• Title/Summary/Keyword: Opener

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Effect of Renal Denervation and Glibenclamide, a selective ATP-sensitive $K^+$ Channel Blocker, on Renal Action of BRL 34915, a ATP-sensitive $K^+$ Channel Opener, in Dog ($K^+$ Channel 개방제인 BRL 34915의 신장작용에 대한 신장 신경제거 와 선택성 ATP-의존성 $K^+$Channel 차단제인 Glibenclamide의 영향)

  • 고석태;최홍석
    • YAKHAK HOEJI
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    • v.44 no.4
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    • pp.362-370
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    • 2000
  • In anesthetized dogs, antidiuretic action of intravenously administered BRL 34915 (10.0~30.0 $\mu$/kg) was blocked by renal denervation, whereas it was not affected by glibenclamide, a selective $K_{ATP}$ blocker, given into renal artery. Diuretic action in ipsilateral kidney produced by intrarenal administration of BRL 34915 was not influenced by renal denervation, but blocked completely by glibenclamide given into the vein. Above results suggest that the antidiuretic action of BRL 34915 is mediated by renal sympathetic nerves and the diuretic action is caused by opening of $K^+$ channel within kidney.

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Effects of Lemakalim, a Potassium Channel Opener, on the Contractility and Electrical Activity of the Antral Circular Muscle in Guinea-Pig Stomach

  • Kim, Sung-Joon;Jun, Jae-Yeoul;Choi, Youn-Baik;Kim, Ki-Whan;Kim, Woo-Gyeum
    • The Korean Journal of Physiology
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    • v.28 no.1
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    • pp.37-50
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    • 1994
  • Synthetic potassium channel openers (KCOs) are agents capable of opening K-channels in excitable cells. These agents are known to have their maximal potency in the smooth muscle tissue, especially in the vascular smooth muscle. Much attention has been focused on the type of K-channel that is responsible for mediating the effects of KCOs. As the KCO-induced changes are antagonized by glibenclamide, an $K_{ATP}$ (ATP-sensitive K-channel) blocker in the pancreatic ${\beta}-cell,\;K_{ATP}$ was suggested to be the channel responsible. However, there also are many results in favor of other types of K-channel $$(maxi-K,\;small\;conductance\;K_{Ca,}\; SK_{ATP}) mediating the effects of KCOs. Effects of lemakalim, (-)enantiomer of cromakalim (BRL 34915), on the spontaneous contractions and slow waves, were investigated in the antral circular muscle of the guinea-pig stomach. Membrane currents and the effects on membrane currents and single channel activities were also measured in single smooth muscle cells and excised membrane patches by using the patch clamp method. Lemakalim induced hyperpolarization and inhibited spontaneous contractions in a dose-dependent manner. These effects were blocked by glibenclamide and low concentrations of tetraethyl ammonium (< mM). Glibenclamide blocked the effect of lemakalim on the membrane potential and slow waves. The mechanoinhibitory effect of lemakalim was blocked by pretreatment with glibenclamide. In a whole ceIl patch clamp condition, lemakalim largely increased outward K currents. These outward K currents were blocked by TEA, glibenclamide and a high concentration of intracelIular EGTA (10 mM). Volatage-gated Ca currents were not affected by lemakalim. In inside-out patch clamp experiments, lemakalim increased the opening frequency of the large conductance $Ca^{2+}-activated$ K channels $(BK_{Ca},\;Maxi-K).$ From these results, it is suggested that lemakalim induces hyperpolarization by opening K-channels which are sensitive to internal Ca and such a hyperpolarization leads to the inhibition of the spontaneous contraction.

