Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.

흰쥐 난소에서 황체내 큰포식세포에 관한 형태학적 연구 : 면역조직화학적 및 투과전자현미경적 연구

김원식,한승로,조근자,김수일,박창식 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

황체는 임신의 수립과 유지에 필수적인 일시적인 내분비샘으로, 주기능을 발정주기의 생리적 기간을 결정하고 성공적인 임신을 달성하는데 결정적인 프로게스테론의 생산이다. 황체의 기능은 뇌하수체 gonadotropin 뿐만 아니라 황체내 큰포식세포에서 분비되는 TNF-α를 포함한 몇가지 cytokines에 의해 조절되는 것으로 알려져 있다. 본 연구에서는 흰쥐 (Sprague-Dawley계통)에서 생식주기별 황체내 큰포식세포의 변화를 면역조직화학적 및 투과전자현미경적으로 관찰 비교하였다. 본 연구에서 흰쥐 황체에서 큰포식세포는 배란기,임신기 및 출산후기 등 모든 시기에 나타나고,그 수와 면역반응성은 배란기에 가장 컸고 출산후기,임신기 순으로 나타났다. 아울러 투과전자현미경 관찰에서는 황체내 큰포식세포를 세포체가 가늘고 돌기가 긴 비포식성 큰포식세포와 포식성 공포와 지방소체들을 많이 함유한 포식성 콘포식세포로 분류할 수 있었다. 본 연구를 통해 황체내 콘포식세포는 발정주기에 따라 그 수나 면역반응성이 다르며,황체퇴화가 활발히 진행되는 배란기와 출산후기에 면역반응성이 증가하고 포식성 큰식세포들이 나타난 것은 큰포식세포에서 TNF-α 와 같은 cytokines의 분비를 활발히 일으키고 그들이 황체세포들의 세포자멸사를 유발,촉진하고 또한 세포자멸 사소체들을 포식,제거하는 방법으로 황체퇴화를 유도하여 정상적인 발정주기를 유지하기 위한 기전으로 생각 되고,임신기에 큰 포식세포의 수와 면역반응성이 작아지고 비포식성 큰포식세포가 주를 이루는 것은 이들이 TNF-α 동의 cytokines 분비를 통해 그들이 황체자극효과를 나타내 황체의 기능을 유지,촉진하는데만 관여하고,한편으로는 황체에서 생산되는 프로게스테론에 의한 큰포식세포 억제작용 때문인 것으로 생각된다. Macrophages in the corpus luteum have many important roles during the periods of functional development and luteal regression. Not only phagocyte the apoptotic luteal cells, but also they secrete many cytokines and exert their effects via autocrine/paracrine actions. In this study, we investigated the changes of number and immunoreactivity of macrophages at various developmental periods of the corpus luteum in the rat ovary. The rats (Sprague- Dawley strain, female) at age of 8 weeks (ovulatory period), GD 6 (pregnant period), and postpartum 5 days (postpartum period) were sacrificed under ether anesthesia and obtained both ovaries, one used for macrophages immunohistochemistry and the other used for TEM. The results were as follows; I. In the corpora lutea of the rat, macrophages were observed all the developmental periods including ovulatory, pregnant and postpartum periods. 2. In the corpora lutea of the rat, number of macrophages was highest in the ovulatory period, and decreased at postpartum period and pregnant period in order. The immunoreactivity of macrophages was high at ovulatory period, moderate at postpartum period, and low at pregnant period. 3. In TEM observations, two types of macro phages were observed: One type was non-phagocytic macrophage and the other type was phagocytic macrophage. Phagocytic macrophages were observed in the corpora lutea at ovulatory and postpartum periods and contained apoptotic bodies, phagocytic vacuoles and many lipid droplets. Non-phagocytic macrophages were observed in the corpora lutea at pregnancy period and showed slender cell body with long cytoplasmic processes and contained no apoptotic bodies. In the rat, the number and the degree of immunoreactivity of macrophages in the corpus luteum varied with the changes of functional state of the corpus luteum. It was suggested that the main function of the macrophages at the ovulatory and postpartum periods was elimination of apoptotic luteal cells and that at pregnancy period was autocrine/paracrine action. Ultrastructurally, two types, phagocytic and nonphagocytic types, of macrophages confirmed. These results will provide valuable informations on the study of the role macrophages during development and regression of corpus luteum.

