Current classification of hypertensive disorders of pregnancy (HDP) is mostly based on temporal classification differentiating HDP according to early and late onset of the disease. However, ...epidemiological and clinical data suggest that there are two different clinical phenotypes of HDP that coexist at any gestational age: HDP associated to intrauterine growth restriction (HDP-IUGR) and HDP associated to appropriate for gestational age fetal growth (HDP-AGAf). The aim of the study was to evaluate the association of first trimester uterine arteries (UtA) by Doppler velocimetry, and maternal risk factors with HDP according to two different classifications: one based on gestational age at delivery (early- and late-HDP), and one based on longitudinal ultrasound evaluation of fetal growth (HDP-IUGR and HDP-AGAf), independently of the gestational age.
Maternal characteristics and mean pulsatility index (PI) of UtA were collected at 11-13 gestational weeks. A longitudinal ultrasound follow-up of fetal growth in each trimester and clinical outcome were obtained in 4290 singleton pregnancies.
UtA-PI was significantly higher in women who developed HDP-IUGR (n = 22) and the odds ratio (OR) to develop HDP-IUGR from 25 to 39 weeks was 8.6 (p < .0001). HDP-AGAf (n = 112) was significantly associated with a higher BMI, multiparity, and maternal age, but not with UtA-PI (OR 1.3; p = .2). In women with an abnormal UtA-PI, the odds of developing early (n = 15) and late-HDP (n = 119) were 3.0 (p = .03) and 1.7 (p = .002), respectively. The AUCs for HDP-IUGR and early-HDP were 0.84 and 0.71, respectively.
UtA Doppler velocimetry in the first trimester was strongly associated with HDP-IUGR all along gestation, as a proxy of placental insufficiency, and showed no association with HDP-AGAf. Our findings suggest an efficacy of first trimester UtA Doppler velocimetry to identify HDP-IUGR independently of the gestational age, and a limited value for HDP not associated with intrauterine growth restriction (IUGR).
Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is ...recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values.
This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings.
This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output ≤5 L/min and/or high systemic vascular resistance ≥1300 dynes/second/cm2) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output >5 L/min and/or low systemic vascular resistances <1300 dynes/second/cm2) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy.
A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 75.0%) and received a hemodynamically appropriate treatment (116 76.3%). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02).
In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.
In this article we evaluated an important complication of pregnancy, the fetal growth restriction (IUGR). IUGR is defined as an estimated fetal weight of fetal abdominal circumference below the 10th ...centile measured by ultrasound according to local standards. We present the prenatal surveillance, the screening tests for late IUGR and the new diagnostic examinations, to establish the best prevention system for IUGR and late IUGR.
Highlights • A non-invasive assessment of maternal cardiovascular indices is proposed. • These indices might identify hypertensive disorders since the first trimester. • A different approach to ...classify hypertensive disorders of pregnancy is suggested.
Maternal hemodynamics varies in different clinical phenotypes of preeclampsia: early placental damage associated with fetal growth restriction; maternal cardiovascular risk factors most frequently ...associated with appropriate feto-placental growth.
We compared maternal hemodynamic profile during pregnancy and at 6–12months postpartum in women affected by Hypertensive Disorder of Pregnancy (HDP), associated with two different feto-placental growth patterns.
89 patients from 24weeks to term were enrolled in this prospective observational study: 24 HDP with appropriate for gestational age fetus (HDP-AGAf), 27 HDP with intrauterine growth restriction (HDP-IUGR), 16 normotensive women with severe IUGR (s-IUGR), 22 controls.
Diagnosis of HDP was made according to the ISSHP criteria, with the exclusion of chronic hypertension. s-IUGR was defined as abdominal circumference <5thcentile and a Doppler velocimetry in umbilical artery >2SD.
Maternal echocardiography was performed by a cardiologist blinded to clinical diagnosis, at recruitment and at 6–12months postpartum.
During pregnancy, HDP-IUGR showed significantly lower heart rate (HR), lower cardiac output (CO) and increased total vascular resistances (TVR), compared to controls. s-IUGR presented significantly lower CO and increased TVR, compared to controls. These profiles remained relatively unchanged at 6–12months postpartum.
HDP-AGAf showed increased CO as in control pregnancies, but significantly higher TVR; this group also presented significantly increased left ventricular mass (LVM) and relative wall thickness (RWT), and a reduced E/A ratio, indicating an impaired myocardial relaxation. In post-partum we observed persistently increased MAP values, due to high TVR, in spite of a return to normal HR and CO values.
