• Environmental Mutagens and Carcinogens
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• v.24 no.1
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• pp.15-18
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• 2004

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• Environmental Mutagens and Carcinogens
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• v.23 no.4
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• pp.131-134
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• 2003

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.444-450
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• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• Journal of Dental Rehabilitation and Applied Science
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• v.18 no.4
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• pp.235-249
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• 2002

This study was accompolished to analyze and compare the number and area of the occlusal contact points in healthy volunteers and athletes with normal occlusion. Before the study, 89 athletes(sports career:8.6 years, average age 20) at Kyung Hee University were selected, and survey was accomplished for athlete's recognition about sports dentistry. For this study, 15 athletes(13 amles and 2 females with average age 20) and 21 healthy volunteers(14 mles and 7 females with average age 20.09) at Kyung Hee University were selected. The visual display acquired by scanning of occlusal record in maximal intercuspation was converted into 16 gray value image. Then, using computer program(J & Lee Occlusal Analyser), the pixel which was in definite range of the gray value was recognized, and the numbers of recognized pixel were calculated to area. The results were as follows : (1) On the survey about sports dentistry, 28% of 89 athletes didn't agree that human occlusion may be important, and 30% didn't have any idea of the influence of human occlusion during their sports activities. (2) The average numbers of total occlusal contact points were 31.05 in control group, and 34.67 in athlete group. The average area of total occlusal contacts was $100.25mm^2$ in control group, and $127.78mm^2$ in athlete group. (3) In control group, the average numbers of occlusal contact points were revealed in order as follows; the first molar(8.48), the second molar(8.24), the second premolar(4.71), the lateral incisor(2.90), the first premor(2.43), the central incisor(2.19), and the canine(2.1). The least average in canine(2.1) was similar to the average(2.19) in central incisor and (2.09) in lateral incisor. In athlete group, the average numbers of occlusal contact points were revealed in order as follows; the first molar(8.87), the second molar(8.47), the second premolar(5.60), the canine(3.80), the lateral incisor(3.33), the first premolar(2.67), and the central incisor(1.93). (4) In control group, the average areas of occlusal contact surface were revealed in order as follows; the first molar($39.47mm^3$), the second molar($37.54mm^3$), the second premolar($9.54mm^3$) the first premolar($6.18mm^3$), canine($3.49mm^3$), the central incisor($2.76mm^3$), and the lateral incisor($1.28mm^3$). In athlete group, the average areas of occlusal contact surface were revealed in order as follows; the first molar($44.11mm^3$), the second molar($40.69mm^3$), the second premolar($16.50mm^3$), the first premolar($9.39mm^3$), the canine($5.08mm^3$), the lateral incisor($3.7mm^3$), and the central incisor($2.25mm^3$). (5). With aging in both control and athlete group, there was a decreasing tendancy in average number of occlusal contact point, and was an increasing tendancy in average area of occlusal contact surface. In comparison at each age, both the numbers and area of occlusal contact were greater in athlete group than in control group. It was not significant in the numbers of occlusal contact points beween athlete and control group(p>0.1), but significant in the area of occlusal contact surface(p<0.05). (6) In comparision as to the kind of sports(Gymnastics:2, Rugby:3, Soccor:5, Ice hocky:5), the numbers of occlusal contact points were the most in ice hocky, and the area of occlusal contact surface was the greatest in gymnastics. With increasing a career in athlete group, there was a decreasing tendancy in average numbers of occlusal contact points, and was an increasing tendancy in average area of occlusal contact surface.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.270-276
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• 1994

Background: The measurement of nonspecific bronchial hyperreactivity is valuable for diagnosis and management of bronchial asthma. Methacholine or histamine is used for the pharmacologic provocation test. Usually a methacholine bronchial provocation test is performed by a dosing technique with counted number of breaths. A dosimeter is indispensable in the dosing technique. Recently a timed tidal breathing technique which dose not need an expensive dosimeter was introduced. We measured the degree of nonspecific bronchial hyperreactivity to histamine using a simple timed tidal breathing technique. Method: Forty two healthy volunteers, 12 patients with bronchial asthma(BA), 10 patients with rhinitis(RH) and 10 patients with upper respiratory infection(URI) participated in the study. The subject's nose was clipped and inhalation continued during tidal breathing for 2 minutes via a face mask. $FEV_1$ was measured at 30 seconds, 90 seconds after inhalation and inhalation of next solution was continued until there was a fall in $FEV_1$ of 20%. Histamine PC20 was defined as the concentration at 20% fall of $FEV_1$ and it was obtained from the log dose-response curve by linear interpolation. Results: Inhalation of serial dilution of histamine could be performed in all patients without significant side effects. The geometric mean${\pm}$standard deviation of histamine PC20 in healthy volunteers is $8.27{\pm}2.22mg/ml$, BA group $0.33{\pm}3.02mg/ml$, RH group $0.85{\pm}3.24mg/ml$, and URI group $1.47{\pm}1.98mg/ml$. Conclusion: Histamine bronchial provocation test using timed tidal breath method is a simple and suitable tool for management of patients with bronchial hyperreactivity.

