• Archives of Pharmacal Research
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• v.26 no.1
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• pp.28-33
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• 2003

Ginsenosides, major active ingredients of Panax ginseng, are known to regulate excitatory ligand-gated ion channel activity such as nicotinic acetylcholine and NMDA receptor channel activity. However, it is not known whether ginsenosides affect inhibitory ligand-gated ion channel activity. We investigated the effect of ginsenosides on human recombinant $GABA_A$ receptor (${\alpha}_1{\beta}_1{\gamma}_{2s}$) channel activity expressed in Xenopus oocytes using a two-electrode voltage-clamp technique. Among the eight individual ginsenosides examined, namely, $Rb_1$, $Rb_2$, Rc, Rd, Re, Rf, $Rg_1$ and $Rg_2$, we found that Rc most potently enhanced the GABA-induced inward peak current ($I_{GABA}$). Ginsenoside Rc alone induced an inward membrane current in certain batches of oocytes expressing the $GABA_A$ receptor. The effect of ginsenoside Rc on $I_{GABA}$ was both dose-dependent and reversible. The half-stimulatory concentration ($EC_{50}$) of ginsenoside Rc was 53.2$\pm$12.3 $\mu$M. Both bicuculline, a $GABA_A$ receptor antagonist, and picrotoxin, a $GABA_A$ channel blocker, blocked the stimulatory effect of ginsenoside Rc on $I_{GABA}$. Niflumic acid (NFA) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), both $CI^{-1}$ channel blockers, attenuated the effect of ginsenoside Rc on I$I_{GABA}$. This study suggests that ginsenosides regulated $GABA_A$ receptor expressed in Xenopus oocytes and implies that this regulation might be one of the pharmacological actions of Panax ginseng.

• Development and Reproduction
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• v.25 no.4
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• pp.199-211
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• 2021

Equine chorionic gonadotropin (eCG), produced by the endometrial cups of the placenta after the first trimester, is a specific glycoprotein that displays dual luteinizing hormone (LH)-like and follicle-stimulating hormone (FSH)-like effects in non-equid species. However, in equidaes, eCG exhibits only LH-like activity. To identify the specific biological functions of glycosylated sites in eCG, we constructed the following site mutants of N- and O-linked glycosylation: eCGβ/αΔ56, substitution of α-subunit⁵⁶ N-linked glycosylation site; eCGβ-D/α, deletion of the O-linked glycosylation sites at the β-subunit, and eCGβ-D/αΔ56, double mutant. We produced recombinant eCG (rec-eCG) proteins in Chinese hamster ovary suspension (CHO-S) cells. We examined the biological activity of rec-eCG proteins in CHO-K1 cells expressing the eLH/CG receptor and found that signal transduction activities of deglycosylated mutants remarkably decreased. The EC₅₀ levels of eCGβ/αΔ56, eCGβ-D/α, and eCGβ-D/αΔ56 mutants decreased by 2.1-, 5.6-, and 3.4-fold, respectively, compared to that of wild-type eCG. The Rmax values of the mutants were 56%-80% those of wild-type eCG (141.9 nmol/10⁴ cells). Our results indicate that the biological activity of eCG is greatly affected by the removal of N- and O-linked glycosylation sites in cells expressing eLH/CGR. These results provide important information on rec-eCG in the regulation of specific glycosylation sites and improve our understanding of the specific biological activity of rec-eCG glycosylation sites in equidaes.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.419-426
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• 2019

