• Title/Summary/Keyword: CYP 3A4

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In Vitro Metabolism of a New Cardioprotective Agent, KR-33028 in the Human Liver Microsomes and Cryopreserved Human Hepatocytes

  • Kim Hyojin;Yoon Yune-Jung;Kim Hyunmi;Cha Eun-Young;Lee Hye Suk;Kim Jeong-Han;Yi Kyu Yang;Lee Sunkyung;Cheon Hyae Gyeong;Yoo Sung-Eun;Lee Sang-Seop;Shin Jae-Gook;Liu Kwang-Hyeon
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1287-1292
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    • 2005
  • KR-33028 (N-[4-cyano-benzo[b]thiophene-2-carbonyl]guanidine) is a new cardioprotective agent for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-33028 in human liver microsomes and to compare its metabolism with that of cryopreserved human hepatocytes. Human liver microsomal incubation of KR-33028 in the presence of NADPH and UDPGA resulted in the formation of four metabolites, M1, M2, M3, and M4. M1 and M2 were identified as 5-hydroxy-KR-33028 and 7-hydroxy-KR-33028, respectively, on the basis of LC/MS/MS analysis with the synthesized authentic standard. M3 and M4 were suggested to be dihydroxy-KR-33028 and hydroxy-KR-33028-glucuronide, respectively. Metabolism of KR-33028 in cryopreserved human hepatocytes resulted in the formation of M1, M2, and M4. These data show a good correlation between major metabolites formed in human liver microsomes and cryopreserved human hepatocytes. In addition, KR­33028 was found to inhibit moderately the metabolism of CYP1A2 substrates. Based on the results obtained metabolic pathway of KR-33028 is proposed.

Changes of Root Yield and Paeoniflorin Content by Cultivated Years in Paeonia lactiflora PALLS (작약(芍藥) 재배년수(栽培年數)에 따른 근수량(根收量) 및 Paeoniflorin함량변화(含量變化))

  • Kim, Ki-Jae;You, Oh-Jong;Jeong, Yeun-Seon;Park, So-Deuk;Shin, Jong-Hee;Hwang, Hyung-Baek;Choi, Boo-Sull
    • Korean Journal of Medicinal Crop Science
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    • v.4 no.1
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    • pp.68-73
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    • 1996
  • Stem length, main root length and main root diameter showed rapid increasement in two-years-old and three-years-old peony. And there after, the increasement was almost finished. Occurrence of disease was increasing every cultivated year, especially the development of leaf spot was most serious. In propagation by root dividing method, the radix yield (kg/10a) was increasing every cultivated year. However, the difference of radix yield at four and five-years-old peony were not significant. The radix yield of four-years-old peony was higher 26% than three-years-old one. As cultivated year goes by, content of paeoniflorin was increasing then the content was highest at four-years-old peony (4.06%). In 1995, the content, had no certain tendency, was highest at three-years-old peony (3.14%). At hot air drying, browing of peony radix was increasing every cultivated year. If we consider radix yield and color, three-years-old peony was proper object of harvesting.

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A Study on the Permeability Reduction Methods of the Riverbed Ground during Urban Railway Tunnel construction (도시철도터널공사 시 하저통과구간의 지반투수저하 공법에 대한 연구)

  • Kim, Joon-Jeong;Cho, Kook-Hwan;Lee, Jun-Seok
    • Proceedings of the KSR Conference
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    • 2007.11a
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    • pp.551-557
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    • 2007
  • This paper describes a study on the permeability reduction of the riverbed ground during urban railway tunnel construction. The research is mainly concentrated on the study of the grouting or injection methods among permeability reduction methods which can be adapted in the riverbed ground. Firstly, the various grouting methods are theoretically reviewed and compared based on the previous research papers and case study results. It is also evaluated the grouting methods in view of a safe construction of the river crossing railway tunnel. Baced on the literature review and previous construction data, the design technology of grouting methods considering the long term hydro-geological behaviour in the riverbed, is suggested. Two injection methods namely, Natural Durable Stabilizer(N.D.S) and Space-Multi Injaction Grouting(S.M.I) methods, are introduced as new approach methods which can be adopted to modify the riverbed ground. In order to evaluate the ground that grouted and modified by the N.D.S and S.M.I method, the pilot test programmes including the field and laboratory permeability tests, are carried out in the river crossing tunnel construction sites. The results obtained from pilot test programme, are also reviewed. In conclusion, the grouting efficiency of the S.M.I method using the non-alcalimeter silica sol is better than that of NDS method using cement. In addition, it hopes that the research results are contributed to develop the grouting design technology.

