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OBJECTIVES:Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Other proteases, namely cysteine-proteases (CPs), increase airway permeability by digesting epithelial tight junction proteins. In this study, we focused on constipation-predominant IBS (IBS-C) and we aimed to (i) evaluate CP levels in two cohorts of IBS patients, (ii) test if IBS-C fecal supernatant (FSN) affects permeability, and visceral sensitivity after repeated administrations in mice, and (iii) evaluate occludin expression in IBS-C colonic biopsies.METHODS:Fecal CP activity was determined using selective substrate and inhibitor (E64). The effect of papain, as positive control, and IBS-C FSN administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice and T84 monolayers. Occludin protein levels were evaluated in IBS-C colonic biopsies. Sensitivity to colorectal distension (CRD) was measured after repeated administrations of IBS-C FSN.RESULTS:We found in a subset of IBS-C patients an enhanced fecal CP activity, in comparison with healthy controls and IBS-D patients. CP activity levels positively correlated with disease severity and abdominal pain scoring. This association was confirmed by receiver operating characteristic curve analysis. In mice, repeated application of IBS-C FSN into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD. Finally, occludin levels were found decreased in colonic biopsies from IBS-C patients, and IBS-C FSNs were able to degrade recombinant human occludin in vitro. All these effects were abolished by preincubation of IBS-C FSN with a CP inhibitor, E64.CONCLUSIONS:These data suggest that luminal CPs may represent a new factor contributing to the genesis of symptoms in IBS. [ABSTRACT FROM AUTHOR]

Pain-related functional gastrointestinal disorders (FGIDs) are characterized by visceral hypersensitivity (VHS) associated with alterations in the microbiota-gut-brain axis. Since human milk oligosaccharides (HMOs) modulate microbiota, gut and brain, we investigated whether HMOs impact VHS, and explored the role of gut microbiota. To induce VHS, C57BL/6JRj mice received hourly water avoidance stress (WAS) sessions for 10 d, or antibiotics (ATB) for 12 d. Challenged and unchallenged (Sham) animals were fed AIN93M diet (Cont) or AIN93M containing 1% of a 6-HMO mix (HMO6). VHS was assessed by monitoring the visceromotor response to colorectal distension. Fecal microbiome was analyzed by shotgun metagenomics. The effect of HMO6 sub-blends on VHS and nociceptive pathways was further tested using the WAS model. In mice fed Cont, WAS and ATB increased the visceromotor response to distension. HMO6 decreased WAS-mediated electromyographic rise at most distension volumes and overall Area Under Curve (AUC=6.12±0.50 in WAS/HMO6 vs. 9.46±0.50 in WAS/Cont; P<.0001). In contrast, VHS in ATB animals was not improved by HMO6. In WAS, HMO6 promoted most microbiota taxa and several functional pathways associated with low VHS and decreased those associated with high VHS. Among the sub-blends, 2'FL+DFL and LNT+6'SL reduced visceromotor response close to Sham/Cont values and modulated serotoninergic and CGRPα-related pathways. This research further substantiates the capacity of HMOs to modulate the microbiota-gut-brain communication and identifies mitigation of abdominal pain as a new HMO benefit. Ultimately, our findings suggest the value of specific HMO blends to alleviate pain associated FGIDs such as infantile colic or Irritable Bowel Syndrome. [ABSTRACT FROM AUTHOR]

Vasopressin and its receptors modulate several gut functions, but their role in intestinal inflammation is unknown. Our aims were to determine 1) the localization of V1b receptors in human and rodent colon, 2) the role of vasopressin and V1b receptors in experimental colitis using two approaches: V1b-/- mice and a selective V1b receptor antagonist, SSR149415, and 3) the mechanisms involved. Vib receptors were localized in normal and inflamed colon from humans and rats. Experimental colitis was induced in rats and mice and some groups were treated before or after colitis induction with oral SSRl494l5 (3-30 mg/kg). Other groups of mice were submitted to dehydration to increase vasopressin plasma levels, prior to colitis induction. Body weight, damage scores, MPO, and TNF-α tissue levels were determined. Finally, colonic segments of wild-type (WT) and V1b-/- mice were mounted in Ussing chambers and paracellular permeability in response to vasopressin was studied. V1b receptors were expressed in enterocytes and ganglia cells of the enteric nervous system of human and rat intestine. Expression levels were independent from inflammatory status. Colitis was less severe in rodents treated by either preventive or curative SSR149415 and in V1b-/- mice. 2,4,6-Trinitrobenzene sulfonic acid induced a strong mortality in dehydrated animals that was reversed by preventive SSR149415 or mast cell stabilizer. Vasopressin significantly increased paracellular permeability in WT, but not in V1b-/- mice. Preincubation of colon tissues with SSR149415 abolished the vasopressin effect. Similarly, vasopressin had no effect in colonic preparations from WT mice pretreated with mast cell stabilizers. Vasopressin, through V1b receptor interaction, has proinflammatory properties linked to mast cell activation and downstream alterations of the colonic epithelial barrier. These findings underline the potential interest of V1b receptor blockers in gut inflammatory diseases. [ABSTRACT FROM AUTHOR]

