Publications by authors named "Sang Hyun Kim"

629 Publications

Risk Factors for Prolonged Hospitalization and Delayed Treatment Completion After Laparoscopic Appendectomy in Patients With Uncomplicated Acute Appendicitis.

Ann Coloproctol 2021 Nov 18. Epub 2021 Nov 18.

Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.

Purpose: We sought to identify the risk factors for prolonged hospitalization and delayed treatment completion after laparoscopic appendectomy in patients with uncomplicated acute appendicitis.

Methods: The study retrospectively analyzed 497 patients who underwent laparoscopic appendectomies for uncomplicated appendicitis between January 2018 and December 2020. The patients were divided into an early discharge group (≤2 days) and a late discharge group (>2 days) based on the length of hospital stay (LOS). The patients were also divided into uneventful and complicated groups according to the need for additional treatment after standard follow-up.

Results: Thirty-seven patients (7.4%) were included in the late discharge group. The mean LOS of the late discharge groups was 3.9 days. There were significant differences according to age, preoperative C-reactive protein (CRP), and operative time between the 2 groups. Only operative time was significantly associated with prolonged LOS in multivariate analysis. Thirty-five patients (7.0%) were included in the complicated group. The mean duration of treatment in the uneventful and complicated groups was 7.4 and 25.3 days, respectively. Significant differences existed between the uneventful and complicated groups in preoperative body temperature, preoperative CRP levels, maximal appendix diameter, and the presence of appendicoliths. In multivariate analysis, preoperative CRP levels and maximal appendix diameter were independent predictors of delayed treatment completion.

Conclusion: Shorter operative time is desirable to ensure minimal hospital stay in patients with uncomplicated appendicitis. Further efforts are needed to ensure that patients with uncomplicated appendicitis do not experience delayed treatment completion after laparoscopic appendectomies.
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http://dx.doi.org/10.3393/ac.2021.00773.0110DOI Listing
November 2021

Inhibition of cathepsin K sensitizes oxaliplatin-induced apoptotic cell death by Bax upregulation through OTUB1-mediated p53 stabilization in vitro and in vivo.

Oncogene 2021 Nov 16. Epub 2021 Nov 16.

Department of Immunology, School of Medicine, Keimyung University, Daegu, 42601, South Korea.

Cathepsin K is highly expressed in various types of cancers. However, the effect of cathepsin K inhibition in cancer cells is not well characterized. Here, cathepsin K inhibitor (odanacatib; ODN) and knockdown of cathepsin K (siRNA) enhanced oxaliplatin-induced apoptosis in multiple cancer cells through Bax upregulation. Bax knockdown significantly inhibited the combined ODN and oxaliplatin treatment-induced apoptotic cell death. Stabilization of p53 by ODN played a critical role in upregulating Bax expression at the transcriptional level. Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. Interestingly, ODN-induced p53 and Bax upregulation were modulated by the production of mitochondrial reactive oxygen species (ROS). Mitochondrial ROS scavengers prevented OTUB1-mediated p53 stabilization and Bax upregulation by ODN. These in vitro results were confirmed by in mouse xenograft model, combined treatment with ODN and oxaliplatin significantly reduced tumor size and induced Bax upregulation. Furthermore, human renal clear carcinoma (RCC) tissues revealed a strong correlation between phosphorylation of OTUB1(Ser16) and p53/Bax expression. Our results demonstrate that cathepsin K inhibition enhances oxaliplatin-induced apoptosis by increasing OTUB1 phosphorylation via CK2 activation, thereby promoting p53 stabilization, and hence upregulating Bax.
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http://dx.doi.org/10.1038/s41388-021-02088-7DOI Listing
November 2021

Novel polyhydroxybutyrate-degrading activity of the genus as confirmed by sp. SOL03 from the marine environment.

J Microbiol Biotechnol 2021 Oct 27;32(1). Epub 2021 Oct 27.

Department of Biological Engineering, College of Engineering, Konkuk University, Seoul, Republic of Korea.

Ever since bioplastics were introduced to a wide range of industries globally, disposal of the used bioplastics has become an inseparable issue with their application. Unlike petroleum-based plastics, bioplastics can be completely decomposed into water and carbon dioxide by microorganisms in a relatively short time, which is an advantage. However, there is little information on the specific degraders and accelerating factors for biodegradation. To elucidate a new strain for biodegradation of poly-3-hydroxybutyrate (PHB), we screened out one PHB-degrading bacterium, sp. SOL03, which is the first reported strain from the genus to show PHB degradation activity, although species are known to be complex carbohydrate degraders found in high-salt environments. In this study, we evaluated its biodegradability using solid- and liquid-based methods in addition to examining the changes in physical properties throughout the biodegradation process. Furthermore, we established the optimal conditions for biodegradation with respect to temperature, salt concentration, and additional carbon and nitrogen sources; accordingly, a temperature of 37°C with the addition of 3% NaCl without additional carbon sources, was determined to be optimal. In summary, we found that sp. SOL03 showed a PHB degradation yield of almost 97% after 10 days. To the best of our knowledge, this is the first study to investigate the potent bioplastic degradation activity of sp., and we believe that it can contribute to the development of bioplastics from application to disposal.
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http://dx.doi.org/10.4014/jmb.2109.09005DOI Listing
October 2021

Gomisin M2 alleviates psoriasis‑like skin inflammation by inhibiting inflammatory signaling pathways.

Mol Med Rep 2021 12 19;24(6). Epub 2021 Oct 19.

Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.

