• Biomolecules & Therapeutics
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• 제15권2호
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• pp.102-107
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• 2007

Cimetidine, a substrate for P-glycoprotein (P-gp), is a well known drug interacting with a variety of drugs and results in alteration of pharmacokinetic parameters by concomitant administration. The aim of present study was to investigate whether cimetidine affects the transport of various quinolone antibiotics in human colorectal cancer cell line (Caco-2) system which has been typically used to investigate drug transport via P-gp. The apparent permeability coefficients (P$_{app}$) value of 9 quinolone antibiotics in the co-treatment with cimetidine was examined. Apical to basolateral (AP-to-BL) transport of fleroxacin in the co-treatment with cimetidine was increased to 1.5-fold (p<0.01) compared with that of fleroxacin alone, whereas basolateral to apical (BL-to-AP) transport of fleroxacin was decreased to 0.83-fold significantly (p<0.05). Ofloxacin was decreased to 0.8-fold (p<0.01) and 0.72-fold (p<0.01) significantly in AP-to-BL and BL-to-AP direction, respectively by cimetidine cotreatment. The P$_{app}$ values of gatifloxacin, moxifloxacin, ciprofloxacin and rufloxacin also were changed by cimetidine. These results have a potential that cimetidine influences on the pharmacokinetics of quinolone antibiotics. It suggests that careful drug monitoring and dosage adjustment may be necessary during the co-administration of quinolone antibiotics with cimetidine.

• 약학회지
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• 제54권4호
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• pp.258-269
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• 2010

As people are easy to access the National Health Insurance, medical health service has been increased. It contributed to extend human's average life expectancy and to get better health care. But also increased unnecessary health service or inappropriate drug use. Therefore, DUR (Drug Use Review) is needed to induce appropriate drug use. The purpose of this study is to evaluate outpatient prescriptions by General Practitioner (GP) and Specialized Practitioner, especially indication for ENT referral including common cold which is the frequent indications that have patient see doctor. This study was reviewed retrospectively prescriptions for ENT referral collected at the A pharmacy for ENT Clinic in Cheong-Ju, B pharmacy for GP Clinic in BoEun from Feb 2nd, 2009 to Feb 28th, 2009. Each pharmacy located closed to the each enrolled clinic. The numbers of collected prescriptions were each A pharmacy (n=2501), B pharmacy (n=1343). This study was classified Drug Related Problems (DRPs) those prescriptions had as total 6 groups according to following 6 categories; 1) Unnecessary Drug, 2) Wrong Drug, 3) Low Dose, 4) Overdose, 5) Wrong Instruction, 6) Wrong Combination. In results, Specialized Practitioner's prescriptions had more DRPs than General Practitioner's prescriptions (ENT 155.34% vs GP 130.01%). In detail, Specialized Practitioner's prescriptions had more DRPs in Low Dose (ENT 16.95% vs GP 4.77%), Overdose (ENT 6.72% vs G.P 5.51%), Wrong Instruction (ENT 7.91% vs GP 5.81%), Wrong Combination (ENT 29.31% vs GP 25.09%). These DRPs would be caused from lack of consideration for dosage and drug interaction. General Practitioner's prescriptions had more DRPs in Unnecessary Drug (ENT 70.37% vs GP 78.85%), Wrong drug (ENT 4.12% vs GP 9.98%). These DRPs would be associated with drug selection. This study was assumed that Specialized Practitioner is better prescriber than General Practitioner because Specialized Practitioner complete additional intern and residency training. But, Specialized Practitioner is not always better prescriber than General Practitioner. Furthermore, prescriptions of both Specialized Practitioner and General Practitioner had many problems. In conclusion, It could be cut down the excessive medical expense and expected more efficient medical care by reducing DRPs, thus contributing to the improvement of national health. In order to pharmacist must have good professional ability of pharmacotherapy to help the physician for the drug selection.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.297-303
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• 2007

