Clinical Effect of Apelin on Portal Hypertension and Prognosis of Liver Cirrhosis

Youn Zoo Cho,Moon Young Kim,Yoon Ok Jang,Soon Koo Baik,Sang Ok Kwon 한국간담췌외과학회 2014 한국간담췌외과학회 학술대회지 Vol.2014 No.4

Original Articles : The usefulness of contrast-enhanced ultrasonography in the early detection of hepatocellular carcinoma viability after transarterial chemoembolization: pilot study

( Youn Zoo Cho ),( So Yeon Park ),( Eun Hee Choi ),( Soon Koo Baik ),( Sang Ok Kwon ),( Young Ju Kim ),( Seung Hwan Cha ),( Moon Young Kim ) 대한간학회 2015 Clinical and Molecular Hepatology(대한간학회지) Vol.21 No.2

Background/Aims: The therapeutic effect of transarterial chemoembolization (TACE) against hepatocellular carcinoma (HCC) is usually assessed using multidetector computed tomography (MDCT). However, dense lipiodol depositions can mask the enhancement of viable HCC tissue in MDCT. Contrast-enhanced ultrasonography (CEUS) could be effective in detecting small areas of viability and patency in vessels. We investigated whether arterial enhancement in CEUS after treatment with TACE can be used to detect HCC viability earlier than when using MDCT. Methods: Twelve patients received CEUS, MDCT, and gadoxetic-acid-enhanced dynamic magnetic resonance imaging (MRI) at baseline and 4 and 12 weeks after TACE. The definition of viable HCC was defined as MRI positivity after 4 or 12 weeks. Results: Eight of the 12 patients showed MRI positivity at 4 or 12 weeks. All patients with positive CEUS findings at 4 weeks (n=8) showed MRI positivity and residual viable HCC at 4 or 12 weeks. Five of the eight patients with positive CEUS findings at 4 weeks had negative results on the 4-week MDCT scan. Four (50%) of these eight patients did not have MRI positivity at 4 weeks and were ultimately confirmed as having residual HCC tissue at the 12-week MRI. Kappa statistics revealed nearperfect agreement between CEUS and MRI (κ=1.00) and substantial agreement between MDCT and MRI (κ=0.67). Conclusions: In the assessment of the response to TACE, CEUS at 4 weeks showed excellent results for detecting residual viable HCC, which suggests that CEUS can be used as an early additive diagnosis tool when deciding early additional treatment with TACE. (Clin Mol Hepatol 2015;21:165-174)

The Accuracy of Ultrasonography for the Evaluation of Portal Hypertension in Patients with Cirrhosis: A Systematic Review

김가은,Youn Zoo Cho,백순구,김문영,Won Ki Hong,권상옥 대한영상의학회 2015 Korean Journal of Radiology Vol.16 No.2

Studies have presented conflicting results regarding the accuracy of ultrasonography (US) for diagnosing portal hypertension (PH). We sought to identify evidence in the literature regarding the accuracy of US for assessing PH in patients with liver cirrhosis. We conducted a systematic review by searching databases, including MEDLINE, EMBASE, and the Cochrane Library, for relevant studies. A total of 14 studies met our inclusion criteria. The US indices were obtained in the portal vein (n = 9), hepatic artery (n = 6), hepatic vein (HV) (n = 4) and other vessels. Using hepatic venous pressure gradient (HVPG) as the reference, the sensitivity (Se) and specificity (Sp) of the portal venous indices were 69–88% and 67–75%, respectively. The correlation coefficients between HVPG and the portal venous indices were approximately 0.296–0.8. No studies assess the Se and Sp of the hepatic arterial indices. The correlation between HVPG and the hepatic arterial indices ranged from 0.01 to 0.83. The Se and Sp of the hepatic venous indices were 75.9–77.8% and 81.8–100%, respectively. In particular, the Se and Sp of HV arrival time for clinically significant PH were 92.7% and 86.7%, respectively. A statistically significant correlation between HVPG and the hepatic venous indices was observed (0.545–0.649). Some US indices, such as HV, exhibited an increased accuracy for diagnosing PH. These indices may be useful in clinical practice for the detection of significant PH.