Psoriasis, a chronic inflammatory skin disease, is characterized by the excessive proliferation and impaired differentiation of epidermal keratinocytes and is accompanied by the increased infiltration of inflammatory cells. The condition requires long‑term treatment and has no definitive cure. Hence, supplements and therapeutic agents have been intensely investigated. Gomisin M2 (GM2), a lignan extracted from (Turcz). Baill. (Schisandraceae; ), has demonstrated diverse pharmacological properties, including anticancer, anti‑inflammatory and antiallergic effects. Based on these findings, the present study examined the effects of GM2 on an imiquimod (IMQ)‑induced psoriasis mouse model and on keratinocytes stimulated by tumor necrosis factor (TNF)‑α and interferon‑γ. IMQ was topically applied to the back skin of mice for 7 consecutive days, and the mice were orally administered CD. These results showed that the oral administration of GM2 suppressed the symptoms of psoriasis, as evidenced by reductions in skin thickness, psoriasis area severity index scores for psoriasis lesions, transepidermal water loss and myeloperoxidase (MPO)‑associated cell infiltration. Furthermore, GM2 reduced the pathologically increased levels of immunoglobulin G2a, MPO and TNF‑α in the serum and T helper (Th)1 and Th17 cell populations in the spleen. GM2 decreased the gene expression of inflammatory‑related cytokines and chemokines and inhibited the expression of signal transducer and activator of transcription 1 and nuclear factor‑κB in the activated keratinocytes. These results suggested that GM2 from is a potential therapeutic candidate to alleviate psoriasis‑like skin inflammation.
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http://dx.doi.org/10.3892/mmr.2021.12499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548952PMC
December 2021

Association between inter-leg blood pressure difference and cardiovascular outcome in patients undergoing percutaneous coronary intervention.

PLoS One 2021 15;16(10):e0257443. Epub 2021 Oct 15.

Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Although the inter-arm blood pressure (BP) difference has been advocated to be associated with cardiovascular events, the implication of inter-leg BP difference has not been well established. This study was conducted to investigate whether inter-arm and -leg BP differences have prognostic value in patients undergoing percutaneous coronary intervention (PCI).

Methods: In this prospective study, we consecutively enrolled 667 patients who underwent PCI. Both arm and leg BPs were measured at the day after PCI. The primary outcome was a major adverse cardiovascular event (MACE) including cardiac death, acute coronary syndrome, coronary revascularization, stroke, and hospitalization for heart failure during the follow-up period.

Results: Mean age was 64.0±11.1 years old, and males were predominant (70.5%). During a mean follow-up period of 3.0 years, MACE occurred in 209 (31.3%) patients. The inter-leg systolic BP difference (ILSBPD) was significantly higher in patients with MACE than those without (9.9±12.3 vs. 7.2±7.5 mmHg, P = 0.004). The inter-arm systolic BP difference was not significantly different between patients with and without MACE (P = 0.403). In multivariable Cox regression analysis, increased ILSBPD was independently associated with the development of MACE (per 5 mmHg; hazard ratio, 1.07; 95% confidence interval, 1.01-1.14). The inter-arm systolic BP difference was not associated with MACE in the multivariable analysis.

Conclusion: Increased ILSBPD was independently associated with worse cardiovascular outcomes after PCI. As ILSBPD is easy to measure, it may be helpful in the risk stratification of patients undergoing PCI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257443PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519463PMC
November 2021

Cudraxanthone D Ameliorates Psoriasis-like Skin Inflammation in an Imiquimod-Induced Mouse Model via Inhibiting the Inflammatory Signaling Pathways.

Molecules 2021 Oct 8;26(19). Epub 2021 Oct 8.

Department of Pharmacology, Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea.

Psoriasis is a chronic inflammatory skin disease accompanied by excessive keratinocyte proliferation. Corticosteroids, vitamin D3 analogs, and calcineurin inhibitors, which are used to treat psoriasis, have diverse adverse effects, whereas natural products are popular due to their high efficiency and relatively low toxicity. The roots of the () are known to have diverse pharmacological effects, among which the anti-inflammatory effect is reported as a potential therapeutic agent in skin cells. Nevertheless, its effectiveness against skin diseases, especially psoriasis, is not fully elucidated. Here, we investigated the effect of cudraxanthone D (CD), extracted from the roots the Bureau, on psoriasis using an imiquimod (IMQ)-induced mouse model and the tumor necrosis factor (TNF)-α/interferon (IFN)-γ-activated keratinocytes. IMQ was topically applied to the back skin of C57BL/6 mice for seven consecutive days, and the mice were orally administered with CD. This resulted in reduced psoriatic characteristics, such as the skin thickness and Psoriasis Area Severity Index score, and the infiltration of neutrophils in IMQ-induced skin. CD inhibited the serum levels of TNF-α, immunoglobulin G2a, and myeloperoxidase, and the expression of Th1/Th17 cells in splenocytes. In TNF-α/IFN-γ-activated keratinocytes, CD reduced the expressions of CCL17, IL-1β, IL-6, and IL-8 by inhibiting the phosphorylation of STAT1 and the nuclear translocation of NF-kB. Taken together, these results suggest that CD could be a potential drug candidate for the treatment of psoriasis.
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http://dx.doi.org/10.3390/molecules26196086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512696PMC
October 2021

Network Analysis on Herbal Formulas from Wenrejingwei and Shang Han Lun.

J Pharmacopuncture 2021 Sep;24(3):138-141

Department of Diagnostics, College of Korean Medicine, Woosuk University, Jeonju, Republic of Korea.

Objectives: This study aims to describe the utilization of herbal formulas from Wenrejingwei by using network analysis and understand the treatment of acute exogenous febrile diseases.

Methods: We constructed a matrix of high-frequency herbal combinations (HCs) from Wenrejingwei and Shang Han Lun and cluster networks based on cohesive analysis. Network analysis was performed to compare the results.

Results: The results of the high-frequency HC network in Wenrejingwei showed cohesive patterns in three categories corresponding to dampness-heat and warm-fever treatment. Compared to the Shang Han Lun network, the Wenrejingwei network indicated a careful approach in the use of pungent and warm herbs such as Guizhitang. Moreover, the combination of and along with the use of herbs strengthening yin, such as Ginseng Radix and Liriopes Radix, provide evidence of a holistic approach in the treatment of exogenous febrile diseases by considering the balance of the human body damaged by heat.

Conclusion: The results of this study could help select appropriate herbal formulas and treatment methods for treating Onbyeong and modern acute febrile infectious diseases.
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http://dx.doi.org/10.3831/KPI.2021.24.3.138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481672PMC
September 2021

Sex-specific associations of brachial-ankle pulse wave velocity with adverse cardiac remodeling and long-term cardiovascular outcome.

J Hypertens 2021 Oct 4. Epub 2021 Oct 4.

Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, Boramae Medical Center, Seoul, South Korea.

Background: It remains unclear whether the cardiovascular consequences of arterial stiffness differ by sex. This study aimed to investigate the sex-specific association of brachial-ankle pulse wave velocity (baPWV) with adverse cardiac remodeling and cardiovascular outcome.

