Publications by authors named "Mi Jin Kim"

254 Publications

Author Correction: COVID-19-related school closing aggravate obesity and glucose intolerance in pediatric patients with obesity.

Sci Rep 2021 Jul 6;11(1):14284. Epub 2021 Jul 6.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.1038/s41598-021-93375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258489PMC
July 2021

Cerebral and Somatic Oxygen Saturation in Neonates with Congenital Heart Disease before Surgery.

J Clin Med 2021 Jun 1;10(11). Epub 2021 Jun 1.

Division of Pediatric Cardiology, Department of pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Background: We investigated preoperative cerebral (ScO) and abdominal (StO) regional oxygen saturations according to cardiac diagnosis in neonates with critical CHD, their time trends, and the clinical and biochemical parameters associated with them.

Methods: Thirty-seven neonates with a prenatal diagnosis of CHD were included. ScO and StO values were continuously evaluated using near-infrared spectroscopy. Measurements were obtained hourly before surgery. A linear mixed effects model was used to assess the effects of time and cardiac diagnosis on regional oxygenation and to explore the contributing factors.

Results: Regional oxygenation differed according to cardiac diagnosis ( < 0.001). ScO was lowest in the patients with severe atrioventricular valvar regurgitation (AVVR) (48.1 ± 8.0%). StO tended to be lower than ScO, and both worsened gradually during the period between birth and surgery. There was also a significant interaction between cardiac diagnosis and time. The factors related to ScO were hemoglobin and arterial saturation, whereas no factor was associated with StO.

Conclusions: Preoperative ScO and StO in critical CHD differed according to cardiac diagnosis. ScO in the patients with severe AVVR was very low, which may imply cerebral hypoxia. ScO gradually decreased, suggesting that the longer the time to surgery, the higher the risk of hypoxic brain injury.
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http://dx.doi.org/10.3390/jcm10112455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199521PMC
June 2021

Infliximab Therapy for Children with Moderate to Severe Ulcerative Colitis: A Step-Up versus a Top-Down Strategy.

Yonsei Med J 2021 Jul;62(7):608-614

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: We aimed to investigate clinical outcomes between top-down (TD) and conventional step-up (SU) therapies in pediatric patients with moderate to severe ulcerative colitis (UC).

Materials And Methods: All patients underwent clinical and endoscopic evaluation at diagnosis and 4 months and 1 year after treatment. Patients who started treatment with corticosteroid were grouped in the SU group, while those that initiated early infliximab (IFX) were grouped in the TD group. Among the SU group, patients who eventually changed to IFX treatment due to steroid resistance or dependency were included in the SU(R) group.

Results: In total, 44 children with moderate to severe UC were included for analysis. Twenty-one patients were included in the SU group, 23 were included in the TD group, and 10 were enrolled in the SU(R) group. Relapse rates were 47.6% (10/21) in the SU group and 17.4% (4/23) in the TD group (=0.033). Among relapsed patients, the durations from remission to relapse were 17.3 months (0.9-46.9) in the SU group and 24.3 months (1.8-44.9) in the TD group. There was no statistically significant difference in the sustained durations of remission after IFX administration between the SU(R) and TD groups [3.9 (1.4-6.3) and 2.3 (0.3-5.2) years, respectively (>0.05)].

Conclusion: According to our study, early use of IFX without corticosteroid treatment for children with moderate to severe UC helps to lower relapse rates. We also found that IFX was a very effective treatment for pediatric UC, with a sustained duration of remission similar between TD and SU(R) groups.
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http://dx.doi.org/10.3349/ymj.2021.62.7.608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236348PMC
July 2021

Albumin-to-Globulin Ratio at 1 Year after Anti-Tumor Necrosis Factor α Therapy Can Serve as a Prognostic Biomarker in Pediatric Crohn's Disease Patients.

Gut Liver 2021 Jun 9. Epub 2021 Jun 9.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background/aims: The efficacy of biologics for the treatment of Crohn's disease (CD) is affected by the drug concentrations. We aimed to evaluate the importance of albumin and globulin which are known to be associated with drug concentrations as prognostic biomarkers in CD.

Methods: In total, 121 pediatric patients with CD who had received anti-tumor necrosis factor (TNF)-α therapy were retrospectively examined between January 2010 and February 2019.

Results: Relapse was observed in 48.8% of patients (59/121). The level of calprotectin (odds ratio, 2.13; p=0.03) and the albumin-to-globulin ratio (AGR) at 1 year after anti-TNF-α therapy (odds ratio, 0.0002; p=0.003) were associated with relapse. The AGR at 1 year after anti-TNF-α therapy was the only factor associated with the time-to-relapse (hazard ratio, 0.02; p<0.001). The optimal AGR cutoff value for the prediction of relapse was 1.47 (area under the curve, 0.916; p<0.001). The median infliximab trough level (TL) was lower in patients with AGRs <1.47 than in those with AGRs ≥1.47. Anti-drug antibody (ADA) concentrations were negatively correlated with the AGR at 1 year of anti-TNF-α therapy (r=-0.413, p=0.032).

Conclusions: AGR can be used to predict relapse. Patients with AGRs <1.47 at 1 year after anti-TNF-α therapy are more likely to have low drug TLs and develop ADAs, which increase the possibility of relapse than those with AGRs ≥1.47. Therefore, if the AGR at 1 year after anti-TNF-α therapy is less than 1.47, clinicians should monitor disease activity, assess the TLs of the anti-TNF-α agents, test for ADAs and determine the appropriate therapeutic strategies.
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http://dx.doi.org/10.5009/gnl20322DOI Listing
June 2021

Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation.