LC : Effect of Mesenchymal Stem Cell on Hepatic Fibrosis in Thioacetamide-Induced Cirrhotic Rat Model

( Boo Sung Kim ),( Youn Zoo Cho ),( Soon Koo Baik ),( Moon Young Kim ),( Won Ki Hong ),( Hye Won Hwang ),( Jin Hyung Lee ),( Myeong Hun Chae ),( Seung Yong Shin ),( Jung Min Kim ),( Mee Yon Cho ),( Sa 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis and no effective therapy except liver transplantation is currently available for decompensated cirrhosis. However, some practical limitations in liver transplantation lead us to a need for new therapeutic paradigm in this field. Recent reports have shown that the mesenchymal stem cells (MSCs) have the plasticity to differentiate into some kinds of tissue cells and improve organ function. Hence, we investigated the effect of direct inoculation of human bone marrow derived MSCs (BM-MSCs) in thioacetamide (TAA)-induced cirrhosis in a rat model. Methods: Adult Sprague-Dawley rats were allocated into three groups (each group, n = 15) as follows: G1, shame; G2, TAAcontrol; G3, TAA+BM-MSC. To induce cirrhosis, 200mg/kg TAA injection was done twice a week for 12weeks in G2 and G3. 2×106 cells of amplified human BM-MSCs were injected directly into the right liver lobe twice, at weeks 6 and 8 in G3. At 12 weeks, the effect of BM-MSCs on cirrhosis was analyzed histomorphologically using Laennec scores. α-Smooth muscle actin(α-SMA) expression by immunohistochemical staining, relative expression of collagen type 1, and transforming growth factor β (TGF-β) were also evaluated by real-time reverse transcriptase- polymerase chain reaction. Results: Laennec scores were 0, 5.4±0.7 and 3.7±1.06 in G1, G2 and G3, respectively. Histologically, BM-MSCs injected group (G3) showed significant suppression of hepatic fibrosis compared with TAA-control group (G2)(P<0.001). Expressions of α-SMA(%) were significantly lower in G3 than in G2 (3.08±1.26 vs. 7.00±4.12, P<0.05). Also, the relative expression of collagen type 1 and TGF-β1 in RT-PCR were 0.64±0.24, 2.06±0.51, 1.32±0.31 and 0.62±0.28, 5.89±3.05, 2.22±1.41 in G1, G2 and G3, respectively P<0.005). Conclusions: Our results showed that BM-MSCs could attenuate liver fibrosis in rats with TAA-induced cirrhosis, raising the possibility for clinical use of BM-MSCs in the treatment of cirrhosis.

이공계열 전공 공부에 필요한 고등학교 물리 선수과목에 대한 대학생들의 인식에 대한 질적 탐구

곽영순 ( Youngsun Kwak ),조향숙 ( Hyang-suk Cho ),이일 ( Il Lee ),손미현 ( Mihyun Son ) 한국현장과학교육학회 2019 현장과학교육 Vol.13 No.4

본 연구의 목적은 고교-대학 연계성 제고를 위해 고등학교 학생들의 교과목 선택권을 실질적으로 보장하는 방안을 탐구하려는 것이다. 이를 위해 총10명의 이공계열 학부 3, 4학년 및 대학원 재학생을 추천받아 초점집단 심층면담을 실시하였으며 대학전공 공부를 위한 고교 물리 선수과목 이수의 필요성, 대학 전공공부에 필요한 물리 선수과목을 고등학교에서 이수하지 않은 이유, 물리 선수과목 이수를 고등학교 후배들에게 권장할 의사, 대학전공 공부에 필요한 고교 물리 선수과목 이수를 보장하는 방안 등을 탐구하였다. 연구결과 물리 과목의 필요성은 인지하고 있으나, 현실적 이유로 인해 물리과목을 기피하고 있으며, 이를 개선하기 위해서 고등학교 교육과정 편성 · 운영 정상화 방안을 소수 선택과목 개설 보장, 과학Ⅱ 과목 내신 및 수능 성적 산출 방식 개선, 고교 필수선수과목에 대한 이공계열별 진로 안내, 과학교사의 수업전문성 및 진로지도 전문성 제고, 이공계열 전공공부에 필요한 필수선수과목 이수를 보장하기 위한 대입전형 시스템을 마련의 필요성 등을 제안하였다. The purpose of this study is to explore ways to secure highschool students’ choice of courses in order to improve highschool - university linkage. For this purpose, we conducted in-depth focus group interviews with a total of 10 students in the second or the third year or graduate student at the science and engineering college, and these interviewees were recommended by their professors. Through interviews, we explored the necessity to complete highschool Physics prerequisite courses, reason for not completing highschool Physics prerequisite courses necessary for college major, their intention to recommend highschool juniors to complete Physics prerequisite courses, and ways to guarantee prerequisite course completion for college major studies. Based on the results, we suggested ways to link highschool - university curriculum for science & engineering majors. Discussed in the conclusion are ways to stabilize highschool curriculum organization and implementation such as opening elective courses with a few students without disadvantage in the school record, improving the grading system for Science Ⅱ courses in the school record as well as the College Scholastic Ability Test, providing career guidance about prerequisite courses by science & engineering majors, improving the science teacher’s professionalism on teaching and career guidance, and developing college entrance systems to guarantee the completion of prerequisite courses for science & engineering college studies.

