• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.5
• /
• pp.1881-1895
• /
• 2015

Background: The vascular endothelial growth factor family has been implicated in tumorigenesis and metastasis. The prognostic value of each vascular endothelial growth factor family member, particular VEGF/VEGFR co-expression, in patients with non-small lung cancer remains controversial. Materials and Methods: Relevant literature was identified by searching PubMed, EMBASE and Web of Science. Studies evaluating expression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in lung cancer tissue were eligible for inclusion. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled by using a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed. Results: 74 studies covering 7,631 patients were included in the meta-analysis. Regarding pro-angiogenesis factors, the expression of VEGFA (HR=1.633, 95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) was associated separately with poor survival. Especially, VEGFA over-expression was an independent prognostic factor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384-2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137). Co-expression of VEGFA/VEGFR2 (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worse survival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611, 95%CI: 1.407-1.844) predicted a poor prognosis. Co-expression of VEGFC/VEGFR3 (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferable prognostic marker. Conclusions: The expression of VEGFA (particularly in SCC and early stage NSCLC), VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with NSCLC. Co-expression VEGFA/VEGFR2 is comparable with VEGFC/VEGFR3, both featuring sufficient discrimination value as preferable as prognostic biologic markers.

• Journal of Pharmaceutical Investigation
• /
• v.38 no.5
• /
• pp.343-348
• /
• 2008

The bioequivalence of two cyclosporine A (CyA) 100 mg soft capsules (Chong Kun Dang's $Cipol-N^{(R)}$ as the test drug; Korea Novartis' Sandimmun $Neoral^{(R)}$ as the reference drug) was assessed in healthy male Korean volunteers after oral administration of 200 mg CyA according to a randomized crossover design. The whole blood samples were analyzed for the determination of parent CyA in the blood by using a validated HPLC/diode array detector method. The mean $AUC_t$ values for reference and test products were $4095.3{\pm}1397.2$ and $3958.3{\pm}1138.2\;ng{\cdot}hr/mL$, respectively. The mean $C_{max}$ values were $1135.9{\pm}293.2\;ng/mL$ for the reference product, and $985.0{\pm}207.9\;ng/mL$ for the test product. $T_{max}$ was $1.6{\pm}0.4\;hr$ for the reference and $1.8{\pm}0.5\;hr$ for the test product. The differences of $AUC_t$, $C_{max}$ and $T_{max}$ were -3.35, -13.28 and +10.63%, respectively. The point estimates and 90% confidence intervals for $AUC_t$ and $C_{max}$ were 0.981 (0.9171 to 1.0514) and 0.876 (0.8229 to 0.9336), respectively. Based on the pharmacokinetic and statistical data, we conclude that these two products are bioequivalent and can be considered interchangeable in the medical practice.

• Korean Journal of Clinical Pharmacy
• /
• v.12 no.2
• /
• pp.71-75
• /
• 2002

This study was carried out to compare the bioavailability of $Ceclex^{(R)}$ (test drug, cefaclor 250 mg/capsule) with that of $Ceclor^{(R)}$ (reference drug) and to estimate the pharmacokinetic parameters of cefaclor in healthy Korean adult. The bioavailability was examined on 20 healthy volunteers who received a single dose (250 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 6hours. Plasma concentrations of cefaclor were determined using HPLC with UV detection. The pharmacokinetic parameters $(AUC_{0-6hr},\;C_{max},\;T_{max},\;AUC_{int},\;K_e,\;t_{1/2},\;Vd)$ F, and CL/F) were calculated with non-compartmental pharmacokinetic analysis. The ANOVA test was utilized for the statistical analysis of the $T_{max},\;log-transformed\;AUC_{0-6hr}\;log-transformed\;C_{max},\;t_{l/2},\;V_d/F$, and CL/F. The ratios of geometric means of AUC0-6hr and $C_{max}$ between test drug and reference drug were $103.2\%\;(6.74\;{\mu}g{\cdot}hr/ml\;vs\;6.53{\pm}g{\cdot}hr/ml)\;and\;100.4\%\;(4.85\;{\mu}g\ml\;vs\;4.82\;{\mu}g/ml)$, respectively. The $T_{max}$ of test drug and reference drug were $0.9\pm0.38\;hr\;and\;0.83\pm0.34$ hrs, respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-6h},\;and\;C_{max}$ were log $0.98{\sim}log$ 1.08 and log $0.88{\sim}log1.15$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The estimated half-life of this study was longer $(1.21\pm0.27\;hrs\;vs\;0.5-1\;hr)$, the Vd/F was larger $(68.89\pm25.72L$ vs 24.9L), and the CL/F was higher $(38.62\pm7.09\;L/hr$ vs 24.9 L/hr) than the previously reported values.

