Sevoflurane modulation of tetrodotoxin-resistant Na+ channels in small-sized dorsal root ganglion neurons of rats.

OBJECTIVE: Volatile anesthetics are widely used for general anesthesia during surgical operations. Voltage-gated Na+ channels expressed in central neurons are major targets for volatile anesthetics; but it is unclear whether these drugs modulate native tetrodotoxin-resistant (TTX-R) Na+ channels, which are involved in the development and maintenance of inflammatory pain. METHODS: In this study, we examined the effects of sevoflurane on TTX-R Na+ currents (INa) in acutely isolated rat dorsal root ganglion neurons, using a whole-cell patch-clamp technique. RESULTS: Sevoflurane slightly potentiated the peak amplitude of transient TTX-R INa but more potently inhibited slow voltage-ramp-induced persistent INa in a concentration-dependent manner. Sevoflurane (0.86 ± 0.02 mM) (1) slightly shifted the steady-state fast inactivation relationship to hyperpolarizing ranges without affecting the voltage-activation relationship, (2) reduced the extent of use-dependent inhibition of Na+ channels, (3) accelerated the onset of inactivation and (4) delayed the recovery from inactivation of TTX-R Na+ channels. Thus, sevoflurane has diverse effects on TTX-R Na+ channels expressed in nociceptive neurons. CONCLUSIONS: The present results suggest that the inhibition of persistent INa and the modulation of the voltage dependence and inactivation might be, at least in part, responsible for the analgesic effects elicited by sevoflurane.

Delayed Spontaneous Eruption of Severely Infraoccluded Primary Second Molar: Two Case Reports.

Infraocclusion occurs at an early age and becomes worse with age, causing increased damage in young children. Extraction of affected teeth is the preferred treatment modality for prevention of possible complications. It is rare for a primary molar to temporarily exhibit secondary failure of eruption, followed by regeneration of full eruptive capacity. This report was written to describe two patients who experienced spontaneous eruption of an infraoccluded primary molar at approximately 7 years of age. While watchful waiting is not always a suitable treatment option, we propose that extraction be deferred until the first permanent molar erupts, unless significant problems occur.

Buccal Bifurcation Cyst: Two Case Reports and a Literature Review.

INTRODUCTION: A buccal bifurcation cyst (BBC) is an uncommon inflammatory odontogenic cyst associated with the permanent mandibular first or second molar in children. CASE REPORTS: These reports present two cases of BBC and describes the clinical and radiographic features leading to the diagnosis and the treatment of this lesion. Two patients complained of mandibular buccal swelling around the permanent first molar. The diagnosis of BBC in both cases was based on the clinical and radiographic features. In both cases, only enucleation was performed without extracting the involved tooth. RESULTS: There were no recurrences during follow up. All teeth remained vital and erupted normally. CONCLUSION: The most appropriate treatment is usually enucleation of the cyst without extraction of the associated tooth. Therefore, knowledge of the distinct features of BBC is important for diagnosis and appropriate treatment.

Factors affecting use of word-of-mouth by dental patients.

OBJECTIVES: Word-of-mouth (WOM) refers to communication among consumers, which greatly influences the marketing strategies of dental clinics. This study aimed to explore factors that affect use of WOM by dental patients and to analyse their pathways. METHODS: The participants were 520 outpatients from four private dental clinics. Data were obtained from a survey using self-reported questionnaires, which included questions regarding seven latent variables: five exogenous variables, including medical service quality (physical environment, customer service, patient relationship quality) and individual characteristic variables (opinion leader tendency, social hub tendency); and two endogenous variables (intention to recommend, WOM experience). Statistical analysis was performed using structural equation modelling. RESULTS: Significant associations were found in the pathways between relationship quality and intention to recommend, intention to recommend and WOM, and opinion leader tendency and WOM (P < 0.001). Higher patient relationship quality and higher intention to recommend were related to positive WOM, as was higher opinion leader tendency. CONCLUSIONS: Improving patient relationship quality can promote positive WOM for dental clinics. Strategies are needed to promote a positive perception of dental clinics by effectively responding to the views of patients with strong opinion leader tendencies.

Conservative Treatment of Multiple Keratocystic Odontogenic Tumors in a Young Patient with Nevoid Basal Cell Carcinoma Syndrome by Decompression: A 7-year Follow-up Study.

Multiple keratocystic odontogenic tumors (KCOT) occurred in a young child is challenging problem in the field of pediatric dentistry, and might have been related to nevoid basal cell carcinoma syndrome (NBCCS). Because of high recurrence rate of KCOTs, complete surgical resection is generally accepted as definitive treatment. However, complete surgical resection could induce negative effect on the development of permanent teeth and growth of jaw. Herein, we reported successful treatment case of young KCOT patient with NBCCS. Although multiple KCOTs occurred continually, the majority of the lesions healed well by decompression and important anatomical structures and permanent teeth were successfully preserved. The purpose of this paper is to report more conservative treatment of multiple keratocystic odontogenic tumors (KCOTs) by repeated decompressions with later peripheral ostectomy during a 7-year follow-up.

Molar root-incisor malformation: considerations of diverse developmental and etiologic factors.

