• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.403-412
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• 2020

Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-β) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-β and NF-κB levels.

• 대한족부족관절학회지
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• 제18권4호
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• pp.159-164
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• 2014

Purpose: The purpose of this study is to confirm the effect of antiplatelet drugs in diabetic peripheral vasculopathy in diabetic foot patients. Materials and Methods: We designed a retrospective study in diabetic foot patients with diabetic peripheral vasculopathy. From October 2007 to December 2013, 278 cases in 139 patients who took antiplatelet drugs over at least a six-month period were included in this study. We categorized these patients according to the type of drug used. The efficacy of antiplatelet drugs was evaluated using anklebrachial index (ABI) and pulse wave velocity (PWV). Results: Only the aspirin group showed a statistically significant increase of ABI after antiplatelet therapy ($1.10{\pm}0.12$ to $1.12{\pm}0.11$). In addition, only the cilostazol group showed a statistically significant decrease of PWV after antiplatelet therapy ($1,701.20{\pm}396.56$ to $1,627.42{\pm}324.98$). Conclusion: Aspirin and cilostazol may be used in treatment of diabetic peripheral vasculopathy, whereas dual antiplatelet therapy with aspirin and clopidogrel has no specific benefits in diabetic peripheral vasculopathy.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.88-89
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• 2003

In recent days, the bioequivalence(BE) study of domestic drugs on original drug are quite, activated in Korea. This BE study provide not only the bioequivalence of test and reference drug but also produce the population pharmacokinetic(PK) parameters in normal healthy Korean. The BE study can also make it possible to establish a PK/PD model of the drug when the additional pharmacodynamic(PD) data are available. (omitted)

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.207-207
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• 2002

• 한국임상약학회지
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• 제22권2호
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• pp.113-122
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• 2012

ACC/AHA/SCAI Guideline recommends for administration dual antiplatelet therapy after drug-eluting stent (DES) to prevent restenosis and stent thrombosis in patients with percutaneous coronary intervention (PCI). Recently triple antiplatelet therapy including cilostazol is known to reduce restenosis and stent thrombosis significantly after DES implantation. However, there is lack of data providing the efficacy of triple antiplatelet therapy. The purpose of this study is to evaluate the clinical effects of the triple therapy after DES implantation compared with the dual therapy. This retrospective study collected data from medical charts of 251 patients who received DES implantation between Jul 2006 and Jun 2008. They received either dual antiplatelet therapy (N = 154 clopidogrel and aspirin; Dual group) or triple antiplatelet therapy (N = 97 cliostazol, clopidogrel and aspirin; Triple group). Major adverse cardiac event rates (MACE, included total death, myocardial infarction, target lesion revascularization) at 12 months, 24 months, stent thrombosis, rates of bleeding complications and adverse drug reactions were compared between these two groups. Compared with the dual group, the triple group had a similar incidence of the MACE rates at 24months (12.3% vs. 12.4%, p = 0.99). There is no difference in overall stent thrombosis between two groups (Dual group 2.6% vs. Triple group 4.1%, p = 0.5). Subgroup analysis showed that diabetic patients got more benefit in reducing MACE rates but, there is no statistical difference. Bleeding complications and adverse drug effects were not different significantly. As compared with dual antiplatelet therapy, triple antiplatelet therapy did not reduce the 12-months, 24-months MACE rates and stent thrombosis. Bleeding complications and adverse drug effects were not different.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.281-285
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• 2015

Statins lower the hyperlipidemia and reduce the incidence of cardiovascular events and related mortality. A 60-year-old man who was diagnosed with a transient ischemic attack was started on acetyl-L-carnitine, cilostazol, and rosuvastatin. After rosuvastatin treatment for 4 weeks, the patient presented with sudden onset fever, cough, and dyspnea. His symptoms were aggravated despite empirical antibiotic treatment. All infectious pathogens were excluded based on results of culture and polymerase chain reaction of the bronchoscopic wash specimens. Chest radiography showed diffuse ground-glass opacities in both lungs, along with several subpleural ground-glass opacity nodules; and a foamy alveolar macrophage appearance was confirmed on bronchoalveolar lavage. We suspected rosuvastatin-induced lung injury, discontinued rosuvastatin and initiated prednisolone 1 mg/kg tapered over 2weeks. After initiating steroid therapy, his symptoms and radiologic findings significantly improved. We suggest that clinicians should be aware of the potential for rosuvastatin-induced lung injury.

• Journal of Yeungnam Medical Science
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• 제29권2호
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• pp.77-82
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• 2012

AMP-activated protein kinase (AMPK) is an important cellular fuel sensor. Its activation requires phosphorylation at Thr-172, which resides in the activation loop of the ${\alpha}1$ and ${\alpha}2$ subunits. Several AMPK upstream kinases are capable of phosphorylating AMPK at Thr-172, including LKB1 and CaMKK${\beta}$ ($Ca^{2+}$/calmodulin-dependent protein kinase kinase${\beta}$). AMPK has been implicated in the regulation of physiological signals, such as in the inhibition of cholesterol fatty acid, and protein synthesis, and enhancement of glucose uptake and blood flow. AMPK activation also exhibits several salutary effects on the vascular function and improves vascular abnormalities. AMPK is modulated by numerous hormones and cytokines that regulate the energy balance in the whole body. These hormone and cytokines include leptin, adiponectin, ghrelin, and even thyroid hormones. Moreover, AMPK is activated by several drugs and xenobiotics. Some of these are in being clinically used to treat type 2 diabetes (e.g., metformin and thiazolidinediones), hypertension (e.g., nifedipine and losartan), and impaired blood flow (e.g., aspirin, statins, and cilostazol). I reviewed the precise mechanisms of the AMPK activation pathway and AMPK-modulating drugs.