• Korean Journal of Food Science and Technology
• /
• v.4 no.3
• /
• pp.200-205
• /
• 1972

Effects of several different petroleum fractions (LGO, HGO, VGO, Diesel oil, SP(E), HGO-wax, L/M-wax), stepwise addition of calculated amounts of HGO at defined intervals, recycling of spent media on cell growth of Candida tropicalis KIST 351 were studied using $2.5{\ell}$ fermenter by batch process. In addition, continuous cultivation of the yeast was also performed in the light of biomass production using $28{\ell}$ fermenter with LGO. 1) Cell concentration, yield on the basis of gas oil and n-paraffin with the petroleum fractions were in the range of $11{\sim}15g/{\ell}$, $10{\sim}12%$ and $77{\sim}82%$, respectively. 2) By stepwise addition of the gas oil, cell concentration and yield on the oil were increased up to 18.9 g/land 13%, respectively. 3) Spent medium slowed emulsifying ability of hydrocarbon and stimulating effect on the cell growth. Without additional supplementation of $Mg^{++}$ up to 20% of spent medium could be reused, while by adding of the $Mg^{++}$, 50% of medium could be recycled. 4) Optimum condition of continuous cultivation for biomass production was attained at the dilution rate of $D=0.1{\sim}0.125\;hr^{-1}$. Maximum yield coefficient on consumed n-paraffin was 0.94 at $D=0.1\;hr^{-1}$, however, 24% of supplied n-paraffin in the media was not utilized at this dilution rate.

• Journal of Pharmaceutical Investigation
• /
• v.40 no.2
• /
• pp.109-115
• /
• 2010

The purpose of the present study was to evaluate the bioequivalence of two choline alphoscerate soft capsules, Gliatilin soft capsule (Daewoong Pharmaceuticals Co., Ltd.) and Cholicerin soft capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Serum concentrations of choline after oral administration of choline alphoscerate were determined using a validated LC/MS/MS method. This method showed linear response over the concentration range of 0.5-20 ${\mu}g$/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 100 ${\mu}L$ of serum was 0.5 ${\mu}g$/mL which was sensitive enough for pharmacokinetic studies. Thirty six healthy male Korean volunteers received each medicine at the choline alphoscerate dose of 1200 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Blood samples were taken at predetermined time intervals up to 8 hr. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 8 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum 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 Cholicerin/Gliatilin were log0.9998-log1.1172 and log0.9938-1.0944, respectively. These values were within the acceptable bioequivalence intervals of log0.80-log1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Cholicerin soft capsule and Gliatilin soft capsule are bioequivalent.

• Biomolecules & Therapeutics
• /
• v.13 no.2
• /
• pp.118-122
• /
• 2005

The objective of the present investigation was to study pharmacokinetics of promethazine in Korean healthy subjects using a validated HPLC method. The HPLC analysis was performed on a Capcell Pak CN column with a mixture of acetonitrile-0.02M potassium dihydrogen phosphate (42:58, v/v, pH 6.0) and the analyte was quantified with UV detection at 251 nm. The calibration curve of the drug was linear over the range of 1-40ng/mL in human serum and the limit of quantification (LOQ) was 1 ng/mL. This analytical method was validated and shown to be specific, accurate, precise and reproducible. This method was applied to pharmacokinetic study of promethazine in Korean healthy volunteers following an oral administration of two 25 mg Himazin tablets (50 mg promethazine ${\cdot}$HCI) after overnight fasting. Serum samples were collected at given intervals over a 36-hour period (12 points) and pharmacokinetic parameters were determined from serum concentration-time profile using WinNonlin program. The estimated $AUC_{0__\infty}$, $AUC_{0_\infty}$, $C_{max}$, $T_{max}$ and $t_{1/2}$ of promethazine obtained from Korean healthy subjects were 103.84 ${\pm}$84.30 ng${\cdot}$hr/mL, 87.94${\pm}$81.02 ng${\cdot}$hr/mL, 13.43${\pm}$10.92 ng/mL, 2.00${\pm}$1.16 hr and 5.88${\pm}$3.47 hr, respectively.

