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Effect of Glutathione on Lead Induced Modulation of NO Synthesis in RAW 264.7 Cell (RAW 264.7 Cell에서 납에 의한 NO 생성의 조절에 미치는 Glutathione의 효과)

  • Oh, Gyung-Jae;Kwon, Keun-Sang;Yoon, Wook-Hee;Shin, Sae-Ron
    • Journal of Preventive Medicine and Public Health
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    • v.35 no.4
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    • pp.269-274
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    • 2002
  • Objectives : To evaluate the elect of glutathione(GSH) on lead induced modulation of nitric oxide(NO) synthesis, and to examine how lead modulates NO production in macrophages. Methods : This study was observed in a culture of RAW 264.7 cells, which originated from a tumor in a Balb/c mouse that was induced by the Abelson murine leukemia virus. The compounds investigated were lead chloride, N-acetyl-cystein(NAC), and Buthionine Sulfoximine( BSO). Results : ATP synthesis in RAW 264.7 cells was unchanged by each lead concentration exposure in a dose dependent manner. The NO synthesis was decreased when exposed to lead($PbCl_2$) concentration $0.5{\mu}M$. The presence of $300{\mu}M$ NAC, used as a pretreatment in the culture medium, caused the recovery of the lead induced decrease in NO synthesis, but in the presence of $300{\mu}M$ BSO as a pretreatment, there was no recoverey. Pretreatment with NAC and BSO had no affect on ATP synthesis at any of the lead concentrations used. Conclusions : These results indicated that GSH has a protective effect toward lead toxicity, and suggested that the inhibition of NO production in macrophage due to lead toxicity may be related to cofactors of iNOS (inducible nitric oxide synthase)

Allomyrina dichotoma larva extract attenuates free fatty acid-induced lipotoxicity in pancreatic beta cells

  • Kim, Kyong;Kwak, Min-Kyu;Bae, Gong-Deuk;Park, Eun-Young;Baek, Dong-Jae;Kim, Chul-Young;Jang, Se-Eun;Jun, Hee-Sook;Oh, Yoon Sin
    • Nutrition Research and Practice
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    • v.15 no.3
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    • pp.294-308
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    • 2021
  • BACKGROUD/OBJECTIVES: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells. MATERIALS/METHODS: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively. RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

Antioxidant and Anti-inflammatory Effects of Plantago asiatica L. Extract (질경이 추출물의 항산화 및 항염증 활성)

  • Choi, Yukyung;Choo, Byung-Kil
    • Korean Journal of Organic Agriculture
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    • v.32 no.1
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    • pp.91-105
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    • 2024
  • Plantago asiatica L. (P. asiatica) is a perennial plant belonging to the plantaginaceae and is useful in treating a various diseases such as wounds, bronchitis, and chronic constipation. The bioactive effects of P. asiatica extract was evaluated to determine its potential for use as a variety materials in the food, pharmaceutical, and agricultural industries. Polyphenol and flavonoid contents, free radical scavenging, reducing power activity, and reactive oxygen species (ROS) expression were measured to identify the antioxidative activity. Anti-inflammatory effects were evaluated via analysis of nitric oxide (NO) and pro-inflammatory protein expression in LPS-induced RAW 264.7 cell. As a result of measuring the antioxidant activities of the P. asiatica extract, the total polyphenol content was 50.91±0.78 mg gallic acid equivalents/g and the flavonoid content was 100.99±0.44 mg rutin equivalents/g, and both DPPH and ABTS radical scavenging activities and reducing power increased depending on the concentration. Also, intracellular ROS production was inhibited by the P. asiatica extract. No cytotoxicity was observed when P. asiatica extract was treated, and NO and inflammatory protein expression were inhibited, and nuclear factor kappa B (NF-κB) phosphorylation was also inhibited in a concentration-dependent manner. In conclusion, P. asiatica is a functional natural resources of antioxidant and anti-inflammatory agents that can be used in various industries, including food and agriculture.

Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation

  • Lijing Wang;Qiao Yu;Jian Xiao;Qiong Chen;Min Fang;Hongjun Zhao
    • IMMUNE NETWORK
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    • v.24 no.2
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    • pp.3.1-3.23
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    • 2024
  • Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68+ cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

  • Youngheon Park;Jimin Jang;Jooyeon Lee;Hyosin Baek;Jaehyun Park;Sang-Ryul Cha;Se Bi Lee;Sunghun Na;Jae-Woo Kwon;Seok-Ho Hong;Se-Ran Yang
    • International Journal of Stem Cells
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    • v.16 no.2
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    • pp.191-201
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    • 2023
  • Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.

Effects Unripe and Ripe Rubus coreanus Miquel on Peritoneal Macrophage Gene Expression Using cDNA Microarray Analysis (미숙과와 성숙과 복분자의 섭취가 복강 Macrophages의 유전자 발현에 미치는 영향)

  • Lee, Jung Eun;Cho, Soo-Muk;Kim, Jin;Kim, Jung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.10
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    • pp.1552-1559
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    • 2013
  • Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.

