Nelumbinis Semen Reverses a Decrease in $5-HT_{1A}$Receptor Binding Induced by Chronic Mild Stress, a Depression-like Symptom

Jang, Choon-Gon,Kang, Moon-Kyu,Cho, Jae-Han,Lee, Sun-Bok,Kim, Hyun-Taek,Park, Soon-Kwon,Lee, Jin-Woo,Park, Seong-Kyu,Hong, Moo-Chang,Shin, Min-Kyu,Shim, In-Sup,Bae , Hyun-Su The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.10

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

臨床化學檢査의 精度管理狀態 分析考察 : Sodium, Potassium, Chloride, Calcium

姜泳圭,金仁仙,李昌珪,白承龍 최신의학사 1981 最新醫學 Vol.24 No.2

肝吸蟲症의 化學豫防에 關한 實驗的 硏究(第1報)

康晳榮,盧忍圭,咸毅根,朱一 대한의학협회 1963 대한의학협회지 Vol.6 No.8

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.

스티렌 폭로 근로자들의 기중 및 혈중 스티렌과 요중 만델산의 관계 분석

정호근,강성규,양정선,김기웅,이종성,조영숙,박인정 大韓産業醫學會 1994 대한직업환경의학회지 Vol.6 No.1

The concentration of styrene in air in blood and mandelic acid in urine were checked for the 60 workers with normal liver function, exposed to styrene. Styrene in air were sampled with personal air sampler at least 4 hours and analyzed by gas chromatography. Blood and spot urine were collected at the end of shift with a vacuum tube and a polythylene bottle and analyzed by gas chromatography and high performance liquid chromatography. Means of air and blood styrene and urine mandelic acid were 8.16 ppm(geometric mean), 0.199 mg/L, and 0.519 g/g creatinine, respectively. The concentration of styrene in air and mandelic acid in urine were high in the FRP factories and low in polymerization factory. Styrene in blood showed large difference by the working process. Styrene in air showed a good correlation with mandelic acid in urine(r=0.6369) and styrene in blood(r=0.6371). The mandelic acid in urine and styrene in blood corresponded to exposure of 50 ppm styrene were 0.890 g/g creatinine and 0.434 mg/L. However, hippuric acid in urine did not show any correlation with styrene in air. Urine mandelic acid excretion expected ratio showed a tendency to decrease according to obesity index and to increase with alcohol consumption.

의료방사선관리의 국제화 연구 : 핵의학분야의 의료방사선관리

김인규,오헌진,김혁주,오현주,박기정,이광용,이병영,정승환,강영규,이현구,김귀야,한상용,김연교,양현규,이명철 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

의료방사선은 인간의 질병진료와 예밤에 활용되어 각종 질병으로부터의 적절한 진단 및 의학발전에 중대한 역할을 담당하고 띤다. 또한 인공방사선원중 가장 큰 비중을 차지하고 있으며, 방사선원을 이웅한 이득과 손실을 생각쌀 때 피폭선량의 최소화 및 곡률적영향의 최소화를 위해 이득을 최대화하는 노력을 하고 있다. 진단뿐만 아니라 치료에도 사응하고 있는 인공방사선원의 적절한 관리를 위한 조사 및 연구는 국내에서는 아픽까진 실시되지 않았으며, 국외에서는 이미 활발한 조사 덴 연구가 이루어 지 고 있다. 일반적으로 의료기관의 핵의학분야에서 환자의 진단 및 치료에 사용되는 방사성의약품으로는 Tc-99in, Ga-67, 1-131, 71-201 등이 있으며 이를 이용한 방사능측정웅장비 및 치료뭉장비에는 Gamma Camera, 감마선재측기, 베타선계측기, Dose CaTibrator, PET(양전자방출전산화단층촬영장치)등이 있다. 이어 식푿의약품안전청f"서는 핵의학분야의 방사선보건학적 연구를 위해 핵의학분야의 진료와 관련된 인력, 시설, 장비, 방사성의약품의 사응, 핵의학적 진료형태 및 핵의학적 진료장치에 대한 성능관리등에 대해 조사·연구하였다. A nationwide survey was conducted in the Korea in 2001 to determine the facilities available and the level of activity at centres where radionuclide and therapy was practised in 2000. A response rate of 75% indicated that 120 centres were providing radionuclide therapy and diagnosis. About the good treatment of radionuclide using in medical, researched so many country, but not yet in. Generally nuclear medical part use Tc-99m, Ga-67, I-131, Tl-201 in diagnosis and therapy, radiation detector and equipment for therapy use Gamma Camera, beta-counter, Dose Calibrator PET(Positron Emission Tomography). 81% rate of centre has Gamma Camera and 97% rate of use Tc-99m, I-131 radionuclide. In-vitro did more than in-vivo test absolutely. So in KFDA researched in unclear medical part in Man-Power, facilities, equipment use of nuclear medicine, part of diagnosis and diagnosis equipment.

