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Coronary artery stents revolutionized the practice of interventional cardiology after they were first introduced in the mid-1980s. Since then, there have been significant developments in their design, the most notable of which has been the introduction of drug-eluting stents. This paper reviews the benefits, risks, and current status of Food and Drug Administration-approved drug-eluting stents.
Exacerbations of chronic obstructive pulmonary disease are of major importance in terms of their prolonged detrimental effects on patients, the acceleration in disease progression and high healthcare costs. There is still debate about how exacerbations should be defined and graded, and their mechanisms are poorly understood. The major causal agents are either bacteria or viral infections, or a combination of the two. Noninfective causes include air pollution and pulmonary embolus but, in some patients, no cause is identified. Exacerbations represent an increase in the inflammation that is present in the stable state, with increased numbers of inflammatory cells (particularly neutrophils), cytokines, chemokines and proteases in the airways, and increased concentrations of certain cytokines and C-reactive protein in the blood. There are presently no reliable biomarkers with which to predict exacerbations. Exacerbations have a long-lasting adverse influence on health status. High doses of bronchodilators are the mainstay of treatment and systemic corticosteroids have some benefit. The routine use of antibiotics remains controversial but they are of benefit with exacerbations of a bacterial origin. Noninvasive ventilation is beneficial in preventing the need for intubation and its important complications but it is not certain whether its use in stable patients prevents exacerbations. Although important advances have been made, more effective treatments are needed in the future for prevention and treatment of exacerbations.
The effect of platelet activating factor (PAF) on the generation of cyclo-oxygenase-derived arachidonic acid metabolites was examined on purified eosinophils harvested from the peritoneal cavity of male guinea pigs. PAF produced a concentration-dependent increase in the amount of immunoreactive thromboxane B2 (TXB2) and PGE1/E2 released from these inflammatory cells at a relative molar ratio of 30:1. The EC50 of PAF was 20 to 40 nM and maximum stimulation (4.5-fold) of both prostanoids occurred at 1 microM PAF. The ability of PAF to generate TXA2 was rapid (t 1/2 = 9 s), transient (40 s), noncytotoxic, and noncompetitively antagonized by the PAF-receptor blocking drug, WEB 2086. On an equimolar (100 nM) basis, PAF was significantly more effective than C5a, fMLP, and PMA at stimulating TXB2 release but markedly less potent than the calcium ionophore, calcimycin. Pretreatment of eosinophils with the cyclo-oxygenase inhibitor flurbiprofen (8 microM for 5 min) abolished the ability of PAF to promote both TXB2 and PGE1/E2 release. Likewise, dazmegrel (50 microM for 5 min), a selective inhibitor of thromboxane synthetase, abolished PAF-stimulated TXB2 release but markedly augmented the elaboration of PGE1/E2. Inhibition of cyclo-oxygenase with flurbiprofen affected neither the ability of PAF to elevate the intracellular calcium ion concentration (measured by fura-2 fluorescence) nor its appetency to generate superoxide anions at any PAF concentration examined. It is concluded that activation of guinea pig eosinophils by PAF is receptor-mediated and independent of the concomitant generation of cyclo-oxygenase-derived excitatory prostanoids. Inasmuch as TXA2 may contribute to the pathogenesis of bronchial hyperreactivity, then these data implicate the eosinophil as a potential source of this lipid mediator.
To answer the question whether intracoronary thrombolysis in patients with acute myocardial infarction is beneficial, a randomised trial was started in June 1981 at the Thoraxcenter: so far, 167 patients admitted less than 4 h after onset of symptoms have been enrolled. This interim report describes the effects of reperfusion versus conventional treatment on early and late mortality as well as on global and regional left ventricular function assessed from contrast angiography 2 weeks after the acute phase. In the conventionally treated group (N = 82), 8 patients died in hospital and 7 after discharge {median follow-up 13 months). In the group assigned to thrombolysis (N = 85), 6 patients died in hospital and 4 after discharge. In contrast to this nonsignificant difference in mortality, the haemodynamic data showed a preservation of global left ventricular function after thrombolysis, even when the results were presented on an 'intention to treat' basis. The left ventricular ejection fraction was 56 ± 10% (mean ± SD) in the thrombolysis group versus 44 ± 14% in the conventionally treated group (P10−5). This preservation of left ventricular function was observed both in patients with anterior and in those with inferior infarction. Thombolysis by the intracoronary route has the potential for myocardial salvage; however, the expected benefit on early and late mortality has not yet been demonstrated and this will require the inclusion of a larger number of patients.