Association of Change in Smoking Status and Subsequent Weight Change with Risk of Nonalcoholic Fatty Liver Disease

Jeong Seogsong,Oh Yun Hwan,Choi Seulggie,Chang Jooyoung,Kim Sung Min,Park Sun Jae,Cho Yoosun,Son Joung Sik,Lee Gyeongsil,Park Sang Min 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.1

Background/Aims: Smoking is considered a risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the association of a weight change after a change in smoking status and the risk of NAFLD remains undetermined. Methods: This study used the Korean National Health Insurance Service-National Sample Cohort. Based on the first (2009 to 2010) and second (2011 to 2012) health examination periods, 139,180 adults aged at least 40 years were divided into nonsmoking, smoking cessation, smoking relapse, and sustained smoking groups. NAFLD was operationally defined using the fatty liver index. The adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated using multivariable-adjusted logistic regression. Results: Compared to nonsmoking with no body mass index (BMI) change, the risk of NAFLD was significantly increased among subjects with BMI gain and nonsmoking (aOR, 4.07; 95% CI, 3.77 to 4.39), smoking cessation (aOR, 5.52; 95% CI, 4.12 to 7.40), smoking relapse (aOR, 7.51; 95% CI, 4.81 to 11.72), and sustained smoking (aOR, 6.65; 95% CI, 5.33 to 8.29), whereas the risk of NAFLD was reduced among participants with BMI loss in all smoking status groups. In addition, smoking cessation (aOR, 1.76; 95% CI, 1.35 to 2.29) and sustained smoking (aOR, 1.64; 95% CI, 1.39 to 1.94) were associated with higher risk of NAFLD among participants with no BMI change. The liver enzyme levels were higher among participants with smoking cessation and BMI gain. Conclusions: Monitoring and management of weight change after a change in smoking status may be a promising approach to reducing NAFLD.

The Roles of the Government in Developing "Sport for All Movement" in Korea: From Intervention / Control to Accommodation / Support

( Ju Ho Chang ),( Seong Sik Cho ) 한국스포츠정책과학원(구 한국스포츠개발원) 2000 International Journal of Applied Sports Sciences Vol.12 No.1

This study attempts to figure out the roles of the government in developing ``sport for all movements`` which from intervention/control to accommodation/support. It discusses the relationships between the development of sport for all and the governmental roles in Korea in terms of political, economic and societal changes. It points out that the governmental intervention and control were the basic orientation of sport-policies when the civil sectors of society and local autonomous administration were underdeveloped and the political regime was authoritarian. With the development and democratization of the civil society and politics, however, this study stresses that non-governmental organizations and local autonomous governments tend to take on the responsibility for the sport for movement. With regard to societal changes, the roles of the government should be more toward accommodation and support rather than intervention and control. This study argues that the expansion and growth of civil sectors will increase the diversification, effectiveness, and efficiency of the sport for all movement and that the increase in the functions and roles of the local governments will help to mobilize the local resources and community-based sport for all movement. Finally, it suggests the strong partnership relationships between the civil sectors and the government, and between the local and the national governments based upon mutual trust and cooperation.

Endoscopy and Imaging Modalities/Basic Science of Gastrointestinal Disorders/Miscellaneous : Changing Pattern Of Digestive And Liver Disease In Korea, 1990-2006 Year; A Single Center Study

( Jung Hyun Kwon ),( Sang Woo Kim ),( In Sik Chung ),( Myung Gyu Choi ),( Kwan Woo Nam ),( Jung Pil Suh ),( Jae Hyuck Chang ),( Won Haing Hur ),( Yu Kyung Cho ),( Jae Myung Park ),( In Seok Lee ) 대한소화기학회 2007 SIDDS Vol.9 No.-

Background/Aims: Westernization in many Asian countries have changed lifestyles and diets, so once rare diseases have now become prevalent. The aim of this study is to investigate the changing pattern of digestive and liver disease in Korea, from 1990 to 2006. Methods: We extracted data specific gastrointestina (GI) disease based on the International Classification of Diseases code from the in-patients records at the Kangnam St. Mary`s Hospital in 1990, 1996 and 2006. This hospital is a tertiary-care hospital in Seoul, Korea, which has a capacity of 800 beds. Results: The admission rate for GI disease increased between 1990 and 2006. Overall in-patients were 1,623 persons in 1990, 2,368 persons in 1996 and 4,166 persons in 2006. The mean age of in-patients increased as time went by. A stomach cancer was the most common diagnosis during all periods, but its prevalence has decreased. Colon cancer ranked the 7th in 1990, but markedly increased and now ranks the second. The third was a hepatocellular carcinoma. The bile duct and gallbladder cancer, pancreas and esophageal cancer ranking followed with little interval change. In cases of cancer patients, a regular admission dramatically increased for chemotherapy. The number of patients admitted with pre-malignant neoplasm of stomach and colon increased remarkably with the development of endoscopy. The liver transplant, inflammatory bowel discase, and reflux esophagitis emerged form mid-1990s with greater frequencies, yet much below the levels found in the West. The admission rate for peptic ulcer, especially ulcer bleeding remained relatively stable, despite a decreased rate for ulcer perforation. Liver cirrhosis, hepatitis, cholelithiasis with cholecystitis-cholangitis, appendicitis, hemorrhoid and gastritis all decreased. Conclusions: The stomach cancer is the leading cause of admission, despite a recent decline. Colon cancer showed a marked rise. The liver transplant, inflammatory bowel disease and reflux esophagitis were new diagnosis with an increased tendency.