Original Article : Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension

( Jae Hyun Kim ),( Jung Min Kim ),( Youn Zoo Cho ),( Ji Hoon Na ),( Hyun Sik Kim ),( Hyoun A Kim ),( Hye Won Kang ),( Soon Koo Baik ),( Sang Ok Kwon ),( Seung Hwan Cha ),( Young Ju Kim ),( Moon Young 대한간학회 2014 Clinical and Molecular Hepatology(대한간학회지) Vol.20 No.4

Background/Aims: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. Methods: Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. Results: The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12.28 mmHg) to 13.5 mmHg (range, 6.20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12.27 mmHg) to 14 mmHg (range, 7.25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3.11 mmHg) vs. 3 mmHg (range, -8.10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. Conclusions: The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended. (Clin Mol Hepatol 2014;20:376-383)

Plenary Session l : Hepatic Vein Arrival Times Using a Microbubble Contrast Ultrasonography can Predict Disease Severity Non-invasively in Patients with Alcoholic Liver Disease

( Won Ki Hong ),( Moon Young Kim ),( Soon Koo Baik ),( Youn Zoo Cho ),( Hye Won Hwang ),( Jin Hyung Lee ),( Myeong Hun Chae ),( Seung Yong Shin ),( Jung Min Kim ),( Mee Yon Cho ),( Sang Ok Kwon ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: A reliable non-invasive assessment of the severity is essential in the management of chronic liver disease. The hepatic vein arrival time (HVAT) as assessed by microbubble contrast-enhanced ultrasonography (CEUS) has been known to show good correlation with histological grade in HCV related liver disease. However, little has been known about the relationship with alcoholic liver disease. We investigated the utility of HVAT in prediction of histological grade of alcohol related chronic liver disease. Methods: One-hundred twenty seven patients with biopsy proven alcohol related chronic liver disease were studied prospectively. Histological grades were estimated by METAVIR fibrosis scoring system (F0-F4). After an overnight fast, a bolus of contrast agent (SonoVue) was injected into an antecubital vein and signals were recorded from the right or middle hepatic veins for analysis. HVATs were calculated as the time from injection to a sustained rise in Doppler signal 10% above baseline. Results: Mean HVAT from F0 to F4 cirrhosis showed a significant progressive shortening of 26.1±5.5 (F0, 7), 20.3±1.4 (F1, 9), 17.4±0.6 (F2, 12), 15.1±1.4 (F3, 34) and 12.7±1.8 (F4, 65) seconds, respectively (P<0.001). The area under the receiver operating characteristic curve (AUROC) was 0.924 for F4 cirrhosis and the sensitivity, specificity for F4 cirrhosis for an HVAT cutoff value of 14.8 sec were 87.7%, 82.3%, respectively. In addition, HVAT also showed significant correlation with Child- Pugh`s score (P<0.001, r2=0.406), the presence of large esophageal varices (P=0.002), ascites (P<0.001) and the history of esophageal variceal hemorrhage (P=0.036). Conclusions: HVAT using a microbubble CEUS could be effective noninvasive method in assessment of the histological severity and disease severity in alcohol related chronic liver disease.

코발트 카르보닐 촉매에 의한 브로모벤질 브로미드의 카르보닐화 (II). 알킬(알콕시메틸)벤조에이트의 선택성 합성

심상철,도칠훈,윤영주,조찬식,우병원,오대희,Shim Sang Chul,Doh Chil Hoon,Youn Young Zoo,Cho Chan Sik,Woo Byung Won,Oh Dae Hee 대한화학회 1991 대한화학회지 Vol.35 No.1

할로벤질 할라이드의 선택적 카르보닐화에 대한 방법을 검토하였다. 알킬(알콕시메틸)벤조에이트는 한 반응기에서 두 반응에 의해 완성되며, 일차로 알코올 용매하에서 알콕시 음이온을 할로벤질 할라이드와 반응시키면, 알킬 할로벤질 에테르가 Williamson ether 합성법에 의해 얻어진다. 이차로 Na$_2$CO$_3$, CH$_3$I 및 Co$_2$(CO)$_8$을 첨가하고, 일산화탄소 기류하에서 반응시키면, 알릴할라이드 부분이 카르보닐화되어 알킬(알콕시메틸)벤조에이트를 높은 수득률로 얻을 수 있었다. A method for the selective syntheses of alkyl (alkoxymethyl)benzoates from halobenzyl halides by two steps in one pot process is described. In the first step, benzyl halide moiety is etherified with alkoxide anion in alcohol by Williamson ether process. In the second step, aryl halide moiety is carbonylated to give alkyl (alkoxymethyl)benzoate with alcohol, Na$_2$CO$_3$, CH$_3$I, and carbon monoxide (1 atm) in the presence of a catalytic amount of Co$_2$(CO)$_8$ in excellent yield.

