Publications by authors named "Jeong-Wook Seo"

76 Publications

Necessity of Assessing Biological Exposure to Arsenic Species by Two Representative Analytical Methods.

Toxics 2021 Jun 11;9(6). Epub 2021 Jun 11.

Environmental Health Center, Dong-A University, Busan 49201, Korea.

Arsenic (As) exists as highly toxic chemical species. Chronic exposure to its inorganic form can cause multiple organ failure and skin cancer in humans, warranting the need to determine the toxicity of each chemical species. This study evaluated the proportions of exposure to four chemical species of As (cAs), namely arsenite (AsIII), arsenate (AsV), monomethylarsinic acid (MMA), and dimethylarsenic acid (DMA), and it confirmed the necessity of evaluating biological exposure to cAs. Urine samples were collected from 457 subjects residing near 103 abandoned metal mines. Hydride generation atomic absorption spectroscopy (HG-AAS) was performed to measure the combined concentration of four cAs (hAs). High-performance liquid chromatography and inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) were performed to determine the concentrations of the individual cAs and the sum of the four cAs (hAs). The proportions of AsV and MMA were relatively higher in the low-hAs concentration section. These findings suggest that hAs, which is mainly used for its cost-efficiency, is limited for evaluating exposure. Though hAs was found to exist in a low concentration, highly toxic AsV and MMA could be observed in high concentrations. Therefore, HPLC-ICP-MS is recommended for assessing cAs in environmentally vulnerable areas such as abandoned metal mines.
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http://dx.doi.org/10.3390/toxics9060138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230710PMC
June 2021

Assessment of Lead and Mercury Exposure Levels in the General Population of Korea Using Integrated National Biomonitoring Data.

Int J Environ Res Public Health 2021 Jun 28;18(13). Epub 2021 Jun 28.

Environmental Health Center, Dong-A University, Busan 49201, Korea.

In Korea, the estimated values of blood lead (Pb) and mercury (Hg) levels differ between two national-level biomonitors, namely the Korean National Environmental Health Survey and the Korea National Health and Nutrition Examination Survey. The present study used integrated data from these surveys to estimate the representative values of the change in concentration and recent distribution characteristics. The yearly trend of age-standardized exposure levels in regular adults was identified, and the geometric mean (GM) adjusted according to demographic characteristics was presented. Age-standardized GM for blood Pb and Hg in the integrated data was 2.06 and 3.64 μg/L in 2008, respectively, which decreased to 1.55 and 2.92 μg/L, respectively, by 2017. Adjusted GMs from most recently conducted surveys (2015-2017) were 1.61 and 2.98 μg/L for blood Pb and Hg, respectively. In particular, the adjusted percentage of blood Hg exceeding the reference value of 5 μg/L was 20.79%. While the blood Pb and Hg exposure levels are decreasing in Korea, the levels remain high relative to those in other countries. The Hg levels exceeded the reference value in many individuals. Therefore, continued biomonitoring must be conducted, and a reduction plan and exposure management are needed for harmful metals, including Hg.
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http://dx.doi.org/10.3390/ijerph18136932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297126PMC
June 2021

Feasibility study on stereotactic radiotherapy for total pulmonary vein isolation in a canine model.

Sci Rep 2021 Jun 11;11(1):12369. Epub 2021 Jun 11.

Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33 Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural fibrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.
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http://dx.doi.org/10.1038/s41598-021-91660-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196028PMC
June 2021

Early Changes in Rat Heart After High-Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation.

J Am Heart Assoc 2021 Mar 4;10(6):e019072. Epub 2021 Mar 4.

Department of Radiation Oncology Seoul National University College of Medicine Seoul Korea.

Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early-period antiarrhythmic effects induced by high-dose irradiation are unknown. This study investigated dose-responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild-type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks' postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high-dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose-responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell-related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high-dose irradiation. ECG indicated intracardiac conduction delay with prominent ST-segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.
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http://dx.doi.org/10.1161/JAHA.120.019072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174197PMC
March 2021

Effects of Exposure to Lead and Cadmium on Health of Inhabitants of Abandoned Metal Mine Area in Korea.

Arch Environ Contam Toxicol 2021 Feb 6;80(2):490-498. Epub 2021 Feb 6.

College of Medicine, Chung-Ang University, Seoul, Korea.

People living near abandoned mines are at increased risk of exposure to toxic metals. We surveyed 4500 inhabitants with the mean age of 68.5 years old (male: 1768, female: 2732) living near 104 abandoned metal mines from 2013 to 2017 (the 2nd phase health survey in Korea). We conducted personal interviews, blood and urine sampling, and analyzed the concentrations of lead (Pb) and cadmium (Cd) in whole blood and Cd in urine using a graphite furnace atomic absorption spectrometer. The geometric means of blood Pb, blood Cd, and urine Cd were 2.27 μg/dL, 1.42 μg/L, and 1.66 μg/g creatinine, respectively. The level of metal exposure was lower than that reported from the first phase health survey in Korea (2008‒2011) but was higher than in the general population of Korea. Blood Pb was higher in males while blood Cd and urine Cd were significantly higher in females. Blood Pb was highest in the 40‒59 age group, while blood and urine Cd levels continuously increased until age 80 or older. The Cd levels in blood and urine were affected by consumption of locally produced rice and duration of residence near abandoned mines. Furthermore, negative correlations were observed between blood Pb and blood and urine Cd levels. Additionally, 252 of the 4500 subjects exceeded the thresholds of blood Cd or urine Cd levels. Together, these findings suggest that Cd has more sustainable and adverse health effects on the abandoned mine inhabitants, who are mostly aged. Therefore, continuous biomonitoring and risk assessment to environmental health risks are necessary for environmental pollution control and health promotion.
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http://dx.doi.org/10.1007/s00244-021-00813-7DOI Listing
February 2021

Visualization of left ventricular Purkinje fiber distribution using widefield optical coherence microscopy.