생체분해성 망막압정을 이용한 망막고정에 대한 실험적 연구

김용백,민병무,김창식,박근성,김승영,길숙종,조항진,이성복,노승무,송규상,강대영,조준식,양준묵,정경수,최선웅,이진호,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

Biodegradable retinal fixation devices obtain mechnical fixation of the retina with desirable chorioretinal scarring and with the potential for local, sustained release of antimetabolites and steroids to inhibit proliferative vitreoretinopathy. We manufactured a biodegradable retinal tack with barb that was designed in order to prevent intrusion from implantation of retinal tacks. This study was carried to evaluate the efficacy for retinal fixation and the capability for sustained release of drugs with a newly designed biodegradable retinal tack Biodegradable retinal tacks were made of polymers of glycolic acids and were designed with barbs in a shape to prevent the disinsertion. Biodegradale retinal tacks are divided into 3 parts, a conical portion that is inserted into the sclera, a cylinder portion that remains in the vitreous, and a neck portion between the pin and the cylinder. The tapered conical end was manufactured to allow easy insertion through the retina and choroid into the sclera. A cylinder portion was manufactured with a tapered angle that fixes firmly into the orifice of 19 gauge spinal needle. A neck portion, 0.4 mm in diameter, was designed to prevent disinsertion from following implantation of retinal tack. The applicator was a 19 gauge spinal needle and its orifice was prepared to 15°angle to accept the tapered cylinder portion of the retinal tack. The retinal tacks, secured in the needles, were passed through the formed vitreous and inserted into the retina, choroid, and sclera and were released by pushing the internal needle, usually within 2-3mm of the medullary ray of the posterior rabbit retina A retinal tack was placed in each of 8 pigmented rabbit eyes. Slit-lamp biomicroscopy, indirect ophthalmoscopy and fundus photography were performed periodically from 1 day to 8 weeks after surgery. Eight eyes were enucleated and studied by light microscopy at 8 weeks. Biomicroscopic evaluation of the animals revealed edemas adjacent to the retinal surfaces immediately after insertion of the biodegradable retinal tacks in all the animals. These edemas disappeared after 1 week. The first noticeable change in the size of retinal tacks was shown after 2weeks. The size of the retinal tacks gradually got smaller, decreasing to about one-half at 4 weeks and about one-third at 8 weeks. All retinal tacks remained in inserted places without any movement for an 8 week period. On light microscopy, epiretinal proliferations were seen to extend into the vitreous cavity. Cellular capsules that lined the inner aspect of the scleral defect caused by tack insertion were found. However the adjacent retina had a normal cytologic appearance and architecture in all specimens. We manufactured a biodegradable retinal tack that is designed to prevent intrusion from implantation of retinal tacks. All biodegradable retinal tacks reduce in size with time, but no retinal tacks extruded from the inserted place. The newly designed biodegradable retinal tack can be used for retinal fixation and may be used as a vehicle for the introduction of pharmacologic agents to prevent the cellular events that promote proliferative vitreoretinopathy.

Menadione에 의해 유발된 간독성에 미치는 홍삼사포닌의 영향

장봉준,배춘식,조용성,차용호,박창원,조대현,장경진,Jang, Bong-jun,Bae, Chun-sik,Cho, Yong-seong,Cha, Yong-ho,Park, Chang-won,Cho, Tae-hyun,Chang, Kyung-jin 대한수의학회 1997 大韓獸醫學會誌 Vol.37 No.3

It is known that 2-methyl-1,4-naphtoquinone(menadione, MD) induces hepatotoxicities both in vivo and in vitro. These toxic effects are believed to result from oxidative damages to hepatocytes by "active oxygen" species via one-electron reduction of the naphtoquinone. The ginsenoside(GS) is a complex mixture of individual ginsenosides which is known to produce a range of effects on the cardiovascular and central nervous systems. In particular, GS has an antioxidant effect. In this experiment we studied the effect of GS from red panax ginseng(red ginseng total saponin, RGTS) on free radical-induced liver injuries by MD. Administration of MD($150{\mu}M$) caused an increase in aspartate aminotransferase(AST) activities and lipid peroxidation, decrease in alkaline phosphatase(ALP) activities and total bilirubin levels in blood, caused depletion of GSH and changes of antioxidant enzyme(superoxide dismutase, catalase) activities are shown in liver tissue. Administration of RGTS restored the AST levels that increased by MD, but catalase showed no significant changes. RGTS also had an effect of restoring the GSH level and had some synergistic effects with SOD. These data suggest that RGTS may have some protective effects on liver injury which is related with the oxygen free radical.

