• Title/Summary/Keyword: CCB

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Celecoxib Enhances Susceptibility of Multidrug Resistant Cancer Cells to 17-Allylamino-17-demethoxy geldanamycin through Dual Induction of Apoptotic and Autophagic Cell Death (Celecoxib의 apoptotic 및 autophagic cell death 유도에 의한 항암제 다제내성 암세포의 17-allylamino-17-demethoxygeldanamycin 감수성 증강)

  • Moon, Hyun-Jung;Park, So-Young;Lee, Su-Hoon;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.28 no.7
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    • pp.778-785
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    • 2018
  • Autophagy is a complex signaling process and has been implicated in tumor suppression and anticancer therapy resistance. Autophagy can produce tumor-suppressive effect by inducing autophagic cell death, either in collaboration with apoptosis. In this current study, we found that celecoxib (CCB), a nonsteroidal anti-inflammatory drug (NSAID) with multifaceted effects, induced autophagy including enhanced LC3 conversion (LC3-I to LC3-II) and reduced autophagy substrate protein p62 level in multidrug-resistant (MDR) cancer cells. CCB sensitized human multidrug resistant (MDR) cancer cells to the ansamycin-based HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin, which causes the degradation of several oncogenic and signaling proteins, by inducing autophagic cell death and apoptosis. CCB significantly augmented 17-AAG-mediated level of LC3-II/LC-I, indicating the combined effect of 17-AAG and CCB on the induction of autophagy. Autophagic degradation of mutant p53 (mutp53) and activation of caspase-3 in 17-AAG-treated MDR cells were accelerated by CCB. Inhibition of caspase-3-mediated apoptotic pathway by Z-DEVD-FMK, a caspase-3 inhibitor, did not completely block CCB-induced cell death in MCF7-MDR cells. In addition, treatment of MDR cells with Z-DEVD-FMK failed to prevent activation of autophagy by combined treatment with 17-AAG and CCB. Based on our findings, the ability of clinically used drug CCB to induce autophagy has important implications for its development as a sensitizing agent in combination with Hsp90 inhibitor of MDR cancer.

Seismic fragility of a typical bridge using extrapolated experimental damage limit states

  • Liu, Yang;Paolacci, Fabrizio;Lu, Da-Gang
    • Earthquakes and Structures
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    • v.13 no.6
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    • pp.599-611
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    • 2017
  • This paper improves seismic fragility of a typical steel-concrete composite bridge with the deck-to-pier connection joint configuration at the concrete crossbeam (CCB). Based on the quasi-static test on a typical steel-concrete composite bridge model under the SEQBRI project, the damage states for both of the critical components, the CCB and the pier, are identified. The finite element model is developed, and calibrated using the experimental data to model the damage states of the CCB and the bridge pier as observed from the experiment of the test specimen. Then the component fragility curves for both of the CCB and the pier are derived and combined to develop the system fragility curves of the bridge. The uncertainty associated with the mean system fragility has been discussed and quantified. The study reveals that the CCB is more vulnerable than the pier for certain damage states and the typical steel-concrete composite bridge with CCB exhibits desirable seismic performance.

Effect of High Dose Insulin/Euglycemia Therapy for Acute Calcium Channel Blocker Intoxication: A Systematic Review (급성 칼슘통로차단제 중독에서 고용량 인슐린/정상혈당치료의 효과: 체계적 고찰)

  • Yang, Jinmo;Ko, Dong Ryul;Kong, Taeyoung;Joo, Young Seon;You, Je Sung;Chung, Sung Phil
    • Journal of The Korean Society of Clinical Toxicology
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    • v.13 no.2
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    • pp.103-110
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    • 2015
  • Purpose: The purpose of this study is to evaluate the effectiveness and the adverse events of high dose insulin/euglycemia therapy in acute calcium channel blocker (CCB) poisoning. Methods: We developed a systematic search strategy and applied it to 4 electronic reference databases. We searched medical journals as well as the bibliographies of relevant articles. All forms of literature relevant to human use of high dose insulin for acute CCB poisoning were included. The literature search was conducted by two investigators in August, 2015 with publication language restricted to English and Korean. Case reports were divided between CCB overdose alone and multi-drug overdose including CCB. The effect and adverse event of high dose insulin and clinical outcome of each case were analyzed. Results: Among 55 searched studies, 20 studies were included. A prospective study, a retrospective study, a systematic review study, and 17 case reports were identified. Case reports consisted of 11 CCB alone and 12 multidrug overdose cases including CCB. Although most cases described significant clinical improvements, one of them showed no beneficial effect. Several adverse events including hypoglycemia and hypokalemia were reported. No significant sequalae from adverse events was reported. Conclusion: Although there were many case reports demonstrating successful use of high dose insulin for CCB poisoning, the effect cannot be estimated due to a possibility of publication bias. Therefore, high dose insulin/euglycemia therapy might be considered adjunctive therapy in cases of CCB intoxication refractory for standard therapy.

