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Pharmacological Action Mechanism(s) of Vasodilator Effect of Calcitonin Gene-related Peptide in Rat Basilar Arteries (흰쥐의 뇌 기저동맥에서 CGRP에 의한 혈관 이완반응의 기전에 대한 연구)

  • Rhim, Byung-Yong;Hong, Sun-Hwa;Kim, Chi-Dae;Lee, Won-Suk;Kim, Dong-Heon;Hong, Ki-Whan
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.39-49
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    • 1996
  • In the present study, we observed change in intracellular $Ca^{2+}$$([Ca^{2+}]_i)$ as measured with the fluorescent $Ca^{2+}-indicator$ fura-2 in association with force development of the rat basilar arteries during activation by$K^+$ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in $[Ca^{2+}]_i$, whereas it did not exert any effect on the $K^+$ (90 mM)-induced contraction and increase in $[Ca^{2+}]_i$, Further, $[Ca^{2+}]_i-force$ relationships were determined by plotting the ratio of $F_{340}/F_{380}$ $([Ca^{2+}]_i)$ as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in $[Ca^{2+}]_i$ with out any change in the sensitivity of contractile apparatus to $Ca^{2+}$. The CGRP-induced attenuation of $[Ca^{2+}]_i$ and force development was significantly inhibited under pretreatment with CGRP $(8{\sim}37)$ fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in $[Ca^{2+}]_i$ caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance $Ca^{2+}-activated$ $K^+$ channel blockers, but not by apamin (300 nM), a small conductance $Ca^{2+}-activated$ $K^+$ channel blocker, and glibenclamide ( 1 ${\mu}M$), an ATP-sensitive $K^+$ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of $Ca^{2+}-activated$ $K^+$ channel and cause to decrease in $[Ca^{2+}]_i$, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the $K^+$ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or $K^+$ channel opening or both actions.

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Regulation of Gb3 Expression on Dendritic Cells (수지상세포에 있어서 베로독소 수용체의 발현조절)

  • Lim, Suk-Hwan;Kim, Gi-Young;Kim, Hyung-Chun;Kim, Young-Hee;Son, Yong-Hae;Oh, Yang-Hyo;Park, Yeong-Min
    • Journal of Life Science
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    • v.17 no.4 s.84
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    • pp.482-492
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    • 2007
  • Infection with Shiga-like toxin (SLT)-producing Escherichia coli causes a spectrum of illnesses with high morbidity and mortality. Host mediators play an important role in the pathogenesis of SLT-I toxicity. We here investigated the effect of SLT-I on tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ production, effect of $TNF-{\alpha}$ on glycolipid globotriaosyleramide (Gb3) expression, and relationship between Gb3 level and differential susceptibility of cells to SLT-I. In this study, we observed that detectable levels of $TNF-{\alpha}$ are produced 6 hrs after induction and continued to increase during 48 hrs by SLT-I. It was also found that Vero cells and dendritic cells expressed high levels of Gb3, 83% and 68%, respectively, and that macrophages had a low level of Gb3 (29%) and showed refractory to cytotoxicity against SLT-I. Vero cells and dendritic cells expressing high levels of Gb3 were highly susceptible to SLT-I. furthermore, macrophages showed a resistance to SLT-I cytotoxicity, despite the fact that Gb3 expression was enhanced. These results suggest that the expression of Gb3 is necessary, but not sufficient to confer sensitivity of macrophages to SLT-I and further underpin the important role of SLT-I and its receptor, Gb3, in the pathogenesis of E. coli O157 infection.

