6,963 publications from this institution
Bioresorbable scaffolds offer the possibility of transient scaffolding of the vessel to prevent acute vessel closure and recoil while also transiently eluting an antiproliferative drug to counteract the constrictive remodeling and excessive neointimal hyperplasia. The concept of a transient coronary device that disappears after doing its job fits the physiological demand to restore the vessel structure and seems attractive both to physicians and patients. Following the successful and intriguing findings observed in the first-in-human trials, the four products, Absorb, Desolve, ART, and Magmaris scaffolds succeeded to acquire a CE mark.
We have characterized the binding of a novel radioligand, [3H] FK888, to neurokinin (NK)1 receptors in guinea pig lung membranes and localized its binding in guinea pig lung sections by autoradiography. Lung membranes were incubated with [3H] FK888 at 25 degrees and the assays were terminated by rapid filtration; nonspecific binding was defined as binding in the presence of 1 microM concentrations of the nonpeptide NK1-selective antagonist CP-96,345. Kinetic analysis showed that specific binding of [3H] FK888 (approximately 70% of total binding) was rapid, reaching a plateau by 20 min, and that binding was reversed by addition of 1 microM CP-96,345, giving a kinetic Kd of 0.46 nM. Binding of [3H] FK888 was saturable at approximately 1 nM, and equilibrium binding analysis gave a Kd of 0.32 +/- 0.03 nM and a Bmax of 46.9 +/- 7.1 fmol/mg of protein (four experiments). In competition studies, substance P, CP-96,345, and FK888 competed for [3H] FK888 binding, but NKA, NKB, and NK2-selective antagonists such as SR48968 and L-659,877 did not. Guanosine-5'-O-(3-thio)triphosphate significantly shifted the competition curve for substance P competition against [3H]FK888 binding to a lower affinity state, confirming that NK1 receptors are coupled to a G protein. Autoradiographic mapping in cryostat sections of lung showed that [3H]FK888 binding was dense over smooth muscle of all airways, with moderate binding over epithelium of bronchi and bronchioles as well as submucosal glands of trachea. No significant labeling of blood vessels was observed. [3H]FK888 binds to NK1 receptors in guinea pig lung and may be a useful tool for studying the expression and regulation of NK1 receptors.
Aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR) is a major predictor of short- and long-term survival. Thus far, no independent quantitative comparison of AR among commercially available transcatheter heart valves (THVs) has been performed.
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Journal of Cardiovascular Pharmacology™ is a peer reviewed, multidisciplinary journal that publishes original articles and pertinent review articles on basic and clinical aspects of cardiovascular pharmacology. Appropriate subjects include new drug development and evaluation, physiological and pharmacological bases of drug action, metabolism, drug interactions and side effects, clinical results with new and established agents and novel methods. The focus is on pharmacology in its broadest applications, incorporating not only traditional approaches, but new approaches to the development of pharmacological agents and the prevention and treatment of cardiovascular diseases.
Under short-circuit conditions, vasoactive intestinal peptide (VIP) did not alter net Na+ movement but selectively stimulated net Cl- secretion across dog tracheal epithelium with a high affinity (Km congruent to 10(-8) M). The increase in Cl- secretion was not different from the rise in short-circuit current (Isc). However, stimulation of Cl- secretion was not maximal, because the addition of isoproterenol (10(-6) M) to VIP-treated tissues further increased the Isc by 54%. The effect of exogenous VIP was not blocked by a combination of atropine, phentolamine, propranolol (10(-5) or 10(-6) M), or tetrodotoxin (10(-6) M). Under open-circuit conditions, VIP caused an increase in the net secretion of Cl- and Na+, but the changes did not reach statistical significance. We conclude that VIP acts directly on receptors on the surface of epithelial cells to stimulate active Cl- secretion. The abundance of VIP nerves in the submucosa suggests that VIP may be important in regulation of fluid movement across the epithelium.
