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      • SCIESCOPUS

        <i>In vitro</i> and <i>in vivo</i> evaluation of a novel polymer-free everolimus-eluting stent by nitrogen-doped titanium dioxide film deposition

        Park, Dae Sung,Bae, In-Ho,Jeong, Myung Ho,Lim, Kyung Seob,Sim, Doo Sun,Hong, Young Joon,Lee, So-Youn,Jang, Eun Jae,Shim, Jae-Won,Park, Jun-Kyu,Lim, Han Chul,Kim, Han Byul Elsevier 2018 Materials Science and Engineering C Vol.91 No.-

        <P><B>Abstract</B></P> <P>Inflammation and thrombosis are linked to the use of polymer-based drug-eluting stents (DES). The aim of this study was to develop a polymer-free everolimus (EVL)-eluting stent using nitrogen-doped titanium dioxide (N-TiO<SUB>2</SUB>) and verify its efficacy by <I>in vitro</I> and <I>in vivo</I> assessment in a porcine coronary model. Various analytical approaches such as scanning electron microscopy and atomic force microscopy, electron spectroscopy, Fourier transform infrared spectrometry and contact angle measurement were employed for the characterization. As a part of biocompatibility assessment, platelet adhesion and smooth muscle cell (SMC) proliferation were examined. Bare metal stent (BMS), N-TiO<SUB>2</SUB> stent, everolimus-eluting N-TiO<SUB>2</SUB> (N-TiO<SUB>2</SUB>-EVL) stent, and commercialized EVL-eluting stent (EES) were randomly placed in forty coronary arteries in twenty pigs. After four weeks of implantation, the stents were subjected to histological and quantitative analysis. The N-TiO<SUB>2</SUB> film used in this study was well coated without any cracks or peeling. Surface hydrophilicity (88.8% of angle decrement) could be associated with the decrease in surface roughness post N-TiO<SUB>2</SUB> deposition (37.0%). The platelet adhesion on the N-TiO<SUB>2</SUB> surfaces was less than that on the BMS surface. The proliferation of SMC was suppressed in the N-TiO<SUB>2</SUB>-EVL group (30.2%) but not in the BMS group. In the animal study, the percent area restenosis was significantly decreased in the N-TiO<SUB>2</SUB>-EVL group compared to that in the BMS group. The results (BMS; 47.0 ± 11.00%, N-TiO<SUB>2</SUB>-EVL; 31.7 ± 10.50%, and EES; 29.1 ± 11.21%, <I>n</I> = 10, <I>p</I> < 0.05) were almost at par with those of the commercialized EVL-eluting stent. The introduction of N-TiO<SUB>2</SUB> deposition during fabrication of polymer-free DES may be an efficient accessorial process for preventing in-stent restenosis and thrombosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> N-TiO<SUB>2</SUB> surfaces can help to reduce the platelet adhesion. </LI> <LI> In porcine model, N-TiO<SUB>2</SUB> everolimus decreased in-stent restenosis and fibrin deposition. </LI> </UL> </P>

      • In-direct localized surface plasmon resonance (LSPR)-based nanosensors for highly sensitive and rapid detection of cortisol

        Jeon, Jinwoo,Uthaman, Saji,Lee, Jiyoung,Hwang, Hyejin,Kim, Gibum,Yoo, Pil J.,Hammock, Bruce D.,Kim, Christine S.,Park, Yeon-Su,Park, In-Kyu Elsevier 2018 Sensors and actuators. B, Chemical Vol.266 No.-

        <P><B>Abstract</B></P> <P>Over-secretion of cortisol from the adrenal cortex is closely related to acute and chronic stress; thus, rapid and sensitive detection of cortisol in serum is of critical importance for preventing the progression of stress-related diseases. The binding of a biological molecule to the surface of metallic nanoparticles changes the local refractive index and in turn induces a shift in the localized surface plasmon resonance (LSPR) wavelength. Utilizing this phenomenon, we designed a novel disposable LSPR-based cuvette-type sensor for detecting cortisol in serum. The developed cuvette-type nanosensor consists primarily of an assembly of plastic unit sensors coated with gold nanoparticles on a single layer wherein cortisol-conjugated bovine serum albumin (BSA) is immobilized. In this system, a redshift in LSPR wavelength is induced by the binding of cortisol antibody onto cortisol-conjugated BSA immobilized on a gold nanoparticle surface in the nanosensor. In a competitive assay, the nanosensor could rapidly detect cortisol in both a PBS solution and serum (within 20 min) at concentrations ranging from 1 to 10,000 ng/mL (2.759–3 × 10<SUP>3</SUP> nmol/L), which is comparable to conventional enzyme-linked immunosorbent assay (ELISA) which typically requires longer than 4 h and complex sample preparation. Thus, we demonstrated that the LSPR-based nanosensor system developed in this study can provide a useful toolkit for a rapid, highly sensitive and reliable detection of cortisol hormone in a commercially available manner.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Novel disposable LSPR-based cuvette-type sensor for detecting cortisol in serum. </LI> <LI> Rapid, convenient, and sensitive method for detecting cortisol hormone in serum. </LI> <LI> Detect cortisol in both PBS solution and serum within 20 min at concentrations ranging from 1 to 10,000 ng/mL. </LI> </UL> </P>

