• Journal of Pharmaceutical Investigation
• /
• v.37 no.6
• /
• pp.369-376
• /
• 2007

Cyclosporine (CsA) and tacrolimus (FK506) have a narrow therapeutic range, and their pharmacokinetic (PK) characteristic varies among individual. They are also substrates for cytochrome P450 (CYP) 3A4, 3A5 genes, and P-glycoprotein, the product of the multidrug resistance 1 (MDR1). The aims were to investigate the relationship between CYP3A and MDR1 genotypes and their PK parameters among healthy subjects. We investigated the genotype for CYP3A and MDR1 gene in human using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. After oral administration of CsA and FK506 (100 mg and 1 mg, respectively), whole blood samples were taken up to 24 hours. Blood CsA and FK506 concentrations were measured by LC/MS/MS. Each PK parameters were compared using Kruskal-Wallis test according to the CYP3A and MDR1 genotype. We found that the values of AVC for CsA were significantly different among CYP3A5 and MDR1 exon 26 (C3435T) genotypes (P=0.037 and P=0.049). On the other hand, the AUC for FK506 was significantly different only among CYP3A5 genotypes (P=0.013). The results clearly demonstrate the effects of CYP3A5 and MDR1 exon 26 on Cys and FK506 disposition.

• Journal of Veterinary Clinics
• /
• v.34 no.4
• /
• pp.234-240
• /
• 2017

Use of ketamine and propofol combination (so-called Ketofol) anesthesiain a fixed ratio (1:1 mg/ml) was reported in dogs. The use of ketofol reduced cardiovascular suppression, but respiratory-related side effects was not significantly different from propofol alone. In this study, we evaluated the quality of ketofol anesthesia and changes in cardiopulmonary function according to the ratio of ketamine to propofol. The experimental groups were divided into three groups: propofol alone (P group), 3:7 ketofol group (PK1 group) and 1:1 ketofol group (PK2). For each group, the dose of 0.8 ml/kgwas administered intravenously at a constant rate until the tracheal intubation was possible and anesthesia was maintained with isoflurane for 120 minutes after induction of anesthesia. There was no significant difference in the anesthetic quality among three groups. Also, there was no difference in respiratory rate, tidal volume, end-tidal carbondioxide, and oxygen saturation. In group P, heart rate was not changed significantly during anesthesia, but arterial blood pressure decreased, while heart rate and arterial blood pressure increased significantly in group PK2. In the PK1 group, heart rate and arterial blood pressure during anesthesia remained similar to pre-anesthetic values. In conclusion, ketofol might be used as induction agent, and 3:7 ratioof ketofol showed more safe and effective anesthetic effect in dogs. Additionally, 1:1 ketofol may be used in patients with severe bradycardia orhypotension with close monitoring during anesthesia.

• Archives of Pharmacal Research
• /
• v.28 no.3
• /
• pp.311-318
• /
• 2005

Oxidative stress has been reported to elevate ceramide level during cell death. The purpose of the present study was to modulate cell death in relation to cellular glutathione (GSH) level and GST (glutathione S-transferase) expression by regulating the sphingolipid metabolism. LLC­PK1 cells were treated with H$_2$O$_2$ in the absence of serum to induce cell death. Subsequent to exposure to H$_2$O$_2$, LLC-PK1 cells were treated with desipramine, sphingomyelinase inhibitor, and N-acetylcysteine (NAC), GSH substrate. Based on comparative visual observation with H202-treated control cells, it was observed that 0.5 $\mu$M of desipramine and 25 $\mu$M of NAC exhibited about 90 and $95\%$ of cytoprotection, respectively, against H$_2$O$_2$-induced cell death. Desipramine and NAC lowered the release of LDH activity by 36 and $3\%$ respectively, when compared to $71\%$ in H$_2$O$_2$-exposed cells. Cellular glutathione level in 500 $\mu$M H202-treated cells was reduced to 890 pmol as compared to control level of 1198 pmol per mg protein. GST P1-1 expression was decreased in H$_2$O$_2$-treated cells compared to healthy normal cells. In conclusion, it has been inferred that H$_2$O$_2$-induced cell death is closely related to cellular GSH level and GST P1-1 expression in LLC-PK1 cells and occurs via ceramide elevation by sphingomyelinase activation.

• Korean Journal of Soil Science and Fertilizer
• /
• v.51 no.2
• /
• pp.111-118
• /
• 2018