OBJECTIVE: The objective of this study was to evaluate the variation in the condition referred to as molar root-incisor malformation (MRIM) and elucidate the distribution of affected teeth. This study further aimed to identify associated environmental stressors. STUDY DESIGN: Individuals were identified through retrospective review of dental radiographs and through referral to the investigators. Histologic evaluation included examination of mineralized and decalcified sections of affected first permanent molar teeth. RESULTS: Thirty cases of MRIM were identified, with all having affected first permanent molars with dysplastic root formation. The primary second molars were affected in 57% of the cases, with permanent anterior teeth being involved in 40% of the cases. A variety of medical conditions were associated with MRIM, the most common being neurologic. Several affected individuals reported no significant past medical history or environmental stressors. CONCLUSIONS: The etiology of MRIM remains unclear, and this unique developmental defect of the first permanent molar roots appears to occur in populations throughout the world. Clinicians identifying the MRIM phenotype should carefully evaluate the permanent incisors for associated developmental defects that could result in pulpal necrosis.

TGF-beta2 stimulates cranial suture closure through activation of the Erk-MAPK pathway.

Cranial sutures are important growth sites of the skull. During suture closure, the dura mater is one of the most important sources of various positive and negative regulatory signals. Previous results indicate that TGF-beta2 from dura mater strongly accelerates suture closure, however, its exact regulatory mechanism is still unclear. In this study, we confirmed that removal of dura mater in calvarial organ culture strongly accelerates sagittal suture closure and that this effect is further enhanced by TGF-beta2 treatment. TGF-beta2 stimulated cell proliferation in the MC3T3-E1 cell line. Similarly, it stimulated the proliferation of cells in the sutural space in calvarial organ culture. Furthermore, TGF-beta2-mediated enhanced cell proliferation and suture closure were almost completely inhibited by an Erk-MAPK blocker, PD98059. These results indicate that TGF-beta2-induced activation of Erk-MAPK is an important signaling component that stimulates cell proliferation to enrich osteoprogenitor cells, thereby promoting their differentiation into osteoblasts to achieve a rapid calvarial bone expansion.

Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder caused by haploinsufficiency of the RUNX2 gene. In this study, we analyzed by direct sequencing RUNX2 mutations from eleven CCD patients. Four of seven mutations were novel: two nonsense mutations resulted in a translational stop at codon 50 (Q50X) and 112 (E112X); a missense mutation converted arginine to glycine at codon 131 (R131G); and an exon 1 splice donor site mutation (donor splice site GT/AT, IVS1 + 1G > A) at exon 1-intron junction resulted in the deletion of QA stretch contained in exon 1 of RUNX2. We focused on the functional analysis of the IVS1 + 1G > A mutation. A full-length cDNA of this mutation was cloned (RUNX2Deltae1) and expressed in Chinese hamster ovary (CHO) and HeLa cells. Functional analysis of RUNX2Deltae1 was performed with respect to protein stability, nuclear localization, DNA binding, and transactivation activity of a downstream RUNX2 target gene. Protein stability of RUNX2Deltae1 is similar to wild-type RUNX2 as determined by Western blot analysis. Subcellular localization of RUNX2Deltae1, assessed by in situ immunofluorescent staining, was observed with partial retention in both the nucleus and cytoplasm. This finding is in contrast to RUNX2 wild-type, which is detected exclusively in the nucleus. DNA binding activity was also compromised by the RUNX2Deltae1 in gel shift assay. Finally, RUNX2Deltae1 blocked transactivation of the osteocalcin gene determined by transient transfection assay. Our findings demonstrate for the first time that the CCD phenotype can be caused by a splice site mutation, which results in the deletion of N-terminus amino acids containing the QA stretch in RUNX2 that contains a previously unidentified second nuclear localization signal (NLS). We postulate that the QA sequence unique to RUNX2 contributes to a competent structure of RUNX2 that is required for nuclear localization, DNA binding, and transactivation function.

Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development.

Calvarial bone is formed by the intramembranous bone-forming process, which involves many signaling molecules. The constitutive activation of the fibroblast growth factor (FGF) signaling pathway accelerates osteoblast differentiation and results in premature cranial suture closure. Bone morphogenetic protein (BMP) signaling pathways, which involve the downstream transcription factors Dlx5 and Msx2, are also involved in the bone-forming processes. However, the relationships between these two main signaling cascades are still unclear. We found that FGF2 treatment of developing bone fronts stimulated Bmp2 gene expression but that BMP2 treatment could not induce Fgf2 expression. Moreover, the disruption of the Runx2 gene completely eliminated the expression of Bmp2 and its downstream genes Dlx5 and Msx2 in the developing primordium of bone, while the expression of Fgf2 was maintained. In addition, cultured Runx2-/- cells expressed very low baseline levels of Bmp2 that were up-regulated by transfection with a Runx2-expressing plasmid. These levels in turn were markedly elevated by FGF2 treatment. FGF2 treatment also strongly enhanced the Bmp2 expression in MC3T3-E1 cells, whose endogenous Runx2 gene is intact and which express Bmp2 at low baseline levels as well. These results indicate that Runx2 is an important mediator of the expression of Bmp2 in response to FGF stimulation in cranial bone development.