• Title/Summary/Keyword: restenosis

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Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells

  • Kim, Jisu;Lee, Kang Pa;Kim, Bom Sahn;Lee, Sang Ju;Moon, Byung Seok;Baek, Suji
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.3
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    • pp.241-248
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    • 2020
  • Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922-mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BB-induced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.

Outcomes of Carotid Endarterectomy according to the Anesthetic Method: General versus Regional Anesthesia

  • Kim, Jong Won;Huh, Up;Song, Seunghwan;Sung, Sang Min;Hong, Jung Min;Cho, Areum
    • Journal of Chest Surgery
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    • v.52 no.6
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    • pp.392-399
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    • 2019
  • Background: The surgical strategies for carotid endarterectomy (CEA) vary in terms of the anesthesia method, neurological monitoring, shunt usage, and closure technique, and no gold-standard procedure has been established yet. We aimed to analyze the feasibility and benefits of CEA under regional anesthesia (RA) and CEA under general anesthesia (GA). Methods: Between June 2012 and December 2017, 65 patients who had undergone CEA were enrolled, and their medical records were prospectively collected and retrospectively reviewed. A total of 35 patients underwent CEA under RA with cervical plexus block, whereas 30 patients underwent CEA under GA. In the RA group, a carotid shunt was selectively used for patients who exhibited negative results on the awake test. In contrast, such a shunt was used for all patients in the GA group. Results: There were no cases of postoperative stroke, cardiovascular events, or mortality. Nerve injuries were noted in 4 patients (3 in the RA group and 1 in the GA group), but they fully recovered prior to discharge. Operative time and clamp time were shorter in the RA group than in the GA group (119.29±27.71 min vs. 161.43±20.79 min, p<0.001; 30.57±6.80 min vs. 51.77±13.38 min, p<0.001, respectively). The hospital stay was shorter in the RA group than in the GA group (14.6±5.05 days vs. 18.97±8.92 days, p=0.022). None of the patients experienced a stroke or restenosis during the 27.23±20.3-month follow-up period. Conclusion: RA with a reliable awake test reduces shunt use and decreases the clamp and operative times of CEA, eventually resulting in a reduced length of hospital stay.

Clinical Experience of Silicone Airway Stent in the Management of Benign Tracheobronchial Stenosis (양성 기도협착질환에서 실리콘 기도스텐트의 임상경험 - Dumon 스텐트와 Natural 스텐트의 비교 -)

  • Ryu, Yon Ju;Yu, Chang-Min;Choi, Jae Chul;Kwon, Yong Soo;Kim, Hojoong;Kim, Jhingook;Suh, Soo Won
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.1
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    • pp.62-68
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    • 2005
  • Background : The clinical results of a Natural stent in patients with a benign tracheobronchial stenosis were examined by comparing the clinical outcomes and complications of those patients who underwent Dumon and Natural stenting in the management of benign airway stenosis. Methods : The medical records of 94 patients (39 Dumon and 55 Natural stent) with a benign tracheobronchial stenosis were reviewed and analyzed. Results : Post-tuberculous stenosis was the leading indication for airway stenting (74%), which was followed by post-intubation stenosis (21%). After intervention, the dyspnea had improved among those patients who underwent Dumon (90%) and Natural (86%) stenting. After stabilizing the dyspnea, the stent could be successfully removed in half of the patients who underwent both Dumon (54%) and Natural (49%) stenting. During the 42 month follow-up period, the complication rate was similar in those patients who underwent Dumon and Natural stenting: migration (46% vs 53%), granulation tissue formation (36% vs 49%), mucostasis (21% vs 16%) and restenosis (51% vs 36%). Conclusion : The clinical results of Natural airway stent was similar to those of Dumon stent in the management of benign tracheobronchial stenosis.