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Clinical Study for Efficacy and Safety of Rabeprazole Sodium(Pariet) in the Treatment of Laryngopharyngeal Reflex(LPR) Disease (인후두위산역류증(Laryngopharyngeal Reflux: LPR)의 치료에 대한 RabeprazoleSodium(Parietd)의 임상효과와 안전성 검토)

  • Jung, K.W.;Jun, B.S.;Ko, S.H.;Kwon, K.H.;Kwon, S.Y.;Kwon, J.K.;Kim,, D.Y.;Kim,, S.C.;Kim,, S.W.;Kim,, Y.M.;Kim,, Y.H.;Kim,, Y.H.;Kim,, J.M.
    • Korean Journal of Bronchoesophagology
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    • v.10 no.2
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    • pp.35-42
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    • 2004
  • Background and objective : Rabeprazole is a new generation proton pump inhibitor, which has a rapid onset after first dose, predictable efficacy in all patients regardless of CYP2C19 genotype status, and less nocturnal acid breakthrough. The aim of the study is to investigate clinical efficacy and safety of rabeprazole sodium (Pariet 10mg qd)when administered once daily to patients with laryngopharyngeal reflux(LPR) disease. Methods : Among the patients who had visited the Department of Otolaryngology, those with LPR symptoms, had undergone laryngoscopy. Symptoms and endoscopic laryngeal sings were recorded initially, at 1 month, 2 months, 3 months, and more than 3 months, All patients were evaluated for clinical efficacy on the basis of symptom scores, reflux finding score(RFS), and side effects. Results : In general, most symptom scores and RFS improved over the time. Efficacy of the Pariet on LPR-related symptoms were $63.2\%,\;77.5\%,\;78.7\%,\;and\;90.9\%$ before 4 weeks, 4 to 8 weeks, 8 to 12 weeks, and after 12 weeks respectively. Efficacy on the RFS were $61.8\%,\;78.4\%,\;82.9\%,\;and\;85.5\%$ before 4 weeks, 4 to 8 weeks, 8 to 12 weeks, and after 12 weeks respectively. Pariet was well tolerated and was associated with few drug-related side effects. Conclusion Because of its efficacy and safety, Pariet may prove to be an alternative to currently available proton pump inhibitors.

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Effects of Growth Regulators, Sucrose and Gelling Agents on Callus Growth and Plant Regeneration in Angelica koreana MAX. (강활(羌活)의 캘러스 증식(增殖) 및 식물체(植物體) 재분화(再分化)에 미치는 생장(生長) 조절제(調節劑), sucrose 및 배지(培地) 응고제(凝固劑)의 영향(影響))

  • Lee, Joong-Ho;Lee, Seung-Yeob;Namkoong, Seung-Bak
    • Korean Journal of Medicinal Crop Science
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    • v.4 no.1
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    • pp.78-85
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    • 1996
  • The effects of growth regulators, sucrose and gelling agents were investigated to increase the efficiency of the callus growth and plant regenerarion in tissue culture of Angelica koreana Max. The fresh weight and dry weight of subcultured callus was highest in MS medium supplemented with 1 mg/l 2,4-D. Callus growth was excellent in 2% sucrose, but it was inhibited in propotion to sucrose content. Effect of gelling agents on callus growth was highest on 1.2% agar and 0.4% Gelrite medium, respectively. The browning of callus was protected on the media supplemented with 10 mg/l ABA and 5 or 10 mg/l $AgNO_3$. In the callus induction and growth from the peduncle of immature inflorescence, 2,4-D was more effective than NAA, and the frequency of callus induction was highest as 81.7% in 2 mg/l 2,4-D. Plant was not regenerated from the callus derived from young leaf. Somatic embryos were developed from the surface of callus drived from the peduncle of immature inflorescence in the medium containing 0.5 mg/l 2,4-D, 1 mg/l kinetin, 5 mg/l ABA and 5 mg/l $AgNO_3$. Plants were developed from the matured somatic embryos in the medium supplemented with 0.2 mg/l 2,4-D and 1 mg/l kinetin.

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Association of PAH-DNA adducts and Urinary PAH metabolites influenced by polymorphisms of xenobiotic metabolism enzymes in industrial wase incinerating workers (산업폐기물 소각장 근로자에서 요중 PAHs 대사산물과 혈중 aromatic-DNA adducts)

