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No abstract is provided for this article.

No abstract is provided for this article.

In A549 pulmonary cells, the dexamethasone‐ and budesonide‐dependent repression of interleukin‐1β‐induced prostaglandin E 2 release was mimicked by the steroid antagonist, RU486. Conversely, whereas dexamethasone and budesonide were highly effective inhibitors of interleukin‐1β‐induced cyclooxygenase (COX)/prostaglandin E synthase (PGES) activity and COX‐2 expression, RU486 (< 1 µ m ) was a poor inhibitor, but was able to efficiently antagonize the effects of dexamethasone and budesonide. In addition, both dexamethasone and RU486 repressed [ 3 H]arachidonate release, which is consistent with an effect at the level of phospholipase A 2 activity. By contrast, glucocorticoid response element‐dependent transcription was unaffected by RU486 but induced by dexamethasone and budesonide, whilst dexamethasone‐ and budesonide‐dependent repression of nuclear factor‐κB‐dependent transcription was maximally 30–40% and RU486 (< 1 µ m ) was without significant effect. Thus, two pharmacologically distinct mechanisms of glucocorticoid‐dependent repression of prostaglandin E 2 release are revealed. First, glucocorticoid‐dependent repression of arachidonic acid is mimicked by RU486 and, second, repression of COX/PGES is antagonized by RU486. Finally, whilst all compounds induced glucocorticoid receptor translocation, no role for glucocorticoid response element‐dependent transcription is supported in these inhibitory processes and only a limited role for glucocorticoid‐dependent inhibition of nuclear factor‐κB in the repression of COX‐2 is indicated.

Objectives This study was designed to determine whether antisense oligodeoxynucleotides (ODN) directed against the nuclear proto-oncogene c-myc could inhibit restenosis when given by local delivery immediately after coronary stent implantation. Background Failure of conventional pharmacologic therapies to reduce the incidence of coronary restenosis after percutaneous revascularization techniques has prompted interest in the use of agents that target intracellular central regulatory mechanisms. Methods Eighty-five patients were randomly assigned to receive either 10 mg of phosphorothioate-modified 15-mer antisense ODN or saline vehicle by intracoronary local delivery after coronary stent implantation. The primary end point was percent neointimal volume obstruction measured by computerized analysis of electrocardiogram-gated intravascular ultrasound (IVUS) at six-month follow-up. Secondary end points included clinical outcome and quantitative coronary angiography analysis. Results Analysis of follow-up IVUS data was performed on 77 patients. In-stent volume obstruction was similar between groups (44 ± 16% and 46 ± 14%, placebo vs. ODN; p = 0.57; 95% confidence interval: −1.13 to 0.85). Minimum luminal diameter increased from 0.84 ± 0.36 and 0.90 ± 0.45 (p = 0.55) to 2.70 ± 0.37 and 2.80 ± 0.37 (p = 0.28) after stent implantation, which decreased to 1.50 ± 0.61 and 1.50 ± 0.53 (p = 0.98) by six months, yielding similar loss indexes (placebo vs. ODN, respectively). There were no differences in angiographic restenosis rates (38.5 and 34.2%; p = 0.81; placebo vs. ODN) or clinical outcome. Conclusions Treatment with 10 mg of phosphorothioate-modified ODN directed against c-myc does not reduce neointimal volume obstruction or the angiographic restenosis rate in this patient population.

No abstract is provided for this article.