Method: We studied 11 767 patients (57.6% men) with cardiovascular risk factors, whose baPWV was measured. The primary endpoint was composite cardiovascular events. Restricted cubic spline (RCS) analyses were performed to delineate the association of baPWV with echocardiography parameters and risks of cardiovascular events.

Results: RCS curves showed that structural/functional echocardiography parameters gradually worsened with increasing baPWV more prominently in women than in men. The prevalence of left ventricular hypertrophy and diastolic dysfunction increases with baPWV increase more steeply in women (P-for-interaction by sex <0.001). During the median follow-up of 3.64 years (interquartile interval, 1.56-5.38 years), 350 cardiovascular events (3.0%) and 155 deaths (1.3%) occurred. Cumulative cardiovascular events and deaths were significantly higher in patients with elevated baPWV in both sexes (P < 0.001). Cox analyses showed that the increase in baPWV was associated with the higher risks of cardiovascular events and deaths more strongly in women [cardiovascular events: men, adjusted hazard ratio 1.10, 95% confidence interval (1.08-1.13), P < 0.001; women, adjusted hazard ratio 1.18, 95% confidence interval (1.13-1.24), P < 0.001 by 100 cm/s increase in baPWV; P-for-interaction by sex = 0.022].

Conclusion: The detrimental effects of baPWV on adverse cardiac remodeling and cardiovascular outcome were stronger in women than in men. The prognostic information provided by baPWV may be particularly crucial for women.
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http://dx.doi.org/10.1097/HJH.0000000000003021DOI Listing
October 2021

Impact of Bilateral Subcostal Plus Lateral Transversus Abdominis Plane Block on Quality of Recovery After Laparoscopic Cholecystectomy: A Randomized Placebo-Controlled Trial.

Anesth Analg 2021 Dec;133(6):1624-1632

From the Department of Anesthesiology and Pain Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si, Republic of Korea.

Background: Previous research has not evaluated the potential effect of transversus abdominis plane (TAP) block on quality of recovery following laparoscopic cholecystectomy. Therefore, we investigated whether addition of the bilateral subcostal and lateral TAP (bilateral dual TAP [BD-TAP]) blocks to multimodal analgesia would improve the quality of recovery as assessed with the Quality of Recovery-40 (QoR-40).

Methods: Patients age 18 to 60 years who were scheduled to undergo elective laparoscopic cholecystectomy were randomized to the BD-TAP or control group. The BD-TAP group received the BD-TAP block with multimodal analgesia under general anesthesia, using 0.25% ropivacaine, and the control group was treated with the same method, except that they received the sham block using 0.9% normal saline. Both groups had the same multimodal analgesia regimen, consisting of intravenous dexamethasone, propacetamol, ibuprofen, and oxycodone. The primary outcome was the QoR-40 score at 24 hours after surgery. Data were analyzed using the independent t test, Mann-Whitney U test, χ2 test, and Fisher exact test.

Results: Thirty-eight patients in each group were recruited. The mean QoR-40 score decreased by 13.6 (95% confidence interval [CI], 8.3-18.8) in the BD-TAP group and 15.6 (95% CI, 6.7-24.5) in the control group. The postoperative QoR-40 score at 24 hours after surgery did not differ between the 2 groups (BD-TAP group, median [interquartile range], 170.5 [152-178]; control group, 161 [148-175]; median difference, 3 [95% CI, -5 to 13]; P = .427). There were no differences between the 2 groups in the pain dimension of the QoR-40: 30.5 (95% CI, 27-33) in the BD-TAP group and 31 (95% CI, 26-32) in the control group; median difference was 0 (95% CI, -2 to 2); P = .77.

Conclusions: Our results indicate that the BD-TAP block does not improve the quality of recovery or analgesic outcomes following laparoscopic cholecystectomy. Our results do not support the routine use of the BD-TAP block for this surgery.
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http://dx.doi.org/10.1213/ANE.0000000000005762DOI Listing
December 2021

Novel phasins from the Arctic Pseudomonas sp. B14-6 enhance the production of polyhydroxybutyrate and increase inhibitor tolerance.

Int J Biol Macromol 2021 Nov 14;190:722-729. Epub 2021 Sep 14.

Department of Biological Engineering, College of Engineering, Konkuk University, Seoul 05029, Republic of Korea; Institute for Ubiquitous Information Technology and Applications, Konkuk University, Seoul 05029, Republic of Korea. Electronic address:

Phasin (PhaP), one of the polyhydroxyalkanoate granule-associated protein, enhances cell growth and polyhydroxybutyrate (PHB) biosynthesis by regulating the number and size of PHB granules. However, few studies have applied phasins to various PHB production conditions. In this study, we identified novel phasin genes from the genomic data of Arctic soil bacterium Pseudomonas sp. B14-6 and determined the role of phaP1 under different PHB production conditions. Transmission electron microscopy and gel permeation chromatography revealed small PHB granules with high-molecular weight, while differential scanning calorimetry showed that the extracted PHB films had similar thermal properties. The phasin protein derived from Pseudomonas sp. B14-6 revealed higher PHB production and exhibited higher tolerance to several lignocellulosic biosugar-based inhibitors than the phasin protein of Ralstonia eutropha H16 in a recombinant Escherichia coli strain. The increased tolerance to propionate, temperature, and other inhibitors was attributed to the introduction of phaP1, which increased PHB production from lignocellulosic hydrolysate (2.39-fold) in the phaP1 strain. However, a combination of phasin proteins isolated from two different sources did not increase PHB production. These findings suggest that phasin could serve as a powerful means to increase robustness and PHB production in heterologous strains.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.236DOI Listing
November 2021

A Randomized, Double-blind, Active-controlled, Two Parallel-Group, Optional Titration, Multicenter, Phase IIIb Study to Evaluate the Efficacy and Safety of Fimasartan Versus Perindopril Monotherapy With and Without a Diuretic Combination in Elderly Patients With Essential Hypertension.

Clin Ther 2021 Oct 7;43(10):1746-1756. Epub 2021 Sep 7.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea. Electronic address:

Purpose: The efficacy and tolerability of fimasartan in elderly patients have not been fully evaluated. This study was therefore conducted to determine the efficacy and tolerability of fimasartan compared with perindopril in elderly Korean patients aged >70 years with essential hypertension (defined by a mean sitting systolic blood pressure [SBP] ≥140 mm Hg).