Int J Clin Exp Pathol 2020 1;13(12):3013-3020. Epub 2020 Dec 1.

Department of Internal Medicine, Seoul National University Hospital Seoul, South Korea.

Background: The distribution and connection of ventricular Purkinje fibers are known to be associated with idiopathic left ventricular arrhythmias. Unusual anatomy is one of the important factors associated with catheter ablation success rate. With the widefield high-speed, swept-source optical coherence microscopy (OCM) and light microscope, we visualized the left ventricular Purkinje fiber distribution.

Methods: Left ventricular walls of five adult ovine hearts were incised from the mitral annulus to the apex. Using the widefield OCM technique and light microscopy, we observed the distribution, direction, depth, and dividing patterns of the Purkinje network with multiple tangential angles and without tissue destruction.

Results: Widefield OCM was used to characterize the ovine heart Purkinje network system in a 4 × 4 mm field. Left ventricular Purkinje fibers traveled in the sub-endocardial area near the left-sided peri-membranous septal area and ran like a wide hair bundle. The distal branching fibers penetrated to the endocardium and connected to the contractile muscle. In this distal area, Purkinje fibers were connected to each other, forming multiple layers. Some Purkinje fibers were directly connected within the false tendon between the papillary muscles or between the trabeculations. Some free-running Purkinje fibers were directly connected to the papillary muscle from the left bundle.

Conclusion: Using widefield OCM, we were able to observe the left bundle and its branching patterns in ovine left ventricle without tissue destruction. This might be applied to future cardiac ablation procedures.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791375PMC
December 2020

Cell-Laden Gelatin Methacryloyl Bioink for the Fabrication of Z-Stacked Hydrogel Scaffolds for Tissue Engineering.

Polymers (Basel) 2020 Dec 17;12(12). Epub 2020 Dec 17.

Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul 05029, Korea.

Hydrogel-based scaffolds have been widely used to fabricate artificial tissues capable of replacing tissues and organs. However, several challenges inherent in fabricating tissues of large size and complex morphology using such scaffolds while ensuring cell viability remain. To address this problem, we synthesized gelatin methacryloyl (GelMA) based bioink with cells for fabricating a scaffold with superior characteristics. The bioink was grafted onto a Z-stacking bioprinter that maintained the cells at physiological temperature during the printing process, without exerting any physical pressure on the cells. Various parameters, such as the bioink composition and light exposure time, were optimized. The printing accuracy of the scaffolds was evaluated using photorheological studies. The internal morphology of the scaffolds at different time points was analyzed using electron microscopy. The Z-stacked scaffolds were fabricated using high-speed printing, with the conditions optimized to achieve high model reproducibility. Stable adhesion and high proliferation of cells encapsulated within the scaffold were confirmed. We introduced various strategies to improve the accuracy and reproducibility of Z-stack GelMA bioprinting while ensuring that the scaffolds facilitated cell adhesion, encapsulation, and proliferation. Our results demonstrate the potential of the present method for various applications in tissue engineering.
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http://dx.doi.org/10.3390/polym12123027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767119PMC
December 2020

Injectable hydrogel derived from chitosan with tunable mechanical properties via hybrid-crosslinking system.

Carbohydr Polym 2021 Jan 6;251:117036. Epub 2020 Sep 6.

Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul, 05029, Republic of Korea. Electronic address:

Thermo-sensitive injectable hydrogels that spontaneously react to physiological temperature have been widely studied to be used in biomedical fields. However, several challenges on their unstable structures with large-sized pores and low mechanical strength under physiological conditions must be addressed to enable their practical applications. We synthesized the hydroxybutyl methacrylated chitosan (HBC-MA) hydrogel that possesses both thermo-sensitive and photo-crosslinkable properties. The HBC-MA showed effective sol-gel transition under physiological temperature as well as a sensitive photo-crosslinkable property with visible light capable of skin penetration. The co-nonsolvency property and thermo-sensitivity of HBC-MA prevented unintended loss of the hydrogel graft after being subcutaneously injected in mice. Subsequently applied visible light on the skin beneath which the hydrogel was injected significantly improved the mechanical strength and stability of the graft. The injectable HBC-MA hydrogel developed in this study can be applicable to a wide range of biomedical fields such as drug delivery system and tissue engineering.
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http://dx.doi.org/10.1016/j.carbpol.2020.117036DOI Listing
January 2021

Kappa-Carrageenan-Based Dual Crosslinkable Bioink for Extrusion Type Bioprinting.

Polymers (Basel) 2020 Oct 15;12(10). Epub 2020 Oct 15.

KU Convergence Science and Technology Institute, Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea.

