• Title/Summary/Keyword: 1,4-DHP

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Pharmacokinetics of Carbapenem Antibiotics in Rats and Guinea pigs

  • Nam, Kweon-Ho;Chang, Woo-Ik;Park, Moon-Jung;Kim, Ji-Yeon;Park, Nam-Jun;Yu, Young-Hyo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.228-228
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    • 1996
  • 1, 흰쥐에서 IPM 단독투여시보다 DHP-I 저해제인 CS와의 병용투여시 AUC가 4배 이상, t$_{1}$2/가 약 3배 증가하였으며 MEPM의 경우는 AUC가 5배 이상, t$_{1}$2/가 약 1.8배 증가하였다. 2. Guinea pig에서 IPM 단독투여시보다 CS와의 병용투여시 AUC가 약 2.5배, t$_{1}$2/가 약 1.4배 증가하였으며 MEPM의 경우는 AUC, t$_{1}$2/ 모두 거의 변함이 없었다. 3. 위의 결과 흰쥐에서 IPM과 MEPM에 대한 CS의 영향이 매우 큰 것으로 나타났으며 따라서 약물동력학적인 파라메타에도 커다란 변화를 주었다. 반대로 Guinea Pig에서는 CS의 병용투여로 IPM의 AUC에만 변동을 주었을 뿐 t$_{l}$ 2/에는 크게 영향을 미치지 않았고 MEPM의 체내동태에는 거의 영향을 미치지 않았다. 4. Guinea pig에서 전체 투여량에 대한 MEPM의 요중회수율은 66.58$\pm$3.44%이었고 IPM의 경우는 7.00$\pm$0.95%이었다. 그러나 DHP-I 저해제인 CS와의 병용투여시 IPM의 요중회수율이 57.77$\pm$11.46%로 증가하여 MEPM과 거의 비슷한 양상을 나타냈다. 이는 guinea pig에서 DHP-I에 의한 IPM의 대사가 CS에 의해 차단됨을 시사하는 것이라고 사료되며 guinea pig에 존재하는 DHP-I은 MEPM보다 IPM에 대해 더 높은 친화도를 갖는 것으로 사료된다. 5. Carbapenem계 항생제의 약물동력학적 스크리닝을 위한 소동물로는 흰쥐보다도 guinea pig가 적합한 것으로 생각되나 동물종차에 의한 약물동력학적 연구 및 DHP-I의 활성에 대한 연구가 더 면밀히 이루어져야 할 것으로 생각되며 BO-2727, panipenem, biapenem 등 다른 carbapenem 항생제에 대한 광범위한 약물동력학적 연구가 진행되어 새로운 carbapenem계 항생제 개발에 따른 인체내 거동을 예측할 수 있는 치적의 실험동물모델이 확립되어야 할 것이다.

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Low Potential Amperometric Determination of Ascorbic Acid at a Single-Wall Carbon Nanotubes-Dihexadecyl Hydrogen Phosphate Composite Film Modified Electrode

  • Fei, Junjie;Wu, Kangbing;Yi, Lanhua;Li, Junan
    • Bulletin of the Korean Chemical Society
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    • v.26 no.9
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    • pp.1403-1409
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    • 2005
  • A sensitive and selective electrochemical method was developed for the amperometric determination of ascorbic acid (AA) at a glassy carbon electrode (GCE) modified with single-wall carbon nanotubesdihexadecyl hydrogen phosphate (SWNT-DHP) composite film. The SWNT-DHP composite film modified GCE was characterized with SEM. The SWNT-DHP composite film modified GCE exhibited excellent electrocatalytic behaviors toward the oxidation of AA. Compared with the bare GCE, the oxidation current of AA increased greatly and the oxidation peak potential of AA shifted negatively to about -0.018 V (vs. SCE) at the SWNT-DHP composite film modified GCE. The experimental parameters, which influence the oxidation current of AA, were optimized. Under the optimal conditions, the amperometric measurements were performed at a applied potential of -0.015 V and a linear response of AA was obtained in the range from 4 ${\times}$ $10^{-7}$ to 1 ${\times}$ $10^{-4}$ mol $L^{-1}$ and with a limit of detect (LOD) of 1.5 ${\times}$ $10^{-7}$ mol $L^{-1}$. The interferences study showed that the SWNT-DHP composite film modified GCE exhibited good sensitivity and excellent selectivity in the presence of high concentration uric acid and dopamine. The proposed procedure was successfully applied to detect AA in human urine samples with satisfactory results.

