• Title/Summary/Keyword: Mechanism of action

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Polymorphisms of the NR3C1 gene in Korean children with nephrotic syndrome (한국 신증후군 환아에서 NR3C1 유전자 다형성 분석)

  • Cho, Hee Yeon;Choi, Hyun Jin;Lee, So Hee;Lee, Hyun Kyung;Kang, Hee Kyung;Ha, Il Soo;Choi, Yong;Cheong, Hae Il
    • Clinical and Experimental Pediatrics
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    • v.52 no.11
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    • pp.1260-1266
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    • 2009
  • Purpose : Idiopathic nephrotic syndrome (NS) can be clinically classified as steroid-sensitive and steroid-resistant. The detailed mechanism of glucocorticoid action in NS is currently unknown. Methods : In this study, we investigated 3 known single nucleotide polymorphisms (SNPs) (ER22/23EK, N363S, and BclI) of the glucocorticoid receptor gene (the NR3C1 gene) in 190 children with NS using polymerase chain reaction-restriction fragment length polymorphism and analyzed the correlation between the genotypes and clinicopathologic features of the patients. Results : Eighty patients (42.1%) were initial steroid nonresponders, of which 31 (16.3% of the total) developed end-stage renal disease during follow-up. Renal biopsy findings of 133 patients were available, of which 36 (31.9%) showed minimal changes in NS and 77 (68.1%) had focal segmental glomerulosclerosis. The distribution of the BclI genotypes was comparable between the patient and control groups, and the G allele frequencies in both the groups were almost the same. The ER22/23EK and N363S genotypes were homogenous as ER/ER and NN, respectively, in all the patients and in 100 control subjects. The BclI genotype showed no correlation with the NS onset age, initial steroid responsiveness, renal pathologic findings, or progression to end-stage renal disease. Conclusion : These data suggested that the ER22/23EK, N363S, and BclI SNPs in the NR3C1 gene do not affect the development of NS, initial steroid responsiveness, renal pathologic lesion, and progression to end-stage renal disease in Korean children with NS.

Sports Biomechanical Analysis of Physical Movements on the Basis of the Patterns of the Ready Poses (준비동작의 형태 변화에 따른 신체 움직임의 운동역학적 분석)

  • Lee, Joong-Sook
    • Korean Journal of Applied Biomechanics
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    • v.12 no.2
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    • pp.179-195
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    • 2002
  • The purpose of this research is to provide a proper model by analyzing the sports biomechanical of physical movements on the basis of the two patterns(open-stance and cross-stance) at the ready-to-start pose. The subjects for this study are composed of five male handball players from P university and five female shooting players from S university. Three-way moving actions at start(right, left, and forward) are recorded with two high-speed video cameras and measured with two Force platforms and a EMG system. Three-dimensional action analyzer, GRF system, and Whole body reaction movement system are used to figure out the moving mechanisms at the start pose. The analytic results of the moving mechanism at the start pose were as follows. 1. Through examining the three-way moving actions at start, I have found the cross-stance pose is better for the moving speed of body weight balance than the open-stance one. 175 degree of knee joint angle at "take-off" and 172 degree of hip joint angle were best for the start pose. 2. The Support time and GRF data shows that the quickest center of gravity shift was occurred when cross-stanced male subjects started to move toward his lefthand side. The quickest male's average supporting time of left and right foot is 0.19${\pm}$0.07 sec., 0.26${\pm}$0.06sec. respectively. The supporting time difference between two feet is 0.07sec. 3. Through analyzing GRF of moving actions at start pose, I have concluded that more than 1550N are overloaded on one foot at the open-stance start, and the overloaded force may cause physical injury. However, at the cross-stance pose, The GRF are properly dispersed on both feet, and maximum 1350N are loaded on one foot.

