<i>In vitro</i> and <i>in vivo</i> evaluation of a novel polymer-free everolimus-eluting stent by nitrogen-doped titanium dioxide film deposition

Park, Dae Sung,Bae, In-Ho,Jeong, Myung Ho,Lim, Kyung Seob,Sim, Doo Sun,Hong, Young Joon,Lee, So-Youn,Jang, Eun Jae,Shim, Jae-Won,Park, Jun-Kyu,Lim, Han Chul,Kim, Han Byul Elsevier 2018 Materials Science and Engineering C Vol.91 No.-

<P><B>Abstract</B></P> <P>Inflammation and thrombosis are linked to the use of polymer-based drug-eluting stents (DES). The aim of this study was to develop a polymer-free everolimus (EVL)-eluting stent using nitrogen-doped titanium dioxide (N-TiO<SUB>2</SUB>) and verify its efficacy by <I>in vitro</I> and <I>in vivo</I> assessment in a porcine coronary model. Various analytical approaches such as scanning electron microscopy and atomic force microscopy, electron spectroscopy, Fourier transform infrared spectrometry and contact angle measurement were employed for the characterization. As a part of biocompatibility assessment, platelet adhesion and smooth muscle cell (SMC) proliferation were examined. Bare metal stent (BMS), N-TiO<SUB>2</SUB> stent, everolimus-eluting N-TiO<SUB>2</SUB> (N-TiO<SUB>2</SUB>-EVL) stent, and commercialized EVL-eluting stent (EES) were randomly placed in forty coronary arteries in twenty pigs. After four weeks of implantation, the stents were subjected to histological and quantitative analysis. The N-TiO<SUB>2</SUB> film used in this study was well coated without any cracks or peeling. Surface hydrophilicity (88.8% of angle decrement) could be associated with the decrease in surface roughness post N-TiO<SUB>2</SUB> deposition (37.0%). The platelet adhesion on the N-TiO<SUB>2</SUB> surfaces was less than that on the BMS surface. The proliferation of SMC was suppressed in the N-TiO<SUB>2</SUB>-EVL group (30.2%) but not in the BMS group. In the animal study, the percent area restenosis was significantly decreased in the N-TiO<SUB>2</SUB>-EVL group compared to that in the BMS group. The results (BMS; 47.0 ± 11.00%, N-TiO<SUB>2</SUB>-EVL; 31.7 ± 10.50%, and EES; 29.1 ± 11.21%, <I>n</I> = 10, <I>p</I> < 0.05) were almost at par with those of the commercialized EVL-eluting stent. The introduction of N-TiO<SUB>2</SUB> deposition during fabrication of polymer-free DES may be an efficient accessorial process for preventing in-stent restenosis and thrombosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> N-TiO<SUB>2</SUB> surfaces can help to reduce the platelet adhesion. </LI> <LI> In porcine model, N-TiO<SUB>2</SUB> everolimus decreased in-stent restenosis and fibrin deposition. </LI> </UL> </P>

Genetic Variations of the Apolipoprotein B Gene in Korean People and Its Association with Hypercholesterolemia

Sung Han Kim,Un Kyung Kim,Jae Jin Chae,Jeong In Baek,Soo Young Choi,Jae Woong Bae,Sang Hyun Kim,Hyo Soo Kim 한국유전학회 2008 Genes & Genomics Vol.30 No.5

Genetic polymorphisms at the apolipoprotein B have been associated with elevated plasma concentrations of LDL, atherosclerosis and increased risk of coronary artery disease. 106 individuals composed of 46 hypercholesterolemic patients and 60 controls were analyzed with Ins/Del length polymorphism, four RFLPs (HincII, PvuII, AluI, EcoRI) and 3`-VNTR to clarify the characteristics of the apolipoprotein B gene and to determine their influence on the lipid profile of hypercholesterolemic patients and controls in Korea. A total of 212 apolipoprotein B alleles from six markers were identified in this study. Heterozygosityranges from zero to 0.32, and the genotyope frequencies in the case of 3`-VNTR are significantly different between two groups. Analysis of linkage disequilibrium revealed paired nonrandom associations between four pairs of polymorphic sites of the apolipoprotein B gene (p<0.05). Moreover, addition of all 4 polymorphic sites provided the highest PIC value. This study also investigated the association of these polymorphisms with the patients and with variation in lipid levels. A significant association between 3`-VNTR genotypes and Lp(a) was observed in hypercholesterolemic patients (p<0.05). The results suggest that genotypes of six polymorphic markers were not significantly associated with TC, TG or LDL-chol level between the patients and controls in the Koreans.

