• 제목/요약/키워드: Safety pharmacology

검색결과 252건 처리시간 0.025초

Effect of Sofosbuvir on rats' ovaries and the possible protective role of vitamin E: biochemical and immunohistochemical study

  • Neven A. Ebrahim;Hussein Abdelaziz Abdalla;Neimat Abd Elhakam Yassin;Aya Elsayed Maghrabia;Amira Ibrahim Morsy
    • Anatomy and Cell Biology
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    • 제56권4호
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    • pp.526-537
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    • 2023
  • Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.

뇌전증의 병인, 변증, 한약 치료에 대한 고찰 -한국, 일본, 중국 데이터베이스를 중심으로- (A Review of Etiology, Syndrome Differentiation, and Herbal Medicine of Epilepsy)

  • 김혜연;김태환;한주희;방미란;장규태;이진용;김효인;이동헌;이선행
    • 대한한방소아과학회지
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    • 제38권3호
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    • pp.66-96
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    • 2024
  • Objectives This study aimed to establish a foundation for research on Korean medicine for epilepsy by analyzing its etiology, syndrome differentiation, and the use of herbal medicines. Methods Articles were extracted from five databases in Korea, Japan, and China: the Oriental Medicine Advanced Searching Integrated System (OASIS), Citation Information by the National Institute of Informatics (CiNii), Chinese National Knowledge Infrastructure (CNKI), Wangfang Database, and Chinese Scientific Journal Database (VIP). The etiology, syndrome differentiation, and herbal medicines used for epilepsy were investigated. Results A total of 64 articles were selected, including seven clinical studies, 16 case reports, and 41 reviews. Epilepsy is a complex disease with various etiologies, and among the five viscera, syndrome differentiation mainly involved the liver, spleen, and kidney, with pathological factors that included phlegm, wind, and blood stasis. Frequently used herbal medicines included Modified Jeongganhwan, Sihogyejitang, Yukgunjatang, and Sihogayonggolmoryotang. Conclusions This study analyzed epilepsy's etiology, syndrome differentiation, and herbal treatments. Further evidence is needed to better understand the efficacy and safety of Korean herbal medicine for treating epilepsy.

Cytotoxicity and DNA Damage Induced by Magnetic Nanoparticle Silica in L5178Y Cell

  • Kang, Jin-Seok;Yum, Young-Na;Park, Sue-Nie
    • Biomolecules & Therapeutics
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    • 제19권2호
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    • pp.261-266
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    • 2011
  • As recent reports suggest that nanoparticles may penetrate into cell membrane and effect DNA condition, it is necessary to assay possible cytotoxic and genotoxic risk. Three different sizes of magnetic nanoparticle silica (MNP@$SiO_2$) (50, 100 and 200 nm diameter) were tested for cytotoxicity and DNA damage using L5178Y cell. MNP@$SiO_2$ had constant physicochemical characteristics confirmed by transmission electron microscope, electron spin resonance spectrometer and inductively coupled plasma-atomic emission spectrometer for 48 h. Treatment of MNP@$SiO_2$ induced dose and time dependent cytotoxicity. At 6 h, 50, 100 or 200 nm MNP@$SiO_2$ decreased significantly cell viability over the concentration of 125 ${\mu}g/ml$ compared to vehicle control (p<0.05 or p<0.01). Moreover, at 24 h, 50 or 100 nm MNP@$SiO_2$ decreased significantly cell viability over the concentration of 125 ${\mu}g/ml$(p<0.01). And treatment of 200 nm MNP@$SiO_2$ decreased significantly cell viability at the concentration of 62.5 ${\mu}g/ml$ (p<0.05) and of 125, 250, 500 ${\mu}g/ml$ (p<0.01, respectively). Furthermore, at 48 h, 50, 100 or 200 nm MNP@$SiO_2$ decreased significantly cell viability at the concentration of 62.5 ${\mu}g/ml$ (p<0.05) and of 125, 250, 500 ${\mu}g/ml$ (p<0.01, respectively). Cellular location detected by confocal microscope represented they were existed in cytoplasm, mainly around cell membrane at 2 h after treatment of MNP@$SiO_2$. Treatment of 50 nm MNP@$SiO_2$ significantly increased DNA damage at middle and high dose (p<0.01), and treatment of 100 nm or 200 nm significantly increased DNA damage in all dose compared to control (p<0.01). Taken together, treatment of MNP@$SiO_2$ induced cytotoxicity and enhanced DNA damage in L5178Y cell.

