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Sphingosine 1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor, is required for lymphocyte trafficking, and is a promising therapeutic target in inflammatory diseases. To find potent S1PR1 antagonists, identification of the structural basis for drug efficacy is important. Here, we synthesized a novel antagonist, KSI-6666, that persistently inhibits S1PR1 activity and effectively suppresses pathogenic inflammation. Metadynamics simulation suggested that the interaction of a benzene ring moiety in KSI-6666 with a methionine residue in the ligand-binding pocket of S1PR1 inhibits the dissociation of KSI-6666 from S1PR1, generating a metastable binding state. Consistently,in vitrofunctional and mutational analyses revealed that KSI-6666 causes pseudoirreversible inhibition of S1PR1, dependent on the methionine residue of the protein and substituents on the distal benzene ring of KSI-6666. Moreover,in vivostudy suggested that this pseudoirreversible inhibition is responsible for the persistent activity of KSI-6666. These findings will contribute to the rational design of potent S1PR1 antagonists for the treatment of inflammatory disorders.

Sodium glucose co-transporter 1 (SGLT1) plays a dominant role in the absorption of glucose in the gut and is considered a promising target in the development of therapeutic options for postprandial hyperglycemia. Previously, we reported potent and selective SGLT1 inhibitors 1 and 2 showing efficacy in oral carbohydrate tolerance tests in diabetic rat models. In a pharmacokinetic (PK) study of 2, excessive systemic exposure to metabolites of 2 was observed, presumably due to the high permeability of its aglycone (2a). To further improve SGLT1 inhibitory activity and reduce aglycone permeability, a series of 4-benzyl-5-isopropyl-1H-pyrazol-3-yl β-D-glycopyranoside derivatives bearing novel hydrophilic substitution groups on the phenyl ring were synthesized and their inhibitory activity toward SGLTs was evaluated. Optimized compound 14c showed an improved profile satisfying both higher activity and lower permeability of its aglycone (22f) compared with initial leads 1 and 2. Moreover, the superior efficacy of 14c in various carbohydrate tolerance tests in diabetic rat models was confirmed compared with acarbose, an α-glucosidase inhibitor (α-GI) widely used in the clinic.

Purpose This study evaluated the bone volume, height, and width that can be obtained in alveolar ridge augmentation using titanium mesh and autogenous bone particles in patients with cleft lip/palate. Patients and Methods Subjects were 15 patients with cleft lip/palate requiring tertiary bone graft for implant therapy. Computed tomography (CT) scans were taken before removing the mesh, from 1 to 21 months after bone grafting. Forty-three reconstructed images corresponding to the positions for implant placement were selected for this study. The percent defect filled with bone (%BONE), defined as the percentage of newly formed bone in the space created by the mesh, was measured for image analyses. In linear analyses, 4 parameters were used: increased bone height (IBH), percent increased bone height (%IBH), increased bone width (IBW), and percent increased bone width (%IBW). Factors influencing the quantitative data and the clinical courses of placed implants were also explored. Results The average %BONE was 91.1%. IBH averaged 4.4 mm, whereas %IBH averaged 88.5%. IBW averaged 4.6 mm, whereas %IBW averaged 86.4%. Little correlation was present between the quantitative data and patient age, or time interval. A significant correlation was identified between the data for span of the grafted area and %BONE (correlation coefficient value = −0.36). However, the diminishing rate was very low. No implants were lost postoperatively. Conclusions Alveolar ridge augmentation with titanium mesh and autogenous bone particles from the anterior iliac crest has very high predictability as a preimplant procedure in patients with cleft lip/palate.

This report describes a case of mediastinum emphysema caused by root canal therapy of the lower first molar.A 54-year-old woman presented with swelling of the right submandibular region and dysphagia. She had momentary pain during root canal disinfection with H2O2and NaOCI in the morning. Palpation and ultrasonic echography revealed subcutaneous emphysema extending to the contralateral side. She complained of dyspnea due to airway obstruction. The symptoms disappeared immediately after administration of methylprednisolone sodium succinate. Computed tomography, performed the next day, demonstrated that the emphysema extended to the upper mediastinum. The clinical course was rather good.We need to recognize the possibility that emphysema caused by dental treatment might extend to the mediastinum and lead to respiratory symptoms. Treatment should be performed promptly and adequately in such cases.

