Early induction of Hes1 by bone morphogenetic protein 9 plays a regulatory role in osteoblastic differentiation of a mesenchymal stem cell line.

Bone morphogenic protein 9 (BMP9) is one of the most potent inducers of osteogenic differentiation among the 14 BMP members, but its mechanism of action has not been fully demonstrated. Hes1 is a transcriptional regulator with basic helix-loop-helix (bHLH) domain and is a well-known Notch effector. In this study, we investigated the functional roles of early induction of Hes1 by BMP9 in a mouse mesenchymal stem cell line, ST2. Hes1 mRNA was transiently and periodically induced by BMP9 in ST2, which was inhibited by BMP signal inhibitors but not by Notch inhibitor. Interestingly, Hes1 knockdown in ST2 by siRNA increased the expression of osteogenic differentiation markers such as Sp7 and Ibsp and matrix mineralization in comparison with control siRNA transfected ST2. In contrast, forced expression of Hes1 by using the Tet-On system suppressed the expression of osteogenic markers and matrix mineralization by BMP9. We also found that the early induction of Hes1 by BMP9 suppressed the expression of Alk1, an essential receptor for BMP9. In conclusion, BMP9 rapidly induces the expression of Hes1 via the SMAD pathway in ST2 cells, which plays a negative regulatory role in osteogenic differentiation of mesenchymal stem cells induced by BMP9.

HIF-1α plays an essential role in BMP9-mediated osteoblast differentiation through the induction of a glycolytic enzyme, PDK1.

Bone homeostasis is regulated by bone morphogenic proteins (BMPs), among which BMP9 is one of the most osteogenic. Here, we have found that BMP9 rapidly increases the protein expression of hypoxia-inducible factor-1α (HIF-1α) in osteoblasts under normoxic conditions more efficiently than BMP2 or BMP4. A combination of BMP9 and hypoxia further increased HIF-1α protein expression. HIF-1α protein induction by BMP9 is not accompanied by messenger RNA (mRNA) increase and is inhibited by the activation of prolyl hydroxylase domain (PHD)-containing protein, indicating that BMP9 induces HIF-1α protein expression by inhibiting PHD-mediated protein degradation. BMP9-induced HIF-1α protein increase was abrogated by inhibitors of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) kinase, indicating that it is mediated by PI3K-AKT signaling pathway. BMP9 increased mRNA expression of pyruvate dehydrogenase kinase 1 (PDK1), a glycolytic enzyme, and vascular endothelial growth factor-A (VEGF-A), an angiogenic factor, in osteoblasts. Notably, BMP9-induced mRNA expression of PDK1, but not that of VEGF-A, was significantly inhibited by small interference RNA-mediated knockdown of Hif-1α. BMP9-induced matrix mineralization and osteogenic marker gene expressions were significantly inhibited by chemical inhibition and gene knockdown of either Hif-1α or Pdk-1, respectively. Since increased glycolysis is an essential feature of differentiated osteoblasts, our findings indicate that HIF-1α expression is important in BMP9-mediated osteoblast differentiation through the induction of PDK1.

Lipoteichoic Acid and Lipopolysaccharides Are Affected by p38 and Inflammatory Markers and Modulate Their Promoting and Inhibitory Effects on Osteogenic Differentiation.

Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are cell wall components of Gram-positive and Gram-negative bacteria, respectively. Notably, oral microflora consists of a variety of bacterial species, and osteomyelitis of the jaw caused by dental infection presents with symptoms of bone resorption and osteosclerosis. However, the effects of LTA and LPS on osteogenic differentiation have not yet been clarified. We examined the effects of LTA and LPS on osteoblasts and found that LTA alone promoted alizarin red staining at low concentrations and inhibited it at high concentrations. Additionally, gene expression of osteogenic markers (ALP, OCN, and OPG) were enhanced at low concentrations of LTA. High concentrations of LPS suppressed calcification potential, and the addition of low concentrations of LTA inhibited calcification suppression, restoring the gene expression levels of suppressed bone differentiation markers (ALP, BSP, and OCN). Moreover, the suppression of p38, a signaling pathway associated with bone differentiation, had opposing effects on gene-level expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), suggesting that mixed LTA and LPS infections have opposite effects on bone differentiation through concentration gradients, involving inflammatory markers (TNF-α and IL-6) and the p38 pathway.

