• 한국임상약학회지
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• 제26권4호
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• 보건교육건강증진학회지
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• 제32권4호
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• pp.79-92
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• 2015

Objectives: The purpose of this study is to identify the trends of jjok-bang research based on the perspective of Community-Based Participatory Research and Social Ecological Model and to provide information for future public health interventions, policy designs, and policy implementations. Methods: Studies used in the systematic review are published from 1999 to 2014 and searched using key words such as 'jjok-bang' and 'single room occupancy' using domestic and international electronic databases. However, there were no studies from abroad published during this period. Search in domestic databases such as KCI, KISS, RISS generated 119 studies. In this paper, 20 cases which meet the criteria of the systematic review were included in the final analysis. Results: The contents of research included are the life of jjok-bang inhabitants(9 cases), the demand for welfare services(4 cases) and welfare need(2 cases), mental health(1 cases), and the history of jjok-bang formation(4 cases). Fourteen cases of empirical study were analyzed focusing Community-Based Participatory Research and Social Ecological Model. Some of research was carried out forming a partnership with various community partners and this trend increased since 2008. There are high frequency of intrapersonal level and interpersonal level studies. However, studies looking at the organization, community or policy level were relatively few. Conclusions: Future studies of jjok-bang area should consider the various social determinants which affect the health delivery system, community organization and policies, as well as individual or community level.

• BMB Reports
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• 제35권6호
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• pp.629-636
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• 2002

Protein kinase CKII (CKII) is required for progression through the cell division cycle. We recently reported that the $\beta$ subunit of protein kinase CKII ($CKII{\beta}$) associates with CKBBP1 that contains the Ring-H2 finger motif in the yeast two-hybrid system. We demonstrate here that the Ring-H2 finger-disrupted mutant of CKBBP1 does not interact with purified $CKII{\beta}$ in vitro, which shows that the Ring-H2 finger motif is critical for direct interaction with $CKII{\beta}$. The CKII holoenzyme is efficiently co-precipitated with the wild-type CKBBP1, but not with the Ring-H2 finger-disrupted CKBBP1, from whole cell extracts when epitope-tagged CKBBP1 is transiently expressed in HeLa cells. Disruption of the Ring-H2 finger motif does not affect the cellular localization of CKBBP1 in HeLa cells. The increased expression of either the wild-type CKBBP1 or Ring-H2 finger-disrupted CKBBP1 does not modulate the protein or the activity levels of CKII in HeLa cells. However, the stable expression of Ring-H2 finger-disrupted CKBBP1 in HeLa cells suppresses cell proliferation and causes the accumulation of the G1/G0 peak of the cell cycle. The Ring-H2 finger motif is required for maximal CKBBP1 phosphorylation by CKII, suggesting that the stable binding of CKBBP1 to CKII is necessary for its efficient phosphorylation. Taken together, these results suggest that the complex formation of $CKII{\beta}$ with CKBBP1 and/or CKII-mediated CKBBP1 phosphorylation is important for the G1/S phase transition of the cell cycle.

• 대한한방내과학회지
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• 제33권2호
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• pp.160-171
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• 2012

Background and Objective : Warfarin is the standard anticoagulation treatment for atrial fibrillation, venous thromboembolism (VTE), and mechanical heart valves. Close monitoring of the International Normalized Ratio (INR) is required due to the drug's very narrow therapeutic window. Many factors can affect INR levels. Drug and food interactions are frequently cited as causes of adverse events with warfarin. We discussed interactions between herbs and warfarin studied in this research. Methods : In this review, PubMed was used to search medical journals. Keywords "warfarin AND interaction" were applied. Results : 55 articles were included. The possibility of correlation between warfarin and single herbal medicines such as Salviae Miltiorrhizae Radix, Angelicae Gigantis Radix, Ginseng Radix Alba, Lycii Fructus, Ginkgo Folium, Menthae Herba, Trigonellae semen was suggested. Furthermore, some herbal compounds interacting with warfarin were reported. The conclusion of studies reporting the effect of herbal medicine on warfarin were controversial due to small size or quality of research. Conculsions : We suggest that we should prescribe therapeutic herbal medicines to patients using warfarin more carefully and do INR follow-up regularly.