Anti-neuroinflammatory Effect of Teleogryllus emma Derived Teleogryllusine in LPS-stimulated BV-2 Microglia (BV-2 미세아교세포에서 왕귀뚜라미 유래 Teleogryllusine의 신경염증 억제 효과)

  • Seo, Minchul;Shin, Yong Pyo;Lee, Hwa Jeong;Baek, Minhee;Lee, Joon Ha;Kim, In-Woo;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.30 no.11
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    • pp.999-1006
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH2) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.

The Study of Cosmeceutical Activities from Lentinula edodes extracts and Application a Natural Cosmetic Material (표고버섯 추출물의 화장품약리활성 검증과 천연화장품 소재로써의 활용에 관한 연구)

  • Seo, Myeong-Seong;Jang, Young-Ah;Lee, Jin-Tae
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.4
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    • pp.1003-1012
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    • 2018
  • This study is for checking the possibility of Lentinula edodes as cosmetic materials. For this we carried out biological active evaluation about anti-oxidant and anti-inflammatory effects by Lentinula edodes extracts. We extracted Lentinula edodes with water and 70% ethanol and then in order to evaluate anti-oxidant activity we treated samples by concentrations (100, 500, 1000) ${\mu}g/ml$ and carried out 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, the activity of 2,2'-azino-bis ( 3-ethylbenzothiazoline-6-sulphonic acid )-diammonium salt (ABTS) cation radical scavenging and superoxide dismutase(SOD) like activity. Also, in order to evaluate effect of anti-inflammatory the samples in macrophages(RAW 264.7 cells), we carried out evaluation of cell viability, nitric oxide inhibitory activity western blot. The results of DPPH, $ABTS^+$ radical scavenging activity and SOD-like activity of the Lentinula edodes extracts increased in dose-dependent manner. The cytotoxic of samples by MTT assay showed no toxicity at the concentrations of 10, 25 and $50{\mu}g/ml$ of Lentinula edodes extract. Nitric oxide inhibition activity results showed that the extracts reduced NO productions in a concentration-dependent manner. Expression of inflammatory cytokines as $TNF-{\alpha}$, $PGE_2$ and $IL-1{\beta}$ decreased in a concentration-dependent manner and iNOS and COX-2 proteins expression rates were decreased significantly in western blot analysis. From the results of the experiment, it was comfirmed that the Lentinula edodes extracts had excellent anti-oxidant and anti-inflammatory effect and could be used as a safe natural cosmetic material in the future.

New Functional Properties of Passion Fruit Extract on Skin (패션 프룻 추출물이 피부에 미치는 새로운 기능적 효과)

  • Jeong, Mi Suk;Kim, Soon-Rae;Han, Chang Woo;Kim, Hyeon Jin;Jang, Se Bok
    • Journal of Life Science
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    • v.32 no.2
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    • pp.101-107
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    • 2022
  • In this research, the anti-inflammatory, antioxidant, antiaging, and skin whitening properties of pulp and seed extracts of passion fruit were studied. The result of the primary skin irritation test using a skin-attached patch determined the skin irritation index to be 0.00 for the passion fruit extract. In addition, RAW 264.7 macrophages produce NO by stimulation of lipopolysaccharides, and the application of extracts to this resulted in significantly lower NOs, confirming the excellent anti-inflammatory properties of passion fruit extracts. The 2,2-diphenyl-1-picrylhydrazyl test further confirmed that the passion fruit extract exhibits a good 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate radical scavenging ability of 5.11% and strong antioxidant properties. The presence of collagen type I in the skin is a measure of aging and various skin diseases. The results obtained from the analysis of the activity of human procollagen I alpha 1 confirmed that the passion fruit extract reduces the synthesis of procollagen. In addition, the skin whitening property of the passion fruit extract was confirmed by the melanin inhibition test, and a sample was obtained that contained more than 2% of arbutin, a whitening agent approved by the Ministry of Food and Drug Safety, which is generally present in the form of a white powder and is used as a functional ingredient. This confirms that the whitening efficacy of the passion fruit extract obtained from nature contributes to the development of functional raw materials for cosmetics and food.

