• Archives of Pharmacal Research
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• v.17 no.2
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• pp.124-130
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• 1994

Plasma phamacokinetics and renal excretion of theophylline (TP) and its metabolities were ivnestigated in rats. Plasma concentrations of TP declined in a monoexponential manner, while those of 1-methyluric (MU) and 1,3-dimethyluric(DMU) declined in a biexponential manner upon respective iv bolus injection of each compound at 6mg/kg dose. The total body clearances $(CL_r)$ of the metabolites were 4-6 fold larger than that of TP, while the distribution volumes of them at steady-state $(Vd_{ss})$ were 40-50% smaller than that of TP. The metabolites showed their plasma peaks in 30 min after iv injection of TP indicating than that to MU. Renal excretion of TP and its metabolites was studied in urine flow rate (UFR)-controlled rats. The renal clearance $(CL_r)$ of TP was inversely related to pasma TP concentrations, and much smaller than the glomerular filtration rate (GFR) suggesting tubular secretion and profound reabsorption in the renal tubule. The $(CL_r)$ of each metabolite also showed that inverse relationship, but far exceeded GFR suggesting that tubular secretion than GFR by ip injection of probenecid (142.7 mg/kg). It supports that the metabolies are secreted in the renal tubule, and suggests that they share a common transport system in their sectrtion processes with probenecid. On the other hand, the $(CL_r)$ of TP was not affected significantly by the probenecid treatment. Considering the inverse relationship of TP between the $(CL_r)$ and its ploasma concentrations,no effect of probenecid on $(CL_r)$ of TP is most likely due to negligible contribution of the secretion to the overall $(CL_r)$ of TP.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.709-717
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• 2002

Hypoxemia is known to induce various physiological changes which can result in alteration in drug pharmacokinetics. To examine the effect of acute moderate hypoxemia on metoclopramide (MCP) pharmacokinetics, a continuous 14-hour infusion of MCP during a normoxemic, hypoxemic and subsequent normoxemic period was conducted in eight adult sheep. Arterial blood and urine samples were collected to examine the effects on the pharmacokinetics of MCP and its deethylated metabolites. MCP and its mono- and di-deethylated metabolites were quantitated using a GC/MS method. Steady-state concentrations of MCP were achieved in each of the three periods. During hypoxemia, MCP plasma steady-state concentration increased significantly from 50.72$\pm$1.06 to 63.62$\pm$1.79 ng/mL, and later decreased to 55.83$\pm$1.15 ng/mL during the post-hypoxemic recovery period. Total body clearance ($CL_{TB}$) of MCP was significantly decreased from 274.2$\pm$48.0 L/h to 205.40$\pm$28.2 L/h during hypoxemia, and later restored to 245.8$\pm$44.2 L/h during the post-hypoxemic period. Plasma mono-deethylated MCP concentration (32.78$\pm$1.73 ng/mL) also increased, compared to the control group (21.20$\\pm$1.39 ng/mL), during hypoxemia and subsequent normoxemic period. Renal excretion of MCP and its metabolites was also decreased during hypoxemia, while urine flow was increased with a concomitant decrease in urine osmolality. Thus, the results indicate that acute moderate hypoxemia affects MCP pharmacokinetics.

• YAKHAK HOEJI
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• v.55 no.3
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• pp.260-266
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• 2011

Two types of water soluble lysine salts of ibuprofen were prepared and evaluated. Physicochemical properties for ibuprofen-l-lysinate (IBL-l), ibuprofen-dl-lysinate (IBL-dl) and ibuprofen (IB) were studied on melting point, specific ratation, UV spectra and $^1H$-NMR spectra. There were not differences between IBL-dl and IBL-l in UV spectra and $^1H$-NMR spectra. The pharmacokinetic parameters of IB were compared to those of its lysine salts (IBL-l and IBL-dl) after i.v. or oral administration at the dose of 50 mg/kg (calculated as IB). Total body clearance ($CL_t$) and area under the plasma concentration-time curve (AUC) were not different between IB group and IBL groups after i.v. administration. On the other hand, IBL-l and IBL-dl produced peak plasma concentrations ($C_{max}$) significantly ealier and higher than IB. Time to reach peak concentration ($T_{max}$) after IBL administration was lower than that after IB administration. There was no difference in AUC across all different groups (IB, IBL-l and IBL-dl) after oral administration. However, absorption rate constant ($k_a$) of IBL-l and IBL-dl were significantly increased than that of IB. These results indicated that the administration of IBL-l and IBL-dl may be advantageous if rapid and reliable onset of pain relief is required.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.188-194
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• 2017

