제2형 당뇨병 동물모델인 OLETF 쥐에서 장기간 라미프릴 투여가 내당능 및 췌도 베타세포에 미치는 효과

고승현,윤건호,김명미,안유배,송기호,유순집,손현식,차봉연,이광우,손호영,강성구 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:최근 소개된 HOPE(Heart Outcomes Prevention Evaluation)study의 결과에 의하면, 심혈관질환이나 이에 대한 위험인자가 1가지 이상인 9,541명을 대상으로 안지오텐신 전환효소 억제제의 일종인 라미프릴을 투여하여 사망율과 뇌졸증, 심부전, 당뇨병 합병증이 개선되었을 뿐 아니라 다른 항고혈압제에 비해 새롭게 당뇨병으로 진단되는 환자가 줄었음을 보고한바 있다. 이에 저자들은 라미프릴(ramipril)을 제2형 당뇨병 동물모델에 장기간 투여함으로써 당뇨병을 예방하거나 고혈당 상태 또는 인슐린 감수성을 개선시킬수 있는지를 알아보고자 하였다. 방법:생후 24주된 체중 400∼450g의 OLETF와 LETO 쥐를 대상으로 6개월간 라미프릴 경구투여 하였고 혈압, 24시간 단백뇨 및 인슐린 내성검사를 시행하였다. 6개월 이후로는 8주간 투여군과 대조군의 체중을 비슷하게 맞추어 내당능 상태를 평가하였고 이후 다시 8주간 고농도 포도당을 투여하였다. 경구당부하검사를 시행한 후 희생시켜 조직표본을 만들어 guinea pig anti­human insulin 항체로 염색후 DAB로 발색하여 point count 법으로 베타세포를 정량하였고, 면역염색으로 췌도의 변화와 섬유화의 정도를 관찰하였다. 결과:라미프릴을 6개월간 투여하였을 때 OLETF 쥐에서 1)체중 증가가 적었으며 2)경구 당부하검사시 포도당하 면적은 의미있게 감소하였고 3)인슐린 내성검사상 Kitt가 증가되는 경향을 보였으며 4)수축기, 이완기 혈압과 24시간 단백뇨양이 의미있게 감소하였고 5)체중을 맞추면 내당능 상태가 비슷해졌다가 고농도 포도당 주입시 다시 포도당하 면적이 대조군에서 더 증가되었다. 라미프릴 투여군에서 췌도변형 및 파괴와 탈과립, 췌도내 섬유화가 감소하였다. 결론:본 실험에서는 인슐린 비의존성 당뇨병 동물 모델인 OLETF 쥐에서 당뇨병 발생 이전 단계부터 장기간 라미프릴을 투여할 경우 체중증가가 적었고, 투여군과 대조군의 체중을 맞추었을 때는 내당능상태의 차이가 없아가 고혈당 투여시 다시 투여군과 대조군에서 의미있는 차이를 보였다. 라미프릴 투여가 베타세포의 기능면에서 이로운 효과를 보일 것으로 생각되었다. 따라서 비만한 환자에서 안지오텐신 전환효소 억제제의 장기투여는 단백뇨 감소, 혈압강하 효과 이외에 체중증가의 억제 및 당뇨병 발생을 억제할 가능성을 시사한다. Background : In a Heart Outcomes Prevention Evaluation HOPE study, ramipril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, significantly reduced the death rates the number of myocardial infarctions, strokes, heart failure as well as the risk of complications related to diabetes and of diabetes itself. However, it is known that ACE inhibitors improve glucose tolerance or insulin sensitivity or reduce the incidence of diabetes. Methods : 24 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 400 ~ 450 g were used in this study. 4 groups of rats were examined in parallel for 40 weeks. The OLETF rats were randomized for treatment with an aqueous solution of ramipril (5 mg/Kg) daily [OL (RMP), n=10)] and with saline [OL (CON), n=10)]. The LETO rats were also randomized in the same was as the OLETF rats (LT(RMP), n=10, LT (CON), n=10). The blood glucose level, body weight, systolic and diastolic blood pressure was assessed every month. At 3 and 6 months, the 24hrs urinary protein concentration was measured, and as insulin tolerance test and oral glucose tolerance test were conducted in all experimental groups. After 6 months, the body·weight was matched for 2 months in each corresponding group. Subsequently, a 15% sucrose loading was done for 2 months. After the glucose tolerance test, the pancreas was excised and immuno histochemical staining was conducted for insulin to quantify the beta cell mass by a point-counting method. In addition, the islet morphology was evaluated in the pancreas. Results : Ramipril treatment for a period of 6 months improved the 2hr blood glucose level, the area under the glucose curve in the oral glucose tolerance test, insulin sensitivity in addition to lowering significantly systolic and diastolic blood pressure and 24hrs urinary protein level significantly in OLETF rats. Of note, a lower weight gain was observed in both the ramipril-treated animals at 6 months. After weight matching, the AUC g and 2hr blood glucose level values were similar between the corresponding groups, but a 15% sucrose loading worsened the AUC g value. Histologically, the islets were less disorganized and the extent of fibrosis was lower in the ramipril-treated OLETF rats in the trichrome stain. Conclusion : Long-term treatment of ramipril, a long acting angiotensin-converting enzyme inhibitor may be useful for suppressing weight gain and proteinuria in addition to having a protective effect on the islet to harmful stimuli such as hyperglycemia (J Kor Diabetes Asso 25:469~482, 2001).

