• Title/Summary/Keyword: Rate Limiting

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Cardioprotective Effects of Low Dose Bacterial Lipopolysaccharide May Not Be Directly Associated with Prostacyclin Production

  • Moon, Chang-Hyun;Kim, Ji-Young;Lee, Soo-Hwan;Baik, Eun-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.3
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    • pp.331-343
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    • 1998
  • Sublethal dose of bacterial lipopolysaccharide (LPS) would induce protection against cardiac ischemic/reperfusion (I/R) injury. This study examines the following areas: 1) the temporal induction of the cardio-protection produced by LPS; and 2) the relations between a degree of protection and the myocardial prostacyclin ($PGI_2$) production. Rats were administered LPS (2 mg/kg, i.v.), and hearts were removed 1, 4, 8, 14, 24, 48, 72,and 96 h later. Using Langendorff apparatus, haemodynamic differences during 25 min of global ischemia/30 min reperfusion were investigated. The concentration of $PGI_2$ in aliquots of the coronary effluent was determined by radioimmunoassay as its stable hydrolysis product $6-keto-PGF1_{\alpha}$ and lactate dehydrogenase release were measured as an indicative of cellular injury. LPS-induced cardiac protection against I/R injury appeared 4 h after LPS treatment and remained until 96 h after treatment. $PGI_2$ release increased 2-3 fold at the beginning of reperfusion compared to basal level except in hearts treated with LPS for 48 and 72 h. In hearts removed 48 and 72 h after LPS treatment, basal $PGI_2$ was increased. To determine the enzymatic step in relation to LPS-induced basal $PGI_2$ production, we examined prostaglandin H synthase (PGHS) protein expression, a rate limiting enzyme of prostaglandin production, by using Western blot analysis. LPS increased PGHS protein expression in hearts at 24, 48, 72, 96 h after LPS treatment. Induction of PGHS expression appeared in both isotypes of PGHS, a constitutive PGHS-1 and an inducible PGHS-2. To identify the correlationship between $PGI_2$ production and the cardioprotective effect against I/R injury, indomethacin was administered in vivo or in vitro. Indomethacin did not inhibit LPS-induced cardioprotection, which was not affected by the duration of LPS treatment. Taken together, our results suggest that $PGI_2$ might not be the major endogenous mediator of LPS-induced cardioprotection.

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Active Materials for Energy Conversion and Storage Applications of ALD

  • Sin, Hyeon-Jeong
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.08a
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    • pp.75.2-75.2
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    • 2013
  • Atomic layer deposition (ALD), utilizing self-limiting surface reactions, could offer promising perspectives for future efficient energy conversion devices. The capabilities of ALD for surface/interface modification and construction of novel architectures with sub-nanometer precision and exceptional conformality over high aspect ratio make it more valuable than any other deposition methods in nanoscale science and technology. In the context, a variety of researches on fabrication of active materials for energy conversion applications by ALD are emerging. Among those materials, one-dimensional nanotubular titanium dioxide, providing not only high specific surface area but also efficient carrier transport pathway, is a class of the most intensively explored materials for energy conversion systems, such as photovoltaic cells and photo/electrochemical devices. The monodisperse, stoichiometric, anatase, TiO2 nanotubes with smooth surface morphology and controlled wall thickness were fabricated via low-temperature template-directed ALD followed by subsequent annealing. The ALD-grown, anatase, TiO2 nanotubes in alumina template show unusual crystal growth behavior which allows to form remarkably large grains along axial direction over certain wall thickness. We also fabricated dye-sensitized solar cells (DSCs) introducing our anatase TiO2 nanotubes as photoanodes, and studied the effect of blocking layer, TiO2 thin films formed by ALD, on overall device efficiency. The photon convertsion efficiency ~7% were measured for our TiO2 nanotubebased DSCs with blocking layers, which is ~1% higher than ones without blocking layer. We also performed open circuit voltage decay measurement to estimate recombination rate in our cells, which is 3 times longer than conventional nanoparticulate photoanodes. The high efficiency of our ALD-grown, anatase, TiO2 nanotube-based DSCs may be attributed to both enhanced charge transport property of our TiO2 nanotubes photoanode and the suppression of recombination at the interface between transparent conducting electrode and iodine electrolytes by blocking layer.