In-hospital mortality in patients with STEMI admitted during off hours

( Sung-Soo Kim ),( Myung Ho Jeong ),( Jeong Gwan Cho ),( Young Keun Ahn ),( Jong Hyun Kim ),( Shung Chull Chae ),( Young Jo Kim ),( Seung Ho Hur ),( In Whan Seong ),( Taek Jong Hong ),( Dong-hoon Choi 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

Conflicting results exist on the outcome of off hours PCI in ST elevation myocardial infarction (STEMI). However, there were only a few studies that have focused on the clinical characteristics and outcomes of off hours PCI in STEMI. So, we studied the clinical characteristics and hospital mortality in STEMI patients treated with primary PCI during regular hours (weekdays 9:00 AM to 6:00 PM) versus off hours Weekdays 6:01 PM to 8:59 AM, weekends, and holidays) in Korea Acute Myocardial Infarction Registry. We analyzed in hospital and one year mortality among 5,665 consecutive ST segment elevation myocardial infarction patients treated with primary PCI between November 2005 to January 2008. Total 2,848 (50.2%) patients were treated during off hours. Baseline finding were similar, although regular hours patients were older. Median symptom to balloon time (304 min, IQR 175 to 750 vs. 270 min, IQR 145 to 551, p=0.001) were longer for regular hours primary PCI. Median door to balloon time (71min, IQR: 48 to 132 vs. 59 min, IQR 39 to 110 min, p=0.001) were longer for off hours pPCI. Also, Cardiac enzyme such as Max CK-MB (212.1±299.3 vs 194.7±303.4, p=0.031) and max TnI (72.6±239.5 vs. 58.9±94.4, p=0.013) were increased in off hours pPCI. However, unadjusted in hospital (6.0% off hours vs. 6.0% regular hours, p=0.946) and one year cardiac mortality (11.3% off hours vs. 11.7% regular hours, p=0.661) were comparable. In multivariate analysis, off hours primary PCI did not predict an adverse outcome. In conclusion, when primary PCI was performed within an appropriate reperfusion strategy, the clinical effectiveness of either off hours or regular hours pPCI is comparable.

공군사관생도의 심폐능력에 따른 심리 · 생리요인 비교

김인기(In-ki Kim),김건희(Gun-hee Kim),송성우(Sung-woo Song),최가람(Ga-ram Choi),엄장원(Jang-won Eom),곽재준(Jae-jun Kwak),유영남(Young-nam You),정덕화(Deok-hwa Jeong),강지훈(Ji-hun Kang) 육군사관학교 화랑대연구소 2019 한국군사학논집 Vol.75 No.2

The purpose of this study was to analyze the differences in psychological and physiological factors between groups by classifying groups based on the 3km running record of fourth grade Air Force Academy cadets. Among the top 46 Air Force Academy cadets who wanted to participate in the study, the study conducted an open survey of the top 13 and the bottom 15 who wanted to provide the data prior to the study. The subjects of the experiment and in-depth interview were studied by a total of 18 people, 9 of each upper and lower members who wished to participate in the study. Psychological factors were structured through inductive content analysis of data extracted from in-depth interviews, and physiological factors were conducted to verify differences between groups of body composition and cardiopulmonary function. The psychological factors of the upper and lower groups were found to be general areas of performance strategy, achievement motivation, emotional response, military spirit, situation perception, and basic physical strength. In the detailed areas, the subjects were also examined in 15 areas including physical fitness indicators, confidence, condition control, task orientation, and positive self-perception. As a result of comparison between upper and lower groups, the upper group was 2.2 times higher than the lower group and the lower group was 1.7 times higher than the upper group in the military spirit and performance strategy of the general area response rate. In general area response, the ratio of mental strength and confidence was different in the general area of military spirit. In addition, the upper group in the achievement motivation showed a high percentage of task tendency at 47%, while the lower group showed a high rate of zero motivation at 50%. In the emotional response, the upper group showed an equal ratio, while the lower group showed an 81% ratio of negative emotions. In the overall response by sub-region, the negative emotions of the subgroup were high at 28%. In the body composition, BFM showed a statistically significant difference between upper and lower groups, and Weight, FFM, and SMM did not show any significant difference between groups. In cardiopulmonary capacity, VO2max showed a statistically significant difference between upper and lower groups, and VE and LT did not show significant differences between groups.