Bioink based 3D bioprinting is a promising new technology that enables fabrication of complex tissue structures with living cells. The printability of the bioink depends on the physical properties such as viscosity. However, the high viscosity bioink puts shear stress on the cells and low viscosity bioink cannot maintain complex tissue structure firmly after the printing. In this work, we applied dual crosslinkable bioink using Kappa-carrageenan (κ-CA) to overcome existing shortcomings. κ-CA has properties such as biocompatibility, biodegradability, shear-thinning and ionic gelation but the difficulty of controlling gelation properties makes it unsuitable for application in 3D bioprinting. This problem was solved by synthesizing methacrylated Kappa-carrageenan (MA-κ-CA), which can be dual crosslinked through ionic and UV (Ultraviolet) crosslinking to form hydrogel using NIH-3T3 cells. Through MA substitutions, the rheological properties of the gel could be controlled to reduce the shear stress. Moreover, bioprinting using the cell-laden MA-κ-CA showed cell compatibility with enhanced shape retention capability. The potential to control the physical properties through dual crosslinking of MA-κ-CA hydrogel is expected to be widely applied in 3D bioprinting applications.
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http://dx.doi.org/10.3390/polym12102377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602869PMC
October 2020

Serial ultrastructural evaluation of myocardial ischemic injury after infusion of del Nido cardioplegia in the human heart.

J Thorac Cardiovasc Surg 2020 Sep 1. Epub 2020 Sep 1.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Republic of Korea.

Objectives: The safe ischemic time after a single-dose del Nido cardioplegia (DNC) infusion has not yet been established. This study evaluated the progression of myocardial ischemic injury to establish the safe ischemic time after a single-dose DNC infusion in the human heart using a transmission electron microscope.

Methods: Seven hearts extracted from heart transplant recipients after infusion of 1000 mL single-dose DNC were evaluated. Serial left ventricular myocardial tissue samples were collected every 30 minutes for 180 minutes. Ischemic injuries in the mitochondria and nuclei were scored from 0 to 3 (0 = normal, 0.5 = slight, 1 = moderate, 2 = severe, and 3 = irreversible).

Results: At the time of extraction, 83.5% of the mitochondria were normal. The proportion of mitochondria with moderate ischemic injury increased gradually from 1.4% at extraction to 52.5% at 180 minutes. From 90 minutes to 180 minutes, the proportion of mitochondria with severe and irreversible injury increased from 0.8% to 4.4% and 0.3% to 1.3%, respectively. A significant linear correlation was identified between the average ischemic injury score of mitochondria and ischemic time (P < .001). Most nuclei showed moderate to severe ischemic injury at every time point (61.0%-85.2%). A significant linear correlation was also found between the average ischemic injury score of nuclei and ischemic time (P < .001).

Conclusions: Myocardial ischemic injury progresses gradually, and irreversible ischemic injury begins to occur 90 minutes after initial DNC infusion in the adult human heart. Therefore, redosing of DNC may be required after 90 minutes of aortic crossclamp time during adult cardiac surgery.
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http://dx.doi.org/10.1016/j.jtcvs.2020.08.083DOI Listing
September 2020

Comparative Evaluation of Heavy Metal Concentrations in Residents of Abandoned Metal Mines.

Int J Environ Res Public Health 2020 08 28;17(17). Epub 2020 Aug 28.

Environmental Health Center, Dong-A University, Busan 49201, Korea.

This study compares the heavy metal exposure levels of the population of abandoned metal mines, with high risks of environmental pollution and health effects. We used data from a two-stage abandoned metal mines survey (AMS, n = 4467). The Korea National Health and Nutrition Examination Survey (KNHANES) and the Korea National Environmental Health Survey (KNEHS) were used as general population data. Based on the sex and age distribution in the AMS, a simple random sampling was performed, so that the two datasets had the same distribution (KNHANES n = 1815, KNEHS n = 2328). Blood lead concentrations were slightly higher in the AMS than in KNEHS. Blood cadmium concentrations were similar between the two groups. However, the difference in urine cadmium concentrations was pronounced and statistically significant. Moreover, 30.6% of the AMS data for urine cadmium concentration exceeded the 95th percentile of the KNEHS data. The concentration of lead and cadmium in the residents of the abandoned metal mines, i.e., the vulnerable regions, was higher than that in the general population. It is necessary to monitor and manage the vulnerable regions via a more active and extensive survey system.
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http://dx.doi.org/10.3390/ijerph17176280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503294PMC
August 2020

Indirect pathological indicators for cardiac sarcoidosis on endomyocardial biopsy.

J Pathol Transl Med 2020 Sep 29;54(5):396-410. Epub 2020 Jul 29.

Department of Pathology, Sejong Hospital, Bucheon, Korea.

Background: The definitive pathologic diagnosis of cardiac sarcoidosis requires observation of a granuloma in the myocardial tissue. It is common, however, to receive a "negative" report for a clinically probable case. We would like to advise pathologists and clinicians on how to interpret "negative" biopsies.

Methods: Our study samples were 27 endomyocardial biopsies from 25 patients, three cardiac transplantation and an autopsied heart with suspected cardiac sarcoidosis. Pathologic, radiologic, and clinical features were compared.

Results: The presence of micro-granulomas or increased histiocytic infiltration was always (6/6 or 100%) associated with fatty infiltration and confluent fibrosis, and they showed radiological features of sarcoidosis. Three of five cases (60%) with fatty change and confluent fibrosis were probable for cardiac sarcoidosis on radiology. When either confluent fibrosis or fatty change was present, one-third (3/9) were radiologically probable for cardiac sarcoidosis. We interpreted cases with micro-granuloma as positive for cardiac sarcoidosis (five of 25, 20%). Cases with both confluent fibrosis and fatty change were interpreted as probable for cardiac sarcoidosis (seven of 25, 28%). Another 13 cases, including eight cases with either confluent fibrosis or fatty change, were interpreted as low probability based on endomyocardial biopsy.