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Treatments of Calcium Channel Blocker Overdose (칼슘통로차단제 중독의 치료)

  • Lee, Sung Woo
    • Journal of The Korean Society of Clinical Toxicology
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    • v.18 no.1
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    • pp.1-10
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    • 2020
  • Pharmaceutical agents are the most common causes of poisoning in Korea. Calcium channel blockers (CCBs) are commonly used in Korea for the management of hypertension and other cardiovascular diseases, but are associated with a risk of mortality due to overdose. Due to the frequent fatalities associated with CCB overdose, it is essential that the emergency physician is capable of identifying CCB intoxication, and has the knowledge to manage CCB overdose. This article reviews the existing clinical guidelines, retrospective studies, and systematic reviews on the emergency management of CCB overdose. The following are the varied treatments of CCB overdose currently administered. 1) For asymptomatic patients: observation with enough time and decontamination, if indicated. 2) For symptomatic patients: infusion of calcium salt, high dose insulin therapy, and vasopressor (norepinephrine) or atropine for bradycardia. 3) For patients refractory to the first line therapy or with refractory shock or impending arrest: lipid emulsion therapy and extracorporeal membrane oxygenation. 4) As adjunct therapy: phosphodiesterase inhibitors, glucagon, methylene blue, pacemaker for AV block. Small CCB ingestion is known to be fatal for pediatric patients. Hence, close observation for sufficient time is required.

Development of Hyaluronic Acid-Functionalized Hydrogel Lens and Characterization of Physical Properties and Lysozyme Adsorption (Hyaluronic acid의 첨가방법에 따른 하이드로겔 콘택트렌즈의 물리적 특성과 lysozyme 흡착량 비교)

  • Lim, Hwa-lim;Kim, Ho-joong;Jun, Jin
    • Journal of Korean Ophthalmic Optics Society
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    • v.20 no.3
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    • pp.285-291
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    • 2015
  • Purpose: The hydrogel lenses have been functionalized with HA(Hyaluronic Acid) using two different methods: construction of an IPN(Interpenetrating Polymer Networks) and formation of CCB(Chemical Covalent Bonding). The lysozyme adsorption and physical properties such as optical transmittance and water content of the hydrogel lenses have been investigated in order to determine whether method is suitable for the application potentials in contact lens industry. Methods: HA have been added to the hydrogel lenses prepared in the Lab using the two different method, e.g. IPN and CCB. The optical transmittance was measured in the wavelength range of 300~800 nm. The water content was measured by the gravimetric method using 0.9% NaCl saline solution. The amounts of adsorbed lysozyme on the contact lenses was analyzed by HPLC after incubation for 12h in artificial tears. Results: The water content of the HA added hydrogel contact lenses was increased, and the lens made by IPN method showed higher water content than the lens made by CCB method. The optical transmittance was over 90% both before and after addition of HA. Comparing the lysozyme adsorption reduction ratio, contact lens manufactured by IPN method was 60.0%, and the lens made by CCB method was 40.4%. Conclusions: CCB method is appropriate to distribute the functional material evenly throughout the lens, whereas IPN method is effective for the case of giving the functionality on the lens surface without phase separation.