Int J Mol Sci 2021 May 25;22(11). Epub 2021 May 25.

Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu 41566, Korea.

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis and restenosis. Glycolysis and glutaminolysis are increased in rapidly proliferating VSMCs to support their increased energy requirements and biomass production. Thus, it is essential to develop new pharmacological tools that regulate metabolic reprogramming in VSMCs for treatment of atherosclerosis. The effects of 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist, have been broadly investigated in highly proliferative cells; however, it is unclear whether DON inhibits proliferation of VSMCs and neointima formation. Here, we investigated the effects of DON on neointima formation in vivo as well as proliferation and migration of VSMCs in vitro. DON simultaneously inhibited FBS- or PDGF-stimulated glycolysis and glutaminolysis as well as mammalian target of rapamycin complex I activity in growth factor-stimulated VSMCs, and thereby suppressed their proliferation and migration. Furthermore, a DON-derived prodrug, named JHU-083, significantly attenuated carotid artery ligation-induced neointima formation in mice. Our results suggest that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis.
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http://dx.doi.org/10.3390/ijms22115602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198131PMC
May 2021

[How Can We Do Transition Successfully from Pediatric to Adult Clinics in Inflammatory Bowel Disease?]

Korean J Gastroenterol 2021 05;77(5):227-230

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

With the increasing incidence of pediatric inflammatory bowel disease (IBD) in children and its impact throughout life, transition care has become an important issue. In Korea, no guidelines have been proposed to support the transition from the pediatric clinic to the adult IBD clinic. This paper reviews the current issues related to IBD patient care during the transition from pediatrics to adults to identify the barriers and critical elements for a successful transition. Thus far, a multi-disciplinary pediatric/adult clinic or alternate visits between pediatric and adult health care providers is the best model for pediatric to adult IBD clinics. Self-reliance and independence of patients with pediatric IBD are also essential for a successful transition. In addition, the timing of the transition from a pediatric clinic to an adult IBD clinic should not be determined because the issue is not the chronological age but rather the individual maturity.
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http://dx.doi.org/10.4166/kjg.2021.065DOI Listing
May 2021

V-9302 inhibits proliferation and migration of VSMCs, and reduces neointima formation in mice after carotid artery ligation.

Biochem Biophys Res Commun 2021 Jun 6;560:45-51. Epub 2021 May 6.

Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, 41566, South Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea; Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, 41566, South Korea. Electronic address:

Rapidly proliferating cells such as vascular smooth muscle cells (VSMCs) require metabolic programs to support increased energy and biomass production. Thus, targeting glutamine metabolism by inhibiting glutamine transport could be a promising strategy for vascular disorders such as atherosclerosis, stenosis, and restenosis. V-9302, a competitive antagonist targeting the glutamine transporter, has been investigated in the context of cancer; however, its role in VSMCs is unclear. Here, we examined the effects of blocking glutamine transport in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using V-9302. We found that V-9302 inhibited mTORC1 activity and mitochondrial respiration, thereby suppressing FBS- or PDGF-stimulated proliferation and migration of VSMCs. Moreover, V-9302 attenuated carotid artery ligation-induced neointima in mice. Collectively, the data suggest that targeting glutamine transport using V-9302 is a promising therapeutic strategy to ameliorate occlusive vascular disease.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.079DOI Listing
June 2021

Mitochondrial Transplantation Modulates Inflammation and Apoptosis, Alleviating Tendinopathy Both In Vivo and In Vitro.

Antioxidants (Basel) 2021 Apr 28;10(5). Epub 2021 Apr 28.

Department of Biotechnology, CHA University, Seongnam 13488, Korea.

Tendinopathy is a common musculoskeletal condition causing pain and dysfunction. Conventional treatment and surgical procedures for tendinopathy are insufficient; accordingly, recent research has focused on tendon-healing regenerative approaches. Tendon injuries usually occur in the hypoxic critical zone, characterized by increased oxidative stress and mitochondrial dysfunction; thus, exogenous intact mitochondria may be therapeutic. We aimed to assess whether mitochondrial transplantation could induce anti-inflammatory activity and modulate the metabolic state of a tendinopathy model. Exogenous mitochondria were successfully delivered into damaged tenocytes by centrifugation. Levels of Tenomodulin and Collagen I in damaged tenocytes were restored with reductions in nuclear factor-κB and matrix metalloproteinase 1. The dysregulation of oxidative stress and mitochondrial membrane potential was attenuated by mitochondrial transplantation. Activated mitochondrial fission markers, such as fission 1 and dynamin-related protein 1, were dose-dependently downregulated. Apoptosis signaling pathway proteins were restored to the pre-damage levels. Similar changes were observed in a collagenase injection-induced rat model of tendinopathy. Exogenous mitochondria incorporated into the Achilles tendon reduced inflammatory and fission marker levels. Notably, collagen production was restored. Our results demonstrate the therapeutic effects of direct mitochondrial transplantation in tendinopathy. These effects may be explained by alterations in anti-inflammatory and apoptotic processes via changes in mitochondrial dynamics.
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http://dx.doi.org/10.3390/antiox10050696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146308PMC
April 2021

Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients With Crohn Disease.

