• Clinical and Experimental Pediatrics
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• v.60 no.6
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• pp.175-180
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• 2017

Purpose: Plasma level of B-type natriuretic peptide (BNP), an emerging, sensitive, and specific biomarker of hemodynamically significant patent ductus arteriosus (PDA), rapidly decreases in infants receiving cyclooxygenase inhibitors for ductal closure. We investigated the usefulness of serial BNP measurement as a guide for individual identification of early constrictive responses to ibuprofen in preterm infants with symptomatic PDA (sPDA). Methods: Before March 2010, the standard course of pharmacological treatment was initiated with indomethacin (or ibuprofen) and routinely followed by 2 additional doses at intervals of 24 hours. After April 2010, individualized pharmacological treatment was used, starting with the first dose of ibuprofen and withholding additional ibuprofen doses if the BNP concentration was <600 pg/mL and clinical symptoms of PDA improved. Results: The BNP-guided group received significantly fewer doses of ibuprofen than the standard group did during the first course of treatment and the entire study period. The need for further doses of cyclooxygenase inhibitors and for surgical ligation was not significantly different between the 2 groups. No significant differences were seen in clinical outcomes and/or complications related to sPDA and/or pharmacological treatment. Conclusion: Individualized BNP-guided pharmacological treatment may be used clinically to avoid unnecessary doses of cyclooxygenase inhibitors without increasing the ductal closure failure and the short-term morbidity related to sPDA.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.313-322
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• 2013

Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration significantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and significantly blocked increases of TH expression in the locus coeruleus (LC). It also significantly enhanced the total number of line crossing in the open-field test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these findings indicate that the administration of CTN prior to high-dose exogenous CORT significantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.581-589
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• 2006

These studies were investigated the effects of Gamicheungpyehwadam-tang (CPHDT) on immune-cell regulation in association with bronchial asthma in OVA-induced mouse model. The administration of 400 mg/kg CPHDT significantly reduced the number of total cells in lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model. The administration of 400 mg/kg CPHDT significantly reduced $CD3^+,{\;}CD19^+$and $CD3^+,{\;}CD69^+$ cell numbers separated from lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model. CPHDT significantly reduced $CD3^+/CCR3^+,{\;}CD4^+,{\;}B220^+/IgE^+$, and $CD3^+/DX5^+$ cell numbers separated from lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model in a dose dependent manner, However, CPHDT significantly reduced $CD8^+$ cell numbers from only lung and spleen. The administration of CPHDT significantly reduced $NK^+$ cell numbers separated from lung of OVA-induced bronchial asthma mouse model in all concentrations, but 200 mg/kg CPHDT reduced $NK^+$ cell numbers separated from peripheral lymph node. These results suggest that CPHDT has anti-asthma and anti-allergy effects. In addition to, CPHDT may be useful treatment of asthma based on the further studies about the individual efficacy search of the components of CPHDT and the adding of variety drugs to CPHDT.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.545-552
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• 2005

The major protocol features of the rodent uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. The rodents were ovariectomized under general anesthesia via bilateral flank incisions and randomly assigned to groups of 5 animals. Chemicals were DEHP, DBP, BPA and NP, were injected sc once daily with combinations of chemicals treatments for 3 days. In the results, the reported estrogenic chemicals DEHP and DBP were both negative in the single dose treatments. But, in the combinations of chemicals treatments, DEHP and DBP increased in bud number of mammary gland. Treatment of ovariectomized mice with combinations of other chemicals resulted in uterine and vaginal hyperplasia. The additive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and DBP treatment. the competitive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and nonylphenol, $17{\beta}$-Bestradiol and bisphenol-A treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. it provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and conform the need for rigorous attention to experimental design and criteria for assessing estrogenic activity.