Macrophages (mф) in the lungs of COPD patients show a pro-inflammatory phenotype and fail to clear pathogens and apoptotic cells. Whether this is due to local pulmonary environmental or to an inherent mф defect is not clear. We have shown that monocyte-derived macrophages (MDM) from COPD patients show similar defects, with reduced phagocytosis and increased release of pro-inflammatory cytokines and proteases. Kruppel-like factor (KLF)-4 is a transcription factor that is important in the differentiation of mф. This study aimed to examine whether KLF-4 expression was altered during differentiation of monocytes to mф in COPD. Monocytes from control (C=7) and COPD patients (COPD=5) were cultured in GM-CSF (pro-inflammatory phenotype) or M-CSF (resolving phenotype) for 18d, and <i>KLF4</i> gene expression measured using qPCR. <i>KLF4</i> increased during differentiation from 0d to 12d in both subject groups, but was markedly higher in controls compared to COPD MDM. This was observed in both GM and M cultured cells, although GM-MDM expressed twice as much <i>KLF4</i> than M-MDM. In control cells, <i>KLF4</i> decreased by day 18, but remained the same in COPD MDM (Fig. 1). These data indicate a role for KLF4 in mф differentiation. Furthermore, low gene expression in COPD MDM suggests that these cells are unable to differentiate correctly, or take longer to do so, resulting in dysfunctional mф phenotype.
Journal Article Cardiology's new crystal ball: machine learning for outcome prediction Get access Patrick W Serruys, Patrick W Serruys CORRIB Research Centre for Advanced Imaging and Core Laboratory, University of Galway, University Road, Galway H91 TK33, Ireland Corresponding author. Tel: +353 91 524411, Email: patrick.w.j.c.serruys@gmail.com https://orcid.org/0000-0002-9636-1104 Search for other works by this author on: Oxford Academic PubMed Google Scholar Shigetaka Kageyama, Shigetaka Kageyama CORRIB Research Centre for Advanced Imaging and Core Laboratory, University of Galway, University Road, Galway H91 TK33, Ireland https://orcid.org/0000-0003-4982-3203 Search for other works by this author on: Oxford Academic PubMed Google Scholar Yoshinobu Onuma Yoshinobu Onuma CORRIB Research Centre for Advanced Imaging and Core Laboratory, University of Galway, University Road, Galway H91 TK33, Ireland Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, Volume 45, Issue 8, 21 February 2024, Pages 610–612, https://doi.org/10.1093/eurheartj/ehad847 Published: 19 January 2024
We have studied the effect of epithelium removal on the contractile responses to exogenous tachykinins and to endogenous tachykinins released by capsaicin in guinea pig trachea. We also studied the effects of inhibition of endopeptidase (by phosphoramidon, 10 microM, and thiorphan, 100 microM), and of inhibition of cyclooxygenase (by indomethacin, 5 microM) on these responses. The order of potency of exogenous tachykinins was neurokinin A (NKA) greater than neurokinin B (NKB) greater than substance P (SP). Epithelium removal enhanced the sensitivity and magnitude of the contractile response to SP, and to a lesser extent NKA and NKB. Capsaicin induced only a weak contractile response in guinea pig trachea. Phosphoramidon and thiorphan increased the sensitivity to SP, but had no effect on acetylcholine responses. The leftwardshift due to epithelium removal was reduced, but not abolished, by phosphoramidon and thiorphan. NKA- and NKB-induced contractions were also enhanced significantly by phosphoramidon. The effect of epithelium removal was abolished for NKA, but not for NKB. Phosphoramidon also increased significantly the contraction to capsaicin in the presence of epithelium, without altering the response obtained in the absence of epithelium. Indomethacin potentiated the sensitivity and maximal contractile response to all the tachykinins with the greatest effect on SP responses, and to capsaicin. The combination of indomethacin with phosphoramidon or thiorphan abolished the effect of epithelium removal for all the tachykinins. We conclude that the effects of exogenous and endogenous tachykinins are enhanced by removal of epithelium and by inhibition of metalloendopeptidase and cyclooxygenase, suggesting that tachykinins may be degraded by epithelial enzymes, and may release relaxant prostanoids in airways.(ABSTRACT TRUNCATED AT 250 WORDS)
