• Toxicological Research
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• v.31 no.4
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• pp.371-392
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• 2015

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.23 no.1
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• pp.87-94
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• 2001

The present study was performed to investigate the effect of $HTR^{(R)}$ (Hard Tissue Replacement) on osteogenesis in the mandibular bone defects. Eight adult male white rabbits weighing 2.5 to 3.0kg were used. Four bone defects (8mm in diameter and 4mm in depth) were made at the both mandibular body. In the control group, the right mesial bone defect was filled with blood clot and spontaneously healed. In the DFDB group, the right distal bone defect was filled with xenogenic demineralized freeze-dried bone. In the $HTR^{(R)}$ group, the left mesial bone defect was filled with $HTR^{(R)}$. In the $HTR^{(R)}-membrane$ group, the left distal bone defect was filled with $HTR^{(R)}$ and covered with BioMesh membrane. The rabbits were sacrified at 2,4,6 and 9 weeks after the operation and microscopic examination was performed. Results obtained were as follows: In the control and DFDB groups, inflammatory cells and the fibrous connective tissue existed and the bone growth was slower than $HTR^{(R)}$ group by 6 week, and there was intervention of the soft tissue at 9 week. In the $HTR^{(R)}$ group, bone trabeculi extended between the $HTR^{(R)}$ particles without intervention of inflammatory cells and the connective tissue at 4 and 6 weeks. In addition, extensive osseous ingrowth into the $HTR^{(R)}$ particles was observed at 9 week. Bone formation was more active in the $HTR^{(R)}$ group than the control and DFDB groups. There was not obvious difference in the bone healing rate between the $HTR^{(R)}$ and the $HTR^{(R)}-membrane$ group. These results suggest that the $HTR^{(R)}$ promotes osteogenesis in the bone defects and the $HTR^{(R)}$ group has no difference in comparison with the $HTR^{(R)}-BioMesh^{(R)}$ membrane group in bone healing.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.38 no.4
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• pp.204-211
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• 2012

Objectives: Dental implants installation in patients with diabetes remains controversial as altered bone healing around implants has been reported. And little is known about the biological factors involved in bone healing around implants. The present study aimed to investigate the biological markers around immediately placed implants in rats with controlled and uncontrolled diabetes. Materials and Methods: Twenty rats (40 sites) were divided into the control, insulin-treated and diabetic groups. The rats received streptozotocin (60 mg/kg) to induce diabetes; animals in the insulin-treated group also received three units of subcutaneous slow-release insulin. Two threaded titanium alloy implant ($1.2{\times}3mm$) were placed in the extraction socket of the both maxillary first molars and allowed for healing. Bone blocks including implant were harvested at 3 days, 1, 2 and 4 weeks. The levels of bone morphogenetic protein (BMP)-4, transforming growth factor (TGF)-${\beta}1$, osteocalcin (OC) and osteonectin (ON) were measured in the peri-implant osseous samples by RT-PCR. Results: The BMP-4 level increased immediately in all groups by day 3, then decreased abruptly in the control and the insulin-treated groups. However, by week 4, all groups showed mostly the same amount of BMP-4 expression. The level of TGF-${\beta}1$ also instantly increased by day 3 in the insulin-treated group. This level elevated again reaching the same values as the control group by week 4, but was not as high as the diabetic group. In addition, the expression of OC and ON in the control and insulin-treated groups was higher than that of the diabetic group at 2 weeks and 4 weeks, indicating active bone formation in these groups. Conclusion: The immediate placement of titanium implants in the maxilla of diabetic rat led to an unwanted bone healing response. Conclusively, the results of this study suggest that immediate implant insertion in patients with poorly controlled diabetes might be contraindicated.

