Alterations of bovine nucleus pulposus cells with aging.

Aging is one of the major etiological factors driving intervertebral disc (IVD) degeneration, the main cause of low back pain. The nucleus pulposus (NP) includes a heterogeneous cell population, which is still poorly characterized. Here, we aimed to uncover main alterations in NP cells with aging. For that, bovine coccygeal discs from young (12 months) and old (10-16 years old) animals were dissected and primary NP cells were isolated. Gene expression and proteomics of fresh NP cells were performed. NP cells were labelled with propidium iodide and analysed by flow cytometry for the expression of CD29, CD44, CD45, CD146, GD2, Tie2, CD34 and Stro-1. Morphological cell features were also dissected by imaging flow cytometry. Elder NP cells (up-regulated bIL-6 and bMMP1 gene expression) presented lower percentages of CD29+, CD44+, CD45+ and Tie2+ cells compared with young NP cells (upregulated bIL-8, bCOL2A1 and bACAN gene expression), while GD2, CD146, Stro-1 and CD34 expression were maintained with age. NP cellulome showed an upregulation of proteins related to endoplasmic reticulum (ER) and melanosome independently of age, whereas proteins upregulated in elder NP cells were also associated with glycosylation and disulfide bonds. Flow cytometry analysis of NP cells disclosed the existence of 4 subpopulations with distinct auto-fluorescence and size with different dynamics along aging. Regarding cell morphology, aging increases NP cell area, diameter and vesicles. These results contribute to a better understanding of NP cells aging and highlighting potential anti-aging targets that can help to mitigate age-related disc disease.

Lipotoxic stress alters the membrane lipid profile of extracellular vesicles released by Huh-7 hepatocarcinoma cells.

Extracellular vesicles (EVs) are well-known mediators in intercellular communication playing pivotal roles in promoting liver inflammation and fibrosis, events associated to hepatic lipotoxicity caused by saturated free fatty acid overloading. However, despite the importance of lipids in EV membrane architecture which, in turn, affects EV biophysical and biological properties, little is known about the lipid asset of EVs released under these conditions. Here, we analyzed phospholipid profile alterations of EVs released by hepatocarcinoma Huh-7 cells under increased membrane lipid saturation induced by supplementation with saturated fatty acid palmitate or Δ9 desaturase inhibition, using oleate, a nontoxic monounsaturated fatty acid, as control. As an increase of membrane lipid saturation induces endoplasmic reticulum (ER) stress, we also analyzed phospholipid rearrangements in EVs released by Huh-7 cells treated with thapsigargin, a conventional ER stress inducer. Results demonstrate that lipotoxic and/or ER stress conditions induced rearrangements not only into cell membrane phospholipids but also into the released EVs. Thus, cell membrane saturation level and/or ER stress are crucial to determine which lipids are discarded via EVs and EV lipid cargos might be useful to discriminate hepatic lipid overloading and ER stress.

Human intestinal pro-inflammatory CD11chighCCR2+CX3CR1+ macrophages, but not their tolerogenic CD11c-CCR2-CX3CR1- counterparts, are expanded in inflammatory bowel disease.

Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45+HLA-DR+CD14+CD64+) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11chighCCR2+CX3CR1+ cells, a phenotype also shared by circulating CD14+ monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11c-CCR2-CX3CR1- phenotype. CD11chigh monocyte-like cells produced IL-1ß, both in resting conditions and after LPS stimulation, while CD11c- Mϕ-like cells produced IL-10. CD11chigh pro-inflammatory monocyte-like cells, but not the others, were increased in the inflamed colon from patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Tolerogenic IL-10-producing CD11c- Mϕ-like cells were generated from monocytes following mucosal conditioning. Finally, the colonic mucosa recruited circulating CD14+ monocytes in a CCR2-dependent manner, being such capacity expanded in IBD. Mϕ subsets represent, therefore, transition stages from newly arrived pro-inflammatory monocyte-like cells (CD11chighCCR2+CX3CR1+) into tolerogenic tissue-resident (CD11c-CCR2-CX3CR1-) Mϕ-like cells as reflected by the mucosal capacity to recruit circulating monocytes and induce CD11c- Mϕ. The process is nevertheless dysregulated in IBD, where there is an increased migration and accumulation of pro-inflammatory CD11chigh monocyte-like cells.