Mosapride accelerates gastric emptying by acting on 5-hydroxytryptamine type 4 ($5-HT_4$) receptor and is frequently used in the treatment of gastrointestinal (GI) disorders requiring gastroprokinetic efficacy. We tested the effect of mosapride on 5-hydroxytryptamine type 3 ($5-HT_3$) receptor currents because the $5-HT_3$ receptors are also known to be expressed in the GI system and have an important role in the regulation of GI functions. Using the whole-cell voltage clamp method, we compared the currents of the $5-HT_3$ receptors when 5-HT was applied alone or was co-applied with mosapride in cultured NCB-20 cells known to express $5-HT_3$ receptors. The $5-HT_3$ receptor current amplitudes were inhibited by mosapride in a concentration-dependent manner. Mosapride blocked the peak currents evoked by the application of 5-HT in a competitive manner because the $EC_{50}$ shifted to the right without changing the maximal effect. The rise slopes of $5-HT_3$ receptor currents were decreased by mosapride. Pre-application of mosapride before co-application, augmented the inhibitory effect of mosapride, which suggests a closed channel blocking mechanism. Mosapride also blocked the opened $5-HT_3$ receptor because it inhibited the $5-HT_3$ receptor current in the middle of the application of 5-HT. It accelerated desensitization of the $5-HT_3$ receptor but did not change the recovery process from the receptor desensitization. There were no voltage-, or use-dependency in its blocking effects. These results suggest that mosapride inhibited the $5-HT_3$ receptor through a competitive blocking mechanism probably by binding to the receptor in closed state, which could be involved in the pharmacological effects of mosapride to treat GI disorders.

• Journal of Environmental Analysis, Health and Toxicology
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• v.21 no.4
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• pp.209-219
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• 2018

In the areas of RoHS, WEEE, ELV and REACH, reinforcement of environmental regulations against harmful substances is a global trend not only in EC but also in all over the world. In the fields of Korea's major export products such as material parts, electrical and electronic products and automobile parts, we are responding to these regulations consistently. To develop reference material for analyzing lead and cadmium in paints, the candidate materials were produced through the screening process which separated shapes and sizes. To secure the traceability of the candidate materials produced, the characteristics and uncertainties are estimated by ICP-AES analysis using the primary reference material. The short-term and long-term stabilities also are evaluated in parallel. In order to calculate the final certification value of the candidate material, the verification were carried out by the performance evaluation through the comparison among the KOLAS (Korea Laboratory Accreditation Scheme) laboratories, and the CRM was produced in accordance with ISO Guide 35. The certified values and uncertainties of Pb and Cd of the final paint standard, determined according to the joint analysis among laboratories, are Pb [($191.4{\pm}3.1$) mg/kg, ($944.1{\pm}5.6$) mg/kg] and Cd [($45.0{\pm}2.6$) mg/kg, ($225.5{\pm}3.5$) mg/kg]. These standard materials were developed to enhance the reliability of measurement analysis, including the validity and traceability of measurement results. Also it is expected that the CRM will be used as QCM (quality control material) for the product design and the process monitoring, so that regulation and management of hazardous heavy metals can be systematically implemented.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.536-542
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• 2022

Background: In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. Methods: The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H₂O₂, and the keratinocyte cells were treated with SYR (0-200 ㎍/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. Results: SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H₂O₂-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC₅₀ value of 10.77 and 10.35 ㎍/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H₂O₂-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. Conclusion: SYR showed antioxidant activity and up-regulated autophagy activity in H₂O₂-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.

• Coupled systems mechanics
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• v.11 no.6
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• pp.505-524
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• 2022

Floods represent extreme hydrological phenomena that affect populations, environment, social, political, and ecological systems. After the catastrophic floods that have hit Europe and the World in recent decades, the flood problem has become more current. At the EU level, a legal framework has been put in place with the entry into force of Directive 2007/60/EC on Flood Risk Assessment and Management (Flood Directive). Two years after the entry into force of the Floods Directive, Bosnia and Herzegovina (B&H), has adopted a Regulation on the types and content of water protection plans, which takes key steps and activities under the Floods Directive. The "Methodology for developing flood hazard and risk maps" (Methodology) was developed for the territory of Bosnia and Herzegovina, following the methodology used in the majority of EU member states, but with certain modifications to the country's characteristics. Accordingly, activities for the preparation of the Preliminary Flood Risk Assessment for each river basin district were completed in 2015 for the territory of Bosnia and Herzegovina. Activities on the production of hazard maps and flood risk maps are in progress. The results of probable climate change impact model forecasts should be included in the preparation of the Flood Risk Management Plans, which is the subsequent phase of implementing the Flood Directive. By the foregoing, the paper will give an example of the development of the hydrodynamic model of the Zujevina River, as well as the development of hazard and risk maps. Hazard and risk maps have been prepared for medium probability floods of 1/100 as well as for high probability floods of 1/20. The results of LiDAR (Light Detection and Ranging) recording were used to create a digital terrain model (DMR). It was noticed that there are big differences between the flood maps obtained by recording LiDAR techniques in relation to the previous flood maps obtained using georeferenced topographic maps. Particular attention is given to explaining the Methodology applied in Bosnia and Herzegovina.

