• Archives of Pharmacal Research
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• v.16 no.3
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• pp.219-226
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• 1993

For the analysis of structure relationship of ar-turmerone analogues, the compounds containing the various substituents on the phenyl ring and 1(or 2)-naphthyl group in the place of phenyl of ar-turmerone were prepared and tested their cytotoxicity against HL-60, K-562, and L1210 leukemia cells in vitro. The substituents at para position are methoxy, phenoxy, methyl, trifluoromethyl, fluoro, and chloro. At meta position methoxy, methyl, trifluoromethyl, or chloro groups at ortho position mathoxy or chloro group were introduced. Against HL-60 and K-562 cells, $ED_{50}$ values of the analogues are ranged from 0.8 to $30.0\;\mu{g/ml}$. Againste L1210 cell, these are located more than $20.0\;\mu{g/ml}$. However, 5-carbone-thoxy-2-methyl-6(1-naphthyl)-2-octen-4-one (5n)possesses $ED_{50}$ valuses 0.8, 2.1, $6.5\;\mu{g/ml}$ against HL-60, L1210 cells, respectively. The electronic nature of the substituents on phenyl ring of ar-tumerone dose not affect the biological activity. Therefore the flat structure of aromatic potion of ar-tumerone analogues is the more important factor for their activity rather than its electronic nature. The potentiation of the cytotoxicity with the enlargement of aromatic ring region also supports the importance of the plane structure of this area. The restriction of the single bond rotation between C-6 and aromatic ring through the introduction of substituents at the ortho position of phenyl ring and the increment of size of alkyl group at C-6 position enhances the activity. Therefore the effective conformation should by the one having the orthogonal arrangement between the aromatic ring and the side chain.

• Korean Journal of Clinical Pharmacy
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• v.10 no.1
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• pp.25-29
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• 2000

Bioequivalence of cisapride-containing $Cisaplus^{(R)}$ tablets (Daewoong Co.) to reference $Prepulsid^{(R)}$ tablets (Janssen Co.) was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy volunteers were divided randomly into two groups and administered orally at a cisapride dose of 10 mg in a $2\times2$ crossover design. There was a 1-week washout period between the treatments. Blood samples were taken at predetermined time intervals for 48 hr and the plasma cisapride concentrations were determined by an HPLC with UV detector. The area under the plasma drug concentration-time curve (AUC) was caltulated from time zero to the last sampling time by a linear trapezoidal method. The maximum observed plasma drug concentration ($C_{max}$) and the time to $C_{max}\;(T_{max})$ were estimated directly from the drug concentration-time data. Analysis of variance (ANOVA) showed that the apparent differences for AUC, $C_{max}\;and\;T_{max}$ were $-7.52\%,\;-8.91\%\;and\;-15.55\%$, respectively. The minimum detectable differences for AUC, $C_{max}\;and\;T_{max}$ between formulations were $14.52\%,\;11.57\%\;and\;28.00\%$ respectively, at $\alpha=0.05\;and\;1-\beta=0.8\;levels.\;The\;90\%$ confidence intervals for AUC, $C_{max}\;and\;T_{max}\;were\;-16.00\sim0.97\%,\;-15.67\sim-2.15\%\;and\;-31.88\%\sim0.84\%$, respectively. These results satisfy the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of cisapride are bioequivalent.

• Journal of Haehwa Medicine
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• v.8 no.1
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• pp.379-401
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• 1999

The effect of KamiTongJonHaaATang extracts on hypercholesterolemia, platelet aggregation, pulm onary thrombosis, KCN-induced coma, forcal brain ischemia, cytotoxicity of PC12 cells induced by amyloid ${\beta}$ protein(25-35), and NO production in RAW cells stimulated lipopolysaccharide were investigated, respectively. The results were summarized as follows; 1. KTJHAT extracts showed a significant decrease of serum total cholesterol, triglyceride, phospholipid, LDL-cholesterol, and VLDL-cholesterol in hypercholesterolemia induced by 2% cholesterol diet in NZW rabbit. 2. KTJHAT extracts induced a significant inhibition of human platelet aggregation induced by thrombin and ADP but did not affect human platelet aggregation induced by collagen. 3. KTJHAT extracts showed a protective effect on pulmonary thrombosis induced by collagen and epinephrine. 4. KTJHAT extracts prolonged the duration of KCN-induced coma. 5. KTJHAT extracts showed a significant decrease of brain ischemic area and edema in MCA occlusion. Also, KTJHAT extracts showed a decrease of neurologic grade in hind limb but did not affect neurologic grade in fore limb. 6. KTJHAT extracts showed a protective effect on cytotoxicity of PC 12 cells induced by amyloid ${\beta}$ protein(25-35) in a dose dependent manner. 7. KTJHAT extracts showed a significant decrease of NO production in RAW cells induced by lipopolysaccharide. These results suggested that KTJHAT extracts might be usefully applied for prevention and treatement of thrombosis and brain damage.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.970-976
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• 2005