• Journal of Korean Neurosurgical Society
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• 제65권6호
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• pp.801-815
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• 2022

Objective : To evaluate the stent apposition of a low-profile visualized intraluminal support (LVIS) device in distal internal carotid artery (ICA) aneurysms, examine its correlation with clinical and angiographic outcomes, and determine the predictive factors of ischemic adverse events (IAEs) related to stent-assisted coiling. Methods : We retrospectively analyzed a prospectively maintained database of 183 patients between January 2017 and February 2020. The carotid siphon from the cavernous ICA to the ICA terminus was divided into posterior, anterior, and superior bends. The anterior bends were categorized into angled (V) and non-angled (C, U, and S) types depending on the morphology and measured angles. Complete stent apposition (CSA) and incomplete stent apposition (ISA) were evaluated using unsubtracted angiography and flat-panel detector computed tomography. Dual antiplatelet therapy with aspirin 200 mg and clopidogrel 75 mg was administered. Clopidogrel resistance was defined as fewer responders (≥10%, <40%) and non-responders (<10%) based on the percent inhibition (%INH) of the VerifyNow system. These were counteracted by a dose escalation to 150 mg for fewer responders or substitution with cilostazol 200 mg for non-responders. IAEs included intraoperative in-stent thrombosis, transient ischemic attack, cerebral infarction, and delayed in-stent stenosis. A multivariate logistic regression analysis was used to determine the predictive factors for ISA and IAEs. Results : There were 33 ISAs (18.0%) and 27 IAEs (14.8%). The anterior bend angle was narrower in ISA (-4.16°±25.18°) than in CSA (23.52°±23.13°) (p<0.001). The V- and S-types were independently correlated with the ISA (p<0.001). However, treatment outcomes, including IAEs (15.3% vs. 12.1%), aneurysmal complete occlusion (91.3% vs. 88.6%), and recanalization (none of them), did not differ between CSA and ISA (p>0.05). The %INH of 27 IAEs (13.78%±14.78%) was significantly lower than that of 156 non-IAEs (26.82%±20.23%) (p<0.001). Non-responders to clopidogrel were the only significant predictive factor for IAEs (p=0.001). Conclusion : The angled and tortuous anatomical peculiarity of the carotid siphon caused ISA of the LVIS device; however, it did not affect clinical and angiographic outcomes, while the non-responders to clopidogrel affected the IAEs related to stent-assisted coiling.

• 대한정형외과학회지
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• 제54권2호
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• pp.127-132
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• 2019

목적: 항 혈소판 제제(아스피린, 클로피도그렐, 실로스타졸)의 술 전 일시적 중단이 슬관절 전치환술 이후의 초기 실혈량 및 동종수혈의 필요성을 증가시키지 않는 안전한 방법인지 알아보고자 한다. 대상 및 방법: 2013년 1월부터 2016년 12월까지 단일 센터에서 단일 술자에 의해서 연속적으로 시행된 네비게이션을 이용한 일차 슬관절 전치환술을 시행 받은 환자를 대상으로 후향적 방식으로 자료를 분석하였다. 총 369건의 환자가 포함되었으며, 항 혈소판 복용 과거력이 없는 271명과 항 혈소판 제제를 술 전 7일간 일시적으로 복용 중지한 98명을 각각의 군으로 나누었다. 두 군 간의 입원 기간 동안의 동종혈액 수혈 빈도와 함께 초기 실혈량을 비교하기 위하여 술 후 1일과 2일에 혈색소 수치 및 적혈구 용적률의 변화량에 대하여 비교하였다. 결과: 수술 7일 전까지 항 혈소판 제제를 복용한 군과 항 혈소판의 복용 과거력이 없는 군 간의 수술 1일과 2일 후의 적혈구 용적률, 혈색소 수치의 변화량, 동종혈액의 수혈 빈도는 통계적으로 유의한 차이를 보이지 않았다. 369명 중에서 입원기간 동안 총 149명이 수혈을 받았다. 수혈을 받은 환자의 군에서 받지 않은 환자군에 비하여 통계적으로 유의하게 상대적으로 고령의 나이, 작은 키, 작은 몸무게, 술 전의 낮은 혈색소와 적혈구 용적률 수치를 보였다. 수혈을 받은 군과 받지 않은 군 간의 성별과 술 전에 시행한 American Society of Anesthesiologists 등급, 수술 7일 전까지 항 혈소판 제제 복용 과거력 유무에 대해서는 통계적으로 유의한 차이점은 없었다. 결론: 항 혈소판 제제의 술 전 7일간의 일시적 중단은 항 혈소판 제제의 복용 과거력이 없는 환자군에 비하여 슬관절 전치환술 이후의 출혈량 및 동종수혈의 필요성을 증가시키지 않는다.