The role of interleukin 35 in atherosclerosis.

Atherosclerosis has been widely recognized as a slow progressing inflammatory disease of the arterial walls involving both inflammation and autoimmune processes with a complex etiology in which the immune system plays a key role. A hallmark of atherosclerosis is that the macrophages pick up the lipids to form the foam cells which build up the plaque in the arterial wall. Consequently, the arteries become narrowed.

Discrepancy between guidelines for stroke prevention in atrial fibrillation and practice patterns in primary care. The nationwide French AFIGP survey.

Background: General practitioners (GPs) play a pivotal role in the long-term management of patients with atrial fibrillation (AF), including anticoagulant prophylaxis for stroke prevention.

Aims: To investigate the antithrombotic prescription behaviours of GPs in France and compare them with the European Society of Cardiology (ESC) guidelines for stroke prevention, and to identify the major determinants of use of antithrombotic therapy.

Methods: We conducted a cross-sectional survey, using data from the French Longitudinal Patient Database, on the use of antithrombotic treatments for stroke prevention in 15,623 patients (≥18years of age) with AF who attended at least one GP consultation between July 2010 and June 2011.

Recent advances in understanding and managing cystic fibrosis transmembrane conductance regulator dysfunction.

Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians and has been extensively studied for many decades. The cystic fibrosis transmembrane conductance regulator gene was identified in 1989. It encodes a complex protein which has numerous cellular functions.

Ventilatory function in young adults and dietary antioxidant intake.

Dietary antioxidants may protect against poor ventilatory function. We assessed the relation between ventilatory function and antioxidant components of diet in young Chileans. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and the ratio FEV1/FVC were measured in 1232 adults aged 22-28 years, using a Vitalograph device.

Cystic Fibrosis Gene Therapy in the UK and Elsewhere.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene was identified in 1989. This opened the door for the development of cystic fibrosis (CF) gene therapy, which has been actively pursued for the last 20 years. Although 26 clinical trials involving approximately 450 patients have been carried out, the vast majority of these trials were short and included small numbers of patients; they were not designed to assess clinical benefit, but to establish safety and proof-of-concept for gene transfer using molecular end points such as the detection of recombinant mRNA or correction of the ion transport defect.

Ventilatory function and cardiovascular disease risk factors: a cross-sectional study in young adults.

Background: The association between impaired lung function and cardiovascular disease (CVD) risk factors has been shown in adults. However, there is little evidence of such an association in young adults, particularly from South America, where the burden of CVD and chronic obstructive pulmonary disease (COPD) is as high as that observed in more developed countries. We therefore investigated the relation between CVD risk factors including metabolic syndrome (MS), and lung function status in young adults from Chile.

Monotherapy with indacaterol once daily reduces the rate of exacerbations in patients with moderate-to-severe COPD: Post-hoc pooled analysis of 6 months data from three large phase III trials.

Background: In patients with COPD, exacerbations are associated with poor quality of life and may shorten survival. Prevention of exacerbations is, therefore, a key objective in COPD management. Indacaterol, a once-daily ultra-long-acting β2-agonist, has been shown to reduce exacerbations in various studies.

Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease.

Background: There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.

Methods: We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012.

Pathogenesis of idiopathic pulmonary fibrosis: review of recent findings.

Idiopathic pulmonary fibrosis (IPF) is likely to result from the interaction between environmental exposures, including cigarette smoke, and genetic predisposition. This review focuses on clues provided by recent genetic association studies and other selected data and hypotheses. In IPF, association with surfactant mutations has highlighted the importance of type II epithelial cells, while shortened telomeres in some patients suggest that accelerated aging may play a role in the pathogenesis of lung fibrosis, possibly by affecting the renewal/differentiation potential of epithelial cells.

Impact of MCP-1 in atherosclerosis.

Monocyte chemotactic protein-1 (MCP-1) (also referred to as chemokine (C-C motif) ligand 2 (CCL2) is expressed by mainly inflammatory cells and endothelial cells. The expression level is upregulated after proinflammatory stimuli and tissue injury which are associated with atherosclerotic lesion. Atherosclerosis is a progressive disease starting with accumulation of lipids, lipoproteins, and immune cells in the arterial wall.

Interrogating causal pathways linking genetic variants, small molecule metabolites, and circulating lipids.

Background: Emerging technologies based on mass spectrometry or nuclear magnetic resonance enable the monitoring of hundreds of small metabolites from tissues or body fluids. Profiling of metabolites can help elucidate causal pathways linking established genetic variants to known disease risk factors such as blood lipid traits.

Methods: We applied statistical methodology to dissect causal relationships between single nucleotide polymorphisms, metabolite concentrations, and serum lipid traits, focusing on 95 genetic loci reproducibly associated with the four main serum lipids (total-, low-density lipoprotein-, and high-density lipoprotein- cholesterol and triglycerides).

Impact of matrix metalloproteinases on atherosclerosis.

Atherosclerosis is now widely recognized as a chronic inflammatory disease that involves innate and adaptive immune responses. Both cellular and humoral components of the immune system have been implicated in atherogenesis. Growing evidence suggests that immune cells play crucial roles in atherogenic plaque formation.

The roles of microRNAs in atherosclerosis.

MicroRNA (abbr. miRNA) is an endogenous small non-coding RNAs (containing ~22 nucleotides) found in plants and animals, which functions in transcriptional and post-transcriptional regulation of gene expression. These endogenous gene expression inhibitors were primarily described in cancer but recent emerging roles in the regulation of autoimmune inflammation which is thought to be associated with cardiovascular diseases (CVDs), including atherosclerosis known as an autoimmune disease.

Respiratory protective equipment reduces occurrence of sensitization to laboratory animals.

Background: Respiratory protective equipment (RPE) has been shown to reduce exposure to laboratory animal allergens, but there are no studies that have examined its effect on the development of sensitization.

Aims: To examine the effect of RPE on the risk of sensitization to laboratory animals.

Methods: Survey of UK laboratory animal workers conducted between 1999 and 2001.

The safety profile of a cationic lipid-mediated cystic fibrosis gene transfer agent following repeated monthly aerosol administration to sheep.

Clinically effective gene therapy for Cystic Fibrosis has been a goal for over 20 years. A plasmid vector (pGM169) that generates persistent expression and reduced host inflammatory responses in mice has raised prospects for translation to the clinic. The UK CF Gene Therapy Consortium is currently evaluating long-term repeated delivery of pGM169 complexed with the cationic lipid GL67A in a large Multidose Trial.

Inflammasome and atherogenesis.

Atherosclerosis is a progressive disease starting with accumulation of lipids, lipoproteins, and immune cells in the arterial wall. Inflammation and the innate immune response are involved in the formation of early atherosclerotic lesion. A protein complex known as the inflammasome is stimulated to activate interleukin-1β (IL-1β) and IL-18, which are responsible for activation of inflammatory processes.

Microarray profiling reveals suppressed interferon stimulated gene program in fibroblasts from scleroderma-associated interstitial lung disease.

Background: Interstitial lung disease is a major cause of morbidity and mortality in systemic sclerosis (SSc), with insufficiently effective treatment options. Progression of pulmonary fibrosis involves expanding populations of fibroblasts, and the accumulation of extracellular matrix proteins. Characterisation of SSc lung fibroblast gene expression profiles underlying the fibrotic cell phenotype could enable a better understanding of the processes leading to the progressive build-up of scar tissue in the lungs.