J Pediatr Gastroenterol Nutr 2021 06;72(6):870-876

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.

Objectives: We investigated the therapeutic drug monitoring of adalimumab (ADL) on clinical remission (CR) and mucosal healing (MH) rates in paediatric patients with Crohn disease (CD). Furthermore, long-term treatment efficacy of ADL in paediatric CD was evaluated through 3-year follow-up.

Methods: We conducted a prospective study of 31 patients with CD who received ADL maintenance therapy and underwent endoscopic evaluation of MH and pharmacokinetic analysis. Patients in CR were identified based on Paediatric Crohn Disease Activity Index (PCDAI) scores less than 10. Patients with MH were identified based on Simple Endoscopic Scores for Crohn Disease (SES-CD) of less than 2.

Results: At 4 months and 1 year of ADL treatment, 28 and 26 patients, respectively, were under CR; 13 and 17 patients, respectively, achieved MH. The median trough levels (TLs) of ADL were higher in patients in CR (7.6 ± 3.5 μg/mL) than in patients with active disease (5.1 ± 2.2 μg/mL). ADL TLs were significantly higher in patients who achieved MH than in those who did not (14.2 ± 7.6 vs 7.8 ± 5.2 μg/mL). The optimal cut-point for predicting MH at 1 year of ADL treatment was 8.18 μg/mL. During long-term follow-up, ADL TLs were stably maintained over 10 μg/mL; not only CR and MH but also histologic remission was obtained at a high rate. ADL administration maintained a positive effect on growth during the maintenance period.

Conclusions: ADL TLs were significantly higher in paediatric patients with CD who achieved CR or MH. ADL treatment showed long-term stable efficacy and positive effects on growth indicators.
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http://dx.doi.org/10.1097/MPG.0000000000003070DOI Listing
June 2021

Therapeutic Lymphatic Embolization in Pediatric Primary Intestinal Lymphangiectasia.

Yonsei Med J 2021 May;62(5):470-473

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Primary intestinal lymphangiectasia (IL) can cause leakage of lymphatic fluids into the gastrointestinal tract, eventually leading to protein-losing enteropathy. A 15-year-old male patient, whose disease began at the age of 8 years, recently felt worsening general weakness. After diagnosing abnormal lymphatic lesions in the duodenum through endoscopy with biopsy and contrast-enhanced magnetic resonance lymphangiography, glue embolization of the leaking duodenal lymphatic channel was successfully performed. This procedure is typically reserved for adult patients, although as shown in this case, it can be properly performed in children. His serum albumin level was initially 1.5 g/dL, but elevated to 5.0 g/dL after two sessions of lymphatic embolization. Accordingly, we suggest that embolization could potentially be considered a first-line treatment for focal lesions of primary intestinal IL.
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http://dx.doi.org/10.3349/ymj.2021.62.5.470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084696PMC
May 2021

Procedural Predictors and Outcomes of Percutaneous Secundum Atrial Septal Defect Closure in Children Aged <6 Years.

Circ J 2021 Apr 21. Epub 2021 Apr 21.

Division of Pediatric Cardiology, Asan Medical Center, University of Ulsan College of Medicine.

Background: Percutaneous atrial septal defect (ASD) closure is the treatment of choice for patients with a suitable ASD anatomy; however, the procedural characteristics and outcomes in children aged <6 years are unclear. The feasibility and safety of percutaneous ASD closure in children aged <6 years was evaluated and the predictors of procedural failure and challenging cases were identified.Methods and Results:Patients from a single center between 2006 and 2018 (n=407) were retrospectively evaluated. There were 265 (65.1%) female patients. The median age at the time of the procedure and ASD size were 3.4 (0.9-5.9) years and 13.3 (3.8-27.0) mm, respectively. Medical records and echocardiographic images were analyzed. A challenging case was indicated by the use of non-conventional techniques. The procedure was completed in 399 patients (98.0%). Post-procedural acute complications occurred in 5 patients, including 1 with device embolization. Two patients underwent surgical device removal. During the follow up (30.3 [3.6-140.8] months), aggravated mitral regurgitation occurred in 5 patients. A multivariate logistic regression revealed large-sized ASD as a predictor of procedural failure (odds ratio=1.828, 95% confidence interval: 1.139-2.934, P=0.012) and challenging cases (odds ratio=1.371, 95% confidence interval: 1.180-1.593, P<0.001).

Conclusions: Percutaneous ASD closure is feasible and safe in children aged <6 years; however, patients with large-sized ASD are at high risk of procedural failure and becoming a challenging case.
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http://dx.doi.org/10.1253/circj.CJ-20-1023DOI Listing
April 2021

Association between Fecal Calprotectin and Mucosal Healing in Pediatric Patients with Crohn's Disease Who Have Achieved Sustained Clinical Remission with Anti-Tumor Necrosis Factor Agents.

Gut Liver 2021 Apr 9. Epub 2021 Apr 9.

Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.

Background/aims: : Although mucosal healing (MH) is acknowledged as the treatment target in the treat-to-target era, there are limitations on repeated endoscopic examinations, especially in pediatric patients. We aimed to investigate whether fecal calprotectin (FC) could serve as a surrogate marker for the assessment of MH in pediatric patients with Crohn's disease (CD) who have achieved sustained clinical remission (CR) while treated with anti-tumor necrosis factor (TNF) agents.