The effect of alpha lipoic acid in a porcine in-stent restenosis model

Lim, Sang Yup,Bae, Eun Hui,Jeong, Myung Ho,Kim, Ju Han,Hong, Young Joon,Sim, Doo Sun,Kim, Yong Sook,Park, In Kyu,Ahn, Youngkeun,Song, Sun-Jung,Cho, Dong Lyun,Kim, Kyoung Seok,Kang, Jung Chaee Elsevier 2009 Journal of cardiology Vol.54 No.3

<P><B>Summary</B></P><P><B>Background</B></P><P>The aim of this study was to investigate the effect of alpha lipoic acid (α-LA) on a porcine in-stent restenosis (ISR) model.</P><P><B>Methods</B></P><P>In protocol 1, porcine vascular smooth muscle cells (PVSMC) were stimulated by granulocyte-colony stimulating factor (G-CSF) in the presence or absence of α-LA. MTT (3-[4,5-dimethylthiazole-2-yl] 2,5-diphenyl tetrazolium bromide) assay and western blotting were used to determine the cell growth inhibitory rate and anti-inflammatory effect associated with nuclear factor-κb (NF-κb) and extracellular signal-regulated kinase (ERK). In protocol 2, 28 days after balloon overdilation injuries, 24 bare metal stents were placed in coronary artery of 12 pigs. The pigs were randomly divided to receive control diet with or without α-LA (100mg/kg). In protocol 3, 8 control stents and 8 α-LA coated stents were randomly implanted in 2 coronary arteries of 8 pigs and follow-up coronary angiogram and histopathologic assessment were performed 4 weeks after stenting.</P><P><B>Results</B></P><P>Protocol 1. The proliferation of PVSMC was inhibited and protein expression of NF-κb and ERK were attenuated by α-LA pretreatment. Protocol 2<I>.</I> On histopathologic analysis, the neointimal area (4.0±1.0mm<SUP>2</SUP> vs. 1.5±0.7mm<SUP>2</SUP>, <I>p</I><0.001) and histopathologic area of stenosis (66.7±10.7% vs. 24.2±9.7%, <I>p</I><0.001) were reduced in the α-LA feeding group compared to controls. Protocol 3. On histopathologic analysis, the neointimal area (3.9±0.8mm<SUP>2</SUP> vs. 1.0±0.4mm<SUP>2</SUP>, <I>p</I><0.001), and the histopathologic area of stenosis (67.1±8.8% vs. 17.4±10.0%, <I>p</I><0.001) were reduced in the α-LA coated stent group compared to the control stent group.</P><P><B>Conclusions</B></P><P>α-LA feeding and α-LA coated stents inhibit neointimal hyperplasia in porcine ISR, possibly through inhibiting the activation of NF-κb pathway and proliferation of PVSMC.</P>

DYNAMIC RESPONSE OF CARBON NANOTUBES DISPERSED IN NEMATIC LIQUID CRYSTAL

YOUNG HEE LEE,SANG YOUN JEON,KYUNG AH PARK,IN-SU BAIK,SEOK JIN JEONG,SEOK HO JEONG,안계혁,SEUNG HEE LEE 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2007 NANO Vol.2 No.1

The alignment and dynamic response of carbon nanotubes (CNTs) in nematic liquid crystal (NLC) medium induced by strong electric field have been observed through polarizing optical microscope. Density-functional calculations suggest that LC molecule anchors helically to the CNT wall to enhance π-stacking with a binding energy of nearly -2.0 eV due to a considerable amount of charge transfer from LC molecule to CNT, resulting in the formation of excess charges and permanent dipole moment in CNTs. Under strong electric field, the motion of CNTs distorted the director of adjacent LC molecules. Our detailed analysis of dynamics revealed that the four-lobe textures in vertical cell and two vertical stripes in in-plane switching cell were strongly correlated, i.e., the side view of textures by the vertical motion of CNTs in vertical cell was similar to the textures in in-plane switching cell. Interestingly, the magnitude of textures in microscope was strongly dependent on the size of CNTs and theapplied field strength. The statistical size distribution of textures similar to that of CNTs provided information for the degree of dispersion of CNTs.

