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Nitric Oxide-cGMP-Protein Kinase G Pathway Contributes to Cardioprotective Effects of ATP-Sensitive $K^+$ Channels in Rat Hearts

  • Cuong, Cang Van;Kim, Na-Ri;Cho, Hee-Cheol;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.2
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    • pp.95-100
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    • 2004
  • Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium $(K_{ATP})$ channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that $K_{ATP}$ channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide $(100\;{\mu}M)$, SNAP $(300\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) $(100\;{\mu}M)$ followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide $(50\;{\mu}M)$, 5-hydroxydecanoate (5-HD) $(100\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) $(100\;{\mu}M)$. These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of $K_{ATP}$ channels in rat ventricular myocytes.

Photoproduction of Hydrogen from Acetate by Rhodopseudomonas: Effect of Culture Conditions and Sequential Dark/Light Fermentation

  • Oh, You-Kwan;Seol, Eun-Hee;Park, Sung-Hoon
    • 한국생물공학회:학술대회논문집
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    • 2003.10a
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    • pp.422-427
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    • 2003
  • Rhodopseudomonas palustris P4 can produce $H_2$ either from CO by water-gas shift reaction or from various sugars by anaerobic fermentation. Fermentative $H_2$ production by P4 is fast, but its yield is relatively low due to the formation of various organic acids. In order to increase $H_2$ production yield from glucose, P4 was investigated for the photo-fermentation of acetate which is a major by-product of fermentative $H_2$ production. Experiments were performed in batch modes using both light-grown and dark-grown cells. When the dark-grown P4 was challenged with light and acetate, $H_2$ was produced with the consumption of acetate after a lag period of 25 h. $H_2$ production was inhibited when a nitrogen source, especially ammonium, is present. When the dark-fermentation broth containing acetate was adopted for photo-fermentation with light-grown cells, $H_2$ production and concomitant acetate consumption occurred without a lag period. The $H_2$ yield was estimated as 2.4 - 2.8 mol $H_2/mol$ acetate and the specific $H_2$ production rate was as 9.8 ml $H_2/g$ cell${\cdot}$h, The fact that a single strain can perform both dark- and light-fermentation gives a great advantage in process development Compared to a one-step dark-fermentation, the combined dark- and light-fermentation can increase the $H_2$ production yield on glucose by two-fold.

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Modulation of Biotransformation Enzymes by Phytochemicals: Impact of Genotypes

  • Lampe Johanna W.
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2004.11a
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    • pp.65-70
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    • 2004
  • Modulation of biotransformation enzymes is one mechanism by which a diet high in fruits and vegetable may influence cancer risk. Inhibition of cytochrome P450s (CYP) and concomitant induction of conjugating enzymes are hypothesized to reduce the impact of carcinogens in humans. Thus, exposure to types and amounts of phytochemicals may influence disease risk. Like other xenobiotics, many classes of phytochemicals are rapodly conjugated with glutathione, glucuronide, and sulfate moieties and excreted in urine and bile. In humans, circulating phytochemical levels very widely among individuals even in response to controlled dietary interventions. Polymorphisms in biotransformation enzymes, such as the glutathione S-transferases (GST), UDP-glucuronosyltransferases (UGT), and sulfotransferases (SULT), may ocntribute to the variability in phytochemical clearance and efficacy; polymorphic enzymes with lower enzyme activity prolong the half-lives of phytochmicals in vivo. Isothiocyanates (ITC) in cruciferous vegetables are catalyzed by the four major human GSTs: however reaction velocities of the enzymes differ greatly. In some observational studies of cancer, polymorphisms in the GSTMI and GSTTI genes that result in complete lack of GSTM1-1 protein, respectively, confer greater protection from cruciferous vegetable in individuals with these genotypes. Similarly, we have shown in a controlled dietary trial that levels of GST-alpha-induced by ITC-are higher in GSTMI-null individuals exposed to cruciferous vegetablse. The selectivity of glucuronosyl conjugation of flavonoids is dependent both on flavonoid structure as well as on the UGI isozyme involved in its conjuagtion. The effects of UGI polymorphisms on flavonoid clearnace have not been examind; but polymorphisms affect glucuronidation of several drugs. Given the strong interest in the chemopreventive effects of flavonoids, systematic evaluation of these polymorphic UGTs and flavonoid pharmacokinetics are warranted. Overall, these studies suggest that for phytochemicals that are metabolized by, and affect activity of, biotransformation enzymes, interactions between genetic polymorphisms in the enzymes and intake of the compounds should be considered in studies of cancer risk. Genetic polymorphisms in biotransformation enzymes may account in prat for individual variation in metabolism of a wide range of phytochemicals and their ultimate impact on health.