Regulation of $LH{\beta}$ subunit mRNA by Ovarian Steroid in Ovariectomized Rats (난소제거된 흰쥐에서 난소호르몬에 의한 $LH{\beta}$ subunit의 유전자 발현조절)

  • Kim, Chang-Mee;Park, Deok-Bae;Ryu, Kyung-Za
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.225-235
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    • 1993
  • Pituitary LH release has been known to be regulated by the hypothalamic gonadotropin releasing hormone (GnRH) and the gonadal steroid hormones. In addition, neurotransmitters and neuropeptides are actively involved in the control of LH secretion. The alteration in LH release might reflect changes in biosynthesis and/or posttranslational processing of LH. However, little is known about the mechanism by which biosynthesis of LH subunits is regulated, especially at the level of transcription. In order to investigate if ovarian steroid hormones regulate the LH subunit gene expression, ${\alpha}\;and\;LH{\beta}$ steady state mRNA levels were determined in anterior pituitaries of ovariectomized rats. Serum LH concentrations and pituitary LH concentrations were increased markedly with time after ovariectomy. ${\alpha}\;and\;LH{\beta}$ subunit mRNA levels after ovariectomy were increased in a parallel manner with serum LH concentrations and pituitary LH contents, the rise in $LH{\beta}$ subunit mRNA levels being more prominent than the rise in ${\alpha}\;subunit$ mRNA. ${\alpha}\;and\;LH{\beta}$ subunit mRNA levels in ovariectomized rats were negatively regulated by the continuous treatment of ovarian steriod hormones for $1{\sim}4\;days$ and $LH{\beta}\;subunit$ mRNA seemed to be more sensitive to negative feedback of estradiol than progesterone. Treatment of estrogen antagonist, LY117018 or progesterone antagonist, RU486 significantly restroed LH subunit mRNA levels as well as LH release which were suppressed by estradiol or progesterone treatment. These results suggest that ovarian steroids negatively regulate the LH synthesis at the pretranslational level by modulating the steady state levels of ${\alpha}\;and\;LH{\beta}\;subunit$ mRNA and $LH{\beta}\;subunit$ mRNA seemed to be more sensitive to negative feedback action of estradiol than progesterone.

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Mechanisms of Tributyltin-induced Leydig Cell Apoptosis (유기주석화합물이 웅성생식세포주에 미치는 영향)

  • Lee, Kyung-Jin;Kim, Deok-Song;Ra, Myung-Suk;Wui, Seong-Uk;Im, Wook-Bin;Park, Hueng-Sik;Lee, Jong-Bin
    • Environmental Analysis Health and Toxicology
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    • v.18 no.2
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    • pp.89-94
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    • 2003
  • Tributyltin (TBT) used world-wide in antifouling paints for ships is a widespread environmental pollutant and cause reproductive organs atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of toxicity in reproductive organs by TBT. In this study, we investigated that the mechanisms underlying DNA fragmentation induced by TBT in the rat leyding cell line, R2C. Effects of TBT on intracellular Ca$\^$2+/ level and reactive oxygen species (ROS) were investigated in R2C cells by fluorescence detector. TBT significantly induced intracellular Ca$\^$2+/ level in a time-dependent manner. The rise in intracellular Ca$\^$2+/ level was followed by a time-dependent generation of reactive oxygen species (ROS) at the cytosol level. Simultaneously, TBT induced the release of cytochrome c from the mitochondrial membrane into the cytosol. Furthermore, ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca$\^$2+/ chelator, indicating the important role of Ca$\^$2+/ in R2C during these early intracellular events. In addition, Z-DEVD FMK, a caspase-3 inhibitor, decreased apoptosis by TBT. Taken together, the present results indicated that the apoptotic pathway by TBT might start with an increase in intracellular Ca$\^$2+/ level, continues with release of ROS and cytochrome c from mitochondria, activation of caspases,and finally results in DNA fragmentation.

