1.The Effects of Nicotine on Re-endothelialization, Inflammation, and Neoatherosclerosis After Drug-Eluting Stent Implantation in a Porcine Model
Seok OH ; Ju Han KIM ; Saleem AHMAD ; Yu Jeong JIN ; Mi Hyang NA ; Munki KIM ; Jeong Ha KIM ; Dae Sung PARK ; Dae Young HYUN ; Kyung Hoon CHO ; Min Chul KIM ; Doo Sun SIM ; Young Joon HONG ; Seung-won LEE ; Youngkeun AHN ; Myung Ho JEONG
Korean Circulation Journal 2025;55(1):50-64
		                        		
		                        			 Background and Objectives:
		                        			Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). 
		                        		
		                        			Methods:
		                        			After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. 
		                        		
		                        			Results:
		                        			Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. 
		                        		
		                        			Conclusions
		                        			Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model. 
		                        		
		                        		
		                        		
		                        	
2.The Effects of Nicotine on Re-endothelialization, Inflammation, and Neoatherosclerosis After Drug-Eluting Stent Implantation in a Porcine Model
Seok OH ; Ju Han KIM ; Saleem AHMAD ; Yu Jeong JIN ; Mi Hyang NA ; Munki KIM ; Jeong Ha KIM ; Dae Sung PARK ; Dae Young HYUN ; Kyung Hoon CHO ; Min Chul KIM ; Doo Sun SIM ; Young Joon HONG ; Seung-won LEE ; Youngkeun AHN ; Myung Ho JEONG
Korean Circulation Journal 2025;55(1):50-64
		                        		
		                        			 Background and Objectives:
		                        			Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). 
		                        		
		                        			Methods:
		                        			After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. 
		                        		
		                        			Results:
		                        			Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. 
		                        		
		                        			Conclusions
		                        			Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model. 
		                        		
		                        		
		                        		
		                        	
3.The Effects of Nicotine on Re-endothelialization, Inflammation, and Neoatherosclerosis After Drug-Eluting Stent Implantation in a Porcine Model
Seok OH ; Ju Han KIM ; Saleem AHMAD ; Yu Jeong JIN ; Mi Hyang NA ; Munki KIM ; Jeong Ha KIM ; Dae Sung PARK ; Dae Young HYUN ; Kyung Hoon CHO ; Min Chul KIM ; Doo Sun SIM ; Young Joon HONG ; Seung-won LEE ; Youngkeun AHN ; Myung Ho JEONG
Korean Circulation Journal 2025;55(1):50-64
		                        		
		                        			 Background and Objectives:
		                        			Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). 
		                        		
		                        			Methods:
		                        			After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. 
		                        		
		                        			Results:
		                        			Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. 
		                        		
		                        			Conclusions
		                        			Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model. 
		                        		
		                        		
		                        		
		                        	
4.The Effects of Nicotine on Re-endothelialization, Inflammation, and Neoatherosclerosis After Drug-Eluting Stent Implantation in a Porcine Model
Seok OH ; Ju Han KIM ; Saleem AHMAD ; Yu Jeong JIN ; Mi Hyang NA ; Munki KIM ; Jeong Ha KIM ; Dae Sung PARK ; Dae Young HYUN ; Kyung Hoon CHO ; Min Chul KIM ; Doo Sun SIM ; Young Joon HONG ; Seung-won LEE ; Youngkeun AHN ; Myung Ho JEONG
Korean Circulation Journal 2025;55(1):50-64
		                        		
		                        			 Background and Objectives:
		                        			Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). 
		                        		
		                        			Methods:
		                        			After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. 
		                        		
		                        			Results:
		                        			Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. 
		                        		
		                        			Conclusions
		                        			Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model. 
		                        		
		                        		
		                        		
		                        	
5.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
		                        		
		                        			 Background and Objectives:
		                        			Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. 
		                        		
		                        			Methods:
		                        			A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). 
		                        		
		                        			Results:
		                        			Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. 
		                        		
		                        			Conclusions
		                        			A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD. 
		                        		
