Kwon Hyeok Choon

학위논문(박사)--아주대학교 일반대학원 :의학과,2009. 2I. INTRODUCTION 1 II. MATERIALS AND METHODS 2 A. Study Subjects 2 B. Blood Tests 2 C. Detection of YMDD and ADV Mutation by RFMP Analysis 2 D. Detection of YMDD and ADV Mutation by Sequencing Analysis 3 E. Statistical Analysis 4 III. RESULTS 5 A. Baseline Characteristics of Patients 5 B. Reversion from YMDD Mutants to Wild-type HBV 6 C. Association between Reversion of YMDD Mutations and Development of ADV Mutation 8 D. Effect of Reverted Wild-type HBV (rt204M) on Virological and Biochemical Response 9 IV. DISCUSSION 11 V. CONCLUSION 14 REFERENCES 15 국문요약 18MasterThe levels of hepatitis B virus (HBV) DNA have been reported to be a predominant viral risk factor associated with increased rates of cirrhosis and hepatocellular carcinoma. Lamivudine (LAM) is the first nucleoside analogue approved for the treatment of Chronic hepatitis B (CHB) with good potency, safety profile and low cost. However, it frequently results in marked drug resistance, which has been reported to occur up to 67% by 4 years of therapy. Adefovir dipivoxil (ADV) has been applied for the LAM-resistant patients, and it has shown to be effective against both wild-type and LAM-resistant forms of HBV. A pilot study in patients with LAM resistance showed no differences in HBV DNA suppression and serum alanine aminotransferase (ALT) normalization between patients treated with the combination of LAM and ADV and those receiving ADV alone. A recent study showed that switching to ADV in patients with LAM-resistant HBV was associated with higher risk of ADV-resistance compared with ADV and LAM combination therapy. This study was undertaken to evaluate the effect of reversion to YMDD wild-type on emergence of adefovir (ADV)-resistant mutation and antiviral activity of ADV in lamivudine (LAM)- resistant patients during ADV monotherapy. We determined YMDD mutations and ADV-resistant mutations before and every 3 months during ADV monotherapy in 33 LAM-resistant patients using RFMP method. Reversion to pure YMDD wild-type HBV occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV-resistant mutations at 48 weeks of therapy. ADV-resistant mutants emerged in all patients after reversion to YMDD wild-type HBV. The mean serum hepatitis B virus (HBV) reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wild-type HBV (-3.1 log10 copies/mL vs -3.4 log10 copies/mL, p>0.05). In conclusion, ADV-resistant mutations emerged after reversion to YMDD wild-type in LAM resistant patients who received ADV monotherapy. Thus, ADV add-on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance

THE EFFECT OF IRIDOID COMPOUND ON THE REMAINING PULP TISSUE AFTER PULPOTOMY

Aucubin, an iridoid glucoside, which is isolated form Aucuba japonica, has some biological effects. This study was to investigate the effect of aucubin on the remainig pulp tissues after pulpotomy. Mongrel dog's coronal pulps were mechanically exposed with a sterile round bur and excised with sterile sharp excarvator. After bleeding was controlled, in control group, Ca(OH)_2 powder was applied on the remaining pulps and the cavities were sealed with Z.O.E cement. In experimental group 1, mixed powder with Ca(OH)_2 and aucubin(1:1 by weight) was applied on the pulotomized pulp surfaces. After th cavities were covered with sterile aluminum foil, they were sealed with Z.O.E. cement. In experimental group 2, only aucubin powder was applied on the remaining pulps and then they were treated the same as experimental group 1. In the all groups, the pulps were histopathologically observed by light microscope at the time intervals of 1, 2 and 4 weeks after experiment. The results were as follows: 1. In control and experimental groups, mild vascular congestion and bleeding were found in most of the specimens. Less inflammatory infiltration was observed in experimental groups than in control group. 2. Dentin bridge formation was found after 1 week at both control and experimental group 1. Dentin birdge had discontinuous osteodentin like appearance of contained some dentin chips. In experimental group 2, dentin bridge was not seen. 3. The coagulation necrosis layer on the remaining pulp tissues was seen in all groups. In experimental group 2, the thickest layer was observed. And in control group, coagulation necrosis layer was similar as in experimental group 1

