Publications by authors named "Gun Kang"

28 Publications

  • Page 1 of 1

Hemodialysis with Cohort Isolation to Prevent Secondary Transmission during a COVID-19 Outbreak in Korea.

J Am Soc Nephrol 2020 07 1;31(7):1398-1408. Epub 2020 Jun 1.

Department of Internal Medicine, Hallym University College of Medicine, Hallym Kidney Research Institute, Seoul, Korea

Background: Health care-associated infections during previous coronavirus epidemics involving severe acute respiratory syndrome and Middle East respiratory syndrome resulted from human-to-human transmission in hemodialysis (HD) facilities. The effect of a strategy of HD with cohort isolation-separate dialysis sessions for close contacts of patients with confirmed coronavirus disease 2019 (COVID-19)-on the prevention of secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in HD units is unknown.

Methods: Our multicenter cohort study of an HD with cohort isolation strategy enrolled close contacts of patients with confirmed COVID-19, including patients on HD and health care workers in HD units. Close contacts had been identified by epidemiologic investigation and tested negative on an immediate screening test for SARS-CoV-2.

Results: As of March 14, 11 patients on HD and 7 health care workers from 11 HD centers were diagnosed as having COVID-19. The immediate screening test was performed in 306 people, and among them, 302 close contacts with negative test results were enrolled. HD with cohort isolation was performed among all close contacts for a median of 14 days in seven centers. During cohort isolation, nine patients showed symptoms but tested negative for SARS-CoV-2. Two health care workers in the HD units (0.66% of the total group) were diagnosed at the termination test for SARS-CoV-2.

Conclusions: The transmission of COVID-19 can be controlled without closure of HD centers by implementing preemptive activities, including early detection with rapid testing, cohort isolation, collaboration between institutions, and continuous monitoring of infection. Our strategy and experience may provide helpful guidance for circumstances involving the rapid spread of infectious diseases such as COVID-19.
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http://dx.doi.org/10.1681/ASN.2020040461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351011PMC
July 2020

Renal hemosiderosis secondary to intravascular hemolysis after mitral valve repair: A case report.

Medicine (Baltimore) 2020 Jan;99(3):e18798

Department of Internal Medicine, Hansung Union Internal Medicine Clinic and Dialysis Center, Daegu, Republic of Korea.

Rationale: Renal hemosiderosis is a disease in which hemosiderin deposits in the renal cortex as a form of iron overload. However, cases of renal hemosiderosis due to intravascular hemolysis following mitral valve repair have been rarely reported.

Patient Concerns: We present the case of a 62-year-old woman who developed asymptomatic urinary abnormalities including microscopic hematuria and proteinuria due to renal hemosiderosis following a mitral valve repair surgery performed two years earlier.

Diagnoses: A percutaneous renal biopsy showed no specific glomerular abnormality, tubular atrophy, or interstitial fibrosis but extensive deposition of hemosiderin in the proximal tubule. The patient was diagnosed with renal hemosiderosis and chronic intravascular hemolysis following mitral valve repair.

Interventions: Our patient refused a mitral valve repeat surgery and hence was treated with oral iron preparations, N-acetylcysteine, and a β-receptor blocker.

Outcomes: Moderate mitral regurgitation with the regurgitant blood striking against the annuloplasty ring was confirmed on follow-up echocardiography. After the 24-month follow-up period, hemolytic anemia persisted, but there was no significant decline of renal function.

Lessons: For cases of chronic intravascular hemolysis accompanied with asymptomatic urinary abnormalities, a renal biopsy is required to exclude underlying kidney pathology and predict potential renal insufficiency.
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http://dx.doi.org/10.1097/MD.0000000000018798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220361PMC
January 2020

Efficacy and Safety of CKD-11101 (Proposed Biosimilar of Darbepoetin-Alfa) Compared with Darbepoetin-Alfa in Patients on Hemodialysis: A Randomized, Double-Blinded, Parallel-Group Phase III Study.

BioDrugs 2020 Feb;34(1):99-110

Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, 1035, Dalgubeol-daero, Dalseo-gu, Daegu, 42601, Korea.

Background: Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs.

Objective: We aimed to evaluate the efficacy and safety of intravenous CKD-11101 (a biosimilar of darbepoetin-alfa) compared with those of darbepoetin-alfa in hemodialysis patients.

Methods: The study was performed in 24 centers in Korea between June 2015 and June 2017. The study subjects were randomized in a double-blind manner. The follow-up duration was 24 weeks, which consisted of 20 weeks of maintenance and 4 weeks of evaluation period. All patients underwent a stabilization period to achieve a target baseline Hb of 10-12 g/dL before randomization. Following randomization, patients received darbepoetin-alfa or CKD-11101 weekly or biweekly.

