Beat-to-beat and spectral analyses of the noninvasive radial pulse and laser-Doppler signals in patients with hypertension.

This study performed beat-to-beat and spectral analyses of 20-minute skin-surface laser-Doppler-flowmetry (LDF) and radial blood-pressure-waveform (BPW) signals in order to compare the blood-flow perfusion condition and regulatory mechanisms between essential-hypertension (EHT) patients and aged-matched control subjects. Beat-to-beat LDF analyses yielded the pulse width (PW), AC-to-DC ratio (AD), and their corresponding variability indices (coefficients of variation [CVs]). The relative energy contributions (RECs) of five characteristic frequency peaks (defined as FR1-FR5) were also calculated. Spectral BPW analysis obtained the amplitude proportion (Cn) and phase angle (Pn) of each harmonic component n. PW, AD, AD_CV, and REC of FR2 were significantly smaller in the EHT group than in the control group. Regarding BPW indices, C1, C2, C4, and C5 were significantly larger and P2-P8 were significantly smaller in EHT patients than in controls. The present results indicate that BPW and LDF indices can be used to evaluate the blood-flow perfusion efficiency and microcirculatory regulatory activities in EHT. Sex differences were found, with the effects being more prominent in female patients. These findings may be partly attributable to impairment of endothelial and neural regulatory functions. The present findings might aid the development of new noninvasive methods for reducing the risk of EHT-induced damage.

Correction to: Risk of adverse outcomes in patients with rheumatoid arthritis hospitalized for stroke-a cross-sectional study.

The authors of the published version of this article incorrectly presented the affiliation of Li-Chin Sung. The revised affiliation is now presented correctly in this article.

Inverse association between statin use and head and neck cancer: Population-based case-control study in Han population.

BACKGROUND: This case-control study aimed to find the relationship between prior statin use and head and neck cancer occurrence using a large population-based database. METHODS: This study used claims data from the Taiwan Longitudinal Health Insurance Database. We included 5515 patients with head and neck cancer as cases and 5515 propensity score-matched patients without head and neck cancer as controls. Conditional logistic regressions were performed to investigate the relationship between head and neck cancer and prior statin exposure. RESULTS: Of the 11 030 total sampled patients, 16.95% had previously received prescriptions for statins. In addition, statin exposure was found in 15.99% of cases and 17.91% of controls. The logistic regression also revealed that the adjusted odds ratio of prior statin exposure for cases was 0.86 (95% confidence interval: 0.77-0.95) compared to propensity score-matched controls. CONCLUSION: This study found an inverse association between statin usage and head and neck cancer occurrence.

Risk of adverse outcomes in patients with rheumatoid arthritis hospitalized for stroke-a cross-sectional study.

Specific data regarding the full range of stroke outcomes among patients with rheumatoid arthritis (RA) are lacking. This study aimed to investigate outcomes in RA patients hospitalized for a stroke. The study retrieved data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 26,336 patients who were hospitalized for stroke treatment. Of these patients, 736 patients with a prior diagnosis of RA before the index hospitalization were selected as the study group. We selected 2208 age-sex-matched patients without RA as the comparison group. We performed conditional logistic regressions to calculate odds ratios (ORs) for in-hospital mortality and secondary diagnoses of pneumonia, urinary tract infections (UTIs), peptic ulcers, acute respiratory failure, and the use of mechanical ventilation to compare RA patients and comparison patients. We also compared the length of stay (LOS) and hospitalization costs between patients with RA and comparison patients. We found that RA patients had a significantly increased risk of peptic ulcer during the stroke hospitalization (OR = 1.52, 95% CI = 1.05-2.20). However, there were no significant differences between patients with RA and comparison patients in terms of in-hospital mortality, pneumonia, UTIs, acute respiratory failure, or the use of mechanical ventilation. Furthermore, the LOS of stroke hospitalization did not differ between the two groups. We concluded that RA patients hospitalized for a stroke do not have a significantly different risk of in-hospital mortality, pneumonia, UTIs, and mechanical ventilator use, but they have a higher risk of peptic ulcers. Additionally, among patients with a subarachnoid/intracerebral hemorrhagic stroke, RA patients were more likely to have received mechanical ventilation than comparison patients (adjusted OR = 1.89, 95% CI = 1.14-3.15).