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Feasibility of New Pesticide Development in Korea (우리나라에서의 신농약 개발전망)

  • Park Young-Sun
    • Korean journal of applied entomology
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    • v.22 no.2 s.55
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    • pp.84-97
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    • 1983
  • Under the limited arable land, the enhancement of agricultural productivity is indispensable to provide the food demand which is concomitant with the rapid increase in population. From this viewpoint, the upbringing and dissemination of high-yielding varieties has been promoted continuously and several modifications in cultural practices, including heavy fertilization, dense planting, and early transplanting, also have been gradually developed. However these changes in cultivation have led to the increased outbreak of insect pests and diseases. And this unexpected results have accelerated the number and complexity of pesticides employed as well as their consumption. Even though pesticides are essential materials contributing to the steady production of agricultural crops, large scale consumption of them has given rise to several adverse impacts, such as mammalian hazard and/or environmental contamination. In this respect, recent development of new pesticides has been concentrated on 'safe pesticide', as it were, that has the highly selective properties without unfavorable side influences on other ecosystem. According to literature cited up to now, feasibilities of safe pesticide development would be summarized as two categories. One of them is the development of chemical pesticides, which include the molecular structure modification of established pesticides for increased safety and synthesis of new safe chemicals which can attack the vulnerable point of physio-ecological characteristics in insect pests and diseases. The other is the biological pesticides which comprise natural enemies and microorganisms to act selectively on confined insect pests and diseases, In addition, improvement of physico-chemical properties of available pesticide formulations would be one of the desirable means for safe pesticide development in view of efficacy enhancement and minimization of hazardous properties or safe pesticide development, various approaches are feasible and needed to study, however, long period and much financial outlay are necessary to develop a new item. And under the present situation in Korea, there are many difficulties for performing research on all the possible routes. Therefore, combined pesticides by the reasonable combination of already registered resticides evaluated as the fairly safe pesticides and safe formulation based on their physico-chemical properties would be developed primarily. And many efforts would be given gradually for the development of new chemical and biological pesticides.

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Simultaneous gap arthroplasty and intraoral distraction and secondary contouring surgery for unilateral temporomandibular joint ankylosis

  • Sharma, Aditi;Paeng, Jun-Young;Yamada, Tomohiro;Kwon, Tae-Geon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.38
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    • pp.12.1-12.6
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    • 2016
  • Background: Temporomandibular joint (TMJ) ankylosis can be accompanied by various degrees of functional and esthetic problems. Adequate mouth opening, occlusal stability, and harmonious facial form are the main goals of treatment for ankylosis. Distraction osteogenesis has proven to be an excellent treatment for lengthening the ramus-condyle unit. However, various timings for distraction have been suggested, and there is no consensus on selection criteria for performing the procedure in stages or simultaneously with other treatments. Case presentation: In this case report, concomitant intraoral distraction and gap arthroplasty was planned to treat TMJ ankylosis and associated facial asymmetry. After gap arthroplasty and 23 mm of distraction, the ramus-condyle segment was successfully lengthened and mouth opening range was significantly increased. The resultant interocclusal space was stably maintained with an occlusal splint for 4 months after distraction. Finally, good occlusion was achieved after prosthetic treatment. The remaining mandibular asymmetry was corrected with osseous contouring and augmentation surgery. The mouth-opening range was maintained at 35 mm 24 months after treatment. Conclusion: Gap arthroplasty with intraoral distraction as a one-stage treatment and subsequent contouring surgery can be applied to correct ankylosis with moderate malocclusion and facial asymmetry.

