• The Korean Journal of Pain
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• v.12 no.1
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• pp.1-7
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• 1999

Background: To study the role of spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in pain behaviors caused by mild burn, we examined the effect of intrathecal administered ACEA 2085, which has been recently characterized as a high potency competitive AMPA receptor antagonist, on the thermal hyperalgesia state induced by mild burn. Methods: A thermal injury was induced by applying the left hind paw to a thermal surface ($52.5^{\circ}C$) for 45 sec. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus. Thirty min after thermal injury, the paw withdrawal latency (PWL) in injured paw of all groups fell from 10~12 sec to 5~7 sec. At that time, ACEA 2085 (0.01~0.1 mcg) and 6-cyano-7-nitroquinoxalinedione (CNQX, 1~30 mcg) were injected through intrathecal heters in rats with mild burn injury on the right hindpaw. And then, PWL were measured in the both hindpaw every 30 minutes for about three hours. Results: The intrathecal injection of ACEA 2085 produced a dose dependent reversal of the hyperalgesia in the right hindpaw and more potent than CNQX, but had no effect upon the response latency of the normal left hind paw even at the largest doses. All effects were observed at doses that had no significant effect upon motor function. Conclusions: Intrathecal ACEA 2085, highly selective AMPA receptor antagonist produce a dose- dependent reversal of the thermal hyperalgesia evoked mild burn injury. These results suggested that spinal AMPA receptor play an important role in the hyperalgesia induced by mild burn injury.

• Journal of Korea Port Economic Association
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• v.40 no.3
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• pp.1-26
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• 2024

This study aims to examine the business diversification status of Global Container Terminal Operators(GTOs) and to determine the impact of business diversification on corporate performance using a quantitative index. To this end, a panel regression analysis was conducted using 10-year time series data of 12 GTOs. The results of the empirical analysis show that, first, the mean of the business diversification index of GTOs is rather low at 0.244; second, the business diversification of GTOs affects ROE and TobinsQ among corporate performance. In the case of the dependent variable ROE, we found that there is a non-linear relationship, with no effect in the early stage, a negative effect after a certain level, and a positive effect after a certain level, while the dependent variable TobinsQ has a positive linear relationship. As a result, it seems that GTOs with strong global influence should pursue business diversification in the direction of strengthening and expanding their core business capabilities, and efficient selection and focus at the corporate level are necessary to avoid excessive diversification due to indiscriminate business expansion.

• Journal of Life Science
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• v.21 no.10
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• pp.1385-1392
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• 2011

It is well known that both insulin-like growth factor-I and suppressor of cytokine signaling-3 (SOCS-3) are known to modulate various aspects of physiology in skeletal muscle cells. Furthermore, although SOCS-3 expression is related to insulin resistance in non-skeletal muscle cells and is known to interact with insulin-like growth factor-I receptor, the effect of IGF-I on SOCS-3 gene expression in skeletal muscle cells is presently unknown. C2C12 myotubes were treated with different concentrations (0-200 ng/ml) of IGF-I or for various periods of time (3-72 hr). Immunofluorescent staining image revealed that IGF-I induced SOCS-3 protein expression in a dose-dependent manner. Western blot data also showed that SOCS-3 proteins were induced by IGF-I (200 ng/ml) in C2C12 myotubes in a time-dependent manner. The level of SOCS-3 mRNA was also significantly increased after 3hr of IGF-I (10-100 ng/ml) treatment. However, the levels of SOCS-3 mRNA were significantly decreased after 24 and 48 hr of IGF-I (10-100 ng/ml) treatment compared to the control. In conclusion, SOCS-3 protein is induced by IGF-I treatment in C2C12 skeletal muscle cells and this induction is regulated pretranslationally. The modulating effect of IGF-I on SOCS-3 expression may be an important regulator of gene expression in skeletal muscle cells.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.5
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• pp.265-272
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• 2004

The present study was attempted to investigate the effect of cilnidipine (FRC-8635), which is a newly synthesised novel dihydropyridine (DHP) type of organic $Ca^{2+}$ channel blockers, on secretion of catecholamines (CA) evoked by acetylcholine (ACh), high $K^+$, DMPP and McN-A-343 from the isolated perfused rat adrenal gland. Cilnidipine $(1{\sim}10{\mu}M)$ perfused into an adrenal vein for 60 min produced relatively dose- and time-dependent inhibition in CA secretory responses evoked by ACh $(5.32{\times}10^{-3}M),\;DMPP\;(10^{-4}M\;for\;2\;min)$ and McN-A-343 $(10^{-4}M\;for\;2\;min)$. However, lower dose of cilnidipine did not affect CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M)$, higher dose of it reduced greatly CA secretion of high $K^{+}$. Cilnidipine itself did fail to affect basal catecholamine output. In the presence of cilnidipine $(10{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10{\mu}M)$, an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid $(10{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase were also inhibited. Moreover, ${\omega}-conotoxin\;GVIA\;(1{\mu}M)$, a selective blocker of the N-type $Ca^{2+}$ channels, given into the adrenal gland for 60 min, also inhibited time-dependently CA secretory responses evoked by Ach, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid. Taken together, these results demostrate that cilnidipine inhibits CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors from the isolated perfused rat adrenal gland without affecting the basal release. However, at lower dose, cilnidipine did not affect CA release by membrane depolarization while at larger dose inhibited that. It seems likely that this inhibitory effect of cilnidipine is exerted by blocking both L- and N-type voltage-dependent $Ca^{2+}$ channels (VDCCs) on the rat adrenomedullary chromaffin cells, which is relevant to inhibition of both the $Ca^{2+}$ influx into the adrenal chromaffin cells and intracellular $Ca^{2+}$ release from the cytoplasmic store. It is thought that N-type VDCCs may play an important role in regulation of CA release from the rat adrenal medulla.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.514-522
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• 2004

