Local Irradiation of Mouse Tooth Germ Gives Insight into the Direct Effects of Irradiation on Root Development.

To elucidate the mechanism underlying the failure of root formation after irradiation, we established a method of local irradiation of the molar tooth germ and demonstrated that radiation directly affected dental root development. In the current study, to locally irradiate the lower first molars of 5-day-old C57BL/6J mice, we used lead glass containing a hole as a collimator. We confirmed that our local irradiation method targeted only the tooth germ. The irradiated root was immature in terms of apical growth, and dentin formation was irregular along the outside of the root apices. Moreover, calcified tissue apically surrounded Hertwig's epithelial root sheath, which disappeared abnormally early. This method using a local irradiation experimental model will facilitate research into radiation-induced disorders of dental root formation.

Histological effects and pharmacokinetics of lipopolysaccharide derived from Porphyromonas gingivalis on rat maxilla and liver concerning with progression into non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the chronic liver diseases that can develop into hepatocirrhosis. The purpose of the present study was to investigate the impact of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P. gingivalis) on NASH onset, and to determine the biodistribution of double-radiolabeled LPS (R-LPS) biosynthesized in P. gingivalis. METHODS: Rats fed a basal diet (BD) or a high-fat diet (HD) were injected with P. gingivalis-LPS or R-LPS into the palatine gingiva around the right maxillary first molar, and were classified into the following 4 groups: BD/LPS (-), BD/LPS (+), HD/LPS (-), and HD/LPS (+) or 2 groups: BD/R-LPS and HD/R-LPS. RESULTS: Inflammation in the gingiva of the LPS (+) groups progressed significantly more than the LPS (-) groups. Furthermore, in the HD/LPS (+) liver, histologic analysis confirmed the presence of NASH, characterized by large fat droplets, ballooning degeneration, and infiltration of inflammatory cells. When 3 H, 14 C-R-LPS was injected into the palatine gingiva, radioactivity in the right palatal mucosa of HD/R-LPS rats was the highest in comparison with other regions and was significantly elevated after 24 hours compared to BD/R-LPS rats. Autoradiographic analysis of the maxilla showed distributions from the palatal mucosa to the hard palate and the interdental region. Radioactivity in organs of both BD/R-LPS and HD/R-LPS rats were mostly localized to the liver even after 24 hours. CONCLUSION: The present study suggests that the transfer of P. gingivalis-LPS from the oral cavity to the liver plays an important role in disease exacerbation of NASH.

Microsomal prostaglandin E synthase-1 is a critical factor of stroke-reperfusion injury.

Although augmented prostaglandin E(2) (PGE(2)) synthesis and accumulation have been demonstrated in the lesion sites of rodent transient focal ischemia models, the role of PGE(2) in neuronal survival has been controversial, showing both protective and toxic effects. Here we demonstrate the induction of microsomal PGE synthase 1 (mPGES-1), an inducible terminal enzyme for PGE(2) synthesis, in neurons, microglia, and endothelial cells in the cerebral cortex after transient focal ischemia. In mPGES-1 knockout (KO) mice, in which the postischemic PGE(2) production in the cortex was completely absent, the infarction, edema, apoptotic cell death, and caspase-3 activation in the cortex after ischemia were all reduced compared with those in wild-type (WT) mice. Furthermore, the behavioral neurological dysfunctions observed after ischemia in WT mice were significantly ameliorated in KO mice. The ameliorated symptoms observed in KO mice after ischemia were reversed to almost the same severity as WT mice by intracerebroventricular injection of PGE(2) into KO mice. Our observations suggest that mPGES-1 may be a critical determinant of postischemic neurological dysfunctions and a valuable therapeutic target for treatment of human stroke.