• Title/Summary/Keyword: human-to-human (H2H)

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Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

  • Peter, Aniekan Imo;Naidu, Edwin CS;Akang, Edidiong;Ogedengbe, Oluwatosin O;Offor, Ugochukwu;Rambharose, Sanjeev;Kalhapure, Rahul;Chuturgoon, Anil;Govender, Thirumala;Azu, Onyemaechi O
    • Toxicological Research
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    • v.34 no.3
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    • pp.221-229
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    • 2018
  • Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

Analgesic effect of acupuncture applied to $SI_6$ in a rat model of neuropathic pain (흰쥐의 신경병증성(神經病症性) 통증(痛症) 모델에서 양로(養老) 자침(刺鍼)의 진통효과(鎭痛效果))

  • Koo, Sung-Tae;Yang, Yoon-Jung;Kim, San;Yoo, In-Sik;Lim, Kyu-Sang
    • Korean Journal of Acupuncture
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    • v.21 no.3
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    • pp.59-76
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    • 2004
  • Objectives : The usage of acupuncture has gained popularity for certain chronic pain conditions. However, the efficacy of acupuncture in various diseases has not been fully established and the underlying mechanism is not clearly understood. In the present study, the effect of electroacupuncture (EA) applied to yangno$(SI_6)$ on the neuropathic pain was examined. Methods : A common source of persistent pain in human is a neuropathic pain. Neuropathic pain was induced by tight ligation of L5 spinal nerve. When rats developed pain behaviors, EA was applied for 30 min. under enflurane anesthesia with repeated train stimuli at the intensity of 10X of muscle twitch threshold. The foot withdraw latency of the hind limb was measured for an indicator of pain level after each manipulation. Results : EA increased the mechanical threshold of the foot in the rat model of neuropathic pain significantly for the duration of 1 hr. suggesting a partial alleviation of pain. EA applied to SI6 point produced a significant improvement of mechanical sensitivity of the foot lasting for at least 1 h. However, $ST_{36}$ point did not produce any significant increase of mechanical sensitivity. The improvement of mechanical threshold was interpreted as an analgesic effect. The analgesic effort was specific to the acupuncture point since the analgesic effect on the neuropathic pain model could not be mimicked by EA applied to a point, $ST_{36}$. In addition, this analgesic effect of EA is mediated by a adrenergic mechanism of descending control of spinal cord from the brain. Conclusions : The data suggest that EA produces a potent analgesic effect on the neuropathic pain model in the rat; and 2) that EA-induced analgesia is mediated by a adrenergic mechanism of descending control in a point specific manner.

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Mitochondrial Damage and Metabolic Compensatory Mechanisms Induced by Hyperoxia in the U-937 Cell Line

  • Scatena, Roberto;Messana, Irene;Martorana, Giuseppe Ettore;Gozzo, Maria Luisa;Lippa, Silvio;Maccaglia, Alessandro;Bottoni, Patrizia;Vincenzoni, Federica;Nocca, Giuseppina;Castagnola, Massimo;Giardina, Bruno
    • BMB Reports
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    • v.37 no.4
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    • pp.454-459
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    • 2004
  • Experimental hyperoxia represents a suitable in vitro model to study some pathogenic mechanisms related to oxidative stress. Moreover, it allows the investigation of the molecular pathophysiology underlying oxygen therapy and toxicity. In this study, a modified experimental set up was adopted to accomplish a model of moderate hyperoxia (50% $O_2$, 96 h culture) to induce oxidative stress in the human leukemia cell line, U-937. Spectrophotometric measurements of mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media, determination of antioxidant enzyme activities, and cell proliferation and differentiation assays were performed. The data showed that moderate hyperoxia in this myeloid cell line causes: i) intriguing alterations in the mitochondrial activities at the levels of succinate dehydrogenase and succinate-cytochrome c reductase; ii) induction of metabolic compensatory adaptations, with significant shift to glycolysis; iii) induction of different antioxidant enzyme activities; iv) significant cell growth inhibition and v) no significant apoptosis. This work will permit better characterization the mitochondrial damage induced by hyperoxia. In particular, the data showed a large increase in the succinate cytochrome c reductase activity, which could be a fundamental pathogenic mechanism at the basis of oxygen toxicity.

