• Journal of Pharmaceutical Investigation
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• 제9권2호
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• pp.11-21
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• 1979

It has been reported from our department that a few agents, such as $K_2S_2O_5,\;NaHSO_3,$ nicotinamide have a marked stabilizing effect in vitro on metoclopramide which is relatively unstable compound. In order to study the effect of these stabilizers on the action of metoclopramide in vitro, the fate of this compound combined with $K_2S_2O_5,\;NaHSO_3$ and nicotinamide, respectively, was studied and furthermore, the change of the biological activity of metoclopramide due to these stabilizers was studied by using the isolated stomach strip of rat. The blood concentration of metoclopramide was measured by using Bakke's method at the various time after intravenous injection of the mixed metoclopramide solution with the stabilizers. In order to study the excretion of the drug, rabbits were anesthesized and catheterized into bladder for withdrawal of urine. After intravenous injection of the mixed metoclopramide solution, urine was collected for 5 hours and the conjugated forms of metoclopramide as well as the free form were determined by using Arita's method. In the biological study of the metoclopramide combined with stabilizers, the contractability of the isolated rat stomach strip was observed by using polygraph recorder. The results were following: 1. When metoclopramide was administered with nicotinamide as stabilizer, the blood concentration of the unchanged from and the rate of the clearance of this compound were very similar to that of metoclopramide alone. On the other hand, other stabilizers, $K_2S_2O_5\;and\;NaHSO_3$, brought about 40% decrease in blood concentration of the unchanged form at 15 min after intravenous injection however, the rate of clearance of metoclopramide with $K_2S_2O_5\;or\;NaHSO_3$ was very slow. 2. In the case of urinary excretion, the excretory pattern of the metabolites of metoclopramide with $NaHSO_3$ or nicotinamide was very similar to that of metoclopramide alone. But metodopramide plus $K_2S_2O_5$ group showed the maked depression of excretion for first 1 hour. 3. In composition of metabolites, when metoclopramide was administered with $K_2S_2O_5$ or $NaHSO_3$, the sulfonate conjugation was predominant. But the glucuronic acid conjugation was predominant in metoclopramide plus nicotinamide gronp. 4. In the experiments on the biological activity of the metoclopramide, this compound exhibited the marked contracting effect in isolatd rat stomach strip. Specially, the meetoclopramide combined with $K_2S_2O_5$ showed the strong contraction of the isolated strip, suggesting the potenciating effect of $K_2S_2O_5$ on the action of metoclopramide in the isolated strip.

• Translational and Clinical Pharmacology
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• 제25권2호
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• pp.67-73
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• 2017

Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3', 5'-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

• 분석과학
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• 제11권5호
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• pp.374-385
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• 1998

주로 음식물의 섭취에 기인하는 phytoestrogen은 말초 신경 및 암 세포내에서 estrogen의 생성을 저해하거나, 농도를 감소시킴으로서 estrogen-dependent cancer의 잠재적인 항 증식 물질(antipromotional compound)로 알려지고 있으며, 이러한 이유로 estrogen 대사 과정에 대한 phytoestrogen의 관련성 여부가 연구의 대상이 되고 있다. 이에, 본 연구에서는 phytoestrogen과 estrogen 대사체들을 동시에 분석하기 위한 방법으로써 Serdolit AD-2 수지를 이용한 고체상 추출과 효소 가수분해, 액체-액체 추출 방법을 이용한 전처리 과정을 확립하였으며, 이를 MSTFA/TMCS 혼합액에 의해 trimethylsilyl(TMS) ether 형태로 유도체화 한 후 GC/MS의 SIM(selected ion monitoring) 방법으로 동시에 분석, 정량할 수 있는 조건을 설정하였다. 본 실험 방법의 정확도와 정밀도는 within-a day 및 day-to-day 시험으로 평가되었으며 회수율과 검출 한계는 각각 71.96~105.66%, 2~4 ng/mL 이었다. 이 방법을 이용하여 정상 성인 남녀의 뇨중에 존재하는 17종의 estrogen과 5종의 phytoestrogen 농도를 측정하였으며, 그 결과 남성과 여성의 뇨중 phytoestrogen과 estrogen의 농도 분포에 현저한 차이가 있음을 알 수 있었다.