		                        		
		                        		
		                        	
6.Toxicological properties of Technekitty injection (Tc-99m) in diagnosing feline hyperthyroidism
Jae Cheong LIM ; So-Young LEE ; Eun Ha CHO ; Yu Mi JUNG ; Ki Hwan PARK ; Young Uk PARK ; Sung Soo NAM ; Tae Hoon LEE ; Jae Won LEE ; Yiseul CHOI ; Inki LEE ; Yeon CHAE ; Byeong-Teck KANG
Journal of Biomedical and Translational Research 2024;25(4):201-210
		                        		
		                        			
		                        			 Following the previous study, which investigated the pharmacological properties of the Technekitty injection (Tc-99m), the toxicity of a single intravenous administration of the Technekittyinjection (Tc-99m) and the side effects that may occur at the diagnostic dose were confirmed.The Technekitty injection (Tc-99m) was administered intravenously once at a dose of 0, 0.67, 2.0, and 6.0 mCi/kg to 5 male and female rats per group. Mortality, general symptom obser-vation, and weight measurement were performed for 2 weeks, followed by observation of autopsy findings. There were no deaths, and no statistically significant weight change was observed. No abnormal systemic signs related to the Technekitty injection (Tc-99m) were observed. These results confirmed that Technekitty injection (Tc-99m) can be safely admin-istered intravenously at doses up to 6.0 mCi/kg. Additionally, technetium-99m at an average dose of 2 mCi (74 MBq) has been verified as a diagnostic dose without adverse effects, al-lowing the Technekitty injection (Tc-99m) to be used safely without side effects at this dosage.This study demonstrates that the Technekitty injection (Tc-99m) has a wide safety margin, supporting its potential for clinical application. Moreover, these findings align with the nonclin-ical safety standards for radiopharmaceuticals, reinforcing its utility in veterinary medicine.The Technekitty injection (Tc-99m) is expected to be applicable for clinical diagnosis as a vet-erinary drug in Korea. 
		                        		
		                        		
		                        		
		                        	
7.Pharmacological properties of Technekitty injection (Tc-99m) in diagnosing feline hyperthyroidism
Jae Cheong LIM ; So-Young LEE ; Eun Ha CHO ; Yu Mi JUNG ; Ki Hwan PARK ; Young Uk PARK ; Sung Soo NAM ; Tae Hoon LEE ; Jae Won LEE ; Jisu SUN ; Hye Kyung CHUNG ; Yong Jin LEE ; Yeon CHAE ; Byeong-Teck KANG
Journal of Biomedical and Translational Research 2024;25(4):185-199
		                        		
		                        			
		                        			 Thyroid scanning using technetium-99m ( 99mTc) is the gold standard for diagnosing feline hyperthyroidism. In cats with an overactive thyroid, a thyroid scan is the most appropriate imaging technique to detect and localize any hyperfunctional adenomatous thyroid tissue. In this study, the pharmacological properties of the Technekitty injection (Tc-99m), developed as a diagnostic agent for feline hyperthyroidism using 99mTc as an active ingredient, were tested in FRTL-5 thyroid follicular cell line and ICR mice. The percentage of cell uptake of the Tc-99m in FRTL-5 thyroid cells was 0.182 ± 0.018%, which was about 6 times higher compared to Clone 9 hepatocytes. This uptake decreased by 38.2% due to competitive inhibition by iodine (sodium iodide). In tissue distribution tests by using ICR mice, the highest distribution was observed in the liver, kidneys, spleen, lungs, and femur at 0.083 hours after administration, and this distribution decreased as the compound was excreted through the kidneys, the pri-mary excretory organ. Maximum distribution was confirmed at 1 hour in the small intestine, 6hours in the large intestine, and 2 hours in the thyroid gland. Additionally, the total amount excreted through urine and feces over 48 hours (2 days) was 78.80% of the injected dose, with 37.70% (47.84% of the total excretion) excreted through urine and 41.10% (52.16% of the total excretion) through feces. In conclusion, the Tc-99m has the same mechanism of action, potency, absorption, distribution, metabolism, and excretion characteristics as 99mTc used for feline hyperthyroidism in the United States, Europe, and other countries, because the Technekitty injection (Tc-99m) contains 99mTc as its sole active ingredient. Based on these results, the Technekitty injection (Tc-99m) is expected to be safely used in the clinical diagnosis of feline hyperthyroidism. 
		                        		
		                        		
		                        		
		                        	
8.Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease
Jae-Jung KIM ; Young Mi HONG ; Sin Weon YUN ; Kyung-Yil LEE ; Kyung Lim YOON ; Myung-Ki HAN ; Gi Beom KIM ; Hong-Ryang KIL ; Min Seob SONG ; Hyoung Doo LEE ; Kee Soo HA ; Hyun Ok JUN ; Jeong Jin YU ; Gi Young JANG ; Jong-Keuk LEE ;
Korean Circulation Journal 2024;54(9):577-586
		                        		
		                        			 Background and Objectives:
		                        			Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. 
		                        		
		                        			Methods:
		                        			A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). 
		                        		
