쿠싱증후군 환자에서 당 대사 이상 정도에 따른 인슐린 감수성과 인슐린 저항성의 변화

정인경,김성훈,정재훈,민용기,이명식,이문규,유형준,안규정,노정현,김동준,김광원 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경 당질 코르티코이드는 당 대사에 매우 중요한 호르몬으로 내인성 당질 코르티코이드 과다상태인 쿠싱증후군에서는 말초조직에서 인슐린 저항이 증가하고 이를 보상하고자 인슐린 분비의 증가로 고인슐린혈증이 동반된다고 보고되고 있다. 하지만 생체 내에서와 달리 시험관내에서는 췌도세포에 당질 코르티코이드를 장시간 처리하면, 인슐린 분비 및 생합성이직접적으로 억제됨이 확인된 바 있어 쿠싱증후군 환자에서 당뇨병의 원인으로는 아마도 말초조직에서 증가된 인슐린 저항성 뿐 아니라 이를 충분히 보상하지 못하는 췌장에서의 인슐린 분비 저하가 같이 동반되어있지 않을까 하는 가설을 세우게 되었고, 아직까지 당질코르티코이드가 당대사 이상을 일으키는 기전에 대해 쿠싱증후군을 당대사 정도에 따라 인슐린 감수성과 분비능을 분석한 연구는 없었기에 이를 알아보고자 하였다. 방법: 삼성서울병원에서 쿠싱증후군으로 진단 받은 환자 15명을 대상으로 하였다. 이에 대한 대조군으로는 쿠싱증후군 환자와 같은 성별 그리고 체질량지수를 갖은 15명의 건강한 성인을 대상으로 비교 하였다 쿠싱증후군 환자를 대상으로 경구당부하 검사를 통해 당대사 정도를 정상군, 내당능장애군, 그리고 당뇨병군으로 나눈 후 정맥 당부하 검사를 시행하여 각군의 인슐린 저항성과 인슐린 분비능의 지표를 비교하고, 수술 후 쿠싱증후군이 완치된 상태에서 수술 전후의 당대사 지표의 변화를 조사하였다. 결과: 1) 쿠싱증후군 환자 중 정상인은 20%, 내당능 장애는 27%, 그리고 당뇨병은 53%였다. 체질량지수, 나이, 그리고 발병 기간은 세 군간에 의미 있는 차이가 없었으나, 24시간 소변검사의 코르티솔 농도는 당뇨병군에서 의미있게 높았다. 2) 정맥당부하 검사 결과, 인슐린 감수성 지표인 Sl는쿠싱증추린」서 1.58±0.10[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 대조군의 3.37±0.49[×10^(-4)(min^(-1)(μU/mL)^(-1)]에 비해 의미있게 낮았으나(P=0.024), 쿠싱증후군 환자 중 NGT, IGT, DM 군간에 서로 통계적인 차이는 없었다. 3) SG는 정상 대조군과 쿠싱증후군 환자간에는 의미있는 차이가 없었고, 쿠싱 증후군에 있어서 당대사가 악화될수록 감소하는 경향을 보였으나 의미있는 차이는 없었다. 4) 인슐린 분비능의 지표인 AIRg는 정상인에 비해 전체 쿠싱증후군 환자의 경우 증가하는 경향을 보였으나 의미있는 차이는 없었다. 하지만 쿠싱증후군 환자중에서 당대사 상태에 따라 NGT군은 1299 (1297∼1310)(mu/g/min ×10^(-2))로 정상 대조군(368.9±98.6[mu/g/min ×10^(-2)]) 보다도 의미있게 높았고, DM군{202.2 (91.1~371.4) [mu/g/min ×10^(-2)}은 NGT군에 비해 의미있게 낮았다(P=0.0031). 5) 15명중 현재 완치 상태에 있는 6명에 대해 수술전과 후로 비교하였다. 수술 전 당대사 상태가 1명은정상, 1명은 내당능 장애, 그리고 4명은 당뇨병이었으나 수술 후 시행한 경구 당부하 검사상 모두 정상 당대사 상태를 보였다. 6) 수술 후 완치된 환자 6명에 있어 인슐린 감수성지표인 Sl는 수술전에 중앙값이 1.22[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 대조군에 비해 의미있게 감고』어 있었으나(p.0.05), 수술후 10.95 [×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 수준으로 회복되었고(P=0.0022), 인슐린 분비능을 나타내는 AIRg [mu/g/min ×10^(-2)] 값도 정상수준으로 회복되었다. 특히 인슐린 분비능의 회복양상은 혈당농도에 따라 판이하게 나타나서, 정상과 내당능장애 상태에 있던 2명은 수술전에 1201 [mu/g/min ×10^(-2)]로 증가되어 있던 AIRg 값이 수술 후 정상 수준으로 감소하였고, 수술 전에 당뇨병 상태에 있던 4명의 경우 245.9 [mu/g/min ×10^(-2)]로 인슐린 분비능이 감고il어 있었는데 이들은 수술 후 모두 정상 수준으로 증가되었다 (P=0.0286). 결론: 쿠싱증후군 환자에서 당대사 이상은 80%로 높은 유병률을 보였다. 모든 쿠싱증후군환자에서 인슐린 감수성은 정상인에 비해 저하되어 있어 말초조직의 인슐린 저항이 선행됨을 시사하며, 인슐린 분비능은 당대사의 정도에 따라 다르게 나타났는데, 정상 당대사군에서는 인슐린의 저항성을 극복할 만큼 정상 대조군보다 더 많은 양의 인슐린 분비를 하다가 고코르티솔혈증이 심할수록 인슐린 분비능의 감소로 당뇨병으로 진행됨을 확인할 수 있었고, 이런 인슐린 저항성과 인슐린 분비장애는 수술 후 다시 회복되는 가역적인변화를 보였다. Background: Glucocorticoid plays an important role in the control of carbohydrate metabolism. Patients with Cushing's syndrome have been reported to have an increased incidence of carbohydrate intolerance due to peripheral insulin resistance and hyperinsulinemia, although