• Molecular & Cellular Toxicology
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• 제1권2호
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• pp.130-136
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• 2005

The purpose of this study was to evaluate whether the interactions between maternal folate deficiency and methylenetetrahydrofolate reductase (MTHFR) polymorphism increase the risk of elevated maternal serum homocysteine, short gestation and reduced infant birthweight. Healthy pregnant (n = 170; 24-28 gestational weeks; 20-40 years old) women were analyzed for the MTHFR genotype and serum levels of folate and homocysteine, and were then followed for gestational age and infant birthweight. The mean infant birthweight was highest in mothers carrying MTHFR CC and with a normal folate range, and they were followed by mothers carrying MTHFR CT or TT and a normal range of folate or a folate deficiency. Birthweight was the lowest in mothers whose carrying MTHFR CC with folate deficiency. Using two way ANOVA, we found that folate level and the MTHFR polymorphism interacted to affect birth-weight of infants (p=0.05). Among those mothers carrying MTHFR CC, those with folate deficiency showed a 543 g reduction in infant birthweight compared with those with normal folate levels. However, infant birthweight was no different for mothers, those who with folate deficiency compared to those with normal range of folate among mothers carrying the MTHFR CT or TT genotypes. This study suggests an interaction between maternal serum folate and the MTHFR polymorphisms of the mother on the risk of delivering reduced birthweight offspring. Folate supplementation of folate deficient pregnant women with the MTHFR wild type is suggested to reduce the risk of low birthweight.

• 한국지반공학회논문집
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• 제33권4호
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• pp.47-56
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• 2017

잔교식 안벽의 내진설계는 보통 다중모드 스펙트럼 해석과 같은 단순 동해석 방법을 적용하여 수행된다. 이러한 단순 해석법은 구조물의 한계상태를 평가하는데 유용할 수 있다. 그러나, 과거에 발생한 잔교식 안벽의 지진피해사례를 살펴보면, 기초지반의 변형 또는 지반-말뚝 사이의 동적 상호작용이 구조물의 전체 거동에 큰 영향을 미치는 것으로 나타났다. 이러한 거동은 지반-말뚝-구조물 동적 상호작용을 정밀하게 모사할 수 있는 비선형 유효응력 해석을 수행하여 평가할 수 있다. 본 연구에서는 잔교식 안벽의 내진성능을 평가할 수 있는 3차원 수치 모델링 기법을 선정하고, 이를 Hyogoken Nambu 지진(1995)시 고베항의 잔교식 안벽 피해사례에 적용하여 그 적용성을 검증하였다. 해석결과, 본 연구에서 적용한 수치 모델링 기법이 안벽의 지진피해 거동을 잘 모사할 수 있으며, 지반의 과잉간극수압증가 및 지반-구조물과의 동적 상호작용이 안벽의 지진거동에 큰 영향을 주는 것으로 나타났다.

• 생물정신의학
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• 제7권1호
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• pp.14-20
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• 2000

Recently atypical antipsychotics have been used as first line agent in the treatment of schizophrenia, and also played a significant role in the treatment of many kinds of psychiatric disorders. The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics are well known through preclinical and early clinical trials. However, it is important to note the limitations of the results due to its relatively short experience. Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life, while 1A2 inhibitors such as SSRIs, especially fluvoxamine can increase its duration of action. Carbamazepine should be avoided in a patient on clozapine because of carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the chances of sedation, delirium and respiratory depression. Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but 9-hydroxyrisperidone has similar biological activity as parental drug, so it has little affect on the outcome. Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2 and 2D6 cytochrome enzymes.

• Journal of the Korean Wood Science and Technology
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• 제33권2호통권130호
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• pp.65-71
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• 2005

