• Mass Spectrometry Letters
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• v.12 no.2
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• pp.53-58
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• 2021

Previous in vitro studies have demonstrated that ginsenoside Rc inhibits UGT1A9, but there are no available data to indicate that ginsenoside Rc inhibits UGT1A9 in vivo. The effect of single and repeated intravenous injection of ginsenoside Rc was evaluated on the pharmacokinetics of mycophenolic acid. After injection of ginsenoside Rc (5 mg/kg for one day or 3 mg/kg for five days), 2-mg mycophenolic acid was intravenously injected, and the pharmacokinetics of mycophenolic acid and mycophenolic acid-β-glucuronide were determined. Concentrations of mycophenolic acid and its metabolite from rat plasma were analyzed using a liquid chromatography-triple quadrupole mass spectrometry. Single or repeated pretreatment with ginsenoside Rc had no significant effects on the pharmacokinetics of mycophenolic acid (P > 0.05): The mean difference in maximum plasma concentration (C_max) and area under the concentration-time curve (AUC_inf) were within 0.83- and 0.62-fold, respectively, compared with those in the absence of the ginsenoside Rc. These results indicate that ginsenoside Rc has a negligible effect on the disposition of mycophenolic acid in vivo despite in vitro findings indicating that ginsenoside Rc is a selective UGT1A9 inhibitor. As a result, ginsenoside Rc has little possibility of interacting with drugs that are metabolized by UGT1A9, including mycophenolic acid.

• BMB Reports
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• v.40 no.6
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• pp.979-985
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• 2007

Induction of growth hormone (GH) by Glycyrrhizae Radix (GR), one of the most popular herbal medicine, and its major ingredients were studied in rat pituitary cells in vitro and in vivo assay. The MeOH extract and the n-hexane (HX) fraction of GR induced rat GH (rGH) release up to 1.89 times ($0.34{\pm}0.04 nM$) and 4.59 times ($0.83{\pm}0.03 nM$), compared to the basal level (p < 0.05). Among many ingredients isolated and purified from GR both glycyrrhetinic acid and glycyrrhizin induced significantly rGH release compared to the control (p < 0.05). After an intravenous injection of rat growth hormone releasing hormone (rGHRH) ($10{\mu}g$/kg) as positive control, in SD rats, $T_{max}$ of plasma rGH level was 10 min, $C_{max}$ was $3.84{\pm}0.01 nM$ (n = 3), and enhanced plasma rGH level returned to the baseline in 90 min. Both $AUC_{0-90}$ (area under the curve) of plasma rGH level after HX fraction and that after rGHRH administration were increased significantly from the basal level, respectively (p < 0.01). In conclusions, HX fraction is the most active fraction of MeOH extract of GR in rGH induction.

• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.65-77
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• 2005

Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

• Journal of Pharmaceutical Investigation
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• v.22 no.2
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• pp.125-131
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• 1992

The effects of domperidone, scopolamine butylbromide and cimetidine on the absorption and bioavailability of ciprofloxacin were studied in female rats. Ciprofloxacin was given in a single oral dose of 30 mg/kg to control group. Ciprofloxacin was concurrently administered with domperidone $(T_1\;group)$, scopolamine butylbromide $(T_2\;group)$, and cimetidine $(T_3\;group)$ to rats, respectively. Significantly changed pharmacokinetic parameters observed in $T_2$group when compared with control group were first-order absorption rate constant, $Ka(4.43{\pm}0.85$\;versus\;2.86{\pm}0.41\;hr^{-1},\;p<0.05)$, time needed to reach peak concentration, $T_{max}\;(32.27{\pm}2.46\;versus\;51.75{\pm}5.51\;min,\;p<0.05)$, area under the plasma concentration-time curve, AUC $(332{\pm}19\;versus\;477{\pm}27\;{\mu}g{\cdot}min/ml,\;p<0.05)$ and absolute bioavailability, Fabs $(60.6{\pm}3.6\;versus\;87.0{\pm}5.0%,\;p<0.05)$. On the other hand, domperidone and cimetidine did not significantly affect the absorption of ciprofloxacin. It is suggested that when scopolamine butylbromide is selected for clinical use, there is need for awareness of the reduction in absorption rate and the enhancement in absorption extent of ciprofloxacin.

