Effects of the novel angiotensin II receptor type I antagonist, fimasartan on myocardial ischemia/reperfusion injury

Han, J.,Park, S.J.,Thu, V.T.,Lee, S.R.,Long, L.T.,Kim, H.K.,Kim, N.,Park, S.W.,Jeon, E.S.,Kim, E.J.,Yoon, C.H.,Cho, G.Y.,Choi, D.J. Elsevier/North-Holland Biomedical Press 2013 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.168 No.3

Background: The aim of this study was to investigate the cardioprotective effect of fimasartan, a newly developed angiotensin II receptor type I blocker (ARB), against myocardial ischemia/reperfusion (I/R) injury and to identify the mechanism by which it reduces mitochondrial damage. Methods: Fimasartan was administered intravenously to Sprague-Dawley rats (3mg/kg), cardiomyocytes (50μM), and H9c2 cells (50μM) before ischemia or hypoxia. Myocardial infarction (MI), echocardiograms, DNA fragmentation, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick-end labeling, immunoblotting, oxygen consumption, confocal microscopic appearance, and L-type Ca<SUP>2+</SUP> current (I<SUB>Ca,L</SUB>) were then assessed. Results: Fimasartan pretreatment remarkably reduced the rate of MI and improved cardiac performance well after I/R (n=9/group). Fimasartan also reduced apoptotic cell death both in vivo and in hypoxia/reoxygenation (H/R)-treated H9c2 cells (n=5~8/group). H/R-induced mitochondrial O<SUB>2</SUB><SUP>-</SUP> production and collapse of membrane potential were markedly attenuated in fimasartan-treated cardiomyocytes (n=4~6/group). Additionally, mitochondrial Ca<SUP>2+</SUP> overload during reoxygenation was suppressed by fimasartan (n=4~6/group), and this was found to be possibly related to the inhibition of I<SUB>Ca,L</SUB> and mitochondrial Ca<SUP>2+</SUP> uniporter. Furthermore, fimasartan pretreatment increased phosphorylations of Akt and glycogen synthase kinase-3β (n=5~7/group), decreased pro-apoptotic p53 levels, and increased anti-apoptotic Bcl-2 levels (n=4) during reperfusion. Conclusions: Fimasartan preconditioning has the potential to modulate Bcl-2 and suppress I/R-induced Ca<SUP>2+</SUP> overload by inhibiting I<SUB>Ca,L</SUB> and MCU. These beneficial effects could prevent the mitochondrial dysfunction and apoptosis accompanied by I/R.

Flowering time quantitative trait Loci analysis of oilseed brassica in multiple environments and genomewide alignment with Arabidopsis.

Long, Y,Shi, J,Qiu, D,Li, R,Zhang, C,Wang, J,Hou, J,Zhao, J,Shi, L,Park, Beom-Seok,Choi, S R,Lim, Y P,Meng, J Genetics Society of America [etc.] 2007 Genetics Vol.177 No.4

<P>Most agronomical traits exhibit quantitative variation, which is controlled by multiple genes and are environmentally dependent. To study the genetic variation of flowering time in Brassica napus, a DH population and its derived reconstructed F(2) population were planted in 11 field environments. The flowering time varied greatly with environments; 60% of the phenotypic variation was attributed to genetic effects. Five to 18 QTL at a statistically significant level (SL-QTL) were detected in each environment and, on average, two new SL-QTL were discovered with each added environment. Another type of QTL, micro-real QTL (MR-QTL), was detected repeatedly from at least 2 of the 11 environments; resulting in a total of 36 SL-QTL and 6 MR-QTL. Sixty-three interacting pairs of loci were found; 50% of them were involved in QTL. Hundreds of floral transition genes in Arabidopsis were aligned with the linkage map of B. napus by in silico mapping; 28% of them aligned with QTL regions and 9% were consistent with interacting loci. One locus, BnFLC10, in N10 and a QTL cluster in N16 were specific to spring- and winter-cropped environments respectively. The number of QTL, interacting loci, and aligned functional genes revealed a complex genetic network controlling flowering time in B. napus.</P>

Do Opioid Receptors Play a Role in Blood Pressure Regulation?

