Search PubMed⌕ Search

PubMed · 16256325

Future perspectives in COPD.

Abstract

The pathophysiology of chronic obstructive pulmonary disease (COPD) is complex. The development of a multidimensional index--such as the BODE index--provides a means of classifying patients with COPD that also correlates with their prognosis. The individual components of the BODE index--body mass index (B), airflow obstruction (O) dyspnoea (D) and exercise capacity (E)--incorporate the pulmonary as well as the systemic effects seen in patients with COPD. Recent research has focussed on examining these impairments (including those of metabolism and inflammation) more carefully, and determining the effects of treatment on both the systemic and physiological aspects of COPD. Ongoing research initiatives by the public and private sector will contribute to our understanding of the disease processes underlying COPD, our understanding of the benefits associated with commonly used pharmacotherapies, as well as laying the foundations for the development of new agents and therapeutic tools. Advances in the use of pharmacotherapy have been mirrored by research to better define the benefits associated with pulmonary rehabilitation. Many questions remain to be answered, but a comprehensive approach is now considered essential to the life-long management of COPD, and will undoubtedly reduce the considerable socio-economic burden of COPD.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bartolome Celli, Roger Goldstein, José Jardim, Katharine Knobil. 2005-10-26. Future perspectives in COPD.. https://doi.org/10.1016/j.rmed.2005.09.014

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Ferulic acid with ascorbic acid synergistically extenuates the mitochondrial dysfunction during beta-adrenergic catecholamine induced cardiotoxicity in rats.

Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.

Adrenergic beta-Agonists↗

The MLCK-mediated alpha1-adrenergic inotropic effect in atrial myocardium is negatively modulated by PKCepsilon signaling.

The present study examined the role of myosin light chain kinase (MLCK), PKC isozymes, and inositol 1,4,5-trisphosphate (IP(3)) receptor in the positive inotropic effect of alpha(1)-adrenergic stimulation in atrial myocardium. We measured inotropic effects of phenylephrine (0.3-300 microM) in isolated left atrial preparations (1 Hz, 37 degrees C, 1.8 mM Ca(2+), 0.3 microM nadolol) from male 8-week FVB mice (n=200). Phenylephrine concentration-dependently increased force of contraction from 1.5+/-0.1 to 2.8+/-0.1 mN (mean+/-s.e.m., n=42), which was associated with increased MLC-2a phosphorylation at serine 21 and 22 by 67% and translocation of PKCepsilon but not PKCalpha to membrane (+30%) and myofilament (+50%) fractions.MLCK inhibition using ML-7 or wortmannin right-shifted the concentration-response curve of phenylephrine, reducing its inotropic effect at 10 microM by 73% and 81%, respectively. The compound KIE1-1 (500 nM), an intracellularly acting PKCepsilon translocation inhibitor peptide, prevented PKCepsilon translocation and augmented the maximal inotropic effect of phenylephrine by 40%. In contrast, inhibition of Ca(2+)-dependent PKC translocation (KIC1-1, 500 nM) had no effect. Chelerythrine, a PKC inhibitor, decreased basal force without changing the inotropic effect of phenylephrine. The IP(3) receptor blocker 2-APB (2 and 20 microM) concentration-dependently decreased basal force, but did not affect the concentration-response curve of phenylephrine. These results indicate that activation of MLCK is required for the positive inotropic effect of alpha(1)-adrenergic stimulation, that the Ca(2+)-independent PKCepsilon negatively modulates this effect, and that PKCalpha and IP(3) receptor activation is not involved.

Adrenergic beta-Agonists↗