Flat Pattern Peaks of Tacrolimus Absorption and Associated Pharmacogenomic Variants in Kidney Transplantation Recipients

Kim Suh Min,Lim Younggyun,Min Sangil,Min Byung-Joo,Seo Myung-Eui,Lee Kye Hwa,김주한,Ha Jongwon 대한의학회 2022 Journal of Korean medical science Vol.37 No.5

Background: Tacrolimus is the most commonly used immunosuppressive drug in solid organ transplantation. After administering a conventional twice-daily dose of tacrolimus, peak levels were achieved within the first 1.5 to 2 hours. A group of patients showed different early absorption phase of tacrolimus after kidney transplantation. Methods: Trough(C0) and 1.5-hour blood levels (C1.5) of tacrolimus were measured in 95 kidney transplantation recipients. Patients with a C1.5/C0 < 1.5 and > 1.5 were defined as those having flat pattern peaks and as controls, respectively. Transplantation outcomes were compared between the groups. Whole exome sequencing was performed to investigate the genetic susceptibility to flat pattern peaks. Results: Twenty-eight patients showed flat pattern peaks. The mean C1.5/C0 values were 1.13 ± 0.22 and 3.78 ± 1.25 in the flat pattern peak and control groups, respectively. In multivariate analysis, flat pattern peak was an independent risk factor for biopsy-proven acute rejection (BPAR) and/or borderline change (P = 0.014). Patients having flat pattern peaks showed significantly lower post-transplant 36-month estimated glomerular filtration rate (P = 0.001). Two single nucleotide variants in ABCB1 genes, rs1922242 and rs2235035, were associated with flat pattern peaks (P = 0.019 and P = 0.027, respectively). Conclusion: Both of C1.5 and C0 should be measured to distinguish the patients showing unique initial absorption. A C1.5/C0 ratio lower than 1.5 was associated with an increased risk of BPAR and/or borderline change. Single nucleotide variants s in ABCB1 gene might influence the flat pattern peaks of tacrolimus absorption.

Synthesis and anti-inflammatory evaluation of <i>N</i>-sulfonyl anthranilic acids via Ir(III)-catalyzed C–H amidation of benzoic acids

Han, Sang Hoon,Suh, Hyo Sun,Jo, Hyeim,Oh, Yongguk,Mishra, Neeraj Kumar,Han, Sangil,Kim, Hyung Sik,Jung, Young Hoon,Lee, Byung Mu,Kim, In Su Elsevier 2017 Bioorganic & medicinal chemistry letters Vol.27 No.10

<P><B>Abstract</B></P> <P>The iridium(III)-catalyzed <I>ortho</I>-C–H amidation of benzoic acids with sulfonyl azides is described. These transformations allow the facile generation of <I>N</I>-sulfonyl anthranilic acids, which are known as crucial scaffolds found in biologically active molecules. In addition, all synthetic products were evaluated for in vitro anti-inflammatory activity against interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compounds <B>4c</B> and <B>4d</B>, generated from <I>p</I>-OMe- and <I>p</I>-Br-sulfonyl azides, were found to display potent anti-inflammatory property stronger than that of well-known NSAIDs ibuprofen.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The iridium(III)-catalyzed <I>ortho</I>-C–H amidation of benzoic acids is described. </LI> <LI> Anti-inflammatory activity of synthetic anthranilic acids is evaluated. </LI> <LI> Some synthetic products display anti-inflammatory effect competitive with ibuprofen. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>The iridium(III)-catalyzed <I>ortho</I>-C–H amidation of benzoic acids with sulfonyl azides is described. All synthetic products were evaluated for in vitro anti-inflammatory activity against interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compounds <B>4c</B> and <B>4d</B> were found to display potent anti-inflammatory property stronger than that of NSAIDs ibuprofen.</P> <P>[DISPLAY OMISSION]</P>

A tactile sensor using single layer graphene for surface texture recognition

Chun, Sungwoo,Choi, Yeonhai,Suh, Dong Ik,Bae, Gi Yoon,Hyun, Sangil,Park, Wanjun The Royal Society of Chemistry 2017 Nanoscale Vol.9 No.29