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The Ca2+-activated K+ (BK) Channel-opener NS 1619 Prevents Hydrogen Peroxide-induced Cell Death and Mitochondrial Dysfunction in Retinal Pigment Epithelial Cells (망막 색소상피세포에서 산화성 세포 손상과 미토콘드리아기능 저해에 미치는 NS 1619의 보호 효과)

  • Kang, Jae Hoon;Woo, Jae Suk
    • Journal of Life Science
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    • v.27 no.11
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    • pp.1349-1356
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    • 2017
  • Potassium channel openers (KCOs) produce physiological and pharmacological defense mechanisms against cell injuries caused by oxidative stress of diverse origins. Openings of mitochondrial and plasmalemmal $K^+$ channels are involved in the defense mechanisms. This study tested whether NS 1619, an opener of large-conductance BK channels, has a similar beneficial influence on the pigment epithelial cells of retinas. The human retinal pigment epithelial cell line ARPE-19 was exposed to $H_2O_2$-induced oxidative stress in the absence and presence of NS 1619. The degrees of the cells' injuries were assessed by analyzing the cells' trypan-blue exclusion abilities and TUNEL staining. NS 1619 produced remarkable protections against cell injuries caused by $H_2O_2$. It prevented apoptotic and necrotic cell deaths. The protective effect of NS 1619 was significantly diminished when the cells were treated with NS 1619 in combination with the BK channel-blocker paxilline. NS 1619 significantly ameliorated cellular ATP deprivations in $H_2O_2$-treated cells. It helped mitochondria preserve their functional integrity, which was estimated by their MTT reduction abilities and mitochondrial membrane potential. In conclusion, it was suggested that NS 1619 had a beneficial effect on mitochondria in regards to preserving their functional integrity under oxidative stress, and it produces defense mechanisms against oxidant-induced cell injuries in ARPE-19 cells.

Acute Toxicity of the BKCa Channel Opener LDD175

  • Choi, Ji-Young;Choi, Jong-Hyun;Lee, Geum-Seon;Ko, Hong-Sook;Park, Chul-Seung;Kim, Yong-Chul;Cheong, Jae-Hoon
    • Biomolecules & Therapeutics
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    • v.14 no.4
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    • pp.253-258
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    • 2006
  • LDD175(4-choloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-l-carboxylic acid) is one of benzofuroindole derivatives that act as a potent $BK_{Ca}$ channel openers. In the process of testing LDD175 as a new drug candidate, an acute toxicity study was carried out in mice. The mice were administered LDD175 intraperitoneally at dose of 0.2, 1, 10, 50, 100, 200, 400, 800mg/kg and orally at dose of 10, 100, 400, 800mg/kg body weight. After administering LDD175, the vital organs such as the liver, kidney and spleen were carefully observed for any significant pathological features or differences from the norm over a l4-day period. LDD175 did not induce any short-term toxicity at doses less than 100mg/kg. A $LD_{50}$ of LDD175 was 2493mg/kg in male mice and 4908mg/kg in female mice. Weight reduction was observed at a dose of 800mg/kg in male, and 400 and 800mg/kg in female. The kidney weight decreased in females after an intraperitoneal injection of LDD175 high dose(>400mg/kg, i.p.), and the spleen weight increased in the male(800mg/kg, i.p.) and female(400mg/kg, i.p.) mice. Inspite of the change in organ weights, there were neither histopathological changes nor any gross morphological abnormalities detected in any organ. LDD175 did not produce significant changes in the general behavior at doses of <200mg/kg, but decreased locomotor activity was observed at an intraperitoneal dose of 400mg/kg. Its effects on the locomotor activity and activity on the rotarod were tested and compared with the effects of diazepam 5mg/kg. The decrement in the locomotor activity and the activity on the rotarod induced by LDD175 was less serious than it by diazepam.

The effect of SKF S25A on SNP-, Ach-, or Pinacidil-Induced Relaxation in the Aorta of Rat (SKF 525A가 휜쥐의 대동맥에서 Sodium nitroprusside, Acetylcholine, Pinacidil에 의한 이완반응에 미치는 효과)

