• Title/Summary/Keyword: bone change

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Subacute Toxicities of All-trans-Retinoic Acid Encapsulated in the Poly(D,L-Lactide) Microspheres

  • Choe, Yong-Du;Park, Gyeong-Sun;Kim, Sang-Yun;Kim, Seon-Hui;Byeon, Yeong-Ro
    • 한국생물공학회:학술대회논문집
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    • 2001.11a
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    • pp.867-870
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    • 2001
  • All-trans-retinoic acid (RA) plays essential roles in the regulation of differentiation and proliferation. It has been proved that RA is effective in the treatments of epithelial and hematologic malignancies. However, in spite of its pronounced effects, the clinical applications of RA are limited due to the retinoid acute resistance. Although RA induces complete remission in a high proportion of the patients of acute promyelocytic leukemia (APL), the cancer was relapsed in many patients after a brief remission in spite of a continued RA treatment. Patients who relapsed from remission that was initially induced by RA had clinically resistant to further RA treatment. That is, specific cytochrome P450 enzymes in the liver were induced by the continuous oral administration of RA, thereby accelerating the metabolism of RA. To overcome this problem, biodegradable microspheres were proposed by us, previously. And, several microsphere formulations for RA delivery have been prepared and studied on their effectiveness. Recently, poly(D,L-lactide) (PDLLA) microsphere formulation was optimized, And, from the animal studies by using a mouse and a rat, it have appeared to be effective on both the inhibition of tumor growth and chemoprevention of a carcinogenesis. In this study, subacute toxicities of the PDLLA microsphere formulation have been investigated as a preclinical test. For the test, the microspheres was injected subcutaneously into the back site of rats, and body weight change, clinical signs, hematological changes, blood biochemistry were evaluated. As a result, severe toxicities such as mortality were observed at the dose of 100mg RA/kg, and toxicities were not observed at the dose of 50mg RA/kg, which is the effective dose against carcinogenesis. Bone fracture, observed at several rats, might be inhibited by treating them with anti-inflammatory drugs.

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Splenic Irradiation in Chronic Myeologenous Leukemia (만성골수성백혈병 15예의 비장조사)

  • Oh Yoon Kyeong;Kwon Hyung Chul;Yoon Sei Chul;Bahk Yong Whee;Kim Choon Choo;Kim Dong Jip
    • Radiation Oncology Journal
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    • v.3 no.2
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    • pp.137-144
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    • 1985
  • Radiation therapy was the treatment of choice for CML in the past, in the form of SI or radioactive phosphorus. Its use has been replaced to a large extent by various chemotherapeutic agents. Recently SI in CML has been used, both to relieve painful splenomegaly and to take advantage of an indirect effect of SI on unirradiated bone marrow. We have treated 15 CML cases who had a huge spleen during chemotherapy or even after chemotherapy by 6 MV linear accelerator during the past two years at the Division of Radiation Therapy, Kang Nam St. Mary's Hospital, Catholic College. Response to SI has been rated according to the scoring system of Roger W. Byhardt, et al. which evaluated the splenic and hematologic response as well as the response of disease-related systems. According to this scoring system, most patients demonstrated a significant relief of splenomegaly along with improvement of hemogram. And we observed the change of Karnofsky Performance Status after SI, and survival after a confirmative diagnosis and SI.

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Comparative Study on Surgical and Conservative Management of Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ) in Disease Stage 2 (비스포스포네이트 관련 악골괴사(BRONJ)의 병기 2기에서의 외과적, 보존적 치료에 대한 비교 연구)

