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Strategies for Public Health Service Development in the Times of Local Autonomy (지방자치시대의 공공보건사업 발전 전략)

  • 박정한
    • Health Policy and Management
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    • v.12 no.3
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    • pp.1-22
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    • 2002
  • Health is a fundamental human right and a sine qua non for happiness of people and for national development. Government has a responsibility for the provision of health services for their people. Recent changes of disease pattern, i.e. decrease of Infectious diseases and increase of chronic and degenerative diseases Including cancer and cardiovascular diseases, together with universal coverage of health insurance and improved living standard have prompted medical care utilization and skyrocketed the national health expenses. The goal of national health policy is improving the quality of life through the betterment of health level. To achieve this goal it is necessary to establish a healthcare system for lifetime, to improve the efficiency of healthcare delivery system, and to strengthen the public health services for disease prevention and health promotion. The current public health service programs are Inefficient due to an inconsistent policy for health service program, lack of health information system, irrational health program planning and evaluation, and Inadequate training of health workers. Local government has a legal responsibility for health service program planning and promoting the competence of health workers. Thus, municipal and provincial health departments should expand their roles and strengthen their function. The strategies for developing public health service programs at local level are ${\circled}1$ stipulating the goals of health policy, ${\circled}2$ promoting the ability for health program planning and evaluation, ${\circled}3$ establishing health information and surveillance system, ${\circled}4$ training of health workers, ${\circled}5$ establishing an institution for health information management and training of health workers, and ${\circled}61$ collaboration with local universities.

Effect of Omija(Schizandra chinensis) Extract on the Growth Inhibition of Food Borne Pathogens in Yoghurt (오미자 추출액 첨가 요구르트의 식중독균 증식 억제 효과)

  • 홍경현;남은숙;박신인
    • Food Science of Animal Resources
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    • v.23 no.4
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    • pp.342-349
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    • 2003
  • Escherichia coli O157:H7, Staphylococcus aureus and Salmonella enteritidis are food borne pathogens involved in food poisoning in numerous countries. This study aimed to obtain knowledges on the survival of Esc coli O157:H7, Sta aureus and Sal. enteritidis in the yoghurt added with water extract of Omija(Schizandra chinensis). The growth inhibition of Schizandra chinensis extract on the food borne pathogens were measured by total microbial count and effect of growth inhibition was correspondent to the concentration of Schizandra chinensis extract. The highest growth inhibition effect of Schizandra chinensis extract was shown on the Sta aureus followed by Sal. enteritidis and Esc. coli O157:H7. The number of surviving Esc. coli O157:H7 cell(3.55${\times}$10$\^$5/ CFU/mL) was decreased to 1.00${\times}$10$^1$∼3.00${\times}$10$^1$ CFU/mL after 24 hours incubation by the addition of 0.4∼l.0% of Schizandra chinensis extract in the yoghurt. And also the viable cell counts of surviving Sta. aureus cells (initial inoculum 1.24${\times}$10$\^$5/ CFU/mL) were decreased gradually to 4.00${\times}$10$^2$∼8.50${\times}$10$^2$ CFU/mL after 48 hours of incubation, but the viable cells of Sal. enteritidis were not detected after 24 hours of incubation. Growth of the food borne pathogens was strongly inhibited by the addition and incubation of Schizandra chinensis extract for 48 hours in the yoghurt.

β-glucan Stimulates Release of TNF-α in Human Monocytic THP-1 Cells (인간 단핵구 THP-1 세포에서 β-glucan으로 인한 TNF-α 분비 증가 효과)

  • Keum, Bo Ram;Hyeon, Jin Yi;Choe, So Hui;Jin, Ji Young;Jeong, Ji Woo;Lim, Jong Min;Park, Dong Chan;Cho, Kwang Keun;Choi, Eun Young;Choi, In Soon
    • Journal of Life Science
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    • v.27 no.11
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    • pp.1256-1261
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    • 2017
  • ${\beta}$-glucan is a constituent of the cell wall of fungi, yeast and plants. It plays an important role in the immune system such as activation of immunocyte, release of pro-inflammatory and anti-cancer effect. The immune system maintains a healthy immune homeostasis. However, when pathogenic substances enter the body, immune homeostasis can break down and disease can be triggered. Therefore, we studied a substance that regulates immune homeostasis. The purpose of the study we demonstrated whether the ${\beta}$-glucan can be applied to the immune-modulation effects in human monocytic THP-1 cells. ${\beta}$-glucan was incubated in THP-1 cells at various concentrations. The $TNF-{\alpha}$ mRNA expression and protein levels were analyzed by ELISA and Real-time PCR. Additionally, the expression of MAPKs (p38 and JNK), $I{\kappa}B-{\alpha}$ and $NF-{\kappa}B$ p50 were analyzed by western blot. ${\beta}$-glucan enhanced the production of $TNF-{\alpha}$ mRNA expression and protein levels in human monocytic THP-1 cells. In addition, activation of MAPKs (p38 and JNK) and $NF-{\kappa}B$ p50 induced by ${\beta}$-glucan were increased. The study suggests that ${\beta}$-glucan contributes to immune-stimulation effect by production $TNF-{\alpha}$ in human monocytic THP-1 cells, and that MAPKs and $NF-{\kappa}B$ p50 are involved in the process. Synthetically, we have suggested ${\beta}$-glucan may be improved to immune system effect in human monocytic THP-1 cells.