  • 박조영;김학림;김주원;신창열;최윤미;김진학;안형수;손의동;허인회
    • YAKHAK HOEJI
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    • v.44 no.1
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    • pp.80-86
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    • 2000
  • TEA, glibenclamide, L-NAME and SKF 525A-induced contraction were investigated using acetylcholine, sodium nitroprusside (SNP, NO donor) and pinacidil (ATP sensitive $K^{+}$ channel opener) in rat abdominal and thoracic aorta. The relaxant effects of acetylcholine, SNP and pinacidil were not different in the abdominal aorta and in the thoracic aorta. Acetylcholine-induced relaxation was dependent on endothelial cell, but pinacidil was independent endothelia cell. In the presence of TEA, glibenclamide, L-NAME, mepacrine and SKF 525A, acetylcholine and SNP did not change, but pinacidil-induced relaxation was significantly reduced in presence of glibenclamide, which is ATP sensitive $K^{+}$ channel blocker. SKF 525A, which is inhibitor of cytochrome P$_{450}$ dependent epoxygenase, partially inhibited the pinacidil-induced relaxation. These results indicate that the pinacidil-induced relaxation may be mediated by ATP sensitive $K^{+}$ channel and partially by EETs, which is produced by cytochrome P$_{450}$ dependent epoxygenase.enase.

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The Role of Mitochondrial ATP-sensitive Potassium Channel on Intestinal Pacemaking Activity

  • Kim, Byung-Joo;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.4
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    • pp.209-213
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    • 2005
  • Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. In the present study, we investigated the effect of mitochondrial ATP-sensitive potassium (mitoKATP) channel on pacemaking activity in cultured ICCs from murine small intestine by using whole-cell patch clamp techniques. Under current clamp mode, at 10μM glibenclamide, there was no change in pacemaking activity of ICCs. At $30{\mu}M$ glibenclamide, an inhibitor of the ATP sensitive $K^+$ channels, we could find two examples. If pacemaking activity of ICCs was irregulating, pacemaking activity of ICCs was changed into regulating and if in normal conditions, membrane potential amplitude was increased. At $50{\mu}M$ glibenclamide, the resting membrane potential was depolarized. At 3mM 5-HDA, an inhibitor of the mitoKATP channels, inhibited the pacemaking activity of ICCs. Both the amplitude and the frequency were decreased. At 5 mM 5-HDA, both the amplitude and the frequency were completely abolished. Diazoxide, an opener of the mitoKATP channels, was applied to examine its effect on pacemaking activity of ICCs. At $50{\mu}M$ concentration, the pacemaking activity of ICCs was inhibited. Both the amplitude and the frequency were decreased. At 1 mM concentration, both the amplitude and the frequency were completely abolished and the resting membrane potential was shaked.These results indicate that mitoKATP channel has an important role in pacemaking activity of ICCs.

Development of An Impact-Type Seed-Metering Device for Rice-Seed Pellets (벼 펠렛 종자용 타격식 파종장치 개발)

  • 최영수;구경본;유수남
    • Journal of Biosystems Engineering
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    • v.26 no.2
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    • pp.115-122
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    • 2001
  • An impact-type seed-metering device was developed for the planting of rice-pellets. In this study, new design of pellet-metering device focused on simplicity and precision seeding for the planting of rice-seed pellets. In addition of seed-metering device, several devices were also developed such as seed-guiding device, seed-supplying tube and furrow opener for precision pellet planting. Field test was conducted to estimate the planting performance of the developed metering device. As a cam rotates, the impact bar of the metering device pushes a rice-seed pellet so that the seed can be discharged from the seed-supplying tube in the impact-type seed-metering device. Results of the tests showed that mean seeding spacing was 12cm at the traveling speed of 1.0m/s, corresponding to a target spacing for planting of rice-seed pellets. Also, both miss-seeded rate and damaged-seed rate were less than 2.0%, indicating acceptable levels for the precision planting. The developed mechanism of the impact-type metering device can be directly applied to the design of metering devices for the precision pellet planting of other crops.