흰쥐에서의 Puromycin Aminonucleoside-유발 단백뇨에 대한 선택적 Thromboxane A₂수용체길항제, KT2-962의 효과

서대규,신인철,고현철,하경란,강주섭 한양대학교 의과대학 1994 한양의대 학술지 Vol.14 No.1

The administration of puromycin aminonucleoside(PAN) to rats caused to nephrotic syndrome which characterized ascites, proteinurisa, hypoalbuminemia, and hyperlipidemia similar to those observed in human minimal change disease. Recently, several studies indicate that renal endogenous thromboxane(Tx) A₂may have an important role in pathophysiology of various renal disease. In this sutdy, we hafve examined the protective effct of a selective TxA₂receptor antagonist, KT2-962(KT2) on PAN-induced proteinuria in rats. Thus, male Wistar rats were given either daily subsutaneous injection of PAN, 20mg/kg, for 10 consecutive days from 3 days before to 7 days with PAN treatment. Urine was collectd, and body weight was measured in interval of 2 days during 2 weeks and urinary N-acetyl-β-Dglucosaminidase(NAG) activity as an index of renal tubular cell damage and urine protein were measured. In addition to measuring BUN, serum creatinine and creatinine clearance were measured to assess the degree of renal functional damage in 14th day. The results(Means SE) otained can be summarized as follows: 1)Body weight(gm) was progressively increased and gained about 46.4gm and 39.2gm on 2 weeks of treatment in the control and KT2 groups respectively. In constrast, there was weight loss about 27.4gm in the PAN group. But, it was increased about 23.2 gm in KT2+PAN grou and means that KT2 has significantly(p<0.05) suppressed weight loss by PAN. 2)Urine flow (ml/24 hours) was slightly increased in both control and KT2 groups during 2 weeks. But, it was significantly(p<0.05) increased after 7th groups during 2 weeks. But, it was significantly(p<0.05) increased after 7th day. But, concurrent administration of KT2 significantly(P<0.05) suppressed PAN-induced polyuria in KT2+PAN group. 3)Urinary protein(mg/24 hours0 was slightly increased in both control and KT2 groups. But, it was progressively increased and reached at the maximal level, 3.2 folds of initial level to 11th day and thereafter slightly reduced proteinuria to 14th day in the PAN group. In contrast, KT2 cotreatment with PAN was significantly(P<0.05) suppressed PAN-induced proteinuria in the KT2+PAN group. 4)Urinary NAG activity was markedly increased and reached to maximal level, 122.03 18.53 U/mg of urine creatinine, 12.7 folds of initial by day 9 and thenafter progressively decreased to 5.4 folds of initial level by day 14 in the PAN group. But, when KT2 was administered with PAN, it was significantly depressed its increment to day 13. But, it was reached to maximal level, 99.05 42.55, 12.7 folds of inital level much than PAN group. This result indicated that KT2 had a partial preventive effect on PAn-induced renal tubular cell damage. 5)The BUN and serum creatinine level(mg/dl) were significantly(p<0.05) increased from initial level, 18.48 1.28 and 0.50 0.03 to 118.42 41.34 and 1.66 0.27 respectively, and creatinine clearance(ml/min) was significantly(P<0.05) decreased from initial level, 0.44 0.02 to 0.28 0.07 by day 14 by PAN treatment. But, when PAN was given together with KT2, the increment of BUN and serum creatinine except for creatinine clearance were significantly(P<0.05) inhibited in the KT2+PAN group. Based on all these results obtained in this study, it is concluded that the coadministration of KT2-962 with PAN can be ingibited protein excretion in urine and suggested that endogenous TxA₂would take part in PAN-induced proteinuria in rats.

