GNRI is a simple and accurate tool for predicting the risk of morbidity and mortality in hospitalized elderly patients and should be recorded systematically on admission.

Citrulline (Cit, C6H13N3O3), which is a ubiquitous amino acid in mammals, is strongly related to arginine. Citrulline metabolism in mammals is divided into two fields: free citrulline and citrullinated proteins. Free citrulline metabolism involves three key enzymes: NO synthase (NOS) and ornithine carbamoyltransferase (OCT) which produce citrulline, and argininosuccinate synthetase (ASS) that converts it into argininosuccinate. The tissue distribution of these enzymes distinguishes three "orthogonal" metabolic pathways for citrulline. Firstly, in the liver, citrulline is locally synthesized by OCT and metabolized by ASS for urea production. Secondly, in most of the tissues producing NO, citrulline is recycled into arginine via ASS to increase arginine availability for NO production. Thirdly, citrulline is synthesized in the gut from glutamine (with OCT), released into the blood and converted back into arginine in the kidneys (by ASS); in this pathway, circulating citrulline is in fact a masked form of arginine to avoid liver captation. Each of these pathways has related pathologies and, even more interestingly, citrulline could potentially be used to monitor or treat some of these pathologies. Citrulline has long been administered in the treatment of inherited urea cycle disorders, and recent studies suggest that citrulline may be used to control the production of NO. Recently, citrulline was demonstrated as a potentially useful marker of short bowel function in a wide range of pathologies. One of the most promising research directions deals with the administration of citrulline as a more efficient alternative to arginine, especially against underlying splanchnic sequestration of amino acids. Protein citrullination results from post-translational modification of arginine; that occurs mainly in keratinization-related proteins and myelins, and insufficiencies in this citrullination occur in some auto-immune diseases such as rheumatoid arthritis, psoriasis or multiple sclerosis.

Previous experimental studies have highlighted that citrulline (CIT) could be a promising pharmaconutrient. However, its pharmacokinetic characteristics and tolerance to loading have not been studied to date. The objective was to characterise the plasma kinetics of CIT in a multiple-dosing study design and to assess the effect of CIT intake on the concentrations of other plasma amino acids (AA). The effects of CIT loading on anabolic hormones were also determined. Eight fasting healthy males underwent four separate oral loading tests (2, 5, 10 or 15 g CIT) in random order. Blood was drawn ten times over an 8 h period for measurement of plasma AA, insulin and growth hormone (Gh). Urine samples were collected before CIT administration and over the next 24 h. None of the subjects experienced side effects whatever the CIT dose. Concerning AA, only CIT, ornithine (ORN) and arginine (ARG) plasma concentrations were affected (maximum concentration 146 (SEM 8) to 303 (SEM 11) mmol/l (ARG) and 81 (SEM 4) to 179 (SEM 10) mmol/l (ORN); time to reach maximum concentration 1·17 (SEM 0·26) to 2·29 (SEM 0·20) h (ARG) and 1·38 (SEM 0·25) to 1·79 (SEM 0·11) h (ORN) according to CIT dose). Even at high doses, urinary excretion of CIT remained low (,5 %). Plasma insulin and Gh were not affected by CIT administration. Short-term CIT administration is safe and well-tolerated. CIT is a potent precursor of ARG. However, at the highest doses, CIT accumulated in plasma while plasma ARG levels increased less than expected. This may be due to saturation of the renal conversion of CIT into ARG.Pharmacokinetics: Arginine: Ornithine: Insulin: Growth hormone Citrulline (CIT) is an amino acid whose name is derived from Citrullus vulgaris (commonly known as watermelon) from which it was first isolated in the 1930 s (for a recent review, see Curis et al.( 1) ). Until recently, CIT had not attracted much interest in the scientific community because (i) it is a non-proteic amino acid and (ii) it was considered only as an intermediate of the urea cycle (2) . In the early 1980 s, Windmueller & Spaeth (3) demonstrated that the small intestine releases large amounts of CIT which is mainly taken up by the kidney (of note, CIT is not taken up by the liver) and, in turn, arginine (ARG) was released in amounts equivalent to about 75 % of the CIT taken up. Then, Castillo et al. (4,5) were the first to characterise the CIT and ARG in vivo kinetics at the whole-body level in healthy subjects. These findings allowed the suggestion of an ARG -CIT -ARG inter-organ cycle which can be seen (6) as a mechanism for protecting dietary ARG from excessive liver degradation (because CIT is not taken up by the liver (7) ) and thus maintaining protein homeostasis. Concurrently, it was also demonstrated that CIT was the endproduct of the NO synthase reaction (8) .The role of the intestine as a key regulator of CIT production was further emphasised in situations where intestinal function is altered (i.e. short-bowel syndrome, coeliac disease, radiation-induced intestinal ...

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Ornithine δ-aminotransferase (OAT, E.C. 2.6.1.13) catalyzes the transfer of the δ-amino group from ornithine (Orn) to α-ketoglutarate (aKG), yielding glutamate-5-semialdehyde and glutamate (Glu), and vice versa. In mammals, OAT is a mitochondrial enzyme, mainly located in the liver, intestine, brain, and kidney. In general, OAT serves to form glutamate from ornithine, with the notable exception of the intestine, where citrulline (Cit) or arginine (Arg) are end products. Its main function is to control the production of signaling molecules and mediators, such as Glu itself, Cit, GABA, and aliphatic polyamines. It is also involved in proline (Pro) synthesis. Deficiency in OAT causes gyrate atrophy, a rare but serious inherited disease, a further measure of the importance of this enzyme.

Studies suggesting that the development of atopy is linked to gut microbiota composition are inconclusive on whether dysbiosis precedes or arises from allergic symptoms. Using a mouse model of cow's milk allergy, we aimed at investigating the link between the intestinal microbiota, allergic sensitization, and the severity of symptoms. Germ‐free and conventional mice were orally sensitized with whey proteins and cholera toxin, and then orally challenged with β‐lactoglobulin (BLG). Allergic responses were monitored with clinical symptoms, plasma markers of sensitization, and the T‐helper Th1/Th2/regulatory‐T‐cell balance. Microbiota compositions were analysed using denaturing gradient gel electrophoresis and culture methods. Germ‐free mice were found to be more responsive than conventional mice to sensitization, displaying a greater reduction of rectal temperature upon challenge, higher levels of blood mouse mast cell protease‐1 (mMCP‐1) and BLG‐specific immunoglobulin G1 (IgG1), and a systemic Th2‐skewed response. This may be explained by a high susceptibility to release mMCP‐1 even in the presence of low levels of IgE. Sensitization did not alter the microbiota composition. However, the absence of or low Staphylococcus colonization in the caecum was associated with high allergic manifestations. This work demonstrates that intestinal colonization protects against oral sensitization and allergic response. This is the first study to show a relationship between alterations within the subdominant microbiota and severity of food allergy.