Purpose: This study investigated the effect of parathyroid hormone (1-34) [PTH(1-34)] on bone reactions after tibial placement of titanium screw implants into ovariectomized rats. Materials and Methods: Twelve-week-old female Wistar rats were divided into 3 groups of 24. The first group (Sham group) was sham-operated; the second group (OVX group) was ovariectomized only; and the third group (PTH group) was subcutaneously administered 30 μg/kg PTH in the dorsal region 3 days per week starting the fourth week after ovariectomy until the end of the experiment. Titanium screw implants were placed in the proximal metaphysis of the tibia of all 3 groups at 168 days after surgery. The animals were killed 7, 14, 28, and 56 days after implantation. Undecalcified sections were prepared and evaluated by light microscopy. Histomorphometric measurements were obtained using a computer-based image analyzer to quantify the unit bone mass around the implant and the rate of implant-bone contact. Results: When PTH administration was started 21 days after ovariectomy, the volume density of bone around implants in the PTH group was almost the same as that of the Sham group throughout the entire observation period. This finding suggests that not only can intermittent human PTH(1-34) administration prevent resorption of newly generated trabeculae around an implant but also it can aid in the recovery of bone volume lost due to ovariectomy. Conclusion: When dental implants are applied to jaw bone showing trabecular bone loss, it may be possible to increase bone density around an implant by intermittent human PTH(1-34) administration and thereby improve clinical results. © 2003 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 61:471-480, 2003

Purpose: The purpose of this study was to clarify the anatomical features of vascularized iliac bone grafts used for mandibular reconstruction and dental implantation. Material and Method: Twenty-six cadavers were dissected to examine vessels and areas of iliac bone that could be used as pedicles and grafts. The length and diameter of vessels of the vascular pedicle were determined, and the length and depths of the iliac bone were measured with respect to points determined by the relative dimensions of the bone. Results: The deep circumflex iliac arteries were classified as double nutrient type (75%), illac-crest type (19%), or iliacus-muscle type (6%). The mean arterial length was 64±15 mm in the double nutrient type. The mean internal diameters at the origin of the deep circumflex iliac artery and vein that could be used for anastomosis were 1.7±0.4 mm and 2.1±0.7 mm respectively. The greatest mean cross-sectional width and height were 18±3 and 42±5 mm respectively. The greatest mean cross-sectional cortical thickness at the intermediate line of the iliac crest was 3.4±0.8 mm. Conclusion: These results should be useful in designing bone grafts for mandibular reconstruction followed by dental implantation. Copyright 2002 European Association for Cranio-Maxillofacial Surgery. Published by Elsevier Science Ltd. All rights reserved.

The syntheses of trans- and cis-isomers of dragmacidin C and 3,4-dihydrohamacanthin A, and dragmacidin B have been accomplished by condensation of two indolylglycines followed by cyclization and reduction. The relative stereochemistry of dragmacidin C was confirmed to be cis, which is distinct from that of other dragmacidins.

The purpose of this study was to evaluate the association between loss of ovarian function and bone mineral density changes in the mandibles of ovariectomized rabbits using peripheral quantitative computed tomography. Twenty-four adult female Japanese white rabbits were used in this experiment. The mandibular incisors were initially extracted to create implant bone. Twelve animals were bilaterally ovariectomized and the other twelve sham-ovariectomized 12 weeks after tooth extraction. All rabbits were sacrificed at 4 and 12 weeks after ovariectomy and sham-ovariectomy, with 6 rabbits in each of the four resultant groups. The edentulous parts of distal mandibular bodies were measured by peripheral quantitative computed tomography. There were significant decreases in total bone mineral density and trabecular bone mineral density in the mandibles of rabbits at 12 weeks post-ovariectomy. The results demonstrate the mineralized bone loss in the mandibles of ovariectomized rabbits.

We investigated the effects of transplantation of osteoblastic cells with a bone morphogenetic protein (BMP)/carrier complex on bone repair by in vitro and in vivo experiments. Poly-D,L-lactic-co-glycolic acid/gelatin sponge (PGS) was used as a carrier for cell transplantation. In the in vitro experiments, three cell types, C3H10T1/2 cells, MC3T3-E1 cells, and primary osteoblastic cells, isolated from newborn rat calvariae (ROB cells), were cultured for 2 weeks on PGS alone or PGS containing BMP-2 (PGS/BMP). C3H10T1/2 cells cultured on PGS/BMP expressed several markers related to differentiation of both osteoblasts and chondrocytes, such as alkaline phosphatase (ALP) activity and mRNAs for osteocalcin and aggrecan, whereas the cells cultured on PGS alone expressed no such markers. MC3T3-E1 cells cultured on PGS/BMP exhibited a more ALP-positive cells than those cultured on PGS alone. PGS/BMP promoted ROB cell differentiation into both osteoblasts and chondrocytes. In the in vivo experiments, we transplanted ROB cells, which had been cultured on PGS alone or PGS/BMP in vitro for 2 weeks, into bone defects created in rat calvariae. Transplantation of ROB cells cultured on PGS alone generated little new bone. Transplantation of ROB cells cultured on PGS, which absorbed a low dose (10 ng) of rhBMP-2,; induced significantly higher bone mineral content than PGS/BMP alone, although application of a high dose (1 microg) of rhBMP-2 induced no difference in bone mineral content between transplantation of PGS/BMP with or without ROB cells. These results show that transplantation of osteoblastic cells after induction of osteoblast maturation in vitro by cultivation on PGS/BMP is a potent technique for cell therapy of bone repair.

