The C3-C3aR axis modulates trained immunity in alveolar macrophages.

Complement protein C3 is crucial for immune responses in mucosal sites such as the lung, where it aids in microbe elimination and enhances inflammation. While trained immunity - enhanced secondary responses of innate immune cells after prior exposure - is well-studied, the role of the complement system in trained immune responses remains unclear. We investigated the role of C3 in trained immunity and found that , trained wild-type mice showed significantly elevated pro-inflammatory cytokines and increased C3a levels upon a second stimulus, whereas C3-deficient mice exhibited a blunted cytokine response and heightened evidence of lung injury.

Lower female survival from an opportunistic infection reveals progesterone-driven sex bias in trained immunity.

Immune responses differ between females and males, although such sex-based variance is incompletely understood. Observing that bacteremia of the opportunistic pathogen Burkholderia gladioli caused many more deaths of female than male mice bearing genetic deficiencies in adaptive immunity, we determined that this was associated with sex bias in the innate immune memory response called trained immunity. Female attenuation of trained immunity varies with estrous cycle stage and correlates with serum progesterone, a hormone that decreases glycolytic capacity and recall cytokine secretion induced by antigen non-specific stimuli.

NOTCH signaling in COVID-19: a central hub controlling genes, proteins, and cells that mediate SARS-CoV-2 entry, the inflammatory response, and lung regeneration.

In the lungs of infected individuals, the downstream molecular signaling pathways induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are incompletely understood. Here, we describe and examine predictions of a model in which NOTCH may represent a central signaling axis in lung infection in Coronavirus Disease 2019 (COVID-19). A pathway involving NOTCH signaling, furin, ADAM17, and ACE2 may be capable of increasing SARS-CoV-2 viral entry and infection.

Non-Randomized Trial of Dornase Alfa for Acute Respiratory Distress Syndrome Secondary to Covid-19.

Background: The most severe cases of Coronavirus-Disease-2019 (COVID-19) develop into Acute Respiratory Distress Syndrome (ARDS). It has been proposed that oxygenation may be inhibited by extracellular deoxyribonucleic acid (DNA) in the form of neutrophil extracellular traps (NETs). Dornase alfa (Pulmozyme, Genentech) is recombinant human deoxyribonuclease I that acts as a mucolytic by cleaving and degrading extracellular DNA.

Neutrophils and secondary infections in COVID-19 induced acute respiratory distress syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the cause of the current global pandemic and has affected more than 188 countries worldwide. Infection by the virus can have diverse clinical manifestations, with one of the most severe clinical manifestation being respiratory failure and the development of acute respiratory distress syndrome. Clinical manifestations of acute respiratory distress syndrome secondary to SARS-CoV-2 are also diverse with a lack of diagnostic tools to distinguish between primary viral infection and secondary bacterial infections.

Consideration of dornase alfa for the treatment of severe COVID-19 acute respiratory distress syndrome.

We propose a likely contribution to severe COVID-19 morbidity by extracellular DNA in neutrophil extracellular traps (NETs). Dornase alfa degrades extracellular DNA to reduce mucus rigidity and accumulation, and was associated with respiratory improvement in a first patient. Dornase alfa should be considered for clinical trials in treatment of severe COVID-19.

Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF-κB activity.

Tracheitis secondary to placement of an endotracheal tube (ETT) is characterized by neutrophil accumulation in the tracheal lumen, which is generally associated with epithelial damage. Mitochondrial DNA (mtDNA), has been implicated in systemic inflammation and organ dysfunction following trauma; however, less is known about the effects of a foreign body on local trauma and tissue damage. We hypothesized that tracheal damage secondary to the ETT will result in local release of mtDNA at sufficient levels to induce TLR9 and NF-κB activation.

Mitochondrial DNA induces Foley catheter related bladder inflammation via Toll-like receptor 9 activation.

Bladder instrumentation engages the innate immune system via neutrophil activation, promoting inflammation and pain. Elevated levels of mitochondrial DNA (mtDNA) have been associated with tissue damage and organ dysfunction. We hypothesized that local bladder trauma induced by a Foley catheter (FC) will result in mtDNA release, migration of neutrophils into the bladder lumen, and activation of the Toll-like receptor 9 (TLR9) and nuclear factor kappa B (NF-κB) pathway leading to bladder tissue damage.

Endotracheal tube-induced sore throat pain and inflammation is coupled to the release of mitochondrial DNA.