Three-Dimensional Quantification of Postoperative Facial Asymmetry in Patients With Unilateral Cleft lip and Palate Using Facial Symmetry Plane.

OBJECTIVE: To quantitatively assess three-dimensional (3D) soft tissue facial asymmetry in patients with unilateral cleft lip and palate (UCLP) who have undergone primary lip repair. DESIGN: Clinical, retrospective, comparative, methodological study. PATIENTS/PARTICIPANTS: Twenty patients with UCLP were selected after a review of the records. INCLUSION CRITERIA: Complete UCLP; surgically treated without secondary repair. An age-matched and sex-matched Control group was employed. MAIN OUTCOME MEASURES: A 3D facial symmetry plane (FSP) was obtained by superimposing the point clouds of the original 3D facial image excluding the surgical site and including lip and nose areas and those of a mirrored facial image using the iterative closest point (ICP) adjustment method. The discrepancies in the depth and angle of the normal vector of the facial surface of each point cloud between right and left sides (cleft and non-cleft sides in the UCLP group, respectively) based on FSP were calculated. RESULTS: Facial asymmetry in the UCLP group was significantly greater than in the Control group regarding both the discrepancies in the depth (1.34 ± 0.62, 0.73 ± 0.32 pixels, respectively) (P = .0004) and surface angle (18.0 ± 5.88, 12.8 ± 4.0°, respectively) (P = .0024). Biaxial assessment of the discrepancies in the depth and surface angle allowed us to visually extract UCLP patients with greater facial asymmetry. CONCLUSIONS: Facial asymmetry analysis based on 3D FSP effectively facilitates the facial asymmetry quantification and soft tissue surgical outcome evaluation in patients with UCLP.

Effectiveness of fibreoptic endoscopic evaluation of swallowing and dietary intervention during home-visit dental care in older individuals.

BACKGROUND: Currently, patients with dysphagia are receiving dietary management that deviates from their original swallowing function. OBJECTIVE: To evaluate the clinical significance of fibreoptic endoscopic evaluation of swallowing (FEES) and dietary intervention (DI) by multi-professional collaboration during visit care for determining the actual oral intake status in patients with dysphagia. METHODS: Five hundred and eighteen patients with dysphagia underwent FEES, focusing on the penetration-aspiration scale, and DI. Oral intake status was categorised using the functional oral intake scale (FOIS). FOIS scores at the first visit, after FEES, and at the reassessment were compared. RESULTS: At the first visit, 34.7% of the patients had an FOIS score of level 1 (no oral intake) and 65.3% had a score of level 2 or higher (capable of oral intake). Following FEES, 7.1% of patients had an FOIS score of level 1, and 44.4% had a score of level 2 with resumption of oral intake. At the reassessment, 489 patients (94.4%) were capable of oral ingestion (FOIS level 2 or higher). There were significant differences between the distributions of FOIS scores at the first visit and following FEES (P < .01) and between those at the first visit and at the reassessment (P < .01). Regarding tube feeding, 17 (5.9%) of 289 patients, who had received tube feeding at the first visit, were completely capable of oral intake following FEES and at the reassessment. CONCLUSION: Appropriate evaluation of swallowing function using FEES and DI helps to understand the definite swallowing function in patients with dysphagia.

A Follow-Up Study on the Clinical Outcomes of Alveolar Reconstruction Using Octacalcium Phosphate Granules and Atelocollagen Complex.

PURPOSE: To observe the long-term postoperative bone formation and eruption of adjacent teeth after octacalcium phosphate granule and atelocollagen complex (OCP/Col) grafting in the treatment of alveolar cleft of patients with unilateral cleft lip with or without cleft palate (UCL ± P). METHODS: Four patients with UCL ± P who underwent OCP/Col grafting (OCP group), and 55 patients with UCL ± P who underwent autologous bone grafting (AB group) were enrolled in this study. OCP/Col or autologous bone grafting was performed before the eruption of canines or lateral incisors in mixed dentition, followed by orthodontic management. Patients in the OCP group underwent radiography before and after surgery at 1, 2, 3, 6, and over 30 months postoperatively. The volume and area of the bony defect in the alveolar cleft area were compared between the OCP and AB groups before and after 6 months of surgery. RESULTS: The bone bridge in all patients in the OCP/Col group was successfully formed, and by 6 months postoperatively, the permanent teeth adjacent to the alveolar cleft had erupted at the site of the OCP/Col complex graft. Comparison of the pre- and postoperative bone defects between the 2 groups revealed almost the same extent of bone bridge formation. CONCLUSIONS: OCP/Col grafting could be considered as an alternative to autologous bone grafting as it yielded successful bone bridge formation and facilitated permanent tooth eruption.