Effect of SoPungDoJeokTang-KaMi on cytokine expression with $CD4^+/CD25^+/foxp3^+$ (Treg) cell induction in atopic dermatitis-like skin lesions and IgE hyperproduction induced in NC/Nga mice (소풍도적탕가미(消風導赤湯加味)가 IgE 과대생산과 피부염이 발진된 NC/Nga생쥐의 비장세포에서 $CD4^+/CD25^+/foxp3^+$ Treg 증진에 의한 유전자 발현에 미치는 영향)

  • Han, Dal-Soo;Han, Jae-Kyung;Kim, Yun-Hee
    • Journal of Haehwa Medicine
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    • v.18 no.1
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    • pp.29-41
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    • 2009
  • Wished to examine closely effect that SoPungDoJeokTang-KaMi (SPDJTK) medicines used to atopy dermatitis disease patient get in atopy eruption control experimentally. SPDJTK medicines controlled $CD4^+/IFN-\gamma$, and $CD4^+/CD25^+/foxp3^+$ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates T cells of a NC/Nga mouse same time by anti-CD40/rmIL-4, and interleukin-$1{\beta}$, IL-6, TNF-$\alpha$, and TGF-$\beta$ mRNA outturn that bear in T and B cells decreased remarkably by SPDJTK medicines. Intracellular staining of splenocytes anti-CD40/rmIL-4 plus rmIL-4 stimulated as described in a, assessed after 24 h, SPDJTK exerts a mainly immunosuppressive effect that acts at least partially through suppression of the transcription factor GATA3 expression in $CD4^+$ T cells. Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen specially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Result that Th1 cell and Th2 cell observe to be shifted by cytokine expression with $CD4^+/CD25^+/foxp3^+$ Treg cells induction by SPDJTK medicines could know that SPDJTK medicines can use usefully in allergy autoimmnune diease.

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Antioxidative Effect and Component Analysis of Eriobotrya japonica Leaf Extracts (비파엽 추출물의 항산화 효능과 성분분석)

  • Kim, Su-Ji;Park, Jin-O;Park, Soo-Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.38 no.1
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    • pp.57-65
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    • 2012
  • In the present study, the antioxidative properties, inhibitory activity on tyrosinase, and active components of Eriobotrya japonica (E. japonica) leaf extract were investigated. The free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activity ($FSC_{50}$) of extract/fraction of E. japonica leaf was in the order 50 % ethanol extract ($22.625{\mu}g/mL$) < ethyl acetate fraction (6.75) < deglycosylated aglycone fraction (5.06). Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) of fraction/extracton ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system using the luminol-dependent chemiluminescenceassay were investigated. $OSC_{50}$ of the ethyl acetate fraction, deglycosylated aglycone fraction, and ethanol extract were 0.75, 0.79, and $1.61{\mu}g/mL$, respectively. The cellular protective effects of E. japonica leaf extract on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The protective effects of extract/fraction of E. japonica leaf were increased in a in a concentration dependent manner ($5{\sim}50{\mu}g/mL$). Especially, ${\tau}50$ of ethyl acetate fraction at concentrations of $10{\mu}g/mL$ and $50{\mu}g/mL$ showed the most protective effects at 390.8 min and 1471.5 min. The inhibitory effect ($IC_50$) on tyrosinase of E. japonica leaf extracts was higher than arbutin, known as a skin-whitening agent. The order of inhibitory effects was acetate fraction ($75.25{\mu}g/mL$) < 50 % extract (74.1) < deglycosylated aglycone fraction (43.35). TLC of the ethyl acetate fraction showed 7 bands (EJL 1 - EJL 7). HPLC of the aglycone fraction exhibited 2 peaks, kaempferol and quercetin. The amounts of kaempferol and quercetin were 53.7 and 46.3 %. respectively. Therefore, The amounts of kaempferol and its glucoside were a little bit higher than quercetin and its glucoside in E. japonica leaf extract. Accordingly, these findings suggest that extracts/fractions of E. japonica leaf can function as antioxidants in biological systems, especially skin exposed to UV radiation, and protect cellular membranes against ROS. Thus, the extract/fraction of E. japonica leaf may be used in novel functional cosmetics as antioxidants against skin photoaging.