Keratins extracted from Merino wool and Brown Alpaca fibres: thermal, mechanical and biological properties of PLLA based biocomposites.

Keratins extracted from Merino wool (KM) and Brown Alpaca fibres (KA) by sulphitolysis and commercial hydrolyzed keratins (KH) were used as fillers in poly(l-lactic) acid based biocomposites processed by solvent casting in chloroform. Different contents (1 wt.% and 5 wt.%) of keratins were considered and the morphological, thermal, mechanical, chemical and biological behaviours of the developed PLLA biocomposites were investigated. The results confirmed that surface morphologies of biocomposites revealed specific round-like surface topography function of different microsized keratin particles in different weight contents, such as the analysis of bulk morphologies which confirmed a phase adhesion strictly dependent by the keratin source. Transparency and thermal responses were deeply affected by the presence of the different keratins and their interaction with the PLLA matrix. Tensile test results underlined the possibility to modulate the mechanical behaviour of PLLA selecting the keratin type and content in order to influence positively the elastic and/or plastic response. It was demonstrated that surface characteristics of PLLA/KA systems also influenced the bovine serum albumin adsorption, moreover PLLA and PLLA biocomposites based on different kinds of keratins supported the culture of human bone-marrow mesenchymal stem cells, indicating that these biocomposites could be useful materials for medical applications.

[Anemia and inflammatory bowel disease]. / Anemia y enfermedad inflamatoria interstinal.

Anemia is a most common complication of inflammatory bowel disease. A high frequency of low hemoglobin values in these patients often leads physicians to subestimate this condition, which translates into ineffective treatment. On the other hand, the complex nature of anemia-inducing mechanisms in inflammatory bowel disease frequently raises doubt about the most appropriate therapy. A correct identification of patients with anemia, and adequate therapy are the essential pillars for improved quality of life. The right use of iron supplementation, and novel parenteral iron formulations, either with or without associated erythropoietin, have revolutionized our approach of this complication in the course of inflammatory bowel disease.

Anemia y enfermedad inflamatoria intestinal / No disponible

La anemia es una de las complicaciones más comunes de la enfermedadinflamatoria intestinal. La alta frecuencia de valores bajosde hemoglobina en estos enfermos provoca en muchas ocasionesuna infravaloración por parte del médico de esta circunstancia, loque se traduce en la falta de un tratamiento eficaz. Por otro lado, elcarácter complejo de los mecanismos de producción de la anemiaen la enfermedad inflamatoria intestinal con frecuencia plantea dudasacerca del tratamiento más adecuado. La identificación correctade los pacientes con anemia así como la instauración del tratamientomás idóneo serán los dos pilares fundamentales para lamejoría de la calidad de vida de los enfermos. El uso correcto delos suplementos de hierro y las nuevas formulaciones de hierro parenteral,con o sin eritropoyetina asociada, han revolucionadonuestro abordaje de esta complicación evolutiva de la enfermedadinflamatoria intestinal

Anemia is a most common complication of inflammatory boweldisease. A high frequency of low hemoglobin values in thesepatients often leads physicians to subestimate this condition,which translates into ineffective treatment. On the other hand, thecomplex nature of anemia-inducing mechanisms in inflammatorybowel disease frequently raises doubt about the most appropriatetherapy. A correct identification of patients with anemia, and adequatetherapy are the essential pillars for improved quality of life.The right use of iron supplementation, and novel parenteral ironformulations, either with or without associated erythropoietin,have revolutionized our approach of this complication in thecourse of inflammatory bowel disease

[Multichannel intraluminal esophageal impedance: a new frontier in motility]. / Impedancia esofágica intraluminal de canal múltiple: una nueva frontera en motilidad.

Multichannel intraluminal impedance is a new technique for evaluating esophageal function and gastroesophageal reflux disease (GERD). This technique relies on the monitoring of electric conductivity in the esophagus though electrodes, and on changes developing in this variable as a result of bolus passage. The proximal distribution and duration of non-acid reflux events can now be quantified, and combined manometry defines the effectiveness of esophageal body function, until now only indirectly evaluated with pH changes. We discuss the case of a woman with persistent cough in whom intraesophageal multichannel impedance demostrates a minor acid reflux that could not be demonstrated with other diagnostic methods previously, and how this technique excludes any association between cough and non-acid reflux.

