• 대한수의학회지
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• 제41권4호
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• pp.571-578
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• 2001

방사선 피폭선량의 예측을 위한 방사선 민감 지표 모델 개발의 일환으로 apoptotic fragment assay법이 방사선에 피폭된 후 체내 피폭선량을 예측할 수 있는 지표로의 이용 가능성을 평가하기 위하여 코발트-60 감마선과 의료용 싸이크로트론 50MeV($p{\rightarrow}Be^+$) fast neutron 을 0.25Gy에서 1Gy의 선량을 마우스에 각각 전신 조사한 후 소장 음와세포내 apoptotic crypt cell의 수적 변화를 관찰하였다. 저선량 조사군에서 apoptotic crypt cell의 출현 빈도가 1Gy까지 급격하게 증가한 것으로 보아 방사선이 stem cell 지역에 있는 crypt cell의 형태학적 변화를 유발하는 것으로 나타났다. 이상의 결과는 아포토시스가 손상된 세포를 제거하므로 손상된 방사선 민감 표적 장기의 항상성 유지에 중요한 역할을 하는 것으로 판단되었다. Apoptotic fragments의 발생빈도에 대한 선량-반응 곡선에 있어서 음와세포는 중성자조사군이 $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$)으로, 반면에 감마선조사군은 $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$)의 식을 얻었다. 이와 같이 중성자조사군과 감마선조사군은 공히 linear quadratic model 로 관찰되었다. apoptotic fragments 의 발생빈도와 조사 선량간에 유의한 효과가 있는 것으로 확인되었다. 이상의 결과에서 조사선량의 증가에 비례하여 방사선 민감 세포의apoptotic fragments 가 수적으로 증가하였으며, 고준위 방사선과 저준위 방사선은 선량 반응 관계식과 시간 경과에 따른 영향이 매우 유사하였으며, 마우스 음와세포의 apoptosis 유도에 대한 중성자선의 방사선 생물학적 효과비(RBE)는 2.072이였다. 그리고 모든 방사선조사군에서 방사선피폭 후 4시간과 6시간에 apoptosis 유도가 가장 많았으며, 음와세포의 형태학적 소견은 정상 대조군에서 관찰되지 않는 전형적인 apoptotic fragments 가 나타났다. 따라서 음와 세포에서의 아포토시스 유도는 방사선 피폭으로 발생된 세포 손상의 생물학적 영향 평가검색, 방사선 방호제의 민감도 검사, 방사성 동위원소의 체내 오염에 대한 체내 피폭선량 예측의 지표 및 방사선 민감 표적장기의 손상정도 파악에 이용 가능할 것임. Apoptotic fragment assay 법은 0.25Gy에서 1Gy 까지의 선량에서 간편하고 빠르며 재현성이 있는 지표로서 방사선 민감 표적 장기의 선량 반응 평가와 방사선 피폭후 조기 피폭선량 예측을 위한 방사선 생물학적 선량측정법의 좋은 지표로 사용할 수 있을 것으로 사료됨.

• 한국임상약학회지
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• 제31권1호
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• pp.44-52
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• 2021

Background: Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with kidney function impairment while mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, can be used for its renal-sparing effects. In this study, we compared the efficacy and safety of everolimus with low dose tacrolimus (EVR+Low TAC) and conventional dose tacrolimus (TAC) in liver transplantation recipients. Methods: Medical records of recipients who received liver transplantation at Seoul National University Bundang Hospital from January 1st 2009 to December 31st 2018 were retrospectively reviewed. Cohort entry date was defined as the day everolimus was initiated and tacrolimus dosage was reduced. All patients were followed up for 1 year. Indicator of efficacy was the incidence of rejection and safety was evaluated by incidence of drug adverse events including renal function. Results: Among 118 patients, there were 40 patients (33.9%) in EVR+Low TAC group. Incidence of rejection, including both biopsy proven acute rejection and clinical rejection, was similar in two groups [7.5% (n=3) vs. 6.4% (n=5), p=1.000]. Renal dysfunction was less frequent in EVR+Low TAC [17.5% (n=7) vs. 35.9% (n=28), p=0.038]. However, incidence rates of dyslipidemia, oral ulcer were more frequent in EVR+Low TAC [45.0% (n=18) vs. 21.8% (n=17), p=0.009; 15.0% (n=6) vs. 1.3% (n=1), p=0.006]. Conclusions: In terms of prevention of rejection, EVR+Low TAC was as effective as TAC and had renal-sparing effect but was associated with increased risk of dyslipidemia and oral ulcer. This study demonstrates that EVR+Low TAC could be an alternative to liver transplant recipients with nephrotoxicity after administration of conventional dose tacrolimus.