피부 병변은 닭 마렉병 진단에 결정적 단서를 제공한다

  • 조경오;박남용
    • Korean Journal of Veterinary Pathology
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    • v.6 no.2
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    • pp.101-104
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    • 2002
  • 닭의 전신장기에 림프종 발생이 특정인 마렉병(Marek's disease; MD)은 림프구성 백혈병(Lymphoid leukosis; LL)과 병리학적 소견이 매우 유사하여 감별이 요구된다. 마렉병 바이러스(Marek's disease virus; MDV)는 질병초기에서 후기에 이르기까지 모낭상피세포에 세포용해성 감염을 지속적으로 일으킨다. 세포용해성 감염이 있는 모낭상피세포는 변성내지 괴사되어 있고 핵내봉입체가 관찰된다. 또한 세포용해성 감염이 있는 모낭상피세포 바로 밑의 진피와 깃털 수질(feather pulp)내의 혈관주위에 림프구 침윤이 관찰된다. 이러한 피부병변은 MD의 특징적인 병변들로서 LL과 감별할 수 있는 결정적인 단서이다. 본 고에서는 MD에 관한 전반적인 것과 특히 MD 진단을 위한 피부병변의 유용성에 대해서 자세히 논하고자 한다. 양계산업에 문제를 야기하고 있는 림프구 증식성 종양은 크게 마렉병(Marek’s disease; MD)과 백혈병(Lymphoid leukosis; LL)이 있다. 이들 질환의 원인체들이 분리되기 전까지는 이들 질병들은 발병부위에 따라 질병명을 붙였다. 즉, 내부장기냐 근육에 발생한 것은 visceral lymphomatosis, 피부에 발생한 것은 skin leukosis, 말초신경의 병변은 poly­n neuritis, neuritis, neurolymphomatosis gallinarum, range paralyis로 불리었다. 또한 눈에 발생한 것은 blindness, gray eye, iritis, uveitis, ocular lymphomatosis라고 불리었다. 1961년에 Biggs는 이러한 림프구 증식성 질병을 마렉병과 백혈병 으로 분류하자는 제안을 하였고, 드디어 1960년대 중반에 림프구 증식성 병변 중의 일부에서 herpesvirus가 분리되어서 Biggs가 제안한 병명인 마렉병을 본격적으로 사용하게 되었다. MD는 마렉병 바이러스(Marek’s disease virus; MDV)가 원 인제로서 닭에 전염성이 강한 염증성에서 종양성의 병변을 내부장기, 피부, 근육, 안구, 중추신경계, 말초신경계 등에 일 으킨다. MDV는 림프종을 유발하기 때문에 처음에는 사람에서 림프종을 유발하는 Epstein-Bar 바이러스와 관련이 있을 것으로 생각되어 gamma-herpesvirus로 분류되었지만, MDV의 게놈 구조와 세포배양에서 빠르게 성장한다는 점 때문에 지금은 alpha-herpesvirus로 재분류 되었다. MDV는 바이러스 중화시험과 한천 겔 침강법에 의해서 3개의 혈청형으로 분류 된다. 혈청형 1은 종양원성 바이러스와 종양원성 바이러스의 계대배양에 의한 약독주가 있다. 혈청형 2는 자연적으로 발 생하는 비종양원성 닭의 MDV이고, 혈정형 3은 바종양원성 칠면조 herpesvirus (HVT)이다. 림프종을 유발하는 MDV 감염은 4개의 과정, 즉 초기 세포용해성 감염, 잠복감염, 후기 세포용해성 감염, 마지막으로 종양화로 나눌 수 있다. 감염의 경로를 보면, 흡입된 MDV는 폐의 대식세포에 감염한 후 전선 장기로 MDV를 전파 시킨다. 특히, 흉선, F냥, 비장 등의 림프구에 초기 세포용해성 감염을 일으키는데, B 림프구가 주로 감염된다. 세포용해성 감염음 방어하기 위해 몰려든 T 림프구가 활성화가 되면, T 세포도 감염되게 된다. 잠복감염은 여러 가지 사이토카인 등 을 포함한 면역반응에 의해서 일어나며, 이 때 잠복감염된 세포는 특히 혈중의 T 세포라고 한다. 혈중 MDV 감염세포 는 피부 모낭상피세포, 선장 등 상피세포 유래의 조직에 MDV를 전파 시켜서 이들 조직에서 후기 세포용해성 감염이 일어나게 한다. 후기 세포용해성 감염을 유발하는 것은 이러한 MDV가 감염된 혈중 림프구라는 증거는 혈중의 세포 외에는 감염성 바이러스가 없기 때문이다. 후기 세포용해성 감염이 있는 후 육안적 혹은 현미경적으로 검출이 가능한 림프종이 여러 장기에서 관찰된다. MDV가 감염되면 병변 발생부위에 따라서 다양한 임상증상이 발생한다. 즉 내부장기에 병변이 있을 경우는 침울, 체중감소, 산란율 저하 등이 발생하며, 신경계는 발생부위별 신경증상이 일어난다. 이러한 장기나 조직에서는 육안적으로 백색에서 회백색의 종양성 병변이 관찰된다. 말초신경에 병변이 발생한 경우에는 특히 좌골신경 및 신경총에서 호발하는데, 이들 조직은 편측성 혹은 양측성으로 종창되어 있다. 안구는 간혹 육안적으로 식별이 가능한 홍채 퇴색 및 증식 병변이 관찰된다. 피부형 MD는 특히 육용계에서 문제가 되고 있으며, 산란계의 내장형 MD가 발생한 경우에도 피부를 자세히 설펴보면 피부형 MD를 간혹 관찰할 수 있다. 피부형 MD는 모낭주위에 원형의 결절형태로 발생하는데, 이들 병변이 커지면 바로 옆의 병변과 융합 되어 큰 결절을 형성하기도 한다. (중략)

