Citrulline: from metabolism to therapeutic use.: citrulline: metabolism and therapeutic

International audienceCitrulline possesses a highly specific metabolism that bypasses splanchnic extraction because it is not used by the intestine or taken up by the liver. The administration of citrulline may be used to deliver available nitrogen for protein homeostasis in peripheral tissues and as an arginine precursor synthesized de novo in the kidneys and endothelial and immune cells. Fresh research has shown that citrulline is efficiently transported across the intestinal luminal membrane by a set of transporters belonging to the B⁰,⁺, L, and b⁰,⁺ systems. Several pharmacokinetic studies have confirmed that citrulline is efficiently absorbed when administered orally. Oral citrulline could be used to deliver arginine to the systemic circulation or as a protein anabolic agent in specific clinical situations, because recent data have suggested that citrulline, although not a component of proteins, stimulates protein synthesis in skeletal muscle through the mammalian target of rapamycin signaling pathway. Hence, citrulline could play a pivotal role in maintaining protein homeostasis and is a promising pharmaconutrient in nutritional support strategies for malnourished patients, especially in aging and sarcopenia

Towards an understanding of the rapid decline of the cosmic star formation rate

We present a first analysis of deep 24 micron observations with the Spitzer Space Telescope of a sample of nearly 1500 galaxies in a thin redshift slice, 0.65<z<0.75. We combine the infrared data with redshifts, rest-frame luminosities, and colors from COMBO-17, and with morphologies from Hubble Space Telescope images collected by the GEMS and GOODS projects. To characterize the decline in star-formation rate (SFR) since z~0.7, we estimate the total thermal infrared (IR) luminosities, SFRs, and stellar masses for the galaxies in this sample. At z~0.7, nearly 40% of intermediate and high-mass galaxies (with stellar masses >2x10^10 solar masses) are undergoing a period of intense star formation above their past-averaged SFR. In contrast, less than 1% of equally-massive galaxies in the local universe have similarly intense star formation activity. Morphologically-undisturbed galaxies dominate the total infrared luminosity density and SFR density: at z~0.7, more than half of the intensely star-forming galaxies have spiral morphologies, whereas less than \~30% are strongly interacting. Thus, a decline in major-merger rate is not the underlying cause of the rapid decline in cosmic SFR since z~0.7. Physical properties that do not strongly affect galaxy morphology - for example, gas consumption and weak interactions with small satellite galaxies - appear to be responsible.Comment: To appear in the Astrophysical Journal 1 June 2005. 14 pages with 8 embedded figure

Features, Causes and Consequences of Splanchnic Sequestration of Amino Acid in Old Rats

RATIONALE: In elderly subjects, splanchnic extraction of amino acids (AA) increases during meals in a process known as splanchnic sequestration of amino acids (SSAA). This process potentially contributes to the age-related progressive decline in muscle mass via reduced peripheral availability of dietary AA. SSAA mechanisms are unknown but may involve an increased net utilization of ingested AA in the splanchnic area. OBJECTIVES: Using stable isotope methodology in fed adult and old rats to provide insight into age-related SSAA using three hypotheses: 1) an increase in protein synthesis in the gut and/or the liver, 2) an increase in AA oxidation related to an increased ureagenesis, and 3) Kupffer cell (KC) activation consequently to age-related low-grade inflammation. FINDINGS: Splanchnic extraction of Leu (SPELeu) was doubled in old rats compared to adult rats and was not changed after KC inactivation. No age-related effects on gut and liver protein synthesis were observed, but urea synthesis was lower in old rats and negatively correlated to liver Arg utilization. Net whole-body protein synthesis and arterial AA levels were lower in old rats and correlated negatively with SPELeu. CONCLUSION: SSAA is not the consequence of age-related alterations in ureagenesis, gut or liver protein synthesis or of KC activity. However, SSAA may be related to reduced net whole-body protein synthesis and consequently to the reduced lean body mass that occurs during aging

Asymmetry of Chromosome Replichores Renders the DNA Translocase Activity of FtsK Essential for Cell Division and Cell Shape Maintenance in Escherichia coli

Bacterial chromosomes are organised as two replichores of opposite polarity that coincide with the replication arms from the ori to the ter region. Here, we investigated the effects of asymmetry in replichore organisation in Escherichia coli. We show that large chromosome inversions from the terminal junction of the replichores disturb the ongoing post-replicative events, resulting in inhibition of both cell division and cell elongation. This is accompanied by alterations of the segregation pattern of loci located at the inversion endpoints, particularly of the new replichore junction. None of these defects is suppressed by restoration of termination of replication opposite oriC, indicating that they are more likely due to the asymmetry of replichore polarity than to asymmetric replication. Strikingly, DNA translocation by FtsK, which processes the terminal junction of the replichores during cell division, becomes essential in inversion-carrying strains. Inactivation of the FtsK translocation activity leads to aberrant cell morphology, strongly suggesting that it controls membrane synthesis at the division septum. Our results reveal that FtsK mediates a reciprocal control between processing of the replichore polarity junction and cell division