Antioxidative Properties of Extract/Fractions of Suaeda asparagoides and Salicornia herbacea Extracts(I) (함초(나문재 및 퉁퉁마디) 추출물의 항산화 작용에 관한 연구(I))

  • Park, Soo-Nam;Jeon, So-Mi;Kim, So-I;Ahn, Jeung-Youb
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.3
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    • pp.145-152
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    • 2007
  • In this study, the antioxidative effects of Sueada asparagoides and Salicornia herbacea extracts were investigated. The free radical(1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activity($FSC_{50}$) of extract/fractions of Sueada asparagoides was in the order: 100 % ethanol extract(329.33 ${\mu}g/mL$) < 50 % ethanol extract(40.73) < ethylacetate fraction(13.87) < deglycosylated aglycone fraction (7.80). In case of Salicornia herbacea, the free radical scavenging activities of ethylacetate fraction and aglycone fraction were 13.87 and 7.80 ${\mu}g/mL$, respectively. Reactive oxygen species(ROS) scavenging activities($OSC_{50}$) of Sueada asparagoides and Solicornia herbacea extracts on ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system were investigated using the luminol-dependent chemiluminescence assay. The order of ROS scavenging activity of Sueada asparagoides extracts was 50 % ethanol extract($OSC_{50}$, $0.99{\mu}g/mL$) < ethylacetate fraction (0.05) < aglycone fraction (0.03). Aglycone fraction showed the most prominent scavenging activity. In case of Salicornia herbacea, the ROS scavenging activities of ethylacetate fraction and aglycone fraction were 0.10 and 0.20 ${\mu}g/mL$, respectively. The protective effects of extract/fractions of Sueada asparagoides and Salicornia herbacea on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The ethanol extract(100%) of Sueada asparagoides diminished photohemolysis in a concentration dependent manner($1{\sim}100{\mu}g/mL$). Particularly deglycosylated aglycone fraction exhibited the most prominent celluar protective effect($\tau_{50}$, 310 min at 50 ${\mu}g/mL$). In case of Salicornia herbacea, ethylacetate fraction exhibited more potent protective effect. These results indicate that extract/fractions of Sueada asparagoides can function as antioxidants in biological systems, particularly skin exposed to UV radiation by scavenging $^1O_2$ and other ROS, and protect cellular membranes against ROS.

Comparative Study on Antioxidative Activity of Glycyrrhiza uralensis and Glycyrrhiza glabra Extracts by Country of Origin (원산지별 감초 추출물의 항산화 활성 비교 연구)

