• Journal of Pharmaceutical Investigation
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• v.9 no.2
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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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• v.25 no.2
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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.

• Analytical Science and Technology
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• v.11 no.5
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• pp.374-385
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• 1998

Phytoestrogens are biologically active compounds derived from plants foods. It had been suggested that phytoestrogens, by inhibiting aromatase in peripheral and/or cancer cells and lowering estrogen levels, may play a protective role as antipromotional compounds during growth of estrogen-dependent cancers. Therefore, simultaneous analysis of estrogens and phytoestrogens is necessary to elucidate the possible involvement of phytoestrogens in estrogen metabolism. In this view, we developed a simple and reproducible procedure to quantitatively determine estrogen and phytoestrogen metabolites. The proposed method consisted of solid phase extraction using preconditioned Serdolit AD-2 resin, enzyme hydrolysis with ${\beta}$-glucuronidase/arylsulfatase from Helix pomatia, liquid-liquid extraction and TMS-ether derivatization. And the final determination was carried out by gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring mode (SIM). The precision and accuracy of this method was evaluated through within-a-day and day-to-day test. Recovery range and detection limit were 71.96~105.66%, 2~4 ng/mL, respectively. Using this method, 17 estrogen and 5 phytoestrogen compositions in urine of normal subjects were analyzed. It was found that amounts and relative distribution of urinary phytoestrigens and estrogens showed different pattern in male and female subjects.

• Journal of the Korean Electrochemical Society
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• v.17 no.3
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• pp.172-178
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• 2014

In this work, we describe an electrochemical immunosensor for simple, fast and quantitative detection of a urinary hippuric acid (HA). Urinary HA, of molecular weight 180 DA, is one of the major metabolites and biological indicators in toluene-exposed humans. Simple and ubiquitous monitoring of exposure to toluene is very important in occupational health care. We propose the electrochemical immunoassay based on the dopamine-antigen conjugate for detecting hippuric acid. Our electrochemical immunoassay system employs a conjugate of dopamine (DA) as an electrochemical active molecule and hippuric acid (HA) as an antigen. As an electrochemical aspect, dopamine (DA) containing two hydroxyl group can show excellent redox signal. Also, dopamine-tethered hippuric acid (DA-HA) shows the reversible redox signal in the immunoassay. The competition between HA and DA-HA generated electric signals proportional to HA concentration. The electrochemical immunoassay was performed with DA-HA on the screen printed carbon electrodes (SPCEs), and then applies the mixture antigen (HA) and HA-antibody. The electrical signals were proportional to HA in the range of 0.010~2.500 mg/mL which is enough range to be used for the point-of-care.

• Journal of Preventive Medicine and Public Health
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• v.29 no.4 s.55
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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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• v.4 no.1
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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.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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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.

• The Korean Journal of Pesticide Science
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• v.20 no.2
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• pp.172-180
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• 2016

This study was conducted to evaluate the relations between the exposure level of organophosphates (OPs) pesticide and application factors among rural farmers. The urinary dialkylphosphates, metabolites of organophosphorus pesticides, including DMP, DEP, DMTP and DETP were analyzed by GC/MSD and GC/MS/MS. The DMP and DMTP were detected more in the use of a speed sprayer without cap than with a capped one. Also, the less farmers wore the personal protective equipment (PPE), the more these were detected. The amount of organophosphorus exposure was the highest in the use of a power sprayer. However, it was low when a farmer applied pesticides with a speed sprayer with cap and wore more PPE. In this study, the detection rate was analyzed by chi-square test, the exposure level of OPs was analyzed by a generalized linear model.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.10-17
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• 2016

The 3-methylglutaconic aciduria (3-MGA-uria) is a heterogeneous group of several inborn errors of metabolism characterized by increased urinary excretion of 3-methylglutaconic acid. In most cases, 3-MGA is only slightly increased and combined with other metabolites. However, repeated and significant excretion of 3-MGA (40->1,000 mmol/mol creatinine) is a hallmark of the disorders of 3-MGA-urias. There have identified five distinct types of disorders: inborn errors of leucine metabolism and four disorders of mitochondrial dysfunction through different mechanism. The range of clinical and biochemical findings in this condition is variable. In the patients with 3-methylglutaconyl-CoA hydratase deficiency, increased 3-hydroxyisovaleric acid is useful in the differential diagnosis. Other forms of 3-MGA-urias are welldefined clinically such as Barth syndrome, Costeff syndrome, TMEM 70 defect, MEGDEL syndrome, and DCMA syndrome. We provide an overview of the expanding clinical spectrum and differential diagnosis of the 3-MGA-urias.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.7
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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.