• Journal of Korean Foot and Ankle Society
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• v.6 no.1
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• pp.40-45
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• 2002

Purpose: To analyze the radiographic results between the simple bone excision and simple bone excision and posterior tibial tendon advancement for prehallux. Materials and Methods: Thirty-four patients who underwent operative treatment for prehallux between 1995 and 2000 were reviewed. Twenty-six patients who underwent simple bone excision and posterior tibial tendon advancement and eight patients who underwent simple bone excision were available for follow-up. Follow-up averaged 44 months(15-59 months). We evaluated and compared the cuboidal height and the talo-1st metatarsal angle in the preoperative and postoperative radiography. Results: The average span of disappearing pain is 3.7 months(2-7 months) after the operation. Mean cuboidal height and talo-1st metatarsal angle were increased $6.7{\pm}1.8mm$, $5.0{\pm}2.1^{\circ}$ before to $7.8{\pm}0.2mm$, $5.6{\pm}0.7^{\circ}$ after simple bone excision and posterior tibial tendon advancement. Mean cuboidal height and talo-1st metatarsal angle were increased $6.6{\pm}0.7mm$, $4.6{\pm}1.1^{\circ}$ before to $7.7{\pm}0.9mm$, $5.1{\pm}0.4^{\circ}$ after simple bone excision and posterior tibial tendon advancement. One case of extra-osseous migration of the Mitek anchor inserted into navicula was seen during the follow-up period. Conclusion: This study shows that the remarkable differences between the two procedures are not found. So, simple bone excision without advancement of posterior tibial tendon for prehallux can generate relatively good results.

• Journal of Periodontal and Implant Science
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• v.39 no.sup2
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• pp.287-291
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• 2009

Purpose: The objective of this clinical presentation was to present a clinical case series report of socket preservation, sinus augmentation, and bone grafting using a horse-derived biomaterial. Methods: A horse-derived biomaterial was used in 8 patients for different indications including socket preservation following tooth extraction, osseous bone grafting, and sinus augementation procedures. Surgeries were performed by a well trained specialist and clinical radiographs were obtained at designated intervals. Biopsy cores of 2 ${\times}$ 8 mm prior to implant placement was obtained following a healing interval of 4 - 6 months. A clinical and histologic evaluation was performed to evaluate the clinical effectiveness and biocompatibility of the biomaterial. Results: All surgeries in 8 patients were successful with uneventful healing except for one case with membrane exposure that eventually resulted with a positive outcome. Radiographic display of the healing phase during different intervals showed increased radiopacity of granular nature as the healing time increased. No signs of adverse effect or infection was observed clinically and the tissues surrounding the biomaterial seemed well-tolerated with good intentional healing. The augmented sinuses healed uneventfully suggesting in part, good biocompatibility of the biomaterial. Dental implants placed following socket preservation were inserted with high initial torque suggesting good initial stability and bone quality. Conclusions: Our results show that at least on a tentative level, a horse-derived biomaterial may be used clinically in socket preservation, sinus augmentation, bone grafting techniques with good intentional healing and positive results.

• Journal of Acupuncture Research
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• v.19 no.6
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• pp.221-233
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• 2002