Conclusions: The presence of micro-granuloma could be an evidence for positive diagnosis of cardiac sarcoidosis. Presence of both confluent fibrosis and fatty change is necessary for probable cardiac sarcoidosis in the absence of granuloma. Either of confluent fibrosis or fatty change may be an indirect pathological evidence but they are interpreted as nonspecific findings.
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http://dx.doi.org/10.4132/jptm.2020.06.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483025PMC
September 2020

The Relationship between Mercury Exposure Indices and Dietary Intake of Fish and Shellfish in Women of Childbearing Age.

Int J Environ Res Public Health 2020 07 7;17(13). Epub 2020 Jul 7.

Environmental Health Center, Dong-A University, Busan 49201, Korea.

Women of childbearing age who are susceptible to mercury exposure were studied to understand the relation between mercury intake through fish and shellfish consumption and mercury exposure indices from blood, hair, and urine samples. A total of 711 women of childbearing age from coastal areas with a high concentration of mercury exposure in Korea were studied. Data were collected on demographic characteristics, dietary intake of fish and shellfish using the simple Food Frequency Questionnaire. Mercury concentration was estimated from the collected samples of blood, hair, and urine. The geometric mean of blood methyl mercury concentration of mercury exposure through seafood was 3.06 μg/L for the low tertile, 3.12 μg/L for the middle tertile, and 3.60 μg/L for the high tertile, indicating a clear tendency of blood methyl mercury to increase as the mercury exposure by fish and shellfish intake ascended. For total blood mercury and hair mercury, the middle and high tertiles had higher values than the low. Mercury exposure through fish and shellfish intake is a main factor for an increase of blood methyl mercury concentration in women of childbearing age. More attention needs to be paid to mercury exposure through seafood intake, considering the serious effect mercury concentration has on women of childbearing age.
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http://dx.doi.org/10.3390/ijerph17134907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370192PMC
July 2020

Hydrogel Production Platform with Dynamic Movement Using Photo-Crosslinkable/Temperature Reversible Chitosan Polymer and Stereolithography 4D Printing Technology.

Tissue Eng Regen Med 2020 08 21;17(4):423-431. Epub 2020 May 21.

Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul, 05029, Republic of Korea.

Background: Three-dimensional (3D) printing using hydrogel has made great strides when it comes to mimicking 3D artificial tissue in the medical field. However, most structures do not mimic the dynamic movement of the tissues. Without imitating dynamic movements, there are limitations on the extent to which the proper implementation of the tissue's own functions can be achieved.

Method: In this study, we intend to present an approach to solving this problem using hydroxybutyl methacrylated chitosan (HBC-MA), a photo-crosslinkable/temperature reversible chitosan polymer. In addition, stereolithography-3D (SLA-3D) printing technology was used, which is more likely to mimic the complex microstructure. As a control, a 3D structure made with pristine poly(ethylene glycol) dimethacrylate (PEG-DMA) was created, and a 4D structure was prepared by adding HBC-MA to poly(ethylene glycol) dimethacrylate (PEG-DMAP) resin.

Results: HBC-MA caused the expansion of water into the polymer matrix at low temperature, and the 4D structure resulted in expansion of the polymer volume, generating dynamic movement due to the expansion of water. Conversely, as the temperature rose, deswelling occurred, followed by a decrease in the volume, showing a shape memory property of returning to the existing structure. Morphological, swelling, and mechanical analysis further confirmed the principle of dynamic movement. In addition, parameters were provided through calculation of the bending ratio angle (θ).

Conclusion: Through this, it is suggested that HBC-MA can be applied as a core polymer for SLA-4D printing, and has high potential for realizing the dynamic movement of tissue.
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http://dx.doi.org/10.1007/s13770-020-00264-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392993PMC
August 2020

A case of life-threatening valvulitis mimicking infective endocarditis in systemic juvenile idiopathic arthritis.

Cardiol Young 2020 May 15;30(5):728-731. Epub 2020 Apr 15.

Department of Pathology, Seoul National University Hospital, Seoul, Korea.

Differential diagnosis of an intracardiac mass is difficult when detected only by echocardiography before a biopsy is completed. However, treatment cannot be postponed until the biopsy results are obtained. We report the case of a 12-year-old girl who presented with an intracardiac mass in the mitral valve mimicking infective endocarditis and severe mitral regurgitation. The mass was finally diagnosed as valvulitis associated with systemic juvenile idiopathic arthritis, which was complicated with macrophage activation syndrome. After careful exclusion of acute infectious disease, we started steroid pulse therapy and administered tocilizumab to treat the cytokine storm before performing the surgery. Finally, we performed mass excision and mitral valve replacement after immunosuppressant therapy.
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http://dx.doi.org/10.1017/S1047951120000608DOI Listing
May 2020

Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis.

J Am Coll Cardiol 2020 02;75(4):380-390

Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

Background: It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis.

Objectives: The purpose of this study was to demonstrate that C-Pittsburgh B compound positron emission tomography (C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition.

Methods: This study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure.

Results: The degree of myocardial C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005).