the exact incidence and nature of this disorder have remained unclear. Few results have been published about insulin resistance and insulin secretion according to the level of glucose concentration, or about the reversibility of such defects in patients with Cushing's syndrome. Methods: To assess the effect of glucocorticoid on the insulin sensitivity and insulin secretion in Cushing's syndrome, 15 patients with Cushing's syndrome were classified into 3 groups (normal glucose tolerance: NGT, impaired glucose tolerance: IGT, diabetes: DM) according to the degree of glucose tolerance based on the oral glucose tolerance test (OGTT). Insulin modified, frequently sampled, intravenous glucose tolerance test (FSIGT) was performed before and after curative surgery on these patients and on 15 healthy control subjects. Data were evaluated by non-parametric statistical analysis. Results: 1) Among the 15 patients with Cushing's syndrome, 3 (20%) were NGT, 4 (27%) IGT, and 8 (53%) DM, based on OGTT. Twenty-four hour urinary free cortisol (UFC) was significantly higher in the DM group. 2) Insulin sensitivity index (SI) of Cushing's syndrome was significantly lower than that of the control group p=0.0024), but was not significantly different among the three Cushing's syndrome groups of NGT, IGT and DM. 3) Glucose mediated glucose disposal (SG) (Ed- confirm this abbreviation; it does not seem to match the definition) of Cushing's syndrome was not significantly different from that of the control group. 4) Insulin secretion (AIRg) of Cushing's syndrome tended to be high, but it was not significantly different from that of control. However, according to the level of glucose concentration there was significant difference in AlRg among the three Cushing's syndrome groups p=0.0031); AIRg of DM was significantly lower than that of NGT. 5) After surgical treatment, parameters of insulin sensitivity and insulin secretion were normalized in 6 cured patients; 1 with NGT, 1 with IGT, and 4 with DM, preoperatively. Median SI of all 6 patients was significantly improved up to the normal range postoperatively p=0.0022). Median AIRg of these 6 patients was balanced around that of normal control postoperatively p=0.0286). Conclusion: Eighty percent of patients with Cushing's syndrome had abnormality of carbohydrate metabolism. Insulin sensitivity was significantly decreased in Cushing's syndrome. Insulin secretion was significantly higher only in the NGT and IGT groups of Cushing's syndrome. As the hypercortisolemia is exacerbated, insulin secretion is significantly decreased and causes DM, suggesting that glucocorticoid has a direct or indirect toxic effect on the pancreatic beta cell (J Kor SOC Endocrinol 18:392-403, 2003).