      • SCOPUSKCI등재

        Uncoupling Protein 3의 골격근 세포내 과발현이 OLETF 백서 및 배양된 골격근 세포에서 포도당대사에 미치는 영향

        한정희,박혜선,고정민,김하영,강호경,이인규,박중열,홍성관,이재담,이기업 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

        연구배경:Uncoupling protein(UCP)는 미토콘드리아의 내막에 위치하는 단백질로 세포내의 과다한 에너지를 열로 발산시키는 기능을 가진다. 최근 동물의 갈색지방조직에만 존재하는 UCP와 유사성을 가진 아형들(UCP2,3)이 사람에게도 존재함이 알려져 큰 관심을 끌도 있는데 이중 UCP3는 그 발현이 골격근세포와 갈색지방조직에만 국한된다. 본 연구에서는 UCP3가 체내 인슐린 감수성을 결정하는데 가장 중요한 조직인 골격근에 국한되어 발현되는 점에 착안하여 UCP3를 골격근세포에 과발현시켰을 때 포도당 대사에 어떠한 영향이 나타나는 지를 조사하였다. 방법:25주령의 8마리의 OLETF 백서를 대상으로 하여 4마리는 골격근에 adenovirus 2mL(1×10¹²pfu/mL)를 주사하여 대조군으로 하였고 4마리는 골격근에 재조합법으로 제작된 adenovirus­UCP3 2mL(1×10¹²pfu/mL)를 주사하였다(UCP3 과발현군). UCP3를 투여한 백서에서 먹이섭취가 증가하는 경향이 있어 그 전날 대조군이 먹은 야의 먹이만큼 투여하였다. 골격근에 adenovirus를 주사한 10일 후에 euglycemic hyperinsulinemic clamp를 시행하였다. Adenovirus­UCP를 C2C12 골격근 세포에 transfection시켜 UCP3를 C2C12 골격근 세포에 transfection시켜 UPS3­C2C12를 만들고 C2C12 골격근 세포와 UPS3­C2C12 골격근 세포에서 포도당 수송 및 당원합성을 측정하였다. 결과:UCP3 과발현 OLETF에서 체중이 감소하는 경향을 보였고 인슐린 감수성이 증가하였다. C2C12세포에서 기저상태 포도당 수송은 1.28±0.17μmol/L/min였고 100nM 인슐린으로 2시간 처리한 후 2.67±0.20 μmol/L/min로 증가하였다. UCP3­C2C12 세포에서는 기저상태 포도당 수송이 3.98±0.13μmol/L/min로 증가되었고 인슐린 처리 후 5.74±0.44μmol/L/min로 증가하였다. 인슐린을 처리한 UCP3­C2C12 세포에 P13K 억제제인 wortmannin을 첨가하였을 때 포도당 수송활성이 3.81±0.20μmol/L/min로 감소하였다. 기저상태 당원합성은 C2C12 세포에서 0.25±0.01μmol/L/min였고 인슐린 처리 후 0.45±0.01μmol/L/min로 증가하였다. UCP3­C2C12 세포에서는 기저상태 당원합성이 0.62±0.01μmol/L/min였고 인슐린 처리 후 1.26±454μmol/L/min로 증가하였다. UCP3­C2C12세포에 wortmannin을 첨가하였을 때 당원합성율이 0.80±0.04μmol/L/min로 감소하였다. 결론:UCP3 과발현이 OLETF 백서에서 인슐린 감수성을 증가시켰고 골격근세포에서 포도당 수송 및 당원합성을 증가시켰다. wortmannin을 첨가하였을 때 포도당 수송 및 당원합성이 감소함으로 보아 이 과정이 인슐린 신호전달체계인 P13K에 일부 의존함을 알 수 있었다. Background : UC P3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. Methods : An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus-UCP3 (UCP3 group) and others were injected with the adenovirus(control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C212 cells transfected with ether an adenovirus or the adenovirus-UCP3. Results : The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. Conclusion : Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism(J Kor Diabetes Asso 25 :460~468, 2001).

