DERDYSHIRE (Reino Unido) (Inglaterra). Mapas generales (1786). 1:130000

Escala gráfica de 10 millas estatutarias inglesas de 69 1/2 al grado [= 12,1 cm]. Coordenadas referidas al meridiano de Londres (O 1°03'30''--O 2°02'10''/N 53°31'30''--N 52°40'00'')Orografía por normalesLímites entre los distintos hundreds que forman este condado diferenciados por colorIndica los condados con los que limita, incluyendo datos sobre los mismosMapa sangrado en algunos punto

Change in maternal cardiac output from preconception to mid-pregnancy is associated with birth weight in healthy pregnancies.

OBJECTIVE: Birth weight (BW) is thought to be determined by maternal health and genetic, nutritional and placental factors, the latter being influenced by anatomical development and perfusion. Maternal cardiovascular changes contribute to uteroplacental perfusion; however, they have not yet been investigated in relation to fetal growth or BW. Our aim was to explore the relationship between maternal cardiovascular adaptation, fetal growth and BW in healthy pregnancies. METHODS: This was a longitudinal prospective study of women planning to conceive a pregnancy. Maternal cardiac output (CO), cardiac index (CI), pulse-wave velocity, aortic augmentation index, central blood pressure and peripheral vascular resistance were assessed prior to pregnancy and at 6, 23 and 33 weeks' gestation. Fetal growth was assessed using serial ultrasound measurements of biometry. RESULTS: In total, 143 women volunteered to participate and were eligible for study inclusion. A total of 101 women conceived within 18 months and there were 64 live births with normal pregnancy outcome. There were positive correlations between BW and the pregnancy-induced changes in CO (ρ = 0.4, P = 0.004), CI (ρ = 0.3, P = 0.02) and peripheral vascular resistance (ρ = 0.3, P = 0.02). There were significant associations between second-to-third-trimester fetal weight gain and the prepregnancy-to-second-trimester increase in CO (Δ, 0.8 ± 1.2 L/min; ρ = 0.3, P = 0.02) and CI (Δ, 0.4 ± 0.6 L/min/m2 ; ρ = 0.3, P = 0.04) and reduction in aortic augmentation index (Δ, -10 ± 9%; ρ = -0.3, P = 0.04). CONCLUSIONS: In healthy pregnancy, incremental changes in maternal CO in early pregnancy are associated with third-trimester fetal growth and BW. It is plausible that this association is causative as the changes predate third-trimester fetal growth and eventual BW. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

© 2016 Elsevier Inc. Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothelial cells and may therefore, reflect disease severity, vascular and endothelial dysfunction, that could influence disease pathogenesis via autocrine/paracrine signalling. The exact function of EMPs in rheumatic disease remains unknown, and this has initiated research to elucidate EMP composition and function, which may be determined by the mode of endothelial activation and the micro environment. To date, EMPs are thought to play a role in angiogenesis, thrombosis and inflammation by transferring specific proteins and microRNAs (miRs) to target cells. Here, we review the mechanisms underlying the generation and composition of EMPs and the clinical and experimental studies describing the involvement of EMPs in rheumatic diseases, since we have previously shown endothelial dysfunction and an elevated risk of cardiovascular disease are characteristics in systemic lupus erythematosus. We will also discuss the potential of EMPs as future biomarkers of cardiovascular risk in these diseases

Glycomimetics; A Novel Class of Drugs to Protect Against Free Fatty Acid-Induced Endothelial Dysfunction

Background Endothelial dysfunction is a key player in cardiovascular disease (CVD) complications and novel drugs are required to treat this pathological process. Glycosaminoglycans (GAGs) are key molecules that regulate signalling in many biological processes and drugs that mimic their structure could be a novel source of therapeutics to target specific CVD pathways. Purpose We have synthesised a set of four glycomimetic compounds and our objective was to determine whether they could activate protective pathways in endothelial cells subjected to fatty acid-induced endothelial dysfunction. Methods Glycomimetics, C1-C4, were synthesised by the stepwise transformation of 2,5-dihydroxybenzoic acid to a range of 2,5-substituted benzoic acid derivatives, incorporating the key sulphate groups to mimic heparan sulphate. Human Umbilical Vein Endothelial Cells (HUVECs) were treated with glycomimetics (1µM) in the presence or absence of the free fatty acid, palmitate. DAF-2 and H2DCF-DA assays were used to determine NO and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity ssays were also carried out. RT-PCR and western blotting were utilised to measure Akt, eNOS, Nrf-2, NQO-1 and HO-1 expression. Endothelial function was determined ex vivo using acetylcholine-induced endothelium-dependent relaxation in mouse thoracic aortic rings by wire myography. Results All four glycomimetics protected against palmitate-induced oxidative stress and enhanced NO production in vitro via upregulation of Akt/eNOS signalling, activation of the Nrf2/ARE pathway and down-regulation of ROS-induced lipid peroxidation. Under palmitate-induced oxidative stress, ex vivo endothelium-dependent relaxation was significantly enhanced by all four glycomimetics. Furthermore, the glycomimetics did not induce HUVEC activation, as determined by lack of ICAM-1 protein. Conclusion We have developed a new set of small molecule glycomimetics that do not activate ECs and protect against free fatty acid-induced endothelial dysfunction both in vitro and ex vivo. Future work will focus on developing the glycomimetics into drug-like therapies that target endothelial damage