Conclusions: These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.
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http://dx.doi.org/10.1016/j.jacc.2019.11.037DOI Listing
February 2020

Moisture-driven shift in the climate sensitivity of white spruce xylem anatomical traits is coupled to large-scale oscillation patterns across northern treeline in northwest North America.

Glob Chang Biol 2020 03 7;26(3):1842-1856. Epub 2020 Jan 7.

Institute of Botany and Landscape Ecology, University of Greifswald, Greifswald, Germany.

Tree growth at northern treelines is generally temperature-limited due to cold and short growing seasons. However, temperature-induced drought stress was repeatedly reported for certain regions of the boreal forest in northwestern North America, provoked by a significant increase in temperature and possibly reinforced by a regime shift of the pacific decadal oscillation (PDO). The aim of this study is to better understand physiological growth reactions of white spruce, a dominant species of the North American boreal forest, to PDO regime shifts using quantitative wood anatomy and traditional tree-ring width (TRW) analysis. We investigated white spruce growth at latitudinal treeline across a >1,000 km gradient in northwestern North America. Functionally important xylem anatomical traits (lumen area, cell-wall thickness, cell number) and TRW were correlated with the drought-sensitive standardized precipitation-evapotranspiration index of the growing season. Correlations were computed separately for complete phases of the PDO in the 20th century, representing alternating warm/dry (1925-1946), cool/wet (1947-1976) and again warm/dry (1977-1998) climate regimes. Xylem anatomical traits revealed water-limiting conditions in both warm/dry PDO regimes, while no or spatially contrasting associations were found for the cool/wet regime, indicating a moisture-driven shift in growth-limiting factors between PDO periods. TRW reflected only the last shift of 1976/1977, suggesting different climate thresholds and a higher sensitivity to moisture availability of xylem anatomical traits compared to TRW. This high sensitivity of xylem anatomical traits permits to identify first signs of moisture-driven growth in treeline white spruce at an early stage, suggesting quantitative wood anatomy being a powerful tool to study climate change effects in the northwestern North American treeline ecotone. Projected temperature increase might challenge growth performance of white spruce as a key component of the North American boreal forest biome in the future, when drier conditions are likely to occur with higher frequency and intensity.
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http://dx.doi.org/10.1111/gcb.14947DOI Listing
March 2020

Cerclage parahisian septal pacing through the septal perforator branch of the great cardiac vein: Bedside-to-bench development of a novel technique and lead.

Heart Rhythm 2019 12 30;16(12):1834-1840. Epub 2019 Aug 30.

Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2019.08.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908823PMC
December 2019

Hemodynamically balanced congenitally corrected transposition of the great arteries with a large ventricular septal defect, and subvalvular pulmonic stenosis: a case report.

J Med Case Rep 2019 Jul 19;13(1):219. Epub 2019 Jul 19.

Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Adults with unoperated congenitally corrected transposition of the great arteries are rare but form a distinct group among adults with congenital heart disease. Patients with congenitally corrected transposition of the great arteries often have one or more associated cardiac anomalies that dictate the need for, and timing of, surgical intervention in childhood. However, in a proportion of patients, the hemodynamics does not require surgical attention during childhood, and, in some patients, a correct diagnosis is not established until adulthood. Here we report an adult case of unoperated congenitally corrected transposition of the great arteries with a large ventricular septal defect and probable pulmonary arterial hypertension.

Case Presentation: Our patient was a 46-year-old Korean man. Transthoracic echocardiography and cardiac catheterization demonstrated hemodynamically balanced ventricles with a non-regurgitant systemic atrioventricular valve, normal pulmonary arterial pressure, and a reasonable difference between the oxygen saturation values of the aorta and pulmonary trunk, even with the presence of a large ventricular septal defect. Further morphological assessments using cardiac computed tomography and three-dimensional modeling/printing of his heart revealed that the mitral valve was straddling over the posteriorly positioned ventricular septal defect, which could explain the functional and anatomical subvalvular pulmonary stenosis and a small amount of shunt flow through the large ventricular septal defect. We interpreted this combination of cardiac defects as able to sustain his stable cardiac function. Thus, we decided to maintain his unoperated status.

Conclusion: A detailed anatomical understanding based on transthoracic echocardiography, cardiac computed tomography, and three-dimensional printing can justify a decision to not operate in cases of congenitally corrected transposition of the great arteries with hemodynamically balanced pulmonary stenosis and a ventricular septal defect, as observed in the present case.
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http://dx.doi.org/10.1186/s13256-019-2145-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639941PMC
July 2019

Marine Biomaterial-Based Bioinks for Generating 3D Printed Tissue Constructs.

Mar Drugs 2018 Dec 4;16(12). Epub 2018 Dec 4.

Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul 05029, Korea.

