Histiocytose langerhansienne multiviscerale avec atteinte auriculaire bilaterale a propos d’une observation

L’histiocytose langerhansienne multi-viscérale est une prolifération clonale des cellules de Langerhans, touchant plusieurs organes. Cette entité se voit surtout chez l’enfant. Dans ce travail, nous rappelons les aspects cliniques avec la fréquence d’atteinte oto-rhino-laryngologique, ainsi que les moyens de diagnostic et le traitement de cette affection rare. Nous présentons le cas d’un enfant âgé de 2 ans qui a été hospitalisé pour une pneumopathie interstitielle, associée à une otorrhée bilatérale. L’examen a montré un comblement des 2 conduits auditifs externes et des lésions cutanées squameuses. La biopsie a conclu à une histiocytose langerhansienne. Malgré la chimiothérapie, l’enfant est décédé après 11 mois.Mots-clés : Histiocytose langerhansienne, atteinte auriculaire

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

Genetic characterization of introduced Tunisian and French populations of pike-perch (Sander lucioperca) by species-specific microsatellites and mitochondrial haplotypes

The pike-perch is among the economically most valuable fish species for both commercial and recreational fishermen. This could be seen as the main reason for its introductions into Western Europe (including France) and Tunisia. Knowledge of the genetic structure of the introduced populations is a prerequisite for their successful long-term management. The present study focuses on the genetic characterization of introduced Tunisian and French pike-perch populations using species-specific microsatellite loci and mitochondrial cytochrome b haplotypes in order to better understand their genetic relationships and to try to trace the origin of the Tunisian populations. Lowered levels of genetic diversity have been observed in the two introduced Tunisian populations and a farmed Czech strain compared to a native wild German population. The reduction of microsatellite genetic variability of these three populations was supported by a genetic bottleneck signature. In contrast, the French populations showed high genetic diversity, probably due to multiple introductions and admixture of genetically differing sources. A high genetic differentiation level (significant F-ST values) between most pike-perch populations and a high average accuracy of self-assignments of individuals to populations of their origin were observed, probably resulting from genetic drift. The average pairwise relatedness values and results of the structure analysis highlighted a closer relationship between Tunisian and French populations than between Tunisian and German ones. Indeed, the two Tunisian populations clustered together with the French populations on a Neighbour-Joining tree based on D-A genetic distances. This was also sustained by the distribution of cytochrome b haplotypes A and B in the studied populations. The present results demonstrate that, despite the genetic differences, the studied populations cluster according to their phylogeographic origin. The Tunisian populations seem to be introduced from a French hatchery where the brood stock had the haplotype B of the mitochondrial cytochrome b gene

Regional Genetic Structure in the Aquatic Macrophyte Ruppia cirrhosa Suggests Dispersal by Waterbirds

The evolutionary history of the genus Ruppia has been shaped by hybridization, polyploidisation and vicariance that have resulted in a problematic taxonomy. Recent studies provided insight into species circumscription, organelle takeover by hybridization, and revealed the importance of verifying species identification to avoid distorting effects of mixing different species, when estimating population connectivity. In the present study, we use microsatellite markers to determine population diversity and connectivity patterns in Ruppia cirrhosa including two spatial scales: (1) from the Atlantic Iberian coastline in Portugal to the Siculo-Tunisian Strait in Sicily and (2) within the Iberian Peninsula comprising the Atlantic-Mediterranean transition. The higher diversity in the Mediterranean Sea suggests that populations have had longer persistence there, suggesting a possible origin and/or refugial area for the species. The high genotypic diversities highlight the importance of sexual reproduction for survival and maintenance of populations. Results revealed a regional population structure matching a continent-island model, with strong genetic isolation and low gene flow between populations. This population structure could be maintained by waterbirds, acting as occasional dispersal vectors. This information elucidates ecological strategies of brackish plant species in coastal lagoons, suggesting mechanisms used by this species to colonize new isolated habitats and dominate brackish aquatic macrophyte systems, yet maintaining strong genetic structure suggestive of very low dispersal.Fundacao para a Cincia e Tecnologia (FCT, Portugal) [PTDC/MAR/119363/2010, BIODIVERSA/0004/2015, UID/Multi/04326/2013]Pew FoundationSENECA FoundationMurcia Government, Spain [11881/PI/09]FCT Investigator Programme-Career Development [IF/00998/2014]Spanish Ministry of Education [AP2008-01209]European Community [00399/2012]info:eu-repo/semantics/publishedVersio