• Proceedings of the Korean Radioactive Waste Society Conference
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• 2003.11a
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• pp.229-232
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• 2003

A waste container, one of the key compartments in a multi-barrier system for a potential high level radioactive waste (HLW) repository in Korea ensures the mechanical stability against the lithostatic pressure of a deep geologic strata and the swelling pressure of the bentonite buffer. Also, it prohibits potential release of radionuclides for a certain period of time. before it is corroded by impurities. Even though the materials of a waste container is carefully chosen and all manufacturing processes are under heavy quality assurance, there might be a slight chance of intial defects in a waste container. Also, during the deposition of a waste container in a repository, there might be a chance of an incident affecting the integrity of a waste container. In this study, the FEP's and the scenarios over radiological impact of a potential initial waste container defect was developed. Then the total system performance assessment on this initial waste container failure (ICF) scenario was carried out by the MASCOT-K, one of the probabilistic safety assessment tools KAERI has developed. Results show that for the data set studied in this paper, the annual individual dose by the ICF scenario well meets the KINS regulation.

• Korean Journal of Community Nutrition
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• v.17 no.6
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• pp.795-804
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• 2012

This study aimed to examine associations between milk intake and metabolic syndrome. The subjects included 1,928 males and 3,103 females, aged 19 to 64 years, from the data of 'The Korean National Health and Nutrition Survey 2007-2010'. Daily intake of milk and dairy products was obtained by a 24 hour dietary recall method and divided into two categories by equivalent weight of one serving. The average individual intakes of milk and dairy products were 59.4 g and 74.1 g per day respectively. Milk intake was inversely associated with metabolic syndrome (OR: 0.69, 95% CI: 0.54~0.89), central obesity (OR: 0.75, 95% CI: 0.62~0.91), and hypertriglyceridemia (OR: 0.73, 95% CI: 0.59~0.90). The total intake of dairy products was also inversely associated with metabolic syndrome (OR: 0.74, 95% CI 0.60~0.92), central obesity (OR: 0.73, 95% CI: 0.62~0.86), hypertension (OR: 0.80, 95% CI: 0.65~0.99). The association between intakes of milk and dairy products and metabolic syndrome was significant in women, but not in men. These results indicate that increased consumption of milk and its products is associated with a reduced likelihood of metabolic syndrome and metabolic syndrome risk factors. Further research on causal relationship and dose-response association between milk intake and metabolic syndrome risk is necessary prior to applying the observed results in nutrition policies and programs to prevent the metabolic syndrome.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.1
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• pp.1-15
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• 2008

Objective : Skin aging is commonly observed in patients with diabetes mellitus, which can be accessed by the amount of skin collagen and matrix metalloproteinase-1 (MMP-1). In the present study, anti-skin-aging effects of Root Cortex of Paeonia Suffruticosa Andrews (PSA), which has been widely used to treat diabetes mellitus, are investigated. Methods : Streptozotocin (STZ) was intraperitoneally injected to rats to induce diabetes. Body weights, feed intake, organ weights, blood glucose, and other biochemical index are determined in both normal and diabetic rats. In order to study the effect of PSA on skin aging, the amount of skin collagen was measured in diabetic rats after PSA treatments. Also, MMP-1 synthesis in UVB-irradiated human skin fibroblasts was investigated. Results : 1. When PSA was administered to STZ-induced diabetic rats, feed intake was significantly increased and blood glucose and total cholesterol were decreased in a dose-dependent manner. However, there are no differences in individual organ weights, GOT, and GPT. 2. A decrease of skin collagen in diabetic rats was significantly suppressed when PSA was treated. 3. PSA also inhibited MMP-1 synthesis in UVB-irradiated normal human skin fibroblasts, similar to retinoid, a well-known effective anti-skin-aging substance. Conclusion: PSA suppressed a collagen decrease in diabetic rats and inhibited MMP-1 synthesis in UVB-irradiated human skin fibroblasts. Therefore, the treatment of PSA is very effective to slow down the skin aging process.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.2 no.4
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• pp.253-262
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• 2004