Alterations in Left ventricular End-systolic Wall Stress During Short-term Follow-up After Correction of Isolated Congenital Aortic Stenosis (선천성 대동맥 협착증의 술전 및 술후 단기간의 수축말기 좌심실 내벽 스트레스의 변화)

  • 김시호
    • Journal of Chest Surgery
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    • v.33 no.10
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    • pp.777-784
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    • 2000
  • Congenital aortic stenosis in children is characterized by "excessive" left ventricular hypertrophy with reduced left ventricular systolic wall stress that allows for supernormal ejection performance. We hypothesized that left ventricular wall stress was decreased immediately after surgical correction of pure congenital aortic stenosis. Also measuring postoperative left ventricular wall stress was a useful noninvasive measurement that allowed direct assessment for oxygen consumption of myocardium than measuring the peak systolic pressure gradient between ascending aorta and left ventricle for the assessment of surgical results. Material and Method: Between September 1993 and August 1999, 8 patients with isolated congenital aortic stenosis who underwent surgical correction at Yonsei cardiovascular center were evaluated. There were 6 male and 2 female patients ranging in age from 2 to 11 years(mean age, 10 years). Combined Hemodynamic-Ultrasonic method was used for studying left ventricular wall stress. We compared the wall stress peak systolic pressure gradient and ejection fraction preoperatively and postoperatively. Result: After surgical correction peak aortic gradient fell from 58.4${\pm}$17.6, to 23.7${\pm}$17.7 mmHg(p=0.018) and left ventricular ejection fraction decreased but it is not statistically significant. In the consideration of some factors that influence left ventricular end-systolic wall stress excluding one patient who underwent reoperation for restenosis of left ventricular outflow tract left ventricular end-systolic pressure and left ventricular end-systolic dimension were fell from 170.6${\pm}$24.3 to 143.7${\pm}$27.1 mmHg and from 1.78${\pm}$0.4 to 1.76${\pm}$0.4 cm respectively and left ventricular posterior wall thickness was increased from 1.10${\pm}$0.2, to 1.27${\pm}$0.3cm but it was not statistically singificant whereas left ventricular end-systolic wall stress fell from 79.2${\pm}$24.9 to 57.1${\pm}$27.6 kdynes/cm2(p=0.018) in 7 patients. For one patient who underwent reoperation peak aortic gradient fell from 83.0 to 59.7 mmHg whereas left ventricular end-systolic wall stress increased from 67.2 to 97.0 kdynes/cm2 The intervals did not change significnatly. Conclusion ; We believe that probably some factors that are related to left ventricular geometry influenced the decreased left ventricular wall stress immediately after surgical correction of isolated congenital aortic stenosis. Left ventricular wall stress is a noninvasive measurement and can allow for more direct assesment than measuring peak aortic gradient particularly in consideration of the stress and oxygen consumption of the myocardium therefore we can conclude it is a useful measurement for postoperative assessment of congenital aortic stenosis.

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Absorbed Dose for the Endovascular Ho-166-DTPA Brachytherapy Using a Balloon Angio Catheter (풍선도자관의 Ho-166-DTPA 흡수선량)

  • 조철우;박찬희;윤석남;강해준;김미화;장지선;박경배
    • Progress in Medical Physics
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    • v.13 no.2
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    • pp.98-103
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    • 2002
  • The purpose of this study was to evaluate the absorbed dose to the coronary artery segment from various sized balloon angio catheters. The liquid form of Ho-166 was produced at the KAERI by (n, ${\gamma}$ ) reaction. We used GafChromic film for the estimation of the absorbed dose by beta particles. The exposed films were read using a videodensitometer. Several film exposures were made with varying irradiation times and activities. A modified micrometer was used for the measurement of the absorbed dose distribution near the balloon surface. Four balloons of coronary catheters evaluated were 30 m long and 2.5, 3.0, 3.5 and 4.0 mm in diameter. All doses are plotted in units of Gy/min/GBq/ml as a function of radial distance in mm from the surface of balloon. The absorbed dose rate was 0.86, 1.01, 1.11 and 1.24 Gy/min/GBq/ml at a balloon surface for various balloon diameter 2.5, 3.0, 3.5 and 4.0 mm respectively. Using a vacuum pump, the air in the balloon was evacuated prior to instillation of the Ho-166 source. By removing air bubbles in the balloon, the absorbed dose distribution was more uniform.