A Defined Terminal Region of the E. coli Chromosome Shows Late Segregation and High FtsK Activity

Background: The FtsK DNA-translocase controls the last steps of chromosome segregation in E. coli. It translocates sister chromosomes using the KOPS DNA motifs to orient its activity, and controls the resolution of dimeric forms of sister chromosomes by XerCD-mediated recombination at the dif site and their decatenation by TopoIV. Methodology: We have used XerCD/dif recombination as a genetic trap to probe the interaction of FtsK with loci located in different regions of the chromosome. This assay revealed that the activity of FtsK is restricted to a,400 kb terminal region of the chromosome around the natural position of the dif site. Preferential interaction with this region required the tethering of FtsK to the division septum via its N-terminal domain as well as its translocation activity. However, the KOPSrecognition activity of FtsK was not required. Displacement of replication termination outside the FtsK high activity region had no effect on FtsK activity and deletion of a part of this region was not compensated by its extension to neighbouring regions. By observing the fate of fluorescent-tagged loci of the ter region, we found that segregation of the FtsK high activity region is delayed compared to that of its adjacent regions. Significance: Our results show that a restricted terminal region of the chromosome is specifically dedicated to the last step

Métabolisme et apports en protéines chez le sportif avec un intérêt particulier pour les acides aminés à chaîne ramifiée

PARIS-BIUP (751062107) / SudocSudocFranceF

La séquestration splanchnique des acides aminés au cours du vieillissement

En France, le nombre de personnes âgées augmente et celui des jeunes diminue. Au 1er janvier 2006, la France comptait 20,7 % de personnes âgées de 60 ans ou plus contre 20 % dix ans auparavant. L'espérance de vie à 60 ans dépasse aujourd'hui 20 ans, et elle atteindra 26 ans en 2050 (Institut National des Statistiques et des Etudes Economiques). Par ailleurs, le vieillissement est associé à une augmentation de l'invalidité et de la perte d'autonomie. Ainsi, l'un des plus grands défis auquel notre société doit faire face est le maintien de la santé et de la qualité de vie de la population âgée pour un vieillissement réussi. Le vieillissement affecte de manières différentes les organes et les tissus de l'organisme, aboutissant à des vitesses différentes d'apparition de déclin fonctionnel. Ainsi, le vieillissement s'accompagne d'une perte de masse et de fonction musculaires survenant de la maturité à la sénescence et définissant la sarcopénie (1).PARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Evaluation de la dénutrition et prise en charge nutritionnelle orale chez des patients hospitalisés dans une unité de soins de suite et réadaptation gériatrique (étude rétrospective)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Long-lasting improved amino acid bioavailability associated with protein pulse feeding in hospitalized elderly patients: a randomized controlled trial

International audienceOBJECTIVE: Aging is associated with a blunted anabolic response to dietary intake, possibly related to a decrease in systemically available amino acids (AAs), which in turn may stem from increased splanchnic AA metabolism. Splanchnic sequestration can be saturated by pulse feeding (80% of daily protein intake in a single meal), enabling increased protein synthesis. The aim of this study was to explore whether protein pulse feeding increased postprandial AA concentrations, and if so whether this increase persisted after 6 wk of dietary treatment. METHODS: This prospective randomized study enrolled 66 elderly malnourished or at-risk patients in an inpatient rehabilitation unit. All were given a controlled diet for 6 wk. In a spread diet (SD) group (n = 36), dietary protein was spread over the four daily meals. In a pulse diet (PD) group (n = 30), 72% of dietary protein (averaging 1.31 g/kg body weight daily) was consumed in one meal at noon. The patients were evaluated on day 1 and at 6 wk for plasma postprandial (five times from 0 to +180 min) AA concentrations (expressed as area under the curve above baseline). RESULTS: Protein pulse feeding was more efficient than protein spread feeding at increasing plasma postprandial AA concentrations, notably of essential AAs. This increased postprandial AA bioavailability was maintained after 6 wk. CONCLUSIONS: This study demonstrates that increased postprandial AA bioavailability induced by protein pulse feeding persists after 6 wk (i.e., that there is no metabolic adaptation blunting AA bioavailability)

Effect of age on body composition.

<p>Values are expressed as means ± SEM.</p><p>*<i>P</i><0.05 and</p>+<p><i>P</i><0.01 <i>vs</i>. adult rats (Student's <i>t</i>-test).</p><p>BW: total body weight.</p