Development of Sensitive Analytical Method of Rhodanthpyrone A by a LC-MS/MS and its Application to Bioavailability Study in Rats

Kang, Bitna,Yoon, Jeong A,Song, Im-Sook,Han, Young Taek,Choi, Min-Koo Korean Society for Mass Spectrometry 2019 Mass spectrometry letters Vol.10 No.3

A sensitive analytical method of rhodanthpyrone A in rat plasma was developed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rhodanthpyrone A and rhodanthpyrone B (internal standard) in rat plasma were extracted by a liquid-liquid extraction method with ethyl acetate. This extraction method gave results in high and reproducible extraction recovery in the range of 73.75-79.90% with no interfering peaks around the peak elution time of rhodanthpyrone A and B. The standard calibration curves for rhodanthpyrone A ranged from 0.5 to 2000 ng/mL were linear with $r^2$ > 0.994 and the inter- and intra-day accuracy and precision and the stability were within acceptance criteria. Using this validated analytical method, pharmacokinetics of rhodanthpyrone A following intravenous and oral administration of rhodanthpyrone A at doses of 2 mg/kg and 30 mg/kg, respectively, were investigated. Rhodanthpyrone A in rat plasma showed multi-exponential elimination pattern with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 3.7%. Collectively, the newly developed sensitive LC-MS/MS analytical method of rhodanthpyrone A could be successfully applied to investigate the pharmacokinetic properties of this compound and would be useful for the further studies on the efficacy, toxicity, and biopharmaceutics of rhodanthpyrone A.

인삼 추출물 함유 한방화장품이 건강한 성인 여성의 삶의 질에 미치는 영향에 관한 예비 연구; Skindex-16을 중심으로

조가영 ( Ga Young Cho ),박효민 ( Hyo Min Park ),권이경 ( Lee Kyung Kwon ),조성아 ( Sung A Cho ),강병영 ( Byung Young Kang ),김윤범 ( Yoon Bum Kim ) 대한화장품학회 2015 대한화장품학회지 Vol.41 No.4