Methods: This multicenter retrospective cross-sectional study included pediatric CD patients who had sustained a CR for at least 6 months with anti-TNF agents and who simultaneously underwent ileocolonoscopy and FC tests during follow-up. MH was defined as the absence of any ulcer on ileocolonoscopy.

Results: A total of 131 patients were included in this study. MH was observed in 87 patients (66.7%). The FC level was significantly lower in patients with MH than in those without MH (median 49.0 mg/kg vs 599.0 mg/kg; p<0.001). According to the multivariate logistic regression analysis, FC was the only factor associated with MH (odds ratio, 0.62; 95% confidence interval [CI], 0.52 to 0.73; p<0.001). According to the receiver operating characteristic curve analysis, the optimal cutoff value for FC for the association with MH was <140 mg/kg (area under the curve 0.890, 95% CI 0.829 to 0.951, sensitivity 78.2%, specificity 88.6%, p<0.001).

Conclusions: FC was associated with MH in pediatric patients with CD who had achieved a sustained CR for at least 6 months with anti-TNF agents. In these patients, FC can be used to stratify patients and guide decisions regarding ileocolonoscopy in the treat-to-target era.
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http://dx.doi.org/10.5009/gnl20300DOI Listing
April 2021

Mercury Chloride but Not Lead Acetate Causes Apoptotic Cell Death in Human Lung Fibroblast MRC5 Cells via Regulation of Cell Cycle Progression.

Int J Mol Sci 2021 Mar 2;22(5). Epub 2021 Mar 2.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

Heavy metals are important for various biological systems, but, in excess, they pose a serious risk to human health. Heavy metals are commonly used in consumer and industrial products. Despite the increasing evidence on the adverse effects of heavy metals, the detailed mechanisms underlying their action on lung cancer progression are still poorly understood. In the present study, we investigated whether heavy metals (mercury chloride and lead acetate) affect cell viability, cell cycle, and apoptotic cell death in human lung fibroblast MRC5 cells. The results showed that mercury chloride arrested the sub-G and G/M phases by inducing cyclin B1 expression. In addition, the exposure to mercury chloride increased apoptosis through the activation of caspase-3. However, lead had no cytotoxic effects on human lung fibroblast MRC5 cells at low concentration. These findings demonstrated that mercury chloride affects the cytotoxicity of MRC5 cells by increasing cell cycle progression and apoptotic cell death.
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http://dx.doi.org/10.3390/ijms22052494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958599PMC
March 2021

COVID-19-related school closing aggravate obesity and glucose intolerance in pediatric patients with obesity.

Sci Rep 2021 03 9;11(1):5494. Epub 2021 Mar 9.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

It is important to pay attention to the indirect effects of the social distancing implemented to prevent the spread of coronavirus disease 2019 (COVID-19) pandemic on children and adolescent health. The aim of the present study was to explore impacts of a reduction in physical activity caused by COVID-19 outbreak in pediatric patients diagnosed with obesity. This study conducted between pre-school closing and school closing period and 90 patients aged between 6- and 18-year-old were included. Comparing the variables between pre-school closing period and school closing period in patients suffering from obesity revealed significant differences in variables related to metabolism such as body weight z-score, body mass index z-score, liver enzymes and lipid profile. We further evaluated the metabolic factors related to obesity. When comparing patients with or without nonalcoholic fatty liver disease (NAFLD), only hemoglobin A1c (HbA1c) was the only difference between the two time points (p < 0.05). We found that reduced physical activity due to school closing during COVID-19 pandemic exacerbated obesity among children and adolescents and negatively affects the HbA1C increase in NAFLD patients compared to non-NAFLD patients.
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http://dx.doi.org/10.1038/s41598-021-84766-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943757PMC
March 2021

Transcriptome Analysis Reveals HgCl Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway.

Int J Mol Sci 2021 Feb 18;22(4). Epub 2021 Feb 18.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl treatment causes inhibition of cell growth via cell cycle arrest at G/G- and S-phase. In addition, HgCl induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl treatment. Altogether, these data show that HgCl induces apoptotic cell death through the dysfunction of mitochondria.
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http://dx.doi.org/10.3390/ijms22042006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922270PMC
February 2021

Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells.

Genes (Basel) 2021 02 11;12(2). Epub 2021 Feb 11.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

Bisphenol A (BPA) is a xenoestrogen chemical commonly used to manufacture polycarbonate plastics and epoxy resin and might affect various human organs. However, the cellular effects of BPA on the eyes have not been widely investigated. This study aimed to investigate the cellular cytotoxicity by BPA exposure on human retinoblastoma cells. BPA did not show cytotoxic effects, such as apoptosis, alterations to cell viability and cell cycle regulation. Comparative analysis of the transcriptome and proteome profiles were investigated after long-term exposure of Y79 cells to low doses of BPA. Transcriptome analysis using RNA-seq revealed that mRNA expression of the post-transcriptional regulation-associated gene sets was significantly upregulated in the BPA-treated group. Cell cycle regulation-associated gene sets were significantly downregulated by exposure to BPA. Interestingly, RNA-seq analysis at the transcript level indicated that alternative splicing events, particularly retained introns, were noticeably altered by low-dose BPA treatment. Additionally, proteome profiling using MALDI-TOF-MS identified a total of nine differentially expressed proteins. These results suggest that alternative splicing events and altered gene/protein expression patterns are critical phenomena affected by long-term low-dose BPA exposure. This represents a novel marker for the detection of various diseases associated with environmental pollutants such as BPA.
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http://dx.doi.org/10.3390/genes12020264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918513PMC
February 2021

Role of p53 in transcriptional repression of SVCT2.

