Emphysema etiology

In the past number of years a number of studies have shown that in a variety of diseases there is a significant oxidation of Met residues to Met(O) in specific proteins that results in a loss of biological activity. These diseases include cataracts, rheumatoid arthritis, adult respiratory distress syndrome and emphysema. The most convincing evidence that Met(O) in proteins may be involved in the etiology of a pathological condition comes from studies with a-l-PI. It is well accepted that a-l-PI is inactivated upon oxidation of its Met residues. A decreased activity of a-l-PI in lung tissue that would result in an increased elastase activity has been associated with pulmonary emphysema. In patients who have a... 

Theophylline reduces contractile activity of smooth musculature, widens bronchi and blood vessels, reduces pulmonary vascular resistance, stimulates the respiratory center, and increases the frequency and power of cardiac contractions. It is used for bronchial asthma, preventing attacks, and systematic treatment. Theophylline is also used for symptomatic treatment of bronchospastic syndrome of a different etiology (chronic obstructive pulmonary disease, chronic bronchitis, and pulmonary emphysema). A large number of combined drags are based on theophylline. Synonyms of theophylline are adophyllin, asthmophyllin, theocin, and many others. 

Weinbaum, G., Giles, R.E. and Krell, R.D., eds. (1991) Pulmonary Emphysema The Rationale for Therapeutic Intervention, Part 2. Putative Etiologies of Emphysema Proteases/Inhibitors/Modulators, Ann. N.Y. Acad. Sci. 624, 45-146. 

It should be pointed out that while the protease-antiprotease theory of emphysema is currently the dominant hypothesis used to explain the etiology of emphysema, other factors must also be considered as contributing to the development of this disease. For example, oxidants, present in smoke, probably contribute in other fashions besides inactivating a -Pl. Such substances are capable of oxidizing a variety of cellular components (lipids, enzymes, and nucleic acids) and in this way may destroy parts of the alveolar epithelium, thus facilitating the exposure of elastin fragments present in the interstitial space to elastase. 

Pulmonary emphysema is a chronic progressive disorder wherein the elastic fibers of the lung become fragmented and dysfunctional with the result of a loss of elastic recoil. One result is that the patient must consciously and forcibly exhale. A prominent proposal for the etiology of the disease has been the lack of proteinase inhibitors that would otherwise prevent proteolytic degradation of the fiber.To help study the disease, a successful animal model for pulmonary emphysema was developed in which direct instillation of the proteolytic enzyme elastase into the lung became the causative agent. ° ... 

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