Influenza vaccination reduces hemorrhagic stroke risk in patients with atrial fibrillation: A population-based cohort study.

PURPOSE: The risk of hemorrhagic stroke in patients with atrial fibrillation (AF) is low but the consequences of its occurrence are extremely severe. In this study, we investigated the association of influenza vaccination with the risk of hemorrhagic stroke to develop an efficient strategy for reducing this risk in patients with AF. METHODS: In this study, data were retrieved from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients who received a diagnosis of AF (n=14,454) before January 1, 2005 (index date) and were followed until December 31, 2012. Propensity scores were calculated using a logistic regression model to determine the effects of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) for hemorrhagic stroke in vaccinated and unvaccinated patients with AF. RESULTS: The study population comprised 6570 patients who did (2547 [38.77%]) and did not receive (4023 [61.23%]) influenza vaccination. The adjusted HRs (aHRs) for hemorrhagic stroke were lower in the vaccinated patients than in the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs=0.97 [0.59-1.60], 0.51 [0.30-0.87], and 0.72 [0.50-1.03], respectively). CONCLUSIONS: Influenza vaccination exerts dose-response and synergistic protective effects against hemorrhagic stroke in patients with AF who have a high risk of hemorrhagic stroke (i.e., male sex, age≥75years, Charlson comorbidity index ≥3, and hypertension) and reduces the incidence of hemorrhagic stroke.

Influenza vaccination might reduce the risk of ischemic stroke in patients with atrial fibrillation: A population-based cohort study.

PURPOSE: Atrial fibrillation (AF) is associated with the risk of ischemic stroke, regardless of the administration of appropriate antithrombotic prophylaxis. This study investigated whether influenza vaccination is associated with the risk of ischemic stroke, to determine a solution to reduce this risk in patients with AF. METHODS: We used data from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients diagnosed as having AF (n = 14 454) before January 1, 2005; these patients were followed until December 31, 2012. The index date was January 1, 2005. A propensity score was derived using a logistic regression model to estimate the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A Cox proportional hazard model was used to calculate the hazard ratios (HRs) of ischemic stroke in vaccinated and unvaccinated patients with AF. RESULTS: We included 6570 patients (2547 [38.77%] with and 4023 [61.23%] without influenza vaccination). The adjusted HRs (aHRs) of ischemic stroke were lower in the vaccinated patients than in the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.59, 0.50, and 0.55; P < 0.001, P < 0.001, and P < 0.001, respectively). CONCLUSIONS: Influenza vaccination might exert a dose-response effect against ischemic stroke in patients with AF who have risk factors for ischemic stroke by reducing the incidence of ischemic stroke, particularly in those aged 65-74 and ≥75 y.

