• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4025-4030
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• 2012

Background and Objective: Cardiotoxicity and oxidative stress is a life-threatening side effect of doxorubicin (DOX). We investigate the effects of short-term exercise as therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity in the rat. Methods: Wistar males (weighing $257{\pm}28g$) were divided into six groups: (1) control+placebo (2) control+DOX $10mg.kg^{-1}$ (3) control+DOX $20mg.kg^{-1}$ (4) training+placebo (5) training+ DOX$10mg.kg^{-1}$ (6) training+DOX $20mg.kg^{-1}$. Cardiotoxicity was induced by DOX (10 and $20mg.kg^{-1}$). The rats in groups 4, 5 and 6 experienced treadmill running of 25 to $39min.day^{-1}$ and 15 to $17m.min^{-1}$, 5 days/wk for 3 wk. At the end of the endurance training program, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, DOX $10mg.kg^{-1}$ and DOX $20mg.kg^{-1}$, respectively. Result: DOX administration (10 and $20mg.kg^{-1}$) caused significant increase in MDA and Apelin, an insignificant increase in NO and a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment endurance exercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificant decrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOX treatment with $10mg.kg^{-1}$ and $20mg.kg^{-1}$, a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant difference between DOX$10mg.kg^{-1}$ and DOX$20mg.kg^{-1}$ treatments in MDA levels only. Conclusion: Pretreatment exercise may improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and up-regulation of antioxidants in heart tissue.

• 대한한의학회지
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• 제32권1호
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• pp.164-174
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• 2011

Objective: The antiplatelet agent aspirin has been widely used for treating atherosclerosis in western medicine, and its efficacy has been proven in cardiac and extracardiac vascular diseases. On the other hand, Hyeolbuchukeo-tang has been widely used for treating blood stasis syndrome in traditional medicine. Therefore we investigated whether Hyeolbuchukeo-tang could have a synergic effect along with aspirin. Methods & Materials: Male $ApoE^{(-/-)}$ mice were randomly divided into three different experimental groups: a non-treated group(Control group), an aspirin-treated group(AP group), and an aspirin with Hyeolbuchukeo-tang-treated group(APH group). The control group was fed only an atherogenic diet, the AP group an atherogenic diet plus Aspirin 5 mg/kg, and the APH group an atherogenic diet plus Aspirin 5 mg/kg with Hyeolbuchukeo-tang 100 mg/kg. We investigated plasma lipid with liver function test, and performed the histological investigation of liver and abdominal aorta. Results: 1. We investigated photomicrographic changes of liver and abdominal aorta tissue. They showed that histological injury of aorta and lipid accumulations of the liver were lower in the AP and APH groups than in the control group. 2. In the APH group, plasma triglyceride levels were significantly lower than those in the control and AP groups. 3. There were no differences in aspartate aminotransferase and alanine aminotransferase levels among the control, AP and APH groups. Conclusion: The above results show that a combined treatment of Hyeolbuchukeo-tang and aspirin has a somewhat synergic effect in terms of inhibiting vessel injury and decreasing lipid deposits on liver cells without liver toxicity.

• Radiation Oncology Journal
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• 제38권2호
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• pp.109-118
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• 2020

Purpose: Hypofractionated radiotherapy (RT) is becoming a new standard in postoperative treatment of patients with early stage breast cancer after breast conservation surgery. However, data on hypofractionation in patients with advanced stage disease who undergo mastectomy followed by local and regional nodal irradiation (RNI) is lacking. In this retrospective study, we report late-term effects of 3 weeks post-mastectomy hypofractionated local and RNI with two-dimensional (2D) technique in patients with stage II and III breast cancer. Methods: Between January 1990 and December 2007, 1,770 women with breast cancer who were given radical treatment with mastectomy, systemic therapy and RT at least 10 years ago were included. RT dose was 35 Gy/15 fractions/3 weeks to chest wall by two tangential fields and 40 Gy in same fractions to supraclavicular fossa (SCF) and internal mammary nodes (IMNs). SCF and IMNs dose was prescribed at d_max and 3 cm depth, respectively. Chemotherapy and hormonal therapy was given in 64% and 74% patients, respectively. Late-term toxicities were assessed with the Radiation Therapy Oncology Group (RTOG) scores and LENT-SOMA scales (the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic scales). Results: Mean age was 48 years (range, 19 to 75 years). Median follow-up was 12 years (range, 10 to 27 years). Moderate/marked arm/shoulder pain was reported by 254 (14.3%) patients. Moderate/marked shoulder stiffness was reported by 219 (12.3%) patients. Moderate/marked arm edema was seen in 131 (7.4%) patients. Brachial plexopathy was not seen in any patient. Rib fractures were noted in 6 (0.3%) patients. Late cardiac and lung toxicity was seen in 29 (1.6%) and 23 (1.3%) patients, respectively. Second malignancy developed in 105 (5.9%) patients. Conclusion: RNI with 40 Gy/15 fractions/3 weeks hypofractionation with 2D technique seems safe and comparable to historical data of conventional fractionation (ClinicalTrial.gov Registration No. NCT04175821).