Purpose: The tissue reaction around hydroxyapatite (HA) implants irradiated at 3 different time points after placement was histologically and histomorphometrically analyzed to further determine the relation between irradiation and tissue reaction. Materials and methods: Cylindrical high-density HA implants were placed in the mandibles of 48 Japanese white rabbits. The mandible was then irradiated with a single 15-Gy dose 5, 14, or 28 days after implantation. The rabbits were sacrificed on days 7, 14, 28, or 90 after irradiation. Nonirradiated rabbits with implants were used as controls. Nondecalcified specimens stained with toluidine blue were used for histologic analysis and histomorphometric measurements. Results: In the rabbits irradiated 5 days after implantation, the HA-bone contact occurred later than in the controls. The bone-implant contact surface ratio was lower than in the controls at each time of sacrifice because of necrosis of the newly formed bone just after irradiation. The HA-bone contact in rabbits irradiated 14 and 28 days after implantation was similar to that of the controls. Bone remodeling was suppressed in the rabbits in each group sacrificed 90 days after irradiation. Conclusions: Therapeutic irradiation shortly after implantation inhibits direct contact between the HA implant and the surrounding bone. Bone contact occurring before irradiation was minimally affected. Regardless of the interval between implantation and irradiation, postimplantation irradiation inevitably delays bone remodeling. © 2001 American Association of Oral and Maxillofacial Surgeons

本研究はインプラントを用いて治療を行った口腔腫瘍術後患者の機能を咀嚼機能の面から評価, インプラント治療によって得られる機能回復の程度と本治療法の抱えている今後の課題を明らかにすることを目的とした。検討対象は, 昭和大学歯学部第一口腔外科学教室, あるいはドイツ・ハノーバー医科大学歯学部口腔顎顔面外科にてインプラント治療を受けた口腔腫瘍術後患者, あるいは一般の歯の欠損患者である。これらの患者の術後機能を「山本の咬度表」をはじめとする主観的評価法, および「低粘着性発色ガム法」,「デンタルプレスケール」を用いた客観的機能評価法により検索した。その結果, (1) 客観評価によると, 一部の患者の機能は健常人と同等であった。(2) 下顎切除例では下顎の連続性の回復が重要であった。(3) 舌下神経切除例の機能は比較的低かった, (4) 患者の主観評価と客観的評価の結果は必ずしも一致しなかった。以上の結果より, インプラント治療により得られる機能回復の程度は症例により大きく異なるため, 患者および術者双方がその意義をよく認識した上で, 治療に入ることが重要と考えられた。

Structural and morphometric investigations of the vessels of the neck region were carried out on 30 cadavers (15 male and 15 female in the age range of 45 to 93 years old) to gain more knowledge of the anatomy for microvascular surgery. Our results briefly are as follows: (1) The non-common-truck type of the external carotid artery (in which each branch arises separately from the external carotid artery) was found in 76.6 percent of cases, the truncus linguofacialis type was found in 21.7 percent, and the truncus thyrolingualis type was found in 1.7 percent. (2) The smallest internal diameter (the average was 1.2 mm) was found in the superficial cervical artery. (3) The largest internal diameter (4.4 mm) was measured in the external carotid artery. (4) The longest arterial section (127.8 mm) was measured between the clavicle and mandibular margin. This vascular section or stem consisted of three parts: the supraclavicular part of the common carotid artery, the proximal section of the external carotid artery, and the first 3 cm of the facial artery. (5) In 46.6 percent of cases, the facial, lingual, and superior thyroid veins joined together and formed a thyrolinguofacialis vein. (6) The type with one external jugular vein accounted for 83.0 percent of cases, and the type with one anterior jugular vein for 67.4 percent of cases. (7) The middle thyroid vein exhibited the smallest internal diameter (average of 2.0 mm). (8) The largest internal diameter (7.9 mm) was measured in the internal jugular vein. (9) The longest vessel to receive a vascular pedicle vein was the external jugular vein, the average length of which was 99.7 mm. (10) The frequency and location of valves in the facial vein were also determined.