Results: A total of 403 patients were randomized into two groups, and a total of 325 patients (80.6%) completed the investigation. The differences between the two groups in terms of change in the average Hb level from baseline to evaluation were not significant. The average administered dose of ESA was similar between the groups. There was no difference in the proportion of patients who maintained the target Hb during the evaluation period [60.4% vs. 66.2% in the CKD-11101 and darbepoetin-alfa groups, respectively (p = 0.3038)]. In addition, the safety analysis, consisting of adverse events and adverse drug reactions, showed comparable results between the two groups.

Conclusion: The changes in the level of Hb, dose of erythropoietin, and achievement rate of the target Hb during the study period were comparable between the groups. CKD-11101 has an equivalent efficacy and safety compared with darbepoetin-alfa in patients undergoing hemodialysis.
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http://dx.doi.org/10.1007/s40259-019-00396-9DOI Listing
February 2020

Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis.

Gynecol Oncol 2019 09 12;154(3):638-650. Epub 2019 Jul 12.

Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: To assess the effect of adjuvant chemotherapy (AC) or radiotherapy (AR) on the risk of recurrence in surgically treated patients with early-stage uterine leiomyosarcoma (uLMS).

Methods: We searched the PubMed, EMBASE, and MEDLINE, and Cochrane databases for publications up to March 2019, which compared patients with early-stage uLMS who received AC or AR with those who did not. The primary endpoint was recurrence rate. Random- or fixed-effects models were used for pooled estimates of the effect of adjuvant treatments on recurrence rates. Subgroup analyses were conducted based on study design, surgical staging, AC regimen (gemcitabine/docetaxel regimen), and type of AR.

Results: Three randomized trials and 9 observational studies (9 studies for AC vs. observation, n = 496; 9 studies for AR vs. observation, n = 425) were included. The meta-analysis indicated that AC did not decrease the risk of recurrence compared with observation (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.37-1.15, P = 0.14; P = 0.09 and I = 42.1). Similarly, AR did not decrease the risk of recurrence compared with observation (OR = 1.11, 95% CI = 0.56-2.21, P = 0.76; P = 0.10 and I = 40.4). Meta-regression analyses revealed no significant association between median follow-up time and recurrence. In subgroup analyses (study design, surgical staging, gemcitabine/docetaxel regimen, type of AR), neither AC nor AR decreased the risk of recurrence significantly.

Conclusion: AC, including gemcitabine/docetaxel regimen, or AR did not reduce the recurrence rate in patients with early-stage uLMS.
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http://dx.doi.org/10.1016/j.ygyno.2019.07.001DOI Listing
September 2019

Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis.

Gynecol Oncol 2019 09 12;154(3):638-650. Epub 2019 Jul 12.

Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: To assess the effect of adjuvant chemotherapy (AC) or radiotherapy (AR) on the risk of recurrence in surgically treated patients with early-stage uterine leiomyosarcoma (uLMS).

Methods: We searched the PubMed, EMBASE, and MEDLINE, and Cochrane databases for publications up to March 2019, which compared patients with early-stage uLMS who received AC or AR with those who did not. The primary endpoint was recurrence rate. Random- or fixed-effects models were used for pooled estimates of the effect of adjuvant treatments on recurrence rates. Subgroup analyses were conducted based on study design, surgical staging, AC regimen (gemcitabine/docetaxel regimen), and type of AR.

Results: Three randomized trials and 9 observational studies (9 studies for AC vs. observation, n = 496; 9 studies for AR vs. observation, n = 425) were included. The meta-analysis indicated that AC did not decrease the risk of recurrence compared with observation (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.37-1.15, P = 0.14; P = 0.09 and I = 42.1). Similarly, AR did not decrease the risk of recurrence compared with observation (OR = 1.11, 95% CI = 0.56-2.21, P = 0.76; P = 0.10 and I = 40.4). Meta-regression analyses revealed no significant association between median follow-up time and recurrence. In subgroup analyses (study design, surgical staging, gemcitabine/docetaxel regimen, type of AR), neither AC nor AR decreased the risk of recurrence significantly.

Conclusion: AC, including gemcitabine/docetaxel regimen, or AR did not reduce the recurrence rate in patients with early-stage uLMS.
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http://dx.doi.org/10.1016/j.ygyno.2019.07.001DOI Listing
September 2019

Efficacy and safety of CKD-11101 (darbepoetin-alfa proposed biosimilar) compared with NESP in anaemic chronic kidney disease patients not on dialysis.

Curr Med Res Opin 2019 06 17;35(6):1111-1118. Epub 2019 Jan 17.

a Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine , The Catholic University of Korea , Seoul , Korea.

Objective: To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP® in treatment of anaemia in patients with chronic kidney disease not on dialysis.

Clinical Trial Registration: NCT03431623.

