Kazuhiro Debari

Showa University, Shinagawa, Tōkyō, Japan

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Publications (45)75.57 Total impact

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    ABSTRACT: The purpose of this study was to compare the fatigue and tensile strengths of radicular dentin. Forty bovine lower central incisors were used, twenty teeth for the fatigue test and twenty teeth for the tensile test. Bovine teeth were each sectioned into coronal and radicular portions. Dentin slabs of 1mm thickness were prepared along the radicular tooth using a low-speed cutting machine and trimmed into dumbbell-shaped specimens. A dentin slab was harvested from each tooth. Subsequently, fatigue and tensile tests were performed in Hank's balanced saline solution at 37 °C. The staircase method was employed to determine fatigue strength and its standard deviation. Fracture surfaces were observed by scanning electron microscopy. Mean fatigue strength and tensile strength were 44.3±5.0 and 84.4±8.3 MPa, respectively. The fatigue strength of radicular dentin was significantly lower than the tensile strength. The fatigue strength of radicular dentin was only approximately one half of the tensile strength.
    Journal of Biomechanics 02/2011; 44(4):586-92. DOI:10.1016/j.jbiomech.2010.11.025 · 2.75 Impact Factor
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    ABSTRACT: The main purpose of the present study is to develop a novel nano-emulsion (NE) formulation of alpha-tocopherol (alpha-TC) with enhanced oral bioavailability and pharmacological effects. Three NE formulations of alpha-TC at different loading amounts (10%, 30% and 50%) were prepared by a mechanochemical method. Physicochemical properties of NE formulations were characterized with a focus on the morphology by transmission electron microscopy (TEM), droplet size distribution and zeta-potential by dynamic light scattering (DLS), and long-term stability. According to the TEM images and DLS data, mean diameters of NE droplets ranged from 80 to 400nm, in proportion to the amount of loaded alpha-TC. Although all NE formulations of alpha-TC were found to be negatively charged with the zeta-potential of ca -40mV, NE formulations at alpha-TC content of 30% or higher exhibited severe aggregation of droplets in NE formulations during long-term storage. After oral administration of 10% alpha-TC-loaded NE formulation (30mg alpha-TC/kg) in rats, higher alpha-TC exposure was observed with a 2.6-fold increase of bioavailability as compared to the control mixture of oil and alpha-TC. In streptozotocin-induced diabetic rats, oral administration of the alpha-TC-loaded NE formulation (30mg alpha-TC/kg) exhibited a significant reduction of lipoperoxidant in several organs, especially the liver; however, the control mixture was less effective. With these findings, the NE approach might be efficacious to improve the oral bioavailability and anti-oxidative activities of alpha-TC.
    International Journal of Pharmaceutics 08/2010; 396(1-2):188-93. DOI:10.1016/j.ijpharm.2010.06.017 · 3.65 Impact Factor
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    ABSTRACT: Tranilast (TL) is an anti-allergic agent and widely used in the clinical treatment of bronchial asthma, atopic rhinitis, atopic dermatitis and keloids. However, therapeutic potential of TL could be partly limited because of its poor solubility, bioavailability, and photostability. To overcome these drawbacks, crystalline solid dispersion of TL (CSD/TL) was prepared by wet-milling technique with aim of improving physicochemical and pharmacokinetic properties. Physicochemical properties of the formulations prepared were characterized by laser diffraction and dynamic light scattering for particle size analysis, scanning electron microscope for morphological analysis, and powder X-ray diffraction and differential scanning calorimetry for crystallinity assessment. TL particles in CSD/TL appeared to be crystalline with diameter of 122 nm, and CSD/TL exhibited marked improvement in the dissolution behavior as compared to crystalline TL. Under irradiation of UVA/B (250 W/m(2)), solution and amorphous solid dispersion of TL were found to be highly photodegradable, whereas high photochemical stability was seen in CSD/TL. After oral administration of CSD/TL, enhanced TL exposure was observed with increase of C(max) and AUC by 60- and 32-fold, respectively, as compared to crystalline TL. According to these observations, taken together with dissolution and pharmacokinetic behaviors, crystalline solid dispersion strategy would be efficacious to enhance bioavailability of TL with high photochemical stability.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 02/2010; 39(4):256-62. DOI:10.1016/j.ejps.2009.12.009 · 3.01 Impact Factor