  • Lee, Ho Kyung;Seo, Mi Hyun;Pang, Kang Mi;Song, Seung Il;Lee, Jeong Keun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.35 no.5
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    • pp.302-309
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    • 2013
  • Purpose: This study evaluated the prognosis of conservative and surgical treatment according to the staging of bisphosphonate-related osteonecrosis of jaw (BRONJ) by American Association of Oral and Maxillofacial Surgeons and American Society for Bone and Mineral Research. Methods: We evaluated 53 patients of BRONJ who visited Department of Dentistry, Ajou University School of Medicine from May 2007 to February 2013. Twenty eight patients in stage 2, were divided into surgical and conservative groups with cessation of bisphosphonate therapy. Fifteen patients belonged to the conservative treatment group, in which mouth rinsing and antibiotics medication were done. Thirteen patients were treated with debridement or sequestrectomy, in the surgical treatment group. Each study list was analyzed by SPSS ver. 14.0 (SPSS Inc., USA) software and the favorable rate was verified by the Fisher exact test. P-values less than 0.05% were deemed significant. Results: Clinical outcome was evaluated on the basis of both clinical and radiographic findings. Of all the 28 patients of stage 2, 15 patients underwent conservative treatment and 13 patients received surgical treatment. In the surgical group, 9 of 13 (69.2%) showed good prognosis, 4 of 13 (30.7%) showed recurrence. In the conservative group, 13 of 15 (86.6%) showed no change duting the follow-up period. Two of 15 patients even showed a bad prognosis, such as pain and pus discharge, which are criteria for stage 3. P-value was 0.067 (>0.05). Conclusion: The results of the present study suggests that surgical intervention is good choice against the conservative treatment, after proper drug holidays period, while further investigation is needed for a definite solution to BRONJ.

The effect of cortical punching on the expression of OPG, RANK, and RANKL in the periodontal tissue during tooth movement in rats (백서의 치아이동 시 피질골 천공이 치주조직의 OPG, RANK, RANKL의 발현에 미치는 영향)

  • Park, Woo-Kyoung;Kim, Seong-Sik;Park, Soo-Byung;Son, Woo-Sung;Kim, Yong-Deok;Jun, Eun-Sook;Park, Mi-Hwa
    • The korean journal of orthodontics
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    • v.38 no.3
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    • pp.159-174
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    • 2008
  • Objective: The purpose of this study was to investigate whether cortical punching could stimulate the expression of OPG, RANK, and RANKL during tooth movement by immunohistochemistry. Methods: 34 sprague-dawley rats (15 weeks old) were allocated into 3 groups: TMC group (experimental group; Tooth Movement with Corticotomy, n = 16), TM group (control group; Tooth Movement only group, n = 16), and non-treatment group (n = 2). 20 gm of orthodontic force was applied to rat incisors by inserting elastic bands. The duration of force application was 1, 4, 7 and 14 days. A microscrew (diameter 1.2 mm) was used for cortical punching of the palatal side of the upper incisors in the TMC group. Results: Distributions of OPG, RANK, and RANKL were evaluated by immunohistochemistry. OPG, RANK and RANKL were observed on experimental and control groups. On the compression side, the degree of the expression of OPG decreased in both groups. The expression of RANK was most prominent in the experimental group of day 4. The expression of RANKL was most intensive and extensive in the experimental group of day 7. However, the expression of OPG was decreased in the experimental and control groups compared to the non treatment group. The expression of OPG, RANK and RANKL after force application were decreased at day 14. Conclusions: These findings suggested that cortical punching might stimulate remodeling of alveolar bone during a 2 week period of tooth movement without any pathologic change.

Differentiation of Malignant from Benign Soft-Tissue Solid Tumors: Clinical and MR Finding Complex (연조직고형종양의 악성과 양성 감별: 임상과 자기공명영상 복합소견)

  • Moon, Tae-Yong;Kim, Jung-Il;Shin, Su-Mi;Choo, Hye-Jeung;Choi, Hyun-Wook;Kim, Soo-Jin
    • The Journal of the Korean bone and joint tumor society
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    • v.10 no.2
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    • pp.79-87
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    • 2004
  • Purpose: The recent development of MR has made to possible radiological diagnosis in various soft tssue tumors. But multifarious components within soft tissue tumors and their periodic change have made to difficult even differentiation of malignant from benign soft tissue tumors solely on the MR. So authors retry to differentiate malignant from benign soft tissue tumors with clinical and MR finding complex. Materials and methods: We were analysed 82 pathologically confirmed soft tissue solid tumors (37 cases as malignancy including intermediate tumors and 45 cases as benign including inflammatory masses) which are correlated with clinical findings such as age, size, and location, MR findings such as tumor border, texture on T2 and contrast-T1 images, and enhancement area retrospectively. Many typical lipoma and cysts including of ganglion and abscess are rejected in the benign soft tissue tumor group because not difficult to diagnose on MR. Results: Malignant soft tissue tumors were more frequent in 21~40 and 61~80 years old of the age, above 3.0 cm of the size, trunk-pelvis-lower extremities of the location, and MR findings with irregular border and above 50% of the enhancement area than those of benign soft tissue tumors. Conclusion: The clinical finding that divided to two locations as trunk-pelvis-lower extremities and upper extremities-shoulder-spine was statistically significant to differentiate malignant from benign soft tissue solid tumors. However, the others would provide some useful informations to differentiate them never specific.