IL-β의 인슐린 분비 자극효과와 그 과정에 관여하는 인자들

정인경,오승훈,강동묵,정재훈,민용기,이명식,이문규,김광원 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.4

연구배경: IL­1β는 용량과 노출시간에 따라 인슐린분비에 대해 상반되는 효과를 가지고 있다. IL­1β의 인슐린 분비 억제효과는 제1혁명 당뇨병의 자가면역 기전과 관련되어 잘 알려져 있으나 인슐린 자극효과에 대해서는 아직 명백히 밝혀지지 않았다. 이에 저자 등은 IL­1β의 다양한 농도에 따라 백서의 췌도세포에서 인슐린 분비에 미치는 영향을 살펴보고, 그 기전으로 인슐린 생합성, iNOS의 발현, 칼슘통로의 활성도 변화여부를 알아보고자 하였다. 방법:200∼300g인 수컷 Sprague­Dawley 백서의 췌도를 변형된 Lacy&Kostianovsky's 방법으로 분리한 후 IL­1β의 다양한 농도(0, 0.5, 5, 50, 500pmol/L)에 2, 6, 24시간 노출시켜 췌도세포의 형태, 생존능을 관찰하고 인슐린 분비능 및 췌도세포내 인슐린 함량을 측정하였으며, 전전구 인슐린 mRNA발현, iNOS mRNA발현을 RT­PCR을 통해 확인하였고, 세포의 칼슘 통로 활성도 변화 여부를 측정하였다. 결과:1) IL­1β에 노출되 췌도의 생존능:2시간 노출시는 대조군과 차이가 없었으나, 6시간 고농도군과 24시간 모든 군에서 생존능이 감소되었다. 2)인슐린 분비능은 IL­1β를 2시간 5poml/L이상의 고농도와 6시간 0.5pmol/L 저농도 처리시 대조군에 비해 의미있게 증가하였으나, 6시간과 24시간 5poml/L이상의 고농도에서는 의미있게 인슐린의 분비가 억제 되었다. 3)췌도내 인슐린양의 변화는 IL­1β의 시간과 농도에 따라 배지내의 인슐린 변화와 비슷한 경향을 보였으나 통계학적으로 의미있는 차이는 없었다. 4)전전구인슐린의 mRNA발현은 2시간 50pmol/L이상 고농도의 IL­1β에서 의미있게 증가하였고, 6시간 처리군에서는 의미있는 차이는 없었으나, 24시간에서 IL­1β의 용량의존적으로 억제되었다. 5)iNOS mRNA는 IL­1β 처리 후 2시간부터 발현되기 시작하여, 6시간에 최고에 달한 후 24시간에는 점차 감소하였다. IL­1β의 처리시간과 무관하게 5poml/L이상의 고농도에서 용량에 따라 발현이 증가하였다. 6)칼슘통로 활성도는 IL­1β의 농도나 시간에 따라 유의한 차이가 없었다. 결론: IL­1β는 단시간 고용량이나 장기간 저용량에서 인슐린 분비와 생합성을 증가시키며, 이런 효과는 iNOS나 칼슘 통로 활성도 변화와는 무관한 것으로 생각된다. Background : The inhibitory effort of IL-1β on the insulin secretion has been validated in pathogenesis of type 1 diabetes, but complex results about the stimulatory effect of IL-1β have been reported. The aims of this study are to clarify the effects of IL-1βon insulin secretion of pancreatic islets and to investigate the mechanisms in terms of preproinsulin synthesis, inducible NOS expression, and calcium channel activity. Method : Islets were isolated from male Sprague-Dawley (SD) rat by modified Lacy-Kostianovsky's method. After islets were treated with different concentrations (0, 0.5, 5, 50, 500 pmol/L) and exposure time (2, 6, 24 hours) of IL-1β, morphology, viability, static stimulation of insulin to glucose, insulin content, preproinsulin mRNA expression, iNOS mRNA expression and calcium channel activity were measured. Results : 1) Viability o islets was reduced in high concentrations of long term exposure of IL-1β. 2) Insulin secretion was stimulated in islets treated with 5, 50, and 500 pmol/L of IL-1β for 2 hours. 3) Insulin content was not significantly different regardless of concentration and exposure time of IL-1β. 4) Preproinsulin mRNA expression increased in islets treated with 50, 500 pmol/L of IL-1β for 2 hours. After 24 hours, it decreased in dose dependent manner. 5) iNOS mRNA expression was detectable after 2 hours in the presence of IL-1β, peaks at 6 hour and decreased after 24 hours. It was increased above 5 pmol/L of IL-1β in dose dependent manner. 6) Activities of the voltage-dependent Ca^2+ channels were not different among groups. Conclusion : IL-1β plays a positive role in terms of insulin secretion and insulin synthesis in high concentration of short term or low concentration of long term. These effects of IL-1β might be neither dependent of iNOS pathway nor Ca^2+ channel activity (J Kor Diabetes Asso 431~443, 2000).

