Chien-Sung Tsai

Tri-Service General Hospital, T’ai-pei, Taipei, Taiwan

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Publications (111)233.15 Total impact

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    ABSTRACT: The effects of intravenous (IV) catheter gauge and pressurization of IV fluid (IVF) bags on fluid flow rate have been studied. However, the pressure needed to achieve a flow rate equivalent to that of a 16 gauge (G) catheter through smaller G catheters and the potential for endothelial damage from the increased kinetic energy produced by higher pressurization are unclear. Constant pressure on an IVF bag was maintained by an automatic adjustable pneumatic pressure regulator of our own design. Fluids running through 16 G, 18 G, 20 G, and 22 G catheters were assessed while using IV bag pressurization to achieve the flow rate equivalent to that of a 16 G catheter. We assessed flow rates, kinetic energy, and flow injury to rabbit inferior vena cava endothelium. By applying sufficient external constant pressure to an IVF bag, all fluids could be run through smaller (G) catheters at the flow rate in a 16 G catheter. However, the kinetic energy increased significantly as the catheter G increased. Damage to the venous endothelium was negligible or minimal/patchy cell loss. We designed a new rapid infusion system, which provides a constant pressure that compresses the fluid volume until it is free from visible residual fluid. When large-bore venous access cannot be obtained, multiple smaller catheters, external pressure, or both should be considered. However, caution should be exercised when fluid pressurized to reach a flow rate equivalent to that in a 16 G catheter is run through a smaller G catheter because of the profound increase in kinetic energy that can lead to venous endothelium injury.
    No preview · Article · Dec 2015 · Shock (Augusta, Ga.)
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    ABSTRACT: Background: The presence of intracellular pH (pHi ) regulators, including Na(+) -H(+) exchanger (NHE), Na(+) -HCO3- co-transporter (NBC), Cl(-) /OH(-) exchanger (CHE), and Cl(-) /HCO3- exchanger (AE), have been confirmed in many mammalian cells. Alcohol consumption is associated with increased risk of cardiovascular disorder. The aims of the study were to identify the possible transmembrane pHi regulators and to explore the effects of ethanol (EtOH) (10 to 300 mM) on the resting pHi and pHi regulators in human aorta smooth muscle cells (HASMCs). Methods: HASMCs were obtained from patients undergoing heart transplant. The pHi was measured by microspectrofluorimetry with the pH-sensitive dye, BCECF-AM. Results: The following results are obtained. (i) In cultured HASMCs, the resting pHi was 7.19 ± 0.04 and 7.13 ± 0.02 for HEPES- and CO2 /HCO3--buffered solution, respectively. (ii) Two different Na(+) -dependent acid-equivalent extruders, including NHE and Na(+) -coupled HCO3- transporter, functionally coexisted. (iii) Two different Cl(-) -dependent acid loaders (CHE and AE) were functionally identified. (iv) EtOH induced a biphasic, concentration-dependent change in resting pHi (+0.25 pH unit at 100 mM but only +0.05 pH unit at 300 mM) in bicarbonate-buffered solution, while caused a concentration-dependent decrease in resting pHi (-0.06 pH unit at 300 mM) in HEPES-buffered solution. (v) The effect of EtOH on NHE activity was also biphasic: increase of 40% at lower concentration of 10 mM, followed by decrease of 30% at higher concentration of 300 mM. (vi) The increase in Na(+) -coupled HCO3- transporter activity by EtOH was concentration dependent. (vii) The effect of EtOH on CHE and AE activities was both biphasic: increase of ~25% at 30 mM, followed by decrease of 10 to 25% at 100 mM, and finally increase of 15 to 20% at 300 mM. Conclusions: This study demonstrated that 2 acid extruders and 2 acid loaders coexisted functionally in HASMCs and that EtOH induced a biphasic, concentration-dependent change in resting pHi by altering the activity of the 2 acid extruders, NHE and Na(+) -coupled HCO3- transporter, and the 2 acid loaders, CHE and AE.
