Effects of N-methyl-d-aspartate receptor antagonist MK-801 (dizocilpine) on bone homeostasis in mice.

OBJECTIVES: To gain insight into the role of the N-methyl-d-aspartate (NMDA) receptor in bone metabolism by examining the effects of its noncompetitive antagonist, MK-801 (dizocilpine), on bone homeostasis and bone healing in mice. METHODS: MK-801 (2.5 mg/kg) or saline (in control groups) was intravenously administered to healthy mice and mice with bone-defects daily for seven to 14 days. Bone defects were artificially created in femurs using a drill and reamer. Following euthanasia, bones were extracted and processed for microcomputed tomography (µCT) and histological analyses. The effects of MK-801 on osteoclast differentiation by bone marrow macrophages (BMMs) were examined in vitro. mRNA expressionlevels of Grin3b levels were also examined using reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Bone volume was significantly decreased in mice administered MK-801 for 14 days. Additionally, the number of osteoclasts was reduced, while number of osteoblasts and rate of bone formation were increased in these mice. MK-801 inhibited osteoclast differentiation dose-dependently in vitro. RT-PCR findings suggested expression of Grin3b, a subunit of the NMDA receptor, in BMMs. During the healing process of artificially created defects in femurs, no significant differences were found between the control and MK-801-treated groups, indicating no stimulatory or inhibitory effects by MK-801 administration. CONCLUSIONS: These results indicate that blockade of the NMDA receptor by MK-801 administration affects bone metabolism but not the healing process of artificial bone defects.

5-HT2A receptor activation enhances NMDA receptor-mediated glutamate responses through Src kinase in the dendrites of rat jaw-closing motoneurons.

KEY POINTS: 5-HT increases the excitability of brainstem and spinal motoneurons, including the jaw-closing motoneurons, by depolarizing the membrane potential and decreasing the medium-duration afterhyperpolarization. In this study, we focused on how 5-HT enhances postsynaptic glutamatergic responses in the dendrites of the jaw-closing motoneurons. We demonstrate that 5-HT augments glutamatergic signalling by enhancing the function of the GluN2A-containing NMDA receptor (NMDAR) through the activation of 5-HT2A receptors (5-HT2A Rs) and Src kinase. To enhance glutamatergic responses, activation of the 5-HT2A Rs must occur within ∼60 µm of the location of the glutamate responses. 5-HT inputs to the jaw-closing motoneurons can significantly vary their input-output relationship, which may contribute to wide-range regulation of contractile forces of the jaw-closing muscles. ABSTRACT: Various motor behaviours are modulated by 5-HT. Although the masseter (jaw-closing) motoneurons receive both glutamatergic and serotonergic inputs, it remains unclear how 5-HT affects the glutamatergic inputs to the motoneuronal dendrites. We examined the effects of 5-HT on postsynaptic responses evoked by single- or two-photon uncaging of caged glutamate (glutamate responses) to the dendrites of masseter motoneurons in postnatal day 2-5 rats of either sex. Application of 5-HT induced membrane depolarization and enhanced the glutamate-response amplitude. This enhancement was mimicked by the 5-HT2A receptor (5-HT2A R) agonist and was blocked by the 5-HT2A/2C R antagonist. However, neither the 5-HT2B R nor the 5-HT2C R agonists altered glutamate responses. Blockade of the NMDA receptors (NMDARs), but not AMPA receptors, abolished the 5-HT-induced enhancement. Furthermore, the selective antagonist for the GluN2A subunit abolished the 5-HT-induced enhancement. 5-HT increased GluN2A phosphorylation, while the Src kinase inhibitor reduced the 5-HT-induced enhancement and GluN2A phosphorylation. When exposure to the 5-HT2A R agonist was targeted to the dendrites, the enhancement of glutamate responses was restricted to the loci of the dendrites near the puff loci. Electron microscopic immunohistochemistry revealed that both the NMDARs and the 5-HT2A Rs were close to each other in the same dendrite. These results suggest that activation of dendritic 5-HT2A Rs enhances the function of local GluN2A-containing NMDARs through Src kinase. Such enhancement of the glutamate responses by 5-HT may contribute to wide-range regulation of contractile forces of the jaw-closing muscles.