Counter-Cyclical Capital Buffer and Regional Development Bank Profitability: An Empirical Study in Indonesia

  • ANDAIYANI, Sri;HIDAYAT, Ariodillah;DJAMBAK, Syaipan;HAMIDI, Ichsan
    • The Journal of Asian Finance, Economics and Business
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    • v.8 no.5
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    • pp.829-837
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    • 2021
  • The study investigates the impact of the Counter-Cyclical Buffer Policy (CCB) on regional development bank profitability in Sumatra, Indonesia. CCB requires banks to hold capital at times when credit is growing rapidly so that the buffer can be reduced if the financial cycle turns down or the economic and financial environment becomes substantially worse. This study employs time series data of regional development banks (RDBs) in Sumatra Island, Indonesia. The methodology applied in this study is a panel dynamic model with Generalized Methods of Moments (GMM). The results show that increasing capital through the implementation of CCB did not have a significant effect on RDBs' profitability. The findings of this study suggest that the activation and implementation of CCB lead to an increase in the amount and cost of loans to companies but do not affect the profitability of RDBs. The value of a Non-Performing Loan (NPL) proved to have a negative and significant effect on bank profitability. The CCB policy aims to overcome the pro-cyclicality of credit growth and improve bank resilience through increased capital which is expected to reduce excessive credit growth as a source of systemic risk. This causes a lack of lending to the community so that the profits obtained by the bank decrease.

Surface Electrochemical Study on the Fixation Properties of New Water-borne Preservatives in Red Pine (새로운 수용성(水溶性) 방부방충제(防腐防蟲劑)의 재중(材中) 정착성(定着性)에 관한 계면전기화학적(界面電氣化學的) 특성(特性))

  • Kim, Yeong-Suk
    • Journal of the Korean Wood Science and Technology
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    • v.24 no.4
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    • pp.93-99
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    • 1996
  • In order to investigate the extent of fixation of new water-borne preservatives in blocks of pinus densiflora sapwoods the streaming potential through the column with preservative treated wood was measured at various conditions. The rates of leachability of ingredients in the treated wood were estimated by the measurement of electric conductivity of the solution with the leached components. The solution was also analyzed by Atomic absorption spectrophotometer (AA). As a results, the experimental data indicated that the fixation of CCB, CCFZ and ACQ in wood were relatively unstable. The fixation rates of CCB, CCFZ were improved by increasing heat and drying time. The amounts of the leached ingredients were apparently higher in CCB and CCFZ than in CCA, while the rate of leaching of ACQ was not changed at various drying temperature.

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The Effect of Cytochalasin B on Cytoskeletal Stability of Mouse Oocyte Frozen by Vitrification (생쥐 난자의 초자화동결 시 Cytochalasin B가 Cytoskeleton에 미치는 영향)

  • Paik, Wong-Young;Choi, Won-Jun;Kim, Se-Na;Lee, Jong-Hak
    • Clinical and Experimental Reproductive Medicine
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    • v.29 no.4
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    • pp.229-236
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    • 2002
  • Objective : The purpose of this study was to evaluate the effect of Cytochalasin B (CCB) on the cytoskeletal stability of mouse oocyte frozen by vitrification. Methods : Mouse oocytes retrieved from cycle stimulated by PMSG and hCG were treated by CCB and then vitrified in EFS-30. These oocytes were placed onto an EM grid and submerged immediately in liquid nitrogen. Thawing of the oocytes was carried out at room temperature for 5 seconds, then the EM grid was placed into 0.75 M, 0.5 M and 0.25 M sucrose at $37^{circ}C$ for 3 minutes, each. These oocytes were fixed in 4% formaldehyde for an hour and then washed in PPB for 15 minutes 3 times, then incubated in PPB containing anti-tubulin monoclonal antibody at $4^{circ}C$ overnight. And then, the oocytes were incubated with FITC-conjugated anti-mouse IgG and propidium iodide (PI) for 45 minutes. Pattern of microtubules and microfilaments of oocytes were evaluated with a confocal microscope. Results: The rate of oocytes containing normal microtubules and microfilaments was significantly decreased after vitrification. The rate of oocyte containing normal microtubules in CCB treated group was higher than those in non-treated group (53.7% vs. 48.9%), but the difference was not significant. The rate of oocyte containing normal microfilaments in CCB treated group was significantly higher than those in non-treated group (64.5% vs. 38.3%, p<0.05). Conclusion: Microfilaments stability could be improved by CCB treatment prior to vitrification. It is suggested that CCB treatment prior to vitrification improve stability of cytoskeleton and then increase success rate in IVF-ET program using vitrification and thawing oocyte.