    No preview · Article · Nov 2015 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: The ability to maintain optimal intracellular pH (pHi) is an essential requirement for all cells. Na⁺-H⁺ exchanger (NHE), a ubiquitously expressed transmembrane protein, has been found widely as a major acid extruder in many different cell types, including human monocytes. We therefore investigated the mechanism of the active pHi recovery from intracellular acidosis (induced by NH₄Cl prepulse) using intracellular 2',7'-bis (2-carboxethyl)-5(6)-carboxyl-fluorescein (BCECF) fluorescence in cultured human monocytes. Indomethacin is a potent, nonselective inhibitor of cyclooxygenases. Due to its toxicity, the clinical use of indomethacin as an analgesic-antipyretic agent is limited. However, it has recently been found that indomethacin can effectively treat many inflammatory/immune disorders. In this study, we further investigated the effect of indomethacin on the pHi and explored the underlying mechanism. In HEPES (nominally HCO₃⁻-free) Tyrode solution, a pHi recovery from induced intracellular acidosis could be blocked completely by 30 μM HOE 694, a specific NHE1 inhibitor, or by removing [Na⁺]₀. Therefore, in the present study, we provided functional evidence, physiologically and pharmacologically, that the HCO₃⁻-independent acid extruder was mostly likely the NHE1 which was involved in acid extrusion in the human monocytes. Moreover, indomethacin (1 μM-1 mM) decreased pHi levels in a concentration-dependent manner and significantly suppressed the activity of the NHE1, suggesting that indomethacin-induced intracellular acidosis is caused both by the inhibition of NHE1 activity and the non-specified NHE1-independent acidifying mechanism. In conclusion, our present study demonstrates that NHE1 exists functionally in human monocytes, and the indomethacin-induced pHi decreasing is summation effects on NHE1-dependent and -independent mechanism.
    No preview · Article · Aug 2015 · The Chinese journal of physiology
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    ABSTRACT: Background. Cardiopulmonary bypass (CPB) causes release of matrix metalloproteinase- (MMP-) 9, contributing to pulmonary infiltration and dysfunction. The aims were to investigate MMP-9 production and associated perioperative variables and oxygenation following CPB. Methods. Thirty patients undergoing elective cardiac surgery were included. Arterial blood was sampled at 6 sequential points (before anesthesia induction, before CPB and at 2, 4, 6, and 24 h after beginning CPB) for plasma MMP-9 concentrations by ELISA. The perioperative laboratory data and variables, including bypass time, PaO2/FiO2, and extubation time, were also recorded. Results. The plasma MMP-9 concentrations significantly elevated at 2-6 h after beginning CPB (P < 0.001) and returned to the preanesthesia level at 24 h (P = 0.23), with predominant neutrophil counts after surgery (P < 0.001). The plasma MMP-9 levels at 4 and 6 h were not correlated with prolonged CPB time and displayed no association with postoperative PaO2/FiO2, regardless of reduced ratio from preoperative 342.9 ± 81.2 to postoperative 207.3 ± 121.3 mmHg (P < 0.001). Conclusion. Elective cardiac surgery with CPB induced short-term elevation of plasma MMP-9 concentrations within 24 hours, however, without significant correlation with CPB time and postoperative pulmonary dysfunction, despite predominantly increased neutrophils and reduced oxygenation.
