• Proceedings of the Korean Society for Bioinformatics Conference
• /
• 2004.11a
• /
• pp.57-63
• /
• 2004

본 연구에서는 3차원 심근조직에서의 회귀성파동에 대한 수치적 해석결과를 제시한다. 심근 조직에서의 회귀성파동은 심실세동(ventricular fibrillation)의 원인으로 지목되고 있으며 심근세포 이온채널 또는 전기전도시스템 등과 같은 여러 가지 요소들이 관련된 복합적 현상으로 생각되고 있다. 지금까지 이에 관한 많은 연구가 전기생리학적 모델을 이용하여 이루어진바 있으며, 주로 동물 심근세포모델에 기반으로 균일한 2차원 또는 3차원 모델에서의 전기전도 현상 해석을 한 바 있다. 그러나 실제 심장조직의 경우, 두께를 가진 3차원적 형상을 지니고 있으며 층을 따라서 전기생리학적으로 상이한 특성을 가진 세포들로 구성된다. 즉 심근은 층을 가로질러 Epi-cardiac, mid-cardiac, endo-cardiac cell들로 구성되며 각기 다른 APD(action potential duration)을 가지고 있다. 따라서 본 연구에서는 이러한 세가지 종류의 인체 심근세포모델을 사용한 3차원 심근조직에서의 활동전위 전도현상에 대한 결과를 제시한다. 이를 위하여 기존의 인체 3가지 종류의 심근세포 모델을 구현하여 그 타당성을 검토한다. 그리고 이를 바탕으로 3차원 조직모델을 구현하는데, simplified bidomain방법을 사용하였다. 3차원 공간상에서 심근세포에 의한 활동전위 전달현상을 해석하기 위하여 유한요소법을 도입한다. 최종적으로는 3가지의 심근세포층을 가진 3차원 심근조직을 구성하고, 여기에 회귀성 파동을 유도한다. 그리고 단일층으로 이루어진 3차원조직에서의 결과와 비교 분석하여 다세포층에 의한 불균일 효과를 분석하였다.

• Korean Journal of Environmental Agriculture
• /
• v.25 no.3
• /
• pp.268-275
• /
• 2006

ALA (5-aminolevulinic acid) has been proposed as a tetrapyrrole-dependent photodynamic herbicide by the action of the protoporphyrinogen IX oxidase (Protox IX). A study was conducted to determine photodynamic herbicidal effect of ALA on seedling growth of rice (Oryza sativa L.) and barnyard grass (Echinochloa crus-galli Beauv. var. oryzicola Ohwi) under dry and wet conditions. ALA effect on early plant growth of rice and barnyardgrass was greatly concentration dependant, suggesting that it promotes plant growth at very low concentration and inhibits at high concentration. No significant difference in herbicidal activity of biologically and synthetically produced ALAs on plant lengths of test plants was observed ALA exhibited significant photodynamic activity regardless of PSDIP and its duration. Significant shoot growth inhibition by ALA soaking treatment exhibited apparently, indicating that ALA absorbed through root system was translocated into shoot part of plants. ALA reduced plant heights of rice and barnyardgrass seedlings by 6% and 27%, respectively, showing more tolerant to ALA in rice under wet condition. Leaf thickness was reduced markedly by ALA with increasing of ALA concentration, due to mainly membrane destruction and severe loss of turgidity in mesophyll cells, although the epidermal was little affected. It was observed that photodynamic herbicidal activity of ALA applied by pre-and post-emergence application exhibited differently on plant species, and that the activity of ALA against susceptible plants was highly correlated with growing condition.

• Archives of Pharmacal Research
• /
• v.28 no.3
• /
• pp.269-273
• /
• 2005

A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC$_{50}$ value of 180 $\pm$ 21 nM at +60 mV. Psoralen accelerated the inactivation kinetics of the hKv1.5 channel, and it slowed the deactivation kinetics of the hKv1.5 current resulting in a tail crossover phenomenon. These results indicate that psoralen acts on the hKv1.5 channel as an open channel blocker. Furthermore, psoralen prolonged the action potential duration of rat atrial muscles in a dose-dependent manner. Taken together, the present results strongly suggest that psoralen may be an ideal antiarrhythmic drug for atrial fibrillation.