Methods: This randomized, double-blind, active-controlled, 2 parallel-group, optional titration, multicenter, Phase IIIb trial (FITNESS [Fimasartan in the Senior Subjects]) enrolled 241 patients from 23 cardiac centers in the Republic of Korea between August 2017 and December 2019. After the placebo run-in period, treatment started with fimasartan 30 mg or perindopril arginine 2.5 mg once daily at a 1:1 ratio; if BP was not controlled at week 4, the dose was doubled. If BP was not controlled at week 8, a diuretic combination (fimasartan 60 mg/hydrochlorothiazide 12.5 mg or perindopril arginine 5 mg/indapamide 1.25 mg) was administered. After 16 weeks of the double-blind treatment, the patients with controlled BP participated in an 8-week open-label extension study, with the 2 groups unified by fimasartan 60 mg with or without hydrochlorothiazide 12.5 mg for 8 weeks. The primary outcome was a change in SBP for 8 weeks. The secondary outcomes included a change in sitting diastolic BP (DBP) for 8 weeks and changes in SBP and DBP for 4, 16, and 24 weeks.

Findings: At week 8, mean SBP significantly decreased from baseline in both groups: -14.2 (14.4) mm Hg in the fimasartan group and -9.0 (16.1) mm Hg in the perindopril group. The difference between the 2 groups was 5.4 (2.1) mm Hg, indicating the noninferiority of fimasartan to perindopril. Moreover, fimasartan exhibited a higher BP-lowering effect than perindopril (P = 0.0108). In addition, reductions in SBP and DBP from baseline to weeks 4, 8, and 16 were significantly greater in the fimasartan group than in the perindopril group, although the SBP reduction was comparable at week 16. Both groups reported an excellent mean compliance rate of 97.4% (4.7%) through week 16. During the study period, 82 adverse events were reported in 52 patients, 40 in the fimasartan group and 42 in the perindopril group (P = 0.4647). Dizziness was the most commonly reported adverse event (7 cases). Remarkably, only 1 case of orthostatic hypotension was reported during the study period.

Implications: In elderly patients with essential hypertension, fimasartan 30 to 60 mg with a possible hydrochlorothiazide 12.5-mg combination was noninferior to perindopril 2.5 to 5 mg with a possible indapamide 1.25-mg combination. Furthermore, fimasartan exhibited higher BP-lowering efficacy than perindopril. There was no difference in tolerability between the 2 groups. Clinicaltrials.gov Identifier: NCT03246555.
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http://dx.doi.org/10.1016/j.clinthera.2021.08.003DOI Listing
October 2021

Phenotypic and Genetic Analyses of Korean Patients with Familial Hypercholesterolemia: Results from the KFH Registry 2020.

J Atheroscler Thromb 2021 Aug 30. Epub 2021 Aug 30.

Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine.

Aims: Familial hypercholesterolemia (FH) is currently a worldwide health issue. Understanding the characteristics of patients is important for proper diagnosis and treatment. This study aimed to analyze the phenotypic and genetic features, including threshold cholesterol levels, of Korean patients with FH.

Methods: A total of 296 patients enrolled in the Korean FH registry were included, according to the following criteria: low-density lipoprotein-cholesterol (LDL-C) >190 mg/dL with tendon xanthoma or family history compatible with FH, or LDL-C >225 mg/dL. DNA sequences of three FH-associated genes were obtained using whole-exome or target exome sequencing. Threshold cholesterol levels for differentiating patients with FH/pathogenic variant (PV) carriers and predictors of PVs were identified.

Results: Of the 296 patients, 104 had PVs and showed more obvious clinical findings, including higher cholesterol levels. PV rates ranged from 30% to 64% when patients were categorized by possible or definite type according to the Simon Broome criteria. Frequent PV types included missense variants and copy number variations (CNVs), while the most frequent location of PVs was p.P685L in LDLR. The threshold LDL-C levels for patient differentiation and PV prediction were 177 and 225 mg/dL, respectively. Younger age, tendon xanthoma, and higher LDL-C levels were identified as independent predictors of PVs, while traditional cardiovascular risk factors were predictors of coronary artery disease.

Conclusions: Korean patients with FH had variable PV rates depending on diagnostic criteria and distinctive PV locations. The reported threshold LDL-C levels pave the way for efficient patient care in this population.
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http://dx.doi.org/10.5551/jat.63062DOI Listing
August 2021

Transient behavior of arsenic in vadose zone under alternating wet and dry conditions: A comparative soil column study.

J Hazard Mater 2022 Jan 19;422:126957. Epub 2021 Aug 19.

Water Cycle Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Energy and Environment Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea; Graduate School of Energy and Environment (KU-KIST Green School), Korea University, Seoul 02841, Republic of Korea. Electronic address:

The water and oxygen contents of the vadose zone change cyclically depending upon the meteorological condition (e.g., intermittent rainfall), which can affect the biogeochemical reactions that govern the fate of arsenic (As). To simulate and evaluate the transient behavior of As in this zone when subjected to repeated wet and dry conditions, soil column experiments with different soil properties were conducted. Three wetting-drying cycles resulted in the fluctuation of water and dissolved oxygen contents, and consequently, the reduction-oxidation potential in the soil columns. Under these circumstances, the biotic reduction of As(V) to As(III) was observed, especially in the column filled with soils enriched in organic matter. Most of the As was found to be associated with soil particles rather than to be dissolved in the pore water in all of the columns tested. Retention of As was more preferable in the soil column with a higher Fe content and bulk density, which provided more sorption sites and reaction time, respectively. However, a considerable amount of soil-bound As could be remobilized and released back to the pore water with the repetition of wetting and drying due to the transformation of As(V) to As(III).
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http://dx.doi.org/10.1016/j.jhazmat.2021.126957DOI Listing
January 2022

Ursolic acid inhibits FcεRI-mediated mast cell activation and allergic inflammation.

Int Immunopharmacol 2021 Oct 13;99:107994. Epub 2021 Aug 13.

