Cystic fibrosis reduction

Cystic fibrosis is the most common lethal autosomal-recessive disease, in which oxidative stress takes place at the airway surface [274]. This disease is characterized by chronic infection and inflammation. Enhanced free radical formation in cystic fibrosis has been shown as early as 1989 [275] and was confirmed in many following studies (see references in Ref. [274]). Contemporary studies also confirm the importance of oxidative stress in the development of cystic fibrosis. Ciabattoni et al. [276] demonstrated the enhanced in vivo lipid peroxidation and platelet activation in this disease. These authors found that urinary excretion of the products of nonenzymatic lipid peroxidation PGF2 and TXB2 was significantly higher in cystic fibrotic patients than in control subjects. It is of importance that vitamin E supplementation resulted in the reduction of the levels of these products of peroxidation. Exhaled ethane, a noninvasive marker of oxidative stress, has also been shown to increase in cystic fibrosis patients [277]. 

Nonpeptide receptors Adenosine Aj Human cDNA Cardiac arrhythmia, asthma, myocardial ischemia, obesity, pain, renal disease, sleep apnea, stroke, cancer, inflammation, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Bradycardia, lipolysis inhibition, reduction of glomerular filtration and natriuresis, tubero-glomerular feedback, antinociception, renal vasodilatation-constriction, reduction of central cholinergic and noradrenergic nerve activity, presynaptic inhibition of excitatory neuro transmission... 

Bayesian probabilities are absolutely reliant upon an accurate family history of the disease in question. Family history affects the prior or a priori likelihood that a propositus is a carrier for a genetic disease. Because many hereditary disorders are autosomal recessives and manifest rarely in a sibship, any record of a known hereditary disorder can be important in providing an accurate risk reduction. This can be particularly important in cystic fibrosis, where one of the mutations is often known in affected individuals while the other is often private and uncharacterized. Fven an affected first cousin can boost the a priori probability in a Caucasian non-Jew from 1/241 to 1/8. 

Unlabeled Uses Treatment of edema associated with CHF, liver cirrhosis, and nephrotic syndrome treatment of hypertension reduces lithium-induced polyuria, slows pulmonary function reduction in cystic fibrosis... 

P. L. Shah, S. Scott, A. Laiulcy, G. Martin, C. Marriott, and M. E. Hodson. Preliminary report on in vivo reduction of sputum viscosity in cystic fibrosis patients treated... 

Q10 Pancreatic insufficiency occurs in approximately 80% of cystic fibrosis patients. There is a marked reduction in the water, electrolyte and enzyme content of pancreatic secretion. Because of deficient digestive enzymes, there is inadequate digestion and absorption of nutrients and some nutritional deficiency occurs. 

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]. 

The role of dornase alfa in modifying bronchial secretions in patients with cystic fibrosis has been evaluated in 54 subjects aged 5 years or over (1). They were treated for 12 months with mesna by nebulizer bd and oral ambroxol (30 mg bd). Dornase alfa was then given once daily by aerosol 2.5 mg for 12 months. Mesna and ambroxol caused reductions in FEVi nd FVC (FEVi feu by 11%, FVC by 13%). After 12 months of dornase aUa, FEVi had increased by 7.7% and FVC by 5.3%. The patients found treatment with dornase alfa more acceptable than mucoljdic therapy. Hemoptysis was the only reported adverse effect, but it occurred frequently in only one patient. 

The search for useful inhaled antibiotics has been driven, in part, by a concern about the adequacy of systemic antimicrobial therapy for respiratory infections. Some agents, including aminoglycoside antibiotics, exhibit limited penetration into respiratory tract secretions. In fact, aminoglycosides may achieve sputum concentrations that are 12% of related serum concentrations. In addition, cystic fibrosis patients are often colonized with mucoid strains of Pseudomonas aeruginosa. This phenotype is associated with a further reduction in penetration of antibiotics. 

Some progress has been made in developing alternative devices for the delivery of inhaled antimicrobial therapies. Colistin has been formulated in a dry powder inhaler and evaluated in healthy individuals and patients with cystic fibrosis [40]. Peak semm concentrations of colistin were 2.5-5 times higher when 25 mg of colistin sulfate dry powder was inhaled compared to 160 mg of colistin sulfomethate delivered by nebulization. Some patients experienced a decrease in pulmonary function and severe cough with the dry powder however, the investigators felt that this may be improved with a reduction in dose. 

Vasconcellos CA. Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. Science 2002, 263, 969-971. 

However, while these findings are of potential significance to the amplification and perpetuation of the airway inflammation in adult cystic fibrosis patients, other studies, especially studies in children with cystic fibrosis, have not consistently detected the marked reductions in IL-10 (73). The reason for these inconsistencies is not immediately apparent, though the discrepancies may in part reflect the time course of evolution of pulmonary inflammation. 

The administration of a diet restricted in sodium chloride induces a normal response of the kidney and reduced electrolytes in urine, but the sweat glands continue to excrete excessive amounts of electrolytes. As a result, patients with cystic fibrosis are oversensitive to heat in that they lose large amounts of sodium chloride in the sweat. The loss of sodium leads to a reduction of the extracellular fluid with vascular collapse. The situation is readily reversed by the intravenous administration of saline [139]. 

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