Endothelial Progenitor Cells: New Targets for Therapeutics for Inflammatory Conditions With High Cardiovascular Risk.

Over the past decade, we have witnessed an exponential growth of interest into the role of endothelial progenitor cells (EPCs) in cardiovascular disease. While the major thinking revolves around EPC angiogenic repair properties, we have used a hypothesis-driven approach to discover disease-related defects in their characteristics and based on these findings, have identified opportunities for functional enhancement, which offer an exciting avenue for translation into clinical intervention. In this review, we focus on two groups; circulating myeloid angiogenic cells (MACs) and late outgrowth endothelial colony forming cells (ECFCs), and will discuss the unique properties and defects of each population, as new insights have been gained into the potential function of each sub-type using current techniques and multiomic technology. We will discuss their role in inflammatory disorders and alterations in mitochondrial function. In addition, we share key insights into the glycocalyx, and propose this network of membrane-bound proteoglycans and glycoproteins, covering the endothelium warrants further investigation in order to clarify its significance in ECFC regulation of vascularization and angiogenesis and ultimately for potential translational therapeutic aspects

The Role of Nrf2 in Cardiovascular Function and Disease

Free radicals, reactive oxygen/nitrogen species (ROS/RNS), hydrogen sulphide and hydrogen peroxide play an important role in both intracellular and intercellular signalling, however their production and quenching needs to be closely regulated to prevent cellular damage. An imbalance, due to exogenous sources of free radicals and chronic upregulation of endogenous production, contributes to many pathological conditions including cardiovascular disease and also the more general processes involved in aging. Nuclear factor erythroid 2 -like 2 (NFE2L2; commonly known as Nrf2) is a transcription factor that plays a major role in the dynamic regulation of a network of anti-oxidant and cytoprotective genes, through binding to, and activating expression of promoters containing the antioxidant response element (ARE). Nrf2 activity is regulated by many mechanisms, suggesting that tight control is necessary for normal cell function and both hypo- and hyperactivation of Nrf2 are indicated in playing a role in different aspects of cardiovascular disease. Targeted activation of Nrf2, or downstream genes may prove to be a useful avenue in developing therapeutics to reduce the impact of cardiovascular disease. We will review the current status of Nrf2 and related signalling in cardiovascular disease and its relevance to current and potential treatment strategies

Small Molecule Glycomimetics Inhibit Vascular Calcification via c-Met/Notch3/HES1 Signalling

© Copyright by the Author(s). Published by Cell Physiol Biochem Press. BACKGROUND/AIMS: Vascular calcification represents a huge clinical problem contributing to adverse cardiovascular events, with no effective treatment currently available. Upregulation of hepatocyte growth factor has been linked with vascular calcification, and thus, represent a potential target in the development of a novel therapeutic strategy. Glycomimetics have been shown to interrupt HGF-receptor signalling, therefore this study investigated the effect of novel glycomimetics on osteogenic signalling and vascular calcification in vitro. METHODS: Primary human vascular smooth muscle cells (HVSMCs) were induced by β-glycerophosphate (β-GP) and treated with 4 glycomimetic compounds (C1-C4). The effect of β-GP and C1-C4 on alkaline phosphatase (ALP), osteogenic markers and c-Met/Notch3/HES1 signalling was determined using colorimetric assays, qRT-PCR and western blotting respectively. RESULTS: C1-C4 significantly attenuated β-GP-induced calcification, as shown by Alizarin Red S staining and calcium content by day 14. In addition, C1-C4 reduced ALP activity and prevented upregulation of the osteogenic markers, BMP-2, Runx2, Msx2 and OPN. Furthermore, β-GP increased c-Met phosphorylation at day 21, an effect ameliorated by C2 and C4 and the c-Met inhibitor, crizotinib. We next interrogated the effects of the Notch inhibitor DAPT and confirmed an inhibition of β-GP up-regulated Notch3 protein by C2, DAPT and crizotinib compared to controls. Hes-1 protein upregulation by β-GP, was also significantly downregulated by C2 and DAPT. GOLD docking analysis identified a potential binding interaction of C1-C4 to HGF which will be investigated further. CONCLUSION: These findings demonstrate that glycomimetics have potent anti-calcification properties acting via HGF/c-Met and Notch signalling