Cell & Matrix Research Institute, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

Background: Mast cells are the primary cells that play a crucial role in the allergic diseases via secretion of diverse allergic mediators. Ursolic acid (UA) is a naturally occurring anti-inflammatory triterpenoid possessing various biological properties such as immune regulation, antioxidant, and anti-fibrotic. The aim of this study was to evaluate the effects of UA in FcεRI-mediated mast cell activation and allergic inflammation.

Methods: In this study, mast cells were stimulated with immunoglobulin E (IgE) and the anti-allergic effects of UA were assessed by measuring the levels of allergic mediators. In vivo effects of UA were observed by generating passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mouse model.

Results: We found that UA inhibited the degranulation of mast cell by suppressing the intracellular calcium level in a concentration-dependent manner. UA inhibited the expression and the release of pro-inflammatory cytokines in mast cells. Anti-allergic effects of UA were demonstrated via suppression of FcεRI-mediated signaling molecules. In addition, UA inhibited the IgE-mediated PCA and ovalbumin-induced ASA reactions in a dose-dependent manner.

Conclusions: Based on these findings, we suggest that UA might have potential as a therapeutic candidate for the treatment of allergic inflammatory diseases via inhibition of FcεRI-mediated mast cell activation.
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http://dx.doi.org/10.1016/j.intimp.2021.107994DOI Listing
October 2021

Pretreatment of outer membrane vesicle and subsequent infection with influenza virus induces a long-lasting adaptive immune response against broad subtypes of influenza virus.

Microbes Infect 2021 Aug 9:104878. Epub 2021 Aug 9.

Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Korea; Department of Biochemistry, Chungnam National University, Daejeon, 34134, Korea; Department of Biomolecular Science, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon, 34113, Korea. Electronic address:

Influenza is an acute respiratory disease and a global health problem. Although influenza vaccines are commercially available, frequent antigenic changes in hemagglutinin might render them less effective or unavailable. We previously reported that modified outer membrane vesicle (fmOMV) provided immediate and robust protective immunity against various subtypes of influenza virus. However, the effect was transient because it was innate immunity-dependent. In this study, we investigated the effects of consecutive administration of fmOMV and influenza virus on the adaptive immune response and long-term protective immunity against influenza virus. When the mice were pretreated with fmOMV and subsequently infected with influenza virus, strong influenza-specific antibody and T cell responses were induced in both systemic and lung mucosal compartments without pathogenic symptoms. Upon the secondary viral challenge at week 4, the mice given fmOMV and influenza virus exhibited almost complete protection against homologous and heterologous viral challenge. More importantly, this strong protective immunity lasted up to 18 weeks after the first infection. These results show that pretreatment with fmOMV and subsequent infection with influenza virus efficiently induces broad and long-lasting protective immunity against various virus subtypes, suggesting a novel antiviral strategy against newly-emerging viral diseases without suitable vaccines or therapeutics.
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http://dx.doi.org/10.1016/j.micinf.2021.104878DOI Listing
August 2021

Improved Prognostic Value in Predicting Long-Term Cardiovascular Events by a Combination of High-Sensitivity C-Reactive Protein and Brachial-Ankle Pulse Wave Velocity.

J Clin Med 2021 Jul 26;10(15). Epub 2021 Jul 26.

Boramae Medical Center, Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, 5 Boramae-ro, Dongjak-gu, Seoul 07061, Korea.

Background: Both C-reactive protein (CRP) and arterial stiffness are associated with the development of cardiovascular disease (CVD). This study was performed to investigate whether a combination of these two measurements could improve cardiovascular risk stratification.

Methods: A total of 6572 consecutive subjects (mean age, 60.8 ± 11.8 years; female, 44.2%) who underwent both high-sensitivity CRP (hs-CRP) and brachial-ankle pulse wave velocity (baPWV) measurement within 1 week were retrospectively analyzed. Major adverse cardiovascular events (MACE), including cardiovascular death, acute myocardial infarction, coronary revascularization, and stroke were assessed during the clinical follow-up.

Results: During a mean follow-up period of 3.75 years (interquartile range, 1.78-5.31 years), there were 182 cases of MACE (2.8%). The elevated baPWV (≥1505 cm/s) (hazard ratio (HR), 4.21; 95% confidence interval (CI), 2.73-6.48; < 0.001) and hs-CRP (≥3 mg/L) (HR, 1.57; 95% CI, 1.12-2.21; < 0.001) levels were associated with MACE even after controlling for potential confounders. The combination of baPWV and hs-CRP further stratified the subjects' risk (subjects with low baPWV and hs-CRP vs. subjects with high baPWV and hs-CRP; HR, 7.08; 95% CI, 3.76-13.30; < 0.001). Adding baPWV information to clinical factors and hs-CRP had an incremental prognostic value (global Chi-square score, from 126 to 167, < 0.001).

Conclusions: The combination of hs-CRP and baPWV provided a better prediction of future CVD than either one by itself. Taking these two simple measurements simultaneously is clinically useful in cardiovascular risk stratification.
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http://dx.doi.org/10.3390/jcm10153291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348415PMC
July 2021

Gomisin M2 Ameliorates Atopic Dermatitis-like Skin Lesions via Inhibition of STAT1 and NF-κB Activation in 2,4-Dinitrochlorobenzene/ Extract-Induced BALB/c Mice.

Molecules 2021 Jul 21;26(15). Epub 2021 Jul 21.

Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41566, Korea.

The extracts of (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.
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http://dx.doi.org/10.3390/molecules26154409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346973PMC
July 2021

Feasibility and effectiveness of endoscopic irreversible electroporation for the upper gastrointestinal tract: an experimental animal study.

Sci Rep 2021 07 28;11(1):15353. Epub 2021 Jul 28.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.

Irreversible electroporation (IRE) is a local non-thermal ablative technique currently used to treat solid tumors. Here, we investigated the clinical potency and safety of IRE with an endoscope in the upper gastrointestinal tract. Pigs were electroporated with recently designed endoscopic IRE catheters in the esophagus, stomach, and duodenum. Two successive strategies were introduced to optimize the electrical energy for the digestive tract. First, each organ was electroporated and the energy upscaled to confirm the upper limit energy inducing improper tissue results, including bleeding and perforation. Excluding the unacceptable energy from the first step, consecutive electroporations were performed with stepwise reductions in energy to identify the energy that damaged each layer. Inceptive research into inappropriate electrical intensity contributed to extensive hemorrhage and bowel perforation for each tissue above a certain energy threshold. However, experiments performed below the precluded energy accompanying hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays showed that damaged mucosal area and depth significantly decreased with decreased energy. Relevant histopathology showed infiltration of inflammatory cells with pyknotic nuclei at the electroporated lesion. This investigation demonstrated the possibility of endoscopic IRE in mucosal dysplasia or early malignant tumors of the hollow viscus.
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http://dx.doi.org/10.1038/s41598-021-94583-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319327PMC
July 2021

Prognostic value of serum soluble ST2 in stable coronary artery disease: a prospective observational study.