Method: In this multi-centre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24 weeks, during which patients were treated every 2 weeks. All patients who completed the EEP were treated with CKD-11101 every 2 weeks for the first 4 weeks and every 4 weeks for the safety evaluation period (SEP), which was from 24 weeks to 52 weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb.

Results: The mean Hb level was increased in both groups during the EEP (both p < 0.001). The difference in mean Hb level change between the two groups was 0.01 g/dL (95% CI = -0.213-0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was -1.40 mcg (95% CI = -6.859-4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group).

Conclusion: CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.
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http://dx.doi.org/10.1080/03007995.2018.1560134DOI Listing
June 2019

The Quality of Life of Hemodialysis Patients Is Affected Not Only by Medical but also Psychosocial Factors: a Canonical Correlation Study.

J Korean Med Sci 2018 Apr 2;33(14):e111. Epub 2018 Apr 2.

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

Background: The quality of life (QoL) of patients with end-stage renal disease (ESRD) is very poor, plausibly due to both psychosocial and medical factors. This study aimed to determine the relationship among psychosocial factors, medical factors, and QoL in patients with ESRD undergoing hemodialysis (HD).

Methods: In total, 55 male and 47 female patients were evaluated (mean age, 57.1 ± 12.0 years). The QoL was evaluated using the Korean version of World Health Organization Quality of Life Scale-Abbreviated Version. The psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, Pittsburgh Sleep Quality Index, and Zarit Burden Interview. The medical factors were assessed using laboratory examinations. Correlation and canonical correlation analyses were performed to investigate the association patterns.

Results: The QoL was significantly correlated with the psychosocial factors, and to a lesser extent with the medical factors. The medical and psychosocial factors were also correlated. The canonical correlation analysis indicated a correlation between QoL and psychosocial factors (1st canonical correlation = 0.696, P < 0.001; 2nd canonical correlation = 0.421, P = 0.191), but not medical factors (1st canonical correlation = 0.478, P = 0.475; 2nd canonical correlation = 0.419, P = 0.751). The medical and psychosocial factors were also correlated (1st canonical correlation = 0.689, P < 0.001; 2nd canonical correlation = 0.603, P = 0.009).

Conclusion: Psychosocial factors influence QoL in patients with ESRD, and should thus be carefully considered when caring for these patients in clinical practice.
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http://dx.doi.org/10.3346/jkms.2018.33.e111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879041PMC
April 2018

Protein kinase C beta II upregulates intercellular adhesion molecule-1 via mitochondrial activation in cultured endothelial cells.

Korean J Physiol Pharmacol 2017 Jul 26;21(4):377-384. Epub 2017 Jun 26.

Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 35015, Korea.

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of PKCβII on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral PKCβII gene transfer and pharmacological inhibitors, the role of PKCβII on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by PKCβi (10 nM), a selective inhibitor of PKCβII. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by PKCβi. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of PKCβII inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of PKCβII using adenoviral PKCβII increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, PKCβII-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that PKCβII plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of PKCβII-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.
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http://dx.doi.org/10.4196/kjpp.2017.21.4.377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507776PMC
July 2017

ethanol extract inhibits monocyte adhesion to tumor necrosis factor-alpha-stimulated endothelial cells.

Integr Med Res 2016 Jun 31;5(2):131-139. Epub 2016 Mar 31.

Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, Korea.

Background: var. Rehder (UD) has long been used in traditional folk medicine in Asia. This study is designed to investigate the antiadhesive activity of the ethanol extract of UD (UDE) and its underlying mechanisms in cultured endothelial cells.

Methods: The dried root bark of UD was extracted with 80% (v/v) ethanol. The antiadhesive activity of the UDE was investigated in cultured human umbilical vein endothelial cells and human embryonic kidney epithelial 293T (HEK 293T) cells stably transfected with pGL3-vascular cell adhesion molecule (VCAM)-1-luc. Monocyte adhesion in endothelial cells was induced by tumor necrosis factor-alpha (TNF-α), and the protective effects of UDE on monocyte-endothelial cell adhesion, VCAM-1 expression, reactive oxygen species production, and nuclear factor-κB activity were determined.

Results: Exposure to UDE at a concentration of 3-30 μg/mL for 24 hours produced no detectable cytotoxicity in human umbilical vein endothelial cells, but it significantly inhibited TNF-α-induced monocyte adhesion and VCAM-1 expression. TNF-α treatment of HEK 293T/ cells resulted in increased luciferase activity of the VCAM-1 promoter, which was inhibited by treatment with UDE. Additionally, TNF-α-induced reactive oxygen species generation, nuclear translocation of nuclear factor-κB, and IκBα degradation in human umbilical vein endothelial cells were effectively reduced by treatment with 30 μg/mL of UDE.

