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

두 마리의 면역매개성 혈고판감소증 개에서의 MMF를 이용한 치료

손혜진,박형진,서경원,송근호 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2012 動物醫科學硏究誌 Vol.19 No.1

Two dogs (case 1: 4-years-old female Dachshund, case 2: 1-years-old male maltese) were reffered with petechia. Result of blood analysis and coagulation test reveled immune-mediated thrombocytopenia in all dogs. Treatment with MMF for them, case 1 present steroid-induced hepatopathy, case 2 present anemia, so treated with Human IgG and blood transfusion. 3(case 1) or 2(case 2) months after initial treatment, clinical features were improved, and continuous monitoring is needed.

개에서 피지선 과형성의 진단 및 치료 증례

박희서,손화영,정성목,송근호,조종기,이영원,신상태,김명철,김덕환,박성준 충남대학교 수의과대학 동물의과학연구소 2004 動物醫科學硏究誌 Vol.12 No.-

An eleven year old castrated male Maltese was presented to the Veterinary Medical Teaching Hospital of Chungnam National University. In physical examination, approximately 0.5 cm round mass was observed on tail base. This small elevated mass has also shown alopecic and firm configuration. It was differentially diagnosed as sebaceous adenoma and hyperplasia by fine needle aspiration. After surgical removal, the sample was diagnosed as sebaceous hyperplasia by histopathological examination. It has not yet shown any signs of recurrence and prognosis has teen good.

인슐린 치료중인 당뇨병환자에서 일시적 갑상선 기능 저하 상태로 발생된 양측성 전 경골 구획증후군

이정민,손호영,차봉연,윤건호,조유경,정지성,고승현 대한내과학회 2001 대한내과학회지 Vol.61 No.3

Acute compartment syndrome is usually caused by local vascular and traumatic involvement. Thyroid disease is not a common cause of compartment syndrome and only two cases of spontaneous compartment syndrome associated with hypothyroid myopathy have been reported. Diabetic muscular infarction is a rare microvascular complication usually occured in type 1 diabetes patients under pjoor diabetic control and intramuscular volume expansion caused by muscle necrosis and increased tissue fluid can iduce compartment syndrome.We report a case of atypical bilateral anterior tibial compartment syndrome and foot drop in a 51-year-old patient with type 2 diabetes in hypothyroid state.(Korean J Med 61:307-312, 2001)

개에 있어서 심장사상충증을 동반한 창상성 횡격막 허니아의 수술적 치료 1례

조승혁,임영환,손정민,노경완,박창식,전무형,김명철,송근호,정성목 忠南大學校 獸醫科大學 動物醫科學硏究所 2005 動物醫科學硏究誌 Vol.13 No.-

A 7-month old, castrated male Shih-tzu dog was referred to the Veterinary Medical Teaching Hospital of Chungnam National University with history of depression, dyspnea, mild scale, tachypnea, exercise intolerance and severe leanness. On physical examination, cardiac arrhythmias was heard and heart worm ELISA test was positive. Microfilaria was found on the direct blood smear. Survey radiographs showed loss of diaphragmatic line and cardiac silhouette, displacement of lung fields and presence of gas filled intestines in the thoracic cavity. Rib fracture and pelvic fracture with callus formation were found incidentally. On the basis of physical examination and radiographic findings, it was diagnosed as traumatic diaphragmatic hernia and heart worm disease. Herniorrhaphy was performed. Postoperatively, it was treated for heart worm disease and scale. There is no evidence of recurrence of diaphragmatic hernia and heart worm disease over 1 year.

개에 있어서 심장사상충증을 동반한 창상성 횡격막 허니아의 수술적 치료 1례

조승혁,임영환,손정민,노경완,박창식,전무형,김명철,송근호,정성목 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

A 7-month old. castrated male Shih-tzu dog was referred to the Veterinary Medical Teaching Hospital of Chungnam National University with history of depression. dyspnea. mild scale. tachypnea. exercise intolerance and severe leanness. On physical examination. cardiac arrhythmias was heard and heart worm ELISA test was positive. Microfilaria was found on the direct blood smear. Survey radiographs showed loss of diaphragmatic line and cardiac silhouette. displacement of lung fields and presence of gas filled intestines in the thoracic cavity. Rib fracture and pelvic fracture with callus formation were found incidentally. On the basis of physical examination and radiographic findings. it was diagnosed as traumatic diaphragmatic hernia and heart worm disease. Herniorrhaphy was performed. Postoperatively. it was treated for heart worm disease and scale. There is no evidence of recurrence of diaphragmatic hernia and heart worm disease over 1 year.