Sci Rep 2021 07 26;11(1):15203. Epub 2021 Jul 26.

Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, Boramae Medical Center, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, Korea.

The role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P < 0.001). In multiple Cox regression model, higher sST2 level (≥ 26.8 ng/ml) was an independent predictor of MACE even after controlling potential confounders (hazard ratio, 13.7; 95% confidence interval 1.80-104.60; P = 0.011). The elevated level of baseline sST2 is associated with an increased risk of adverse clinical events in stable CAD patients. Studies with larger sample size are needed to confirm our findings.
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http://dx.doi.org/10.1038/s41598-021-94714-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313553PMC
July 2021

Comparative Study of the Difference in Behavior of the Accessory Gene Regulator (Agr) in USA300 and USA400 Community-Associated Methicillin-Resistant (CA-MRSA).

J Microbiol Biotechnol 2021 Aug;31(8):1060-1068

Department of Biological Engineering, College of Engineering, Konkuk University, Seoul 05029, Republic of Korea.

Community-associated Methicillin-Resistant (CA-MRSA) is notorious as a leading cause of soft tissue infections. Despite several studies on the Agr regulator, the mechanisms of action of Agr on the virulence factors in different strains are still unknown. To reveal the role of Agr in different CA-MRSA, we investigated the LACΔ mutant and the MW2Δ mutant by comparing LAC (USA300), MW2 (USA400), and Δ mutants. The changes of Δ mutants in sensitivity to oxacillin and several virulence factors such as biofilm formation, pigmentation, motility, and membrane properties were monitored. LACΔ and MW2Δ mutants showed different oxacillin sensitivity and biofilm formation compared to the LAC and MW2 strains. Regardless of the strain, the motility was reduced in Δ mutants. And there was an increase in the long chain fatty acid in phospholipid fatty acid composition of Δ mutants. Other properties such as biofilm formation, pigmentation, motility, and membrane properties were different in both Δ mutants. The Agr regulator may have a common role like the control of motility and straindependent roles such as antibiotic resistance, biofilm formation, change of membrane, and pigment production. It does not seem easy to control all MRSA by targeting the Agr regulator only as it showed strain-dependent behaviors.
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http://dx.doi.org/10.4014/jmb.2104.04032DOI Listing
August 2021

Polyhydroxyalkanoates (PHAs) degradation by the newly isolated marine Bacillus sp. JY14.

Chemosphere 2021 Nov 12;283:131172. Epub 2021 Jun 12.

Department of Biological Engineering, College of Engineering, Konkuk University, Seoul, Republic of Korea; Institute for Ubiquitous Information Technology and Application, Konkuk University, Seoul, Republic of Korea. Electronic address:

Polyhydroxyalkanoates (PHAs) are bioplastic substitutes for petroleum-derived plastics that may help to reduce the increasing environmental impact of plastic pollution. Among them, polyhydroxybutyrate (PHB) is a promising biopolymer, incentivizing many researchers to search for PHB-producing and PHB-degrading bacteria for improved PHB utilization. Many novel PHB-producing microorganisms have been discovered; however, relatively few PHB-degrading bacteria have been identified. Six PHB-degrading bacteria were found in marine soil and investigated their PHB-degrading abilities under various temperature and salinity conditions using solid-media based culture. Finally, thermotolerant and halotolerant PHB-degrader Bacillus sp. JY14 was selected. PHB degradation was confirmed by monitoring changes in the physical and chemical properties of PHB films incubated with Bacillus sp. JY14 using scanning electron microscopy, Fourier-transform infrared spectroscopy, and gel permeation chromatography. Further, PHB degradation ability of Bacillus sp. JY14 was measured in liquid culture by gas chromatography. After 14 days of cultivation with PHB film, Bacillus sp. JY14 achieved approximately 98% PHB degradation. Applying various bioplastics to assess the bacteria's biodegradation capabilities, the result showed that Bacillus sp. JY14 could also degrade P(3HB-co-4HB) and P(3HB-co-3HV). Overall, this study identified a thermotolerant and halotolerant bacteria capable of PHB degradation under solid and liquid conditions. These results suggest that this bacteria could be utilized to degrade various PHAs.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131172DOI Listing
November 2021

Abdominal periaortic and renal sinus fat attenuation indices measured on computed tomography are associated with metabolic syndrome.

Eur Radiol 2021 Jun 22. Epub 2021 Jun 22.

Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul, Korea.

Objectives: To investigate the association between abdominal periaortic (APA) and renal sinus (RS) fat attenuation index (FAI) measured on MDCT and metabolic syndrome in non-obese and obese individuals.

Methods: Visceral, subcutaneous, RS, and APA adipose tissue were measured in preoperative abdominal CT scans of individuals who underwent donor nephrectomy (n = 84) or bariatric surgery (n = 155). FAI was defined as the mean attenuation of measured fat volume. Participants were categorized into four groups: non-obese without metabolic syndrome (n = 64), non-obese with metabolic syndrome (n = 25), obese without metabolic syndrome (n = 21), and obese with metabolic syndrome (n = 129). The volume and FAI of each fat segment were compared among the groups. Receiver operator characteristics curve analysis was used to assess the association between the FAIs and metabolic syndrome.

Results: FAIs of all abdominal fat segments were significantly lower in the obese group than in the non-obese group (p < 0.001). RS, APA, and the visceral adipose tissue FAIs were significantly lower in participants with metabolic syndrome than in those without metabolic syndrome in the non-obese group (p < 0.001, p = 0.006, and p < 0.001, respectively). The area under the curve for predicting metabolic syndrome was significantly higher for APA FAI (0.790) than subcutaneous, visceral, and RS FAI in all groups (0.649, 0.647, and 0.655, respectively).