Effects of Arginine Vasopressin(AVP) Infusion on the Patients with Catecholamine-dependent Septic Shock (카테콜아민계 승압제를 투여중인 패혈성 쇼크 환자에서 아르기닌 바소프레신(AVP)의 효과)

  • Sheen, Seung Soo;Lim, Seung Guan;Jo, Sook Kyoung;Song, Kyoung Eun;Lee, Hyoung No;Oh, Yoon Jung;Park, Kwang Joo;Hwang, Sung Chul
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.5
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    • pp.506-515
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    • 2003
  • Background : A decreased level of serum arginine vasopressin(AVP) and an increased sensitivity to an exogenous AVP is expected in patients with septic shock who often require a high infusion rate of catecholamines. The goal of the study was to determine whether an exogenous AVP infusion to the patients with septic shock would achieve a significant decrement in infusion rate of catecholamine vasopressors while maintaining hemodynamic stability and adequate urine output. Method : Eight patients with septic shock who require a high infusion rate of norepinephrine had received a trial of 4-hour AVP infusion with simultaneous titration of norepinephrine. Hemodynamic parameters and urine output were monitored during the AVP infusion and the monitoring continued up to 4 hours after the AVP infusion had stopped. Results : Mean arterial pressure showed no significant changes during the study period(p=0.197). Norepinephrine infusion rate significantly decreased with concurrent AVP administration(p=0.001). However, beneficial effects had disappeared after the AVP infusion was stopped. In addition, hourly urine output showed no significant changes throughout the trials(p=0.093). Conclusion : Concurrent AVP infusion achieved the catecholamine vasopressor sparing effect in the septic shock patients, but there was no evidence of the improvement of renal function. Further study may be indicated to determine whether AVP infusion would provide an organ-protective effect to the septic shock patients.

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.

Immunomodulatory and Anti-Inflammatory Activity of Mulberry (Morus alba) Leaves Fermented with Hericium erinaceum Mycelium by Solid-State Culture (Solid-State Culture를 이용하여 조제한 노루궁뎅이버섯 균사체-뽕잎발효물의 면역 및 항염증 활성)

  • Kim, Hoon;Jeong, Jae-Hyun;Shin, Ji-Young;Kim, Dong-Goo;Yu, Kwang-Won
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.9
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    • pp.1333-1339
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    • 2011
  • After mulberry (Morus alba) leaves were fermented with Hericium erinaceum mycelium by solid-state culture to enhance physiological activity, fermented mulberry leaves (MA-HE) was extracted by hot-water (MA-HEHW) and ethanol (MA-HE-E). MA-HE-HW showed enhanced mitogenic and intestinal immune system modulating activities (1.41 and 1.52 fold of saline control, respectively) compared to hot-water extracts of non-fermented mulberry leaves (MA-HW) and H. erinaceum mycelium (HE-HW) at $100\;{\mu}g$/mL. Meanwhile, when we tested the inhibitory effects of extracts on nitric oxide (NO), tumor necrosis factor (TNF)-${\alpha}$, and interleukin (IL)-$1{\beta}$ and IL-6 production, MA-HE-E significantly inhibited these pro-inflammatory mediators in LPS-stimulated RAW 264.7 cells (45.1, 41.3, 70.2, and 55.7% inhibition of LPS control at $1,000\;{\mu}g$/mL). In addition, MA-HE-HW and MA-HE-E did not show any cytotoxicity on RAW 264.7 cells at $1,000\;{\mu}g$/mL whereas HE-E and MA-E indicated cytotoxicity (80.1 and 30.7% cell viability of saline control). These results suggest that mulberry leaves fermented with H. erinaceum by solid-state culture might have enhanced immunomodulatory and anti-inflammatory effects compared to non-fermented mulberry leaves, resulting in ingredients biotransformed for fermentation with H. erinaceum mycelium.