• 대한의용생체공학회:의공학회지
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• 제43권1호
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• pp.19-26
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• 2022

The Comprehensive in vitro Proarrhythmic Assay(CiPA) project was launched for solving the hERG assay problem of being classified as high-risk groups even though they are low-risk drugs due to their high sensitivity. CiPA presented a protocol to predict drug toxicity using physiological data calculated based on the in-silico model. in this study, features calculated through the in-silico model are analyzed for correlation of changing action potential in the near future, and features are verified through predictive performance according to drug datasets. Using the O'Hara Rudy model modified by Dutta et al., Pearson correlation analysis was performed between 13 features(dVm/dtmax, APpeak, APresting, APD90, APD50, APDtri, Ca_peak, Ca_resting, CaD90, CaD50, CaDtri, qNet, qInward) calculated at 100 pacing, and between dVm/d_{tmax_repol} calculated at 1,000 pacing, and linear regression analysis was performed on each of the 12 training drugs, 16 verification drugs, and 28 drugs. Indicators showing high coefficient of determination(R²) in the training drug dataset were qNet 0.93, AP resting 0.83, APDtri 0.78, Ca resting 0.76, dVm/dt_max 0.63, and APD90 0.61. The indicators showing high determinants in the validated drug dataset were APDtri 0.94, APD90 0.92, APD50 0.85, CaD50 0.84, qNet 0.76, and CaD90 0.64. Indicators with high coefficients of determination for all 28 drugs are qNet 0.78, APD90 0.74, and qInward 0.59. The indicators vary in predictive performance depending on the drug dataset, and qNet showed the same high performance of 0.7 or more on the training drug dataset, the verified drug dataset, and the entire drug dataset.

• 생명과학회지
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• 제31권4호
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• pp.442-451
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• 2021

미세 플라스틱은 입자의 크기가 5 mm 이하인 플라스틱 조각을 말하며 미세 플라스틱의 오염은 해양 생태계와 인간의 건강과 관련되어 전 세계적인 관심사이다. 광범위하게 오염되어 있는 관계로, 미세 플라스틱은 물고기, 담치, 굴, 조개, 가리비와 같이 다양한 동물에 섭취되어 체내에 축적된다. 게다가, 섭취된 미세 플라스틱은 소장, 간, 신장 그리고 심지어 뇌에서도 높은 농도로 관찰된다. 해산물은 인간에게 있어 주요 단백질 공급원 중 하나이므로, 해산물의 소비는 인간이 미세 플라스틱에 노출되는 경로가 될 수 있다. 많은 근거들은 설치류에서 미세 플라스틱의 반복적인 경구 투여가 생식, 심장, 소화기, 내분비 그리고 심지어 신경계에서 병리적, 기능적 변화를 유도함을 가리킨다. 더욱이, 임신기와 수유기 동안 모체가 미세 플라스틱에 노출되면 새끼에서 대사의 항상성에 변화가 일어난다. 해산물은 세계적으로 3억 1천만 명 이상의 사람들에게 20% 이상의 단백질 공급원이라는 사실을 고려할 때, 미세 플라스틱은 인간의 몸에 축적되어 생리적 기능에 장애를 유발할 수 있다고 가정하는 것이 타당하다. 본 리뷰에서 우리는 해양에서 미세 플라스틱 오염의 현재 실태와 해양 동물 및 설치류에서 미세 플라스틱의 축적과 독성, 그리고 인간에게의 노출과 인간 건강에 미치는 잠재적인 영향에 대해 요약하였다.

