BACKGROUND AND OBJECTIVES: Artemisinin and dihydroartemisinin are drugs used to treat malaria. These drugs suppress inflammatory reactions. The aim of this study was to examine the anti-intima hyperplasia effect of a novel drug-eluting stent with artemisinin or dihydroartemisinin in a porcine coronary restenosis model. MATERIALS AND METHODS: Pigs were randomized into four groups; in the first, the coronary arteries (20 pigs, a total of 40 coronary arteries, with 10 coronary arteries in each group) was implanted with bare metal stents (BMS, n=10); the second group was given polymer-coated stents (PCS, n=10); the third group was treated with artemisinin-eluting stents (AES, n=10); and the fourth group was given dihydroartemisinin-eluting stents (DAES, n=10). Histopathologic analysis was performed 28 days after stenting. RESULTS: The injury and fibrin scores among the four groups were not significantly different. However, the internal elastic lamina, lumen area, and neointima area were significantly different. Moreover, the percent area of stenosis (46.2±18.66% in BMS vs. 89.4±10.92% in PCS vs. 83.3±17.07% in AES vs. 36.7±11.20% in DAES, p<0.0001) and inflammation score (1.0 [range: 1.0-1.0] vs. 3.0 [range: 2.25-3.0] vs. 3.0 [range: 1.0-3.0] vs. 2.0 [range: 1.75-3.0] in BMS, PCS, AES, and DAES, respectively; p<0.001) were markedly decreased in the DAES group compared to the PCS group. CONCLUSION: DES, which uses a natural substance, dihydroartemisinin, showed a neointima and inflammatory suppressive effect in a porcine coronary restenosis model.
Constriction, Pathologic ; Coronary Restenosis* ; Coronary Vessels ; Drug-Eluting Stents ; Fibrin ; Hyperplasia ; Inflammation ; Malaria ; Neointima ; Stents* ; Swine

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.
Autophagy ; Cell Aging* ; Fibroblasts ; Humans ; Skin ; Skin Aging

BACKGROUND AND OBJECTIVES: We sought to evaluate the effect of the early use of ezetimibe/simvastatin (Vytorin(R)) on arterial healing and endothelialization after the implantation of a drug-eluting stent (DES) in a porcine model of coronary restenosis. MATERIALS AND METHODS: A total of 20 pigs (40 coronary arteries) were randomly allocated to a pretreatment or no treatment group. The pretreatment group (n=20) received oral ezetimibe/simvastatin (10/20 mg) daily for 7 days before stenting and the no pretreatment group (n=20) did not. All pigs were treated with ezetimibe/simvastatin (10/20 mg) daily after stenting for 4 weeks. Stenting was performed using a bare-metal stent (BMS, n=10) and three types of DES: biolimus A9-eluting stent (BES, n=10), zotarolimus-eluting stent (ZES, n=10), and everolimus-eluting stents (EES, n=10). Four weeks later, pigs underwent a follow-up coronary angiography and were sacrificed for histopathologic analysis. RESULTS: There were no significant differences between the pretreatment and no pretreatment groups in the internal elastic lamina area, lumen area, neointima area, stenotic area, injury score, fibrin score, and inflammation score. In both groups, the fibrin score was higher in pigs with DES than in BMS, particularly in ZES and EES. The inflammatory score was not different between DES and BMS. CONCLUSION: In a porcine model of coronary restenosis, pretreatment with ezetimibe/simvastatin before DES implantation failed to improve arterial healing and endothelialization compared to treatment after stenting.
Coronary Angiography ; Coronary Restenosis* ; Drug-Eluting Stents* ; Fibrin ; Follow-Up Studies ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammation ; Neointima ; Stents ; Swine ; Ezetimibe

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.
3-Iodobenzylguanidine ; Angiotensin II Type 1 Receptor Blockers/therapeutic use ; Angiotensin Receptor Antagonists/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Animals ; Anterior Wall Myocardial Infarction/*drug therapy/physiopathology ; Biphenyl Compounds/*therapeutic use ; Cardiotonic Agents/*therapeutic use ; Disease Models, Animal ; Echocardiography ; Fluorodeoxyglucose F18 ; Perindopril/therapeutic use ; Positron-Emission Tomography ; Pyrimidines/*therapeutic use ; Random Allocation ; Swine ; Tetrazoles/*therapeutic use ; Tomography, Emission-Computed, Single-Photon ; Valsartan/therapeutic use ; Ventricular Function, Left/*physiology