Biologically active materials from marine sources have been receiving increasing attention as they are free from the transmissible diseases and religious restrictions associated with the use of mammalian resources. Among various other biomaterials from marine sources, alginate and fish gelatin (f-gelatin), with their inherent bioactivity and physicochemical tunability, have been studied extensively and applied in various biomedical fields such as regenerative medicine, tissue engineering, and pharmaceutical products. In this study, by using alginate and f-gelatin's chemical derivatives, we developed a marine-based interpenetrating polymer network (IPN) hydrogel consisting of alginate and f-gelatin methacryloyl (f-GelMA) networks via physical and chemical crosslinking methods, respectively. We then evaluated their physical properties (mechanical strength, swelling degree, and degradation rate) and cell behavior in hydrogels. Our results showed that the alginate/f-GelMA hydrogel displayed unique physical properties compared to when alginate and f-GelMA were used separately. These properties included high mechanical strength, low swelling and degradation rate, and an increase in cell adhesive ability. Moreover, for the first time, we introduced and optimized the application of alginate/f-GelMA hydrogel in a three-dimensional (3D) bioprinting system with high cell viability, which breaks the restriction of their utilization in tissue engineering applications and suggests that alginate/f-GelMA can be utilized as a novel bioink to broaden the uses of marine products in biomedical fields.
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http://dx.doi.org/10.3390/md16120484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315353PMC
December 2018

Climate Regimes Override Micro-Site Effects on the Summer Temperature Signal of Scots Pine at Its Northern Distribution Limits.

Front Plant Sci 2018 8;9:1597. Epub 2018 Nov 8.

Institute of Botany and Landscape Ecology, University of Greifswald, Greifswald, Germany.

Tree growth at northern boreal treelines is generally limited by summer temperature, hence tree rings serve as natural archives of past climatic conditions. However, there is increasing evidence that a changing summer climate as well as certain micro-site conditions can lead to a weakening or loss of the summer temperature signal in trees growing in treeline environments. This phenomenon poses a challenge to all applications relying on stable temperature-growth relationships such as temperature reconstructions and dynamic vegetation models. We tested the effect of differing ecological and climatological conditions on the summer temperature signal of Scots pine at its northern distribution limits by analyzing twelve sites distributed along a 2200 km gradient from Finland to Western Siberia (Russia). Two frequently used proxies in dendroclimatology, ring width and maximum latewood density, were correlated with summer temperature for the period 1901-2013 separately for (i) dry vs. wet micro-sites and (ii) years with dry/warm vs. wet/cold climate regimes prevailing during the growing season. Differing climate regimes significantly affected the temperature signal of Scots pine at about half of our sites: While correlations were stronger in wet/cold than in dry/warm years at most sites located in Russia, differing climate regimes had only little effect at Finnish sites. Both tree-ring proxies were affected in a similar way. Interestingly, micro-site differences significantly affected absolute tree growth, but had only minor effects on the climatic signal at our sites. We conclude that, despite the treeline-proximal location, growth-limiting conditions seem to be exceeded in dry/warm years at most Russian sites, leading to a weakening or loss of the summer temperature signal in Scots pine here. With projected temperature increase, unstable summer temperature signals in Scots pine tree rings might become more frequent, possibly affecting dendroclimatological applications and related fields.
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http://dx.doi.org/10.3389/fpls.2018.01597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235909PMC
November 2018

Unsolved Questions on the Anatomy of the Ventricular Conduction System.

Korean Circ J 2018 Dec;48(12):1081-1096

Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

We reviewed the anatomical characteristics of the conduction system in the ventricles of human and ungulate hearts and then raised some questions to be answered by clinical and anatomical studies in the future. The ventricular conduction system is a 3-dimensional structure as compared to the 2-dimensional character of the atrial conduction system. The proximal part consisting of the atrioventricular node, the bundle of His and fascicles are groups of conducting cells surrounded by fibrous connective tissue so as to insulate from the underlying myocardium. Their location and morphological characters are well established. The bundle of His is a cord like structure but the left and right fascicles are broad at the proximal and branching at the distal part. The more distal part of fascicles and Purkinje system are linear networks of conducting cells at the immediate subendocardium but the intra-mural network is detected at the inner half of the ventricular wall. The papillary muscle also harbors Purkinje system not in the deeper part. It is hard to recognize histologically in human hearts but conducting cells as well as Purkinje cells are easily recognized in ungulate hearts. Further observation on human and ungulate hearts with myocardial infarct, we could find preserved Purkinje system at the subendocardium in contrast to the damaged system at the deeper myocardium. Further studies are necessary on the anatomical characteristics of this peripheral conduction system so as to correlate the clinical data on hearts with ventricular arrhythmias.
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http://dx.doi.org/10.4070/kcj.2018.0335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221866PMC
December 2018

Atrial Innervation Patterns of Intrinsic Cardiac Autonomic Nerves.

J Korean Med Sci 2018 Sep 27;33(39):e253. Epub 2018 Aug 27.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Background: Although ganglionated plexi (GPs) are important in the pathogenesis of arrhythmia, their patterns of atrial innervation have remained unclear. We investigated patterns of GP innervation to cardiac atria and the neuroanatomical interconnections among GPs in an animal model.

Methods: Atrial innervation by GPs was evaluated in 10 mongrel dogs using a retrograde neuronal tracer (cholera toxin subunit B [CTB] conjugated with fluorescent dyes). In Experiment 1, CTB was injected into the atria. In Experiment 2, CTB was injected into the major GP, including the anterior right GP (ARGP), inferior right GP (IRGP), superior left GP (SLGP), and ligament of Marshall (LOM). After 7 days, the GPs were examined for the presence of tracer-positive neurons.

Results: GPs in either right or left-side were innervating to both the same and opposite sides of the atrium. In quantitative analysis, right-sided GPs, especially ARGP, showed numerical predominance in atrial innervation. Based on the proportion of CTB-labeled ganglion in each GP, atrial innervation by GPs showed a tendency of laterality. In Experiment 2, CTB that was injected to a particular GP widely distributed in different GP. ARGP projected the largest number of innervating neurons to the IRGP, SLGP and LOM.