Connected objects are deployed all over the world. Thus, they are contributing to improving communications. In urban areas, technological challenges are gradually being overcome, and advances in this area are exponential. Unfortunately, isolated territories such as northern Quebec do not beneficiate from this technological progress. Yet, northern Quebec relies on abundant natural resources, with notably its huge hydroelectric dams and iron mines, and therefore, the region's economic life revolves essentially around the exploitation of these resources and is heavily reliant on rail transportation. However, according to Transport Canada, 1246 railroad accidents were reported in 2019 to the Transportation Safety Board (TSB). Thirty-eight people described as trespassers lost their lives, and five railroad employees were fatally injured. In this context, we present the implementation of a security system in an isolated environment for employees intervening on the railroad track to warn them of the imminent arrival of a train. Due to the context of the isolated environment, i.e., without an electrical network, without internet, and without an LTE network, a solution for employees has been developed using a Zigbee telecommunication system and a connected watch. A case study on a train operating in a remote and isolated area in northern Quebec is presented to validate the performance of the proposed system based on an open-source and customizable solution. [ABSTRACT FROM AUTHOR]

This study explores the influence of typical size during a categorization task. The specificity of this experimental work is based on the homogeneity of the graphic stimuli size. We have created a typical size standard of our stimuli, that concerns the real size of the objects represented by the drawings of homogeneous sizes. Then, a priming experiment was performed in which the prime and target drawings had two types of relations: a typical size, and a categorial. The paticipants are nïive as to the typical size relation between prime and target. The results show a positive priming effect of the typical size but not of the category. The results are discussed in term of theoretical approach developed by Barsalou and his colleagues (1999, 2003). In this theoretical framework, the typical size can be considered as a perceptual knowledge. In that way, we propose that participants could automatically simulate the typical size as soon as they perceived the drawings of objects with homegenous sizes. [ABSTRACT FROM AUTHOR]

Peptide YY (PYY) is involved in the regulation of several gastro-intestinal functions, including motility. The aims of the present study were (i) to characterize the effects of PYY on smooth muscle strips obtained from the different gastro-intestinal segments in rats and in humans and (ii) to realize a map of the Y receptors expression. Contractions of strips were recorded under isometric conditions, using PYY and acetylcholine as control. We observed that PYY induced a contraction of muscle strips from rat proximal colon, but displayed no effect on other gut segments. Using RT-PCR, mRNA encoding the Y1 and Y4 receptors were detected in muscle strips depending on the segment. In humans, the muscle preparations responded to ACh but not to PYY. Moreover, only Y2 receptor mRNA was found in the ileum and the left colon, but not in other segments. Our study shows the heterogeneity in the expression of Y receptors along the gastro-intestinal tract, and reveals great discrepancies between rats and humans both concerning the expression of Y receptor, and the response of smooth muscle strips to PYY. [Copyright &y& Elsevier]

Smart objects are deployed globally, contributing to improved communications and the growth of industrial systems' performances. Unfortunately, isolated territories are generally excluded from this progress. Remote areas in Canada are no exception. Thus, about two hundred thousand people are living in isolated regions in Canadian territory. The development of these communities is slowed down not only by an outdated energy supply, but they are also dependent on telecommunication systems not fully deployed in those regions, thus contributing to the amplification of those populations' isolation. Furthermore, the magnetic field in some regions of the planet and very often in isolated areas undergoes partial or total absorption, known as white areas, making the propagation of the signal very delicate. As a part of this article, a state of the art of telecommunication solutions available in an isolated environment is applied with a critical analysis based on several criteria. It shows the ability to use an original approach based on a captive balloon. Despite the proposed solution's feasibility, several challenges need to be addressed before formally adopting it. These challenges include: (i) controlling the height of the balloon; (ii) stabilization of the balloon; and (iii) powering the system. The list of references given at the end of the paper should offer aids for the industry and for researchers working in this field. [ABSTRACT FROM AUTHOR]

Presents information on a study investigated the effect of short-chain fatty acids (SCFA) in modifying colonic motility. Methodology; Effects of different pharmacological compounds on colonic motility in response to infusion of either saline or SCFA into rat colon; Results.