선천성 비후성 유문협착증에 대한 임상적 고찰

김인구,강민규 충남대학교 의과대학 지역사회의학연구소 1988 충남의대잡지 Vol.15 No.2

Congenital hypertrophic pyloric stenosis is a frequent neonatal disease which is caused by marked hypertrophy of muscular layer in pylorus. Main clinical manifestations are non-bile stained projectile vomiting, visible peristaltic wave and olive-like mass, and it induces severe dehydration and metabolic derangement. Proper preoperative management is required for dehydration and metabolic derangement and Fredet-Ramstedt Pyloromyotomy is widely used as a definitive surgical treatment. The authors studied on 31 cases of congenital hypertrophic pyloric stenosis, treated at the Department of General surgery, Chungnam National University Hospital from July 1985 to June 1988. The results were as follows: 1) The congenital hypertrophic pyloric stenosis was 31 cases which was 4.9% in incidence in total 638 admission to the department of pediatric surgry during the same period. 2) The most prevalent age group was between 5th week and 6th week and the ratio of male to female was 9:1. 3) Among 31 cases, breast-fed infants were 10 cases(29.1%), milk-fed 19 cases (58.3%), and mixed-fed 2 cases(6.5%). 4) The body weight percentile at admission was lower than 25 percentile in 31 cases and the body weight at admission was lower than birth weight in 6 cases(19.4%). 5) In 29.2%, clinical manifestations were noted between 2nd week and 3rd week. 6) Non-bile stained projectile vomiting was noted in 30 cases(96.8%). 7) The most frequent physical findings were pyloric mass(77.4%), visible peristaltic wave (48.4%)and jaundice(19.4%) in order of freguency. 8) At the time of admission, the accompanied jaundice was noted in 6 cases(19.4%) and most of them was breast-fed infants. 9) The higher the value of CO_2, content, the more severe hypochloremia and hypokalemia were noted. 10) The longer duration of symptoms, the more hypochloremic, hypokalemic metabolic alkalosis was noted. 11) In 6 cases(10.4%), associated anomalies were noted. 12) All 31 cases were surgically treated with Fredet-Ramstedt pyloromyotomy and morta lity was nil.

노인에서의 외과 환자에 대한 임상적 연구

배진선,강민규,송인상 충남대학교 의과대학 지역사회의학연구소 1989 충남의대잡지 Vol.16 No.2

378 patients over 65 years old were reviewed, who were admitted during the period from June. 1. 1985 to December 31. 1988 in the Department of Surgery, Chungnam National University Hospital. The results were as followings: 1. The rate of patients over 65 years to all who were admitted during same period was 11.3%. 2. The number of male patients was 183, that of female 195, the overall ratio of male to female being 1:1.07. In benign diseases, that was 1:0.95, and in malignant diseases 1:1.26. 3. Hemoglobin value at admission was below 10.0gm% in 7.5% of patients with benign diseases and in 15.0% of patients with malignant diseases. 4. Serum albumin at admission was below 3.5gm% in 60% of patients with benign diseases and in 50% of patients with malignant diseases. 5. As to the distribution of benign diseases, disease in biliary system was most frequent(33%), followed by appendicitis(25%), ileus and trauma in jejunum and ileum(13%), and peptic ulcer(6%) in the order of frequency. 6. As to the distribution of malignant diseases, stomach cancer(51%) was most frequent, followed by colorectal cancer(25%), and hepatobiliary cancer(10%) in the order of frequency. 7. 47% of patients with benign diseases and 44% of that with malignant diseases had associated diseases, among which hepertension was most frequent, followed by lung disease, hearth disease, diabetes mellitus, liver disease and renal disease in the order of frequency. 8. Complications were most prevalent in the patients with hepatobiliary diseases, followed by appendicitis and colorectal cancer, and among complications, would infection was most frequent, followed by urinary tract infection and respiratory infection in the order of freguency. In the patients with colorectal cancer, mechanical lieus was second frequent complication after wound infection. 9. The mortality rate was highest in the patient with colorectal cancer(22.2%), followed by in those with benign biliary disease(10%), overall mortality rate being 4.3%. 10. Major causes of deaths were sepsis, respiratory failure, bile peritonitis and renal failure.