• Title/Summary/Keyword: Korean healthy volunteers

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The Role of Protein Kinase C and Protein Tyrosine Kinase in the Signal Transduction Pathway of Stimulus Induced by Endotoxin in Peripheral Blood Monocyte (말초혈액 단핵구에 대한 내독소 자극의 신호 전달에서 Protein Kinase C와 Protein Tyrosine Kinase의 역할)

  • Kim, Jae-Yeol;Park, Jae-Suk;Lee, Gwi-Lae;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.338-348
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    • 1997
  • Background : Endotoxin, the component of outermembrane of gram negative organism, plays an important role in the initiation and amplification of inflammatory reaction by its effects on inflammatory cells. Until recently, there have been continuing efforts to delinate the mechanisms of the signal trasduction pathway of endotoxin stimuli on inflammatory cells. By uncovering the mechanisms of signal transduction pathway of endotoxin stimuli, we can expect to have tools to control the excessive inflammatory responses which sometimes may be fatal to the involved host. It was generally accepted that endotoxin exerts its inflammatory effects through inflammatory cytokines that are produced by endotoxin-stimulated inflammatory cells and there were some reports on the importance of protein kinase C and protein tyrosine kinase activation in the production of inflammatory cytokines by endotoxin So we evaluated the effect of pretreatment of protein kinase C inhibitors (H7, Staurosporin) and protein tyrosine kinase inhibitors(Herbimycin, Genistein) on the endotoxin-stimulated cytokines(IL-8 & TNF-$\alpha$) mRNA expression. Method : Peripheral blood monocytes were isolated from healthy volunteers by Ficoll-Hypaque density gradient method and purified by adhesion to 60mm Petri dishes. Endotoxin(LPS 100ng/ml) was added to each dishes except one control dish, and each endotoxin-stimulated dishes was preincubated with H7, Staurosporin(protein kinase C inhibitor), Herbimycin or Genistein(protein tyrosine kinase inhibitor) respectively except one dish. Four hours later the endotoxin stimulation, total RNA was extracted and Northern blot analysis for IL-8 mRNA and TNF-$\alpha$ mRNA was done. Result : Endotoxin stimulation increased the expression of IL-8 mRNA and TNF-$\alpha$ mRNA expression in human peripheral blood monocyte as expected and the stimulatory effect of endotoxin on TNF-$\alpha$ mRNA expression was inhibited by protein kinase C inhibitors(H7, Staurosporin) and protein tyrosine kinase inhibitors (Herbimycin, Genistein). The inhibitory effect of each drugs was increased with increasing concentration. The stimulatory effect of endotoxin on IL-8 mRNA was also inhibited by H7 and protein tyrosine kinase inhibitors (Herbimycin, Genistein) dose-dependently but not by Staurosporin. Conclusion : Protein kinase C and protein tyrosine kinase are involved in the endotoxin induced signal transduction pathway in human peripheral blood monocyte.

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The Dose-Dependent Effects of Nitric Oxide on Human Sperm Cell Function (Nitric Oxide가 인간 정자세포의 기능에 미치는 효과에 대한 연구)