Statins Dose-Dependently Exert Significant Chemopreventive Effects Against Various Cancers in Chronic Obstructive Pulmonary Disease Patients: A Population-Based Cohort Study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with an increased cancer risk. We evaluated the chemopreventive effect of statins against all cancers in COPD patients and identified the statin with the strongest chemopreventive effect. PATIENTS AND METHODS: All patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) from January 1, 2001, to December 31, 2012, were recruited. Each patient was followed to assess the following protective and risk factors for all cancers: age; sex; comorbidities (diabetes, hypertension, dyslipidemia) and the Charlson comorbidity index [CCI]); urbanization level; monthly income; and nonstatin drug use. The index date of statins use was the date of COPD confirmation. Propensity scores (PSs) were derived using a logistic regression model to estimate the effect of statins by considering the covariates predicting intervention (statins) receipt. To examine the dose-response relationship, we categorized statin use into four groups in each cohort (<28 [statin nonusers], 28-90, 91-365, and >365 cumulative defined daily dose). RESULTS: After PS adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income, we analyzed the all-cancer risk. The adjusted hazard ratios (aHRs) for the all-cancer risk were lower among statin users than among statin nonusers (aHR = 0.46, 95% confidence interval: 0.43 to 0.50). The aHRs for the all-cancer risk were lower among patients using rosuvastatin, simvastatin, atorvastatin, pravastatin, and fluvastatin than among statin nonusers (aHRs = 0.42, 0.55, 0.59, 0.66, and 0.78, respectively). Sensitivity analysis indicated that statins dose-dependently reduced the all-cancer risk. CONCLUSION: Statins dose-dependently exert a significant chemopreventive effect against various cancers in COPD patients. In particular, rosuvastatin has the strongest chemopreventive effect.

Statins dose-dependently exert a chemopreventive effect against lung cancer in COPD patients: a population-based cohort study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk. We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential. RESULTS: After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37). Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly. By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively). Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use). MATERIALS AND METHODS: The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012. Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not. Patients were followed up to assess lung cancer risk or protective factors. In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use. The index date of statin use was the COPD confirmation date. To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs). Patients receiving < 28 cDDDs were defined as nonstatin users. CONCLUSIONS: Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.

Statins dose-dependently exert a significant chemopreventive effect on colon cancer in patients with chronic obstructive pulmonary disease: A population-based cohort study.

PURPOSE: We evaluated the chemopreventive effect of statins on colon cancer in patients with chronic obstructive pulmonary disease (COPD) and identified the statin exerting the strongest chemopreventive effect. METHODS: Using the National Health Insurance Research Database, we identified patients who received a COPD diagnosis in Taiwan between January 1, 2001, and December 31, 2012, and included them in the study cohort. Each patient was followed to assess the colon cancer risk and protective factors. A propensity score was derived using a logistic regression model to estimate the effect of statins by accounting for covariates predicted during the intervention (statins). To examine the dose-response relationship, we categorized statin doses into four groups in each cohort [<28, 28-90, 91-365, and >365 cumulative defined daily dose]. RESULTS: Compared with the statin nonusers, the adjusted hazard ratio (aHR) for colon cancer decreased in the statin users (aHR = 0.52, 95% confidence interval = 0.44, 0.62). Hydrophilic statins exerted a stronger preventive effect against colon cancer. Regarding the statin type, lovastatin, pravastatin, and fluvastatin nonsignificantly reduced the colon cancer risk in the patients with COPD. Compared with the statin nonusers, the aHRs for colon cancer decreased in the individual statin users (rosuvastatin, simvastatin, and atorvastatin: aHRs = 0.28, 0.64, and 0.65, respectively). In the sensitivity analysis, statins dose-dependently reduced the colon cancer risk. CONCLUSIONS: Statins dose-dependently exert significant chemopreventive effects on colon cancer in patients with COPD, with rosuvastatin exerting the largest chemopreventive effect.

Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study.