Conclusion: Both metabolic syndrome and obesity were associated with lower RS and APA adipose tissue FAI, and APA FAI performed best for predicting metabolic syndrome.

Key Points: • The volume and FAI of RS, APA, and visceral adipose tissue showed opposite trends with regard to metabolic syndrome or obesity. • Both metabolic syndrome and obesity were associated with lower RS FAI and APA FAI. • APA FAI performed best for predicting metabolic syndrome among FAIs of abdominal fat segments.
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http://dx.doi.org/10.1007/s00330-021-08090-7DOI Listing
June 2021

Protectin D1 reduces imiquimod-induced psoriasiform skin inflammation.

Int Immunopharmacol 2021 Sep 19;98:107883. Epub 2021 Jun 19.

CMRI, Departments of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

Specialized proresolving mediators are enzymatically oxygenated natural molecules derived from polyunsaturated fatty acids and are considered novel. These novel mediators include lipoxins from arachidonic acid, resolvins and protectins from omega-3 essential fatty acids, and new maresins. These mediators harbor potent dual proresolving and anti-inflammatory properties. Resolvins and protectins are known to be potent when administered to various inflammation-associated animal models of human diseases. Although psoriasis' etiology remains unknown, there is accumulating evidence indicating that cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-23, and IL-17, play pivotal roles in its development. Experimentally, resolvins, maresins, and lipoxins downregulate the cytokine expression of the IL-23/IL-17 axis and inhibition of mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) cell signaling transduction pathways. Here, we assessed the effects of protectin D1 (PD1) on imiquimod (IMQ)-induced psoriasiform skin inflammation and keratinocytes. PD1 showed clinical improvement in skin thickness, redness, and scaling in psoriasis mouse models. Moreover, PD1 decreased IL-1β, IL-6, IL-17, and CXCL1 mRNA expressions and reduced STAT1 and NF-κB signaling pathway activation in lesions. Serum myeloperoxidase, IgG2a, IL-1β, IL-6, IL-17, and TNF-α and spleen CD4IFN-γIL-17 T lymphocytes were reduced after PD1 treatment in IMQ-induced psoriasiform mouse models. In addition, IL-1β, IL-6, IL-8, and IL-18BP gene expressions were decreased in PD1-treated keratinocytes. Moreover, a decrease in the expression levels of CCL17 and IL-6 and an inhibition of the STAT1 and NF-κB signaling transduction pathways was observed in keratinocytes. These PD1 anti-inflammatory effects suggest that it is a good therapeutic candidate for psoriasis.
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http://dx.doi.org/10.1016/j.intimp.2021.107883DOI Listing
September 2021

Endoscopic submucosal dissection using a detachable assistant robot: a comparative in vivo feasibility study (with video).

Surg Endosc 2021 10 18;35(10):5836-5841. Epub 2021 Jun 18.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk gu, Seoul, 02841, South Korea.

Background: Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe endoscopic submucosal dissection (ESD). We developed a robotic assistive traction device for flexible endoscopy and compared its safety and efficiency in ESD between experienced and novice endoscopists.

Methods: Robotic ESD was performed by experienced and novice endoscopist groups (n = 2, each). The outcomes included time to complete each ESD step, total procedure time, size of the dissected mucosa, rate of en bloc resection, and major adverse events. Furthermore, incision and dissection speeds were compared between groups.

Results: Sixteen gastric lesions were resected from nine live pigs. The submucosal incision speed was significantly faster in the expert group than in the novice group (P = 0.002). There was no significant difference in the submucosal dissection speed between the groups (P = 0.365). No complications were reported in either group.

Conclusions: When the robot was assisting in the ESD procedure, the dissection speed improved significantly, especially in the novice surgeons. Our robotic device can provide simple, effective, and safe multidirectional traction during ESD.
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http://dx.doi.org/10.1007/s00464-021-08510-1DOI Listing
October 2021

Paradoxical paramagnetic calcifications in the globus pallidus: An ex vivo MR investigation and histological validation study.

NMR Biomed 2021 10 15;34(10):e4571. Epub 2021 Jun 15.

Department of Anatomy, Catholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

MR images based on phase contrast images have gained clinical interest as an in vivo tool for assessing anatomical and histological findings. The globus pallidus is an area of major iron metabolism and storage in the brain tissue. Calcium, another important metal in the body, is frequently deposited in the globus pallidus as well. Recently, we observed dense paramagnetic deposition with paradoxical calcifications in the globus pallidus and putamen. In this work, we explore detailed MR findings on these structures, and the histological source of the related findings using ex vivo CT and MR images. Ex vivo MR was obtained with a maximum 100 μm isotropic resolution using a 15.2 T MR system. 3D gradient echo images and quantitative susceptibility mapping were used because of their good sensitivity to metallic deposition, high signal-to-noise ratio, and excellent contrast to iron and calcium. We found dense paramagnetic deposition along the perforating arteries in the globus pallidus. This paramagnetic deposition was hyperdense on ex vivo CT scans. Histological studies confirmed this finding, and simultaneous deposition of iron and calcium, although more iron dominant, was observed along the vessel walls of the globus pallidus. This was an exclusive finding for the penetrating arteries of the globus pallidus. Thus, our results suggest that several strong and paradoxical paramagnetic sources at the globus pallidus can be associated with vascular degeneration.
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http://dx.doi.org/10.1002/nbm.4571DOI Listing
October 2021

Apparent treatment-resistant hypertension among ambulatory hypertensive patients: a cross-sectional study from 13 general hospitals.

Korean J Intern Med 2021 07 7;36(4):888-897. Epub 2021 Jun 7.

Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Korea.

Background/aims: To examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients.

Methods: We enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics.

Results: Among 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses.

Conclusion: Apparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.
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http://dx.doi.org/10.3904/kjim.2019.361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273811PMC
July 2021

Clinical factors associated with reduced global longitudinal strain in subjects with normal left ventricular ejection fraction.

Int J Cardiovasc Imaging 2021 Nov 1;37(11):3225-3232. Epub 2021 Jun 1.

Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine, 5 Boramae-ro, Dongjak-gu, Seoul, 07061, Republic of Korea.

