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The Inhibitory Effect of Metronidazole and Doxycycline-HCl on proMMP-3 Production in Gingival Fibroblast (치은섬유아세포에서 proMMP-3 생성에 대한 metronidazole과 doxycycline-HCl의 억제효과)

  • Kim, Hak-Joo;Lim, Ki-Jung;Kim, Sang-Mok;Kim, Byung-Ock;Han, Kyung-Yoon
    • Journal of Periodontal and Implant Science
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    • v.30 no.2
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    • pp.335-347
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    • 2000
  • 치주질환의 진행에 따른 치주조직파괴에 있어 치주조직내 다양한 세포외기질성분을 분해하는 matrix metalloproteinase-3(MMP-3)는 염증반응에 관여하는 세포들로부터 분비된 interleukin-$1{\beta}$(IL-$1{\beta}$)에 의해 유도될 수 있다. 이전 연구에서 치주인대세포에서의 MMP-3 생성이 tetracycline 및 tetracycline 유도체에 의하여 억제될 수 있음이 보고되었다. 이 연구의 목적은 metronidazole 및 doxycycline-HCl을 적용한 후 치은섬유아세포에 IL $1{\beta}$를 적용하여 MMP-3의 생성을 유도한 후 이들 약물들이 치은섬유아세포의 MMP-3 생성에 미치는 영향을 조사하기 위한 것이다. 건강한 성인으로부터 치주질환이 이환되지않은 상악 제2대구치 후방의 건강한 치은결합 조직을 절취하여 치은섬유아세포를 배양한 후 다양한 농도의 metronidazole (10-$200{\mu}g/m{\ell}$) 및 doxycyline-HCl(10-$200{\mu}g/m{\ell}$)을 각각 적용하여 1시간 배양하고 proMMP-3의 활성화를 유도하기 위하여 25ng/ml의 IL-$1{\beta}$을 투여한 후 24시간 배양하여 배양된 세포의 상층 배양액을 추출하고 proMMP-3 ELISA kit를 이용하여 비색정량하였다. 비색정량을 통하여 얻어진 자료들은 독립 t-test와 일원분산분석(ANOVA) 및 사후검정으로 Duncan test를 시행하여 다음과 같은 결과를 얻었다. 1. Metronidazole 경우 10-$200{\mu}g/ml$의 모든 농도군에서 proMMP-3의 활성도가 억제되었다(p<0.05). 2. Doxycycline-HCl의 경우 $100{\mu}g/ml$ 이하의 농도군에서는 proMMP-3의 활성도가 억제되었으나(p<0.05), $200{\mu}g/ml$ 농도에서는 proMMP-3의 활성도가 상승되었다(p<0.05). 3. Metronidazole과 doxycycline-HCl의 대조군에 대한 각 실험농도군의 proMMP-3 생성의 감소비율 비교시 모든 농도군에서 metronidazole이 doxycycline-HCl보다 더 높은 감소율을 보였다. 이상과 같은 결과는 metronidazole(10-$200{\mu}g/ml$)이 doxycycline-HCl($100{\mu}g/ml$ 이하) 보다 더 광범위한 혈중농도에서 IL-$1{\beta}$의한 인체치은섬유아세포내 MMP-3의 활성도를 효과적으로 억제할 수 있음을 시사하였다.

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Effects of Direct Cell Contact Between Monocytes and Fibroblasts on the Interleukin-6 Production and Cell Proliferation of Human Gingival and Peri - odontal Ligament Fibroblasts (치은섬유아세포와 치주인대섬유아세포의 interleukin-6 분비 및 세포성장에 미치는 단핵구세포주와 섬유아세포의 세포간 접촉작용)