Rhee, H.M.,Holaday, J.W.,Long, J.B.,Gaumann, M.D.,Yaksh, T.L.,Tyce, G.M.,Dixon, W.R.,Chang, A.P.,Mastrianni, J.A.,Mosqueda-Garcia, R.,Kunos, G. The Korean Society of Pharmacology 1988 대한약리학잡지 Vol.24 No.2

The potential role of endogenous opioid peptides (EOPS) in cardiovascular regulation has only recently been entertained. EOPS have been localized in brain, spinal cord, autonomic ganglia, particularly the adrenal gland, and many other peripheral tissues. There are at least five major types of opioid receptors; namely ${\mu},\;{\delta},\;k,\;{\sigma},\;and\;{\varepsilon}$ and Experimental evidence indicates that cardiovascular actions of the peptide are mediated primarily by ${\mu},\;{\delta}$ and k receptors, and that these receptor types may be allosterically coupled. In anesthetized rabbits met-enkephalin decreased blood pressure and heart rate, which closely paralleled a reduction in sympathetic discharge. Naloxone, but not naloxone methobromide, antagonized these effects, which suggests a central site of action of met-enkephalin. A number of autonomic agents, particularly adrenergic ${\alpha}$-and, ${\beta}-agonists$ and antagonists modify the cardiovascular actions of met-enkephalin. Experiments in reserpine-treated and adrenalectomized rats provide no evidence of sympathetic nervous system involvement in the pressor responses to intravenous injection of opioid peptides, but rather suggest a direct peripheral action. Finally, activation of a beta-endorphinergic pathway projecting from the arcuate nucleus to the nucleus tractos solitarii in rats can cause naloxone reversible hypotension and bradycardia. There is evidence to implicate this pathway in antihypertensive drug action and in the modulation of baroreflex activity.

제3발표장 : 생물공정공학 분야 ; 전분을 이용한 Cycloamylose 생산수율에 Debranching 효소가 미치는 영향

추선 ( S Chu ),Longsolida ( Long Solida ),노신정 ( S J Rho ),김용노 ( Y R Kim ) 한국농업기계학회 2013 한국농업기계학회 학술발표논문집 Vol.18 No.1

Isoamylase를 이용한 전분의 탈분지 반응은 전분 농도 5%내에서 8 시간 이내에 완결되었음을 확인했으며, 효소 농도에 다른 반응 시간의 영향도 관찰할 수 있었다. 또한 탈분지에 의해 CA생산 수율이 획기적으로 향상했음을 확인했으며, 전분의 아밀로스 함량에 따란 생산 수율이 영향을 받을 수 있음을 관찰했다. 본 결과는 탈분지 효소와 4-a-glucanotransferase 복합처리를 통해 저단가, 고수율 CA 생산 공정 개발이 가능함을 시사한다.

Conjugated Linoleic Acid in Rumen Fluid and Milk Fat, and Methane Emission of Lactating Goats Fed a Soybean Oil-based Diet Supplemented with Sodium Bicarbonate and Monensin

Li, X.Z.,Yan, C.G.,Long, R.J.,Jin, G.L.,Shine Khuu, J.,Ji, B.J.,Choi, S.H.,Lee, H.G.,Song, Man K. Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.11

A metabolic study was conducted with four ruminally-cannulated lactating goats (Saanen, 29 weeks lactation, 65${\pm}$5 kg) in a 4${\times}$4 Latin square design with 4 dietary treatments. The goats were fed a basal mixed diet consisting of 80% concentrate and 20% chopped rye grass hay (DM basis, CON). The goats were also fed the CON diet supplemented with soybean oil at a 5% level of the concentrate (SO), the SO diet supplemented with 0.5% of sodium bicarbonate (SO-B) or the SO-B diet supplemented with 30 ppm monensin (SO-BM). The goats were housed in individual pen and the study was conducted for 8 weeks. An increased molar proportion of propionate (C3) was observed at 1 h (p<0.003) and 6 h (p<0.029) post-feeding from all the supplemented diets. Calculated methane emission was markedly decreased prior to morning feeding (p<0.01), and at 1 h (p<0.05) and 6 h post-feeding (p<0.05) in goats fed the supplemented diets. All the supplements increased (p<0.0001) cis9, trans11-CLA content in rumen fluid. Concentrations of both cis9, trans11-CLA (p<0.0001) and trans10, cis12-CLA (p<0.026) were also increased in the milk fat of lactating goats fed the supplemented diets. The SO-B and SO-BM diets further increased CLA content in goat milk compared to the SO diet. All supplements increased unsaturated (UFA, p<0.002), monounsaturated (MUFA, p<0.002) and polyunsaturated fatty acids (p<0.014) and reduced SFA to UFA ratio (p<0.023). The concentration of MUFA was even greater (p<0.002) for SO-BM than for the SO-B diet. In conclusion, feeding soybean oil (5% of concentrate) to lactating goats was a useful way to improve milk fat and to improve fatty acid profile in the milk by increasing potentially healthy fatty acids such as CLA. Supplementation of sodium bicarbonate or sodium bicarbonate with monensin to the soybean oil-based diet increased CLA content further in goat milk. Supplementation of soybean oil may be an effective method to reduce methane emission in lactating goats.