  • ;Masayoshi Ichiba
    • Environmental Mutagens and Carcinogens
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    • v.22 no.4
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    • pp.303-311
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    • 2002
  • This study evaluated the concentrations of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in industrial waste incineration workers. The effect of genetic polymorphisms of xenobiotic metabolism enzymes on urinary concentration of PAH metabolites was assessed. And, aromatic DNA adduct levels were also determined in total white blood cells. Fifty employees were recruited from a company handling industrial wastes located in Ansan, Korea: non-exposed group (n=21), exposed group (n=29). Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects near incinerators. Urinary 1-hydroxypyrene glucuronide (1-OHPG), a major pyrene metabolite, was assayed by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11 (SFS/IAC). Multiplex PCR was used for genotyping for GSTMI/TI and PCR-RFLP for genotyping of CYP1A1 (MspI and Ile/Val). PAH-DNA adducts in peripheral blood WBC were measured by the nuclease P1-enhanced postlabeling assay. Smoking habit, demographic and occupational information were collected by self-administered questionnaire. The range of total ambient PAH levels were 0.00-7.00 mg/㎥ (mean 3.31). Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (p=0.006, by Kruskal-Wallis test). There was a statistically significant dose-response increase in 1-OHPG levels with the number of cigarettes consumed per day (Pearson correlation coefficient=0.686, p<0.001). Urinary 1-OHPG levels in occupationally exposed smoking workers were highest compared with non-occupationally exposed smokers (p=0.053, by Kruskal-Wallis test). Smoking and GSTMI genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R²=0.565, p<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R²=0.249, p=0.201). Aromatic DNA adducts was also a significantly correlation between log transferred urinary 1-OHPG levels (pearson's correlation coefficient=0.307, p=0.04). However, the partial correlation coefficient adjusting for Age, Sex, and cigarette consumption was not significant (r=0.154, p=0.169). The significant association exists only in individuals with the GSTMI null genotype (pearsons correlation coefficient=0.516, p=0.010; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.363, p=0.038). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTMI genotype. There results remain to be confirmed in future larger studies.

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Effect of Glutathione S-Transferase Polymorphisms on the Antioxidant System (Glutathione S-Transferase 유전적 다형성이 항산화 체계에 미치는 영향)

  • Jeon, Gyeong-Im;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.6
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    • pp.708-719
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    • 2007
  • Glutathione S-transferase genotypes GSTT1, GSTM1 and GSTP1 were characterized in 104 healthy male and female subjects and compared with parameters of oxidative stress at the level of DNA and lipids, with antioxidant enzymes, and with plasma antioxidants in smokers and non.smokers. Of the 104 subjects studied, 57.4% were GSTT1 present and 47.6% were GSTM1 present. The GSTP1 polymorphisms a and b were represented as follows: a/a, 75.5%; a/b, 21.6%; b/b type, 2.9%. The GSTT1 null genotype was associated with decreased glutathione in erythrocytes and elevated lymphocytes DNA damage. GST-Px was higher in GSTT1 null compared with GSTT1 present type. The homozygous GSTP1 genotype was not associated with any antioxidant status or DNA damage. The difference in plasma ${\alpha}$-carotene and erythrocytes GSH-Px and GST activities between smokers and non-smokers was detected in the GSTT1 null genotype. Plasma ${\gamma}$-tocopherol and ${\beta}$-carotene decreased significantly in smokers having GSTM1 null genotype. When GSTT1 and GSTM1 were combined, plasma lycopene and erythrocyte GST were reduced in smokers in both null types of these genes. As for GSTP1 genotype, plasma ${\alpha}$-carotene and erythrocytes GSH-Px decreased significantly in smokers with GSTP1 b/b, while erythrocytes GSH-Px activities decreased in smokers with GSTP1 a/b. The different ${\beta}$-carotene level between smokers and non-smokers was seen with both GSTP1 a/a and a/b genotype. It seems that polymorphisms in the phase II metabolizing enzyme glutathione S-transferase may be important determinants of commonly measured biomarkers.

Problems in the Korean National Family Planning Program (한국가족계획사업(韓國家族計劃事業)의 문제점(問題點))

