scholarly journals Endothelial Dysfunction in Pregnancy Complications

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1756
Author(s):  
Jakub Kornacki ◽  
Paweł Gutaj ◽  
Anastasia Kalantarova ◽  
Rafał Sibiak ◽  
Maurycy Jankowski ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Experimental Studies ◽  
Diagnostic Value ◽  
Endothelial Damage ◽  
Fine Tuning ◽  
Clinical Markers ◽  
Standard Clinical Practice ◽  
Clinically Significant ◽  
The Moment ◽  
And Function

The endothelium, which constitutes the inner layer of blood vessels and lymphatic structures, plays an important role in various physiological functions. Alterations in structure, integrity and function of the endothelial layer during pregnancy have been associated with numerous gestational complications, including clinically significant disorders, such as preeclampsia, fetal growth restriction, and diabetes. While numerous experimental studies have focused on establishing the role of endothelial dysfunction in pathophysiology of these gestational complications, their mechanisms remain unknown. Numerous biomarkers of endothelial dysfunction have been proposed, together with the mechanisms by which they relate to individual gestational complications. However, more studies are required to determine clinically relevant markers specific to a gestational complication of interest, as currently most of them present a significant overlap. Although the independent diagnostic value of such markers remains to be insufficient for implementation in standard clinical practice at the moment, inclusion of certain markers in predictive multifactorial models can improve their prognostic value. The future of the research in this field lies in the fine tuning of the clinical markers to be used, as well as identifying possible therapeutic techniques to prevent or reverse endothelial damage.

scholarly journals Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 486
Author(s):  
Valerio Ciccone ◽  
Shirley Genah ◽  
Lucia Morbidelli
Keyword(s):  
Endothelial Dysfunction ◽  
Vessel Wall ◽  
Redox Reactions ◽  
Single Layer ◽  
Fine Tuning ◽  
Therapeutic Approaches ◽  
Impaired Wound Healing ◽  
Blood Fluidity ◽  
And Function ◽  
And Control

The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vascularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools.

scholarly journals The Role of the Adipokines in the Most Common Gestational Complications

2020 ◽  
Vol 21 (24) ◽  
pp. 9408
Author(s):  
Paweł Gutaj ◽  
Rafał Sibiak ◽  
Maurycy Jankowski ◽  
Karina Awdi ◽  
Rut Bryl ◽  
...  
Keyword(s):  
Experimental Studies ◽  
Diagnostic Value ◽  
Potential Contribution ◽  
Protein Levels ◽  
Standard Clinical Practice ◽  
Early Markers ◽  
Exact Etiology ◽  
Molecular Pathophysiology ◽  
Growth Abnormalities

Adipocytokines are hormonally active molecules that are believed to play a key role in the regulation of crucial biological processes in the human body. Numerous experimental studies established significant alterations in the adipokine secretion patterns throughout pregnancy. The exact etiology of various gestational complications, such as gestational diabetes, preeclampsia, and fetal growth abnormalities, needs to be fully elucidated. The discovery of adipokines raised questions about their potential contribution to the molecular pathophysiology of those diseases. Multiple studies analyzed their local mRNA expression and circulating protein levels. However, most studies report conflicting results. Several adipokines such as leptin, resistin, irisin, apelin, chemerin, and omentin were proposed as potential novel early markers of heterogeneous gestational complications. The inclusion of the adipokines in the standard predictive multifactorial models could improve their prognostic values. Nonetheless, their independent diagnostic value is mostly insufficient to be implemented into standard clinical practice. Routine assessments of adipokine levels during pregnancy are not recommended in the management of both normal and complicated pregnancies. Based on the animal models (e.g., apelin and its receptors in the rodent preeclampsia models), future implementation of adipokines and their receptors as new therapeutic targets appears promising but requires further validation in humans.

A G protein–biased S1P1 agonist, SAR247799, protects endothelial cells without affecting lymphocyte numbers

2020 ◽  
Vol 13 (634) ◽  
pp. eaax8050 ◽  
Author(s):  
Bruno Poirier ◽  
Veronique Briand ◽  
Dieter Kadereit ◽  
Matthias Schäfer ◽  
Paulus Wohlfart ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
G Protein ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Vascular Diseases ◽  
Endothelial Damage ◽  
Renal Protection ◽  
And Function