Taiwan has the highest prevalence of chronic kidney disease (CKD) worldwide. CKD, a manifestation of vascular diseases, is associated with a high risk of dementia. Here, we estimated the association between influenza vaccination and dementia risk in patients with CKD. Data from the National Health Insurance Research Database of Taiwan were used in this study. The study cohort included all patients diagnosed with CKD (according to International Classification of Disease, Ninth Revision, Clinical Modification codes) at healthcare facilities in Taiwan (n = 32,844) from January 1, 2000, to December 31, 2007. Each patient was followed up to assess dementia risk or protective factors: demographic characteristics of age and sex; comorbidities of diabetes, hypertension, dyslipidemia, cerebrovascular diseases, parkinsonism, epilepsy, substance and alcohol use disorders, mood disorder, anxiety disorder, psychotic disorder, and sleep disorder; urbanization level; monthly income; and statin, metformin, aspirin, and angiotensin-converting enzyme inhibitor (ACEI) use. A propensity score was derived using a logistic regression model for estimating the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) of dementia among vaccinated and unvaccinated CKD patients. The study population comprised 11,943 eligible patients with CKD; 5745 (48%) received influenza vaccination and the remaining 6198 (52%) did not. The adjusted HRs (aHRs) of dementia decreased in vaccinated patients compared with those in unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.68, 0.58, and 0.64; P < 0.0001, P < 0.0001, and P < 0.0001, respectively). In the sensitivity analysis, adjustments were made to estimate the association of age and sex; diabetes, dyslipidemia, hypertension, cerebrovascular diseases, anxiety disorder; and statin, metformin, ACEI, and aspirin use with the incidence of dementia in various models. A stronger protective effect against dementia risk was demonstrated during the noninfluenza season. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor and dose-dependently reduced the risk of dementia in CKD patients. Influenza vaccination exerts dose-response and synergistic protective effects against dementia in CKD patients with dementia risk factors by reducing the incidence of dementia.

Influenza Vaccination is Associated with Lower Risk of Acute Coronary Syndrome in Elderly Patients with Chronic Kidney Disease.

Elderly patients with chronic kidney disease (CKD) are at a higher risk of hospitalization for cardiovascular diseases (CVD). Previous studies have showed that influenza vaccination could reduce the risk of recurrent major cardiovascular events in patients with CVD. However, the effects of influenza vaccination on the reduction of first hospitalizations for acute coronary syndrome (ACS) in elderly patients with CKD remain unknown.We conducted a cohort study using data from the Taiwan Longitudinal Health Insurance Database 1997 to 2008. This cohort study comprised elderly patients (ages ≥55 years) with a recorded diagnosis of CKD (n = 4406) between January 1, 1999, and December 31, 2007. Each patient was followed up until the end of 2008. To minimize the selection bias of vaccine therapy, a propensity score adjustment was applied. The hazard ratio (HR) and 95% confidence interval (CI) for the association between the influenza vaccination and the occurrence of first hospitalization for ACS was evaluated by Cox proportional hazards regression. We further categorized the patients into 4 groups according to their vaccination status (unvaccinated, and total number of vaccinations: 1, 2-3, and ≥4).We found that elderly CKD patients without prior CVD history receiving influenza vaccination exhibited a lower risk of hospitalization for ACS (adjusted HR = 0.35, 95% CI 0.30-0.42; P < 0.001). We observed consistent protective effects regardless of age groups (55-64, 65-74, and ≥75), gender, and seasonality of influenza. When the patients were stratified according to the total number of vaccinations, the adjusted HRs for first ACS hospitalization were 0.62 (95% CI 0.52-0.81), 0.35 (95% CI 0.28-0.45), and 0.13 (95% CI 0.09-0.19) for patients who received 1, 2 to 3, and ≥4 vaccinations. There was a significant trend of decreasing risk of ACS hospitalization with an increasing number of vaccinations.The results of our observational study could strengthen the annual vaccination policy and physicians should be aware of missed opportunities to vaccinate elderly patients with CKD against influenza. The potential public health impact of influenza vaccination, particularly in the elderly CKD patients without a history of CVD, who are at risk for ACS, should be further explored.

A Lethal Complication after Coronary Angiography in a Patient with Ehlers-Danlos Syndrome.