• Journal of Yeungnam Medical Science
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• 제10권2호
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• pp.451-474
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• 1993

전신마취, 부위 또는 국소 마취시, 그리고 향부정맥제로 술중 및 중환자실에서 흔히 쓰이는 lidocaine의 용량과, 국소 마취제로 인한 중추 신경계의 독성을 예방 또는 중단시키기 위해 사용되는 diazepam의 전투여시 이로 인한 심혈관계 변화 및 lidocaine의 혈중농도를 관찰, 측정하여 환자의 관리 및 치료에 도움을 얻고자 본 실험을 하였다. Nitrous oxide, halothane으로 마취된 개에서 근육이완제 사용 후 조절호흡하에서 혈중 이산화탄소를 35-45mmHg로 유지하면서 국소 마취체인 lidocaine의 용량을 100 mcg/kg/min, 200 mcg/kg/min, 300 mcg/kg/min로 각각 30분간 지속적 침제하면서, diazepam 전투여 유무에 따른 심혈 역학치의 변화 및 lidocaine의 혈중농도를 측정하고, 억제된 심혈관계에 $CaCl_2$를 투여하여 회복 정도를 관찰하였던 바 아래와 같은 결과를 얻었다. Lidocaine의 지속적 침제량이 증가됨에 따라 심혈관계의 억제가 심하게 나타났으며 평균 동맥압, 심장지수, 일회 박출지수, 좌심실 박출 작업지수, 우심실 박출 작업지수 등은 감소하였고 (p<0.05), 폐동맥 쐐기압, 중심 정맥압, 전신혈관 저항지수 등은 증가하였으나 (p<0.05), 심박동수, 평균 폐동맥압, 폐혈관 저항지수의 변화는 거의 없었다. Lidocaine 100 mcg/kg/min 지속적 침제시는 diazepam을 투여한 II군에서만 평균 동맥압의 의의있는 감소를 보였으며 (p<0.05), lidocaine의 혈중농도는 diazepam투여하지 않은 I군에서는 $3.97{\pm}0.22$에서 $4.48{\pm}0.36$ mcg/ml 범위였고 II 군에서는 $3.70{\pm}0.32$에서 $4.10{\pm}0.22$ mcg/ml범위였다. Lidocaine 200 mcg/kg/min의 지속적 침제시는 I군에서는 평균 동맥압의 감소, 중심정액압의 증가를 나타내었고 (p<0.05), II 군에서는 심장지수의 감소, 폐동백 쐐기압의 증가를 나타내었으며 (p<0.05), lidocaine의 혈중농도는 I군은 $7.50{\pm}0.66$에서 $7.91{\pm}0.77$ mcg/ml, II군에서는 $7.64{\pm}0.79$에서 $8.23{\pm}1.18$ mcg/ml범위로 증가하였다. Lidocaine 300 mcg/kg/min의 지속적 침제시는 I군에서는 평균동맥압, 일회 박출지수, 좌심실 박출 작업지수의 감소가 있었고 (p<0.05), 폐동맥 쐐기압, 중심 정맥압, 전신혈관 저항지수의 증가를 나타내었다 (p<0.05). II군에서는 심장지수, 일회 박출지수, 좌심실 박출 작업지수의 감소가 있었으며 (p<0.05), 폐동맥 쐐기압, 중심 정맥압, 전신혈관 저항지수의 증가를 나타내었다 (p<0.05). 그러나 심박동수, 폐동맥압의 변화는 거의 관찰할 수 없었다. 또한 이때의 혈중 lidocaine의 농도는 I군에서는 $11.30{\pm}2.11$에서 $11.83{\pm}0.59$ mcg/ml범위 로, II군에서는 $12.95{\pm}0.71$에서 $13.79{\pm}0.82$mcg/ml의 범위로 나타내었다. $CaCl_2$ 투여 후는 억제된 심장지수, 일회 박출지수, 전신혈관 저항지수, 폐혈관 저항지수, 좌심실 박출작업지수 및 우심실 박출 작업지수는 회복시켰으나 (p<0.05), 폐동맥 쐐기압, 중심정맥압 등은 오히려 억제시켰다 (p<0.05). 이상에서 자율신경계에 손상이 없으며 산혈증 및 과탄산증이 없는 개에서는 lidocaine의 높은 혈중 농도치에서도 혈역학에 내성이 있었으며, ljdocaine의 중추신경계 독성의 예방 및 치료 목적으로 사용되는 diazepam의 전투여 시에도 추가적인 심혈관계의 억제가 없음을 알 수 있었다. 그러나 자율신경계 이상이 있거나 자율신경계를 억압할 수 있는 약을 사용할 때 또는 산혈증, 과탄산증 및 저산소증이 동반된 환자에 사용할 때에는 세심한 주의가 요할 것으로 생각된다.