Evaluation of ion implantation for anti-thrombogenic coronary stent in vitro and in vivo

Shim, Jae-Won,Bae, In-Ho,Park, Dae Sung,Lim, Kyung-Seob,Lee, So-Youn,Jang, Eun-Jae,Park, Jun-Kyu,Kim, Ju Han,Jeong, Myung Ho Elsevier 2017 Journal of industrial and engineering chemistry Vol.54 No.-

<P><B>Abstract</B></P> <P>The aim of this study was to evaluate the effect of ion implantation on the surface of anti-thrombogenic coronary stent. Nitrogen (N) was implanted into the cobalt–chromium surface by using an ion source under a plasma environment to enhance its hardness and surface modification. The N ion dosage was 1×10<SUP>15</SUP> ions/cm<SUP>2</SUP>. All analysis results of the ion implanted stent were compared with those of bare metal stent. The N component and distribution were confirmed by auger electron spectroscopy. Microhardness was significantly increased after 40min of implantation (415.3±12.38 HV, 18.9±2.62%). The surface was altered to hydrophobic status through ion implantation (30.6±1.12% in contact angle increment). Platelet adhesion, and smooth muscle cell migration and proliferation were prevented in the ion implanted group (43.9%, 11.2%, and 45.1%, respectively). To verify the in vitro result, stents were implanted to rabbit iliac artery and isolated at 4 weeks post implantation. Then, the stents were subjected to histological analysis. No significant differences in injury score, internal elastic lamina, lumen area, and restenosis rate were found. However, the fibrin score was more significantly decreased in the ion beam-implanted group (2.5±0.15) than in the bare metal stent group (1.8±0.31, <I>n</I> =10, <I>p</I> <I><</I> 0.05). Taken together, ion beam implantation may be an efficient accessorial tool for preventing in-stent restenosis and in-stent thrombosis.</P>

Low serum bilirubin level predicts the develop-ment of chronic kidney disease in patients with type 2 diabetes mellitus

( Kang Hee Ahn ),( Sang Soo Kim ),( Won Jin Kim ),( Jong Ho Kim ),( Yun Jeong Nam ),( Su Bin Park ),( Yun Kyung Jeon ),( Bo Hyun Kim ),( In Joo Kim ),( Yong Ki Kim ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.5

Background/Aims: We evaluated whether serum bilirubin levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T₂DM). Methods: This was a retrospective observational longitudinal study of patients presenting at the Pusan National University Hospital. A total of₃₄₉ patients with T₂DM and preserved kidney function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m²) were enrolled. The main outcome was the development of CKD stage 3 or greater. The patients were divided into four groups according to the quartiles of the total serum bilirubin levels at baseline. Results: The group with the lowest range of total serum bilirubin level (Q₁) showed the highest cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q₁ vs. Q₄; hazard ratio [HR], 6.75; 95% confidence in-terval [CI], 1.54 to 29.47; p = 0.011). In multivariate analysis, the risk of developing CKD stage 3 or greater was higher in the second lowest quartile of the serum bili-rubin level than that in the highest quartile of the serum bilirubin level (Q₂ vs. Q₄; HR, 9.36; 95% CI, 1.33 to 65.73; p = 0.024). In the normoalbuminuria subgroup (n = 236), multivariate analysis showed that the risk of developing CKD stage 3 or greater was higher in the lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q1 vs. Q4; HR, 7.36; 95% CI, 1.24 to 35.82; p = 0.019). Conclusions: Serum bilirubin might be an early clinical marker for predicting the progression of CKD in patients with T₂DM and preserved renal function.