根治手術後に即時再建手術を行った口底癌19症例の術後の構音機能と手術との関連性を分析した。評価方法は日本語100語音による発語明瞭度検査である。対象症例の内訳を軟組織の再建方法別にみると, 遊離前腕皮弁移植症例が12例, 大胸筋皮弁移植症例と腹直筋皮弁移植症例がそれぞれ3例, 前腕皮弁と大胸筋皮弁の併用症例が1例であった。舌の切除範囲別では, 舌部分切除症例が14例, 可動部半側切除症例が1例, 半側切除症例が1例, 亜全摘出症例が3例であった。これらの症例について原発腫瘍の大きさ, 切除範囲, 切除様式, 軟組織の再建方法, 下顎骨の再建方法と術後の構音機能の関連について検討した。その結果, 原発腫瘍の大きさによる術後の構音機能の差は少なかったが, 舌の切除範囲が大きくなると構音機能は低下していた。切除様式については側方型の切除を受けた症例の明瞭度は前方型の切除を受けた症例よりも明らかに高く, 切除様式による発音機能の差異が明らかであった。前方型の切除を行った症例の術後の発音障害を防ぐためには, 手術法の改善が必要であり補綴物の応用が有用であることが示唆された。

In this study we investigated the clinicoanatomic basis of the scapular flap by morphometric examinations of 42 cadavers. Our findings were as follows: With common-trunk type scapular vessels, the maximal lengths of arteries and veins that could be used for a flap pedicle were 93 and 91 mm. With direct-type scapular vessels, the maximal lengths were 95 and 71 mm. In common-trunk type vessels, the mean internal diameter 2 mm distal from the confluence of the scapular vessel was 2.8 mm for arteries and 3.3 mm for veins. In the direct-type vessels, the mean internal diameter 2 mm distal from the confluence of the circumflex scapular vessel was 1.8 mm for arteries and 3.3 mm for veins. The maximal superoinferit>r dimension of the scapular graft was 28 mm. The maximal lateral dimension of the scapular graft was 12 mm.

より多くの口腔癌術後患者の咀嚼機能を, より高度に回復させるための指針を得るため, 多数例の口腔癌術後患者の現在の咀嚼機能を多角的に評価するとともに, 患者の機能回復に対する関心度について検討を行った。対象は当科外来を受診している口腔癌術後患者53名 (男性23名,女性30名, 41歳～85歳, 平均61.1歳) である。咀嚼機能の主観的評価には山本の咬度表を用い, 客観的評価には低粘着性発色ガムおよびオクルーザルプレスケールを用いた。機能回復の関心度については現在の機能の満足度, 今後の治療の要求度についてアンケートを行った。その結果, 機能評価値は低いが, これ以上の治療を望まない患者がみられ, 口腔癌術後患者全体の咀嚼機能を高めるためには, 機能回復のための治療に対する患者の意識を高めることの重要性が示唆された。

In order to three-dimensionally evaluate the morphologic charcteristics of the maxilla in patients with jaw deformities, the accuracy of measurement on three-dimensional images on CT (3-D CT) scans as well as the appropriate CT values for the depiction of the morphologic characteristics of the maxilla were examined. As for the accuracy of measurement of three-dimensional images on CT scans, the difference between the mean value of the measured length and that of the image was 1.5 mm at maximum and 0.4 mm on average.In addition, no difference was observed in the accuracy of measurements on images taken from the coronal and horizontal directions.The results suggest that the measurement of distance on three-dimensional images is relatively accurate and efficient for measuring the morphologic characteristics of the maxilla.

