• Title/Summary/Keyword: Agent Model

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Pharmacokinetic analysis for the development of new potent anti-HIV-1 agents, the KR-V series (새로운 항HIV-1제, KR-V series의 개발을 위한 약물동태연구)

  • Lee, Young-mi;Kim, Jin-suk;Han, Sang-seop;Shin, Ho-chul
    • Korean Journal of Veterinary Research
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    • v.40 no.3
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    • pp.471-478
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    • 2000
  • The pharmacokinetic properties of KR-V compounds, recently developed as new anti-HIV agents, were studied after i.v. and p.o. administration in rats. The concentrations of the KR-V series were determined in rat plasma using an high-performance liquid chromatography (HPLC)-UV detection system. Of the 19 KR-V compounds investigated in the present study, only KR-V 3, 10, 14, 16 and 18-1 showed oral bioavailability. The plasma concentration-time data could be adequately described by an one-compartment open model. In the i.v. kinetic study (10mg/kg), the CLt of KR-V 3, 10, 14 and 16 (>4L/hr/kg) were significantly higher than that of KR-V 18-1 (1.1 L/hr/kg). The AUC of KR-V 18-1 was greater ($8.97{\mu}g{\cdot}hr/ml$) than that of the other compounds, but the Vd (0.58 L/kg) was lower. In the p.o. kinetic study (50mg/kg), although the t-1/2 of KR-V 18-1 was shorter than that of the other compounds, the AUC ($3.659{\mu}g{\cdot}hr/ml)$ and $C_{max}(1.891{\mu}g/ml$) were markedly higher. In a seperated in vitro experiment, only KR-V 18-1, of the 5 compounds with bioavailibility, exhibits potent activity against HIV-1 mutant strains. Therefore, KR-V 18-1 is expected to become a new potent anti-AIDS drug candidate/lead compound.

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The Effects of Sangbaekpi(SBP) on Immune Cell & Serum OA-specific IgE in BALF in Rat Asthma Model (상백피(桑白皮)가 제 I형 알레르기 천식(喘息)모델 흰쥐의 BALF내(內) 면역세포(免疫細胞) 및 혈청(血淸) IgE에 미치는 영향(影響))

  • Kim Dae-Kyeom;Lee Sang-Jae;Kim Kwang-Ho
    • Journal of Society of Preventive Korean Medicine
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    • v.6 no.1
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    • pp.140-155
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    • 2002
  • Background: SBP(桑白皮)is an herbal medicine which has been used in oriental medicine as a traditional therapeutic agent of bronchial asthma. Objective: This study was performed to investigate the effect of SBP on the anti-hypersensitivity and immune response in the murine of type I hypersensitivity induced by the experiment. Materials and Methods: Laboratory rats were primary sensitized with OA(ovalbumin); on day 1, rats of a Control group and Sample group (SBP group) were systemically immunized by subcutaneous injection of 1 mg OA and 300mg of Al(OH)3 in a total volume of 2ml saline. The rats of the sample group were orally administered with an SBP water extract for 14 days after primary immunization. On day 14 after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2%(wt/vol) OA. A day after local immunization, BAL fluid and serum were collected from the rats. Total cell, lymphocyte, CD4+ T cell, CD8+ T cell, CD4+/CD8+ ratio in the BALF, and IgE level in serum were measured and evaluated. Results: SBP showed a suppressive effect on the immune response in the rats. 1. Total cells in the BALF decreased in the SBP treated group in comparision to the control group, but statistic differences were not observed. 2. Total lymphocytes in the BALF were statistically decreased in SBP treated group in comparision to the control group. 3. CD4+ T cells in the BALF were statistically decreased in SBP treated group in comparision to the control group. 4. CD8+ T cells in the BALF were not statistically different in SBP treated group and the control group. 5. The ratio of CD4+/CD8+ in the BALF was statistically decreased in SBP treated group in comparision to the control group. 6. The IgE level in serum decreased in the SBP treated group in comparision to the control group, but statistic differences were not observed.

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An Empirical Study on Debt Financing of Family Firms : Focused on Packing Order Theory (가족기업의 부채조달에 관한 실증연구 : 자본조달순위이론을 중심으로)

  • Jung, Mingeu;Kim, Dongwook;Kim, Byounggon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.3
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    • pp.337-345
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    • 2018
  • The purpose of this study is to analyze the relationship between the characteristics of Korean family firms and the impact of debt financing. The analysis period was 10 years from 2004 to 2013, and the sample consisted of 4,008 non-financial firms listed on the Korea Exchange. For the analysis, the unbalanced panel data with time - series, cross - section data were formed and analyzed using panel data regression analysis. The results are as follows. First, Korean family firms use relatively less debt than non - family firms. It can be understood that family firms in which the dominant family owns and dominates the corporation are less likely to increase their debt because the agent problem is alleviated and the need for the control effect of Jensen (1986) is lowered. Second, in the verification of the packing order theory using the model proposed by Shyam-Sunder and Myers (1999), family firms have higher compliance with the packing order theory than non-family firms do. When financing is needed, debt is preferred over equity issuance. However, for Korean family firms, 24.38% of the deficit funds are financed through the issuance of net debt, which is relatively low compared to the 75% shown in the analysis of Shyam-Sunder and Myers (1999). These results reveal the limit to the strong claim that the Korean family firms follow the packing order theory.