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Effects of Stem Bark Extracts of Cornus walteri Wanger on the Lipid Lowering, Anti-oxidative Activity and Concentration of Proinflammatory Cytokines in Rat Fed High Fat Diet (모래지엽(毛棶枝葉)(Cornus walteri Wanger) 추출물이 비만 쥐의 지질강하, 항산화효과 및 전염증성 cytokines 농도에 미치는 영향)

  • Park, Won-Hyung;Cha, Yun-Yeop
    • Journal of Korean Medicine Rehabilitation
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    • v.19 no.4
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    • pp.59-78
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    • 2009
  • Objective : This study was designed to examine the effects of stem bark extracts of Cornus walteri Wanger on the lipid lowering, anti-oxidative activity and concentration of proinflammatory cytokines in hyperlipidemic rat. Methods : Male rats weighing $195.21{\pm}5.85g$ fed high fat diet for 8 weeks and 40 rats(above 400 g) were divided into 4 groups. Each groups were divided into a control group and 3 experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1 time/1 day) for 4 weeks. And we fed each experimental group of rats Basal diet and administered an extract of Cornus walteri Wanger(100 mg/kg, 200 mg/kg, 300 mg/kg, 1 time/1 day) for 4 weeks. At the end of the experiment, the rats were sacrificed to determine their chemical composition. We measured lipid of plasma and liver, concentration of proinflammatory cytokines, anti-oxidative activity and gene expression. Results : 1. Concentration of plasma free fatty acid, LDL-cholesterol showed a tendency to decrease in Cornus walteri Wanger ext. groups. Concentration of plasma triglyceride, total cholesterol showed a significantly decrement in all Cornus walteri Wanger ext. group than that of control group. HDL-cholesterol showed a significantly increment in the 300 mg/kg Cornus walteri Wanger ext. group. 2. Concentration of liver total cholesterol showed a tendence to decrease in Cornus walteri Wanger ext. groups. Concentration of triglyceride liver showed a significantly decrement in all Cornus walteri Wanger ext. group than that of control group. 3. Concentration of plasma and liver TBARS showed a tendence to decrease in Cornus walteri Wanger ext. groups. The values of GSH-Px, SOD and CAT activity showed a significantly increment in the 300 mg/kg Cornus walteri Wanger ext. group than that of control group. 4. The values of plasma AST and ALT activity showed no significantly different in all treatment groups. 5. Concentration of plasma $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ showed a tendency to decrease in the Cornus walteri Wanger ext. groups. However the concentration of IL-10 in the 200 and 300 mg/kg Cornus walteri Wanger ext. groups showed a significantly increment than that of control group. Concentration of liver $IL-1{\beta}$, $TNF-{\alpha}$ and IL-10 showed no significantly difference in all treatment groups. However concentration of IL-6 in the 200 and 300 mg/kg Cornus walteri Wanger ext. groups showed a significantly decrement than that of control group. 6. In the analysis of RT-PCR, gene expression of $TNF-{\alpha}$, Apo-B, Apo-E and leptin in the Cornus walteri Wanger ext. groups showed a lower expression than that of control group. 7. The ratio of $TNF-{\alpha}$, Apo-E and leptin expression per $\beta$-actin expression in the 200 and 300 mg/kg Cornus walteri Wanger ext. showed a significantly decrement than that of control group. The ratio of Apo-B expression per $\beta$-actin expression in the 300 mg/kg Cornus walteri Wanger ext. showed a significantly decrement than that of control group. Conclusions : According to above results, in lowering lipid effect, antioxidative activity and antiinflammatory effect, the Cornus walteri Wanger ext. gives positive effect.

