th percentile) and most (above 80th percentile) progress toward important objectives of education in a school. The situation of each student in low 20% and high 20% groups is then examined as a basis for broad (noncategorical) approaches to improvement of learning opportunities. Case studies of two schools are present. Policy implications are considered briefly.

Evaluation of hydroxylapatite graft materials in canine cervical spine fusions.

The efficacy of ceramic hydroxylapatite implant materials as graft materials for cervical spine fusion was evaluated in canines. Bioresorbable and non-bioresorbable systems were evaluated at time periods ranging from 1 to 24 weeks. Implant interbody position and progression of fusion were evaluated radiographically and histologically. Implant fracture and extrusion into adjacent soft tissues occurred in nine of 23 cases. Implant fracture occurred in many of the remaining 14 cases, however, the implant materials remained within the interspace. Implant fracture occurred with both implant systems. Radiographically little evidence of fusion was observed at less than 6 weeks, however by 12 weeks evidence of fusion was noted and was confirmed histologically. No difference in fusion rate or degree of fusion was observed between the two implant systems.

Atraumatic osteolysis of the distal clavicle: histologic evidence of synovial pathogenesis. A case report.

Osteolysis of the distal clavicle was diagnosed in a young male athlete following many years as a baseball pitcher with a supplementary weightlifting program. There was no history of ligamentous injuries, contusions, fractures or separation of the acromioclavicular joint. As such, this case was categorized as "atraumatic" osteolysis. Non-decalcified histologic sections from the resected clavicle suggest that the pathogenesis of this atraumatic osteolysis arose from the synovium.

Thermoradiation inactivation of naturally occurring bacterial spores in soil.

Samples of soil collected from the Kennedy Space Center near the spacecraft assembly facilities were found to contain microorganisms very resistant to conventional sterilzation techniques. The inactivation kinetics of the naturally occurring spores in soil were investigated by using dry heat and ionizing radiation, first separately and then simultaneously. Dry-heat inactivation kinetics of spores was determined at 105 and 125 C; radiation inactivation kinetics was determined for dose rates of 660 and 76 krads/h at 25 C. Simultaneous combinations of heat and radiation were then investigated at 105, 110, 115, 120, and 125 C, with a dose rate of 76 krads/h. Combined treatment was found to be highly synergistic, requiring greatly reduced radiation doses to accomplish sterilization of the population.