• 방사성폐기물학회지
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• 제13권1호
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• pp.73-86
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• 2015

방사성폐기물 처분시설을 보유하고 있는 국가들은 방사성폐기물 처분시설 시스템의 이해도 제고 및 신뢰성 증진을 위해서는 다양한 보조지표를 선정하여 평가하고 있다. 본 논문에서는 처분시설에 적용되는 국외 처분시설의 보조지표들을 조사하고, 우리나라 월성 중·저준위 방사성폐기물 처분시설에서 근계지역의 공학적 방벽과 원계지역의 자연방벽 성능평가를 위해 연속적인 방벽에서의 방사성 핵종 이동을 보여줄 수 있는 방벽 간의 방사성 핵종 플럭스를 보조안전지표로 선정하여 적용하였다. 처분시설의 정상시나리오를 콘크리트 사일로의 건전조건과 열화조건으로 나누어 방벽별 성능평가를 수행하였으며, 방사성 핵종에서 방벽별 지연성능 기여도를 확인하였다. 콘크리트가 건전한 경우에서 공학적 방벽의 방벽별 상세성능을 파악하였으며, 열화콘크리트의 경우, 공학적 방벽의 성능저하도 및 자연암반과의 상대적 중요도를 정량적으로 확인하였다. 향후본 연구 결과는 2단계 표층처분시설 설계 최적화 및 방벽성능의 검증방법으로 활용할 수 있다. 아울러, 향후에는 처분시설의 Safety Case 구축과 안전성의 이해 제고 및 신뢰성 증진을 위하여 지속적으로 보조지표를 추가 선정하여 평가하고자 한다.

• Advances in Traditional Medicine
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• 제10권1호
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• pp.1-6
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• 2010

The efficacy of the radioprotective effect of Callophyllis japonica ethyl acetate (CJEA) extract was studied by comparing it to that of amifostine, a well-known radioprotective agent, and by evaluating the dose reduction factor, an indicator of radioprotective efficacy. Pretreatment with CJEA extract (100 mg/kg body weight) prior to receiving 12 Gy irradiation significantly improved the survival of jejunal crypts at 3.5 day post-irradiation, but attenuated the level of malondialdehyde compared to vehicle alone (P < 0.01). A similar gastroprotective effect was also obtained in the amifostine-treated irradiated group (P < 0.01). The efficacy of the radioprotective effect was further confirmed by the dose reduction factor, 1.41. Collectively, these results suggest that CJEA extract is a useful radioprotectant whose efficacy is similar to that of amifostine and whose radioprotective mechanism is in part the reduction of lipid peroxidation caused by gamma irradiation.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.333-342
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• 2001