      • SCIESCOPUSKCI등재

        Nelumbinis Semen Reverses a Decrease in $5-HT_{1A}$Receptor Binding Induced by Chronic Mild Stress, a Depression-like Symptom

        Jang, Choon-Gon,Kang, Moon-Kyu,Cho, Jae-Han,Lee, Sun-Bok,Kim, Hyun-Taek,Park, Soon-Kwon,Lee, Jin-Woo,Park, Seong-Kyu,Hong, Moo-Chang,Shin, Min-Kyu,Shim, In-Sup,Bae , Hyun-Su The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.10

        Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

      • 신원방우황청심원액의 심혈관계에 관한 약효

        조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

        Abstract-In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10^-6 M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD_90 and V_max at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.

      • KCI등재

        장시간 불가피한 공복(fasting)후 인체의 내분비 변화 : 삼풍백화점 붕괴 사고후 구조된 3인의 증례 THREE CASES IN COLLAPSE OF SAMPOONG DEPARTMENT STORE

        박규남,황주일,박조현,오동렬,이원재,오승택,김세경,김인철 대한응급의학회 1995 大韓應急醫學會誌 Vol.6 No.2

        The interactions between nutrition and the endocrine system are more intimate and complex that previously thought. Nutrition modulates secretion and activity of many hormones, as part of the stress adaptation process. Fasting, in particular, produces a number of important changes in the endocrine system, with teleological purpose of helping the body tolerate the lack of food ingestion. These changes are therefore beneficial and protective, although at times they may not appear to be that way. The endocrine changes of fasting mediate the metabolic response. We must emphasize that these changes are completely reversible when appropriate nutrition is established. These changes are as followes: 1) decreased insulin and increased glucagon levels, 2) decreased thyroid effect, 3) decreased sympathetic activity, 4) hypothalamic hypogonadism, 5) decreased growth, 6) altered glucocorticoid secretion and metabolism, 7) impaired mineralocorticoid response, 8) decreased ADH secretion and effect. We experienced three cases of involuntary prolonged fasting after collapse of Sampoong department store. They were released from collapsed field after 11(case Ⅰ), 13(case Ⅱ), 17days(case Ⅲ) respectively. In each case, the endocrine changes of plasma levels were as followes: decrease of cortisol in case Ⅰ, increase of GH in case Ⅱ, decrease of free T3, T3, cortisol and increase of reverse T3, insulin in case Ⅲ. Each one did not show the same endocrine changes of plasma levels. But we think these changes of fasting are beneficial in metabolic response of human.

      • 외과계 감염증에 대한 Sulperazon(Sulbactam/cefoperazone) 및 Cefoperazone의 임상효과 비교연구

        박규주,노동영,김상준,권오중,정중기,홍인규 대한화학요법학회 1990 대한화학요법학회지 Vol.8 No.2

        Despite recent advances in development of antibiotics and antiseptic techniques, infection still remains to be one of the major problems in the surgical field. Due to development of bacterial resistance to commonly used antibiotics, there is always a need to develop a new antimicrobial agent which would overcome such resistance. Sulperazon (Sulbactam/Cefoperazone) is a combination drug of potent β-lactamase inhigitor, sulbactam, and cefoperazone which has broad antibacterial spectrum, which was developed to combat against β-lactamase producing microorganisms. In an effort to evaluate the efficacy and safety of sulperazone, we have randomly divided 40 patients (12 with perforated appendicitis, 10 with peritionitis, 6 with GB empyema, 6 with periproctal abscess, 3 with wound infection, 1 liver abscess, 1 pancreatic abscess, and 1 acute cholangitis) into 2 groups (20 patients in each group). One group received daily dose of 2 to 3 grams of sulperazon and the other group received daily dose of 2 to 3 grams of cefoperazone. Following results were obtained : 1. Clinical effect of sulperazon was cure in 16 patients (80%), improvement in 3 patients (15%), compaired to cure in 14 patients (70%), improvement in 4 patients (20%) for the cefoperazone group. 2. Using disc diffusion method, sulperazon was sensitive to all of the isolated microorganisms except β-hemolytic streptococci, which was moderately sensitive. Cefoperazone was sensitive to only E. coli, Pseudomonas aeruginosa and Serratia. 3. Microbiological effect of sulperazon was eradication of offending microorganisms in 16 patients (80%), compared to 14 patients (70%) in Cefoperazone group. 4. Overall clinical efficacy of sulperazon was 95%, compared to 80% for cefoperazone. 5. Adverse effects due to sulperazon was nausea and diarrhea which occurred in 1 patient respectively. 2 patients receiving cefoperazone experienced diarrhea. It can be concluded that sulperazon is a safe and effective antibiotic agent which can be used in surgical infection patients.

