• Archives of Pharmacal Research
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• v.27 no.4
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• pp.407-414
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• 2004

The expression of CYP3A4 gene is induced by a variety of structurally unrelated xenobiotics including the antibiotic rifampicin, pregnenolone 16-carbonitrile (PCN), and endogenous hormones, that might mediate through steroid and xenobiotic receptor (SXR) system. The molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood. In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter in human hepatoma HepG2 cells. Also we have investigated to see if SXR is involved in the regulation of CYP3A4 proximal promoter activity in human hepatoma HepG2 cells. HepG2 cells were transfected with a plasmid PCYP3A4-Luc containing ${\~}1kb$ of the CYP3A4 proximal promoter region (-863 to +64 bp) in front of a reporter gene, luciferase, in the presence or absence of pSAP-SXR. In HepG2 cells, CYP3A4 inducers, such as rifampicin, PCN and RU486 showed minimal stimulation of CYP3A4 proximal promoter activity in the absence of SXR and histone deacetylase (HDAC) inhibitors. 4-Dimethylamino-H-[4-(2-hydroxycarbamoylvinyl)benzyl]benzamide (IN2001), a new class HDAC inhibitor significantly increased CYP3A4 proximal promoter activity over untreated control cells and rifampicin concomitant treatment with IN2001 increased further CYP3A4 proximal promoter activity that was stimulated by IN2001 The results of this study demon-strated that both HDAC inhibitors and SXR are essential to increase of CYP3A4 proximal promoter activity by CYP3A4 inducers such as PCN, rifampicin, and RU486. Especially SXR seems to be important for the dose dependent response of CYP3A4 inducing chemicals to stimulate CYP3A4 proximal promoter activity. Also this data suggested that HDAC inhibitors seemed to facilitate the CYP3A4 proximal promoter to be activated by chemicals.

• Archives of Pharmacal Research
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• v.27 no.4
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• pp.396-401
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• 2004

The effects of lipopolysaccharide (LPS) and several cytokines or the c-fos and c-jun mRNA expression were examined in primary cultured astrocytes. Either LPS (500 ng/mL) or inter-feron-$\gamma$ (IFN-$\gamma$ 5 ng/mL) alone increased the level of c-fos mRNA (1 h). However, tumor necro-sis factor-$\alpha$ (TNF-$\alpha$; 10 ng/mL) or interleukin-4 (IL-1$\beta$: 5 ng/mL) alone showed no significant induction of the level of c-fos mRNA. TNF-$\alpha$ showed a potentiating effect in the regulation of LPS-induced c-fos mRNA expression, whereas LPS showed an inhibitory action against IFN-Y-induced c-fos mRNA expression. LPS, but not TNF-$\alpha$, IL-1$\beta$ and IFN-$\gamma$, increased the level of c-jun mRNA (1 h). TNF-$\alpha$ and IFN-$\gamma$ showed an inhibitory action against LPS-induced c-jun mRNA expression. Both phorbol 12-myristate 13-acetate (PMA; 2.5 mM) and forskolin (FSK, 5 mM) increased the c-fos and c-jun mRNA expressions. In addition, the level of c-fos mRNA was expressed in an antagonistic manner when LPS was combined with PMA. When LPS was co-treated with either PMA or FSK, it showed an additive interaction for the induction of c-jun mRNA expression. Our results suggest that LPS and cytokines may be actively involved in the regulation of c-fos and c-jun mRNA expressions in primary cultured astrocytes. Moreover, both the PKA and PKC pathways may regulate the LPS-induced c-fos and c-jun mRNA expressions in different ways.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.873-878
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• 2002