In order to undertake a quantitative evaluation of balance occlusal load, the use of the Dental Prescale System was investigated. The method uses a test sheet that undergoes a colour-developing chemical reaction, for detecting contact area, and a computerized analysis system, for evaluating the balance of occlusal load. Twenty natural dentate subjects and 10 hemimaxillectomy patients participated in the study. Each subject bit a test sheet as hard as possible for 3 s. The balance of occlusal load was expressed as a percentage of the load on the side with the lesser occlusive load (%OLR). The %OLR ranged from 39.7% to 49.4% in the natural dentate subjects, and from 0% to 31.3% in the hemimaxillectomy patients at their resection site. The patients' low %OLRs were attributed to loss of sustaining structure and subjective occlusal adjustment by clinicians. Combining technical simplicity, relatively high reproducibility, and diverse analysis capability, this system is useful for quantitative evaluation of balance of occlusal load in clinical situations.

a Purpose This study determined the level of masticatory function that can be achieved with osseointegrated implants in postoperative tumor patients. Patients and Methods Masticatory function was evaluated in 15 postoperative tumor patients with implants, 22 nontumor patients with implants, and 15 natural dentate controls. The area of occlusal contact was evaluated with a pressure-sensitive, color-developing bite sheet analyzed by computer. Chewing performance was evaluated by a low-adhesive, color-developing, chewing-gum system. Results Subjects in the tumor group had load-bearing tooth contacts similar to those of the natural dentate controls and nontumor implant patients. Continuity of the mandible was essential to sustain occlusal load. The presence of the hypoglossal nerve was the main factor in determining restoration of chewing performance. Conclusions Surgical efforts to preserve the mobility of the residual tongue and prosthetic approaches to restore impaired mobility to as great an extent as possible are especially important for better functional rehabilitation of patients who have defects of the hypoglossal nerve.

Purpose: Patterns of healing were investigated in mandibles reconstructed with three different techniques to assess their readiness for implant placement. Patients and Methods: The subjects were 10 patients who had undergone mandibular reconstruction with either nonvascularized iliac block bone grafts (group 1; 3 patients), particulate cancellous bone and marrow (PCBM) grafts (group 2; 3 patients) for mandibular discontinuity, or PCBM grafts for mandibular marginal defects (group 3; 4 patients). Six (groups 2 and 3) or 12 months (group 1) after mandibular reconstruction, bone biopsy specimens were obtained for histologic examination with a trephine bur. As controls, bone specimens were obtained from ungrafted mandibles of patients undergoing dental implant placement. Undecalcified specimens were embedded in polyester resin and examined by routine light microscopy and microradiography. Results: The morphology of the specimens from group 1 was similar to that of group 2, but not to that of the control subjects. However, the morphology of specimens from group 3 was generally similar to that of control subjects. Conclusion: These results suggest that mandibular reconstruction with PCBM grafts allows the placement of dental implants sooner than reconstruction with block bone grafts.

本研究では当科の上顎切除症例にインプラント義歯を応用した経験について述べた。本研究にはアパタイトプラズマスプレーチタン人工歯根, あるいはアパタイトフレームスプレーチタン人工歯根を使用した。さらにインプラント義歯による咀嚼機能ならびに構音機能について検討し, その結果, デンタルプレスケール, 発色ガムの測定結果は健常者よりも低い値を示したが, 山本の咬度では, 4～6であり, 咀嚼機能の回復を示す結果であった。インプラント義歯の応用により構音機能の回復が得られた。これらのことより, インプラント義歯は上顎切除症例の咀嚼および構音機能の回復に有用であると考えられた。

本研究では当科の腫瘍術後症例におけるインプラント義歯による咀嚼機能ならびに構音機能の回復, 再建について検討した。その結果, 代表症例の構音機能では, インプラント義歯の応用により構音機能の回復が得られた。咀嚼機能の結果では, 代表症例の山本の咬度は3～6であり, 咀嚼機能の回復が認められた。デンタルプレスケールの測定結果では, 口腔腫瘍患者群は健常群より低い数値を示したが, 一般患者とほぼ同等の数値を示した。発色ガム法の結果では, 口腔腫瘍患者群は健常者, 一般患者群よりも低い値を示した。これらのことはインプラント義歯が咀嚼および構音機能の回復に有用であることを強く示唆するものと考えられた。

Sodium glucose co-transporter 1 (SGLT1) plays a dominant role in the absorption of glucose in the gut and is considered a promising target in the development of treatments for postprandial hyperglycemia. A series of 4-benzyl-1H-pyrazol-3-yl β- d -glucopyranoside derivatives have been synthesized, and its inhibitory activity toward SGLTs has been evaluated. By altering the substitution groups at the 5-position of the pyrazole ring, and every position of the phenyl ring, we studied the structure–activity relationship (SAR) profiles and identified a series of potent and selective SGLT1 inhibitors. Representative derivatives showed a dose-dependent suppressing effect on the escalation of blood glucose levels in oral mixed carbohydrate tolerance tests (OCTT) in streptozotocin–nicotinamide-induced diabetic rats (NA-STZ rats).