Enhanced Antitumor Effect of the Combination of Bacille Calmette-Guérin and an Immune Checkpoint Inhibitor in Bladder Cancer-On-a-Chip

Choi Se Young,Kim Mirinae,Kang Su Jeong,Choi Young Wook,맹세정,Kim Sung-Hwan,Chang In Ho 한국바이오칩학회 2023 BioChip Journal Vol.17 No.4

We upgraded preexisting bladder cancer-on-a-chip (BCOC) by adding T cells and evaluated the antitumor eff ect of a combina- tion of intravesical Bacille Calmette-Guérin (BCG) and pembrolizumab. We fabricated bioprinted BCOC with microfl uids, incorporating HT1376, MRC-5, HUVEC, THP-1 and Jurkat cells. We evaluated the eff ector-to-target cytotoxicity, cytokine, and cell viability in 2D culture, live/dead assay, migration assay, and cytokine assay in BCOC. Additionally, we evaluated the antitumor effi cacy of the combination of BCG and pembrolizumab in an orthotopic mouse model. The combination group showed the most eff ective reduction compared to the control in 2D culture (100.0 ± 0.8% vs. 36.4 ± 0.8%, p < 0.001). In BCOC, cancer cell viabilities were decreased at 3 days in the BCG group (70.1 ± 9.8%, p = 0.013) and combination group (49.3 ± 8.1%, p < 0.001). The combination group showed the highest immune reaction in the cytokine assay (interferon-γ, p = 0.045; interleukin-6, p = 0.037) and migration assay (fold change 1.3 ± 0.1, p < 0.001), whereas in the in vivo model, it showed lower signal intensities from days 10 to 14 compared to that in the control group ( p = 0.031 and p = 0.014, respec- tively). No signifi cant weight changes were observed among the groups. We developed a 3D bioprinted BCOC via use of the monocytic THP-1 cells and Jurkat T cells to assess the effi cacy of immunotherapy. The combination of BCG and pem- brolizumab showed the best antitumor effi cacy in BCOC and animal models.

S-244 : Long Term Prognostic Value of HbA1C in Acute Myocardial Infarction Patients without Known Diabetes

( Il Hyung Jung ),( Chung Kang ),( Dong In Nam ),( Sang Cheol Cho ),( Wan Kim ),( Myung Ho Jeong ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

Background: The prognostic role of glycosylated hemoglobin (HbA1C) in non-diabetic (non-DM) patients with acute myocardial infarction (AMI) is still controversial. We evaluated the prognostic role of HbA1C in AMI patients without previously known diabetes. Methods: From January 2008 to August 2011, 3,292 in AMI patients with non-DM [65.6±13.1 years, 2,460 men (74.8%)] who underwent laboratory testing of HbA1C were enrolled retrospectively. Patients were divided into two groups by HbA1C [Group 1 ≤ 6.5%, n=2,864 (87%); Group 2 > 6.5%, n=428 (13%)]. The primary end point was composite major adverse cardiac events (MACEs) including all cause death, cardiac death, re-MI, and revascularization of target or non-target vessel during 12 months follow up. Results: Patients of in-hospital all cause death and cardiac death were 202 [169 (6.0%) vs. 33 (6.8%), p>0.05) and 145 [124 (4.4%) vs. 21 (4.3%), p>0.05], respectively. BMI (24.0±3.1 vs. 24.9±3.6), blood glucose (145±55 vs. 207±90 mg/dL), total cholesterol (184±44 vs. 196±47 mg/dL), triglyceride (121±88 vs. 157±118 mg/dL), LDL (118±39 vs. 127±41 mg/dL) and hs-CRP (5.35±20.3 vs. 8.76±34.9 mg/dL) were higher and HDL (44.4±14.7 vs. 42.2±11.7 mg/dL) was lower in group 2 (p of all variables < 0.01). The incidence of hyperlipidemia (9.2% vs. 12.4%, p=0.036), obesity (BMI ≥ 30, 3.3% vs. 8.2%, p<0.01), current smoker (44.7% vs. 50.2%, p=0.032), and left ventricular (LV) dysfunction (ejection fraction<40%, 11.3% vs. 15.4%, p=0.021) were more frequent in group 2. There were no significant difference in clinical outcomes at 12 months. In subgroup analysis (group 1 was divided by 5.5% of HbA1C), there were no significant difference in short and long term clinical outcomes. Old Age (age ≥ 65 years), high Killip class (III & IV), LV dysfunction, and renal insufficiency (GFR <60 mL/min) were independent predictors of 12 months composite MACEs. Conclusion: Korean AMI patients with non-DM and HbA1C > 6.5% were not associated with worse outcomes during 12 months follow up.