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Capsaicin Ameliorates Cisplatin-Induced Renal Injury through Induction of Heme Oxygenase-1

  • Jung, Sung-Hyun;Kim, Hyung-Jin;Oh, Gi-Su;Shen, AiHua;Lee, Subin;Choe, Seong-Kyu;Park, Raekil;So, Hong-Seob
    • Molecules and Cells
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    • v.37 no.3
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    • pp.234-240
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    • 2014
  • Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1(HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.

Effects of Dietary Xylooligosaccharides on Hepatic HMG-CoA Reductase Activity and Morphological Exchange of liver in Rats Fed High Fat Diets (고지방 식이를 섭취한 흰쥐에 있어서 Xylooligo당이 간의 HMG-CoA Reductase 활성 및 간조직의 형태학적 변화에 미치는 영향)

  • 손효현;이순재
    • Journal of Nutrition and Health
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    • v.35 no.10
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    • pp.1015-1022
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    • 2002
  • This study was conducted to examine the effects of dietary xylooligosaccharides on hepatic HMG-CoA reductase activity and morphological exchange of liver in rats fed high fat diet. Sprague-Dawley male rats weighing 100 $\pm$ 10 g were randomly divided into four groups, two normal diets and two high fat diets containing 1% cholesterol and 10% lard. Two normal diets were classified into a basal diet (normal group) and 10% xylooligosaccharide diet (NX group). The high fat diet groups were classified into a HF group without xylooligosaccharides diet and HFX group supplemented 10% xylooligosacchride diet. Experimental diets were fed ad libidum to the rats for 4 weeks and then they were sacrificed. The body weight of high fat diet (HF group) was increased more than that of normal group, but it was significantly decreased by xylooligosacchrides supplementation. The food intake was not significantly different among the all groups. The weight of liver, small intestine and cecum of all xylooligosaccharide supplemented groups were significantly heavier than those of normal and HF groups. The activity of hepatic HMG-CoA reductase, a rate limiting enzyme of cholesterol biosynthesis, in xylooligosaccharide supplemented groups was higher than that of HF group. Light micrographs revealed that the structures of hepatocytes in xylooligosaccharide supplemented groups were preserved well, compared to HF group. The xylooligosaccharide supplementation exerted a lipid-lowering action by decreasing cholesterol and triglycerides contents in hepatic tissue. In conclusion, the activity of hepatic HMG-CoA reductase and damage of liver in rats fed high fat diets were improved by dietary xylooligosaccharides.

Isotopic Study on Energy Store and Consumption in Voluntary Exercising Mice (생쥐내 동위원소 이용에 의한 열량소비 및 축적에 관한 연구)

  • 오승호
    • Journal of Nutrition and Health
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    • v.22 no.1
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    • pp.1-8
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    • 1989
  • The study was attempted to observe effects of voluntary exercise on energy expenditure and on storage of excessive energy into body fat in adult mice. Mice, body weight 25-30g, were divided into two groups, exercise and sedentary group. Voluntary exercize by running wheel was allowed for former group but not for the mice of the latter group which were restricted by limiting space allowance 13.5$\times$11.5$\times$15.0cm per mouse. During a period of 4 weeks of feeding trial, they were fed ad libitum starch-casein based diet added with $^3\textrm{H}$-glucose (D-[1-$^3\textrm{H}$(N)]-glucose) at a level of 20 nCi per g of diet. Measurements were made to study hematology, lipase activity in epididymal adipose tissue, total contents of body waste and fat, and radiactivity of $^3\textrm{H}$-glucose incoporated into body fat. Dietary intake, body weight gain and amount of voluntary physical activities were also measured. The results obtained ard summarized as follows; 1) Amount of metabolizable energy intake, body weight gain and body fat were not statistically different between the two group. However, mice of the exercise group tended to show lower body weight gain body fat contants, but higher energy expenditure than those of the sedentary group. 2) Radioactivity of $^3\textrm{H}$-glucose incoporated into body fat appeared lower for exercise group expressd on a whole body fat basis. The activity was, however, higher for exercise group when expressed based on per g of fat compared to that of sedentary group. 3) Exercise group showed also higher activity of lipase in epididymal adipose tissue than the other group. 4) Mice whose physical activities were restricted appeared to have lower levels of hemoglobin and hematocrit values than of the exercise group. These results seem to support the theory that turn-over rate of body fat is activated by exercise and to suggest that consumed energy is to be converted primarily into body fat before its use as energy source by oxidation even during a period of continuous energy expenditure by exercise.