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Estimation of Natural frequencies in Osteoporotic Mouse Femur: A finite Element Analysis and a Vibration Test (골다공증에 걸린 쥐 대퇴골의 고유진동수 예측: 유한 요소 해석 및 진동 실험)

  • Kim, Yoon-Hyuk;Byun, Chang-Hwan;Oh, Taek-Yul
    • Journal of the Korean Society for Nondestructive Testing
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    • v.25 no.4
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    • pp.239-246
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    • 2005
  • In this study, a finite element analysis and a vibration test were performed to estimate the natural frequencies of mouse femurs with osteoporosis. Three groups of the femurs include the osteoporotic group, the treated group and the normal group. For the finite element analysis, the micro finite element model of the femur was reconstructed using the Micro-CT images and the Voxel mesh generation algorithm. In the vibration test, the natural frequencies were measured by the mobility test. from the results, the averaged natural frequencies in the osteoporotic group were the highest, followed by those in the treated group. The finite element models were validated within 15% errors by comparing the natural frequencies in the finite element analysis with those in the vibration test. The developed Micro-CT system, the Yokel mesh generation algorithm, the presented finite element analysis, and vibration test could be useful for the investigation of the structural change of the bone tissue, and the diagnosis and the treatment in the osteoporosis.

Induction of Apoptosis in Human Osteosarcoma Cell Lines(Saos-2) by Single Fraction High Dose Irradiation (고용량 방사선 조사 후 골육종 세포주(Saos-2)의 아포프토시스 발생)

  • Kim, Jae-Do;Chung, So-Hak;Hong, Young-Gi;Choi, Jang-Seok
    • The Journal of the Korean bone and joint tumor society
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    • v.5 no.1
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    • pp.1-8
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    • 1999
  • A single fraction of 50 Gy extracorporeal irradiation, as a modality of limb-sparing operation, has been used to achieve tumor necrosis in osteosarcoma. Although this modality of radiation therapy preserving the mobility of a joint is commonly practiced, the precise knowledge on the radiobiological response of osteosarcoma cell has remained to be elucidated. We therefore observed whether a single high dose irradiation caused apoptosis in osteosarcoma cells and whether the commitment to apoptosis was associated with cell kinetics. We also investigated radiation dose response along the time course for development of apoptosis following single high dose irradiation. The morphologic change in apoptosis was observed by fluorescence with Hoechst 33258 and the degree and the fraction of cells by flow cytometry. Irradiation of osteosarcoma cells with 10, 30 and 50 Gy resulted in chromatin condensation and apoptotic body formation. The degree of apoptosis in osteosarcoma cells was $29.5{\pm}3.56%$, $39.9{\pm}4.83%$ at 24 and 48 hours after 10 Gy irradiation ; $41.1{\pm}3.93%$, $66.9{\pm}5.21%$ at 24 and 48 hours after 30 Gy irradiation ; and $48.0{\pm}3.69%$, $75.6{\pm}4.65%$ at 24 and 48 hours after 50 Gy irradiation. The fraction of cells in cell-cycle kinetic was $39.2{\pm}4.3%$ in G2/M, $22.1{\pm}4.65%$ in G1 at 24 hours after 10 Gy irradiation ; $51.0{\pm}4.3%$ in G2/M, $20.4{\pm}4.7%$ in G1 at 48 hours after 10 Gy irradiation ; $40.3{\pm}3.9%$ in G2/M, $26.1{\pm}4.7%$ in G1 at 24 hours after 30 Gy irradiation ; $59.2{\pm}3.9%$ in G2/M, $5.9{\pm}5.1%$ in G1 at 48 hours after 30 Gy irradiation ; and $44.3{\pm}4.2%$ in G2/M, $21.1{\pm}3.5%$ in G1 at 24 hours after 50 Gy irradiation. The fraction of cells at 48 hours after 50 Gy irradiation could not be observed because of irradiation induced cell death of most of cells. All values for irradiated cells showed accumulation in G2/M phase and reduction in G1 phase, irrespective of irradiation dose. The results suggest that a single fraction of high dose irradiation with 50 Gy results in accumulation of cells at G2/M phase, leading to apoptosis.