Conclusion: Our results indicated that UDE treatment inhibited TNF-α-induced monocyte adhesion in endothelial cells, suggesting that UD may reduce vascular endothelial inflammation.
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http://dx.doi.org/10.1016/j.imr.2016.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381430PMC
June 2016

Hypersensitivity pneumonitis associated with azathioprine therapy in a patient with granulomatosis with polyangiitis.

Rheumatol Int 2016 Jul 7;36(7):1027-32. Epub 2016 May 7.

Division of Pulmonary and Critical Medicine, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.

Granulomatosis with polyangiitis (GPA), an autoimmune disease characterized by inflammatory granulomas and necrotizing small-vessel vasculitis, primarily affects the respiratory tract and kidneys. Azathioprine (AZA) is a purine analog that is commonly used for maintaining GPA remission after induction therapy with cyclophosphamide. While the dose-dependent side effects of AZA are common and well known, hypersensitivity reactions such as pulmonary toxicity are rare. Here, we describe a case involving a 38-year-old man with GPA-associated pauci-immune crescentic glomerulonephritis who developed subacute hypersensitivity pneumonitis (HP) during AZA maintenance therapy. Five months after the initiation of AZA administration (100 mg/day), the patient was admitted with a 7-day history of cough, dyspnea, and fever. High-resolution computed tomography of the chest showed ill-defined centrilobular nodules and diffuse ground-glass opacities in both lung fields. Bronchoscopy with bronchoalveolar lavage was negative for infectious etiologies. A transbronchial lung biopsy specimen revealed poorly formed non-necrotizing granulomas. A chest radiograph obtained at 2 weeks after discontinuation of AZA showed normal findings. The findings from this case suggest that AZA-induced HP should be considered as a differential diagnosis when a patient with GPA exhibits fresh pulmonary lesions accompanied by respiratory symptoms during AZA therapy.
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http://dx.doi.org/10.1007/s00296-016-3489-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101638PMC
July 2016

Secreted APE1/Ref-1 inhibits TNF-α-stimulated endothelial inflammation via thiol-disulfide exchange in TNF receptor.

Sci Rep 2016 Mar 11;6:23015. Epub 2016 Mar 11.

Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of KOREA.

Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) is a multifunctional protein with redox activity and is proved to be secreted from stimulated cells. The aim of this study was to evaluate the functions of extracellular APE1/Ref-1 with respect to leading anti-inflammatory signaling in TNF-α-stimulated endothelial cells in response to acetylation. Treatment of TNF-α-stimulated endothelial cells with an inhibitor of deacetylase that causes intracellular acetylation, considerably suppressed vascular cell adhesion molecule-1 (VCAM-1). During TSA-mediated acetylation in culture, a time-dependent increase in secreted APE1/Ref-1 was confirmed. The acetyl moiety of acetylated-APE1/Ref-1 was rapidly removed based on the removal kinetics. Additionally, recombinant human (rh) APE1/Ref-1 with reducing activity induced a conformational change in rh TNF-α receptor 1 (TNFR1) by thiol-disulfide exchange. Following treatment with the neutralizing anti-APE1/Ref-1 antibody, inflammatory signals via the binding of TNF-α to TNFR1 were remarkably recovered, leading to up-regulation of reactive oxygen species generation and VCAM-1, in accordance with the activation of p66(shc) and p38 MAPK. These results strongly indicate that anti-inflammatory effects in TNF-α-stimulated endothelial cells by acetylation are tightly linked to secreted APE1/Ref-1, which inhibits TNF-α binding to TNFR1 by reductive conformational change, with suggestion as an endogenous inhibitor of vascular inflammation.
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http://dx.doi.org/10.1038/srep23015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786854PMC
March 2016

The 18-kDa Translocator Protein Inhibits Vascular Cell Adhesion Molecule-1 Expression via Inhibition of Mitochondrial Reactive Oxygen Species.

Mol Cells 2015 Dec 25;38(12):1064-70. Epub 2015 Nov 25.

Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.

Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10-100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO (0.1-0.5 μM), a specific mitochondrial antioxidants, and cyclosporin A (1-5 μM), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam (1-50 μM), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells.
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http://dx.doi.org/10.14348/molcells.2015.0165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696997PMC
December 2015

Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood Pressure Via Inhibition of p66shc Activation.

Korean J Physiol Pharmacol 2015 Sep 20;19(5):467-72. Epub 2015 Aug 20.

Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.

Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I (AT1R) inhibitor, valsartan (10 µM), but not by the AT2R inhibitor, PD123319. TSA (1~10 µM) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing AT1R. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through AT1R.
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http://dx.doi.org/10.4196/kjpp.2015.19.5.467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553407PMC
September 2015

Clinical and psychosocial factors predicting health-related quality of life in hemodialysis patients.

Hemodial Int 2015 Jul 3;19(3):439-46. Epub 2015 Feb 3.