어린 브리티쉬 숏헤어 고양이에서 발생한 비대성심근병증

임수정,이선희,손선호,최호정,송근호 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2008 動物醫科學硏究誌 Vol.15 No.1

A l0-month-old, neutered male, British shorthair cat was referred to the Veterinary Medical Teaching Hospital of Chungnam National University with the history of tachypnea, anorexia and depression which onset were two days ago. On physical examination, increased respiratory rate and no murmur were found. A complete blood count indicated thrombocytosis. Results from a serum biochemical profile demonstrated elevations in CK, ALP, BUN and Ca, and decreases in sodium, potassium and chloride. Thoracic radiographs revealed patchy interstitial opacity increase and left atrium enlargement. Echocardiographs showed the evidences of hypertrophic cardiomyopathy which were hypertrophy of diastolic interventricular septum and left ventricular free wall. Other findings on echocardiography were the reverse E:A ratio(tranmitra1 inflow pattern) and absence of systolic anterior motion of mitral valve. Electrocardiographs demonstrated wide P and R wave, which mean left atrium enlargement and left bundle branch block, respectively. Medications including furosemide (2mg/kg), enalapril (0.25mg/kg), and spironolactone (1mg/kg) were prescribed twice a day and orally. Client education about exercise restriction and possibility of aggressive progress was given. Clinical signs suggestive of thromboembolism were developed on 6th day after showing tachypnea; right forelimb lameness, bilateral hindlimb lameness, loss of femoral pulse and severe pain. After all, euthanasia was performed at local animal hospital, according to the owner's request.

Protective Effect of Baicalin Against Carbon Tetrachloride–Induced Acute Hepatic Injury in Mice

Park, Sang-Won,Lee, Chan-Ho,Kim, Yeong Shik,Kang, Sam Sik,Jeon, Su Jin,Son, Kun Ho,Lee, Sun-Mee The Japanese Pharmacological Society 2008 JOURNAL OF PHARMACOLOGICAL SCIENCES Vol.106 No.1

<P>This study examined the effects of baicalin, a bioactive flavonoid isolated from <I>Scutellariae Radix</I>, on carbon tetrachloride (CCl<SUB>4</SUB>)-induced liver injury. Mice were treated intraperitoneally with 0.5 ml/kg CCl<SUB>4</SUB> and different groups of animals received 25, 50, 100, and 200 mg/kg baicalin. At 24 h after the CCl<SUB>4</SUB> treatment, the level of serum aminotransferases and lipid peroxidation was significantly elevated, whereas the hepatic glutathione content was decreased. These changes were attenuated by baicalin. The histological studies showed that baicalin inhibited the portal inflammation, centrizonal necrosis, and Kupffer cell hyperplasia, which are the three most common characteristics of CCl<SUB>4</SUB>-induced liver damage. The serum level and mRNA expression of tumor necrosis factor-α were markedly increased by the CCl<SUB>4</SUB> treatment but suppressed by baicalin. The mRNA and protein expression levels of inducible nitric oxide synthase and heme oxygenase-1 increased significantly at 24 h after the CCl<SUB>4</SUB> treatment. Baicalin attenuated the increase in the protein and gene expression of inducible nitric oxide synthase but augmented the increase in those of heme oxygenase-1. These findings suggest that baicalin protects hepatocytes from the oxidative damage caused by CCl<SUB>4</SUB>, and this protection is likely due to the induction of HO-1 expression and the inhibition of the proinflammatory mediators.</P>

동종골수이식 후 혈당 및 혈중 지질농도의 변화양상 및 관련인자

이원영,강무일,오은숙,오기원,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘주 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.6

