• The Korean Journal of Pain
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• 제12권1호
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• pp.27-35
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• 1999

Background: Fibromyalgia is a common syndrome of musculoskeletal pain and fatigue. Lacking distinctive histological or laboratory abnormality in diagnosis, it has often been considered a form of "psychogenic rheumatism". Fibromyalgia causes much distress to the affected patients and often frustrates physicians, who are unable to start rational therapy on any logical disease pathology. Methods: Growth hormone is essential for muscular homeostasis. In the present study, the notion that the stage-4 sleep anomaly typically seen in the fibromyalgia syndrome may disrupt growth hormone secretion was tested. Because growth hormone has a very short half-life, serum levels of somatomedin C were measured; somatomedin C is the major mediator of growth hormone's anabolic actions and is a prerequisite for normal muscle homeostasis. Serum levels of somatomedin C using acid-extraction procedure and two-site immunoradiome-tric assay (IRMA) and number of tender points were measured in 27 female patients with fibromyalgia from 40 to 60 years old and 27 healthy controls. Results: There were no differences in the concentration of somatomedin C between fibromyalgia patients and controls ($mean{\pm}SD$: $178.3{\pm}75.5$ ng/ml versus $166.3{\pm}76.6$ ng/ml; p=0.55). And there were no correlations between number of tender point and serum somatomedin C level by linear regression analysis. Conclusions: These findings did not support that there is a distinctive disruption of the growth hormone-somatomedin C neuroendocrine axis in a fibromyalgia syndrome. But we can not discard the hypothesis that disturbed sleep predispose to muscle pain.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.265-271
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• 2001

In order to elucidate the influence of intestinal and hepatic first-pass effect on the pharmacokinetics of triflusal, the biotransformation of triflusal in the gastrointestinal tract and liver was designed. Moreover, we tried to establish an HPLC method applicable for bioassay and available to pharmacokinetics, not only with the simultaneous determination of triflusal and its active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), but also with improving sensitivity. After the administration of triflusal (10 mg/kg) and HTB (10 mg/kg) into femoral vein, portal vein (only triflusal) and oral route (only triflusal), pharmacokinetic parameters were investigated from the plasma concentration-time profiles of triflusal and HTB in rats. An HPLC method was developed for the simultaneous determination of triflusal and HTB in rat plasma, urine and bile. The HPLC analysis was carried out using a C18 column and acetonitrile-methanol-water (25:10:65, v/v/v) as the mobile phase and UV detection at 234 nm. Furosemide was used as the internal standard. The calibration curves were linear over the concentration range $0.05-5.0\;{\mu}g/ml$ for triflusal and $0.2-200.0\;{\mu}g/ml$ for HTB with correlation coefficients greater than 0.999 and with intra-day or inter-day coefficients of variation not exceeding 10.0%. This assay procedure was applied to the study of metabolite pharmacokinetics of triflusal and HTB in rats. It was supposed that triflusal was almost metabolized in vivo because urinary and biliary excreted amounts of triflusal could be ignored as it was lower than 1.2% of the administered dose. According to the gastrointestinal and hepatic biotransformation pathways of triflusal, it was found that triflusal was hydrolyzed by about 5% in intestine and metabolized by about 53% in liver, and that the bioavailability of triflusal after oral administration of triflusal was 0.44, and also that the fraction of total elimination rate of triflusal which formed HTB in liver $(F_{mi},\;%)$ was about 98%. These results showed that triflusal was almost metabolized in liver, and the total elimination of triflusal in the body was dependent to the formation rate of HTB from triflusal in liver.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.101-107
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• 2010