The purpose of this study was to histomorphometrically evaluate the use of hydroxylapatite (HA) implants in 60Co-irradiated bone. HA implants were installed in rabbit mandibles 3 months, 6 months, and 12 months after 15-Gy irradiation. Nonirradiated rabbits served as controls. The rabbits were killed 7, 14, 30, 60, and 90 days after the HA implantation. The histologic features of the healing process were examined and histomorphometric measurements were made to quantify the percentage of HA-bone contact and trabecular bone in the medullary cavity. In the irradiated groups, although HA-bone contact was observed later than that in the controls, recovery increased with time after irradiation and the rate of HA-bone contact bone-contacting implant surface ratio; BCSR exceeded 90% in all groups examined before 90 days. In the radiated groups, the average trabecular bone-specific volume was lower than that in the controls and began to decrease before BCSR exceeded 90%. Based on the present data, as well as data from the literature, it is suggested that the success rate of HA implants in irradiated bone increases with the interval after radiotherapy. It is also recommended that HA implants in irradiated bone be installed so that bearing by the cortical bone is increased.

腸骨の Particulate cancellous bone and marrow (PCBM) は生存する細胞成分が豊富で骨新生が早いこと, 下顎骨再建の際の加工性が高いことなどの長所を有している。このため当科ではPCBMを応用した腸骨の再構成法による下顎再建法を行っている。最近では, さらに下顎再建例に人工歯根を応用し, インプラント義歯による口腔機能の回復を図っている。人工歯根を併用した腸骨再構成法による下顎再建法は有用な方法と思われるので, 当科の経験を基礎的検討とともに報告した。

Surgical and prosthetic treatments for speech disorders attributable to surgically acquired soft palate defects were investigated. Ten patients who had undergone soft palate resection for extensive cancer served as the subjects. In four patients, the resected portion of the soft palate was confined to the anterior or middle segments, with an intact posterior band, whereas in the remaining six patients the resected portion extended into the posterior edge. An obturator with or without a speech appliance was adapted to all patients in the former group and to one patient in the latter group. The remaining five patients in the latter group underwent surgical reconstruction using a free radial forearm flap immediately after resection of the soft palate. The speech of each patient was evaluated either before and after surgery in those treated only surgically or with and without the obturator in the other patients using a standard intelligibility test of 100 Japanese syllables. These tests showed that two of the four patients with a posterior band of soft palate remaining postsurgically achieved excellent restoration of speech and improvement of velopharyngeal function following placement of a special prosthesis. The patients who had resection extending into the posterior edge of the soft palate obtained better restoration of speech and function from surgical reconstruction rather than prosthetic management. All three patients who had surgical reconstruction, in whom the special obturator was applied achieved a slight increase in speech intelligibility scores resulting from the improvement of velopharyngeal function. These results suggest that surgical reconstruction and prosthetic management may best be applied selectively based on the extent of resection of the soft palate.

The purpose of this study was to investigate the effectiveness of using guided tissue regeneration (GTR) with an absorbable membrane for the preparation of immediate dental implants.Osseous defects were create in the edentulous region of rabbit mandibles. After implanting cylindrical hydroxylapatite (HA). half of the defects were covered with VicrylR woven mesh and the other half were not.The animals were sacrificed 1, 2, 4 and 8 weeks postoperatively.Non-decalcified specimens, 15 pm in thickness, were prepared, stained with toluidine blue and examined histologically.The following results were obtained:1. In the non-covered defects, connective tissue existed between the new bone and the upper half of the HA implant by 8 weeks.2. In the mesh-covered defects, direct bonding between newly formed bone and the HA surface under the mesh, without connective tissue in the upper half, was observed 4 weeks postoperatively.3. Mononuclear and multinuclear cells were observed around the mesh at 1 week. The structure of the mesh became unclear at 4 weeks and the mesh was completely absorbed at 8 weeks. A tendency to cause tissue reactions was not observed. These results indicate that guided tissue regeneration with an absorbable membrane is useful for the preparation of immediate dental implants.

