Function and expression differences between ergot and non-ergot dopamine D2 agonists on heart valve interstitial cells.

Background And Aim Of The Study: The symptoms of Parkinson's disease are alleviated by dopamine D2 agonists, which are classified as ergot dopamine D2 agonists and non-ergot D2 agonists. Among the former, pergolide has been associated with valvular heart disease, since it has both potent D2 receptor and serotonin 5-HT(2B) receptor agonistic properties. Among the latter, pramipexole has few incidences of heart valve disease onset, since it has an absence of 5-HT(2B) receptor agonism.

Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.

Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified.

Overweight causes left ventricular diastolic asynchrony and diastolic dysfunction: a study based on speckle tracking echocardiography in healthy subjects.

Background: Left ventricular (LV) diastolic dysfunction is often observed in healthy subjects and can be a cause of heart failure with preserved ejection fraction (EF). We aimed to investigate the role of LV diastolic asynchrony as a cause of diastolic dysfunction in healthy subjects.

Methods: In 40 healthy subjects, two-dimensional speckle tracking imaging (2DSTI) was performed to measure the peak early diastolic longitudinal strain rates (Esr) of the apical, mid-ventricular, and basal segments of the septum and posterior wall.

Synthesis and evaluation of anticancer natural product analogues based on angelmarin: targeting the tolerance towards nutrient deprivation.

Inspired by nature: Angelmarin is an anticancer natural product with potent antiausterity activity, that is, selective cytotoxicity towards nutrient-deprived, resistant cancer cells. Through structure-activity relationship studies, three analogues were identified as lead compounds for the develpoment of molecular probes for the investigation of the mode of action and biological targets of the antiausterity compounds.

Early diastolic mitral annular velocity at the interventricular septal annulus correctly reflects left ventricular longitudinal myocardial relaxation.

Aims: Early diastolic mitral annular velocity (e') obtained by tissue Doppler imaging (TDI) is widely used to evaluate left ventricular (LV) diastolic function based on the assumption that it reflects myocardial relaxation in the long-axis direction. In this study, we aimed to determine whether or not e' truly reflects early diastolic longitudinal myocardial relaxation, and which is the most useful for evaluating LV diastolic function among e' measured at the interventricular-septal annulus (IS-e'), that measured at the lateral annulus (LW-e') or their mean value (M-e').

Methods And Results: IS-e', LW-e', and M-e' were measured using colour TDI in 15 patients with hypertrophic cardiomyopathy, 13 patients with hypertension, and 19 control subjects.

Novel strain rate index of contractility loss caused by mechanical dyssynchrony. - A predictor of response to cardiac resynchronization therapy-.

Background: Time-delay indexes are limited in predicting the response to cardiac resynchronization therapy (CRT), partly because they do not reflect the residual left ventricular (LV) contractility. We computed a novel index of LV contractility loss due to dyssynchrony (the strain rate (SR) dispersion index: SRDI) by using the speckle-tracking SR and compared the efficacy of the SRDI, time-delay indexes, and strain delay index (SDI), the previously reported index of wasted energy due to dyssynchrony, for predicting the acute response to CRT.

Methods And Results: Echocardiography was performed in 19 heart failure patients (LV ejection fraction (EF) 25 ± 6%) before and 2 weeks after CRT.

Hypoglycemic/hypoxic condition in vitro mimicking the tumor microenvironment markedly reduced the efficacy of anticancer drugs.

Tumor tissues are often hypoxic because of defective vasculature. We previously showed that tumor tissues are also often deprived of glucose. The efficacy of anticancer drugs is affected by the tumor microenvironment, partly because of the drug delivery and cellular drug resistance; however, the precise mechanisms remain to be clarified.

Angiotensin II receptor blocker, valsartan, increases myocardial blood volume and regresses hypertrophy in hypertensive patients.

Background: Although a reduction in myocardial blood volume (MBV), an in vivo index of the myocardial microvasculature, measured by myocardial contrast echocardiography in patients with hypertension (HT), can be demonstrated, it is still unknown whether a decreased MBV can be improved by antihypertensive treatment.

Methods And Results: Eleven HT patients (mean age 58 years, 7 men) with left ventricular hypertrophy (LVH) and 10 age- and sex-matched normal controls were studied. Harmonic power Doppler images were acquired at end-diastole of every 6(th) beat and MBV was calculated as 10(X/10)x100%, where X (dB) is myocardial contrast intensity minus the contrast intensity of the adjacent intracavity blood pool.