Palaeoclimatic conditions in the Mediterranean explain genetic diversity of Posidonia oceanica seagrass meadows

Past environmental conditions in the Mediterranean Sea have been proposed as main drivers of the current patterns of distribution of genetic structure of the seagrass Posidonia oceanica, the foundation species of one of the most important ecosystems in the Mediterranean Sea. Yet, the location of cold climate refugia (persistence regions) for this species during the Last Glacial Maximum (LGM) is not clear, precluding the understanding of its biogeographical history. We used Ecological Niche Modelling together with existing phylogeographic data to locate Pleistocene refugia in the Mediterranean Sea and to develop a hypothetical past biogeographical distribution able to explain the genetic diversity presently found in P. oceanica meadows. To do that, we used an ensemble approach of six predictive algorithms and two Ocean General Circulation Models. The minimum SST in winter and the maximum SST in summer allowed us to hindcast the species range during the LGM. We found separate glacial refugia in each Mediterranean basin and in the Central region. Altogether, the results suggest that the Central region of the Mediterranean Sea was the most relevant cold climate refugium, supporting the hypothesis that long-term persistence there allowed the region to develop and retain its presently high proportion of the global genetic diversity of P. oceanica.Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [SFRH/BPD/85040/2012]; FCT [UID/Multi/04326/2013, FCT-BIODIVERSA/004/2015]; Pew foundation (USA)info:eu-repo/semantics/publishedVersio

Drivers of population structure of the bottlenose dolphin (Tursiops truncatus) in the Eastern Mediterranean Sea

The drivers of population differentiation in oceanic high dispersal organisms, have been crucial for research in evolutionary biology. Adaptation to different environments is commonly invoked as a driver of differentiation in the oceans, in alternative to geographic isolation. In this study, we investigate the population structure and phylogeography of the bottlenose dolphin (Tursiops truncatus) in the Mediterranean Sea, using microsatellite loci and the entire mtDNA control region. By further comparing the Mediterranean populations with the well described Atlantic populations, we addressed the following hypotheses: (1) bottlenose dolphins show population structure within the environmentally complex Eastern Mediterranean Sea; (2) population structure was gained locally or otherwise results from chance distribution of preexisting genetic structure; (3) strong demographic variations within the Mediterranean basin have affected genetic variation sufficiently to bias detected patterns of population structure. Our results suggest that bottlenose dolphin exhibits population structures that correspond well to the main Mediterranean oceanographic basins. Furthermore, we found evidence for fine scale population division within the Adriatic and the Levantine seas. We further describe for the first time, a distinction between populations inhabiting pelagic and coastal regions within the Mediterranean. Phylogeographic analysis suggests that current genetic structure, results mostly from stochastic distribution of Atlantic genetic variation, during a recent postglacial expansion. Comparison with Atlantic mtDNA haplotypes, further suggest the existence of a metapopulation across North Atlantic/Mediterranean, with pelagic regions acting as source for coastal environments