Adriamycin is a commonly used chemotherapeutic agent for cancer, including acute leukemia, lymphoma, and a number of solid human tumors. However, recent studies have recognized severe cardiotoxicity after an acute dose, which are likely the result of generation of free radicals and lipid peroxidation. Therefore, the clinical uses of adriamycin have been limited. Melatonin, the pineal gland hormone known for its ability to modulate circardian rhythm, has recently been studied in its several functions, including cancer growth inhibition, stimulating the immune system, and acting as an antioxidant and radical scavenging effects. In the present study, we evaluated the effect of melatonin administration on adriamycin-induced cardiotoxicity in rat. Heart slices were prepared using a Stadie-Riggs microtome for the measurement of malondialdehyde (MDA) content used as an index of lipid peroxidation and lactate dehydrogenase (LDH) release as an indicator of lethal cell injury. Serious adriamycin-induced lethality was observed in rat by a single intraperitoneal injection in a dose-dependent manner. A single injection of adriamycin (25 mg/kg, i.p.) induced a lethality rate of 86%, with melatonin (10 mg/kg s.c. for 6 days) treatment reducing the adriamycin-induced lethality rate to 20%. The severe body weight loss caused by adriamycin was also significantly attenuated by melatonin treatment. Treatment of melatonin marked reduced adriamycin-induced the levels of MDA formation and LDH release. A cell damage indicated by the loss of myofibrils, swelling of the mitochondria as well as cytoplasmic vacuolization was seen in adriamycin-treated group. Melatonin attenuated the adriamycin-induced structural alterations. These data provide evidence that melatonin prevents adriamycin-induced cardiotoxicity and might serve as a combination with adriamycin to limit free radical-mediated cardiotoxicity.

• Journal of Ginseng Research
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• 제21권2호
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• pp.132-140
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• 1997

The effects of ginsenosides purified from red ginseng on platelet aggregation were investigated. Preincubation of washed platelets from rats with either ginsenoside Rg3, ginsenosides non-polar fraction (G-NPF), ginsenoside Rg1(Rg1) or ginsenosides polar fraction(G-PF) reduced the plytelet aggrelation induced by collagen in a dose-dependent manner, whereas ginsenoside Rg2 failed to inhibit the aggregation. Their IC50 values of Rg3, G-NPF, Rgl, and G-PF were 8.7$\pm$1.0, 150.3$\pm$0.1, 369.9$\pm$ 1.0, 606.211.3 $\mu\textrm{g}$/ml, respectively. Aggrelation induced by thrombin was also inhibited by Rg3 and G-NPF with IC50 being 5.2$\pm$ 1.1 and 66.5$\pm$0.8 $\mu\textrm{g}$/ml, respectively. The alterations of Intracellular Ca2+ concentration in platelets were monitored using fura-2 as a fluorescent Ca2+ indicator. Both Ca2+ release from internal stores and Ca2+ influx into cytosol were suppressed by Rg3. Rg3 also inhibited granular release of ATP and TXA2 formation induced by thrombin in a dose-dependent manner in the washed platelets. Rg3 also inhibited Aggregation and ATP release from human platelets induced by collagen to a similar extent as were observed in rat platelets. In conclusion, Rg3 is a Potent anti-aggregating component in ginsenosides and may exert its anti-aggrega1ing activity by decreasing TXAa formation and granular secretion in platelets, most likely by inhibiting Ca2+ influx and Ca2+ mobilization from intracellular stores. Thus ginseng may contribute to the prevention and treatment of thrombosis.

• 한국작물학회지
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• 제50권2호
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• pp.84-90
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• 2005

The effects of UV-B radiation on the seedling growth, carbohydrate metabolism and antioxidants activities of rice (Oryza sativa L.) were investigated under environmentally controlled chamber. Supplementary UV­B radiation reduced dry matter as well as leaf area, there­fore, relative growth rates (RGR) of seedlings were decreased by up to half compared to control. Photosynthetic products such as soluble sugars and starch were rapidly and significantly reduced by within 1 day of enhanced UV-B radiation due to the inhibition and degradation of photosynthetic processes and thylakoid membrane integrity. In our study, nonstructural carbohydrate levels were proved to be a main indicator on UV-B­induced stress. The behavior of SOD, CAT, APX and POD activities was monitored in the leaves of rice seedlings subjected to UV-B radiation. Under UV-B treatments, SOD activity was initially increased, whereas CAT and POD activities were slowly and slightly increased. However, APX activity showed no presumable results with an increase of UV-B dose. In leaves of rice seedlings, supplementary UV-B radiation caused an increase in free putrescine and spermidine, however spermine remained unaltered, although 24-hrs UV-B treatment slightly increased. This result presumes that an excess UV-B dose may induce ethylene biosynthesis (senescence) rather than polyamine biosynthesis (defense).

