• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.50-57
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• 1995

Background: Transcather arterial embolization has been established as an effective means to control hemoptysis, especially in patients with decreased pulmonary function such as postpneumonectomy patients and those with advanced chronic obstructive pulmonary disease. We evaluated the effect of arterial embolization and analysed the correlation of the clinical and angiographic characteristics and investigated the clinical course and outcome after arterial embolization in the patients with significant hemoptysis. Method: 58 patients with massive or recurrent hemoptysis underwent transcatheter arterial embolization for the treatment of hemoptysis from April 1992 to Sept. 1993. Results: Most common cause of hemoptysis was pulmonary tuberculosis(34 cases, 58.3%). Embolized vessels responsible for hemoptysis were 56 bronchial arteries and 32 nonbronchial systemic arteries. Initial most common angiographic findings were hypervascularity and shunt. Initial success rate of hemoptysis control revealed 81.1%. However, 15 of 58 patients(25.9%) showed recurrence of hemoptysis after transcatheter arterial embolization. The complications(18 cases, 31%) such as chest pain, fever, voiding difficulty, atelectasis, paralytic ileus and unwanted embolization were occured. Conclusion: Transcatheter arterial embolization is useful and relatively safe treatment modality for immediate bleeding control of patients with massive hemoptysis or inoperable cases. The further evaluation of the long term results according to the embolized material and underlying pulmonary disease will be required.

• 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.40 no.1
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• pp.16-22
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• 1993

Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

• Journal of dental hygiene science
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• v.10 no.3
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• pp.131-139
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• 2010

The purpose of this study was to evaluate smoking patterns, oral health behavior and perception of dental healthcare of military personnel in the South Korea Army. All 367 subjects were surveyed by the structured questionnaires with convenience sampling method. The questionnaires were consisting of 22 items. Depending on the conditions of military training, the distribution and differences of smoking patterns and oral behaviors were evaluated by frequency test, Weighted Kappa, Paired t-test and ANOVA. The differences of oral health perception on smoking were demonstrated by Mantel-Haenszel Chi-square test. In addition, Generalized Estimating Equation (GEE) was used to estimate the effects of oral behavior for the conditions of military training and smoking. The number of cigarette during military training period was similar to that during non-military training (p=0.109). The perception of smokers such as smoking effect on oral health, oral health and systemic health, and need of education for smoking cessation was significantly lower than non-smokers (p=0.0095, p=0.0007, and p<0.0001). The probability that toothbrush frequency per day was only one was associated with higher during military training period than non-military training (OR=9.29, 95% CI 5.05-17.07). Moreover, the probability that hours of toothbrush were less than one minute was associated with higher during military training than non-military training (OR=2.19, 95% CI 1.78-2.71). To improve knowledge, attitude, and behavior of oral health for the members, the army needs to develop oral health education and tobacco cessation programs. In particular, motivation and practice for oral health care are required to improve poor oral health behavior during the military training.

• Journal of Chest Surgery
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• v.34 no.7
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• pp.524-533
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• 2001

Background: Hyperoxemic cardiopulmonary bypass (CPB) has been recognized as a safe technique and is widely used in cardiac surgery. However, hyperoxemic CPB may produce higher toxic oxygen species and cause more severe oxidative stress and ischemia/reperfusion injury than normoxemic CPB. This study was undertaken to compare inflammatory responses and myocardial injury between normoxemic and hyperoxemic CPB and to examine the beneficial effect of normoxemic CPB. Material and method: Thirty adult patients scheduled for elective cardiac surgery were randomly divided into normoxic group (n=15), who received normoxemic CPB (about Pa $O_{2}$ 120 mmHg), and hyperoxic group (n=15), who received hyperoxemic CPB (about Pa $O_{2}$ 400 mmHg). Myeloperoxidase (MPO), malondialdehyde (MDA), adenosine monophosphate (AMP), and troponin-T (TnT) concentrations in coronary sinus blood were determined at pre- and post-CPB. Total leukocyte and neutrophil counts in arterial blood were measured at the before, during, and after CPB. Lactate concentration in mixed venous blood was analyzed during CPB, and cardiac index (Cl) and pulmonary vascular