  • Kim, Soo-Ah;Lee, Ho;Kim, Hyung-Seop;Oh, Kwi-Ok
    • Journal of Periodontal and Implant Science
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    • v.29 no.4
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    • pp.803-823
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    • 1999
  • In order to reveal immunopathogenesis of periodontal tissue destruction, it is important to clarify the molecular mechanism of trafficking and retention of activated leukocytes, including monocytes/macrophages. Gingival fibroblasts may be involved in the regulation of inflammatory cell accumulation in the extravascular periodontal connective tissues via cytokine production and surface expression of adhesion molecules. In this study, it was investigated the molecular basis for the adhesive interactions between monocytes and fibroblasts such as peri-odontal ligament fibroblast(PDLF), human gingival fibroblast(HGF), and human dermal fibroblast(HDF). First, it was examined the evidence whether monocyte-fibroblast cell contact may cause signal transduction in fibroblasts. Being directly in contact with fixed human monocyte cell line THP-1, or U937, upregulation of IL-6 production, $TNF-{\alpha}$ mRNA expression and increased cell proliferation could be seen for fibroblasts. IL-6 production induced by monocyte- fibroblast coculture were further increased when fibroblasts had been pretreated with $IFN-{\gamma}$ or $IL-1{\beta}$ , and monocytes with LPS. Next, it was examined the expression of ICAM-1 which has been known to be involved in accumulation and activation of leukocytes in inflammatory diseases such as periodontitis. ICAM-1 was upregulated up to 10-fold on PDLF, HGF, and HDF by exposure to $IFN-{\gamma}$ or $IL-1{\beta}$. Furthermore, anti-ICAM-1 monoclonal antibody clearly blocked cocultureinduced IL-6 production by fibroblasts, suggesting that $ICAM-1/{\beta}_2$integrin pathway is involved in periodontal fibroblastmonocyte interaction. Overall, these findings provide evidence that periodontal fibroblasts could be involved in the accumulation and retention of monocytes/macrophages in periodontal inflammatory lesion at least in part by ICAM-1 expression. In addition, periodontal fibroblast-monocyte interaction could cause activation signals in fibroblasts intracellularly which result in cytokine production and cell proliferation. Thus, periodontal fibroblasts are speculated to play an important role in immunoregulation and tissue destruction in chronic periodontal diseases by interaction with monocytes/macrophages.

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Inhibiton of MMP-13 mRNA expression by Doxycycline combination with Mefenamic Acid in the rat Periodontal ligament cells (백서 치주인대세포에서 Doxycycline의 Mefenamic Acid 병용사용 시 MMP-13mRNA 발현 억제 효과)

  • Seo, Jin-Hee;Ciu, De-Zhe;Kim, Young-Joon
    • Journal of Periodontal and Implant Science
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    • v.35 no.1
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    • pp.99-109
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    • 2005
  • It has been focused on the importance of the host inflammatory response in periodontal pathogenesis and progression, treatment has been introduced to control the host response and the method, which diminishes production and activity of MMP by doxycycline, has been used in periodontal field. MMP is a proteolytic enzyme which plays a major role in tissue destruction and MMP-1 is secreted in the periodontally healthy tissue, while MMP-8, 9, 13, etc in the inflammatory state. Among these, MMP-13 has been discovered lately and reported to degrade primarily type II collagen. Periodontal ligament (PDL) cell plays a role in destruction of periodontal tissue. This study was to evaluate the effect of doxycycline and mefenamic acid, non-steroidal antiinflammatory drug on MMP-13 mRNA expression in the rat PDL cell. Doxycycline concentration of $1{\sim}100\;{\mu}g/ml$ was added rat PDL cell and cell activity was measured by MIT assay at day 1 and 3. MMP-13 gene expression was evaluated by RT-PCR after PDL cells were pre-treated for 1hour with doxycycline (50 ${\mu}g/ml$) alone or with mefenamic acid ($10^{-6}M$), then added $IL-1{\beta}$(1.0 ng/ml) and incubated for 16-18 hours. The results are as follows: 1. Cell activity decreased Significantly at 24 and 72 hours in 100 ${\mu}g/ml$ (p<0.05). 2. Level of MMP-13 mRNA was in 20.2% increase by $IL-1{\beta}$ and in pre-treating doxycycline group, expression of $IL-1{\beta}$ induced MMP-13 mRNA was inhibited by 31% than $IL-1{\beta}$ treated only. 3. Mefenamic acid did not inhibit on the expression of $IL-1{\beta}$ induced MMP-13 mRNA, while mefenamic acid in combination with doxycycline inhibited the expression by 41% compared to only $IL-1{\beta}$ stimulation. These results suggest that doxycycline synergistically inhibit the expression of $IL-1{\beta}$ induced MMP-13 mRNA in combination with mefenamic acid.