Effect of Jaeumkanghwatang (JEKHT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (1)

Min A Kwak,Soo Jin Park,Sung Hwan Park,Young Joon Lee,Sae Kwang Ku 대한한의학회 2016 대한한의학회지 Vol.37 No.2

Effect of Jaeumkanghwatang (JEKHT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (1) - Single Oral Combination Treatment of Tamoxifen 50 mg/kg with JEKHT 100 mg/kg within 5 min -

Kwak, Min A,Park, Soo Jin,Park, Sung Hwan,Lee, Young Joon,Ku, Sae Kwang The Society of Korean Medicine 2016 대한한의학회지 Vol.37 No.2

Objectives: The objective of this study was to elucidate the effect of Jaeumkanghwatang (JEKHT) on the plasma concentration and pharmacokinetics of tamoxifen in combination therapy as a process of the comprehensive and integrative medicine against breast cancer. Methods: After 50 mg/kg of tamoxifen treatment, JEKHT 100 mg/kg was orally administered within 5 min. The plasma were collected at 30 min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of JEKHT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results: JEKHT did not influenced on the plasma concentrations and pharmacokinetics of tamoxifen after single oral co-administration, within 5min except for some negligible effects on plasma concentration. The $T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$ of tamoxifen in co-administered rats were quite similar to those of tamoxifen single treated rats. Conclusions: Based on the results of the present study, JEKHT did not influenced on the oral bioavailability of tamoxifen, when they were single co-administered within 5min. However, more detail pharmacokinetic studies should be tested to conclude the possibilities that can be used as comprehensive and integrative therapy with JEKHT and tamoxifen for breast cancers, when they were co-administered, like the effects on the pretreatment of JEKHT and after repeat co-administrations.

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.

총경동맥 폐쇄시간에 따르는 국소 뇌혈류 변화 : 실험적 연구 An Experimental Cat Model

강준기,성태경,조병일,백민우,김문찬,허춘웅,하영수,송진언 대한신경외과학회 1983 Journal of Korean neurosurgical society Vol.12 No.3

The microvasculature of the brain is also quite susceptible to ischemic insult, and substantial portions of the brain are not reperfused after restoration of the blood supply following overtime of critical ischemic periods. The purpose of this series of experiments was to determine the effects of ischemia on subsequential regional cerebral blood flow measurements and cortical electric activities following reperfusion after ischemia and also to define the proper time of vascular occlusion without irreversible neural damage. Cerebral ischemia was induced in cat by bilateral common carotid occlusions for periods of 10, 30, to 60 minutes, and the blood supply was reperfused for 3 hours after clamp-off. Regional cerebral blood flow(rCBF) was measured by hydrogen clearance technique following ischemia, restoration of blood supply and electroencephalogram recovery could be predicted according to the rCBF. Forty adult cats weighing 2.7 to 4.0㎏ were used in this study. The animals were divided into 4 groups of 10 cats each : normal control, 10 min-clamped, 30 min-clamped, and 60 min-clamped groups. The results obtained were as follows : 1) The mean rCBF was 24.6±7.0㎖/100g/min in control group. 2) Bilateral carotid occlusions resulted in a reduction of the rCBF(12.4±4.1㎖/100g/min) to 50% of control flow on both hemispheres. 3) Sequential changes of the rCBF after reperfusion : (1) There was restored the rCBF(21.3±5.1㎖/100g/min) to control flow in the 10 minutes-clamped group. (2) There was a 85% recovery of control flow in the 30 minutes-clamped group. (3) There was a only 25% recovery of control flow in the 60 minutes-clamped group. 4) A close correlation was found between cortical electrical activity and rCBF suggesting a threshold relationship. (1) The changes of cortical electric activity began to notice at rCBF less than 17.4±4.7㎖/100g/min. (2) The recovery of cortical electric activity noted at rCBF more than 10.2±2.3㎖/100g/min. 5) There was no evidence of ischemic involvement at the cortex, white matter and basal ganglia in the 10 minutes clamped group, but demonstrated a dense wedge shaped infarct at the cortex and uncus herniation in the 60 minutes clamped group. The rCBF and cortical electric activity restored to normal values in reperfusion within 10 minutes after occlusion of both common carotid arteries.

