ABSTRACT
BACKGROUND: The aetiology of biliary atresia (BA) is still unresolved. The study's aim was to investigate the distribution of extracellular matrix proteins and cellular adhesion molecules in children with BA compared to other cholestatic liver disease (CLD) and normal liver architecture (NLA). PATIENTS: Liver biopsies were obtained from children with BA (n=13), CLD (n=6) and NLA (n=8). METHOD: We systematically analysed ultra thin frozen sections from the liver hilum stained with 25 monoclonal antibodies for cellular characterisation, extracellular matrix proteins and adhesion molecules. RESULTS: 2 changes were specifically found in BA: laminin beta1 was reduced in children with BA vs. NLA and CLD. Conversely, integrin alpha 3 was increased in BA vs. NLA and CLD (p<0.05). Furthermore, we detected changes in a similar pattern for both BA and CLD vs. NLA: in BA and CLD perlecan was increased. On the contrary, integrin beta1 and entactin were decreased vs. NLA (p<0.05). DISCUSSION: Extracellular matrix proteins and adhesion molecules mediate cellular polarity and integrity, development of tubular structures, and proliferation. Therefore, our findings can be important for the understanding of the genesis of BA. CONCLUSION: The composition of extracellular matrix proteins and adhesion molecules in children with BA differs from NLA and other CLD in distribution of laminin beta1 and integrin alpha 3, which may have implications for genetic, immunologic and environmental associations in BA.
Subject(s)
Biliary Atresia/pathology , Cell Adhesion Molecules/metabolism , Extracellular Matrix Proteins/metabolism , Integrins/metabolism , Liver/pathology , Bile Ducts, Intrahepatic/pathology , Biopsy , Child , Child, Preschool , Cholestasis, Intrahepatic/pathology , Female , Humans , Infant , Integrin alpha3/metabolism , Integrin beta1/metabolism , Laminin/metabolism , Male , Membrane Glycoproteins/metabolism , Reference ValuesABSTRACT
UNLABELLED: Standardised, concentrated neonatal parenteral nutrition (PN) regimens can overcome early nutritional deficits in very preterm infants. A PN regimen with increased macronutrient content (standardised, concentrated, added macronutrients parenteral (SCAMP)) has been shown to improve early head growth in a randomised controlled trial. Line complications including late onset sepsis were secondary outcomes of this study. Infants were started on standardised, concentrated PN at birth and randomised at 2-5 days to either switch to SCAMP or remain on control PN. Central venous catheter (CVC), blood culture (BC) and inflammatory marker data were collected for the 28-day intervention period. 150 infants were randomised with mean (SD) birth weight (g) of 900 (158) versus 884 (183) in SCAMP (n=74) and control (n=76) groups, respectively. There were no differences in CVC use/type or duration or in positive/negative BC with/without associated C reactive protein rise in SCAMP versus control groups. Increasing the macronutrient content of a standardised, concentrated neonatal PN regimen does not increase CVC complication rates. TRIAL REGISTRATION NUMBER: ISRCTN 76597892.