Background and Purpose : MRI(Magnetic Resonance Imaging) has become one of the most sensitive diagnostic tool no evaluate problems of the knee, because it enables us to identify not only osseous tissue but also soft tissues including muscle, fascia, tendon, ligament, meniscus and fat around the knee joint. Objective : To compare between MRI reading and pain, duration, physical examination in patients with pain of knee joint. Methods : 20 patients with pain of knee joint included in this study. This study researched pain-degree, duration, physical examination with pain of knee joint. Using MRI(Horizon Lx 1.0T-GE), we obtained the results. Results : 1. In the distribution of sex; Female rate was 80.0% and male rate was 20.0%. In the distribution of age, above sixty group was the largest group by each 55.0%. 2. In the distribution of MRI reading; 'Meniscus horm tear' was 70.0%, 'Osteoarthritis' was 55.5%, 'ACL partial tear' was 15.0%, 'Bone bruise at tibia, femur' was 15.0%. 3. Correlation between duration of pain and MRI reading showed that acute and subacute stage related various MRI reading, that chronic stage related 'Osteoarthritis' and 'Meniscus horn tear' by each 69.2%, 92.3%. 4. Correlation between pain and MRI reading showed that severe pain(GVI) related 'ACL partial tear, PCL partial tear' by each 100%, that mild pain(GII) related 'Osteoarthritis, Meniscus horn tear' by each 70.0%, 80.0%. 5. Correlation between physical examination and MRI reading showed that Drawer test related ACL partial tear by each 60.0%, that McMurray test related 'Meniscus horn tear' by each 75.0%. 6. Correlation between effect of treatment and MRI reading showed that 'Osteoarthritis, Meniscus horn tear' related good effect, that ACL partial tear related poor effect. Conclusions : These results suggest that acute and sever pain relate 'ACL partial tear, PCL partial tear', that chronic and mild pain related 'Osteoarthritis, Meniscus horn tear'. So it is responsibility to use MRI as a sensitive diagnostic tool in the knee problems.

• Imaging Science in Dentistry
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• v.45 no.1
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• pp.15-22
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• 2015

Purpose: This study was performed to assess the reproducibility of identifying the sella turcica landmark in a three-dimensional (3D) model by using a new sella-specific landmark reference system. Materials and Methods: Thirty-two cone-beam computed tomographic scans (3D Accuitomo$^{(R)}$ 170, J. Morita, Kyoto, Japan) were retrospectively collected. The 3D data were exported into the Digital Imaging and Communications in Medicine standard and then imported into the Maxilim$^{(R)}$ software (Medicim NV, Sint-Niklaas, Belgium) to create 3D surface models. Five observers identified four osseous landmarks in order to create the reference frame and then identified two sella landmarks. The x, y, and z coordinates of each landmark were exported. The observations were repeated after four weeks. Statistical analysis was performed using the multiple paired t-test with Bonferroni correction (intraobserver precision: p<0.005, interobserver precision: p<0.0011). Results: The intraobserver mean precision of all landmarks was <1 mm. Significant differences were found when comparing the intraobserver precision of each observer (p<0.005). For the sella landmarks, the intraobserver mean precision ranged from $0.43{\pm}0.34mm$ to $0.51{\pm}0.46mm$. The intraobserver reproducibility was generally good. The overall interobserver mean precision was <1 mm. Significant differences between each pair of observers for all anatomical landmarks were found (p<0.0011). The interobserver reproducibility of sella landmarks was good, with >50% precision in locating the landmark within 1 mm. Conclusion: A newly developed reference system offers high precision and reproducibility for sella turcica identification in a 3D model without being based on two-dimensional images derived from 3D data.

• Journal of Periodontal and Implant Science
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• v.34 no.1
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• pp.177-193
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• 2004

Several experimental studies showed that the application of small amounts of electric current to bone stimulated osteogenesis at the site of the cathode and suggested that electrical currents promote osseointegration around dental implants. The purpose of this study was to determine the effect of direct microcurrent to endosseous titanium implants placed in bone defects. The right and left 2nd, 3rd and 4th mandibular premolars in ten mongrel dogs (15Kg of weight) were extracted. One monthe later, Ti-machined screw type implants(3.8 mm diameter x 8.5 mm length, $AVANA^{(R)}$, Ostem) were placed in surgically created circumferential defect area(width 5mm, depth 4mm). The implants were divided into three groups according to the treatment modalities: Control group- implants without electrical stimulation; Experimental group I- implants with allogenic demineralized freeze dried bone grafting; and Experimental group II-implants allogenic demineralized freeze dried bone grafting and electric stimulation. The animals were sacrificed in the 4th and 8th week after implant placement and un-decalcified specimens were prepared for histological and histometrical evaluation of bone-implant contact ratio (BIC) and bone formation area ratio (BFA) in defect area. Some specimens at 8 weeks after implantation were used for removal torque testing. Histologically, there was connective tissue infiltration in the coronal part of defect area in control and the experimental group I, whereas direct bone contact was found in the experimental group II without connective tissue invasion. Average BIC ratios at 4 weeks of healing were 60.1% in the experimental group II, 47.4% in the experimental group I and 42.7% in the control. Average BIC ratios at 8 weeks after implantation were 67.6% in the experimental group II, 55.9% in the experimental group I and 54.6% in the control. The average BFA ratio was 84.0% in the experimental group II, 71.8% in the experimental group I and 58.8% in the control at 4 weeks, and the BFA ratios were 89.6% in the experimental group II, 81.4% in the experimental group I and 70.5% in the control at 8 weeks after implantation. The experimental group II showed also significantly greater BIC and BFA ratios compared to the control and the experimental group I (p<0.05). The removal torque values at 8 weeks after implantation were 56 Ncm in the experimental group II, 49 Ncm in the experimental group I and 43 Ncm in the control. There was a statistically significant difference among 3 groups (p<0.05). These results suggest that electrical stimulation improve and accelerate bone healing around endosseous titanium implants in bone defect.