구치부 광중합 복합레진 수복시 여러 광조사 방법에 따른 미세변연누출에 관한 연구

목적 - 최근 복합레진의 미세변연누출을 줄이기 위한 새로운 광중합 조사방법이 연구되고 있다. 또한 구치용 복합레진이 개발되면서 그 제조회사에서는 5mm 깊이까지 광중합이 가능하다고 소개하고 있다. 본 연구에서는 논리적 가설에 근거한 몇가지 광중합 조사방법이 구치부 class II 와동의 복합레진 충전시 미세변연누출에 어떠한 영향을 미치는지를 관찰하였다. 재료 및 방법 - 100개의 우식증이 없는 사람의 상하악 대구치를 사용했다. 각 치아에 교합-치은방향으로 4mm, 협설 4mm, 깊이 2mm의 class II 와동을 형성하여 인접치와 함께 베이스플레이트 왁스에 매몰하고 구치용 복합레진인 Surefil을 제조 회사의 지시대로 충전하였다. 이때 5가지의 광조사방법을 이용하여 5개의 군으로 나누어 중합하였다(Table 1). 수복된 치아들을 5와 55의 수조에서 번갈아 1분씩 총 500회의 온도변화를 주어 thermocycling을 실시한 후 근첨을 폐쇄하고 수복와동의 치은경계를 제외한 전 표면에 nail varnish를 2회 도포하였다. 2%의 methylene blue용액에 24시간 침적시키고 흐르는 물에 세척한 후 시편을 투명한 에폭시 레진에 매몰하였다. 매몰된 시편을 치아 장축에 평행하게 절단 연마하였다. 입체 현미경으로 미세변연누출을 관찰하고 Kruskal-Wallis One Way ANOVA 와 Dunn's Method로 통계처리 하였다. 결과 - 1. 미세누출은 1군, 4군과 5군, 2군 3군 순으로 증가였다. 이때 1군, 4군과 5군은 통계적 유의성이 없었다(P>0.05). 2. 2군의 경우 1군, 4군, 5군에 비교하여 유의성 있게 미세누출이 많았으며(P<0.05) 3군에 비하여 유의성 있게 적게 나타났다(P<0.05). 3. 3군의 경우 다른 방법들에 비교하여 통계적으로 유의성 있게 미세누출이 많았다(P<0.05)

THE EFFECT OF VISCOSITY, SPECIMEN GEOMETRY AND ADHESION ON THE LINEAR POLYMERIZATION SHRINKAGE MEASUREMENT OF LIGHT CURED COMPOSITES

The aim of study was to investigate the effect of flow, specimen geometry and adhesion on the measurement of linear polymerization shrinkage of light cured composite resins using linear shrinkage measuring device. Four commercially available composites - an anterior posterior hybrid composite Z100, a posterior packable composite P60 and two flowable composites, Filtek flow and Tetric flow-were studied. The linear polymerization shrinkage of composites was determined using 'bonded disc method' and 'non-bond-ed' free shrinkage method at varying C-factor in the range of 1∼8 by changing specimen geometry. These measured linear shrinkage values were compared with free volumetric shrinkage values. The viscosity and flow of composites were determined and compared by measuring the dropping speed of metal rod under constant load. In non-bonded method, the linear shrinkage approximated one third of true volumetric shrink-age by isotropic contraction. However, in bonded disc method, as the bonded surface increased the linear shrinkage increased up to volumetric shrinkage value by anisotropic contraction. The linear shrinkage value increased with increasing C-factor and approximated true volumetric shrinkage and reached plateau at about C-factor 5∼6. The more flow the composite was, reduced linear shrinkage was measured by compensation radial flow.서울대학교병원 집중육성연구

RHEOLOGIC STUDY ON THE VISCOELASTIC PROPERTIES OF FLOWABLE AND CONDENSABLE RESIN COMPOSITES

The purpose of this investigation was to observe the viscoelastic properties of five commercial flowable(Aeliteflo, Flow it, Revolution, Tetric flow, Compoglass flow) , three conventional hybrid(Z-100,Z-250,P-60) and two condensable(Synergy compact, SureFil) resin composites. A dynamic oscillatory shear test was done to evaluate the storage shear' modulus (G' ) , loss shear modulus(G") , loss tangent(tan ) and complex viscosity(* ) of the resin composites as a function of frequency dynamic frequency sweep test from 0.01 to 100 rad/s at 25 - by using Advanced Rheometric Exparusion SystemtARES) . To investigate the effect On the viscosity of resin composites of filler volume fraction, the filler weight % and volume % were measured by means of Archimedes' principle using a pyknometer. The results were as follows 1.The complex viscosity * of flowable resins was lower than that of hybrid resins and significant differences were observed between brands. The complex viscosity * of condensable resins was higher than that of hybrid resins. The order of complex viscosity * at = 10 rad/s was as follows. Surefil, Synergy compact, P-60, Z-250, Z-100. Aeliteflo, Tetric flow, Compoglass flow, Flow it, Revolution. The relative complex viscosity of flowable resins compared to Z-100 was 0.04-0.56 but Surefil was 30.4 times higher than that of Z-100. 2.The storage shear modulus G' and the loss shear modulus G" of flowable resins were lower than those of hybrid resins but those of condensable resins were higher. The patterns of the change of loss tangent, tan of resin composites with increasing frequency were significantly different between brands.The phase angles,, ranged from 30.2-78.1at = 10 rad/s. 3.A11 composite resins represent pseudoplastic nature with increasing shear rate. 4.The complex shear modulus G* and the phase angle was represented by the frequency domain phaser form, G*( )= G* eI = G* . The locus Of frequency domain phaser plots in a complex plane was a valuable method that represent the viscoelastic properties of composite resins. 5.There was no direct linear correlationship but a weak positive relation was observed between filler volume % or weight % and the viscosity of the resin composites.보건복지부 보건의료기술연구개발

