• Clinical and Experimental Pediatrics
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• v.57 no.12
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• pp.526-532
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• 2014

Purpose: Matrix metalloproteinases (MMPs) have been implicated in atherosclerosis, and therefore, are considered risk factors for metabolic dysfunction in adults. However, there is little data on circulating levels of MMPs and tissue inhibitors of MMPs (TIMPs) with regard to obesity-related biomarkers in the general adolescent population. In the present study, we determined the associations of MMP-8, MMP-9, and TIMP-1 levels and MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios with obesity-related biomarkers in apparently healthy adolescent boys. Methods: We measured MMP and TIMP concentrations in plasma samples using the enzyme-linked immunosorbent assay and analyzed their associations with obesity-related biomarkers, such as liver enzymes and lipid profiles, in a sample of 91 Korean boys aged 13-14 years who participated in a general health check-up. Results: The mean age of the boys was $13.8{\pm}0.3years$; 72 boys were normal weight and 19 were overweight/obese. The Pearson correlation coefficients revealed a significant correlation between MMP-8 and aspartate aminotransferase (r=0.217, P=0.039) and alanine aminotransferase (r=0.250, P=0.017) and between TIMP-1 and aspartate aminotransferase (r=0.267, P=0.011). In a multivariate linear regression analysis, serum alanine aminotransferase was positively associated with the MMP-8 level. There were no significant differences in the MMP-8, MMP-9, and TIMP-1 levels or MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios between control and overweight/obese subjects. Conclusion: We found a significant association between the MMP-8 level and alanine aminotransferase in the apparently healthy adolescent boys. These findings indicate that there may be a pathophysiological mechanism underlying the relationship between MMP-8 and liver enzymes in young adolescents.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.423-429
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• 2005

A selective and sensitive reversed-phase HPLC method for the determination of fenoprofen in human serum was developed, validated, and applied to the pharmacokinetic study of fenoprofen calcium. Fenoprofen and internal standard, ketoprofen, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Luna C18(2) column with the mobile phase of acetonitrile-3 mM potassium dihydrogen phosphate (32:68, v/v, adjusted to pH 6.6 with phosphoric acid). Detection wavelength of 272 nm and flow rate of 0.25 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed fenoprofen concentration $(2\;{\mu}g/mL)$ with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of $0.05-100\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was $0.05\;{\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.27 to 109.20% for fenoprofen with overall precision (% C.V.) being 5.51-11.71 %. The relative mean recovery of fenoprofen for human serum was 81.7%. Stability (freeze-thaw, short and long-term) studies showed that fenoprofen was not stable during storage. But, extracted serum sample and stock solution were allowed to stand at ambient temperature for 12 hr prior to injection without affecting the quantification. The peak area and retention time of fenoprofen were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of fenoprofen in human serum samples for the pharmacokinetic studies of orally administered Fenopron tablet (600 mg as fenoprofen) at three different laboratories, demonstrating the suitability of the method.

• Analytical Science and Technology
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• v.26 no.4
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• pp.221-227
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• 2013

A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the investigation of the ginsenoside Rg1 in human plasma. After addition of internal standard (digoxin), plasma was diluted with acetone and methanol (80:20), the supernatant was concentrated and analyzed by LC-MS/MS. The optimal chromatographic separation was achieved on an Agilent Eclipse XDB-C18 column ($4.6{\times}150mm$, $5{\mu}m$) with a mobile phase of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.9 mL/min gradient mode. The standard calibration curve for ginsenoside Rg1 was linear ($r^2=0.9995$) over the concentration range 1~500 ng/mL in human plasma. The intra- and inter-day precision over the concentration range of ginsenoside Rg1 was lower than 7.53% (correlation of variance, CV), and accuracy exceeded 98.28%. This LC-MS/MS assay of ginsenoside Rg1 in human plasma is applicable for quantifying in the pharmacokinetic study.

• Asian-Australasian Journal of Animal Sciences
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• v.12 no.3
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• pp.395-399
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• 1999

