P 2 ‐purinoceptors have been characterized in the systemic circulation of a variety of species but little is known about their nature in the pulmonary vasculature. In the isolated, blood perfused and ventilated lung of the rat the P 2x selective analogues α,β‐methylene ATP(α,β‐meATP) (25 μg) and β,γ‐methylene ATP (400 μg) caused a rise in pulmonary artery pressure (127 ± 32% and 110 ± 23% increase respectively, n = 6), demonstrating the existence of vasoconstrictor P 2 receptors in the pulmonary circulation. Repeated boluses of α,β‐meATP resulted in complete desensitization of the constrictor response to β,γ‐meATP, but a small vasodilator response remained indicating unopposed stimulation of P 2y receptors. The desensitization by α,β‐meATP had no effect on angiotensin II‐induced vasoconstriction. After desensitization of the vasoconstrictor P 2 receptors with α,β‐meATP, hypoxic pulmonary vasoconstriction remained intact, indicating that these receptors are not involved in this response.
Transcatheter aortic valve implantation underwent progressive improvements until it became the default therapy for inoperable patients, and a recommended therapy in high-risk operable patients with symptomatic severe aortic stenosis. In the lower-risk patient strata, a currently costly therapy that still has important complications with questionable durability is competing with the established effective and still-improving surgical replacement. This report tries to weigh the clinical evidence, the recent technical improvements, the durability, and the cost-effectiveness claims supporting the adoption of transcatheter aortic valve implantation in intermediate-low risk patients. The importance of appropriate patients’ risk stratification and a more comprehensive approach to estimate that risk are also emphasized in the present report.
Patients with coronary artery disease who have prognostically significant lesions or symptoms despite optimum medical therapy require mechanical revascularization with coronary artery bypass grafting ( CABG ), percutaneous coronary intervention ( PCI ) or both. In this review, we will evaluate the evidence‐based use of the two revascularization approaches in treating patients with coronary artery disease. CABG has been the predominant mode of revascularization for more than half a century and is the preferred strategy for patients with multivessel disease, especially those with diabetes mellitus, left ventricular systolic dysfunction or complex lesions. There have been significant technical and technological advances in PCI over recent years, and this is now the preferred revascularization modality in patients with single‐vessel or low‐risk multivessel disease. Percutaneous coronary intervention can also be considered to treat complex multivessel disease in patients with increased risk of adverse surgical outcomes including frail patients and those with chronic obstructive pulmonary disease. Improvements in both CABG (including total arterial revascularization, off‐pump CABG and ‘no‐touch’ graft harvesting) and PCI (including newer‐generation stents, adjunctive pharmacotherapy and intracoronary imaging) mean that they will continue to challenge each other in the future. A ‘heart team’ approach is strongly recommended to select an evidence‐based, yet individualized, revascularization strategy for all patients with complex coronary artery disease. Finally, optimal medical therapy is important for all patients with coronary artery disease, regardless of the mode of revascularization.
<b>Introduction:</b> Chronic obstructive pulmonary disease (COPD) is associated with accelerated lung aging. In the COPD lung, there is an accumulation of senescent cells that may, in part, be due to a lack of clearance. To investigate this, a robust source of well-characterised senescent cells is required. Doxorubicin (DOXO) and etoposide (Etop) at sub-cytotoxic concentrations activate the DNA-damage response (DDR) pathway, leading to the induction of cellular senescence and could be used to generate a senescent cell population for study. <b>Aim:</b> To induce senescence in BEAS-2B cells using DOXO and Etop. <b>Methods:</b> Senescent BEAS-2B cells were generated by repeated exposure to 50nM DOXO or 1mM Etop for a total of 6 days. Cell cycle checkpoint inhibitors, anti-aging molecule sirtuin-1 and senescence associated secretory phenotype (SASP) marker expression were measured using western blotting and ELISA. Senescent cells were identified by senescence-associated-b-galactosidase (SA-β-gal) expression. <b>Results:</b> In BEAS-2B cells, 50nM DOXO treatment induced senescence in ~60% of cells (n=7, p<0.01), p21 protein expression (4-fold, p<0.01), reduced sirtuin-1 protein expression (~50%, p<0.05) and induced secretion of IL-6 (10-fold, p<0.05), CXCL-8 (6-fold, p<0.05) and PAI-1 (3-fold, p<0.01). 1mM etoposide treatment induced ~60% SA-b-gal (n=5, p<0.001), p21 protein expression (8-fold, p=0.1), secretion of IL-6 (19-fold, p=0.09), CXCL-8 (11-fold, p<0.05) and PAI-1 (3-fold, p<0.01). <b>Conclusion:</b> Sub-cytotoxic double-hit DOXO and Etop treatments are required to induce senescence in BEAS-2B cells via p21 induction of cell cycle arrest and may provide a model that can be used in future experiments.
A recent two-dimensional prototype model for the initiation of kink banding in compressed layered structures is extended to embrace the two propagation mechanisms of band broadening and band progression. As well as interlayer friction, overburden pressure and layer bending energy, the characteristics of transverse layer compressibility and foundation stiffness are now included. Experiments on constrained layers of paper show good agreement with the predictions of angle of orientation, kink band width and post-kink load-deflection response obtained from the model.
Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.
