• 대한환경공학회지
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• 제31권9호
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• pp.783-792
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• 2009

서울 인근의 하수처리장에서 채취한 유입/유출수에 내포되어 있는 31개의 미량 EDC/PPCPs(내분비계장애물질/의 약 개인관리용품물질)의 발현 특성에 대한 조사 연구를 수행하였다. 유입수에서 검출된 EDC/PPCPs의 용도별 분류에 따른 총농도 관점의 발현 비율은 각성제(59.67%), X선 조영제(20.20%), 난연제(9.00%), 기타 등의 순으로 나타났으며, 유출수의 경우에는 베타 차단제(30.54%), 난연제(20.49%), X선 조영제(18.17%), 기타 등의 순으로 발현 빈도가 나타났다. 본 연구에서 검출된 대상 미량물질의 전반적인 농도 검출 범위는 다른 국내 선행연구에 비해 다소 낮은 것으로 나타났으며, 국외의 연구결과와 비교해서는 상당한 낮은 수준으로 검출되는 것으로 나타났다. 특히 유럽 지역의 연구결과와 비 교하면 일부 의약물질항목에 따라서는 수천 배의 농도차이를 보여주는 것으로 나타났다. 한편, 선택된 9개의 의약물질에 대해 유입수와 유출수의 예상환경농도(PEC)를 계산하고 실제 측정된 농도(MEC)와 비교한 결과 물질별 발현 농도 수치 관점에서는 큰 편차를 보였으나, 물질별 상대적 발현 빈도 순서 관점에서는 대체적으로 유사한 것으로 나타났다.

• 대한약리학회지
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• 제30권2호
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• pp.191-203
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• 1994

$K^+$ channel openers (KCOs) are known to have a wide range of effects by opening the $K^+$ channel in plasma membranes of various smooth muscles, cardiac muscle and pancreatic ${\beta}-cell$. In the present study, we investigated the effects of 5 types of KCOs, cromakalim, RP49356, pinacidil, nicorandil and diazoxide on the contractility of isolated rat uterus. All KCOs tested inhibited the uterine contraction induced by 0.2 nM oxytocin in a dose-dependent manner. Individual KCO and its $pD_2$ values were cromakalim 6.5, RP49356 6.3, pinacidil 5.92, nicorandil 4.43 and diazoxide 4.18. The relaxant effects of KCO were inhibited by glibenclamide (0.3, 1 and $10\;{\mu}M$) with $pA_2$ values of cromakalim 6.91, RP49356 6.59, pinacidil 6.55, nicorandil 5.97 and diazoxide 6.37. In addition, the relaxant effect of cromakalim or pinacidil was antagonised by TEA, a non-selective $K^+$ channel blocker, but not by apamin. Contractions induced by low concentration of KCI (< 40 mM) were inhibited by cromakalim $(100{\mu}M)$ and nicorandil $(300{\mu}M)$, but those evoked by higher concentration (> 40 mM) of KCI were little affected. In ovariectomized rat uterus, cromakalim dose-dependently inhibited oxytocin-induced contraction and glibenclamide $(10{\mu}M)$ inhibited the relaxant effect of cromakalim with $pD_2$ and $K_B$ values of 7.48 and $1.26{\times}10^{-7}M$, respectively. In estrogen-primed rat uterus, these values were 6.51 and $1.57{\times}10^{-7}M$, respectively, indicating that the cromakalim is less effective on the estrogen-treated uterine smooth muscle. Our results suggest that the KCO-sensitive $K^+$ channels participate in the motility of uterine smooth muscle and such channels are, at least in part, under the control of estrogen. In addition, our data Indicate that the type of $K^+$ channels activated by KCO is ATP-sensitive $K^+$ channels which is blocked by glibenclamide.