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of N-(-4-Chlorophenyl)-6-hydroxy-7-methoxy-2-chromanecarboxamide (KAL-1120), a novel anti-inflammation agent, in the rat plasma. The method was applied to analyze the compound in the biological fluids such as bile, urine and tissue homogenates. After liquid-liquid extraction, the compound was analyzed on an HPLC system with ultraviolet detection at 275 nm. HPLC was carried out using reversed-phase isocratic elution with a $C_{18}$ column, a mobile phase of a mixture of acetonitril (40 v/v%) at a flow rate of 1.0 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma was linear over the concentration range of 0.05-50 ${\mu}g$/mL. The intra- and inter-day assay accuracies of this method ranged from 0.06% to 9.33% of normal values and the precision did not exceed 6.28% of relative standard deviation. The plasma concentration of KAL-1120 decreased to below the quantifiable limit at 1.5 hr after the i.v. bolus administration of 2-10 mg/kg to rats ($t_{1/2,({\alpha})}$ and $t_{1/2,({\beta})$ of 2.15 and 26.7 min at a dose of 2 mg/kg, 3.91 and 33.0 min at a dose of 10 mg/kg, respectively). The steady-state volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) were not significantly altered in rats given doses from 2 to 10 mg/kg. Of the various tissues tested, KAL-1120 was mainly distributed in the lung and heart after i.v. bolus administration. KAL-1120 was detected in the bile by 30 min after its i.v. bolus administration. However, the concentration in the urine after i.v. bolus administration became too low to measure, suggesting that KAL-1120 is mostly excreted in the bile. In conclusion, this analytical method was suitable for the preclinical pharmacokinetic studies of KAL-1120 in rats.

• 대한임상검사과학회지
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• 제39권1호
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• pp.31-36
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• 2007

The purpose of the clinically reportable range (CRR) in clinical chemistry is to estimate linearity in working range. The reportable range includes all results that may be reliably reported, and embraces two types of ranges: the analytical measurement range (AMR) is the range of analyte values that a method can directly measure on the specimen without any dilution, concentration, or other pretreatment not part of the usual assay process. CAP and JCAHO require linearity on analyzers every six months. The clinically reportable range is the range of analyte values that a method can measure, allowing for specimen dilution, concentration, or other pretreatment used to extend the direct analytical measurement range. The AMR cannot exceed the manufacturer's limits. Establishing AMR is easily accomplished with Calibration Verification Assessment and experimental Linearity. For example: The manufacturer states that the limits of the AST on their instrument are 0-1100. The lowest level that could be verified is 2. The upper level is 1241. The verified AMR of the instrument is 2-1241. The lower limit of the range is 2, because that is the lowest level that could be verified by the laboratory. The laboratory could not use the manufacturer's lower limit of 2 because they have not proven that the instrument values below 2 are valid. The upper limit of the range is 1241, because although the lab has shown that the instrument is linear to 1241, the manufacturer does not make that claim. The laboratory needs to demonstrate the accuracy and precision of the analyzer, as well the validation of the patient AMR. Linearity requirements have been eliminated from the CLIA regulations and from the CAP inspection criteria, however, many inspectors continue to feel that linearity studies are a part of good lab practice and should be encouraged. If a lab chooses to continue linearity studies, these studies must fully comply with the calibration/calibration verification requirements of CLIA and/or CAP. The results of lower limit and upper limit of clinically reportable range were total protein (2.1 - 79.9), albumin (1.3 - 39), total bilirubin (0.2 - 106.2), alkaline phosphatase (13 - 6928.2), aspartate aminotransferase (24 - 7446), alanine aminotransferase (13 - 6724.2), gamma glutamyl transpeptidase (16.64 - 9904.2), creatine kinase (15.26 - 4723.8), lactate dehydrogenase (127.66 - 13231.8), creatinine (0.4 - 129.6), blood urea nitrogen (8.67 - 925.8), uric acid (1.6 - 151.2), total cholesterol (48.52 - 3162), triglycerides (36.91 - 3367.8), glucose (31 - 4218), amylase (21 - 6694.2), calcium (3.1 - 118.2), inorganic phosphorus (1.11 - 108), HDL (11.74 - 666), NA (58.3 - 1800), K (1.0 - 69.6), CL (38 - 1230).

• 한국축산식품학회지
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• 제28권2호
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• pp.222-231
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• 2008

모발에 축적되는 중금속은 한약박 및 유기셀레늄 같은 기능성 원료에 의해 효과적으로 억제되며, 이는 간 및 혈액으로 대별되는 조직 분석과도 밀접한 상관관계가 보여진다. 또한, 기능성 원료의 여타 효과 즉, 항산화 효과, 항염증 효과 등 부가적인 기능성도 동시에 부여할 수 있는 가치가 있어 산업적인 효용성이 충분히 보장된다고 할 수 있다. 더불어 침체 되어있는 국내 사료산업에 고 부가가치 산업으로서의 기능성 원료를 공급하여 사료산업 활성화에 일조할 수 있으리라 전망한다.

