Despite developments in percutaneous transluminal coronary angioplasty, the success of this treatment method remains clouded by early and late reocclusion. Increased experience, advances in technology, and the introduction of adjunctive devices have contributed to a higher procedural success rate (90% to 95%) and to a lower complication rate (4% to 5%), in spite of the expanded indications for angioplasty. Late renarrowing of the treated coronary artery, in combination with recurrence of angina pectoris, occurs in 15% to 40% of angioplasty patients. Several multicenter randomized trials of pharmaceutical agents have been conducted or are in progress, in an effort to diminish the rate of late reocclusion. No major breakthrough has been reported, although a clear progression has been made in the understanding of the restenosis phenomenon. It is evident that thrombin plays a detrimental role in the vascular wall injury resulting from angioplasty procedures. Current pharmacologic research concentrates on direct inhibition of prothrombin conversion and thrombus formation. Animal experimental work in this field is encouraging, and the results of clinical trials will elucidate important questions about the safety, efficacy, and immuno-allergic potential of modern antithrombotic medication.
No abstract is provided for this article.
The increased expression of inflammatory genes in inflammatory lung diseases is regulated by acetylation of core histones, whereas histone deacetylase-2 (HDAC2) suppresses inflammatory gene expression. Corticosteroids suppress inflammatory genes in asthma by inhibiting histone acetyltransferase and in particular by recruiting HDAC2 to the nuclear factor-kappaB-activated inflammatory gene complex. This involves deacetylation of the acetylated glucocorticoid receptor. In COPD, severe asthma and asthmatics who smoke, HDAC2 is reduced, thus preventing corticosteroids from suppressing inflammation. The reduction in HDAC2 appears to be secondary to increased oxidative and nitrative stress in the 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. Theophylline is a direct inhibitor of oxidant-activated phosphoinositide-3-kinase-delta, which is involved in inactivation of HDAC2. In the future selective PI3Kdelta inhibitors and more direct activators of HDAC2 may be used to treat corticosteroid-resistant inflammatory diseases of the lung, including COPD, severe asthma and asthma in smokers.
Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective. In COPD there is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterized by increased numbers of alveolar macrophages, neutrophils and cytotoxic T lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines and growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence of the involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases. The inflammation and proteolysis observed in COPD are an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.
A nalyst projections for the drug-eluting stent (DES) market estimated that the total number of DES implanted in 2010 would go beyond 4.5 million worldwide.Although the initial results seemed promising, longer-term follow-up in a broader range of patients revealed some pitfalls.][3][4][5][6][7][8] The number of stents currently under investigation is substantial.They are all loaded with drugs that interfere with pathways in the process of inflammation and neointimal proliferation.However, the process of restenosis is a sequence of complex events that has been only partly elucidated over the last 2 decades. 9Locally acting DES provide the opportunity to interfere with the various mechanisms responsible for each step in the restenotic cascade, and a wide variety of different agents are currently available.Although only sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) have received US Food and Drug Administration (FDA) approval to date, multiple alternative devices are attempting to find their way to achieve the same goal, namely a reduction of restenosis and the need for repeat interventions. EverolimusA second derivative of the Limus family is everolimus, a sirolimus analog with a single minimal alteration in its
No abstract is provided for this article.