Right ventricular diastolic dysfunction in patients with left ventricular hypertrophy: analysis of right ventricular myocardial relaxation using two-dimensional speckle tracking imaging.

Background: Although several previous studies have suggested the presence of right ventricular (RV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM) and those with hypertensive left ventricular hypertrophy (HT-LVH), the mechanisms are still unclear. This study aimed to clarify the relationship between the RV global diastolic dysfunction in these patients and the regional myocardial diastolic function, including synchronicity of the interventricular septum and RV free wall.

Methods: In 20 age-matched patients with HT-LVH, 20 patients with HCM and 22 control subjects without pulmonary hypertension, RV isovolumic relaxation time (IRTR) was measured using continuous-wave Doppler echocardiography.

Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry.

Most cancer cells predominantly produce energy by glycolysis rather than oxidative phosphorylation via the tricarboxylic acid (TCA) cycle, even in the presence of an adequate oxygen supply (Warburg effect). However, little has been reported regarding the direct measurements of global metabolites in clinical tumor tissues. Here, we applied capillary electrophoresis time-of-flight mass spectrometry, which enables comprehensive and quantitative analysis of charged metabolites, to simultaneously measure their levels in tumor and grossly normal tissues obtained from 16 colon and 12 stomach cancer patients.

Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer's disease.

Increasing evidence suggests that the elevation of beta-amyloid (Abeta) peptides in the brain is central to the pathogenesis of Alzheimer's disease (AD). Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, enhances cAMP/protein kinase A/extracellular signal-regulated kinase/cAMP response element-binding protein signaling in cultured hippocampal neurons and ameliorates Abeta-induced memory impairment in AD model rats. For the first time, we report that this natural compound improves memory deficits in amyloid precursor protein (APP) transgenic mice that overexpress human APP695 harboring the double Swedish and London mutations [APP-SL 7-5 transgenic (Tg) mice].

Pravastatin attenuates left ventricular remodeling and diastolic dysfunction in angiotensin II-induced hypertensive mice.

Background: A substantial proportion of patients with heart failure have a normal ejection fraction and diastolic dysfunction. However, there are few data available to guide the therapy of these patients. The effects of statins on cardiac remodeling are well documented in animal models and it is reported that statin therapy revealed a survival benefit in patients with diastolic heart failure (DHF).

Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition.

Human pancreatic cancer cells such as PANC-1 are known to exhibit marked tolerance to nutrition starvation that enables them to survive for prolonged period of time even under extremely nutrient-deprived conditions. Thus, elimination of this tolerance to nutrition starvation is regarded as a novel approach in anticancer drug development. In this study, the MeOH soluble extract of Brazilian red propolis was found to kill 100% PANC-1 cells preferentially in the nutrient-deprived condition at the concentration of 10 microg/mL.

Nobiletin, a citrus flavonoid, reverses learning impairment associated with N-methyl-D-aspartate receptor antagonism by activation of extracellular signal-regulated kinase signaling.

Recent studies have indicated that learning-induced activation of extracellular signal-regulated kinase (ERK) signaling via N-methyl-D-aspartate (NMDA) receptors is required for consolidation of the resultant learning. These findings raise an idea that control of ERK signaling may be a potential target for treatment of cognitive dysfunction. Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from Citrus depressa, enhances cAMP/protein kinase A/ERK signaling in cultured rat hippocampal neurons and PC12D cells.

Prevalence and clinical importance of spontaneous echo contrast within the carotid artery in patients with ischemic cerebrovascular disease.

Objective: Spontaneous echo contrast (SEC) is composed of numerous microechoes swirling in the cardiovascular lumen, usually appearing during blood stasis. This study aimed to clarify the clinical importance of SEC in the carotid artery (CA) in patients with ischemic cerebrovascular disease (ICVD).

Methods: In 264 CAs of 132 consecutive patients with ICVD and in 40 CAs of 20 healthy control subjects, SEC was classified as none, faint, or dense, and CA abnormalities, including plaque, plaque ulcer, mural thrombus, and internal CA stenosis, were assessed with 10-MHz sonography.

Role of left ventricular regional diastolic abnormalities for global diastolic dysfunction in patients with hypertrophic cardiomyopathy.