The effects of bamboo salt solution on remineralization of artificial caries-like lesions (죽염이 초기인공우식법랑질의 재광화에 미치는 영향)

  • Oh, Han-Na;Hong, Suk-Jin;Lee, Hye-Jin;Choi, Choong-Ho
    • Journal of Korean society of Dental Hygiene
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    • v.12 no.2
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    • pp.335-343
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    • 2012
  • Objectives : The aim of this investigation was to evaluate the remineralization effect of Bamboo salt and NaF+Bamboo salt solutions on bovine enamel formed incipient artificial enamel caries by microcomputed tomography (micro CT). Methods : Experimental solutions were distilled water(negative control), 2% sodium fluoride solution (2% NaF group), 3% bamboo salt solution (3% BS group) and the solution mixed 2% sodium fluoride solution and 3% bamboo salt solution (2% NaF+3% BS group). Specimens were prepared from extracted bovine teeth and divided into 4 groups of 10 specimens each by randomized blocks according to density. Then the specimens surface were divided equally into three parts to observe sound enamel area, incipient enamel carious area and remineralized enamel area. Only one-third of specimen surface was coated with nail varnish and these were exposed to a lactate carbopol buffer system for 72 hours. Then one-half of the demineralized enamel area was coated with nail varnish. The specimens were carried out under pH cycling model for 14 days as follows; samples were immersed in each experimental solution for 2 mins 3 times per day, demineralized for 4 hours and in mixed saliva for the remaining hours. After pH cycling, density was measured using micro CT. Results : All experimental groups showed remineralization effects except for negative control group(p<0.05). The differences of density after experimental solution treatment were statistically significant difference among 4 groups (p<0.01). The density difference values of groups were $0.04{\pm}0.01$ in negative control group, $0.19{\pm}0.01$ in 2% NaF group, $0.14{\pm}0.01$ in 3% BS group, and $0.21{\pm}0.01$ in 2% NaF+3% BS group. Conclusions : The bamboo salt solution showed remineralization effects on incipient artificial enamel caries and the solution mixed sodium fluoride solution and bamboo salt solution showed more remineralization effects than the bamboo salt solution. Thus, it is suggested that bamboo salt can be used as remineralization agent in incipient enamel caries lesion.

Cornu cervi pantotrichum Pharmacopuncture Solution Facilitate Hair Growth in C57BL/6 Mice

  • Lee, Seon-Yong;Lee, Dong-Jin;Kwon, Kang;Lee, Chang-Hyun;Shin, Hyun Jong;Kim, Jai Eun;Ha, Ki-Tae;Jeong, Han-Sol;Seo, Hyung-Sik
    • Journal of Pharmacopuncture
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    • v.19 no.2
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    • pp.122-128
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    • 2016
  • Objectives: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. Methods: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. Results: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. Conclusion: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up-regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia.

Postchilling Accumulation of Superoxide in Cells and Chilling Injury in Rice Plant (Superoxide의 세포내 축적과 벼냉해의 발현)

  • Kim, Jong-Pyung;Hyun, Il;Jung, Jin
    • Applied Biological Chemistry
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    • v.30 no.4
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    • pp.364-370
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    • 1987
  • The $O_2^-$ level of the extract from young rice leaves, which was cold treated for 2 days and then placed at room temperature for a period of time significantly higher than that from tissues untreated. $O_2^-$ level in leaves was practically unchanged during cold treatment for 48 hours. But it started to increase to arrive at maximum in 8 hours, once the plants were placed under room temperature. The abnormal production of $O_2^-$ in mitochondria during postchilling process was interpreted as a biochemical consequence of accumulation of glycolysis product(s) in cytosol and/or NADH in mitochondrial matrix due to disruption of catabolic balance at low temperature. Mitochondria isolated from the chilling injured tissue was found to have lost considerably their respiratory activity. This fact may imply the involvement of intramitochondrial accumulation of $O_2^-$ in the inactivation of electron transport chain system. The observation that mitochondria in the presence of the $O_2^--producing$ enzymatic system (Xanthine/Xanthine oxidase) lost their respiratory activity supports this inference. It was also found in this work that Superoxide dismutase (SOD) is a substrate inducible enzyme, and that SOD is a possible protective agent in plant cell against chilling injury.