  • Hong, Jong-Kwan
    • Clinical and Experimental Reproductive Medicine
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    • v.2 no.2
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    • pp.27-36
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    • 1975
  • The success of the family planning program in Korea is reflected in the decrease in the growth rate from 3.0% in 1962 to 2.0% in 1971, and in the decrease in the fertility rate from 43/1,000 in 1960 to 29/1,000 in 1970. However, it would be erroneous to attribute these reductions entirely to the family planning program. Other socio-economic factors, such as the increasing age at marriage and the increasing use of induced abortions, definitely had an impact on the lowered growth and fertility rate. Despite the relative success of the program to data in meeting its goals, there is no room for complacency. Meeting the goal of a further reduction in the population growth rate to 1.3% by 1981 is a much more difficult task than any one faced in the past. Not only must fertility be lowered further, but the size of the target population itself will expand tremendously in the late seventies; due to the post-war baby boom of the 1950's reaching reproductive ages. Furthermore, it is doubtful that the age at marriage will continue to rise as in the past or that the incidence of induced abortion will continue to increase. Consequently, future reductions in fertility will be more dependent on the performance of the national family planning program, with less assistance from these non-program factors. This paper will describe various approaches to help to the solution of these current problems. 1. PRACTICE RATE IN FAMILY PLANNING In 1973, the attitude (approval) and knowledge rates were quite high; 94% and 98% respectively. But a large gap exists between that and the actual practice rate, which is only 3695. Two factors must be considered in attempting to close the KAP-gap. The first is to change social norms, which still favor a larger family, increasing the practice rate cannot be done very quickly. The second point to consider is that the family planning program has not yet reached all the eligible women. A 1973 study determineded that a large portion, 3096 in fact, of all eligible women do not want more children, but are not practicing family planning. Thus, future efforts to help close the KAP-gap must focus attention and services on this important large group of potential acceptors. 2. CONTINUATION RATES Dissatisfaction with the loop and pill has resulted in high discontinuation rates. For example, a 1973 survey revealed that within the first six months initial loop acceptance. nearly 50% were dropouts, and that within the first four months of inital pill acceptance. nearly 50% were dropouts. These discontinuation rates have risen over the past few years. The high rate of discontinuance obviously decreases the contraceptive effectiveness. and has resulted in many unwanted births which is directly related to the increase of induced abortions. In the future, the family planning program must emphasize the improved quality of initial and follow-up services. rather than more quantity, in order to insure higher continuation rates and thus more effective contraceptive protection. 3. INDUCED ABORTION As noted earlier. the use of induced abortions has been increase yearly. For example, in 1960, the average number of abortions was 0.6 abortions per women in the 15-44 age range. By 1970. that had increased to 2 abortions per women. In 1966. 13% of all women between 15-44 had experienced at least one abortion. By 1971, that figure jumped to 28%. In 1973 alone, the total number of abortions was 400,000. Besides the ever incre.sing number of induced abortions, another change has that those who use abortions have shifted since 1965 to include- not. only the middle class, but also rural and low-income women. In the future. in response to the demand for abortion services among rural and low-income w~men, the government must provide and support abortion services for these women as a part of the national family planning program. 4. TARGET SYSTIi:M Since 1962, the nationwide target system has been used to set a target for each method, and the target number of acceptors is then apportioned out to various sub-areas according to the number of eligible couples in each area. Because these targets are set without consideration for demographic factors, particular tastes, prejudices, and previous patterns of acceptance in the area, a high discontinuation rate for all methods and a high wastage rate for the oral pill and condom results. In the future. to alleviate these problems of the methodbased target system. an alternative. such as the weighted-credit system, should be adopted on a nation wide basis. In this system. each contraceptive method is. assigned a specific number of points based upon the couple-years of protection (CYP) provided by the method. and no specific targets for each method are given. 5. INCREASE OF STERILIZA.TION TARGET Two special projects. the hospital-based family planning program and the armed forces program, has greatly contributed to the increasing acceptance in female and male sterilization respectively. From January-September 1974, 28,773 sterilizations were performed. During the same time in 1975, 46,894 were performed; a 63% increase. If this trend continues, by the end of 1975. approximately 70,000 sterilizations will have been performed. Sterilization is a much better method than both the loop and pill, in terms of more effective contraceptive protection and the almost zero dropout rate. In the future, the. family planning program should continue to stress the special programs which make more sterilizations possible. In particular, it should seek to add the laparoscope techniques to facilitate female sterilization acceptance rates. 6. INCREASE NUMBER OF PRIVATE ACCEPTORS Among the current family planning users, approximately 1/3 are in the private sector and thus do not- require government subsidy. The number of private acceptors increases with increasing urbanization and economic growth. To speed this process, the government initiated the special hospital based family planning program which is utilized mostly by the private sector. However, in the future, to further hasten the increase of private acceptors, the government should encourage doctors in private practice to provide family planning services, and provide the contraceptive supplies. This way, those do utilize the private medical system will also be able to receive family planning services and pay for it. Another means of increasing the number of private acceptors, IS to greatly expand the commercial outlets for pills and condoms beyond the existing service points of drugstores, hospitals, and health centers. 7. IE&C PROGRAM The current preferred family size is nearly twice as high as needed to achieve a stable poplation. Also, a strong boy preference hinders a small family size as nearly all couples fuel they must have at least one or more sons. The IE&C program must, in the future, strive to emphasize the values of the small family and equality of the sexes. A second problem for the IE&C program to work. with in the: future is the large group of people who approves family planning, want no more children, but do not practice. The IE&C program must work to motivate these people to accept family planning And finally, for those who already practice, an IE&C program in the future must stress continuation of use. The IE&C campaign, to insure highest effectiveness, should be based on a detailed factor analysis of contraceptive discontinuance. In conclusion, Korea faces a serious unfavorable sociodemographic situation- in the future unless the population growth rate can be curtailed. And in the future, the decrease in fertility will depend solely on the family planning program, as the effect of other socio-economic factors has already been maximumally felt. A second serious factor to consider is the increasing number of eligible women due to the 1950's baby boom. Thus, to meet these challenges, the program target must be increased and the program must improve the effectiveness of its current activities and develop new programs.

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