Key role of activated platelets in the enhanced adhesion of circulating leucocyte-platelet aggregates to the dysfunctional endothelium in early-stage COPD.

Background: Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF.

Targeting systemic inflammation in metabolic disorders. A therapeutic candidate for the prevention of cardiovascular diseases?

Cardiovascular disease (CVD) remains the leading cause of death and disability worldwide. While many factors can contribute to CVD, atherosclerosis is the cardinal underlying pathology, and its development is associated with several metabolic risk factors including dyslipidemia and obesity. Recent studies have definitively demonstrated a link between low-grade systemic inflammation and two relevant metabolic abnormalities: hypercholesterolemia and obesity.

Overview of Cellular and Soluble Mediators in Systemic Inflammation Associated with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease in Western countries, affecting approximately 25% of the adult population. This condition encompasses a spectrum of liver diseases characterized by abnormal accumulation of fat in liver tissue (non-alcoholic fatty liver, NAFL) that can progress to non-alcoholic steatohepatitis (NASH), characterized by the presence of liver inflammation and damage. The latter form often coexists with liver fibrosis which, in turn, may progress to a state of cirrhosis and, potentially, hepatocarcinoma, both irreversible processes that often lead to the patient's death and/or the need for liver transplantation.

Revealing 2-dimethylhydrazino-2-alkyl alkynyl sphingosine derivatives as sphingosine kinase 2 inhibitors: Some hints on the structural basis for selective inhibition.

Sphingosine kinase (SphK), which catalyzes the transfer of phosphate from ATP to sphingosine (Sph) generating sphingosine-1-phosphate (S1P) has emerged as therapeutic target since the discovery of connections of S1P with cancer progress. So far, most effort has focused on the development of inhibitors of SphK1, and selective inhibitors of SphK2 have been much less explored. Here, we describe the syntheses of new sphingosine derivatives bearing a tetrasubstituted carbon atom at C-2, dimethylhydrazino or azo moieties in the polar head, and alkane, alkene or alkyne moieties as linkers between the polar ahead and the fatty tail.

Beneficial effects of PCSK9 inhibition with alirocumab in familial hypercholesterolemia involve modulation of new immune players.

Familial hypercholesterolemia (FH) is associated with low-grade systemic inflammation, a key driver of premature atherosclerosis. We investigated the effects of inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) function on inflammatory state, endothelial dysfunction and cardiovascular outcomes in patients with FH. Fourteen patients with FH were evaluated before and 8 weeks after administration of a PCSK9 blocking monoclonal antibody (alirocumab, 150 mg/subcutaneous/14 days).

Primary hypercholesterolemia and development of cardiovascular disorders: Cellular and molecular mechanisms involved in low-grade systemic inflammation and endothelial dysfunction.

Primary hypercholesterolemia, a metabolic disorder characterized by elevated circulating levels of cholesterol products, mainly low-density lipoproteins, is associated with arteriosclerosis development. Cardiovascular disease, predominantly myocardial infarction and stroke, remains the main cause of death worldwide, with atherosclerosis considered to be the most common underlying pathology. In addition to elevated plasma levels of low-density lipoproteins, low-grade systemic inflammation and endothelial dysfunction seem to be the main drivers of premature atherosclerosis.

Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients.

Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting. To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state.

Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CXCL1/CXCR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion.

Background: Metabolic syndrome is associated with low-grade systemic inflammation, which is a key driver of premature atherosclerosis. We characterized immune cell behavior in metabolic syndrome, its consequences, and the potential involvement of the CXCL1/CXCR1 and CCL2/CCR2 chemokine axes.

Methods: Whole blood from 18 patients with metabolic syndrome and 21 age-matched controls was analyzed by flow cytometry to determine the leukocyte immunophenotypes, activation, platelet-leukocyte aggregates, and CXCR1 expression.

Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation.

Primary hypercholesterolemia (PH) is associated with a low grade systemic inflammation that is likely the main driver of premature atherosclerosis. Accordingly, we characterized the immune cell behaviour in PH and its potential consequences. Whole blood from 22 PH patients and 21 age-matched controls was analysed by flow cytometry to determine the percentage of leukocyte immunophenotypes, activation, and platelet-leukocyte aggregates.

Functional role of endothelial CXCL16/CXCR6-platelet-leucocyte axis in angiotensin II-associated metabolic disorders.

Aims: Angiotensin-II (Ang-II) is the main effector peptide of the renin-angiotensin system (RAS) and promotes leucocyte adhesion to the stimulated endothelium. Because RAS activation and Ang-II signalling are implicated in metabolic syndrome (MS) and abdominal aortic aneurysm (AAA), we investigated the effect of Ang-II on CXCL16 arterial expression, the underlying mechanisms, and the functional role of the CXCL16/CXCR6 axis in these cardiometabolic disorders.

Methods And Results: Results from in vitro chamber assays revealed that CXCL16 neutralization significantly inhibited mononuclear leucocyte adhesion to arterial but not to venous endothelial cells.

Drug-related problems at discharge: results on the Spanish pharmacy discharge programme CONSULTENOS.

Objectives: The aim of this study was to describe the most common drug-related problems (DRPs) found after discharge, pharmacist interventions and their results for the patients enrolled on the CONSULTENOS programme.

Methods: An observational, prospective, multicentre study was conducted to evaluate the results of a pharmaceutical care programme at discharge. Patients from 10 hospitals participating in the CONSULTENOS programme were enrolled.