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.290-298
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• 2013

This study examined the effects of calcium (Ca) gluconate on collagen-induced DBA mouse rheumatoid arthritis (CIA). A single daily dose of 200, 100 or 50 mg/kg Ca gluconate was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) were measured from histopathological changes in the spleen, left popliteal lymph node, third digit and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the Ca gluconate-administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in Ca gluconate-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dose-dependent manner in the Ca gluconate group. Finally, the production of IL-6 and TNF-${\alpha}$, involved in rheumatoid arthritis pathogenesis, were suppressed by treatment with Ca gluconate. Taken together, these results suggest that Ca gluconate is a promising candidate anti-rheumatoid arthritis agent, exerting anti-inflammatory, anti-oxidative and immunomodulatory effects in CIA mice.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.505-510
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• 2002

An improved kinetic assay for prekallikrein activator (PKA), a potential vasodilator, has been developed to be used as an indicator for quality control during production of human albumin preparations. It consists of two reaction stages. In the first stage, PKA and prekallikrein are incubated at $37^{\circ}C$ for 45 min to allow the transformation into kallikrein. Kallikrein, a serine protease, catalyzes the splitting of p-nitroaniline (pNA) from its substrate H-D-Pro-Phe-Arg-pNA(S-2302). The rate at which pNA is released was measured spectrophotometrically at 405 nm. Prekallikrein, a substrate of PKA was purified by DEAE ion-exchange chromatography and the major potential variations in the assay were optimized; pH 8.0 and 150 mM sodium chloride were chosen to give a proper ionic strength. Reaction times in the range of 10 to 360 min provided linear dose-response curves. The concentration of prekallikrein was adjusted to fall between 1:1 and 1:3 dilutions to generate a linear standard calibration curve. Under the optimized conditions, reproducibility was checked. In a precision test, the coefficient of variation (CV) stayed within ${\pm}4%$ and the dose-response curve showed a good correlation (${r^2}=0.999$). An accuracy test with an international standard of PKA afforded a mean recovery of 97.5%.

• 한국방사선학회논문지
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• 제10권7호
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• pp.477-482
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• 2016

유방촬영검사(Mammography)에서 선량지표를 분석하여 한국식품의약품안전처(Korea Food & Drug Administ ration)에서 제시하는 가이드라인과 비교분석하여 의료방사선의 관리가 잘 이루어지고 있는지 파악하고자 하였다. 방법으로는 유방촬영검사를 시행한 후 의료영상저장정보시스템(Picture Archiving Communication System, PACS)으로 전송되어진 선량 보고서(dose report)와 의료전자차트(Electronic Medical Record, EMR)를 참고하여 양쪽 유방 상하방향촬영(cranio-caudal, CC), 내외 사방향 촬영(medio-lateral oblique, MLO)검사에서 관전압(kVp), 조사시간(exposure time), 관전류량(mAs), 유방압박두께(compressed breast thickness), 평균유선선량(average glandular dose), 체질량지수(Body Mass Index, BMI)를 분류하여 분석하였다. 결과적으로 연령별에 따른 검사부위 CC, MLO에서 유방압박두께는 50-59세에서 45.6 mm, 49.6 mm로 가장 두껍게 나타났으며 전체적인 평균유방압박두께는 CC에서 44.2 mm, MLO 48.9 mm로 MLO가 4.7 mm 더 두껍게 나타났다. 평균유선선량은 CC에서 1.05 mGy, MLO에서 1.14 mGy로 CC보다 MLO에서 0.09 mGy가 더 높게 나타났으며 유방압박두께가 10 mm 증가할수록 CC와 MLO에서는 0.15 mGy, 0.17 mGy가 증가하는 것으로 나타났다. 한국식품의약품안전처에서 제시하는 유방 CC에서 1매 촬영 시 환자가 받는 평균유선선량 1.16 mGy 평가와 비교했을 시 1.05 mGy로 나타났으나 60 mm이상에서는 1.30 mGy로 초과하는 것으로 나타났다. 또한 유방압박두께가 높을수록 체질량지수가 높게 나타났으며 체질량지수에 따른 비만기준 25이상인 경우는 유방압박두께가 50 mm 이상일 경우에 비만인 것으로 나타났다.