    Preview · Article · Aug 2015 · Mediators of Inflammation
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    ABSTRACT: Cannabinoid receptor type 1 (CB1R) plays an important role in the development of myocardial hypertrophy and fibrosis-2 pathological features of uremic cardiomyopathy. However, it remains unknown whether CB1R is involved in the pathogenesis of uremic cardiomyopathy. Here, we aimed to elucidate the role of CB1R in the development of uremic cardiomyopathy via modulation of Akt signalling. The heart size and myocardial fibrosis were evaluated by echocardiography and immunohistochemical staining, respectively, in 5/6 nephrectomy chronic kidney disease (CKD) mice treated with a CB1R antagonist. CB1R and fibrosis marker expression levels were determined by immunoblotting in H9c2 cells exposed to the uremic toxin indoxyl sulfate (IS), with an organic anion transporter 1 inhibitor or a CB1R antagonist or agonist. Akt phosphorylation was also assessed to examine the signaling pathways downstream of CB1R activation induced by IS in H9c2 cells. CKD mice exhibited marked left ventricular hypertrophy and myocardial fibrosis, which were reversed by treatment with the CB1R antagonist. CB1R, collagen I, transforming growth factor (TGF)-β, and α-smooth muscle actin (SMA) expression showed time- and dose-dependent upregulation in H9c2 cells treated with IS. The inhibition of CB1R by either CB1R antagonist or small interfering RNA-mediated knockdown attenuated the expression of collagen I, TGF-β, and α-SMA in IS-treated H9c2 cells, while Akt phosphorylation was enhanced by CB1R agonist and abrogated by CB1R antagonist in these cells. In summary, we conclude that CB1R blockade attenuates LVH and Akt-mediated cardiac fibrosis in a CKD mouse model. Uremic toxin IS stimulates the expression of CB1R and fibrotic markers and CB1R inhibition exerts anti-fibrotic effects via modulation of Akt signaling in H9c2 myofibroblasts. Therefore, the development of drugs targeting CB1R may have therapeutic potential in the treatment of uremic cardiomyopathy. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Jun 2015 · Journal of Molecular and Cellular Cardiology
  • Li-Wei Wang · Shu-Hua Ou · Chien-Sung Tsai · Yue-Cune Chang · Chi-Wen Kao
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    ABSTRACT: Patient education has been shown to be more effective when delivered using multimedia than written materials. However, the effects of using multimedia to assist patients in cardiac rehabilitation have not been investigated. The purpose of this study is to examine the effect of an inpatient multimedia exercise training program on distance walked in the 6-minute walking test (6MWT), heart rate recovery, and walking self-efficacy of patients who had undergone heart surgery. For this longitudinal quasi-experimental study, 60 consecutive patients were assigned to an experimental (n = 20; inpatient multimedia exercise training program) or control (n = 40; routine care) group. Data were collected at 3 times (before surgery, 1 to 2 days before hospital discharge, and 1 month after hospital discharge) and analyzed with the generalized estimating equation approach. Most subjects were men (66.7%), had a mean age of 61.32 ± 13.4 years and left ventricular ejection fraction of 56.96% ± 13.28%, and underwent coronary artery bypass graft surgery (n = 34, 56.7%). Subjects receiving the exercise training program showed significantly greater improvement than those in the control group in the 6MWT walking distance (P < .001), heart rate recovery (P = .04), and self-efficacy (P = .002) at hospital discharge. Furthermore, the intervention effects on 6MWT distance (P < .001) and self-efficacy (P < .001) were sustained at 1 month after hospital discharge. Our inpatient multimedia exercise training program safely improved distance walked in the 6MWT, heart rate recovery, and self-efficacy at hospital discharge in patients after heart surgery and maintained their improvement in 6MWT and self-efficacy 1 month later.