• Journal of Pharmaceutical Investigation
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• 제36권5호
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• pp.331-338
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• 2006

A rapid, selective and sensitive reverse-phase HPLC methods for the determination of atenolol and chlorthalidone in human serum and whole blood were validated, and applied to the pharmacokinetic study of atenolol and chlorthalidone combination therapy. Atenolol and an internal standard, pindolol, were extracted from human serum by liquid-liquid extraction, and analyzed on a $\mu$-Bondapak C18 $10-{\mu}$ column in a mobile phase of methanol-0.01 M potassium dihydrogenphosphate(30:70, v/v, adjusted to pH 3.5) and fluorescence detection(emission: 300 nm, excitation: 224 nm). Chlorthalidone and an internal standard, probenecid, were extracted form human whole blood by liquid-liquid extraction, and analyzed on a Luna C18 $5-{\mu}$ column in a mobile phase of acetonitrile containing 77% 0.01 M sodium acetate and UV detection at 214 nm. These analysis were performed at three different laboratories using the same quality control(QC) samples. The chromatograms showed good resolution, sensitivity, and no interference by human serum and whole blood, respectively. The methods showed linear responses over a concentration range of 10-1,000 ng/mL for atenolol and 0.05-20 ${\mu}g/mL$ for chlorthalidone, with correlation coefficients of greater than 0.999 at all the three laboratories. Intra- and inter-day assay precision and accuracy fulfilled international requirements. Stability studies(freeze-thaw, short-, long-term, extracted sample and stock solution) showed that atenolol and chlorthalidone were stable. The lower limit of quantitation of atenolol and chlorthalidone were 10 ng/mL and 0.05 ${\mu}g/mL$, respectively, which was sensitive enough for pharmacokinetic studies. These methods were applied to the pharmacokinetic study of atenolol and chlorthalidone in human volunteers following a single oral administration of Hyundai $Tenoretic^{\circledR}$ tablet(atenolol 50 mg and chlorthalidone 12.5 mg) at three different laboratories.

• Archives of Pharmacal Research
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• 제26권1호
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• pp.70-75
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• 2003

The objective of the present study was to investigate the uptake process of 4-Phenylazobenzoxycarbonyl-Pro-Leu-Gly-Pro-D-Arg (Pz-peptide), a hydrophilic and collagenase-labile pentapeptide, by isolated hepatocytes. For comparison, the uptake of Pz-peptide by Caco-2 cells and colonic cells, two known paracellular routes of Pz-peptide, was also evaluated. A simple and sensitive reversed-phase HPLC assay method using UV detection has been developed. The coefficient of variation for all the criteria of validation were less than 15%. The method was, therefore, considered to be sutable for measuring the concentration of Pz-peptide in the biological cells. Pz-peptide was extensively uptaked into hepatocytes. The initial velocity of Pz-peptide uptake assessed from the initial slope of the curve was plotted as Eadie-Hofstee plots. The maximum velocity ($V_{max}$) and the Michaelis constant ($K_m$) were 0.190$\pm$0.020 $nmol/min/10^6$ cells and 12.1$\pm$3.23 $\mu$M, respectively. The permeability-surface area product ($PS{influx}$) was calculated to be 0.0157 ml/min/10^6$ cells. $V_{max}$ and $K_m$ values for Caco-2 cells were calculated to be 6.22$\pm$0.930 pmol/min/10^6$ cells and 82.8$\pm$8.37 $\mu$M, respectively, being comparable with those of colonocytes (6.04$\pm$1.03 pmol/min/10^6$ cells and 87.8$\pm$13.2 $\mu$M, respectively). $PS_{influx}$ values for Caco-2 cells and colonocytes were calculated to be 0.0751 $\mu$l/min/10^6$ cells and 0.0688 $\mu$l/min/10^6$ cells, respectively. The more pronounced uptake of Pz-peptide by hepatocytes, when compared with Caco-2 cells and colonocytes, is probably due to its specific transporter. In conclusion, Pz-peptide, a paracellularly transported pentapeptide in the intestine and ocular epithelia, was uptaked into hepatocytes extensively. Although Pz-peptide is able to be uptaked into the Caco-2 cells and colonocytes, it is less pronounced when compared with hepatocytes. $PS_{influx}$ values of Caco-2 cells and colonocytes for unbound Pz-peptide under linear conditions were less than 0.4% when compared with that of hepatocytes.