• The Korean Journal of Air & Space Law and Policy
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• v.31 no.2
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• pp.73-98
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• 2016

This is a case review of the Korean Supreme Court about international jurisdiction over a foreign-related case. This case is a guideline to other following cases how Korean court has international jurisdiction over the foreign elements cases. This case was an air crash accident in Busan, Korea. And the applicant was a chinese who was parents of flight attendant. The defendant was Air China. The applicant suid the defendant in Korea court, requesting for compensation for damages based on the contract of employment between died employee and the defendant and tort. The trial court rejected jurisdiction. But Supreme court granted jurisdiction on Korean court. The court determined the jurisdiction by the Korean Private International Law Act(KPILA). The KPILA has a concept of 'substantial connection', it is a main legal analysis to determine the jurisdiction. In the act, Article 2 Paragraph 1 says "In case a party or a case in dispute is substantively related to the Republic of Korea, a court shall have the international jurisdiction. In this case, the court shall obey reasonable principles, compatible to the ideology of the allocation of international jurisdiction, in judging the existence of the substantive relations." And Article 2 Paragraph 2 declares "A court shall judge whether or not it has the international jurisdiction in the light of jurisdictional provisions of domestic laws and shall take a full consideration of the unique nature of international jurisdiction in the light of the purport of the provision of paragraph (1)." In this case review find concepts, theories and cases out to clarify the meaning about Article 2 of the KPILA. Also it quoted from the concept of "the base rule" in Rome I (Regulation (EC) 593/2008 on the law applicable to contractual obligations) to apply the contract of employment between flight attendant and Air carrier.

• The Korean Journal of Air & Space Law and Policy
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• v.33 no.2
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• pp.225-266
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• 2018