Department of Psychiatry, Catholic University of Daegu School of Medicine, Daegu, Korea.

Many patients with end-stage renal disease have significant impairment in health-related quality of life (HRQoL). Most previous studies have focused on clinical factors; however, quality of life can also be affected by psychosocial factors. The aim of this study was to identify the possible predictors of HRQoL among clinical and psychosocial factors in hemodialysis (HD) patients. The study included 101 patients who were undergoing HD. Psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, and Pittsburgh Sleep Quality Index. We also assessed laboratory and clinical factors, including albumin, Kt/V as a marker of dialysis adequacy, normalized protein catabolic rate, and duration of HD. The Euro Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D) was used to evaluate HRQoL. The mean EQ-5D index score was 0.704 ± 0.199. The following variables showed a significant association with the EQ-5D index: age (P < 0.001), depression (P < 0.001), anxiety (P < 0.001), support from friends (P < 0.001), cognitive function (P < 0.001), duration of HD (P = 0.034), triglyceride (P = 0.031), total iron-binding capacity (P = 0.036), and phosphorus (P = 0.037). Multiple regression analysis showed that age (95% confidence interval [CI] -0.008 to -0.002), anxiety (95% CI -0.025 to -0.009), and support from friends (95% CI 0.004 to 0.018) were independent predictors of impaired HRQoL. This study explored determinants of impaired HRQoL in HD patients. We found that impaired HRQoL was independently associated with age, anxiety, and support from friends. We should consider psychosocial as well as clinical factors when evaluating ways to improve HRQoL in HD patients.
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http://dx.doi.org/10.1111/hdi.12271DOI Listing
July 2015

Cytoplasmic localization and redox cysteine residue of APE1/Ref-1 are associated with its anti-inflammatory activity in cultured endothelial cells.

Mol Cells 2013 Nov 6;36(5):439-45. Epub 2013 Nov 6.

Department of Physiology, School of Medicine, Chungnam National University, Daejeon, 301-747, Korea.

Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and transcriptional regulation of gene expression. APE1/Ref-1 is mainly localized in the nucleus, but cytoplasmic localization has also been reported. However, the functional role of cytoplasmic APE1/Ref-1 and its redox cysteine residue are still unknown. We investigated the role of cytoplasmic APE1/Ref-1 on tumor necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expressions in endothelial cells. Endogenous APE1/Ref-1 was mainly observed in the nucleus, however, cytoplasmic APE1/Ref-1 was increased by TNF-α. Cytoplasmic APE1/Ref-1 expression was not blunted by cycloheximide, a protein synthesis inhibitor, suggesting cytoplasmic translocation of APE1/Ref-1. Transfection of an N-terminus deletion mutant APE1/Ref-1(29-318) inhibited TNF-α-induced VCAM-1 expression, indicating an anti-inflammatory role for APE1/Ref-1 in the cytoplasm. In contrast, redox mutant of APE1/Ref-1 (C65A/C93A) transfection led to increased TNF-α-induced VCAM-1 expression. Our findings suggest cytoplasmic APE1/Ref-1 localization and redox cysteine residues of APE1/Ref-1 are associated with its anti-inflammatory activity in endothelial cells.
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http://dx.doi.org/10.1007/s10059-013-0195-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887937PMC
November 2013

Severe lactic acidosis and acute pancreatitis associated with cimetidine in a patient with type 2 diabetes mellitus taking metformin.

Intern Med 2013 1;52(19):2245-8. Epub 2012 Mar 1.

Department of Internal Medicine, Catholic University of Daegu School of Medicine, Korea.

An 82-year-old woman with type 2 diabetes mellitus, hypertension, and unstable angina presented with severe lactic acidosis and acute kidney injury (AKI) accompanied by acute pancreatitis. Her medical history revealed that she had taken cimetidine for two weeks while taking other medications, including metformin. Continuous veno-venous hemodiafiltration (CVVHDF) was initiated under diagnosis of lactic acidosis due to metformin and AKI caused by cimetidine-induced acute pancreatitis. In three days of CVVHDF, the levels of serum biochemical markers of lactic acidosis and AKI improved and the patient's urine output reached over 1 L/day. The pancreatitis improved over time.
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http://dx.doi.org/10.2169/internalmedicine.52.0697DOI Listing
May 2014

Kienböck's disease associated with radiocephalic fistula formation in a patient with end-stage renal disease.

Hemodial Int 2013 Oct 25;17(4):648-51. Epub 2013 Apr 25.

Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.