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Cardioprotective and Antihypertensive Effects of KR-31281, KR-31282 and KR-31299, Newly Synthesized $K_{ATP}$ Openers, in Conscious Rats and Isolated Ischemic Rat Hearts (신규 합성 $K_{ATP}$ 통로 개방제인 KR-31281, KR-31282 및 KR-31299의 흰쥐 적출 허혈 심장 및 비마취 흰쥐에 대한 심장보호 및 혈압강하 작용)

  • Lee, Sun-Sook;Yun, Yeo-Pyo;Shin, Hwa-Sup
    • Korean Journal of Clinical Pharmacy
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    • v.7 no.1
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    • pp.33-39
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    • 1997
  • Cardiac and antihypertensive effects of BMS-180448, a cardiac-selective ATP-sensitive potassium channel opener, and its newly synthesized derivatives KR-31281, KR-31282 and KR-31299 were evaluated in isolated perfused rat hearts (25 min global ischemia/30 min reperfusion) and conscious rats. Three new compounds $(10\;{\mu}M)$ induced positive inotropism as evidenced by increased LVDP (left ventricular developed pressure) and RPP (Rate-Pressure Product) in nonischemic rat heart. HR-31299 increased CF (coronary flow) and HR (heart rate) but the other two had no effects. KR-31282, KR-31281 and HR-31299 had a tendency to increase reperfusion LVDP and RPP compared with vehicle, while the latter two significantly reduced reperfusion EDP with a tendency to inclose TTC (time to contracture). All three KR-compounds had very weak effects on MBP and HR in conscious rats. These results indicate that KR-31281 and HR-31299 may have some cardioprotective effects, although weaker than BMS-180448, and their mode of action different from that of BMS-180448, despite the similarity in major structural moeity.

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Legal Status of Medical Personnel on Medical Records (환자의 의무기록 관련 의료인의 법적 지위)

  • Lee, Baek-Hyu
    • The Korean Society of Law and Medicine
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    • v.11 no.2
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    • pp.309-335
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    • 2010
  • This study is a paper reviewed legal status of medical personnel and issues of law on recently discovered medical records. As the increase of medical personnel who have gone through the administrative disposal in regards to the medical records, it is needed to examine the legal issue or dispute on the medical records under the current law. Medical records are the statement on patient's medical conditions made by the medical personnel. This records are used as important source for patient's further treatment. This becomes the communication route between the patients and the other medical personnel, and it provides the patients a right to find out their medical information. According to the Medical Service Act (Article 21), a medical personnel shall prepare respectively a record book of medical examination and treatment. And medical personnel shall make a signature. Furthermore, the medical personnel or the opener of the medical institutions must preserve the record book (including an electronic medical record). Meanwhile, the issues of a ban on false entry, additional record, revision or manipulation on the medical record have been recently on the rise. This paper briefly examined the major issues in regards to the medical records. It especially clarified the legal duty on medical records and its major-contentious-issues. At the same time, it pointed out the problems of the unreasonable over interpretation of the law. Furthermore, this suggested the guidelines for the further discussion and review.

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Survey on 'Go Bag' Items in Internet Shopping Malls

  • PARK, Sang-Kyu;UHM, Tai-Hwan
    • Journal of Distribution Science
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    • v.17 no.7
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    • pp.39-44
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    • 2019
  • Purpose - This research was to help distribution of Go Bags (Survival Bag or Disaster Supplies Kit), which are useful for disaster preparedness, by surveying precomposed Go Bag items in internet shopping malls. Research design, data, and methodology - We checked 15 items including food, water, first aid kit, radio, flashlight or candles, battery, lighter or matches, whistle, blanket, towel, toilet paper, personal sanitations, raincoat, can opener, disaster manual in Go Bags based on the recommendations by the Ministry of the Interior and Safety. The number of items and price, domestic product, accreditation were compared using a Chi-square test. The Pearson's R was also used to summarize the strength of the linear relationship between the number of items and price, sub-items. Results - Mean of the sub-items was 21, and mean of the items was 8. There was a statistically significant difference between the number of items size and the price level (p=.014). There was also a statistically significant difference between the number of items and sub-items (p<.001), and correlation coefficient was a positive linear relationship of .467. Conclusions - Only eight were sold in the internet shopping malls as a precomposed Go Bag items. Even the approved Go Bags had no difference in the number of items. Higher prices had a relatively greater number of items, and it had a positive correlation between the size of sub-items and items.