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    ABSTRACT: Glucagon-like peptide-1 (GLP-1), an incretin hormone, is recognized to be potent drug candidate for treatment of diabetes, however its clinical application has been highly limited, because of rapid enzymatic degradation by dipeptidyl-peptidase IV. To protect GLP-1 from enzymatic degradation and improve pharmacological effects, liposomal formulations of GLP-1 were prepared using three types of lyophilized empty liposomes such as anionic, neutral and cationic liposomes. Electron microscopic and dynamic light scattering experiments indicated the uniform size distribution of GLP-1-loaded liposomes with mean diameter of 130-210 nm, and inclusion of GLP-1 did not affect the dispersibility and morphology of each liposome. Of all liposomal formulations tested, anionic liposomal formulation exhibited the highest encapsulation efficiency of GLP-1 (ca. 80%). In intraperitoneal glucose tolerance testing in rats, marked improvement of hypoglycemic effects were observed in anionic liposomal formulation of GLP-1 (100 nmol/kg) with 1.7-fold higher increase of insulin secretion, as compared to GLP-1 solution. In pharmacokinetic studies, intravenous administration of anionic liposomal formulation of GLP-1 (100 nmol/kg) resulted in 3.6-fold higher elevation of serum GLP-1 level as compared to GLP-1 injection. Upon these findings, anionic liposomal formulation of GLP-1 would provide the improved pharmacokinetics and insulinotropic action, possibly leading to efficacious anti-diabetic medication.
    International Journal of Pharmaceutics 09/2009; 382(1-2):111-6. DOI:10.1016/j.ijpharm.2009.08.013 · 3.65 Impact Factor
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    ABSTRACT: This study investigated the hardness and Young's modulus of coronal and radicular intertubular dentin. Ten bovine teeth were each divided into coronal and radicular groups, and the flat surfaces of the coronal and radicular dentin were subsequently processed along the tooth axis. The hardness and Young's modulus of the coronal and radicular intertubular dentin were evaluated using nanoindentation tests, at two locations per tooth. Mean hardness and Young's modulus values were statistically compared by one-way ANOVA and Fisher's PLSD test. The hardness of coronal intertubular dentin was 0.81 +/- 0.05 GPa and that of radicular dentin was 0.55 +/- 0.02 GPa. Additionally, the Young's modulus of coronal intertubular dentin was 26.60 +/- 2.19 GPa and that of radicular dentin was 20.89 +/- 1.10 GPa. Findings of this study revealed that the hardness and Young's modulus of coronal intertubular dentin were greater than those of radicular intertubular dentin.
    Dental Materials Journal 06/2009; 28(3):295-300. DOI:10.4012/dmj.28.295 · 0.94 Impact Factor
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    ABSTRACT: It is known that the fat content of breast milk is higher in hindmilk than in foremilk. However, it has not been determined if this increased fat content results from an increase in the number of milk fat globules (MFGs), an increase in the size of MFGs, or both. This study aims to determine which factor plays the most important role. Thirteen breastfeeding mothers were enrolled in the study and we obtained 52 samples from 26 breasts before (foremilk) and after (hindmilk) a breastfeeding session. The fat content was evaluated by creamatocrit (CrCt) values. MFG size was measured with the laser light scattering method. We compared CrCt values and MFG size between foremilk and hindmilk. Although the CrCt values were higher in the hindmilk (8.6 +/- 3.6%) than in the foremilk (3.7 +/- 1.7%), the MFG size did not change (4.2 +/- 1.0 mum and 4.6 +/- 2.1 mum, foremilk and hindmilk, respectively). There was no relationship between the changes in CrCt versus MFG size from foremilk to hindmilk. The results indicate that the increase in fat content results mainly from the increased number of MFGs, which may be released into the milk flow as the mammary lobe becomes progressively emptied.