A Rotating Flux Pump Employing a Magnetic Circuit and a Stabilized Coated Conductor HTS Stator

Z. Jiang,C. W. Bumby,R. A. Badcock,N. J. Long,H. J. Sung,M. Park 한국자기학회 2016 Journal of Magnetics Vol.21 No.2

High temperature superconductor (HTS) magnet systems usually employ metal current leads which bridge between the cryogenic environment and room temperature. Such current leads are the dominant heat load for these magnet systems due to a combination of electrical resistance and heat conduction. HTS flux pumps enable large currents to be injected into a HTS magnet circuit without this heat load. We present results from an axialtype HTS mechanically rotating flux pump which employs a ferromagnetic circuit and a Cu-stabilized coated conductor (CC) HTS stator. We show the device can be described by a simple circuit model which was previously used to describe barrel-type flux pumps, where the model comprises an internal resistance due to dynamic resistance and a DC voltage source. Unlike previously reported devices, we show the internal resistance and DC voltage in the flux pump are not exactly proportional to frequency, and we ascribe this to the presence of eddy currents. We also show that this axial-type flux pump has superior current injection capability over barrel-type flux pumps which do not incorporate a magnetic circuit.

Effects of Addition Level and Chemical Type of Propionate Precursors in Dicarboxylic Acid Pathway on Fermentation Characteristics and Methane Production by Rumen Microbes In vitro

Li, X.Z.,Yan, C.G.,Choi, S.H.,Long, R.J.,Jin, G.L.,Song, Man K. Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.1

Two in vitro experiments were conducted to examine the effects of propionate precursors in the dicarboxylic acid pathway on ruminal fermentatation characteristics, $CH_4$ production and degradation of feed by rumen microbes. Fumarate or malate as sodium salts (Exp. 1) or acid type (Exp. 2) were added to the culture solution (150 ml, 50% strained rumen fluid and 50% artificial saliva) to achieve final concentrations of 0, 8, 16 and 24 mM, and incubated anaerobically for 0, 1, 3, 6, 9 and 12 h at $39^{\circ}C$. For both experiments, two grams of feed consisting of 70% concentrate and 30% ground alfalfa (DM basis) were prepared in a nylon bag, and were placed in a bottle containing the culture solution. Addition of fumarate or malate in both sodium salt and acid form increased (p<0.0001) pH of culture solution at 3, 6, 9 and 12 h incubations. The pH (p<0.0001) and total volatile fatty acids (VFA, p<0.05) were enhanced by these precursors as sodium salt at 3, 6 and 9 h incubations, and pH (p<0.001) and total VFA (p<0.01) from fumarate or malate in acid form were enhanced at a late stage of fermentation (9 h and 12 h) as the addition level increased. pH was higher (p<0.001) for fumarate than for malate as sodium salt at 3 h and 6 h incubations. Propionate ($C_3$) proportion was increased (p<0.0001) but those of $C_2$ (p<0.05) and $C_4$ (p<0.01 - p<0.001) were reduced by the addition of sodium salt precursors from 3 h to 12 incubation times while both precursors in acid form enhanced (p<0.011 - p<0.0001) proportion of $C_3$ from 6h but reduced (p<0.018 - p<0.0005) $C_4$ proportion at incubation times of 1, 3, 9 and 12 h. Proportion of $C_3$ was increased (p<0.05 - p<0.0001) at all incubation times by both precursors as sodium salt while that of $C_3$ was increased (p<0.001) from 6h but $C_4$ proportion was decreased by both precursors in acid form as the addition level increased. Proportion of $C_3$ was higher (p<0.01 - p<0.001) for fumarate than malate as sodium salt from 6 h incubation but was higher for malate than fumarate in acid form at 9 h (p<0.05) and 12 h (p<0.01) incubation times. Increased levels (16 and 24 mM) of fumarate or malate as sodium salt (p<0.017) and both precursors in acid form (p<0.028) increased the total gas production, but no differences were found between precursors in both chemical types. Propionate precursors in both chemical types clearly reduced (p<0.0001 - p<0.0002) $CH_4$ production, and the reduction (p<0.001 - p<0.0001) was dose dependent as the addition level of precursors increased. The $CH_4$ generated was smaller (p<0.01 - p<0.0001) for fumarate than for malate in both chemical types. Addition of fumarate or malate as sodium type reduced (p<0.004) dry matter degradation while both precursors in both chemical types slightly increased neutral detergent fiber degradability of feed in the nylon bag.