Three-Dimensional Kinematic Model of the Human Knee Joint during Gait

  • Mun, Joung-Hwan;Seichi Takeuchi
    • Journal of Biomedical Engineering Research
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    • v.23 no.3
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    • pp.171-179
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    • 2002
  • It is well known that the geometry of the articular surface plays a major role in the kinematic and kinetic analysis to understand human knee joint function during motion. The functionality of the knee joint cannot be accurately modeled without considering the effects of sliding and lolling motions. We Present a 3-D human knee joint model considering sliding and rotting motion and major ligaments. We employ more realistic articular geometry using two cam profiles obtained from the extrusion of the sagittal Plain view of the representative Computerized Tomography image of the knee joint compared to the previously reported model. Our model shows good agreement with the already reported experimental results on Prediction of the lines of force through the human joint during gait. The contact point between femur and tibia moves toward the Posterior direction as the knee undergoes flexion, reflecting the coupling of anterior and Posterior motion with flexion/extension. The anterior/posterior displacement of the contact Point on the tibia plateau during one gait cycle is about 16 mm. for the lateral condyle and 25 mm. for the medial condyle using the employed model Also. the femur motion on the tibia undergoes lateral/medial movement about 7 mm. and 10 mm. during one gait cycle for the lateral condyle and medial condyle. respectively. The developed computational model maybe Potentially employed to identify the joint degeneration.

The Indication of Ankle Lateral Ligament Reconstruction Using Tendon Graft in Chronic Ankle Instability (만성 족관절 불안정증에서 건이식을 이용한 외측 인대 재건술의 적응증)

  • Park, Jae Yong;Choi, Gi-Won;Cho, Jae-ho;Kang, Chan;Choi, Kyungjin;Chung, Jin-Wha;Kim, Hak Jun;Bae, Su-Young;Cha, Seung-Do;Kim, Ki Chun;Han, Seung Hwan;The Insurance Committee of Korean Foot and Ankle Society
    • Journal of Korean Foot and Ankle Society
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    • v.20 no.1
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    • pp.12-18
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    • 2016
  • Purpose: The purpose of this study is to review the indications of ankle lateral complex reconstruction using tendon graft. Materials and Methods: We searched PubMed using the index, "ankle, instability, lateral ligament, reconstruction" from 1990 to present (September 30, 2015). We excluded 1) modified Brőstrom operation (MBO), 2) conventional tenodesis surgery, 3) review article, 4) technical note, and 5) articles written in another foreign language. We reviewed 24 papers through the publication events, operational method, the indications of surgery, and the specific features of the patient group. Results: There were the indications of 1) previous ligament surgery failure, 2) situation when ligament repair is impossible due to the ligament defect, 3) severe instability (preoperative talar tilt >$15^{\circ}$, anterior draw >10 mm or the difference of contralateral side talar tilt >$5^{\circ}$, anterior draw >3 mm), and 4) overweight (body mass index >$30kg/m^2$). Other considerations included 1) generalized joint laxity and 2) workers, highly-demanded or athlete highly-affected by instability. Conclusion: The ankle lateral complex reconstruction using tendon graft could be indicated in patients with the possibility of MBO failure with several considerations.

Prolotherapy in Orthopedic Field (정형외과 영역에서의 증식치료)

  • Shon, Min Soo;Yoo, Jae Chul
    • The Journal of Korean Orthopaedic Ultrasound Society
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    • v.4 no.2
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    • pp.101-110
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    • 2011
  • To describe the background, mechanism, clinical results and complications of prolotheapy based on the literature review. Prolotherapy is a minimally invasive injection-based treatment of chronic musculoskeletal pain, including ligament and joint laxity. The mechanism of this injection-based technique is to initiate a local inflammatory response with resultant tissue healing. The used proliferants are classified by bio-mechanism to act in three different ways as osmotic, irritants, and chemotatics. The most commonly used proliferant is hyperosmolar (10~25%) dextrose to act by osmotic rupture of cells. High resolution ultrasound imaging of musculoskeletal structure provide a more accurate diagnosis. Also ultrasound-guided intervention provides a more high efficacy and low rate of complications. The most common complication is local pain at the injected site, that is self-limited and good responsive to anti-inflammatory agents. Other complications are rare. It is reported that prolotherapy appears safe when performed by an experienced clinician. Prolotherapy has grown in popularity and has received significant recent attention. However there are limited evidence-based data supporting the indication and efficacy of prolotherapy in the treatment of chronic musculoskeletal pain or soft tissue injuries. Future studies are necessary to determine whether prolotherapy can play an independent and definitive role in a treatment for chronic musculoskeletal pain.

