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Acute Pulmonary Toxicity and Body Distribution of Inhaled Metallic Silver Nanoparticles

  • Kwon, Jung-Taek;Minai-Tehrani, Arash;Hwang, Soon-Kyung;Kim, Ji-Eun;Shin, Ji-Young;Yu, Kyeong-Nam;Chang, Seung-Hee;Kim, Dae-Seong;Kwon, Yong-Taek;Choi, In-Ja;Cheong, Yun-Hee;Kim, Jun-Sung;Cho, Myung-Haing
    • Toxicological Research
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    • v.28 no.1
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    • pp.25-31
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    • 2012
  • The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at $1.93{\times}10^7$ particles/$cm^3$, $1.09{\times}10^{10}\;nm^2/cm^3$, $2.72{\times}10^{11}\;nm^3/cm^3$, and 2854.62 ${\mu}g/m^3$, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.

The agonistic action of URO-K10 on Kv7.4 and 7.5 channels is attenuated by co-expression of KCNE4 ancillary subunit

  • Lee, Jung Eun;Park, Christine Haewon;Kang, Hana;Ko, Juyeon;Cho, Suhan;Woo, JooHan;Chae, Mee Ree;Lee, Sung Won;Kim, Sung Joon;Kim, Jinsung;So, Insuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.6
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    • pp.503-516
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    • 2020
  • KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50, the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the β ancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQ-specific agonist in the tissue.

The Increased Expression of Gelatinolytic Proteases Due to Cigarette Smoking Exposure in the Lung of Guinea Pig (기니픽에서 흡연 노출에 의한 젤라틴 분해 단백 효소의 발현 양상에 관한 연구)

  • Kang, Min-Jong;Lee, Jae-Ho;Yoo, Chul-Gyu;Lee, Choon-Taek;Chung, Hee-Soon;Seo, Jeong-Wook;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.4
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    • pp.426-436
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    • 2001
  • Background : Chronic obstructive pulmonary disease(COPD) is one of the major contributors to morbidity and mortality among the adult population. Cigarette smoking(CS) is undoubtedly the single most important factor in the pathogenesis of COPD. However, its mechanism is unclear. The current hypothesis regarding the pathogenesis of COPD postulates that an imbalance between proteases and antiproteases leads to the destructive changes in the lung parenchyma. This study had two aims. First, to evaluate the effect of CS exposure on histologic changes of the lung parenchyme, and second, to evaluate the effect of CS exposure on the expression of the gelatinolytic enzymes in BAL fluid cells in guinea pigs. Methods : Two groups of five guinea pigs were exposed to the whole smoke of 20 commercial cigarettes per day, 5 hours/day, 5 days/week, for 6weeks, and 12 weeks, respectively, using a smoking apparatus. Five age-matched guinea pigs exposed to room air were used as controls. Five or more sections were microscopically extamined(${\times}400$) and the number of cellular infiltration of the alveolar wall was measured in order to evaluate the effect of CS exposure on the histologic changes of lung parenchyme. The statistical significance was analyzed by a linear regression method. To evaluate the expression of the gelatinolytic enzymes in intraalveolar cells, BAL fluid was obtained and the intraalveolar cells were separated by centrifugation (500 g for 10 min at $4^{\circ}C$). Two sets of culture plates were loaded with $1{\times}10^6$ intraalveolar cells. One plate, contained O.1mM EDTA, a inhibitor of matrix metalloproteases(MMPs), and the other plate had no EDTA. Both plates were incubated for 48 hours at $37^{\circ}C$. After incubation, gelatinolytic protease expression in the supernatants was analyzed by gelatin zymography. Results : At the end of CS exposure, the level of blood carboxy Hb had increased significantly(4.1g/dl in control group, 24g/dl immediately after CS exposure, 18g/dl 30 min after CS exposure, 15g/dl 1 hour after CS exposure). Alveolar inflammatory cells were identified in the CS exposed guinea pigs. The number of alveolar cellular cells observed in a microscopic field ($400{\times}$) was $121.4{\pm}7.2$, $158.0{\pm}20.2$, $196.8{\pm}32.8$, in the control, the 6 weeks, and the 12 weeks group, respectively. The increased extent of inflammatory cellular infiltration of the lung parenchema showed a statistically significant linear relationship with the duration of CS exposure(p=0.001, $r^2=0.675$). Several types of gelatinolytic enzymes in the intraalveolar cells of CS exposed guinea pigs were expressed, of which some were inhibited by EDT A. However, the gelatinolytic enzymes were not expressed in the control groups. Conclusion : CS exposure increases inflammatory cellular infiltration of the alveolar wall and the expression of gelatinolytic proteases in guinea pigs. EDTA inhibits some of the gelatinolytic proteases. These findings suggest a possibility that CS exposure may increase MMP expression in the lungs of guinea pigs.