• Biomolecules & Therapeutics
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• 제10권2호
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• pp.71-77
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• 2002

Heme oxygenase-1 (HO-1) is the inducible from of the rate-limiting enzyme of heme degradation; it regulates the cellular contents of heme. HO-1 is up-regulated by various stimuli including oxidative stress so that it is thought to participate in general cellular defense mechanisms against oxidative stress in mammalian cells. To investigate the role of the cAMP-dependent protein kinase A (PKA) signaling pathway on nitrogen oxidative stress-induced HO-1 gene expression, RAW 264.7 cell cultures were treated with sodium nitroprusside (SNP). SNP increased the expression of HO-1 mRNA and protein, time- and concentration-dependently. Treatment with H89, PKA inhibitor, but not LY83583, guanylate cyclase inhibitor, significantly diminished the HO-1 expression by SNP, indicating that cAMP plays a crucial role in the induction of HO-1. Incubation with cAMP-elevating agents, such as forskolin or isoproterenol resulted in up-regulation of the expression of HO-1. Forskolin-induced expression of HO-1 was inhibited by H89. Furthermore, propranolol, $\beta$-adrenoceptor blocker, inhibited the isoproterenol-induced HO-1 expression, supporting the importance of cAMP in the induction of HO-1 expression. Higenamine-S, but not higenamineR, enhanced the HO-1 expression induced by SNP. Furthermore, cellular toxicity induced by hydrogen peroxide was attenuated by the presence of SNP, which was further increased by the presence of ZnPPIX, HO-1 inhibitor. Collectively, these results strongly suggest that up-regulation of HO-1 expression in RAW 264.7 cells involves PKA signal pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제9권2호
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• pp.103-108
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• 2005

To study the direct effect of somatostatin (SS) on calcium channel current ($I_{Ba}$) in guinea-pig gastric myocytes, $I_{Ba}$ was recorded by using whole-cell patch clamp technique in single smooth muscle cells. Nicardipine ($1{\mu}M$), a L-type $Ca^{2+}$ channel blocker, inhibited $I_{Ba}$ by $98{\pm}1.9$% (n=5), however $I_{Ba}$ was decreased in a reversible manner by application of SS. The peak $I_{Ba}$ at 0 mV were decreased to $95{\pm}1.5$, $92{\pm}1.9$, $82{\pm}4.0$, $66{\pm}5.8$, $10{\pm}2.9$% at $10^{-10}$, $10^{-9}$, $10^{-8}$, $10^{-7}$, $10^{-5}$ M of SS, respectively (n=3∼6; $mean{\pm}SEM$). The steady-state activation and inactivation curves of $I_{Ba}$ as a function of membrane potentials were well fitted by a Boltzmann equation. Voltage of half-activation ($V_{0.5}$) was $-12{\pm}0.5$ mV in control and $-11{\pm}1.9$ mV in SS treated groups (respectively, n=5). The same values of half-inactivation were $-35{\pm}1.4$ mV and $-35{\pm}1.9$ mV (respectively, n=5). There was no significant difference in activation and inactivation kinetics of $I_{Ba}$ by SS. Inhibitory effect of SS on $I_{Ba}$ was significantly reduced by either dialysis of intracellular solution with $GDP_{\beta}S$, a non-hydrolysable G protein inhibitor, or pretreatment with pertussis toxin (PTX). SS also decreased contraction of guinea-pig gastric antral smooth muscle. In conclusion, SS decreases voltage-dependent L-type calcium channel current ($VDCC_L$) via PTXsensitive signaling pathways in guinea-pig antral circular myocytes.