In 2017, 1,252 cases of damages relief related to air passenger transport service were received by the Korea Consumer Agency, a 0.8% drop from 1,262 cases in 2016, the first decline since 2013. In 2017, 444 cases (35.4%) out of received cases of damages relief in the field of air passenger service received by the Korea Consumer Agency were agreed on, and out of cases that were not agreed on, the most number of 588 cases (47.0%) were concluded due to information provision and counseling, and 186 cases (14.9%) were applied to the mediation of the Consumer Dispute Mediation Committee. Major legislations that contain regulations for the damages relief and disputes resolution of air service consumers include the Aviation Business Act and the Consumer Fundamental Act, etc. The Aviation Business Act provides the establishment and implementation of damage relief procedure and handling plan, and the receiving and handling of request of damage relief by air transport businessman, and the notice of protection standard for air traffic users. The Consumer Fundamental Act provides the establishment and management of the consumer counseling organization, the damage relief by the Korea Consumer Agency, the consumer dispute mediation, and the enactment of the criteria for resolving consumer disputes. The procedures for damages relief of air service consumers include the receiving and handling of damages relief by air transport businessman, the counseling, and receiving and handling of damages relief by the Consumer Counseling Center, the advice of mutual agreement by the Korea Consumer Agency, and the dispute mediation system by the Consumer Dispute Mediation Committee. The current system of damage relief and dispute mediation for air service consumer have the problem in the exemption from obligation of establishment and implementation of damage relief plan by air transport businessman under the Aviation Business Act, the problem in the exemption from liability in case of nonfulfillment and delay of transport by aviation businessman under the criteria for resolving consumer disputes in the aviation sector, and the uppermost limit in procedure progress and completion of consumer dispute mediation under the Consumer Fundamental Act. Therefore, the improvement measurements of the relevant system for proper damage relief and smooth dispute mediation for air service consumer are to be suggested as follows: First is the maintenance of the relevant laws for damage relief of air service consumer. The exemption regulation from obligation of establishment and implementation of damage relief plan by air transport businessman under the Aviation Business Act shall be revised. To enhance the structualization and expertise of the relevant regulation for protection and damage relief of air service consumer, it will be necessary to prepare the separate legislation similar to the US Federal Regulation 14 CFR and EU Regulation EC Regulation 261/2004. Second is the improvement of criteria for resolving air service consumer disputes. For this, it will be necessary to investigate whether the cause of occurrence of exemption reason was force majeure, and distinguish the exemption from liability in case of nonfulfillment and delay of transport by aviation businessman under the criteria for resolving consumer disputes in the aviation sector, and revise the same as exemption reasons regulated under the air transport chapter of the Commercial Act and Montreal Convention 1999, and unify the compensation criteria for the nonfulfillment of transport that the substitute flight was provided and the delay of transport. Third is the reinforcement of information provision for damage relief of air service consumer. Aviation-related government agencies and concerned agencies should cooperate with airlines and airports to provide rapidly and clearly diverse information to the air traffic users, including laws and policies for damages relief of air service consumers. Fourth is the supplement to the effectiveness, etc. of consumer dispute mediation. If there is no sign of acceptance for dispute mediation, it is not fair to regard it as acceptance, therefore it will be necessary to add objection system. And if a dispute resolution is requested to another dispute settlement agency in addition to the Consumer Dispute Mediation Committee, it is excluded from the damage relief package, but it should be allowed for the party to choose a mediation agency. It will be necessary to devise the institutional measures to increase the completion rate of mediation so that the consumer dispute can be resolved efficiently through the mediation. Fifth is the introduction of the air service consumer arbitration system. A measure to supplement the limitations of the consumer dispute mediation system is to introduce the consumer arbitration system, but there are two measurements which are the introduction of the consumer arbitration under the Consumer Fundamental Act and the introduction of the consumer arbitration under the Arbitration Act. The latter measurement is considered to be appropriate. In conclusion, as a policy task, the government should prepare laws and system to enhance the prevention and relief of damages and protection of the rights and interests of air service consumers, and establish and implement the consumer-centric policy for the advancement of air service.

• The Korean Journal of Air & Space Law and Policy
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• v.32 no.1
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• pp.3-51
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• 2017