The purposes of this study were to clarify the involvement of P-glycoprotein (P-gp) in the efflux of levosulpiride in knockout mice that lack the mdr1a1b gene and to evaluate the relationship between the genetic polymorphisms in MDR1 gene (exon 21) and levosulpiride disposition in healthy Korean subjects. After oral administration ($10\;{\mu}g/g$) of levosulpiride to mdr1a/1b(-/-) and wild-type mice, plasma and brain samples were obtained at 45 min. We also investigated the genotype for MDR1 (exon 21) gene in humans using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A single oral dose of 25 mg levosulpiride was administered to 58 healthy subjects, who were based on the MDR1 genotype for the G2677T SNP. Blood samples were taken up to 36 hr after dosing. The concentrations of levosulpiride in mouse plasma and brain were statistically significant difference between the two animal groups (P<0.05). In addition, the average brain-to-plasma concentration ratio (Kp) of levosulpiride was 3.4-fold (P<0.01) higher in the mdr1a/1b(-/-) mice compared with the wild-type mice. We also found that the values of $AUC_{0-{\infty}$, partial AUC ($AUC_{0-4h}$) and $C_{max}$ were significantly different between homozygous 2677TT subjects and the subjects with at least one wild-type allele (GG and GT subjects, P=0.012 for $AUC_{0-{\infty}$; P=0.008 for $AUC_{0-4h}$; P=0.038 for $C_{max}$). The results confirm that levosulpiride is a P-gp substrate in vivo, and clearly demonstrate the effect of SNP 2677G>T in exon 21 of the MDR1 gene on levosulpiride disposition.

• 대한바이러스학회지
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• 제28권4호
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• pp.383-391
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• 1998

A murine monoclonal antibody (mAb) specific for the envelope glycoprotein gp120 of human immunodeficiency virus type-I (HIV -1) was chemically coupled to pokeweed antiviral protein (PAP) from Phytolacca americana. The immunotoxin was purified by FPLC using S200 colum. The purified immunotoxin efficiently bound to HIV-infected T cells as evidenced by fluorescenceactivated cell sorter analysis. The immunotoxin selectively killed human T lymphoid lines infected with $HIV-1_{IIIB}$ at less than 250 pM of the immunotoxin cells, while PAP or mAb alone did not have any significant effect on infected cells. The uninfected control T cell lines were not affected. Human cells infected with HIV-2 or other HIV-1 strains were not killed, suggesting that the killing depends completely on the antibody used for coupling. These in vitro results suggest that the PAP-mAb conjugate may be used to selectively remove cells expressing viral antigens from individuals infected with HIV.

• Journal of Microbiology and Biotechnology
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• 제20권6호
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• pp.1022-1026
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• 2010

The different cleavage patterns of pYBamy59 plasmid isolated from E. coli $DH5{\alpha}$ and B. longum MG1 by the cell extract of B. longum MG1 suggested that the main reason for its low transformation efficiency was related to the restriction modification (R-M) system. To confirm the correlation between the R-M system and transformation efficiency, in vitro methylation and site-directed mutagenesis were performed in pYBamy59. Sequence analysis of pYBamy59 fragments digested by the cell extract of B. longum MG1 revealed that all fragments were generated by restriction of the sequence recognized by SacII endonuclease. When pYBamy59 from E. coli was methylated in vitro by CpG or GpC methyltransferase, it was protected from SacII digestion. Site-directed mutagenesis, which removed SacII sites from pYBamy59, or in vitro methylation of pYBamy59 showed 8- to 15-fold increases in the transformation efficiency over intact pYBamy59. Modification of the SacII-related R-M system in B. longum MG1 and in vitro methylation in pYBamy 59 can improve the transformation efficiency in this strain. The results showed that the R-M system is a factor to limit introduction of exogenous DNA, and in vitro modification is a convenient method to overcome the barrier of the R-M system for transformation.

• Restorative Dentistry and Endodontics
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• 제42권4호
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• pp.273-281
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• 2017

Objectives: The aims of this study were to quantify tug-back by measuring the pulling force and investigate the correlation of clinical tug-back pulling force with in vitro gutta-percha (GP) cone adaptation score using micro-computed tomography (${\mu}CT$). Materials and Methods: Twenty-eight roots from human single-rooted teeth were divided into 2 groups. In the ProTaper Next (PTN) group, root canals were prepared with PTN, and in the ProFile (PF) group, root canals were prepared using PF (n = 14). The degree of tug-back was scored after selecting taper-matched GP cones. A novel method using a spring balance was designed to quantify the tug-back by measuring the pulling force. The correlation between tug-back scores, pulling force, and percentage of the gutta-percha occupied area (pGPOA) within apical 3 mm was investigated using ${\mu}CT$. The data were analyzed using Pearson's correlation analysis, one-way analysis of variance (ANOVA) and Tukey's test. Results: Specimens with a strong tug-back had a mean pulling force of 1.24 N (range, 0.15-1.70 N). This study showed a positive correlation between tug-back score, pulling force, and pGPOA. However, there was no significant difference in these factors between the PTN and PF groups. Regardless of the groups, pGPOA and pulling force were significantly higher in the specimens with a higher tug-back score (p < 0.05). Conclusions: The degree of subjective tug-back was a definitive determinant for master cone adaptation in the root canal. The use of the tug-back scoring system and pulling force allows the interpretation of subjective tug-back in a more objective and quantitative manner.