Examines the colonic motor effect and mechanism of short-chain fatty acids (SCFA). How SCFA are produced; Biological and clinical properties of SCFA; How SCFA modulates colonic motility.

The article reports on the significance of increased human colonic permeability in corticotrophin-releasing hormone (CRH). It discusses the pathologies of intestinal barrier impairment including gastrointestinal symptoms of non-digestive pathologies. It is not yet established whether the barrier defects are consequences or do they trigger the pathologies.

Presents a study that evaluated body composition in dogs by isotopic dilution. Techniques used for evaluation of body composition; List of isotopes that are commonly used as water labels; Experimental procedures; Results and discussion.

Seeing objects usually grasped with a power or a precision grip (e.g., an apple vs a cherry) potentiates power- and precision-grip responses, respectively. An embodied account suggests that this effect occurs because object conceptual representations would lie on a motor simulation process. A new account, named the size-coding account, argues that this effect could be rather due to an overlapping of size codes used to represent both manipulable objects and response options. In this article, we investigate whether this potentiation effect could be merely due to a low-level visual feature that favours a size-coding of stimuli: the visual size in which objects are presented. Accordingly, we conducted two experiments in which we presented highly elementary and non-graspable stimuli (i.e., ink spots) either large or small rather than graspable objects. Our results showed that the mere visual size automatically potentiates power- and precision-grip responses that are in line with the size-coding account of the potentiation effect of grasping behaviours. Moreover, these results appeal to improve the methodological control of the size of stimuli especially when researchers try to support the embodied account. [ABSTRACT FROM AUTHOR]

The Simon effect usually refers to the observation that responding to a nonspatial feature of a stimulus is faster when the position of the stimulus (task-irrelevant) matches the position of the to-be-executed response. The Simon effect can disappear when the Simon task is preceded by a spatial compatibility task with an incompatible mapping. In this experiment, during a preliminary phase, 20 children had to decide whether the outline of a colored stimulus was dotted or continuous. Green stimuli were presented exclusively on the right, whereas red stimuli were presented on the left (the color was task-irrelevant). The participants then had to perform a Simon task. When the instructions required them to press either the left or the right button for red or green stimuli, respectively (Group A), the Simon effect on response latencies was not significant. With the opposite instructions (the right or left button for red or green stimuli, respectively; Group B), the Simon effect was significant on response latencies. The Simon effect was significant on movement times for both groups. These results suggest that during the preliminary phase, each color became associated with the manual response automatically activated by that color's position. In the subsequent Simon task, the presentation of the color activated the associated response. This modulated the planning of the to-be-executed response. [ABSTRACT FROM AUTHOR]

Proinflammatory cytokines produced by immune cells play a central role in the increased intestinal epithelial permeability during inflammation. Expansion of visceral adipose tissue (VAT) is currently considered a consequence of intestinal inflammation. Whether VAT per se plays a role in early modifications of intestinal barrier remains unknown. The aim of this study was to demonstrate the direct role of adipocytes in regulating paracellular permeability of colonic epithelial cells (CECs). We show in adult rats born with intrauterine growth retardation, a model of VAT hypertrophy, and in rats with VAT graft on the colon, that colonic permeability was increased without any inflammation. This effect was associated with altered expression of tight junction (TJ) proteins occludin and ZO-1. In coculture experiments, adipocytes decreased transepithelial resistance (TER) of Caco-2 CECs and induced a disorganization of ZO-1 on TJs. Intraperitoneal administration of leptin to lean rats increased colonic epithelial permeability and altered ZO-1 expression and organization. Treatment of HT29-19A CECs with leptin, but not adiponectin, dose-dependently decreased TER and altered TJ and F-actin cytoskeleton organization through a RhoA-ROCK-dependent pathway. Our data show that adipocytes and leptin directly alter TJ function in CECs and suggest that VAT could impair colonic epithelial barrier. [ABSTRACT FROM AUTHOR]