A Study of Determinants and Outcome of Customer Citizenship Behavior: Focusing on Long-Term Orientation between Service Organization and Customer (고객시민행동의 주요 선행 및 결과 변수에 관한 연구: 기업과 고객 간의 장기지향성에 미치는 영향을 중심으로)

  • Park, Mi-Young;Park, Jeong-Eun;Lee, Sungho
    • Asia Marketing Journal
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    • v.11 no.4
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    • pp.1-19
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    • 2010
  • The role of customers in product, service production and delivery is getting more important. Especially, customers' progressive participation in service circumstance bring to success of service delivery and improve service quality. Recently, the studies related to Customer Citizenship Behavior (CCB) which leaves to the discretion of customer is conducting in marketing area. However, the prior study concentrates on antecedents of CCB but it mixed antecedents of CCB and customer participation behavior. Also, there is insufficient related to the consequence of CCB in long-term relationship between service organization and customer. This study examines the effect of customer citizenship behavior on long-term orientation between service organization and customer. The results show that significant effects of citizenship behavior of customer. First, the relationship between customer's perception of justice and CCB was significant. Second, the relationship between customer's perception of support from service organization and CCB was significant. Third, the relationship between customer's perception of value and CCB was significant. Lastly, CCB significantly affect on Long-Term Orientation between service organization and customer.

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The Evaluation of Potential Hepatotoxicity by Calcium Channel Blockers, Renin-Angiotensin System Blockade and Diuretics (칼슘채널차단제, 레닌-안지오텐신시스템 차단제, 이뇨제의 잠재적 간독성 평가)

  • Kim, Jae Yun;Lee, Ok Sang;Jung, Sun Hoi;Lee, Hye-Suk;Lee, Chang Ho;Kim, Sang Geon;Lim, Sung Cil
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.4
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    • pp.330-339
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    • 2012
  • Background : Hypertension is treated with both lifestyle modification and pharmacotherapy. The Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), published in 2003, provides a streamlined management approach to hypertension for the primary care physician. The JNC-7 is the gold standard also in Korea. According to the JNC-7, special therapeutic considerations are recommended for high-risk individuals with compelling indications. The presence of compelling indications in any given patient should be considered when selecting specific pharmacotherapy to treat hypertension. However, in patients with compelling indications, it is unknown that hepatotoxicity is caused by Calcium Channel Blocker (CCB), one of 1st anti-hypertensive drugs. Now, the CCB is the most used 1st anti-hypertensive drug in Korea Therefore, we evaluated the changes in blood liver function parameters (ALT, AST, Total bilirubin, serum albumin) for the study group. Methods : We randomly collected and retrospectively analyzed Electronic Medical Record data (n=28,788) of patients, and who took calcium channel blockers(non-dihydropyridines; diltiazem, verapamil, dihydropyridines; amlodipine, barnidipine, benidipine, clinidipine, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine), with having liver function tests (LFTs) from July 1st 2009 to June 30th 2010 at the Seoul National University Hospital in Korea. Control groups are two antihypertensive agents: RAS blockade (ARB; candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, ACE-I; cilazapril, enalapril, fosinopril, imidapril, perindopril, ramipril) and, Diuretics (loop; furosemide, torsemide, thiazide; hydrochlorothiazide[HCTZ], indapamide). Patients not having LFT results at these three standard points of time(baseline, during, medication, and after finishing medication) were excluded. The collected data were analyzed by using the SPSS (Version12.0) and Microsoft Excel (Version2007). Results : 711 patients who were treated CCB (297), RAS blockade (232) or Diuretics (182) monotherapy were selected for the study. In selected patients, liver damage degree(changes of each LFTs value) was higher in diuretics group than other groups, followed by RAS blockade and CCB. In diuretics group's was loop-diuretics group was higher than thiazide-diuretics group. In CCB group, Nondihydropyridine-CCB's damage degree was higher than Dihydropyrine-CCB's that. Conclusions : Despite the limitations due to the retrospective study, among patients with abnormal LFTs, the use of CCBs led to a less liver damage than other 1st anti-hypertensive agents. It can be recommended CCBs as one of the initial treatments of hypertension in patients with liver disease.