Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula

At present, not much is known about the absorption and metabolism of human milk (HM) oligosaccharides in term and preterm infants. We investigated the renal excretion of lactose and complex oligosaccharides in preterm infants fed HM ( n = 9, mean actual body weight 2290 g) or a cow's milk-based infant formula ( n = 9, mean actual body weight 2470 g). We found that the renal excretion of lactose in HM-fed infants was slightly lower than in formula-fed infants (14.0 ± 7.4 versus 20.4 ± 8.7 mg kg^-1 day^-1, mean ± SD). The excretion of neutral sugars deriving from oligosaccharides was similar in HM-fed and formula-fed infants (3.8 ± 2.1 versus 2.9 ± 0.9mgkg^-1 day^1-); the difference between means was not statistically significant. The separation and characterization of oligosaccharides by high-pH anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) and subsequent analysis by fast atom bombardment-mass spectrometry (FAB-MS) revealed a more complex pattern in HM-fed infants compared to the formula-fed group. Lactose-derived oligosaccharides characteristic for HM (e.g lacto- N -tetraose, and lacto- N -fucopentaoses I and II) were excreted in HM-fed but not in formula-fed infants. These results indicate that nutrition has a significant impact on the oligosaccharide composition in urine of preterm infants.     

The anti‐inflammatory effect of combined complement and CD14 inhibition is preserved during escalating bacterial load

Combined inhibition of complement and CD14 is known to attenuate bacterial-induced inflammation, but the dependency of the bacterial load on this effect is unknown. Thus, we investigated whether the effect of such combined inhibition on Escherichia coli- and Staphylococcus aureus-induced inflammation was preserved during increasing bacterial concentrations. Human whole blood was preincubated with anti-CD14, eculizumab (C5-inhibitor) or compstatin (C3-inhibitor), or combinations thereof. Then heat-inactivated bacteria were added at final concentrations of 5 × 10⁴−1 × 10⁸/ml (E. coli) or 5 × 10⁷−4 × 10⁸/ml (S. aureus). Inflammatory markers were measured using enzyme-linked immunosorbent assay (ELISA), multiplex technology and flow cytometry. Combined inhibition of complement and CD14 significantly (P < 0.05) reduced E. coli-induced interleukin (IL)-6 by 40–92% at all bacterial concentrations. IL-1β, IL-8 and macrophage inflammatory protein (MIP)-1α were significantly (P < 0.05) inhibited by 53–100%, and the effect was lost only at the highest bacterial concentration. Tumour necrosis factor (TNF) and MIP-1β were significantly (P < 0.05) reduced by 80–97% at the lowest bacterial concentration. Monocyte and granulocyte CD11b were significantly (P < 0.05) reduced by 63–91% at all bacterial doses. Lactoferrin was significantly (P < 0.05) attenuated to the level of background activity at the lowest bacterial concentration. Similar effects were observed for S. aureus, but the attenuation was, in general, less pronounced. Compared to E. coli, much higher concentrations of S. aureus were required to induce the same cytokine responses. This study demonstrates generally preserved effects of combined complement and CD14 inhibition on Gram-negative and Gram-positive bacterial-induced inflammation during escalating bacterial load. The implications of these findings for future therapy of sepsis are discussed.     

Diagnostic and therapeutic applications of bentiromide screening test for exocrine pancreatic insufficiency in patients with cystic fibrosis

The bentiromide test for exocrine pancreatic function was carried out in normal volunteers, patients with cystic fibrosis (CF) without clinical evidence of pancreatic dysfunction, and CF patients with clinically significant exocrine pancreatic insufficiency. The test was performed with and without the concomitant administration of a Lundh test meal.p-Aminobenzoic acid was given on a separate occasion to eliminate false positives due to factors unrelated to pancreatic disease. Correct classification of 25 CF patients with pancreatic insufficiency and 9 CF patients without clinical pancreatic dysfunction was possible by interpreting the results of the above three tests. Isoamylase determinations would have misclassified 20% of the CF patients with pancreatic insufficiency, but were able to detect the CF patients without clinical pancreatic dysfunction on the basis of an elevated pancreatic amylase isoenzyme. The bentiromide test results were normal in CF patients without clinical pancreatic dysfunction despite previous findings of decreased bicarbonate secretion in this group. However, the bentiromide test did appear to be useful in the evaluation of therapeutic intervention with exogenous pancreatic enzymes and other adjunctive therapy.This study was presented in part at the 8th International Congress on Cystic Fibrosis, Toronto, Ontario, May 1980.