UNLABELLED: A 51-year-old man with Ehlers-Danlos syndrome presented to our emergency department with the chief complaint of chest tightness. The patient was diagnosed with acute coronary syndrome, due to his crescendo pattern of typical angina without elevated troponin-I, which was managed with dual-antiplatelet agents and intravenous heparinization. However, the symptoms persisted, and coronary angiography was performed smoothly via the left radial artery with manual compression applied for wound closure. Nonetheless, a left arm hematoma with compartment syndrome due to delayed arterial leakage developed, which was treated with an emergency fasciotomy. Three days later, during general anesthesia for surgical wound closure, extensive subarachnoid hemorrhage occurred due to a remarkable fluctuation of blood pressure. The patient remained comatose in the following months. This case suggests that the undertaking of an endovascular procedure should be reserved for life-threatening scenarios to avoid any life-threatening complications for patients with Ehlers-Danlos Syndrome, especially the vascular type. Moreover, prolonged manual direct compression or trans-radial band may be mandatory for post-angiographic hemostasis. KEY WORDS: Coronary angiography; Endovascular procedure; Vascular Ehlers-Danlos syndrome; Vascular rupture.

Structural characterization and antioxidative activity of low-molecular-weights beta-1,3-glucan from the residue of extracted Ganoderma lucidum fruiting bodies.

The major cell wall constituent of Ganoderma lucidum (G. lucidum) is ß-1,3-glucan. This study examined the polysaccharide from the residues of alkaline-extracted fruiting bodies using high-performance anion-exchange chromatography (HPAEC), and it employed nuclear magnetic resonance (NMR) and mass spectrometry (MS) to confirm the structures. We have successfully isolated low-molecular-weight ß-1,3-glucan (LMG), in high yields, from the waste residue of extracted fruiting bodies of G. lucidum. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay evaluated the capability of LMG to suppress H2O2-induced cell death in RAW264.7 cells, identifying that LMG protected cells from H2O2-induced damage. LMG treatment decreased H2O2-induced intracellular reactive oxygen species (ROS) production. LMG also influenced sphingomyelinase (SMase) activity, stimulated by cell death to induce ceramide formation, and then increase cell ROS production. Estimation of the activities of neutral and acid SMases in vitro showed that LMG suppressed the activities of both neutral and acid SMases in a concentration-dependent manner. These results suggest that LMG, a water-soluble ß-1,3-glucan recycled from extracted residue of G. lucidum, possesses antioxidant capability against H2O2-induced cell death by attenuating intracellular ROS and inhibiting SMase activity.

A potent sphingomyelinase inhibitor from Cordyceps mycelia contributes its cytoprotective effect against oxidative stress in macrophages.

A novel water-soluble polysaccharide fraction, CME-1, with a molecular mass of 27.6 kDa and containing mannose and galactose in a respective ratio of 4:6, was prepared from Cordyceps sinensis mycelia and identified by NMR and GC-MS. In the current study, we examined whether CME-1 has anti-inflammatory effects in RAW264.7 cells. The ability of CME-1 to inhibit H(2)O(2)-induced cell death in RAW264.7 cells was assessed by using an MTT assay and annexin V/propidium iodide double staining; we found that CME-1 protected cells against H(2)O(2)-induced injury. H(2)O(2)-induced intracellular oxidative stress and mitochondrial membrane depolarization were also diminished with CME-1 treatment. We evaluated the hydroxyl radical scavenging ability of CME-1 by using the DMPO-electron spin resonance technique, which indicated that CME-1 acts as an intracellular antioxidant in a concentration-dependent manner through a mechanism other than its scavenging activity. Activities of both neutral and acid sphingomyelinases (SMases) were assessed in vitro, and results showed that the CME-1 inhibited activities of both neutral and acid SMases in a concentration-dependent manner. CME-1 reduced H(2)O(2) treatment-elevated C16- and C18-ceramide levels measured by LC/MS/MS in RAW264.7 cells. Results suggest that CME-1 protects RAW264.7 cells against oxidative stress through inhibition of SMase activity and reduction of C16- and C18-ceramide levels.

Pulmonary valve endocarditis in a pregnant woman with a ventricular septal defect.