Clinical Implications of the Serum Apelin Level on Portal Hypertension and Prognosis of Liver Cirrhosis

( Yoo Li Lim ),( Eunhee Choi ),( Yoon Ok Jang ),( Youn Zoo Cho ),( Yong Seok Kang ),( Soon Koo Baik ),( Sang Ok Kwon ),( Moon Young Kim ) 대한소화기기능성질환·운동학회 2016 Gut and Liver Vol.10 No.1

Background/Aims: Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD). Methods: From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0±12.9 months for decompensation and mortality. Results: A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R2=0.263, p<0.001) and collagen proportional area (R2=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R2=0.356, p<0.001). In a multivariate analysis using a Cox regression hazard model, s-apelin was a weakly significant predictor of decompensation (hazard ratio [HR], 1.002; p<0.001) and mortality (HR, 1.003; p<0.001). Conclusions: s-apelin showed a significant relationship with CLD severity. However, its significance as a noninvasive biomarker for disease severity and prognosis was weak. (Gut Liver 2016;10:109-116)

류마티스 관절염 환자에서 제2형 콜라겐의 치료효과

홍연식 ( Yeon Sik Hong ),김완욱 ( Wan Uk Kim ),이신석 ( Shin Seok Lee ),주영실 ( Yeong Sil Zoo ),민준기 ( Jun Ki Min ),박성환 ( Sung Hwan Park ),이상헌 ( Sang Heon Lee ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.2

연구목적: 류마티스 관절염 환자를 대상으로 CII을 경구 투여하여 CII의 치료효과와 안정성을 평가하고자 하였다. 대상 및 방법: RA 환자를 무작위로 2군(콜라겐 투여군 25명, 대조군 20명)으로 나누어 bovine CII을 하루에 100μg 3개월 동안 복용하고 1, 2, 3개월 후에 효과를 평가하였다. 반응 여부는 임상증상 호전에 관한 ACR 기준, Paulus 기준 및 부종과 동통관절수가 30% 이상 호전되었을 때 반응했다고 평가하고 시험기간 중 어느 때라도 기준을 만족하면 반응군이라 하고 전혀 반응을 보이지 않으면 비반응군이라 하였다. 결과: Paulus 기준을 적용했을 때 위약 투여군은 10%, CII 투여군은 40%가 반응하여 유의한 (p=0.04) 호전을 보였고, 환자 활동 및 상태 지표에 관한 평가(MHAQ)는 CII 투여군에서 3개월 후 유의한 감소를 보였다. 종창 몇 압통 관절수, 환자와 의사가 평가하는 VAS는 CII 투여군과 위약 투여군 사이에 통계적인 유의성은 없었다. 두 군 모두에서 약제에 의한 위중한 부작용은 없었으며 CII 투여군에서 투여전에 비해 투약 3개월 후 혈청 항 2형 콜라겐 항체의 의미있는 감소를 보였다. 결론: 저자들의 연구는 CII의 경구투여가 류마티스 관절염 치료에 효과적이며 안전한 치료법임을 보여준다. 혈청 항 2형 콜라겐 항체가 CII의 경구투여에 의해 감소된다는 사실은 CII의 경구투여에 의해 자가 항체 생성의 면역학적 관용이 유발될 수 있음을 시사한다. Objective: To investigate the efficacy and safety of oral bovine type II collagen(CII) in the treatment of rheumatoid arthritis(RA). Methods: Forty-five patients with active RA were enrolled and randomized to receive placebo or oral CII for 3 months. Efficacy parameters were assessed monthly. Cumulative response rates(percentages of patients meeting the criteria for response at anytime during the study) were analyzed utilizing 3 set of composite criteria: Paulus criteria, ACR criteria for improvement in RA, and a requirement for≥30% reduction in both swollen and tender joint counts. Results: The CII-treated group(n=25) showed significant higher response rate by the Paulus criteria compared to placebo group(n=20) (p=0.04), and MHAQ scores between baseline and 3 months of treatment were also significantly decreased in the CII-treated group(p<0.05). However, there were no significant differences in tender and swollen joint count, and physician and patient global scores between CII-treated and placebo groups. Only one patient treated with CII had a urticarica 1 week after administration, but no serious side effects were found in the two groups. Patients treated with CII(n=15) showed the decreased levels of circulating IgG antibodies to bovine CII 3 months after treatment(p=0.02), whereas significant changes of IgG antibodies to CII were not found in placebo group(n=12). Conclusion: Oral administration of CII was safe and effective for the treatment of rheumatoid arthritis. The finding that serum IgG antibodies to bovine CII was decreased in patients who treated with CII suggest that autoimmune response to CII could be decreased by repetitive administration of CII.