Kienböck's disease, which consists of osteonecrosis and collapse of the lunate bone, causes chronic pain and dysfunction of the wrist. Patients on hemodialysis are occasionally present with wrist pain, but Kienböck's disease is rarely reported in dialysis patients. This case study describes Kienböck's disease in a patient with end-stage renal disease on hemodialysis. A 39-year-old male with a 1-year history of hemodialysis presented with left wrist pain that increased progressively over 6 months. The patient had no history of trauma or any other risk factors known to be associated with Kienböck's disease. Physical examination of the wrist at the site of the arteriovenous fistula showed swelling and tenderness with decreased range of motion. Radiographic examination showed articular collapse and fracture of the body of lunate consistent with stage IIIb Kienböck's disease. An intercarpal arthrodesis with autogenous bone graft was performed.
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http://dx.doi.org/10.1111/hdi.12048DOI Listing
October 2013

Cerebral oxygenation monitoring of patients during arthroscopic shoulder surgery in the sitting position.

Korean J Anesthesiol 2012 Oct 12;63(4):297-301. Epub 2012 Oct 12.

Department of Orthopedic Surgery, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Korea.

Background: Cerebral hypotension and desaturation can occur during shoulder surgery in the seated position. We evaluated the correlation of cerebral oxygen saturation (rSO(2)) using near infra-red spectroscopy (NIRS) and mean arterial pressures (MAP) (at the levels of the brain and heart).

Methods: Fifty patients, scheduled for the arthroscopic shoulder surgery in the seated position, were enrolled to monitor the rSO(2), bispectral Index (BIS), and MAPs at the levels of the brain and heart. The values of each parameter were collected at 5 min after intubation, immediately after placing the patient in the sitting position, 5 min after the patient was seated, immediately after the surgical incision, and every 30 min after incision.

Results: A correlation between the cerebral rSO(2) and the MAP at the level of brain were statistically significant. Cerebral rSO(2) and MAP after a change of posture from supine to sitting position were significantly decreased, compared to the baseline value.

Conclusions: Monitoring cerebral rSO(2) and MAP at the level of brain can be helpful to detect the possibility of cerebral deoxygenation earlier.
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http://dx.doi.org/10.4097/kjae.2012.63.4.297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483486PMC
October 2012

Vasorelaxing Activity of Ulmus davidiana Ethanol Extracts in Rats: Activation of Endothelial Nitric Oxide Synthase.

Korean J Physiol Pharmacol 2011 Dec 27;15(6):339-44. Epub 2011 Dec 27.

Infection Signaling Network Research Center, Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-131, Korea.

Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD (10~100µg/ml) did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of 0.1~10µg/ml with an ED(50) value of 2µg/ml. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high K(+) and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium.
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http://dx.doi.org/10.4196/kjpp.2011.15.6.339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282221PMC
December 2011

Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and p62/SQSTM1.

Immunol Cell Biol 2012 Jul 30;90(6):601-10. Epub 2011 Aug 30.

Department of Microbiology, Chungnam National University School of Medicine, Daejeon, Korea.

Numerous atypical mycobacteria, including Mycobacterium abscessus (Mabc), cause nontuberculous mycobacterial infections, which present a serious public health threat. Inflammasome activation is involved in host defense and the pathogenesis of autoimmune diseases. However, inflammasome activation has not been widely characterized in human macrophages infected with atypical mycobacteria. Here, we demonstrate that Mabc robustly activates the nucleotide binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome via dectin-1/Syk-dependent signaling and the cytoplasmic scaffold protein p62/SQSTM1 (p62) in human macrophages. Both dectin-1 and Toll-like receptor 2 (TLR2) were required for Mabc-induced mRNA expression of pro-interleukin (IL)-1β, cathelicidin human cationic antimicrobial protein-18/LL-37 and β-defensin 4 (DEFB4). Dectin-1-dependent Syk signaling, but not that of MyD88, led to the activation of caspase-1 and secretion of IL-1β through the activation of an NLRP3/apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) inflammasome. Additionally, potassium efflux was required for Mabc-induced NLRP3/ASC inflammasome activation. Furthermore, Mabc-induced p62 expression was critically involved in NLRP3 inflammasome activation in human macrophages. Finally, NLRP3/ASC was critical for the inflammasome in antimicrobial responses to Mabc infection. Taken together, these data demonstrate the induction mechanism of the NLRP3/ASC inflammasome and its role in innate immunity to Mabc infection.
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http://dx.doi.org/10.1038/icb.2011.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389799PMC
July 2012

[A case of Chlamydia trachomatis peritonitis mimicking tuberculous peritonitis].

Korean J Gastroenterol 2011 Dec;58(2):111-6

Departments of Internal Medicine and Surgery, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.