<P>Tactile sensors capable of texture recognition are essential for artificial skin functions. In this work, we describe a tactile sensor with a single sensor architecture made of single layer graphene that can recognize surface texture based on the roughness of the interacting surface. Resistance changes due to the local deformation of a local area of the single layer graphene are reflected in the resistance of the entire sensor. By introducing microstructures inspired by human finger prints, surface texture was successfully defined through fast Fourier transform analysis, and spatial resolution was easily achievable. This work provides a simple method utilizing a single sensor for surface texture recognition at the level of human sensation without using a matrix architecture which requires high density integration technology with force and vibration sensor elements.</P>

엠보싱 무늬 강판 적용 고강성 경량 센터플로어 개발

김정섭(Jungsub Kim),이상일(Sangil Lee),서정식(Jeongsik Suh) 한국자동차공학회 2014 한국자동차공학회 학술대회 및 전시회 Vol.2014 No.11

Regional glucose metabolism due to the presence of cerebral amyloidopathy in older adults with depression and mild cognitive impairment

Youn, HyunChul,Lee, Eun Seong,Lee, Suji,Suh, Sangil,Jeong, Hyun-Ghang,Eo, Jae Seon Elsevier 2018 Journal of affective disorders Vol.239 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Depression is a risk factor for mild cognitive impairment (MCI) and for the conversion from MCI to Alzheimer's disease (AD). This study investigated regional cerebral glucose metabolism (rCMglc) in older adults with depression and MCI, either with or without amyloidopathy.</P> <P><B>Methods</B></P> <P>We recruited 31 older adults diagnosed with depression and MCI, and 21 older adults with normal cognition (NC). All participants completed demographic questionnaires and were examined with a standardized neuropsychological battery, F-18 fluorodeoxyglucose positron emission tomography (PET), and F-18 florbetaben PET. We classified subjects with depression and MCI into amyloid-β-positive (CDAP; <I>n</I> = 16) and amyloid-β-negative (CDAN; <I>n</I> = 15) groups. Pairwise rCMglc analyses were conducted between all three groups (CDAP vs. NC, CDAN vs. NC, and CDAP vs. CDAN).</P> <P><B>Results</B></P> <P>In comparison with the NC group, the CDAP group showed reduced rCMglc predominantly in temporoparietal regions, whereas the CDAN group showed lower rCMglc in regions of the frontal lobe, in addition to the temporoparietal regions. The CDAN group also showed lower rCMglc in right anterior cingulate and left inferior orbitofrontal regions, in a comparison between the CDAP and CDAN groups.</P> <P><B>Limitations</B></P> <P>The generalizability of the findings is limited because this study has a relatively small number of participants. In addition, this study used cross-sectional design rather than longitudinal design.</P> <P><B>Conclusions</B></P> <P>Our findings may provide a reference to assess the risk of future cognitive deterioration. Consequently, this study is expected to contribute to prevention and early identification of dementia associated with AD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Some depressed elders report cognitive decline in the prodromal Alzheimer's disease. </LI> <LI> Depressed elders have different cerebral metabolism due to the cerebral amyloidopathy. </LI> <LI> The results of 18F-FDG PET may predict cerebral amyloidopathy in depressed elders. </LI> </UL> </P>

The Effect of Antidepressants on Functional Connectivity in First-Episode Drug-Naïve Adolescents with Major Depressive Disorder

Jongha Lee,Hojun Lee,Jihyun Kim,Sangil Suh,Moon-Soo Lee 대한소아청소년정신의학회 2018 대한소아청소년정신의학회 학술대회논문집 Vol.2018 No.11

First-Pass Recanalization with EmboTrap II in Acute Ischemic Stroke (FREE-AIS): A Multicenter Prospective Study