Analysis of Antipsychotic Induced Concomitant Prescribing of Antiparkinson Agents in Korea (항정신병약물 사용으로 인한 항파킨슨제 병용 현황 연구)

  • Park, So-Huon;Lee, Yu-Jeung
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.2
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    • pp.137-142
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    • 2012
  • Background & Purpose: It is well known that Extrapyramidal symptoms (EPS) is induced by atypical antipsychotic agents less frequently than by typical antipsychotic agents. The purpose of this study was to evaluate differences in rates of the use of antiparkinson agent, most commonly prescribed for the management of EPS, between patients with atypical agents and those with typical agents. Methods: This cross-sectional study was conducted in a retrospective way with the Electronic Medical Record (EMR) of the 312 patients for whom the Antipsychotics were prescribed by the Psychiatry Department of the Inje University Ilsan Paik Hospital, from January of 2005 to February of 2011. They received either typical agents (N=15) or atypical agents (N=297) and those 2 groups were compared in terms of antiparkinson agent use. Also, we assessed the difference between individual atypical antipsychotic agents regarding antiparkinson agent use. Results: There was no significant difference in the rates of antiparkinson agent use between the two groups (the typical agent 13.33% vs. the atypical agent 9.76%, p = 0.6512). Meanwhile, the rates of antiparkinson agent use with aripiprazole versus quetiapine (aripirazole 25% vs. quetiapine 3.57%, p = 0.003) were significantly different, Also the rates of antiparkinson agent use with aripiprazole versus risperidone (aripiprazole 25% vs. risperidone 9.52%, p = 0.0216) had a statistical meaning. Conclusions: There was no significant difference in the rates of antiparkinson agent use between patients with atypical agents and those with typical agents. However the rate of antiparkinson agent use was significantly lower with aripiprazole compared with quetiapine or risperidone.

MAXILLARY MOLAR DISTALIZATION AND PREMOLAR ALIGNMENT WITH A JONES JIG APPLIANCE: CASE REPORTS (Jones jig 장치를 이용한 상악 대구치 원심이동 및 소구치 배열의 증례 보고)

  • Jeon, Eun-Kyung;Hyun, Hong-Keun;Kim, Young-Jae;Kim, Jung-Wook;Jang, Ki-Taeg;Kim, Chong-Chul;Hahn, Se-Hyun;Lee, Sang-Hoon
    • Journal of the korean academy of Pediatric Dentistry
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    • v.37 no.4
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    • pp.497-504
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    • 2010
  • The treatment of Class II non-extraction cases, especially when premolar space is lost due to premature loss of the deciduous molars, usually requires distal movement of the maxillary molars. The Jones jig appliance is a non-compliant intraoral appliance and is effective for the distalization of the maxillary molars. It has unfavorable side-effects, however, so caution is needed to adjust the appliance and select appropriate cases. We reported four cases in which maxillary molar distalizations were concomitant with the alignment of palatally erupted premolars.

Post-cancer treatment of Condurango 30C, traditionally used in homeopathy, ameliorates tissue damage and stimulates reactive oxygen species in benzo[a]pyrene-induced lung cancer of rat

  • Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • CELLMED
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    • v.3 no.3
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    • pp.25.1-25.8
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    • 2013
  • Homoeopathically prepared Condurango 30C is traditionally used in amelioration of certain types of cancer by homeopathic practitioners. In this study, ability of Condurango 30C in amelioration of the conventional benzo[a]pyrene (BaP)-induced lung cancer in rat has been tested. After one month of scheduled oral feeding of BaP, lung cancer is routinely developed after four months in rats. Tumorbearing rats were then treated with Condurango 30C for the next one ($5^{th}$), two ($6^{th}$) and three ($7^{th}$) months, respectively, and sacrificed. Efficacy of post-cancer treatment by Condurango 30C was evaluated against controls (placebo) by different study parameters like: body and lung weights, number and diameter of lung tumour nodules, lung architecture, DNA damage, anti-oxidant activity and reactive oxygen species (ROS) accumulation. Administration of this homeopathic remedy caused increase of body weight and decrease of lung weight, decrease in number and diameter of lung tumour nodules, particularly after one and two months of drug treatment. BaP intoxication significantly increased lipid peroxidase (LPO) with concomitant decrease in activities of different antioxidants, while Condurango 30C administration certainly reduce their levels than normal and cancerous groups, notably after one and two months' of drug treatment. Condurango 30C showed capability to induce ROS-mediated cell death evidenced from the study of ROS activities at different time-points. Further, the remedy possibly achieved its anticancer goal through mediation of DNA-nicks that possibly led cancer cells to the apoptotic pathway. Thus, Condurango 30C has anticancer potential in BaP-induced lung cancer of rats via tissue damage recovery and ROS-mediated programmed cell death.

