Rosalie Mccauley

Branched-chain amino acids

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.

The Influence of Parenteral Glutamine and Branched-Chain Amino Acids on Total Parenteral Nutrition—Induced Atrophy of the Gut

We tested the hypothesis that the provision of glutamine and branched-chain amino acids would reverse the gut atrophy that accompanies parenteral nutrition. Three hundred seventy-five rats were randomized into 15 groups to receive either conventional parenteral nutrition, rat food, glutamine-enriched parenteral nutrition (0.5% to 2.5%), branched-chain amino acid-enriched parenteral nutrition (0.8% to 2.0%), or glutamine plus branched-chain amino acid-enriched parenteral nutrition (0.5%/0.4% to 1.25%/1/0%). When compared with effects of conventional parenteral nutrition, the infusion of either glutamine or branched-chain amino acids partially reversed, in a dose-dependent manner, atrophy of the small bowel as assessed by gut weight (p < .05), mucosal weight (p < .05), villous height (p < .05), crypt cell production rate (p < .05), and mucosal protein concentration (p < .05). There was no effect on the large bowel. These results suggest that the parenteral infusion of either glutamine or branched-chain amino acids partially reverses the small-bowel atrophy that is associated with the infusion of solutions of conventional parenteral nutrients.

Review: Glutamine and Nucleotide Metabolism Within Enterocytes

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.

REVIEW: Peyer's patches

The function of Peyers patches as antigenic sampling sites involves the complex interplay of a variety of mechanisms that aim to recognize luminal antigens, induce an immunological response and decrease the incidence of antigen translocation across the mucosal epithelium. This is achieved by M cells, which facilitate the uptake of luminal antigens, a vascular architecture that promotes the retention of absorbed antigens within the patch interstitium (allowing for maximal antigenic activation of lymphocytes) and the presence of lymphoid follicles that contain antigen‐presenting cells and lymphocytes. Lymphocytes encountering antigen in the Peyers patches proliferate, differentiate into fully mature antigen‐specific effector cells and migrate to the mesenteric lymph nodes where they undergo final maturation. The mature lymphocytes then enter the systemic circulation and migrate throughout the other mucosa‐associated lymphoid tissues of the body and ‘home’ into the gut via high endothelial venules and gut‐associated lymphoid tissue‐specific adhesion molecules, providing antigen‐specific lymphocytes at sites likely to re‐encounter the antigen.

Influence of glycine on intestinal ischemia-reperfusion injury

BACKGROUND It has been reported that glycine may protect donor small intestine against hypothermic ischemia before transplantation. This is consistent with the documented role of glycine as a natural cytoprotectant. OBJECTIVE Using an in vivo rodent model, we sought to determine whether exposure to a 20% glycine solution reduces the extent of warm ischemia-reperfusion injury. METHODS Wistar rats (n = 50) underwent laparotomy. A baseline group did not receive any further intervention. The remaining animals had cannulation of the aorta before the initiation of intestinal ischemia (30 minutes) followed by reperfusion (30 minutes). Using a factorial design, rats were randomized to receive local tissue perfusion with either normal saline or a 20% glycine solution during either the preischemia or the prereperfusion phase. Standardized segments of small intestine were removed at the end of the study period to determine the extent of ischemia-reperfusion injury. RESULTS Perfusion with 20% glycine increased mucosal protein content (p < .05), increased mucosal DNA content (p < .05), reduced intestinal myeloperoxidase activity (p < .05), and maintained mucosal glutaminase activity. This was true regardless of whether glycine was administered during the preischemia phase or the prereperfusion phase. CONCLUSIONS 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.

The role of glutaminase in the small intestine.

Glutaminase is the enzyme which hydrolyses glutamine, the main respiratory fuel of the intestine, to yield glutamate and ammonia. Glutaminase has a central role in intestinal metabolism: the products of the reaction catalyzed by glutaminase can be transaminated, catabolized to yield energy or used for the biosynthesis of pyrimidine nucleotides. Experimental treatments which deprive the intestine of glutamine induce intestinal atrophy. In this review, attention is paid to the role of glutaminase in intestinal metabolism. Background information on the structure, kinetics and distribution of glutaminase precede a discussion of the metabolism of glutamine within the intestine. In closing, we review the factors known to regulate glutaminase activity and emphasise that the regulation of glutaminase within the intestine is poorly understood.