Three experiments were conducted to determine the effects of conditioning a complex (20% whey, 10% lactose, 4% plasma protein, 4% wheat gluten and 2% blood meal) diet on growth performance of weanling pigs. In Exp. 1,180 pigs (average initial BW of 6.4 kg) were fed the experimental diet (1.7% lysine) during a 7-d growth assay. Treatments were a meal control (M), standard (ST), and expander (EX) conditioned mash or pellets. Rate and efficiency of gain were decreased by 39% and 21% (p<0.005) respectively, for pigs fed EX diets compared to those fed the ST diet. In Exp. 2,196 pigs (average initial BW of 6.5 kg) were used to determine the effects of EX operating conditions on nutritional value of a pelleted complex diet. When steam conditioning temperature (prior to expanding) was $54^{\circ}C$, increasing cone pressure of the EX from 0 to 7 to 14 kg/cm2 resulted in linear decreases in rate of gain of weaned pigs (p<0.006), suggesting heat damage of the diet. Increasing conditioning temperature (i.e., adding steam) of the diets from 46 to 54 to $63^{\circ}C$ (cone pressure at $12kg/cm^2$) resulted in improved rate of gain (p<0.04) of the pigs. However, none of the pigs fed expanded diets compared favorably to the pigs fed the conditioned $(54^{\circ}C)$ pellets processed with no cone pressure. In Exp. 3,168 pigs (average initial BW of 6.6 kg) were used to determine the effects of expanding the various components of the diet. Treatments were M and ST pellets as controls, EX-corn, EX-corn soybean-meal, EX corn-soybean meal-oil, and EX-complete diet. Efficiency of gain was increased by 13% with EX portions of the diet compared to the mash control, but there was a marked decrease in performance when the complete diet was expanded (p<0.001). Expanded corn-soybean meal-oil supported the greatest ADG with a 19% increase compared to the average of the EX corn and EX corn-soybean meal treatments (p<0.005). In conclusion, our results suggest no benefit from expanding complete phase-I diets.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.135-141
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• 2013

A rapid, sensitive and selective analytical method was developed and validated for the determination of compound K, a major intestinal bacterial metabolite of ginsenosides in human plasma. Liquid-liquid extraction was used for sample preparation and analysis, followed by liquid chromatography tandem spectrometric analysis and an electrospray-ionization interface. Compound K was analyzed on a Phenomenex Luna C18 column ($100{\times}2.00$ mm, 3 ${\mu}m$) with the mobile phase run isocratically with 10 mM ammonium acetate-methanol-acetonitrile (5:47.5:47.5, v/v/v) at a flow rate of 0.5 mL/min. The method was validated for accuracy (relative error <12.63%), precision (coefficient of variation <9.14%), linearity, and recovery. The assay was linear over the entire range of calibration standards i.e., a concentration range of 1 ng/mL to 1,000 ng/mL ($r^2$ >0.9968). The recoveries of compound K after liquid-liquid extraction at 1, 2, 400, and 800 ng/mL were $106.00{\pm}0.08%$, $103.50{\pm}0.19%$, $111.45{\pm}5.21%$, and $89.62{\pm}34.46%$ for intra-day and $85.40{\pm}0.08%$, $94.50{\pm}0.09%$, $112.50{\pm}5.21%$, and $95.87{\pm}34.46%$ for inter-day, respectively. The lower limit of quantification of the analytical method of compound K was 1 ng/mL in human plasma. The developed method was successfully applied to a pharmacokinetic study of compound K after oral administration in ten of healthy human subjects.

• Journal of Radiation Protection and Research
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• v.22 no.3
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• pp.153-160
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• 1997

The frequencies of ${\gamma}$-ray-induced micronuclei (MN) in cytokinesis-blocked (CB) lymphocytes at several doses were measured in three donors of human and C57BL/6 mice. Measurements performed after irradiation showed a dose-related increases in MN frequency in each of the donors studied. The relative sensitivity of mouse in spleen lymphocytes (SLs) compared with human peripheral blood lymphocytes (PBLs) was estimated by best fitting linear-quadratic model based on the radiation-induced MN data over the range from 0 cGy to 400 cGy. In the case of MN frequency with 0.2 per CB cell, the relative sensitivity of mouse SLs was 1.67. Compared with the radiation-induced MN formation in the PBLs of human, the SLs of mouse were more radiosensitive. Using this MN assay with human PBLs and mouse SLs, studies were performed to determine whether the water fraction of ginseng (Panax ginseng C.A.Meyer) against radiation-induced MN in human PBLs after in vitro irradiation (3Gy) and in SLs of C57BL/6 mice after in vivo irradiation (3Gy). The frequency of MN in human PBLs was reduced by water fraction of ginseng (0.5mg/ml of medium) both pre-and post treatment (p<0.0l) in vitro. In addition, the frequency of MN in mouse SLs was also reduced by pretreatment of ginseng (2mg/ml of drinking water for 7days) in vivo. The data suggested that the ginseng may reduce cell damage caused by ${\gamma}$-rays in vitro and in vivo. Further studies are needed to characterize better the protective nature of ginseng extract, its fractions and compounds.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7169-7174
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• 2014

