Biomedical subjects

Tzung-Dau Wang

Publications and source records attributed to Tzung-Dau Wang.

12 recordsLinked to original sources

PubMed2006

Relation of improvement in endothelium-dependent flow-mediated vasodilation after rosiglitazone to changes in asymmetric dimethylarginine, endothelin-1, and C-reactive protein in nondiabetic patients with the metabolic syndrome.

The mechanisms by which thiazolidinediones exert beneficial effects on the endothelium are still not clear. We examined the effects of rosiglitazone on the plasma markers of metabolic control (glucose, insulin, adiponectin, resistin, and lipid profiles), markers of inflammation (high-sensitivity C-reactive protein [CRP], interleukin-6, soluble CD40 ligand, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1), and markers of vasoreactivity (asymmetric dimethylarginine [ADMA] and endothelin-1) and analyzed the relations between changes in endothelium-dependent flow-mediated dilation of the brachial artery and changes in these markers to elucidate their roles in mediating the vascular protective effects of rosiglitazone. Of 70 nondiabetic patients who met a modified National Cholesterol Education Program definition of the metabolic syndrome, 35 were randomized to receive rosiglitazone (4 mg/day) and 35 to receive placebo for 8 weeks. At study end, treatment with rosiglitazone had significantly reduced plasma insulin (-25%, p = 0.004) and resistin (-16%, p <0.001), increased adiponectin (164%, p <0.001), low-density lipoprotein cholesterol (16%, p = 0.005), and apolipoprotein-B (14%, p = 0.003), and decreased CRP (-30%, p = 0.005), soluble CD40 ligand (-20%, p = 0.014), ADMA (-16%, p <0.001), and endothelin-1 (-11%, p <0.001) concentrations and systolic and diastolic blood pressures. Rosiglitazone treatment significantly improved flow-mediated dilation (p <0.001) and nitroglycerin-induced vasodilation (p = 0.001) of the right brachial artery. On multivariate analysis, changes in ADMA, endothelin-1, and CRP were independent predictors of improved endothelial reactivity with rosiglitazone. In conclusion, we have, for the first time, demonstrated the independent associations between the improvement in flow-mediated dilation and reductions in ADMA, endothelin-1, and CRP after 8 weeks of treatment with rosiglitazone in nondiabetic patients with the metabolic syndrome. These findings suggest that decreases in ADMA, endothelin-1, and CRP may serve as possible mechanisms for the improvement in endothelial function conferred by rosiglitazone treatment.

Arginine↗

PubMed2006

The relation of amino-terminal propeptide of type III procollagen and severity of coronary artery disease in patients without myocardial infarction or hibernation.

OBJECTIVES: The association of cardiac fibrosis and coronary artery disease (CAD) in patients without infarction or hibernation is unclear. We investigated the relationship between serum concentrations of procollagen propeptides and severity of CAD in such patients. DESIGN AND METHODS: Forty-six patients (32 men; mean age 64 years) with chest pain were enrolled. All patients received stress thallium-201 single photon emission computed tomography (SPECT) and analysis of the serum levels of the amino-terminal propeptide of type I and III procollagen (PINP and PIIINP). RESULTS: In patients with thallium-201 perfusion defects, the number of diseased vessels was associated significantly with PIIINP (p=0.024) rather than PINP (p=0.613). Follow-up serum PINP and PIIINP levels after coronary intervention (mean 84 days) revealed no significant decrease. CONCLUSIONS: Serum PIIINP level is significantly associated with the severity of CAD in patients without myocardial infarction or hibernation.

Aged↗

PubMed2006

Dyslipidemia is associated with ventricular tachyarrhythmia in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Ventricular tachyarrhythmia developing in the acute stage of myocardial infarction (MI) is an important cause of sudden cardiac death. The aim of this study was to determine whether dyslipidemia is associated with the occurrence of ventricular tachycardia/fibrillation (VT/VF) during the acute stage of ST-segment elevation MI (STEMI). METHODS: A total of 58 patients experiencing VT/VF within 24 hours after the onset of MI were selected as the study group. A group of 58 patients with MI but without VT/VF was selected as the control group matched for sex (overall, 104 males), age (overall, 58 +/- 10 years), and the use of thrombolytic therapy (n = 82). The lipid profiles including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride were measured during the first week and at the third month after the index MI. Other coronary risk factors, and clinical, hemodynamic and angiographic characteristics were also included in the assessment. RESULTS: During the acute stage, patients with VT/VF had higher levels of LDL-C and lower blood pressure on initial arrival at our hospital. At the 3-month follow-up, those patients with VT/VF showed higher levels of TC, LDL-C and triglyceride. Multivariate analysis revealed that LDL-C (p < 0.001) at the 3-month follow-up, mean blood pressure on arrival (p < 0.01), and the difference in triglyceride levels between the first week and the third month (p < 0.05) were independent predictors for the occurrence of VT/VF in the acute stage of MI. CONCLUSION: This study suggests that dyslipidemia imposes a higher risk of developing tachyarrhythmia in the acute phase of STEMI.