Development and application of a direct method to observe the implant/bone interface using simulated bone.

BACKGROUND: Primary stability after implant placement is essential for osseointegration. It is important to understand the bone/implant interface for analyzing the influence of implant design on primary stability. In this study rigid polyurethane foam is used as artificial bone to evaluate the bone-implant interface and to identify where the torque is being generated during placement. METHODS: Five implant systems-Straumann-Standard (ST), Straumann-Bone Level (BL), Straumann-Tapered Effect (TE), Nobel Biocare-Brånemark MKIII (MK3), and Nobel Biocare-Brånemark MKIV (MK4)-were used for this experiment. Artificial bone blocks were prepared and the implant was installed. After placement, a metal jig and one side artificial bone block were removed and then the implant embedded in the artificial bone was exposed for observing the bone-implant interface. A digital micro-analyzer was used for observing the contact interface. RESULTS: The insertion torque values were 39.35, 23.78, 12.53, 26.35, and 17.79 N cm for MK4, BL, ST, TE, and MK3, respectively. In ST, MK3, TE, MK4, and BL the white layer areas were 61 × 103 µm(2), 37 × 103 µm(2), 103 × 103 µm(2) in the tapered portion and 84 × 03 µm(2) in the parallel portion, 134 × 103 µm(2), and 98 × 103 µm(2) in the tapered portion and 87 × 103 µm(2) in the parallel portion, respectively. CONCLUSIONS: The direct observation method of the implant/artificial bone interface is a simple and useful method that enables the identification of the area where implant retention occurs. A white layer at the site of stress concentration during implant placement was identified and the magnitude of the stress was quantitatively estimated. The site where the highest torque occurred was the area from the thread crest to the thread root and the under and lateral aspect of the platform. The artificial bone debris created by the self-tapping blade accumulated in both the cutting chamber and in the space between the threads and artificial bone.

Influence of the Conditioning Method for Pre-Sintered Zirconia on the Shear Bond Strength of Bilayered Porcelain/Zirconia.

This study evaluated the bond strength of veneering porcelain with an experimental conditioner-coated zirconia. Pre-sintered Y-TZP specimens (n = 44) were divided in two groups based on conditioning type. After sintering, all sample surfaces were sandblasted and layered with veneering porcelain. Additionally, half of the specimens in each group underwent thermal cycling (10,000 cycles, 5-55 °C), and all shear bond strengths were measured. After testing, the failure mode of each fractured specimen was determined. Differences were tested by parametric and Fisher's exact tests (α = 0.05). The differences in bond strength were not statistically significant. Adhesive fractures were dominantly observed for the non-thermal cycled specimens. After thermal cycling, the conditioner-coated group showed cohesive and mixed fractures (p = 0.0021), whereas the uncoated group showed more adhesive fractures (p = 0.0021). Conditioning of the pre-sintered Y-TZP did not change the shear bond strength of the veneering porcelain, but did improve the failure mode after thermal cycling.

Immediate loading of two freestanding implants placed by computer-guided flapless surgery supporting a mandibular overdenture with magnetic attachments.

