• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.733-742
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• 1998

Background: We have previously reported that not only cGMP but also 8-Br-cGMP or 8-pCPT-cGMP, specific and potent stimulators of cGMP-dependent protein kinase (cGMP-PK), increased basal L-type calcium current $(I_{Ca})$ in rabbit ventricular myocytes. Our findings in rabbit ventricular myocytes were entirely different from the earlier findings in different species, suggesting that the activation of cGMP-PK is involved in the facilitation of $I_{Ca}}$ by cGMP. However, there is no direct evidence that cGMP-PK can stimulate $I_{Ca}}$ in rabbit ventricular myocytes. In this report, we focused on the direct effect of cGMP-PK on $I_{Ca}}$ in rabbit ventricular myocytes. Methods and Results: We isolated single ventricular myocytes of rabbit hearts by using enzymatic dissociation. Regulation of $I_{Ca}}$ by cGMP-PK was investigated in rabbit ventricular myocytes using whole-cell voltage clamp method. $I_{Ca}}$ was elicited by a depolarizing pulse to +10 mV from a holding potential of -40 mV. Extracellular 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP), potent stimulator of cGMP-dependent protein kinase (cGMP-PK), increased basal $I_{Ca}}$. cGMP-PK also increased basal $I_{Ca}}$. The stimulation of basal $I_{Ca}}$ by cGMP-PK required both 8-Br-cGMP in low concentration and intracellular ATP to be present. The stimulation of basal $I_{Ca}}$ by cGMP-PK was blocked by heat inactivation of the cGMP-PK and by bath application of 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP), a phosphodiesterase-resistant cGMP-PK inhibitor. When $I_{Ca}}$ was increased by internal application of cGMP-PK, IBMX resulted in an additional stimulation of $I_{Ca}}$. In the presence of cGMP-PK, already increased $I_{Ca}}$ was potentiated by bath application of isoprenaline or forskolin or intracellular application of cAMP. Conclusions: We present evidence that cGMP-PK stimulated basal $I_{Ca}}$ by a direct phosphorylation of L-type calcium channel or associated regulatory protein in rabbit ventricular myocytes.

• 한국가정관리학회:학술대회논문집
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• 한국가정관리학회 2000년도 학술대회
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• pp.147-148
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• 2000

• 약학회지
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• 제49권5호
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• pp.428-436
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• 2005

DNA topoisomerase I(TOP1) helps the control of DNA replication, transcription and recombination by assist­ing breaking and rejoining of DNA double strand. Camptothecin (CPT) and its derivative, topotecan, are known to inhibit TOP1 by intercalating into TOP1-DNA complex. Recently various non-CPT intercalators are synthesized for a new class of TOP1 inhibitors. In this study, six compounds isolated from Poria cocos were investigated for their interaction with TOP1­DNA complex using the flexible docking program, FlexiDock. The binding modes were analyzed and compared with the TOP1 inhibition activities. The compounds that showed potent activity were intercalated between the + 1/-1 base pairs of DNA, located near the active site phosphotyrosine723 and formed hydrogen bonds with active site residues. On the other hand, compounds with no activity were not docked at all. The binding modes were well correlated with the inhibition activity, suggesting the possibility that potent inhibitors can be designed from the information presented by the docking study.

• Food Science and Biotechnology
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• 제16권6호
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• pp.894-901
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• 2007

This study investigated the effects of cell cultured Acanthopanax senticosus extract (ASE) supplementation and swimming exercise on lipid profiles and carnitine concentrations in C57BL/6J mice fed high fat diets. Male C57BL/6J mice (n=50), aged 4 weeks, were divided into 5 groups based on exercise and/or ASE supplementation (0.5 g/kg of body weight): normal diet (N-C), high fat diet (H-C), high fat diet non-supplement & exercise (H-NSE), high fat diet supplement & no exercise (H-SNE), high fat diet supplement & exercis (H-SE). Liver nonesterified carnitine (NEC) was significantly higher in the H-SNE group than in the H-C group, and liver total carnitine (TCNE) levels were significantly higher in the H-SNE group than in the H-NSE and H-SE groups. Liver and muscle carnitine palmitoyltransferase-I (CPT-I) mRNA levels tended to be higher with ASE supplementation and/or exercise. These results suggest that supplementation with ASE and/or exercise might have a role in improving lipid oxidation.