Effects of fresh and aged traffic-related particles on breathing pattern, cellular responses, and oxidative stress

Diaz, E. A.,Chung, Y.,Lamoureux, D. P.,Papapostolou, V.,Lawrence, J.,Long, M. S.,Mazzaro, V.,Buonfiglio, H.,Sato, R.,Koutrakis, P. Springer Science + Business Media 2013 AIR QUALITY ATMOSPHERE AND HEALTH Vol.6 No.2

Linolenic Acid in Association with Malate or Fumarate Increased CLA Production and Reduced Methane Generation by Rumen Microbes

Li, X.Z.,Choi, S.H.,Jin, G.L.,Yan, C.G.,Long, R.J.,Liang, C.Y.,Song, Man K. Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.6

An in vitro study was conducted to investigate the effect of malate or fumarate on fermentation characteristics, and production of conjugated linoleic acid (CLA) and methane ($CH_4$) by rumen microbes when incubated with linolenic acid (${\alpha}-C_{18:3}$). Sixty milligrams of ${\alpha}-C_{18:3}$ alone (LNA), or ${\alpha}-C_{18:3}$ with 24 mM malic acid (M-LNA) or ${\alpha}-C_{18:3}$ with 24 mM fumaric acid (F-LNA) were added to the 150 ml culture solution consisting of 75 ml strained rumen fluid and 75ml McDougall's artificial saliva. Culture solution for incubation was also made without malate, fumarate and ${\alpha}-C_{18:3}$ (Control). Two grams of feed consisting of 70% concentrate and 30% ground alfalfa (DM basis) were also added to the culture solution of each treatment. In vitro incubation was made anaerobically in a shaking incubator up to 12 h at $39^{\circ}C$. Supplementation of malate (M-LNA) or fumarate (F-LNA) increased pH at 6 h (p<0.01) and 12 h (p<0.001) incubation times compared to control and linolenic acid (LNA) treatments. Both malate and fumarate did not influence the ammonia-N concentration. Concentration of total VFA in culture solution was higher for M-LNA and F-LNA supplementation than for control and LNA treatments from 6 h (p<0.040) to 12 h (p<0.027) incubation times, but was not different between malate and fumarate for all incubation times. Molar proportion of $C_3$ was increased by F-LNA and M-LNA supplementation from 6 h (p<0.0001) to 12 h (p<0.004) incubation times compared to control and LNA treatments. No differences in $C_{3}$ proportion, however, were observed between M-LNA and F-LNA treatments. Accumulated total gas production for 12h incubation was increased (p<0.0002) by M-LNA or F-LNA compared to control or LNA treatment. Accumulated $CH_4$ production for 12 h incubation, however, was greatly reduced (p<0.0002) by supplementing malate or fumarate compared to the control, and its production from M-LNA or F-LNA treatment was smaller than that from LNA treatment. Methane production from LNA, M-LNA or F-LNA treatment was steadily lower (p<0.01 - p<0.001) from 3 h incubation time than that from the control, and was also lower for M-LNA or F-LNA treatment at incubation times of 6 h (p<0.01) and 9 h (p<0.001) than for LNA treatment. Methane production from LNA, however, was reduced (p<0.01 - p<0.001) from 3 h to 9 h incubation times compared to the control. Both malate and fumarate increased concentration of trans11-$C_{18:1}$ from 3 h to 12 h incubation (p<0.01), cis9,trans11-CLA up to 6 h incubation (p<0.01 - p<0.01), trans10,cis12-CLA at 3 h (p<0.05) and 12 h (p<0.01), and total CLA for all incubation times (p<0.05) compared to corresponding values for the ${\alpha}-C_{18:3}$ supplemented treatment (LNA). In conclusion, malate and fumarate rechanneled the metabolic $H_2 pathway to production of propionate and CLA, and depressed the process of biohydrogenation and methane generation. Linolenic acid alone would also be one of the optimistic alternatives to suppress the $CH_4$ generation.