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Occurrence and Prognosis for the Thrombosis in the Drug-Eluting Stents and Bare-Metal Stents (약물 용출 스텐트와 일반 금속 스텐트에서 혈전증에 대한 발생과 예후)

  • Kim, In-Soo;Choi, Nam-Gil;Jang, Seong-Joo;Han, Jae-Bok;Jang, Young-Ill
    • The Journal of the Korea Contents Association
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    • v.12 no.7
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    • pp.273-283
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    • 2012
  • Drug-eluting stents (DES) have significantly reduced in-stent restenosis, compared to bare-metal stents (BMS). However, there remains concern for the increased risk of stent thrombosis (ST) associated with DES. The present study sought to evaluate the incidence, clinical characteristics and outcome of ST in patients with acute myocardial infarction (MI) during a 1-year follow-up. 80 patients who developed ST were divided into 2 groups according to stent type: group I (DES-ST, n = 57 ) and group II (BMS-ST, n = 23 ). There were no differences between group I and II in the overall incidence of ST (2.7% vs. 4.3%, p=0.064) and in the incidence of each type of ST: acute ST (8.8% vs. 2.3%), subacute ST (50.9% vs. 60.9%), late ST (19.3% vs. 8.7%), and very late ST (21.1% vs. 17.4%) (p=0.605). Predictors of 1-year mortality were the occurrence of ST (OR 8.12, 95% CI 2.83-23.61, p<0.001), left ventricular ejection fraction<40% (OR 6.41, 95% CI 2.42-16.96, p<0.001), and age${\geq}$75 years (OR 4.98, 95% CI 1.95-12.74, p=0.001).

5,8-Dimethoxy-2-Nonylamino-Naphthalene-1,4-Dione Inhibits Vascular Smooth Muscle Cell Proliferation by Blocking Autophosphorylation of PDGF-Receptor ${\beta}$

  • Kim, Yohan;Lee, Jung-Jin;Lee, Sang-Gil;Jung, Sang-Hyuk;Han, Joo-Hui;Yang, So Young;Yun, Eunju;Song, Gyu-Yong;Myung, Chang-Seon
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.3
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    • pp.203-208
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    • 2013
  • As the abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis and vascular restenosis, a candidate drug with antiproliferative properties is needed. We investigated the antiproliferative action and underlying mechanism of a newly synthesized naphthoquinone derivative, 5,8-dimethoxy-2-nonylamino-naphthalene-1,4-dione (2-nonylamino-DMNQ), using VSMCs treated with platelet-derived growth factor (PDGF). 2-Nonylamino-DMNQ inhibited proliferation and cell number of VSMCs induced by PDGF, but not epidermal growth factor (EGF), in a concentration-dependent manner without any cytotoxicity. This derivative suppressed PDGF-induced $[^3H]$-thymidine incorporation, cell cycle progression from $G_0/G_1$ to S phase, and the phosphorylation of phosphor-retinoblastoma protein (pRb) as well as the expression of cyclin E/D, cyclin-dependent kinase (CDK) 2/4, and proliferating cell nuclear antigen (PCNA). Importantly, 2-nonylamino-DMNQ inhibited the phosphorylation of PDGF receptor${\beta}$(PDGF-$R{\beta}$) enhanced by PDGF at $Tyr^{579}$, $Tyr^{716}$, $Tyr^{751}$, and $Tyr^{1021}$ residues. Subsequently, 2-nonylamino-DMNQ inhibited PDGF-induced phosphorylation of STAT3, ERK1/2, Akt, and $PLC{\gamma}1$. Therefore, our results indicate that 2-nonylamino-DMNQ inhibits PDGF-induced VSMC proliferation by blocking PDGF-$R{\beta}$ autophosphorylation, and subsequently PDGF-$R{\beta}$-mediated downstream signaling pathways.

Bronchoplastic Procedures in Patients with Benign Bronchial Stenosis ann'Obstruction -Review of 13 cases- (양성 기관지 협착 및 폐쇄환자에서의 기관지 성형술 -13례 보고-)