An Effect of Rhythmic Movement Therapy for Adaptation State in Mastectomy Patients (율동적 운동요법이 유방절제술 환자의 퇴원후 적응상태에 미치는 영향)

  • Lee Myung-Hwa
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.2 no.1
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    • pp.67-85
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    • 1995
  • The purpose of this study was to determine the effects of rhythmic movement therapy for adaptation state in mastectomy patients. The quasi-experimental study was designed using nonequivalent control group pretest-posttest design within the framework of Laszarus & Folkman's stress-adaptation model. The subjects of the study were composed thirty-two mastectomy patients, of these fifteen were assigned to the experimental group and seventeen to the control group. Rhythmic movement therapy was carried out twice a week for thirty-five, minutes or forty minutes for six weeks period from August 22 to September 30 in 1994. Data was collected before and after the experimentation. Collected data was analyzed by mens of chi-square test, t-test, two-way ANOVA, Pearson's correlation coefficient with $SPSS/PC^+$. The results were summarized as follows : 1. Physical symptom score in the experimental group and control group was not significant difference. 2. Joint Movement Parameter in the experimental group and control group was significant difference. 3. Depression score in the experimental group and contrl group was significant difference. 4. Body image score in the experimental group and control group was significant difference. 5. Stress perception score in the experimental group and control group was significant difference. 6. Social adjustment score in the experimental group and control group was significant difference. 7. Each adaptational level in the experimental group and control group according to type of Health Locus of Control were partially significant difference. Depression score and social adjustment score between the experimental group and control group according to others Health Locus of control were significant difference. This data suggest that rhythmic movement therapy was more effective in the group of Others health Locus of Control. 8. Each adaptational level between the experimental group and control group according to amount of spouse support were not significant difference. 9. The significant positive correlation between physical symptom score and body image, between body image and social adjustment, were observed. The significant negative correlation between stress perception score and social adjustment, between depression and body image, between depression and social adjustment, were observed. This data suggest that the more physical symptom score increased, the more body image increased and the more body image, the more social adjustment. And then the more stress perception score decreased, the more social adjustment increasded and the more depression score, the more body image and social adjustment. Thus it is concluded that the rhythmic movement therapy was a useful nursing intervention for adaptation of mastectomy patients.

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Anti-Inflammatory Effect of Ethanolic Extract from Polyopes affinis through Suppression of NF-κB and MAPK Activation in LPS-Stimulated RAW 264.7 Cells (LPS로 자극된 대식세포에서의 NF-κB와 MAPK 활성 조절을 통한 참까막살(Polyopes affinis) 에탄올 추출물의 항염증 효과)

  • Kim, Min-Ji;Kim, Koth-Bong-Woo-Ri;Park, Sun-Hee;Park, So-Young;Choi, Hyeun-Deok;Choi, Jung-Su;Jang, Mi-Ran;Im, Moo-Hyeog;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.5
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    • pp.537-544
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    • 2017
  • In this study, the anti-inflammatory effect of Polyopes affinis ethanol extract (PAEE) was investigated using LPS-stimulated RAW 264.7 cells and a croton oil-induced ICR mice model. Treatment with PAEE significantly reduced production of nitric oxide (NO) and pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, and $IL-1{\beta}$] in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. PAEE treatment also reduced expression of inducible NO synthase, cyclooxygenase-2, nuclear $factor-{\kappa}B$, and mitogen-activated protein kinases in LPS-stimulated RAW 264.7 cells. In the croton oil-induced ear edema test, application of PAEE (10~250 mg/kg body weight) reduced ear edema in a dose-dependent manner, and PAEE treatment at 50 mg/kg body weight showed similar inhibitory effects compared with prednisolone (10 mg/kg body weight). Histological analysis revealed reduced dermal thickness and lower number of infiltrated mast cells. These results suggest that PAEE might be used as a promising anti-inflammatory agent for inhibition of LPS-induced inflammation and ear edema formation.

Compound K (CK) Rich Fractions from Korean Red Ginseng Inhibit Toll-like Receptor (TLR) 4- or TLR9-mediated Mitogen-activated Protein Kinases Activation and Pro-inflammatory Responses in Murine Macrophages (고려홍삼으로부터 분리한 compound K 함유분획에 의한 대식세포의 toll-like receptor-의존성 신호전달로 활성조절 분석)

  • Yang, Chul-Su;Ko, Sung-Ryong;Cho, Byung-Goo;Lee, Ji-Yeon;Kim, Ki-Hye;Shin, Dong-Min;Yuk, Jae-Min;Sohn, Hyun-Joo;Kim, Young-Sook;Wee, Jae-Joon;Do, Jae-Ho;Jo, Eun-Kyeong
    • Journal of Ginseng Research
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    • v.31 no.4
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    • pp.181-190
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    • 2007
  • Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-${\kappa}B$, and expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-${\kappa}B$ activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.

