Ultrasound imaging versus morphopathology in cardiovascular diseases. Coronary collateral circulation and atherosclerotic plaque

Left ventricular hypertrophy is an important risk factor in cardiovascular disease and echocardiography has been widely used for diagnosis. Although an adequate methodologic standardization exists currently, differences in measurement and interpreting data is present in most of the older clinical studies. Variability in border limits criteria, left ventricular mass formulas, body size indexing and other adjustments affects the comparability among these studies and may influence both the clinical and epidemiologic use of echocardiography in the investigation of the left ventricular structure. We are going to review the most common measures that have been employed in left ventricular hypertrophy evaluation in the light of some recent population based echocardiographic studies, intending to show that echocardiography will remain a relatively inexpensive and accurate tool diagnostic tool.     

Vitamin D Supplementation and Breast Cancer Prevention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I² test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L.     

Purification,characterization, sequence determination,and mass spectrometric analysis of a trypsin inhibitor from seeds of the brazilian treeDipteryx alata (leguminosae)

Dipteryx alata trypsin inhibitor (DATI) has been purified and completely sequenced. It showed homology to members of the Bowman-Birk family of inhibitors. The last step of DATI purification by RP-HPLC (narrow-bore C18 column) suggested the existence of some isoforms of the inhibitor due to the presence of a cluster of very close peaks in the chromatogram. By using electrospray ionization mass spectrometry (ESIMS) and laser desorption mass spectrometry (LDIMS), the identification of DATI isoforms was made possible. From the ESIMS data, the following molecular masses were found: 6803.22±0.92 for isoforma; 6890.94±0.73 forb; 6977.58±0.39 for c; 7065.07±0.67 ford; 7151.42±0.86 for e; and 7291.70±0.43 forf. Similar masses were found when using LDIMS. Isoformb was the most abundant and its molecular mass matched the molecular mass of 6893 calculated from the sequence of DATI. The mass differences betweena andb, b andc, c andd, andd ande were equal to 87, which corresponds to Ser. Isoforma might not have the N-terminal Ser present in isoformb, while the other additional Ser residues might comprise a row localized in the C- or N-terminal. The appearance of all these isoforms could result from posttranslational N- and C-terminal processing.     

The Endothelin/Sarafotoxin‐Induced Increase of the Proliferation of Undifferentiated and DMSO‐Differentiated GEM‐81 Goldfish Erythrophoroma Cells is Mediated by ETB Receptors

Endothelins (ETs) and sarafotoxins (SRTXs) have been reported to exert ET_B‐mediated effects on vertebrate pigment cells. GEM‐81 cell line, a red pigment cell‐derived cutaneous tumor of the teleost Carassius auratus, expresses ET_B receptors and can be differentiated with 1.5% DMSO treatment, thus constituting an useful model to investigate ET and SRTX effects on cultured fish pigment cells. Our aim was to characterize the pharmacology and biological effects mediated by ET receptors in DMSO‐differentiated and undifferentiated cells. ET subtype receptors and their respective Ki values in both cell types were determined by competitive binding assays using ¹²⁵I ET‐1 and BQ‐485 (an ET_A antagonist) or BQ‐788 (an ET_B antagonist). BQ‐788, but not BQ‐485, significantly reduced ¹²⁵I‐ET‐1 binding in both cell types, with similar low (Ki > nM) affinities. To determine the proliferation effects of ETs/SRTXs, cells were treated for 72 h with the hormones, and counted in a hemocytometer. The proliferation assays were repeated for SRTX S6c in the presence or absence of BQ‐788. The results demonstrated that, with the exception of ET‐1 (biphasic effect) and ET‐3 (no significant effect) in undifferentiated GEM‐81 cells, all the tested hormones induced increases in the proliferation of both types of cells. The hormones were equipotent in DMSO‐differentiated cells, which exhibited increased sensitivity to ETs, but not to SRTXs, as compared with undifferentiated cells. The BQ‐788 antagonistic effect was also exerted on the proliferation responses to SRTX S6c. These results corroborate the long and important evolutionary history of the ET/SRTX receptor system in vertebrate pigment cells.     

Bindarit Inhibits Human Coronary Artery Smooth Muscle Cell Proliferation,Migration and Phenotypic Switching

Bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs) synthesis, reduces neointimal formation in animal models of vascular injury and recently has been shown to inhibit in-stent late loss in a placebo-controlled phase II clinical trial. However, the mechanisms underlying the efficacy of bindarit in controlling neointimal formation/restenosis have not been fully elucidated. Therefore, we investigated the effect of bindarit on human coronary smooth muscle cells activation, drawing attention to the phenotypic modulation process, focusing on contractile proteins expression as well as proliferation and migration. The expression of contractile proteins was evaluated by western blot analysis on cultured human coronary smooth muscle cells stimulated with TNF-α (30 ng/mL) or fetal bovine serum (5%). Bindarit (100–300 µM) reduced the embryonic form of smooth muscle myosin heavy chain while increased smooth muscle α-actin and calponin in both TNF-α- and fetal bovine serum-stimulated cells. These effects were associated with the inhibition of human coronary smooth muscle cell proliferation/migration and both MCP-1 and MCP-3 production. The effect of bindarit on smooth muscle cells phenotypic switching was confirmed in vivo in the rat balloon angioplasty model. Bindarit (200 mg/Kg/day) significantly reduced the expression of the embryonic form of smooth muscle myosin heavy chain, and increased smooth muscle α-actin and calponin in the rat carodid arteries subjected to endothelial denudation. Our results demonstrate that bindarit induces the differentiated state of human coronary smooth muscle cells, suggesting a novel underlying mechanisms by which this drug inhibits neointimal formation.     