본 연구에서는 건강한 성인 여성을 대상으로 인삼 추출물을 함유한 스킨케어 제품의 시료 제시 방법과 여성들의 삶의 질 개선 효과 간의 상관 관계를 분석하였다. 삶의 질이란 질병이나 건강 상태가 일상생활에 미치는 신체적, 정신적 그리고 사회적 영향에 대한 개인적인 반응을 나타내는 개념이다. 이에 저자들은 45명의 건강한 성인 여성을 두 그룹으로 나누어 한 그룹(Group A)에는 브랜드 고유의 패키지를 유지한 인삼 크림 시료를 제공하였고, 다른 그룹(Group B)은 브랜드와 제품명을 알 수 없는 하얀색 통에 담은 동일한 시료를 제공하여 8주간 사용하게 하였다. 피부 관련 삶의 질 평가는 Skindex-16 설문지를 사용하여 시험 초기와 4주 후, 8주 후에 걸쳐 시행되었다. 시험 참여를 중지한 2명의 피험자를 제외한 43명의 Skindex-16 초기값의 평균은 22.70 ± 4.82점이었다. 8주 후, 그룹 A의 Skindex-16 지표는 초기값 23.30 ± 5.14에서 20.20 ± 4.83으로, 그룹 B는 22.17 ± 4.58에서 20.52 ± 3.60로 통계적으로 유의한 정도로 개선되었다. 세부 항목에서는 그룹 A의 ‘증상’ 항목이 4주 후, ‘감정’ 항목이 8주 후에 통계적으로 유의하게 개선되었으며, ‘기능’ 항목은 어느 그룹에서도 통계적으로 유의한 변화가 관찰되지 않았다. 또한, 총합과 세부 항목 모두 측정 시기 및 그룹에 따른 교호작용은 통계적으로 유의한 차이가 확인되지 않았다. 본 실험을 통해 인삼 크림이 포함된 스킨케어가 건강한 성인 여성의 삶의 질에 긍정적인 영향을 줄 수 있음을 확인하였으며, 스킨케어 행위 자체가 패키지에 대한 영향보다 삶의 질의 개선에 주는 영향이 큼을 추측할 수 있다. 장기적으로 ‘삶의 질’이란 기존의 피부과학 지표의 개선과 주관적 만족도의 개념을 넘어 신규한 화장품 효능 영역으로 추가적인 연구가 필요할 것으로 생각된다. This study is designed to analyze the effect of skincare using cosmetic containing ginseng extract, on improving quality of life (QOL) of healthy women, with blind testing. QOL is a concept that represents how one’s disease or health condition can physically, psychologically, and socially influence his or her daily life. The study was conducted to assess the effect of a ginseng cosmetic preparation on quality of life (QOL) using the Skindex-16 score, stratified by blind versus non-blinded option. 45 healthy women aged between 30 and 49 years with no skin disease were recruited for this study. Volunteers were divided into two groups. Group A (n = 22) received anti-aging cream with ginseng extract in the original packaging, which included the brand name and logo. Group B (n = 23) received the same cream in a plain white jar without any package decoration or logo. Both groups used the cream for 8 weeks. For the skin-related QOL assessment, Skindex-16 was used at baseline, forth, and eighth week. All volunteers except two dropouts in Group A completed the dermatology-specific QOL measure, Skindex-16, at baseline, after 4 weeks, and after 8 weeks of treatment with the provided samples. As a result, the mean score of 43 participants at baseline was 22.70 ± 4.82. There was a significant difference between the baseline score and the score after 8 weeks in both groups: The scores changed from 23.30 ± 5.14 to 20.20 ± 4.83 in Group A, from 22.17 ± 4.58 to 20.52 ± 3.60 in Group B. The “Symptom” subscale of Skindex-16 improved after 4 weeks and the “Emotion” subscale improved after 8 weeks in Group A. The “Function” subscale did not show improvement in either groups. Both groups showed no interaction effect between follow up time and groups in Skindex-16 and subscale. This research opens up the possibility of skincare using ginseng cream having a positive effect on QOL in healthy women. Moreover, one can predict that skincare ritual itself may have greater impact on the improvement of QOL, compared to the product packaging.

Protective Effects of a Monoclonal Antibody to a Mannose-Binding Protein of Acanthamoeba culbertsoni

A-Young Park,A-Young Kang,Suk-Yul Jung 대한의생명과학회 2018 Biomedical Science Letters Vol.24 No.4

Acanthamoeba culbertsoni is the causative agent of granulomatous amoebic encephalitis (GAE), a condition that predominantly occurs in immunocompromised individuals and which is typically fatal. A mannose-binding protein (MBP) among lectins was shown to have strong A. castellanii pathogenic potential when correlated with major virulence proteins. In this study, protective effects were analyzed using the monoclonal antibody to A. culbertsoni MBP by quantification and were also compared with other free-living amoebae. For the amoebial cytotoxicity to the target cell, amoeba trophozoites were incubated with Chinese hamster ovary (CHO) cells. For the protective effects of antibodies, amoebae were preincubated with them for 4 h and then added to the target cells. After 24 h, the supernatants were collected and examined for host cell cytotoxicity by measuring lactate dehydrogenase (LDH) release. The cytotoxicity of A. culbertsoni to the CHO cells showed about 87.4%. When the monoclonal antibody was pre-incubated with A. culbertsoni, the amoebial cytotoxicity was remarkably decreased as shown at LDH release (1.858 absorbance), which was represented with about 49.9%. Taken together, it suggested that the monoclonal antibody against MBP be important to inhibit the cytotoxicity of A. culbertsoni trophozoites to the target cell. The antibody will be applied into an in vivo functional analysis, which would help to develop therapeutics.