해조류 5종의 아미노산 조성 및 계통 다양성 비교 분석 (Comparative Analysis of the Amino Acid Composition and Phylogenetic Diversity of Five Seaweed Species)

  • 손승원;이혜영
    • 생명과학회지
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    • 제34권3호
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    • pp.145-152
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    • 2024
  • 해조류는 풍부한 필수 영양소 공급으로 인해 귀중한 해양 자원으로 여겨지며 특히 단백질과 아미노산이 풍부하게 함유되어 있다. 한국에서는 500종 이상의 해조류가 서식하며 그 중 50종 이상이 식품용으로 이용되어 일상 식단의 중심 역할을 한다. 본 연구는 한국에서 가장 흔히 섭취되는 해조류 5종(매생이, 톳, 김, 다시마, 미역; Capsosiphon fulvescens, Hizikia fusiforme, Porphyra yezoensis, Saccharina japonica, Undaria pinnatifida)의 단백질 구성 아미노산을 분석하였다. 고성능 액체 크로마토그래피 분석 결과, 아스파르트산, 글루탐산, 알라닌, 류신이 가장 풍부한 아미노산 성분임을 알 수 있었다. 주성분 분석에서는 이 다섯 종류의 해조류가 아미노산 구성에 따라 세 개의 군집으로 분류될 수 있었고, 이는 부분적으로 계통 분류 결과와 일치하였다. 다양한 아미노산 중에서도 글루탐산, 아스파르트산, 알라닌이 구분을 주도하는 주요 아미노산이였다. 특히, 가까운 계통적 근접성을 보이는 Undaria pinnatifida와 Capsosiphon fulvescens는 뚜렷하게 유사한 아미노산 프로필을 나타내었다. 그에 비해 Porphyra yezoensis와 Saccharina japonica는 계통적 관계를 공유하더라도 다른 아미노산 구성을 보였다. Hizikia fusiforme는 두 분석 모두에서 독특한 군집으로 나타났다.

식약처 고시 9종 한약서에 수록된 뇌전증 치료 한약 처방의 네트워크 분석 (Network Analysis of Epilepsy Formulas from Ministry of Food and Drug Safety's 9 Herbal Manuscripts)

  • 김태환;김혜연;한주희;방미란;장규태;이진용;김효인;이동헌;이선행
    • 대한한방소아과학회지
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    • 제38권3호
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    • pp.53-65
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    • 2024
  • Objectives This study aimed to analyze herbal formulas for epilepsy recorded in nine herbal manuscripts regulated by the Ministry of Food and Drug Safety (MFDS). The goal was to identify the frequency and associations of the included herbs and to determine effective herbal combinations for epilepsy treatment. Methods The study analyzed formulas for epilepsy (癲癎) from nine herbal manuscripts regulated by the MFDS: 東醫寶鑑, 方藥合編, 鄕藥集成方, 景岳全書, 醫學入門, 濟衆新編, 廣濟秘笈, 東醫壽世保元, and 本草綱目. We examined the frequency of herbs, herb pairs, and their degree centrality within the network using Netminer 4.5. Results The analysis identified 143 different herbs across the 159 formulas. Frequently included herbs were 朱砂, 人蔘, 天南星, 麝香, 茯笭. The most common herb pairs included 朱砂-麝香, 茯笭-人蔘, 朱砂-天南星, 朱砂-人蔘, 朱砂-遠志, 半夏-天南星. Network analysis revealed four distinct clusters: Group 1 (tranquillizing by heavy settling and opening the orifices), Group 2 (dispelling phlegm and regulating qi), Group 3 (tonifying and tranquillizing), and Group 4 (pacifying the liver and extinguishing wind). Conclusion The herbal formulas for epilepsy in the nine MFDS-regulated manuscripts have antiepileptic effects through central nervous system sedation and neuroprotective actions.