Thc purpose of this study was to compare the tissue response to titanium implants coated with hydroxylapatite by flame spraying (AFC implants) and conventional titanium (Ti) implants. Eight beagle dogs were studied. Three months after the extraction of their premolars, two AFC implants were inserted in one side of the mouth and two Ti implants were inserted in the other. The animals were sacrificed after 2 weeks and 1, 3 and 6 months. Non-decalcified sections, 15 μm in thickness, were made with a cutting-grinding system and stained with toluidinc blue for histological examination.The following results were obtained:1) Direct bone bonding to the AFC surface occurred earlier than direct bone contact to the Ti surface.2) Comparable bone remodelling occurred around both types of implants at 6 months postoperatively.3) Non-cellular solubilization of HA granules and phagocytosis of HA granules by mononuclear and multinuclear cells were detected around the bone-free HA surface. At the apex of sonic AFC implants, the coating layer had disappeared at 6 months postoperatively.4) Mononuclear cells were observed on Ti implants. The number of these cells diminished 3 months after implantation.5) These results suggested that AFC implants had the advantage of earlier stabilization by bone than Ti implants. However, further studies are warranted on reactions to the HA coating during long-term application.

The syntheses of trans- and cis-isomers of dragmacidin C and 3,4-dihydrohamacanthin A, and dragmacidin B have been accomplished by condensation of two indolylglycines followed by cyclization and reduction. The relative stereochemistry of dragmacidin C was confirmed to be cis, which is distinct from that of other dragmacidins.

The purpose of this study was to investigate the effect of aging on the healing process afterinstallation of hydroxylapatite (HA) implant into bone tissue. Three groups of eight male Wistar rats, aging 6 weeks (Young group), 12 weeks (Adult group), and approximately two years (Old group) were used in this experiment. Two implants were installed into the rats tibiae bilaterally. The animals were sacrificed 7, 14, 28, and 56 days after the installation, and 15μm hematoxvlin-eosin stained undecalcified sections were prepared. The healing processes were examined histologically.In the Young group, new trabecular bone was formed actively around the HA implant, and good HA-bone bonding was achieved rapidly compared to the Adult group. In the Old group, both the quantity of newly formed trabecular bone around the implant and the extent of HA-bone bonding were less than in the other groups. These results suggested that the activity of new bone formation after implantation declines with increasing age. Therefore, it is concluded that aging has disadvantages in the achievement of good HA-bone bonding.

This study concerns the histologic examination of apatite-titanium complex dental implants (two-piece, cylindrical type) in dogs. There was no plaque control. One to 3 months after implantation, the surface of the apatite root was directly bound to newly formed, woven bone. Seven-and-a-half months to 1 year after implantation, the apatite root was directly bound to the newly formed lamellar bone, which provided strong bone bonding (apatite-bone bonding). There appear to be two types of mechanisms for the resorption of apatite ceramics: first, cellular-type resorption by both multinuclear and mononuclear macrophages; and second, a noncellular, fluid mechanism (dissolution). The gingival sulcus around implants and downward growth of the epithelial cells could be observed in almost all of the implants. There was no cellular inflammation in the tissue around the implants, in the nasal cavity, or in the maxillary sinus. From this study we concluded that clinical application of this dental implant system would be practical.

In orthognathic surgery (sagittal split ramus osteotomy of the mandible: SSO) there are problems such as postoperative arthrotic symptoms or relapse of the mandibular position. Prevention of such problems may require accurate repositioning of the external (proximal) fragments of the mandibular ramus. Consequently, some techniques for repositioning condyles and external fragments of the mandibular ramus have been reported.However, these techniques are not always successful in exact three-dimensional repositioning, so we devised a system consisting of repositioning and rigid fixation, and have been using these techniques in clinical applications. Our system has the following advantages:1. exact repositioning of external fragments of the mandibular ramus including condyles of the mandible.2. rigid fixation under repositioning.3. exact confirmation of repositioning is relatively easy.We thus concluded that our system is very valuable for SSO and modified techniques.

Objective: To evaluate the long-term prognosis of dental implants placed into cleft sites after bone grafting in a relatively large number of cases in order to clarify the usefulness of the modality. Patients: Forty-seven patients with unilateral (dental, n = 32) or bilateral (n = 15) clefts of the alveolar process were included in this study. Interventions: A total of 71 implants, including smooth- or rough-surface titanium, and hydroxyapatite (HA)-coated implants, were placed after bone grafting from the anterior iliac crest and/or mandible. The placed implants were 13 to 15 mm in length. Main outcome: The follow-up period was from 21 to 120 months (average = 60 months). Implant survival rates were calculated as cumulative survival. Marginal bone loss (MBL) from the implant shoulder was examined, with statistical analyses performed on the influence of simultaneous bone graft and surface characteristics. Results: At the end of the clinical follow-up period, all implants except one were in situ and stable. Thus, the overall survival rate was 98.6% at the end of the first year and remained the same until the end of observation. Titanium implants with smooth surfaces had the lowest MBL with almost negligible regression slope, although some implants had relatively high MBL by the end of the first year. Conclusions: Implant therapy in the cleft site offers a reliable option for patients. Particular attention should be focused preoperatively on whether bone volume can provide primary implant stability.