From a historical point of view, while the Warsaw Convention was passed in 1924 to regulate the unified judicial responsibility in the global air transportation industry, protection of airline consumers was somewhat lacking in protecting air carriers. In principle, the air carrier does not bear any obligation or liability when the aircraft is not operated normally due to natural disasters such as typhoon or heavy snowfall. However, in recent years, in developed countries such as the US and Europe, there has been a movement in which regulates the air carriers' obligation to protect their passengers even if there is no misconduct or negligence. Furthermore, the legislation of such advanced countries imposes an obligation on the airlines to compensate the loss separately from damages in case the abnormal operation of the aircraft is not caused by force majeure but caused by their negligence. Under this historical and international context, Korea is also modifying the system of aviation consumer protection by referring to other foreign legislation. However, when compared with foreign countries, our norm has a few drawbacks. First, the airline's protection or care obligations are mixed with the legal liability for damages in the provision, which seems to be due to the lack of understanding of the airline's passenger protection obligation. The liability for damages, which is governed by the International Convention or the Commercial Act, shall be determined by judging the cause of the airline's liability in respect of the damage of the individual passenger in the course of the air transportation. However, the duty to care and the burden for compensation shall be granted to all passengers who feel uncomfortable with the abnormal operation regardless of the cause of the accident. Also, our compensation system for denied boarding due to oversale is too low compared to the case of foreign countries, and setting the compensation amount range differently based on the time for the re-routing is somewhat unclear. Regarding checked-baggage claim, it will be necessary to refund the fee only from the fact that the baggage is delayed without asking whether there is any damage occurred from the delayed baggage. This is the content of the duty to care, which is different from the current Commercial Act or the international convention, in which responsibility is different depending on whether the airline takes all the necessary measures in order to prevent delaying of the baggage. The content of force majeure, which is a requirement for exemption from the obligation to care passengers on the airplane, shall be reconsidered. Maintenance for safe navigation is not considered to be included in force majeure, and connection to airplanes, airport conditions are disputable. According to the EC Regulation, if the cause of the abnormal operation of the airline is force majeure, the airline's compensation obligation is exempted but the duty to care of airline company is still meaningful. Furthermore, even if the main role of aviation consumer protection is on an airline, it is the responsibility of government agencies to supervise the fulfillment of such protection obligations. Therefore, it is necessary for the Korean government to actively take measures such as enforcing incentives for airlines that faithfully fulfill their obligation to care and imposed penalties on the contrary.

• The Korean Journal of Air & Space Law and Policy
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• v.35 no.2
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• pp.3-40
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• 2020

The term "accident" in the Warsaw Convention of 1929 and the Montreal Convention of 1999, which govern carrier liability in international air transport, is an important criterion for determining carrier liability. However, because there is no explicit definition of the term in the treaty provisions, the term is largely subjected to the judgment and interpretation of the courts. Although there have been numerous changes in purpose and circumstance in the transition from the Warsaw regime to the conclusion of the Montreal Convention, there was no discussion on the concept of "accident" therefore, even after the adoption of the Montreal Convention, there is no doubt that the term is to be interpreted in the same manner as before. On this point, the United States Supreme Court's Air France v. Saks clarified the concept of "accident" and is still cited as an important precedent. Recently, the CJEU, in GN v. ZU, presented a new concept of "accident" introduced in the Montreal Convention: that "reference must be made to the ordinary meaning" in interpreting "accident" and that the term "covers all situations occurring on aboard an aircraft." Furthermore, the CJEU ruled that the term does not include the applicability of "hazards typically associated with aviation," which was controversial in previous cases. Such an interpretation can be reasonably seen as the court's expansion of the concept of "accident," with a focus on "protecting consumer interests," a core tenet of both the Montreal convention and the European Union Regulations(EC: No 889/2002). The CJEU's independent interpretation of "accident" is a departure from the Warsaw Convention and the Saks case, with their focus on "carrier protection," and instead focuses on the "passenger protection" standard of the Montreal Convention. Consequently, this expands both the court's discretion and the carrier's risk management liability. Such an interpretation by the CJEU can be said to be in line with the purpose of the Montreal Convention in terms of "passenger protection." However, there are problems to be considered in tandem with an expanded interpretation of "accident." First, there may be controversy concerning "balance" in that it focused on "passenger protection" in relation to the "equitable balance of interests" between air carriers and passengers, which is the basic purpose of the agreement. Second, huge losses are expected as many airlines fly to countries within the European Union. Third, there is now a gap in the interpretation of "accident" in Europe and the United States, which raises a question on the "unity of rules," another basic tenet of the Convention. Fourth, this interpretation of "accident" by the CJEU raises questions regarding its scope of application, as it only refers to the "hazards typically associated with aviation" and "situations occurring aboard an aircraft." In this case, the CJEU newly proposed a novel criterion for the interpretation of "accident" under the Montreal Convention. As this presents food for thought on the interpretation of "accident," it is necessary to pay close attention to any changes in court rulings in the future. In addition, it suggests that active measures be taken for passenger safety by recognizing air carriers' unlimited liability and conducting systematic reforms.