MICROLEAKAGE AND SHEAR BOND STRENGTH OF FLOWABLE COMPOSITE RESIN

Flowable composite resin has lower filler content, increased flow, and lower modules of elasticity. It is suggested that flowable composite resin can be bonded to the tooth structure intimately and absorb or dissipate the stress. Therefore, it may be advantageous to use flowable composite resin for the base material of class II restoration and for the class V restoraton. The purpose of this study was to evaluate the microleakage and shear bond strength of four flowable composite resins (Aeliteflo, Flow-It, Revolution, Ultraseal XT Plus) compared to Z100 using Scotchbond Multi Purpose dentin bonding system. To evaluate the microleakage, notch-shaped class V cavities were prepared on buccal and lingual surfaces of 80 extracted human premolars and molars on cementum margin. The teeth were randomly divided into non-thermocycling group (group 1) and thermocycling group (group 2) of 40 teeth each. The experimental teeth of each group were randomly divided onto five subgroups of eight samples (sixteen surfaces). The Scotchbond Multi-Purpose and composite resin were applied for each group following the manufacturer's instructions. the teeth of group 2 were thermocycled five hundred times between 5 and 55. The teeth of group 2 were placed in 2% methylene blue dye for 24 hours, then rinsed with tab water. The specimens were embedded in clear resin, and sectioned longitudinally with a diamond saw. The dye penetration on each of the specimen were observed with a stereomicioscope at 20 magnification. To evaluate the shear bond strength, 60 teeth were divided into five groups of twelve teeth each. The experimental teeth were ground horizontally below the dentinoenamel junction, so that no enamel remained. After applying Scotchbond Multi-Purpose on the dentin surface, composite resin was applied in the shape of cylinder. The cylinder was 4mm in diameter and 2mm in thickness. Shear bond strength was measured using Instron with a cross-head speed of 0.5mm/min. After shear bond strength measurement, mode of failure was evaluated with a stereomicroscope at 30 magnification. All data were statistically analyzed by One Way ANOVA and Student-Newman-Keuls method. The correlation between microleakage and shear bond strength was analyzed by linear regression. The results of this study were as follows ; 1. In non-thermocycling group, the leakage value of Z100 was significantly lower than those of flowable composite resins at the enamel and dentin margin, margin, except that Revolution showed the lower leakage value than that of Z100 at the dentin margin (p<0.05). 2. In thermocycling group, the leakage values of Z100 and Ultraseal XT Plus were lower than those of other subgroup at the enamel and dentin margin, except that Flow-It showed the lower leakage value than that of Ultraseal XT Plus at the dentin margin (p<0.05). 3. The leakage value of Z100 and Ultraseal XT Plus in thermocycling group were not higher than that in non-thermocycling group at the enamel margin. The leakage value of Z100 in thermocycling group was not higher than that in non-thermocycling group at the dentin margin (p<0.05). 4. As for the shear bond strength measurement, there were no statistically significant differences among groups (p<0.05). The shear bond strengths given in descending order were as follows: Z100(16.812.98 MPa), Flow-It(14.84.43 MPa), Aeliteflo(14.343.69 MPa), Revolution(13.464.23 MPa), Ultraseal XT Plus(12.833.16 MPa). 5. Failure modes of all specimens were adhesive failures. 6. There was no correlation between microleakage and shear bond strength

