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Function of the Neuronal $M_2$ Muscarinic Receptor in Asthmatic Patients (천식 환자에서 $M_2$ 무스카린성 수용체 기능에 관한 연구)

  • Kwon, Young-Hwan;Lee, Sang-Yeup;Bak, Sang-Myeon;Lee, Sin-Hyung;Shin, Chol;Cho, Jae-Youn;Shim, Jae-Jeong;Kang, Kyung-Ho;Yoo, Se-Hwa;In, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.4
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    • pp.486-494
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    • 2000
  • Background : The dominant innervation of airway smooth muscle is parasympathetic fibers which are carried in the vagus nerve. Activation of these cholinergic nerves releases acetylcholine which binds to $M_3$ muscarinic receptors on the smooth muscle causing bronchocontraction. Acetylcholine also feeds back onto neuronal $M_2$ muscarinic receptors located on the postganglionic cholinergic nerves. Stimulation of these receptors further inhibits acetylcholine release, so these $M_2$, muscarinic receptors act as autoreceptors. Loss of function of these $M_2$ receptors, as it occurs in animal models of hyperresponsiveness, leads to an increase in vagally mediated hyperresponsiveness. However, there are limited data pertaining to whether there are dysfunctions of these receptors in patients with asthma. The aim of this study is to determine whether there are dysfunction of $M_2$ muscarinic receptors in asthmatic patients and difference of function of these receptors according to severity of asthma. Method : We studied twenty-seven patients with asthma who were registered at Pulmonology Division of Korea University Hospital. They all met asthma criteria of ATS. Of these patients, eleven patients were categorized as having mild asthma, eight patients moderate asthma and eight patients severe asthma according to severity by NAEPP Expert Panel Report 2(1997). All subjects were free of recent upper respiratory tract infection within 2 weeks and showed positive methacholine challenge test ($PC_{20}$<16mg/ml). Methacholine provocation tests were performed twice on separate days allowing for an interval of one week. In the second test, pretreatment with the $M_2$ muscarinic receptor agonist pilocarpine($180{\mu}g$) through inhalation was performed be fore the routine procedures. Results : Eleven subjects with mild asthma and eight subjects with moderate asthma showed significant increase of $PC_{20}$ from 5.30$\pm$5.23mg/ml(mean$\pm$SD) to 20.82$\pm$22.56mg/ml(p=0.004) and from 2.79$\pm$1.51mg/ml to 4.67$\pm$3.53mg/ml(p=0.012) after pilocarpine inhalation, respectively. However, in the eight subjects with severe asthma significant increase of $PC_{20}$ from l.76$\pm$1.50mg/ml to 3.18$\pm$4.03mg/ml(p=0.161) after pilocarpine inhalation was not found. Conclusion : In subjects with mild and moderate asthma, function of $M_2$ muscarinic receptors was normal, but there was a dysfunction of these receptors in subjects with severe asthma. ηlese results suggest that function of $M_2$ muscarinic receptors is different according to severity of asthma.

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A Study on Garden Design Principles in "Sakuteiki(作庭記)" - Focused on the "Fungsu Theory"(風水論) - (「사쿠테이키(作庭記)」의 작정원리 연구 - 풍수론(風水論)을 중심으로 -)

  • Kim, Seung-Yoon
    • Journal of the Korean Institute of Landscape Architecture
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    • v.41 no.6
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    • pp.1-19
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    • 2013
  • This study tries to review 'Sakuteiki(作庭記)', the Book of Garden Making, compiled at the end of the 11th Century during the Heian Period of Japan, from the East-Asian perspective. 'Sakuteiki' is a Garden Theory Book, the oldest in the world as well as in Asia, and it contains the traditional knowledge of Japanese ancient garden culture, which originated from the continent(Korea and China). Traditional knowledge related to East-Asian garden culture reviewed in this paper is "Fungsu Theory"(風水, Asian traditional ecology: Fengshui in Chinese; Fusui in Japanese), stemmed from the culture to seek sound and blessed places to live in. Viewed from modern landscape architecture, the Fungsu Theory corresponds to ecology(science). The Fungsu Theory was established around the Han Dynasty of China together with the Yinyangwuxing(陰陽五行) Theory and widely used for making human residences including gardens. It was transmitted to Japan via Korea as well as through direct transaction between Japan and China. This study reinterprets garden design principles represented in Sakuteiki, which were selected in 5 key words according to the Fungsu Theory. The 5 key words for the Fungsu Theory are "the place in harmony of four guardian gods(四神相應地)", "planting trees in the four cardinal directions", "flow of Chi(氣)", "curved line and asymmetry", and "mountain is the king, water is the people". Garden design principles of "the place in harmony of four guardian gods(四神相應地)" and "planting trees in the four cardinal directions" are corresponding to "Myeongdang-ron(明堂論, Theory of propitious site)". The place in harmony of four guardian gods mentioned in Sakuteiki is a landform surrounded by the flow of water to the east, the great path to the west, the pond to the south, and the hill to the north. And the Theory originated from Zhaijing(宅經, Classic of dwelling Sites) of China. According to this principle, the city was planned and as a miniature model, the residence of the aristocrat during the Heian period was made. At the residence the location of the garden surrounded by the four gods(the flow of water, the great path, the pond, and the hill) is the Myeongdang(明堂, the propitious site: Mingtang in Chinese; Meido in Japanese). Sakuteiki explains how to substitute for the four gods by planting trees in the four cardinal directions when they were not given by nature. This way of planting originated from Zhaijing(宅經) and also goes back to Qiminyaoshu (齊民要術), compiled in the 6th Century of China. In this way of planting, the number of trees suggested in Sakuteiki is related to Hetu(河圖) and Luoshu(洛書), which are iconography of Yi(易), the philosophy of change, in ancient China. Such way of planting corresponds to that of Yongdoseo(龍圖墅, the villa based on the principle of Hetu) presented in Sanrimgyeongje (山林經濟), an encyclopedia on agriculture and living in the 17th Century of Korea. And garden design principles of "the flow of Chi(氣)", "curved line and asymmetry" is connected to "Saenggi Theory(生氣論, Theory of vitality)". Sakuteiki explains the right flow of Chi(氣) through the proper flow and the reverse flow of the garden stream and also suggests the curved line of the garden stream, asymmetric arrangement of bridges and stones in the garden, and indented shape of pond edges, which are ways of accumulating Chi(氣) and therefore lead to "Saenggi Theory" of the Fungsu Theory. The last design principle, "mountain is the king, water is the people", is related to "Hyeongguk Theory(形局論, Theory of form)" of the Fungsu Theory. Sakuteiki explains the meaning of garden through a metaphor, which views mountain as king, water as the people, and stones as king's retainers. It compares the situation in which the king governs the people with the help of his retainers to the ecological phenomena in which mountain(earth) controls water with the help of stones. This principle befits "Hyeongguk Theory(形局論, Theory of form)" of the Fungsu Theory which explains landform on the analogy of social systems, people, animals and things. As above, major garden design principles represented in Sakuteiki can be interpreted in the context of the Fungsu Theory, the traditional knowledge system in East Asia. Therefore, we can find the significance of Sakuteiki in that the wisdom of ancient garden culture in East-Asia was integrated in it, although it described the knowhow of a specific garden style in a specific period of Japan.