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Analysis of the reasons why patients cancel shoulder surgery despite recommendation

  • Lee, Kyung Jae;Kim, Jangwoo;Kim, Yuna;Yang, Eunkyu;Yun, Kuk-ro;Kim, Sae Hoon
    • Clinics in Shoulder and Elbow
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    • v.25 no.2
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    • pp.121-128
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    • 2022
  • Background: To determine the reasons and factors that contribute to the cancellations of shoulder surgeries at a tertiary referral center and to analyze the characteristics of these patients. Methods: Patients scheduled for shoulder surgery from June 2017 to July 2019 were allocated to a surgery group (n=224) or a cancellation group (n=96). These groups were compared with respect to patient characteristics, types of surgery, distance from patient's home to the hospital, traveling time to the hospital, and waiting period before surgery. Reasons for cancellation and responses were acquired using a telephone interview and were subsequently analyzed. Results: The cancellation group was older, had a less frequent history of trauma, and had a lower proportion of patients undergoing arthroscopic rotator cuff repair than the surgery group (p=0.009, p=0.014, and p=0.017, respectively). In addition, mean distance from the patients' homes to the hospital and preoperative waiting time were both longer in the cancellation group (p=0.001 and p<0.01, respectively). The most common reason given for cancellation was another medical condition (28.1%). Conclusions: Older age, need for arthroscopic rotator cuff repair surgery, longer distance from the patient's home to the hospital, and longer waiting period significantly increased the chance of cancellation. The main reason for canceling surgery was a concurrent medical condition. Therefore, identification of other medical conditions in advance is an important consideration when surgeons recommend shoulder surgery to patients. Surgeons should also consider patient's age, type of surgery, distance from the hospital, and waiting time when assessing the possibility of surgery cancellation.

Genome-Wide Association Study of Bone Mineral Density in Korean Men

  • Bae, Ye Seul;Im, Sun-Wha;Kang, Mi So;Kim, Jin Hee;Lee, Soon Hang;Cho, Be Long;Park, Jin Ho;Nam, You-Seon;Son, Ho-Young;Yang, San Deok;Sung, Joohon;Oh, Kwang Ho;Yun, Jae Moon;Kim, Jong Il
    • Genomics & Informatics
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    • v.14 no.2
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    • pp.62-68
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    • 2016
  • Osteoporosis is a medical condition of global concern, with increasing incidence in both sexes. Bone mineral density (BMD), a highly heritable trait, has been proven a useful diagnostic factor in predicting fracture. Because medical information is lacking about male osteoporotic genetics, we conducted a genome-wide association study of BMD in Korean men. With 1,176 participants, we analyzed 4,414,664 single nucleotide polymorphisms (SNPs) after genomic imputation, and identified five SNPs and three loci correlated with bone density and strength. Multivariate linear regression models were applied to adjust for age and body mass index interference. Rs17124500 ($p=6.42{\times}10^{-7}$), rs34594869 ($p=6.53{\times}10^{-7}$) and rs17124504 ($p=6.53{\times}10^{-7}$) in 14q31.3 and rs140155614 ($p=8.64{\times}10^{-7}$) in 15q25.1 were significantly associated with lumbar spine BMD (LS-BMD), while rs111822233 ($p=6.35{\times}10^{-7}$) was linked with the femur total BMD (FT-BMD). Additionally, we analyzed the relationship between BMD and five genes previously identified in Korean men. Rs61382873 (p = 0.0009) in LRP5, rs9567003 (p = 0.0033) in TNFSF11 and rs9935828 (p = 0.0248) in FOXL1 were observed for LS-BMD. Furthermore, rs33997547 (p = 0.0057) in ZBTB and rs1664496 (p = 0.0012) in MEF2C were found to influence FT-BMD and rs61769193 (p = 0.0114) in ZBTB to influence femur neck BMD. We identified five SNPs and three genomic regions, associated with BMD. The significance of our results lies in the discovery of new loci, while also affirming a previously significant locus, as potential osteoporotic factors in the Korean male population.

