Myocardial infarct size measurement in the mouse chronic infarction model: comparison of area-and length-based approaches. J Appl Physiol 102: 2104 -2111, 2007. First published March 8, 2007; doi:10.1152/japplphysiol.00033.2007.-Efficacy of potential treatments for myocardial infarction (MI) is commonly assessed by histological measurement of infarct size in rodent models. In experiments involving an acute MI setting, measurement of the infarcted area in tissue sections of the left ventricle is a standard approach to determine infarct size. This approach has also been used in the chronic infarct setting to measure infarct area several weeks post-MI. We tested the hypothesis that, because wall thinning is known to occur in the chronic setting, the area measurement approach would be less appropriate. We compared infarct measurements in tissue sections based on 1) infarct area, 2) epicardial and endocardial infarct arc lengths, and 3) midline infarct arc length. Infarct sizes from all three measurement approaches correlated significantly with left ventricular ejection fraction and wall motion abnormality. However, the infarct size values derived from the area measurement approach were significantly smaller than those from the other two measurement approaches, and the range of values obtained was compressed 0.4-fold. The midline method allowed detection of the expected size differences between infarcts of variable severity resulting from proximal vs. distal ligation of the coronary artery. Segmental infarct size was correlated with segmental wall motion abnormality. We conclude that both area-and length-based measurements can be used to determine relative infarct size over a wide range of severity, although the area-based measurements are substantially more compressed due to wall thinning, and that the estimation of infarct midlines is a simple, reliable approach to infarct size assessment. cardiac remodeling; area-based measurement; length-based measurement; histology RODENT MODELS OF MYOCARDIAL infarction (MI) have been frequently used to elucidate the pathophysiological and molecular mechanisms of cardiac remodeling after the onset of MI (5,7,18,19,23,24). In recent years, the delivery of potentially therapeutic genes and the implantation of stem cells have attracted much interest and have been evaluated with the use of rat or mouse MI models (2,4,9,12,14,21,22). In many published studies exploring these potential therapies, success has commonly been evaluated by determination of infarct size, as well as by functional and other histological parameters. In experiments involving an acute MI setting, infarct size is typically based on histological measurement of the area of the infarcted region in tissue sections of the left ventricle (LV) (13,16,20,26). In contrast, histological measurement of the arc length of the infarct scar has been commonly used in a chronic MI setting (8,14,18,19). Although it is well known that there is progressive thinning of the infarcted wall with reduction in the volume of the infarcted...

Background-A number of noninvasive techniques have been used to predict the effectiveness of cardiac resynchronization therapy (CRT) in heart failure patients, in particular left ventricular (LV) reverse remodeling. This study compared the relative predictive values of tissue Doppler imaging (TDI) and strain-rate imaging (SRI) parameters for LV reverse remodeling in patients who received CRT and examined for potential differences in ischemic (nϭ22) and nonischemic (nϭ32) heart failure. Methods and Results-TDI and SRI were performed at baseline and 3-month follow-up. Eighteen parameters of intraventricular and interventricular asynchrony based on the time to peak myocardial contraction (Ts) and time to peak strain rate (Tsr) were compared, along with postsystolic shortening (PSS). Reverse remodeling with reduction of LV end-diastolic and end-systolic volumes and gain in ejection fraction (all PϽ0.001) was observed in the whole study population. The standard deviation of Ts of 12 LV segments (Ts-SD) is the most powerful predictor of reverse remodeling in both the ischemic (rϭϪ0.65, PϽ0.001) and nonischemic (rϭϪ0.79, PϽ0.001) groups. The PSS of 12 LV segments was a good predictor only for the nonischemic (rϭϪ0.64, PϽ0.001) but not the ischemic (rϭ0.32, PϭNS) group. However, parameters of SRI and interventricular asynchrony failed to predict reverse remodeling. By multiple regression analysis, independent parameters included Ts-SD in both groups (PϽ0.005) and PSS of 12 LV segments in the nonischemic group (Pϭ0.03). The area of the receiver operating characteristic curve was largest for Ts-SD (0.94; CIϭ0.88 to 1.00). Conclusions-Ts-SD is the most powerful predictor of LV reverse remodeling and was consistently useful for ischemic and nonischemic heart failure. However, PSS is useful only for nonischemic pathogenesis, whereas the role of SRI parameters was not supported by the present study.