Potential Roles of Hedgehog and Estrogen in Regulating the Progression of Fatty Liver Disease (지방간 진행 조절에 대한 헤지호그와 에스트로겐의 잠재적 역할)

  • Hyun, Jeong-Eun;Jung, Young-Mi
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1795-1803
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    • 2011
  • Non-alcoholic fatty liver disease accompanies the rise in the prevalence of obesity, diabetes and the tendency toward high-fat dietary habits. Specifically, the higher prevalence of non-alcoholic fatty liver disease in men and postmenopausal women seems to be caused by the protective effects of estrogen against liver fibrosis, or lack thereof. There are no effective preventive therapies for liver diseases because the mechanisms underlying the progression of fatty liver diseases to chronic liver diseases and the protective effects of estrogen against fibrogenesis remain unclear. Recently, it has been reported that the hedgehog signaling pathway plays an important role in the progression of chronic liver diseases. Hedgehog, a morphogen regulating embryonic liver development, is expressed in injured livers but not in adult healthy livers. The level of hedgehog expression parallels the stages of liver diseases. Hedgehog induces myofibroblast activation and hepatic progenitor cell proliferation and leads to excessive liver fibrosis, whereas estrogen inhibits the activation of hepatic stellate cells to myofibroblasts and prevents liver fibrosis. Although the mechanism underlying the opposing actions of hedgehog and estrogen on liver fibrosis remain unclear, the suppressive effects of estrogen on the expression of osteopontin, a profibrogenic extracellular matrix protein and cytokine, and the inductive effects of hedgehog on osteopontin transcription suggest that estrogen and hedgehog are associated with liver fibrosis regulation. Therefore, further research on the estrogen-mediated regulatory mechanisms underlying the hedgehog-signaling pathway can identify the mechanism underlying liver fibrogenesis and contribute to developing therapies for preventing the progression of fibrosis to chronic liver diseases.

Elementary School Teachers' and Company Teachers' Recognitions of the Informal Science Education Activity: 'Korea Junior Engineering Achievement' Case (비정규 과학교육 활동에 대한 초등 현직 교사와 기업 교사의 인식: '주니어 공학기술 교실' 사례를 중심으로)

  • Choi Jaehyeok;Yoon Hye-Gyoung
    • Journal of Korean Elementary Science Education
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    • v.24 no.4
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    • pp.391-398
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    • 2005
  • Recent studies say that informal learning is influential to students as much as formal teaming. Nowadays we can see various informal teaming inside and outside of the country. In 2004, it was the first attempt in Korea that engineer had gone to the elementary school fur activity that included scientific experiment and engineering work with students. National Academy of Engineering of Korea (NAEK) progressed activity with companies and elementary schools for students' making sense of engineer and what they are doing. To do that, NAEK had developed the network that company could support its local school's science education circumstance by engineers' visiting program. In 2004, seventeen companies including both large and small ones took part in the program called' Korea Junior Engineering Achievement (KJEA)'. In this program, engineers played the role of teacher (we call them company teacher), elementary school teachers played the role of organizing classes as a mediator. Elementary school teachers and company teachers' recognition is very important to make students' activity meaningful. The aim of this study was to give implication for informal science education activity for which engineers visit their local school. We got the result by survey and interview of company teachers and elementary school teachers. This study's result shows that almost company teachers and school teachers were in favor of purpose of this informal science education activity and satisfied with their participation. But some company teachers were not satisfied with worksheets, materials provided and relationship between school and company). Elementary school teachers and company teachers, both of them believed students' program as the key factor of success of informal science education activity. To make informal science education grow, school administrator and teacher need to have a will to utilize the activities more actively.

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