Calcineurin inhibitors such as cyclosporine A and FK506 have been used for transplant therapy and treatment of autoimmune diseases. However, the inhibition of calcineurin outside the immune system has a number of side effects, including hyperglycemia. In the search for safer drugs, we developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide provided immunosuppression for fully mismatched islet allografts in mice. In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically.

A coordinated reciprocal interaction between epithelium and mesenchyme is involved in salivary gland morphogenesis. The submandibular glands (SMGs) of Wnt1-Cre/R26R mice have been shown positive for mesenchyme, whereas the epithelium is ␤-galactosidase-negative, indicating that most mesenchymal cells are derived from cranial neural crest cells. Platelet-derived growth factor (PDGF) receptor ␣ is one of the markers of neural crest-derived cells. In this study, we analyzed the roles of PDGFs and their receptors in the morphogenesis of mouse SMGs. PDGF-A was shown to be expressed in SMG epithelium, whereas PDGF-B, PDGFR␣, and PDGFR␤ were expressed in mesenchyme. Exogenous PDGF-AA and -BB in SMG organ cultures demonstrated increased levels of branching and epithelial proliferation, although their receptors were found to be expressed in mesenchyme. In contrast, short interfering RNA for Pdgfa and -b as well as neutralizing antibodies for PDGF-AB and -BB showed decreased branching. PDGF-AA induced the expression of the fibroblast growth factor genes Fgf3 and -7, and PDGF-BB induced the expression of Fgf1, -3, -7, and -10, whereas short interfering RNA for Pdgfa and Pdgfb inhibited the expression of Fgf3, -7, and -10, indicating that PDGFs regulate Fgf gene expression in SMG mesenchyme. The PDGF receptor inhibitor AG-17 inhibited PDGF-induced branching, whereas exogenous FGF7 and -10 fully recovered. Together, these results indicate that fibroblast growth factors function downstream of PDGF signaling, which regulates Fgf expression in neural crest-derived mesenchymal cells and SMG branching morphogenesis. Thus, PDGF signaling is a possible mechanism involved in the interaction between epithelial and neural crest-derived mesenchyme.

BackgroundAccidental displacement of a dental implant into the maxillary sinus is an infrequent although not uncommon complication encountered in dental clinical practice, with the main cause thought to be inadequate bone height in the posterior maxilla. We report a case of migration of a dental implant into the maxillary sinus, and discuss the benefits of its removal by a combination of endoscopically assisted and bone repositioning techniques.Case presentationA 35-year-old Japanese man with a partially edentulous maxilla underwent implant placement at a private clinic. Three months later, at the time of abutment connection, the implant at the site of his maxillary right first molar was accidentally pushed into the sinus. The hole on the alveolar ridge made for placement of the implant was small and far from the dislocated implant, thus access was achieved in a transoral manner via the frontal wall of his maxillary sinus with an endoscopic approach. Piezoelectric instruments were used to perform an osteotomy. The bone lid was removed, and the implant was identified using a rigid endoscope and removed with a surgical aspirator, followed by repositioning of the bony segment; the area was secured with an absorbable suture. Removal of migrated implants should be considered in order to prevent possible sinusal disease complications.ConclusionsIn the present case, removal of a dental implant displaced into the maxillary sinus by use of a combination of endoscopically assisted and bone repositioning techniques proved to be a safe and reliable procedure.

An in situ approach was used to identify amyloid-β (Aβ) accumulation and oxidative damage to nucleic acids in postmortem brain tissue of the hippocampal formation from subjects with Alzheimer disease. When carboxyl-terminal specific antibodies directed against Aβ40 and Aβ42 were used for immunocytochemical analyses, Aβ42 was especially apparent within the neuronal cytoplasm, at sites not detected by the antibody specific to Aβ-oligomer. In comparison to the Aβ42-positive neurons, neurons bearing oxidative damage to nucleic acids were more widely distributed in the hippocampus. Comparative density measurements of the immunoreactivity revealed that levels of intraneuronal Aβ42 were inversely correlated with levels of intraneuronal 8-hydroxyguanosine, an oxidized nucleoside (r = − 0.61, p < 0.02). Together with recent evidence that the Aβ peptide can act as an antioxidant, these results suggest that intraneuronal accumulation of non-oligomeric Aβ may be a compensatory response in neurons to oxidative stress in Alzheimer disease.

Awat2 knockout mice exhibit severe dry eye phenotypes Awat1 knockout mice exhibit mild dry eye phenotypes Awat2 is responsible for the production of wax monoesters and type 2u wax diesters Awat1 is involved in (Oacyl)-u-hydroxy fatty acid production