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The Alignment and Deformity of the Upper Extremity in Hereditary Multiple Exostoses (유전성 다발성 외골종 환자에서 상지 변형)

  • Chung, Young-Woo;Park, Gi-Heon;Park, Hyeong-Won;Jung, Sung-Taek
    • The Journal of the Korean bone and joint tumor society
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    • v.17 no.1
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    • pp.11-16
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    • 2011
  • Purpose: This study was aimed to analyze the incidence and the anatomical distributions of HME (Hereditary Multiple Exostoses) on upper limbs and its related change in alignment of the upper limbs in HME patients. Materials and Methods: Thirty eight patients who had been diagnosed HME between 2001 and 2009, were categorized into two groups; (1) group A (1-2 involvements); (2) group B (${\geq}$3 involvements). We checked the carrying angle, VAS (Visual Analogue Scale), limitations in daily activities, cosmetic satisfaction according to the number of exostoses invasion. Results: Among the 38 patients, 23 patients (43 cases) had exostoses in the upper limbs. The locations of exostoses in the upper limbs were proximal humerus in 33 cases (30%), distal ulna in 31 cases (28.2%), and distal radius in 24 cases (21.8%). The carrying angle of group A and B was $10.7^{\circ}$, $13.8^{\circ}$, VAS was 1.3, 3.5, and the limitations in daily activities was 7.3, 6.6 of 8 points. The cosmetic satisfactory cases were 13 and 10 cases, respectively. Conclusion: The deformity in upper limbs was observed in 65% of the HME patients. As the number of invasion increases, carrying angle and VAS were increased but limitations in daily activities and cosmetic satisfaction were decreased.

The Vegetation Structure of Beomseom Islet, Jeju-do (제주도 범섬의 식생구조)

  • Kim Chan-Soo;Song Gwan-Pil;Moon Myong-Ok;Kang Young-Jae;Byun Gwang-Ok;Kim Moon-Hong
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.7 no.3
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    • pp.201-210
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    • 2005
  • This study was conducted to prepare efficient and systematic measures for nature conservation and management in Beomseom Islet, and to provide for basic data to investigate the process of vegetation change in the future. The vegetation of Beomseom Islet was classified to six vegetation type; i.e., Miscanthus sinensis community, Pinus thunbergii community, Iythophyte vegetation, evergreen broad leaf community, shrub community, and Pseudosasa japonica community. The size of each vegetation type was 40,230 $m^2$ ($23.3\%$) for shrub community, 39,366 $m^2$($22.8\%$) for Iythophyte vegetation, 30,012 $m^2$ ($17.4\%$) fur Pinus thunbergii community, 29,853 $m^2$ ($17.3\%$) for Miscanthus sinensis community, 5,564 $m^2$ ($3.2\%$) for evergreen broad leaf community, and 3,325 $m^2$ ($1.9\%$) for Pseudosasa japonica community. The area of non-vegetated sea cliff Bone that composed of bare rocks is 24,246 $m^2$($14.1\%$). We estimated that these distribution patterns of vegetation were the result of various environmental factors such as the steepness of slope and shallowness of soil as well as the cultivation of exotic plants causing disruption of native vegetation.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

  • Lee, JooBuom;Lee, Kyungsun;Choe, Keunbum;Jung, Hyunseob;Cho, Hyunseok;Choi, Kiseok;Kim, Taegon;Kim, Seojin;Lee, Hyeong-Seok;Cha, Mi-Jin;Song, Si-Whan;Lee, Chul Kyu;Chun, Gie-Taek
    • 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.