Pretreatment with glycine reduces the severity of warm intestinal ischemic-reperfusion injury in the rat.

Free jejunal flaps may experience adverse effects immediately after revascularization because of ischemic-reperfusion injury. In this study the authors evaluated the ability of glycine to protect the small intestine against the effects of a warm ischemic-reperfusion injury. Male Wistar rats (N = 30) were randomized to either a baseline group (no intervention), a control group (local arterial infusion with normal saline), or a glycine group (local arterial infusion with 20% glycine). Pretreatment with 20% glycine increased significantly (p < 0.05) mucosal protein and deoxyribonucleic acid content, reduced intestinal myeloperoxidase activity, and maintained mucosal glutaminase activity. These results indicate that some of the indicators of ischemic-reperfusion injury are improved by pretreatment with a 20% glycine solution.

Effects of Glutamine Infusion on Colonic Anastomotic Strength in the Rat

Glutamine is one of the primary respiratory fuels of the colon. However, it is not included in commercial preparations of parenteral nutrients because of its short shelf life. It has been suggested that colonic atrophy induced by conventional parenteral nutrition can be reversed by the intravenous infusion of fresh solutions of glutamine. This study evaluated the hypothesis that glutamine-enriched parenteral nutrition would enhance the strength of a standard colonic anastomosis in undernourished rats. After surgery, the rats were randomized to receive 6 days of postoperative support with either rat chow, conventional parenteral nutrition, or parenteral nutrition containing 1.2% glutamine. Measurement of colonic bursting tension failed to demonstrate any significant differences between the groups under study. In conclusion, the administration of 1.2% glutamine-enriched parenteral nutrition failed to influence the healing of colonic anastomoses in undernourished rats.

The effect of minimum luminal nutrition on bacterial translocation and atrophy of the jejunum during parenteral nutrition

In situations of catabolic stress, the gut becomes atrophic and may have diminished barrier function as evidenced by an increase in bacterial translocation. The aim of this study was to examine the effect of minimum luminal nutrition during parenteral nutrition on the extent of jejunal atrophy and rate of bacterial translocation. Central venous lines were inserted into 30 rats before they underwent randomization to receive nutritional support with: (a) conventional parenteral nutrition; (b) conventional parenteral nutrition with 3 g/day of rat food (i.e., minimum luminal nutrition); or (c) rat food ad libitum. The rats were assessed after 10 days for nutritional status, extent of jejunal atrophy, caecal flora, as well as the extent of bacterial translocation to the mesenteric lymph nodes, liver and spleen. Rats in the rat food ad libitum group lost the smallest amount of weight and had the least amount of jejunal atrophy, yet had a similar rate of bacterial translocation as the parenterally nourished groups. When compared with the conventional parenteral nutrition group, the minimum luminal nutrition group had better preservation of the weight of the small bowel and its isolated mucosa (P < 0.01), but had a similar rate of bacterial translocation. Minimum luminal nutrition reduced the extent of atrophy of the gut but did not affect the incidence of bacterial translocation. It is inferred that there is no direct relationship between the extent of mucosal atrophy and incidence of bacterial translocation.

The effect of minimum luminal nutrition on mucosal cellularity and immunity of the gut

Many catabolic patients can only consume small volumes of enteral nutrients. The aim of this study was to evaluate markers of cellularity and immunity in the small intestine of rats randomized to receive 6 days of parenteral nutrition, 25% enteral and 75% parenteral nutrition (i.e. minimum luminal nutrition) or enteral nutrition. The same glutamine‐enriched solution was used for both parenteral and enteral nutrition. Enteral nutrition was associated with the least amount of jejunal atrophy (P < 0.01), with the results from the minimum luminal nutrition group approximating those of the parenteral nutrition group. Parenteral nutrition was associated with the greatest number of CD2+ cells ( P < 0.05) and the lowest CD4/CD8 cell ratio ( P < 0.01) in the jejunal mucosa. In essence, we failed to demonstrate that there are any appreciable benefits associated with the enteral consumption of 25% of a nutrient load.