Clinical Impact of Exosomal microRNA as a Novel Biomarker of Liver Fibrosis

( Young Chang ),( Jae-a Han ),( Suk Min Kang ),( Soung Won Jeong ),( Tom Ryu ),( Han Seul Park ),( Jeong-ju Yoo ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Young Seok Kim ),( Hong Soo Kim ),( So Young Jin 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Many approaches have been suggested for the non-invasive diagnosis of liver fibrosis, including the use of serum biomarkers and ultrasound-based elastography, but none has yet replaced liver biopsy. MicroRNAs (miRNAs) have been suggested as potential diagnostic tools for liver diseases. We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at a large-volume academic hospital in Korea. Exosomes were extracted from serum samples, and next-generation sequencing (NGS) of miRNAs was conducted in patients from different stages of liver fibrosis. Differential expression of miRNAs was quantified using targeted real-time quantitative polymerase chain reaction (RT-qPCR). A model was derived to discriminate advanced fibrosis based on miRNA levels using multivariate logistic regression. The performance of this model was evaluated and compared using area under the receiver operator characteristic (ROC) curve (AUC) and De- Long’s test. Results: NGS data revealed the relationship between exosomal miR-122 expression and liver fibrosis progression. The level of miR-122 decreased as the pathologic fibrosis grade progressed from stage 0 to 4. Patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P<0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis with an AUC of 0.77, which improved to 0.86 in combination with fibrosis-4 score (FIB-4) and transient elastography (TE). This value was higher than that reported for any other non-invasive modalities, including TE (AUC of 0.80) or FIB-4 (AUC of 0.57) alone. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker improved, evident from the increase in the AUC value to 0.87. In this subpopulation, the combination model of miR- 122, FIB-4, and TE showed the best discrimination ability (AUC of 0.90), which was significantly higher than that of TE alone (AUC of 0.83; DeLong’s test P=0.046). Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of collagen- 1A, a-smooth muscle actin, fibronectin, and transforming growth factor-ß. Conclusions: Exosomal miR-122 may serve as a novel biomarker for discriminating advanced liver fibrosis, and its accuracy may enhanced in combination with other non-invasive tests such as FIB-4 and TE.

으름 어린잎 식초의 품질특성과 생리활성

권우영(Woo-Young Kwon),이은경(Eun-Kyoung Lee),윤진아(Jin-A Yoon),정강현(Kang-Hyun Chung),이권재(Kwon-Jai Lee),송병춘(Byeong Chun Song),안정희(Jeung Hee An) 한국식품영양과학회 2014 한국식품영양과학회지 Vol.43 No.7

We investigated the characteristics and biological activities of vinegars added with different levels (0%, 0.5%, 1%, 2%, and 3%) of young leaves of Akebia quinata. During alcohol fermentation, alcohol and total acidity contents of vinegars increased. During acid fermentation, total acidity and amino acid contents increased. Vinegar added with 3% A. quinata leaf showed the highest total sensory score. The contents of total polyphenols, flavonoids, and tannin significantly increased during fermentation according to the amount of A. quinata leaf. After 22 days of fermentation, total polyphenol, total flavonoid, and tannin contents of vinegar added with 3% A. quinata were 4,079.08 mg GAE/100 g, 2,927.08 mg CE/100 g, and 3,618.00 mg TAE/100 g, respectively. ABTS radical scavenging activity of vinegar added with 3% A. quinata was 79.63%. Anti-cancer activities of vinegar added with 3% A. quinata were 48.65% and 52.90% against MCF-7 and HepG2 cells, respectively. Vinegar added with 3% A. quinata showed anti-bacterial activities against Bacillus cereus, Shigella flexneri, Salmonella enterica, Bacillus subtilis, and Klebsiella pneumoniae. Our results demonstrate that the biological activities of vinegar added with 3% A. quinata leaf (22 days of fermentation) were excellent, and their enhanced total polyphenol, flavonoid, and tannin contents were associated with antioxidant, anti-cancer and anti-microbial activities. Thus, A. quinata can be used as a functional material in vinegar and other foods.