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.

Possibility of Soil Solarization in Korea (한국(韓國)에 있어서 태양열(太陽熱)을 이용(利用)한 토양소독(土壤消毒)의 가능성(可能性))

  • Ki, Kye-Un;Kim, Ki-Chung
    • Korean journal of applied entomology
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    • v.24 no.2 s.63
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    • pp.107-114
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    • 1985
  • This experiment was performed to see the possibility if soil-borne disease in green house can be controlled by soil solarization in Korea. Thermal death profiles of propagules of some soil-borne fungi, Fusarium oxysporum f. lycopersici, Fusarium oxysporum f. niveum, Rhizoctonia salani, Sclerotinia sclerotiorum, Sclerotium rolfsii and Pythium debaryanum, were obtained under the conditions in water-suspension and in soil. Except Pythium debaryanum, all the fungal units in water-suspension that were colonized on barley grains lost a viability within 7 days in water bath at $45^{\circ}C$. When the soil in test tubes in which barley grains infected with the fungi were also buried all the fungi tested including Pythium debaryanum were completely killed within 7 days in water bath at $45^{\circ}C$. From July to August in Korea, soil temperature at depth of 5cm and 15cm within tunnel in plastic house reached $38^{\circ}C\;to\;57^{\circ}C$ and $40^{\circ}C\;to\;47^{\circ}\C$, in 1982 and 1983 respectively. Even at 15cm depth, soil temperature were kept over $43^{\circ}C$ for 12 hours a day. Adiabatic material set under ground or under mulching with the transparent polyethylene-film on the soil surface had a boostering effect for higher soil-temperature and longer duration. Fungi buried in adiabatic block of the soil in plastic house were completely killed at 15cm depth 14 days after, and at 20cm depth 21 days after soil solarization. The exposure of the pathogens to fluctuating temperature was much more effective than to constant. From the above results, soil-borne diseases may be effectively controlled by soil solarization in the closed plastic house in hot summer season in Korea.

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Effects on Growth and Yield Whole-crop Barley by Soil-borne Virus Infection (토양 전염성 바이러스 감염이 청보리 품종별 생육 및 수량에 미치는 영향)

  • Kim, Kyeong-Hoon;Seo, Eun-Jo;Shin, Sang-Hyun;Choi, Jae-Seong;Lee, Mi-Ja;Park, Tae-Il;Park, Jong-Chul
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.32 no.3
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    • pp.237-244
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    • 2012
  • Barley yellow mosaic virus (BaYMV) and Barley mild mosaic virus (BaMMV) cause severe diseases in winter barley in Europe and East Asia. We investigated the effect of different level of resistance to virus disease on the plant growth and yield in whole-crop barley. In the virus infection, BaYMV was detected all tested cultivars in first diagnosis at 30th March. BaYMV infection was identified only in the susceptible Sunwoobori in 6th April, but not in the Yuyeon (moderate, M) and Youngyang (moderate resistant, MR) cultivars. Plant height was restrained about 14.6~32.9% in overwintered plant regeneration stage depending on the resistance of each cultivar. The tiller numbers also reduced to 8.7~19.7% by BaYMV infection in overwintering season. We evaluated culm length, spike length, and spike number in the virus-infected field and non-infected field. For the culm length, Youngyang (MR) reduced only 14.5% by BaYMV. However Sunwoo (susceptible, S) and Yuyeon (M) cultivars were decreased to 24.8~42.7%. The spike length and spike number also affected to 8.9~21.3% and 24.3~31.0%, respectively, depending on the resistance. After harvesting, dry-matter yield of whole crop yield reduced by approximately 21.6~58.0% according to cultivar resistant degrees. For example, Sunwoobori (S) decreased 58.0% in comparing to non-infected field. The grain yield was also significantly reduced in virus infected cultivars. Sunwoobori (S) was severely decrease more than 60.0%. Yuyeonbori (M) and Youngyangbori (MR) also decreased 30.0~47.5% by the viral infection comparing to those in the non-infected field.