연구배경:골수이식은 비교적 젊은 연령의 환자들을 대상으로 하며 면역억제제의 사용기간이 비교적 짧으므로, 주로 고령의 만성 질환 환자에서 시행되는 고형장기이식에서와는 달리 당대사 및 지단백 대사에 있어서 많은 차이점이 있을 것으로 추측된다. 저자들은 전향적 연구를 통하여 골수이식 후 시기별로 혈당 및 혈중지단백 변화 양상을 알아보고 이와 관련된 임상인자들을 규명하고자 하였다. 방법:1998년 10월부터 1999년 8월까지 가톨릭대학교 성모병원에서 동종골수이식을 시행한 환자들 중 43명을 대상으로 이식 전 및 이식 후 1, 2, 3, 4주와 3개월, 6개월에 공복 혈당, 혈중 총 콜레스테롤, 중성지방, 고밀도지단백을 측정하여 골수이식 후 시기별 변화를 관찰하고 여러 임상인자들에 따른 차이를 알아보았다. 결과:1. 공복혈당은 골수이식 수 첫4주 동안 상승하였고 이후 감소하였으나 이식 6개월 시점의 평균 공복혈당은 이식 전보다 유의하게 높게 관찰되었다. 혈중 총 콜레스테롤은 이식 후 1주에 최고치를 형성하였고 이후 기저수준으로 회복되었다가 이식 수 3,6개월에 다시 증가하여 기저치에 비해 유의하게 높았다. 혈중 중성지방은 이식 후 1개월까지 유의하게 증가하였고 이후 감소하여, 3,6개월에는 기저치와 유의한 차이가 관찰되지 않았다. 혈중 고밀도지단백은 이식 후 2,3주에 이식 전보다 유의하게 감소하였고 이후 이식 전 수준으로 회복되었다. 혈중 저밀도지단백은 총 콜레스테롤의 변화와 매우 유사하였다. 2. 골수이식 후 6개월 시점에서 공복 혈당이 126㎎/dL이상인 환자는 7명(16%)이었다. 이들 환자들과 공복혈당 126㎎/dL 미만의 환자 36명을 비교한 결과, 공복혈당이 126㎎/dL 이상인 환자군에서 스테로이드 평균 투여량이 많았고 고밀도지단백이 유의하게 낮았다. 3. 이식편대숙주질환이 발생한 환자는 그렇지 않은 환자보다 이식 후 1, 2, 3주 및 6개월의 총 콜레스테롤이 더 낮았고, 3개월의 공복혈당이 더 높았다. 혈연골수이식 환자군은 비혈연골수이식 환자에 비해 투여된 스테로이드 용량이 더 적음에도 불구하고 이식 후 1, 2, 3주 및 6개월의 총 콜레스테롤 수치가 더 높았다. 스테로이드 고용량 투여군(하루 평균 7.5㎎기준)은 저용량군보다 이식 후 3개월 시점의 공복혈당이 더 높았으나 나머지 시점의 혈당, 혈중 지질농도에 있어서는 유의한 차이가 관찰되지 않았다. 결론:골수이식 후 초기시기에 주로 당 대사 및 지질대사이상이 관찰되며 이는 면역억제제 투여와 관련이 있음을 알 수 있었다. 면역억제제가 고용량 투여되는 합병증 발생 시 이들 대사이상에 관심을 기울여 대처해야 할 것이다. Background: In bone marrow transplantation(BMT), recipients are usually younger and immunosuppressants are open used in shorter period than in solid organ transplantation. Therefore, there might be a difference in glucose and lipid metabolism between BMT and solid organ transplantation. However, the serial changes of metabolic parameters following BMT have not been studied. Therefore, the aim of this study is to investigate the serial changes of blood glucose, lipids and the putative factors that are related with these changes after BMT. Methods: We have prospectively investigated 43 patients who underwent allogeneic BMT. Fasting plasma glucose(FPG), total cholesterol, triglyceride and high-density lipoprotein(HDL) were measured before BMT, and at 1, 2, 3, 4, 12 weeks and 6 months after BMT. The serial changes of these metabolic parameters according to clinical factors including type of BMT, mean daily steroid dosage, and occurrence of graft versus host disease (GVHD) were examined. Results: 1. Mean FPG level increased during 4 weeks after BMT and remained above basal value at post-transplant 6 months. Total Cholesterol level was increased during initial 4 weeks after BMT and was above basal value at post-BMT of 3 and 6 months. Triglyceride level was progressively increased during initial 4 weeks after BMT, but returned to basal value there after. HDL-cholesterol level was significantly decreased during initial 4 weeks after BMT, but returned to basal value there after. 2. Patients with FPG above 126 mg/dL and the other patients, the former received larger amounts of daily steroid and had lower HDL-cholesterol level. 3. The changes of metabolic parameters were different according to type of BMT, steroid dose, and occurrence of GVHD. Conclusion: Although there was increase of FPG, TC, TG and decrease of HDL-C during initial 4 weeks after BMT, these metabolic changes recovered slowly thereafter. Immunosuppressants are thought to be associated with these changes. Further observation will be needed for the long-term effect of BMT on metabolic changes(J Kor Diabetes Asso 24:689~698, 2000).