• Imaging Science in Dentistry
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• 제33권2호
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• pp.97-105
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• 2003

Purpose : To evaluate the effect of all-trans-retinoic acid (ATRA) on the radiosensitivity of normal human oral keratinocyte (NHOK). Materials and methods: Relative cell survival fraction including SF2 (survival fraction at 2 Gy) was calculated on the basis of colony formation assay. Data were fitted to the linear-quadratic model to establish the survival curve and calculate α and β values. Using flow cytometry at 1, 2, 3, 4, and 5 days after exposure to 2 and 10 Gy irradiation, cell cycle arrest and apoptosis were analysed. To understand the molecular mechanism of the radiosensitization of ATRA on NHOK, proteins related with apoptosis and cell cycle arrest were investigated by Western blot analysis. Results: Treatment with ATRA resulted in a significant decrease of SF2 value for NHOK from 0.63 to 0.27, and increased α and β value, indicating that ATRA increased radiosensitivity of NHOK. ATRA increased LDH significantly, but increasing irradiation dose decreased LDH, suggesting that the radiosensitizing effect of ATRA is not directly related with increasing cell necrosis by ATRA. ATRA did not induce appotosis but increased G2 arrest after 10 Gy irradiation, implying that the increased radiosensitivity of NHOK may be due to a decrease in mitosis casued by increasing G2 arrest. ATRA inhibited the reduction of p53 at 3 days after l0Gy irradiation and increased p21 at 1 day after 10 Gy irradiation. Further study is required to determine the precise relationship between this effect and the radiosensitizing effect of A TRA. Conclusion: These results suggested that ATRA increase radiosensitivity by inhibiting mitosis caused by increasing G2 arrest.

• 대한화학회지
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• 제41권2호
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• pp.98-104
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• 1997

한국에서 전통적으로 사용되고 있는 생약제제 중 베르베린, 계피산 및 글리시리진의 정량을 위한 간단하고, 정확하고, 재현성 있는 모세관 전기이동법을 개발하였다. 이 성분들의 분리는 25$^{\circ}C$, 20 mM 인산완충액(pH 7.5)에서 실리카 캐필러리($57 cm{\times}75 {\mu}m$ i.d.)를 사용하여 수행하였다. 350 V/cm의 전기장으로 베르베린, 계피산 및 글리시리진의 동시 정량을 13분내에 할 수 있었다. 검정곡선은 베르베린에 대해서는 1~100 ${\mu}g/mL$, 계피산은 0.3~100 ${\mu}g/mL$, 글리시리진은 2.5~100 ${\mu}g/mL$의 농도 범위 안에서 좋은 직선성을 보여 주었다. 이 성분들에 대한 상대 표준편차(n=5)의 범위는 0.96∼2.35%이었다. 베르베린, 계피산 및 글리시리진에 대한 검출한계(S/N=3)는 각각 0.5, 0.1 및 2.0 ${\mu}g/mL$이었다. 이론단수는 181,000(베르베린), 88,000(계피산) 및 169,000(글리시리진)이었다. HPLC에서는 3,100~4,800이었다.

• 대한화학회지
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• 제55권1호
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• pp.63-69
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• 2011

이 작업은 수송체로서 N,N'-bis(2-hydroxybenzyl)-1,3-diaminopropane (L1)과 N,N'-bis(2-hydroxybenzyl)-2,2-dimethyl-1,3-diaminopropane (L2)에 기초한 $Ag^+$ 이온-선택 전극의 제조, 개발 그리고 전압반응에 대해 토의한다. $Ag^+$에 대하여 L1에 기초한 전극은 58.7 mV/dec에 도달하는 안정한 Nernst에 가까운 기울기와 $1.0{\times}10^{-6}M$의 검출한계를 갖는 등급의 최소 다섯가지 순서의 선형범위에서 최적의 전압 반응 특징을 보이는 것을 나타낸다. 제안된 전극은 다른 테스트한 양이온과 비교하여 $Ag^+$에 우위의 선택성을 보였다. 훌륭한 전압 분석적 특징은 중요한 진짜 샘플에서 은의 순도분석의 성공적인 응용을 이끌 것이다. 그리고 그것은 제안된 $Ag^+$-ISE가 측정 능력의 중요한 진보를 보여준다는 것을 나타내고 있다. 그러나 L2에 기초한 전극에 대해서는, 약한 전압 반응 특징들이 전체 실험 과정에서 관측되었다.