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Characteristics of electrically conductive adhesives filled with silver-coated copper

  • Nishikawa, Hiroshi;Terad, Nobuto;Miyake, Koich;Aoki, Akira;Takemoto, Tadashi
    • Proceedings of the KWS Conference
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    • 2009.11a
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    • pp.217-220
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    • 2009
  • Conductive adhesives have been investigated for use in microelectronics packaging as a lead-free solder substitute due to their advantages, such as low bonding temperature. However, high resistivity and poor mechanical behavior may be the limiting factors for the development of conductive adhesives. The metal fillers and the polymer resins provide electrical and mechanical interconnections between surface mount device components and a substrate. As metal fillers used in conductive adhesives, silver is the most commonly used due to its high conductivity and the stability. However the cost of conductive adhesives with silver fillers is much higher than usual lead-free solders and silver has poor electro-migration performance. So, copper can be a promising candidate for conductive filler metal due to its low resistivity and low cost, but oxidation causes this metal to lose its conductivity. In this study, electrically conductive adhesives (ECAs) using surface modified copper fillers were developed. Especially, in order to overcome the problem associated with the oxidation of copper, copper particles were coated with silver, and the silver-coated copper was tested as a filler metal. Especially the effect of silver coating on the electrical resistance just after curing and after aging was investigated. As a result, it was found that the electrical resistance of ECA with silver-coated copper filler was clearly lower and more stable than that of ECA with pure copper filler after curing process. And, during high temperature storage test, the degradation rate of electrical resistance for ECA with silver coated copper filler was quite slower than that for ECA with pure copper filler.

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Administration of antibiotics contributes to cholestasis in pediatric patients with intestinal failure via the alteration of FXR signaling

  • Xiao, Yongtao;Zhou, Kejun;Lu, Ying;Yan, Weihui;Cai, Wei;Wang, Ying
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.14.1-14.14
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    • 2018
  • The link between antibiotic treatment and IF-associated liver disease (IFALD) is unclear. Here, we study the effect of antibiotic treatment on bile acid (BA) metabolism and investigate the involved mechanisms. The results showed that pediatric IF patients with cholestasis had a significantly lower abundance of BA-biotransforming bacteria than patients without cholestasis. In addition, the BA composition was altered in the serum, feces, and liver of pediatric IF patients with cholestasis, as reflected by the increased proportion of primary BAs. In the ileum, farnesoid X receptor (FXR) expression was reduced in patients with cholestasis. Correspondingly, the serum FGF19 levels decreased significantly in patients with cholestasis. In the liver, the expression of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1), increased noticeably in IF patients with cholestasis. In mice, we showed that oral antibiotics (gentamicin, GM or vancomycin, VCM) reduced colonic microbial diversity, with a decrease in both Gram-negative bacteria (GM affected Eubacterium and Bacteroides) and Gram-positive bacteria (VCM affected Clostridium, Bifidobacterium and Lactobacillus). Concomitantly, treatment with GM or VCM decreased secondary BAs in the colonic contents, with a simultaneous increase in primary BAs in plasma. Moreover, the changes in the colonic BA profile especially that of tauro-beta-muricholic acid ($T{\beta}MCA$), were predominantly associated with the inhibition of the FXR and further altered BA synthesis and transport. In conclusion, the administration of antibiotics significantly decreased the intestinal microbiota diversity and subsequently altered the BA composition. The alterations in BA composition contributed to cholestasis in IF patients by regulating FXR signaling.

Active Reaction Sites and Oxygen Reduction Kinetics on $La_1_{-x}Sr_xMnO_{3+\delta}$(x=0.1-0.4)/YSZ (Yttria-Stabilized Zirconia) Electrodes for Solid Oxide Fuel Cells