Anemia-inducing Murine Friend Virus 감염에 대한 2',3'-dideoxycytidine 및 $Interferon-{\alpha}-A$의 항retrovirus효과 (Antiretroviral Effects of 2',3'-Dideoxycytidine and Recombinant $Interferon-{\alpha}-A$ on the Infection of Anemia-inducing Murine Friend Virus)

  • 안형수;안령미;김동섭
    • 대한약리학회지
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    • 제31권3호
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    • pp.365-375
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    • 1995
  • Anemia-inducing strain of Friend virus (FVA)는 적혈구 progenitor cell의 증식을 촉진하는 생쥐 retrovirus의 일종이다. FVA에 감염된 생쥐는 생성이 촉진된 progenitor cell이 분화되지 못하고 비장내에 축적되므로서 비장비대를 초래한다. 이에 본 실험에서는 FVA에 감염된 생쥐의 비장비대를 지표로 사용하여 2',3'-dideoxycytidine (ddC) 및 $interferon-{\alpha}-A\;(rIFN-{\alpha}-A)$의 항retrovirus효과를 측정하였다. 매일 ddC (100 mg/kg) 및 $rIFN-{\alpha}-A$ (10 KU/mouse)를 각각 단독 또는 병용하여 18일간 복강내 투여시 비장의 비대가 각각 15.1%, 52.7%, 61.6% 억제되었다. 또 다른 실험군으로 ddC를 식수중에 용해하여 (0.1 mg/ml) 경구로 18일간 투여시, 그리고 ddC의 경구투여와 병용하여 $rIFN-{\alpha}-A$을 위와 마찬가지 용량으로 복강내 투여시, 비장비대를 각각 38.4% 및 83.2% 억제하였다. 이 결과는 ddC의 투여시 복강내 주사보다는 경구투여가 더 유효하며, ddC와 $rIFN-{\alpha}-A$는 병용투여시 상가적인 효과가 있음을 제시한다. ddC 투여시 progenitor cell의 특성상 변화를 검토하기 위해, $Ca^{++}$ uptake $[^3H]cyclohexyladenosine$ (CHA) binding 실험을 실시하였다. CHA bindng 실험결과 성숙된 적혈구에서는 저친화성의 결합부위 하나뿐인데 반해, progenitor cell에서는 고친화성과 저친화성의 두가지 결합부위를 나타내었다. $Ca^{++}$ uptake 측정결과 성숙된 적혈구에 비해 대조군의 정상적인progenitor cell은 약 20배 증가를 나타내었으며, ddC를 연속투여한 군에서도 유사한 결과를나타내었다. 이때 CHA에 의한 $Ca^{++}$ uptake의 억제효과를 측정한 바, ddC 100 mg/kg 투여군의 경우 76%로 대조군의 86% 보다 억제효과가 크게 나타났으며, 이들 모두는 adenosine 길항약인 theophylline의 전처치시 대조군과 유사하게 회복되었다.

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Rapid HPLC Method for the Simultaneous Determination of Eight Urinary Metabolites of Toluene, Xylene and Styrene

