Selective Activation of Estrogen Receptor-β Transcriptional Pathways by an Herbal Extract

Novel estrogenic therapies are needed that ameliorate menopausal symptoms and have the bone-sparing effects of endogenous estrogens but do not promote breast or uterine cancer. Recent evidence suggests that selective activation of the estrogen receptor (ER)-beta subtype inhibits breast cancer cell proliferation. To establish whether ERbeta-selective ligands represent a viable approach to improve hormone therapy, we investigated whether the estrogenic activities present in an herbal extract, MF101, used to treat hot flashes, are ERbeta selective. MF101 promoted ERbeta, but not ERalpha, activation of an estrogen response element upstream of the luciferase reporter gene. MF101 also selectively regulates transcription of endogenous genes through ERbeta. The ERbeta selectivity was not due to differential binding because MF101 binds equally to ERalpha and ERbeta. Fluorescence resonance energy transfer and protease digestion studies showed that MF101 produces a different conformation in ERalpha from ERbeta when compared with the conformations produced by estradiol. The specific conformational change induced by MF101 allows ERbeta to bind to an estrogen response element and recruit coregulatory proteins that are required for gene activation. MF101 did not activate the ERalpha-regulated proliferative genes, c-myc and cyclin D1, or stimulate MCF-7 breast cancer cell proliferation or tumor formation in a mouse xenograft model. Our results demonstrate that herbal ERbeta-selective estrogens may be a safer alternative for hormone therapy than estrogens that nonselectively activate both ER subtypes

Delayed Senescence in Soybean: Terminology, Research Update, and Survey Results from Growers

The terms used to describe symptoms of delayed senescence in soybean often are used inconsistently or interchangeably and do not adequately distinguish the observed symptoms in the field. Various causes have been proposed to explain the development of delayed senescence symptoms. In this article, we review published reports on delayed senescence symptoms in soybean, summarize current research findings, provide examples of terms related to specific symptoms, and present an overview of the results of a multi-state survey directed to soybean growers to understand their concerns about delayed soybean senescence. Some of these terms, such as green bean syndrome and green stem syndrome, describe symptoms induced by biotic factors, while other terms describe symptoms associated with abiotic factors. Some delayed senescence terms involve the whole plant remaining green while other terms include just the stem and other plant parts such as pods. In the grower survey, 77% reported observing soybean plants or plant parts that remained green after most plants in the field were fully mature with ripe seed. Most respondents attributed these symptoms to changes in breeding and choice of cultivars. At the end of this article, we standardized the terms used to describe delayed senescence in soybean

Estrogenic Plant Extracts Reverse Weight Gain and Fat Accumulation without Causing Mammary Gland or Uterine Proliferation

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women

Right ventricular dysfunction in patients with Brugada-like electrocardiography: a two dimensional strain imaging study

<p>Abstract</p> <p>Background</p> <p>Sodium channel blockers augment ST-segment elevation in the right precordial leads in patients undergoing Brugada-type electrocardiography (ECG). However, their effect on echocardiographic features is not known. We address this by assessing global and regional ventricular function using conventional Doppler and two- dimensional (2D) speckle tracking techniques.</p> <p>Methods</p> <p>Thirty-one patients with Brugada-type ECG were studied. A pure sodium channel blocker, pilsicainide, was used to provoke an ECG response. The percentage longitudinal systolic myocardial strain at the base of both the right ventricular (RV) free wall and the interventricular septum wall was measured using 2D speckle tracking. Left ventricular (LV) and RV myocardial performance (TEI) indices were also measured.</p> <p>Results</p> <p>The pilsicainide challenge provoked a positive ECG response in 13 patients (inducible group). In the inducible group, longitudinal strain was significantly reduced only at the RV (-27.3 ± 5.4% vs -22.1 ± 3.6%, <it>P </it>< 0.01), and both RV and LV TEI indices increased (RV: 0.19 ± 0.09 vs 0.27 ± 0.11, <it>P </it>< 0.05; LV: 0.30 ± 0.10 vs 0.45 ± 0.10, <it>P </it>< 0.01) after pilsicainide administration.</p> <p>Conclusions</p> <p>Temporal and spatial analysis using the TEI index and 2D strain imaging revealed the deterioration of global ventricular function associated with conduction disturbance and RV regional function in patients with Brugada-type ECG and coved type ST elevation due to administration of a sodium channel blocker.</p

Cystic appearance of low-grade endometrial stromal sarcoma in the right atrium: case report

A 71-year-old woman presented with a right adnexal solid mass invading the right gonadal vein and inferior vena cava up to the hepatic veins revealed by CT and confirmed by MRI. A thin-walled cyst and a solid mass were unexpectedly found in the right atrium by transesophageal echocardiography (TEE) in the operating room. Using color Doppler and air bubbles as contrast material a circumscribed cyst was confirmed and localized close to the IVC. The cyst was connected to the mass in the inferior vena cava. The tumor, including the cyst, was removed without using cardiopulmonary bypass and described as a low-grade endometrial stromal sarcoma, a rare slowly growing tumor. This is the first TEE description of endometrial stromal sarcoma manifesting as a right atrial cyst

Tissue Doppler echocardiographic quantification. Comparison to coronary angiography results in Acute Coronary Syndrome patients

BACKGROUND: Multiples indices have been described using tissue Doppler imaging (DTI) capabilities. The aim of this study was to assess the capability of one or several regional DTI parameters in separating control from ischemic myocardium. METHODS: Twenty-eight patients with acute myocardial infarction were imaged within 24-hour following an emergent coronary angioplasty. Seventeen controls without any coronary artery or myocardial disease were also explored. Global and regional left ventricular functions were assessed. High frame rate color DTI cineloop recordings were made in apical 4 and 2-chamber for subsequent analysis. Peak velocity during isovolumic contraction time (IVC), ejection time, isovolumic relaxation (IVR) and filling time were measured at the mitral annulus and the basal, mid and apical segments of each of the walls studied as well as peak systolic displacement and peak of strain. RESULTS: DTI-analysis enabled us to discriminate between the 3 populations (controls, inferior and anterior AMI). Even in non-ischemic segments, velocities and displacements were reduced in the 2 AMI populations. Peak systolic displacement was the best parameter to discriminate controls from AMI groups (wall by wall, p was systematically < 0.01). The combination IVC + and IVR< 1 discriminated ischemic from non-ischemic segments with 82% sensitivity and 85% specificity. CONCLUSION: DTI-analysis appears to be valuable in ischemic heart disease assessment. Its clinical impact remains to be established. However this simple index might really help in intensive care unit routine practice

A selected bibliography on parameter optimization methods suitable for hybrid computation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68333/2/10.1177_003754976700800610.pd

Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute–National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.