Change in maternal cardiac output from pre-conception to mid-pregnancy is associated with birth weight in healthy pregnancies

OBJECTIVE: Birth weight (BW) is thought to be determined by maternal health, and genetic, nutritional and placental factors; the latter being influenced by anatomical development and perfusion. Maternal cardiovascular changes contribute to uteroplacental perfusion, however they have not been investigated in relation to fetal growth/BW. Our aim was to explore the relationship between maternal cardiovascular adaptation, fetal growth and BW in healthy pregnancies. METHODS: This was a longitudinal prospective study of women planning to conceive a pregnancy. Maternal cardiac output (CO), cardiac index (CI), pulse-wave velocity, aortic augmentation index (AIx), central blood pressure and peripheral vascular resistance (PVR) were assessed prior to pregnancy and at 6, 23 and 33 weeks' gestation. Fetal growth was assessed by serial ultrasound measurements of biometry. RESULTS: In total, 143 women volunteered to participate and were eligible for study inclusion. One hundred and one women conceived within 18 months and there were 64 live births with normal pregnancy outcome. There were positive correlations between BW and the prepregnancy-to-second trimester changes in CO (ρ = 0.4, P = 0.004), CI (ρ = 0.3, P = 0.02) and PVR (ρ = 0.3, P = 0.02). There were significant associations between third-trimester estimated fetal weight gain and the prepregnancy-to-second trimester increase in CO (Δ, 0.8 ± 1.2 L/min; ρ = 0.3, P = 0.02) and CI (Δ, 0.4 ± 0.6 L/min/m(2) ; ρ = 0.3, P = 0.04) and reduction in AIx (Δ, -10 ± 9%; ρ = -0.3, P = 0.04). CONCLUSIONS: In healthy pregnancy, third-trimester fetal growth and BW are associated with incremental changes in maternal CO in early pregnancy. It is plausible that this association is causative, as changes predate third-trimester fetal growth and eventual BW

INGLATERRA (Reino Unido). Mapas generales (177). 1:460000

Comprende además la parte meridional de Escocia y la oriental de Irlanda del Norte e IrlandaFecha deducida por comparación con otros documentos existentes en el atlasEscala gráfica de 24 millas estatutarias de 69 al grado [= 8,4 cm]. Coordenadas referidas al meridiano de Londres (E 8°16'--O 3°20'/N 55°50'--N49°49'). Red geográfica de 20' en 20'. Orientado con lis en rosa de ocho vientosOrografía por normalesEn los márgenes superior e inferior de cada hoja queda reflejado el territorio comprendido en cada una de ellasTítulo, mención de responsabilidad y editor contenidos en cartela flanqueada por dos personajes y decorada por un cofre con tesoros y otros objetos. Esta cartela ocupa por sí sola una de las doce hojas que conforman el mapaDivisiones administrativas diferenciadas por colore

REINO UNIDO. Mapas generales (1795). 1:590000

Se ha tomado esta fecha de publicación por ser la única a la que los editores pudieron trabajar juntos, teniendo en cuenta las sedes de sus talleresEscalas gráficas de 25 millas geométricas de 60 al grado [= 7,9 cm], 8 leguas inglesas y francesas de 3 millas geométricas, 30 millas estatutarias inglesas, 20 millas irlandesas, 20 millas de 48 al grado y 10 leguas comunes francesas de 25 al grado. Coordenadas referidas al meridiano de Londres (O 10°00'00''-E 2°00'00''/N 55°40'05''-N 49°38'00''). Red geográfica de 20' en 20'. Orientado con lis en rosa de treinta y dos vientosRelieve de perfilSeñala con colores las divisiones administrativasTabla de signos convencionales para indicar distintos tipos de población, fortificaciones, lugares donde tuvieron lugar batallas, y carreteras en las que se señalan las distancias, en millas entre distintos puntosTítulo, autor y editores enmarcado en cartela barroca con escena bélica y escudo de la casa real inglesa y las escalas con otra decorada con motivos vegetales y geográficosForma parte de la Colección MendozaInserta: "A Map of Scotland, containing all ye Cities, Market and Borough Towns, with ye principal Roads and Distances in Computed Miles". Escala [ca. 1:2670000], 30 millas escocesas [= 2,5 cm] ; Mapa de las islas Setland y Orkney ; "2d. Chart of the Coast of France, from Ostende, Ambleteuse