Dry etching of polydimethylsiloxane using microwave plasma

Hwang, Sung Jin,Oh, Dong Joon,Jung, Phill Gu,Lee, Sang Min,Go, Jeung Sang,Kim, Joon-Ho,Hwang, Kyu-Youn,Ko, Jong Soo IOP 2009 JOURNAL OF MICROMECHANICS AND MICROENGINEERING - Vol.19 No.9

<P>This paper presents a new polydimethylsiloxane (PDMS) dry-etching method that uses microwave plasma. The applicability of the method for fabricating microstructures and removing residual PDMS is also verified. The etch rate of PDMS was dominantly influenced by the gas flux ratio of CF<SUB>4</SUB>/O<SUB>2</SUB> and the microwave power. While the PDMS etch rate increased as the flux ratio of CF<SUB>4</SUB> was increased, the etch rate decreased as the flux ratio of O<SUB>2</SUB> was increased. The maximum etch rate of 4.31 µm min<SUP>−1</SUP> was achieved when mixing oxygen (O<SUB>2</SUB>) and tetrafluoromethane (CF<SUB>4</SUB>) at a 1:2 ratio at 800 W power. The PDMS etch rate almost linearly increased with the microwave power. The ratio of the vertical etch rate to the lateral etch rate was in a range of 1.14–1.64 and varied with the gas fluxes. In consideration of potential applications of the proposed PDMS etching method, array-type PDMS microwells and network-type microprotrusion structures were fabricated. The contact angle was dramatically increased from 104° (non-etched PDMS surface) to 148° (etched PDMS surface) and the surface was thereby modified to be superhydrophobic. In addition, a thin PDMS skin that blocked holes and PDMS residues affixed in nickel microstructures was successively removed.</P>

붕장어 부산물로 제조한 붕장어탕의 식품학적 특성

허민수(Min Soo Heu),이택상(Take Sang Lee),김혜숙(Hye-Suk Kim),지성준(Seung Joon Jee),이재형(Jae Hyoung Lee),김형준(Hyung Jun Kim),윤민석(Min Seok Yoon),박신호(Shin Ho Park),김진수(Jin-Soo Kim) 한국식품영양과학회 2008 한국식품영양과학회지 Vol.37 No.4

붕장어 가공부산물인 머리와 frame를 효율적으로 이용하기 위한 일련의 연구로 붕장어 부산물을 이용한 붕장어탕의 개발을 시도하였고, 아울러 이의 식품성분 특성에 대하여도 살펴보았다. 살균조건 및 가온일수에 따른 붕장어탕의 저장성 부여를 위한 최적 살균조건은 F? value=8분으로 판단되었다. 붕장어탕의 일반성분은 수분의 경우 90.7%, 조단백질의 경우 4.8%, 조지방의 경우 2.6%, 조회분의 경우 1.5%를 나타내었다. 붕장어탕의 엑스분 질소 함량은 243.1 ㎎/100 g으로 시판 추어탕의 208.0 ㎎/100 g보다 높았다. 붕장어탕의 총 아미노산 함량은 4,310 ㎎/100 g이었고, 주요 구성아미노산은 glutamic acid(637.3 ㎎/100 g, 14.8%), glycine(409.1 ㎎/100 g, 9.5%) 및 alanine(404.4 ㎎/100 g, 9.3%)등이었다. 붕장어탕은 관능적인 비린내는 거의 감지되지 않았고, 맛은 우수하였으며, 항산화능이 인정되었으나 ACE 저해능은 크게 기대할 수 없었다. For the effective use of the conger eel by-products, such as head and frame, Tang, which is the Korean-type soup, from conger eel by-products (TCEB) was developed and its food component characterization was compared with that of commercial Chueotang, loach Tang. According to the results of viable cells and coliform group of TCEB heated at 115oC for various times, the reasonable F0 value was 8 min. The proximate composition of TCEB was 90.7% for the moisture, 4.8% for the protein, 2.6% for the lipid, and 1.5% for the ash. The extractive-nitrogen content of TCEB was 243.1 ㎎/100 g, which was higher than that of commercial Chueotang, 208.0 ㎎/100 g. The total amino acid content of TCEB was 4,310 ㎎/100 g and its major amino acids were glutamic acid (637.3 ㎎/100 g, 14.8%), glycine (409.1 ㎎/100 g, 9.5%) and alanine (404.4 ㎎/100 g, 9.3%). TCEB was not felt in the sensual fish odor and its sensual taste was good. The health functional properties for health of TCEB were 1.29 as a PF (protection factor) for antioxidative activity and 39.4% for angiotensin Ⅰ converting enzyme (ACE) inhibiting activity.