Background: Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential. Methods: The free radical scavenging activity of FBG was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the protective effect against cisplatin-induced renal damage was tested in rats. FBG was orally administered every day at a dose of 150 mg/kg body weight for 10 d, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) with 0.9% saline on the $4^{th}$ d. Results: The DPPH radical-scavenging activity of FBG ($IC_{50}=384{\mu}g/mL$) was stronger than that of raw ginseng. The improved DPPH radical-scavenging activity was mediated by the generation phenolic compounds. The decreased cell viability by cisplatin was recovered significantly after treatment with FBG in a dose-dependent manner. Then, the protective effect of FBG on cisplatin-induced oxidative renal damage was investigated in rats. The decreased creatinine clearance levels, which are a reliable marker for renal dysfunction in cisplatin-treated rats, were reduced to the normal level after the administration of FBG. Moreover, FBG showed protective effects against cisplatin-induced oxidative renal damage in rats through the inhibition of $NF-{\kappa}B/p65$, COX-2, and caspase-3 activation. Conclusion: These results collectively show that the therapeutic evidence for FBG ameliorates the nephrotoxicity via regulating oxidative stress, inflammation, and apoptosis.

• Solar Energy
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• v.15 no.3
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• pp.127-140
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• 1995

This experimental study was carried out to examine the heat transfer characteristics of a 2-dimensional impinging air jet on a flat plate with a set of square rods. The objectives of the study were to investigate the flow and heat transfer characteristics caused by the square rods. Experiment was carried out first without using the rods to establish the baseline heat transfer performance. Then, rods of different widths and clearances were installed to cause the turbulence on the fluid flow. When rods are installed in front of the plate, the acceleration of the flow and the turbulence generation due to the rods and reattachment of the flow seem to contribute to the observed heat transfer augmentation and the heat transfer augmentation increases as the clearance decreases. With wider individual rod the heat transfer coefficient is higher, which is due to the increased acceleration and development of the eddies just before the rods.

• Transactions of Materials Processing
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• v.24 no.1
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• pp.37-43
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• 2015

The purpose of the current study is to improve the clinching joint strength of aluminum and fiber metal laminates (FMLs) comprised of three layers. The joining of FML and Al 5052 by a conventional clinching joint has some disadvantages such as necking of the upper sheet, lack of interlocking, defects caused by the vertical load, and especially loss of strength of the composite material due to the low ductility. In the current study, a tapered-hole clinching method is proposed as an alternative for the joining of Al 5052 and FMLs. A hole with a tapered shape is formed before the joining process. The design parameters were evaluated using the Taguchi method for the geometry of the tapered hole in order to determine the maximum separation load. The diameter of the punch corner, clearance, punch stroke and the tapered length were used as the main variables in the Taguchi method. In conclusion, the contribution ratio for each of the fours variable examined was 35.07%, 22.44%, 21.32% and 14.11%, respectively. In addition, the appropriate combination of the design parameters can make a 5% improvement in the vertical direction joint strength.

• Journal of Veterinary Clinics
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• v.24 no.1
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• pp.5-9
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• 2007

The purpose of this study was to examine the allometric analysis of roxithromycin using pharmacokinetic data. The pharmacokinetic parameters used were $half-life(t_{1/2})$, mean residence time (MRT), clearance (Cl) and volume of distribution at steady state $(V_{ss})$. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula $Y=aW^b$, where 'Y' is $t_{1/2}$, MRT, Cl, or $V_{ss}$, W the body weight and 'a' is an allometric coefficient (intercept) that is constant for a given drug. The exponential term, 'b', is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. As results of the allometric analyses, the logarithms of $t_{1/2}$, MRT, Cl, and $V_{ss}$ were linearly related to the logarithms of body weight. Results of the current analyses could provide information on appropriate doses of roxithromycin for all species.

