Pingtung, Taiwan
Pingtung, Taiwan

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Wang C.-P.,I - Shou University | Lu L.-F.,I - Shou University | Yu T.-H.,I - Shou University | Hung W.-C.,I - Shou University | And 6 more authors.
Atherosclerosis | Year: 2010

Objective: p-Cresylsulphate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. We aimed to investigate the relationship of total PCS with traditional biomarkers associated with chronic coronary atherosclerosis. In addition, the relationship between serum total PCS levels and the severity of coronary artery stenosis was also explored. Methods and results: Serum total PCS concentrations were measured by using the Ultra Performance LC System in 202 consecutive stable angina patients, and their associations with angiographic indexes of the number of diseased vessels and modified Gensini score were estimated. Patients with significant coronary artery stenosis have higher median serum total PCS levels than patients with normal coronary arteries. Statistically significant associations were observed between the serum total PCS levels and the number of diseased vessels (β= 0.261, p= 0.0002), and modified Gensini score (β= 0.171, p= 0.016). Using multivariate analysis, serum total PCS level was independently associated with the presence and severity of CAD. Conclusions: This study indicates that serum total PCS levels are significantly higher in the presence of CAD and are correlated with the severity of the disease, which suggest that increased serum total PCS may be involved in the pathogenesis of coronary atherosclerosis. © 2010 Elsevier Ireland Ltd.


Lee Y.-J.,Lee's Endocrinologic Clinic | Wang M.-Y.,Jen Ai Hospital | Lin M.-C.,Yang Ming Hospital | Lin P.-T.,Chung Shan Medical University
Nutrients | Year: 2016

Diabetes is considered an oxidative stress and a chronic inflammatory disease. The purpose of this study was to investigate the correlations between vitamin B-12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. We enrolled 154 patients with type 2 diabetes (54 vegetarians and 100 omnivores). Levels of fasting glucose, glycohemoglobin (HbA1c), lipid profiles, oxidative stress, antioxidant enzymes activity, and inflammatory makers were measured. Diabetic vegetarians with higher levels of vitamin B-12 (>250 pmol/L) had significantly lower levels of fasting glucose, HbA1c and higher antioxidant enzyme activity (catalase) than those with lower levels of vitamin B-12 (≤250 pmol/L). A significant association was found between vitamin B-12 status and fasting glucose (r = -0.17, p = 0.03), HbA1c (r = -0.33, p = 0.02), oxidative stress (oxidized low density lipoprotein-cholesterol, r = -0.19, p = 0.03), and antioxidant enzyme activity (catalase, r = 0.28, p = 0.01) in the diabetic vegetarians; vitamin B-12 status was significantly correlated with inflammatory markers (interleukin-6, r = -0.33, p < 0.01) in diabetic omnivores. As a result, we suggest that it is necessary to monitor the levels of vitamin B-12 in patients with diabetes, particularly those adhering to a vegetarian diet. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


Wang C.-P.,I - Shou University | Lu L.-F.,I - Shou University | Yu T.-H.,I - Shou University | Hung W.-C.,I - Shou University | And 6 more authors.
Journal of Nephrology | Year: 2013

Background: Cardiovascular disease is prevalent among patients with chronic kidney disease (CKD). Patients with CKD have elevated levels of p-cresylsulfate (PCS), which has been linked with cardiovascular mortality in this population. The aim of this study was to evaluate the clinical significance of CKD in coronary artery disease (CAD) patients and to investigate whether a significant correlation exists between CKD, total PCS and poor clinical outcomes in CAD patients. Methods: We assessed the occurrence of major adverse cardiac events (MACEs) among 340 consecutive CAD patients who enrolled in a disease management program after the patients were discharged from the hospital. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 ml/min per 1.73 m2. Results: Kaplan-Meier analysis revealed that CKD and high total PCS levels (>1.66 mg/L) were significantly associated with the occurrence of MACE. A multivariate Cox hazard regression model revealed that the predictive independent risk factor for the occurrence of MACE was high total PCS level (relative risk = 1.387). We divided the patients with or without CKD and high or low total PCS levels into 4 groups according to their eGFR and total PCS levels, respectively. The hazard ratio for MACE in the group with both CKD and high total PCS level was 1.721, relative to the group without CKD that had low total PCS level (p=0.005). Conclusions: A high serum level of total PCS may be a predictor of elevated risk of MACE in CAD patients with low eGFR. © 2012 Società Italiana di Nefrologia - ISSN 1121-8428.