OBJECTIVES: Children are one of the most vulnerable populations to the impact of disasters. We aimed to examine children's mental health in the area affected by the Hebei Spirit oil spill accident on December 7, 2007. METHODS: A cross-sectional questionnaire survey was conducted using the Korean versions of the Children's Depression Inventory and State Anxiety Inventory for Children on 1,362 children attending elementary schools in the affected area. The information on distances between the nearest contaminated coastline to the child's residential house or attending school were obtained using a web-based map by inputting two address points. The symptom risks of depression and state anxiety were estimated by multiple logistic regression analyses adjusted for age, gender, and other covariates. RESULTS: Children with the closest distance (in the fourth quartile) to the school from the contaminated coastline showed a significantly higher symptom risk of depression compared to those with the farthest distance (first quartile)(odds ratio, 2.73; 95% confidence interval, 1.40-5.33), while there was no significant association between anxiety symptoms and distance. CONCLUSIONS: Children, a vulnerable population for mental health impact by the oil spill accident, should be included in mental health programs in the community along with their family as victims of the disaster.
Anxiety ; Child ; Depression ; Disasters ; Humans ; Logistic Models ; Mental Health* ; Petroleum Pollution* ; Vulnerable Populations ; Surveys and Questionnaires

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the histolopathogical effects among the biolimus, zotarolimus, and everolimus eluting stent (EES) in the porcine coronary restenosis model. SUBJECTS AND METHODS: Pigs were randomized into three groups in which the coronary arteries (15 pigs, 10 coronaries in each group) had either a biolimus A9 eluting stent (BES, n=10), zotarolimus eluting stent (ZES, n=10) or an EES (n=10). Histopathologic analysis was performed at 28 days after stenting. RESULTS: There were no significant differences in the injury score among the three groups. There was a significant difference in the internal elastic lamina, lumen area, neointima area, percent area stenosis, and the fibrin and inflammation score among the three groups (4.3+/-0.53 mm2, 2.5+/-0.93 mm2, 1.8+/-1.03 mm2, 40.7+/-20.80%, 1.7+/-0.41, 1.4+/-0.72 in the BES group vs. 5.1+/-0.55 mm2, 2.3+/-1.14 mm2, 2.8+/-1.00 mm2, 55.4+/-21.23%, 2.0+/-0.39, 1.6+/-0.76 in the ZES group vs. 4.4+/-0.53 mm2, 1.7+/-1.22 mm2, 2.8+/-1.23 mm2, 64.0+/-26.00%, 1.8+/-0.76, 2.1+/-0.90 in the EES group, respectively). BES is more effective in inhibiting neointimal hyperplasia compared to ZES and EES (p<0.0001). According to the fibrin and inflammation score, BES and EES are more effective in decreasing the fibrin deposition compared to ZES (p<0.001). Moreover, BES and ZES are more effective in reducing the inflammatory reaction compared to EES (p<0.001). CONCLUSION: The result demonstrates that BES shows better histopathological characteristics than ZES and EES at one month after stenting in the porcine coronary restenosis model.
Alkanesulfonic Acids ; Constriction, Pathologic ; Coronary Restenosis* ; Coronary Vessels ; Drug-Eluting Stents ; Fibrin ; Hyperplasia ; Inflammation ; Neointima ; Percutaneous Coronary Intervention ; Sirolimus ; Stents* ; Swine ; Everolimus

The aim of this study was to compare the stent designed by Chonnam National University Hospital (designated as CNUH) with commercial cobalt-chromium coronary stent in a porcine coronary overstretch restenosis model. CNUH stent was subjected to mechanical performance tests. Pigs were randomized into two groups in which the coronary arteries (10 pigs, 10 coronaries in each group) had either CNUH stent or control commercial bare metal stent. Histopathologic analysis was assessed at 28 days after stenting. In mechanical performance tests, CNUH stent showed 2.65N, 35.1N, 0.52N, 1.94%, 4.29% in the flat plate radial compression, radial force, 3 point bending, Foreshortening and recoil test, respectively. There was no significant difference in the injury score, internal elastic lamina (IEL), lumen area, neointima area, percent area stenosis, inflammation score and fibrin score between the two groups (1.2+/-0.35, 4.1+/-0.41 mm2, 2.7+/-0.56 mm2, 1.6+/-0.47 mm2, 36.7+/-11.2%, 1.2+/-0.62, 0.2+/-0.34 in CNUH stent group vs. 1.2+/-0.38, 3.7+/-0.64 mm2, 2.5+/-0.49 mm2, 1.5+/-0.61 mm2, 36.3+/-12.17%, 1.1+/-0.12, 0.4+/-0.46 in commercial stent group, respectively). In the mechanical performance test, CNUH stent showed the moderated performance under the guideline of FDA. CNUH stent demonstrated similar histological reactions compared with commercial cobalt-chromium stent in a porcine coronary overstretch restenosis model.
Constriction, Pathologic ; Coronary Restenosis ; Coronary Vessels ; Fibrin ; Inflammation ; Neointima ; Percutaneous Coronary Intervention ; Stents ; Swine