Antioxidant-rich plant foods can inhibit starch and lipid digestions that are relevant to diabetes management. Two high-antioxidant black legumes, black soybean (Glycine max) and black turtle bean (Phaseolus vulgaris), belonging to two different genera were used to investigate their capacity against digestive enzymes. Phenolic substances were compared in crude, semi-purified extracts (semi-purified by XAD-7 column), and fractions (fractionationed by Sephadex LH-20 column) from these two legumes. In addition, their antioxidant capacities and abilities to inhibit digestive enzymes were characterized. Results showed that Fraction V from black soybean was the most effective (IC50: 0.25mg/mL) against α-amylase; Fraction V from black turtle bean was the most potent (IC50: 0.25μg/mL) against α-glucosidase; Fraction IV from black turtle bean was the most powerful (IC50: 76μg/mL) against lipase. Of the pure phenolic compounds tested, myricetin showed the highest inhibition of α-amylase, α-glucosidase and lipase (IC50: 0.38mg/mL, 0.87μg/mL and 15μg/mL, respectively).

Disrupted in schizophrenia 1 (DISC1), a genetic risk factor for multiple serious psychiatric diseases including schizophrenia, bipolar disorder and autism, is a key regulator of multiple neuronal functions linked to both normal development and disease processes. As these diseases are thought to share a common deficit in synaptic function and architecture, we have analyzed the role of DISC1 using an approach that focuses on understanding the protein– protein interactions of DISC1 specifically at synapses. We identify the Traf2 and Nck-interacting kinase (TNIK), an emerging risk factor itself for disease, as a key synaptic partner for DISC1, and provide evidence that the DISC1–TNIK interaction regulates synaptic composition and activity by stabilizing the levels of key postsynaptic density proteins. Understanding the novel DISC1–TNIK interaction is likely to provide insights into the etiology and underlying synaptic deficits found in major psychiatric diseases.

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp ing this period. 8-10 Therefore, the association of obesity with CVD remains to be investigated, especially in terms of differences in the association by time period as well as how the association (if any) would be mediated by the established risk factors. 11 Also, there may be differences in the threshold of BMI where significant BMI would be observed, because significant differences exist in the prevalence of obesity by sex and ethnicity. Hence, we set 2 aims in this review. The first aim was to provide an overview of global trends of overweight and obesity according to the WHO regions and countries within each region by sex. The second aim was to provide upto-date information on cohort studies that have investigated the associations of BMI with coronary artery disease (CAD) and stroke in various parts of the world. Methods Overweight and Obesity TrendsThe review compiles the prevalence of overweight and obesity for every country in the WHO's 6 regions of the world (Africa, the Americas, Eastern Mediterranean, South-East Asia, Western Pacific, and Europe).besity is a state of excess fat accumulation that accompanies wide range of health disadvantages. The World Health Organization (WHO) defines a body mass index (BMI) of ≥25 kg/m 2 as overweight, and a BMI of ≥30 kg/m 2 as obesity. 1 The global prevalence of the overweight and obese is on the rise. 2 The Global Burden of Disease Study estimated that the proportion of overweight or obese adults in 2013 was 36% in men and 37% in women worldwide. 3 Globally, the epidemic has affected both developed and developing countries, men and women, and adults and children, although there are great variations in their prevalence and trends among regions or countries, and sexes.Because obesity is believed to cause a number of established risk factors for cardiovascular diseases (CVD) such as hypertension, dyslipidemia, and diabetes, 4 the growing prevalence of obesity is assumed to increase the global CVD burden. However, it is also known that other changes in diet and lifestyle have led to changes in the prevalence of these risk factors, and presumably in CVD incidence. 5, 6 An example of this would be a dramatic decrease in stroke mortality observed after World War 2 in Japan because of the decrease in severe hypertension, 7 although the average BMI also increased dur- Global Trend in Overweight and Obesity and Its Association With Cardiovascular Disease IncidenceHiroshi Yatsuya, MD, PhD; Yuanying Li, PhD; Esayas Haregot Hilawe, PhD; Atsuhiko Ota, MD, PhD; Chaochen Wang, BSc; Chifa Chiang, PhD; Yan Zhang, BSc; Mayu Uemura, BSc; Ayaka Osako, BSc; Yukio Ozaki, MD, PhD; Atsuko Aoyama, MD, PhDAlthough the global prevalence of both the overweight and obese is on the rise, there are variations among regions or countries, and sexes. Approximately half or more than half of the population are overweight/obese defined as body mass index ≥25 kg/m 2 in the Americas (61.1%), Europe (54.8%...