• The Korean Journal of Physiology and Pharmacology
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• 제15권1호
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• pp.61-66
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• 2011

P2Y receptors are metabotropic G-protein-coupled receptors, which are involved in many important biologic functions in the central nervous system including retina. Subtypes of P2Y receptors in retinal tissue vary according to the species and the cell types. We examined the molecular and pharmacologic profiles of P2Y purinoceptors in retinoblastoma cell, which has not been identified yet. To achieve this goal, we used $Ca^{2+}$ imaging technique and western blot analysis in WERI-Rb-1 cell, a human retinoblastoma cell line. ATP ($10\;{\mu}M$) elicited strong but transient $[Ca^{2+}]_i$ increase in a concentration dependent manner from more than 80% of the WERI-Rb-1 cells (n=46). Orders of potency of P2Y agonists in evoking $[Ca^{2+}]_i$ transients were 2MeS-ATP>ATP>>UTP=${\alpha}{\beta}$-MeATP, which was compatible with the subclass of $P2Y_1$ receptor. The $[Ca^{2+}]_i$ transients evoked by applications of 2MeS-ATP and/or ATP were also profoundly suppressed in the presence of $P2Y_1$ selective blocker (MRS 2179; $30\;{\mu}M$). $P2Y_1$ receptor expression in WERI-Rb-1 cells was also identified by using western blot. Taken together, $P2Y_1$ receptor is mainly expressed in a retinoblastoma cell, which elicits $Ca^{2+}$ release from internal $Ca^{2+}$ storage sites via the phospholipase C-mediated pathway. $P2Y_1$ receptor activation in retinoblastoma cell could be a useful model to investigate the role of purinergic $[Ca^{2+}]_i$ signaling in neural tissue as well as to find a novel therapeutic target to this lethal cancer.

• 정신신체의학
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• 제7권2호
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• pp.263-273
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• 1999

두통은 인류의 가장 흔한 호소 중의 하나로 임상에서 흔히 보는 장애이다. 두통은 뇌막염, 뇌출혈, 또는 뇌종양과 같은 다른 질환의 증상일수 있으나, 또한 편두통이나 군발두통 등과 같은 질병 자체로 표현된다. 일차적으로 두통 장애의 역학이나 국제 두통학회의 진단기준을 이해하고 흔치 않으나 심각한 이차적인 두통장애와 감별에 관심을 둬야 한다. 환자가 일차 두통장애의 기준에 맞으면 신경학적 진단검사의 보충이 없어도 치료를 시작한다. 두통 유형, 표현 양상, 동통기간과 강도 등에 따라 진통소염제나 혼합진통제, 혈관작용의 항편두통 약물 또는 신경이완제나 corticosteroid등을 선택한다. 편두통의 빈도와 강도에 따라 예방치료가 보통 4~6개월간 조절한다. 긴장형 두통은 발작성과 만성두통으로 구분되나 치료적으로는 급성완화와 예방치료로 시도된다. 많은 만성매일두통 환자들이 진통제나 ergotamine을 과용하고 있으며 그들의 의존성과 내재된 갈등조절, 수면장애, 우울등으로 과용된 약물의 제한이 쉽지 않다. 치료의 첫단계는 약물을 끊고 조심스럽게 대치요법을 시행한다.

• 대한환경공학회지
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• 제35권1호
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• pp.45-56
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• 2013

본 연구는 낙동강수계의 잔류의약물질을 관리하기 위한 기초자료로 제시되었다. 낙동강 본류에서 Iopromide는 $0.0015{\sim}0.37{\mu}g/L$, Mefenamic acid은 $0.0087{\sim}0.056{\mu}g/L$, Diclofenac은 $N.D.{\sim}0.01{\mu}g/L$, Atenolol은 $N.D.{\sim}0.024{\mu}g/L$, Propranolol은 $N.D.{\sim}0.0038{\mu}g/L$, Lincomycin은 $0.0005{\sim}0.038{\mu}g/L$, Trimethoprim은 $N.D.{\sim}0.0083{\mu}g/L$의 농도범위로 검출되었다. 유역의 하수처리장에서는 대부분 고농도로 검출되었으며, 특히 Iopromide가 최고 $5.38{\mu}g/L$까지 검출되었다. 축산폐수처리장에서는 린코마이신이 최고 $477{\mu}g/L$로 가장 높게 검출되었다. 조사결과, 낙동강 본류에서 의약물질은 구미하수처리장과 대구 금호강의 유입으로 농도가 높아져 인구 산업밀집지역의 영향이 큰 것으로 판단된다. 따라서 낙동강의 잔류의약물질을 효율적으로 관리하기 위해서는 금호강과 하 폐수처리장을 지속적으로 모니터링하고 관리하는 것이 바람직한 것으로 사료된다.