Characteristics of subjects with reduced GLS but no overt left ventricular dysfunction have been poorly characterized. We sought to find clinical factors associated with reduced GLS despite having normal LVEF. Subjects without documented cardiovascular disease who underwent measurement of GLS using 2D speckle-tracking echocardiography were retrospectively reviewed. All subjects had normal LVEF (≥ 55%). Because GLS is a negative value, we took the absolute value |x| for a simpler interpretation. Reduced GLS was defined as < 18%, and normal GLS was defined as ≥ 18%. Of 690 study subjects (mean age, 58 years and females, 51.2%), 208 (30.1%) had reduced GLS. Subjects with reduced GLS were more frequently male, and had more cardiovascular risk factors than those with normal GLS. In multivariable binary logistic regression analysis, male sex (odds ratio [OR] 3.02; 95% confidence interval [CI] 2.02‒4.50; P < 0.001), hypertension (OR 1.52; 95% CI 1.02‒2.28; P = 0.043) and cigarette smoking (OR 1.80; 95% CI 1.14‒2.85; P = 0.012) were independently associated with reduced GLS. The greater the number of these 3 risk factors (male sex, hypertension and cigarette smoking), the higher the probability of having reduced GLS (P < 0.001). In subjects without overt cardiovascular disease who had normal LVEF, a relevant proportion (30.1%) of subjects had reduced GLS. Male sex, hypertension and cigarette smoking were independently associated with reduced GLS. GLS measurement should be emphasized for subjects with these clinical characteristics.
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http://dx.doi.org/10.1007/s10554-021-02304-1DOI Listing
November 2021

A sensitive analytical method for the determination of SG-SP1 in rat plasma by HPLC-MS/MS and its application to a pharmacokinetic study.

J Pharm Biomed Anal 2021 Aug 19;202:114151. Epub 2021 May 19.

College of Pharmacy, Chung-Ang University, Seoul, 06974, South Korea. Electronic address:

SG-SP1, a newly synthesised gallic acid derivative, blocks histamine release by reducing calcium influx in mast cells and inhibits inflammatory cytokine expression. This derivative has promising anti-allergic potential. Our research was designed to establish a quantitative determination method for SG-SP1 in rat plasma using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), to validate the analytical method including stability and to characterise its pharmacokinetic behaviour in rats. After simple protein precipitation with acetonitrile including an internal standard, SG-SP1 was eluted on a reversed-phase column using a mobile phase of water and acetonitrile (2:8 v/v, including 0.1 % formic acid). The protonated precursor ion [M+H] and major fragment ion were confirmed at m/z 588.2 and 180.1, respectively. The substance was stable under bench and storage conditions. The analytical method met the criteria of FDA-validated bioanalytical methods and was successfully applied to a pharmacokinetic study for the first time. SG-SP1 decayed in a biphasic pattern with terminal half-life of 5.1 h and clearance of about 3.2 L/h/kg. Double peaks were observed following oral administration, and the absolute oral bioavailability was ∼1 %.
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http://dx.doi.org/10.1016/j.jpba.2021.114151DOI Listing
August 2021

Associations of Brachial-Ankle Pulse Wave Velocity With Left Ventricular Geometry and Diastolic Function in Untreated Hypertensive Patients.

Front Cardiovasc Med 2021 10;8:647491. Epub 2021 May 10.

Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea.

Although brachial-ankle pulse wave velocity (baPWV) is simple and convenient, its usefulness as an initial screening test for hypertensive patients is not well-known. This study aimed to investigate the association of baPWV with left ventricular (LV) geometry and diastolic function in treatment-naive hypertensive patients. A total of 202 untreated hypertensive patients (mean age, 62 years; males, 51.5%) without documented cardiovascular diseases were prospectively enrolled. Both baPWV and transthoracic echocardiography were performed on the same day before antihypertensive treatment. In multiple linear regression analysis after adjustment for potential confounders, baPWV had significant correlations with structural measurements of LV including relative wall thickness (β = 0.219, = 0.021) and LV mass index (β = 0.286, = 0.002), and four diastolic parameters including septal e' velocity (β = -0.199, = 0.018), E/e' (β = 0.373, < 0.001), left atrial volume index (β = 0.334, < 0.001), and maximal velocity of tricuspid regurgitation (β = 0.401, < 0.001). The baPWV was significantly increased in patients with LV hypertrophy, abnormal LV remodeling, or diastolic dysfunction, compared to those without ( = 0.008, = 0.035, and < 0.001, respectively). In the receiver operating characteristic curve analysis, the discriminant ability of baPWV in predicting LV hypertrophy and diastolic dysfunction had an area under the curve of 0.646 (95% confidence interval 0.544-0.703, = 0.004) and 0.734 (95% confidence interval 0.648-0.800, < 0.001), respectively. baPWV was associated with parameters of LV remodeling and diastolic function in untreated hypertensive patients. The baPWV could be a useful screening tool for the early detection of adverse cardiac features among untreated hypertensive patients.
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http://dx.doi.org/10.3389/fcvm.2021.647491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143267PMC
May 2021

Engineering of Shewanella marisflavi BBL25 for biomass-based polyhydroxybutyrate production and evaluation of its performance in electricity production.

Int J Biol Macromol 2021 Jul 20;183:1669-1675. Epub 2021 May 20.

Department of Biological Engineering, College of Engineering, Konkuk University, Republic of Korea. Electronic address:

Polyhydroxybutyrate (PHB) is a biodegradable plastic with physical properties similar to petrochemically derived plastics. Here, Shewanella marisflavi BBL25 was engineered by inserting the pLW487 vector containing polyhydroxyalkanoates synthesis genes from Ralstonia eutropha H16. Under optimal conditions, the engineered S. marisflavi BBL25 produced 1.99 ± 0.05 g/L PHB from galactose. The strain showed high tolerance to various inhibitors and could utilize lignocellulosic biomass for PHB production. When barley straw hydrolysates were used as a carbon source, PHB production was 3.27 ± 0.19 g/L. In addition, PHB production under the microbial fuel cell system was performed to confirm electricity coproduction. The maximum electricity current output density was 1.71 mA/cm, and dry cell weight (DCW) and PHB production were 11.4 g/L and 6.31 g/L, respectively. Our results demonstrated PHB production using various lignocellulosic biomass and the feasibility of PHB and electricity production, simultaneously, and it is the first example of PHB production in engineered Shewanella.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.105DOI Listing
July 2021
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