Lipoxin-mediated signaling: ALX/FPR2 interaction and beyond.

In the aftermath of tissue injury or infection, an efficient resolution mechanism is crucial to allow tissue healing and preserve appropriate organ functioning. Pro-resolving bioactive lipids prevent uncontrolled inflammation and its consequences. Among these mediators, lipoxins were the first described and their pro-resolving actions have been mainly described in immune cells.

Beneficial effect of TLR4 blockade by a specific aptamer antagonist after acute myocardial infarction.

Experimental evidence indicates that the control of the inflammatory response after myocardial infarction is a key strategy to reduce cardiac injury. Cellular damage after blood flow restoration in the heart promotes sterile inflammation through the release of molecules that activate pattern recognition receptors, among which TLR4 is the most prominent. Transient regulation of TLR4 activity has been considered one of the potential therapeutic interventions with greater projection towards the clinic.

Functional Crosstalk between PCSK9 Internalization and Pro-Inflammatory Activation in Human Macrophages: Role of Reactive Oxygen Species Release.

Atherosclerosis is a cardiovascular disease caused mainly by dyslipidemia and is characterized by the formation of an atheroma plaque and chronic inflammation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that induces the degradation of the LDL receptor (LDLR), which contributes to increased levels of LDL cholesterol and the progress of atherosclerosis. Given that macrophages are relevant components of the lipidic and inflammatory environment of atherosclerosis, we studied the effects of PCSK9 treatment on human macrophages.

Specialized Proresolving Mediators Protect Against Experimental Autoimmune Myocarditis by Modulating Ca Handling and NRF2 Activation.

Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum-adenosine triphosphatase 2A down-regulation and Ca mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.

Resolution-Based Therapies: The Potential of Lipoxins to Treat Human Diseases.

Inflammation is an a physiological response instead an essential response of the organism to injury and its adequate resolution is essential to restore homeostasis. However, defective resolution can be the precursor of severe forms of chronic inflammation and fibrosis. Nowadays, it is known that an excessive inflammatory response underlies the most prevalent human pathologies worldwide.

Innate Immune Receptors, Key Actors in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of death in the industrialized world. Most CVDs are associated with increased inflammation that arises mainly from innate immune system activation related to cardiac damage. Sustained activation of the innate immune system frequently results in maladaptive inflammatory responses that promote cardiovascular dysfunction and remodeling.

BML-111 treatment prevents cardiac apoptosis and oxidative stress in a mouse model of autoimmune myocarditis.

Myocarditis is an inflammation of the myocardium that can progress to a more severe phenotype of dilated cardiomyopathy (DCM). Three main harmful factors determine this progression: inflammation, cell death, and oxidative stress. Lipoxins and their derivatives are endogenous proresolving mediators that induce the resolution of the inflammatory process.

GRK2 levels in myeloid cells modulate adipose-liver crosstalk in high fat diet-induced obesity.

Macrophages are key effector cells in obesity-associated inflammation. G protein-coupled receptor kinase 2 (GRK2) is highly expressed in different immune cell types. Using LysM-GRK2 mice, we uncover that a reduction of GRK2 levels in myeloid cells prevents the development of glucose intolerance and hyperglycemia after a high fat diet (HFD) through modulation of the macrophage pro-inflammatory profile.

Epidemiological study of pediatric severe sepsis in Argentina.

Introduction: Severe sepsis (SS) is one of the leading causes of pediatric mortality in Argentina. The objective was to describe the epidemiological characteristics and to analyze risk factors associated with mortality from SS among patients hospitalized in pediatric intensive care units (PICU) in Argentina.

Population And Methods: Observational, prospective cohort study among patients with SS hospitalized in PICUs in Argentina from 8/1/2008 to 9/30/2008.

Self-defense of macrophages against oxidative injury: Fighting for their own survival.

Activated macrophages play a central role in both the development and resolution of inflammation. These immune cells need to be functional in harmful conditions with high levels of reactive oxygen and nitrogen species that can damage their basic cell components, which may alter their metabolism. An excessive accumulation of these cell alterations drives macrophages inexorably to cell death, which has been associated to the development of several inflammatory diseases and even with aging in a process termed as "immunosenescence".

Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort.

Background: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2 (COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.

Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer: An update.

The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2 (PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions.

High mortality in patients with influenza A pH1N1 2009 admitted to a pediatric intensive care unit: a predictive model of mortality.

Objective: To describe the clinical characteristics and outcome of patients admitted to pediatric intensive care with influenza A (pH1N1) 2009 in Argentina.

Design: Retrospective observational study.

Setting: Thirteen pediatric intensive care units in Argentina.

Critically ill infants and children with influenza A (H1N1) in pediatric intensive care units in Argentina.

Objective: To determine the epidemiological features, course, and outcomes of critically ill pediatric patients with Influenza A (H1N1) virus.

Design: Prospective cohort of children in pediatric intensive care units (PICUs) due to Influenza A (H1N1) virus infection.

Setting: Seventeen medical-surgical PICUs in tertiary care hospital in Argentina.

Morphological and functional characterization of beige mouse adrenomedullary secretory vesicles.

We tested whether the giant secretory granules observed in the mast cells of the naturally occurring mutant beige mouse (BM) (C57BL/6N-bg) were also present in the adrenal chromaffin cells. The presence of large chromaffin granules (CG) would be a valuable tool for the study of exocytosis in neuronal tissues. Conversely, the observation of large vesicles within chromaffin cells that are different from CG could indicate that CG are of a different origin than granules of mast cells.

Calcium channel subtypes and exocytosis in chromaffin cells: a different view from the intact rat adrenal.

In the intact rat adrenal gland perfused with an oxygenated Krebs-bicarbonate solution at 37 degrees C, the electrical field stimulation of splanchnic nerves (100 V, 0.5 ms duration, 10 Hz during 10 s) produced transient catecholamine release peaks that were reproduced in subsequent stimuli, applied at 8-min intervals. Omega-Conotoxin GVIA (0.

Replacement of the common carotid artery by a plastic prosthesis. Report of a case with forty years of follow-up.

An 18-year-old man suffered a 38 caliber gunshot wound to the right side of the neck on 25 September 1957. On 16 October 1957, a traumatic arteriovenous aneurysm between the common carotid artery and the internal jugular vein was resected. The jugular vein was ligated and the common carotid was replaced by a nylon prosthesis.

Aorto-left atrial fistula.

The authors present a case of fistula between the ascending aorta and the left atrium, with four large aneurysmal sacs and marked enlargement of the left atrium. The 10-year-old patient was treated by closing the fistula with a Dacron patch. The results were satisfactory in this extremely rare case of a congenital cardiac lesion.

Effects of ketamine on canine cardiovascular function.

Left ventricular contractility was assessed before and during the peak effect of ketamine in eight canine right heart bypass preparations. Myocardial contractility was defined in terms of maximum left ventricular dp/dt, the ejection fraction, and left ventricular end-diastolic and left atrial pressures at constant heart rate and cardiac inflow. Ketamine produced significant decreases in contractility and there were some indications of a dose-response pattern.

Ascending aorta-right pulmonary artery anastomosis in children with complex cardiac malformations. Long-term results in 30 cases.

In this report, we shall analyze the results obtained with palliative treatment in 30 patients with congenital heart disease who were operated upon at the University Hospital of Caracas during the period 1968 to 1972. In all cases, an ascending aorta-right pulmonary artery anastomosis was performed. Although we believe that the Blalock-Taussig and Potts shunt are satisfactory operations in some cases, at the present time we prefer the aorta-right pulmonary branch anastomosis in Fallots tetralogy and other congenital heart diseases such as single ventricle.