Tsai Y.-D.,I - Shou University | Wang C.-P.,I - Shou University | Chen C.-Y.,I - Shou University | Lin L.-W.,I - Shou University | And 6 more authors.
Head and Neck | Year: 2014

Background The purpose of this study was to investigate whether the pretreatment total and differential leukocyte counts can predict the prognosis of patients with oral cavity cancer. Methods In a retrospective analysis of patients treated between 2004 and 2011, medical records of 202 patients with oral cavity cancer were evaluated. Results Patients with oral cavity cancer, the peripheral total white blood cell (WBC) count, monocyte, and neutrophil counts and neutrophil lymphocyte ratio increased with the advancement of clinical stage. In contrast, the lymphocyte count decreased. Further, total WBC, monocyte, and neutrophil counts were increased in those with pathologic stage T4 and poor tumor differentiation, and the monocyte count was also increased in those with lymph node metastasis. Moreover, the pretreatment circulating monocyte count was an independent prognostic factor for cancer-specific survival. Conclusion A higher pretreatment circulating monocyte count can be considered as a useful prognostic marker in patients with oral cavity cancer. © 2014 Wiley Periodicals, Inc.


Lu Y.-C.,I - Shou University | Wang C.-P.,I - Shou University | Hsu C.-C.,I - Shou University | Chiu C.-A.,I - Shou University | And 7 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2013

Background: Secreted frizzled-related protein 5 (Sfrp5), an endogenous inhibitor of wingless-type MMTV integration site family (Wnt) signalling, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes mellitus (T2DM). Wnt member 5a (Wnt5a) is a representative ligand, and recent reports suggest that Wnt5a is involved in inflammatory diseases and metabolic disorders. The aim of this study was to investigate whether plasma Wnt5a and Sfrp5 levels are altered in patients with T2DM. Methods: Plasma Sfrp5 and Wnt5a concentrations were measured through enzyme-linked immunosorbent assay in type 2 diabetic and nondiabetic subjects. Results: A total of 82 patients with T2DM and 42 nondiabetic subjects were studied. Plasma Sfrp5 levels were found to be elevated in patients with T2DM (9.4±9.0 vs 7.4±10.9ng/mL, p=0.006). In contrast, Wnt5a levels were decreased (6.8±12.6 vs 9.1±4.0ng/dL, p<0.001). Increasing concentrations of Sfrp5 were independently and significantly associated with T2DM. Multiple logistic regression analysis revealed Sfrp5 as an independent association factor for T2DM, even after full adjustment of known biomarkers. In a multiple linear regression analysis, only the fasting glucose level was positively associated with the plasma Sfrp5 level. Conclusions: Our results indicate that Sfrp5 may play a role in the pathogenesis of T2DM. © 2013 John Wiley & Sons, Ltd.


Lu L.-F.,I - Shou University | Wang C.-P.,I - Shou University | Yu T.-H.,I - Shou University | Hung W.-C.,I - Shou University | And 7 more authors.
Cytokine | Year: 2012

Visfatin is a cytokine that is expressed in many tissues, including the heart, and has been proposed to play a role in plaque destabilization leading to acute myocardial injury. The present study evaluates plasma levels of visfatin in acute ST-elevation myocardial infarction (STEMI) patients and examines the temporal changes in visfatin levels from the acute period to the subacute period to determine a correlation with the degree of myocardial ischemia. We evaluated 54 patients with STEMI. Circulating levels of visfatin and brain natriuretic peptide (BNP) were measured by ELISA. In addition, local expression of visfatin and BNP were detected by quantitative real-time polymerase chain reaction and immunohistochemical (IHC) analysis of left ventricular myocytes in a mouse model of myocardial infarction (MI). Plasma levels of visfatin were significantly increased in patients with STEMI on admission, relative to controls (effort angina patients and individuals without coronary artery disease). The visfatin levels reached a peak 24. h after percutaneous coronary intervention (PCI) and then decreased toward the control range during the first week after PCI. The basal plasma visfatin levels were found to correlate with peak troponin-I, peak creatine kinase-MB, total white blood cell count, and BNP levels. Trend analyses confirmed that visfatin levels correlated with the number of diseased coronary arteries. Further, in MI mice, mRNA levels of visfatin and BNP were found to be higher than in sham-treated mice. IHC analysis showed that visfatin and BNP immunoreactivity was diffusely observable in left ventricular myocytes of the MI mice. This study indicates that plasma visfatin levels are significantly higher in STEMI patients and that these higher visfatin levels correlate with elevated levels of cardiac enzymes, suggesting that increased plasma visfatin may be closely related to the degree of myocardial damage. © 2011 Elsevier Ltd.