Difference in the Effects of Lidocaine With Epinephrine and Prilocaine With Felypressin on the Autonomic Nervous System During Extraction of the Impacted Mandibular Third Molar: A Randomized Controlled Trial.

PURPOSE: Complications during local anesthesia include increased blood pressure and vasovagal reflex, which are caused by changes in the autonomic nervous system. The commonly used local anesthetic preparations are lidocaine to which the vasoconstrictor epinephrine is added (lidocaine-epinephrine) and prilocaine to which the vasoconstrictor felypressin is added (prilocaine-felypressin); however, their effects during dental treatment are unclear. We examined the effects of these 2 different local anesthetic preparations on the autonomic nervous system and circulation during extraction of the impacted mandibular third molar. MATERIALS AND METHODS: In this randomized controlled trial, 40 female patients scheduled for extraction of an impacted mandibular third molar were randomized to the lidocaine-epinephrine group or prilocaine-felypressin group. Heart rate variability, heart rate, and systolic blood pressure were recorded during the experiment. Descriptive and bivariate statistics were computed, and the P value was set at .05. RESULTS: The low frequency-high frequency ratio was significantly increased in the prilocaine-felypressin group during extraction compared with that in the lidocaine-epinephrine group (P < .05). In the lidocaine-epinephrine group, a significant decrease in the high-frequency component was observed during bone removal and extraction compared with that at rest (P < .05). In both groups, a significant increase in systolic blood pressure was observed during local anesthesia, incision and reflection of the flap, bone removal, separation of the tooth crown, extraction, and suturing compared with that at rest (P < .01). CONCLUSIONS: This study is the first to investigate the differences in the influence of 2 different local anesthetic preparations on the autonomic nervous system during extraction of the mandibular third molar. Changes in circulatory dynamics during tooth extraction with the 2 different local anesthetic preparations were the result of a decrease in parasympathetic nervous activity with lidocaine-epinephrine and an increase in sympathetic nervous activity with prilocaine-felypressin.

Reliability of Americleft Yardstick Nasolabial Appearance Assessment With/Without Basal View for Japanese Children With Unilateral Complete Cleft Lip and Palate.

OBJECTIVE: There is debate on the reliability of the Americleft Yardstick (AY) global nasolabial appearance assessment method. The objective was to analyze the effect of the additional basal view (BV) feature on the reliability of the AY method for Japanese children with complete cleft lip and palate (CUCLP). DESIGN: Blind retrospective analysis of clinical records on 43 patients (5- to 7-year-old) with nonsyndromic CUCLP who underwent primary lip repair from 2005 to 2011. MAIN OUTCOME MEASURE: Color pictures published in AY and Rubin's studies were used as reference pictures. Patients' photographs were cropped and rated on a 5-point scale for the vermilion border (VB), nasolabial frontal (NLF), and nasolabial profile (NLP) according to AY with/without BV assessment by Rubin's methods. Rating was performed twice by 3 oral surgeons. Intra- and inter-rater reliabilities were analyzed using weighted κ, and correlations between BV and other features were analyzed. RESULTS: Overall average assessment scores were 2.742 (0.573) with AY and 2.702 (0.489) with AY+BV methods (P = .728). Average intra-rater reliabilities were 0.605 and 0.611 and average inter-rater reliabilities were 0.525 and 0.48 with AY and AY+BV, respectively. Inter-rater reliability was the lowest for NLP. ρ scores between BV versus VB, NLF, and NLP were 0.025, 0.659, and 0.092, respectively. CONCLUSIONS: Present study demonstrates moderate intra- and inter-rater reliabilities obtained with the AY assessment method for Japanese children with CUCLP. Nasolabial profile standard ambiguity may lead to the poor reliability of AY assessment. Addition of the BV feature does not improve overall reliability.

