A dermal phototoxicity study following intravenous infusion administration of ciprofloxacin hydrochloride in the novel microminipigs.

The authors evaluated dermal phototoxicity using the world smallest minipig (MMPig: Microminipig). MMPigs were administered 100 mg/kg ciprofloxacin hydrochloride with an infusion pump. The dorsal area of each animal was irradiated with ultraviolet-A irradiation. The left dorsal skin was irradiated at intensities of 5, 10, 15, and 20 J/cm(2), and the right dorsal back skin was set as a nonirradiated site. Gross and histopathological examinations were conducted before irradiation and from 1 to 72 hr after irradiation. Initial changes in the skin were necrosis of the basal and/or prickle cell layer and cellular infiltration from 24 hr after irradiation. Vesicle formation observed from 48 hr after irradiation was considered similar to bullous eruptions, a known side effect of fluoroquinolones in humans. Therefore, the authors suggest that the MMPig may be a useful experimental animal model for dermal phototoxicity studies.

Evaluation of a Newly Designed Microperforated Pure Titanium Membrane for Guided Bone Regeneration.

PURPOSE: This study aimed to evaluate the safety and efficacy of newly designed, laser-perforated pure titanium membranes for guided bone regeneration and to compare them with an existing product, the FRIOS BoneShield (FBS). MATERIALS AND METHODS: Acute-type lateral ridge defects were bilaterally created in the mandibles of 13 dogs (two defects per animal). The defects were randomly divided into three groups and were reconstructed with particulate autologous bone (PAB) in combination with three different titanium membranes: (1) F001M0 (prototype without a frame), (2) F001M1 (prototype with a frame), and (3) FBS as a standard membrane. All animals were observed periodically and sacrificed 26 or 27 weeks postoperatively. At 26 weeks, approximately half of the dogs in each group underwent membrane removal to examine the postoperative condition of the titanium membranes. The samples were dissected and processed for radiographic, histologic, and histomorphometric analyses. RESULTS: Membrane exposure was not found in the F001M0 or F001M1 groups, and their membranes were removed easily without adhesion to the surrounding tissue. Regenerated bone tissue volume was largest in the F001M1 group, followed by the F001M0 and FBS groups. A significant difference was observed only between the F001M1 and FBS groups (P = .047). In contrast, bone mineral density was similar among the three groups. Histologically, a layer of fibrous tissue was present underneath the titanium membrane, overlying the regenerated cortical bone in all the groups. Notably, the tissue was highly vascular in the F001M1 and F001M0 groups compared with the FBS group. In addition, there was little difference in the semiquantitative soft tissue evaluation and histologic findings of bone regeneration among the three groups. The histomorphometric analysis revealed that the regenerated bone area was larger in the F001M1 and F001M0 groups than in the FBS group, and a significant difference was observed only between the F001M1 and FBS groups (P = .045). Calcific osseous area was similar among the three groups. CONCLUSION: The safety and efficacy of both F001M0 and F001M1 were equivalent to or greater than those of FBS, thereby indicating their potential for future clinical applications.

Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leukocyte antigen type is safe and efficacious for total pulp regeneration.

BACKGROUND: We recently demonstrated that autologous transplantation of mobilized dental pulp stem cells (MDPSCs) was a safe and efficacious potential therapy for total pulp regeneration in a clinical study. The autologous MDPSCs, however, have some limitations to overcome, such as limited availability of discarded teeth from older patients. In the present study, we investigated whether MDPSCs can be used for allogeneic applications to expand their therapeutic use. METHODS: Analysis of dog leukocyte antigen (DLA) was performed using polymerase chain reaction from blood. Canine allogeneic MDPSCs with the matched and mismatched DLA were transplanted with granulocyte-colony stimulating factor in collagen into pulpectomized teeth respectively (n = 7, each). Results were evaluated by hematoxylin and eosin staining, Masson trichrome staining, PGP9.5 immunostaining, and BS-1 lectin immunostaining performed 12 weeks after transplantation. The MDPSCs of the same DLA used in the first transplantation were further transplanted into another pulpectomized tooth and evaluated 12 weeks after transplantation. RESULTS: There was no evidence of toxicity or adverse events of the allogeneic transplantation of the MDPSCs with the mismatched DLA. No adverse event of dual transplantation of the MDPSCs with the matched and mismatched DLA was observed. Regenerated pulp tissues including neovascularization and neuronal extension were quantitatively and qualitatively similar at 12 weeks in both matched and mismatched DLA transplants. Regenerated pulp tissue was similarly observed in the dual transplantation as in the single transplantation of MDPSCs both with the matched and mismatched DLA. CONCLUSIONS: Dual allogeneic transplantation of MDPSCs with the mismatched DLA is a safe and efficacious method for total pulp regeneration.