      • 배양조건이 'Campbell Early' 포도의 기내 및 기외 생장에 미치는 영향

        박재혁,손인창,김선규 충북대학교 한국과학재단 지정 첨단원예기술개발 연구센터 2002 연구보고서 Vol.6 No.-

        배지내 당농도와 PPF 및 배양조건이 포도 Campbell Early의 기내생장과 순화 및 배지와 수분조건이 기외 생장에 미치는 영향을 조사하였다. 포도의 기내배양시 배지 내 당농도를 30gL^-1로 하였을 때 신초의 길이와 엽면적이 증가하였고, 15gL^-1와 0gL^-1에서는 신초의 건물중에는 차이가 없었지만, 지하부의 생체중과 건물중은 감소하였다. PPF 100∼200㎛olm^-2s^-1에서 신초의 신장과 지상부의 생체중 및 건물중이 증가하였으며, 뿌리의 생체중과 건물중이 증가하는 경향이었으나 유의성은 없었다. 기내에서 생육한 포도 식물체를 vermiculite, peatmoss, 그리고 perlite+ peatmoss (6:4)로 혼용한 배지에 이식했을 때, 순화 초기에는 신초와 뿌리의 발달이 peatmoss, perlite+ peatmoss 배지에서 증가하였으나, 순화 후기로 갈수록 peatmoss에 심겨진 식물체가 vermiculite와 perlite+ peatmoss(6:4)로 혼용한 배지의 식물체보다 지상부와 지하부의 생육이 저조하였다. perlite+ peatmoss 혼용배지의 식물체는 신초의 길이, 생체중, 그리고 엽수가 가장 많이 증가하였다. Photomixotrophic 조건이 Photomixotrophic이나 heterotrophic에 비해 유묘의 생장, 생체중, 건물중이 높았고, 지하부는 photoautotrophic에 비해 당을 포함한(3%) 처리구에서 생육이 좋았다. Photomixotrophic, photoautotrophic의 처리구에서 엽록소 a, b, a+b의 함량, 생존율, 그리고 생체중과 건물중이 증가하였다. 식물체의 이식 후 생육은 Photomixotrophic 생장한 식물체가 photoautotrophic과 heterotrophic 처리에서 생장한 식물체에 비해 좋았다. 순화 기간 내 식물체의 CO_2 uptake, 기공전도도, 증산율과 Fv/Fm는 증가하였다. Photomixotrophic와 photoautotrophic 처리구에서 생장한 식물체의 잎의 sucrose와 starch 함량이 순화 후 15일까지 증가하였고, 그 후 급격한 증가는 보이지 않고, 소폭으로 감소하거나 증가하였다. 순화를 거친 포도 식물체를 상토, 모래+상토의 배양토에 정식했을 때, FV/Fm은 건조 스트레스를 받는 식물체에서 재관수를 하기까지 일정하게 감소한 반면에 수분공급이 잘 된 처리구에서 Fv/Fm값은 일정하게 유지되었다. 상대수분함량(RWC)은 건조스트레스를 받은 잎에서 감소하였고 재관수 후 약간 회복되었다. 기공의 크기와 수는 건조스트레스를 받은 식물체의 잎이 그렇지 않는 처리에 비해 감소하였고 기공도 닫혀 있었으며, 재관수 실시 후 기공의 수와 크기가 증가하였다. 배지의 함수량은 일반 상토에 비해 상토에 모래를 혼합한 토양이 높았으며, 건조 스트레스를 가했을 경우 모래를 혼합한 상토의 식물체가 잎의 상대수분함량이 높게 나타내었다. Effect of sucrose concentration, PPF, and phototrophic condition on in vitro growth of 'Campbell Early' grape, and the response of in vitro-grown plantlets to various media and water stress was investigated. Shoot growth and leaf area increased in media supplemented with 30gL^-1 sucrose, while fresh and dry weight of root decreased in media with 0 or 15gL^-1 sucrose. Shoot dry weight was not affected by sucrose concentration. PPF of 100 to 200㎛olm^-2s^-1 increased the shoot length and shoot fresh and dry weight, while root fresh and dry weight tended to increase without significant difference. When in vitro-grown plantlets were transplanted to various media, peatmoss and perlite+peatmoss favored the growth early stage of acclimation (to 12days after transplanting), but the growth of plants planted on vermiculite and perlite+peatmoss surpassed that of peatmoss in later stage of acclimation(from 13 to 30 days after transplanting). The highest shoot growth and plant fresh weight, and leaf number were achieved with perlite+peatmoss medium. Plant growth and plant fresh and dry weight were better in photomixotrophic condition than photoautotrophic or heterotrophic condition, while root growth was favored with heterotrophic or photomixotrophic condition. CO_2enrichment increased the chlorophyⅡ content (a, b, a+b), survival rate, and fresh and Dry weight. Ex vitro growth of photomixotrophically grown plantlets was much better than grown under photoautotrophic or heterotrophic condition. CO_2 uptake, stomatal conductance, transpiration rate, and maximum photochemical efficiency(Fv/Fm) of plants grown under photomixotrophic or photoautotrophic condition were increased during acclimation. Leaf sucrose and starch content of plants grown under photomixotrophic or photoautotrophic condition showed a gradual increase till 15 days of acclimation, then slightly fluctuated with the new leafing. When grape plantlets were planted on new soil after acclimation, the Fv/Fm ratio of water stressed-plantlets showed a gradual decrease till rewatering, while that of well-watered plantlets was constant. Relative water content(RWC) was decreased in water stressed plantlets, and was slowly recovered by rewatering. The size and number of stomata were decreased, and the stomata were closed in water stressed plantlets, and the size and number of stomata were recovered slowly with rewatering. Water content was higher in commercial soil mix+sand than commercial soil mix alone, and leaf RWC was also high in commercial soil mix+sand when water stressed.

