• Korean Journal of Clinical Pharmacy
• /
• v.8 no.2
• /
• pp.122-132
• /
• 1998

SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.

• Environmental Analysis Health and Toxicology
• /
• v.28
• /
• pp.13.1-13.5
• /
• 2013

Objectives: Potential environmental risks caused by chemicals that could be released from a recycled plastic product were assessed using a screening risk assessment procedure for chemicals in recycled products. Methods: Plastic slope protection blocks manufactured from recycled plastics were chosen as model recycled products. Ecological risks caused by four model chemicals - di-(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), cadmium (Cd), and lead (Pb)-were assessed. Two exposure models were built for soil below the block and a hypothetic stream receiving runoff water. Based on the predicted no-effect concentrations for the selected chemicals and exposure scenarios, the allowable leaching rates from and the allowable contents in the recycled plastic blocks were also derived. Results: Environmental risks posed by slope protection blocks were much higher in the soil compartment than in the hypothetic stream. The allowable concentrations in leachate were $1.0{\times}10^{-4}$, $1.2{\times}10^{-5}$, $9.5{\times}10^{-3}$, and $5.3{\times}10^{-3}mg/L$ for DEHP, DINP, Cd, and Pb, respectively. The allowable contents in the recycled products were $5.2{\times}10^{-3}$, $6.0{\times}10^{-4}$, $5.0{\times}10^{-1}$, and $2.7{\times}10^{-1}mg/kg$ for DEHP, DINP, Cd, and Pb, respectively. Conclusions: A systematic ecological risk assessment approach for slope protection blocks would be useful for regulatory decisions for setting the allowable emission rates of chemical contaminants, although the method needs refinement.

• Journal of the Korean Society for Railway
• /
• v.9 no.3 s.34
• /
• pp.291-297
• /
• 2006

The present study investigated the effect of fire suppression using a mid-low pressure water mist in a carriage fire. The fire extinguishing time and temperature distributions below ceiling in the enclosed compartment of $2.9m{\times}2.8m{\times}5.0m$ were measured by stopwatch and k-type thermocouples for various fire positions. The numerical simulations were extensively performed using. Fire Dynamics Simulator(FDS, Ver. 4.0) code and the predictions were compared with experimental data. The prediction results showed good agreement with the measured maximum temperature in the all cases. Whereas the predicted temperature was about $40^{\circ}C$ higher than the measured one after operating of water mist. The predicted fire extinguishing times were compared with those of measured data. Fires are extinguished within 200 seconds at the experiment in Case 2 and Case 3. But in Case 1 fire was not extinguished in the numerical simulation. The reason of the discrepancy between predicted and measured data was that a simple suppression algorithm has been implemented in FDS. Also, various databases of fire properties for combustible materials and more elaborate model considering the water mist were required fur better predictions of the cooling and suffocation effect.

• BMB Reports
• /
• v.37 no.2
• /
• pp.239-245
• /
• 2004

We have previously demonstrated that the redox reactant pyruvate prevents apoptosis in the oxidant model of bovine pulmonary artery endothelial cells (BPAEC), and that the anti-apoptotic mechanism of pyruvate is mediated in part via the mitochondrial matrix compartment. However, cytosolic mechanisms for the cytoprotective feature of pyruvate remain to be elucidated. This study investigated the pyruvate protection against endothelial cytotoxicity when the glycolysis inhibitor 2-deoxy-D-glucose (2DG) was applied to BPAEC. Millimolar 2DG blocked the cellular glucose uptake in a concentration- and time-dependent manner with >85% inhibition at $\geq$5 mM within 24 h. The addition of 2DG evoked BPAEC cytotoxicity with a substantial increase in lipid peroxidation and a marked decrease in intracellular total glutathione. Exogenous pyruvate partially prevented the 2DG-induced cell damage with increasing viability of BPAEC by 25-30%, and the total glutathione was also modestly increased. In contrast, 10 mM L-lactate, as a cytosolic reductant, had no effect on the cytotoxicity and lipid peroxidation that are evoked by 2DG. These results suggest that 2DG toxicity may be a consequence of the diminished potential of glutathione antioxidant, which was partially restored by exogenous pyruvate but not L-lactate. Therefore, pyruvate qualifies as a cytoprotective agent for strategies that attenuate the metabolic dysfunction of the endothelium, and cellular glucose oxidation is required for the functioning of the cytosolic glutathione/NADPH redox system.