Pilot Study of Visual and Quantitative Image Analysis of Facial Surface Asymmetry in Unilateral Complete Cleft Lip and Palate.

OBJECTIVE: To visualize and quantitatively analyze facial surface asymmetry following primary cleft lip repair in patients with unilateral cleft lip and palate (UCLP) and to compare this with noncleft controls. DESIGN: Retrospective comparative study. PATIENTS: Twenty-two patients with complete UCLP who underwent primary lip repair from 2009 to 2013 were enrolled in this study. The preserved 3-dimensional (3D) data of 23 healthy Japanese participants with the same age were used as controls. INTERVENTIONS: All patients had received primary labioplasty in accordance with Cronin triangular flap method with orbicular oris muscle reconstruction. MAIN OUTCOME MEASURES: Shadow and zebra images established from moiré images, which were reconstructed from 3D facial data using stereophotogrammetry, were bisected and reversed by the symmetry axes (the middle line of the face). The discrepancies of the gravity and density between cleft and noncleft sides in 2 regions of interest, facial and lip areas, were then calculated and compared with those of healthy participants. RESULTS: In the UCLP group, the mean discrepancies of gravity on shadow and zebra images were 1.76 ± 0.70 and 2.63 ± 1.72 pixels, respectively, in the facial area and 1.31 ± 0.36 and 3.83 ± 2.08 pixels, respectively, in the lip area. There was a significant difference in the mean discrepancies of gravity and density on zebra images in the lip area between the UCLP and control groups. CONCLUSIONS: Our image analysis of digital facial surface asymmetry in patients with UCLP provides visual and quantitative information, and it may contribute to improvements in muscle reconstruction on cleft lip repair.

Vascular endothelial growth factor-C induces osteogenic differentiation of human mesenchymal stem cells through the ERK and RUNX2 pathway.

Vascular endothelial cell growth factor C (VEGF-C) is a member of the VEGF family and plays a role in a variety of biological activities including lymphangiogenesis, angiogenesis, and neurogenesis through VEGF receptor 2 (VEGFR2) and 3 (VEGFR3). However, it has not been elucidated whether VEGF-C promotes osteogenic differentiation. Herein, we investigated the effects of VEGF-C on osteogenic differentiation in human mesenchymal stem cells (MSCs) and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly increased RUNX2 expression, and led to the promotion of osteogenic marker gene expression and mineralization of MSCs. VEGF-C treatment induced the phosphorylation of VEGFR2 and VEGFR3 in MSCs. Treatment with the VEGFR3-specific ligand VEGF-C156S also promoted MSC mineralization. Furthermore, co-treatment with VEGFR2 and VEGFR3 kinase inhibitors blocked VEGF-C-induced MSC mineralization. VEGF-C treatment activated ERK signaling in MSCs, and inhibition of ERK signaling effectively suppressed VEGF-C-induced RUNX2 expression and mineralization. These results indicate that VEGF-C-induced MSC osteogenesis is mediated through VEGFR2 and VEGFR3, and followed the activation of the ERK/RUNX2 signaling pathway.

C55 bacteriocin produced by ETB-plasmid positive Staphylococcus aureus strains is a key factor for competition with S. aureus strains.

Exfoliative toxin (ET) produced by Staphylococcus aureus is closely associated with the onset of bullous impetigo. To date, three ETs (ETA, ETB and ETD) have been identified. The gene encoding ETB is located in a plasmid designated pETB. Bacteriocin synthesis genes are also located in this plasmid and pETB-positive strains reportedly produce the C55 bacteriocin. In this study, the antibacterial activity against S. aureus strains of the bacteriocin produced by the pETB-positive strain TY4 was investigated. This bacteriocin demonstrated antibacterial activity against all pETB-negative but not pETB-positive strains, including TY4. Additionally, a TY4- strain from which the pETB plasmid had been deleted exhibited susceptibility to the bacteriocin. Further experiments revealed that two immunity factors (orf 46-47 and orf 48) downstream of the bacteriocin synthesis genes in the pETB plasmid are associated with immunity against the bacteriocin produced by TY4. The TY4- with orf46-47 strain exhibited complete resistance to bacteriocin, whereas the TY4- with orf48 strain exhibited partial resistance. Whether bacteriocin affects the proportion of each strain when co-cultured with S. aureus strains was also investigated. When TY4 or TY4- was co-cultured with 209P strain, which is susceptible to the bacteriocin, the proportion of 209P co-cultured with TY4 was significantly less than when 209P was co-cultured with TY4-, whereas the proportion of TY4- with orf46-48 co-cultured with TY4 was greater than with TY4-. These results suggest that the C55 bacteriocin produced by pETB-positive strains affects the proportion of each strain when pETB-positive and -negative strains co-exist.