Our hypothesis, that prioritizes the feto-placental phenotype, allowed us to observe a significantly poor cardiovascular adaptation to pregnancy metabolic demands in HDP-IUGR and s-IUGR. This was profoundly different from uneventful pregnancies, characterized by increased HR and CO and low TVR.
HDP-AGAf presented similar increase in HR and CO as in controls, but at the cost of diastolic function impairment and of left ventricle remodeling. In postpartum, HR and CO returned to normal, but TVR and MAP remained higher.
Sex steroids play a key role in cell movement and tissue organization. Cell migration requires the integration of events that induce changes in cell structure such as protrusion, polarization and ...traction toward the direction of migration. These actions are driven by actin remodeling and are stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that facilitates cell migration via the control of the turnover of focal adhesion complexes. In this work, we demonstrated that 17β-estradiol (E(2)) regulates actin remodeling and cell movement in human umbilical vein endothelial cells through the recruitment of FAK. E(2) induces phosphorylation of FAK and its translocation toward membrane sites where focal adhesion complexes are assembled. This process is triggered via a Gα/Gβ protein-dependent, rapid extra-nuclear signaling of estrogen receptor-α (ERα) that interacts in a multiprotein complex with c-Src, phosphatidylinositol 3-OH kinase and FAK. Phosphorylation of FAK is fundamental for its activation, translocation to the plasmatic membrane and the subsequent formation of focal adhesion complexes. In conclusion, we found that ERα enhances endothelial cell motility through the dynamic control of actin arrangement and the formation of focal adhesion complexes. The identification of these processes broadens the understanding of the actions of estrogens on endothelial cells and could be relevant in physiological or pathological settings.
Postmenopausal hormone therapy is associated with increased incidence of breast cancer. For this reason alternative therapeutic options to treat menopausal symptoms have been developed. Red clover ...extracts (RCE) are rich in isoflavones, particularly genistein and daidzein and they have been proved to be effective in reducing vasomotor symptoms in a number of studies. Due to their partial selectivity of action on estrogen receptors (ERs) these compounds have been claimed to be safer on the breast. In this article, we explored the action of RCE on motility and invasion of ER positive breast cancer cells and we partially characterized the signaling mechanisms. The principal isoflavones contained in RCE acted as weak estrogenic compounds when administered alone. However, when provided in association with physiological amounts of estradiol, RCE acted as estrogen antagonist on remodeling of actin cytoskeleton that are requested to enact cell movement and with related modifications of the activity of actin-binding proteins, such as moesin. These results offer novel information on the molecular actions of isoflavones contained in red clover on breast cancer cells, supporting a possible action of these molecules as natural selective estrogen receptor modulators in the presence of physiological amounts of estrogens.
Molecular imaging generates large volumes of heterogeneous biomedical imagery with an impelling need of guidelines for handling image data. Although several successful solutions have been implemented ...for human epidemiologic studies, few and limited approaches have been proposed for animal population studies. Preclinical imaging research deals with a variety of machinery yielding tons of raw data but the current practices to store and distribute image data are inadequate. Therefore, standard tools for the analysis of large image datasets need to be established. In this paper, we present an extension of XNAT for Preclinical Imaging Centers (XNAT-PIC). XNAT is a worldwide used, open-source platform for securely hosting, sharing, and processing of clinical imaging studies. Despite its success, neither tools for importing large, multimodal preclinical image datasets nor pipelines for processing whole imaging studies are yet available in XNAT. In order to overcome these limitations, we have developed several tools to expand the XNAT core functionalities for supporting preclinical imaging facilities. Our aim is to streamline the management and exchange of image data within the preclinical imaging community, thereby enhancing the reproducibility of the results of image processing and promoting open science practices.
Biological and biomedical imaging datasets record the constitution, architecture and dynamics of living organisms across several orders of magnitude of space and time. Imaging technologies are now ...used throughout the life and biomedical sciences to achieve discovery and understanding of biological mechanisms in the basic sciences as well as assessment, diagnosis and therapeutic intervention in clinical trials and animal and human medicine. The universal application and use of imaging raises an important question and opportunity: what is the value and ultimate destination of biological and medical imaging data? In the last few years, several informatics and data science technologies have matured sufficiently so that routine publication of these datasets is now possible. Participants in Global BioImaging from 15 countries and all populated continents have agreed on the need for recommendations and guidelines for the establishment of image data repositories and the formats they use for delivering data to the global scientific community. This white paper presents a shared, global view of criteria for these common, globally applicable guidelines and provisional proposals for open tools and resources that are available now and can provide a foundation for future development.
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