  • Joo, Bo-Sun;Moon, Hwa-Sook;Park, Sue-Jin;Moon, Jae-Yeoun; Cho, Jae-Dong;Kim, Han-Do
    • Clinical and Experimental Reproductive Medicine
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    • v.25 no.1
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    • pp.43-50
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    • 1998
  • This study was performed to determine the effects of nitric oxide on human sperm cell function. Semen samples were obtained from normal healthy volunteers. Motile spermatozoas collected by swim-up method were incubated up to 24 hours in Ham's F-10 medium supplemented with a various concentration of sodium nitroprusside (nitric oxide releasing agent). Sperm motility, hyperactivation, acrosome reaction rate, and acrosin activity were determined. The results are as follows; 1. 1mM of SNP resulted in a significant decrease in sperm motility ($44.8%{\pm}8.9%:78.1%{\pm}6.3%$, and hyperactivation $(10.4%{\pm}6.4%:47.7%:{\pm}9.5%)$ after incubation for 3 hours compared with the control group (Ham's F-10 alone), but had no effect on acrosome reaction. 2. At $100{\mu}M$ SNP, sperm motility was reduced after incubation for 6 hours $(54.8%{\pm}3.2%)$ compared with that of the control group $(82.7%{\pm}8.9%)$, but hyperactivation and acrosome reaction were not affected. 3. However, a lower concentration (less than $10{\mu}M$) of SNP had no effect on sperm motility and hyperactivation for 8 hours of incubation but significantly decreased them when incubation periods were increased up to 24 hours compared with the control group. On the other hand, $1{\mu}M$ and $10{\mu}M$ SNP significantly increased the acrosome reaction rate in both acrosomal status ($17.3%{\pm}5.2%$, $23.5%{\pm}4.7%$, respectively) and acrosin activity ($34.3{\mu}IU{\pm}10.5{\mu}IU,\;45.6{\mu}IU{\pm}5.6{\mu}IU$, respectively) as compared with the control group $(7.0%{\pm}4.0%,\;9.5{\mu}IU{\pm}3.4{\mu}IU)$. These results indicate that SNP, NO releasing agent, has a dose-dependent effects on the sperm cell function. Therefore it may positively affect the fertilization by promoting acrosomal reaction at a lower concentration (less than $10{\mu}M$).

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Plasma and Urine Endothelin Concentrations in Patients with Diffuse Interstitial Lung Disease (미만성간질성폐질환 환자에서 혈장 및 요 중 Endothelin에 관한 연구)

  • Lee, Jong-Deog;Lee, Sang-Do;Lim, Chae-Man;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.2
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    • pp.360-368
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    • 1998
  • Background: Endothelin(ET), a potent vasoconstrictor peptide produced by endothelial cells and degraded predominantly in the pulmonary vasculature, have been implicated in the development of various organ dysfunctions. Plasma concentrations of ET-1 are reported to be elevated in patients with diffuse interstitial lung disease(DILD). But, there is no study to establish the exact source and mechanisms involved in the increased plasma ET-1 concentrations in DILD patients. Methods: 12 patients with IPF, 2 patients with sarcoidosis, 2 patients with scleroderma, 1 patient with SLE and 11 healthy volunteers were studied. ET was detected by radioimmunoassay in plasma and bronchoalveolar lavage fluid(BALF) as well as in 24-hr urine specimens. For each subjects, arterial/venous(A/V) ET ratio and renal ET clearance were calculated. Results: Elevated plasma, urine and BALF ET concentrations were found in patients with DILD compared with controls. But, no significant difference was observed in ET A/V ratio and ET renal clearance between patients with DILD and controls. Conclusion: We observed that plasma ET concentrations were elevated in patients with DILD, and that the main site of ET production may be lung parenchyme.

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Effects of Panax ginseng on Alcohol Detoxification (인삼의 알콜해독 효과)

  • Lee F.C.;Ko J.H.;Park J.K.;Lee J.S.
    • Proceedings of the Ginseng society Conference
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    • 1988.08a
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    • pp.25-27
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    • 1988
  • To assess the effect of Panax ginseng on the detoxification of ethanol. we examined its effect on blood ethanol clearance in both man and experimental animals and on the rate of ethanol oxidation to carbon dioxide in experimental animals. Fourteen healthy male volunteers were subject to studies. The blood alcohol level in the test group receiving ginseng extract (3g/kg b.w.) along with alcohol (70g/65kg b.w.) was about $35\%$ lower than their control levels at 40 min after ethanol intake. When the blood alcohol level was compared on individual bases. blood alcohol concentrations in 10 subjects ranged from 32 to $51\%$ lower than their control values. The remaining 4 subjects appeared to have a high tolerance level. In experimental animals. the blood alcohol clearance was also much faster in test animals receiving ginseng along with ethanol. The rate of ethanol elimination was determined by the amount of $^{14}CO_2$ in exhaled air following the administration of [$^{14}C$] ethanol. During the first 7 1/4 hr (Phase I) after the ethanol administration. the $CO_2$ output was greater in test animals receving ginseng along with ethanol. whereas from beyond 7 1/4 hr to the near end (Phase II). the $CO_2$ output in control animals was over twice that in test animals. The present studies clearly demonstrate that ginseng promotes the overall metabolism of ethanol. resulting in an enhanced blood alcohol clearance and alcohol elimination.