• Journal of Chest Surgery
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• 제39권1호
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• pp.42-47
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• 2006

배경: 새로 나온 다절편 전산화흥부단층촬영(Multidetector Computed Tomography: MDCT)은 관상동맥 영상화에 유용하다. 본 교실에서는 관상동맥우회로 술을 시행한 환자에서 술 후 관상동맥 이식편의 평가를 위하여 비침습적 MDCT와 기존의 침습적 관상동맥조영 술의 유용성을 비교하였다. 대상 및 방법: 2003년 11월부터 2004년 11월까지 관상동맥우회로 술을 시행한 후 16 Channel MDCT와 관상동맥조영 술 모두에 동의한 15명을 대상으로 52개의 이식편의 개존성을 분석하였다. MDCT를 이용하여 3차원으로 재조합된 영상과 관상동맥조영술을 통해 얻은 영상을 비교하여 민감도, 특이도, 양성 예측치, 음성 예측치 등을 계산하였다 결과: 환자당 평균 3.4$\pm$0.8개의 도관을 사용하였다. MDCT 도중 환자들의 평균 심박동수는 86회/분(범위, 60$\∼$110회/분)이어서 베타차단제는 사용하지 않았다. 모든 환자들이 필요한 시간만큼 호흡을 참을 수 있었다. 관상동맥조영 술을 통해 얻은 전체 이식편 개존율은 96.2$\%$였다. MDCT의 진단력은 민감도 100$\%$,특이도 98.0$\%$, 양성 예측치 100$\%$,음성 예측치 66$\%$였다. 결론: 관상동맥우회로 술 후 16 Channel MDCT는 기존의 관상동맥조영 술과 비교하여 이식편의 개존상태와 혈류 정도 파악에 신뢰할 수 있는 수준이며, 비침습적이며 저렴하므로 관상동맥조영 술을 대체할 수 있을 것이다.

• 동의생리병리학회지
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• 제28권6호
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• pp.630-635
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• 2014

The purpose of this study was to investigate the effects of Naeso-san in interstitial cells of Cajal (ICCs) in murine small intestine. First, we isolated ICCs from murine small intestine. After that, we cultured these cells for 1 days. The patch-clamp technique was applied on ICCs that formed network-like structures in culture (1 days). Spontaneous rhythms were routinely recorded from cultured ICCs under current-clamp conditions, and the ICCs within networks displayed more robust electrical rhythms (pacemaker potentials). To understand the relationship between Naeso-san and pacemaker activity in ICCs, we examined the effects of Naeso-san on pacemaker potentials of ICCs. In current clamp mode (I = 0), the addition of Naeso-san (10 mg/ml - 50 mg/ml) decreased the amplitude and frequency of the pacemaker potentials of ICCs in a dose dependent manner. However, these effects were blocked by intracellular $GDP{\beta}S$, a G-protein inhibitor, and glibenclamide, a specific ATP-sensitive K+ channels blocker. Pretreatment with SQ-22536, an adenylate cyclase inhibitor, did not block the Naeso-san induced effects, whereas pretreatment with ODQ, a guanylate cyclase inhibitor, or L-NAME, an inhibitor of nitric oxide (NO) synthase blocked the Naeso-san induced effects. Our findings provide insight into unraveling the modulation of Naeso-san in pacemaker potentials of ICCs and developing therapeutic agents against gastrointestinal motility disorders.

• The Korean Journal of Physiology
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• 제28권1호
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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.