A field experiment was conducted to investigate the effect of long-term (21-year) fertilizer and compost treatments on the yield of red pepper and chemical properties in top-dong, Suwon. Six treatments were chosen for this work: No fertilization (No fert.), NPK fertilizers (NPK), NPK and compost (NPK+Compost), NP and compost (NP+Compost), NK and compost (NK+Compost), PK and compost (PK+Compost). The yield of red pepper for 21 years indicated the significant differences among the No fertilization, the PK+Compost, and other treatments. The relative yield index was 13% and 59% respectively, for the No fertilization and the PK+Compost if the average yield of red pepper for the NPK regards $20,048kg\;ha^{-1}$ as the yield index with 100%. Soil organic matter at the compost applied treatments significantly increased compared with the No fert. and the NPK. The average increase rates of soil organic matter by applying the compost ranged from 0.69 to $0.73g\;kg^{-1}\;yr^{-1}$. Available phosphate content in soil appeared the significant increase all treatments excluding the No fert. It is estimated that the available phosphate in soil was increased by $7.0mg\;kg^{-1}\;yr^{-1}$ by applying compost and $14.2mg\;kg^{-1}\;yr^{-1}$ by applying P fertilizer. Application of K fertilizer or the compost alone, the NPK, the NP+Compost, continuously caused soil K depletion whereas K fertilization plus the compost maintained at a constant level of exchangeable K. The results indicated that the addition of compost to NPK fertilizer is recommended for the maximum stable yield for red pepper and enhancement of organic matter though it is also needed for adjusting of P and K fertilization.

• Journal of Pharmaceutical Investigation
• /
• v.40 no.6
• /
• pp.363-366
• /
• 2010

Identification of compounds that function as P-glycoprotein (P-gp) substrates or inhibitors can facilitate the selection and optimization of new drug candidates. The purpose of this study is to optimize the experimental conditions for in vitro P-gp assay using LLC-GA5 cells, which is a well-known transformant cell line derived by transfecting LLC-PK1 with human MDR1. The amount of rhodamine123 transported by the LLC-GA5 and LLC-PK1 cells was evaluated under the following experimental conditions: 3 different types of transport media, colchicine pretreatment or nontreatment of the cells in the culture media, and with and without poly-L-lysine coating of the culture plates. The assay sensitivity was found to considerably differ depending on the diluents used in the transport media. P-gp-mediated transport in LLC-GA5 cells was most clearly characterized in the Hanks' balanced salt solution based transport media. The sensitivity of P-gp-mediated transport was not changed by colchicine pretreatment or poly-L-lysine coating of the culture plates.

• KOREAN JOURNAL OF CROP SCIENCE
• /
• v.25 no.2
• /
• pp.23-30
• /
• 1980

Experiments were conducted to know N, P, and K top dressing effects on yield and other agronomic characters of rice plants grown in 5-year differently fertilized soils. Four levels of nitrogen, 0, 1.2, 2.4, and 3.6kg/10a, were applied 32 days before heading in 5-year non-fertilized and PK applied plots. Four levels of P_2 $O_{5}$ and K_2 O of 0, 4, 8 and 12kg/l0a were applied 40 days before heading in 5-year NK and NP applied plots, respectively. 1. Heading was delayed by seven days in 5-year non-fertilized and PK applied plots compared to NK, NP, or NPK applied plots where nitrogen was applied as basal. However, in 5-year non-fertilized and PK applied plots heading was delayed from 1 to 4 days as amounts of nitrogen top dressing increased. Phosphorus and potassium did not affect heading date of rice plants. 2. In 5-year non-fertilized plot grain yield increased as amounts of nitrogen top dressing increased up to 2.4kg/l0a due to both increased number of panicles per hill and spikelets per panicle. However, in 5-year PK applied plot amounts of nitrogen top dressing did not affect grain yield; the number of panicle per hill increased, but the percentage of ripened grains and grain weight tended to decrease as nitrogen levels increase. 3. The number of panicle/maximum tillers ratio in percentage increased markedly as amounts of nitrogen top dressing increased in 5-year non-fertilized and PK applied plots with maximum value of 130% on the basis of maximum tillers at vegetative stage. 4. Top dressing of phosphorus and potassium did not affect yield and other agronomic characters in NK and NP applied plots.

• Korean Journal of Medicinal Crop Science
• /
• v.22 no.1
• /
• pp.8-16
• /
• 2014

The present study was carried out to evaluate the antioxidant and anti-inflammatory activities of three extracts (hot water, 50% ethanol and mixed solvent;water, ethanol, butylene glycol, propylene glycol) of dried chestnut, chestnut shell, chestnut leaves and dried chestnut leaves obtained from Castanea crenata tree. When conducted DPPH assay, radical scavenging activity of ethanol extract of chestnut shell was the highest with $IC_{50}$ $10.8{\mu}g/mL$ among four extracts from these parts (p < 0.05). In additional results by the xanthine oxidase assay, antioxidant activity showed that water extract of chestnut leaves showed the highest xanthine oxidase inhibitory activity in the tested extracts (p < 0.05). Futhermore, extracts of chestnut shell and leaves exhibited no cytotoxicity in RAW 264.7 cells (p < 0.05). Also, anti-inflammatory activity by NO assay showed LPS-induced NO was significantly inhibited following treatment with extracts of chestnut shell and leaves of 3mg/mL (p < 0.05). These data suggest that extract of chestnut shell have antioxidant and anti-inflamantory activity including chestnut leaves. Therefore, it is considered that Castanea crenata research range and selection of functional material can broaden chestnut shell to other fractions such as chestnut and chestnut leaves.