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Effect of a Combinacon of Mental Activity with Experimental Subway Noise on Hematology (실험적 지하철 소음에서의 지적활동이 혈액생리에 미치는 영향)

  • Choi, Seok-Cheol;Hyun, Kyung-Yae;Park, Jae-Hyun;Kwon, Heun-Young
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1174-1180
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    • 2006
  • The present study was sought to clarify whether the combination of mental activity with subway noise affects hematological variables. Fifty-six healthy volunteers participated in this experiment and underwent a stress task consisting of combination_of mental activity (mental arithmetic) with subway noise for 50 min and 60min of recovery after the end of the stress task. Venous blood samples were collected for measuring CBC, prothrombin time (PT), activated partial thromboplastin time (aPTT), erythrocyte sedimentation rate (ESR), fibrinogen concentration, D-dimer and high sensitive C-reactive protein (H-CRP) levels before (baseline), 50min of stress task (S-50m), and 60 min of recovery (R-60m). Total leukocyte, neutrophil and lymphocyte counts significantly increased at R-60m compared with baselines. RBC count at S-50m was higher, while monocyte counts at S-50m and R-60m were lower than those of baselines. aPTTs shortened at S-50m and R-60m, but PT reduced at R-60m as compared with baselines. D-dimer and H-CRP levels at S-50m and R-60m were significantly higher than those of baselines. These findings imply that a combination of mental activity with subway noise nay cause leukocytosis, homo-concentration, shortened PT and aPTT, decreased ESR, and raised D-dimer and H-CRP levels, suggesting possible development of inflammation and prothrombogenic reaction attributable to a subway environment.

Inter-Rater Reliability of Abdominal Muscles Thickness Using Ultrasonography for Different Probe Locations and Thickness Measurement Techniques

  • Lim, One-Bin;Hong, Ji-A;Yi, Chung-Hwi;Cynn, Heon-Seock;Jung, Doh-Heon;Park, Il-Woo
    • Physical Therapy Korea
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    • v.18 no.4
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    • pp.60-67
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    • 2011
  • Ultrasonography (US) is a recent technique that has proven to be useful for assessing muscle thickness and guiding the rehabilitation decision-making of clinicians and researchers. The purpose of this study was to determine the inter-rater reliability of the US measurement of transversus abdominis (TrA), internal oblique (IO), and external oblique (EO) thicknesses for different probe locations and measurement techniques. Twenty healthy volunteers were recruited in this study. Muscle thicknesses of the transversus TrA, IO, and EO were measured three times in the hook-lying position. The three different probe locations were as follows: 1) Probe location 1 (PL1) was below the rib cage in direct vertical alignment with the anterior superior iliac spine (ASIS). 2) Probe location 2 (PL2) was halfway between the ASIS and the ribcage along the mid-axillary line. 3) Probe location 3 (PL3) was halfway between the iliac crest and the inferior angle of the rib cage, with adjustment to ensure the medial edge of the TrA. The two different techniques of thickness measurement from the captured images were as follows: 1) Muscle thickness was measured in the middle of the muscle belly, which was centered within the captured image (technique A; TA). 2) Muscle thickness was measured along a horizontal reference line located 2 cm apart from the medial edge of the TrA in the captured image (technique B; TB). The intraclass correlation coefficient (ICC [3,k]) was used to calculate the inter-rater reliability of the thickness measurement of TrA, IO and EO using the values from both the first and second examiner. In all three muscles, moderate to excellent reliability was found for all conditions (probe locations and measurement techniques) (ICC=.70~.97). In the PL1-TA condition, inter-rater reliability in the three muscle thicknesses was good to excellent (ICC=.85~.96). The reliability of all measurement conditions was excellent in IO (ICC=.95~.97). Therefore, the findings of this study suggest that TA can be applied to PL1 by clinicians and researchers in order to measure the thickness of abdominal muscles.