• Korean Journal of Medicinal Crop Science
• /
• v.17 no.3
• /
• pp.204-209
• /
• 2009

This study was conducted to assess water movement in paddy-upland rotation soil scheduled for ginseng cultivation through the measurement of infiltration and permeability of soil water. Soil sample was divided with four soil layers. The first soil layer (to 30cm from top soil) was loamy sand, the second and the third soil layers (30$\sim$70 ㎝) were sand, and the fourth (< 120 ㎝) was sandy loam. The soil below 130 ㎝ of fourth soil layer was submerged under water. The shear strength, which represents the resisting power of soil against external force, was 3.1 kPa in the first soil layer. This corresponded to 1/8 of those of another soil layer and this value could result in soil erosion by small amount of rainfall. The rates of infiltration and permeability depending on soil layers were 39.86 cm $hr^{-1}$ in top soil, 2.34 cm $hr^{-1}$ in 30$\sim$70 ㎝ soil layer, 5.23 cm $hr^{-1}$ and 0.18 cm $hr^{-1}$ in 70$\sim$120 ㎝ soil layer, with drain tile, and without drain tile, respectively. We consider that ground water pooled in paddy soil and artificial formation of soil layer could interrupt water canal within soil and affect negatively on water movement. Therefore, we suggest that to drain at 5 m intervals be preferable when it makes soil dressing or soil accumulation to cultivate ginseng in paddy-upland rotation soil to reduce failure risk of ginseng cultivation.

• The Korean Journal of Physiology
• /
• v.15 no.1
• /
• pp.9-18
• /
• 1981

For centuries, ginseng has been used for the therapeutic purpose in oriental herb medicine. Several studies have been conducted in the past to evaluate the effect of ginseng on erythropoiesis. However the results were controversial. We therefore attempted in the present studies to evaluate the effect of ginseng on the erythropoietic activity. In one series of experiments, the recovery pattern of peripheral blood(red cell count, hemoglobin content, hematocrit and reticulocyte count) was studied in posthemorrhagic anemic rabbits. After animals were maintained with normal(control group) or 1 gm% ginseng (experimental group) diet for 2 weeks, hemorrhagic anemia was induced by withdrawing blood equivalent to 25% of the total blood volume and then changes in peripheral blood were followed for following 30 days. In other series of experiments, we studied effect of ginseng on erythrokinetics using $^{59}Fe$. $^{59}Fe(10{\sim}40\;{\mu}Ci/animal)$ was injected intravenously after animals were fed with normal (control group) or 1 gm% ginseng(experimental group) diet for 2 weeks. And radioactivities in the blood compartments were measured at appropriate intervals for 15 days. Front these various erythrokinetic parameters were estimated. Results are summarized as follows: 1) Reticulocyte count was higher in the experimental group than in the control group after 2 weeks of administration of experimental diet. During the posthemorrhagic period, the reticulocyte count increased in both the control and experimental groups, but the increase appeared much earlier in the experimental group. 2) The posthemorrhagic recoveries of hematocrit, hemoglobin content and red cell count appeared to be faster in the experimental group as compaired with the control group. 3) The half life$(T_{1/2})$ of $^{59}Fe$ in the plasma was significantly(P<0.05) shorter in the experimental group(82.6 min, N=8) than in the control group(121 min, N=6). Plasma iron turnover (PIT) of the experimental group (1.78 mg/dl/24 hr.) was approximately 4 times greater than that of the control group(0.45 mg/dl/24 hr.). 4) The maximum red cell utilization(RC-U) was 82.1% in the experimental group ana 74.5% in the control group. Red cell iron turnover(RIT) of the experimental group(1.62 mg/dl/24 hr.) was slightly higher than that of the control group(0.35 mg/dl/24 hr). 5) Erythron turnover was significantly(p<0.05) greater in the experimental group(1.27 mg/dl/24 hr.) than in the control group(0.24 mg/dl/24 hr.). Marrow transit time of the experimental group(2.05 days) tended to he faster than that of the control group(2.84 days). These results suggest that the gingseng improves the recovery of posthemorrhagic anemia and stimulates the erythropoiesis in rabbits.

