INTESTINAL GLYCOSAMINOGLYCANS IN NEONATAL NECROTIZING ENTEROCOLITIS

Advanced necrotizing enterocolitis (NEC) is a common neonatal surgical emergency of unknown aetiology. Despite improvements in the prognosis , the aggressive form of the disease is still associated with Signific ant rates of morbidity and mortality. Recent evidence indicates that t he extracellular matrix (ECM) is important in gastrointestinal develop ment and glycosaminoglycans, major constituents of the ECM, are attenu ated in inflammatory bowel disease. The hypothesis of this study was t hat changes in the nature and distribution of intestinal glycosaminogl ycans occur in NEC. The distribution and nature of glycosaminoglycans were determined in 31 sections of well preserved resection margins and severely diseased bowel from eight neonates affected by NEC. An estab lished histological method of glycosaminoglycans analysis using cation ic gold with silver enhancement was employed in this study. The identi ty of specific glycosaminoglycans was also elucidated using a digestio n. In well preserved tissue, staining was seen throughout the full thi ckness of the bowel. The epithelial basement membrane and basolateral surfaces, lamina propria and submucosa were particularly prominent, In moderate disease, patchy loss of anionic sites was frequently observe d with glycosaminoglycans-deficient areas adjacent to intact sites. In severe NEC, there was extensive loss of glycosaminoglycans in most of the sections examined. Glycanase analysis revealed that the glycosami noglycans in well preserved tissue were sensitive to chondroitinase AB C and only vascular sites were sensitive to heparinase III. The conseq uences of glycosaminoglycans loss in NEC as demonstrated in this study are not known but modulation of gastrointestinal glycosaminoglycans c ould be important in the pathogenesis of NEC and map underlie some of the clinical manifestations of this condition.