Inflammatory Reponse of the Lung to Hypothermia and Fluid Therapy after Hemorrhagic Shock in Rats (흰쥐에서 출혈성 쇼크 후 회복 시 저체온법 및 수액 치료에 따른 폐장의 염증성 변화)

  • Jang, Won-Chae;Beom, Min-Sun;Jeong, In-Seok;Hong, Young-Ju;Oh, Bong-Suk
    • Journal of Chest Surgery
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    • v.39 no.12 s.269
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    • pp.879-890
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    • 2006
  • Background: The dysfunction of multiple organs is found to be caused by reactive oxygen species as a major modulator of microvascular injury after hemorrhagic shock. Hemorrhagic shock, one of many causes inducing acute lung injury, is associated with increase in alveolocapillary permeability and characterized by edema, neutrophil infiltration, and hemorrhage in the interstitial and alveolar space. Aggressive and rapid fluid resuscitation potentially might increased the risk of pulmonary dysfunction by the interstitial edema. Therefore, in order to improve the pulmonary dysfunction induced by hemorrhagic shock, the present study was attempted to investigate how to reduce the inflammatory responses and edema in lung. Material and Method: Male Sprague-Dawley rats, weight 300 to 350 gm were anesthetized with ketamine(7 mg/kg) intramuscular Hemorrhagic Shock(HS) was induced by withdrawal of 3 mL/100 g over 10 min. through right jugular vein. Mean arterial pressure was then maintained at $35{\sim}40$ mmHg by further blood withdrawal. At 60 min. after HS, the shed blood and Ringer's solution or 5% albumin was infused to restore mean carotid arterial pressure over 80 mmHg. Rats were divided into three groups according to rectal temperature level($37^{\circ}C$[normothermia] vs $33^{\circ}C$[mild hypothermia]) and resuscitation fluid(lactate Ringer's solution vs 5% albumin solution). Group I consisted of rats with the normothermia and lactate Ringer's solution infusion. Group II consisted of rats with the systemic hypothermia and lactate Ringer's solution infusion. Group III consisted of rats with the systemic hypothermia and 5% albumin solution infusion. Hemodynamic parameters(heart rate, mean carotid arterial pressure), metabolism, and pulmonary tissue damage were observed for 4 hours. Result: In all experimental groups including 6 rats in group I, totally 26 rats were alive in 3rd stage. However, bleeding volume of group I in first stage was $3.2{\pm}0.5$ mL/100 g less than those of group II($3.9{\pm}0.8$ mL/100 g) and group III($4.1{\pm}0.7$ mL/100 g). Fluid volume infused in 2nd stage was $28.6{\pm}6.0$ mL(group I), $20.6{\pm}4.0$ mL(group II) and $14.7{\pm}2.7$ mL(group III), retrospectively in which there was statistically a significance between all groups(p<0.05). Plasma potassium level was markedly elevated in comparison with other groups(II and III), whereas glucose level was obviously reduced in 2nd stage of group I. Level of interleukine-8 in group I was obviously higher than that of group II or III(p<0.05). They were $1.834{\pm}437$ pg/mL(group I), $1,006{\pm}532$ pg/mL(group II), and $764{\pm}302$ pg/mL(group III), retrospectively. In histologic score, the score of group III($1.6{\pm}0.6$) was significantly lower than that of group I($2.8{\pm}1.2$)(p<0.05). Conclusion: In pressure-controlled hemorrhagic shock model, it is suggested that hypothermia might inhibit the direct damage of ischemic tissue through reduction of basic metabolic rate in shock state compared to normothermia. It seems that hypothermia should be benefit to recovery pulmonary function by reducing replaced fluid volume, inhibiting anti-inflammatory agent(IL-8) and leukocyte infiltration in state of ischemia-reperfusion injury. However, if is considered that other changes in pulmonary damage and inflammatory responses might induce by not only kinds of fluid solutions but also hypothermia, and that the detailed evaluation should be study.