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.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

TRANSIENT ISCHEMIA-INDUCED EXPRESSION AND CHANGES OF TYROSINE KINASE A IN THE HIPPOCAMPAL DENTATE GYRUS OF THE GERBIL

HWANG, IN,LEE, HYEON,YOO, KI-YEON,KIM, DAE,KIM, JUNG,KIM, CHANG,LIM, BEONG,KANG, TAE-CHEON,BANG, KYUNG,SEONG, NAK,LEE, HAK,KIM, JONG,WON, MOO Taylor Francis 2006 International journal of neuroscience Vol.116 No.8

<P>The present study examined ischemia-related changes in tyrosine kinase A (trkA) immunoreactivity and its protein content in the dentate gyrus after 5 min of transient forebrain ischemia in gerbils. One day after ischemic insult, cresyl violet-positive polymorphic cells showed ischemic degeneration. The ischemia-induced changes in trkA immunoreactivity were found in the polymorphic layer (PL) and granule cell layer (GCL) of the dentate gyrus. In the sham-operated group, trkA immunoreactivity in the dentate gyrus was very weak. From 30 min after ischemia, trkA immunoreactivity was increased in the dentate gyrus and peaked in the dentate gyrus at 12 h after ischemia-reperfusion. Thereafter, trkA immunoreactivity was decreased time-dependently after ischemia-reperfusion. Four days after ischemic insult, trkA immunoreactivity was similar to that of the sham-operated group. In addition, it was found that ischemia-related changes in trkA protein content were similar to the immunohistochemical changes. These results suggest that the chronological changes of trkA in the dentate gyrus after transient forebrain ischemia may be associated with ischemic damage in polymorphic cells of the dentate gyrus.</P>

Causes and Predictive Factors Associated with "Diagnosis Changed" Outcomes in Patients Notified as Tuberculosis Cases in a Private Tertiary Hospital

Kang, Byung Ju,Jo, Kyung-Wook,Park, Tai Sun,Yoo, Jung-Wan,Lee, Sei Won,Choi, Chang-Min,Oh, Yeon-Mok,Lee, Sang-Do,Kim, Woo Sung,Kim, Dong Soon,Shim, Tae Sun The Korean Academy of Tuberculosis and Respiratory 2013 Tuberculosis and Respiratory Diseases Vol.75 No.6

Background: The aim of our study was to evaluate the "diagnosis changed" rate in patients notified as tuberculosis (TB) on the Korean TB surveillance system (KTBS). Methods: A total of 1,273 patients notified as TB cases on the KTBS in one private tertiary hospital in 2011 were enrolled in the present study. Patients were classified into three groups: "diagnosis maintained", "diagnosis changed" (initially notified as TB, but ultimately diagnosed as non-TB), and "administrative error" (notified as TB due to administrative errors). Results: Excluding 17 patients in the "administrative error" group, the "diagnosis maintained" and "diagnosis changed" groups included 1,097 (87.3%) and 159 patients (12.7%), respectively. Common causes of "diagnosis changed" were nontuberculous mycobacterial (NTM) disease (51.7%, 61/118), and pneumonia (17.8%) in cases notified as pulmonary TB, and meningitis (19.5%, 8/41) and Crohn's disease (12.2%) in cases notified as extrapulmonary TB. Being older than 35 years of age (odds ratio [OR], 2.18) and a positive acid-fast bacilli stain (OR, 1.58) were positive predictors and a TB-related radiological finding (OR, 0.42) was a negative predictor for a "diagnosis changed" result via multivariate logistic regression analysis in pulmonary TB cases. Conclusion: Because of a high "diagnosis changed" rate in TB notifications to the KTBS, the TB incidence rate measured by the KTBS may be overestimated. Considering the worldwide trend toward increased NTM disease, the "diagnosis changed" rate may increase over time. Thus, when reporting the annual TB notification rate in Korea, the exclusion of "diagnosis changed" cases is desirable.