Clinical and 3-Dimensional Analyses of Nasal Forms After Secondary Correction of Cleft Lip-Nose Deformities Using Extended Spreader Cartilage Graft With a Cross-Lap Joint Technique.

PURPOSE: A surgical strategy for definitive cleft lip-nasal correction that stably provides symmetric and natural nasal forms has not been established to date. The purpose of this study was to describe our surgical techniques and 3-dimensional (3D) assessment results after the definitive correction of cleft lip-nose deformity using an extended spreader cartilage graft with a cross-lap joint technique to achieve a rigid strut for lower lateral cartilage repositioning to obtain a desirable nasal tip projection. PATIENTS AND METHODS: This study enrolled 14 patients with unilateral cleft lip (UCL) with or without cleft palate and 8 patients with bilateral cleft lip (BCL) with or without cleft palate who underwent definitive nose correction and were followed for 1 to 3 years. All patients were treated by open rhinoplasty, repositioning of the lower lateral cartilage, use of an extended spreader cartilage graft with a cross-lap joint technique for nasal tip support, and medial-upward advancement of nasolabial components with vestibular expansion by a free mucosal graft. For the BCL nose, pedicle flaps from rim skin were used for columella lengthening. Preoperative and postoperative nasal forms were 3-dimensionally analyzed by use of 3D images serially obtained in 12 patients. RESULTS: The postoperative nasal forms were satisfactorily improved in all patients, without any serious postoperative complications. Preoperative and postoperative 3D analyses showed a significantly projected nasal tip in the postoperative noses of patients in both the UCL group and the BCL group (P < .01 and P < .05, respectively) and a sharper nasal tip angle in the BCL group (P < .05). Lateral deviation of the nasal tip was significantly improved in the center of the face in patients in the UCL group (P < .01). CONCLUSIONS: The results of this study suggest that the extended spreader cartilage graft using the cross-lap joint graft technique is useful to provide a desirable projection of the nasal tip in the center of the face on definitive correction of both UCL and BCL nose deformities.

Preliminary Analysis of the 3-Dimensional Morphology of the Upper Lip Configuration at the Completion of Facial Expressions in Healthy Japanese Young Adults and Patients With Cleft Lip.

PURPOSE: To develop criteria for the analysis of upper lip configuration of patients with cleft lip while they produce various facial expressions by comparing the 3-dimensional (3D) facial morphology of healthy Japanese adults and patients with cleft lip. PATIENTS AND METHODS: Twenty healthy adult Japanese volunteers (10 men, 10 women, controls) without any observed facial abnormalities and 8 patients (4 men, 4 women) with unilateral cleft lip and palate who had undergone secondary lip and nose repair were recruited for this study. Facial expressions (resting, smiling, and blowing out a candle) were recorded with 2 Artec MHT 3D scanners, and images were superimposed by aligning the T-zone of the faces. The positions of 14 specific points were set on each face, and the positional changes of specific points and symmetry of the upper lip cross-section were analyzed. Furthermore, the configuration observed in healthy controls was compared with that in patients with cleft lip before and after surgery. RESULTS: The mean absolute values for T-zone overlap ranged from 0.04 to 0.15 mm. Positional changes of specific points in the controls showed that the nose and lip moved backward and laterally upward when smiling and the lips moved forward and downward medially when blowing out a candle; these movements were bilaterally symmetrical in men and women. In patients with cleft lip, the positional changes of the specific points were minor compared with those of the controls while smiling and blowing out a candle. The left-versus-right symmetry of the upper lip cross-section exceeded 1.0 mm in patients with cleft lip, which was markedly higher than that in the controls (0.17 to 0.91 mm). These left-versus-right differences during facial expressions were decreased after surgery. CONCLUSION: By comparing healthy individuals with patients with cleft lip, this study has laid the basis for determining control values for facial expressions.