OA-8159, a new Phosphodiesterase (PDE) 5 inhibitor, has exhibited potent erectogenic potential in a penile erection test in rats and anesthetized dogs. In this study, we investigated the mechanism of its erectogenic activity by measuring the activity of OA-8159 against a various PDE isozymes and assessing cGMP and cAMP formation in a rabbit corpus cavernosum in vitro. DA-8159 inhibited the PDE 5 activity in rabbit and human platelets, which the $IC_{50}$ was 5.84$\pm$1.70 nM and 8.25$\pm$2.90 nM, respectively. The $IC_{50}$ of DA-8159 on PDE 1, PDE2, PDE 3 and PDE 6 were 870$\pm$57.4 nM, $101\pm$5 $\mu$M, 52.0$\pm$3.53 $\mu$M and 53.3$\pm$2.47 nM, respectively. This suggests that DA-8159 is a potent, highly selective, competitive inhibitor of PDE 5-catalyzed cGMP hydrolysis. The rates of cGMP hydrolysis catalyzed by human platelets-derived PDE 5 as a function of the cGMP concentration (5~100 nM) and two-fixed DA-8159 concentration (11.3 and 18.8 nM) were investigated in order to characterize the mode of PDE 5 inhibition by DA-8159. DA-8159 increased the apparent 4K_{m}$ value for cGMP hydrolysis but had no effect on the apparent $V_{max}$, indicating a competitive mode of inhibition. DA-8159 increased the cGMP concentrations in the rabbit corpus cavernosum dose dependently. In the presence of sodium nitroprusside (SNP), DA-8159 significantly sti\mulated the accu\mulation of cGMP when compared to the control level. This indicated that the enhancement of a penile erection by DA-8159 involved the relaxation of the cavernosal smooth \muscle by NO-sti\mulated cGMP accu\mulation. In conclusion, DA-8159 is a selective inhibitor of PDE 5-catalyzed cGMP hydrolysis and the enhancement of a penile erection by DA-8159 is mediated by the relaxation of the cavernosal smooth \muscle by the NO-sti\mulated cGMP accu\mulation.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.910-916
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• 2002

Endotoxin tolerance reduces the capacity of monocytes to produce proinflammatory cytokines, results in cellular immune paralysis, and down-regulates the production of helper T (Th)1 type cytokines with a shift toward a Th2 cytokine response. Prostaglandin (PG)E$_2$ in the immune system also results in macrophage inactivation and the suppression of Th1 activation and the enhancement of Th2 activation. However, the inhibitory effects of PGE$_2$ on the altered polarization of the Th cell and macrophage interleukin (IL)-6 production characterized in part by cellular immune paralysis in a state of endotoxin tolerance is unclear. This study was undertaken, using indomethacin, to investigate the role of endogenous PGE$_2$ on the Th cytokines and macrophage IL-6 production in a state of endotoxin tolerance compared to those with endotoxemia mice, wherein, in this latter case, the increased production of proinflammatory cytokines and PGE$_2$ is exhibited. Endotoxemia was induced by injection of lipopolysaccharide (LPS; 10 mg/kg in saline) i.p. once in BALB/c mice, and endotoxin tolerance was induced by pretreatment with LPS (1 mg/kg in saline) injected i.p. daily for two consecutive days and then with LPS 10 mg/kg on day 4. Splenocytes or macrophages were obtained from endotoxemia and endotoxin tolerance models pretreated with indomethacin, and then cytokine production was induced by Con A-stimulated splenocytes for the Th cytokine assays and LPS-stimulated macrophages for the IL-6 assay. Our results showed that endotoxemia led to significantly reduced IL-2 and IL-4 production, to significantly increased IL-6 production, whereas interferon $(IFN)-{\gamma}$ production was not affected. Indomethacin in the case of endotoxemia markedly attenuated $IFN-{\gamma}$ and IL-6 production and didnt reverse IL-2 and IL-4 production. Endotoxin tolerance resulted in the significantly reduced production of IL-2 and $IFN-{\gamma}$ and the significantly increased production of IL-4 and IL-6. Indomethacin in endotoxin tolerance greatly augmented IL-2 production, significantly decreased IL-4 production, and slightly attenuated IL-6 production. These findings indicate that endogenous PGE$_2$ may mediate the suppressed Th1 type immune response, with a shift toward a Th2 cytokine response in a state of endotoxin tolerance, whereas endotoxemia may be regulated differentially. Also, endogenous PGE$_2$ may mediate macrophage IL-6 production in the case of endotoxemia to a greater extent than in the case of endotoxin tolerance.

• Korean Journal of Clinical Pharmacy
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• v.18 no.2
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• pp.114-119
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• 2008