SYNTHETIC DEVELOPMENT OF NEW 1$\beta$-SUBSTITUTED CARBAPENEMS

  • Nagao, Yoshimitsu
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.34-35
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    • 1993
  • The Development of new asymmetric induction methods useful for syntheses of biologically active natural products and drugs, using C4-chiral 1,3-th-iazolidine-2-thiones, has been a recent focus of interest. 1-8) The present account describes the significance of particular heterocycles in the synthetic development of new 1${\beta}$-substituted carbapenems. A fungal metabolite, (+)-thienamycin (1) has attracted one's attention as a hopeful candidate for new-generation antibiotic drugs because of its strong antimicrobial activities and wide antimicrobial spectra due to the extensive inhibition against various ${\beta}$-lactamases. However, it has been serious problems toward a practically useful drug that (+)-thienamycin is fairly labile in the solution and can be metabolized by renal dehydropept- idase-I (DHP-I). Recently, a Merck Sharp & Dohme research group exploited a non-natural ${\beta}$-lactam, imipenem (2) which has been appeared in the drug market as the first carbapenem-type antibiotic drug. 9) However 2 must be used with a DHP-I inhibitor, cilastatin sodium (3).9) Thus, a 1,${\beta}$-methyl- carbapenem derivative 4 has been disclosed by the same group. 10) It seems to be more hopeful candidate as a new-generation antibiotic because it can directly resist against metabolism by the renal DHP-1 without an enzyme inhibitor 3. 10)

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Effects of Head Posture on Resting EMG Activity of Craniocervical Muscles and on Occlusal Contacts (두부자세에 따른 두경부 근활성 및 교합접촉양태의 변화)

  • Chang-Kweon Song;Kyung-Soo Han;Chan Chung
    • Journal of Oral Medicine and Pain
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    • v.21 no.1
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    • pp.89-101
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    • 1996
  • This study was performed to investigate influence of the changes of head posture on resting electromyographic (EMG) activity in anterior temporalis, masseter, sternocleidomastoid muscle and trapezius, and on status of occlusal contacts. For this study twenty-nine patients with temporomandibular disorders(TMD) and thirty dental students without any masticatory symptoms were selected as patients group and control group, respectively. EMG activity($\mu$V) at rest was observed in four kind of head postures such as natural or normal head posture(NHP), forward head posture(FHP), upward head posture(UHP), downward head posture(DHP), and in NHP and FHP, EMG activity with flat occlusal splint was also checked. BioEMG$^\textregistered$(Bioelectromyograph, Bioresearch Inc., USA) was used to record EMG activity in the above four muscles with eight locations on both sides. The author used T-Scan$^\textregistered$(Tekscan Co., USA) system to investigate the changes of oclusal contats on clenching in the four head postures about number, force, time(duration) and total left-right statistis(TLR, occlusal stability crossing left-right dental arch on clenching). For taking in upward or downward head posture, head was inclined $10^{\circ}$ upward or downward and CROM$^\textregistered$ (cervical-range-of motion, Performance attainment Inc., USA) was used to maintain same posture during the procedure. The results obtained were as follows : 1. For resting EMG activity, anterior temporalis did not show any difference by change of head posture, but masseter and sternocleidomastoid muscle showed higher value of EMG activity in FHP and UHP, and trapezius showed higher value of EMG activity in FHP and DHP. 2. EMG activity of trapezius was higher than that of any other muscles in NHP, FHP, and DHP, but in UHP, the activity was the lowest reversely. 3. Patients group showed higher EMG activity than control group did in all the muscles in NHP. And significant difference between the two groups were also observed in anterior temporalis in FHP, in sternocleidomastoid muscle in UHP, and in sterno-cleidomastoid muscle and trapezius in DHP with higher activity in patients group. 4. There was no change of EMG activity in NHp with splint, but EMG activity in anterior temporalis and masseter was decreased in FHP with splint. 5. In general, status of occlusal contacts was not changed with head posture in all subjects, and difference between patients group and control group was only noted for number and force of tooth contact in UHP and DHP with more value in control group. 6. Correlationship between EMG activity and number ad force of tooth contacts was shown negatively with regard to masseter in NHP, and trapezius in UHP and DHP.