Bioequivalence of Podox Tablet to Banan Tablet (Cefpodoxime Proxetil 100 mg) (바난 정(세프포독심 프록세틸 100mg)에 대한 포독스 정의 생물학적 동등성)

  • Cho, Seong-Wan;Lee, Ji-Hye;Song, Il-Yong;Lee, Sang-Kil;Cha, Young-Joo;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.29 no.3
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    • pp.241-245
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    • 1999
  • Bioequivalence study of two cefpodoxime preparations, the test drug ($Banan^{\circledR}$: Hanil Pharmaceutical Co., Ltd.) and the reference drug ($Podox^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers, $23.8{\pm}2.13$ years old and $63.34{\pm}4.84kg$ of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 200 mg as cefpodoxime proxetil in a $2{\times}2$ crossover study. Plasma concentrations of cefpodoxime were analysed by HPLC method for 12 hr after administration. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$, and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 4.31, 1.99 and 4.30% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences (%) between the formulations at ${\alpha}=\;0.05$ and $1-{\beta}=\;0.8$ were less than 20% (e.g., 13.89, 13.88, and 16.97% for AUC, $C_{max}$, and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\times}20%$ (e.g., $-5,58{\sim}14.20$, $-7.89{\sim}11.88$, and $-7.78{\sim}16.38%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of cefpodoxime were bioequivalent.

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Bioequivalence of EtodolTM Tablet to KuhnillodineTM Tablet (Micronized Etodolac 200 mg) (건일로딘 정(미결정에토돌락 200 mg)에 대한 에토돌 정의 생물학적동등성)

  • Lee, Jung-Ae;Lee, Yun-Young;Cho, Tae-Seob;Park, Young-Joon;Moon, Byoung-Seok;Kim, Ho-Hyun;Lee, Ye-Rie;Lee, Hee-Joo;Lee, Kyung-Ryul
    • Journal of Pharmaceutical Investigation
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    • v.34 no.4
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    • pp.319-325
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    • 2004
  • A bioequivalence of $Etodol^{TM}$ tablets (Yuhan corporation) and $Kuhnillodine^{TM}$ tablets (Kuhnil Pharm. Co., Ltd.) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 200 mg dose of etodolac of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a $2{\times}2$ crossover design. Concentrations of etodolac in human plasma were monitored by a high-performance liquid chromatography. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Etodol^{TM}/Kuhnillodine^{TM}$ were 1.01-1.10 and 0.87-1.06, respectively. This study demonstrated a bioequivalence of $Etodol^{TM}$ and $Kuhnillodine^{TM}$ with respect to the rate and extent of absorption.

Bioequivalence of Tagamet Tablet to Sinil CIMETIDINE Tablet (cimetidine 400 mg) (타가메트정 400 mg에 대한 신일시메티딘정 400 mg의 생물학적동등성시험)