• Pediatric Infection and Vaccine
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• v.7 no.1
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• pp.120-128
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• 2000

Purpose : Active immunization against hepatitis A with an inactivated vaccine reveals excellent immunogenicity, tolerability and protective efficacy. Inactivated hepatitis A vaccines have been selectively used since 1996 in Korea to prevent hepatitis A. This study was performed to assess the immunogenicity and reactogenicity after two doses of HM175 strain hepatitis A vaccine in healthy Korean children. Methods : 128 healthy children(M/F; 65/63) aged 1 to 15 years, who were seronegative for hepaitatis A, participated in this study. A alum-adsorbed vaccine containing 720 EL.U of antigen form HM175 hepatitis A strain per 0.5 mL dose was injected intramuscularly on the deltoid area. The second dose was given 6 months later, Anti-HAV antibodies were measured by ELISA before and 1 month after each vaccination to assess the immunogenicity. Any local and general adverse events were reported by patients parents with the prepared questionnaire after each vaccination. Results : 120 volunteers(M/F; 60/60) completed the whole series of the study. Seroconversion occurred in all cases after primary and booster vaccination. The mean anti-HAV antibody titer after primary vaccination was 389.2mIU/mL, and 3,609mIU/mL after booster vaccination. And levels of anti-HAV antibodies after booster immunization were significantly higher in female children. The most common local adverse event was soreness on the injection site, but it was mild and resolves within 3 days. Fever was not reported after booster vaccination. Conclusion : Based on these data, we conclude that the inactivated HM175 strain hepatitis A vaccine is highly immunogenic and tolerable in healthy Korean children.

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.495-509
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• 2003

Background : Neutrophil-mediated inflammation is usually self-limiting, because neutrophils have a remarkably short life span. Prolonged neutrophil survival, which is caused by decreased spontaneous apoptosis, leads to persistent inflammation in sepsis. Because many inflammatory cytokines, which generate signals that delay apoptosis, are regulated by nuclear factor-${\kappa}B$ transcription factor, we hypothesized that nuclear factor-${\kappa}B$ might be related to the reduced neutrophil apoptosis observed in sepsis. Methods : Neutrophils of healthy volunteers and sepsis patients were freshly isolated from venous blood. Neutrophil apoptosis was assayed with two approaches : by counting apoptotic cells under a microscope and by flow cytometry using Annexin V. The activity of nuclear factor-${\kappa}B$ was assessed by immunofluorescent staining or electrophoretic mobility shift assay. Expression of X-linked inhibitor of apoptosis was measured by western blot assay. Results : We confirmed reduced spontaneous neutrophil apoptosis in patients with sepsis. The number of apoptotic neutrophils in patients with sepsis increased to the level of that in healthy controls after cycloheximide treatment, suggesting that decreased spontaneous neutrophil apoptosis is dependent on de novo protein synthesis. In patients with sepsis, basal neutrophil nuclear factor-${\kappa}B$ was activated compared to the level in healthy controls. Moreover, a blockade of nuclear factor-${\kappa}B$ activity reversed the decreased spontaneous neutrophil apoptosis in sepsis patients. Meanwhile, X-linked inhibition of apoptosis expression, which is regulated by nuclear factor-${\kappa}B$, decreased 24 hours after incubation in healthy persons, but persisted for 24 hours in patients with sepsis. Conclusion : These observations suggest that the reduced spontaneous neutrophil apoptosis observed in patients with sepsis may be related to the induction of survival protein by nuclear factor-${\kappa}B$.