Endothelial dysfunction is a hallmark of tissue injury and is believed to initiate the development of vascular diseases. Sphingosine-1 phosphate receptor-1 (S1P1) plays fundamental physiological roles in endothelial function and lymphocyte homing. Currently available clinical molecules that target this receptor are desensitizing and are essentially S1P1 functional antagonists that cause lymphopenia. They are clinically beneficial in autoimmune diseases such as multiple sclerosis. In patients, several side effects of S1P1 desensitization have been attributed to endothelial damage, suggesting that drugs with the opposite effect, namely, the ability to activate S1P1, could help to restore endothelial homeostasis. We found and characterized a biased agonist of S1P1, SAR247799, which preferentially activated downstream G protein signaling to a greater extent than β-arrestin and internalization signaling pathways. SAR247799 activated S1P1 on endothelium without causing receptor desensitization and potently activated protection pathways in human endothelial cells. In a pig model of coronary endothelial damage, SAR247799 improved the microvascular hyperemic response without reducing lymphocyte numbers. Similarly, in a rat model of renal ischemia/reperfusion injury, SAR247799 preserved renal structure and function at doses that did not induce S1P1-desensitizing effects, such as lymphopenia and lung vascular leakage. In contrast, a clinically used S1P1 functional antagonist, siponimod, conferred minimal renal protection and desensitized S1P1. These findings demonstrate that sustained S1P1 activation can occur pharmacologically without compromising the immune response, providing a new approach to treat diseases associated with endothelial dysfunction and vascular hyperpermeability.

Computational and experimental studies of the strength of full-scale samples of pipes with defects "metal loss" and "dent with groove"

2020 ◽  
Vol 10 (3) ◽  
pp. 226-233
Author(s):  
Dmitry A. Neganov ◽  
◽  
Victor M. Varshitsky ◽  
Andrey A. Belkin ◽  
◽  
...  
Keyword(s):  
Internal Pressure ◽  
Experimental Studies ◽  
Full Scale ◽  
The Other ◽  
Metal Loss ◽  
Calculation Methods ◽  
Reliable Operation ◽  
Sufficient Stability ◽  
Comparative Results ◽  
The Moment

The article contains the comparative results of the experimental and calculated research of the strength of a pipeline with such defects as “metal loss” and “dent with groove”. Two coils with diameter of 820 mm and the thickness of 9 mm of 19G steel were used for full-scale pipe sample production. One of the coils was intentionally damaged by machining, which resulted in “metal loss” defect, the other one was dented (by press machine) and got groove mark (by chisel). The testing of pipe samples was performed by applying static internal pressure to the moment of collapse. The calculation of deterioration pressure was carried out with the use of national and foreign methodical approaches. The calculated values of collapsing pressure for the pipe with loss of metal mainly coincided with the calculation experiment results based on Russian method and ASME B31G. In case of pipe with dent and groove the calculated value of collapsing pressure demonstrated greater coincidence with Russian method and to a lesser extent with API 579/ASME FFS-1. In whole, all calculation methods demonstrate sufficient stability of results, which provides reliable operation of pipelines with defects.

scholarly journals Why school-related content knowledge for pre-service chemistry teachers should include basic concepts in organic chemistry

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jolanda Hermanns ◽  
Nico Ermler
Keyword(s):  
Organic Chemistry ◽  
Mixed Methods ◽  
Content Knowledge ◽  
Structure And Function ◽  
Mixed Methods Study ◽  
Chemistry Teacher ◽  
Chemistry Teachers ◽  
Basic Concepts ◽  
The Moment ◽  
And Function

Abstract In this paper we describe and evaluate a study on the use of concepts in organic chemistry while solving tasks that are designed after the concept of school-related content knowledge (SRCK). The study was designed as a mixed methods study and conducted at a German university for the content of “organic chemistry”. As the results of this study show, the students rate the tasks and the use of anchoring concepts as for example “bonds” or “structure and function” as relevant for their future profession as a chemistry teacher. They therefore propose that concepts should be an integral part of their university studies as they find it lacking at the moment. Concepts can also be seen as an opportunity to build a bridge between school knowledge and university knowledge.

Intelligent diagnosis and analysis of brain lymphoma based on imaging features

2021 ◽  
pp. 1-11
Author(s):  
Yipu Mao ◽  
Muliang Jiang ◽  
Fanyu Zhao ◽  
Liling Long
Keyword(s):  
Imaging Techniques ◽  
Experimental Studies ◽  
Diagnostic Value ◽  
Imaging Features ◽  
Flow Properties ◽  
Brain Lymphoma ◽  
Diagnosis And Prognosis ◽  
Primary Brain Lymphoma ◽  
Set Up ◽  
Prognosis Evaluation

Currently, DSC has been extensively studied in the diagnosis, differential diagnosis and prognosis evaluation of brain lymphoma, but it has not obtained a uniform standard. By combining DSC imaging features, this study investigated the imaging features and diagnostic value of several types of tumors such as primary brain lymphoma. At the same time, this study obtained data from brain lymphoma patients by data collection and set up different groups to conduct experimental studies to explore the correlation between IVIM-MRI perfusion parameters and DSC perfusion parameters in brain lymphoma. Through experimental research, it can be seen that the combination of two perfusion imaging techniques can more fully reflect the blood flow properties of the lesion, which is beneficial to determine the nature of the lesion.