  • Yoon, Mi-Kyeong;Lee, Byoung-Moo;Lee, Sung-Jae;Kim, Sun-Kyu;Lee, Jae-Hwi;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.34 no.6
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    • pp.521-527
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    • 2004
  • Cimetidine is a histamine $H_2-receptor$ antagonist, used for the treatment of endoscopically or radiographically comfirmed duodenal ulcer, pathologic GI hypersecretory conditions, and active, benign and gastric ulcer. Simple method for determining cimetidine in human plasma has been developed and validated. The analytical procedure for cimetidine showed a linear relationship in the concentration ranges from $0.05\;to\;5\;{\mu}g/ml$. Coefficient of variance (CV, %) for intraday and interday validation and relative error (RE, %) were less than ${\pm}15%$. Based on this analytical method, the bioequivalence of two cimetidine 400 mg tablets, reference (Tagamet 400 mg) and test drug (Sinil CIMETIDINE 400 mg) was evaluated according to the guidelines set by the Korea Food and Drug Administration (KFDA). Release of cimetidine from the tablets in vitro was tested using KP VIII Apparatus II with various dissolution media (pH 1.2, 4.0, 6.8 buffer solutions and water). Twenty-four healthy volunteers, $21.38{\pm}1.86$ years in age and $68.71{\pm}8.68\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was performed. After oral administration of a tablet containing 400 mg of cimetidine, blood samples were taken at predetermined time intervals and concentrations of cimetidine in plasma were determined using HPLC equipped with UV detector. The dissolution profiles of the two tablet formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as $AUC_t$ and $C_{max}$ were calculated and ANOVA was employed for the statistical analysis of parameters. The results were revealed that the differences in $AUC_t$ and $C_{max}$ between the two tablets were 4.17 % and 0.97% respectively. At 90% confidence intervals, the differences in these parameters were also within ${\pm}20%$. All of the above mentioned parameters have met the criteria of KFDA guidelines for bioequivalence, indicating that the test drug tablet (Sinil CIMETIDINE tablet) is bioequivalent to Tagamet 400 mg tablet.

Muscle Fatigue Assessment using Hilbert-Huang Transform and an Autoregressive Model during Repetitive Maximum Isokinetic Knee Extensions (슬관절의 등속성 최대 반복 신전시 Hilbert-Huang 변환과 AR 모델을 이용한 근피로 평가)

  • Kim, H.S.;Choi, S.W.;Yun, A.R.;Lee, S.E.;Shin, K.Y.;Choi, J.I.;Mun, J.H.
    • Journal of Biosystems Engineering
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    • v.34 no.2
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    • pp.127-132
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    • 2009
  • In the working population, muscle fatigue and musculoskeletal discomfort are common, which, in the case of insufficient recovery may lead to musculoskeletal pain. Workers suffering from musculoskeletal pains need to be rehabilitated for recovery. Isokinetic testing has been used in physical strengthening, rehabilitation and post-operative orthopedic surgery. Frequency analysis of electromyography (EMG) signals using the mean frequency (MNF) has been widely used to characterize muscle fatigue. During isokinetic contractions, EMG signals present strong nonstationarities. Hilbert-Haung transform (HHT) and autoregressive (AR) model have been known more suitable than Fourier or wavelet transform for nonstationary signals. Moreover, several analyses have been performed within each active phase during isokinetic contractions. Thus, the aims of this study were i) to determine which one was better suitable for the analysis of MNF between HHT and AR model during repetitive maximum isokinetic extensions and ii) to investigate whether the analysis could be repeated for sequential fixed epoch lengths. Seven healthy volunteers (five males and two females) performed isokinetic knee extensions at $60^{\circ}/s$ and $240^{\circ}/s$ until 50% of the maximum peak torque was reached. Surface EMG signals were recorded from the rectus femoris of the right thigh. An algorithm detecting the onset and offset of EMG signals was applied to extract each active phase of the muscle. Following the results, slopes from the least-square error linear regression of MNF values showed that muscle fatigue of all subjects occurred. The AR model is better suited than HHT for estimating MNF from nonstationary EMG signals during isokinetic knee extensions. Moreover, the linear regression can be extracted from MNF values calculated by sequential fixed epoch lengths (p> 0.0I).