Publications

We investigated the in vivo effects of a glucocorticoid on beta-agonist-induced downregulation of beta 1- and beta 2-adrenergic receptors (determined by [125I]iodocyanopindolol binding), mRNA expression (assessed by Northern blotting), and gene transcription (using nuclear run-on assays) in rat lung. Dexamethasone (Dex) (0.2 mg/kg/d, days 1-8) increased beta 1- and beta 2-receptor numbers by 70 and 69% above control, respectively, but did not change their mRNA expression. Isoproterenol (Iso) (0.96 mg/kg/d, days 2-8) decreased beta 1- and beta 2-receptor numbers by 48 and 51%, respectively, and also reduced mRNA expression by 69 and 57%, respectively. The combination of Dex and Iso resulted in no net change in beta 2-receptor number and its mRNA expression, although there was a significant reduction in beta 1-receptor number and mRNA expression. The mapping of beta 1- and beta 2-receptors by receptor autoradiography confirmed these findings over alveoli, epithelium, endothelium, and airway and vascular smooth muscle. We also measured the activation of the transcription factor, cyclic AMP response element binding protein (CREB) using an electrophoretic mobility shift assay. CREB-like DNA-binding activity was decreased after Iso treatment but this decrease was prevented after treatment with Dex. Nuclear run-on assays revealed that the transcription rate of the beta 1-receptor gene did not alter after Dex treatment, but was reduced after Iso treatment. The transcription rate of the beta 2-receptor gene was increased after Dex treatment by approximately twofold, but there was no change after Iso treatment. We conclude that glucocorticoids can prevent homologous downregulation of beta 2-receptor number and mRNA expression at the transcriptional level without affecting beta 1-receptors and that the transcription factor CREB may be involved in this phenomenon. Such an effect may have clinical implications for preventing the development of tolerance to beta 2-agonists in asthmatic patients treated with beta-agonist bronchodilators.

The European Respiratory Society (ERS), in order to serve better its members and achieve its mission objectives (table 1) [1], organised a Strategy Meeting to plan its core strategic priorities for the period 2013–2018, taking into account changes occurring both within the society and within the respiratory field in Europe and beyond. This meeting was held on July 3 and 4, 2013 in Lausanne, Switzerland to formulate future directions. We took into account the Executive Summary of the 2006–2007 Strategy Meeting [2] summarising the ERS pillars (fig. 1) and the recently published ERS Presidential plans as an operational guide [3–5]. View this table: Table 1– Objectives and means of action of the European Respiratory Society (ERS) Figure 1– The three pillars of the European Respiratory Society. The Strategy Meeting involved the ERS Leadership represented by the members of the Steering Committee (fig. 2). It was prepared by an ad hoc meeting preceding the event, involving the Past President and the Secretary General Elect (the officers designated to act as chair and moderator), as well as the Executive Director and the Head of the Executive Office. This was used as the starting point to develop the strategic meeting agenda. Participants were encouraged to express their opinions freely and to think “outside the box” in order to bring fresh ideas to the table. Whilst the focus of the exercise was definitely the future, the importance of the past as the basis of all change was emphasised by the presence of the former Executive Director who attended in an observer role to recall the history of the ERS and previous decisions. Figure 2– The European Respiratory Society Strategy Meeting in Lausanne, Switzerland. Operational minutes discussions were first drafted to allow an accurate summary of the decisions taken, which were then approved by the Steering and Executive Committees following ERS regulations. As it was felt that …

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100 µm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10-20 µm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review we summarize the performance of the two intracoronary imaging modalities - IVUS and OCT, and discuss the expected potential of the novel hybrid IVUS-OCT catheter system in the clinical field.

No abstract is provided for this article.

A 69 year old man was admitted with unstable angina (Class IIB). He had a history of chronic renal impairment, diabetes mellitus, hypertension and coronary bypass surgery in 1997 (LIMA graft to the LAD anf diagonal branch, saphenous vein grafts to the RCA and first marginal branch of LCx.Coronary angiography.Unstable angina (Class IIB). Occlusion of the LCx and RCA. Functionally occluded LIMA on the LAD and diagonal branch. Diffuse disease of the LAD with two significant lesions at the LAD-first diagonal and mid-distal LAD.Revascularisation.

Background Stented segment length was a predictive factor for restenosis in the bare metal stent era. The objective of the study was to evaluate the medium-term clinical outcome and the potential for adverse effects when very long segments (ie, ≥64 mm of stented length) are treated by drug-eluting stent (DES) implantation, an approach colloquially referred to as a “full metal jacket.” Methods Since April 2002, we have used DES as the default stent for all percutaneous coronary interventions. From our prospective institutional database we identified 122 consecutive patients, with de novo coronary lesions, in whom a coronary artery was treated with at least 64 mm of overlapping DES: 81 patients were treated with sirolimus-eluting stents and 41 with paclitaxel-eluting stents. Results The mean number of stents per lesion was 3.3 ± 1.1, and the median stented length was 79 mm (range 64-168 mm). Periprocedural Q-wave myocardial infarction (MI) occurred in 2 patients (1.6%) and subacute stent thrombosis in 1 patient (0.8%). During 1-year follow-up, 5 patients (4.1%), including 3 patients treated for acute MI with cardiogenic shock, died and 10 patients (8.2%) had nonfatal MI (creatine kinase–MB >3 times). The 1-year target vessel revascularization rate was 7.5% and the overall incidence of major adverse cardiac events was 18%. Outcomes in sirolimus-eluting stents and paclitaxel-eluting stents groups did not differ statistically. Conclusions The use of DES for the treatment of diffuse lesions was associated with a low rate of repeat revascularization, irrespective of stent type. No safety concerns were raised at medium-term follow-up.

In recent years, a new method to measure transverse blood flow based on the decorrelation of the radiofrequency (RF) signals of intravascular ultrasound (IVUS) rotating single-element scanners was introduced. We report here in vitro, animal and patient testing to evaluate the correlation-based method using an IVUS array catheter. A new correlation-based method to dynamically correct the correlation coefficients for noise is implemented. The decorrelation due to noise was estimated from the correlation coefficients from flowing blood obtained at increasing time lags. First, blood flow experiments were carried out with different catheters in a tissue-mimicking flow phantom with an inner diameter ranging from 3.0 to 5.0 mm. A calibrated electromagnetic flow meter (EMF, range: 0 to 250 cc/min) was used as a reference. Good linear relationships were found between the IVUS-derived flow and the calibrated EMF (all R2> 0.96). The catheter position within the flow phantom and the size of the ring-down were theoretically analyzed. These elements, and noise in the RF signals, have an important influence on the IVUS blood flow measurements reflected by the offset and the slope of the linear relationships. By placing the IVUS catheter outside the flow phantom, parabolic blood flow profiles were also measured. Second, IVUS blood flow measurements were performed in the carotid artery of two Yorkshire pigs, which showed linear relationships (all R2> 0.85) between the IVUS-derived flow and the calibrated EMF. Experimentally, the offset was lower than 3 mL/min and the slope was close to 1. Third, IVUS blood flow measurements were performed in coronary arteries in patients. Preliminary results for the coronary flow reserve (CFR = high flow/baseline flow) in patients using the decorrelation method of RF signals of an array IVUS scanner were comparable with CFR based on Doppler measurements. (E-mail: a.vandersteen@erasmusmc.nl)

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H(2)O(2)) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H(2)O(2)-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r=0.92, p<0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.