strengthFILLER함량이 BONDING AGENT의 전단접착강도에 미치는 영향

목적 : 최근 개발된 bonding agent 중 일부는 다양한 함량의 filler를 포함하고 있으며 filler의 첨가는 bonding agent의 기계적인 물성을 향상시킴으로써 접착력의 향상에 기여한다는 주장이 있다. 본 연구에서는 다양한 함량의 filler를 포함한 adhesive를 실험적으로 만들어, filler의 함량이 전단접착강도에 미치는 영향을 살펴보고 임상적으로 가장 적절한 filler의 함량을 알아보고자 하였다. 또 adhesive의 간접인장강도를 측정하여 adhesive의 기계적인 물성과 접착력과의 상관관계를 알아보았다. 방법 : 발거된 건전한 70개의 대구치를 투명 레진에 매몰하고 상아질면을 노출시켰다. 3M사의 Scotchbond Multipurpose의 etchant와 primer를 제조사의 지시대로 적용하고 1크기의 barium glass filler를 0, 5, 10, 15, 20, 30, 45wt% 포함하도록 실험적으로 제작한 adhesive를 도포한 후 레진을 충전하여 시편을 완성하였다. Instron으로 0.5mm/min의 속도에서 전단접착강도를 측정하고 그 단면을 입체현미경으로 관찰하여 파절의 양상을 확인하였다. Filler함량에 따른 adhesive의 후경을 측정하기 위해 상기한 방법으로 시편을 제작하여 주사 전자현미경으로 관찰한 후 Sigmascan을 이용하여 그 후경을 측정하였다. 또, 지름 4mm 높이 6mm의 원통형 시편을 제작하여 Instron로 간접인장강도의 측정을 시행하였다. 얻어진 결과는 Kruskal-Wallis test와 Mann-Whitney test를 시행하여 분석하였으며, 상관관계를 분석을 위해 Pearson Product Moment Correlation Coefficient를 구하였다. 결과 : 1) Filler함유량에 따라 전단접착강도는 유의할 만한 차이를 보였다(p0.05), 30% 이상에서는 유의할 만한 감소를 보였다(p<0.05). 4) Adhesive의 후경은 0% 수준에서 5.971.23부터 45%수준에서 73.3711.7까지 유의하게 증가하였다(p<0.05). 5) Filler함량에 따른 Adhesive의 간접인장강도와 전단접착강도는 상관관계가 없었다.보건복지부 보건의료기술 연구개발사

AGING EFFECT ON THE MICROTENSILE BOND STRENGTH OF SELF-ETCHING ADHESIVES

자가부식 상아질 접착제의 중합 후 시간 경과에 따른 접착강도의 변화를 관찰하고, 중합률의 영향을 평가하고자 하였다. 36개의 상하악 대구치를 Single Bond (SB, 3M ESPE, USA), Clearfil SE Bond (SE, Kuraray, Japan), Xeno-III (XIII, Dentsply, Germany), 및 Adper Prompt (AP, 3M ESPE, USA)를 적용하는 4군으로 나누고, 이를 다시 미세인장접착강도 측정 시점에 따라 22C의 증류수에 보관 후 48시간에 측정한 군과 7일 후 측정한 군, 및 접착된 시편을 5000회 열순환을 시행하고 측정한 군으로 나누었다. 모래시계 형태의 접착시편을 제작하여 만능시험기 (Model 4466; Instron Co., USA)로 1 mm/min의 하중속도 하에서 미세인장접착강도를 측정하였다. 접착제의 중합률은 Fourier 변환 적외선 분광법을 이용하여 중합 직후, 48시간, 1주일에 측정하였으며, 주사전자현미경을 이용하여 파절 단면을 관찰하였다. 미세인장접착강도와 중합률 모두 시간의 경과에 따라 유의한 증가를 보였으며, 시간 경과와 재료간에 교호작용이 있었다 (미세인장접착강도, 2-way ANOVA, p = 0.018; 중합률, Repeated Measures ANOVA, p < 0.001) . XIII와 AP의 낮은 미세인장접착강도는 낮은 중합률 때문임을 확인할 수 있었다. 48시간 이후에 SE와 AP에서 접착강도가 증가 되는 것은 중합률과는 관련이 없고, 전자현미경에서 관찰되는 접착제층의 성숙에 따른 취성의 증가가 원인일 가능성이 제기된다. In this study, the changes in the degree of conversion (DC) and the microtensile bond strength (MTBS) of self-etching adhesives to dentin was investigated according to the time after curing. The MTBS of Single Bond (SB, 3M ESPE, USA), Clearfil SE Bond (SE, Kuraray, Japan), Xeno-III (XIII, Dentsply, Germany), and Adper Prompt (AP, 3M ESPE, USA) were measured at 48h, at 1 week and after thermocycling for 5,000 cycles between 5C and 55C. The DC of the adhesives were measured immediately, at 48h and at 7 days after curing using a Fourier Transform Infra-red Spectrometer. The fractured surfaces were also evaluated with scanning electron microscope. The MTBS and DC were significantly increased with time and there was an interaction between the variables of time and material (MTBS, 2-way ANOVA, p = 0.018; DC, Repeated Measures ANOVA, p < 0.001). The low DC was suggested as a cause of the low MTBS of self-etching adhesives, XIII and AP, but the increase in the MTBS of SE and AP after 48h could not be related with the changes in the DC. The microscopic maturation of the adhesive layer might be considered as the cause of increasing bond strength.한국과학재단 지능형생체계면공학연구센