Causes and Predictive Factors Associated with “Diagnosis Changed” Outcomes in Patients Notified as Tuberculosis Cases in a Private Tertiary Hospital

( Byung Ju Kang ),( Kyung Wook Jo ),( Tai Sun Park ),( Jung Wan Yoo ),( Sei Won Lee ),( Chang Min Choi ),( Yeon Mok Oh ),( Sang Do Lee ),( Woo Sung Kim ),( Dong Soon Kim ),( Tae Sun Shim ) 대한결핵 및 호흡기학회 2013 Tuberculosis and Respiratory Diseases Vol.75 No.6

Background: The aim of our study was to evaluate the “diagnosis changed” rate in patients notified as tuberculosis (TB) on the Korean TB surveillance system (KTBS). Methods: A total of 1,273 patients notified as TB cases on the KTBS in one private tertiary hospital in 2011 were enrolled in the present study. Patients were classified into three groups: “diagnosis maintained”, “diagnosis changed” (initially notified as TB, but ultimately diagnosed as non-TB), and “administrative error” (notified as TB due to administrative errors). Results: Excluding 17 patients in the “administrative error” group, the “diagnosis maintained” and “diagnosis changed” groups included 1,097 (87.3%) and 159 patients (12.7%), respectively. Common causes of “diagnosis changed” were nontuberculous mycobacterial (NTM) disease (51.7%, 61/118), and pneumonia (17.8%) in cases notified as pulmonary TB, and meningitis (19.5%, 8/41) and Crohn`s disease (12.2%) in cases notified as extrapulmonary TB. Being older than 35 years of age (odds ratio [OR], 2.18) and a positive acid-fast bacilli stain (OR, 1.58) were positive predictors and a TB-related radiological finding (OR, 0.42) was a negative predictor for a “diagnosis changed” result via multivariate logistic regression analysis in pulmonary TB cases. Conclusion: Because of a high “diagnosis changed” rate in TB notifications to the KTBS, the TB incidence rate measured by the KTBS may be overestimated. Considering the worldwide trend toward increased NTM disease, the “diagnosis changed” rate may increase over time. Thus, when reporting the annual TB notification rate in Korea, the exclusion of “diagnosis changed” cases is desirable.

무증상 갑상선기능저하증 환자에서 Thyroxine 치료에 따른 혈청 지질 및 아포지단백의 변화

조보연,신찬수,김원배,고창순,김성연,박혜영,박건상,이홍규,박형규,김숙경 대한내분비학회 1996 Endocrinology and metabolism Vol.11 No.1

Background: Subclinical hypothyroidism(SCH) is a common biochemical abnormality which can be found in routine screening tests of thyroid function. We are increasingly faced with the question of whether its an indication for thyroxine replacement therapy. The effect of thyroxine replacement on lipid profile in SCH has aroused a great interest because of an association of overt hypothyroidism(OVH) with hyperlipidemia and increased risk of coronary artery disease. Method: We prospectively evaluated the changes in lipids and apoproteins before and after thyroxine replacement therapy in 23 patients with SCH and in 37 patients with OVH. We measured serum total cholesterol and triglyceride using autoanalyzer, high density lipoprotein(HDL) chole-sterol by dextran sulfate method, Apo A1 and Apo B by immunonephelometric assay. Results: Thyroxine replacement therapy significantly decreased total cholesterol, low density lipoprotein(LDL) cholesterol and apo B levels, but did not affect the level of triglyceride, HDL cholesterol or apo AI in patients with OVH. In SCH, thyroxine replacement therapy with the doses to normalize serum TSH concentrations also decreased significantly the level of cholesterol and LDL cholesterol albeit apo B levels did not change. Moreover, in most of patients with OVH (11 of 12) and in all of patients with SCH(5 of 5) who had had hyperchlesterolemia before treatment, thyroxine replament normalized their cholesterol and LDL cholesterol levels. Conclusion: In regard to the beneficial changes in blood lipid levels, patients with SCH should be treated, especially in cases who have other risk factors for the development of atherosclerosis. If thyroxine replacement only will reduce the incidence of coronary artery disease in SCH remains to be elucidated by long-term prospective studies(J Kor Soc Endocrinol 11:41-51, 1996).