Effect of Jaeumkanghwatang (JEKHT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (2) - Oral Combination Treatment of Tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day Repeated Pretreated Rats with 8-day Repeated

Park, Soo Jin,Kwak, Min A,Park, Sung Hwan,Lee, Young Joon,Ku, Sae Kwang Society of Preventive Korean Medicine 2016 대한예방한의학회지 Vol.20 No.2

Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

Comparative evaluation of the algorithms for parametric mapping of the novel myocardial PET imaging agent ¹⁸ F-FPTP

Kim, Ji Who,Seo, Seongho,Kim, Hyeon Sik,Kim, Dong-Yeon,Lee, Ho-Young,Kang, Keon Wook,Lee, Dong Soo,Bom, Hee-Seung,Min, Jung-Joon,Lee, Jae Sung Springer Japan 2017 Annals of nuclear medicine Vol.31 No.6

<P><B>Objective</B></P><P>(<SUP>18</SUP>F-fluoropentyl)triphenylphosphonium salt (<SUP>18</SUP>F-FPTP) is a new promising myocardial PET imaging tracer. It shows high accumulation in cardiomyocytes and rapid clearance from liver. We performed compartmental analysis of <SUP>18</SUP>F-FPTP PET images in rat and evaluated two linear analyses: linear least-squares (LLS) and a basis function method (BFM) for generating parametric images. The minimum dynamic scan duration for kinetic analysis was also investigated and computer simulation undertaken.</P><P><B>Methods</B></P><P><SUP>18</SUP>F-FPTP dynamic PET (18 min) and CT images were acquired from rats with myocardial infarction (MI) (<I>n</I> = 12). Regions of interest (ROIs) were on the left ventricle, normal myocardium, and MI region. Two-compartment (<I>K</I><SUB>1</SUB> and <I>k</I><SUB>2</SUB>; 2C2P) and three-compartment (<I>K</I><SUB>1</SUB>–<I>k</I><SUB>3</SUB>; 3C3P) models with irreversible uptake were compared for goodness-of-fit. Partial volume and spillover correction terms (<I>V</I><SUB><I>a</I></SUB> and <I>α</I> = 1 − <I>V</I><SUB><I>a</I></SUB>) were also incorporated. LLS and BFM were applied to ROI- and voxel-based kinetic parameter estimations. Results were compared with the standard ROI-based nonlinear least-squares (NLS) results of the corresponding compartment model. A simulation explored statistical properties of the estimation methods.</P><P><B>Results</B></P><P>The 2C2P model was most suitable for describing <SUP>18</SUP>F-FPTP kinetics. Average <I>K</I><SUB>1</SUB>, <I>k</I><SUB>2</SUB>, and <I>V</I><SUB><I>a</I></SUB> values were, respectively, 6.8 (ml/min/g), 1.1 (min<SUP>−1</SUP>), and 0.44 in normal myocardium and 1.4 (ml/min/g), 1.1 (min<SUP>−1</SUP>), and 0.32, in MI tissue. Ten minutes of data was sufficient for the estimation. LLS and BFM estimations correlated well with NLS values for the ROI level (<I>K</I><SUB>1</SUB>: <I>y</I> = 1.06<I>x</I> + 0.13, <I>r</I><SUP><I>2</I></SUP> = 0.96 and <I>y</I> = 1.13<I>x</I> + 0.08, <I>r</I><SUP><I>2</I></SUP> = 0.97) and voxel level (<I>K</I><SUB>1</SUB>: <I>y</I> = 1.22<I>x</I> − 0.30, <I>r</I><SUP><I>2</I></SUP> = 0.90 and <I>y</I> = 1.26<I>x</I> + 0.00, <I>r</I><SUP><I>2</I></SUP> = 0.92). Regional distribution of kinetic parametric images (<I>αK</I><SUB>1</SUB>, <I>K</I><SUB>1</SUB>, <I>k</I><SUB>2</SUB>, <I>V</I><SUB>a</SUB>) was physiologically relevant. LLS and BFM showed more robust characteristics than NLS in the simulation.</P><P><B>Conclusions</B></P><P>Fast kinetics and highly specific uptake of <SUP>18</SUP>F-FPTP by myocardium enabled quantitative analysis with the 2C2P model using only the initial 10 min of data. LLS and BFM were feasible for estimating voxel-wise parameters. These two methods will be useful for quantitative evaluation of <SUP>18</SUP>F-FPTP distribution in myocardium and in further studies with different conditions, disease models, and species.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s12149-017-1171-6) contains supplementary material, which is available to authorized users.</P>