Alendronate is a bisphosphonate that selectively inhibits osteoclast-mediated bone resorption. Dosing convenience is an important element for the enhancement of patient compliance and the effective management of osteoporosis. The purpose of this study was to compare the effectiveness and compliance among alendronate pharmaceutical products (oral once-weekly alendronate 70 mg, daily alendronate 10 mg, and once-weekly alendronate 70 mg with Vitamin $D_3$ 2800 IU) in terms of the change in bone mineral density (BMD), biochemical markers, and compliance estimates. A retrospective chart review was conducted in patients with osteoporosis who received alendronate 70 mg (Group 1), alendronate 10 mg (Group 2), or alendronate 70 mg with Vitamin D3 2800 IU (Group 3) at the endocrinology department of a hospital in Korea from Jan. 1, 1998 to Mar. 31, 2008. The primary endpoints were the increases in spine antero-posterior BMD T-score and femur trochanter BMD T-score, and the compliance of alendronate products. Secondary endpoints included changes in bone turnover-related biochemical markers including bone-specific alkaline phosphatase, urinary N-terminal telopeptides (NTX) and osteocalcin, and in serum vitamin $D_3$ concentration. There was no statistical difference in the BMD increase among the three alendronate products; spine BMD T-score increased by $0.49{\pm}0.52$, $0.39{\pm}0.48$ and $0.50{\pm}0.41$, and femur trochanter BMD T-score by $0.29{\pm}0.42$, $0.21{\pm}0.53$ and $0.24{\pm}0.22$ in Group 1, 2 and 3, respectively. With respect to the increases in femur trochanter BMD T-score and the decreases in NTX and osteocalcin, 70 mg once-weekly group was remarkably superior to 10 mg daily group (p < 0.05) The compliance of 70 mg once-weekly group was significantly higher than that of 10 mg daily treatment group (p < 0.001). In conclusion, all three alendronate treatment groups were equivalent in effectiveness, and the compliance of 70 mg once-weekly group was better than that of 10 mg daily treatment group.

• Korean Journal of Clinical Pharmacy
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• v.25 no.2
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• pp.74-79
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• 2015

Objective: Treatment with sulfonylureas in combination with metformin improves glycemic control in type 2 diabetes mellitus (T2DM), but is associated with hypoglycemia and weight gain. This retrospective study aims to compare the effectiveness of dipeptidylpeptidase-4 (DPP-4) inhibitors and sulfonylureas as an add-on therapy to metformin in patients with T2DM. Methods: Data from medical records of 355 T2DM patients received therapy either DPP-4 inhibitors (DPP-4 inhibitor group) or sulfonylurea (SU group) in combination with metformin from 1 March 2009 to 30 September 2011 were retrospectively reviewed. Of total 355 patients, 231 patients were in DPP-4 inhibitor group and 124 patients were in SU group. Baseline Hemoglobin $A_{1c}$ ($HbA_{1c}$) level in SU group was higher than DPP-4 inhibitor group with a statistically significant difference (8.6% vs. 7.8%). Comparative analysis between DPP-4 inhibitor group and SU group was performed for $HbA_{1c}$ values, amounts of $HbA_{1c}$ changes, and rates of $HbA_{1c}$ changes from baseline at 6-month intervals and incidence rates of major cardiocerebral events. Results: SU group showed larger $HbA_{1c}$ changes in both amounts and rates compared to DPP-4 inhibitor group, although statistical significance was not found in all study periods. Proportions of patients with stable $HbA_{1c}$ <6.5% or 7% were significantly higher in DPP-4 inhibitor group than SU group (<6.5%: 30.4% vs. 13.4%, <7%: 72.3% vs. 41.2%). Time to achieve stable $HbA_{1c}$ <6.5% was not significantly different, but time to achieve stable $HbA_{1c}$ <7% was shorter in DPP4 inhibitor group than SU group with a significant difference. The incidence rate of cardiocerebral events in group of patients with or without previous events was 1.7%, not significantly lower than that in DPP-4 inhibitor group (4.0%). For newly encountered cardiocerebral events during the treatment, incidence rates of two groups did not differ significantly. Conclusion: DPP-4 inhibitors were as effective as sulfonylureas in achieving the $HbA_{1c}$ goal of less than 6.5% or 7% and cardiocerebral event rates did not differ between the two drugs.

• Journal of the East Asian Society of Dietary Life
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• v.23 no.6
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• pp.733-741
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• 2013

The objective of this study is to prepare functional beverages with dandelion (Taraxacum mongolicum H.) extracts. As a result of sensory evaluation, 10% water extracts of dandelion containing beverage, which was the highest value of overall preference, was chosen for further examinations. Moisture content of developed beverage was $99.6{\pm}0.5%$ and sugar content decreased from 0.8 to $0.7^{\circ}Brix$ whereas pH increased from 3.4 to 3.7 by addition of 10% dandelion extracts. Total phenolic and flavonoid contents of beverage were $295.8{\pm}5.8mg/L$ and $122.8{\pm}18.4mg/L$, respectively. The developed beverage showed higher DPPH radical scavenging activity of $98.2{\pm}0.6%$ than the beverage without extract. Moreover, concentration of silibinin in the T. mongolicum H. beverage was $0.3{\pm}0.04mg/L$.