Baek Jang-Hyun,Kim Byung Moon,Suh Sang Hyun,Jeon Hong-Jun,Ihm Eun Hyun,Park Hyungjong,Kim Chang-Hyun,Cha Sang-Hoon,Choi Chi-Hoon,Yi Kyung Sik,Kim Jun-Hwee,Suh Sangil,Kim Byungjun,Chang Yoonkyung,Kim S 대한영상의학회 2023 Korean Journal of Radiology Vol.24 No.2

Objective: We aimed to evaluate the efficacy of EmboTrap II in terms of first-pass recanalization and to determine whether it could yield favorable outcomes. Materials and Methods: In this multicenter, prospective study, we consecutively enrolled patients who underwent mechanical thrombectomy using EmboTrap II as a front-line device. The primary outcome was the first pass effect (FPE) rate defined by modified Thrombolysis In Cerebral Infarction (mTICI) grade 2c or 3 by the first pass of EmboTrap II. In addition, modified FPE (mFPE; mTICI grade 2b–3 by the first pass of EmboTrap II), successful recanalization (final mTICI grade 2b–3), and clinical outcomes were assessed. We also analyzed the effect of FPE on a modified Rankin Scale (mRS) score of 0–2 at 3 months. Results: Two hundred-ten patients (mean age ± standard deviation, 73.3 ± 11.4 years; male, 55.7%) were included. Ninetynine patients (47.1%) had FPE, and mFPE was achieved in 150 (71.4%) patients. Successful recanalization was achieved in 191 (91.0%) patients. Among them, 164 (85.9%) patients underwent successful recanalization by exclusively using EmboTrap II. The time from groin puncture to FPE was 25.0 minutes (interquartile range, 17.0–35.0 minutes). Procedure-related complications were observed in seven (3.3%) patients. Symptomatic intracranial hemorrhage developed in 14 (6.7%) patients. One hundred twenty-three (58.9% of 209 completely followed) patients had an mRS score of 0–2. Sixteen (7.7% of 209) patients died during the follow-up period. Patients who had successful recanalization with FPE were four times more likely to have an mRS score of 0–2 than those who had successful recanalization without FPE (adjusted odds ratio, 4.13; 95% confidence interval, 1.59–10.8; p = 0.004). Conclusion: Mechanical thrombectomy using the front-line EmboTrap II is effective and safe. In particular, FPE rates were high. Achieving FPE was important for an mRS score of 0–2, even in patients with successful recanalization.

정신과적 투약력이 없는 초발 주요 우울장애 청소년 환아들에서의 백질 구조적 연결성 감소

서은수,김지현,서상일,박소영,이전호,이종하,김인성,이문수,Suh, Eunsoo,Kim, Jihyun,Suh, Sangil,Park, Soyoung,Lee, Jeonho,Lee, Jongha,Kim, In-Seong,Lee, Moon-Soo 한국정신신체의학회 2017 정신신체의학 Vol.25 No.2