Influence of Hypoxia on Catecholamine Secretion Evoked by DMPP, McN-A-343, Excess $K^+$ and ACh from The Perfused Rat Adrenal Gland (저산소증이 흰쥐 관류부신에서 DMPP, McN-A-343, Excess $K^+$ 및 Ach의 카테콜아민 분비작용에 미치는 영향)

  • Lim Dong-Yoon;Heo Jae-Bong;Park Yoo Han
    • The Korean Journal of Pharmacology
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    • v.31 no.1 s.57
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    • pp.63-74
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    • 1995
  • It has been known that, during hypoxia, the adrenal medulla is activated to release catecholamines (CA) while hypoxia also inhibits high $K^+$ -induced CA secretion in the cultured bovine adrenal chromaffin cells. The present study was attempted to examine the effect of hypoxia on CA secretion evoked by chlinergic stimulation and membrane-depolarization from the isolated perfused rat adrenal glands and also to clarify its mechanism of action. For this purpose, using the isolated rat adrenal glands, the effects of hypoxia on CA release evoked by nicotinic ($N_1$) and muscarinic ($M_1$) receptor agonists, membrane-depolarizing agent, $Ca^{++}$-channel activator, intracellular $Ca^{++}$-releaser and ACh were determined. Experiments were carried out, perfusing Krebs solution pre-equilibrated with a gas mixture of 95% N_2$ and 5% $CO_2$. Hypoxia was maintained for $3{\sim}4$ hours through the experiments. Hypoxia gradually caused a time-dependent seduction in CA secretion evoked by DMPP ($100{\mu}M$), McN-A-343 ($100{\mu}M$), ACh (5.32 mM), Bay-K-8644 ($10{\mu}M$) and high $K^+$ (56 mM) respectively. How-ever, it did not affect CA secretion evoked by cyclopiazonic acid ($10{\mu}M$). Hypoxia itself also did fail to produce any influence on spontaneous secretory response of CA. These experimental results suggest that hypoxia depresses CA release evoked by both cholinergic stimulation and membrane-depolarization from the isolated rat adrenal medulla, and that this inhibitory activity may be due to the result of the direct inhibition of $Ca^{++}$ influx into the chromaffin cells without any effect on the calcium mobilization from the intracellular store.

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Neuroprotective effects of Momordica charantia extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SK-N-MC cells (산화적 스트레스에 대한 여주 (Momordica charantia) 추출물의 항산화 효과 및 세포사멸 억제 기전을 통한 신경세포보호효과)

  • Kim, Kkot Byeol;Lee, Seonah;Heo, Jae Hyeok;Kim, Jung hee
    • Journal of Nutrition and Health
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    • v.50 no.5
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    • pp.415-425
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    • 2017
  • Purpose: Many studies have suggested that neuronal cells protect against oxidative stress-induced apoptotic cell death by polyphenolic compounds. We investigated the neuroprotective effects and the mechanism of action of Momordica charantia ethanol extract (MCE) against $H_2O_2-induced$ cell death of human neuroblastoma SK-N-MC cells. Methods: The antioxidant activity of MCE was measured by the quantity of total phenolic acid compounds (TPC), quantity of total flavonoid compounds (TFC), and 2,2-Diphenyl-1-pycrylhydrazyl (DPPH) radical scavenging activity. Cytotoxicity and cell viability were determined by CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Antioxidant enzyme (SOD-1,2 and GPx-1) expression was determined by real-time PCR. Mitogen-activated protein kinases (MAPK) pathway and apoptosis signal expression was measured by Western blotting. Results: The TPC and TFC quantities of MCE were 28.51 mg gallic acid equivalents/extract g and 3.95 mg catechin equivalents/extract g, respectively. The $IC_{50}$ value for DPPH radical scavenging activity was $506.95{\mu}g/ml$ for MCE. Pre-treatment with MCE showed protective effects against $H_2O_2-induced$ cell death and inhibited ROS generation by oxidative stress. SOD-1,2 and GPx-1 mRNA expression was recovered by pre-treatment with MCE compared with the presence of $H_2O_2$. Pre-treatment with MCE inhibited phosphorylation of p38 and the JNK pathway and down-regulated cleaved caspase-3 and cleaved PARP by $H_2O_2$. Conclusion: The neuroprotective effects of MCE in terms of recovery of antioxidant enzyme gene expression, down-regulation of MAPK pathways, and inhibition apoptosis is associated with reduced oxidative stress in SK-N-MC cells.

