Chao-Ping Wang

Serum levels of total p-cresylsulphate are associated with angiographic coronary atherosclerosis severity in stable angina patients with early stage of renal failure

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 (beta=0.261, p=0.0002), and modified Gensini score (beta=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.

Increased levels of total P-Cresylsulphate and indoxyl sulphate are associated with coronary artery disease in patients with diabetic nephropathy.

BACKGROUND Indoxyl sulphate (IS) and p-cresylsulphate (PCS) are uremic toxins with similar protein-binding, dialytic clearance, and proinflammatory features. Few studies have evaluated the possible associations between these solutes and coronary artery disease (CAD) in type 2 diabetes (T2D) patients. METHODS A hospital-based case control study was performed. A total of 209 T2D patients were divided into two groups based on the presence/absence of significant CAD (≥50% luminal reduction). Serum total PCS and IS levels were measured using the Ultra Performance LC System. The relationship between total PCS and IS levels were investigated. Coronary calcium scores and the modified Gensini score were analyzed. RESULTS Serum total PCS and IS levels were significantly higher in patients with both T2D and significant CAD, than in non-diabetic control subjects and T2D patients without CAD (all p < 0.05). Logistic regression analysis revealed independent and significant associations between the two solutes and CAD status. Serum total PCS, IS, and numbers of diseased vessels were elevated in groups with estimated glomerular filtration rate (eGFR) of 60-89 ml/min/1.73 m2 and below. Also, serum total PCS and IS levels were significantly associated with eGFR, coronary calcium scores, Gensini score, adipocytokines (adiponectin, visfatin, and leptin), and total white blood cell count. CONCLUSIONS Serum total PCS and IS levels were elevated in patients with T2D and CAD. These increases were associated with renal function deterioration, inflammation, and coronary atherosclerosis.

Pretreatment circulating monocyte count associated with poor prognosis in patients with oral cavity cancer

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.

Circulating secreted frizzled-related protein 5 (Sfrp5) and wingless-type MMTV integration site family member 5a (Wnt5a) levels in patients with type 2 diabetes mellitus

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.

Associations among chronic kidney disease, high total p-cresylsulfate and major adverse cardiac events

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 m(2). 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.

Interpretation of elevated plasma visfatin concentrations in patients with ST-elevation myocardial infarction

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 24h 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.

Polymorphism of angiotensin I-converting enzyme gene is related to oral cancer and lymph node metastasis in male betel quid chewers

OBJECTIVES Angiotensin I-converting enzyme (ACE), a type I cell surface zinc metallopeptidase, is differentially expressed in several malignancies and plays a role in tumor cell proliferation, tumor cell migration, angiogenesis, and metastatic behavior. We aimed to investigate the effects of ACE gene (rs1799752) variants on oral cancer risk. MATERIALS AND METHODS Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) 32 was used to measure ACE gene polymorphisms in 88 patients with oral precancerous lesion (OPL), 186 33 patients with oral cancer, and 120 control subjects without any oral lesions. All study subjects were male 34 betel quid chewers. RESULTS Patients with oral cancer or OPL had a higher frequency of the DD genotype than the control patients did. Oral cancer patients with the DD genotype had a significantly higher prevalence of lymph node metastases than patients with the II/ID genotype did. After adjusting for age, smoking, drinking, and betel quid chewing status, we found that individuals with the DD genotype of the ACE gene had a 5.46-fold and 3.13-fold higher risk of developing oral cancer or OPL, respectively, than those with the II genotype did. Furthermore, oral cancer patients with the DD genotype of the ACE gene had a 2.16-fold higher likelihood of lymph node metastasis. CONCLUSION Our data suggest that the ACE gene polymorphisms may be associated with increased susceptibility to OPL and oral cancer and lymph node metastasis from oral cancer.

Anti-inflammatory effects of Siegesbeckia orientalis ethanol extract in in vitro and in vivo models.

This study aims to investigate the anti-inflammatory responses and mechanisms of Siegesbeckia orientalis ethanol extract (SOE). In cell culture experiments, RAW264.7 cells were pretreated with SOE and stimulated with lipopolysaccharide (LPS) for inflammatory mediators assay. In animal experiments, mice were tube-fed with SOE for 1 week, and s.c. injected with λ-carrageenan or i.p. injected with LPS to simulate inflammation. The degree of paw edema was assessed, and cytokine profile in sera and mouse survival were recorded. Data showed that SOE significantly reduced NO, IL-6, and TNF-α production in LPS-stimulated RAW264.7 cells. In vivo studies demonstrated that mice supplemented with 32 mg SOE/kg BW/day significantly lowered sera IL-6 level and resulted a higher survival rate compared to the control group (P = 0.019). Furthermore, SOE inhibited LPS-induced NF-κB activation by blocking the degradation of IκB-α. The SOE also reduced significantly the phosphorylation of ERK1/2, p38, and JNK in a dose-dependent manner. In summary, the in vitro and in vivo evidence indicate that SOE can attenuate acute inflammation by inhibiting inflammatory mediators via suppression of MAPKs- and NF-κB-dependent pathways.

Relationship between shift work and peripheral total and differential leukocyte counts in Chinese steel workers

Relationship between shift work and peripheral total and differential leukocyte counts in Chinese steel workers: Li‐Fen Lu, et al. Division of Cardiac Surgery, Department of Surgery, E‐Da Hospital, I‐Shou University, Taiwan

Associations among chronic kidney disease, high total p-cresylsulfate and left ventricular systolic dysfunction.

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS High serum concentrations of total PCS or CKD, or both, represent an increased risk of impaired LV systolic function in stable angina patients.