• Title/Summary/Keyword: CYP3A4

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Involvement of Kupffer Cell in $CCl_4$ induced Liver Injury: The Role of Calcium (사염화 탄소에 의한 간손상에 있어 Kupffer cell 칼슘의 역할)

  • Yang, Mie-Rha
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.75-82
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    • 1996
  • The hypothesis that calcium provoke $O_2^-$ formation by Kupffer cells and may contribute to carbon tetrachloride $(CCl_4)$ induced liver injury was studied in SD rats. In $CCl_4-treated$ animals, hepatic malonaldehyde (nmole/gm liver) and plasma ALT (IU/ml) levels elevated significantly from $119.63{\pm}13.00$ to $268.97{\pm}14.82$ and from $17.3{\pm}0.18$ to $806.08{\pm}37.63$, respectively, compared to those in controls. Activation of Kupffer cells with high dose of retinol (250,000 IU/kg/day, po, for 7 day) significantly enhanced ALT levels, while inactivation of Kupffer cells with gadolinium chloride (7.5 mg/kg/day, ip, for 2 day) attenuated the increase of serum ALT level following $CCl_4$ treatment. Diltiazem (10 mg/kg/day, ip for 2 day) given in combination with retinol led to a marked decrease in ALT levels compare to the level in rats treated only with retinol against $CCl_4$ treatment. In order to determine any alterations in cytochrome P450 activities, the P450 content and the CYP2E1 activity were measured and all $CCl_4-treated$ rats showed significantly lower levels compared to those in controls and vehicle-treated animals. There were significant increases in glutathione peroxidase in all $CCl_4-treated$ rats except diltiazem treated groups. No difference was found among untreated and vehicle-treated rats. It is concluded that Kupffer cells contribute to $CCl_4-induced$ liver injury and that calcium antagonist attenuated the increased $CCl_4-induced$ liver injury due to activation of Kupffer cells.

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INHIBITORY EFFECT OF Er:YAG LASER ON THE GROWTH OF STREPTOCOCCUS MUTANS (Er:YAG 레이저 조사가 Streptococcus mutans의 증식억제에 미치는 효과)

  • Song, Gwang-Chul;Lee, Chang-Seop;Lee, Sang-Ho;Lee, Nan-Young
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.1
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    • pp.15-24
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    • 2003
  • The purpose of this study is to investigate the sterilization effect of Er:YAG laser against the intraoral acid producing bacterium, S. mutans, by irradiating the culture solution containing S. mutans KCTC 3065 with Er:YAG laser having a $650{\mu}m$ diameter beam through the non-contact method. We obtained the following results after examining the temperature changes of the culture solution, numbers of bacterial colonies, and acid-producing ability and attaching ability on teeth by measuring the amount of extracellular polysaccharide produced by S. mutans. The number of bacterial colony was decreased in $10{\mu}l$ culture solution irradiated with laser in overall compared to the control solution. The number decreased as the irradiation intensity and pulse repetition rate were larger and as the exposure time was increased. However, it did not change significantly in $100{\mu}l$ culture solution compared to the control solution. Although the acid-producing ability of S. mutans was inhibited for a certain duration after laser irradiation in 10r1 bacterial culture solution, it did not change in $100{\mu}m$ solution compared with the control solution. The amount of extracellular polysaccharide synthesized by S. mutans was partially decreased through laser irradiation in $10{\mu}m$ culture solution but did not change in $100{\mu}m$ culture solution. Based on these findings, we concluded that Er:YAG laser has an sterilization effect on S. mutans in which we presume that the mechanism is through the heat effect rather than the mechanical effect from development of ultrasound.

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CASE REPORTS OF TREATMENT OF ERUPTION-DISTURBED MX. FIRST MOLAR BY SURGICAL EXPOSURE (맹출 장애를 가진 상악 제1대구치의 외과적 노출을 이용한 치험례)

  • Seok, Choong-Ki;Nam, Dong-Woo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.1
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    • pp.11-18
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    • 2004
  • The eruption of permanent teeth represents the movement in the alveolar bone before appearance in oral cavity, to the occlusal plane after appearance in oral cavity, and additive movement after reaching th the occlusal plane. Tooth eruption is mostly controlled by genetic signals. The eruption stage is divided to preeruptive alveolar stage, alveolar bone stage, mucosal stage according to the process of growth and development. If the disturbance is occured in any stage of eruption, tooth does not erupt. The cause of eruption disturbance are ectopic position of the tooth germ, obstruction of the eruption path and defects in the follicle or PDL. In the treatment of eruption disturbance, surgical procedures are commonly used. There are three kind of surgical procedure ; surgical exposure, surgical repositioning, surgical exposure and traction Surgical exposure is basic procedure. This involves removal of mucosa, bone, lesion that are surrounding the teeth, dental sac when necessary to maintain a patent channel between the crown and the normal eruptive path into the oral cavity. To ensure this patency, many techniques including cementation of a celluloid crown, packing with gutta-percha or zinc oxide-eugenol, or a surgical pack, are used. When surgical exposure is conducted, operators should not expose any part of cervical root cement and not injure periodontium or root of adjunct tooth. After surgical exposure, tooth should be surrounded by keratinized gingiva. There is direct relationship between the extent of development of pathophysiologic aberrations and the intensity of the manipulative injury inflicted on the tooth by surgical treatment, so operator should consider this thing. In these cases, surgical exposure is conducted on Maxillary 1st milars that have a eruption disturbance and improve the eruption disturbance effectively.

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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.