• Applied Microscopy
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• v.31 no.3
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• pp.287-305
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• 2001

To investigate a role of cartilage canals in osteogenesis and growth of the vertebrae, in human fetuses ranging from 50 mm to 260 mm crown rump length were studied by electron microscopy. The initial appearance of cartilage canals of the vertebral body was observed at 60 mm fetus. In 80 mm fetus, primary ossification center in the vertebral body was first noted. The vertebral body showed calcified chondrocytes surrounded by a tone of hypertrophied chondrocytes and deep canals which terminated in calcified matrix. Most hypertrophied chondrocytes in the centrum showed in various stage of degeneration in disorderly arrangement. At the blind end of deep canal, osteogenic cells, osteoblasts and chondroclasts were observed. Resorption of unmineralized cartilage septa was undertaken by perivascular cells within cartilage canals. The ruffled border of the chondroclast was restricted to resorption site of calcified cartilagenous matrix. The periosteal bone formation was followed by the appearance of primary center of the centrum at 120 mm fetus. The osteoblasts of the perichondrium started to lay down a thin membranous bony lamella on the outer surface of the osseous trabeculae of the centrum. The processes of bone formation in the vertebral bodies were found to possess morphological similarities to that occurring at secondary center of the epiphysis of a long bone. These results indicate that the connective tissue cells within the cartilage canals proliferate and differentiate into osteoblasts at the site of endochondral ossification of the vertebrae.

• The Journal of Korean Academy of Prosthodontics
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• v.45 no.1
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• pp.131-143
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• 2007

Statement of the problem: In case of poor bone quality or immediately loaded implant, various strategies have been developed focusing on the surface of materials to improve direct implant fixation to the bone. The microscopic properties of implant surfaces play a major role in the osseous healing of dental implant. Purpose of study: This study was undertaken to evaluate bone response of ion beam-assisted deposition(IBAD) of hydroxyapatite(HA) on the anodized surface of subperiosteal titanium implants. Material and methods: Two half doughnut shape subperiosteal titanium implants were made. The control group was treated with Anodized surface treatment and the test group was treated with IBAD of HA on control surface. Then two implants inserted together into the subperiosteum of the skull of 30 rats and histological response around implant was observed under LM(light microscope) and TEM(transmission electron microscope) on 4th, 6th and 8th week. Results: Many subperiosteal implants were fixed with fibrous connective tissue not with bony tissue because of weak primary stability. The control group observed poor bone response and there was no significant change at any observation time. However the test group showed advanced bone formation and showed direct bone to implant contact under LM on 8th week. The test group observed much rER in the cell of osteoblast but the control group showed little rER under TEM. Conclusions: The test group showed better bone formation than the control group at the condition of weak primary stability. With these results IBAD surface treatment method on Anodized surface, may be good effect at the condition of weak primary stability.