아시아 지역 폐렴 구균의 항균제 내성 현황 및 변화 양상 : Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study

정숙인,김나영,손준성,기현균,고관수,서지연,장현하,김연숙,오원섭,백경란,이남용,송재훈,항생제 내성 감시를 위한 아시아 연합 (ANSORP) 대한감염학회 2004 감염과 화학요법 Vol.36 No.1

목적 : 1980년대부터 페니실린을 비롯한 β-lactam 계열과 비 β-lactam 계열 항균제에 대한 폐렴구균의 항생제 내성이 급격하게 증가하여 국내 뿐 아니라 세계적인 문제로 대두되고 있다. ANSORP 에서는 아시아 지역에서 폐렴구균의 항균제 내성과 그 변화 추이, 내성의 기전 및 위험인자를 분석하고자 본 국제 공동 연구를 시행하였다. 재료 및 방법 : 1999년 11월부터 2001년 8월까지 아시아 지역 12개국의 14개 기관에서 폐렴구균 감염증 환자의 임상 검체로 분리된 침습성 폐렴구균을 대상으로 액체배지 미량희석법을 이용하여 16개 항생제의 MIC를 구하였다. 위험인자의 분석을 위하여 폐렴구균 감염증 환자를 대상으로 의무기록지를 조사하였다. Quellung 반응을 통해 혈청형을 결정하였다. 결과 : 총 685균주 중 52.4%가 페니실린에 대하여 비감수성(중등도 내성 22.9%, 내성 29.5%)을 보였고, 그 빈도는 베트남(92.1%), 스리랑카(85.7%), 홍콩(67.9%), 한국(64.5%)의 순이었다. Erythromycin에 대한 비감수성 비율은 베트남(92.1%), 대만(87.7%), 한국(80.6%), 홍콩(76.8%) 등에서 높게 나타났고, 베트남, 대만, 한국, 홍콩 등의 erythromycin의 MIC_(90)이 32㎍/mL를 넘는 고도내성을 보였다. 홍콩, 싱가포르, 대만, 인도에서는 fluoroquinolone에 대한 내성 균주가 출현하였다. 전체 균주 중 다제내성 균주의 비율은 47.7%였다. 혈청형은 19형과 23형이 가장 많았고, 그 외 6형, 14형 등이 있었다. 페니실린 비감수성 감염증의 위험인자로는 5세 미만(OR=1.7; 95%, CI, 1.2-2.4; P=0.002), 기관지폐질환(OR=2.0; 95%, CI, 1.3-3.1; P=0.003), 악성종양(OR=2.3; 95%, CI, 1.2-4.6; P=0.015), 스테로이드의 사용(OR=2.8; 95%, CI, 1.1-7.4; P=0.032)이 확인되었다. 결론 : 침습성 폐렴구균 균주를 대상으로 한 본 연구의 결과 아시아 국가들에서 페니실린, β-lactam 및 macrolide에 대한 폐렴구균의 내성률 및 내성 정도가 급증하고 있음을 확인하였다. Background : Emergence of pneumococcal resistance became a global issue since 1990s. According to the ANSORP studies with clinical isolates and carriage isolates between 1996 and 1999, some Asian countries showed alarmingly high prevalence of resistance to penicillin and other antimicrobial agents. To investigate the changing trends of pneumococcal resistance, ANSORP study group has performed a multinational surveillance study with invasive pneumococcal isolates from Asian countries. Methods : All isolates from various invasive pneumococcal diseases were prospectively collected from 14 centers in 12 countries between November 1999 to August 2001. Broth microdilution tests with 16 antimicrobial agents were performed according to the NCCLS procedures. Serotyping was performed by means of Quelling reaction with use of group-specific antisera. Results : A total of 685 isolates were collected. Overall, 52.4% of invasive isolates from Asian countries were not susceptible to penicillin (intermediate (1), 22.9%, Resistant (R), 29.5%). Vietnam showed the highest prevalence of penicillin non-susceptibility (1 20.6%, R 71.4%) followed by Sri Lanka (1 71.4%, R 14.3%), Hong Kong (1 24.1%, R 76%) and Korea (1 9.7%, R 54.8%). China (I 19.8%, R 23.4%) and Malaysia (1 9.1%, R 29.5%) also showed remarkable increase in penicillin resistance compared with previous ANSORP data, which were less than 10%. Vietnam (92.1%), Taiwan (87.7%), Korea (80.6%), and Hong Kong (76.8%) showed high prevalence of erythromycin resistance. MIG_(90)S for ciprofloxacin were 4 ㎍/mL (Hong Kong) and 2 ㎍/mL (11 Asian countries except Hong Kong), respectively. Conclusion : Compared with previous data from ANSORP studies, antimicrobial resistance among invasive pneumococcal isolates has markedly increased in Vietnam, Sri Lanka, Taiwan, China, and Malaysia. Continuous surveillance of pneumococcal resistance in Asia is strongly warranted.