• 전기화학회지
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• 제17권3호
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• pp.172-178
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• 2014

이 논문에서는 체내에 존재하는 작은 유기물의 하나인 마뇨산을 빠르고 정량적으로 검출하기 위하여 전기화학적 면역분석법을 이용하였다. 마뇨산은 톨루엔이 인체에 노출되었을 때의 주된 신진 대사 물질로서 대표적인 생화학적 지표물질이다. 톨루엔 노출에 대한 신속하고 정확한 관찰은 산업현장에서 건강관리를 위하여 매우 중요하다. 그래서 마뇨산을 빠르고 정확하게 검출하기 위하여 전기화학적 면역분석법을 실시하였다. 본 연구에서 제시하는 새로운 면역분석방법은 전기화학적 활성물질의 하나인 도파민을 측정물질인 마뇨산과 직접 공유결합을 통하여 항원이 포함된 복합체를 합성하였다. 전기화학적 측면에서 도파민은 두 개의 하이드록시기를 가지고 있어 매우 뛰어난 산화/환원 신호를 보인다. 또한 도파민-마뇨산 복합물도 뛰어난 산화/환원 신호를 보이기 때문에 면역 분석에 적합하다. 도파민-마뇨산 복합물과 마뇨산의 항체와의 균질경쟁반응을 전기화학적인 방법을 통하여 관찰하였다. 본 면역분석을 통하여 실시한 결과는 마뇨산의 농도가 0.010~2.500 mg/mL 까지 정량적으로 분석됨으로써 실제 면역 센서에 적용할 수 있음을 확인하였다.

• Journal of Preventive Medicine and Public Health
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• 제29권4호
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• pp.863-875
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• 1996

In order to prepare the fundamental data for the health promotion by assessing the exposure level of styrene, the author determined the concentration of mandelic acid and phenylglyoxylic acid in urine of 42 workers who were exposed to styrene by high performance liquid chromatography and surveyed 16 symptoms, by questionnaire and also tested neurobehavioral test(digit symbol, benton visual retention) in 2 FRP plants of Kyung Nam area from July to September, 1995. Control was sampled by age sex matching method. The concentration of styrene in air was determined by gas chromatography. The results were as follows; 1. Geometric mean concentration of styrene in air was 17.4ppm, geometric mean concentration of mandelic acid(MA) in urine were 404.3mg/g creatinine for exposure group, 46.4mg/g creatinine for control group, geometric mean concentration of phenylglyoxylic acid(PGA) in urine were 57.5mg/g creatinine for exposure group, 9.5mg/g creatinine for control group. Mean concentration of MA and PGA showed statistically significant difference between exposure group and control group(p<0.01). 2. Number of symptom were 2.9 for exposure group, 3.3 for control group, number of digit symbol were 24.1 for exposure group, 32.5 for control group, number of Benton visual retention test were 6.1 for exposure group, 6.0 for control group, respectively. As result of adjusting the education year, number of Benton visual retention test showed statistically significant difference between exposure group and control group(p<0.05). 3. Excellent correlation were observed between environmental styrene exposure and urinary MA(r=0.80), PGA(r=0.73), and MA+PGA(r=0.81).

• Molecular & Cellular Toxicology
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• 제4권1호
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• pp.5-10
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• 2008

The effect of obesity on the drug-metabolizing enzymes remains an important issue for clinician since obesity is a world wide epidemic problem. However, little is known about the effects of obesity on flavincontaining monooxygenase (FMO) production and activity. We show here for the first time that in vivo FMO activity determined by urinary ranitidine (RA) metabolites ratio in human, was higher in subjects with a high body mass index (BMI, kg/$m^2$, 21.97-30.32) than in those with an intermediate BMI (range 19.38-21.83). Moreover, there was a significant correlation between FMO activity and BMI in 209 subjects. In high fat diet-induced obese mice, we also observed that the hepatic expression of FMO (225% of lean mice) and the activity measured by the RA Noxidation rate ($513{\pm}58.1$ vs. $349{\pm}66.0$ pmol/hr per mg protein) were significantly higher than in lean mice fed a control diet. Unknown factors rather than leptin or insulin appeared to regulate the hepatic FMO production. Thus, FMO activity may be increased in obese or overweight individuals. Moreover, the regulation of FMO activity in subjects with morbid obesity, with or without complications and its clinical implications, should be investigated further.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.248-254
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• 2002

Single cell gel electrophoresis assay was carried out to evaluate DNA damage in T-and B-lymphocytes from rats exposed to benzene and the correlation between DNA damage and the level of t,t-muconic acids, which are urinary benzene metabolites, was investigated. In control rats, the mean values of Olive tail moments in T-and B-lymphocytes were 1.507$\pm$0.187 and 1.579$\pm$0.206 respectively. DNA damages of T-lymphocytes in rats exposed for 4 weeks showed the highest Olive tail moments at each benzene concentration examined (2.72-4.351). However this DNA damage was decreased after 6 weeks of exposure (1.74-2.09). DNA damages of B-lymphocytes did not show such differences with exposure time or benzene concentration (1.49-2.07) except at 200 ppm at 4 weeks. T-lymphocytes show significantly more damages than B-lymphocyte upon acute exposure to benzene.