Anomalous Behavior of the Ethyl Group in the Aminolysis of S-Phenyl Acetate with Benzylamine in Acetonitrile

  • Lee, Ik-Choon;Lee, Hai-Whang;Lee, Byung-Choon;Choi, Jin-Heui
    • Bulletin of the Korean Chemical Society
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    • v.23 no.2
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    • pp.201-204
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    • 2002
  • The rates of the aminolysis of S-phenyl substituted-acetate series $(RC(=O)SC_6H_4Z$, with R=Me, Et, i-Pr, t-Bu and Bn) with benzylamines $(XC_6H_4CH_2NH_2)$ are not correlated simply with the Taft's polar $({\sigma}^{\ast})$ and/or steric effect constants $(E_s)$ of the substituents due to abnormally enhanced rate of the substrate with R=Et. Furthermore, the cross-interaction constant, ${\rho}x_z$ , is the largest with R=Et. These anomalous behaviors can only be explained by invoking the vicinal bond $({\sigma})$-antibond $({\sigma}^{\ast})$ charge transfer interaction between C-$C{\alpha}$ and C-S bonds. In the tetrahedral zwitterionic intermediate, $T^{\pm}$ , formed with R=Et the vicinal ${\sigma}_{c-c}-{\sigma}^{\ast}_{c-s}$ delocalization is the strongest with an optimum antiperiplanar arrangement and a narrow energy gap, ${\Delta}{\varepsilon}={\varepsilon}_{{\sigma}^{\ast}}-{\varepsilon}_{\sigma}$. Due to this charge transfer interaction, the stability of the intermediate increases (with the concomitant increase in the equilibrium constant K (= $k_a/k_{-a}$)) and also the leaving ability of the thiophenolate leaving group increases (and hence $k_b$ increases) so that the overall rate, $k_n\;=\;Kk_b$, is strongly enhanced. Theoretical support is provided by the natural bond orbital (NBO) analyses at the B3LYP/6-31+$G^{\ast}$ level. The anomaly exhibited by R=Et attests to the stepwise reaction mechanism in which the leaving group departure is rate limiting.

Chemical Modification of Bovine Brain Succinic Semialdehyde Reductase by Diethylpyrocarbonate

  • Lee, Byung-Ryong;Jeon, Seong-Gyu;Bahn, Jae-Hoon;Choi, Kyung-Soon;Yoon, Byung-Hak;Ahn, Yoon-Kyung;Choi, Eun-A;Lee, Kil-Soo;Cho, Sung-Woo;Choi, Soo-Young
    • BMB Reports
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    • v.32 no.3
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    • pp.254-258
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    • 1999
  • The NADPH-dependent succinic semialdehyde reductase is one of the key enzymes in the brain GABA shunt, and it catalyzes the formation of the neuromodulator $\gamma$-hydroxybutyrate from succinic semi aldehyde. This enzyme was inactivated by diethylpyrocarbonate (DEP) with the second-order rate constant of $1.1{\times}10^3\;M^{-1}min^{-1}$ at pH 7.0, $25^{\circ}C$, showing a concomitant increase in absorbance at 242 nm due to the formation of N-carbethoxyhistidyl derivatives. Complete inactivation of succinic semialdehyde reductase required the modification of five histidyl residues per molecule of enzyme. However, only one residue was calculated to be essential for enzyme activity by a statistical analysis of the residual enzyme activity. The inactivation of the enzyme by DEP was prevented by preincubation of the enzyme with the coenzyme NADPH but not with the substrate succinic semialdehyde. These results suggest that an essential histidyl residue involved in the catalytic activity is located at or near the coenzyme binding site of the brain succinic semialdehyde reductase.

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