Hsu C.-C.,I - Shou University | Lu Y.-C.,I - Shou University | Chiu C.-A.,I - Shou University | Yu T.-H.,I - Shou University | And 6 more authors.
Clinical and Investigative Medicine | Year: 2013

Purpose: Indoxyl sulfate (IS) is linked to endothelial damage, NF-B activation and induced development of atherosclerosis. The purpose of this study was to investigate the relationship between serum IS levels and the severity of coronary artery stenosis. In addition, the relationship among IS and various cardiovascular risk factors was also explored. Methods: Serum IS concentrations were measured using ultra performance liquid chromatography in 191 consecutive patients presenting with stable angina. The associations between serum IS levels and angiographic indexes of the number of diseased vessels, modified Gensini scores and calcium scores were determined. Results: Patients with significant coronary artery stenosis were found to have higher serum IS levels than patients with normal coronary arteries. Using multivariate analysis, serum IS levels were found to be independently associated with the presence and severity of coronary artery disease (CAD). Furthermore, statistically significant correlation was observed between the serum IS levels and age, Agatston calcium score, volume calcium score, modified Gensini score, coronary lesions, coronary disease and Framingham-10 year risk score. Conclusion:This study indicates that serum IS levels are significantly higher in the presence of CAD and correlate with the severity of the disease and coronary atherosclerosis scores, which suggest that increased serum IS may be involved in the pathogenesis of coronary atherosclerosis. © 2013 CIM.


PubMed | I - Shou University, National Cheng Kung University, Kaohsiung Medical University and Lees Endocrinologic Clinic
Type: | Journal: Clinica chimica acta; international journal of clinical chemistry | Year: 2016

A significant number of patients with chronic kidney disease (CKD) have cardiac abnormalities, and left ventricular systolic dysfunction (LVSD) is a common manifestation. p-Cresylsulfate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. Furthermore, the associations among serum total PCS, major adverse cardiovascular events, all-cause mortality, and QTc prolongation have also been found in previous studies. We thus investigated the association of total PCS and CKD with LVSD in the clinical setting.We included 403 consecutive patients with stable angina. To evaluate LV function, all patients underwent echocardiography. To measure the serum total PCS concentrations and estimated glomerular filtration rate (eGFR), blood samples were obtained.Multiple regression analysis showed that left atrium diameter, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-systolic diameter, left ventricular end-systolic volume, stroke volume, left ventricular end-systolic volume index, left ventricular ejection fraction (LVEF), and the interventricular septum/posterior wall of the left ventricle were independently associated with total PCS (all p<0.05). In addition, a significantly decreased LVEF was present in patients with lower and higher serum total PCS and with CKD, and with higher serum total PCS and without CKD than from those with lower serum total PCS concentrations and without CKD (p=0.004). In the multivariate logistic regression analysis, when patients without CKD and lower PCS were used as reference group, patients with the higher total PCS concentration and without CKD had an odds ratio of 3.59 for the risk of LVSD, the lower total PCS concentration and with CKD had an odds ratio of 3.89 for the risk of LVSD, and the higher total PCS concentration and with CKD had an odds ratio of 4.04 for the risk of LVSD (p=0.039, p=0.038, and p=0.020, respectively).High serum concentrations of total PCS or CKD, or both, represent an increased risk of impaired LV systolic function in stable angina patients.


PubMed | Chung Shan Medical University, Jen Ai Hospital, Yang Ming Hospital and Lees Endocrinologic Clinic
Type: Comparative Study | Journal: Nutrients | Year: 2016

Diabetes is considered an oxidative stress and a chronic inflammatory disease. The purpose of this study was to investigate the correlations between vitamin B-12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. We enrolled 154 patients with type 2 diabetes (54 vegetarians and 100 omnivores). Levels of fasting glucose, glycohemoglobin (HbA1c), lipid profiles, oxidative stress, antioxidant enzymes activity, and inflammatory makers were measured. Diabetic vegetarians with higher levels of vitamin B-12 (>250 pmol/L) had significantly lower levels of fasting glucose, HbA1c and higher antioxidant enzyme activity (catalase) than those with lower levels of vitamin B-12 ( 250 pmol/L). A significant association was found between vitamin B-12 status and fasting glucose (r = -0.17, p = 0.03), HbA1c (r = -0.33, p = 0.02), oxidative stress (oxidized low density lipoprotein-cholesterol, r = -0.19, p = 0.03), and antioxidant enzyme activity (catalase, r = 0.28, p = 0.01) in the diabetic vegetarians; vitamin B-12 status was significantly correlated with inflammatory markers (interleukin-6, r = -0.33, p < 0.01) in diabetic omnivores. As a result, we suggest that it is necessary to monitor the levels of vitamin B-12 in patients with diabetes, particularly those adhering to a vegetarian diet.


PubMed | I - Shou University, National Cheng Kung University, Kaohsiung Medical University and Lees Endocrinologic Clinic
Type: Journal Article | Journal: PloS one | Year: 2015

Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD). In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS) is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc) prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK) was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD) and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

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