Mercury Exposure and Endothelial Dysfunction

2015 ◽  
Vol 34 (4) ◽  
pp. 300-307 ◽  
Author(s):  
Swati Omanwar ◽  
M. Fahim
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Endothelium ◽  
Circulatory System ◽  
Vital Role ◽  
Mercury Exposure ◽  
And Function ◽  
The Impact ◽  
And Oxidative Stress

Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.

scholarly journals Centromere Protein B Null Mice are Mitotically and Meiotically Normal but Have Lower Body and Testis Weights

1998 ◽  
Vol 141 (2) ◽  
pp. 309-319 ◽  
Author(s):  
Damien F. Hudson ◽  
Kerry J. Fowler ◽  
Elizabeth Earle ◽  
Richard Saffery ◽  
Paul Kalitsis ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Mammalian Species ◽  
Experimental Studies ◽  
Conflicting Evidence ◽  
Body Weights ◽  
Reduced Rate ◽  
And Function ◽  
Centromere Assembly ◽  
Mitosis And Meiosis

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.

Abstract 135: Endothelial Dysfunction in Acute Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation. In vitro Evidence of the Protective Effect of Defibrotide

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Enrique Mir ◽  
Marta Palomo ◽  
Enric Carreras ◽  
Maribel Diaz-Ricart ◽  
Montse Rovira ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Protective Effect ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Endothelial Damage ◽  
Hematopoietic Cell ◽  
Graft Versus Host ◽  
Acute Graft

Acute Graft-Versus-Host Disease (aGVHD) is the most common early complication after allogeneic Hematopoietic Cell Transplantation (allo-HCT). We demonstrated endothelial dysfunction (ED) in association with allo-HCT. According to this data, aGVHD has been linked to an inflammatory process that may affect the endothelium. To investigate the differential degree of endothelial damage in patients developing or not aGVHD, to identify potential biomarkers, and to explore the protective effect of defibrotide (DF) in this scenario. DF has orphan designation for GVHD prevention. Patients blood samples were collected before allo-HCT, at day 0, and every week till day 28 after HCT. Plasma proteins (sTNFR1, sVCAM-1, VWF and ADAMTS-13) were measured as biomarkers of ED in individual samples from patients developing (GVHD, n=24), or not (NoGVHD, n=13), aGVHD. In in vitro assays, endothelial cells (EC) in culture were exposed to media containing pooled sera from patients to evaluate changes in the: a) expression of VCAM-1 and ICAM-1 on cell surfaces; b) presence of VWF on the extracellular matrix (ECM) and c) reactivity of the ECM towards platelets, under flow. The effect of DF was explored in the in vitro experiments by previous exposure of the EC (for 24h) followed by continuous incubation (100 μg/ml, added every 24h). Levels of sTNFRI, sVCAM-1 and VWF in samples from group GVHD were significantly higher than in NoGVHD (increases of 100, 37 and 150% respectively, at diagnose, p<0.01). ADAMTS-13 activity and VWF levels were inversely related. In in vitro studies, cell surface expression of VCAM-1 and ICAM-1, presence of VWF and platelet adhesion on the ECM in response to GVHD samples were always superior (increases vs NoGVHD of 80, 40, 100 and 21%, respectively, at diagnose). In vitro exposure of EC to DF attenuated signs of endothelial injury reducing significantly (p<0.05) the expression of VCAM-1, ICAM-1 and VWF (reductions of 22, 30 and 30%, respectively) in the GVHD condition. Our results demonstrate endothelial damage in association with aGVHD, as evidenced by elevated plasma levels of several biomarkers. The in vitro approach showed a marked proinflammatory and prothrombotic phenotype in association with aGVHD, which could be significantly prevented by defibrotide.

L'etica nella professione forense

2009 ◽  
pp. 163-172
Author(s):  
Angelo Abignente
Keyword(s):  
Public Interests ◽  
Legal Proceedings ◽  
Legal Professionals ◽  
Positive Law ◽  
Conflicting Interests ◽  
Discursive Participation ◽  
The Moment ◽  
The One ◽  
And Function ◽  
Role And Function

- The positive law tradition has hitherto had nothing to say about the legal profession's role and function, focusing more interest on questions of justice, of the legitimisation of power and of the genesis and organisation of normative material. This trend is now subject to a reversal promoted by new, neo-constitutionalist, narrativist, analytical and hermeneutic experiences, which no longer focuses attention on the moment when law is produced, but on the one when it is applied, reappraising and revitalising the function of the judge, of the attorneys and of other legal professionals. The attorney becomes an active protagonist, an intermediary not only between conflicting interests in a controversy, but also between opposing public interests, while the reappraisal of his role stimulates thinking about the ethical dimension of how the legal profession is practised. Referring to the theories of Habermas and of Alexy, the author treats the reasonable status of argumentation as the supreme ethical instance necessary for a decision that interferes in the sphere of another person's action. At the same time, however, the control of the reasonable status of the respective arguments on both sides is the ethical instance required of the attorneys taking part in the legal proceedings. It takes the form of compliance with the rules characteristic of the practical discourse, primarily the rule of free discursive participation that enables the onus of the argumentation to be explained. Ernesto de

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