Upward Advancement of the Nasolabial Components at Unilateral Cleft Lip Repair Prevents Postoperative Long Lip.

OBJECTIVE: To prevent the occurrence of postoperative long lip, longitudinal postoperative changes in nasolabial forms of patients with unilateral cleft lip who underwent primary lip repair with or without upward advancement of the nasolabial components were compared. PATIENTS: Forty-three subjects (24 unilateral cleft lip and palate [UCLP] and 19 unilateral cleft lip solely, and cleft lip and alveolus [UCL/UCLA]) who underwent primary lip repair with upward advancement of the nasolabial components (NA group) and 30 subjects (16 UCLP and 14 UCL/UCLA) without upward advancement (LA group) were enrolled. OUTCOME MEASURES: Postoperative photos taken at 1 and 6 months and at 1, 2, and 3 years were used for measuring the heights of the nasal alar base (NBH), the columellar base (CBH), Cupid's peak (CPH), and the upper lip (ULH). The ratios of these measurements between the affected and unaffected sides were calculated in both groups. RESULTS: In the LA group, the 3-year postoperative all-items ratios of UCLP were significantly larger than those at 1 month postoperatively, demonstrating drooping of the nasolabial tissues in the affected side (all P < .01). Furthermore, the 3-year postoperative CPH and ULH ratio of UCL/UCLA was significantly larger than that at 1 month postoperatively, demonstrating the long lip (P < .01). In the NA group, the NBH, CBH, and CPH ratios of both UCLP and UCL/UCLA did not show significant differences between 1 month and 3 years postoperatively. CONCLUSION: Upward advancement of the nasolabial components prevents postoperative long lip.

Perceptual-Speech, Nasometric, and Cephalometric Results After Modified V-Y Palatoplasties With or Without Mucosal Graft.

OBJECTIVE: Although the goal of cleft palate (CP) repair is to achieve normal speech, no standard procedure ensures that patients' speech will be at the same level as speech in children without CP. In this study, postoperative speech outcomes following primary CP repair combined with or without a mucosal graft was analyzed in comparison with that of control subjects without CP. PARTICIPANTS: Eighty-two patients who underwent modified V-Y palatoplasty with a mucosal graft on the nasal side for symmetrical muscular reconstruction during 2006-2012 (MG group) and 109 patients who previously underwent modified V-Y palatoplasty without a mucosal graft (non-MG group) were enrolled in this study. Speech data on 37 Japanese subjects without CP were used as a control. MAIN OUTCOME MEASURES: Perceptual rating of resonance and nasal emission and nasometry were carried out for all participants. Furthermore, cephalometric analyses were performed to assess postoperative velopharyngeal morphology and velar movement. RESULTS: Normal resonance was achieved at a significantly higher rate (90.3% of patients) in the MG group than in the non-MG group (68.8%) (P < .01). The mean nasalance scores in the MG group were significantly lower (P < .01) and were almost at the same level as in controls. Cephalometric analyses revealed a greater velar length and velar elevation angle during phonation in the MG group (P < .01 and P < .05, respectively). CONCLUSIONS: Modified V-Y palatoplasty combined with a mucosal graft on the nasal side of the velum for symmetrical muscular reconstruction facilitates speech outcomes for children with cleft palate that are comparable with those for peers without CP.

Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma.

Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas.

Luliconazole: a review of a new antifungal agent for the topical treatment of onychomycosis.

Luliconazole is a novel, broad-spectrum, imidazole antifungal under development in the USA as a treatment for dermatophytic skin and nail infections. In vitro, luliconazole is one of the most potent antifungal agents against filamentous fungi including dermatophytes. Luliconazole has been formulated in a 10% solution with unique molecular properties, which allow it to penetrate the nail plate and rapidly achieve fungicidal levels in the nail unit. These properties make luliconazole a potent compound in the treatment of onychomycosis. This article reviews the development of luliconazole solution, 10% its molecular properties, preclinical and clinical data and its future perspectives for the treatment of fungal infections.