Production of a monoclonal antibody against a mannose-binding protein of <i>Acanthamoeba culbertsoni</i> and its localization

Kang, A-Young,Park, A-Young,Shin, Ho-Joon,Khan, Naveed Ahmed,Maciver, Sutherland K.,Jung, Suk-Yul Elsevier 2018 Experimental parasitology Vol.192 No.-

<P>Amoebae from the genus Acanthamoeba are facultative pathogens of humans and other animals. In humans they most frequently infect the eye causing a sight threatening infection known as Acanthamoeba keratitis (AK), and also cause an often fatal encephalitis (GAE). A mannose-binding protein (MBP) has been identified as being important for Acanthamoeba infection especially in AK. This lectin has previously been characterized from Acanthamoeba castellanii as consisting of multiple 130 kDa subunits. MBP expression correlates with pathogenic potential and is expressed in a number of Acanthamoeba species. Here we report the purification of a similar lectin from Acanthamoeba culbertsoni and the production of a monoclonal antibody to it. The A. culbertsoni MBP was isolated by affinity chromatography using alpha-D-mannose agarose and has an apparent molecular weight of 83 kDa. The monoclonal antibody is an IgM that is useful in both western blots and immunofluorescence. We expect that this antibody will be useful in the study of the pathology of A. culbertsoni and in its identification in clinical samples.</P>

S-510 A case of peritoneal dialysis-associated peritonitis caused by Agromyces mediolanus

( Ju Hwan Oh ),( Min Woo An ),( Hyun Kwon Ju ),( Na Yun Kang ),( A Young Cho ),( In O Sun ),( Kwang Young Lee ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

Introduction:?Agromyces mediolanus (A.mediolanus) is an unusual pathogen in human infection. No case of peritoneal dialysis (PD)-associated peritonitis by A.mediolanus has been reported. This is the first case report of PD-associated peritonitis by A.mediolanus in the world. We describe a case of PD-associated peritonitis by A.mediolanus that was cured after catheter removal.?Case: A 59-year-old man who had been treated with CAPD was admitted to our hospital because of turbid peritoneal effluent accompanied by constant diffuse abdominal pain. The patient had an exit-site infection with purulent secretion. The laboratory findings showed PD peritonitis: the white blood cell (WBC) count of the peritoneal effluents was 1157/mm3 with a neutrophil predominance (91.3%). Cefazolin and ceftazidime were given intraperitoneally per day. The peritoneal WBC decreased, but the patient’s clinical condition didn’t improve on the 5th day after starting intraperitoneal antibiotics. Culture of the peritoneal dialysate revealed Agromyces species, which was susceptible to meropenem, imipenem, vancomycin, but resistant to ceftriaxone. Thus, we changed antibiotics to intraperitoneal vancomycin and meropenem on the 5th day. Despite the intraperitoneal antibiotics for 4 days, the patient’s abdominal pain persisted and the peritoneal WBC count became elevated. Therefore, we removed the PD catheter and the patient was switched to hemodialysis on the 9th day. Vancomycin and imipenem was continued for another 2 weeks and the patient’s clinical condition improved. The patient has been maintained on hemodialysis.?Conclusions: There is no previous report of peritonitis associated with A.mediolanus in a CAPD patient. In this case, we used intraperitoneal cefazolin and ceftazidime and changed to vancomycin and imipenem according to the result of peritoneal dialysate. However the patient improved after removal of catheter. Therefore, early removal of the PD catheter in A. mediolanus related peritonitis without prompt reaction to antibiotic therapy should be considered.

Preparation and characterization of a poly(vinylbenzyl sulfonic acid)-grafted FEP membrane

Fei, Geng,Shin, Junhwa,Kang, Sung-A,Ko, Beom-Seok,Kang, Phil-Hyun,Lee, Youn-Sik,Nho, Young Chang Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of polymer science Part A, Polymer chemist Vol.48 No.3