Overexpression of Insulin Degrading Enzyme could Greatly Contribute to Insulin Down-regulation Induced by Short-Term Swimming Exercise

Min Sun Kim,Jun Seo Goo,Ji Eun Kim,So Hee Nam,Sun Il Choi,Hye Ryun Lee,In Sik Hwang,Sun Bo Shim,Seung Wan Jee,Su Hae Lee,Chang Joon Bae,Jung Sik Cho,Jun Yong Cho,Dae Youn Hwang 한국실험동물학회 2011 Laboratory Animal Research Vol.27 No.1

Exercise training is highly correlated with the reduced glucose-stimulated insulin secretion (GSIS), although it enhanced insulin sensitivity, glucose uptake and glucose transporter expression to reduce severity of diabetic symptoms. This study investigated the impact of short-term swimming exercise on insulin regulation in the Goto-Kakizaki (GK) rat as a non-obese model of non-insulin-dependent diabetes mellitus. Wistar (W/S) and GK rats were trained 2 hours daily with the swimming exercise for 4 weeks, and then the changes in the metabolism of insulin and glucose were assessed. Body weight was markedly decreased in the exercised GK rats compare to their non-exercised counterpart, while W/S rats did not show any exercise-related changes. Glucose concentration was not changed by exercise, although impaired glucose tolerance was improved in GK rats 120 min after glucose injection. However, insulin concentration was decreased by swimming exercise as in the decrease of GSIS after running exercise. To identify the other cause for exercise-induced insulin down-regulation, the changes in the levels of key factors involved in insulin production (C-peptide) and clearance (insulin-degrading enzyme; IDE) were measured in W/S and GK rats. The C-peptide level was maintained while IDE expression increased markedly. Therefore, these results showed that insulin down-regulation induced by short-term swimming exercise likely attributes to enhanced insulin clearance via IDE over-expression than by altered insulin production.

백서의 복강내에 투여한 Mitomycin-C-Polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

송규상,강대영,최정목,노승무,정경수,오정연,김진향,양준목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

To evaluate the in-vivo effects of mitomycin-C-polyglycolic acid composite(MMC-PGA) the disk: shaped composite were implanted into the peritoneal cavity of the Sprague-Dawley rats. The pathologic changes were examined at various time points up to 12 weeks. Initially the soft tissue around the inserted disks showed capillary congestion at 3 days. Inflammatory infiltrates with foreign body giant cells appeared from the 2nd week and reached peak response at 6-8 weeks. These reaction diminished prominently at 12 weeks. No specific pathologic change was found in the liver, the kidneys, and the heart. The above results suggest that the MMC-PGA composite can serve as a new device for intraperitoneal chemotherapy of various types of cancers.

위암에 의한 간 전이의 CT 진단에 있어 조영제의 급속 정맥주사방법을 이용한 문맥기 역동적 CT의 유용성 : Usefulness of Bolus Dynamic CT During Portal Phase

조준식,송창준,김종철,이병철 충남대학교 의과대학 지역사회의학연구소 1994 충남의대잡지 Vol.21 No.2

Purpose : We evaluated the usefulness of dynamic CT during portal phase with faster injection rate of contrast material in detecting hepatic metastases from gastric cancers. Subjects and Methods : We retrospectively analyzed two-phase dynamic CT findings (portal phase and equilibrium phase) in 17 patients with pathologically proven gastric cancers and hepatic metastases. In 13 patients, a total of 150ml of nonionic contrast material was administered with a power injector at a flow rate of 5ml/sec for 30 sec, and two-phase images were obtained at 45-70 sec (portal phase) and 2-4 min (equilibrium phase) after the start of bolus injection. In four patients, two-phase dynamic CT with spiral technique was performed with the same method. Results : In cases of metastases less than 1 cm in diameter, 65 lesions were detected in the portal phase that showed clearly defined hypodense lesions in highly enhanced hepatic parenchyma. Whereas, only nine (14%) lesions were detected in the equilibrium phase and the remaining 56(86%) lesions showed isoattenuation. In cases of metastases more than 1 cm in diameter, 37 lesions were detected in the portal phase that showed clearly defined hypoattenuations. whereas, the images of equilibrium phase showed isoattenuation in five (14%), mixed attenuation in three (8%), and hypoattenuation in 29 (78%). The lesions detected in the equilibrium phase showed poorly defined hypodense lesions and tended to decrease in size due to peripheral enhancement of lesions. Conclusion : Dynamic CT during portal phase with faster injection rate of IV contrast material is an useful technique in detecting hepatic metastases from gastric cancers, particularly small lesions less than 1 cm in diameter.