• Journal of Microbiology
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• v.43 no.6
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• pp.537-545
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• 2005

Even though neutralizing antibodies against the Hantaan virus (HTNV) has been proven to be critical against viral infections, the cellular immune responses to HTNV are also assumed to be important for viral clearance. In this report, we have examined the cellular and humoral immune responses against the HTNV nucleocapsid protein (NP) elicited by virus infection or DNA vaccination. To examine the cellular immune response against HTNV NP, we used $H-2K^b$ restricted T-cell epitopes of NP. The NP-specific $CD8^+$ T cell response was analyzed using a $^{51}Cr-release$ assay, intracellular cytokine staining assay, enzyme-linked immunospot assay and tetramer binding assay in C57BL/6 mice infected with HTNV. Using these methods, we found that HTNV infection elicited a strong NP-specific $CD8^+$ T cell response at eight days after infection. We also found that several different methods to check the NP-specific $CD8^+$ T cell response showed a very high correlation among analysis. In the case of DNA vaccination by plasmid encoding nucleocapsid gene, the NP-specific antibody response was elicited $2\~4$ weeks after immunization and maximized at $6\~8$ weeks. NP-specific $CD8^+$ T cell response reached its peak 3 weeks after immunization. In a challenge test with the recombinant vaccinia virus expressing NP (rVV-HTNV-N), the rVV-HTNV-N titers in DNA vaccinated mice were decreased about 100-fold compared to the negative control mice.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.349-357
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• 1998

The aim of this experiments was to investigate the effect of Semen Plantaginis extract on. the renal function, plasma renin activity, plasma levels of atrial natriuretic peptide and aldosterone in rats. The results obtained were as follows: 1. Water balance decreased significantly after the administration of Semen Plantaginis extract. 2. Urine volume increased significantly after the administration of Semen Plantaginis extract, 0.1ml/200g. 3. Urinary excretion of sodium decreased significantly after the administration of Semen Plantaginis extract, 0.1 ml/200 g, 2week. 4. Urinary excretion of potassium decreased significantly after the administration of Semen Plantaginis extract, 0.1 ml/200 g, 2week. 5. Urinary excretion of chloride decreased significantly after the administration of Semen Plantaginis extract. 6. Free water clearance increased significantly after the administration of Semen Plantaginis extract 0.1 ml/200 g, 2 week and 0.2 ml/200 g. 7. Urinary excretion of creatinine increased significantly after the administration of Semen Plantaginis extract. 8. Plasma renin activity decreased significantly after the administration of Semen Plantaginis extract, 0.2 ml/200 g. 9. Plasma levels of aldosterone decreased significantly after the administration of Semen Plantaginis extract. 10. Plasma levels of atrial natriuretic peptide (ANP) decreased significantly after the administration of Semen Plantaginis extract.

• Clinical and Experimental Pediatrics
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• v.55 no.4
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• pp.136-142
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• 2012

Purpose: Urinary excretion of N acetyl-beta-D glucosaminidase (NAG) and ${\beta}_2$-microglobulin (${\beta}_2$-M) was increased in the presence of proximal tubular damage. Based on these urinary materials, we investigated the ability of expecting renal function in chronic glomerular diseases. In this study, we evaluated the relationship between glomerular filtration rate (GFR) urinary NAG, and urinary ${\beta}_2$-M. Methods: We evaluated 52 children with chronic kidney disease at the Chung-Ang University Hospital between January 2003 and August 2009. We investigated the 24-hour urinalysis and hematologic values in all 52 patients. Serum creatinine, creatinine clearance (Ccr), serum cystatin C, urinary ${\beta}_2$-M and urinary NAG were measured. Results: Out of 52 patients, there were 13 children with minimal change in disease, 3 children with focal segmental glomerulosclerosis, 17 children with immunoglobulin A nephropathy, 15 children with Henoch-Sch$\ddot{o}$nlein purpua nephritis, 3 children with poststreptococcal glomerulonephritis, and 1 child with thin glomerular basement membrane disease. In these patients, there were significant correlation between the Ccr and urinary NAG (r=-0.817; $P$ <0.01), and between the GFR (as determined by Schwartz method) and urinary NAG (r=-0.821; $P$ <0.01). In addition, there was a significant correlation between the GFR (as determined by Bokencamp method) and urinary NAG (r=-0.858; $P$ <0.01). Conclusion: In our study, there was a significant correlation between the GFR and urinary NAG, but there was no correlation between the GFR and urinary ${\beta}_2$-M, suggesting that the GFR can be predicted by urinary NAG in patients with chronic glomerular disease.