Background: NPAS2 is a product of the circadian clock gene. It acts as a putative tumor suppressor by playing an important role in DNA damage responses, cell cycle control and apoptosis. Chronic lymphocytic leukemia (CLL) appears to be an apoptosis related disorder and alteration in the NPAS2 gene might therefore be directly involved in the etiology of CLL. Here, the Ala394Thr polymorphism (rs2305160:G>A) in the NPAS2 gene was genotyped and melatonin concentrations were measured in a total of seventy-four individuals, including thirty-seven CLL cases and an equal number of age- and sex-matched healthy controls in order to examine the effect of NPAS2 polymorphism and melatonin concentrations on CLL risk in a Pakistani population. Materials and Methods: Genotyping of rs2305160:G>A polymorphism at NPAS2 locus was carried out by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Melatonin concentrations were determined by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistical Package for Social Sciences software. Results: Our results demonstrated no association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with risk of CLL. Similarly, no association of rs2305160 with CLL was observed in either females or males after stratification of study population on a gender basis. Moreover, when the subjects with CLL were further stratified into shift-workers and non-shift-workers, no association of rs2305160 with CLL was seen in either case. However, significantly low serum melatonin levels were observed in CLL patients as compared to healthy subjects (p<0.05). Also, lower melatonin levels were seen in shift-workers as compared to non-shift-workers (p<0.05). There was no significant difference (p>0.05) in the melatonin levels across NPAS2 genotypes in all subjects, subjects with CLL who were either shift workers or non-shift-workers. General Linear Model (GLM) univariate analysis revealed no significant association (p>0.05) of the rs2305160 polymorphism of the NPAS2 gene with melatonin levels in any of the groups. Conclusions: While low melatonin levels and shift-work can be considered as one of the risk factors for CLL, the NPAS2 rs2305160 polymorphism does not appear to have any association with risk of CLL in our Pakistani population.

• Korean Journal of Plant Resources
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• v.29 no.5
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• pp.539-546
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• 2016

The aim of this study was to analyze antioxidant activity, total phenolics, and vitamin C content in unripe and ripe jujube cultivar and to investigate correlation between antioxidant and chemical constituents including total phenolics and vitamin C. The antioxidant activity was measured by the DPPH radical scavenging activity, ABTS radical scavenging activity, and reducing power. Although, the weight, diameter and soluble solids of Zyziphus jujuba fruit were increased with the progress of ripening, antioxidant activity and total phenolics were decrease during ripening. The highest free-radical scavenging activity (at 2.5 ㎎/㎖) and reducing power (at 1 ㎎/㎖) in fruit were 81.75% (Bokjo, unripe) and 0.80 (Mudeung, unripe), respectively. The highest total phenolic content in unripe fruit of Mudeung was 62.50 ㎍/g. A linear correlation (r=0.911) was shown between DPPH radical scavenging activity and total phenolic content.

• Clinical and Experimental Pediatrics
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• v.59 no.5
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• pp.231-238
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• 2016

Purpose: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. Methods: The study included 87 adolescents aged 12-13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. Results: The mean age of the participants was $12.9{\pm}0.3$ years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants ($7.8{\pm}1.9{\mu}g/mL$ vs. $6.0{\pm}1.6{\mu}g/mL$, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. Conclusion: LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.120-129
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• 1999

Purpose : Serum squamous cell (SCC) antigen levels were examined in uterine cervix cancer undergoing radiation therapy, and authors analyzed the relationship between SCC antigen levels and treatment results. Materials and Methods :This is a retrospective study of 181 conical carcinoma patients who received radiotherapy and examined serial serum SCC antigen from 1991 to 1997 at Soonchunhyang University Hospital. One hundred and eighteen patients underwent SCC antigen evaluation at diagnosis The relationship between the serum tumor marker level and disease free survival, recurrence pattern, and other prognostic factors were analyzed according to various statistical methods. Results : The Positivity rate (initial serum value above 2.5 ng/ml) was increased with FIGO stage (IB-IIA 57% to IV 91%) and more discriminative than cutoff value of 1.5 ng/ml. Five year disease free survival rates for the stage IB-IIA, IIB, III and IV were 79.2%, 68.7%, 33.4% and 0%, respectively. The 5-year disease free survival rate for patients with serum SCC antigen levels above 5.0 ng/ml was 34% versus 55~62% for patients with normal range (>1.5 ng/ml) or mildly elevated levels (1.5~5.0 ng/ml). Rising SCC antigen levels preceded the clinical detection of disease by a mean of 4.8 months (range 1 ~13 months). Negative linear correlation was observed between initial SCC antigen levels and relapse free survival (r=-0.226), and by multivariate analysis, initial SCC antigen level had a large impact on the relapse free survival. Conclusion : SCC antigen assay is a useful aid to predict the prognosis of squamous cell carcinoma of the uterine cervix and to detect recurrence.