  • Lee, Cheol-Woo;Lee, Jeong-Mi;Lee, Jae-Hyun;Eom, Han-Young;Kim, Min-Kyung;Suh, Joon-Hyuk;Yeom, Hye-Sun;Kim, Un-Yong;Youm, Jeong-Rok;Han, Sang-Beom
    • Bulletin of the Korean Chemical Society
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    • 제30권9호
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    • pp.2021-2026
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    • 2009
  • Toluene, xylene and styrene are volatile organic solvents that are commonly used in mixtures in many industries. Because these solvents are metabolized and then excreted in urine, their urinary metabolites are thought to be biomarkers of occupational exposure to these solvents. Therefore, a simple, rapid, and yet reliable analytical method for determining the metabolites is required for accurate biological monitoring. In the present study, a simple and rapid HPLC-UV method was developed for the simultaneous determination of eight major metabolites of toluene, xylene and styrene: hippuric acid (HA), mandelic acid (MA), o-, m- and p-methylhippuric acids (o-, m- and p-MHAs), and o-, m- and p-cresols. A monolithic column was employed as the stationary phase and several conditions, including flow rate, composition of mobile phase and column temperature, were variables for the optimization of the chromatographic resolution. All eight metabolites were successfully resolved within 5 minutes in 10% aqueous ethanol containing 0.3% acetic acid and 1.6% $\beta$-cyclodextrin, using a flow rate gradient of 1.0 - 5.0 mL/min at 25 ${^{\circ}C}$. The performance of this method was validated by linearity, intra- and inter-day accuracy, and precision. The linearity was observed with correlation coefficients of 0.9998 for HA, 0.9999 for MA, 0.9989 for o-MHA, 0.9998 for m-MHA, 0.9991 for p-MHA, 0.9997 for o-cresol, 0.9998 for m-cresol, and 0.9986 for p-cresol. The intra- and inter-day precision of the method were less than 5.89% (CV) and the accuracy ranged from 92.95 to 106.62%. The validity was further confirmed by analysis of reference samples that were prepared by the inter-laboratory quality assurance program of the Korea Occupational Safety and Health Agency (KOSHA, Seoul, Korea). All measured concentrations of the analytes agreed with the certified values.

소면적 재배작물의 농약 잔류성 시험 후 작물 그룹화를 통한 외삽적용 (An Extrapolation from Crop Classifications Based on Pesticide Residues Trial Data within Vegetables in Minor Crops)

  • 박종혁;;;최정희;임건재;오창환;심재한
    • 농약과학회지
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    • 제13권1호
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    • pp.28-38
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    • 2009
  • Bifenthrin, chlorothalonil, cypermethrin, diazinon, fenvalerate, phenthoate 및 procymidone 등 7종의 농약에 대한 잔류시험을 통해 외삽적용을 위한 연구를 실시하였다. 실험을 위해 소면적 재배작물 중 잔류농약 부적합 사례가 많은 작물을 중심으로 11종의 엽채류, 5종의 근채류, 그리고 6종의 경채류를 포함한 총 22종의 작물을 선정하여 재배한 후 7종의 농약을 각각 처리하여 24시간 경과 시점을 1일로 하여 1, 3, 5, 7 일차에 수확하여 분석하였다. 실험결과 회수율은 엽채류는 $72.0{\sim}117.0%$, 경채류는 $81.3{\sim}105.0%$, 그리고 근채류는 $70.1{\sim}108.1%$ 수준이었고 검출한계는 엽채류는 0.005-0.1 mg/kg, 경채류와 근채류는 0.001-0.005mg/kg 수준이었다. 농약의 감소경향과 작물의 표면 형태학적 차이에 의한 농약 잔류특성을 파악 비교하여 선정된 작물을 고잔류군과 저잔류군으로 그룹화하였고 이 내용을 바탕으로 대상 농약들에 대하여 경채류 및 근채류 작물을 대상으로 농약데이터의 외삽을 통한 안전사용기준 및 MRL의 설정이 가능할 것으로 판단된다.