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Cytotoxicity and Antitumor Effects of Insambaekhaptang on C57BL/6 Mice Melanoma-induced Lung Metastasis (인삼백합탕(人蔘百合湯)이 B16세포에 대한 세포독성능 및 C57BL/6계 생쥐의 폐전이암의 억제에 미치는 영향)

  • Hwang, Ho-Jun;Ha, Ji-Yong
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.3 no.1
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    • pp.85-98
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    • 1997
  • Oriental medicine as a candidate for effective cancer treatment recently gain positive concerns in fields of therapeutic oncology. that is why some herbal medicines have been empirically safer in toxicity than anticancer drugs used in western medicine, and to show excellent therapeutic efficacy in human trial. Thus, these effects by clinically applied-herbs have not yet fully demonstrated in experimental tumor model. This study was initiated to evaluate the antitumor effect of Insambaekhaptang as candidate of antitumor-herbal agent against B16 melanoma metastasized into C57BL/6 mice lung. In experiment to test whether Insambaekhaptang can directly kill cancer cells in vitro or not, Insambaekhaptang showed direct killing action in concentration or higher against B16 melanoma cells using MTT assay, and showed lower IC50. Another experiment to know whether Insambaekhaptang can inhibit growth and metastasis of cancer cell or not, Insambaekhaptang significantly inhibited Solid tumor by intraperiperal injected-melanoma and lung metastasis induced by intravenous injected-melanoma in inbred C57BL/6 mice. When quantitative survival time increasing, we could obtain results that increased 113% in treated by Insambaekhaptang. These results show that Insambaekhaptang can inhibit growth of B16 melanoma cells through various biological mechanisms.

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The Effect of Genistein on Melanin Synthesis and In vivo Whitening (제니스테인의 멜라닌 생성 억제 및 In vivo 미백 효과)

  • Yang, Eun-Soon;Hwang, Jae-Sung;Choi, Hyun-Chung;Hong, Ran-Hi;Kang, Sang-Mo
    • Microbiology and Biotechnology Letters
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    • v.36 no.1
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    • pp.72-81
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    • 2008
  • The effect of genistein on melanin synthesis was studied using in vitro and in vivo model. Genistein inhibited melanin synthesis in cultured melan-a cells dose dependently. Tyrosinase activity was decreased by genistein treatment in melan-a cells, but genistein did not inhibit tyrosinase directly. Genistein did not affect the expression of tyrosinase in melan-a cells. Genistein inhibited the activity of ${\alpha}$-glucosidase in virtro and the glycosylation of tyrosinase in melan-a cells. The resulting unsaturated glycosylation of tyrosinase makes it unstable and disturb correct transportation. To further clarify the effect of genistein on the melanogenesis, we established UVB-induced hyperpigmentation on the shaved backs of brown guinea pigs. The animals were exposed to UVB radiation once a week for three consecutive weeks. Genistein (1 and 2%) or vehicle alone as a control were then topically applied to the hyperpigmented areas daily. Genistein showed significant lightening effect on the UVB-induced hyperpigmentation in five weeks. Depigmenting effect was prominent in 2% genistein treatment with Fontana-Masson staining. In conclusion, genistein may be a useful agent for skin whitening.

The Effect of UV Intensity and Wavelength on the Photolysis of Triclosan (TCS) (광반응을 이용한 Triclosan 분해에서의 UV 광세기와 파장의 효과)

  • Son, Hyun-Seok;Choi, Seok-Bong;Khan, Eakalak;Zoh, Kyung-Duk
    • Journal of Korean Society of Environmental Engineers
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    • v.27 no.9
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    • pp.1006-1015
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    • 2005
  • We investigated the effect of hydroxyl radicals on the photolysis of triclosan (TCS), which is a potent broad-spectrum antimicrobial agent. TCS degradation during the initial reaction time of 5 min followed a pseudo-first order kinetic model ai all light intensities at a wavelength of 365 nm and at the low light intensities at a wavelength of 254 nm. The photodegradation rate significantly increased with decreasing wavelength and increasing the UV intensities. The activity of hydroxyl radicals was suppressed when methanol was used as the solvent instead of water. An increase in the photon effect was observed when the UV intensity was higher than $5.77{\times}10^{-5}$ einstein $L^{-1}min^{-1}$ at 254 nm, and lower than $1.56{\times}10^{-4}$ einstein $L^{-1}min^{-1}$ at 365 nm. The quantum yield efficiency for the photolysis of TCS was higher at 365 nm than at 254 nm among the above mentioned UV intensities. Dibenzodichloro-p-dioxin (DCDD) and dibenzo-p-dioxin were detected as intermediates at both UV intensities of $1.37{\times}10^{-4}$ and $1.56{\times}10^{-4}$ einstein $L^{-1}min^{-1}$ at 365 nm. Dichlorophenol and phenol were also detected in all cases. Based on our findings, we presented a possible mechanism of TCS photolysis.

A Simple Dosing Scheme for Intravenous Busulfan Based on Retrospective Population Pharmacokinetic Analysis in Korean Patients

  • Choe, Sang-Min;Kim, Gayeong;Lim, Hyeong-Seok;Cho, Sang-Heon;Ghim, Jong-Lyul;Jung, Jin-Ah;Kim, Un-Jib;Noh, Gyu-Jeong;Bae, Kyun-Seop;Lee, Dong-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.4
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    • pp.273-279
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    • 2012
  • Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.