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Renal dehydropeptidase-I (DHP-I) Stability and Pharmacokinetics of DA-1131, A New Carbapenem Antibiotic

  • Kim, Ji-Young;Kim, Gye-Won;Park, Seong-Hak;We, Jeoung-Soon;Park, Haeng-Soon;Junnick Yang
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.238-238
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    • 1996
  • 각종 동물 및 인체 신장 유래 DHP-I에 의한 DA-1131, imipenem(IPM) 및 meropenem(MEPM)의 속도 상수를 측정한 결과, DA-1131은 동물종에 관계없이 가장 안정성이 큰 결과를 나타내었고, 인체 DHP-I에 대한 Vmax/Km 값이 IPM의 21.9%로 관찰되어 IPM보다 하위 기질인 것으로 확인되었다. DA-1131, IPM/CS 및 MEPM/CS의 20mg/kg투여 후의 혈중농도 반감기(T$_{1}$2/)는 각각 11.4분, 8.9분, 10.3분이었으며, 1$\mu\textrm{g}$/$m\ell$ 이상의 혈중농도룰 유지하는 시간은 66.6 분, 55.9 분, 63.1 분이었다. DA-1131, DA-l131/CS, IPM/CS, MEPM 및 MEPM/CS의 40 mg/kg 투여 후 24시간 동안의 뇨중 배설율은 57.9 %, 61.3%, 22.6 %, 11.3% 및 65.9%이었으며, 각 약물을 40 mg/kg 투여 15분 후 DA-ll3l의 폐중 농도는 11.2$\mu\textrm{g}$/g으로 DA-l131/CS, IPM/CS 및 MEPM/CS와 비슷한 결과를 나타내었으며 T/P ratio도 DA-1131, DA-l131/CS, IPM/CS 와 MEPM/CS 투여군에서 거의 동일한 것으로 확인되었다. 신장중 농도는 DA-1131 과 DA-l131/CS의 경우 29.l$\mu\textrm{g}$/g 및 34.2$\mu\textrm{g}$/g으로 큰 차이를 나타내지 않았으나, IPM/CS, MEPM 및 MEPM/CS 투여군에 비하여는 높은 결과로 나타났고 T/P ratio도 DA-1131과 DA-l131/CS 투여군이 IPM/CS, MEPM 및 MEPM/CS 투여군보다 놓은 것으로 확인되었다.

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An Expeditious Oxidative Aromatization of Hantzsch 1,4-Dihydropyridines to Pyridines Using Cetyltrimethylammonium Peroxodisulfate: A Phase Transferring Oxidant

  • Kumar, Parvin;Kumar, Ashwani
    • Bulletin of the Korean Chemical Society
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    • v.31 no.8
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    • pp.2299-2303
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    • 2010
  • A new approach to the use of potassium peroxodisulphate as an oxidizing reagent is proposed and applied to the case of oxidative aromatization of 1, 4-dihydropyridines with cetyltrimethylammonium peroxodisulfate, a phase transfer oxidant. We demonstrate how it is possible to increase the reactivity of potassium peroxodisulphate in the presence of phase transfer catalyst. Dealkylation in case of 4-n-alkyl/n-alkenyl was not obtained.