Construction of tunnels in a deep crystalline host rock for a potential High-Level Radioactive Waste(HLW) repository inevitably generates an excavation disturbed zone (EDZ). There have been a series of debates on whether a permeability in an EDZ increases or not and what would be the maximum depth of an EDZ. Recent studies show mixed opinions on permeability. However, there has been an international consensus on the thickness of an EDZ; 30 cm for TBM and 1 meter for controlled blast. One of the impacts of an EDZ is on determining the distance between adjacent deposition holes. The void gap by the excavation hinders relaxation of temperature profiles so that the current Korean reference designing distance between holes should be stretched out more to keep the maximum temperature in a buffer region below 100 degrees Celsius. The other impact of an EDZ is on the long-term post closure radiological safety. To estimate the impact, the reference scenario, the well scenario, is chosen. Released nuclides diffuse through a bentonite buffer region experiencing strong sorption and reach a fracture surrounded by a porous medium. Inside a fractured porous region, radionuclides migrate by advection and dispersion with matrix diffusion into a porous medium. Finally, they reach a well assumed to be a source of potable water for local residents. The annual individual dose is assessed on this well scenario to find out the significance of an EDZ. A profound sensitivity study was performed, but all results show that the impact is negligible. Even though the role of an EDZ turns out to be limited on overall safety assessment, still it is worthwhile to study the chemical role of an EDZ, such as a potential source for natural colloids, potential sealing of an open fracture by fine clay particles generated by the process of an EDZ, and alteration of a sorption mechanism by an EDZ in the future.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.28-33
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• 2003

Ginsenosides, major active ingredients of Panax ginseng, are known to regulate excitatory ligand-gated ion channel activity such as nicotinic acetylcholine and NMDA receptor channel activity. However, it is not known whether ginsenosides affect inhibitory ligand-gated ion channel activity. We investigated the effect of ginsenosides on human recombinant $GABA_A$ receptor (${\alpha}_1{\beta}_1{\gamma}_{2s}$) channel activity expressed in Xenopus oocytes using a two-electrode voltage-clamp technique. Among the eight individual ginsenosides examined, namely, $Rb_1$, $Rb_2$, Rc, Rd, Re, Rf, $Rg_1$ and $Rg_2$, we found that Rc most potently enhanced the GABA-induced inward peak current ($I_{GABA}$). Ginsenoside Rc alone induced an inward membrane current in certain batches of oocytes expressing the $GABA_A$ receptor. The effect of ginsenoside Rc on $I_{GABA}$ was both dose-dependent and reversible. The half-stimulatory concentration ($EC_{50}$) of ginsenoside Rc was 53.2$\pm$12.3 $\mu$M. Both bicuculline, a $GABA_A$ receptor antagonist, and picrotoxin, a $GABA_A$ channel blocker, blocked the stimulatory effect of ginsenoside Rc on $I_{GABA}$. Niflumic acid (NFA) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), both $CI^{-1}$ channel blockers, attenuated the effect of ginsenoside Rc on I$I_{GABA}$. This study suggests that ginsenosides regulated $GABA_A$ receptor expressed in Xenopus oocytes and implies that this regulation might be one of the pharmacological actions of Panax ginseng.

• Korean Journal of Clinical Pharmacy
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• v.19 no.1
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• pp.50-60
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• 2009

Highly variable drugs (within-subject variability greater than 30%) have been difficult to meet current regulatory acceptance criteria using a reasonable number of study subjects. In this study, we reviewed previous studies presenting alternative approaches for bioequivalence evaluation of highly variable drugs, and focused on an approach for widening the bioequivalence acceptance limits using within-subject variability. We discussed the suggested five solutions for highly variable drug including the deletion of $C_{max}$ of the bioequivalence criteria, direct expansion of bioequivalence limit, multiple dose studies in steady state, bioequivalence assessment on the metabolite, add-on study, and widening the bioequivalence acceptance limits based on reference variability. The methods for widening of bioequivalence limits based on reference variability are scaled average bioequivalence containing within-subject variability on reference drug (${\sigma}_{WR}$), population bioequivalence derived from total variability on reference drug (${\sigma}_{TR}$) and test drug (${\sigma}_{TT}$), and individual bioequivalence derived from subject by formulation interaction variability (${\sigma}_D$) and within subject variability on reference drug (${\sigma}_{WR}$) and test drug (${\sigma}_{TR}$). To apply these methods, the switching variability (${\sigma}_0$) will have to be set by the regulatory authorities. The proposals of bioequivalence evaluation approach for the highly variable in Korea are presented for both of new drug and reevaluation drug.