Potentiation of anti-angiogenic eNOS-siRNA transfection by ultrasound-mediated microbubble destruction in ex vivo rat aortic rings.

Nitric oxide (NO) regulates vascular homeostasis and plays a key role in revascularization and angiogenesis. The endothelial nitric oxide synthase (eNOS) enzyme catalyzes NO production in endothelial cells. Overexpression of the eNOS gene has been implicated in pathologies with dysfunctional angiogenic processes, such as cancer.

Temporal relationship between sarcoidosis and malignancies in a nationwide cohort of 1942 patients.

Purpose: To investigate the phenotype of sarcoidosis according to the time when a malignancy is diagnosed (preexisting to the diagnosis of sarcoidosis, concomitant, or sequential) and to identify prognostic factors associated with malignancies in a large cohort of patients with sarcoidosis.

Methods: We searched for malignancies in the SARCOGEAS cohort, a multicenter nationwide database of consecutive patients diagnosed with sarcoidosis according to the ATS/ESC/WASOG criteria. Solid malignancies were classified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) nomenclature, and hematological malignancies using the 2016 WHO classification.

Cellular shortening and calcium dynamics are improved by noisy stimulus in a model of cardiomyopathy.

Noise is present in cell biology. The capability of cells to respond to noisy environment have become essential. This study aimed to investigate whether noise can enhance the contractile response and Ca handling in cardiomyocytes from a cardiomyopathy model.

Caveolin Delivered by Ultrasound-Mediated Microbubble Destruction Prevents Endothelial Cell Proliferation.

Introduction: The nitric oxide synthase (eNOS) is an important regulator of vascular homeostasis. eNOS is modulated by intracellular mechanisms that include protein-protein interaction with Caveolin-1 (Cav). Cav binds to and impairs eNOS activation reducing vascular permeability and angiogenesis.

Computer-assisted image analysis of agonist-mediated microvascular constriction response in mouse cremaster muscle.

In this work, we implemented an automated method using a correlation coefficient to select a time interval with a minimum movement or rest interval, together with analysis of variance for measurement of blood vessel diameter in the cremaster muscle. Video images binarization using analysis of variance resulted in an enhanced and a clearly defined vessel wall. Histamine (1 mM) induced a marked reduction in vascular diameter (vasoconstriction) in the cremaster muscle from mice fed with standard (SD) and high fat diet (HFD).

Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment.

In the presence of a vascular thrombus, the recovery of blood flow and vascular recanalization are very important to prevent tissue damage. An alternative procedure to thrombolysis is required for patients who are unable to receive surgery or thrombolytic drugs due to other physical conditions. Recently, the performance of thrombolysis combined with microbubbles has become an attractive and effective therapeutic procedure.

Thromboxane-dependent coronary vasoconstriction in obese mice: Role of peroxynitrite.

Obesity leads to chronic oxidative stress promoting the development of cardiovascular diseases including coronary artery disease and endothelial dysfunction. Increased reactive oxygen species production associated with obesity might lead to endothelial dysfunction through cyclooxygenase (COX) pathway. We evaluated arachidonic acid (AA)-dependent coronary vascular responses and explored COX metabolism in obese C57BL/6 mice.

Effect of Empagliflozin on Sphingolipid Catabolism in Diabetic and Hypertensive Rats.

The profile of sphingomyelin and its metabolites shows changes in the plasma, organs, and tissues of patients with cardiovascular, renal, and metabolic diseases. The objective of this study was to investigate the effect of empagliflozin on the levels of sphingomyelin and its metabolites, as well as on the activity of acid and neutral sphingomyelinase (aSMase and nSMase) and neutral ceramidase (nCDase) in the plasma, kidney, heart, and liver of streptozotocin-induced diabetic and Angiotensin II (Ang II)-induced hypertension rats. Empagliflozin treatment decreased hyperglycemia in diabetic rats whereas blood pressure remained elevated in hypertensive rats.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease).

Characterization and Outcomes of SARS-CoV-2 Infection in Patients with Sarcoidosis.

To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population.

Release of vascular agonists from liposome-microbubble conjugate by ultrasound-mediated microbubble destruction: effect on vascular function.

The endothelium is a single cell layer of the vessel wall and a key regulator of blood flow in vascular beds. Local and systemic pathologies have been associated with alterations in endothelial function. However, targeting the endothelium with vasoconstrictor or vasodilator drugs is often accompanied by systemic effects.

Localized Delivery of Caveolin-1 Peptide Assisted by Ultrasound-Mediated Microbubble Destruction Potentiates the Inhibition of Nitric Oxide-Dependent Vasodilation Response.

In the endothelium, nitric oxide synthase (eNOS) is the enzyme that generates nitric oxide, a key molecule involved in a variety of biological functions and cancer-related events. Therefore, selective inhibition of eNOS represents an attractive therapeutic approach for NO-related diseases and anticancer therapy. Ultrasound-mediated microbubble destruction (UMMD) conjugated with cell-permeable peptides has been investigated as a drug delivery system for effective delivery of anticancer molecules.

[Zika virus embryopathy in Argentina: clinical characteristics in newborns].

Introduction: Microcephaly and brain abnormalities may be due to multiple etiologies, one of them is the congenital infection by Zika virus (ZIKV). From 2016 to the present, there has been a series of ZIKV outbreaks in Argentina.