• Journal of Life Science
• /
• v.28 no.4
• /
• pp.389-397
• /
• 2018

The structure of glycan residues attached to glycoproteins can influence the biological activity, stability, and safety of pharmaceutical proteins delivered from transgenic pig milk. The production of therapeutic glycoprotein in transgenic livestock animals is limited, as the glycosylation of mammary gland cells and the production of glycoproteins with the desired homogeneous glycoform remain a challenge. The ${\beta}$-1,3-N-acetylglucosaminylatransferase1 (B3GNT1) gene is an important enzyme that attaches N-acetylglucosamine (GlcNAc) to galactose (Gal) residues for protein glycosylation; however, there is limited information about pig glycosyltransferases. Therefore, we cloned the pig B3GNT1 (pB3GNT1) and investigated its functional properties that could attach N-acetylglucosamine to galactose residue. Using several different primers, a partial pB3GNT1 mRNA sequence containing the full open reading frame (ORF) was isolated from liver tissue. The ORF of pB3GNT1 contained 1,248 nucleotides and encoded 415 amino acid residues. Organ-dependent expression of the pB3GNT1 gene was confirmed in various organs from adult and juvenile pigs. The pB3GNT1 mRNA expression level was high in the muscles of the heart and small intestine but was lower in the lungs. For functional characterization of pB3GNT1, we established a stable expression of the pB3GNT1 gene in the porcine kidney cell line (PK-15). As a result, it was suggested that the glycosylation pattern of pB3GNT1 expression in PK-15 cells did not affect the total sialic acid level but increased the poly N-acetyllactosamine level. The results of this study can be used to produce glycoproteins with improved properties and therapeutic potential for the generation of desired glycosylation using transgenic pigs as bioreactors.

• Journal of Life Science
• /
• v.33 no.10
• /
• pp.797-807
• /
• 2023

To improve the functionality of mulberry, samples were fermented with Lactobacillus plantarum JCM 1149 (LP) or Pichia kudriavzevii Atz-EN-01 (PK), and their antioxidant and anti-obesity activities were compared to those of unfermented mulberry. After fermenting for 60 hr, the total polyphenol and flavonoid content of the PK-fermented mulberry (PKFM) and LP-fermented mulberry (LPFM) was 1.5-fold and 2-fold higher, respectively, while the total anthocyanin content was 1.3-fold and 1.5-fold higher in the PKFM and LPFM, respectively. DPPH radical scavenging activity was found to be 16.3% higher (86% vs. 100%) after PK fermentation and 8.1% higher (86% vs. 93%) after LP fermentation. The lipase inhibitory activity of the LPFM and PKFM was 62.9% and 52.5%, respectively. 3T3-L1 preadipocytes were treated with unfermented mulberry, LPFM, or PKFM at 200, 400, or 800 ㎍/ml and stained with oil-red-O. A slight difference in the staining was observed in samples treated with 400 ㎍/ml. However, treatment with 800 ㎍/ml significantly reduced staining compared to the control, and the LPFM exhibited relatively higher adipogenesis inhibitory activity than the PKFM. Blood triglyceride content increased by 9.5% in the high-fat diet group, but decreased by 17.1% in the control group, 37.1% in the LPFM group, and 41.6% in the PKFM group. The blood triglyceride content of the LPFM group decreased by 43.1% and 21.4% compared to the high-fat diet group and the control group, respectively, and that of the PKFM group decreased by 48.6% and 28.9% compared to the same groups. In conclusion, the results indicate that fermented mulberry has increased antioxidant activity, lipase inhibitory activity, and adipogenesis inhibition activity, and decreased blood triglyceride content compared to unfermented mulberry.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.11
• /
• pp.1674-1680
• /
• 2014

The aim of this study was to investigate the protective effects of methanolic extracts of cooked mixed grain rice samples, including grain rice (sorghum, black bean, proso millet, and Job's tears) mixed with fermented brown rice (GR), GR added with 0.5% water extract of Sanghwang mushroom (GRS) or 0.1% curry (GRK), and traditional five grain mixed rice (TMR, Ohgokbap), on $H_2O_2$-induced oxidative injury in LLC-PK1 pig renal epithelial cells. White rice (WR) was used as a positive control. Cells were first exposed to $H_2O_2$ ($250{\mu}M$) for 4 hr, followed by treatment with $100{\mu}g/mL$ of different GR extracts for 24 hr. $H_2O_2$ significantly induced cell damage (P<0.05). Cellular levels of reactive oxygen species (ROS), lipid peroxidation, and antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px), were measured. In addition, mRNA levels of antioxidant enzymes were determined by RT-PCR assay. Mixed grain rice, particularly GRS and GRK, were able to reduce cellular levels of ROS, decrease lipid peroxidation, and also increase mRNA expression of antioxidant enzymes compared to other samples. These results suggest that mixed grain rice, specifically GRS and GRK, have strong protective effects against $H_2O_2$-induced oxidative injury in LLC-PK1 cells through inhibition of lipid peroxidation, reduction of ROS levels, and elevation of antioxidant enzyme activities.