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Cellular senescence, the irreversible loss of replicative capacity in somatic cells, plays a causal role in the development of age-related pathology and in a number of age-related chronic inflammatory diseases. The ageing lung is marked by an increasing number of senescent cells, and evidence is mounting that senescence may directly contribute to a number of age-related respiratory diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Telomere dysfunction and alterations in mitochondrial homeostasis frequently occur in cellular senescence and are important to the development of the often detrimental senescence-associated secretory phenotype (SASP). The roles of telomeres, the mitochondria and cellular senescence in lung ageing and disease are discussed. Therapeutic interventions targeting cellular senescence are considered for delaying or potentially reversing age-related respiratory disease.
To evaluate, during cardiac catheterization, what constitutes a physiologically significant obstruction to blood flow in the human coronary system, computer-based quantitative analysis of coronary angiograms was performed on the angiograms of 31 patients with isolated disease of the proximal left anterior descending coronary artery. The angiographic severity of stenosis was compared with the transstenotic pressure gradient measured with the dilation catheter during angioplasty and with the results of exercise thallium scintigraphy. A curvilinear relationship was found between the pressure gradient across the stenosis (normalized for the mean aortic pressure) and the residual minimal area of obstruction (after subtracting the area of the angioplasty catheter). This relationship was best fitted by the equation: normalized mean pressure gradient = a + b . log [obstruction area], r = .74. The measurements of the percent area of stenosis (cutoff 80%) and of the transstenotic pressure gradient (cutoff 0.30) obtained at rest correctly predicted the occurrence of thallium perfusion defects induced by exercise in 83% of the patients.
Objective To determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination. Design Meta-analysis of 354 randomised double blind placebo controlled trials of thiazides, blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose. Subjects 40 000 treated patients and 16 000 patients given placebo. Main outcome measures Placebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs. Results All five categories of drug produced similar
No abstract is provided for this article.
No abstract is provided for this article.
Ring segments of bovine left circumflex coronary artery were pre‐contracted with 5‐hydroxytryptamine or phenylephrine and then exposed to increasing concentrations of calcitonin gene‐related peptide (CGRP) and other drugs. CGRP administration resulted in dose‐dependent inhibition of induced tone. Maximal relaxation to CGRP was 89 ± 5% and the concentration required to achieve 50% maximal relaxation (EC 50 ) was 2.11 ± 1.35 × 10 −9 m . CGRP‐induced relaxation was not affected by removal of endothelial cells nor was it significantly altered by incubation of coronary vessels with atropine, propranolol, phentolamine (all 10 −6 m ) or indomethacin (10 −5 m ). From these data we conclude that CGRP is a potent inhibitor of coronary artery vasomotor tone which appears to act directly on vascular smooth muscle rather than through the release of a secondary mediator. These data support the possibility that CGRP may play a role in non‐adrenergic, non‐cholinergic regulation of coronary artery tone.
Treatment of bifurcation lesions with the Tryton Sidebranch stent has been shown to be feasible with an acceptable clinical outcome and low side branch late loss in the first in man trial.To report acute procedural and six month clinical follow-up after the use of the Tryton Sidebranch stent in an "all comer" registry.The first 100 coronary bifurcation lesions assigned for treatment with the Tryton stent were included in a prospective registry. Procedural and angiographic success rates were determined from patient charts and pre- and postprocedural quantitative coronary angiography.Totally, 96 patients with 100 lesions were included in the study. Seventy-two percent presented with stable angina, 25% with unstable angina/NSTEMI, and 3% STEMI. The bifurcation was located in the left main in 8%. Two lesions were chronic total occlusions. Sixty-nine percent were true bifurcation lesions. One failure of stent delivery occurred. Acute gain in SB was 0.76 ± 0.64 mm and three patients had residual stenosis of >30%. Angiographic success rate was 95%; procedural success rate reached 94%. Peri-procedural MI occurred in two and there was one cardiac death during hospitalization. At a median six months follow-up, TLR rate was 4%, MI 3%, and cardiac death 1%. The percentage MACE-free survival at six months was 94%. No cases of definite stent thrombosis occurred.In a real world the use of the Tryton Sidebranch stent is associated with good procedural safety and angiographic success rate and acceptable outcome at six months of follow-up.
Adrenoceptor subtypes have been localized in human lung by an autoradiographic method, using [125I]iodocyanopindolol (ICYP) to label beta-receptors in tissue sections. The ICYP was incubated with cryostat sections of microscopically normal human lung method on microscope slides for 2 h at 37 degrees C. Nonspecific binding was determined by incubating adjacent serial sections in the presence of 200 microM (-)-isoproterenol. Specific binding, which accounted for greater than 90% of total counts bound to the sections, was saturable, of high affinity, and stereoselective, having the same pharmacologic characteristics as binding to homogenates prepared from the same lungs. Competition with selective beta-receptor antagonists ICI 118,551 (beta 2-selective) and betaxolol (beta 1-selective) showed that the ratio of beta 2 to beta 1-receptors in the sections was approximately 3:1. Autoradiography revealed that beta-receptors were widely distributed, with dense labeling over airway epithelium, alveolar walls, and submucosal glands, and a lower density of grains over airway and vascular smooth muscle. The beta-receptors of airway smooth muscle from large and small airways were entirely of the beta 2-receptor subtype, which is consistent with functional studies. Similarly, beta-receptors of airway epithelium and vascular smooth muscle were also entirely of the beta 2-receptor subtype. In bronchial submucosal glands and alveolar walls, both receptor subtypes appeared to coexist with beta 2-receptors, making up 10% of the total in glands and 30% in alveoli. The significance of beta 1- and beta 2-receptors in alveolar walls (which account for greater than 90% of total beta-receptors in human lung) remains to be determined.
