Ischaemia-reperfusion injury (IRI) is of obvious relevance in situations where there is an interruption of blood supply to the gut, as in vascular surgery, or in the construction of free intestinal grafts. It is now appreciated that IRI also underlies the gut dysfunction that occurs in early shock, sepsis, and trauma. The events that occur during IRI are complex. However, recent advances in cellular biology have started to unravel these underlying processes. The aim of this review is to provide an outline of current knowledge on the mechanisms and consequences of IRI.Initially, IRI appears to be mediated by reactive oxygen metabolites and, at a later stage, by the priming and activation of polymorphonuclear neutrophils (PMN). Ischaemia-reperfusion injury can diminish the barrier function of the gut, and can promote an increase in the leakage of molecules (intestinal permeability) or the passage of microbes across the wall of the bowel (bacterial translocation). Ischaemia-reperfusion injury to the gut can result in the generation of molecules that may also harm distant tissues.

The branched‐chain amino acids (BCAA), isoleucine, leucine and valine, are unique in that they are principally metabolized extrahepatically in the skeletal muscle. This observation led to the investigation of these nutrients in a number of clinical scenarios. By far the most intensively studied applications for BCAA have been in patients with liver failure and/or patients in catabolic disease states. However, the resulting studies have not demonstrated a clear clinical benefit for BCAA nutritional supplements. In patients with liver failure, the BCAA did improve nitrogen retention and protein synthesis, but their effect on patient outcome was less clear. Similarly, in critically ill septic patients, BCAA did not improve either survival or morbidity. The BCAA are important nutrients, and it seems that any specific benefits associated with their use will be based upon a greater understanding of the underlying cellular biology. Potential areas of further research may include the combination of BCAA supplements with other anabolic factors (e.g. growth hormone) in managing patients with catabolic disease states.

As dietary sources of gamma-linolenic acid [GLA; 18:3(n-6)], borage oil (BO; 24-25 g/100 g GLA) and evening primrose oil (PO; 8-10 g/100 g GLA) are efficacious in treating skin disorders. The triglycerol stereospecificity of these oils is distinct, with GLA being concentrated in the sn-2 position of BO and in the sn-3 position of PO. To determine whether the absolute level and/or the triglycerol stereospecificity of GLA in oils affect biological efficacy, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut oil (HCO) diet for 8 wk. Subsequently, guinea pigs were fed diets of PO, BO or a mixture of BO and safflower oil (SO) for 2 wk. The mixture of BO and SO (BS) diet had a similar level of GLA as PO but with sn-2 stereospecificity. As controls, two groups were fed SO and HCO for 10 wk. Epidermal hyperproliferation was reversed by all three oils in the order of BO > BS > PO. However, proliferation scores of group PO were higher than of the normal control group, SO. The accumulations of dihomo-gamma-linolenic acid [DGLA; 20:3(n-6)], an elongase product of GLA, into phospholipids and ceramides, of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent antiproliferative metabolite of DGLA, and of ceramides, the major lipid maintaining epidermal barrier, in the epidermis of group BO were greater than of groups BS and PO. Group BS had higher levels of DGLA, 15-HETrE and ceramides than group PO. With primary dependence on absolute levels, our data demonstrate that the antiproliferative efficacy of GLA in the epidermis is preferably exerted from sn-2 stereospecificity of GLA in BO.

Glutamine has an important role as a source of energy for enterocytes. However, it may also have a key role as a source of nitrogen for the synthesis of nucleotides. The relative contribution of de novo synthesis and salvage pathways seems to be affected by the position of enterocytes within the crypt-villus axis as well as the dietary intake of nucleic acids and glutamine. Nucleotides are especially important to enterocytes during intestinal development, maturation, and repair. Hence an understanding of nucleotide metabolism within enterocytes has important implications regarding both the composition and route of administration of nutrient solutions. Many important questions remain unanswered, in particular: Does glutamine stimulate intestinal de novo pyrimidine synthesis via the action of carbamoyl phosphate synthetase I? Can de novo purine synthesis maintain intestinal purine pools in the absence of dietary nucleic acids? And, what are the specific effects of parenterally administered nucleotides on the metabolism and well-being of enterocytes? A greater understanding of these issues will lead to a more rational approach toward the nutritional modulation of gut dysfunction.

Local perfusion with 20% glycine can diminish warm ischemia-reperfusion injury to the rat small intestine in an in vivo model. The role of glycine supplementation should be evaluated in situations where hemodynamic instability may be responsible for breakdown in the gut barrier.