  • Lee, Hee Y.;Cho, Woo S.;오승모
    • Bulletin of the Korean Chemical Society
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    • v.19 no.6
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    • pp.661-666
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    • 1998
  • Active reaction sites and electrochemical O2 reduction kinetics on La_{1-x}Sr_xMnO_{3+{\delta}} (x=0.1-0.4)/YSZ (yttria-stabilized zirconia) electrodes are investigated in the temperature range of 700-900 ℃ at $Po_2=10^{-3}$-0.21 atm. Results of the steady-state polarization measurements, which are formulated into the Butler-Volmer formalism to extract transfer coefficient values, lead us to conclude that the two-electron charge transfer step to atomically adsorbed oxygen is rate-limiting. The same conclusion is drawn from the $Po_2$-dependent ac impedance measurements, where the exponent m in the relationship of $I_o$ (exchange current density) ∝ $P_{o_{2}}^m$ is analyzed. Chemical analysis is performed on the quenched Mn perovskites to estimate their oxygen stoichiometry factors (δ) at the operating temperature (700-900 ℃). Here, the observed δ turns out to become smaller as both the Sr-doping contents (x) and the measured temperature increase. A comparison between the 8 values and cathodic activity of Mn perovskites reveals that the cathodic transfer coefficients $({\alpha}_c)$ for oxygen reduction reaction are inversely proportional to δ whereas the anodic ones $({\alpha}_a)$ show the opposite trend, reflecting that the surface oxygen vacancies on Mn perovskites actively participate in the $O_2$ reduction reaction. Among the samples of x= 0.1-0.4, the manganite with x=0.4 exhibits the smallest 8 value (even negative), and consistently this electrode shows the highest ${\alpha}_c$ and the best cathodic activity for the oxygen reduction reaction.

The inhibitory effects of 3,4,5-Trimethoxy cinnamate thymol ester(TCTE, Melasolv$\circledR$) on Melanogenesis

  • Hwang, Jae-Sung;Hyunjung Shin;Noh, Ho-Sick;Park, Hyunjung;Ahn, Soo-mi;Park, Dong-Soon;Kim, Duck-Hee;Lee, Byeong-Gon;Ihseop Chang
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.28 no.1
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    • pp.135-149
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    • 2002
  • To date, research on the regulation of melanogenesis has focused on factors which affect tyrosinase, the rate-limiting enzyme in the melanogenic pathway, by searching for chemicals which competitively inhibit tyrosinase function. Many types of tyrosinase inhibitors have been developed, but no satisfactory results have been made clinically until now, To find a new whitening agent, which effectively inhibits melanogenesis, we synthesized several compounds and selected compounds by cell-based assay system. Finally, 3, 4, 5-trimethoxy cinnamaie thymol ester(TCTE, Melasolv) was selected and the effects of TCTE on melanogenesis were investigated. Treatment of mouse-derived melanocyte melan-a cells with TCTE results in a marked down-regulation of tyrosinase activity. 80% decrease of tyrosinase activity occurs with 30uM TCTE treatment for 72 hours without affecting cell growth. The inhibition of tyrosinase activity is dose-dependent and melanin content was also decreased to 40%. From the in vitro tyrosinase assay using cell extract, TCTE does not act as a direct inhibitor of the enzyme. Treatment of melan-a cultures with TCTE blocks the increase in tyrosinase activity by either forskolin, 3-isobutyl-1-methtyl-xanthine. TCTE decreased the expression of tyrosinase, TRP-1 without effects on TRP-2 protein expression through the down regulation of tyrosinase and TRP-1 mRNA. From the results of cAMP immunoassays, intracellular levels of the cyclin nucleotide are unaffected in cells treated with TCTE. The inhibitory effects of melanin synthesis were also shown in reconstitute human epidermis model by topical application. These findings suggest that TCTE can be used for studying the regulation of melanogenesis and depigmenting agent.

Improving Productivity of Pravastatin, HMG-CoA Reductase Inhibitor (HMG-CoA Reductase Inhibitor인 Pravastatin의 생산성 향상)

  • Jeon, Dong-Soo;Bai, Dong-Hoon
    • Food Engineering Progress
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    • v.13 no.4
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    • pp.243-250
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    • 2009
  • Pravastatin sodium, competitive inhibitors of HMG-CoA(3-hydroxy-3-methylglutaryl coenzyme A) reductase, is produced from the culture broth of Streptomyces carbophilus KCCM 10370, The production of Pravastatin sodium was increased about 45 fold compared to wild type by UV mutation. Production of Pravastatin was also improved by continuous feeding of Compactin sodium to 24% and bioconversion ratio was also increased to 4.3% by intermittent addition. In main culture, concentration of Compactin sodium was kept less than 0.1%(w/v) under continuous feeding of Compactin sodium then product was 0.49% and bioconversion was 70%. After finishing the fermentation, Pravastatin was purified by various chromatographies such as Diaion HP20 resin column, Partition, and ODS(Octa-Decylsilyl Silicagel) resin column with a final yield of 70~72% and over 99.7% purity. The IR, UV, and NMR study of the purified Pravastatin sodium showed the same pattern as that of EP(European Pharmacopoeia).