The Current Status of the Warsaw Convention and Subsequent Protocols in Leading Asian Countries (아시아 주요국가(主要國家)들에 있어서의 바르샤바 체제(體制)의 적용실태(適用實態)와 전망(展望))

  • Lee, Tae-Hee
    • The Korean Journal of Air & Space Law and Policy
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    • v.1
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    • pp.147-162
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    • 1989
  • The current status of the application and interpretation of the Warsaw Convention and its subsequent Protocols in Asian countries is in its fredgling stages compared to the developed countries of Europe and North America, and there is thus little published information about the various Asian governments' treatment and courts' views of the Warsaw System. Due to that limitation, the accent of this paper will be on Korea and Japan. As one will be aware, the so-called 'Warsaw System' is made up of the Warsaw Convention of 1929, the Hague Protocol of 1955, the Guadalajara Convention of 1961, the Guatemala City Protocol of 1971 and the Montreal Additional Protocols Nos. 1,2,3 and 4 of 1975. Among these instruments, most of the countries in Asia are parties to both the Warsaw Convention and the Hague Protocol. However, the Republic of Korea and Mongolia are parties only to the Hague Protocol, while Burma, Indonesia and Sri Lanka are parties only to the Warsaw Convention. Thailand and Taiwan are not parties only to the convention or protocol. Among Asian states, Indonesia, the Phillipines and Pakistan are also parties to the Guadalajara Convention, but no country in Asia has signed the Guatemala City Protocol of 1971 or the Montreal Additional Protocols, which Protocols have not yet been put into force. The People's Republic of China has declared that the Warsaw Convention shall apply to the entire Chinese territory, including Taiwan. 'The application of the Warsaw Convention to one-way air carriage between a state which is a party only to the Warsaw Convention and a state which is a party only to the Hague Protocol' is of particular importance in Korea as it is a signatory only to the Hague Protocol, but it is involved in a great deal of air transportation to and from the united states, which in turn is a party only to the Warsaw Convention. The opinion of the Supreme Court of Korea appears to be, that parties to the Warsaw Convention were intended to be parties to the Hague Protocol, whether they actually signed it or not. The effect of this decision is that in Korea the United States and Korea will be considered by the courts to be in a treaty relationship, though neither State is a signatory to the same instrument as the other State. The first wrongful death claim in Korea related to international carriage by air under the Convention was made in Hyun-Mo Bang, et al v. Korean Air Lines Co., Ltd. case. In this case, the plaintiffs claimed for damages based upon breach of contract as well as upon tort under the Korean Civil Code. The issue in the case was whether the time limitation provisions of the Convention should be applicable to a claim based in tort as well as to a claim based in contract. The Appellate Court ruled on 29 August 1983 that 'however founded' in Article 24(1) of the Convention should be construed to mean that the Convention should be applicable to the claim regardless of whether the cause of action was based in tort or breach of contract, and that the plaintiffs' rights to damages had therefore extinguished because of the time limitation as set forth in Article 29(1) of the Convention. The difficult and often debated question of what exactly is meant by the words 'such default equivalent to wilful misconduct' in Article 25(1) of the Warsaw Convention, has also been litigated. The Supreme Court of Japan dealt with this issue in the Suzuki Shinjuten Co. v. Northwest Airlines Inc. case. The Supreme Court upheld the Appellate Court's ruling, and decided that 'such default equivalent to wilful misconduct' under Article 25(1) of the Convention was within the meaning of 'gross negligence' under the Japanese Commercial Code. The issue of the convention of the 'franc' into national currencies as provided in Article 22 of the Warsaw Convention as amended by the Hague Protocol has been raised in a court case in Korea, which is now before the District Court of Seoul. In this case, the plaintiff argues that the gold franc equivalent must be converted in Korean Won in accordance with the free market price of gold in Korea, as Korea has not enacted any law, order or regulation prescribing the proper method of calculating the equivalent in its national currency. while it is unclear if the court will accept this position, the last official price of gold of the United States as in the famous Franklin Mint case, Special Drawing Right(SDR) or the current French franc, Korean Air Lines has argued in favor of the last official price of gold of the United States by which the air lines converted such francs into us Dollars in their General Conditions of Carriage. It is my understanding that in India, an appellate court adopted the free market price valuation. There is a report as well saying that if a lawsuit concerning this issue were brought in Pakistan, the free market cost of gold would be applied there too. Speaking specifically about the future of the Warsaw System in Asia though I have been informed that Thailand is actively considering acceding to the Warsaw Convention, the attitudes of most Asian countries' governments towards the Warsaw System are still wnot ell known. There is little evidence that Asian countries are moving to deal concretely with the conversion of the franc into their own local currencies. So too it cannot be said that they are on the move to adhere to the Montreal Additional Protocols Nos. 3 & 4 which attempt to basically solve many of the current problems with the Warsaw System, by adopting the SDR as the unit of currency, by establishing the carrier's absolute liability and an unbreakable limit and by increasing the carrier's passenger limit of liability to SDR 100,000, as well as permiting the domestic introduction of supplemental compensation. To summarize my own sentiments regarding the future, I would say that given the fact that Asian air lines are now world leaders both in overall size and rate of growth, and the fact that both Asian individuals and governments are becoming more and more reliant on the global civil aviation networks as their economies become ever stronger, I am hopeful that Asian nations will henceforth play a bigger role in ensuring the orderly and hasty development of a workable unified system of rules governing international commercial air carriage.

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