• Proceedings of the International Microelectronics And Packaging Society Conference
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• 2001.11a
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• pp.37-39
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• 2001

21세기의 벽두부터 국내외적으로 활발히 논의되고 있는 나노기술에 대한 정의를 생각해보는 것으로부터 우리가 나아갈 방향을 살펴보고자 한다. 나노기술이란, 원자 하나 하나 혹은 분자단위의 조작을 통해 1~100nm정도의 범위 안에서 근본적으로 새로운 물질이나 구조체를 만들어 내는 기술을 말한다. 즉 앞으로 우리는 경험해 보지 못한 새로운 현상에 대한 이해를 할 수 있어야 하고, 새로운 물질 자체를 다룰 수 있는 방법이 우리가 해야 할 구체적인 일이 될 것이란 말이 된다. 뿐만 아니라 나노기술은 종래의 정보.통신.전자 분야에서 주로 추구하던 마이크로화와 달리 재료, 기계, 전자, 의학, 약학, 에너지, 환경, 화학, 생물학, 농학, 정보, 보안기술 등 과학기술 분야 전반을 위시하여 사회분야가지 새로운 인식과 철학적인 이해가 필요하게 되었다. 21세기를 맞은 인류가 나아갈 방향을 나노세계에 대한 도전으로 보아야 하며, 과학기술의 새로운 틀을 제공할 것 임에 틀림 없다. 그러나, 이와 같은 나노기술의 출발점을 살펴보면 VLSI기술로 통칭할 수 있는 마이크로전자소자 기술이란 점이다. 국내의 VLSI기술은 메모리기술이라고 해도 과언이 아닐 것이다. 문제는 종래의 메모리기술은 대규모 투자와 집중적인 인력양성을 통해서 세계 최고 수준에 도달 할 수 있었다. 그러나 여기까지 오는 동안 사식 우리는 선진국의 뒷꽁무니를 혼신의 힘을 다해 뒤쫓아 온 결과라고 보아도 틀리지 않는다. 즉, 앞선자를 보고 뒤쫓는 사람은 갈방향과 목표가 분명하므로 최선을 다하면 따라 잡을 수 있다. 그런데 나노기술은 앞선 사람이 없다는 점이 큰 차이이다 따라서 뒷껑무니를 쫓아가는 습성을 가지고는 개척해 나갈 수 없다는 점을 깨닫지 않으면 안된다. 그런 점에서 이 시간 나노기술의 국내외 현황을 살펴보고 우리가 어떻게 할 것인가를 생각해 보는데 의미가 있을 것이다.하여 분석한 결과 기존의 제한된 RICH-DP는 실시간 서비스에 대한 처리율이 낮아지며 서비스 시간이 보장되지 못했다. 따라서 실시간 서비스에 대한 새로운 제안된 기법을 제안하고 성능 평가한 결과 기존의 RICH-DP보다 성능이 향상됨을 확인 할 수 있었다.(actual world)에서 가상 관성 세계(possible inertia would)로 변화시켜서, 완수동사의 종결점(ending point)을 현실세계에서 가상의 미래 세계로 움직이는 역할을 한다. 결과적으로, IMP는 완수동사의 닫힌 완료 관점을 현실세계에서는 열린 미완료 관점으로 변환시키되, 가상 관성 세계에서는 그대로 닫힌 관점으로 유지 시키는 효과를 가진다. 한국어와 영어의 관점 변환 구문의 차이는 각 언어의 지속부사구의 어휘 목록의 전제(presupposition)의 차이로 설명된다. 본 논문은 영어의 지속부사구는 논항의 하위간격This paper will describe the application based on this approach developed by the authors in the FLEX EXPRIT IV n$^{\circ}$EP29158 in the Work-package "Knowledge Extraction & Data mining"where the information captured from digital newspapers is extracted and reused in tourist information context.terpolation performance of CNN was relatively better than NN.콩과 자연 콩이 성분 분석에서 차이를 나타내지 않았다는 점, 네 번째. 쥐를 통한 다양섭취 실험에서 아무런 이상 반응이 없었다는 점등의 결과를 기준으로 알레르기에 대한 개별 검사 없이 안전한

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.158-166
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• 2013