• 농약과학회지
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• 제20권2호
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• pp.172-180
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• 2016

본 연구는 국내 일부 농업인을 대상으로 유기인계 농약 노출수준과 농약살포 특성의 관련성을 규명하기 위하여 수행되었다. 소변시료를 채취하여 GC/MSD와 GC/MS/MS를 이용하여 분석하였으며, 소변 중 DMP, DMTP, DEP, DETP를 대상으로 검출률 및 노출수준을 평가 하였다. 검출률은 DMP, DMTP에서 캡이 없는 SS살포기가 캡이 있는 SS살포기보다 높았고, 보호구 착용률이 낮을수록 높았다. 노출수준은 동력 분무기가 가장 높았고, 캡이 있는 SS살포기에서 낮게 나타났다. 또한, 착용 보호구 개수가 증가할수록 노출수준이 낮아짐을 확인할 수 있었다. 검출률은 카이제곱, 노출수준 비교는 연령 및 살포방법을 보정한 GLM을 이용하여 분석하였다.

• 대한유전성대사질환학회지
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• 제16권1호
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• pp.10-17
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• 2016

3-Methylglutaconic aciduria (3-MGA-uria)는 임상적 및 유전적으로 다양한 대사질환들을 총칭하는 질환군이다. 대부분의 경우 소변에서 3-MGA가 약간 증가되어 있거나 다른 대사물질이 같이 분비되는 경우에는 다른 대사질환이나 미토콘드리아 질환 등을 감별해야 한다. 그러나 지속적이며 반복적으로 소변 유기산 분석에서 3-MGA가 40-1,000 mmol/mol creatinine으로 상승되어 있는 경우에는 3-MGA-uria를 일으키는 질환을 감별해야 한다. 3-MGA-uria는 5가지 타입의 질환으로 분류되어 있고 Leucine 대사 질환인 일차성 3-MGA-uria와 4가지의 미토콘드리아 이상질환이 포함되어 있으며 임상적 및 생화학적 소견은 다양하게 나타날 수 있다. 일차성 3-MGA-uria인 3-methyl-glutaconyl-CoA hydratase 결핍증 환자에서는 소변의 3-MGA가 다른 질환군에 비해 많이 증가되어 있고 소변에서 3-hydroxyisovaleric acid가 분비되는 것이 감별점이라 할 수 있다. 다른 종류의 3-MGA-uria의 경우에는 대개 임상적으로 잘 분류가 되어 있는 Barth 증후군, Costeff 증후군, TMEM 70 결핍, MEGDEL 증후군, and DCMA 증후군 등이 포함되어 있어 시신경 검사, 심장초음파 검사 및 발달 검사 등을 통하여 감별진단에 이를 수 있다. 이에 본 종설에서는 선별검사를 통해 3-MGA-uria가 양성이 나온 환자들의 적절한 진단 및 치료를 위한 지침을 제시하고자 한다.

• Asian-Australasian Journal of Animal Sciences
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• 제13권7호
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• pp.967-973
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• 2000

A metabolism trial was conducted with 28 Najdi rams allocated into seven dietary groups to evaluate the effect of dietary inclusion of Salicornia bigelovii Torr biomass on nutrient digestibility, rumina I fluid metabolites and nitrogen and mineral balances. Either the stems (ST) or spikes (SP) of this seawater-irrigated halophyte were incorporated into complete diets at rates of 0, 10, 20 and 30% levels, replacing equal amounts of rhodesgrass hay in a ground mixed control diet. Digestibility of DM, OM, EE, NFE and fecal and urinary nitrogen were not affected by increased level of ST in the diet. As level of ST increased from 0 to 20% in the diets, CP digestibility and nitrogen retention approached their maximum (p<0.01), whereas CF digestibility reached its minimum (p<0.01). On the other hand, except for EE, digestion of all nutrients and nitrogen retention were linearly depressed (p<0.01) as SP increased in the diets from 10 to 30% level. Concentration of ammonia-N, total VFA and pH values in the rumen fluid were lower (p<0.01) with the ST- or SP-fed diets than with the control diet. Increasing level of ST or SP in the diet was associated with an increase (p<0.01) in the proportion of acetate and a decline (p<0.01) in molar percentage of propionate in the ruminal fluid. Sodium absorption increased (p<0.01) with increased ST and SP in the diets up to the 10 and 20% level, respectively, followed by constant absorption values up to the 30% level. When the level of ST in the diet gradually increased to 30%, a concomitant increased (p<0:01) in Ca and P absorption were obvious; whereas, increased level of SP in the diets from 0 to 30% resulted in noticeable (p<0.01) depression in Ca and P apparent absorption.