• Journal of Obesity & Metabolic Syndrome
• /
• v.27 no.4
• /
• pp.213-222
• /
• 2018

Bariatric surgery has evolved from a surgical measure for treating morbid obesity to an epochal remedy for treating metabolic syndrome as a whole, which is represented by type 2 diabetes mellitus. Numerous clinical trials have advocated bariatric or metabolic surgery over nonsurgical interventions because of markedly superior metabolic outcomes in morbidly obese patients who satisfy traditional criteria for bariatric surgery (body mass index [BMI] >$35kg/m^2$) and in less obese or simply overweight patients. Nevertheless, not all diabetes patients achieve the most desirable outcomes; i.e., diabetes remission after metabolic surgery. Thus, candidates for metabolic surgery should be carefully selected based on comprehensive preoperative assessments of the risk-benefit ratio. Predictors for diabetes remission after metabolic surgery may be classified into two groups based on mechanism of action. The first is indices for preserved pancreatic beta-cell function, including younger age, shorter duration of diabetes, and higher C-peptide level. The second is the potential for an insulin resistance reduction, including higher baseline BMI and visceral fat area. Several prediction models for diabetes remission have been suggested by merging these two to guide the joint decision-making process between clinicians and patients. Three such models, DiaRem, ABCD, and individualized metabolic surgery scores, provide an intuitive scoring system and have been validated in an independent external cohort and can be utilized in routine clinical practice. These prediction models need further validation in various ethnicities to ensure universal applicability.

• The Korean Journal of Physiology and Pharmacology
• /
• v.23 no.6
• /
• pp.483-491
• /
• 2019

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. ${\beta}$-Amyloid ($A{\beta}$) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in $A{\beta}$ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine $A_1$ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the $A{\beta}$ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of $A_1R$ is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

• The Korean Journal of Physiology and Pharmacology
• /
• v.26 no.5
• /
• pp.313-323
• /
• 2022

Atrial fibrillation (AF) is the most common supraventricular arrhythmia, and it corresponds highly with exercise intensity. Here, we induced AF in mice using acetylcholine (ACh)-CaCl₂ for 7 days and aimed to determine the appropriate exercise intensity (no, low, moderate, high) to protect against AF by running the mice at different intensities for 4 weeks before the AF induction by ACh-CaCl₂. We examined the AF-induced atrial remodeling using electrocardiogram, patch-clamp, and immunohistochemistry. After the AF induction, heart rate, % increase of heart rate, and heart weight/body weight ratio were significantly higher in all the four AF groups than in the normal control; highest in the high-ex AF and lowest in the low-ex (lower than the no-ex AF), which indicates that low-ex treated the AF. Consistent with these changes, G protein-gated inwardly rectifying K⁺ currents, which were induced by ACh, increased in an exercise intensity-dependent manner and were lower in the low-ex AF than the no-ex AF. The peak level of Ca²⁺ current (at 0 mV) increased also in an exercise intensity-dependent manner and the inactivation time constants were shorter in all AF groups except for the low-ex AF group, in which the time constant was similar to that of the control. Finally, action potential duration was shorter in all the four AF groups than in the normal control; shortest in the high-ex AF and longest in the low-ex AF. Taken together, we conclude that low-intensity exercise protects the heart from AF, whereas high-intensity exercise might exacerbate AF.

• The Korean Journal of Physiology and Pharmacology
• /
• v.27 no.3
• /
• pp.267-275
• /
• 2023

Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (human iPSC-CMs) has become an attractive human-based platform for predicting cardiotoxicity. Moreover, electrophysiological assessment of multiple cardiac ion channel blocks is emerging as an important parameter to recapitulate proarrhythmic cardiotoxicity. Therefore, we aimed to establish a novel in vitro multiple cardiac ion channel screening-based method using human iPSC-CMs to predict the drug-induced arrhythmogenic risk. To explain the cellular mechanisms underlying the cardiotoxicity of three representative TdP high- (sotalol), intermediate- (chlorpromazine), and low-risk (mexiletine) drugs, and their effects on the cardiac action potential (AP) waveform and voltage-gated ion channels were explored using human iPSC-CMs. In a proof-of-principle experiment, we investigated the effects of cardioactive channel inhibitors on the electrophysiological profile of human iPSC-CMs before evaluating the cardiotoxicity of these drugs. In human iPSC-CMs, sotalol prolonged the AP duration and reduced the total amplitude (TA) via selective inhibition of I_Kr and I_Na currents, which are associated with an increased risk of ventricular tachycardia TdP. In contrast, chlorpromazine did not affect the TA; however, it slightly increased AP duration via balanced inhibition of I_Kr and I_Ca currents. Moreover, mexiletine did not affect the TA, yet slightly reduced the AP duration via dominant inhibition of I_Ca currents, which are associated with a decreased risk of ventricular tachycardia TdP. Based on these results, we suggest that human iPSC-CMs can be extended to other preclinical protocols and can supplement drug safety assessments.