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Characteristics and Trends of Ski Injuries (스키손상의 특징과 경향)

  • Ha, Kee-Young;Kim, Yang-Su;Ryoo, Seung-Joon;Koh, In-Jun
    • Journal of Korean Orthopaedic Sports Medicine
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    • v.2 no.2
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    • pp.153-157
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    • 2003
  • Purpose: To identify injuries and profile the characteristics of injured skiers and to use this information in designing injury-prevention programs and protective equipment. Materials and Methods: Injured skiers treated at a clinic of a ski resort located in Kangwon province in Korea were reviewed from 1998 to 2001. An injury was defined as any accident occurred during alpine skiing that required medical treatment. All injured skiers were asked to fill in a questionnaire which documented the mechanism of injury, their experiences , and the slope where they were injured Results: 1197 patients experienced ski injuries over a three-year-period. The overall incidence of ski injuries was 6.4 injuries per 1000 skiers. There was a slightly higher proportion of men than women and the mean age was in the third decade. The injury rate was higher for beginners and for less difficult slopes . The sprain and ligament injuries were most common and knee injuries accounted for 30$\%$ of all ski injuries . Conclusion: In our study , ski injuries occurred more often compared with foreign reports. it was concluded that an insufficient injury prevention system, an increasing number of skiers and a growing proportion of beginners was responsible for such a result.

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KNEE: Basic Science and Injury of Bone (슬관절 주위 글격의 기초과학 및 스포츠 손상)

  • Kim Hee-Chun
    • Journal of Korean Orthopaedic Sports Medicine
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    • v.2 no.2
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    • pp.77-81
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    • 2003
  • Purpose: The biomechanics and kinematics of knee joint were reviewed in this article. And then the common sports injuries were presented. Anatomy and Kinetics: None of the pairs of bearing surfaces in the knee joint is exactly congruent This allows the knee six degrees of freedom of motion. Tibiofemoral Kinematics: In flexion and extension, the axis of motion is not perpendicular to the medial-lateral plane of the joint, nor is it perpendicular to the axis of longitudinal rotation. This results in coupled varus angulation and internal rotation with flexion and in valgus angulation and external rotation with extension. Patellofemoral Articulation: Loads across the patellofemoral joint are indirectly related to the angle of knee flexion and directly related to the force generated within the quadriceps mechanism. Fractures of the Patella: Nonoperative treatment is indicated if the extensor mechanism is intact and if displacement of fragment is minimal. The specific type of internal fixation depends on the fracture pattern. It is important to repair retinaculum. Acute and Recurrent Patellar Instability: The degree of dysplasia and the extent of the instability play a large part in determining the success of nonoperative treatment. Patients who experience recurrent dislocations and patients with major anatomic variations require surgery to minimize their instability. Sports Injuries in School-age Atheletes: Patellar pain in young athletes groups a number of conditions, including Idiopathic Adolescent Anterior Knee Pain, Osgood- Schlatter Disease, and Sinding-Larsen-Johansson Disease.