    International Breastfeeding Journal 02/2009; 4(1):7. DOI:10.1186/1746-4358-4-7
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    ABSTRACT: We have developed a mouse bone marrow culture system in which multinucleated osteoclast (OC)-like cells are formed within 8 days. Using this culture system, we examined the effect of prostaglandins (PGs), potent bone-resorbing agents, on OC-like cell formation. Four PGs (PGE1 and PGE2 at 10(-8)-10(-5) M, 6-keto-PGF1 alpha at 10(-5) M, and PGF2 alpha at 10(-6)-10(-5) M) significantly stimulated the formation of OC-like cells. The potency of the PGs in inducing OC-like cell formation was the highest in PGE1 and PGE2, followed by PGF2 alpha and 6-keto-PGF1 alpha in that order, and the order was highly correlated with the order of the potency in increasing the production of cyclic adenosine 3',5'-monophosphate (cAMP) in bone marrow cells. Addition of dibutyryl-cAMP also induced OC-like cell formation. Moreover, isobutylmethylxanthine (IBMX), a potent inhibitor of phosphodiesterase, potentiated the OC-like cell formation induced by PGE2, whereas salmon calcitonin greatly inhibited it. Calcitonin induced cAMP production in cultures treated with PGE2, but not in cultures with vehicle. When bone marrow mononuclear cells were cultured on dentine slices in the presence of PGE2, multinucleated OC-like cells were similarly formed and they resorbed calcified dentine, resulting in so-called Howship's lacunae. These results suggest that PGs stimulate resorption of calcified tissues by promoting osteoclast formation. The activity of PGs in inducing OC-like cell formation is considered mediated mainly by a mechanism involving cAMP.
    Journal of Bone and Mineral Research 02/2009; 4(1):29-35. DOI:10.1002/jbmr.5650040106 · 6.59 Impact Factor
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    ABSTRACT: This study investigated chemical components of coronal and radicular dentin using Fourier transform infrared spectroscopy. Five bovine teeth were divided into coronal and radicular portions, and coronal and radicular dentin slabs were prepared horizontally. The area intensities of amide I, amide II, amide III and phosphate of the coronal and radicular dentin were evaluated by Fourier transform infrared spectroscopy at two locations per tooth. The mean area intensities were compared statistically by one-way ANOVA and Fisher's PLSD tests. The amide I area intensity of coronal dentin was 8.67±2.20 and that of radicular dentin was 12.29±2.47. The amide II area intensity of coronal dentin was 0.84±0.25 and that of radicular dentin was 1.94±0.45. The amide III area intensity of coronal dentin was 0.17±0.03 and that of radicular dentin was 0.50±0.10. Additionally, the phosphate area intensity of coronal dentin was 24.45±9.23 and that of radicular dentin was 42.05±3.67. All of the area intensities of coronal dentin were lower than those of radicular dentin.
    01/2009; 29(2):134-138. DOI:10.7881/dentalmedres.29.134
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    ABSTRACT: The fine structure of prostatic calculi has not been elucidated yet, although the chemical components were reported in detail. We studied the primary or endogenous calculi removed from eight human prostates by secondary scanning electron microscopy, backscattered electron imaging, energy-dispersive X-ray microanalysis and X-ray diffraction. The primary calculi containing Mg, Zn and S, besides Ca and P were basically classified into four stone groups (I-IV) by fine structure and mineral components. Stone I had the core deposits of calcospherites showing concentric rings and the laminated deposits concentrically around the core. Their deposits were identified as apatite. Stone II was occupied with the calcospherite deposits of apatite although the stone growth showed a rough concentric formation. Stone III contained the core of calcospherites and concentric laminated structures, similar to a smaller type of group I, whereas the wider peripheral region was deposited with needle-like structures, identified as calcium oxalates. Stone IV had the core deposits containing small hexahedral structures, identified as whitlockite, which were surrounded with several incompletely concentric laminated bands of apatite. Whitlockite crystals were also found between the fused large calculi. The initial and formative calculi were basically observed as the deposition of mineralizing spherical structures suggesting variously sized corpora amylaceous bodies. Thus, the primary prostatic calculi of stones I-III will begin from the mineralization of amylaceous bodies as a core, while the organic substances, which form stone IV, might be derived from the simple precipitation of prostatic secretion.
    Journal of electron microscopy 09/2008; 57(4):133-41. DOI:10.1093/jmicro/dfn013 · 1.63 Impact Factor
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    ABSTRACT: Glucagon, a polypeptide hormone consisting of 29 amino acid residues, tends to form gel-like fibrillar aggregates, and the glucagon fibril, as well as other pathologically related fibrils including prion, amylin, and beta-amyloid, have been found to be cytotoxic through the activation of apoptotic signaling pathways. To understand the aggregation properties of glucagon fibril, we have characterized and compared the physicochemical properties of glucagon, secretin, a member of the glucagon superfamily, and amylin using analytical techniques including capillary electrophoresis (CE), circular dichroism (CD), FT-IR, FT-Raman, transmission electron microscopy (TEM), and beta-sheet-imaging probe. Aging treatment of glucagon resulted in the formation of fibrillar aggregates in time- and concentration-dependent manner, and FT-IR and FT-Raman analyses showed the spectral shift of amide I band, suggesting the conformational changes from alpha-helix to beta-sheet structure. Interestingly, secretin, having high sequential and secondary structural homology with glucagon, did not generate the fibrillar aggregates at the conditions tested. In addition, we evaluated the association state of glucagon at various pHs raging from pH 2.0 to 3.5 using CE. Based on the CE data, the rate constants of glucagon aggregation were calculated to be 0.002 +/- 0.004/h and 0.080 +/- 0.011/h for aging at pH 2.0 and 3.5, respectively, suggesting the pH dependence of self-association. CE showed the potential to separate and detect the glucagon aggregates and intermediates during aging process.