Statins have pleiotropic effects, which include the inhibition of neointima hyperplasia, the inhibition of vascular inflammation, and platelet inhibition. The aim of this study was to examine the effect of an atorvastatin-eluting stent (AES) in a rabbit iliac artery overstretch restenosis model. Ten rabbits were used in this study (10 rabbits, 10 iliac arteries for each stent). An AES and paclitaxel-eluting stent (PES) were implanted in the left and right iliac arteries in a rabbit (2 stents in each rabbit). The stents were deployed with oversizing (stent/artery ratio 1.3:1), and histopathologic analysis was assessed at 28 days after stenting. There were no significant differences in the injury score, lumen area, or inflammation score. There were significant differences in the neointimal area (0.7+/-0.18 mm2 in the AES group vs. 0.4+/-0.25 mm2 in the PES group, p<0.01), in the percentage stenosis area (14.8+/-5.06% in the AES group vs. 10.5+/-6.80% in the PES group, p<0.05), and in the fibrin score (0.4+/-0.51 in the AES group vs. 2.7+/-0.48 in the PES group, p<0.001). Although the AES did not suppress neointimal hyperplasia compared with the PES, it showed a superior arterial healing effect in a rabbit iliac artery overstretch restenosis model.
Blood Platelets ; Constriction, Pathologic ; Coronary Restenosis ; Drug-Eluting Stents ; Fibrin ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hyperplasia ; Iliac Artery ; Inflammation ; Neointima ; Rabbits ; Stents

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of a stent coated with abciximab and alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model. MATERIALS AND METHODS: A total of 10 pigs were randomized into two groups (10 pigs, 10 coronaries in each group) in which the coronary arteries were stented with a dual-coated stent and a bare metal stent (control) by randomization. Stents were deployed with oversizing (stent/artery ratio 1.3 : 1) in the porcine coronary arteries, and histopathology was assessed 28 days after stenting. RESULTS: There was no significant difference in the injury score between the two groups. In the neointima, the lymphohistiocyte count was significantly lower in dual-coat stent group compared with the control stent group (120+/-85 cells vs. 159+/-80 cells, p=0.048). There was no significant difference in the fibrin score between the two groups (0.16+/-0.34 in the dual-coated stent group vs. 0.25+/-0.48 in the control stent group, p=0.446). The neointima area was not significantly different between both groups (1.55+/-0.8 mm2 in dual-coated stent group vs. 1.40+/-0.86 mm2 in the control stent group, p=0.447). CONCLUSION: Although the dual-coated stent with abciximab and ALA showed no significant difference in inhibition of neointimal hyperplasia when compared with the bare metal stent, it was associated with a reduced inflammatory reaction when compared with the control stent in a porcine coronary restenosis model.
Antibodies, Monoclonal ; Antioxidants ; Coronary Restenosis ; Coronary Vessels ; Drug-Eluting Stents ; Fibrin ; Hyperplasia ; Immunoglobulin Fab Fragments ; Neointima ; Platelet Aggregation Inhibitors ; Random Allocation ; Stents ; Swine ; Thioctic Acid

BACKGROUND AND OBJECTIVES: The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model. SUBJECTS AND METHODS: Pigs were randomized into two groups in which the coronary arteries {16 pigs (16 coronaries in each group)} had a 3.0x17 mm ramiprilat-coated MAC stent or a 3.0x17 mm control MAC stent (AMG, Munich, Germany) implanted with oversizing (stent-to-artery ratio, 1.3 : 1) in porcine coronary arteries, and histopathologic analysis was assessed 28 days after stenting. RESULTS: There were no significant differences in the injury and inflammation scores between the two groups (1.20+/-0.43 vs. 1.23+/-0.57, p=0.8; and 1.21+/-0.39 vs. 1.25+/-0.49, p=0.6, respectively). Within the neointima, most inflammatory cells were lymphohistiocytes. Significant positive correlations existed between inflammatory cell counts and the neointima areas (r=0.567, p<0.001), and between inflammatory cell counts and the percent area stenosis (r=0.478, p<0.001). There was no significant difference in the inflammatory cell counts normalized to the injury (110+/-89 vs. 123+/-83, p=0.4) and fibrin scores (0.15+/-0.06 vs. 0.17+/-0.07, p=0.8) between the 2 groups. There were trends toward a smaller neointima area (1.06+/-0.51 mm2 vs. 1.28+/-0.35 mm2, p=0.083) and a smaller percent area stenosis (18.9+/-8.7% vs. 21.8+/-7.2%, p=0.088) in the ramiprilat-coated stent group. CONCLUSION: Although the ramiprilat-coated stent did not show significant inhibitory effects on neointimal hyperplasia, the ramiprilat-coated stent showed good effects on the inflammatory reaction and arterial healing similar to the control stent in a porcine coronary restenosis model.
Angiotensin II ; Angiotensin-Converting Enzyme Inhibitors ; Cell Count ; Constriction, Pathologic ; Coronary Restenosis ; Coronary Vessels ; Fibrin ; Hyperplasia ; Inflammation ; Muscle, Smooth, Vascular ; Neointima ; Renin-Angiotensin System ; Stents ; Swine