van Beusekom, Heleen M.M.; Serruys, Patrick W.; van der Giessen, Willem J. Author Information
Chronic obstructive pulmonary disease (COPD), characterized by progressive inflammation in the small airways and lung parenchyma, is mediated by the increased expression of multiple inflammatory genes. The increased expression of these genes is regulated by acetylation of core histones, whereas histone deacetylase 2 (HDAC2) suppresses inflammatory gene expression. In COPD, HDAC2 activity and expression are reduced in peripheral lung and in alveolar macrophages, resulting in amplification of the inflammatory response. Corticosteroid resistance in COPD occurs because corticosteroids use HDAC2 to switch off activated inflammatory genes. The reduction in HDAC2 appears to be secondary to the increased oxidative and nitrative stress in COPD lungs. Antioxidants and inhibitors of nitric oxide synthesis may therefore restore corticosteroid sensitivity in COPD, but this can also be achieved by low concentrations of theophylline and curcumin, which act as HDAC activators.
In this study it is argued that the clinical manifestations of unstable angina pectoris, with at its extreme end impending myocardial infarction, may be due to increased coronary arterial vasomotion superimposed on a pre-existing obstruction in a coronary artery. As nifedipine, a powerful calcium antagonist, has initially proven its efficacy in relieving the symptoms of Prinzmetal's angina, a condition in which severe spasm of the coronary artery is now proven to be the main cause, the drug was given to two groups of patients in whom abnormal vasomotion was suspected and its effects scrutinized. Twelve patients with symptoms of coronary artery disease (CAD) were studied with repeated arteriograms after injection of 0.15 mg nifedipine in the left coronary artery. Two control cine-angiograms were made prior to drug administration and two cinefilms were repeated 30 s and 5 min after administration of nifedipine. The mean diameter of the normal, stenotic and poststenotic segments showed a statistically significant increase after drug administration. Vasodilalion persisted after coronary O 2 saturation, and presumably coronary flow, had returned to normal. In 52 other patients, who were seen in the coronary care unit for impending myocardial infarction and who had been treated with maximal beta-adrenergic blockade, nitrates and bedrest, but who remained symptomatic, nifedipine 60 mg orally for 24 h was added to the treatment. Within 2 h after administration 42 of the 52 became asymptomatic. In the 10 non-responders, all with extensive multi-vessel disease, two sustained a myocardial infarction and eight received urgent coronary artery bypass grafting in an effort to alleviate their symptoms. All had severe 3 vessel disease in contrast to the responders in whom 1 or 2 vessel disease was predominant. These data show that increased coronary artery vasomotion can be influenced by nifedipine. The excellent clinical response to the drug in this group of patients with unstable angina pectoris indicates that nifedipine may become the preferred agent to be used particularly when the cause of the angina pectoris is suspected to be the result of abnormal coronary vasomotor tone.
Biological agents such as omalizumab and monoclonal antibodies (mAbs) that inhibit type 2 (T2) immunity significantly reduce exacerbations, which are mainly due to viral infections, when added to inhaled corticosteroids in patients with severe asthma. The mechanisms for the therapeutic benefit of T2 inhibitors in reducing virally induced exacerbations, however, remain to be fully elucidated. Pre-clinical and clinical evidence supports the existence of a close counter-regulation of the high-affinity IgE receptor and interferon (IFN) pathways, and a potential dual mechanism of action and therapeutic benefit for omalizumab and other T2 inhibitors that inhibit IgE activity, which may enhance the prevention and treatment of virally induced asthma exacerbations. Similar evidence regarding some novel T2 inhibitor therapies, including mAbs and small-molecule inhibitors, suggests that such a dual mechanism of action with enhancement of IFN production working through non-IgE pathways might also exist. The specific mechanisms for this dual effect could be related to the close counter-regulation between T2 and T1 immune pathways, and potential key underlying mechanisms are discussed. Further basic research and better understanding of these underlying counter-regulatory mechanisms could provide novel therapeutic targets for the prevention and treatment of virally induced asthma exacerbations, as well as T2- and non-T2-driven asthma. Future clinical research should examine the effects of T2 inhibitors on IFN responses and other T1 immune pathways, in addition to any effects on the frequency and severity of viral and other infections and related exacerbations in patients with asthma as a priority.