      • Glucotoxicity in the INS-1 Rat Insulinoma Cell Line Is Mediated by the Orphan Nuclear Receptor Small Heterodimer Partner

        Park, Keun-Gyu,Lee, Kyeong-Min,Seo, Hye-Young,Suh, Ji-Ho,Kim, Hye-Soon,Wang, Li,Won, Kyu-Chang,Lee, Hyoung-Woo,Park, Joong-Yeol,Lee, Ki-Up,Kim, Jung-Guk,Kim, Bo-Wan,Choi, Hueng-Sik,Lee, In-Kyu American Diabetes Association 2007 Diabetes Vol.56 No.2

        <P>Prolonged elevations of glucose concentration have deleterious effects on beta-cell function. One of the hallmarks of such glucotoxicity is a reduction in insulin gene expression, resulting from decreased insulin promoter activity. Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that inhibits nuclear receptor signaling in diverse metabolic pathways. In this study, we found that sustained culture of INS-1 cells at high glucose concentrations leads to an increase in SHP mRNA expression, followed by a decrease in insulin gene expression. Inhibition of endogenous SHP gene expression by small interfering RNA partially restored high-glucose-induced suppression of the insulin gene. Adenovirus-mediated overexpression of SHP in INS-1 cells impaired glucose-stimulated insulin secretion as well as insulin gene expression. SHP downregulates insulin gene expression via two mechanisms: by downregulating PDX-1 and MafA gene expression and by inhibiting p300-mediated pancreatic duodenal homeobox factor 1-and BETA2-dependent transcriptional activity from the insulin promoter. Finally, the pancreatic islets of diabetic OLETF rats express SHP mRNA at higher levels than the islets from LETO rats. These results collectively suggest that SHP plays an important role in the development of beta-cell dysfunction induced by glucotoxicity.</P>