Background: The usefulness of Doppler strain rate imaging for assessment of left ventricular regional diastolic function has not been fully determined.

Objective: We aimed to clarify the relationships between diastolic strain rates and global diastolic function and find a useful index for regional diastolic function in patients with hypertrophic cardiomyopathy (HCM).

Methods: Strain rate curves were obtained using an apical approach at 12 different sites of the left ventricular myocardium in 25 patients with HCM and 20 control subjects, and peak early diastolic strain rate (ESR), peak late diastolic strain rate, and the time from QRS to ESR were measured.

A fundamental study for quantitative measurement of ultrasound contrast concentration by low mechanical index contrast ultrasonography.

Purpose: In high mechanical index (MI) contrast ultrasonography it has been shown that the power of contrast signal intensity (CI) has a strong linear correlation with the concentration of the ultrasound contrast agent under conditions of constant applied acoustic pressure. However, it is unclear whether the linearity is preserved in low-MI contrast ultrasonography. Thus, we investigated the relationship between ultrasound contrast concentration and CI in vitro.

[Dilation of the brachial artery in response to sublingual nitroglycerin can predict the antihypertensive effects of valsartan: a study using novel high-frequency high-frame-rate ultrasound imaging].

Objectives: The efficacy of antihypertensive agents can vary in patients. Four to 8 weeks may be required before antihypertensive agents become fully effective. Predicting the efficacy can help agent selection and dose setting.

[Effects of low-dose pergolide therapy on cardiac valves in patients with Parkinson's disease].

Background: Pergolide mesilate is widely used to treat Parkinson's disease in both the USA and Japan, but the maintenance dose is distinctly different between the USA (usually more than 1.5 mg/day) and Japan (usually less than 1.5 mg/day).

Increased plasma concentrations of N-terminal pro-brain natriuretic peptide reflect the presence of mildly reduced left ventricular diastolic function in hypertension.

Background: The potential use of assays of N-terminal pro-brain natriuretic peptide for detection of diastolic abnormalities associated with alterations in blood pressure has not been elucidated. This study was designed to determine whether increased plasma concentrations of N-terminal pro-brain natriuretic peptide sensitively reflect abnormal diastolic function associated with hypertension.

Methods: Concentrations of N-terminal pro-brain natriuretic peptide in plasma were assayed in 40 previously untreated hypertensive patients without overt congestive heart failure and in 20 age and sex-matched controls.

Loss of insulin receptor substrate-1 signaling induces the cardiovascular and proteo(fibrino)lytic system derangements typical of insulin resistance.

Background: Type 2 diabetes and insulin resistance have been associated with several cardiac features including diastolic heart failure, impaired ventricular function, perimicrovascular fibrosis and increased expression of plasminogen activator inhibitor type-1 (PAI-1) in coronary arterial walls. Insulin receptor substrate-1 (IRS-1) is one mediator of insulin signaling. This study was performed to determine whether induction of cardiac manifestations typical of insulin resistance and increased PAI-1 expression occur developmentally or post-developmentally as a result of loss of IRS-1-mediated signaling.

Novel quantitative assessment of myocardial perfusion by harmonic power Doppler imaging during myocardial contrast echocardiography.

Objective: To test the hypothesis that the power of the received signal of harmonic power Doppler imaging (HPDI) is proportional to the bubble concentration under conditions of constant applied acoustic pressure, and to determine whether a new quantitative method can overcome the acoustic field inhomogeneity during myocardial contrast echocardiography (MCE) and identify perfusion abnormalities caused by myocardial infarction.

Methods: The relation between Levovist concentration and contrast signal intensity (CI) of HPDI was investigated in vitro under conditions of constant acoustic pressure. MCE was performed during continuous infusion of Levovist with intermittent HPDI every sixth cardiac cycle in 11 healthy subjects and 25 patients with previous myocardial infarction.

Sensitive detection of myocardial viability in chronic coronary artery disease by ultrasonic integrated backscatter analysis.

Background: Myocardial viability is not synonymous with contractile reserve and identifiable in a significant percentage of dysfunctional myocardial segments without contractile reserve. The usefulness of ultrasonic tissue characterization by the phase-corrected magnitude of cyclic variation of integrated backscatter (MVIB) in chronic coronary artery disease is not fully validated. Thus, whether MVIB predominantly reflects the contractile reserve or myocardial viability of chronically dysfunctional myocardium was determined.