연구목적 최근의 신경영상 연구들은 주요 우울장애의 기전을 인지 회로와 감정 회로 연결의 기능장애 즉, 후외방 전두피질과 전전두엽을 번연계로 연결하는 전측대상피질의 연결성 장애에 초점을 맞추고 있다. 소아청소년 주요 우울장애에서 확산텐서영상(diffusion tensor image, DTI)을 사용한 종전의 연구들은 양측 구상회속, 양측 하측 전두후두속, 좌측 전측대상피질, 좌측 상종속 등에서 신경연결의 감소를 보고하였다. 이 연구에서 우리는 정신과적 투약력이 없는 초발 주요 우울장애 청소년에서의 신경 연결성을 DTI를 이용하여 정상 대조군과 비교하였다. 방 법 고려대학교 구로병원을 내원한 청소년 환아들 중 정신과적 투약력이 없으며 주요 우울장애를 처음으로 진단받은 환아들(n=26, 남성 10명, 여성 16명) 및 대조군(n=27, 남성 5명, 여성 22명)을 모집하였다. 정신과적 면담, 지능지수, 해밀턴 우울척도를 포함한 심리검사, 확산강조영상을 포함한 MRI 검사가 항우울제 투약 전에 시행되었다. Fractional anisotropy(FA), radial diffusivity, mean diffusivity, axial diffusivity가 DTI를 사용하여 계산되었다. 통계적 분석을 위해 FMRIB Software Library-Tract Based Spatial Statistic가 사용되었다. 결 과 전체 뇌의 분석에서는 유의한 구조적 변화를 관찰할 수 없었다. 그러나 관심영역을 지정하여 시행한 분석을 하였을 때, 환아군에서 대조군에 비해 우측 상종속 부위에 유의미한 FA값의 감소를 보인 3개의 다발이 관찰되었다. 결 론 주요 우울장애를 진단받은 청소년 환아군에서 대조군에 비해 DTI에 기반하여 우측의 상종속에 연결성 감소를 보였다. 따라서 DTI를 통한 구조적 연결성은 정신과적 투약력이 없는 초발 주요 우울장애 청소년에서도 생체 표지자로 사용될 수 있을 것이라 생각된다. Objectives : Recent neuroimaging studies focus on dysfunctions in connectivity between cognitive circuits and emotional circuits: anterior cingulate cortex that connects dorsolateral orbitofrontal cortex and prefrontal cortex to limbic system. Previous studies on pediatric depression using DTI have reported decreased neural connectivity in several brain regions, including the amygdala, anterior cingulate cortex, superior longitudinal fasciculus. We compared the neural connectivity of psychotropic drug naïve adolescent patients with a first onset of major depressive episode with healthy controls using DTI. Methods : Adolescent psychotropic drug naïve patients(n=26, 10 men, 16 women; age range, 13-18 years) who visited the Korea University Guro Hospital and were diagnosed with first onset major depressive disorder were registered. Healthy controls(n=27, 5 males, 22 females; age range, 12-17 years) were recruited. Psychiatric interviews, complete psychometrics including IQ and HAM-D, MRI including diffusion weighted image acquisition were conducted prior to antidepressant administration to the patients. Fractional anisotropy(FA), radial, mean, and axial diffusivity were estimated using DTI. FMRIB Software Library-Tract Based Spatial Statistics was used for statistical analysis. Results : We did not observe any significant difference in whole brain analysis. However, ROI analysis on right superior longitudinal fasciculus resulted in 3 clusters with significant decrease of FA in patients group. Conclusions : The patients with adolescent major depressive disorder showed statistically significant FA decrease in the DTI-based structure compared with healthy control. Therefore we suppose DTI can be used as a bio-marker in psychotropic drug-naïve adolescent patients with first onset major depressive disorder.

Decreased Cortical Thickness and Local Gyrification in Individuals with Subjective Cognitive Impairment

HyunChul Youn,Myungwon Choi,Suji Lee,Daegyeom Kim,Sangil Suh,Cheol E. Han,정현강 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.4

Objective: Subjective cognitive impairment (SCI) is associated with future cognitive decline. This study aimed to compare cortical thickness and local gyrification index (LGI) between individuals with SCI and normal control (NC) subjects. Methods: Forty-seven participants (27 SCI and 20 NC) were recruited. All participants underwent brain magnetic resonance imaging scanning and were clinically assessed using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery of tests. We compared cortical thickness and LGI between the two groups and analyzed correlations between cortical thickness/LGI and scores on CERAD protocol subtests in the SCI group for region of interests with significant between-group differences. Results: Cortical thickness reduction in the left entorhinal, superior temporal, insular, rostral middle frontal, precentral, superior frontal, and supramarginal regions, and right supramarginal, precentral, insular, postcentral, and posterior cingulate regions was observed in the SCI compared to the NC group. Cortical thickness in these regions correlated with scores of constructional praxis, word list memory, word list recall, constructional recall, trail making test A, and verbal fluency under the CERAD protocol. Significantly decreased gyrification was observed in the left lingual gyrus of the SCI group. In addition, gyrification of this region was positively associated with scores of constructional praxis. Conclusion: Our results may provide an additional reference to the notion that SCI may be associated with future cognitive impairment. This study may help clinicians to assess individuals with SCI who may progress to mild cognitive impairment and Alzheimer’s dementia.