• YAKHAK HOEJI
• /
• v.39 no.6
• /
• pp.636-644
• /
• 1995

Comparison of bioavailabflity (BA) of three brands of ranitidine (RT) tablets has been studied m rats. The purpose of this study was to characterize the pharniacolunetics of RT tablets in the rat and to coinpare phannacolunetic parameters of three brands of RT tablets. In addition, it was investigated whether plasma RT concentrations m humans can be predicted from pharmacokinetic parameters obtained in rats. RT was administered intravenously in dose of RT.HCI 10mg/kg and orally in dose of RT.HCI 50mg/kg as solution or crushed sample of thablets. Plasma RT concentrations were determned by HPLC. Plasma RT concentrations as a function of time were fitted to two compartment model. Plasma RT concentrations declined with a terminal half life ($t_{{1}/2{\betha}}$) of 40.9 min. The plasma RT concentration-time curve showed two peak plasma concentrations following an oral administration of solution or crushed sample in rats like humans. No significant difference among pharmacokinetic parameters was observed except $T_{max2}$ (p<0.05). The BA for crushed sample A, B and C were found to be 54.6 40.7 and 40.0%, respectively. Equivalence of $C_{max1}$ and $T_{max2}$ were guaranteed in this study. However, it was concluded that three brands of RT tablets are bioequivalent, taking the following characteristics of RT into consideration;(1) rapid onset of the effect is not required, (2) $C_{max1}$ and $T_{max2}$ do not seem to influence the effectiveness of the drug during a long-term treatment by the usual administration of twice a day. Results from this study were combined with plarmacokinetic data for RT in dogs and humans to develop a basis for interspecies scale-up of the disposition characteristics of the drug. there were similarities in the general disposition of the drug. Allometric relationships were sought between pharmacokinetic parameters nd species body weight. Significant interspecies correlations were found for total body clearance($Cl_{t}$) and steady state volume of distribution ($Bd_{ss}$). Thus, plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats.

• The Journal of the Acoustical Society of Korea
• /
• v.27 no.3
• /
• pp.103-110
• /
• 2008

Strategically, the Patrol Killer Medium (PKM) ought to run at high speed that produces largely vibration by propeller, in a consequence, the vibration gradually deterioratescrews' working condition and increases the possibility of SONAR detection. In this paper, we propose the propeller damper, which is one of waysto reduce the vibration induced by the propeller, and simulate the ability of the damper numerically. The propeller damper was designed to apply to an isolated plate at the bottom flat board of ship which is directly affected by the fluctuating pressure. The dynamic pressure for the stern part of the PKM is calculated by using the DnV rule and the numerical analysis when the propeller damper applied or not, is performed with ANSYS at the isolated plate that simplified. From the analysis, the damping effect of the proposed propeller damper is confirmed and the reduction ratio for each compartment is estimated based on the experimental data in the PKM.

• The Korean Journal of Nuclear Medicine
• /
• v.32 no.1
• /
• pp.32-49
• /
• 1998

For estimation of regional myocardial blood flow with O-15 water PET, a few modifications considering partial volume effect based on single compartment model have been proposed. In this study, we attempted to quantify the degree of heterogeneity and to show the effect of tissue flow heterogeneity on partition coefficient(${\lambda}$) and to find the relation between perfusable tissue index(PTI) and ${\lambda}$ by computer simulation using two modified models. We simulated tissue curves for the regions with homogeneous and heterogeneous blood flow over a various flow range(0.2-4.0ml/g/min). Simulated heterogeneous tissue composed of 4 subregions of the same or different size of block which have different homogeneous flow and different degree of slope of distribution of blood flow. We measured the index representing heterogeneity of distribution of blood flow for each heterogeneous tissue by the constitution heterogeneity(CH). For model I, we assumed that tissue recovery coefficient ($F_{MME}$) was the product of partial volume effect($F_{MMF}$) and PTI. Using model I, PTI, flow, and $F_{MM}$ were estimated. For model II, we assumed that partition coefficient was another variable which could represent tissue characteristics of heterogeneity of flow distribution. Using model II, PTI, flow and ${\lambda}$ were estimated. For the simulated tissue with homogeneous flow, both models gave exactly the same estimates, of three parameters. For the simulated tissue with heterogeneous flow distribution, in model I, flow and $F_{MM}$ were correctly estimated as CH was increased moderately. In model II, flow and ${\lambda}$ were decreased curvi-linearly as CH was increased. The degree of underestimation of ${\lambda}$ obtained using model II, was correlated with CH. The degree of underestimation of flow was dependent on the degree of underestimation of ${\lambda}$. PTI was somewhat overestimated and did not change according to CH. We conclude that estimated ${\lambda}$ reflect the degree of tissue heterogeneity of flow distribution. We could use the degree of underestimation of ${\lambda}$ to find the characteristic heterogeneity of tissue flow and use ${\lambda}$ to recover the underestimated flow.