Development of the Korean Developmental Screening Test for Infants and Children (K-DST)

  • Chung, Hee Jung;Yang, Donghwa;Kim, Gun-Ha;Kim, Sung Koo;Kim, Seoung Woo;Kim, Young Key;Kim, Young Ah;Kim, Joon Sik;Kim, Jin Kyung;Kim, Cheongtag;Sung, In-Kyung;Shin, Son Moon;Oh, Kyung Ja;Yoo, Hee-Jeong;Yu, Hee Joon;Lim, Seoung-Joon;Lee, Jeehun;Jeong, Hae-Ik;Choi, Jieun;Kwon, Jeong-Yi;Eun, Baik-Lin
    • Clinical and Experimental Pediatrics
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    • v.63 no.11
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    • pp.438-446
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    • 2020
  • Background: Most developmental screening tools in Korea are adopted from foreign tests. To ensure efficient screening of infants and children in Korea, a nationwide screening tool with high reliability and validity is needed. Purpose: This study aimed to independently develop, standardize, and validate the Korean Developmental Screening Test for Infants and Children (K-DST) for screening infants and children for neurodevelopmental disorders in Korea. Methods: The standardization and validation conducted in 2012-2014 of 3,284 subjects (4-71 months of age) resulted in the first edition of the K-DST. The restandardization and revalidation performed in 2015-2016 of 3.06 million attendees of the National Health Screening Program for Infants and Children resulted in the revised K-DST. We analyzed inter-item consistency and test-retest reliability for the reliability analysis. Regarding the validation of K-DST, we examined the construct validity, sensitivity and specificity, receiver operating characteristic curve analysis, and a criterion-related validity analysis. Results: We ultimately selected 8 questions in 6 developmental domains. For most age groups and each domain, internal consistency was 0.73-0.93 and test-retest reliability was 0.77-0.88. The revised K-DST had high discriminatory ability with a sensitivity of 0.833 and specificity of 0.979. The test supported construct validity by distinguishing between normal and neurodevelopmentally delayed groups. The language and cognition domain of the revised K-DST was highly correlated with the K-Bayley Scales of Infant Development-II's Mental Age Quotient (r=0.766, 0.739), while the gross and fine motor domains were highly correlated with Motor Age Quotient (r=0.695, 0.668), respectively. The Verbal Intelligence Quotient of Korean Wechsler Preschool and Primary Scales of Intelligence was highly correlated with the K-DST cognition and language domains (r=0.701, 0.770), as was the performance intelligence quotient with the fine motor domain (r=0.700). Conclusion: The K-DST is reliable and valid, suggesting its good potential as an effective screening tool for infants and children with neurodevelopmental disorders in Korea.

The Effect of Endoscopic Resection on Short-Term Surgical Outcomes in Patients with Additional Laparoscopic Gastrectomy after Non-Curative Resection for Gastric Cancer

  • Lee, Eun-Gyeong;Ryu, Keun-Won;Eom, Bang-Wool;Yoon, Hong-Man;Kim, Yong-Il;Cho, Soo-Jeong;Lee, Jong-Yeul;Kim, Chan-Gyoo;Choi, Il-Ju;Kim, Young-Woo
    • Journal of Gastric Cancer
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    • v.17 no.1
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    • pp.33-42
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    • 2017
  • Purpose: Endoscopic submucosal dissection (ESD) in early gastric cancer causes an artificial gastric ulcer and local inflammation that has a negative intraprocedural impact on additional laparoscopic gastrectomy in patients with noncurative ESD. In this study, we analyzed the effect of ESD on short-term surgical outcomes and evaluated the risk factors. Materials and Methods: From January 2003 to January 2013, 1,704 patients of the National Cancer Center underwent laparoscopic gastrectomy with lymph node dissection because of preoperative stage Ia or Ib gastric cancer. They were divided into 2 groups: (1) with preoperative ESD or (2) without preoperative ESD. Clinicopathologic factors and short-term surgical outcomes were retrospectively evaluated along with risk factors such as preoperative ESD. Results: Several characteristics differed between patients who underwent ESD-surgery (n=199) or surgery alone (n=1,505). The mean interval from the ESD procedure to the operation was 43.03 days. Estimated blood loss, open conversion rate, mean operation time, and length of hospital stay were not different between the 2 groups. Postoperative complications occurred in 23 patients (11.56%) in the ESD-surgery group and in 189 patients (12.56%) in the surgery-only group, and 3 deaths occurred among patients with complications (1 patient [ESD-surgery group] vs. 2 patients [surgery-only group]; P=0.688). A history of ESD was not significantly associated with postoperative complications (P=0.688). Multivariate analysis showed that male sex (P=0.008) and laparoscopic total or proximal gastrectomy (P=0.000) were independently associated with postoperative complications. Conclusions: ESD did not affect short-term surgical outcomes during and after an additional laparoscopic gastrectomy.