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Surgical Treatment for Type 11 Distal Clavicle Fracture using Mersilene tape and K-wire (Mersilene tape와 K-강선을 이용한 제 II형 원위부 쇄골 골절의 수술적 치료)

  • Byun, Jae-Yong;Kim, Bo-Hyun;Kang, Shin-Taek;Whang, Chan-Ha;Hong, Chang-Wha;Lee, Bum-Sung
    • Journal of Korean Orthopaedic Sports Medicine
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    • v.5 no.2
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    • pp.123-128
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    • 2006
  • Purpose: Surgical reconstruction is usually indicated for type II distal clavicle fracture due to high rate of nonunion and delayed union. We report the clinical outcome of a surgical technique for type II distal clavicle fracture using Mersilen tape and K-wire. Materials and Methods: From 1999 through 2003, this technique has been used on 11 patients with type II distal clavicle fracture. The procedure consist of fracture reduction with a Mersilene tape, repair of torn coracoclavicular ligament, and K-wire fixation of the fracture fragment. All patients with at least 12 months of complete postoperative follow-up were included for functional and radiographic evaluation. We used simple X-ray and UCLA scoring system and constant scoring system for evaluation at last follow up in OPD. Results: Solid union of the fracture could be achieved at 11 weeks after operation in all patients. All patients could return to the same level of preinjury activity. Good and excellent results were obtained in all patients according to UCLA system. Conclusion: This technique was simple procedure and allowed for stable fixation with early mobilization and early return to work and sports.

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Recent Trends of the Ski Injuries - An Eleven years Surgery - (스키손상의 특성과 발생양상 - 11년 간 조사보고 -)

  • Yoo Myung Chul;Chung Duke Whan;Cho Yoon Je;Lee Jae Hoon
    • The Academic Congress of Korean Shoulder and Elbow Society
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    • 1995.05a
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    • pp.7-7
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    • 1995
  • 최근에 스키가 동계스포츠로 각광받으면서 스키인구가 폭발적으로 증가함에 따라 스키손상도 많이 발생하게 되어 스키손상은 스포츠외상에서 중요한 비중을 차지하게 되었다. 스키인구의 증가에 따라 스키손상에 대한 정확한 분석과 이에 대한 예방대책이 절실히 요구되며 이에 경희대학교 의과대학 정형외과학 교실에서는 1982년 12월부터 1995년 3월까지( 1986년과 1987년을 제외 ) 11년간 용평스키장내에 동계스포츠클리닉을 개설하여 상기 기간 중 내장한 총 스키인구 3,093,667명중 스키손상으로 동계스포츠클리닉에 내원한 7,172명의 환자$(0.23\%)$에 대하여 스키손상의 년도별 발생빈도, 스키손상의 특징 스키골절과 탈구의 발생빈도 및 특징 등에 대하여 11년 간의 변화추세를 분석하였다. 11년 간의 스키장의 내장객수는 1983년을 기준 (83,100)으로 하였을 때 1995년에 $977\%로 국부 큰 증가를 보였으며, 스키인구 1000명당 손상율은 1983년의 3.4에서 1995년의 1.4(평균 2.3)로 감소하는 추세를 보였다. 스키손상의 형태는 단순열상 및 타박상등을 제외하고 슬관절 인대손상이 $22.6\%로 가장 많이 발생하였으며, 조사기간동안 수치상의 의미 있는 변화는 없었다. 스키골절 및 탈구는 스키인구 1000명당 평균 0.35였으며, 1983년의 0.90으로부터 점차 감소하여 1995년에는 0.21에 이르렀다. 연령별 스키골절 및 탈구는 20세 이하에서 평균 $41.6\%로 전체적으로 성인에서 더 많이 발생하였으며, 이는 처음 3년 간 20세 이하 골절 및 탈구가 $70.5\%로 높은 발생빈도를 보였으나 1995년도의 20세 이하 골절 및 탈구가$30.3\%까지 감소하게되어 년도가 증가함에 따라 청장년 층에 비하여 소아골절 및 탈구가 전체적으로 감소하는 경향을 보였다. 스키골절의 부위별 발생빈도는 1990년 이전까지 하지골절 및 탈구가 많았으나 이후 점차 상지의 골절 탈구가 증가하였다 하지에서 가장 많은 골절은 경골 골절이었으며, 경골골절은 회전력에 의한 나선형골절이 $76.5\%로 가장 많았고 년도에 따른 변화는 보이지 않았다. 스키손상의 발생빈도는 초기에 비하여 점차 감소하는 경향을 보였으며, 손상의 특성도 부위별, 연령별로 다양한 변화를 나타내었다.

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