    Journal of Chromatography A 04/2006; 1109(2):167-73. DOI:10.1016/j.chroma.2005.11.130 · 4.26 Impact Factor
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    ABSTRACT: Some therapeutic peptides exhibit amyloidogenic properties that cause insolubility and cytotoxicity against neuronal cells in vitro. Here, we characterize the conformational change in monomeric therapeutic peptide to its fibrillar aggregate in order to prevent amyloidogenic formation during clinical application. Therapeutic peptides including glucagon, porcine secretin, and salmon calcitonin were dissolved in acidic solution at concentrations ranging from 1 mg/ml to 80 mg/ml and then aged at 37 degrees C. Amyloidogenic properties were assessed by circular dichroism (CD), electron microscopy (EM), staining with beta-sheet-specific dyes, and size-exclusion chromatography (SEC). Cytotoxic characteristics were determined concomitantly. By aging at 2.5 mg/ml or higher for 24 h, monomeric glucagon was converted to fibrillar aggregates consisting of a beta-sheet-rich structure with multimeric states of glucagon. Although no aggregation was observed by aging at the clinical concentration of 1 mg/ml for 1 day, 30-day aging resulted in the generation of fibrillar aggregates. The addition of anti-glucagon serum significantly inhibited fibrillar conversion of monomeric glucagon. Glucagon fibrils induced significant cell death and activated an apoptotic enzyme, caspase-3, in PC12 cells and NIH-3T3 cells. Caspase inhibitors attenuated this toxicity in a dose-dependent manner, indicating the involvement of apoptotic signaling pathways in the fibrillar formation of glucagon. On the contrary to glucagon, salmon calcitonin exhibited aggregation at a much higher concentration of 40 mg/ml and secretin showed no aggregation at the concentration as high as 75 mg/ml. These results indicated that glucagon was self-associated by its beta-sheet-rich intermolecular structure during the aging process under concentrated conditions to induce fibrillar aggregates. Glucagon has the same amyloidogenic propensities as pathologically related peptides such as beta-amyloid (Abeta)1-42 and prion protein fragment (PrP)106-126 including conformational change to a beta-sheet-rich structure and cytotoxic effects by activating caspases. These findings suggest that inappropriate preparation and application of therapeutic glucagon may cause undesirable insoluble products and side effects such as amyloidosis in clinical application.
    Pharmaceutical Research 08/2004; 21(7):1274-83. DOI:10.1023/B:PHAM.0000033016.36825.2c · 3.95 Impact Factor
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    Takako Sahara · Kanami Itoh · Kazuhiro Debari · Takahisa Sasaki
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    ABSTRACT: We report the effects of specific and potent inhibitors of vacular-type H(+)-ATPase and lysosomal cysteine proteinases, cathepsins, on the ultrastructure, expression of these enzymes, and resorptive functions of cultured osteoclasts. Osteoclasts were formed by co-culture of marrow cells and calvarial primary osteoblasts of ddY mice. Formed osteoclasts were cultured on dentine slices for 6-48 hr with either an H(+)-ATPase inhibitor, bafilomycin A1, or a cysteine proteinase inhibitor, E-64. In control cultures with no additive, osteoclasts were structurally characterized by the development of ruffled borders and clear zones, and formed many resorption lacunae on dentine slices. Both H(+)-ATPase and cathepsin K were strongly expressed in the ruffled borders of these osteoclasts. In bafilomycin A1-treated cultures, osteoclasts lacked ruffled borders, and resorption lacuna formation was markedly diminished. This effect of bafilomycin A1 on osteoclast structure was reversible by removal of the compound. Bafilomycin A1 treatment altered the subcellular localization and decreased the expression of H(+)-ATPase molecules. H(+)-ATPase expression was observed throughout the cytoplasm, but not along the plasma membranes facing dentine slices. On the other hand, E-64 treatment did not affect the ultrastructure of osteoclasts and the expression of enzyme molecules. Although E-64 showed no effect on demineralization of dentine slices, it dose-dependently reduced resorption lacuna formation. Our results suggest that 1) bafilomycin A1 dose-dependently inhibits resorption lacuna formation via inhibition of ruffled border formation, 2) H(+)-ATPase expression is closely associated with the cytoskeleton of osteoclasts, and 3) E-64 treatment decreases the depth of resorption lacunae, by inhibition of secreted cathepsin K activity, but does not impair ruffled border formation and the associated expression of H(+)-ATPase and cathepsin K in osteoclasts.