  • Han, Saet Byeol;Gu, Hyun A;Kim, Su Ji;Kim, Hye Jin;Kwon, Soon Sik;Kim, Hae Soo;Jeon, So Ha;Hwang, Jun Pil;Park, Soo Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.39 no.1
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    • pp.1-8
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    • 2013
  • In this work, comparative study on antioxidative activities of extracts from Glycyrrhiza uralensis (G. uralensis) produced in Korea and in China and Glycyrrhiza glabra (G. glabra) produced in Uzbekistan was conducted. Among three origins, 50% ethanol extracts (21.15 ${\mu}g/mL$), ethyl acetate fraction (29.15 ${\mu}g/mL$) and aglycone fraction (3.26 ${\mu}g/mL$) of G. uralensis from Korea showed the higher free radical (1,1-phenyl-2-picrylhydrazyl, DPPH) scavenging activity ($FSC_{50}$) than extracts from other origins. Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) of extracts from three origins on ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system were investigated using luminol-dependent chemiluminescence assay 50% ethanol extract (1.00 ${\mu}g/mL$) and ethyl acetate fraction (0.34 ${\mu}g/mL$) of G. uralensis from China showed the most prominent ROS scavenging activity. The protective effects of extract/fractions of G. uralensis and G. glabra extracts on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. 50% ethanol extract and aglycone fraction of G. uralensis and G. glabra extracts from three origins showed cellular protective effects in a concentration dependent manner (5 ~ 50 ${\mu}g/mL$). Aglycone fraction of G. uralensis from Korea (${\tau}_{50}$ = 847.4 min)especially showed cellular protective effects four times higher than that from China (${\tau}_{50}$ = 194.3 min). These results indicate that G. uralensis and G. glabra extracts, which have been used as whitening agent, could be applicable to functional cosmetic ingredient as a natural antioxidant. Judging from the prominent cellular protecitve effects, it is concluded that G. uralensis and G. glabra extracts can protect the skin from $^1O_2$ and various ROS induced by UV.

Distribution and Bacteriological Characteristics of Vibrio vulnificus (Vibrio vulnificus 균의 분포 및 세균학적 특성)

  • CHANG Dong-Suck;SHIN Il-Shik;CHOI Seung-Tae;KIM Young-Man
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.19 no.2
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    • pp.118-126
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    • 1986
  • Vibrio vulnificus is a recently recognized halophilic organism that nay cause serious human infections. Patients infected with V. vulnificus often have a history of exposure to the sea, suggesting that the organism may be common inhabitant of marine environment. The purpose of this experiment is to investigate the distribution and bacteriological characteristics of V. vulnificus. The strain used in this experiment was isolated from sea water and sea products such as common octopus (Octopus variabilis), ark shell (Anadara broughtonii), blue crab (Ericheir japonica), and sea squirt (Synthia roretzi) collected in Pusan area from July to October in 1985. V. vulnificus was frequently isolated in August when temperature of sea water was around $26^{\circ}C$ and rarely isolated in October when temperature of sea water was around $18.5^{\circ}C$. The distinctive biochemical characteristics of V. vulnificus were ONPG hydrolysis positive and fermented lactose and not grown in peptone water contained $8\%$ NaCl. The optical density at 660 nm of the growth of V. vulnificus was reached maximum level after 8 hours of culture at $35^{\circ}C$ in brain heart infusion broth but that of V. vulnificus was little increased at $15^{\circ}C$ for 14 hours. Optimum temperature and pH for the growth of V. vulnificus were around $35^{\circ}C$ and 8.0. The specific growth rate and the generation time of V. vulnificus isolated from the samples were $1.21\;hr^{-1}$, 34 min at $35^{\circ}C$ and $0.61\;hr^{-1}$, 69 min at $25^{\circ}C$, respectively. V. vulnificus did not grow on eosin-methylene-blue agar, salmonella-shigella agar, deoxycholate agar but grew well on Endo agar, xylose-lysine-deoxycholate agar and hektoen enteric agar. On Endo agar, the colonies of V. vulnificus were red and achieved a diameter of 2 to 4 mm as a feature enabling differentiation of V. vulnificus from other Vibrio spp. V. vulnificus grow well on TCBS agar forming green colonies. V. vulnificus refrigerated at $4^{\circ}C$ exhibited a linear decline of its viablity as 1 log cycle in every 16 hours storage, while V. vulnificus freezed at $-18^{\circ}C$ almost became extinct.