Dihydropyridine계 칼슘 Channel효능제 및 길항제가 Muscarinic Receptor에 미치는 영향

  • 이신웅;박영주;이해태;장태수
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1992.05a
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    • pp.45-45
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    • 1992
  • Calcium channel에 작용하는 dihydropyridine(DHP) 계열의 calcium channel 효능제와 길항제의 caicium channel에 대한 작용과 muscarinic receptor에 대한 작용과의 관계를 조사하기 위하여 [$^3$H]QNB와 [$^3$H]nitrendipine 결합실험을 시행하고 이를 지표로 하여 칼슘효능제와 길항제의 이들 receptors에 대한 결합성질을 검토하였다. 본 연구결과 칼슘 channel 효능제인 Bay K 8644는 칼슘길항제인 nicardipine 및 nimodipine과 같이 고농도에서 muscarinic receptor에 대한 [$^3$H]QNB결합을 경쟁적으로 억제하였으며 이들 약물의 muscarinic receptor에 대한 Ki치는 각각 16.7 $\mu$M, 3.5 $\mu$M, 및 15.5 $\mu$M이었다. 한편, 이들 약물은 다같이 칼슘 channel의 high affinity DHP결합부위에 대한 [$^3$H]nitrendipine 결합을 억제하였으나 이 부위에 대한 Bay K 8644, nicardipine, 및 nimodipine의 Ki치는 각각 4 nM, 0.1 nM, 및 0.2 nM로서 muscarinic receptor에 대한 Ki치 보다 4,000-75,000배 작았다. 뿐만 아니라 [$^3$H]QNB결합을 완전히 차단하는 고농도의 atropine(1 $\mu$M)에 의해서도 [$^3$H]nitrendipine결합이 전혀 영향을 받지 않았다. 따라서 DHP계 약물의 muscarinic receptor에 대한 작용은 칼슘channel에 대한 이들 약물의 작용을 연구하거나 임상적 치료 목적으로 사용할때는 나타나지 않을 것으로 생각된다.

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A study on the efficient 1-pass password-based key exchange protocol (효율적인 1-pass 패스워드 기반 키 분배 프로토콜에 관한 연구)

  • Ahn, Sang-Man;Oh, Soo-Hyun;Won, Dong-Ho
    • Proceedings of the Korea Information Processing Society Conference
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    • 2002.11b
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    • pp.1119-1122
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    • 2002
  • 본 논문에서는 Ford와 Kaliski[6]가 제안한 패스워드 은닉 기술을 적용하여 클라이언트와 서버의 은닉 변수로 은닉된 값을 서버가 패스워드 검증자로 사용하는 새로운 패스워드 기반 키 교환 프로토콜을 제안한다. 제안하는 프로토콜은 패스워드 검증자를 비밀리에 보관하여야하는 다른 검증자 기반 방식과 달리 클라이언트와 서버의 은닉 변수가 적용된 검증자를 사용하여 서버의 패스워드 검증자에 대한 안전성을 증가시켰다. 또한 Nyberg-Ruppel 방식[4]을 적용하여, 한번의 통신으로 사용자 인증과 키 교환을 할 수 있다. 본 논문에서 제안하는 프로토콜 안전성은 이산대수문제인 DLP(Discrete logarithm Problem)와 DHP(Diffie-Hellman Problem)[6]에 의존한다. 따라서 DLP와 DHP의 가정하에, 제안된 프로토콜은 오프라인 사진공격(off-line dictionary attack), 서버 데이터 도청(server data eavesdropping), 전향적 안전성(forward secrecy), Denning-Sacco 공격[1]에 대하여 안전하다.