    The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology 02/2003; 270(2):152-61. DOI:10.1002/ar.a.10020
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    ABSTRACT: The effects of enamel matrix derivative (EMD; Emdogain) on new trabecular bone induction after pure bioinert titanium (Ti) implantation in the rat femur were examined by means of routine light and transmission electron microscopy, immunohistochemistry, and backscattered electron image analysis. Newly designed mini-Ti implants (3.5 mm in length and 1.6 mm in diameter) were placed in the corticotrabecular area of the femur with either EMD or its carrier, propylene glycol alginate, as control. On post-implantation days 4, 7, 14, and 30, the dissected femur was examined in the transverse direction through Ti implants. In both control and EMD-applied femurs, trabecular bone formation was recognized over the implant surfaces and within medullary cavities even at 4 days post-implantation. These newly formed bone trabeculae around the Ti implants were immunoreactive for bone sialoproteins as a bone matrix marker, and osteoclastic bone resorption became evident in these bone trabeculae after 7 days post-implantation. Although trabecular bone area around the implants was markedly decreased at 30 days post-implantation compared with those at 14 days, the trabecular bone areas in EMD-applied femurs were significantly greater than those in propylene glycol alginate-applied femurs at both 14 and 30 days post-implantation. Our results suggest that EMD is an effective biological matrix for enhancing new trabecular bone induction and resulting attachment of orthopedic prostheses to the recipient bone.
    Journal of Biomedical Materials Research 05/2002; 60(2):269-76. DOI:10.1002/jbm.10064
  • Tetsuo Kodaka · Kazuhiro Debari
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    ABSTRACT: We examined afibrillar cementum (AFC) and cementicle-like structures (CLS) in human teeth by scanning electron microscopy and energy-dispersive X-ray microanalysis. The AFC showed a spur- or island-, plate- and mass-like structure with appositional laminations, while large masses in the enamel fissures enclosed CLS showing concentric appositional rings. Such AFC was observed in enamel fissures, an abnormal enamel pit, dens invaginatus and root furcations with enamel droplets, as well as on the cervical enamel surfaces, where ameloblasts are differentiated at the later or last stage of enamel formation. Cementicle-like structures were occasionally found independent from AFC and some CLS contained epithelial cell-like or ameloblast-like remnants in the core, surrounded by a few or many concentric rings. In addition, cementicles (CEC) in the root furcations also contained the remnants of Malassez's epithelial-rest cells surrounded by a few concentric rings. In some areas, AFC was mixed with enamel structures. These results show that the organic material in some parts of AFC and CLS may be derived from epithelial cells similar to that of CEC. Calcification values of AFC and CLS were significantly higher than that of fibrillar cementum, and the minute crystals are probably apatite.
    Journal of Electron Microscopy 02/2002; 51(5):327-35. DOI:10.1093/jmicro/51.5.327 · 1.63 Impact Factor
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    ABSTRACT: To elucidate the effects of enamel matrix derivative (EMD: Emdogain) on bone regeneration in rat femurs after drill-hole injury, defects in bone were filled with either EMD or its carrier, PGA, as control. On postoperative days 4 to 28, dissected femurs were examined by means of various morphological approaches. In both experimental groups, formation of trabecular bone, which was immunostained for bone sialoproteins (BSP), had occurred in the medullary cavities at cylindrical bone defects on Day 7 postoperatively. Cuboidal osteoblasts were clearly observed on these newly-formed BSP-positive bone trabeculae. On Days 7 and 14, many multinucleated giant cells, which strongly expressed cathepsin K, had appeared on these bone trabeculae, indicating active bone remodeling. In these bone trabeculae, Ca and P weight % and Ca/P ratio were similar to those of cortical bone, and there was no significant difference between the PGA- and EMD-applied groups. Bone volume fraction of newly-formed bone trabeculae on Day 7 postoperatively was significantly higher in the EMD-applied group than in the PGA-applied controls. Because of active bone remodeling and the marked decrease of bone volume, on Days 14 and 28 postoperatively, however, there was no longer a significant difference in trabecular bone volume fraction between the experimental groups. Our results suggest that EMD possesses an osteo-promotive effect on bone and medullary regeneration during wound healing of injured long bones.