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Effect of Hot Water and Microwave Heating on the Inactivation of Enterobacter sakazakii in Reconstituted Powdered Infant formula and Sunsik (열수(熱水)와 마이크로웨이브 가열이 조제분유 및 선식 용해 중 Enterobacter sakazakii 사멸에 미치는 영향)

  • Kim, Jung-Beom;Park, Yong-Bae;Lee, Myung-Jin;Kim, Ki-Cheol;Huh, Jeong-Weon;Kim, Dae-Hwan;Lee, Jong-Bok;Kim, Jong-Chan;Choi, Jae-Ho;Oh, Deog-Hwan
    • Journal of Food Hygiene and Safety
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    • v.23 no.2
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    • pp.157-162
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    • 2008
  • Enterobacter sakazakii was initially referred to as yellow-pigmented Enterobacter cloacae and reclassified in 1980. E. sakazakii infection cause life-threatening meningitis, septicemia, and necrotizing enterocolitis in infants. Powdered infant formula (PIF) and baby foods may be the important vehicle of E. sakazakii infection. It has been reported that E. sakazakii was isolated from PIF and sunsik ingredients produced in Korea. Some infants have been fed sunsik as a weaning diet. Therefore, it is necessary that this organism should be inactivated on preparing PIF and sunsik at homes and in hospitals. The cocktail of three Korean E. sakazakii strains (human, sunsik and soil isolates) were used to investigate the inactivation of this organism with hot water at 50, 60, 65, 70 and $80^{\circ}C$ and microwave heating for 60, 75, 90, 105 and 120 sec. Reconstituted PIF and sunsikwere inoculated with cocktailed vegetative cells of E. sakazakii at 6 log CFU/mL. Thermal inactivation of vegetative cells of E. sakazakii were achieved by reconstituted PIF and sunsik with hot water at $60^{\circ}C$ or greater and with microwave heating at 2,450 MHz for 75 sec or longer. Considering that biofilm formation of E. sakazakii was adapted to survive the dry environment that is PIF and sunsik and thermal resistance increased, it is suggested that inactivation of E. sakazakii was used by hot water at $70^{\circ}C$ or greater and microwave heating for 90 sec or longer. Reconstituted PIF and sunsik were inoculated with cocktailed vegetative cells of E. sakazakii at 2 to 3 log CFU/mL to investigate the growth curve of this organism and stored at 5, 10, 15, 20, 25, 30 and $35^{\circ}C$. Viable counts slightly changed at 5, $10^{\circ}C$ during 48 h but grew at $15^{\circ}C$ or greater. Considering that E. sakazakii is able to grow in infant formula milk at refrigerator temperature, reconstituted PIF and sunsik that are not immediately consumed should be discarded or stored at refrigeration temperatures within 24 h.

A Study on the Organization Design of Regional Innovation Councils for Establishing Strategic Regional Innovation Systems: Based on Kang-Won Province Case (전략적 지역혁신체재 구축을 위한 지역혁신협의회 조직에 관한 연구 - 강원도 사례를 중심으로)

  • Lee, J.H.
    • Korean Business Review
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    • v.21 no.2
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    • pp.195-214
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    • 2008
  • In 2004, in order to create core competences and major growth drivers for endogenous regional developments, the Korean government adopted the policies for establishing regional innovation systems, The main organization for the policies is the regional innovation council which is composed of diverse groups of scholars, professionals, and government officials. The regional innovation council of Kang-won Province consists of a couple of sub-divisions such as Operation Committee, Administration Office, Planning and Moderation Department, Strategic Industry Department, Culture and Tourism Industry Department, Regional Industry Department, and Regional Human Resource Development Department. The primary roles and jobs are planning, reviewing, evaluating and finalizing regional innovation policies. However, because of conflicts with local government, insufficient budget problems, organization structure problems, and decision making process problems, the regional innovation councils could not perform their original roles and functions. They could not adopt radical or non-traditional strategies. Although it's failure, a lot of people recognize the importance of regional innovation councils' roles and functions, I believe there would be another regional innovation councils coming continuously which would be take more important roles and have more power over budgeting problems. The purpose of this article is to identify the primary sources of strategies and organization structure problems of the previous regional innovation councils and to provide a couple of answers. In this paper, the author primarily analyze the problems of the Kang-won innovation council. A couple of answers to the desirable organization structures and the desirable roles of regional innovation councils will be presented for discussion.

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