담배의 잎조직 배양에 있어서 기관형성과 동위효소 유형에 미치는 생장조절제의 영향

成淳基,金濬喆,成敏雄 慶尙大學校 1986 論文集 Vol.25 No.2

담배(N. tabacum cv. NC 2326) 잎조직 배양에서 기관형성에 가장 효과적인 생장조절제의 배지조성을 찾기위하여 NAA와 kinetin의 농도별 혼합처리 5종류 및 picloram과 BAP의 농도별 혼합처리 5종류의 배지에서 26℃ 조건으로 35일간 잎조직을 배양시켜 각 처리구에 대한 기관형성률을 조사하고, 6종류의 효소에 대한 동위효소 유형 및 단백질 함량은 기관형성이 가장 잘된 0.01㎎/l pocloram+0.6㎎/lBAP 처리구와 0.5㎎/l NAA+0.5㎎/l kinetin 처리구의 두 처리구의 배양체를 대상으로 조사한 결과는 다음과 같다. 1. NAA와 kinetin을 혼합처리한 5종류의 배지중 0.5㎎/l+0.5㎎/l kinetin 처리구에서 shoot와 뿌리가 각각 100% 및 50%로서 가장 높은 기관형성률을 나타냈다. picloram과 BAP 혼합처리구에서 callus형성률은 평균 6%로 callus 형성에는 효과적인 배지는 아니었으나 기관형성률은 높게 나타났다. 그 중 0.01㎎/l pocloram+0.5㎎/lBAP 처리구에서 shoot와 뿌리가 각각 100% 및 90%의 형성률을 나타내어 기관형성에 가장 효과적이었다. multiple shoot 형성에는 picloram과 BAP 혼합배지가 NAA와 kinetin 혼합배지보다 더욱 효과적임을 알 수 있었다. 2. 배양제의 단백질 함량은 기관형성 과정에서 배양이 진행됨에 따라 두 처리구에서 모두 감소하였으나 picloram과 BAP 혼합처리구는 NAA와 kinetin 혼합처리구보다 낮았다. peroxidase의 활성은 이와 반대로 picloram과 BAP 혼합처리구에서 약 8배 높게 나타났다. 3. peroxidase와 malate dehydrogenase 동위효소들의 활성은 shoot가 형성됨에 따라 두 처리구 모두 증가하였으나, lactate dehydrogenase 동위효소들은 두 처리구 모두 감소하였다. 이러한 경향은 두 처리구 중에서 picloram과 BAP 혼합처리구에서 더욱 뚜렷하였다. 그러나 esterase, acid phosphatase, aspartate aminotransferase 동위효소들의 활성은 shoot 형성중에 두 처리구 모두 뚜렷한 변화가 없었다. 4. 6종류의 효소에서 분리된 동위효소의 수는 두 처리구를 합쳐 peroxidase에서 12개, acid phosphatase에서 6개, aspartate aminotransferase에서 9∼13개, lactate dehydrogenase에서 3∼5개, esterase에서 10∼16개가 각각 확인되었다. Tabaco (Nicotiana tabacum cv. NC 2326) leaf tissues were cultured on Murashige and Skoog medium containing various concentrations and combinations of some growth regulators at 26℃ for 35 days. The obtained results were summarized as follow; 1. Organ formation was 100% in shoot and 50% in root on the medium containing 0.5㎎/l NAA and 0.5㎎/l kinetin. On the medium containing 0.01㎎/l picloram and 0.5㎎/l BAP, organ formation displayed 100% multiple shoot formation and 90% root formation without callus formations. Multiple shoot formations were enhanced more by picloram and BAP groups than by NAA and kinetin groups. 2. During the shoot formation, protein content in the cultures on the medium containing picloram and BAP was lower than NAA and kinetin groups, but peroxidase activity in the former medium was higher about eight times than that in the latter medium. 3. The activity of anodic peroxidase and malate dehydrogenase isozyme increased during the shoot formation, whereas that of lactate dehydrogenase isozyme decreased. However the activity of esterase, acid phosphatase, and aspartate aminotransferase did not change. 4. All the isozymes were separated with 12 bands in peroxidase, 6 in acid phosphatase, 9∼13 in malate dehydrogenase, 3∼5 in lactate dehydrogenase, 10∼16 in esterase, 6 in aspartate aminotransferase during the shoot formation.