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.97-113
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• 1998

The sympathoadrenal system plays an important role in homeostasis in widely varing external environments. Conflicting findings, however, have been reported on its response to hypoxia. We investigated the effect of hypoxia on the sympathoadrenal system in dogs under halothane anesthesia by measuring levels of circulating catecholamines in response to graded hypoxia. Ten healthy mongreal dogs were mechanically ventilated with different hypoxic gas mixtures. Graded hypoxia and reoxygenation were induced by progressively decreasing the oxygen fraction in the inhalation gas mixture from 21%(control) to 15%, 10% and 5% at every 5 minutes, and then reoxygenated with 60% oxygen. Mean arterial pressure, central venous pressure and mean pulmonary arterial pressure were measured directly using pressure transducers. Cardiac output was measured by the thermodilutional method. For analysis of blood gas, saturation and content, arterial and mixed venous blood were sampled via the femoral and pulmonary artery at the end of each hypoxic condition. The concentration of plasma catecholamines was determined by radioenzymatic assay. According to the exposure of graded hypoxia, not only did arterial and mixed venous oxygen tension decreased markedly at 10% and 5% oxygen, but also arterial and mixed venous oxygen saturation decreased significantly. An increased trend of the oxygen extraction ratio was seen during graded hypoxia. Cardiac output, mean arterial pressure and systemic vascular resistance were unchanged or increased slightly. Pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR) were increased by 55%, 76% in 10% oxygen and by 82%, 95% in 5% oxygen, respectively(p<0.01). The concentrations of plasma norepinephrine, epinephrine and dopamine increased by 75%, 29%, 24% in 15% oxygen and by 382%, 350%, 49% in 5% oxygen. These data suggest that the sympathetic nervous system was activated to maintain homeostasis by modifying blood flow distribution to improve oxygen delivery to tissues by hypoxia, but hemodynamic changes might be blunted by high concentration of nitrous oxide except PAP and PVR. It would be suggested that hemodynamic changes might not be sensitive index during hypoxia induced by high concentration of nitrous oxide exposure.

• Development and Reproduction
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• v.11 no.3
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• pp.245-251
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• 2007

Vinclozolin(VCZ), a systemic dicarboximide fungicide, has been used in the control of diseases caused by microorganism of some species in fruits, vegatables and ornamental plants. Although VCZ itself is a very weak antagonist for androgen receptor binding, both melabolites M1 and M2 are effective antagonists. The present study was undertaken to examine whether prepubertal exposure to VCZ affects on the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in female rats. VCZ(10 mg/kg/day) was administered daily from postnatal day 21(PND 21) through the day when the first vaginal opening(V.O.) was observed. Gross anatomy and weight of reproductive tissues were compared to test the VCZ's effects on the cell proliferation. Furthermore, histological studies were performed to assess the structural alterations in the tissues. To determine the transcriptional changes in progesterone receptor(PR), total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a result, delayed V.O. was shown in the VCZ group(PND $34.00{\pm}1.22$) compared to the control group(PND $38.20{\pm}1.92$; p<0.01). VCZ treatment significantly decreased the wet weight of ovaries and uteri compared to the control group(p<0.01). Graafian follicles and corpora lutea were observed only in the ovaries from the control animals, while numerous primary, secondary follicles and small atretic follicles were observed in the ovaries from VCZ group. Similarly, hypotrophy of luminal and glandular uterine epithelium was found in the VCZ group. In the semi-quantitative RT-PCR studies, the transcriptional activity of PR in ovary(p<0.01) from VCZ group were significantly lower than those from the control group while in uterus were similar compared with the control group. The present studies demonstrated that the acute exposure to VCZ during the critical period of prepubertal stage could inactivate the reproductive system resulting delayed puberty in female rats.

• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

• Korean Journal of Food Science and Technology
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• v.35 no.5
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• pp.980-987
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• 2003

In this report, we investigated the detoxication effects of Saururus chinenis, Geranium nepalense, Lonicera japonica, Cassia obtusifolia, Glycyrrhiza uralensis, or their mixtures by employing acute toxicity tests for nicotine and dioxin. When fatal doses $(LD_{100}\;=\;42\;mg/kg)$ of nicotine were injected into the abdominal cavities of ICR mice, those treated with OHEM showed delayed paralysis, half the duration of hyperactivity, and a 73 % survival rate. The results revealed the strong detoxicating effects of the mixtures. We also measured the amount of the degradation product of nicotine and cotinine in humans. Consumption of OHEM promoted (he more specific) the metabolic pathways of nicotine, increasing continine excretion by 1.5 times. As a result the amount of cotinine in urine was reduced to less than 5% after treatment with OHEM. In order to test the toxicity of dioxin, we used TcnN(SD)BR rats exposed to TCDD. While TCDD treatment reduced the blood levels of hemoglobin and platelet, OHEM consumption relieved these effects and, furthermore, helped to recover the number of platelet to the normal level (p<0.05). Moreover, neutrophils (%) and monocytes (%), which were reduced by the injection of TCDD, recovered to normal levels upon treatment with OHEM. The amount albumin reduced by TCDD (p<0.05) normalized, while the activities of GOT and GTP increased by TCDD were reduced. Increases in total cholesterol and neutral fatty acids induced by TCDD were also reduced by OHEM injection (p<0.05). In the kidney, TCDD-induced rises in creatinine were suppressed by OHEM treatment, while decreases in iron levels from TCDD were raised to normal. The treatment of TCDD had more toxic effects in the blood and pancreas than on the liver, kidney and heart. On the other hand, the detoxication of OHEM had significant effects on the liver and pancreas. The normalization by OHEM of various clinical abnormalities induced by TCDD demonstrates the detoxicating effect of OHEM that ameliorates systemic metabolism not properly functioning.

• Tuberculosis and Respiratory Diseases
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• v.55 no.6
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• pp.560-569
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• 2003

Background : A large number of pollutants such as sulfur dioxide, nitric oxide, carbon monoxide, particulate matter, and ozone influence on the body. These pollutants put a burden on the lung and the sequelae resulting from the oxidative stress are thought to contribute to the development of fibrotic lung disease, emphysema, chronic bronchitis and lung cancer. Also, carbon monoxide generated from the incomplete combustion of carbon-containing compounds is an important component of air pollution caused by traffic exhaust fumes and has the toxic effect of tissue hypoxia and produce various systemic and neurologic complications. The objective of this study is to compare the difference of pulmonary function and serum carboxyhemoglobin(CO-Hb) level between the traffic policemen and clerk policemen. Method : Three hundred and twenty-nine of traffic policemen, and one hundred and thirty clerk policemen were included between 2001 May and 2002 August. The policemen who took part in this study were asked to fill out a questionnaire which included questions on age, smoking, drinking, years of working, work-related symptoms and past medical history. The serum CO-Hb level was measured by using carboxyoximeter. Pulmonary function test was done by using automated spirometer. Additional tests, such as elecrocardiogram, urinalysis, chest radiography, blood chemistry, and CBC, were also done. Results : $FEV_1(%)$ was $97.1{\pm}0.85%$, and $105.7{\pm}1.21%$(p<0.05). FVC(%) was $94.6{\pm}0.67%$, and $102.1{\pm}1.09%$, respectively(p<0.05). Serum CO-Hb level was $2.4{\pm}0.06%$, and $1.8{\pm}0.08%$(p<0.05). After correction of confounding factors (age, smoking), significant variables were FVC(%), $FEV_1(%)$ and serum CO-Hb level(%)(p<0.05). Conclusion : Long exposure to air pollution may influence the pulmonary function and serum CO-Hb level. But, further prospective cohort study will be needed to elucidate detailed influences of specific pollutants on pulmonary function and serum carboxyhemoglobin level.