골수이식 후 골밀도 및 골대사의 변화 : 2년 추적관찰 2-Year Prospective Study

이원영,강무일,오은숙,오기원,한제호,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

산 표면처리된 상아질 표층의 교원섬유 용해가 레진-상아질간 결합에 미치는 영향

손호현 大韓齒科保存學會 1995 Restorative Dentistry & Endodontics Vol.20 No.2

상아질-레진 계면의 공초점 현미경적 형태 및 전단결합강도와의 관계

손호현,조병훈,최낙원 大韓齒科保存學會 1999 Restorative Dentistry & Endodontics Vol.24 No.2

Glutaraldehyde계 상아질 과민증 탈감작제에 의한 치수신경 활동성 변화 및 상아세관 폐쇄양상

손호현,이광원,김종화 大韓齒科保存學會 1996 Restorative Dentistry & Endodontics Vol.21 No.2

복합례진 충전시 와연우각 각도변화와 산부식이 변연누출에 미치는 영향

손호현 全北大學校 齒醫學硏究所 1985 전북치대논문집 Vol.3 No.1

This study was performed to evaluate the effect of carvosurface angle and acid-etching on marginal leakage. ClassV cavities were prepared on the cervical 1/3 of buccal and lingual surface of freshly extracted human posterior teeth. 40 posterior teeth were divided into 4 group. A group had butt joint as control, B group were beveled at 30 degree, C group 45 degree, and D group 60 degree. In each group, 5 teeth were acid-etched and were applicated with bonding resin and Clearfil Sc composite resin were inserted. Remaining 5 teeth in each group were not acid-etched and Clearfil Sc composite resin were inserted directely into the cavities. All teeth were thermocycled with usual method and were soaked in 2% aqueous methylene blue for 24 hours at 37℃. All teeth were sectioned mesiodistally through the center of teeth and each segment was sectioned again buccolingually to divide the classV cavity restoration into 3 parts equally. Dye penetration were examined on the sectioned surface. The results were as follows : 1. Carvosurface angle design had no significant effect on the occlusal marginal leakage. 2. Microleakage on the occlusal margin was significantly reduced after acidetching and bonding resin application, and microleakage on the gingival margin was reduced some degree but not so much reduced than occlusal margin. 3. Microleakage on the occlusal margin was less than microleakage on gingival margin regardless of acid-etching and bonding resin application. 4. There is no significant difference between control and experimental group. 5. Other factors such as thickness of remaining enamel may be more important in choosing a design of carvosurface margin for a composite resin restoration.

