Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR). Female SHR were divided into four groups (N = 7 each): sham-operated (SHAM), sham-operated and treated with tamoxifen (10 mg/kg) by gavage for 90 days (TAMOX), ovariectomized (OVX), and ovariectomized and treated with tamoxifen (OVX+TAMOX). Mean arterial pressure (MAP), heart rate (HR), coronary perfusion pressure (CPP), and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67%, respectively) in the OVX+TAMOX group compared to the OVX group (P < 0.01). The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg) when compared to the OVX group (P < 0.01) and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05). Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg) than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01). Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

ChIP-seq analysis of histone H3K9 trimethylation in peripheral blood mononuclear cells of membranous nephropathy patients

Membranous nephropathy (MN), characterized by the presence of diffuse thickening of the glomerular basement membrane and subepithelial in situimmune complex disposition, is the most common cause of idiopathic nephrotic syndrome in adults, with an incidence of 5-10 per million per year. A number of studies have confirmed the relevance of several experimental insights to the pathogenesis of human MN, but the specific biomarkers of MN have not been fully elucidated. As a result, our knowledge of the alterations in histone methylation in MN is unclear. We used chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to analyze the variations in a methylated histone (H3K9me3) in peripheral blood mononuclear cells from 10 MN patients and 10 healthy subjects. There were 108 genes with significantly different expression in the MN patients compared with the normal controls. In MN patients, significantly increased activity was seen in 75 H3K9me3 genes, and decreased activity was seen in 33, compared with healthy subjects. Five positive genes, DiGeorge syndrome critical region gene 6 (DGCR6), sorting nexin 16 (SNX16), contactin 4 (CNTN4), baculoviral IAP repeat containing 3 (BIRC3), and baculoviral IAP repeat containing 2 (BIRC2), were selected and quantified. There were alterations of H3K9me3 in MN patients. These may be candidates to help explain pathogenesis in MN patients. Such novel findings show that H3K9me3 may be a potential biomarker or promising target for epigenetic-based MN therapies.

Expression of beclin 1 in primary salivary adenoid cystic carcinoma and its relation to Bcl-2 and p53 and prognosis

Beclin 1 plays a critical role in autophagy and functions as a haploinsufficient tumor suppressor. The expression and prognostic significance of beclin 1 in head and neck adenoid cystic carcinoma (ACC) are largely unexplored. Therefore, we investigated the expression of beclin 1, Bcl-2, and p53 in head and neck ACC tissue. Tissue samples from 35 cases (15 females, 20 males) of head and neck ACC were utilized for immunohistochemistry. Beclin 1 expression was observed in 32 cases (91.4%) and considered to be high in 15 cases (42.9%) and low in 20 cases (57.1%). Beclin 1 expression was significantly correlated with a histological growth pattern (P=0.046) and histological grade (P=0.037). Beclin 1 expression was inversely correlated with Bcl-2 expression (P=0.013) and significantly associated with overall survival (P=0.006). Bcl-2 and p53 expression were observed in 21 cases (60.0%) and 16 cases (45.7%). Bcl-2 expression was significantly correlated with perineural invasion (P=0.041) and not associated with overall survival (P=0.053). p53 expression was directly correlated with beclin 1 expression (P=0.044). Our results indicated that beclin 1 may be a novel, promising prognostic factor for clinical outcome in head and neck ACC patients and may play a part in the development of head and neck ACC by interacting with Bcl-2 and p53.

Effects of 5-aza-2′deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma

Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2′deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECKgene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.

Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP) in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF). Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23), a group that received chemotherapy + tamoxifen (n=21), and a group that received only tamoxifen (n=16). Plasma levels of NT-proBNP were assessed at 0 (T0), 6 (T6), and 12 (T12) months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150–180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Assessment of the diagnostic value of diffusion tensor imaging in patients with spinal cord compression: a meta-analysis

We investigated the diagnostic value of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of magnetic resonance diffusion tensor imaging (DTI) in patients with spinal cord compression (SCC) using a meta-analysis framework. Multiple scientific literature databases were exhaustively searched to identify articles relevant to this study. Mean values and standardized mean differences (SMDs) were calculated for the ADC and FA in normal and diseased tissues. The STATA version 12.0 software was used for statistical analysis. Of the 41 articles initially retrieved through database searches, 11 case-control studies were eligible for the meta-analysis and contained a combined total of 645 human subjects (394 patients with SCC and 251 healthy controls). All 11 studies reported data on FA, and 9 contained data related to the ADC. The combined SMDs of the ADC and FA showed that the ADC was significantly higher and the FA was lower in patients with SCC than in healthy controls. Subgroup analysis based on the b value showed higher ADCs in patients with SCC than in healthy controls at b values of both ≤500 and >500 s/mm2. In summary, the main findings of this meta-analysis revealed an increased ADC and decreased FA in patients with SCC, indicating that DTI is an important diagnostic imaging tool to assess patients suspected to have SCC.