The purpose of this study was to investigate the effect of morin, a flavonoid, on the pharmacokinetics of diltiazem and one of its metabolites, desacetyldiltiazem in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after oral administration of diltiazem (15 mg/kg) in rats pretreated with morin (1.5, 7.5, and 15 mg/kg). Compared with the control group (given diltiazem alone), pretreatment of morin significantly increased the absorption rate constant $(K_a)$ and peak concentration $(C_{max})$ of diltiazem (p<0.05, p<0.01). Area under the plasma concentration-time curve (AUC) of diltiazem in rats pretreated with morin were significantly higher than that in the control group (p<0.05, p<0.01), hence the absolute bioavailability $(AB\%)$ of diltiazem was significantly higher than that of the control group (p<0.05, p<0.01). Relative bioavailability $(RB\%)$ of diltiazem in rats pretreated with morin was increased by 1.36- to 2.03-fold. The terminal half-life $(t_{1/2})$ and time to reach the peak concentration $(T_{max})$ of diltiazem were not altered significantly with morin pretreatment. AUC of desacetyldiltiazem was increased significantly (p<0.05) in rats pretreated with morin at doses of 7.5 and 15 mg/kg, but metabolite-parent ratio (MR) of desacetyldiltiazem was decreased significantly (p<0.05), implying that pretreatment of morin could be effective to inhibit the CYP 3A4-mediated metabolism of diltiazem. There were no apparent changes of $T_{max}$ and $t_{1/2}$ of desacetyldiltiazem with morin pretreatment. Collectively, the pretreatment of morin significantly altered pharmacokinetics of diltiazem, which can be attributed to increased intestinal absorption as well as reduced first-pass metabolism. Based on these results, dose modification should be taken into consideration when diltiazem is used concomitantly with morin or morin-containing dietary supplements in clinical setting.

• YAKHAK HOEJI
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• v.39 no.2
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• pp.161-168
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• 1995

Brain dopamine systems play a central role in the control of movement, hormone release, and many complex behavior. The action of dopamine at its synapse is terminated predominately by high affinity reuptake into presynaptic terminals by dopamine transporter (DAT). The dopamine transporter(DAT) is membrane protein localized to dopamine-containing nerve terminals and closely related with cocaine abuse, Parkinsonism, and schizophrenia. In present study, the recombinant plasmid pRc/CMV-DAT, constructed by subcloning of a cDNA encoding a bovine DAT into eukaryotic expression vector pRc/CMV, was stably transfected into CV-1 cells(monkey kidney cell line). The DAT activities in the cell lines selected by Geneticin$^{R}$ were determined by measuring the uptake of $[^3H]$-dopamine. The transfected cell lines showed 30-50 fold higher activities than untransfected CV-1 cell line, and this result implies that DAT is well expressed and localized in transfected cells. The transfected cells accumulated $[^3H]$-dopamine in a dose-dependent manner with a $K_{m}$ of 991.6nM. Even though high doses of norepinephrine, epinephrine, serotonin, and choline neurotransmitters inhibited the uptake of $[^3H]$-dopamine, DAT in transfected cell line was proven to be much more specific to dopamine. The psychotropic drugs such as GBR12909, CFT, normifensine, clomipramine, desipramine, and imipramine inhibited significantly the dopamine uptake in tissue culture cells stably transfected with DAT cDNA. Radioactive in situ hybridization was done to map the cellular localization of DAT mRNA-containing cells in the adult rat central nervous system. The strong hybridization signals were detected only in the substantia nigra pars compacta and ventral tegmental area. The restricted anatomical localization of DAT mRNA-containing cells confirms the DAT as a presynaptic marker of dopamine-containing cells in the rat brain.

• Journal of Radiation Protection and Research
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• v.28 no.2
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• pp.127-135
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• 2003

The primary contributors to the total occupational radiation exposure in operating nuclear power plants are operation and maintenance activities doting refueling outages. The Advanced Power Reactor 1400 (APR1400) includes a number of design improvements and plans to utilize advanced maintenance methods and robotics to minimize the annual collective dose. The major radiation exposure reduction features implemented in APR1400 are a permanent refueling pool seal, quick opening transfer tube blind flange, improved hydrogen peroxide injection at shutdown, improved permanent steam generator work platforms, and more effective temporary shielding. The estimated average annual occupational radiation exposure for APR1400 based on the reference plant experience and an engineering judgment is determined to be in the order of 0.4 man-Sv, which is well within the design goal of 1 man-Sv. The basis of this average annual occupational radiation exposure estimation is an eighteen (18) month fuel cycle with maintenance performed to steam generators and reactor coolant pumps during refueling outage. The outage duration is assumed to be 28 days. The outage work is to be performed on a 24 hour per day basis, seven (7) days a week with overlapping twelve (12) hour work shifts. The occupational radiation exposure for APR1400 is also determined by an alternate method which consists of estimating radiation exposures expected for the major activities during the refueling outage. The major outage activities that cause the majority of the total radiation exposure during refueling outage such as fuel handling, reactor coolant pump maintenance, steam generator inspection and maintenance, reactor vessel head area maintenance, decontamination, and ICI & instrumentation maintenance activities are evaluated at a task level. The calculated value using this method is in close agreement with the value of 0.4 man-Sv, that has been determined based on the experience aid engineering judgement. Therefore, with the As Low As Reasonably Achievable (ALARA) advanced design features incorporated in the design, APR1400 design is to meet its design goal with sufficient margin, that is, more than a factor of two (2), if operated on art eighteen (18) month fuel cycle.