• Journal of Nutrition and Health
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• v.39 no.3
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• pp.244-251
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• 2006

The purpose of this study was to observe the effects of cellulose and pectin on glucose and plasma lipid concentrations in healthy women. Eight female collage students were participated voluntarily. All subjects received a fiber-free control diet (CD), cellulose diet (CED), pectin diet (PTD) with each diet for a period of three days with a 4 day interval. The food intake of subjects were monitored every day and plasma level of glucose, triglyceride, total cholesterol were determined at last day. Blood glucose, plasma triglyceride, total cholesterol were measured at fasting state and 30, 60, 90, 120, and 180 minute after consuming each diet. Plasma glucose concentrations (AUC: Area Under the Curve) of pectin diet was $122.7{\pm}4.0mg/dl$ and that of cellulose diet was $147.6{\pm}8.4mg/d$, but they were significantly lower than in comparison with those of control diet ($197.1{\pm}11.6mg/dl$) (p<0.05) Plasma triglyceride concentrations of the CED ($-83.9{\pm}22.2mg/dl$) PTD ($-9.7{\pm}26.1mg/dl$) showed gradual decrease after each test diet feeding but not significantly different in each dietary fiber added diet (p<0.05). Plasma cholesterol concentrations of the CD was not significantly different in PTD, but PTD was significantly lower than the CED until 3 hours after consuming each test meal (p<0.05). In conclusion, in spite of total cholesterol was reduced only by pectin, glucose and triglyceride were lower than control diet in dietary fiber intake. But there were no significant differences each dietary fiber.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.9
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• pp.1266-1273
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• 2015

The effect of starch infusion on production, metabolic parameters and relative mRNA abundance was investigated in low yield lactating cows from 86 days in milk. Six Holstein cows fitted with permanent ruminal cannulas were arranged into one of two complete $3{\times}3$ Latin squares and infused with a starch solution containing 800 grams starch for 16 days. The three treatments were: i) ruminal and abomasal infusion with water (Control); ii) ruminal infusion with cornstarch solution and abomasal infusion with water (Rumen); iii) ruminal infusion with water and abomasal infusion with cornstarch solution (Abomasum). There were no significant differences (p>0.05) among the three treatments with low yield lactating cows in feed and energy intake, milk yield and composition, plasma metabolism, or even on gene expression. However, cows receiving starch through rumen performed better than directly through the abomasum during the glucose tolerance test procedure with a higher area under the curve (AUC; p = 0.08) and shorter half-time ($t^{1/2}$; p = 0.11) of plasma insulin, therefore, it increased glucose disposal, which stated a lipid anabolism other than mobilization after energy supplementation. In conclusion, extra starch infusion at concentration of 800 g/d did not enhance energy supplies to the mammary gland and improve the lactating performance in low yield lactating cows.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2851-2855
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• 2015

Background: Recent reports have shown that nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), contributes to the precise control of gene expression and is related to several human malignancies. However, limited data are available on the expression and function of NEAT1 in lung cancer. The major objective of the current study was to profile the expression and clinicopathological significance of NEAT1 in non-small cell lung cancers (NSCLCs). Materials and Methods: NEAT1 expression in 125 NSCLC cases and paired adjacent non-cancer tissues was assessed by real-time quantitative reverse transcription-PCR (qRT-PCR). Relationships between NEAT1 and clinicopathological factors were also investigated. Results: The relative level of NEAT1 was $6.98{\pm}3.74$ in NSCLC tissues, significantly elevated as compared to that of the adjacent non-cancer lung tissues ($4.83{\pm}2.98$, p<0.001). The area under curve (AUC) of high expression of NEAT1 to diagnose NSCLC was 0.684 (95% CI: 0.619~0.750, p<0.001). NEAT1 expression was positively correlated with patient age (r=-2.007, p=0.047), lymphatic metastasis (r=-2.731, p=0.007), vascular invasion (r=-3.617, p=0.001) and clinical TNM stage (r=-4.134, p<0.001). Conclusions: This study indicates that NEAT1 might be associated with oncogenesis and progression in NSCLC, and suggests application in molecular targeted therapy.