구치부 충전용 복합레진의 변연누출

손호현 全北大學校 齒醫學硏究所 1983 전북치대논문집 Vol.1 No.1

This study was performed to evaluate the marginal leakage of composite resins using in occlusal cavities. Class l occiusal cavities were prepared on the occlusal surfaces of freshly extracted human posterior teeth. Amalgam, CLEARFIL-Posterior, CLEARFIL-Poste, rior with acid etching and p-10, with acidetching were filled and the teeth with filling materials were dipped in the 4℃ normal saline and in the 60℃ normal saline alternately 10 times for 1 minute each. Then the teeth were soaked in 2℃ aqueous methylene blue for 24hours and were sectioned bucco-lingually through the center of filling materials with diamond disc. Dye penetrations were examined the sectioned surfaces. The results were as follows : 1. The marginal sealing ability of amalgam restoration was a little more effective or nearly identical to that two composite resins with no acid-etching techinique. 2. Between two composite resins, the marginal sealing ability was similar. 3. Resin restoration with acid-etching technique showed greater marginal sealing ability than resin restoration with no acid-etching technique. 4. Amalgam restoration showed more marginal leakage than resin restoration with acid-etching. 5. All filling materials showed some degree of marginal leakage with 2% methylene blue dye.

CAD/CAM으로 제작된 세라믹 인레이의 변연 및 내면 적합성

손호현 大韓齒科保存學會 1998 Restorative Dentistry & Endodontics Vol.23 No.2

曲管덕트 입구 영역에서 遷移定常流動의 速度分布와 壁面剪斷應力分布에 관한 연구

손현철,김명호,박길문 朝鮮大學校 機械技術硏究所 1998 機械技術硏究 Vol.1 No.1

In the present study, the flow characteristics of developing transitional steady flows in a square - sectional 180° curved duct are investigated experimentally. The experimental study for air flow in a square - sectional 180° curved duct is carried out to measure the axial velocity profiles and wall shear stress distributions by using Laser Doppler Velocimeter (LDV) system with data acquisition and processing the system of FIND software at 7 sections from the inlet (ø=0°) to the outlet (ø=180°) in 30° intervals of a curved duct. The results obtained from experimental studies are summarized as follows : (1) The critical Dean number of transitional steady flow is about 450. They show that critical Reynolds number in a curved duct is larger than that in a straight duct. (2) For transitional steady flows, the maximum velocity position of axial velocity profiles begins to incline toward the outer wall from ø=30°bended angle, velocity profiles in center of the duct have lower value than those of the inner and outer walls because of the centrifugal forces. (3) Wall shear stress distributions of transitional steady flows are increased at the entrance region because of increasing shear stress and pressure loss by the influence of flows.

"Clearfil FⅡ" 複合레진에 對한 家犬齒髓의 反應

孫鎬賢 全北大學校 齒醫學硏究所 1984 전북치대논문집 Vol.2 No.1

The biocompatibility of Clearfil FII to the dog's pulp tissue was studied with 60 teeth from 6 dogs. As control materials, zinc-oxide eugenol and silicate cement were used. Class V cavities were prepared and filled with each material. After 3 days, 4, and 8 weeks, the teeth were processed routinly and stained with hematoxylin and eosin. Histopathological tissue changes were observed by light microscope. Following were the results : 1. In the group of zinc-oxide eugenol, slight tissue changes were observed in 4 week cases. In 8 week cases, the pulp tissue was normalized. 2. In the group of unlined silicate cement, the pulp tissue was more severely changed according to the days elapsed. 3. In the group of Clearfil FII, 1 of 10 cases showed moderate pulp tissue change, 6 cases slight change, and 3 cases normal pulp tissue in 4 week cases. In 8 week cases, 2 0f 10 cases showed slight pulp tissue change and the rest showed normal pulp tissue. 4. Clearfil FII was less biocompatible to the pulp tissue than zinc-oxide eugenol, but much more biocompatible than unlined silicate cement.