Background : In the ABSORB study cohort A the changes in the amount of dense calcium and necrotic core have not been reported in comparison to the prestenting phase; this evaluation could be useful to better clarify the bioabsorption process. Aim of this study was therefore to evaluate the dynamic changes in plaque size and plaque tissue composition observed between 6 months and 2 years follow‐up, and to compare these findings to the prestenting phase. Methods : Angiography, intravascular ultrasound and derived parameters (virtual histology, palpography, and echogenicity) were serially assessed postprocedure, at 6 months and at 2 years in 20 patients. In a subset of 8 patients the same measurements were also recorded in the prestenting phase. Results : In the total population a reduction of 18% in the plaque area was observed between 6 month and 2 year follow‐up (7.56 ± 2.32 mm 2 at 6 months vs. 6.16 ± 2.10 mm 2 at 2 year follow‐up; P < 0.01). In the subgroup of eight patients who underwent IVUS during the pre‐stenting phase, the plaque area at 2 year follow‐up was not significantly different when compared to the prestenting plaque area (7.29 ± 2.29 mm 2 at prestenting vs. 7.48 ± 1.45 mm 2 at 2 year follow‐up, P = NS). Necrotic core area was reduced by 24% between the 6 month and 2 year follow‐up (0.97 ± 0.66 mm 2 at 6 months vs. 0.74 ± 0.53 mm 2 at 2 year follow‐up; P = NS), whilst dense calcium was reduced by 14% from 6 month to 2 year follow‐up (0.83 ± 0.50 mm 2 at 6 months vs 0.72 ± 0.64 mm 2 at 2 year follow‐up; P = NS). Whilst the necrotic core at 2 years follow‐up was not significantly different when compared to the pre‐stenting phase (0.62 ± 0.42 mm 2 prestenting vs 1.07 ± 0.56 mm 2 at 2 year follow‐up; P = NS), the area of dense calcium was significantly higher at follow‐up compared to prestenting (0.35 ± 0.35 mm 2 pre‐stenting vs. 0.84 ± 0.66 mm 2 at 2 year follow‐up; P < 0.05). Conclusions : The reduction in the necrotic core component between 6 month and two year follow‐up could be related to a synergistic effect of the bio‐absorption process and the anti‐inflammatory action of everolimus. © 2010 Wiley‐Liss, Inc.

This study explores the possibility to use the Hounsfield unit (HU) distribution of a coronary plaque to quantify its composition when imaged with multi-slice computed tomography (MSCT). Explanted left anterior descending specimens were imaged with different contrast strengths. In one specimen, 5 sections of 0.9 to 1.4 mm long were 3D-quantitatively evaluated against quantitative volumetric histopathology. There were no substantial differences found between the two quantitative methodologies. Both quantitative methodologies showed a remarkable positive correlation. This ex-vivo multi-modality imaging study shows encouraging results for quantitative MSCT-CA based plaque composition measurements compared against quantitative histopathology.

No abstract is provided for this article.

Clinical and Scientific Background The current pharmacotherapy for congestive heart failure,1 including neurohormonal inhibition, with angiotensin-converting enzyme (ACE) inhibitors and β-blockers, improves the clinical outcome, but fails to stop the progression of the disease. Similarly, despite the best available treatment, the cumulative incidence of mortality and heart failure increases time-dependently in patients with a previous myocardial infarction.2Therefore, novel treatment methods that improve cardiac function and prevent heart failure are in demand. The mechanisms leading to congestive heart failure after an acute myocardial infarction are only partially understood,3 and, according to current belief, a progressive decrease in the number of viable myocytes after an acute myocardial infarction could at least partially explain this transition. Therefore, myocardial infarction and subsequent heart failure can be viewed as a disease of cellular deficiency.4

The MeRes-1 trial sought to study the safety and effectiveness of a novel sirolimus-eluting bioresorbable vascular scaffold (MeRes100 BRS) in treating de novo native coronary artery lesions by clinical evaluation and using multiple imaging modalities.The MeRes-1 first-in-human trial was a single-arm, prospective, multicentre study, which enrolled 108 patients with de novo coronary artery lesions (116 scaffolds were deployed to treat 116 lesions in 108 patients). At six months, quantitative coronary angiography revealed in-scaffold late lumen loss of 0.15±0.23 mm with 0% binary restenosis. Optical coherence tomography demonstrated minimum scaffold area (6.86±1.73 mm2) and percentage neointimal strut coverage (99.30%). Quantitative intravascular ultrasound analysis confirmed a 0.14±0.16 mm2 neointimal hyperplasia area. At one year, major adverse cardiac events, a composite of cardiac death, any myocardial infarction and ischaemia-driven target lesion revascularisation, occurred in only one patient (0.93%) and there was no scaffold thrombosis reported. At one year, computed tomography angiography demonstrated that all scaffolds were patent and in-scaffold mean percentage area stenosis was 11.33±26.57%.The MeRes-1 trial demonstrated the safety and effectiveness of MeRes100 BRS. The favourable clinical outcomes and effective vascular responses have provided the basis for further studies in a larger patient population. The MeRes-1 trial is registered at the Clinical Trials Registry-India.