    No preview · Article · Mar 2015 · The Journal of cardiovascular nursing
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    ABSTRACT: Intracellular pH (pHi) is a critical factor influencing many important cellular functions. Acid extrusion carriers such as an Na⁺/H⁺ exchanger (NHE) Na⁺/HCO₃ ⁻ cotransporter (NBC) and monocarboxylate transporters (MCT) can be activated when cells are in an acidic condition (pHi < 7.1). Human radial artery smooth muscle cells (HRASMC) is an important conduit in coronary artery bypass graft surgery. However, such far, the pHi regulators have not been characterized in HRASMCs. We therefore investigated the mechanism of pHi recovery from intracellular acidosis and alkalosis, induced by NH₄Cl-prepulse and Na-acetate-prepulse, respectively, using intracellular 2',7'-bis(2-carboxethyl)-5(6)- carboxy-fluorescein (BCECF)-fluorescence in HRASMCs. Cultured HRASMCs were derived from the segments of human radial artery that were obtained from patients undergoing bypass grafting. The resting pHi is 7.22 ± 0.03 and 7.17 ± 0.02 for HEPES- (nominally HCO₃ ⁻-free) and CO₂/HCO₃⁻- buffered solution, respectively. In HEPES-buffered solution, a pHi recovery from induced intracellular acidosis could be blocked completely by 30 μM HOE 694 (3-methylsulfonyl-4-piperidinobenzoyl, guanidine hydrochloride) a specific NHE inhibitor, or by removing [Na⁺]₀. In 3% CO₂/HCO₃ ⁻-buffered solution, HOE 694 slowed the pHi recovery from the induced intracellular acidosis only, while adding together with DIDS (a specific NBC inhibitor) or removal of [Na⁺]₀ entirely inhibited the acid extrusion. Moreover, α-cyano-4-hydroxycinnamate (CHC; a specific blocker of MCT) blocked the lactate-induced pHi changes. In conclusion, we demonstrate, for the first time, that 3 different pHi regulators responsible for acid extruding, i.e. NHE and NBC, and MCT, are functionally co-existed in cultured HRASMCs.
    No preview · Article · Oct 2014 · The Chinese journal of physiology
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    ABSTRACT: Background and Purpose Regulation of the homeostasis of vascular endothelium is critical for the processes of vascular remodeling and angiogenesis under physiological and pathological conditions. Urotensin II (U-II), a potent vasoactive peptide, participates in vascular and myocardial remodeling after injury. We investigated the protective effect of U-II on doxorubicin (DOX)-induced apoptosis in cultured human umbilical vein endothelial cells (HUVECs) and the potential mechanisms involved in this process. Experimental Approach Cultured HUVECs were treated with vehicle, DOX (1 µM), U-II, or U-II plus DOX. Apoptosis was evaluated by DNA strand break level with TdT-mediated dUTP nick-end labeling (TUNEL) staining. Western blot analysis was employed to determine the related protein expression and flow cytometry assay was used to determine the TUNEL positive cells. Key Results U-II reduced the quantity of cleaved caspase-3 and cytosol cytochrome c and increased Bcl-2 expression, which results in protecting HUVECs from DOX-induced apoptosis. U-II induced Activating transcription factor 3 (ATF3) at both mRNA and protein levels in U-II-treated cells. Knockdown of ATF3 with ATF3 siRNA significantly reduced ATF3 protein levels and U-II protective effect under DOX-treated condition. U-II downregulated p53 expression in DOX-induced HUVECs apoptosis, and it rapidly activated extracellular signal-regulated protein kinase (ERK) and Akt. The DOX induced change of p53 was not affected by U-II antagonist (urantide) under ATF-3 knockdown. The inhibitory effect of U-II on DOX-increased apoptosis was attenuated by inhibitors of ERK (U0126) and PI3K/Akt (LY294002). Conclusion and Implications Our observations provide evidence that U-II protects HUVECs from DOX-induced apoptosis. ERK-Akt phosphorylation, ATF3 activation, and p53 downregulation may play a signal-transduction role in this process.
    Full-text · Article · Sep 2014 · PLoS ONE
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    Jui-Chi Tsai · Yi-Wen Lin · Chun-Yao Huang · Feng-Yen Lin · Chien-Sung Tsai
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    ABSTRACT: Human platelets express Toll-like receptors (TLR) 4. However, the mechanism by which TLR4 directly affects platelet aggregation and blood coagulation remains to be explored. Therefore, in this study, we evaluated the platelet TLR4 expression in patients who underwent CABG surgery; we explored the correlation between platelet TLR4 expression and the early outcomes in hospital of patients. Additionally, C57BL/6 and C57BL/6-Tlr (LPS-/-) mice were used to explore the roles of platelet TLR4 in coagulation by platelet aggregometry and rotation thromboelastometry. In conclusion, our results highlight the important roles of TLR4 in blood coagulation and platelet function. Of clinical relevance, we also explored novel roles for platelet TLR4 that are associated with early outcomes in cardiac surgery.