Bacterial endocarditis in pregnancy causes maternal and fetal mortality rates of 22.1% and 14.7%, respectively. The mortality rates differ according to the involved valves, and the size of vegetation has a prognostic correlation. This report is of a pregnant woman with an unrepaired ventricular septal defect and pulmonary valve endocarditis with a vegetation size of 3.29 cm. She and her baby were treated successfully. An emergency surgical plan would be appropriate for pregnant women in the third trimester with a large vegetation in the right side of the heart, and dental disease should be treated aggressively with appropriate prophylactic antibiotics.

Effects of hesperidin on cyclic strain-induced endothelin-1 release in human umbilical vein endothelial cells.

1. Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species and has been reported to have antihypotensive and vasodilator properties. However, the mechanism of action of hesperidin in the prevention and treatment of vascular diseases remains unclear. 2. The vascular endothelium can produce potent contracting factors, such as endothelin (ET)-1, and endothelium-derived relaxing factors, such as nitric oxide (NO). The aims of the present study were to test the hypothesis that hesperidin may alter strain-induced ET-1 secretion and NO production and to identify the putative underlying signalling pathways in human umbilical vein endothelial cells (HUVEC). 3. Hesperidin (10 and 100 micromol/L) inhibited strain-induced ET-1 secretion. Hesperidin also inhibited strain-induced increases in the formation of reactive oxygen species and extracellular signal-regulated kinase (ERK) phosphorylation. 4. Hesperidin treatment of HUVEC enhanced NO production, endothelial NO synthase (eNOS) activity and the phosphorylation of eNOS and Akt. Furthermore, hesperidin modulated strain-induced ET-1 release and suppressed ERK phosphorylation in part via the NO/protein kinase G pathway. 5. In summary, we have demonstrated that hesperidin inhibits strain-induced ET-1 secretion and enhances NO production in HUVEC.

Effects of the angiotensin II type 1 receptor antagonist valsartan on the expression of superoxide dismutase in hypertensive patients.

The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro-oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT(1)) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double-blind, placebo-controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD-mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration-dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The erythrocyte superoxide dismutase activity before treatment was more than 2 times higher in hypertensive subjects compared to normal controls. Superoxide dismutase activity decreased significantly after 12 weeks of treatment with valsartan but did not change with placebo. The amount of SOD-mRNA in the polymorphonuclear leukocytes decreased progressively over 3 months in the hypertensive subjects receiving valsartan treatment but did not change in the placebo group. The production of reactive oxygen species is increased in hypertension, and superoxide dismutase activity is increased, presumably as a compensatory mechanism. Treatment with valsartan but not placebo resulted in a progressive down-regulation of SOD-mRNA expression and a reduction in superoxide dismutase activity, suggesting antioxidant activity and a reduction of reactive oxygen species generation. These findings imply that AT(1) receptor antagonists may provide benefits to hypertensive patients beyond blood pressure reduction.

Changes of serum beta-endorphin by programmed exercise training are correlated with improvement of clinical symptoms and quality of life in female mitral valve prolapse syndrome.

BACKGROUND: Mitral valve prolapse (MVP) is a common entity in female population. Although this is a minor disease, it may cause annoying symptoms that impair quality of life (QOL), and no established therapy for this problem. The aim of this study isto examine whether programmed exercise training by treadmill in female MVP syndrome would improve clinical symptoms and QOL. METHODS: An interventional study of 39 females with MVP syndrome with treadmill exercise endurance training for 12 weeks. Every individual received training for 30 min a day, thrice a week for 12 weeks. Baseline and post-exercise at 12 weeks serum beta-endorphins were measured. Symptom improvement was assessed by the MVP symptom checklist questionnaire and the Euro-QOL-5D was used to measure QOL improvement in these females. RESULTS: The mean serum beta-endorphin increased from 0.5 to 1.68 ng/ml (p = 0.001) in the exercise group (n = 18) after 12 weeks exercise, whereas the control group (n = 21) did not show any significant changes (0.44 vs. 0.43 ng/ml). Major symptoms of MVP such as chest pain, palpitation, fatigue were improved significantly by the assessment of MVP symptom checklist. The QOL of the exercised females also showed significant changes. CONCLUSIONS: Through programmed exercise training in these MVP females, the improvement of symptoms and QOL is parallel to the increase of serum beta-endorphin. This result implicates that MVP females should initiate exercise to tackle this annoying problem.