Short-term molding effects on the upper alveolar arch following unilateral cleft lip repair with/without nasal vestibular expansion.

Objective : To elucidate the various effects on maxillary growth following different procedures for vestibular expansion at the time of primary lip repair for unilateral cleft lip and palate (UCLP). Participants : Thirty patients with complete UCLP who underwent primary lip repair using a triangular-flap technique with nasal vestibular expansion (NVE; the NVE group) and 30 patients who underwent the same lip repair with closure of the nasal floor (non-NVE group) were enrolled in this study. Interventions : Serial dental casts on lip and palatal repair were scanned with a laser scanner. The three-dimensional coordinates of seven anatomical landmarks and their growth changes, the curvature radius rate between major/minor segments, and the collapse rates were compared between the two groups. Results : At the time of lip repair, the incisal point was located slightly anteriorly in the non-NVE group. At the time of palatal repair, the cleft edge of the alveolar process in the minor segment was located significantly anteriorly and laterally in the NVE group, showing the significantly forward change of the minor segment. The minor segment collapsed in the non-NVE group. The collapse rate of the NVE group (3.3%) was significantly lower than that of the non-NVE group (40.0%). Conclusions : NVE following simultaneous advancement of nasolabial components on the affected side at the time of primary lip repair for UCLP facilitates the forward molding of the maxilla, resulting in a more symmetrical alveolar arch form.

Changes in grafted autogenous bone during edgewise treatment in patients with unilateral cleft lip/palate or alveolus.

Objective : To examine the changes in autogenous bone from 6 to 12 months after alveolar bone grafting (ABG) (T1) through completion of edgewise treatment (T2). Design : Retrospective longitudinal study. Setting : Multidisciplinary long-term follow-up at Kagoshima University Hospital. Patients : Forty-three patients with unilateral cleft lip and palate or alveolus. Main Outcome Measures : At T1 and T2, the bone bridge and quantity of grafted bone were evaluated using the Chelsea scale and the ABG scale. The cleft-adjacent tooth angles before ABG and at T2, as well as the number of orthodontic space closures, were examined. Patients were classified as having either adequate (type A or C; adequate group) or poor bone bridges (type B, D, E, or F; poor group) by the assessment at T1. Results : At T1, the ABG scores for the cleft-adjacent central incisor side of patients in the adequate group were higher than those of patients in the poor group (P < .001). At T2, the adequate group had higher ABG scores for the cleft-adjacent central incisor side (P = .022) and the canine sides (P = .034). No significant differences in tooth angles or the number of orthodontic space closures were noted between the groups. Conclusions : These results suggest that the quantity of grafted bone in the cleft-adjacent central incisor at 6 to 12 months post-ABG may be an indicator of the quantity of grafted bone that will be present after edgewise treatment.

Outcome following secondary autogenous bone grafting before and after canine eruption in patients with unilateral cleft lip and palate.

OBJECTIVE: To determine whether the long axis and eruption of the cleft-adjacent canine affect postoperative outcomes in secondary autogenous bone grafting (SABG). DESIGN: Retrospective longitudinal study. SETTING: Multidisciplinary long-term follow-up at Kagoshima University Hospital. SUBJECTS AND METHODS: Twenty-five patients with complete unilateral cleft lip and palate (11 male, 14 female) were compared between unerupted and erupted groups for canine developmental stage, canine angle, and vertical height at bone grafting at 1 year and more than 4 years after SABG. The interalveolar septal heights at 1 and more than 4 years were evaluated by orthopantomograms. RESULTS: All patients in both groups accomplished dental rehabilitation with orthodontic treatment alone without prosthetic appliances. Although the rate of an acceptable bone bridge tended to be lower in the unerupted group (62.5%) than in the erupted group (88.8%), the difference was not significant (P = .158). The canine angle at bone grafting was significantly different between acceptable (69.2° ± 12.2°) and poor cases (77.3° ± 6.2°) at more than 4 years in the unerupted group (P = .049). The acceptable bone bridge rate might reflect mechanical stress added by natural eruption and orthodontic force. CONCLUSIONS: We suggest that SABG should be planned in accordance with the canine angle, crown and root development, the eruption position of the cleft-adjacent canine, and the timing of added mechanical stress in the alveolar cleft, considering the bone formation in the alveolar cleft.