    Full-text · Article · Aug 2014 · Mediators of Inflammation
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    ABSTRACT: Patients who receive heart transplantation surgery following end-stage cardiac failure benefit from efforts to improve their post-surgical quality of life. Assessing and managing perioperative care play an important role in heart transplantation. Evaluations of donor and recipient should be conducted carefully and recommended candidates should by vetted by a qualified heart transplantation committee. The operative procedure is different from general cardiac surgery, and organ preservation is a key step in linking the donor to the recipient. Postoperative infection control and administration of immunosuppressive agents further affect the outcome of heart transplantation. Based on a review of articles and our clinical care experience, we focus on the assessment and the management of heart transplantation in this article.
    No preview · Article · Aug 2014 · Hu li za zhi The journal of nursing
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    ABSTRACT: Porphyromonas gingivalis is a major periodontal pathogen that contains a variety of virulence factors. The antibody titer to P. gingivalis GroEL, a homologue of HSP60, is significantly higher in periodontitis patients than in healthy control subjects, suggesting that P. gingivalis GroEL is a potential stimulator of periodontal disease. However, the specific role of GroEL in periodontal disease remains unclear. Here, we investigated the effect of P. gingivalis GroEL on human periodontal ligament (PDL) cells in vitro, as well as its effect on alveolar bone resorption in rats in vivo. First, we found that stimulation of PDL cells with recombinant GroEL increased the secretion of the bone resorption-associated cytokines interleukin (IL)-6 and IL-8, potentially via NF-κB activation. Furthermore, GroEL could effectively stimulate PDL cell migration, possibly through activation of integrin α1 and α2 mRNA expression as well as cytoskeletal reorganization. Additionally, GroEL may be involved in osteoclastogenesis via receptor activator of nuclear factor κ-B ligand (RANKL) activation and alkaline phosphatase (ALP) mRNA inhibition in PDL cells. Finally, we inoculated GroEL into rat gingiva, and the results of microcomputed tomography (micro-CT) and histomorphometric assays indicated that the administration of GroEL significantly increased inflammation and bone loss. In conclusion, P. gingivalis GroEL may act as a potent virulence factor, contributing to osteoclastogenesis of PDL cells and resulting in periodontal disease with alveolar bone resorption.
    Full-text · Article · Jul 2014 · PLoS ONE
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    ABSTRACT: Ruptured abdominal aortic aneurysm is life-threatening without immediate management. The initial clinical presentation is non-specific and impending rupture is easily missed, especially without a CT scan. We present a case of a 56-year-old man with low-back pain and left lower-extremity numbness, which was diagnosed as a herniated intervertebral disc (HIVD) with left acute sciatica syndrome. He also complained of persistent fever and abdominal discomfort. Routine blood work-up revealed leukocytosis and decreasing haemoglobin levels. CT angiography (CTA) showed impending rupture of the left aorto-iliac aneurysm. We therefore performed endovascular aneurysm repair (EVAR). Blood culture revealed Salmonella enterica, for which he received antibiotics. No acute sciatica syndrome was present immediately after the EVAR. No EVAR-related complications were noted in the one-year CTA follow up.