<P>In this study, a novel polymer electrolyte membrane, poly(vinylbenzyl sulfonic acid)-grafted poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP-g-PVBSA), has been successfully prepared by simultaneous irradiation grafting of vinylbenzyl chloride (VBC) monomer onto a FEP film and taking subsequent chemical modification steps to modify the benzyl chloride moiety to the benzyl sulfonic acid moiety. The chemical reactions for the sulfonation were carried out via the formation of thiouronium salt with thiourea, base-catalyzed hydrolysis for the formation of thiol, and oxidation with hydrogen peroxide. Each chemical conversion process was confirmed by FTIR, elemental analysis, and SEM-EDX. A chemical stability study performed with Fenton's reagent (3% H<SUB>2</SUB>O<SUB>2</SUB> solution containing 4 ppm of Fe<SUP>2+</SUP>) at 70 °C revealed that FEP-g-PVBSA has a higher chemical stability than the poly(styrene sulfonic acid)-grafted membranes (FEP-g-PSSA). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 563–569, 2010</P> <B>Graphic Abstract</B> <P>A novel polymer electrolyte membrane, FEP-g-PVBSA, has been successfully prepared by using a simultaneous irradiation grafting of vinylbenzyl chloride monomer onto a poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) film and taking subsequent chemical modification steps to modify the benzyl chloride moiety to the benzyl sulfonic acid moiety. <img src='wiley_img/0887624X-2010-48-3-POLA23762-gra001.gif' alt='wiley_img/0887624X-2010-48-3-POLA23762-gra001'> </P>

과학적 창의성검사의 타당화

강정하(Jung-Ha Kang),임지영(Ji-Young Lim),김아영(A-Young Kim) 한국영재교육학회 2017 영재와 영재교육 Vol.16 No.1

The purpose of this study is to develop a creativity test that measures the potential for creative achievement in the field of science of the middle school students. For this, the researcher has proposed a framework based on the confluence approaches to the creativity, Creativity Systems Model, Scientific Evolution Systems Model, and the development of creativity. The creativity test (preliminary) has consisted of 3 upper-systems_9 subsystems_20 factors_131 indexes. This has been validated through preliminary implementation and main. With collecting data from 538 students of A middle school in A city, the first test was conducted to examine the indexes quality analysis of creativity test. The main test was conducted to validate creativity test(main) model on B, C, D schools and 1,129 students. Next, 3 upper-systems_9 subsystems_79 indexes model has been fitted for the hypothesis model and the creativity(last) model. Finally, creativity (last) model which has constructed 3 upper-systems_9 subsystems_79 indexes was examined criterion-related validity using a criterion-related test. In conclusion, creativity(last) model was accepted by ‘K-Creativity Test’. 본 연구는 과학에 관심 있는 중학생의 창의적 특성을 측정하여 세계 과학자로의 성장가 능성을 예측하는 자기보고식 창의성검사 타당화 연구이다. 먼저, 통합적 이론에 기반을 두고 창의성 시스템 모델, 과학적 창의성 진화 모델, 그리고 과학적 창의성 발달 모델 등의 재구성을 통해 새로운 개념틀이 수립되었다. 이를 토대로, 3상부시스템_9하부시스템_20요 인_131문항 모형의 창의성검사(예비척도)가 조직되었다. 이를 활용한 예비검사 실시로, A 시 소재 A중학교 1, 2, 3학년 538명의 자료를 수집하여, 창의성검사(예비척도)에 대한 문항 양호도 검증이 진행되었다. 그 결과를 바탕으로 3상부시스템_9하부시스템_86문항 모형의 창의성검사(본척도)가 재조직되었다. 재조직한 검사를 활용한 본검사 실시로, B, C, D 시 소재 B, C, D 중학교 1, 2, 3학년 1,129명의 자료를 수집하여, 창의성검사(본척도)에 대한 모형 적합도가 검증되었다. 결과, 3상부시스템_9하부시스템_79문항 모형이 .81-.92의 신뢰도(Cronbach의 )와 CFI .86-.95, TLI .83-.93, RMSEA .07-.12의 적합도 지수를 나타 냈으며, 이에 대한 이론적 중요성을 종합했을 때, 모형의 요인구조가 적합한 것으로 평가 되었다. 이 모형은 창의성검사(최종척도)로 채택되었고, 준거관련 검사와 .28-.74의 상관을 보여, 적절한 준거관련 타당도를 확보함으로써, 마침내, 3상부시스템_9하부시스템_79문항 모형은 K-창의성검사로 명명, 산출되었다. K-창의성검사는 중학생의 잠재력 측정을 위한 자기보고식 특성검사로, 변화와 도전을 모색하는 창의적 성취에 준거를 둠으로써 학생들의 미래 성장가능성을 예측하는데 기여할 것으로 기대한다.