In the absence of infection, the pathophysiology of endotracheal tube-induced sore throat pain is unclear. Activated neutrophils release elastase, reactive oxygen species, and inflammatory cytokines known to contribute to neuropathic pain. Sterile tissue injury can cause the release of damage-associated molecular patterns such as mitochondrial DNA that promote neutrophil activation.

Vascular access and contrast media.

Over the past several years, the Food and Drug Administration (FDA) has received more than 250 adverse event reports in which vascular access devices have ruptured when used with power injectors. The adverse events include rupture and device fragmentation. The outcome of these events affects both the patient and the care provider.

Inflammatory cytokines and antioxidants in midtrimester amniotic fluid: correlation with pregnancy outcome.

Objective: Elevated interleukin-6 (IL-6) level in midtrimester amniotic fluid is associated with preterm delivery. We hypothesized that, in patients with elevated IL-6, vitamin C and alpha-fetoprotein may provide protection from spontaneous preterm delivery through antioxidant functions.

Study Design: Antioxidant potential of alpha-fetoprotein was assessed in vitro.

Intracoronary eptifibatide bolus administration during percutaneous coronary revascularization for acute coronary syndromes with evaluation of platelet glycoprotein IIb/IIIa receptor occupancy and platelet function: the Intracoronary Eptifibatide (ICE) Trial.

Background: Eptifibatide reduces major adverse cardiac events in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). Intracoronary bolus administration of eptifibatide may result in higher levels of platelet glycoprotein IIb/IIIa receptor occupancy in the local coronary bed, disaggregate thrombus in the epicardial artery and microvasculature, and thereby improve coronary flow.

Methods And Results: Patients undergoing PCI for an acute coronary syndrome were randomized to either intracoronary or intravenous bolus administration of eptifibatide.

Transplacental transfer and metabolism of bupropion.

Objective: In order to evaluate the potential use of bupropion as smoking cessation therapy during pregnancy, the aim of this investigation was to determine transplacental transfer and metabolism of bupropion and its distribution among placental tissue and maternal and fetal circuits of the dually perfused placental lobule.

Methods: Placentas obtained from healthy term pregnancies were perfused with bupropion at two concentrations 150 ng/ml and 450 ng/ml, along with the marker compound antipyrine 20 microg/ml. Radioactive isotopes of the two drugs were co-transfused to enhance their detection limits.

Variability of platelet aggregate dispersal with glycoprotein IIb-IIIa antagonists eptifibatide and abciximab.

Background: Utilization of glycoprotein IIb-IIIa (GPIIb-IIIa) inhibitors improves outcomes of patients with acute coronary syndromes (ACS), including those undergoing percutaneous coronary intervention (PCI). These results may be related to the ability of the inhibitors to destabilize coronary thrombi, reduce microembolization, and restore vessel patency.

Objective: To evaluate in vitro the ability of GPIIb-IIIa antagonists, abciximab and eptifibatide, to promote the disaggregation of platelet-rich thrombus.

Regulation of CD40L (CD154) and CD62P (p-selectin) surface expression upon GPIIb-IIIa blockade of platelets from stable coronary artery disease patients.

Introduction: The aim of this study was to further characterize the effect of the antiplatelet agents, aspirin and eptifibatide, on the surface expression of CD40L and CD62P on platelets from patients with stable coronary artery disease.

Materials And Methods: Platelet function was evaluated using standard light transmission aggregometry. Measurements of CD62P and CD40L were carried out by flow cytometry and ELISA assays.

The validity of cervical dilation as an indication of true labor between 32 and 36 weeks 6 days of gestation.

Objective: Cervical dilation with regular contraction traditionally has been used to differentiate between true and false labor. This diagnostic criterion has not been tested as most patients receive tocolytics. Our objective was to determine the time from admission to delivery in women with preterm contractions and advanced cervical dilation without tocolytics.

Assessing pediatric patients for vascular access and sedation.

Central venous catheters have been established as a reliable source of vascular access since the 1970s. Peripherally inserted central catheters became a popular central catheter in the early 1990s for adults and children. The management of vascular access in children is an essential part of inpatient and outpatient care.

Diagnostic tools and therapeutic interventions that may influence the integrity of vascular and nonvascular access devices.

Current technology introduces many new vascular and nonvascular devices to the medical field. With the assistance of these devices, patients can be offered many more diagnostic tests and therapeutic treatments that aid in the diagnosis and treatment of diseases. As with any new infusion technology, these devices can be associated with complications attributable to the rapid rate of infusion.