Mol Biol Rep 2021 Feb 12;48(2):1651-1658. Epub 2021 Feb 12.

Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.

SVCT2, Sodium-dependent Vitamin C Transporter 2, uniquely transports ascorbic acid (also known as vitamin C and ascorbate) into all types of cells. Vitamin C is an essential nutrient that must be obtained through the diet and plasma levels are tightly regulated by transporter activity. Vitamin C plays an important role in antioxidant defenses and is a cofactor for many enzymes that enable hormone synthesis, oxygen sensing, collagen synthesis and epigenetic pathways. Although SVCT2 has various functions, regulation of its expression/activity remains poorly understood. We found a p53-binding site, within the SVCT2 promoter, using a transcription factor binding-site prediction tool. In this study, we show that p53 can directly repress SVCT2 transcription by binding a proximal- (~-185 to -171 bp) and a distal- (~-1800 to -1787 bp) p53-responsive element (PRE), Chromatin immunoprecipitation assays showed that PRE-bound p53 interacts with the corepressor-histone deacetylase 3 (HDAC3), resulting in deacetylation of histones Ac-H4, at the proximal promoter, resulting in transcriptional silencing of SVCT2. Overall, our data suggests that p53 is a potent transcriptional repressor of SVCT2, a critical transporter of diet-derived ascorbic acid, across the plasma membranes of numerous essential tissue cell types.
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http://dx.doi.org/10.1007/s11033-021-06179-2DOI Listing
February 2021

Clinical brightening efficacy and safety of Melasolv™ (3,4,5-trimethoxy cinnamate thymol ester, TCTE) in Southeast Asian women.

J Cosmet Dermatol 2021 Feb 2. Epub 2021 Feb 2.

AMOREPACIFIC Research and Development Center, Gyeonggi-do, Korea.

Background: Skin darkening because of increased and irregular synthesis of melanin causes melasma, solar lentigo, and freckles. Melasolv™, produced in the early 2000s, shows potent depigmenting effect and has low cytotoxicity. It has been used as a brightening agent in cosmetics for decades.

Aims: This study was conducted to investigate whether Melasolv™ is effective for the skin of ASEAN (Southeast Asia) women.

Methods: We recruited ASEAN women in Singapore and divided them into two groups (active group vs. placebo group). Melasolv and placebo formulations were applied twice a day for 12 weeks. The changes in the pigmented spots were visually evaluated by an expert and assessed using a spectrophotometer and Mexameter at 0, 4, 8, and 12 weeks.

Results: The visual evaluation revealed significant improvements, in both size and color intensity, in the active group compared with those in the placebo group at 12 weeks. In the spectrophotometric evaluation, the L* value of the pigmented spots in the active group was significantly higher than that in the placebo group at 12 weeks. Similar results were obtained in the evaluation using the Mexameter. After 12 weeks, the melanin index of the pigmented spots significantly decreased, and it was significantly higher than that in the placebo group. There was no significant change in the erythema index. In the image analysis, there were no significant differences in skin color brightness and evenness in the active group compared with those in the placebo group.

Conclusion: Melasolv can be effective used for skin brightening.
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http://dx.doi.org/10.1111/jocd.13969DOI Listing
February 2021

Predictive Parameters of Decreased Left Ventricular Global Longitudinal Strain at 1 Month After Pediatric Heart Transplantation.

Pediatr Cardiol 2021 Apr 19;42(4):784-792. Epub 2021 Jan 19.

Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-Gil, Songpa-Gu, Seoul, 138-736, Republic of Korea.

Previous reports indicate that the decreased left ventricular global longitudinal strain (LVGLS) seen in the early postoperative period of pediatric heart transplant patients generally recovers over the course of 1-2 years. In this study, we investigate the predictive capacity of preoperative parameters on the LVGLS decline seen at 1 month post transplant. Forty-six transplant subjects with 2D echocardiographic images sufficient for speckle tracking echocardiography were enrolled. We excluded patients diagnosed with cardiac allograft vasculopathy or with an episode of rejection 1 month before or after their echocardiographic examinations. The mean LVGLS was significantly reduced at 1 month when compared to 1 year following transplant (- 15.5% vs. - 19.4%, respectively, p < 0.001). The predictors of LVGLS that decline at 1 month were the LV mass z-score [odds ratio (OR) 1.452; 95% confidence interval (CI) 1.007-2.095, p = 0.046], recipient age (OR 1.124; 95% CI 1.015-1.245, p = 0.025), and donor age (OR 1.081; 95% CI 1.028-1.136, p = 0.002) in the univariate logistic regression analyses. Although multivariate analysis yielded no significant predictors, higher LV mass z-scores showed a trend associated with the decline of LVGLS (p = 0.087). The donor/recipient weight ratio was associated with the LV mass z-score (R = 0.412, p < 0.001).
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http://dx.doi.org/10.1007/s00246-021-02542-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814263PMC
April 2021

Individual approach for treatment of primary intestinal lymphangiectasia in children: single-center experience and review of the literature.

BMC Pediatr 2021 01 7;21(1):21. Epub 2021 Jan 7.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

Background: Intestinal lymphangiectasia is a rare disease. Thus, prospective studies are impossible, and therapy is still controversial. Several medicines are suggested for treatment but there are no existing indications for drug choice and treatment guidelines. We aimed to introduce the action mechanism of each drug and treatment overview in a single-center experience and a review of the literature on second-line therapy for primary intestinal lymphangiectasia.