모 제약회사 근로자들의 직업성 천식 유병률과 약제 분말 노출수준

오성수,최용휴,김은아,이영목,장재길,유장진,박승현,김태균,정수영,김규상,강성규 大韓産業醫學會 2006 대한직업환경의학회지 Vol.18 No.2

목적: 제약회사에서 직업상 천식의 유병 규모를 파악하고 작업공정에 대한 작업환경 측정을 통해 제약회사의 약제 분말에 대한 노출수준을 평가하고자 하였다. 방법: 제약회사에서 약제 분말에 노출되는 근로자를 대상으로 천식을 선별하기 위하여 설문조사 및 진찰, 혈액검사, 폐기능 검사 그리고 피부단자시험을 실시하였고, 각 부서별 공정에 따라서 총분진과 항생제 또는 효소제 분말에 대한 작업환경 측정을 실시하였다. 직업상 천식이 의심되는 근로자에 대하여 기관지과민성에 대한 검사(메타콜린을 이용한 비특이 기관지유발시험)와 약제 분말 기관지유발시험을 실시하여 확진하였다. 결과: 설문조사 및 진찰에서 작업 관련 천식 증상이 있는 근로자는 11명(34.4%)이었고, 약제 분말을 이용한 피부단자시험에서 1+ 이상 반응을 보인 근로자 10명(31.2%)이었다. 비특이 기관지유발시험 결과 8명(25.0%)이 양성(PC20 ≤16 mg/ml)이었다. 약제 분말 기관지유발시험을 통해 직업상 천식으로 확진된 근로자는 5명(15.6%)이었다. 작업환경 측정에서 원료를 충진하거나 투입하는 작업 그리고 정립작업에서 약제 분말에 대한 노출이 많았다. 결론: 제약회사에서 직업상 천식은 주로 제조공정 중 약제 분말에 노출된 근로자에서 발생하여, 증상 및 직업성 천식의 유병률이 높았다. 따라서 원료를 충진 또는 투입하는 작업과 정립작업 등 제조과적에서 약제 분말 노출을 줄이기 위한 세심한 주의가 필요하여, 약제 분말을 취급하는 근로자에 대해서는 천식 증상 조사뿐 아니라 정기적으로 피부단자시험, 비특이 기관지유발시험 등을 실시하여야 할 것이다. Objectives: After the investigation of one worker with occupational asthma, we surveyed the preva- lence of occupational asthma and the exposure level of pharmaceutical dust of 32 workers in a pharmaceutical company. Methods: Thirty-two of the 90 employees participated in the survey which consisted of questionnaire, blood sampling, spirometry and skin prick tests with 8 common allergens as well as 9 antibiotics and 2 enzymes. Various indices of the working environment were also measured. Subjects who had a symptom suggestive of work-related asthma or positive skin prick test were further investigated by PC20 methacholine. Nine subjects who had a PC20 result of 16 mg/ml or less (n=7) or had work-related symptoms and positive skin prick test (n=2) were referred to undergo a specific bronchial provocation test to phar- maceutical dust in an academic allergic disease center. Results: Eleven of 32 workers (34.4%) had a work-related symptom suggestive of occupational asthma. Ten (31.2%) showed positive skin prick test. 8 (25.0%) had a PC20 result of 16 mg/ml or less (indicative of significant bronchial hyperresponsiveness), and 5 (15.6%) had a positive result on the specific bronchial provocation test. Exposure levels of stuffing, input of raw materials and screening process were relatively high. Conclusions: This survey showed that pharmaceutical workers have an increased risk of occupational asthma. Although pharmaceutical factories maintain a relatively good working environment, careful control of respiratory tract exposures, especially during stuffing, input or raw materials and screening process, is important to prevent occupational asthma. Pharmaceutical workers need to undergo regular skin prick and methacholine bronchial provocation tests, as well as asthmatic symptom survey, to ensure the early detection and prevention of occupational asthma.