This study was performed to understand the interaction between Ophiostomataceae and basidiomycetes fungi during cultures, and whether the basidiomycetes fungi inhibit the growth and decolorize dark pigments of blue staining fungi. The conjoint cultivation was studied on 2% malt extract agar. The ability of basidial cultures to decolorize dark pigments of ophiostomatoid fungi was the main characteristics estimated during this study. More than half of basidial cultures were characterized by deadlock interaction with blue staining fungi. In the dual cultures, where basidial partners were presented by Agaricus bisporus(64), Laetiporus sulphureus(L01/89), Trametes versicolor(09) and unknown fungus(02), antagonism was found at the phase of primary contact of colonies. Replacement interaction resulted usually in decreasing dark colour of substrate was observed for 11 basidial cultures that were belonging mainly to white-rot fungi. Among them Abortiporus biennis(123), Antrodiella hoehnelii(S28/91), Bjerkandera fumosa (137), and Gleophyllum odoratum(124) were characterized by the absence of deadlock-phase: they began to grow over dark colonies of their partners just after primary contact. Basidiomycetes did not affect strongly the pigments of Ceratocystis spp. and Leptographium sibirica isolates, but completely decolorized colonies of Ophiostoma ips and to a smaller degree Ophiostoma minus. Antrodiella hoehnelii(S28/91), Bjerkandera fumosa(137), Gleophyllum odoratum(124) and Trametes versicolor(B18/91) cultures were found to be the most active in decreasing dark color of blue staining fungi colonies. The cultures were recommended for further development as agents of biopulping of wood chips and bio-control of blue stain in woods.

• Macromolecular Research
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• 제16권8호
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• pp.725-733
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• 2008

Polyimide (PI) multilayer thin films were prepared by spin-coating from a poly(amic acid) (PAA) and poly(amic acid) ammonium salt (PAAS). PI was prepared from pyromellitic dianhydride (PMDA) and 4,4'-oxydianiline (ODA) PAA. Different compositions of PAAS were prepared by incorporating triethylamine (TEA) into PMDA-ODA PAA in dimethylacetamide. PI multilayer thin films were spin-coated from PMDA-ODA PAA and PAAS. The PAAS comprising cationic and anionic moieties were spherical with a particle size of $20{\sim}40\;nm$. Some particles showed layers with ammonium salts, despite poor ordering. Too much salt obstructed the interaction between the polymer chains and caused phase separation. A small amount of salt did not affect the interactions of the interlayer structure but did interrupt the stacking between chains. Thermogravimetric analysis (TGA) showed that the average decomposition temperature of the thin films was $611^{\circ}C$. All the films showed almost single-step, thermal decomposition behavior. The nanostructure of the multilayer thin films was confirmed by X -ray reflectivity (XRR). The LF 43 film, which was prepared with a 4:3 molar ratio of PMDA and ODA, was comprised of uniformly spherical PAAS particles that influenced the nanostructure of the interlayer by increasing the interaction forces. This result was supported by the atomic force microscopy (AFM) data. It was concluded that the relationship between the uniformity of the PAAS particle shapes and the interaction between the layers affected the optical and thermal properties of PI layered films.

• Molecules and Cells
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• 제39권3호
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• pp.229-241
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• 2016

We have previously reported the role of miR-326-HDAC3 loop in anti-cancer drug-resistance. CAGE, a cancer/testis antigen, regulates the response to anti-cancer drug-resistance by forming a negative feedback loop with miR-200b. Studies investigating the relationship between CAGE and HDAC3 revealed that HDAC3 negatively regulated the expression of CAGE. ChIP assays demonstrated the binding of HDAC3 to the promoter sequences of CAGE. However, CAGE did not affect the expression of HDAC3. We also found that EGFR signaling regulated the expressions of HDAC3 and CAGE. Anti-cancer drug-resistant cancer cell lines show an increased expression of $pEGFR^{Y845}$. HDAC3 was found to negatively regulate the expression of $pEGFR^{Y845}$. CAGE showed an interaction and co-localization with EGFR. It was seen that miR-326, a negative regulator of HDAC3, regulated the expression of CAGE, $pEGFR^{Y845}$, and the interaction between CAGE and EGFR. miR-326 inhibitor induced the binding of HDAC3 to the promoter sequences in anti-cancer drug-resistant $Malme3M^R$ cells, decreasing the tumorigenic potential of $Malme3M^R$ cells in a manner associated with its effect on the expression of HDAC3, CAGE and $pEGFR^{Y845}$. The down-regulation of HDAC3 enhanced the tumorigenic, angiogenic and invasion potential of the anti-cancer drug-sensitive Malme3M cells in CAGE-dependent manner. Studies revealed that $PKC{\delta}$ was responsible for the increased expression of $pEGFR^{Y845}$ and CAGE in $Malme3M^R$ cells. CAGE showed an interaction with $PKC{\delta}$ in $Malme3M^R$ cells. Our results show that HDAC3-CAGE axis can be employed as a target for overcoming resistance to EGFR inhibitors.