Method: Children under 18 years old diagnosed with intestinal lymphangiectasia from June 2000 to June 2020 were included and retrospectively reviewed in the study. Capsule endoscopy, MR lymphangiography, or whole-body MRI for investigating the extent of abnormal lymphatic vessels in addition to endoscopy and biopsy were conducted. The individual treatment approaches depended upon the lymphangiectasis locations involved.

Results: Only one patient showed a response to dietary therapy. One patient was successfully cured after two therapeutic lymphatic embolization. Octreotide was tried for two patients who had extensive lymphangiectasis. Lymphangiectasis recurred when octreotide was used for 3 months in one patient, and there was no effect in the other patient. Sirolimus was tried for four patients. Two of them had abnormal lymphatic lesions only in the intestine, and the others had extensive lymphangiectasis. The former group showed clinical improvement after 3-4 months of sirolimus treatment, whereas the latter group showed clinical improvement only after 1 month of sirolimus treatment.

Conclusion: Surgery or embolization is a potential therapeutic option for patients with focal abnormal lymphatic lesions. Octreotide is not an optimal choice for patients with extensive lymphangiectasis. Sirolimus is an effective and safe drug and can be the first drug of choice for patients with extensive lymphangiectasis.
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http://dx.doi.org/10.1186/s12887-020-02447-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789338PMC
January 2021

Anti- Antibody in Pediatric Crohn's Disease Patients without Mucosal Healing Is a Useful Marker of Mucosal Damage.

Gut Liver 2020 Dec 30. Epub 2020 Dec 30.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background/aims: We evaluated whether anti-Saccharomyces cerevisiae antibody (ASCA) titers are associated with diagnostic findings, disease activity, Paris classification phenotypes, and persistence after infliximab (IFX) treatment in children with Crohn's disease (CD). We also investigated the role of ASCA as a predictor of mucosal healing (MH) and clinical remission (CR).

Methods: This study included 61 CD patients aged 19 years or younger who were diagnosed and treated between September 2010 and January 2019 and followed for at least 1 year. ASCA was regularly measured at the diagnosis of CD and at least 1 year after IFX therapy.

Results: The average follow-up period was 3.8±3.4 years (range, 1.0 to 7.2 years). Regression analysis showed that the ASCA titer was the only factor associated with Simple Endoscopic Score for Crohn's Disease (SES-CD) or CR among all the parameters. In patients who had achieved MH (SES-CD=0), ASCA immunoglobulin G (IgG) was not associated with MH, but in patients without MH, ASCA IgG was associated with SES-CD (p=0.005) and CR (p<0.001). The cutoff value of ASCA IgG in patients with CR was 21.8 units. However, there was no difference in the relapse rate between the ASCA IgG-positive and -negative groups during the follow-up period.

Conclusions: In patients who have not achieved MH, ASCA IgG is closely related to mucosal damage and CR. Unlike western studies, ASCA IgG may be more helpful in predicting prognosis than IgA in Korean patients, but it is not an appropriate indicator to predict the relapse of CD.
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http://dx.doi.org/10.5009/gnl20212DOI Listing
December 2020

Comparison of the Clinical Outcomes between Angiojet Pharmacomechanical Thrombectomy and Hybrid Surgical Thrombectomy for Thrombotic Occlusion of Hemodialysis Access.

Vasc Specialist Int 2020 Dec;36(4):241-247

Division of Vascular Surgery, Department of Surgery, Presbyterian Medical Center, Jeonju, Korea.

Purpose: This retrospective study aimed to compare the clinical outcomes between hybrid surgical thrombectomy (ST) and AngioJet pharmacomechanical thrombectomy (PMT) for thrombotic occlusion of arteriovenous graft.

Materials And Methods: This study enrolled patients who underwent either hybrid ST or AngioJet PMT in Presbyterian Medical Center from July 2018 to December 2018. We primarily compared the technical and clinical success rates between the two groups immediately after the procedures. Subsequently, the postprocedure clinical outcomes, including the primary and secondary patency rates and complications, were also compared.

Results: The hybrid ST group had a significantly higher bleeding amount than the AngioJet PMT group (P=0.02). The technical and clinical success rates were 96.7% and 93.3% in the AngioJet PMT group and 100% and 100% in the hybrid ST group, respectively. There was no significant difference in complications between the groups. The primary and secondary patencies at 12 months were not statistically different between the groups.

Conclusion: Comparable clinical outcomes were observed between the AngioJet PMT and hybrid ST groups, highlighting an equivalent efficacy of these two methods. Although the cost is more expensive, AngioJet PMT lowered the bleeding amount. Therefore, it can be considered in selected patients who are at risk of bleeding or reluctant to surgery.
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http://dx.doi.org/10.5758/vsi.200052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790690PMC
December 2020

The Identification of a Novel Thiopurine S-Methyltransferase Allele, , in Korean Patient with Crohn's Disease.

Pharmgenomics Pers Med 2020 26;13:665-671. Epub 2020 Nov 26.