Background : Non-steroidal anti-inflammatory drugs (NSAID) are useful in chemoprevention of colorectal cancers. Continuous NSAID administation causes 40% to 50% reduction in relative risk for colorectal cancer. Sulindac possesses an antiproliferative effect and induces apoptosis and tumor regression on colon cancer and other types of cancers. We intended to analyze the effects of sulindac in three non-small cell lung cancer cell lines. Materials and Methods : The human lung cancer cell lines, A549, NCI-H157 and NCI-H460 were used for this study. Viability was tested by MTT assay, and cell death rate was measured by lactate dehydrogenase(LDH) release. Apoptosis was estimated by flow cytometric analysis and nuclear staining. Results: Sulindac was able to decrease the viability of non-small cell lung cancer cells in a dose- and time- dependent manner. In a parallel effect of sulindac on cell death rate, LDH release was increased in sulindac-treated lung cancer cells. Sulindac significantly increased apoptosis characterized by an increase of $sub-G_0/G_1$ fraction and morphological change of nuclei. The rate of apoptotic cells after sulindac treatment in lung cancer cells increased in a time- and dose- dependent manner in flow cytometric analysis. Apoptotic cells were defined as nuclear shrinkage, chromatin condensation and nuclear fragmentation of cells. Conclusion : Sulindac decreases viability and induces the apoptosis of lung cancer cells. Further studies will be needed to elucidate the potential mechanism of sulindac-induced apoptosis in lung cancer cells.

• The Korean Journal of Pharmacology
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• v.13 no.2
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• pp.11-17
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• 1977

The effects of varing concentrations of extracellular potassium on the positive inotropic actions of Aconiti tuber butanol fraction and ouabain were studied on isolated left atrium of rat. The patterns of active tension increment, such as time to peak and total duration of tension development, was contrasted in Aconiti tuber butanol fraction to ouabain. Ouabain did not induce significant shortening in time to peak and total duration of tension development, but Aconiti tuber produce significant shortening. The isometric tension and peak dF/dt were not significantly different at the range of extracellular potassium concentration $2mEq{\sim}10mEq$ per. liter in control studies. The ouabain-induced increase in active tension and peak dF/dt at 2mEq. per. liter potassium concentration was significantly different from that of 6mEq or 10mEq. per. liter, but there was no difference between 6mEq and 10mEq. per. liter. but Aconiti tuber is not. In contrast to ouabain, Aconiti tuber butanol fraction did not show potassium dependent positive inotropic effect. It produced almost same increment of tension and peak dF/dt at all the concentration of extracellular potassium concentrations in this experiment.

• Journal of Yeungnam Medical Science
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• v.21 no.2
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• pp.177-190
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• 2004

Background: Secretory phospholipase $A_2$ ($sPLA_2$) are a group of extracellular enzymes that release fatty acids at the sn-2 position of phospholipids. Group IIA $sPLA_2$ ($sPLA_2$-IIA) has been detected in the inflammatory fluids, and its plasma level increases in the inflammatory disease. This study examined the effect of $sPLA_2$-IIA on mouse macropahges in order to investigate the potential mechanism of $sPLA_2$-induced inflammation. Materials and Methods: Wild type $PLA_2$ and mutant H48Q $PLA_2$ were purified from HEK293 cells transfected with the corresponding plasmids, and the $PLA_2$ activities were measured using 1-palmitoyl-2-[1-$^{14}C$]linoleoyl-3-phosphatidylethanolamine as substrates. The TNF-${\alpha}$ and IL-6 released in the supernatants were determined by ELISA. In addition, the TNF-${\alpha}$ and IL-6 mRNA were analyzed by RT-PCR. Results: $sPLA_2$-IIA stimulated the production of TNF-${\alpha}$ and IL-6 in a dose- and time-dependent manner. In addition, the effect of $sPLA_2$-IIA on cytokine production from the macrophage was found to be associated with the accumulation of their specific mRNA. The mRNA levels of TNF-${\alpha}$ and IL-6 peaked at 2 and 6 hours in a time-dependent manner, respectively. Conclusion: In conclusion, the production of proinflammatory cytokine might be mediated by the binding of $sPLA_2$-IIA to the receptors.