• 한국환경보건학회지
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• 제38권5호
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• pp.380-385
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• 2012

Background: Manganese (Mn) has been found to increase the signal intensity of the globus pallidus (GP) on T1-weighted magnetic resonance images (MRI). We performed this study in order to determine the features of liver disease that correlate with pallidal signal intensities. Methods: We assessed blood Mn levels and pallidal signals in T1-weighted MRI in 49 patients with liver cirrhosis and 23 healthy controls. Results: Increased signal intensity in the GP was observed in 30 of 49 (61.2%) patients with liver cirrhosis, with the pallidal index (PI) in patients with Child-Pugh classes B and C differing significantly from the PI in controls. Multiple linear regression analysis showed that blood Mn concentrations and Child-Pugh scores in cirrhotics were significantly associated with increased PI after controlling for other confounders (p<0.05 each). Conclusions: Pallidal signals on T1-weighted MRI are mainly observed in advanced liver cirrhosis. The present study suggests that advanced liver cirrhosis may be a human model for manganism.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9249-9258
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• 2014

Background: The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur-NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrugresistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo. Materials and Methods: First, we determined the MDR-reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions. Results: The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions. Conclusions: Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.

• 한국지하수토양환경학회지:지하수토양환경
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• 제27권4호
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• pp.1-9
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• 2022

This study was conducted to supplement new-normal strategies on management plans of rural groundwater resources in the era of Post COVID-19. Global outbreak of COVID-19 has damaged across all areas including public policy, economics, industrial services, and others without exception, which has resulted in establishing new-normal strategies in order to restore balance and functions as for these areas. The new-normal ones were represented as enhancing preventative management on infectious diseases, expanding non face-to-face services, enhancing protective trades and food securities, and preparing growth policies on public services using the 4^th industrial revolution techniques. In this study, G-WASH_AD (Groundwater supply, sanitation, and hygiene with attraction and digitization) was suggested to be new-normal strategies on rural groundwater resources. The G-WASH_AD was consisted of three detailed action plans: a preventative plan on waterborne-diseases of groundwater (PP), a groundwater-tourism plan with rural heritage (GP), and an application plan of the 4^th industrial revolution techniques to groundwater facilities and its data (P4). The PP can contribute to protect human health from waterborne-diseases and minimize hazardous effects on crop cultivation. The GP accompanied with high-quality groundwater resources is able to strengthen rural tourism, to promote marketing activities on local agricultural products, and to increase household incomes of rural communities. The P4 can reinforce fast, comfortable, and scientific management on groundwater facilities and its data, creating a virtuous cycle between innovative management on groundwater and growth of technology related to it. Results of the G-WASH_AD strategies can encourage a green growth engine in field of rural groundwater management keeping up with Post COVID-19.

• Korean Journal of Radiology
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• 제22권12호
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• pp.2017-2025
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• 2021

Objective: To evaluate the accuracy and clinical efficacy of a hybrid Greulich-Pyle (GP) and modified Tanner-Whitehouse (TW) artificial intelligence (AI) model for bone age assessment. Materials and Methods: A deep learning-based model was trained on an open dataset of multiple ethnicities. A total of 102 hand radiographs (51 male and 51 female; mean age ± standard deviation = 10.95 ± 2.37 years) from a single institution were selected for external validation. Three human experts performed bone age assessments based on the GP atlas to develop a reference standard. Two study radiologists performed bone age assessments with and without AI model assistance in two separate sessions, for which the reading time was recorded. The performance of the AI software was assessed by comparing the mean absolute difference between the AI-calculated bone age and the reference standard. The reading time was compared between reading with and without AI using a paired t test. Furthermore, the reliability between the two study radiologists' bone age assessments was assessed using intraclass correlation coefficients (ICCs), and the results were compared between reading with and without AI. Results: The bone ages assessed by the experts and the AI model were not significantly different (11.39 ± 2.74 years and 11.35 ± 2.76 years, respectively, p = 0.31). The mean absolute difference was 0.39 years (95% confidence interval, 0.33-0.45 years) between the automated AI assessment and the reference standard. The mean reading time of the two study radiologists was reduced from 54.29 to 35.37 seconds with AI model assistance (p < 0.001). The ICC of the two study radiologists slightly increased with AI model assistance (from 0.945 to 0.990). Conclusion: The proposed AI model was accurate for assessing bone age. Furthermore, this model appeared to enhance the clinical efficacy by reducing the reading time and improving the inter-observer reliability.