Antisense therapy to block the Kallikrein-kinin pathway in COVID-19: The ASKCOV randomized controlled trial.

Purpose: To assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients.

Material And Methods: Randomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use.

Protein disulfide isomerase redox-dependent association with p47(phox): evidence for an organizer role in leukocyte NADPH oxidase activation.

Mechanisms of leukocyte NADPH oxidase regulation remain actively investigated. We showed previously that vascular and macrophage oxidase complexes are regulated by the associated redox chaperone PDI. Here, we investigated the occurrence and possible underlying mechanisms of PDI-mediated regulation of neutrophil NADPH oxidase.

Loss of CD40 endogenous S-nitrosylation during inflammatory response in endotoxemic mice and patients with sepsis.

Signal transduction through the surface molecule CD40 is critical for cellular activation in immunoinflammatory states such as sepsis. The mechanisms regulating this pathway are not completely understood. Because CD40 displays potentially regulatory cysteine residues and CD40 is probably exposed to NO in the inflammatory milieu, we hypothesized that S-nitrosylation, the interaction of NO with cysteines residues, acts as a post-translational modification on CD40, coregulating the signaling activity and, therefore, the level of cellular activation.

Platelet-derived exosomes from septic shock patients induce myocardial dysfunction.

Introduction: Mechanisms underlying inotropic failure in septic shock are incompletely understood. We previously identified the presence of exosomes in the plasma of septic shock patients. These exosomes are released mainly by platelets, produce superoxide, and induce apoptosis in vascular cells by a redox-dependent pathway.

Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction.

Introduction: Several studies link hematological dysfunction to severity of sepsis. Previously we showed that platelet-derived microparticles from septic patients induce vascular cell apoptosis through the NADPH oxidase-dependent release of superoxide. We sought to further characterize the microparticle-dependent vascular injury pathway.

Noxa1 is a central component of the smooth muscle NADPH oxidase in mice.

NADPH oxidase is the most important source of oxygen-derived radicals (ROS) in the vascular wall. In vascular smooth muscle cells (VSMC), NADPH oxidase is characterized by the expression of the membrane subunit Nox1, which is activated by cytoplasmic proteins binding to its activation domain. We set out to identify the cytoplasmic protein involved in NADPH oxidase activation in mouse VSMC.

Regulation of NAD(P)H oxidase by associated protein disulfide isomerase in vascular smooth muscle cells.

NAD(P)H oxidase, the main source of reactive oxygen species in vascular cells, is known to be regulated by redox processes and thiols. However, the nature of thiol-dependent regulation has not been established. Protein disulfide isomerase (PDI) is a dithiol/disulfide oxidoreductase chaperone of the thioredoxin superfamily involved in protein processing and translocation.

Direct detection of reactive oxygen species ex vivo.

Oxidative stress is thought to play an important role in the initiation and progression of renal, cardiovascular, neoplastic, and neurodegenerative diseases. It is also widely believed that oxidative stress is a main cause of aging. Although considerable progress has been made in the understanding of the sources and actions of oxidative stress, the true role of oxygen-derived free radicals in the pathology of most human diseases largely remains to be determined.

Brazilian Sepsis Epidemiological Study (BASES study).

Introduction: Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome

Methods: This is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil.

Functional role of NADPH oxidase in activation of platelets.

Involvement of phagocyte NADPH oxidase in host defense response is well established. In contrast, little is known about the functional role of NADPH oxidase in platelets. In this study, we analyzed involvement of platelet NADPH oxidase in aggregation of human platelets and in amplification of production of reactive oxygen species (ROS) by activated human neutrophils.

Platelet-derived exosomes of septic individuals possess proapoptotic NAD(P)H oxidase activity: A novel vascular redox pathway.

Objective: Vascular dysfunction in sepsis may involve apoptosis of vascular cells through redox signaling mechanisms, which are still poorly investigated. Platelets have been shown to produce reactive oxygen species and to release microparticles, related to thrombotic and inflammatory processes. The present study was undertaken to investigate whether, in severe sepsis, platelet-derived microparticles could produce reactive oxygen species through a phagocyte-type nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and if such particles may induce vascular cell apoptosis through a reactive oxygen species-dependent mechanism.

Protective effect of ascorbic acid in experimental gastric cancer: reduction of oxidative stress.

Aim: Oxidative stress participates in the cell carcinogenesis by inducing DNA mutations. Our aim was to assess whether ascorbic acid, an antioxidant, could have a role in preventing ROS (Reactive Oxygen Species) generation in experimental gastric carcinoma in a rat model.

Methods: Experimental gastric cancer was induced in twelve Wistar male rats (weighting 250-350 g) by profound duodeno-gastric reflux throught split gastrojenunostomy.

Overestimation of NADH-driven vascular oxidase activity due to lucigenin artifacts.

Several limitations have recently been described for lucigenin, a probe frequently used to assess the activity of vascular NAD(P)H oxidase, a major superoxide source. The preferential reducing substrate of such oxidase remains unclear. We assessed whether lucigenin artifacts could affect detection of NAD(P)H oxidase activity.