1,721,401 research outputs found
Controllo della broncopneumopatia cronica ostruttiva in Italia
No full textRassegna della letteratura sul ttrattamento necessario per il controllo della BPC
Cross-talk between pro-inflammatory transcription factors and glucocorticoids
No full textAsthma is a chronic inflammatory disease of the airway that is characterized by cellular infiltration and activation. These processes are induced by overexpression of chemokines and cytokines, such as eotaxin, IL-1beta and GM-CSF. These mediators are downstream targets for the transcription factors activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), which control the expression of most immunomodulatory genes and whose activity and expression are elevated in asthma. Glucocorticoids are the most effective anti-inflammatory drugs used in the treatment of chronic inflammatory diseases such as asthma. They act by binding to a specific glucocorticoid receptor (GR) that on activation translocates to the nucleus and either increases (transactivates) or decreases (transrepresses) the expression of responsive genes. Transrepression is the major mechanism of glucocorticoid action in inhibiting inflammatory gene expression. Thus, the ability of the transcription factors AP-1 and NF-kappaB to induce gene transcription is attenuated by GR. Although only 5-10% of asthmatic subjects are glucocorticoid-insensitive, these subjects account for over 50% of the health-care costs for asthma (> $6 billion per annum). Examining these patients also gives an insight into important aspects of glucocorticoid action in controlling inflammation and into the development of potential new drugs. Biochemical and genomic studies have indicated abnormal induction of the c-Jun N-terminal kinase (JNK) pathway in some of these patients. The ability of most patients to respond to dexamethasone with induction of histone acetylation correlated with nuclear translocation of GR. However, a subgroup of these patients had an inability to correctly interact with the basal transcription complex in spite of high levels of nuclear GR. This suggests that cross-talk between pro- and anti-inflammatory transcription factors may modulate activation of the transcriptional complex and thereby reduce steroid actions
Gene-environment interactions in the development of chronic obstructive pulmonary disease
No full textThe completion of the Human Genome Project, the HapMap project, technological advances in single-nucleotide-polymorphism genotyping and the potential of genome-wide association analysis will allow the identification of susceptibility genes for chronic obstructive pulmonary disease. The challenge is to understand the influence of multiple genetic factors and multiple environmental factors as well as gene-gene and gene-environment interactions. Careful clinical characterization of phenotypes for chronic obstructive pulmonary disease is essential and this will include comparison of biomarkers of distinct pathologies including radiological assessment to separate the components of pulmonary emphysema and small-airway disease
Kinase targets and inhibitors for the treatment of airway inflammatory diseases: the next Generation of drugs for severe asthma and COPD?
No full textKinases are believed to play a crucial role in the expression and activation of inflammatory mediators in the airway, in T-cell function, and in airway remodeling. Important pro-inflammatory transcription factors such as activating protein-1 and nuclear factor kappaB, which are activated in airway disease, require kinase activation to switch on inflammatory genes, while other kinases can regulate mRNA half-life. Selective kinase inhibitors have been developed that reduce inflammatory gene expression and some characteristics of disease in animal models. Targeting specific kinases that are overexpressed or overactive in disease should allow for selective treatment of airway inflammatory diseases. Interest in this area has intensified due to the success of the specific Abelson murine leukemia viral oncogene homolog tyrosine kinase inhibitor, imatinib mesylate, in the treatment of chronic myelogenous leukemia. Encouraging data from animal models and primary cells and early phase I and II studies in other diseases suggest that inhibitors of p38 mitogen-activated protein kinase and inhibitor of kappaB kinase-2 may prove to be useful novel therapies in the treatment of severe asthma and chronic obstructive pulmonary disease
Chemokines and asthma.
No full textThe migration of cells towards and into the site of an inflammatory insult is critical for maintenance of the inflammatory response and its resolution. This is particularly so in the case of asthma where recruitment of key effector cells may control disease severity, responsiveness to current therapies and the airway remodelling associated with the disease. Chemokine receptor antagonists have the hope of preventing inflammatory cell recruitment to the airway and perhaps as a consequence affect the resolution of airway remodelling. A number of selective antagonists directed at various CC and CXC receptors thought to be important in asthma are currently at various stages of clinical development. Results from these studies will determine whether chemokine receptor antagonists will prove beneficial in severe glucocorticoid-dependent and -resistant asthmatic subjects. Furthermore, it is possible that early treatment with these agents may prevent the disease from becoming established
Pathogenic link between chronic obstructive pulmonary disease and squamous cell lung cancer
No full textSmoking history effect on peripheral lung inflammation and gene transcription in chronic obstructive pulmonary disease
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Pathogenic link between chronic obstructive pulmonary disease and squamous cell lung cancer
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