Aged↗

PubMed2005

Fasting serum levels of adiponectin, ghrelin, and leptin in men with spinal cord injury.

OBJECTIVES: To measure serum levels of adiponectin, ghrelin, and leptin in men with spinal cord injury (SCI) and to investigate possible correlations between these serum levels and various factors, such as body mass index (BMI), age, injury level, and duration of injury. DESIGN: Cross-sectional. SETTING: A university hospital that is a tertiary referral center. PARTICIPANTS: Eighty-nine men with traumatic neurologically complete SCI (30 with tetraplegia, 59 with paraplegia) and 37 age- and BMI-matched male controls. Subjects with SCI were injured at the mean age +/- standard error of 28.5+/-1.0 years (range, 14.7-59.1 y) and the mean injury duration was 10.8+/-0.7 years (range, 1.1-27.7 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Serum levels of adiponectin, ghrelin, and leptin and BMI. RESULTS: Serum leptin levels in subjects with SCI (mean, 7.0+/-0.5 mg/mL) [corrected] were significantly higher than those in able-bodied controls (mean, 4.7+/-0.6 mg/mL) [corrected] (P<.01). The group with tetraplegia had higher serum leptin levels than the group with paraplegia, but this did not reach a statistically significant level (8.2+/-1.1 ng/mL vs 6.4+/-0.5 mg/mL [corrected] P=.097). There were significant differences in serum leptin levels among the 3 groups by 1-way analysis of variance (P=.008). Serum adiponectin levels in subjects with SCI (7.1+/-0.5 mg/mL) [corrected] were higher than those in able-bodied controls (5.6+/-0.5 mg/mL) [corrected] but this was not statistically significant (P=.08). In contrast, serum levels of ghrelin in subjects with SCI (302.0+/-17.5 pg/mL) were similar to those in the controls (264.0+/-27.0 pg/mL) (P=.24). Serum leptin levels correlated positively with BMI (SCI, r=.698, P<.001; controls, r=.782, P<.001), whereas serum adiponectin (SCI, r=-.527, P<.001; controls, r=-.315, P=.057) and ghrelin (SCI, r=-.368, P<.001; controls, r=-.447, P=.006) levels correlated negatively with the BMI in both subjects with SCI and controls. CONCLUSIONS: Men with SCI have significantly higher serum leptin levels than able-bodied controls, and serum leptin levels correlated with the degree of neurologic deficit. Men with SCI had a tendency toward higher serum adiponectin level than able-bodied controls. Serum levels of ghrelin in men with SCI were similar to those of controls.

Adult↗

PubMed2005

Gene expression profiles in hypoxic preconditioning using cDNA microarray analysis: altered expression of an angiogenic factor, carcinoembryonic antigen-related cell adhesion molecule 1.

Hypoxic preconditioning has been shown to exhibit cardioprotective effects on myocardium from ischemic or reperfusion injury. The specific regulated gene involved in the hypoxia-induced cardioprotective effects is profiled in this study. Young male Wistar rats and ICR mice were exposed to sea level (as normal control) or simulated high altitude for 15 h/day for 2, 4, or 8 weeks, or for 4 weeks at high altitude after 2 weeks at sea level. The left ventricles of the animals were isolated for mRNA isolation and cDNA microarray analysis. Our data demonstrated that hypoxic preconditioning significantly ameliorated cardiac ischemic injury by minimizing the infarct size. After cluster analysis of expression profiles after different courses of hypoxic preconditioning (0, 2, 4, and 8 weeks), 386 genes showed an ascending pattern, whereas 301 genes showed a descending pattern. The ascending genes include several angiogenic factors: FGF receptor 4, vascular endothelial growth factor (vEGF), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1). The microvessel density was also significantly increased in hypoxic hearts. Using Western blotting and immunohistochemical analysis, the protein expression level and localization of CEACAM-1 were observed in hypoxic myocardium. The results also indicated that CEACAM-1 was upregulated as with other hypoxic angiogenic factors, heme oxygenase 1 (HO-1) and hypoxia inducible factor-1alpha (HIF-1alpha), in in vitro cultured cardiomyocytes (H9c2) after hypoxia treatment and in vivo hypoxic preconditioning. Furthermore, incubation with recombinant vEGF could also increase the expression level of CEACAM-1 in H9c2 cells. These results demonstrated that hypoxic preconditioning resulted in transcriptional changes, and some of these genes have been correlated with angiogenesis. The HIF-1/vEGF/CEACAM-1 pathway might be important for hypoxia-induced angiogenesis in the heart during hypoxic preconditioning.