• Korean Journal of Clinical Pharmacy
• /
• v.14 no.2
• /
• pp.85-90
• /
• 2004

Bisoprolol, one of the $\beta_1-adrenorecepter$ antagonist, has been used for the treatment of mild to moderate essential hypertension anti stable angina pectoris. The oral bloavailability of bisoprolo1 is high $(90\%)$ and the drug has a long elimination half-life, $9{\sim}12\;hr$, which allows once-daily administration. The bioequivalence of two bisoprolol preparations was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Concor $tablet^{(R)}$ made by Newgenpharm and the reference product was Monocor $tablet^{(R)}$ made by Wyeth Korea. Twenty healthy male subjects, 23.8 (21-30) years old and 03.8(52-92) kg, were randomly divided into two groups and a randomized $2\times2$ cross-over study was employed. After two tablets containing 10 mg bisoprolol hemifumarate were orally administered, blood was taken at predetermined time intervals and the concentration of bisoprolol in plasma was determined using an HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t\;and\;C_{max}$ were calculated and analyzed statistical]y for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The $90\%$ confidence intervals of $AUC_t\;and\;C_{max}$ were log $0.95{\sim}1og\;1.04\;and\;1og\;0.96{\sim}1og\;1.07,\;respectively.$ These values were within the acceptable bioequivalence intervals of log $0.8{\sim}log\;1.23$. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Concor tablet is bioequivalent to Monocor tablet.

• Sleep Medicine and Psychophysiology
• /
• v.4 no.2
• /
• pp.164-171
• /
• 1997

Introduction : Periodic limb movement disorder (PLMD) is shown to common in patients with OSA and may become evident or worsened when treated with nasal continuous positive airway pressure (CPAP). Whether this is due to im proved sleep continuity. adverse nocturnal body positioning, uncovered by CPAP, or due to the CPAP stimulus is still debat-ed. We hypothesized that the increase in PLM activity following CPAP is associated with more supine-sleeping tendencies when being treated with CPAP. In the present work, we compared differences in the PLMD index (PLMI) and sleeping position of patients with sleep disordered breathing before and after CPAP treatment. Method : We studied 16 patients (mean age 46 yr, 9M, 7F) with OSA (11 patients) or UARS (5 patients) who either had PLMD on initial polysomnogram (baseline PSG) or on nasal CPAP trial (CPAP PSG). All periodic leg movements were scored on anterior tibialis EMG during sleep according to standard criteria (net duration; 0.5-5.0 seconds, intervals; 4-90 seconds. 4 consecutive movements). Paired t-tests compared PLMD index (PLMI), PLMD-related arousal index (PLMD-ArI), respiratory disturbance index (RDI), and supine sleeping position spent with baseline PSG and CPAP PSG. Results : Ten patients (63%) on baseline PSG and fifteen patients (94%) on CPAP PSG had documented PLMD ($PLMI{\ge}5$) respectively with significant increase on CPAP PSG(p<0.05). Ten patients showed the emergence (6/10 patients) or substantial worsening (4/10 patients) of PLMD during CPAP trial. Mean CPAP pressure was $7.6{\pm}1.8\;cmH_2O$. PLMI tended to increase from baseline PSG to CPAP PSG, and significantly increase when excluding 2 outlier (baseline PSG, $19.0{\pm}25.8/hr$ vs CPAP PSG, $29.9{\pm}12.5/hr$, p<0.1). PLMD-ArI showed no significant change, but a significant decrease was detected when excluding 2 outlier (p<0.1). There was no significant sleeping positional difference (supine vs non-supine) on baseline PSG, but significantly more supine position (supine vs non-supine, p<0.05) on CPAP PSG. There was no significant difference in PLMI during supine-sleeping and nonsupine-sleeping position on both of baseline PSG and CPAP PSG. There was also no significant difference in PLMI during supine-sleeping position between baseline PSG and CPAP PSG. With nasal CPAP, there was a highly significant reduction in the RDI (baseline PSG, $14.1{\pm}21.3/hr$ vs CPAP PSG, $2.7{\pm}3.9/hr$, p<0.05). Conclusion : This preliminary data confirms previous findings that CPAP is a very effective treatment for OSA, and that PLMD is developed or worsened with treatment by CPAP. This data also indicates that supine-sleeping position is more common when being treated with CPAP. However, there was no clear evidence that supine position is the causal factor of increased PLMD with CPAP. It is, however, suggested that the relative movement limitation induced by CPAP treatment could be a contributory factor of PLMD.