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Pediatric Crohn's disease (CD) carries a higher genetic susceptibility and an increased risk of a more aggressive disease course than adult CD. Treatment of CD is based on immunomodulatory drugs, such as thiopurines. The enzyme mainly involved in drug metabolism is thiopurine S-methyltransferase (TPMT). An increased concentration of drug metabolites can cause adverse drug effects, such as myelosuppression and hepatotoxicity; therefore, assessing the activity of TPMT is essential both before and during treatment. genotyping result is not affected by previous thiopurine dose and currently is the primary component of TPMT activity and disease monitoring. Until now, more than 40 allelic variants of the gene have been reported, with most of them having an uncertain or no enzyme function. In this article, we report the first case of a novel allele, , that was identified in a Korean girl with CD whose findings suggested decreased TPMT activity. This newly observed variant is caused by a single nucleotide polymorphism resulting in nonsense mutation (c.676C>T, p.R226*) and the partial loss of amino acids in the TPMT protein. Initially, the patient began azathioprine at a standard dosage (1.5 mg/kg/day), and her laboratory results, including red blood cell (RBC) TPMT activity (6-methylmercaptopurine 2.68 nmol/mL/h and 6-methylmercaptopurine riboside 4.82 nmol/mL/h) along with thiopurine metabolite levels (6-thioguanine nucleotides 479.3 pmol/8×10 RBC), suggested an enzyme deficiency. The thiopurine dose was reduced to half (0.7 mg/kg/day), and the follow-up metabolite results as well as the associated inflammatory markers were continuously within reference ranges. Along with an improvement in the patient's subjective reports and clinical symptoms, the patient demonstrated a good treatment response to the adjusted dose. The results of our report illustrate the importance of genotyping and pharmacogenetic-based thiopurine dose adjustment. Further research should focus on the functional characterization and impact on this novel allele's treatment effect.
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http://dx.doi.org/10.2147/PGPM.S279446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705256PMC
November 2020

Upper gastrointestinal tract involvement is more prevalent in Korean patients with pediatric Crohn's disease than in European patients.

Sci Rep 2020 11 4;10(1):19032. Epub 2020 Nov 4.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.

In pediatric Crohn's disease (CD) patients, it is important to define the disease phenotype at diagnosis for stratifying risk. In this retrospective study, we aimed to assess the disease phenotype compared to EUROKIDS registry and analyze disease outcome of pediatric CD patients according to upper gastrointestinal (GI) tract involvement. A total of 312 patients were included. The median age at diagnosis was 13.7 years and 232 patients (74.4%) were identified to have upper GI involvement at diagnosis. In Korean pediatric CD patients, there were significant differences in male predominance (72.8% vs. 59.2, p < 0.001), proportion of upper GI involvement (74.4% vs. 46.2%, p < 0.001), and perianal disease (62.1% vs. 8.2%, p < 0.001) compared to data in the EUROKIDS registry. Younger age (OR 2.594, p = 0.0139) and ileal involvement (OR 2.293, p = 0.0176) at diagnosis were associated with upper GI involvement. There were no significant differences in disease outcomes between patients with and without upper GI tract involvement. This study revealed that upper GI involvement is more prevalent in Korean patients with pediatric Crohn's disease than in European patients, and the disease outcome did not appear to differ according to upper GI tract involvement.
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http://dx.doi.org/10.1038/s41598-020-75938-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642352PMC
November 2020

Pediatric Crohn's disease with severe morbidity manifested by gastric outlet obstruction: two cases report and review of the literature.

Intest Res 2020 Oct 29. Epub 2020 Oct 29.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Crohn's disease (CD) presenting as gastric outlet obstruction is rare but serious clinical presentation of CD causing severe morbidity. However, there have been few case reports concerning this disorder in East Asian children and adolescents. The current case report describes 2 pediatric patients with CD who had had gastric outlet obstruction as an initial symptom of CD. Two pediatric patients developed postprandial vomiting, bloating, and unintentional weight loss. The upper endoscopy result indicated that there was pyloric obstruction with mucosal edema, inflammation and ulcers. The serologic test and colonoscopy results suggested CD. These patients were treated with infliximab, and endoscopic balloon dilation without surgery and showed remarkable improvement in obstructing symptoms with maintaining clinical and biochemical remission. This case report elucidates the benefits of early intervention using infliximab and endoscopic balloon dilation to improve gastric outlet obstruction and achieve baseline recovery in patients with upper gastrointestinal B2 phenotype of CD.
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http://dx.doi.org/10.5217/ir.2020.00072DOI Listing
October 2020

Fursultiamine Alleviates Choroidal Neovascularization by Suppressing Inflammation and Metabolic Reprogramming.

Invest Ophthalmol Vis Sci 2020 10;61(12):24

Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Kyungpook National University, Daegu, Republic of Korea.

Purpose: To assess the therapeutic effects of fursultiamine on choroidal neovascularization (CNV) through its modulation of inflammation and metabolic reprogramming in the retinal pigment epithelium (RPE).

Methods: The anti-angiogenic effects of fursultiamine were assessed by measuring vascular leakage and CNV lesion size in the laser-induced CNV mouse model. Inflammatory responses were evaluated by quantitative polymerase chain reaction, western blot, and ELISA in both CNV eye tissues and in vitro cell cultures using ARPE-19 cells or primary human RPE (hRPE) cells under lipopolysaccharide (LPS) treatment or hypoxia. Mitochondrial respiration was assessed by measuring oxygen consumption in ARPE-19 cells treated with LPS with or without fursultiamine, and lactate production was measured in ARPE-19 cells subjected to hypoxia with or without fursultiamine.