• Journal of fish pathology
• /
• v.24 no.1
• /
• pp.29-37
• /
• 2011

Effects of temperature ($13{\pm}1.5^{\circ}C$, $23{\pm}1.5^{\circ}C$) on the pharmacokinetic properties of nalidixic acid (NA) and piromidic acid (PA) were studied after oral administration to cultured black rockfish, Sebastes schlegeli. Serum concentrations of NA and PA were determined using HPLC-UV detector after a single dosage of 60 mg/kg body weight. At $23{\pm}1.5^{\circ}C$, the peak serum concentrations of NA and PA, which attained at 24 h post-dose, were 5.87 and $0.43\;{\mu}g/ml$, respectively. At $13{\pm}1.5^{\circ}C$, the peak serum concentrations of NA and PA, which attained at 10 h post-dose, were 6.22 and $1.57\;{\mu}g/ml$, respectively. Better absorption of PA was noted at $13{\pm}1.5^{\circ}C$ compared to $23{\pm}1.5^{\circ}C$. However, absorption of NA was not affected significantly by temperature. The elimination of NA and PA from serum of black rockfish was considerably faster at $23{\pm}1.5^{\circ}C$ than at $13{\pm}1.5^{\circ}C$. The kinetic profile of absorption, distribution and elimination of NA and PA in serum were analyzed by fitting to a one compartment model, with WinNonlin program. The AUC, $T_{1/2}$, $T_{max}$ and $C_{max}$, respectively, were: $161.25\;{\mu}g{\cdot}h/ml$, 0.15 h, 12.29 h and $8.91\;{\mu}g/ml$ at $23{\pm}1.5^{\circ}C$, and $134.12{\mu}g{\cdot}h/ml$, 0.18 h, 8.79 h and $5.00\;{\mu}g/ml$ at $13{\pm}1.5^{\circ}C$ with NA; $41.57\;{\mu}g{\cdot}h/ml$, 0.58 h, 8.24 h and $0.21\;{\mu}g/ml$ at $23{\pm}1.5^{\circ}C$, and $40.36\;{\mu}g{\cdot}h/ml$, 0.59 h, 5.04 h and $1.20\;{\mu}g/ml$ at $13{\pm}1.5^{\circ}C$ with PA.

• Korean Journal of Veterinary Research
• /
• v.42 no.1
• /
• pp.45-54
• /
• 2002

The study was carried out to characterize the pharmacokinetics after intravenous (iv, 20 mg/kg) and oral (p.o. 100 mg/kg) administration as oxytetracycline (OTC) and tiamulin (TIA) mixture in swine and to determine interaction between OTC and TIA against various pig pathogenic bacteria. The antibacterial effects of OTC in combination with TIA in vitro showed synergistic effect against Salmonella typhimurium 1925, Pasteurella multocida Type A, P. multocida Type D, Krebsiella Pneumoniae 2001, K. Pneumoniae 1560, K. Pneumoniae 2208, Haemophillus pleuropneumonia S 2, and H. pleuropneumonia S 5, but against additive effect E. coli K88ab and S. choleraesuis on the basis of fractional inhibitory concentration (FIC) index. On the while, after i.v. and p.o. administration of OTC and TIA mixture, each OTC and TIA concentrations in plasma were fitted to an open two-compartment model. After i.v. administration of OTC-TIA mixture, the mean distribution half-life ($T_{1/2{\alpha}}$) of OTC and TIA in plasma showed 0.29 h and 0.17 h, and the mean elimination half-life ($T_{1/2{\beta}}$) of those was 4.36 h and 6.64 h, respectively. The mean volume of distribution at steady state ($Vd_{ss}$) of OTC and TIA was $0.85{\ell}/kg$ and $2.44{\ell}/kg$, respectively. After oral administration of OTC and TIA mixture, the mean maximal absorption concentrations ($C_{max}$) of OTC and TIA were $0.60{\mu}g/m{\ell}$ at 1.07 h ($T_{max}$) and $1.68{\mu}g/m{\ell}$ at 1.85 h ($T_{max}$), respectively. The mean elimination half-life ($T_{1/2{\beta}}$) of those showed 6.84 h and 6.36 h. In conclusion, we could suggest in this study that the combination of OTC and TIA may be recommended for the antibacterial therapy against polymicrobial infections, and both OTC and TIA showed large distribution to tissues and high $C_{max}$ after p.o. administration.

• Journal of Environmental Health Sciences
• /
• v.49 no.6
• /
• pp.334-343
• /
• 2023

Background: South Korea's Act on Registration and Evaluation, etc. of Chemicals (known as K-REACH) was established to protect public health and the environment from hazardous chemicals. 4,4'-Methylenedianiline (MDA), which is used as a major intermediate in industrial polymer production and as a vulcanizing agent in South Korea, is classified as a toxic substance under the K-REACH act. Although MDA poses potential ecological risks due to industrial emissions and hazards to aquatic ecosystems, no ecological risk assessment has been conducted. Objectives: The aim of this study is to assess the ecological risk of MDA by identifying the actual exposure status based on the K-REACH act. Methods: Various toxicity data were collected to establish predicted no effect concentrations (PNECs) for water, sediment, and soil. Using the SimpleBox Korea v2.0 model with domestic release statistical data and EU emission factors, predicted environmental concentrations (PECs) were derived for ten sites, each referring to an MDA-using company. Hazard quotient (HQ) was calculated by ratio of the PECs and PNECs to characterize the ecological risk posed by MDA. To validate the results of modeling-based assessment, concentration of MDA was measured using in-site freshwater samples (two to three samples per site). Results: PNECs for water, sediment, and soil were 0.000525 mg/L, 4.36 mg/kg dw, and 0.1 mg/kg dw, respectively. HQ for surface water and sediment at several company sites exceeded 1 due to modeling data showing markedly high PEC in each environmental compartment. However, in the results of validation using in-site surface water samples, MDA was not detected. Conclusions: Through an ecological risk assessment conducted in accordance with the K-REACH act, the risk level of MDA emitted into the environmental compartments in South Korea was found to be low.