      • Gymnemic acid의 간장 및 신장의 조직에 미치는 영향에 대한 실험적 연구

        박순록,신인철,강주섭,서대규 漢陽大學校 環境科學硏究所 1994 環境科學論文集 Vol.15 No.-

        생체에 투여된 물질은 생체내에서 아무 변화없이 체외로 배설되는 경우도 있지만, 대부분은 체내에서 여러가지 생화학적 변화를 거쳐 배설된다. 이런 체내에서의 생화학적 변화는 주로 간장에서 일어나고, 이런 물질과 그 대산사물의 배설은 주로 신장에서 이루어지며, 일부는 다른 경로를 통하기도 한다. 그러므로, 약물의 대사 및 배설장기인 간장과 신장에 이런 물질이 축적되면 그 장기가 손상되는 악순환을 거치게 된다. 이에, 본 실험은 2000여년 전부터 오늘에 이르기까지도 인도지방에서 비만이나 당뇨병에 대한 민간요법제로 이용되어 온 Gymnema sylvestre 잎의 유효성분인 gymnemic acid의 신장과 간장의 조직에 미치는 영향을 검토하고자 실시하였다. 실험동물은 정상 Wistar계 웅성 흰쥐(체중 200gm 내외)를 사용하였고, 실험기간중에 먹이와 물은 자유로이 공급하였다. 실험군은 정상대조군과 동일한 조건하에서 15일동안 gymnema산을 각각 500㎎/㎏, 800㎎/㎏의 용량으로 하루 3회, 즉 오전 7시, 오후 2시, 오후 7시에 각각 경구투여하고, gymnema산 투여 15일째 24시간동안 절식시킨 후 경동맥사혈로 희생시킨 다음 개복하여 간우측 전엽과 우측 신장을 적출하여 일반 육안적 소견과 Hematoxylin 및 eosin 이중염색상의 광학 현미경적 소견을 관찰하여 다음과 같은 결과를 얻었다. 1. 흰쥐 신장의 육안적 소견과 Hematoxylin 및 eosin 이중염색 소견에서는 정상 대조군과 GA투여군에서 특기할 만한 소견이 관찰되지 않았다.(Fig 1-a, 1-b, 1-c). 2. GA(500㎎/㎏)투여군 흰쥐 간장에서 Hematoxylin 및 eosin 이중염색 소견상 간소엽의 중심대와 일부 중간대에서 동양혈관이 확장되었고, 간세포대의 배열이 불규칙해졌으며, 간세포내의 간세포배열이 불규칙해졌고, 공포변성이 초래된 간세포도 관찰도었다(Fig. 3-a,3-b). 3. GA(800㎎/㎏) 투여군 흰쥐 간장에서 Hematoxylin 및 eosin 이중염색 소견상 간소염 전반에 걸쳐 동양혈관이 확장되었고, 간세포대배열이 불규칙해졌으며, 간세포대내의 간세포 배열이 불규칙해졌고, 공포변성이 초래된 간세포도 관찰되었다(Fig. 4-a, 4-b). The majority of the chemicals that enter a living system is taken to elimination by hepatic biotransformation and renal excretion of its metabolites and unchanged form. But, some chemicals are also excreted into feces or through other routes. Therefore, the accumulation of the chemicals in the liver and kidney have damaged the organs. It was more than 3000 yours ago that Gymnema sylvestre. Asclepaidaceae piant indegenous to certain regionss of the tropical and subtropical countries, began to be used a popular folk medicine among native population in India in order to treat obesity and "Madhumeha(DM)" and its use still continues to today in India. Theorefore, this study has the purpose to investigate the effect of gymnemic acid(GA) Which is an effective ingredient of Gymnema sylvestre on the liver and the kidney. In the study, Wistar albino male rats weighing around 200gm were divided into three groups, basic diet group(control), GA(500㎎/㎏)group, GA(800㎎/㎏)group, and administered orally the gymnemic acid for 15 days in dose of 500㎎ and 800㎎ per ㎏ of body weight triple a day. All animals were sacrificed at 15 days after the daministration of gymnemic acid and starved for 24 hours sacrificing them, the specimens and eosin. The specimens have been examined grossly and light microscopically. The results were as follows. 1. In the gross and light microscopic observations of the kidney, the control and all experimental groups were not observed pathologic findings. 2. The gross observations of the liver of the of the control and all experimental groups wrer not observed pathologic findings. 3. The sinusoidal dilation, hepatic cord irregularity and disarrangement of hepatocyte were observed in the central zone and a part of intermediate zone of the hepatic lobule of the 15 days GA(500㎎/㎏) administered group. 4. The sinusoidal dilatation, hepatic cord irregularity, disarrangement of hepatocyte and abnormal shaped hepatocytes were observed in all zonesof the hepatic lobule of the 15 days GA(800㎎/㎏) administered gruop. Consequently, it is suggested that administration of large dose of gymnemic acid in the normal rats induces hepatic cellular damages.

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