• The Korean Journal of Physiology and Pharmacology
• /
• v.16 no.5
• /
• pp.327-332
• /
• 2012

Sertraline is a commonly used antidepressant of the selective serotonin reuptake inhibitors (SSRIs) class. In these experiments, we have used the whole cell patch clamp technique to examine the effects of sertraline on the major cardiac ion channels expressed in HEK293 cells and the native voltage-gated $Ca^{2+}$ channels in rat ventricular myocytes. According to the results, sertraline is a potent blocker of cardiac $K^+$ channels, such as hERG, $I_{Ks}$ and $I_{K1}$. The rank order of inhibitory potency was hERG > $I_{K1}$ > $I_{Ks}$ with $IC_{50}$ values of 0.7, 10.5, and 15.2 ${\mu}M$, respectively. In addition to $K^+$ channels, sertraline also inhibited $I_{Na}$ and $I_{Ca}$, and the $IC_{50}$ values are 6.1 and 2.6 ${\mu}M$, respectively. Modification of these ion channels by sertraline could induce changes of the cardiac action potential duration and QT interval, and might result in cardiac arrhythmia.

• Korean Journal of Biological Psychiatry
• /
• v.7 no.1
• /
• pp.14-20
• /
• 2000

Recently atypical antipsychotics have been used as first line agent in the treatment of schizophrenia, and also played a significant role in the treatment of many kinds of psychiatric disorders. The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics are well known through preclinical and early clinical trials. However, it is important to note the limitations of the results due to its relatively short experience. Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life, while 1A2 inhibitors such as SSRIs, especially fluvoxamine can increase its duration of action. Carbamazepine should be avoided in a patient on clozapine because of carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the chances of sedation, delirium and respiratory depression. Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but 9-hydroxyrisperidone has similar biological activity as parental drug, so it has little affect on the outcome. Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2 and 2D6 cytochrome enzymes.

• Journal of Pharmaceutical Investigation
• /
• v.41 no.3
• /
• pp.173-178
• /
• 2011

Injectable chitosan hydrogels have attracted great potential due to sustained-release property and safety. Here, palmityl-acylated glycol chitosan (Pal-GC) was used to generate physically cross-linked hydrogels by virtue of hydrophobic attraction of linear fatty carbons. Glycol chitosan was chemically modified with N-hydroxysuccinimide-activated palmitic acid in dimethylsulfoxide (DMSO) containing dimethylaminopyridine. Through a series of preparation steps of (i) dialysis with DMSO, (ii) addition of palmityl-acylated exendin-4 (Ex4-C16), and (iii) dialysis with water, Pal-GC was self-assembled to form physically cross-linked hydrogels entrapped with Ex4-C16. The Pal-GC derivative was analyzed by using 1H NMR, and the surface morphology of Pal-GC hydrogels formed was examined by scanning electron microscopy. Also, the hypoglycemic effect induced by Pal-GC hydrogels containing Ex4-C16 (250 nmol/kg) was evaluated in non-fasted type 2 diabetic db/db mice and compared with GC hydrogels containing native Ex4 at the same dose. Results showed that palmityl group was successfully conjugated with the amines of glycol chitosan, and that Pal-GC efficiently generated the hydrogels formation. Moreover, Pal-GC hydrogels containing Ex4-C16 was found to greatly prolong the hypoglycemia duration (~ 4 days). This was due to the dual-functions of the palmityl groups present in both GC and exendin-4 such as hydrophobic attraction and plasma albumin-binding. We consider this new type of self-assembled GC hydrogels loaded with Ex4-C16 would be a promising long-acting sustained-release system with anti-diabetic property.