Tangential microfiltration of orange juice in bench pilot

The aim of this study was to introduce the tangential microfiltration (TMF) technique on the production of orange juice (TMFJ), and compare it with pasteurised juice (control) as regards chemical composition and sensorial characteristics. We used a TMF pilot equipped with four monotubular ceramic membranes (0.1, 0.2, 0.8 and 1.4mm) arranged in series with a filtering area of 0.005 m² each. Commercial flash-pasteurised orange juice was used as the initial product. Experiments were divided into three parts: a) the characterisation of the TMF pilot; b) optimisation of operational conditions; c) production of the TMFJ. In the second part, membrane with 0.8-mm pores presented best flux followed by those with 1.4-, 0.1-, and 0.2-mm pores. However, to guarantee permeate sterility, we chose the membrane with 0.1-mm pores for TMFJ production. Initially, the orange juice was sieved in order to separate part of the pulp, being subsequently submitted to TMF. A mixture of retentate and pulp was made, and was subsequently pasteurised. We obtained the TMFJ by adding the permeate to the mixture. TMFJ presented soluble solids content (&deg;Brix), pulp, pH, and titrable acidity similar to the initial pasteurised juice (control). Nevertheless, 28% of vitamin C was lost during the TMFJ production. According to the juice taster panel, the control juice presented best sensorial characteristics (greater aroma intensity and fruity flavour) when compared with the TMJF.

Convective, vacuum and microwave drying kinetics of mallow leaves and comparison of color and ascorbic acid values of three drying methods

Mallow leaves (Malva sylvestris L.) with initial moisture of 5.02±0.003 on dry basis (82.5% on wet basis) were dried using three different drying methods, microwave, convective and vacuum. The leaves that weigh 75 g each were dried until their moisture fell down to 0.10±0.005 on dry basis (approximately 9% on wet basis). The following drying levels were used in each of the drying processes: 6.67, 8.67, 10, 11.33 W g-1 microwave power density; 50, 75, 100 and 125 °C for convective drying; and 3, 7 kPa at 50 and 75 °C for vacuum drying. Drying periods ranged from 6-10, 26-150 and 38-130 min. for microwave, convective and vacuum drying, respectively. Effective moisture diffisuvities ranged from 2.04403 10-10-3.63996 10-12 m2 s-1, 1.70182 10-11-1.10084 10-10 m2 s-1 and 1.85599 10-11-5.94559 10-10 m2 s-1 for microwave, convective and vacuum drying, respectively. According to ascorbic acid content and color parameters, the best microwave power density was found 10 W g-1 with a drying period of 6.5 min.

Mathematical modeling of microwave dried celery leaves and determination of the effective moisture diffusivities and activation energy

Celery (Apium graveolens L. var. secalinum Alef) leaves with 50±0.07 g weight and 91.75±0.15% humidity (~11.21 db) were dried using 8 different microwave power densities ranging between 1.8-20 W g-1, until the humidity fell down to 8.95±0.23% (~0.1 db). Microwave drying processes were completed between 5.5 and 77 min depending on the microwave power densities. In this study, measured values were compared with predicted values obtained from twenty thin layer drying theoretical, semi-empirical and empirical equations with a new thin layer drying equation. Within applied microwave power density; models whose coefficient and correlation (R²) values are highest were chosen as the best models. Weibull distribution model gave the most suitable predictions at all power density. At increasing microwave power densities, the effective moisture diffusivity values ranged from 1.595 10-10 to 6.377 10-12 m2 s-1. The activation energy was calculated using an exponential expression based on Arrhenius equation. The linear relationship between the drying rate constant and effective moisture diffusivity gave the best fit.

Official Opening

Pictured here at the Official Opening from left to right are: Mrs. J. A. Gibson; D. G. Willmot, Chairman Founders' Committee; His Excellency Governor General Vanier; Dr. J. A. Gibson; Madame Vanier; Honourable W. G. Davis, Minister of University Affairs; Mrs. Willmot.

Brief memories of Niagara : its rapids, falls, and whirlpool /

On cover and spine: Memories of Niagara.

One hundred glimpses of Niagara. --

Exhibiting the grandeur and mystery of the greatest natural wonder in the world. Illustrating the American and Horseshoe Falls from many points of view, the famous, Niagara Gorge, the Whirlpool, the Parks and Island and other scenes about Niagara, inlcuding a number of interesting winter scenes.

The wars of the gulls; : an historical romance in three chapters; chap. I, Shewing how and why and with whom the gulls went to war: chap. II, Shewing how the gulls make the deep to boil like a pot: chap. III, Shewing how a certain doughty general of the gulls goes forth to play the game of hull-gull in Upper Canada.

Transcribed on front paste-down: W.G. Phelps Oct. 29 1890.