PURPOSE: The present article describes a novel clinical procedure for mandibular overdentures supported by two freestanding implants loaded immediately after placement via computer-guided flapless surgery. METHODS: A conventional acrylic complete denture was fabricated, and CT scans obtained using the denture as a radiographic guide. Preoperative computer-assisted planning was performed using commercially available software, permitting simulation of implant placement at optimal positions. Using simulation data, a surgical guide was manufactured and used during surgery. The surgical guide was placed and local anesthesia injected for drilling of anchor pins to stabilize the surgical guide. The drilling protocol for each osteotomy site achieved an insertion torque greater than 35 Ncm. Immediately after implant placement, a keeper of the magnetic attachment was connected to each implant, and the magnetic assembly incorporated into the denture. The mucosal surface of the denture around the magnet was relieved to avoid excessive tissue pressure. The patients were instructed to wear the denture in place continually for the following 7 days. After six months of healing and follow-up, a final denture with a metal framework may be fabricated if necessary. CONCLUSION: A novel treatment protocol for immediately loaded implant-supported mandibular overdentures is described in detail. The protocol ensures secure precise and safe implant placement, successful osseointegration, and immediate improvement of oral health-related quality of life for patients with unstable complete dentures.

Effect of implant design on primary stability using torque-time curves in artificial bone.

BACKGROUND: Primary stability following implant placement is essential for osseointegration and is affected by both implant design and bone density. The aim of this study was to compare the relationships between torque-time curves and implant designs in a poor bone quality model. METHODS: Nine implant designs, with five implants in each category, were compared. A total of 90 implants (Straumann: Standard RN, Bone Level RC, Tapered Effect RN; Nobel Biocare: Brånemark MKIII, MKIV) were placed in type IV artificial bone. Torque-time curves of insertion and removal were recorded at the rate of 1000 samples/s by a torque analyzer. RESULTS: The torque-time curves were divided into initial, parallel, tapered, and platform areas. The mean torque rise rate of the parallel area was smallest at 0.36 N · cm/s, with a significant difference from those of the other areas (p < 0.05). Values of 2.14, 2.33, and 2.65 N · cm/s were obtained for the initial, tapered, and platform areas, respectively. The removal torque for six of the implant designs (Bone Level RC 8, 10, and 12 mm; Tapered Effect RN 10 mm; Brånemark MKIII 10 mm, MKIV 10 mm) was significantly smaller than the corresponding insertion torque (p < 0.05). However, the removal torque for ST6, 8, and 10 was almost the same as or slightly greater than the corresponding insertion torque. CONCLUSIONS: The insertion torque-time curves and design features of the implants were accurately transferred. Increasing implant taper angle appeared to increase the torque rate. Torque was mainly generated from the superior surface to the valley of the thread and the inferior and axial surfaces of the platform, while the inferior and axial surfaces of the thread did not significantly affect torque generation.

Inguinal porokeratosis in a Japanese man.

Inguinal and genital porokeratosis are rare but seem to be more common in Asians. We report a case of a 69-year-old Japanese man with multiple lesions of porokeratosis in both inguinal regions. The lesions first appeared in the inguinal region and subsequently spread to the trunk. The patient reported that his father had had similar lesions. Dermoscopy demonstrated central brown pigmentation and blue-gray dots surrounded by a single "white track" at the periphery. The exterior border of the white track also showed light brown pigmentation. Genital or inguinal porokeratosis is uncommon and may be misdiagnosed as Bowen's disease, lichen planus or extramammary Paget's disease. However, awareness of this entity and the use of dermoscopy are helpful to establish a correct diagnosis.

Unilateral linear syringoma in a Japanese female: dermoscopic differentiation from lichen planus linearis.

A dermoscopy of linear unilateral syringoma has never been described in the English literature. The authors report the case to elucidate the dermoscopic features of syringoma. Clinical, dermoscopic and pathological features of a 38-year-old Japanese female case of linear unilateral syringoma on the left upper arm were described and compared with those of lichen planus linearis. Although the clinical appearance of linearly arranged dusky erythemas in the present case was quite similar to that of lichen planus linearis, dermoscopy did not show Wickham's striae but rather homogeneous light brown pigmentation with multifocal whitish areas and a delicate pigment network at the periphery. Dermoscopy might be helpful to differentiate linear unilateral syringoma from lichen planus linearis.