		                        			Results:
		                        			Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. 
		                        		
		                        			Conclusions
		                        			A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD. 
		                        		
		                        		
		                        		
		                        	
9.Toxicological properties of Technekitty injection (Tc-99m) in diagnosing feline hyperthyroidism
Jae Cheong LIM ; So-Young LEE ; Eun Ha CHO ; Yu Mi JUNG ; Ki Hwan PARK ; Young Uk PARK ; Sung Soo NAM ; Tae Hoon LEE ; Jae Won LEE ; Yiseul CHOI ; Inki LEE ; Yeon CHAE ; Byeong-Teck KANG
Journal of Biomedical and Translational Research 2024;25(4):201-210
		                        		
		                        			
		                        			 Following the previous study, which investigated the pharmacological properties of the Technekitty injection (Tc-99m), the toxicity of a single intravenous administration of the Technekittyinjection (Tc-99m) and the side effects that may occur at the diagnostic dose were confirmed.The Technekitty injection (Tc-99m) was administered intravenously once at a dose of 0, 0.67, 2.0, and 6.0 mCi/kg to 5 male and female rats per group. Mortality, general symptom obser-vation, and weight measurement were performed for 2 weeks, followed by observation of autopsy findings. There were no deaths, and no statistically significant weight change was observed. No abnormal systemic signs related to the Technekitty injection (Tc-99m) were observed. These results confirmed that Technekitty injection (Tc-99m) can be safely admin-istered intravenously at doses up to 6.0 mCi/kg. Additionally, technetium-99m at an average dose of 2 mCi (74 MBq) has been verified as a diagnostic dose without adverse effects, al-lowing the Technekitty injection (Tc-99m) to be used safely without side effects at this dosage.This study demonstrates that the Technekitty injection (Tc-99m) has a wide safety margin, supporting its potential for clinical application. Moreover, these findings align with the nonclin-ical safety standards for radiopharmaceuticals, reinforcing its utility in veterinary medicine.The Technekitty injection (Tc-99m) is expected to be applicable for clinical diagnosis as a vet-erinary drug in Korea. 
		                        		
		                        		
		                        		
		                        	
10.Pharmacological properties of Technekitty injection (Tc-99m) in diagnosing feline hyperthyroidism
Jae Cheong LIM ; So-Young LEE ; Eun Ha CHO ; Yu Mi JUNG ; Ki Hwan PARK ; Young Uk PARK ; Sung Soo NAM ; Tae Hoon LEE ; Jae Won LEE ; Jisu SUN ; Hye Kyung CHUNG ; Yong Jin LEE ; Yeon CHAE ; Byeong-Teck KANG
Journal of Biomedical and Translational Research 2024;25(4):185-199
		                        		
		                        			
		                        			 Thyroid scanning using technetium-99m ( 99mTc) is the gold standard for diagnosing feline hyperthyroidism. In cats with an overactive thyroid, a thyroid scan is the most appropriate imaging technique to detect and localize any hyperfunctional adenomatous thyroid tissue. In this study, the pharmacological properties of the Technekitty injection (Tc-99m), developed as a diagnostic agent for feline hyperthyroidism using 99mTc as an active ingredient, were tested in FRTL-5 thyroid follicular cell line and ICR mice. The percentage of cell uptake of the Tc-99m in FRTL-5 thyroid cells was 0.182 ± 0.018%, which was about 6 times higher compared to Clone 9 hepatocytes. This uptake decreased by 38.2% due to competitive inhibition by iodine (sodium iodide). In tissue distribution tests by using ICR mice, the highest distribution was observed in the liver, kidneys, spleen, lungs, and femur at 0.083 hours after administration, and this distribution decreased as the compound was excreted through the kidneys, the pri-mary excretory organ. Maximum distribution was confirmed at 1 hour in the small intestine, 6hours in the large intestine, and 2 hours in the thyroid gland. Additionally, the total amount excreted through urine and feces over 48 hours (2 days) was 78.80% of the injected dose, with 37.70% (47.84% of the total excretion) excreted through urine and 41.10% (52.16% of the total excretion) through feces. In conclusion, the Tc-99m has the same mechanism of action, potency, absorption, distribution, metabolism, and excretion characteristics as 99mTc used for feline hyperthyroidism in the United States, Europe, and other countries, because the Technekitty injection (Tc-99m) contains 99mTc as its sole active ingredient. Based on these results, the Technekitty injection (Tc-99m) is expected to be safely used in the clinical diagnosis of feline hyperthyroidism. 
		                        		
		                        		
		                        		
		                        	
            
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