• Tuberculosis and Respiratory Diseases
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• v.67 no.5
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• pp.430-435
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• 2009

Background: Thus far, research studies on community-acquired pneumonia (CAP) have focused on its clinical severity. Recently, it has been determined that procalcitonin (PCT) level is correlated with severity of CAP. A retrospective study conducted at our hospital used risk predictability and PCT to determine whether or no PCT is useful in assessing the severity of CAP. Methods: This study covered 92 CAP cases that were admitted to the respiratory department at Changwon Fatima Hospital between July 1, 2008 and June 30, 2009. All enrolled subjects were measured for infection markers and risk predictability. Results: Based on hospital admission data, enrolled subjects had Pneumonia Severity Index (PSI) scores serving as risk predictors showed that both PCT and white blood cell (WBC) were statistically significant as infection markers (p=0.001, 0.037). Thus, this study used ROC curves in PSI for data analysis. As a result, it was determined that the area under curve (AUC) of PCT and WBC was 0.694 and 0.593 respectively, indicating that PCT has a higher test value for WBC, when PCT was higher than 0.745 ng/mL. In addition, it was found that PCT levels higher than 0.745 ng/mL had higher PSI scores than the group with PCT lower than 0.745 ng/mL (p=0.032). Conclusion: In order to predict risk of pneumonia cases admitted due to symptoms of CAP, it is important to consider PCT as well as PSI, and follow-up monitoring of PCT cases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4695-4698
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• 2012

Objective: To analyze differential diagnostic accuracy of urinary human epidydimis secretory protein 4 (HE4) in patients with ovarian tumors. Materials and methods: In the case-control study 23 patients with ovarian cancer, 37 patients with benign ovarian tumors and 18 women in the control group were included. Serum CA125 values and urinary concentrations of HE4were assessed quantitatively. Urinary creatinine concentrations and glomerular filtration rate were also determined and used to calculate ratios to HE4. Results: Higher urinary HE4 concentrations were observed in patients with late stage ovarian cancer (p=0.001) and also in patients with early stage ovarian cancer when compared to patients with benign ovarian tumors (p=0.044). On analysis where all ovarian cancer patients were included, higher diagnostic accuracy was observed with calculated ratio of HE4 to glomerular filtration rate (GFR) to unchanged urinary HE4 concentrations -AUC 0.861 vs. 0.858. When discriminatory accuracy was calculated for urinary HE4/GFR ratio and unchanged urinary HE4 concentrations, the last demonstrated a higher area under the curve - 0.701 vs. 0.602. The urinary HE4/creatinine ratio had lower discriminatory characteristics than unchanged concentrations of urinary HE4. However, HE4 serum concentration was more accurate for discrimination of patients with benign and malignant ovarian tumors when compared to urinary HE4 and CA125 in sera (AUCs were 0.868 for serum HE4 and 0.856 and 0.653 for urinary HE4 and CA125, respectively). Conclusions: Ovarian cancer patients have higher urinary concentrations of human epidydimis secretory protein 4 than patients with benign ovarian tumors. Urinary HE4 has comparable discriminatory accuracy with serum HE4 for benign and malignant ovarian tumors and can be recommended as a non-invasive ovarian cancer risk assessment method.

• Journal of Pharmaceutical Investigation
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• v.33 no.4
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• pp.299-304
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• 2003

The purpose of this study was to investigate the effect of coadministration (2.5, 10, 20 mg/kg) and 3 or 7 days-pretreatment (10 mg/kg) of diltiazem on the pharmacokinetic parameters of paclitaxel (50 mg/kg) given orally in rats. The plasma concentrations of paclitaxel coadministered or pretreated with diltiazem were significantly (p<0.05 at 20 mg/kg coadmin., p<0.05 at pretreat.) increased compared to that of control, from 0.5 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel coadministered or pretreated with diltiazem was significantly (p<0.05 at 20 mg/kg coadmin., p<0.01 at pretreat.) higher than that of control. Peak concentrations $(C_{max})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg coadmn. and pretreat.) increased compared to that of control. Elimination rate constants $(K_{el})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg and 7 days-pretreat.) reduced compared to those of control. Half-life $(t_{1/2})$ and mean residence time (MRT) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg ad 7 days-pretreat.) prolonged compared to those of control. Absolute bioavailability (AB%) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg and 3 days-pretreat, p<0.01 at 7 days -pretreat.) increased compared to that of control. Based on these results, it might be considered that diltiazem may inhibit cytochrome $P_{450}$ and P-glycoprotein, which are respectively engaged in paclitaxel absorption and metabolism in liver and gastrointestinal mucosa.