This study was undertaken to investigate the action of bisphosphonate on bone reactions after the placement of titanium screw implants into the tibiae of ovariectomized rats.Twelve-week-old female Wistar rats were divided into 4 groups of 18 animals each. The first group (Sham) was sham-operated, the second group (OVX) was ovariectomized only, the third group (Estrogen) was ovariectomized and received continuous estrogen with a 17beta-estradiol pellet, and the fourth group (YM-175) was ovariectomized and received bisphosphonate at a dose of 10 microg/kg of body weight. Titanium screw implants were placed in the proximal metaphyses of the tibiae 168 days after surgery. The animals were sacrificed 7, 14, and 56 days after implant placement. Undecalcified sections were prepared and evaluated by light microscopy. Histomorphometric measurements were obtained with a computer-based image analyzer to quantify the unit bone mass around the implant and the rate of implant-bone contact.Ovariectomies significantly reduced implant-bone contact and the bone volume around the implants. However, in the YM-175 group, only slight differences in both bone contact and bone volume were noted compared with the Sham and Estrogen group. The woven structure of new bone in the YM-175 group was also replaced by mature lamellar bone, as in the other groups.These results suggested that bisphosphonate preserved the implant-bone contact and bone volume around the implants.

Recently, microvascular tissue transplantation has come to be generally used for oral and maxillofacial reconstruction. The present status of clinical use of microvascular tissue transplantation for maxillofacial lesions was investigated at 335 oral and maxillofacial surgery centers in Japan. The number of reported was cases 687. Among these, 497 (72.4%) received forearm flap transplantation. A rectus abdominis flap was employed in 104 cases (15.2%). The total survival rate of all transplants was 89.1%

Purpose: This study evaluated the location of the mandibular canal in the ramus of the mandible before bilateral sagittal split ramus osteotomy and examined its relationship with postoperative neurosensory disturbance. Patients and Methods: The subjects consisted of 20 patients undergoing bilateral sagittal split ramus osteotomy. Before surgery, the region from a plane containing the lowest point of the mandibular foramen to 22 mm below it was observed on transaxial computed tomograms acquired with a slice thickness of 2 mm and a slice interval of 2 mm. The relationship between the distance from the mandibular canal to the external cortical bone and neurosensory disturbance in the lower lip or mentum more than 1 year after surgery was evaluated. Results: The mandibular canal came into contact with the external cortical bone on 10 sides (25%); neurosensory disturbance occurred on all these sides, an incidence significantly greater than that (20%) on the 30 sides (75%) without contact between the canal and the external cortical bone (P

To clarify basic clinico-anatomic factors associated with cranio-maxillofacial rehabilitation using implants.Morphometrically evaluated were items such as the length and width of bone and the thickness of cortical bone at important sites for implant placement into cranial and maxillofacial bones in 30 cadavers at autopsy.At sites corresponding to potential placement sites for implants as the fixation source for ocular epitheses, the mean length of bone was 7.8 mm, and the mean width was 8.3 mm.Useful data have been obtained for the selection of the placements sites, direction, length, and external diameter of cranio- and maxillofacial implants.

Purpose: The purpose of this study was to examine the effects of estrogen deficiency on bone remodeling adjacent to implants in the tibia of mature rats. Materials and Methods: Hydroxyapatite-coated implants were placed bilaterally in the proximal metaphysis of the tibia of 18 female Wistar rats (48 weeks old), and ovariectomy was performed 168 days later. As a control, sham ovariectomy was performed in a similar group of 18 rats. Six animals from each group were killed at 28, 84, and 168 days after ovariectomy. Undecalcified sections were prepared, and changes in the bone tissue around the implants were evaluated histologically. Histomorphometric measurements were made with a computer-based image analyzer to quantify the unit bone mass around each implant and the amount of implant-bone contact. Results: In the cortical bone area, ovariectomy induced only a slight decrease in bone contact with the implant, compared with that in the sham-operated rats. However, both the bone volume around the implant and implant-bone contact were significantly decreased in the cancellous bone area in ovariectomized rats compared with the sham-operated rats. Conclusion: Thinning of the bone trabeculae holding dental implants may occur with estrogen deficiency. © 2000 American Association of Oral and Maxillofacial Surgeons