• Journal of Yeungnam Medical Science
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• v.10 no.1
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• pp.179-189
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• 1993

It has recently become possible to record electrical activity originating from abnormally conducting myocardium from the body surface with high - gain amplification and averaging technique. These signals, which result from delayed ventricular activation(late potentials), have been recorded in patients with documented ventricular tachyarrythmia. Several electrode lead system for detecting ventricular late potential were introduced. Pyramidal electrode lead system(PLS) is useful. Also interpretation of SAECG in the young could be of value in detecting those at risk for episodic ventricular tachycardia, but suffer from a lack of data in normal young people. Selection of subjects : For this study, normal healthy young adult volunteers (age: mean 24 years) were recruited from the medical students at Yeungnam University Hospital, Internal Medicine. Twenty fourths male and seventeenths female subjects were selected. All subjects had normal resting ECGs as judged from both the standard 12 channel lead and echocardiography, and none had a history of cardiovascular disease. All subjects were considered to be in good general physical condition. Signal-averaged electrocardiography : In order to obtain low noise recordings with a small number of averaging cycles, all subject ware asked to relax completely in the supine position. Silver/silver chloride electrodes were attached after the skin was cleaned with alcohol, to constitute classic flank lead system(FLS) and pyramidal lead system(PLS). Signals were recorded and processed using a commercially available microprocessor-augmented ECG cart(Marquette Electronics, USA) suitable for portable bedside recording. There was no difference between normal values, determined by FLS and PLS at high pass filtering of 25 Hz and 80 Hz, but significant, difference was found in HFLAD and RMS-40 of 40 Hz(p<0.05). These results will provide a basis for interpretations of SAECG, determined by FLS and PLS in healthy young adults with normal QRS duration.

• Investigative Magnetic Resonance Imaging
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• v.17 no.4
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• pp.286-293
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• 2013

Purpose : The objective of this study was to analyze the brain volume according to the brain image of healthy adults in the 20s taken with different inversion time (TI). Materials and Methods: Brain images of healthy adults in the 20 s were acquired using magnetization prepared rapid acquisition gradient echo (MPRAGE) pulse sequence with 1.5 mm thickness of pieces and four inversion times (1100 ms, 1000 ms, 900 ms, 800 ms). The acquired brain images were analyzed to measure the volume of white matter (WM), gray matter (GM), intracranial volume (ICV). The statistical difference according to brain volume and gender was analyzed for each TI. Results: The brain volume calculated using Freesurfer was WM$486.52{\pm}48.64cm^3$ and GM=$646.83{\pm}57.12cm^3$ in mean when adjusted by mean ICV=$1278.94{\pm}154.92cm^3$. Men's brain volume(WM, GM, ICV) was larger than women's brain volume. In the intrarater reliability test, all of the intraclass correlation coefficients were high (0.992 for WM, 0.988 for GM, and 0.997 for ICV). In the repeated measures analysis of variance, GM and ICV did not show a significant difference at each TI (GM p=0.143, ICV p=0.052), but WM showed a significant (p=0.001). In the linear structure relation analysis, all of the Pearson correlation coefficients were high. Conclusion: WM, GM, and ICV indicated high reliability and solid linear structure relations, but WM showed significant differences at each TI. The brain volume of healthy adults in the 20s could be used in comparison with that of patients for reference purposes and to predict the structural change of brain. It would be needed to conduct additional studies to examine the contract, SNR, and lesion detection ability according to variable TI.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.6
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• pp.683-693
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• 2009

This study was designed to investigate the effect of dandelion juice supplementation on attenuation of oxidative stress and hangover after drinking alcohol in healthy college male students. This human trial was conducted by two phase cross over design with two weeks wash out period. The subjects (age $24{\sim}28$ years) were volunteers who had more than 72 g of ethanol drinking capacity. Dandelion group was given dandelion juice 220 mL daily for 7 days. Biochemical markers were determined in blood samples taken at 0 and 150 minutes after administration 72 g of alcohol. The levels of plasma glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase and bilirubin, the indicators of liver cell damage, were not significantly different between groups. No significant differences in lymphocyte DNA damage level between groups was observed. However, plasma acetaldehyde dehydrogenase (ALDH) and high density lipoprotein cholesterol levels were significantly (p<0.01) increased in dandelion supplemented group compared to that of control group. Furthermore, activities and protein expressions of glutathione-reductase and catalase of erythrocytes were significantly elevated in dandelion supplemented group compared to that of control group. From the above results, it is concluded that dandelion juice supplementation can reduce oxidative stress and hangover syndrome through the elevation of ALDH and antioxidative enzyme system in healthy male adults.