Lymphocytic ascites with low serum-ascites albumin gradient (SAAG) are observed mainly in tuberculous peritonitis, peritoneal carcinomatosis, and pancreatic disease. However, pelvic inflammatory disease (PID) induced generalized peritonitis causing diffuse ascites has been rarely described. We report a 26-year old female patient, who was diagnosed as generalized peritonitis with diffuse ascites due to Chlamydia trachomatis infection. Gynecologic examination did not show the clue of PID and in the analysis of ascites, low SAAG, predominant lymphocyte count and high level of adenosine deaminase were noted. Although the best impression was tuberculous peritonitis on the base of these findings, the laparoscopic finding was consistent with PID and the PCR for C. trachomatis infection in cervical swab was positive. This case suggests that C. trachomatis peritonitis should be considered as a rare cause of low SAAG and lymphocytic ascites in sexually active women and should be intensively evaluated including laparoscopic examination.
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http://dx.doi.org/10.4166/kjg.2011.58.2.111DOI Listing
December 2011

Ileal stenosis occurred 3 months after blunt abdominal trauma.

Korean J Gastroenterol 2011 Jun;57(6):370-3

Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.

We present a case of ileal stenosis with delayed presentation 3 months after car accident. Ileal stenosis after blunt abdominal trauma is a rare clinical entity. We present CT and small bowel series 3 months after trauma. Image showed segmental thickening of intestinal wall and proximal bowel dilation. At surgery, a stenotic bowel loop was adjacent to a fibrotic mesentery. Histological examination showed ulcers, inflammatory cells and fibroblasts infiltrated to the muscularis mucosae, submucosa, and mesentery. The most likely cause, supported by most authors, implicates an injury to the mesentery. Post-traumatic ischemic bowel stenosis may result from even small tears and contusions of mesentery. Posttraumatic intestinal stenosis should be included in the differential diagnosis in a patient with a history of blunt abdominal trauma and signs of intestinal obstruction.
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http://dx.doi.org/10.4166/kjg.2011.57.6.370DOI Listing
June 2011

Endoplasmic reticulum stress response is involved in Mycobacterium tuberculosis protein ESAT-6-mediated apoptosis.

FEBS Lett 2010 Jun 21;584(11):2445-54. Epub 2010 Apr 21.

Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, South Korea.

Mycobacterium tuberculosis (Mtb) infection leads to the induction of the apoptotic response, which is associated with bacilli killing. The early secreted mycobacterial antigen ESAT-6 of Mtb has been shown to induce apoptosis in human macrophages and epithelial cells. In the present study, we demonstrate that the stimulation of human epithelial A549 cells by ESAT-6 induces the endoplasmic reticulum (ER) stress response. We observed that ESAT-6 treatment increases intracellular Ca(2+) concentration, which results in ROS accumulation, and therefore induces the onset of ER stress-induced apoptosis. Our results uncover a novel apoptotic mechanism of ESAT-6 through ER stress responses in pathologic conditions such as tuberculosis.
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http://dx.doi.org/10.1016/j.febslet.2010.04.050DOI Listing
June 2010

A phase II trial of paclitaxel, 5-fluorouracil (5-FU) and cisplatin in patients with metastatic or recurrent gastric cancer.

Cancer Res Treat 2008 Sep 30;40(3):106-10. Epub 2008 Sep 30.

Department of Internal Medicine, College of Medicine, Inje University, Sanggye Paik Hospital, Seoul, Korea.

Purpose: We wanted to assess the effectiveness and safety of combination chemotherapy with paclitaxel, 5-fluorouracil (5-FU) and cisplatin for treating advanced gastric cancer.

Materials And Methods: Patients with metastatic or recurrent gastric cancer were entered into this study. Paclitaxel at a dose of 135 mg/m(2) on day 1, 5-FU 1 g/m(2)/day in a 24 hour continuous infusion from day 1 to day 4 and cisplatin 60 mg/m(2) on day 1 were administered. This regimen was repeated every 3 weeks.

Results: A total of 34 patients were enrolled in this study. Among them, 33 patients were finally evaluable for their response. 17 (51.5%) patients had a partial response (95% CI: 26.0 approximately 77.0%). The median duration of overall survival was 13.2 months. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15.2% and 1.1% of all the cycles, respectively. Grade 3 stomatitis and neurotoxicity were observed in 20.6% and 1.1% of all patients, respectively. Grade 4 non-hematologic toxicity was not observed.

Conclusions: The regimen of paclitaxel, 5-FU and cisplatin demonstrated activity and acceptable toxicity for treating metastatic gastric cancer.
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http://dx.doi.org/10.4143/crt.2008.40.3.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697463PMC
September 2008

New approach for fabrication of folded-structure SiO2 using oyster shell.

Micron 2009 Oct 18;40(7):713-8. Epub 2009 May 18.

Department of Chemical & Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 335 Gwahangno Yuseonggu, Daejeon 305-701, Republic of Korea.

