Adherens junctions remain dynamic

One of the four principal categories of cell-cell junctions that hold together and shape distinct tissues and organs in vertebrates, adherens junctions (AJs) form cell-cell contacts that connect transmembrane proteins with cytoskeletal actin filaments to provide architectural strength, aid in morphogenesis, and help to maintain proper tissue homeostasis. The classical organization of AJs, consisting of transmembrane cadherins and cytoplasmically attached β-catenins and α-catenins assembled together into a multiprotein complex, was once thought obligatory to craft a robust and stable connection to actin-based cytoskeletal elements, but this architecture has since been challenged and questioned to exist. In a stimulating paper published in a recent issue of BMC Biology, Millán et al. provide convincing evidence that in confluent vascular endothelial cells a novel dynamic vascular endothelial (VE)-cadherin-based AJ type exists that interacts with and physically connects prominent bundles of tension-mediating actin filaments, stress fibers, between neighboring cells. Stress fibers were known previously to link to integrin-based focal adhesion complexes but not to cell-cell adhesion mediating AJs. These new findings, together with previous results support the concept that different AJ subtypes, sharing the same transmembrane cadherin types, can assemble in various configurations to either increase barrier function and promote physical cell-cell adhesion, or to lessen cell-cell adhesion and promote cell separation and migration

Quality of life and metabolic status in mildly depressed patients with type 2 diabetes treated with paroxetine: A double-blind randomised placebo controlled 6-month trial

<p>Abstract</p> <p>Background</p> <p>Depression is prevalent in people with type 2 diabetes and affects both glycaemic control and overall quality of life. The aim of this investigator-initiated trial was to evaluate the effect of the antidepressant paroxetine on quality of life, metabolic control, and mental well-being in mildly depressed diabetics aged 50–70 years.</p> <p>Methods</p> <p>We randomised 49 mildly depressed primary care outpatients with non-optimally controlled diabetes to a 6-month double-blind treatment with either paroxetine 20 mg per day or matching placebo. Primary efficacy measurements were quality of life and glycaemic control. The primary global outcome of the study was defined as a 10 points improvement in the SF-36 quality of life score. The primary metabolic outcome of the study was defined as a 0.8%-units decrease in glycosylated haemoglobin A_1c(GHbA_1c). Psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale.</p> <p>Results</p> <p>Six patients withdrew their consent before starting medication and six dropped out later in the study. We performed analysis of covariance with the baseline value as a covariate. Quality of life and glycaemic control as well as symptoms of depression and anxiety improved in both groups over the 6-month study period. After three months of treatment we found a statistically significant difference between the two treatment groups in GHbA_1c(mean difference = 0.59%-units, p = 0.018) and in SF-36 score (mean difference = 11.0 points, p = 0.039). However, at the end of the study, no statistically significant differences between the treatment groups were observed. No severe adverse events occurred.</p> <p>Conclusion</p> <p>This pragmatic study of primary care patients did not confirm earlier preliminary findings indicating a beneficial effect of paroxetine on glycaemic control. The study indicates that in pragmatic circumstances any possible benefit from administration of paroxetine in diabetic patients with sub-threshold depression is likely to be modest and of short duration. Routine antidepressant prescription for patients with diabetes and sub-threshold depressive symptoms is not indicated.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN55819922</p

Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: A single-blind randomised placebo controlled trial

BACKGROUND: Depression is prevalent in people with type 2 diabetes and affects both glycemic control and overall quality of life. The aim of this trial was to evaluate the effect of the antidepressant paroxetine on metabolic control, quality of life and mental well-being in mildly depressed women with type 2 diabetes. METHODS: We randomised 15 mildly depressed women with non-optimally controlled type 2 diabetes to a 10-week single-blind treatment with either paroxetine 20 mg per day or placebo. Primary efficacy measurements were glycemic control and quality of life. Glycosylated hemoglobin A(1c )(GHbA(1c)) was used as a measure of glycemic control. Quality of life was evaluated using RAND-36. Mental state was assessed using two clinician-rated scoring instruments, Hamilton's Anxiety Scale (HAM-A) and Montgomery-Åsberg's Depression Rating Scale (MADRS), and a patient-rated scoring instrument, Beck's Depression Inventory (BDI). RESULTS: At the end of the study no significant difference between groups in improvement of quality of life was found. A trend towards a superior improvement in glycemic control was found in the paroxetine group (p = 0.08). A superior increase in sex-hormone-binding-globuline (SHBG) levels was evidenced in the paroxetine group (p = 0.01) as a sign of improved insulin sensitivity. There was also a trend for superior efficacy of paroxetine in investigator-rated anxiety and depression. This notion was supported by a trend for superior decrease of serum cortisol levels in the paroxetine group (p = 0.06). CONCLUSION: Paroxetine has a beneficial effect on measures of insulin sensitivity and may improve glycemic control. Larger studies of longer duration are needed to verify the benefits of paroxetine in type 2 diabetes. While waiting for more conclusive evidence it seems sensible to augment standard care of type 2 diabetes with paroxetine even in patients who do not fulfil routine psychiatric criteria for initiation of antidepressant drug treatment