Animals↗

PubMed2004

Ascorbate supplement reduces oxidative stress in dyslipidemic patients undergoing apheresis.

OBJECTIVE: The effect of ascorbate treatment on apheresis-induced oxidative stress in uremic and dyslipidemic patients was evaluated. METHODS AND RESULTS: We developed a chemiluminescence-emission spectrum and high-performance liquid chromatography analysis to assess the effect of ascorbate supplement on plasma reactive oxygen species (ROS) scavenging activity and oxidized lipid/protein production in hyperlipidemic and uremic patients undergoing apheresis. Apheresis was efficient in reduction of atherogenic lipoproteins, complement, fibrinogen, soluble intercellular adhesion molecule-1, and oxidative parameters including phosphatidylcholine hydroperoxide (PCOOH), malonaldehyde, methylguanidine, and diotyrosine. Apheresis itself, however, activated leukocytes to increase ROS activity and reduced the plasma ROS scavenging activity. Ascorbate administration selectively diminished apheresis-enhanced H2O2 and inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant protein-1. Chronically dyslipidemic and uremic patients undergoing biweekly apheresis plus ascorbate treatment had lower levels of C-reactive protein and PCOOH than did those without ascorbate treatment during a 6-month follow-up study period. CONCLUSIONS: We demonstrate that apheresis with ascorbate treatment provides a therapeutic potential in reducing atherosclerotic risk via inhibition of H2O2-induced oxidative stress in patients with uremia or dyslipidemia.

Adult↗

PubMed2004

Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome.

Fifty nondiabetic patients who met a modified National Cholesterol Education Program definition for the metabolic syndrome were randomized to receive either rosiglitazone (4 mg/day; n = 25) or placebo (n = 25) for 8 weeks. Compared with those receiving placebo, patients in the rosiglitazone group achieved significant reductions in fasting plasma insulin levels (-40%), homeostasis model assessment indexes (-45%), systolic and diastolic blood pressures, and high-sensitivity C-reactive protein levels (-31%). There were no changes in fasting plasma glucose with either treatment. Although rosiglitazone treatment greatly increased plasma levels of low-density lipoprotein cholesterol (18%) and apolipoprotein B (16%), it significantly improved both endothelium-dependent flow-mediated vasodilation (p <0.001) and endothelium-independent nitroglycerin-induced vasodilation (p = 0.01) of the right brachial artery.

Adult↗

PubMed2004

Improving the rate of return of spontaneous circulation for out-of-hospital cardiac arrests with a formal, structured emergency resuscitation team.

OBJECTIVE: To assess the impact of a formal, structured resuscitation team in the emergency department (ED) on the success rate of cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) patients. METHODS: This is a "three-phase" (organized, transitional, and re-organized), prospective study in which medical records of all OHCA patients who needed resuscitation in the ED during the three 6-month periods were reviewed and data were coded in out-of-hospital Utstein style formats. An organized resuscitation team existed in the organized and re-organized phases but not in the transitional phase. The study population consisted of adult patients with non-traumatic cardiac arrest (>18 years of age). RESULTS: The rates of return of spontaneous circulation (ROSC) were 51.3% for the organized phase, 31.0% for the transitional phase, and 53.1% for the re-organized phase ( P=0.013 ). The rates of ROSC from pulseless electrical activity (PEA)/asystole were significantly higher in periods with organized and re-organized teams ( P=0.007 ). The rates of ROSC for the ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT) sub-groups were not significantly different in all three periods ( P=0.406 ). The chance of survival-to-discharge was 9.2% in the organized period, 11.2% in the transitional period, and 15.6% in the re-organized period ( P=0.496 ). The existence of a formal, structured emergency resuscitation team in the ED (odds ratio: 2.56, 95% confidence interval: 1.35-4.80) and witness at the scene (odds ratio: 2.45, 95% confidence interval: 1.34-4.45) were the only independent predictors of successful ROSC of OHCA patients by multiple logistic regression analysis. CONCLUSION: The establishment of a formal and structured emergency resuscitation team in the ED is associated with an increased rate of ROSC for OHCA patients.