Conclusion: This study demonstrated that GPs project axons widely to both the same and opposite sides of atria. ARGP played a dominant role in atrial innervation. Furthermore, there were numerous neuroanatomical interconnections among GPs. These findings about neuronal innervation and interconnections of GPs could offer useful information for understanding intrinsic cardiac nervous system neuroanatomy.
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http://dx.doi.org/10.3346/jkms.2018.33.e253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146147PMC
September 2018

Comparative Screening Analytic Methods for Elderly of Blood Methylmercury Concentration between Two Analytical Institutions.

Comput Math Methods Med 2018 26;2018:2509413. Epub 2018 Jun 26.

Department of Preventive Medicine, College of Medicine, Dong-A University, Busan, Republic of Korea.

Methylmercury is widely known to be a toxic substance in the human, especially a nervous system. However, it is difficult to accurately measure the amount of methylmercury in blood, and the form of methylmercury is variously presented. The purpose of study was to compare the total mercury and methylmercury measurements techniques and detection levels between analytical institutions in two countries using the same elderly human blood samples. Total mercury using gold amalgamation direct mercury analysis method (both) and methylmercury using the dithizone extraction and gas chromatography-electron capture detector (GC-ECD) method (N Lab in Japan) and the cold vapor atomic fluorescence spectrophotometer (CVAFS) method (D Lab in Korea) were measured in 47 subjects who agreed to participate in this study. Total mercury concentrations in both analytical laboratories were observed at similar levels (9.4 versus 9.5 ug/kg, p=0.898) and the distribution was highly correlated. However, the concentration of methylmercury showed some difference between two laboratories (9.1 versus 8.6 ug/kg, p<0.001). Due to different recovery rates by different analytical methods, it is assumed that the methyl/total mercury ratio in N lab in Japan was higher than D lab in Korea (96.8 versus 90.4%, p<0.001). The GC-ECD was more sensitive method than CVAFS in methylmercury analytic techniques.
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http://dx.doi.org/10.1155/2018/2509413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038686PMC
December 2018

Lower versus upper leg saphenous vein composite grafts based on the left internal thoracic artery: A randomized study.

J Thorac Cardiovasc Surg 2018 09 11;156(3):986-994.e2. Epub 2018 Apr 11.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: The "lower versus upper leg saphenous vein (SV) composite graft based on the left internal thoracic artery (ITA) for coronary artery bypass grafting" trial was designed to compare the histologic, immunohistochemical, and angiographic findings of lower versus upper leg SV composite grafts.

Methods: Twenty-six patients with multivessel coronary artery disease were prospectively randomized to undergo revascularization using a lower leg (n = 13) or upper leg (n = 13) SV composite graft based on the in situ left ITA. The SV was harvested with a "no-touch" technique, and 2 excess segments were removed from the distal and proximal portions of each SV conduit. Another proximal segment was removed from the reversed SV composite graft, which had been dilated by the native ITA pressure. Hematoxylin and eosin staining, immunohistochemistry, and early and 1-year postoperative angiographic results were compared.

Results: The histologic study showed that the proximal and dilated proximal SV conduit lumen diameters were smaller in the lower leg group than in the upper leg group (proximal, 623 ± 143 μm vs 858 ± 266 μm; P = .008; dilated proximal, 1138 ± 419 μm vs 1477 ± 353 μm; P = .047). However, there were no differences in the lumen diameters of the distal SV segments in terms of immunohistochemical comparisons, diameters, patency rates, or filling frame counts of the SV conduits on early and 1-year postoperative angiograms between the 2 groups.

Conclusions: Although the proximal segment luminal diameters were smaller in the lower leg SV, there were no differences in the immunohistochemical results or patency rates on early and 1-year postoperative angiograms between the lower and upper leg "no-touch" SV conduits.
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http://dx.doi.org/10.1016/j.jtcvs.2018.03.148DOI Listing
September 2018

Automated extraction of Biomarker information from pathology reports.

BMC Med Inform Decis Mak 2018 05 21;18(1):29. Epub 2018 May 21.

Interdisciplinary Program for Bioengineering, Graduate School, Seoul National Universty, Seoul, Republic of Korea.

Background: Pathology reports are written in free-text form, which precludes efficient data gathering. We aimed to overcome this limitation and design an automated system for extracting biomarker profiles from accumulated pathology reports.

Methods: We designed a new data model for representing biomarker knowledge. The automated system parses immunohistochemistry reports based on a "slide paragraph" unit defined as a set of immunohistochemistry findings obtained for the same tissue slide. Pathology reports are parsed using context-free grammar for immunohistochemistry, and using a tree-like structure for surgical pathology. The performance of the approach was validated on manually annotated pathology reports of 100 randomly selected patients managed at Seoul National University Hospital.

Results: High F-scores were obtained for parsing biomarker name and corresponding test results (0.999 and 0.998, respectively) from the immunohistochemistry reports, compared to relatively poor performance for parsing surgical pathology findings. However, applying the proposed approach to our single-center dataset revealed information on 221 unique biomarkers, which represents a richer result than biomarker profiles obtained based on the published literature. Owing to the data representation model, the proposed approach can associate biomarker profiles extracted from an immunohistochemistry report with corresponding pathology findings listed in one or more surgical pathology reports. Term variations are resolved by normalization to corresponding preferred terms determined by expanded dictionary look-up and text similarity-based search.