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Plasma Sex Steroid Hormone and Vitellogenin Profiles during Ovarian Development of the Wild Marbled Sole (Limanda yokohamae) (자연산 문치가자미 (Limanda yokohamae)의 난소 발달에 따른 혈중 성호르몬과 난황단백전구체 농도 변동)

  • Kim, Dae-Jung;An, Cheul-Min;Min, Kwang-Sik
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.39 no.5
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    • pp.391-397
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    • 2006
  • This study correlated changes in estradiol-l7$\beta$ ($E_2$), testosterone (T), 17$\alpha$,20-dihydroxy-4-pregnen-3-one (DHP), and vitellogenin (VTG) levels with changes in the gonadosomatic index (GSI) and ovarian histology during the annual reproductive cycle of the wild marbled sole, Limanda yokohamae. Synchronous oocyte development occurs in this fish. Ovary maturity was classified into four periods, based on histological observations: the spawning (December to February), post-spawning (February to April), recovery (May to August), and vitellogenic (September to November) periods. Seasonal changes in the GSI were inversely correlated with water temperatures and reflected the degree of ovarian maturity. Plasma VTG levels were correlated with changes in the GSI, which increased from September to a peak in January, and levels remained comparatively high until February. Estradiol-17$\beta$ was at baseline levels (<0.11 ng/mL) during the spring and summer, and peaked rapidly (1.55$\pm$0.445 ng/mL) from October to January. Plasma T and DHP levels had a similar profile; they rose markedly during the spawning period and remained low (or were not detectable) from spring through autumn. These data indicate that changes in plsama steroid hormones and VTG levels are correlated with the annual ovarian activity of the marbled sole. Based on these results and published reports, it appears that in this species DHP is the most important maturation-inducing steroid and that T is also related to final maturation.

A Study on the Selection of Evaluation Factors on Forest Carbon Cycle Community(F.C.C.C) using DHP Analysis Method (DHP분석을 이용한 산림탄소순환마을 대상지 평가기준 선발에 관한 연구)

  • Seo, Jeong-Weon;Kwak, Kyung-Ho;Jeong, Se-Myong;Kang, Sung-Pyo;An, Ki-Wan
    • Journal of Korean Society of Forest Science
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    • v.100 no.4
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    • pp.672-680
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    • 2011
  • The purpose of this study has been carried to develop a criterion for the selection of evaluation factors on Forest Carbon Cycle Community(F.C.C.C) based on the result of survey of 96 participants who were operation managers on mountain eco village(31), relevant experts(33), and officers of local government(32). For analysis of the results of survey, DHP(Delphi Hierarchy Process) method was used which is a combination of Delphi method and AHP(Analytic Hierarchy Process) method. The key factors on selection of a suitable area to launch F.C.C.C. project of Korea Forest Service was selected under three hierarchical classes. Class 1 comprises 3 indices(Physical resource index, Human resource index, Vision index), and Class 2 which contains 10 indices (Existing resource, Surroundings resource, Forest biomass resource, Humanities Social quality, Local resident participation, Leader's ability, External support, Planning of operation, Capability of operation, and Effect of operation). Class 3 is sub-level class of class which possess 38 indices. From the results of analysis, Consistency Index(C.I) of each index in the 3 classes was used as evaluation factor. In Class 1, index 'human resources' showed highest Consistency Index(0.454). In Class 2, index 'forest biomass resources' was the highest Consistency Index(0.376) in 'physical resources' of Class 1, index 'leader's ability' was the highest Consistency Index(0.326) in 'human resources' of Class 1, and index 'planning of operation' was the highest Consistency Index(0.346) in 'vision' of Class 1. In Class 3, relative importance of 38 index including 'Joint ownership land security(C.I.-0.266)' was evaluated. Based on the result of this study, a criterion for the selection of evaluation factors for F.C.C.C was developed and the evaluation criterion is expected to be use to select of a suitable area to launch F.C.C.C. project since 2011.