• Advances in nano research
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• v.12 no.5
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• pp.501-514
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• 2022

This study aimed to investigate the effects and potential mechanisms of Chikusetsusaponin V (CsV) on endothelial nitric oxide synthase (eNOS) and vascular endothelial cell functions. Different concentrations of CsV were added to animal models, bovine aorta endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) cultured in vitro. qPCR, Western blotting (WB), and B ultrasound were performed to explore the effects of CsV on mouse endothelial cell functions, vascular stiffness and cellular eNOS mRNA, protein expression and NO release. Bioinformatics analysis, network pharmacology, molecular docking and protein mass spectrometry analysis were conducted to jointly predict the upstream transcription factors of eNOS. Furthermore, pulldown and ChIP and dual luciferase assays were employed for subsequent verification. At the presence or absence of CsV stimulation, either overexpression or knockdown of purine rich element binding protein A (PURA) was conducted, and PCR assay was employed to detect PURA and eNOS mRNA expressions, Western blot was used to detect PURA and eNOS protein expressions, cell NO release and serum NO levels. Tube formation experiment was conducted to detect the tube forming capability of HUVECs cells. The animal vasodilation function test detected the vasodilation functions. Ultrasonic detection was performed to determine the mouse aortic arch pulse wave velocity to identify aortic stiffness. CsV stimulus on bovine aortic cells revealed that CsV could upregulate eNOS protein levels in vascular endothelial cells in a concentration and time dependent manner. The expression levels of eNOS mRNA and phosphorylation sites Ser1177, Ser633 and Thr495 increased significantly after CsV stimulation. Meanwhile, CsV could also enhance the tube forming capability of HUVECs cells. Following the mice were gavaged using CsV, the eNOS protein level of mouse aortic endothelial cells was upregulated in a concentration- and time-dependent manner, and serum NO release and vasodilation ability were simultaneously elevated whereas arterial stiffness was alleviated. The pulldown, ChIP and dual luciferase assays demonstrated that PURA could bind to the eNOS promoter and facilitate the transcription of eNOS. Under the conditions of presence or absence of CsV stimulation, overexpression or knockdown of PURA indicated that the effect of CsV on vascular endothelial function and eNOS was weakened following PURA gene silence, whereas overexpression of PURA gene could enhance the effect of CsV upregulating eNOS expression. CsV could promote NO release from endothelial cells by upregulating the expression of PURA/eNOS pathway, improve endothelial cell functions, enhance vasodilation capability, and alleviate vessel stiffness. The present study plays a role in offering a theoretical basis for the development and application of CsV in vascular function improvement, and it also provides a more comprehensive understanding of the pharmacodynamics of CsV.

• Journal of Life Science
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• v.25 no.7
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• pp.773-779
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• 2015

This study examined extracts from five different kinds of lees and nuruk and their organic solvent fractions in terms of several biological functions, such as anti-adipogenic, anti-inflammatory, and anti-proliferative activities. The anti-adipogenic activity was investigated by treating mouse pre-adipocyte 3T3-L1 cells with one extract (YE) and four organic solvent fractions (YAc, PAc, RAc, and WPAc) during adipogenesis. Among the treated samples, the ethyl acetate fraction of W-Ju lees (WPAc) showed the strongest anti-adipogenic effect, which was confirmed with oil red O staining and down-regulation of pro-adipogenic genes such as PPAR-gamma and SCD-1. Treatment with WPAc also reduced the expression of PPAR-gamma in a time-dependent manner. The effects of five different extracts were examined on nitric oxide (NO) production in mouse RAW 264.7 cells to determine anti-inflammatory activity. The ethyl acetate fraction of B-Ju lees (PAc) significantly decreased NO production in LPS-stimulated RAW 264.7 cells and it also inhibited NO production in a dose-dependent manner. The PAc fraction also dramatically decreased the viability of human colorectal cancer HCT116 cells in a dose-dependent manner. In addition, PAc increased the expression of NAG-1 and ATF3 genes in a dose dependent manner. Overall, these results indicate that lees and nuruk have several biological functions, including anti-adipogenic, anti-inflammatory, and anti-proliferative activities.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.241-248
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• 2010

The present sutdy aimed to determine whether olmesartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor blocker, can influence the CA release from the isolated perfused model of the rat adrenal medulla. Olmesartan ($5{\sim}50{\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane-depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Olmesartan did not affect basal CA secretion. Also, in adrenal glands loaded with olmesartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of voltage-dependent L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), veratridine (100 ${\mu}M$, an activator of voltage-dependent $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations ($150{\sim}300{\mu}M$), olmesartan rather enhanced the ACh-evoked CA secretion. Taken together, these results show that olmesartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by direct membrane depolarization from the rat adrenal medulla, but at high concentrations it rather potentiates the ACh-evoked CA secretion. It seems that olmesartan has a dual action, acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of olmesartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement on the CA secreton.