Tetramethylpyrazine downregulates angiotensin II-induced endothelin-1 gene expression in vascular endothelial cells.

1. Tetramethylpyrazine (TMP) is one of the active ingredients of the Chinese herb Ligusticum wallichii Franchat. It is well documented that TMP exerts a cardiovascular protective effect. The aims of the present study were to examine whether TMP alters angiotenisn (Ang) II-induced endothelin (ET)-1 gene expression and to identify the putative underlying signalling pathways in vascular endothelial cells. 2. Cultured vascular endothelial cells were pre-incubated with TMP, stimulated with AngII and ET-1 gene expression was then examined. The effects of TMP pretreatment on AngII-induced extracellular signal-regulated kinase (ERK) phosphorylation were investigated to elucidate the intracellular mechanism responsible for the effects of TMP on ET-1 gene expression. 3. Tetramethylpyrazine inhibited AngII-induced ET-1 gene expression, as revealed by nothern blotting and a promoter activity assay. Tetramethylpyrazine also inhibited the AngII-induced increase in intracellular reactive oxygen species (ROS), as measured by the redox sensitive fluorescent dye 2' 7'-dichlorofluorescin diacetate and ERK phosphorylation. 4. In summary, we have demonstrated, for the first time, that TMP inhibits AngII-induced ROS generation, ERK phosphorylation and ET-1 gene expression in vascular endothelial cells. Thus, the present study delivers important new insights into the molecular pathways that may contribute to the proposed beneficial effects of TMP in the cardiovascular system.

Molecular mechanism of the inhibitory effect of trilinolein on endothelin-1-induced hypertrophy of cultured neonatal rat cardiomyocytes.

Trilinolein, isolated from the traditional Chinese herb Sanchi ( Panax notoginseng), has been shown to have myocardial protective effects via its antioxidant ability. However, the cellular and molecular mechanisms of the protective effect of trilinolein in the heart remain to be elucidated. Oxidative mechanisms have been implicated in neonatal cardiomyocyte hypertrophy. We therefore have examined whether trilinolein attenuates reactive oxygen species (ROS) production and thus ET-1-induced hypertrophy of cardiomyocytes. Cultured neonatal rat cardiomyocytes were stimulated with ET-1 (10 nM), [3H]leucine incorporation and the beta-myosin heavy chain (beta-MyHC) promoter activity were examined. Trilinolein (1 and 10 microM) inhibited the ET-1-induced increase of [3H]-leucine incorporation in a concentration-dependent manner. Trilinolein (1 and 10 microM) also inhibited ET-1-induced beta-MyHC promoter activity in cardiomyocytes. We further examined the effects of trilinolein on ET-1-induced intracellular ROS generation by measuring a redox-sensitive fluorescent dye, 2',7'-dichlorofluorescin diacetate, fluorescence intensity. Trilinolein (1 and 10 microM) inhibited ET-1-increased intracellular ROS levels in a concentration-dependent manner. This increase of ROS by ET-1 (10 nM) or H2O2 (25 microM) was significantly inhibited by trilinolein (10 microM) and N-acetylcysteine (10 mM). Moreover, ET-1- or H2O2-induced beta-MyHC promoter activity and protein synthesis were also inhibited by trilinolein (10 microM). These data indicate that trilinolein inhibits ET-1-induced beta-MyHC promoter activity, and subsequent hypertrophy via its antioxidant ability in cardiomyocytes.