• Preventive Nutrition and Food Science
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• 제8권2호
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• pp.119-123
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• 2003

To investigate the effects of the supplementation of carnitine and/or ${\gamma}$ -aminobutric acid (GABA), Sprague-Dawley male rats were orally treated with either an AIN-76 diet (control), a control diet plus ethanol (CE, 4 g ethanol/kg bw), CE plus L-carnitine (CEC, 0.5 g/kg bw), CE plus GABA (CEG, 0.5 g/kg bw), or CE plus L-carnitine plus GABA (CECG, 0.25 g/kg bw each) for 6 weeks. Serum triglyceride levels were increased in the CE group and were decreased significantly in the CEC, CEG and CECG groups. HDL-cholesterol was increased and LDL-cholesterol was decreased in the CEG and CECG groups compared with the CE group. Serum GOT and GPT levels increased by the chronic ethanol administration were decreased in the CEC group. In addition, we have evaluated the mRNA levels of carnitine palmitoyltransferase-I in those groups. Supplementation of carnitine/GABA had some recovery effects on the liver CPT-I mRNA levels which decreased by chronic ethanol administration. These results may suggest that supplementations of either L-carnitine or GABA aye effective on the recovery of chronic ethanol-related symptoms, but no combined effects were shown.

• 생물정신의학
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• 제25권1호
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• pp.9-15
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• 2018

Objectives This study intended to identify the deficits of cognitive control among patients with bipolar I disorder and their first-degree relatives, and identify the possibility of cognitive control as an endophenotype of bipolar disorder. Methods The study included three groups: euthymic states patients with bipolar I disorder (n = 55), unaffected first-degree relatives of probands with bipolar I disorder (n = 30), and a healthy control group (n = 51), that was matched on age, sex, and years of education. The AX version of the continuous performance test (CPT) was used to examine cognitive control. Error rate, correct response times of each subsets (AX, BX, AY, BY), and d' as an indication of accuracy sensitivity index were calculated. Psychopathology, intelligence, and psychomotor speed were also assessed. Results Patients with bipolar I disorder showed significantly worse error rates in the AX (p = 0.01) and BX (p = 0.02) subsets and d' (p = 0.05) than the others. They also showed more delayed correct response times than the healthy control group and first-degree relatives in all subsets (p < 0.01). But first-degree relatives showed neither high error rates nor delayed correct response times than healthy control group. Conclusions These findings suggest that cognitive control is impaired in bipolar I disorder but less likely to be an endophynotype of bipolar I disorder.

• 한국영양학회:학술대회논문집
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• 한국영양학회 2003년도 연합학술대회
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• pp.174.2-174.2
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• 2003

• Geomechanics and Engineering
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• 제5권4호
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• pp.343-362
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• 2013

Simple relationships are proposed in this paper by modifying the Schmertmann's equation for settlement estimations of footings (i.e., $B/L{\approx}1$) carrying vertical loads in saturated and unsaturated sandy soils. The modified method is developed using model plate load tests (PLTs) and cone penetration tests (CPTs) results conducted in saturated and unsaturated sand in a controlled laboratory environment. Seven in-situ large-scale footings tested under both saturated and unsaturated conditions in sands were used to validate the proposed technique. The results of the study are encouraging as they provide reliable estimates of the settlement of shallow footings in both saturated and unsaturated sands using the conventional CPT results.

• The Korean Journal of Physiology and Pharmacology
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• 제8권2호
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• pp.95-100
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• 2004

Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium $(K_{ATP})$ channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that $K_{ATP}$ channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide $(100\;{\mu}M)$, SNAP $(300\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) $(100\;{\mu}M)$ followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide $(50\;{\mu}M)$, 5-hydroxydecanoate (5-HD) $(100\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) $(100\;{\mu}M)$. These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of $K_{ATP}$ channels in rat ventricular myocytes.

• Preventive Nutrition and Food Science
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• 제8권1호
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• pp.40-45
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• 2003

Acanthopanax senticosus was grown by a novel, proprietary method, of culturing isolated cells in a bioreactor. An extract from the cells was evaluated for its effect on lipid metabolism in rats fed a high fat diet. Male Sprague-Dawley rats (n＝6) were fed either an AIN-76 diet (control, NDCon), control diet plus Acanthopanax senticosus extract (ND＋Ex), a modified AIN-76 diet supplemented with 20% beef tallow (high fat, HFCon), or a high fat diet plus Acanthopanax senticosus extract (HF＋Ex), for 5weeks. Body weight gain was significantly higher in the HFCon group than the NDCon group. Feed consumption was significantly lower, but energy intake higher, in the groups fed high fat diets compared with the groups fed control diets. Serum HDL-cholesterol concentrations were significantly increased but serum LDL-cholesterol concentrations were decreased in the groups fed the Acanthopanax senticosus extract. Abdominal fat accumulation and serum leptin levels were significantly higher in the HFCon group than the other groups. Carnitine palmitoyltransferase-I (CPT-I) mRNA levels were increased in the groups fed Acanthopanx senticosus extract. These results suggest that supplementation of cell cultured Acanthopanax senticosus extract regulates CPT-I mRNA levels in liver and has an effect on the normalization of lipids in rats fed a high fat diet.