  • 조건현;조민섭
    • Journal of Chest Surgery
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    • v.29 no.12
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    • pp.1366-1372
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    • 1996
  • Bronchoplasty has gained popularity in the selected cAses of bronchogenic carcinoma with poor pulmonary reserve, and also has been a choice of treatment for obstructive bronchial diseases since it can cure patient completely with preservation of pulmonary function. From Apr. 1990 to hpr. 19'96 two methods of bronchoplastic procedures, d patch dilating bronchoplasty and a segmental bronchial resection with end-to-end anastomosis, were performed with or without concominant pulmonary resection in 13 patients with benign bronchial stenosis and obstruction. The patients were 8 men and 5 women with average age of 43years(range 19 to 64 years). Patch dilating bronchoplasty using autogenous perichondrium and pericardium was applied in 5 cases of bronchial stenosis. Antecedan diseases of bronchial stenosls were 3 inflammatory bronchiectas is, and 2 endobronchial tuberculose is mixed with bronchi,ectas is. Segmental bronchial resection with end-to-end anastomosis was applied in 8 cases of bronchial obstruction, which were caused by endobronchial tuberculosis in 6 and cicatrization after trauma and foreign body in one case each. Bronchial obstructive symptoms and signs including recurrent pulmonary infection, dyspnea and wheezing were disappeared postoperatively with satisfactory recovery of physical activity. There was no operative mortality. Morbidity occured in 2 patients which were one case of unstability of applied bronchial patch resulting atelectasis and one case of bronchial restenosis at the anastomotic site. Based upon our experiences, we conclude that bronchoplastic procedure can be done with great success in patients with lung atelectasis caused by bronchial obstruction or stenosis and it restores physiologic function of collapsed lung with acc ptable complication.

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Effect of Drug Eluting Uniformity for Biodegradable Stent by Solid Freeform Fabrication (쾌속조형기법을 이용한 생분해성 스텐트용 메쉬필름의 약물방출거동 효과)

  • Cheong, Sin Young;Kim, Yang Eun;Koh, Young Joo;Shin, Wang Soo;Lee, Jun Hee;Kim, Wan Doo;Yoo, Young Eun;Park, Su A
    • Polymer(Korea)
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    • v.38 no.1
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    • pp.93-97
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    • 2014
  • Biodegradable drug-eluting stent has dual functions of supporting the lumen and treating internal tumor preventing the restenosis by releasing drug. In this study, the polycaprolactone (PCL) based three dimensional (3D) mesh loaded with paclitaxel (PTX) was presented by rapid prototyping (RP) technique of solid freeform fabrication (SFF) for biodegradable drug-eluting stent application. PCL has many advantageous properties such as good biocompatibility, good mechanical properties, and good drug permeability. PTX is widely used in the cancer treatment by inhibiting tumor cell proliferation. Analytical methods of HPLC and NMR were used for simultaneous quantification of PTX. Scanning electron microscopy (SEM) was performed to observe the architecture and morphologies of 3D mesh. The cytotoxicity assay results indicated released PTX's biological activity. This study provided that PCL based 3D mesh loaded with PTX by RP technique has great potential for biodegradable drug-eluting stent application.

The Developing Trend of Cardiovacular Drug Coated Balloon Catheter (심장혈관용 약물코팅풍선카테터의 개발 동향)

  • Park, Junghun;Jo, Won-Il;Byeon, Dae-Heung;Kang, So Young;Nam, Choong-hyun;Seo, Kyoung-Woo;Park, Jun-Kyu
    • Applied Chemistry for Engineering
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    • v.33 no.5
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    • pp.545-550
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    • 2022
  • As a result of the rapid entry into an aging society and westernized eating habits, the number of heart disease patients caused by angina pectoris, myocardial infarction, and high blood pressure has increased by more than 100,000 over five years. Heart disease has consistently ranked second in the cause of death in Korea over the past eight years, and medical expenses consumed annually reach 6 trillion won. While various treatments are being proposed for more patients, drug-coated balloon catheters have been developed and gradually commercialized to solve the disadvantages of stent implantation such as restenosis and increased risk of bleeding due to long-term double antiplatelet medication. In Korea, it began to use a drug-coated balloon catheter with the first release of it called "SeQuent Please (Bibrown Korea)" in 2010. Its demand increased gradually as insurance benefits were applied in 2012. Drug-coated balloon angioplasty is increasing in use not only in Korea but also around the world, especially in the Asia-Pacific region, including Japan. Until now, the demand for domestic products is increasing, and if the efficiency in vivo and clinical trials is proven in the future, it is expected to be an effective procedure compared to high-risk stent implantation.