Background: Colorectal cancer shows a significant increase in South Korea due to westernization of diet, lack of dietary fiber, drinking and smoking, irregular defecation. There are surgery, chemotherapy, radiation therapy in treatment of colorectal cancer. There may be a medication errors in the process of chemotherapy because of its high toxicity, narrow therapeutic index and the health status of cancer patients. Consequently medication errors can cause increasing the risk of death, prolonging hospital stay and increasing the cost. Among medication errors on medication use process, prescribing errors are of particular concern due to higher risk of serious consequences. It is important for pharmacist to prevent the prescribing errors before reaching patient. Therefore we analyzed the prescriptions of colorectal cancer, classified prescribing errors, suggested guideline to reduce prescribing errors and verified the importance of pharmacist's role in prevention of medication errors activity. Methods: We collected the numbers of prescriptions of colorectal cancer(n=2,373) through anti cancer management program and EMR and analyzed the errors of prescriptions by categories from Oct 1st 2011 to Sep 30th 2012 at Chungbuk National University Hospital. We reviewed the prescriptions as follows - patients' characteristics, the result of test, previous prescriptions, characteristics of antineoplastic agents and patients' allergy, drug sensitivity, adverse events. Prescriptions are classified into inpatient and outpatient and analyzed the errors of prescriptions by categories (dosage form, dose, input, diluents, regimen, product). Results: Total prescription number of inpatient and outpatient of colorectal cancer was 1,193 and 1,180 and that of errors was 107(9%) and 22(1.9%), respectively. In case of errors of categories, the number of errors of dosage form is 69 and 8, errors of dose is 15 and 5, errors of input is 9 and 9 in inpatient and outpatient prescriptions, respectively. Errors of diluents is 8, errors of regimen is 3, errors of product is 3 in only inpatient prescriptions. In case of errors of categories by inpatient department, the number of errors of dosage form is 34 and 35, errors of dose is 7 and 8, errors of input is 6 and 3, errors of diluents is 4 and 4, errors of regimen is 2 and 1, errors of product is 2 and 1 in SG and HO, respectively. In case of outpatient department, the number of errors of dosage form is 8 in HO, errors of dose is 5 in HO, errors of input is 5 and 4 in SG and HO, respectively. Conclusions: The rate of errors of inpatient is higher than that of outpatient. Junior doctors are engaged in prescriptions of inpatient and pharmacist need to pay attention to review all prescriptions. If prescribing errors are discovered, pharmacist should contact the prescriber and correct the errors without delay. The guideline to reduce prescribing errors might be upgrading software of anti cancer management program, education for physicians as well as pharmacists and calling prescriber's attention to preventing recurrence of errors.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.151-157
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• 2013

Purpose: Warfarin is the most widely used anticoagulant drug for preventing cardiovascular diseases after ischemic stroke and thromboembolism related to atrial fibrillation, artificial heart valves, deep vein thrombosis, and pulmonary embolism. Warfarin is commonly used in combination with other drugs such as diuretics in order to treat the comorbidity. Although several warfarin-diuretics interactions have been reported, the results are conflicting. Therefore, the initial aim of this study was to identify the effects of diuretics on the warfarin response in patients with atrial fibrillation. Methods: One hundred forty six patients with atrial fibrillation who were on anticoagulation therapy with warfarin and maintained INR levels of 2-3 for three consecutive times were followed up, retrospectively. Stable warfarin doses and INR per stable warfarin dose were compared according to age, gender, comorbidity, and concurrent medication. The stable warfarin dose was defined as the maintenance dose of warfarin of the measured patient whose INR was within the target INR range more than 3 times consecutively. Results: The differences of stable warfarin doses in patients with ($3.22{\pm}1.21$ mg/day) and without ($3.58{\pm}1.14$ mg/day) diuretics were marginally significant (P=0.069). On the other hand, stable warfarin doses were $2.97{\pm}1.10$ mg/day in patients with thiazide (n=36) and $3.58{\pm}1.14$ mg/day in patients without diuretics (n=82), which was statistically significant (p=0.009). INR values per stable warfarin dose in patients with diuretics and thiazide were $0.84{\pm}0.31$ and $0.90{\pm}0.34$, respectively, which were statistically different from those without diuretics ($0.72{\pm}0.21$, P=0.010 and P=0.006, respectively). Age, gender, and concurrent use of thiazide diuretics were found to have significant influence on the warfarin response from multivariate analysis. Conclusion: Our study showed that the concurrent use of thiazide diuretics could increase the response of warfarin in patient with atrial fibrillation. Therefore, clinicians should be aware that warfarin dose needs to be adjusted when it is used with thiazide diuretics concomitantly.