Methods: National Network of Congenital Anomalies (RENAC) and the National Institute of Viral Diseases (INEVH), under the National Administration of Laboratories and Health Institutes “Carlos Malbrán” (ANLIS), carry out the intensified surveillance of newborns with microcephaly and brain abnormalities.

Functional Activity and Endothelial-Lining Integrity of Ex Vivo Arteries Exposed to Ultrasound-Mediated Microbubble Destruction.

Ultrasound-mediated microbubble destruction (UMMD) is a promising strategy to improve local drug delivery in specific tissues. However, acoustic cavitation can lead to harmful bioeffects in endothelial cells. We investigated the side effects of UMMD treatment on vascular function (contraction and relaxation) and endothelium integrity of ex vivo Wistar rat arteries.

Systemic phenotype of sarcoidosis associated with radiological stages. Analysis of 1230 patients.

Background: To analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe.

Methods: The SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al.

Role of sodium/glucose cotransporter inhibition on a rat model of angiotensin II-dependent kidney damage.

Background: Renal proximal tubular sodium and glucose reabsorption are regulated by the sodium-glucose cotransporter (SGLT2). Changes in this transporter can play a role in hyperglycaemia and reactive oxygen species (ROS) production. We demonstrated increased glucose absorption in proximal tubule membrane vesicles and increased expression of SGLT2 in hypertensive rats.

Abnormal synchronization patterns in the electrical stimulation-contractile response coupling decrease with noise.

Synchronization theory predicts that if an oscillator interacts with a rhythmical external force, then it should react to a rhythmical force by adjusting its frequency. Furthermore, noise is present in nature, and it affects the nervous and cardiovascular systems. In this paper, we analyze the heart as an oscillator, where noisy periodic electrical stimulation can be regarded as an external forcing.

Comparative effects of nitric oxide dependent and independent vasodilation on impaired hindlimb revascularization in eNOS mice.

Ischemia due to vascular occlusion induces vasodilation as an initial response, followed by arteriogenesis or angiogenesis. Vasodilation through nitric oxide (NO) independent and dependent mechanisms may be sufficient to restore the altered neovascularization in pathological situations where the NO is altered. Using a posterior limb claudication model to evaluate ischemia-induced revascularization in eNOS mice, we compared the effects of sodium nitrite, a NO-dependent vasodilator, and prazocin, an alpha-adrenergic blocker and NO-independent vasodilator, on hindlimb revascularization.

Peroxynitrite-Induced Intracellular Ca2+ Depression in Cardiac Myocytes: Role of Sarco/Endoplasmic Reticulum Ca2+ Pump.

Several studies have shown that peroxynitrite (ONOO-), formed upon the reaction of •NO and O2-, is increased in many cardiovascular diseases and is detrimental to myocardial function. Proteins associated with Ca2+ homeostasis regulation in the heart may be involved in these effects. Thus, the aim of this study was to elucidate the mechanisms associated with ONOO--induced effects.

Venous thrombosis and relapses in patients with Behçet's disease. Descriptive analysis from Spanish network of Behçet's disease (REGEB cohort).

Objectives: To describe the characteristics of patients with Behçet's disease (BD) who presented with venous thrombosis. In addition, we identified the factors associated with this venous involvement and those related with recurrent venous thrombosis.

Methods: Up to January 2015, 544 BD patients from 20 Spanish hospitals had been included in the REGEB (REGistro de la Enfermedad de Behçet as Spanish nomenclature).

Androgens Mediate β-adrenergic Vasorelaxation Impairment Using Adenylyl Cyclase.

Cardiovascular disease development has been associated with sex differences, suggesting that sex hormones are implicated in vascular function and development of hypertension. Vascular tone comparison at different stages of rat growth represents a good model to study testosterone-related vascular response. We explored the role of testosterone in modulation of age-dependent impaired β-adrenergic vasodilation.

Noise enhanced the electrical stimulation-contractile response coupling in isolated mouse heart.

Background: Stochastic resonance is a phenomenon that allows a system to improve its capability to detect stimulus when a limited amount of noise is added to the stimuli. It has experimentally been shown that noise enhances the homeostatic function of the blood pressure regulatory system. This study aimed to investigate whether the noise can enhance the contractile response in the whole heart.

Role of adenylyl cyclase in reduced β-adrenoceptor-mediated vasorelaxation during maturation.

Beta-adrenergic receptor (βAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of βAR subtypes (β1AR, β2AR, and β3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium.

Oxidative Stress-Dependent Coronary Endothelial Dysfunction in Obese Mice.

Obesity is involved in several cardiovascular diseases including coronary artery disease and endothelial dysfunction. Endothelial Endothelium vasodilator and vasoconstrictor agonists play a key role in regulation of vascular tone. In this study, we evaluated coronary vascular response in an 8 weeks diet-induced obese C57BL/6 mice model.

Combined effects of flow-induced shear stress and electromagnetic field on neural differentiation of mesenchymal stem cells.

Differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into neural phenotype has been induced by either flow-induced shear stress (FSS) or electromagnetic fields (EMF). However, procedures are still expensive and time consuming. In the present work, induction for 1 h with the combination of both forces showed the presence of the neural precursor nestin as early as 9 h in culture after treatment and this result lasted for the following 6 d.