French Pregnancy Physical Activity Questionnaire Compared with an Accelerometer Cut Point to Classify Physical Activity among Pregnant Obese Women

Given the high risk for inactivity during pregnancy in obese women, validated questionnaires for physical activity (PA) assessment in this specific population is required before evaluating the effect of PA on perinatal outcomes. No questionnaire was validated in pregnant obese women. The Pregnancy Physical Activity Questionnaire (PPAQ) has been designed based on activities reported during pregnancy and validated in pregnant women. We translated the PPAQ to French and assessed reliability and accuracy of this French version among pregnant obese women. In this cross-sectional study, pregnant obese women were evenly recruited at the end of each trimester of pregnancy. They completed the PPAQ twice, with an interval of 7 days in-between, to recall PA of the last three months. Between PPAQ assessments, participants wore an accelerometer (Actigraph GT1M) during 7 consecutive days. Fourty-nine (49) pregnant obese women (29.8±4.2 yrs, 34.7±5.1 kg.m−2) participated to the study. The intraclass correlation coefficients (ICCs) between the two PPAQ assessments were 0.90 for total activity, 0.86 for light and for moderate intensity, and 0.81 for vigorous intensity activities. It ranged from 0.59 for “Transportation” to 0.89 for “Household and Caregiving” activities. Spearman correlation coefficients (SCCs) between the PPAQ and the Matthews’ cut point used to classify an activity of moderate and above intensity were 0.50 for total activity, 0.25 for vigorous intensity and 0.40 for moderate intensity. The correlations between the PPAQ and the accelerometer counts were 0.58 for total activity, 0.39 for vigorous intensity and 0.49 for moderate intensity. The highest SCCs were for “Occupation” and “Household and Caregiving” activities. Comparisons with other standard cutpoints were presented in files S1, S2, S3, S4, S5, S6, S7. The PPAQ is reliable and moderately accurate for the measure of PA of various intensities and types among pregnant obese women

Placenta Growth Factor-1 Exerts Time-Dependent Stabilization of Adherens Junctions Following VEGF-Induced Vascular Permeability

Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows

A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn

<p>Abstract</p> <p>Background</p> <p>Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn.</p> <p>Methods and design</p> <p>320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: <it>1. Control group: </it>usual prenatal care (PC) and placebo (maltodextrine). <it>2. Exercise group: </it>PC, placebo and aerobic physical exercise. <it>3. Micronutrients group: </it>PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg)<it>. 4. Combined interventions Group: </it>PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions.</p> <p>Discussion</p> <p>Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00872365">NCT00872365</a>.</p

Water exercises and quality of life during pregnancy

<p>Abstract</p> <p>Background</p> <p>In Brazil, concern with the quality of life of pregnant women is one of the points emphasized in the Program for the Humanization of Prenatal Care and Childbirth launched in 2000. However, there are few references in the literature on the role of either land or water-based physical exercise on women's quality of life during pregnancy. The purpose of this study was to evaluate the effects of a physical exercise program of water aerobics on the quality of life (QOL) of sedentary pregnant women.</p> <p>Methods</p> <p>A comparative observational study involving sedentary low-risk pregnant women bearing a single fetus with gestational age less than 20 weeks at the time of admission to the study, who were receiving antenatal care at a public health service. One group of 35 women was given routine antenatal care, while another group of 31 women, in addition to receiving the same routine care as the first group, also participated in three classes of water aerobics per week. QOL was evaluated by applying the WHOQOL-BREF questionnaire in both groups at the 20^th, 28^thand 36^thweeks of pregnancy. In the same occasions, women also answered another questionnaire about their experience with pregnancy and antenatal care.</p> <p>Results</p> <p>The great majority of the participants considered that the practice of water aerobics had benefitted them in some way. QOL scores were found to be high in both groups during follow-up. There was no association between the practice of water aerobics and QOL.</p> <p>Conclusions</p> <p>Further studies involving larger sample sizes should be conducted in different sociocultural contexts and/or using other instruments to adequately evaluate the QOL of women during pregnancy.</p

Differential Effects of Bartonella henselae on Human and Feline Macro- and Micro-Vascular Endothelial Cells

Bartonella henselae, a zoonotic agent, induces tumors of endothelial cells (ECs), namely bacillary angiomatosis and peliosis in immunosuppressed humans but not in cats. In vitro studies on ECs represent to date the only way to explore the interactions between Bartonella henselae and vascular endothelium. However, no comparative study of the interactions between Bartonella henselae and human (incidental host) ECs vs feline (reservoir host) ECs has been carried out because of the absence of any available feline endothelial cell lines

A Role for VEGFR2 Activation in Endothelial Responses Caused by Barrier Disruptive OxPAPC Concentrations

Introduction: Oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (OxPAPC) differentially modulate endothelial cell (EC) barrier function in a dose-dependent fashion. Vascular endothelial growth factor receptor-2 (VEGFR2) is involved in the OxPAPC-induced EC inflammatory activation. This study examined a role of VEGFR2 in barrier dysfunction caused by high concentrations of OxPAPC and evaluated downstream signaling mechanisms resulting from the effect of OxPAPC in EC from pulmonary and systemic circulation