The role of endothelium in covid-19

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection

Death by SARS-CoV 2: a Romanian COVID-19 multi-centre comorbidity study

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection

The role of Bosniak classification in the assessment of renal cystic masses and in the therapeutical protocol

One of the most frequent kidney pathologies encountered in daily practice is represented by the presence of renal cysts. Most of them are asymptomatic and are found accidentally during periodical check-ups because they don’t have clinical signs until they grow and compress the surrounding organs. We have reviewed the current data regarding this pathology, in order to underline the risk of malignant transformation and its impact on the patient’s life. It is estimated that the prevalence rate of renal cysts in the general population is approximately 10% and it increases with age.Imaging investigations, such as contrast tomography or magnetic resonance imaging, are essential for establishing the cysts characteristics, especially when ultrasonography raises the suspicion of a modified renal cyst, as well as in guiding the therapeutical protocol. The Bosniak classification is based on contrast tomography scans and has allowed the standardization of the kidney cysts, considering their characteristics. More attention should be given to Bosniak IIF and III cystic renal masses, which contain thickened walls and more septa, but no enhanced nodules/soft tissue components, because more than half of these cysts can have a malignant component

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Nlrp3 inflammasome biomarker—could be the new tool for improved cardiometabolic syndrome outcome

Metabolomics, the research area studying chemical processes involving metabolites, finds its utility in inflammasome biomarker discovery, thus representing a novel approach for cardiometabolic syndrome pathogeny acknowledgements. Metabolite biomarkers discovery is expected to improve the disease evolution and outcome. The activation of abundantly expressed NLRP3 inflammasome represents the background process of the diabetes mellitus disturbances like hyperglycemia and insulin resistance, as well as for myocardial cell death and fibrosis, all of them being features characteristic for cardiometabolic syndrome. Many molecules like troponins, brain natriuretic protein (BNP), ST2/IL-33, C-reactive protein (CRP), TNF, IL-1β, and IL-18 cytokines have been already examined as molecular markers for diagnosing or predicting different cardiac disturbances like myocardial infarction, heart failure, or myocarditis. In addition, metabolomics research comes with new findings arguing that NLRP3 inflammasome becomes a promising molecular tool to use for clinical and therapeutical management providing new targets for therapies in cardiometabolic syndrome. Inflammasome markers analyses, along with other molecular or genetic biomarkers, will result in a better understanding of cardiometabolic syndrome pathogenesis and therapeutic targets. Screening, diagnostic, and prognostic biomarkers resulted from inflammasome biomarker research will become standard of care in cardiometabolic syndrome management, their utility becoming the first magnitude

Thrombosis and Haemostasis challenges in COVID-19 – Therapeutic perspectives of heparin and tissue-type plasminogen activator and potential toxicological reactions-a mini review

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs. © 2021 Elsevier Lt

Predictors associated with treatment initiation and switch in a real-world chronic hepatitis B population from five European countries

International audienc

Halmyris: Geoarchaeology of a fluvial harbour on the Danube Delta (Dobrogea, Romania)

In Northern Dobrogea, north of the Dunavăţ promontory, the Roman fortress of Halmyris was founded in the late 1st century AD on a Getic settlement dating to the middle of the 1st millennium BC, probably associated with a Greek emporium of the Classical and Hellenistic periods. At the time of the foundation of Halmyris, the Danube delta had already prograded several kilometres to the east leading to the progressive retreat of the sea and the formation of a deltaic plain characterised by numerous lakes and river channels. Here, we present the results of a multiproxy study combining sedimentology and palaeoecology to (1) understand the evolution of fluvial landscapes around Halmyris since ca. 8000 years BP and (2) identify the fluvial palaeoenvironments close to the city in Getic/Greek and Roman times, in order to locate and characterise the waterfront and the harbour. Our overriding objective was to improve understanding of human–environment relations in river delta settings. We demonstrate that Halmyris, protected by the Danubian floods due to its location on a palaeo-cliff top, had direct access to the river. A secondary channel of the Saint George, flowing north of the site, has been elucidated between the 7th century BC and the 7th century AD and could have been used as a natural harbour