Conclusions: Our proposed approach for biomarker data extraction addresses key limitations regarding data representation and can handle reports prepared in the clinical setting, which often contain incomplete sentences, typographical errors, and inconsistent formatting.
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http://dx.doi.org/10.1186/s12911-018-0609-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963015PMC
May 2018

A Case-Control Study of Skin Cancer and Exposure of Toxic Heavy Metals.

Ann Dermatol 2018 Apr 21;30(2):238-240. Epub 2018 Feb 21.

Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea.

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http://dx.doi.org/10.5021/ad.2018.30.2.238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839902PMC
April 2018

Investigation of Health Effects According to the Exposure of Low Concentration Arsenic Contaminated Ground Water.

Int J Environ Res Public Health 2017 11 27;14(12). Epub 2017 Nov 27.

Environmental Health Center, Dong-A University, Busan 49201, Korea.

Recent epidemiological studies have reported adverse health effects, including skin cancer, due to low concentrations of arsenic via drinking water. We conducted a study to assess whether low arsenic contaminated ground water affected health of the residents who consumed it. For precise biomonitoring results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of arsenic were separately quantified by combining high-performance liquid chromatography and inductively coupled plasma mass spectroscopy from urine samples. In conclusion, urinary As III, As V, MMA, and hair arsenic concentrations were significantly higher in residents who consumed arsenic contaminated ground water than control participants who consumed tap water. But, most health screening results did not show a statistically significant difference between exposed and control subjects. We presume that the elevated arsenic concentrations may not be sufficient to cause detectable health effects. Consumption of arsenic contaminated ground water could result in elevated urinary organic and inorganic arsenic concentrations. We recommend immediate discontinuation of ground water supply in this area for the safety of the residents.
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http://dx.doi.org/10.3390/ijerph14121461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750880PMC
November 2017

Role of atrial wall thickness in wave-dynamics of atrial fibrillation.

PLoS One 2017 21;12(8):e0182174. Epub 2017 Aug 21.

Yonsei University Health System, Seoul, Republic of Korea.

Background/aims: Atrial anatomy and thickness may affect the electrical wave-dynamics of atrial fibrillation (AF). We explored the relationship between left atrial (LA) wall thickness (LAWT) or LA geometry and AF wave-dynamics.

Methods: We included 15 patients with persistent AF (age, 62.3 ± 11.9 years) who underwent AF catheter ablation. We measured the LAWT, LA endocardial curvature, and SD-curvature (surface bumpiness) from preprocedural computed tomography images. We compared those anatomical characteristics with electrophysiologic parameters such as dominant frequency (DF), Shannon entropy (ShEn), or complex fractionated atrial electrogram (CFAE)-cycle length (CL), calculated from intracardiac bipolar electrograms (300-500 points, 5 s), acquired during ablation procedures.

Results: 1. LAWT (excluding fat) varied widely among patients, locations, and types of AF. LAWT was inversely correlated with LA volume (r = -0.565, p = 0.028) and positively correlated with SD-curvature (r = 0.272, p < 0.001). 2. LAWT was positively correlated with ShEn (r = 0.233, p < 0.001) and negatively correlated with CFAE-CL (r = -0.107, p = 0.038). 3. In the multivariate linear regression analyses for AF wave-dynamics parameters, DF (β = -0.29 [95% CI -0.44--0.14], p < 0.001), ShEn (β = 0.19 [95% CI 0.12-0.25], p < 0.001), and CFAE-CL (β = 7.49 [95% CI 0.65-14.34], p = 0.032) were independently associated with LAWT.

Conclusion: Regional LAWT is associated with LA structural features, and has significant correlations with the wave-dynamics parameters associated with electrical wavebreaks or rotors in patients with persistent AF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182174PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565105PMC
October 2017

Case-control study of chronic low-level exposure of inorganic arsenic species and non-melanoma skin cancer.

J Dermatol 2017 Dec 16;44(12):1374-1379. Epub 2017 Aug 16.

Department of Dermatology, College of Medicine, Dong-A University, Busan, Korea.

A significant relationship between arsenic exposure and non-melanoma skin cancer (NMSC) is well known. The toxicity of arsenics which develop NMSC is dependent on their species. Accordingly, total arsenic levels are unreliable for risk assessment of NMSC. However, there are few studies on quantitative exposure assessment of arsenic species in NMSC patients. To validate the contribution of each arsenic species to NMSC, we compared the creatinine-adjusted urinary concentration of arsenic species in NMSC patients and community controls. A total of 124 biopsy-proven NMSC cases and 125 age- and sex-matched community controls, drinking tap water with low-level arsenic concentration (<5 μg/L), were included in the study. High-performance liquid chromatography and inductively coupled plasma mass spectrometry were used for the measurement. The NMSC group was found to have significantly higher levels of total inorganic arsenic, trivalent and pentavalent arsenic and monomethylarsonic acid than the control group. Total arsenic, organic arsenic and dimethylarsonic acid levels were lower in the NMSC group. We suggest that inorganic arsenic species, trivalent arsenic and pentavalent arsenic may influence the prevalence of NMSC, in spite of these levels being lower than the Agency for Toxic Substances and Disease Registry-recommended standard or the levels reported by other highly contaminated areas and neighboring countries in East Asia. Furthermore, it also suggests that total arsenic level cannot represent the risk of NMSC.
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http://dx.doi.org/10.1111/1346-8138.13993DOI Listing
December 2017
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