Inspired by the phenomenological differences of layers in oyster shell and the morphological mimicry of SiO(2) thin film, a folded-structure SiO(2) was created by simple spray deposition system. The folded-structure SiO(2) was analyzed by scanning electron microscopy, energy dispersive spectrometer and microindentation. At the molecular level, the chalky and the folia were assembled and determined through biomineralization based on the differences of soluble protein in layers. At the macro-scale, the granular SiO(2) particles deposited at the surface of shell layers or Ca(OH)(2) and grew into thin film, thus leading to mimic the morphology of substrate.
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http://dx.doi.org/10.1016/j.micron.2009.05.002DOI Listing
October 2009

The effects of interleukin-6 on the contraction and relaxation responses of the cavernous smooth muscle from rats.

Eur J Pharmacol 2008 Jul 5;589(1-3):228-32. Epub 2008 May 5.

Department of Urology, Chung-Ang University Hospital, Seoul, Republic of Korea.

The purpose of this study is to elucidate the effect of IL-6 on the vasomotor reactivity of the corpus cavernosum of the rats. The strips were either left untreated or treated with 1 ng/ml of IL-6 for 60 min. By increasing concentrations of phenylephrine, acetylcholine, or sodium nitroprusside, we assessed concentration-contraction or relaxation responses. The IL-6-treated strips were incubated for 30 min with or without L-NAME (N(W)-nitro-L-arginine methyl ester), L-arginine, indomethacin, BQ-123 (an endothelin receptor A inhibitor), or SQ 29,548 (a thromboxane A(2) [TXA(2)] receptor blocker), and the effects on phenylephrine-induced contraction or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured. The contractile responses to phenylephrine were significantly enhanced in the IL-6-treated strips, compared with the IL-6-nontreated strips, and the relaxation responses to acetylcholine were significantly inhibited in the IL-6-treated group compared with the IL-6-nontreated group. But after endothelial denudation, there was no difference between the IL-6-treated strips and the IL-6-nontreated strips on the contraction-relaxation responses to phenylephrine or acetylcholine. The relaxation responses to sodium nitroprusside were not inhibited in both groups. L-NAME completely inhibited the relaxation response to acetylcholine in the IL-6-treated strips, as well as the IL-6-nontreated strips. Indomethacin and SQ 29,548 significantly inhibited the increased contractile responses to phenylephrine in the IL-6-treated strips. But BQ 123 rarely affected the same responses. L-arginine reversed the inhibited relaxation responses to acetylcholine in the IL-6-treated strips. Therefore, IL-6 inhibits endothelium-dependent, NO-mediated relaxation and also enhances alpha(1)-adrenergic receptor-mediated contraction via an endothelium-dependent TXA(2)-mediated mechanism in the corpus cavernosum of the rat.
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http://dx.doi.org/10.1016/j.ejphar.2008.04.053DOI Listing
July 2008

Serotonin inhibits GABA synaptic transmission in presympathetic paraventricular nucleus neurons.

Neurosci Lett 2008 Jul 10;439(2):138-42. Epub 2008 May 10.

Research Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Joong-gu, Daejeon, 301-131, Republic of Korea.

Activation of serotonin (5-hydroxytryptamine, 5-HT) receptors produces various autonomic and neuroendocrine responses in the hypothalamic paraventricular nucleus (PVN), including increased blood pressure and heart rate. However, the role(s) of 5-HT on the local GABA synaptic circuit have not been well understood in the PVN, where the inhibitory neurotransmitter GABA plays a key role in the modulation of sympathoexcitatory outflow. In the present study, we examined the effects of 5-HT on GABA synaptic transmission in presympathetic PVN neurons projecting to spinal cord using patch-clamp electrophysiology combined with tract-tracing techniques. Bath application of 5-HT (0.01-100 microM) reversibly decreased the frequency of spontaneous GABAergic inhibitory postsynaptic currents (sIPSC) in a concentration dependent manner (IC50, 0.07 microM), with no significant changes in the amplitudes and decay kinetics of sIPSC. The sIPSC inhibition of 5-HT was mimicked by 5-HT1A agonist, 8-OH-DPAT (8-hydroxy-2(di-n-propylamino)tetralin, 10 microM), and blocked by 5-HT1A antagonist WAY-100635 but not by 5-HT1B antagonist SB224289. 5-HT also reduced the frequency of miniature IPSC (mIPSC) (2.59+/-0.51 Hz, control vs. 1.25+/-0.31 Hz, 5-HT, n=16) in similar extent with 5-HT induced reduction of sIPSC frequency (sIPSCs, 55.8+/-6.2%, n=11 vs. mIPSCs, 52.30+/-5.85%, n=16; p>0.5). All together, our results indicate that 5-HT can inhibit presynaptic GABA release via presynaptic 5-HT1A receptors in presympathetic PVN neurons projecting to spinal cord.
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http://dx.doi.org/10.1016/j.neulet.2008.05.012DOI Listing
July 2008