Amelioration of radiation-induced oral cavity mucositis and distant bone marrow suppression in fanconi anemia Fancd2-/- (FVB/N) mice by intraoral GS-nitroxide JP4-039.

The altered DNA damage response pathway in patients with Fanconi anemia (FA) may increase the toxicity of clinical radiotherapy. We quantitated oral cavity mucositis in irradiated Fanconi anemia Fancd2(-/-) mice, comparing this to Fancd2(+/-) and Fancd2(+/+) mice, and we measured distant bone marrow suppression and quantitated the effect of the intraoral radioprotector GS-nitroxide, JP4-039 in F15 emulsion. We found that FA mice were more susceptible to radiation injury and that protection from radiation injury by JP4-039/F15 was observed at all radiation doses. Adult 10-12-week-old mice, of FVB/N background Fancd2(-/-), Fancd2(+/-) and Fancd2(+/+) were head and neck irradiated with 24, 26, 28 or 30 Gy (large fraction sizes typical of stereotactic radiosurgery treatments) and subgroups received intraoral JP4-039 (0.4 mg/mouse in 100 µL F15 liposome emulsion) preirradiation. On day 2 or 5 postirradiation, mice were sacrificed, tongue tissue and femur marrow were excised for quantitation of radiation-induced stress response, inflammatory and antioxidant gene transcripts, histopathology and assay for femur marrow colony-forming hematopoietic progenitor cells. Fancd2(-/-) mice had a significantly higher percentage of oral mucosal ulceration at day 5 after 26 Gy irradiation (59.4 ± 8.2%) compared to control Fancd2(+/+) mice (21.7 ± 2.9%, P = 0.0063). After 24 Gy irradiation, Fancd2(-/-) mice had a higher oral cavity percentage of tongue ulceration compared to Fancd2(+/+) mice irradiated with higher doses of 26 Gy (P = 0.0123). Baseline and postirradiation oral cavity gene transcripts were altered in Fancd2(-/-) mice compared to Fancd2(+/+) controls. Fancd2(-/-) mice had decreased baseline femur marrow CFU-GM, BFUe and CFU-GEMM, which further decreased after 24 or 26 Gy head and neck irradiation. These changes were not seen in head- and neck-irradiated Fancd2(+/+) mice. In radiosensitive Fancd2(-/-) mice, biomarkers of both local oral cavity and distant marrow radiation toxicity were ameliorated by intraoral JP4-039/F15. We propose that Fancd2(-/-) mice are a valuable radiosensitive animal model system, which can be used to evaluate potential radioprotective agents.

Nonfatal sport-related craniofacial fractures: characteristics, mechanisms, and demographic data in the pediatric population.

BACKGROUND: Few reports exist on sport-related craniofacial fracture injuries in the pediatric population. Most patients with craniofacial injuries are adults, and most studies on pediatric sport injuries do not focus specifically on craniofacial fractures. The authors' goal was to provide a retrospective, descriptive review of the common mechanisms of sport-related craniofacial injuries in the pediatric population, identifying the characteristics of these injuries and providing a description of the demographics of this population. METHODS: The study population included children between the ages of 0 and 18 years who were seen in the emergency department at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center between 2000 and 2005. Of the 1508 patients identified, 167 had injuries caused by sport-related trauma (10.6 percent). RESULTS: After evaluation in the emergency department, 45.5 percent were hospitalized, and 15.0 percent of these were admitted to the intensive care unit. The peak incidence of sport-related injuries occurred between the ages of 13 and 15 years (40.7 percent). Nasal (35.9 percent), orbital (33.5 percent), and skull fractures (30.5 percent) were most common, whereas fractures of the maxilla (12.6 percent), mandible (7.2 percent), zygomaticomaxillary complex (4.2 percent), and naso-orbitoethmoid complex (1.2 percent) were observed less frequently. Baseball and softball were most frequently associated with the craniofacial injuries (44.3 percent), whereas basketball (7.2 percent) and football (3.0 percent) were associated with fewer injuries. The most common mechanisms of injury were throwing, catching, or hitting a ball (34.1 percent) and collision with other players (24.5 percent). CONCLUSION: These data may allow targeted or sport-specific craniofacial fracture injury prevention strategies.