Effects of vitamin C as antioxidant on recovery of left ventricular function after ischemia and reperfusion in isolated rat heart (항산화제로서 비타민 C가 적출된 쥐심장에서 허혈 및 재관류후 좌심실 기능회복에 미치는 영향)

  • 류한영;이철주
    • Journal of Chest Surgery
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    • v.29 no.6
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    • pp.593-598
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    • 1996
  • The large number of past investigation on extended myocardial protection clearly indicates that cold potassium cardioplegia and topical cooling have limited capabilities. Accordingly, more recent experimen- tal approaches have focused on the modalities of reperfusion and their implication on postischemic myo- cardial recovery. Oxygen may play a crucial role in the development of ischemic and reperfusion injury. Reactive oxygen radicals may be produced during ischemia or reperfusion after incomplete reduction of molecular oxygen or from other pathway and then induce fatal injury of the heart. The important obser- vation of oxygen-induced myocardial damage during reperfusion has led to the concept of applying oxy- gen free radical scavengers. So, this study is on dietary vitamin C supplementation as antioxidant in rats to determine whether or not they have a higher tolerance against cardiac ischemia-reperf'usion injury under Langendorff system. Male or female Sprague-Dawley rats (190-33Og) were randomly separated into two groups. Group A was not treated(n=10). Group B received vitamin C supplement (n=10). Experiment was performed 24 hours after vitamin C 200mg fed orally as injectable ascorbic acid. There were significant differences in contractile parameters between control and vitamin C-treated group. The RLVP (r te of post/preischemic left ventricular pressure) and Rdp/dt (rate of post/preischemic dp/dt) were significant statistically between two groups (p<0.05). But, RHR (rate of post/preischemic heart rate), time to first beat and sta'utilization were not significant. In conclusion, pretreatment with the antioxidant, ascorbic acid, was found to preserve left ventricular contractile function. But the precise mechanism of action of ascorbic acid has not as yet been determined, so further study will be required.

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Improvement in Antagonistic Ablility of Antagonistic Bacterium Bacillus sp. SH14 by Transfer of the Urease Gene. (Urease gene의 전이에 의한 길항세균 Bacillus sp. SH14의 길항능력 증가)

  • 최종규;김상달
    • Microbiology and Biotechnology Letters
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    • v.26 no.2
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    • pp.122-129
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    • 1998
  • It were reported that antifungal mechanism of Enterobacter cloacae is a volatile ammonia that produced by the strain in soil, and the production of ammonia is related to the bacterial urease activity. A powerful bacterium SH14 against soil-borne pathogen Fusarium solani, which cause root rot of many important crops, was selected from a ginseng pathogen suppressive soil. The strain SH14 was identified as Bacillus subtilis by cultural, biochemical, morphological method, and $API^{circledR}$ test. From several in vitro tests, the antifungal substance that is produced from B. subtilis SH14 was revealed as heat-stable and low-molecular weight antibiotic substance. In order to construct the multifunctional biocontrol agent, the urease gene of Bacillus pasteurii which can produce pathogenes-suppressive ammonia transferred into antifungal bacterium. First, a partial BamH I digestion fragment of plasmid pBU11 containing the alkalophilic B. pasteurii l1859 urease gene was inserted into the BamH I site of pEB203 and expressed in Escherichia coli JM109. The recombinant plasmid was designated as pGU366. The plasmid pGU366 containing urease gene was introduced into the B. subtilis SH14 with PEG-induced protoplast transformation (PIP) method. The urease gene was very stably expressed in the transformant of B. subtilis SH14. Also, the optimal conditions for transformation were established and the highest transformation frequency was obtained by treatment of lysozyme for 90 min, and then addition of 1.5 ${mu}g$/ml DNA and 40% PEG4000. From the in vitro antifungal test against F. solani, antifungal activity of B. subtilis SH14(pGu366) containing urease gene was much higher than that of the host strain. Genetical development of B. subtilis SH14 by transfer of urease gene can be responsible for enhanced biocontrol efficacy with its antibiotic action.