• YAKHAK HOEJI
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• v.54 no.2
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• pp.75-90
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• 2010

Biomarkers are likely to be important in the study of various pulmonary diseases for many reasons. Research efforts in developing biomarkers and surrogate endpoints of lung diseases have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in new drug development and advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Though the area of pulmonology has received much attention in the past decades, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review critically summarized several biomarker researches such as Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study with objectives of identifying the parameters that predict disease progression of COPD, as well as biomarkers that may serve as surrogate end-points.

• Journal of Environmental Science International
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• v.16 no.3
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• pp.323-331
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• 2007

Polycyclic aromatic hydrocarbons (PAHs) are well known for strong carcinogen. However, the human exposure analysis of PAHs is quite difficult and unreliable because of hard for estimation of actual expose dose. Then urinary 1-hydroxypyrene (1-OHP) has been a biological marker of exposure to PAHs. The purpose of this study was to investigate total amount from exposure to PAHs soused by indoor occupational exposure, and residence at Seoul metropolitan area and Kyeonggi province in Korea. Thirty-five housewives were included in this study from April 2003 through February 2004. Dietary habit and general characteristics such as age, type of building, existence of passive smoking, period of residence, fuel type for heating and ventilation type were obtained by self administered questionnaire. Urine samples were collected at morning and freeze quickly. Urinary creatinine was measured for converting into 24 hr urine. Concentration of the indoor PAHs was examined by NIOSH method number 5506. Urinary 1-OHP and PAHs were analysed by HPLC. Correlation coefficient between urinary 1-OHP levels and pyrene concentration of indoor air was 0.66 and statistically significant(P<0.01). The difference of urinary 1-OHP level due to dietary habits were not significant. Urinary 1-OHP level of Spring, Summer, Autumn, and Winter were $0.21{\pm}0.12,\;0.10{\pm}0.17,\;0.16{\pm}0.12,\;0.17{\pm}0.14{\mu}g/g$ cr, respectively. The arithmetic means of urinary 1-OHP for four season tee $0.16{\pm}0.14 {\mu}g/g$ cr. There was a trend that urinary 1-OHP level of residents who dwelling in apartment were higher compared with detached home, Comparison of 1-OHP level between heating by kerosene and LPG, Much higher gas heating type than kerosene type (P<0.05). This result implies that the urinary 1-OHP can be applied as the PAHs exposure indices.

• The Transactions of the Korean Institute of Electrical Engineers C
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• v.52 no.12
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• pp.545-552
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• 2003

When a Si PIN diode is exposed to fast neutrons, it results in displacement damage to the Si lattice structure of the diode. Defects induced from structural dislocation become effective recombination centers for carriers which pass through the base of a PIN diode. Hence, increasing the resistivity of the diode decreases the current for the applied forward voltage. This paper involves the development of a neutron sensor based on the phenomena of the displacement effect damaged by neutron exposure. The neutron effect on the semiconductor was analyzed. Several PIN diode arrays with various thickness and cross-section area of the intrinsic layer(I layer) were fabricated. Under irradiation tests with a neutron beam, the manufactured diodes have a good linearity to neutron dose and show that the increase of thickness of I layer and the decrease of cross-section of PIN diodes improve the sensitivity. Newly developed PIN diodes with thicker I layer and various cross section, were retested and then showed the best neutron sensitivity at the condition that the I layer thickness was similar to a side length. On the basis of two test results, final discrete PIN diodes with a rectangular shape were manufactured and the characteristics as neutron detectors were analyzed through the neutron beam test using on-line electronic dosimetry system. Developed PIN diode shows a good linearity as dosimetry in the range of 0 to 1,000cGy(Tissue) and its neutron sensitivity is 13mV/cGy at constant current of 5mA, that is three times higher than that of commercially available neutron detectors. And the device shows little dependency on the orientation of the neutron beam and a considerable stability in annealing test for a long period.

• Journal of Pharmaceutical Investigation
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• v.34 no.4
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• pp.311-317
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• 2004

A bioequivalence study of $Gomcillin^{TM}$ capsules (DAEWOONG Pharmaceutical Co., Korea) to $Famoxin^{TM}$ capsules (Dong Wha Pharm. Ind. Co., Korea) was conducted according to the guideline of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the amoxicillin dose of 500 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of amoxicillin were monitored by a high-performance liquid chromatography for over a period of 8 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 8 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Gomcillin^{TM}/Famoxin^{TM}$ were $log0.91\;{\sim}\;log1.03$ and $;log0.93\;{\sim}\;log1.10$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80\;{\sim}\;log1.25$. Thus, our study demonstrated the bioequivalence of $Gomcillin^{TM}$ and $Famoxin^{TM}$ with respect to the rate and extent of absorption.