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Supplementation of the diet with eicosapentaenoic acid and docosahexaenoic acid, the main long-chain omega-3 fatty acids in cell membranes, may have beneficial effects in patients with cystic fibrosis.A prospective study involving 30 patients and 20 control subjects was carried out; eicosapentaenoic plus docosahexaenoic acid was equal to 1.3% of caloric intake in the cystic fibrosis patients. Our present study included the evaluation of eicosapentaenoic and docosahexaenoic acid incorporation into erythrocyte membranes and biological and clinical effects in response to long-term (8 months) supplementation with fish oil as a source of eicosapentaenoic and docosahexaenoic acids in patients with cystic fibrosis.Baseline erythrocyte membrane fatty acids showed low levels of linoleic acid and eicosapentaenoic acid and mild elevation of 18:3n6, but similar docosahexanoic acid and other fatty acids in cystic fibrosis patients compared with controls. Fish oil supplementation led to a 1.7-fold (p.05) and 1.3-fold (not significant) increase of eicosapentaenoic acid in erythrocyte membrane phospholipids after 4 and 8 months of supplementation, respectively, and to a 1.67-fold (p.05) and 1.38-fold (p.05) increase of docosahexanoic acid, respectively. Along with these changes, there was a progressive decrease of arachidonic acid (from 8.51 to 6.67 g/100 fatty acids at 4 months and 4.83 g/100 fatty acids at 8 months; p.05) and an increase of linoleic acid (p.05) in membrane phospholipids. Analysis of inflammatory markers showed a significant decrease of serum immunoglobulin G (IgG) and of alpha-1 antitrypsin (p.05) concentrations. Pulmonary function testing showed mild but significant improvement of forced expiratory volume (FEV)-1 from 61% +/- 19% to 57% +/- 19% of predicted values (p.05). The number of days of antibiotic therapy during the study period was markedly lower compared with the preceding 8-month period (392 versus 721 days; p.05).Long-term eicosapentaenoic plus docosahexanoic acid supplementation (8 months) has positive effects, such as decreasing inflammation, in cystic fibrosis.

Summary: Peptidase activities have been investigated in the brush border of human proximal jejunum by using dipeptides and tripeptides and β-naphthylamides of glycyl-L-proline and amino acids as substrates. The activities hydrolyzing glycyl-L-leucine, L-phenylalanyl-L-alanine, and L-leucylglycylglycine in the brush border were found to be only 1.5, 15, and 16% of the total peptidase activities present in the intestinal mucosa, but the specific activities for the hydrolysis of these substrates appeared in the brush border to be as high as or higher than that of sucrase. The enzyme(s) hydrolyzing L-phenylalanyl-L-alanine in the brush border showed different properties from the enzyme(s) hydrolyzing the same substrate in the cytosol, the former being completely resistant to p-hydroxymercuribenzoate, partially resistant to heating, and inhibited by puromycin by about 50%. On the other hand, the enzymatic activities hydrolyzing the β-naphthylamides of glycyl-L-proline, L-leucine, and α-L-glutamic acid as well as N-carbobenzoxy-L-prolyl-L-alanine were shown to be almost totally localized in the brush border. All the peptidase and β-naphthylamidase activities studied were well solubilized by papain from the brush border membrane with the only exception being the activity hydrolyzing glycyl-L-leucine. By acrylamide gel electrophoresis, three enzymatic activities were clearly separated from each other as well as from the oligoaminopeptidase- (EC 3.4.11.2) splitting L-leucyl-β-naphthylamide: (1) the aminopeptidase A (EC 3.4.11.7) hydrolyzing α-L-glutamyl-β-naphthylamide; (2) the dipeptidylaminopeptidase IV (EC 3.4.14.-) liberating glycyl-L-proline from glycyl-L-prolyl-β-naphthylamide; and (3) a carboxypeptidase hydrolyzing N-carbobenzoxy-L-prolyl-L-alanine (EC 3.4.12.-). Brush border peptidases (oligoaminopeptidase, aminopeptidase A, dipeptidylaminopeptidase IV, and carboxypeptidase) and cytosol dipeptidase and tripeptidase activities were measured in intestinal biopsies of celiac patients utilizing specific substrates. These enzymatic activities were normal in eight children with celiac disease in histologic remission, with only aminopeptidase A being reduced to 70% of control values. On the contrary, in the atrophic mucosa of 12 children with active celiac disease, these were all significantly but not equally reduced. Speculation: The identification of the above-mentioned peptidases in the intestinal brush border demonstrates the importance of this sub-cellular organelle in the digestion of protein and peptides complementary to intraluminal and intracellular digestion. Brush border peptidases are probably involved in the digestion of gliadin, which is very rich in glutamic acid and proline residues; as these activities are lowered in the atrophic celiac mucosa, digestibility of gliadin peptides might be reduced during active celiac disease.