Impedancia esofágica intraluminal de canal múltiple: una nueva frontera en motilidad / No disponible

La impedancia esofágica multicanal constituye una de las másrecientes herramientas diagnósticas aplicadas a la evaluación de laenfermedad por reflujo gastroesofágico. Esta técnica se basa en lamonitorización continua de la conductividad eléctrica en un medio,en este caso el esófago, a través de electrodos situados en lalongitud de una sonda, y en los cambios que un elemento como elbolo alimentario puede producir en dicha variable. De esta técnicase derivan nuevas perspectivas en la exploración de la funciónesofágica y de la enfermedad por reflujo gastroesofágico, hastaahora sólo cuantificable de forma indirecta por las fluctuacionesgeneradas por los cambios en el pH del reflujo ácido. Presentamosel caso de una paciente con tos persistente evaluada con esteprocedimiento, en quien se demostró la presencia de reflujo gastroesofágicodébilmente ácido que no pudo ser demostrado previamentecon otras exploraciones, y de cómo la impedancia descartóla asociación entre este síntoma y el reflujo no ácido

Multichannel intraluminal impedance is a new technique for evaluatingesophageal function and gastroesophageal reflux disease(GERD). This technique relies on the monitoring of electric conductivityin the esophagus though electrodes, and on changes developingin this variable as a result of bolus passage. The proximal distributionand duration of non-acid reflux events can now be quantified,and combined manometry defines the effectiveness of esophagealbody function, until now only indirectly evaluated with pH changes.We discuss the case of a woman with persistent cough in whom intraesophagealmultichannel impedance demostrates a minor acidreflux that could not be demonstrated with other diagnostic methodspreviously, and how this technique excludes any association betweencough and non-acid reflux

Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure.

BACKGROUND: A quadruple therapy has been generally recommended as rescue regimen for Helicobacter pylori eradication failures. AIMS: To systematically review the efficacy and tolerance of levofloxacin-based rescue regimens, and to conduct a meta-analysis of studies comparing these regimens with quadruple therapy for H. pylori eradication failures. METHODS: Selection of studies -- levofloxacin-based rescue regimens. For the meta-analysis, randomized-controlled trials comparing levofloxacin-based and quadruple regimens. Search strategy -- electronic and manual. Assessment of study quality -- independently by two reviewers. Data synthesis --'intention-to-treat' eradication rate. RESULTS: Mean eradication rate with levofloxacin-based regimens was 80%. Ten-day regimens were more effective than 7-day combinations (81% vs. 73%; P < 0.01). The meta-analysis showed better results with levofloxacin than with the quadruple combination (81% vs. 70%; OR = 1.80; 95% CI = 0.94-3.46). This difference reached statistical significance and heterogeneity markedly decreased when a single outlier study was excluded or when only high-quality studies were considered. Meta-analysis showed less adverse effects with levofloxacin than with quadruple regimen, both overall (19% vs. 44%; OR = 0.27; 95% CI = 0.16-0.46) and regarding severe adverse effects (0.8% vs. 8.4%; OR = 0.20; 95% CI =0.06-0.67). CONCLUSIONS: After H. pylori eradication failure, levofloxacin-based rescue regimen is more effective and better tolerated than the generally recommended quadruple therapy. A 10-day combination of levofloxacin-amoxicillin-proton pump inhibitor constitutes an encouraging second-line alternative.

Development of a distributed hydrological model based on urban databanks--production processes of URBS.

The objective of this study is to present a distributed hydrological model especially dedicated to urban catchments, and able to represent hydrological processes usually neglected in urban modelling, such as evapotranspiration, infiltration in roads, or direct infiltration of soil water in sewers. This model, called URBS (as Urban Runoff Branching Structure) is distributed considering the spatial variability of land use which is well known thanks to urban databanks managed by GIS. The production function is detailed at each cadastral parcel scale, and the runoff produced is routed by a simple transfer function. The estimation of the input parameters of the model is mostly based on physical considerations, and the model is applied on a suburban catchment in Nantes (France) in order to evaluate the interest of the distribution of the hydrological variables.