Anti-inflammatory Activities of an Ethanol Extract of Sargassum macrocarpum in Lipopolysaccharide (LPS)-stimulated RAW 264.7 Macrophages (Lipopolysaccaride로 유도된 Raw 264.7 세포에서 큰열매모자반 에탄올 추출물의 항염증 활성)

  • Cheon, Ji Min;Kim, Hyang Suk;Choi, Eun Ok;Kwon, Da Hye;Choi, Yung Hyun;Kim, Byung Woo;Hwang, Hye Jin
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1437-1444
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    • 2017
  • Sargassum macrocarpum is a widely distributed marine brown algae found in the North Pacific. The objective of this study was to evaluate the anti-inflammatory activity of an ethanol extract of S. macrocarpum (EESM). First, we investigated the anti-inflammatory activities of EESM in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. EESM treatment suppressed nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production and inhibited the expressions of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, the expression of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-1 beta ($IL-1{\beta}$), was decreased in a dose dependent manner. Investigation of the signaling pathways of nuclear factor kappa B ($NF-{\kappa}B$), phosphoinositide-3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) revealed suppression of $NF-{\kappa}B$ translocation from the cytosol to nucleus by EESM treatment. The phosphorylation of the Akt and ERK proteins was also inhibited by EESM treatment. EESM treatment also stimulated the expression of the heme oxygenase-1 (HO-1) enzyme and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2). These results suggest that EESM has anti-inflammatory activity and could have potential uses in the field of nutraceuticals.

Various Cultural Factors Associated with Disease Development of Garlic White Rot Caused by Two Species of Sclerotium (마늘 흑색썩음균핵병 발생에 관여하는 여러가지 경종적 요인)

  • Kim, Yong-Ki;Kwon, Mi-Kyung;Shim, Hong-Sik;Kim, Tack-Soo;Yeh, Wan-Hae;Cho, Weon-Dae;Choi, In-Hu;Lee, Seong-Chan;Ko, Sug-Ju;Lee, Yong-Hwan;Lee, Chan-Jung
    • Research in Plant Disease
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    • v.11 no.1
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    • pp.28-34
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    • 2005
  • This study was conducted to investigate the control possibility of garlic white rot causing severe yield losses of Allium species and cultivars using cultural practices such as optimal sowing date and burial depth, and lime application. Inoculum density in infested field soil was investigated at different soil depth, and that on the diseased plant debris was done. Inoculum density and recovery ratio of white rot pathogen of garlic was highly different between two species of Sclerotium cepivorum forming comparatively small sclerotia and Sclerotium sp. forming comparatively large ones. It was confirmed that S. cepivorum formed more sclerotia on bulbs of garlic than S. sp., and sclerotial recovery of S. cepivorum was higher than that of S. sp. Inoculum density of white rot pathogen in the infested field at garlic seeding period ranged from one to thirteen sclerotia per 30 g soil. Inoculum density of white rot pathogen decreased remarkably with increasing soil depth and above 95% of sclerotia were distributed within 5 cm of soil depth. Disease severity of white rot was higher on slightly planted garlics than deeply-planted ones. Garlic seed bulbs infected by white rot pathogens were confirmed to be one of main inoculum sources of white rot in the field and the disease incidences caused by garlic seed transmission showed big differences among garlic varieties. When nine garlic varieties harvested from infested plots were sown in the field, highly susceptible varieties, ‘Wando’, ‘Daeseo’, ‘Namdo’ and ‘Kodang’ showed high disease incidences, whereas other five varieties were not infected at all. It was confirmed that white rot occurred higher on early-sown garlics, before middle October, than on late-sown ones, after late October. Meanwhile, increasing application rate of lime ranged from 100 to 300 g reduced disease severity of white rot.