    No preview · Article · Jun 2014 · Cardiovascular journal of Africa
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    ABSTRACT: Hyperphosphatemia-induced endothelial dysfunction has been shown to play a pathogenic role in the development of atherosclerosis in chronic kidney disease (CKD) through unclear mechanisms. Emerging evidence indicates that autophagy is involved in the maintenance of normal cardiovascular function. However, it is unclear whether autophagy participates in the molecular mechanism underlying high phosphate (Pi)-induced endothelial dysfunction. The autophagy activity was determined by the immunofluorescence staining of the expression of endothelial microtubule-associated protein 1 light chain 3 (LC3) in the 5/6 nephrectomy rat model of CKD and sham-operated control rats. The LC3-II/LC3-I ratio and the activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway were determined in cultured human microvascular endothelial cell (HMEC-1) endothelial cells that were exposed to a high concentration of Pi with or without the Pi influx blocker phosphonoformic acid, the autophagy inhibitor 3-methyladenine, and the autophagy inducer rapamycin. The impacts of autophagy on Pi-induced apoptotic damage were assessed by flow cytometry. The in vivo rat model of CKD revealed that hyperphosphatemia is associated with increased endothelial LC3 staining. The exposure of HMEC-1 cells to high Pi induced both dose-dependent and time-dependent increases in the LC3-II/LC3-I expression ratio accompanied by the inhibition of the Akt/mTOR signaling pathway. In HMEC-1 cells, high Pi-induced autophagy and the inhibition of Akt/mTOR signaling were reversed by phosphonoformic acid through the blockage of Pi influx. Apoptosis, characterized by the levels of cleaved caspase 3 and poly(ADP-ribose) polymerase, along with autophagy was induced by high Pi, and the inhibition of autophagy by 3-methyladenine significantly aggravated high Pi-induced apoptosis. The flow cytometry results confirmed that the blockage of autophagy promoted the apoptosis of endothelial cells. Hyperphosphatemia induces endothelial autophagy, possibly through the inhibition of the Akt/mTOR signaling pathway, which may play a protective role against high Pi-induced apoptosis.
    No preview · Article · May 2014 · Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
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    ABSTRACT: The Na(+)-H(+) exchanger (NHE) and the Na(+)-HCO3(-) co-transporter (NBC) have been confirmed as two major active acid extruders in many mammalian cells. Whether the NHE and NBC functional co-exist in human internal mammary artery smooth muscle cells (HIMASMCs) remains unclear. The aims of the present study were to investigate the acid-extruding mechanisms and to explore the effects of urotensin-II (U-II), a powerful vasoconstrictor, on pHi regulators in HIMASMCs. We investigated the changes of pHi by BCECF-fluorescence in HIMASMCs. We found that (a) two Na(+)-dependent acid extruders, i.e. NHE and NBC, functionally co-exist; (b) U-II (3 ∼ 100nM) induced a concentration-dependent intracellular acidosis; and (c) U-II (3 ∼ 100nM) caused a concentration-dependent increase on NHE activity, while decrease on NBC activity. In summary, we demonstrate for the first time that two acid-extruders, NHE and NBC, functionally co-exist in HIMASMCs. Moreover, U-II induces a concentration-dependent intracellular acidosis through the balanced effect of its effect on increasing NHE activity and decreasing NBC activity.
    Full-text · Article · Apr 2014 · Peptides
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    ABSTRACT: Dehydroevodiamine alkaloid (DeHE), a bioactive component of the Chinese herbal medicine Wu-Chu-Yu (Evodiae frutus), exerted antiarrhythmic effect in guinea-pig ventricular myocytes. We further characterize the electromechanical effects of DeHE in human atrial and ventricular tissues obtained from hearts of patients undergoing corrective cardiac surgery or heart transplantation. The transmembrane potentials of human myocardia were recorded with a traditional microelectrode technique while sarcolemmal Na(+) and Ca(2+) currents in single human cardiomyocytes were measured by whole-cell patch-clamp technique. The intracellular pH (pHi) and Na(+)-H(+) exchanger (NHE) activity were determined using BCECF-fluorescence in human atria. In human atria, DeHE (0.1~0.3μM) depressed upstroke velocity, amplitude of action potential, and contractile force, both in slow and fast response action potential. Moreover, the similar depressant effects of DeHE were found in human ventricular myocardium. Both in isolated human atrial and ventricular myocytes, DeHE (0.1~1μM) reversibly, concentration-dependently decreased the Na(+) and Ca(2+)currents. Moreover, DeHE (0.1 and 0.3μM) suppressed delayed afterdepolarizations and aftercontractions, induced by epinephrine and high [Ca(2+)]o in atria. In human ventricular myocardium, the strophanthidin-induced triggered activities were attenuated by pretreating DeHE (0.3μM). The resting pHi and NHE activity were also significantly increased by DeHE (0.1~ 0.3μM). We concluded for the first time that, in the human hearts, DeHE could antagonize triggered arrhythmias induced by cardiotonic agents through a general reduction of the Na(+) and Ca(2+) inward currents, while increase of resting pHi and NHE activity.