Effects of Ovarian Hormones and Oral Contraceptive Pills on Cardiac Vagal Withdrawal at the Onset of Dynamic Exercise

The purpose of this study was to investigate the effects of the ovarian hormones and the use of oral contraceptive pills (OCP) on cardiac vagal withdrawal at the onset of dynamic exercise. Thirty physically active women aged 19–32 years were divided into two groups: OCP users (n = 17) and non-OCP users (n = 13). Participants were studied randomly at three different phases of the menstrual cycle: early follicular (day 3.6 ± 1.2; range 1–5), ovulatory (day 14.3 ± 0.8; range 13–16) and midluteal (day 21.3 ± 0.8; range 20–24), according to endogenous (in non-OCP users) or exogenous (in OCP users) estradiol and progesterone variations. The cardiac vagal withdrawal was represented by the cardiac vagal index (CVI), which was obtained by the 4-s exercise test. Additionally, resting heart rate, systolic (SBP) and diastolic blood pressure (DBP) were obtained. The CVI was not significantly different between the three phases of the menstrual cycle in either the non-OCP users (early follicular: 1.58 ± 0.1; ovulatory: 1.56 ± 0.1; midluteal: 1.58 ± 0.1, P > 0.05) or OCP users (early follicular: 1.47 ± 0.1; ovulatory: 1.49 ± 0.1; midluteal: 1.47 ± 0.1, P > 0.05) (mean ± SEM). Resting cardiovascular responses were not affected by hormonal phase or OCP use, except that the SBP was higher in the OCP users than non-OCP users in all phases of the cycle (P < 0.05). In summary, our results demonstrate that cardiac vagal withdrawal at the onset of dynamic exercise was not impacted by the menstrual cycle or OCP use in physically active women.     

Vegetation ordination at the southern Chihuahuan Desert (San Luis Potosi,Mexico)

Cover data for 93 perennial plant species from fifty 1 ha sites, were used to ordinate desert vegetation in relation to 50 environmental variables at El Huizache Corridor. Cumulative variance recovered in the Bray and Curtis variance-regression ordination was substantial (80%). Community structure of desert plant communities at El Huizache Corridor may be influenced primarily by a combination of landscape and edaphic variables, which in turn may determine the distribution and abundance of moisture and nutrients, and perhaps promote habitat specialization and or competitive exclusion. Secondly, to a lesser extent, climate variables could be influencing community organization at small scale gradients, the longer the gradient the more relevant climatic factors become. First axis represented a landscape gradient; it was positively correlated to exposure, geology, slope angle, rocks, stoniness, iron, January mean temperature, and organic matter content; it was negatively correlated with latitude, longitude, soil depth, and potassium content. The second axis represented mainly a climatic gradient; it was positively correlated with mean precipitation of January, February, July, August, September, November, December, annual mean precipitation, Lang's Index, organic matter content, and stoniness. The third axis represented an edaphic gradient; it was positively correlated with electrical conductivity, Mn, Zn and elevation, and negatively correlated with pH, nitrates, Ca, and disturbance. These findings should guide conservation efforts to maintain species diversity and endemism at this area. This revised version was published online in June 2006 with corrections to the Cover Date.     

Demography of the seedling bank of Manilkara zapota (L.) Royen,in a subtropical rain forest of Mexico

Selection of individuals in tropical trees, occurs mainly in the seedling phase, which in part explains the low densities of most species. The main objective of this work was to gain an insight into those factors that influence growth and survival of Manilkara zapota seedlings, one of the most abundant species in the lowland forests of Mexico and Central America. Eight 10-m² rectangular plots (5m×2m) were established, in which all < 35-cm-high M. zapota seedlings were marked, measured and enumerated at bimonthly intervals. In each census seedling height, number of leaves, length of largest leaf, type of damage and seedling death were registered. Seedling survival during 2 yr was high, reaching 82% including newly emerged seedlings. A maximum likelihood regression analysis showed that both number of leaves and length of largest leaf had a direct influence on seedling survival; however, neither type of damage nor seedling density and height had significant effect. Seedling height growth averaged 2.8 cm in the 2 yr of study. The combined effect of high seedling survival, reduced growth, and impact of physical damage mainly due to falling branches and leaves reveals the occurrence of a persistent seedling bank. Such a bank would contribute to recruitment of individuals in the juvenile and eventually in the adult stages. This seedling bank could explain the high density of individuals of M. zapota in the tropical forests of Mexico.     

Prediction of the secondary structure of the carboxy-terminal third of rat thyroglobulin

A secondary structure prediction has been made using the available primary sequence data of the proposed carboxy-terminal of rat thyroglobulin. The model predicts 22% alfa-helix, 28% beta-structure and 17% beta turns. Out of the 8 possible carbohydrate acceptor-sites (Asn-x-Ser/Thr), 3 (residues 136, 368, 782) are associated with peptide sequences which favour the formation of beta-turn or loop-structures and are located in high hydrophilic regions. The entire sequence is predicted to be made up of two domains: one of them is highly structured, contains the hormonogenic sites, a cluster of tyrosines and at least one carbohydrate acceptor site.