Comparative Drug Evaluation of Atorvastatin versus Rosuvastatin in Pharmacotherapy of Korean Patients with Dyslipidemia

  • Park, Seon-Young;Lee, Myung-Koo;Lim, Sung-Cil
    • Biomolecules & Therapeutics
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    • 제16권1호
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    • pp.54-60
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    • 2008
  • Dyslipidemia is the multiple lipid metabolic disorders which is one of the high risk factors for the atherosclerotic diseases. It increases the morbidity and mortality and therefore, must be treated with antilipidemic agents. HMG-Co A reductase inhibitors (statins), one of many antidyslipidemic agents, have shown to be significant improvement from the various cholesterol levels. Especially, data from many comparative trials suggest that rosuvastatin is more effective than atorvastatin among many other statins. The aims of this study were to evaluate the efficacy and safety between rosuvastatin and atorvastatin in the treatment of Korean patients with dyslipidemia. Currently the Korean Society of Lipidology and Atherosclerosis based on the Korean health screening data suggests that Korean patients with dyslipidemia should be treated by the target cholesterol levels according to the Adult Treatment Panel III guidelines of the US National Cholesterol Education Program (NCEP-ATP III). We reviewed retrospectively all medical histories of the total 392 dyslipidemic patients with atorvastatin or rosuvastatin from June 1st, 2004 to August 31st, 2006 in Chungbuk National University Medical Center. Patients were classified as total 4 groups by the NCEP-ATP III Guidelines. The numbers of enrolled patients were each 5 mg atorvastatin (n=34), 10 mg atorvastatin (n=148), 5 mg rosuvastatin (n=94) and 10 mg rosuvastatin (n=82). In comparison between groups, rosuvastatin groups in the lowering LDL-C had better efficacies, and the results were each 22% (5 mg atorvastatin), 33.3% (10 mg atorvastatin), 35% (5 mg rosuvastatin) and 41.3% (10 mg rosuvastatin) with the dose relationship (P=0.000). Rosuvastatin groups also have shown to be more significantly reducing Total Cholesterol levels compared to atorvastatin groups with the no dose relationship (P=0.000). In the lowering of non-HDL cholesteroles, rosuvastatin groups showed significantly better efficacies than atorvastatin with the dose-relationship (P=0.000). Each medication groups did not demonstrate the differences in the changing of HDL cholesterol and triglyceride levels (P=0.096, 0.309, respectively). In conclusion, rosuvastatin was better efficacious than atrovastatin in reducing LDL-C Total Chol, and Tg. Therefore, rosuvastatin is a good antilipidemic agents for Korean patients with dyslipidemia and it can use to minimize the morbidity and mortality related to the cardiovascular diseases in Korean.

개에서 케타민-자일라진 마취동안 심박변이도에 대한 아트로핀과 글리코피롤레이트의 자율신경적 특성 (Autonomic Nervous Properties of Atropine and Glycopyrrolate on Heart Rate Variability during Anesthesia with Ketamine-Xylazine in Dogs)

  • 박우영;배춘식;이수한;박우대
    • 한국임상수의학회지
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    • 제26권3호
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    • pp.212-219
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    • 2009
  • 개의 마취에서 부작용을 예방하기 위하여 전마취제로 가장 일반적으로 사용되어지는 항콜린제는 심장에 부작용을 일으킬 수 있다. 비글견에서 케타민 마취 동안 심장의 교감신경과 부교감 신경의 균형에 대한 아트로핀과 글리코피롤레이트의 효과를 검증하기 위하여, 심박변이도, 마취 기간 그리고 행동 변화가 평가 되어졌다. 아트로핀과 글리코피롤레이트에서는 어떠한 일시적인 domain 차이도 없었다. 주파수 영역과 연관되어서는, 아트로핀과 글리코피롤레이트 효과는 모두 대조군에 비해 유의하게 낮게 나타났다(P<0.05). 그러나, 아트로핀의 RMSSD와 SD1은 기준선보다 낮았으며(P<0.05), 글리코피롤레이트의 LF:HF ratio는 기준선보다 높은 유의한 변화를 보였다(P<0.05). SD1의 변화는 주파수 도메인의 HF와 일치하는 변화를 보였으며 호흡수와 $SpO_2-R$의 변화와도 일치하는 변화를 보였다. 우리의 결과는 심장의 자율신경적 특성을 이용하여 글리코피롤레이트가 안전성과 작용 시간을 고려하여 개에서 케타민 마취 시 항콜린제로 더욱 적당하다는 것을 증명한 것이다.