Antiplatelet and Antithrombotic Activities of Korean Red Ginseng

  • Yu, Ji-Yeon;Jin, Yong-Ri;Lee, Jung-Jin;Chung, Jin-Ho;Noh, Ji-Yoon;You, Soon-Hyang;Kim, Ki-Nam;Im, Ji-Hyun;Lee, Ju-Hyun;Seo, Ji-Min;Han, Hyeong-Jun;Lim, Yong;Park, Eun-Seok;Kim, Tack-Joong;Shin, Kyeong-Soeb;Wee, Jae-Joon;Park, Jong-Dae;Yun, Yeo-Pyo
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.898-903
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    • 2006
  • The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its anti platelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with $IC_{50}$ values of $620{\pm}12$, $823{\pm}22$, $722{\pm}21$ and $650{\pm}14\;{\mu}g/mL$, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.

Analysis for the Effect on Satisfaction after Education of Cardiovascular Pulmonary Resuscitation in Emergency Medical Information Center (일부지역에서의 응급처치 교육전후의 효과분석)

  • Kim, Jin-Woo;Jo, Jean-Man;Kim, Chang-Kook;Lee, Mi-Ok
    • The Korean Journal of Emergency Medical Services
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    • v.9 no.1
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    • pp.55-78
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    • 2005
  • The purpose of this study is to analyze the effect on satisfaction after education of cardiovascular pulmonary resuscitation(CPR) in Daejon Emergency Medical information Center in Korea. The major instruments of this study were Korean Self-Analysis Student Opinionnaire. Questionnaire contains 12 items which measure student's satisfaction or attitude factor. To take the analysis of data, the total of 308 students were investigated in Medical Information Center in Dae-jon Metropolitan City from 2004. 2. September to 2004. 16. September. The data were analyzed by the path analysis SPSS program. The result are as follows: 1. After education of CPR, there was significant satisfaction of CPR knowledge P=0.0011). 2. After education of CPR, there was significant satisfaction of CPR skill(P=0.00001).

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Evaluation of the Korean Isolate-1 Tachyzoite Antigen for Serodiagnosis of Toxoplasmosis

  • Shin, Eun-Hee;Kim, Dong-Hee;Lin, Aifen;Lee, Jo-Woon-Yi;Kim, Hyo-Jin;Ahn, Myoung-Hee;Chai, Jong-Yil
    • Parasites, Hosts and Diseases
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    • v.46 no.1
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    • pp.45-48
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    • 2008
  • To evaluate the usefulness of the Korean Isolate-1 (KI-1) antigen for serodiagnosis of toxoplasmosis, antigen profiles of KI-1 tachyzoites were analyzed in comparison with RH tachyzoites by SOS-PAGE and immunoblotting. ELISA was performed on latex agglutination (LA)-positive and negative serum samples using KI-1 and RH antigens. Immunoblotting of the KI-1 antigen showed multiple antigen bands with molecular sizes of 22-105 kDa. Among them, 1 and 6 common bands were noted against a KI-1-infected and a RH-infected human serum, respectively, which represented differences in antigenic profiles between KI-1 and RH tachyzoites. However, all 9 LA-positive human sera were found positive by ELISA, and all 12 LA-negative sera were negative by ELISA; the correlation between the ELISA titers and LA titers was high (r = 0.749). Our results suggest that tachyzoites of KI-1 may be useful for serodiagnosis of human toxoplasmosis.