    Full-text · Article · Mar 2014 · Journal of ethnopharmacology
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    ABSTRACT: Studies have demonstrated that using a left internal mammary artery (LIMA) graft yields excellent long-term results in coronary artery bypass grafting (CABG). The growth arrest-specific 6 (Gas6) gene and its receptor, Axl, are crucial in vascular haemostasis and atherosclerosis. The objective of this study was to determine the expression of Gas6 and Axl molecules in the aorta and LIMA in patients undergoing CABG. Plasma and tissue specimens were collected from 19 patients undergoing elective CABG. The expression of the Gas6 and Axl in the injured aorta and LIMA was examined using reverse transcription PCR (RT-PCR), real-time RT-PCR, western blot and immunohistochemical staining. In CABG patients, the mRNA, immunoreactivity and protein expressions of the Gas6 and Axl were considerably higher in the LIMA than those in the aorta. Further analysis revealed that the expression of the Gas6 positively correlated with that of Axl in the LIMA and aorta. The plasma Gas6 level was considerably and positively correlated with the expression of Gas6 protein in the LIMA and aorta. The present study discovered that the higher expression of Gas6/Axl pathway components in the LIMA compared with that in the aorta may partly explain the less frequent atherosclerotic events involving the LIMA compared with other arteries. Moreover, Gas6 may play a critical and protective role in human vascular biology.
    No preview · Article · Feb 2014 · Journal of clinical pathology
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    ABSTRACT: Toll-like receptors (TLRs) plays a critical role in innate immunity. In 2004, Aslam R. and Shiraki R. first determined that murine and human platelets express functional TLRs. Additionally, Andonegui G. demonstrated that platelets express TLR4, which contributes to thrombocytopenia. However, the underlying mechanisms of TLR4 expression by platelets have been rarely explored until now. The aim of this study was to identify the mechanism of TLR4 expression underlying thrombin treatment. The human washed platelets were used in this study. According to flowcytometry and western blot analysis, the surface levels of TLR4 were significantly enhanced in thrombin-activated human platelets and decreased by TMB-8, calpeptin, and U73122, but not Y27632 (a Rho-associated protein kinase ROCK inhibitor) indicating that thrombin-mediated TLR4 expression was modulated by PAR/PLC pathway, calcium and calpain. Co-immunoprecipitation (co-IP) assay demonstrated that the interaction between TLR4 and myosin-9 (a substrate of calpain) was regulated by calpain; cleavage of myosin-9 enhanced TLR4 expression in thrombin treated platelets. Transmission electron microscope data indicated that human platelets used α-granules to control TLR4 expression; the co-IP experiment suggested that myosin-9 did not coordinate with Rab7b to negatively regulate TLR4 trafficking in thrombin treated platelets. In summary, phospholipase Cγ-calpain-myosin 9-Rab7b axis was responsible for the mechanism underlying the regulation of TLR4 containing α-granules trafficking in thrombin-stimulated platelets, which was involved in coagulation.
    Full-text · Article · Jan 2014 · PLoS ONE
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    ABSTRACT: Although acute pulmonary injury after cardiopulmonary bypass has been detailed in the literature, it was seldom mentioned in the context of following implantation of a ventricular assist device. We report on a 65-year-old male with end-stage ischemic cardiomyopathy who underwent implantation of Levitronix CentriMag (Levitronix, Waltham, MA) for cardiac support and was listed for heart transplantation. Acute pulmonary injury with profound hypoxaemia was noted 6 h after the implantation. Despite optimal medical treatment and maximal ventilator support, refractory hypoxaemia persisted, and veno-venous extracorporeal membrane oxygenation (oxygenator: Affinity-NT; centrifugal pump: BPX-80 Bio-Pump, Medtronic, Minneapolis, MN, USA) was applied for ventilation support. The patient was weaned from the extracorporeal membrane oxygenation 4 days later and from the ventilator on the next 2 days. He underwent a successful orthotopic heart transplant after a total of 77 days on Levitronix left ventricular device cardiac support.