알코올에 의한 α-Tocopherol의 혈중 효소농도에 관한 연구

김동연,이상한,김창세,조만희 순천향의학연구소 1995 Journal of Soonchunhyang Medical Science Vol.1 No.1

The α-tocopherol has an anti-oxidant and protective action of the liver tissue against free radical which results to hematological changes, tissue damage and metabolic disturbances. To investigate the effects of α-tocopherol on the alcohol administered rats(SD) the rats were divided 4 groups; control, alcohol, α-tocopherol, and both alcohol and α-tocopherol administration. The following results were obtained 1. In alcohol administered group the blood enzyme activities were higher than control and were significantly lower in α-tocopherol administered. The blood enzyme activities in both alcohol and α-tocopherol administered group were not significantly lower than alcohol adiministered group. 2. The liver enzyme activities in alcohol administered group were higher than control and were changed, especially GOT, ALP, LDH and CPK. The liver enzyme activities in both alcohol and α-tocopherol administered group were significantly lower than alcohol administered group. 3. From the above results there were found that the α-tocopherol has a protective action against liver damage due to administration of alcohol, which caused a free radical from the lipid peroxidation and also caused the increasing enzyme activities in the blood and the liver.

카드뮴폭로후 혈액과 요중 카드뮴의 변화양상

박정덕,김미정,최병선,홍연표,장임원 大韓産業醫學會 1994 대한직업환경의학회지 Vol.6 No.2

The changes of cadmium(Cd) in plasma, whole blood, erythrocyte and urine in Sprangue-Dawley male rats exposed to intravenous singleinjection of 0.8 ㎎ CdCl₂/kg of body weight were investigated. Blood was taken at 0.5 to 672 hours, and 24 hour-urine was collected by using metabolic cage for the same period. The plasma level of Cd was reached to peak at 0.5 hour after injection and reduced rapidly in 1 hour. The Cd level in blood was the highest in plasma and the lowest in erythrocyte at 0.5 hour after injection. However, in one hour postinjection, the levels of Cd were higher in order of erythrocyte, whole blood and plasma, up to 4 weeks. The changes of urinary volume and creatinine were not significant between Cd-treated and saline-treated groups. However, urinary protein was slightly increased with time in Cd-treated group. Urinary Cd level was higher in Cd treated group than control. These results suggest that the measurement of Cd in erythrocyte and urine is valuable for the biological index to estimate recent Cd exposure.

The effects of a single bout pilates exercise on mRNA expression of bone metabolic cytokines in osteopenia women

( Chang Sun Kim ),( Ji Yeon Kim ),( Hyo Jin Kim ) 한국운동영양학회 2014 Physical Activity and Nutrition (Phys Act Nutr) Vol.18 No.1

[Purpose] The purpose of this study was to examine the effect of a single bout pilates exercise on mRNA expression of bone metabolic cytokines in elderly osteopenia women. [Methods] We selected 11 people of elderly osteopenia women and loaded a single bout pilates exercise about RPE 10-14 level. The blood samples were collected before, immediately after and 60 minute after pilates exercise, then examined calcium metabolic markers in serum and extracted peripheral blood mononuclear cell (PBMC) from whole blood and confirmed mRNA expression of bone metabolic cytokines from PBMC. To clarify the changes during exercise, we designed repeated measure ANOVA as the control group to perform blood sampling without exercise. [Results] As a result, serum P showed significant interaction effect between group and time (p<.001), the pilates exercise group decreased about 9% at immediately after exercise and 13% during recovery after exercise (p<.05), while the control group showed a tendency to increase. Serum CK also showed a significant interaction between group and time (p<.05), the pilates group significantly increased at immediately after exercise and during recovery after exercise (p<.05) but the control group didn`t have changes. TNF-α and IL-6 mRNA expression in PBMC was significantly increased in the pilates group (p<.01, p<.05), although INF-γ mRNA expression didn`t show statistically significant difference, it tended to increase in the pilates group (NS). [Conclusion] These results suggested that a single bout pilates exercise of elderly osteopenia women cause hypophosphatemia with temporary muscle damage, and it leading high turnover bone metabolic state with to activate both of bone formation and bone resorption.