Results: In laser-induced CNV, fursultiamine significantly decreased vascular leakage and lesion size, as well as the numbers of both choroidal and retinal inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α. In LPS-treated ARPE-19 cells, fursultiamine decreased proinflammatory cytokine secretion and nuclear factor kappa B phosphorylation. Furthermore, fursultiamine suppressed LPS-induced upregulation of IL-6, IL-8, and monocyte chemoattractant protein-1 in a dose-dependent and time-dependent manner in primary hRPE cells. Interestingly, fursultiamine significantly enhanced mitochondrial respiration in the LPS-treated ARPE-19 cells. Additionally, fursultiamine attenuated hypoxia-induced aberrations, including lactate production and inhibitory phosphorylation of pyruvate dehydrogenase. Furthermore, fursultiamine attenuated hypoxia-induced VEGF secretion and mitochondrial fission in primary hRPE cells that were replicated in ARPE-19 cells.

Conclusions: Our findings show that fursultiamine is a viable putative therapeutic for neovascular age-related macular degeneration by modulating the inflammatory response and metabolic reprogramming by enhancing mitochondrial respiration in the RPE.
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http://dx.doi.org/10.1167/iovs.61.12.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594589PMC
October 2020

Delayed Establishment of Gut Microbiota in Infants Delivered by Cesarean Section.

Front Microbiol 2020 11;11:2099. Epub 2020 Sep 11.

Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South Korea.

The maternal vaginal microbiome is an important source for infant gut microbiome development. However, infants delivered by Cesarean section (CS) do not contact the maternal vaginal microbiome and this delivery method may perturb the early establishment and development of the gut microbiome. The aim of this study was to investigate the early gut microbiota of Korean newborns receiving the same postpartum care services for two weeks after birth by delivery mode using fecal samples collected at days 3, 7, and 14. Early gut microbiota development patterns were examined using 16S rRNA gene-based sequencing from 132 infants either born vaginally (VD, = 64) or via Cesarean section (CS, = 68). VD-born neonates showed increased alpha diversity in infant fecal samples collated at days 7 and 14 compared to those from day 3, while those of CS infants did not differ ( < 0.015). Bacterial structures of infants from both groups separated at day 7 ( < 0.001) and day 14 ( < 0.01). The bacterial structure of VD infants gradually changed over time (day 3 vs. day 7, < 0.012; day 3 vs. day 14, < 0.001). Day 14 samples of CS infants differed from day 3 and 7 samples (day 3 vs. day 14, < 0.001). VD infant relative abundance of (days 7, 14), (days 7, 14), and (day 7) significantly increased compared to CS infants, with a lower abundance of (found in all periods of the CS group) (LDA > 3.0). Relative abundances of , , and were significantly increased in both VD and CS groups at day 14 (LDA > 3.0). Predicted functional analysis showed that VD infants had overrepresented starch/sucrose, amino acid and nucleotide metabolism in gut microbiota with depleted lipopolysaccharide biosynthesis until day 14 compared to CS infants. This study confirmed that delivery mode is the major determinant of neonatal intestinal microbiome establishment and provides a profile of microbiota perturbations in CS infants. Our findings provide preliminary insight for establishing recovery methods to supply the specific microbes missing in CS infants.
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http://dx.doi.org/10.3389/fmicb.2020.02099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516058PMC
September 2020

Correction: Autophagy induction by leptin contributes to suppression of apoptosis in cancer cells and xenograft model: Involvement of p53/FoxO3A axis.

Oncotarget 2020 Jul 28;11(30):2956-2957. Epub 2020 Jul 28.

College of Pharmacy, Yeungnam University, Gyeongsangbuk-do, Republic of Korea.

[This corrects the article DOI: 10.18632/oncotarget.3347.].
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http://dx.doi.org/10.18632/oncotarget.27467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392625PMC
July 2020

Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell.

Diabetes Metab J 2021 Mar 10;45(2):260-269. Epub 2020 Jul 10.

Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.

Background: Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.

Methods: Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.

Results: Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.

Conclusion: UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.
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http://dx.doi.org/10.4093/dmj.2019.0191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024157PMC
March 2021

Myositis as an Initial Presentation of Ulcerative Colitis before Gastrointestinal Symptoms.

Pediatr Gastroenterol Hepatol Nutr 2020 May 8;23(3):297-303. Epub 2020 May 8.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The musculoskeletal system can be involved as an extra-intestinal manifestation of inflammatory bowel disease. Among these, myositis in ulcerative colitis (UC) is very rare. A 14-year-old girl was admitted due to severe shoulder tenderness. She had complained of left jaw pain and swelling for the past 10 days. Inflammatory markers were elevated with no evidence of infectious etiology. Myositis was suspected by shoulder magnetic resonance imaging. Three days after admission, she developed hematochezia. Muscle biopsy and colonoscopy was performed due to worsening left mandibular area pain and persistent hematochezia. Colonoscopy showed consistent findings with UC. She was finally diagnosed with UC with myositis as an extra-intestinal manifestation. She showed a dramatic response to UC treatment. Gastrointestinal symptoms were well-controlled. After 14 months, UC symptoms and muscle pain were aggravated, which were relieved after steroid and cyclosporin treatment. We report a unique case of UC initially presented with myositis, preceding gastrointestinal symptoms.
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http://dx.doi.org/10.5223/pghn.2020.23.3.297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231739PMC
May 2020