    No preview · Article · Jan 2014 · Journal of Artificial Organs
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    ABSTRACT: The number and function of endothelial progenitor cells (EPCs) are sensitive to hyperglycemia, hypertension, and smoking in humans, which are also associated with the development of atherosclerosis. GroEL1 from Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis. However, the actual effects of GroEL1 on EPC function are unclear. In this study, we investigate the EPC function in GroEL1-administered hind limb-ischemic C57BL/B6 and C57BL/10ScNJ (a toll-like receptor 4 (TLR4) mutation) mice and human EPCs. In mice, laser Doppler imaging, flow cytometry, and immunohistochemistry were used to evaluate the degree of neo-vasculogenesis, circulating level of EPCs, and expression of CD34, vWF, and endothelial nitric oxide synthase (eNOS) in vessels. Blood flow in the ischemic limb was significantly impaired in C57BL/B6 but not C57BL/10ScNJ mice treated with GroEL1. Circulating EPCs were also decreased after GroEL1 administration in C57BL/B6 mice. Additionally, GroEL1 inhibited the expression of CD34 and eNOS in C57BL/B6 ischemic muscle. In vitro, GroEL1 impaired the capacity of differentiation, mobilization, tube formation, and migration of EPCs. GroEL1 increased senescence, which was mediated by caspases, p38 MAPK, and ERK1/2 signaling in EPCs. Furthermore, GroEL1 decreased integrin and E-selectin expression and induced inflammatory responses in EPCs. In conclusion, these findings suggest that TLR4 and impaired NO-related mechanisms could contribute to the reduced number and functional activity of EPCs in the presence of GroEL1 from C. pneumoniae.
    Full-text · Article · Dec 2013 · PLoS ONE
  • Yeu-Chin Chen · Chih-Yuan Lin · Chien-Sung Tsai
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    ABSTRACT: There are few studies on heparin-induced thrombocytopenia (HIT) reported from Taiwan and Asian countries. We conducted a prospective study to investigate the frequency of HIT in patients undergoing cardiopulmonary bypass surgeries. A cohort of 54 patients was enrolled from January 01, 2010 to October 31, 2011. Patients' clinical information was obtained for 4T score classification. Plasma (2-4 mL) was also collected before surgery and on Days 5 and 10 following heparin administration during the bypass procedure. This was tested for anti-heparin/PF4 antibodies and functional assay using flow cytometry (FC). The mean platelet count for this cohort followed the expected pattern in the postoperative setting. Seven of the 54 (13%) patients had positive antibodies assays before bypass surgery. This increased to 32% on Day 5 and was markedly elevated to 63% on Day 10 after surgery. Only one of the 54 patients (1.8%) was found to have both positive antibody assay and platelet activation, but no clinical HIT/thrombosis developed. Our study is the first report on the rates of HIT in the setting of cardiopulmonary bypass surgery in Taiwan and demonstrated no clinical HIT occurrence, despite the high frequency of HIT antibody in our cohort.
    No preview · Article · Dec 2013 · Journal of the Formosan Medical Association

Publication Stats

748 Citations
233.15 Total Impact Points

Institutions

  • 2003-2015
    • Tri-Service General Hospital
      T’ai-pei, Taipei, Taiwan
    • National Taipei University
      T’ai-pei, Taipei, Taiwan
  • 2001-2015
    • National Defense Medical Center
      • • Department of Surgery
      • • Tri-Service General Hospital
      • • Graduate Institute of Life Sciences
      T’ai-pei, Taipei, Taiwan
  • 2007
    • National Yang Ming University
      T’ai-pei, Taipei, Taiwan
  • 2002-2005
    • Cheng Hsin General Hospital
      • Department of Surgery
      T’ai-pei, Taipei, Taiwan