    The Anatomical Record 12/2001; 264(4):438-46. DOI:10.1002/ar.10016
  • S Tanaka · M Shimizu · K Debari · R Furuya · T Kawawa · T Sasaki
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    ABSTRACT: Acute effects of ovariectomy on the bone wound healing processes after maxillary molar extraction in aged rats were examined by means of quantitative scanning electron microscopy (SEM), backscattered electron image (BSE) analysis and energy-dispersive X-ray (EDX) microanalysis. Six-month-old female rats underwent either sham operation or bilateral ovariectomy, and 7 days postoperatively, the maxillary first molars were extracted. On post-extraction days 7, 30 and 60, the dissected maxillary bone surfaces were examined by SEM to reveal the bone formative and resorptive areas around the extracted alveolar sockets. In addition, the resin-embedded maxillae were micromilled in the transverse direction through the extracted alveolar sockets, and the newly-formed bone mass on the buccal bone surfaces and within the extracted sockets was examined by BSE analysis. Compared with sham-operated controls, the extent of newly-formed bone mass on the buccal bone surfaces in OVX rats was significantly decreased, due to increased bone resorption. On the other hand, new bone formation within the extracted sockets was similar in the experimental groups. In EDX microanalysis of these newly-formed bone matrices, both Ca and P weight % and Ca/P molar ratio were similar in the experimental groups. Our results suggest that 1) acute estrogen deficiency induced by ovariectomy stimulates sustained bone resorption, but has less effect on bone formation, and 2) bone wound healing after maxillary molar extraction within extracted alveolar sockets is not significantly delayed by ovariectomy, but bony support by newly-formed bone mass on the maxillary bone surfaces at the buccal side of the extracted sockets is significantly decreased, due to increased bone resorption.
    The Anatomical Record 03/2001; 262(2):203-12.
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    ABSTRACT: Acute effects of ovariectomy on the bone wound healing processes after maxillary molar extraction in aged rats were examined by means of quantitative scanning electron microscopy (SEM), backscattered electron image (BSE) analysis and energy-dispersive X-ray (EDX) microanalysis. Six-month-old female rats underwent either sham operation or bilateral ovariectomy, and 7 days postoperatively, the maxillary first molars were extracted. On post-extraction days 7, 30 and 60, the dissected maxillary bone surfaces were examined by SEM to reveal the bone formative and resorptive areas around the extracted alveolar sockets. In addition, the resin-embedded maxillae were micromilled in the transverse direction through the extracted alveolar sockets, and the newly-formed bone mass on the buccal bone surfaces and within the extracted sockets was examined by BSE analysis. Compared with sham-operated controls, the extent of newly-formed bone mass on the buccal bone surfaces in OVX rats was significantly decreased, due to increased bone resorption. On the other hand, new bone formation within the extracted sockets was similar in the experimental groups. In EDX microanalysis of these newly-formed bone matrices, both Ca and P weight % and Ca/P molar ratio were similar in the experimental groups. Our results suggest that 1) acute estrogen deficiency induced by ovariectomy stimulates sustained bone resorption, but has less effect on bone formation, and 2) bone wound healing after maxillary molar extraction within extracted alveolar sockets is not significantly delayed by ovariectomy, but bony support by newly-formed bone mass on the maxillary bone surfaces at the buccal side of the extracted sockets is significantly decreased, due to increased bone resorption. Anat Rec 262:203–212, 2001. © 2001 Wiley-Liss, Inc.