Ambulances↗

PubMed2003

Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles.

Given that combination therapy with statin plus fibrate confers a risk of myopathy, it is worthwhile to determine whether statin or fibrate monotherapy is associated with greater clinical benefit in individuals with combined hyperlipidemia. In this randomized double-blind study, we compared the efficacy of simvastatin and fenofibrate on indexes of endothelial function (flow-mediated dilation (FMD) of the brachial artery) and inflammatory markers (plasma high-sensitivity C-reactive protein (CRP), interleukin-1 beta (IL-1 beta), soluble CD40, and soluble CD40 ligand (sCD40L) levels), as surrogate indicators of future coronary heart disease (CHD), in patients with combined hyperlipidemia. A total of 70 patients with plasma triglyceride levels between 200 and 500 mg/dl and total cholesterol levels of >200 mg/dl were randomly assigned to receive either simvastatin (20 mg/day) (n=35) or micronized fenofibrate (200 mg/day) (n=35) for 8 weeks. Treatment with simvastatin was associated with significantly greater reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), while the decrease in triglycerides was significantly greater in patients receiving fenofibrate. Both fenofibrate and simvastatin markedly reduced plasma levels of high-sensitivity CRP, IL-1 beta, and sCD40L, and improved endothelium-dependent FMD without mutual differences. The changes in plasma inflammatory markers did not correlate with baseline clinical characteristics in both groups. However, the improvement in FMD with fenofibrate treatment correlated inversely with baseline high-density lipoprotein cholesterol (HDL-C) levels, whereas the improvement in FMD with simvastatin treatment was positively related to HDL-C levels. Accordingly, in the subgroup with a baseline HDL-C of < or =40 mg/dl, only fenofibrate significantly improved the endothelium-dependent FMD. On the other hand, in the subgroup with HDL-C >40 mg/dl, only treatment with simvastatin achieved significant improvement in FMD. The data here indicate that in patients with combined hyperlipidemia, both fenofibrate and simvastatin have comparative beneficial effects on various inflammatory markers and differential beneficial effects on endothelial function according to baseline HDL-C levels. These findings should be validated by additional prospective studies, in which patients are stratified by baseline HDL-C prior to randomization.

C-Reactive Protein↗

PubMed2003

Attenuation of increased myocardial ischaemia-reperfusion injury conferred by hypercholesterolaemia through pharmacological inhibition of the caspase-1 cascade.

1. Hypercholesterolaemia has been shown to be associated with greater myocardial ischaemia-reperfusion injury, in which apoptosis and inflammation-mediated necrosis both play a key role. 2. Caspase-1 is involved in the activation of both apoptosis and inflammation, through the intermediate of interleukin-1beta (IL-1beta). We herein examined whether pharmacological inhibition of the caspase-1 cascade, using Ac-Tyr-Val-Ala-Asp-CH(2)Cl (Ac-YVAD.cmk), after myocardial ischaemia have greater protective effects on myocardial ischaemia-reperfusion injury in diet-induced hypercholesterolaemic rabbits. 3. Male rabbits fed with standard chow or chow supplemented with 0.5% cholesterol and 10% coconut oil for 8 weeks were subjected to 30 min of left circumflex artery occlusion followed by 4 h of reperfusion. An intravenous bolus of Ac-YVAD.cmk (1.6 mg kg(-1)) or vehicle was given 20 min after coronary occlusion. 4. Postischaemic administration of Ac-YVAD.cmk markedly decreased infarct size from 26+/-3% to 12+/-2% in normally fed rabbits (P=0.005) and from 41+/-6% to 14+/-2% in cholesterol-fed rabbits (P<0.001). 5. In the ischaemic non-necrotic area, treatment with Ac-YVAD.cmk markedly reduced the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL)-positive cardiomyocytes from 15.5+/-0.8% to 2.2+/-0.1% in normally fed rabbits (P<0.001) and from 39.0+/-2.3% to 2.2+/-0.1% in cholesterol-fed rabbits (P<0.001). 6. Ac-YVAD.cmk treatment resulted in a reduction not only of IL-1beta and caspase-1, but also of caspase-3 in the ischaemic myocardium in both normally fed and cholesterol-fed rabbits. 7. No differences in infarct size, the percentage of TUNEL-positive cardiomyocytes, IL-1beta levels or activity of caspase-1 and caspase-3 were observed between Ac-YVAD.cmk-treated normally fed and cholesterol-fed rabbits. 8. This study demonstrates that injection of a selective caspase-1 inhibitor after myocardial ischaemia markedly reduced the detrimental effect conferred by hypercholesterolaemia on myocardial ischaemia-reperfusion injury by attenuating both necrotic as well as apoptotic cell death pathways through inhibition of IL-1beta production and activation of caspase-1 and caspase-3.

