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 ...

This pilot study investigated the immunomodulatory properties of seven probiotic strains. Eighty-three healthy volunteers aged 18-62 years consumed 2 x 10(10) CFU of bacteria or a placebo (maltodextrin) over 3 weeks (D0-D21). Subjects received an oral cholera vaccine at D7 and at D14; blood and saliva samples were collected at D0, D21 and D28. Serum samples were analyzed for specific IgA, IgG and IgM, and saliva samples were analyzed for specific IgA only, by ELISA. Statistical analyses were based on Wilcoxon's signed-rank test (intragroup analyses) and exact median t-test (intergroup analyses). Salivary analysis showed no difference in specific IgA concentrations between groups. Serum analysis indicated an effect of some of the tested strains on specific humoral responses. Between D0 and D21, IgG increased in two probiotic groups, for example, Bifidobacterium lactis Bl-04 and Lactobacillus acidophilus La-14, compared with controls (P=0.01). Trends toward significant changes in immunoglobulin serum concentrations compared with controls (P<0.1) were found for six out of the seven probiotic strains. In conclusion, some strains of probiotics demonstrated a faster immune response measured with serum immunoglobulin indicators, especially IgG, although overall vaccination was not influenced. Specific strains of probiotics may thus act as adjuvants to the humoral immune response following oral vaccination.

The purpose of this study was to explore patient and family views on the sharing of their medical data in the context of compiling a European leukodystrophies database. A survey questionnaire was delivered with help from referral centers and the European Leukodystrophies Association, and the questionnaires returned were both quantitatively and qualitatively analyzed. This study found that patients/families were strongly in favor of participating. Patients/families hold great hope and trust in the development of this type of research. They have a strong need for information and transparency on database governance, the conditions framing access to data, all research conducted, partnerships with the pharmaceutical industry, and they also need access to results. Our findings bring ethics-driven arguments for a process combining initial broad consent with ongoing information. On both, we propose key item-deliverables to database participants.