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Prevention of Discoloration and Storage Stability in Canned Ark Shell (새고막 통조림 변색방지 및 저장중 품질변화)

  • 배태진;김귀식
    • The Korean Journal of Food And Nutrition
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    • v.11 no.2
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    • pp.243-248
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    • 1998
  • Ark shell was known as shellfish that had hemoglobin as blood pigment and the action of mecidine, was consumed the great part of it as raw material, though it was produced about 13,000 M/T per year. Ark shell was processed the infinitesimal quantity as conned product, bout canned ark shell had problem that occurrenced discoloration after heat treatment during processing and storage. This discoloration mechanism during processing and storage was not cleared. This study was carried out to understand characteristics of the hemoglobin as blood pigment and carotenoid as meat pigment in ark shell and management of proper processing conditions for prevention of oxidation and discoloration by thermal treatment. When treated by digestion of 0.1% BHA, 0.1% Tenox-II, 0.5% Na2EDTA, 0.05% NDGA and 3% salt soln., 0.1% BHA solution was most suitable for stability of carotenoid that the retention ratio of carotenoids were 63.1% after heating to 116$^{\circ}C$ for 120 minutes. In preparation of canned ark shell and storage at 37$\pm$1$^{\circ}C$ for 60 days, the chemical composition, pH and salinity ere stable. And contents of total carotenoid were decreased slightly from 0.83mg% to 0.727mg%. The viable cell count were 6.92$\times$103 cfu/ml at raw ark shell, after processed and storage were not detected. The predominant amino acids in the raw ark shell were glutamic acid(19.7%), arginine(16.0%), glycine(12.6%), alanine(12.2%) and aspartic acid(7.6%). When 60 days stored, the contents of amino acid were stable. And the predominant nuclotide and their related compounds in the raw ark shell were hypoxanthine(2.14$\mu$mol/g), IMP(1.94$\mu$mol/g) and ATP(0.87$\mu$mol/g), and storage at 37$\pm$1$^{\circ}C$ for 60 days, the quantity order were same as raw material.

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Analysis on Practicality of Seed Treatments for Medicinal Plants Published in Korean Scientific Journals (국내 학술지에 발표된 약용작물 종자처리의 실용성 분석)

  • Kang, Jin-Ho;Yoon, Soo-Young;Jeon, Seung-Ho
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.4
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    • pp.328-341
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    • 2004
  • Presowing seed treatments used to enhance the rates of germination and afterward seedling emergence have not occasionally shown the same rate in indoor and field. The treatments considering germination mechanism and factors affecting germination must be totally included in indoor experiments so that the results drawn can be reproduced in the field. Seed germination is controlled by Phytochrome-mediated action changed with composition rates of red and far-red lights. Sunlight can penetrate soil into $6{\sim}9\;mm$ depth, which in turn means that seeds having $2{\sim}3\;mm$ in their width may receive the light if soil was covered 3 times over them. The penetrating light, moreover, turns to more far-red light than red light reverse to the sunlight. For germination tests after the artificial presowing seed treatments, therefore, seeds of smaller than 2 mm (< 2 mm), $2{\sim}3\;mm$, and larger than 3 mm (> 3 mm) must be done with incandescent lamp (IL) having more far-red light, with IL or in darkness, and in darkness, respectively. The 96 papers published in 13 Korean scientific journals up to the end of 2003 were analysed on the basis of the above explanation. 91 species were used 147 times as experimental materials; 101 times for < 2 mm seeds, 24 times for $2{\sim}3\;mm$ seeds and 22 times for > 3 mm seeds. If they were analysed as the light sources used for germination tests, correct applications reached more and less than 60% in both $2{\sim}3\;mm$ and > 3 mm seeds but 23% in < 2 mm seeds, conclusionally meaning that when the experimental results in the scientific papers were applied into farming practices, care was taken of their application because most of medicinal plant seeds were very small.