    The Anatomical Record 02/2001; 262(2):203 - 212. DOI:10.1002/1097-0185(20010201)262:2<203::AID-AR1030>3.0.CO;2-#
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    ABSTRACT: We examined the effects of a nonantimicrobial tetracycline analogue, CMT-8, on bone loss and osteoclasts in ovariectomized (OVX) rats. Three-month-old female rats were OVX, and, one week later, distributed into three groups: sham-operated non-OVX controls, untreated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily drug administration (p.o.), the femurs were dissected and examined histologically. Ovariectomy markedly decreased trabecular and cortical bone volume in the metaphyses compared to sham-operated controls. Treating the OVX rats with CMT-8 produced a significant inhibition of trabecular and cortical bone loss and induced new bone formation, in which connectivity of the trabecular struts was increased by bridging the adjacent longitudinal bone trabeculae. Ultrastructurally, CMT-8 reduced ruffled border formation in osteoclasts, while it caused no structural impairment in osteoblasts. To further evaluate the effects of CMT-8 on the resorbing activity of osteoclasts, osteoclasts were cultured on dentine slices pretreated with CMT-8 at concentrations of 2, 10, or 50 micrograms/ml, and resorption lacuna formation on the dentine surface was found to be reduced, dose-dependently, by the bound CMT-8. Our results suggest that CMT-8 therapy effectively inhibits post-ovariectomy bone loss not only by inducing new bone formation, but also by inhibiting osteoclastic bone resorption, and that CMT-8 binding to bone may provide a prolonged release delivery of this anti-resorptive therapy.
    Annals of the New York Academy of Sciences 07/1999; 878(1):347-60. DOI:10.1111/j.1749-6632.1999.tb07694.x · 4.31 Impact Factor
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    ABSTRACT: Postmenopausal oestrogen deficiency results in bone loss (osteoporosis) in humans and experimental animals. The loss of trabecular bone in the ovariectomized (OVX) rat provides a useful experimental model of post-menopausal osteoporosis. At 5 months after ovariectomy of 3-month-old female rats, the mid and distal femurs and maxillae were dissected and processed for quantitative backscattered electron microscopic examinations. Histomorphometric analysis of femurs in OVX rats showed significant loss in metaphyseal trabecular bone areas compared with sham-operated controls; no significant bone loss was observed in the cortical bone areas of mid-diaphyses in OVX rats. Net bone areas in the maxillae of OVX rats was similar to that of sham-operated controls. Bone structure of maxillae in OVX rats was also similar to that in controls. Our results suggest that, in this animal model of osteoporosis, prominent bone loss occurs mainly in the bone areas formed by endochondral ossification such as distal femurs, but those areas formed by intramembranous ossification such as mid-femurs and maxillae sustained less effects by OVX.
    Journal of Electron Microscopy 02/1999; 48(4):465-9. DOI:10.1093/oxfordjournals.jmicro.a023703 · 1.63 Impact Factor
  • Takahisa Sasaki · T W Kim · Kazuhiro Debari · Haruyo Nagamine
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    ABSTRACT: The cellular mechanisms of cartilage-bone replacement in endochondral bone formation, in mandibular condylar heads, are poorly understood. In particular, there is no definitive evidence indicating whether cartilage is resorbed by so-called chondroclasts. Using 3-week-old male beagle dogs, we examined the cartilage-bone replacement processes in mandibular condylar heads by means of light and electron microscopy. Calcification of the cartilage matrix occurred in the central area of the longitudinal septa but not in thin transverse septa. Chondrocytic lacunae were opened by the removal of transverse septa by perivascular rough-surfaced endoplasmic reticulum (RER)-rich mononuclear cells. These cells also phagocytosed calcified cartilage fragments in the surface layer of longitudinal septa. Shortly thereafter, a thin bone layer was deposited on the remaining longitudinal septa by invading osteoblasts. Preosteoclastic multinucleated cells in lacunar canals developed neither ruffled borders nor clear zones in the cartilage matrix, but once the bone layer had been deposited on the remaining cartilage, these structures formed. Our results suggest that the cartilage-bone replacement in mandibular condylar heads involves four sequential processes: 1) degradation of the transverse septal cartilage by RER-rich mononuclear cells, 2) phagocytosis of calcified cartilage fragments in the longitudinal septa by these cells, 3) bone deposition of the remaining longitudinal septa, and 4) degradation of both bone and calcified cartilage by differentiated osteoclasts.
    Journal of Electron Microscopy 07/1996; 45(3):213-22. DOI:10.1093/oxfordjournals.jmicro.a023435 · 1.63 Impact Factor

Publication Stats

642 Citations
75.57 Total Impact Points

Institutions

  • 1984–2011
    • Showa University
      • • School of Dentistry
      • • Department of Oral Anatomy
      Shinagawa, Tōkyō, Japan