Overview - Richard Hamilton
Intestinal Repair - Decker Butzner
Nitric Oxide - Nick Anstey

J. Decker Butzner. Department of Pediatrics, University of Calgary. Calgary, Alberta, Canada.

Infants have very limited nutritional reserves and are extremely susceptible to protein-energy malnutrition. In addition the intestine of the infant relies on its luminal contents as the major energy source to support epithelial development. Normally intestinal epithelial cells divide in the crypts and migrate up to the tips of the villi where they are shed after three to five days. Over the course of this migration, the epithelium matures by synthesising proteins that function to digest and transport nutrients.

Protein-energy malnutrition markedly impairs epithelial turnover and maturation. The rate of cell division is decreased and migration up the crypt-villus unit is slowed. Malnutrition also disrupts epithelial function, as evidenced by increased permeability, decreased disaccharidase activities, increased secretion and altered digestion and absorption of nutrients.

When the intestine of a malnourished infant is subjected to intestinal injury, such as that caused by an acute enteric viral or bacterial infection, epithelial development and repair are further disrupted. The malnourished infant’s injured intestine cannot support normal rates of epithelial division and maturation. This results in a prolongation of the diarrhoeal illness and a further reduction in nutrient digestion and absorption. Intestinal regulation of water and electrolyte balance is impaired. Intestinal recovery is markedly delayed or totally absent. Both experimental and clinical studies have demonstrated that careful refeeding of foods containing protein and complex carbohydrates can stimulate repair and recovery of intestinal function. Careful early refeeding decreases the severity and duration of diarrhoeal illness by stimulating intestinal repair in infants, including those with severe protein-energy malnutrition.

NM Anstey^{1 2}, RH Kukuruzovic², DR Brewster^{2 1}. Menzies School of Health Research, and ²Northern Territory Clinical School, Darwin, Northern Territory, Australia

Among the earliest pieces of evidence for endogenous NO production in humans was the serendipitous demonstration in 1982 of markedly high urinary excretion of NO metabolites occurring during an episode of diarrhoeal disease. Nitric oxide mediates and modulates a multitude of physiological and pathophysiological processes in all organ systems. Constitutive low-level NO production is from endothelial (eNOS) and neuronal (nNOS) isoforms of nitric oxide synthases (NOS). In contrast, inducible NOS (iNOS) is induced by a wide variety of inflammatory stimuli and results in high level NO production. NO is known to have both disease-protective and disease-producing effects in a wide variety of disease states, and a similar dual role is likely to occur in diarrhoeal disease. In the gut, in vitro and animal studies have shown NO mediates increased gastric mucous secretion, modulates intestinal epithelial fluid secretion, increases intestinal permeability, increases mucosal blood flow, mediates mucosal repair, decreases leucocyte adhesion to vascular endothelium, decreases neutrophil aggregation/secretion, and down-regulates production of pro-inflammatory cytokines such as TNF and IL-1. NO is known to mediate macrophage antimicrobial activity against viruses, bacteria and protozoa.