Contribution à une étude biopharmaceutique de la citrulline

L administration entérale de la citrulline (Cit) peut être avantageuse dans certaines situations d insuffisance intestinale. La Cit représente une source d arginine disponible pour la synthèse protéique dans les tissus. L objectif de notre travail est de supplémenter les patients en citrulline afin d améliorer leur statut nutritionnel. Cependant, la biodisponibilité tissulaire et l action de la Cit sont conditionnées par son absorption intestinale. Nous avons montré, en utilisant les cellules Caco-2 comme modèle d étude du transport intestinal, que la Cit est captée par les cellules entérocytaires grâce à deux types de transporteurs, un Na+-dépendant (Système B0,+) et deux Na+- indépendants (Systèmes L et b0,+). Ce nombre important de systèmes de transport pourrait compenser le faible taux de Cit dans l alimentation afin d améliorer sa disponibilité dans l organisme. Notre deuxième objectif a été de contourner l intestin et d atteindre directement le côlon pour administrer la Cit. Nous avons élaboré des formes galéniques par microencaspsulation en utilisant deux techniques différentes : le spray drying et la formulation de microsphères de pectinate de calcium par cross-linking . La technique de spray drying a abouti à la formulation de microsphères ayant de bonnes propriétés physiques en termes de morphologie et de taille, en revanche la libération de la Cit a été rapide en milieu gastrique. La formulation de microsphères de pectinate de calcium a permis d améliorer le contrôle de la libération de la Cit dans le milieu gastrique en réduisant le pourcentage de dissolution des microsphères à pH acide et de prolonger la durée de libération de la Cit au niveau coliqueCitrulline (Cit) is a major precursor of arginine by de novo synthesis in the kidneys. Thus, oral Cit supplementation may be beneficial in situations of intestinal failure. However, Cit bioavailability depends on its intestinal absorption. Since the mechanism of Cit transport across the intestine has not been established yet, this study was first designed to characterize Cit uptake by enterocytes. We have demonstrated, using Caco-2 cells as a model of intestinal transport, that citrulline uptake is mediated by the Na+-dependent carrier system B0,+ and two Na+- independent carriers : systems L and b0,+. The second aim of this work was to bypass the intestine and reach the colon directly to administer Cit; since intestinal absorption is reduced in patients with intestinal failure. For this purpose, we have developed microspheres by using two different techniques of microencapsulation: the spray drying technique and the formulation of calcium pectinate microspheres intented for colonic drug delivery. The spray drying technique led to the formulation of microspheres with suitable physical properties in terms of size and morphology; however the release of Cit has been rapid in the stomach. The formulation of calcium pectinate microspheres improved the control of Cit release by reducing its release at acidic pHPARIS-BIUP (751062107) / SudocSudocFranceF

Impact of crystal polymorphism of rifaximin on dissolution behavior

Introduction: Rifaximin is an intestinal antiseptic which has five (pseudo) polymorphs α, β, γ, δ and ε. These last (pseudo)polymorphs have different physicochemical properties. The objective of the study is to assess the impact of rifaximin polymorphism on its dissolution rate which could affect its bioavailability. Material and methods: The analytical validation of dissolution assay method by UV–Visible spectrophotometry was carried out according to ICH Q2. The physicochemical characterization (solubility test, FTIR, DSC, XRD) was carried out on four active pharmaceutical ingredient (MP1, MP2, MP3, MP4). MP1 and MP2 were used by the manufacturer of generic brand 1 (G1) and MP3 and MP4 were used by the manufacturer of generic brand 2 (G2). The comparative in-vitro dissolution study was carried out on the leader brand (P), G1 and G2. Results: The four MPs were analyzed by XRD. The results of analysis showed that MP1 and MP4 were a mixture of α form and amorphous form. MP2 had an amorphous form and MP3 had a crystalline form β. The spectra of FTIR showed that the four MP had characteristics bands of rifaximin in the domain 4000-400 cm−1. The differences between the spectra of the four MPs were observed among the amorphous form (MP2), around the region 1800 to 1820 cm−1 which is attributed to the vibration of the CO group. An additional difference observed among the amorphous form (MP2) is around the region 1400 cm−1 which is attributed to the banding OH. The thermograms of MP1, MP2 and MP4 showed endothermic peaks which are probably attributed to the departure of water which indicate that MP1, MP2 and MP4 are pseudopolymoph (hydrate). For the four MPs, probably the melting points are interrupted by the phenomenon of phase transformations (Crystallization) which are reflected by exothermic peaks around 200°C–250 °C.Our results showed that the crystalline polymorphism of rifaximin influences its solubility. According to the results of the solubility test, the β crystal form of rifaximin (MP3) had the lowest solubility (3.47 μg/ml). MP2 had the highest solubility (8.35 μg/ml) and MP1 and MP4 had intermediate solubilities (5.47 μg/ml and 6.74 μg/ml). Comparative in vitro dissolution results showed that the dissolution profile of P was not similar to that of G1 and G2 (% dissolution (P)30min = 60%; % dissolution (G1) 30 min = 100% and % dissolution (G2) 30 min = 115%; f1(P versus G1) = 44; f1(P versus G2) = 61) in M1, while G1 and G2 had comparatively similar dissolution profiles (% dissolution (G1) 30 min = 100%; % dissolution (G1) 30 min = 110%; f1 (G1 versus G2) = 14) in M1. Conclusion: This study highlighted the impact of rifaximin polymorphism on its physico-chemical properties (crystal structure, thermal behavior, solubility) and on its dissolution behavior which could affect the rifaximin bioavailability