Cystic fibrosis alpha

Griese M ci al. Reduced proteolysis of surfactant protein A and changes of the bronchoalveolar lavage fluid proteome by inhaled alpha 1-protease inhibitor in cystic fibrosis. Electrophoresis 2001 22 165-171. 

Norez C, Noel S, Wilke M, Bijvelds M, Joma H, Melin P, DeJonge H, Becq F. Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the alpha-glucosidase inhibitor miglustat. FEES Lett. 2006 580 2081-2086. 

In particular, excessive proteolysis of elastin by HLE has been implicated in pulmonary emphysema [19]. In this case, the imbalance appears to result from reduced levels of active extracellular alpha,-proteinase inhibitor (a,-PI), the primary plasma inhibitor of HLE. This decrease is caused either by a genetic disorder (PiZZ phenotype individuals) or by reduction in the elastase inhibitory capacity (EIC) of ai-PI due to its oxidative inactivation by tobacco smoke [20]. The detailed evidence supporting the potential role of elastase in the development of emphysema has been extensively reviewed [21] and will not be repeated here. The fact that HLE is also a potent secretagogue [22] may play a role in several disease states, including cystic fibrosis [23], chronic bronchitis [24], and acute respiratory distress syndrome (ARDS) [25]. The mechanism of the secretagogue activity is not known, but, since the HLE-induced secretion can be blocked by specific HLE inhibitors, it appears to require catalytic activity by the enzyme [26]. 

Meyer KC, Lewandoski JR, Zimmerman JJ, Nunley D, Calhoun WJ, Dopico GA Human neutrophil elastase and elastase/alpha 1-antiprotease complex in cystic fibrosis. Am J Respir Dis 144 (1991) 580-5. 

Duma.se alpha is indicated for the treatment of cystic fibrosis in conjunction with other available therapies, such as antibiotics, brunchodilators, and corticosteroids. Adult dosage is 2.S mg inhaled once daily, administered via a recommended nebulizer. Dornase alpha. should not be mixed or diluted with other agents in the nebulizer becau.se of the possibility of adverse physicochemical changes that may affect activity. Common adverse effects include sure throat. hoarsene.s.s. and facial edema. 

Domase alpha, a recombinant human deoxyribonuclease I, a mucolytic enzyme with respiratory stimulant properties, is nsed to improve pulmonary function and reduce the frequency of moderate to severe respiratory infections in patients with cystic fibrosis. 

Congenital alpha-1 antitrypsin deficiency cystic fibrosis... 

There are other diseases whose incidence is likely to remain static. Cystic fibrosis is the most common genetic disorder in Caucasian populations. It afflicts between one in 1600 and one in 8000. In the UK, about 400 infants per year are bom with the disorder and less than 25% would be expected to live until their thirties. The population of sufferers depends on survival rates but, with a United States incidence of one in 3800, a figure of the order of 10 000 is probable, well within the orphan drag Umit. Recombinant DNase, Pulmozyme (doraase alpha) is an orphan drug that breaks down the thick mucous secretions associated with the disease. It gained regulatory approval in 1994 but the cost per patient is about 10 000 per year. °... 

Esophageal varices in children are a manifestation of portal hypertension that causes hepatofugal flow through esophageal collateral veins to drain into the superior vena cava. The most common children s diseases that cause portal hypertension include umhilical venous catheterization, biliary atresia, alpha-1 antitrypsin deficiency, autosomal recessive polycystic renal disease and cystic fibrosis. 

Black HR, Yankaskas JR, Johnson LG, Noah TL. Interleukin-8 production by cystic fibrosis nasal epithehal cells after tumor necrosis factor-alpha and respiratory syncytial virus stimulation. Am J Respir Cell Mol Biol 1998 19 210. 

Tabary O, Escotte S, Couetil JP, Hubert D, Dusser D, PucheUe E, and Jacquot J. High susceptibility for cystic fibrosis human airway gland cells to produce IL-8 through the I kappa B kinase alpha pathway in response to extracellular NaCl content. J Immunol 2000 164 3377. 

Inborn errors of metabolism Wilson s disease Alpha-l-antitrypsin deficiency Glycogen storage disease Tyrosinaemia Galactosaemia Cystic fibrosis Defects of fatty acid oxidation Other... 

This work was supported by grants fiom the NHLBI (HL51811, HL59412), the NIDDK (DK51809, DK58327), the Cystic Fibrosis Foundation and the Alpha One Foundation. 

Canonico AE, Brigham KL, Carmichael LC, Plitman JD, King GA, Blackwell TR, Christman JW. Plasmid-liposome transfer of the alpha 1-antitrypsin gene to cystic fibrosis bronchial epithelial cells prevents elastase-induced cell detachment and cytokine release. Am J Respir Cell Mol Biol 1996 14 348-355. 

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