Animals↗

PubMed2002

Increased cardiomyocyte apoptosis following ischemia and reperfusion in diet-induced hypercholesterolemia: relation to Bcl-2 and Bax proteins and caspase-3 activity.

It has been reported that apoptosis is a significant contributor to myocardial cell death as a result of reperfusion injury. However, whether the extent of cardiomyocyte apoptosis following ischemia and reperfusion varies in different pathophysiological backgrounds is still uncertain. In this study, we examined whether hypercholesterolemia increases the extent of myocardial reperfusion injury by aggravating cardiomyocyte apoptosis and the effects of hypercholesterolemia on the expression of Bcl-2 and Bax proteins and the activation of caspase-3. Twenty-eight male New Zealand white rabbits were fed standard chow (control, n = 14) or chow supplemented with 10% cholesterol (hypercholesterolemic, n = 14) for 8 wk. Anesthetized rabbits were then subjected to 30 min of left circumflex artery occlusion followed by 4 h of reperfusion. Apoptosis was identified as "DNA ladders" by gel electrophoresis and confirmed histologically using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The infarct size (% of risk region) was significantly greater in hypercholesterolemic rabbits than in controls (39 +/- 6 vs. 23 +/- 2%, P = 0.02). Very few TUNEL-positive cardiomyocytes could be identified in the nonischemic regions in both groups, consistent with an absence of DNA laddering. In contrast, TUNEL-positive cardiomyocytes were significantly displayed in the ischemic, nonnecrotic myocardium, and DNA ladder occurred in all animals. The percentage of TUNEL-positive cardiomyocytes in the ischemic nonnecrotic myocardium was significantly higher in hypercholesterolemic rabbits compared with controls (40 +/- 5 vs. 17 +/- 11%, P < 0.001). Western blot analysis showed that, in the nonischemic myocardium, hypercholesterolemic rabbits exhibited an approximately 50% increase in the expression of Bcl-2 (P < 0.05), but not Bax, than control rabbits. However, compared with controls, hypercholesterolemic rabbits exhibited a more pronounced decrease in the expression of Bcl-2 (42 +/- 4 vs. 26 +/- 2%, P < 0.01) and a similar extent of increase in the expression of Bax in the ischemic myocardium. Furthermore, hypercholesterolemic rabbits were associated with a markedly increased activation of caspase-3 within the ischemic myocardium compared to control rabbits. This study demonstrates that although hypercholesterolemia is associated with an increased myocardial Bcl-2/Bax ratio at baseline, it still significantly exacerbates cardiac reperfusion injury, not only by increasing the infarct size but also by increasing the extent of cardiomyocyte apoptosis.

Animals↗

PubMedDate not supplied

Assessment of myocardial viability using F-18 fluorodeoxyglucose/Tc-99m sestamibi dual-isotope simultaneous acquisition SPECT: comparison with Tl-201 stress-reinjection SPECT.

BACKGROUND: This study compared technetium 99m sestamibi/fluorine 18 fluorodeoxyglucose dual-isotope simultaneous acquisition (DISA) with stress-reinjection thallium 201 single photon emission computed tomography (SPECT) with regard to their ability to detect myocardial viability. METHODS AND RESULTS: The study cohort consisted of 42 angiographically significant coronary artery disease patients with symptomatic congestive heart failure or regional wall motion abnormalities. In total, 398 dysfunctional segments in 40 patients were analyzed (2 patients were excluded because of poor-quality F-18 fluorodeoxyglucose images). Of the segments, 217 were diagnosed as viable and 144 as nonviable by both DISA and Tl-201, 33 were viable by DISA but nonviable by Tl-201, and 4 were viable by Tl-201 but nonviable by DISA. Most discrepancies were in the inferior wall. Of the 40 patients, 16 underwent revascularization. From the follow-up results for the 105 dysfunctional segments in these 16 patients, DISA viability appears to be a significant predicting factor (P = .014) for functional recovery after revascularization statistically whereas Tl-201 viability does not (P = .09). CONCLUSION: Our study suggests that DISA viability provides more accurate prediction of postrevascularization functional recovery than Tl-201 viability. Given the small number of patients who underwent revascularization, the superiority of DISA over Tl-201 in detecting myocardial viability may be firmly established by further study on a large scale for patients with profound left ventricular dysfunction.

Adult↗