Glycitein metabolism was compared with other isoflavones to begin to understand the effect of this compound. Total isoflavones of 4.5 micromol/kg body weight from soymilk (high in genistein and daidzein) and soygerm (high in daidzein and glycitein) was fed to seven women and seven men. To minimize interindividual variation, only subjects with moderate fecal isoflavone degradation rates (half-lives of daidzein and genistein were 15.7 and 8.9 h, respectively) were included. The average 48-h urinary excretion of glycitein, daidzein and genistein was approximately 55, 46 and 29% of the dose ingested, respectively, which was significantly different from each other in men and women (P < 0.001). Plasma isoflavone concentrations at 6 and 24 h after soymilk feeding paralleled relative amounts of isoflavones in soymilk (genistein > daidzein > glycitein) (P < 0.05) in men and women, but plasma isoflavone concentrations after soygerm feeding did not parallel soygerm isoflavone concentrations in women because genistein and glycitein did not differ from each other at 6 h after feeding. Six hours after soygerm dosing, plasma isoflavone concentrations paralleled soygerm isoflavone levels in men. Based on plasma isoflavone concentrations at 6 h after dosing, the bioavailabilities of daidzein and genistein were similar in men and women. At the high glycitein dose (soygerm), plasma concentration at 24 h after dosing suggested a modest gender difference in glycitein bioavailability.

Taken together, our findings indicate that DKK3 acts as a cardioprotective regulator of pathological cardiac hypertrophy and that this function largely occurs via the regulation of ASK1-JNK/p38 signalling.

Impaired long-axis motion is a sensitive marker of systolic myocardial dysfunction, but no data are available that relate long-axis changes in systole with those in diastole, particularly in subjects with diastolic dysfunction and a 'normal' left ventricular (LV) ejection fraction. A total of 311 subjects (including 105 normal healthy volunteers) aged 20-89 years with variable degrees of systolic function (LV ejection fraction range 0.15-0.84) and diastolic function were studied using tissue Doppler echocardiography and M-mode echocardiography to determine mean mitral annular amplitude and peak velocity in systole and early and late diastole. The LV systolic mitral annular amplitude (S(LAX), where LAX is long-axis amplitude) and peak velocity (S(m)) correlated well with the respective early diastolic components (E(LAX) and E(m)) and late diastolic (atrial) components (A(LAX) and A(m)). A non-linear equation fitted better than a linear relationship (non-linear model: S(LAX) against E(LAX), r(2)=0.67; S(m) against E(m), r(2)=0.60; S(LAX) against A(LAX) and S(m) against A(m), r(2)=0.42). After adjusting for age, sex and heart rate, linear relationships of early diastolic (E(LAX), r(2)=0.70; E(m), r(2)=0.60) and late diastolic (A(LAX), r(2)=0.61; A(m), r(2)=0.64) long-axis amplitudes and velocities with the respective values for S(LAX) and S(m) were found, even in those subjects with apparently 'isolated' diastolic dysfunction. Long-axis changes in systole or diastole did not correlate with Doppler mitral velocities. We conclude that ventricular long-axis changes in early diastole are closely related to systolic function, even in subjects with diastolic dysfunction. 'Pure' or isolated diastolic dysfunction is uncommon.