Abstract: Neonatal stress is known to alter immune responses in adults and parasitic infection is modulated by the immune status of the host. The present study aimed to establish whether neonatal maternal deprivation affects the time course of Nippostrongylus brasiliensis infection and associated intestinal alterations in adult rats. Rat pups were separated from their dam 3h daily during postnatal days 2–14, or left undisturbed. At 12 weeks of age, N. brasiliensis infection was induced by subcutaneous administration of 3000 L3 larvae. At 7 and 12 days after primary infection, the number of intestinal adult worms, fecal egg output, jejunal paracellular permeability, and myeloperoxidase (MPO) activity were measured. On days 7 and 12 after a secondary infection, numbers of adult worms and egg production were determined. Maternal deprivation increased the number of jejunal adult worms and fecal eggs and larvae on day 7 after primary infection, and exacerbated the increase in jejunal MPO activity induced by the infection. On day 12, adult worms were only observed in deprived rats. N. brasiliensis infection did not potentiate the increase in jejunal paracellular permeability induced by maternal deprivation. After the second infection, no egg was detected in both control and deprived rats. In conclusion, maternal deprivation in rats facilitates primary infection by N. brasiliensis and enhances the inflammatory response of the jejunum, but does not induce severe breakdown of immunity to N. brasiliensis. [Copyright &y& Elsevier]

Rationale: Intestinal permeability plays an important role in gut-brain axis communication. Recent studies indicate that intestinal permeability increases in neonate pups during maternal separation (MS). Objectives: The present study aims to determine whether pharmacological inhibition of myosin light chain kinase (MLCK), which regulates tight junction contraction and controls intestinal permeability, in stressed neonates, protects against the long-term effects of MS. Methods: Male Wistar rats were exposed to MS (3 h per day from post-natal day (PND)2 to PND14) or left undisturbed and received daily intraperitoneal injection of a MLCK inhibitor (ML-7, 5 mg/kg) or vehicle during the same period. At adulthood, emotional behaviors, corticosterone response to stress, and gut microbiota composition were analyzed. Results: ML-7 restored gut barrier function in MS rats specifically during the neonatal period. Remarkably, ML-7 prevented MS-induced sexual reward–seeking impairment and reversed the alteration of corticosterone response to stress at adulthood. The effects of ML-7 were accompanied by the normalization of the abundance of members of Lachnospiraceae, Clostridiales, Desulfovibrio, Bacteroidales, Enterorhabdus, and Bifidobacterium in the feces of MS rats at adulthood. Conclusions: Altogether, our work suggests that improvement of intestinal barrier defects during development may alleviate some of the long-term effects of early-life stress and provides new insight on brain–gut axis communication in a context of stress. [ABSTRACT FROM AUTHOR]

Olive oil consumption is beneficial for health as it is associated with a decreased prevalence of cancer and cardiovascular diseases. Oleic acid is, by far, the most abundant component of olive oil. Since it can be made through de novo synthesis in animals, it is not an essential fatty acid. While it has become clear that dietary oleic acid regulates many biological processes, the signaling pathway involved in these regulations remains poorly defined. In this work we tested the impact of an oleic acid-rich diet on hepatic gene expression. We were particularly interested in addressing the contribution of Liver X Receptors (LXR) in the control of genes involved in hepatic lipogenesis, an essential process in whole body energy homeostasis. We used wild-type mice and transgenic mice deficient for both α and β Liver X Receptor isoforms (LXR-/-) fed a control or an oleate enriched diet. We observed that hepatic-lipid accumulation was enhanced as well as the expression of lipogenic genes in the liver of wild-type mice fed the oleate enriched diet. In contrast, none of these changes occurred in the liver of LXR-/- mice. Strikingly, oleate-rich diet reduced cholesterolemia in wild-type mice and induced signs of liver inflammation and damage in LXR-/- mice but not in wild-type mice. This work suggests that dietary oleic acid reduces cholesterolemia while promoting LXR-dependent hepatic lipogenesis without detrimental effects to the liver. [ABSTRACT FROM AUTHOR]

Despite well-known intestinal epithelial barrier impairment and visceral hypersensitivity in irritable bowel syndrome (IBS) patients and IBS-like models, structural and physical changes in the mucus layer remain poorly understood. Using a water avoidance stress (WAS) model, we aimed at evaluating whether 1) WAS modified gut permeability, visceral sensitivity, mucin expression, biochemical structure of O-glycans, and related mucus physical properties, and 2) whether Lactobacillus farciminis treatment prevented these alterations. Wistar rats received orally L. farciminis or vehicle for 14 days; at day 10, they were submitted to either sham or 4-day WAS. Intestinal paracellular permeability and visceral sensitivity were measured in vivo. The number of goblet cells and Muc2 expression were evaluated by histology and immunohistochemistry, respectively. Mucosal adhesion of L. farciminis was determined ex situ. The mucin O-glycosylation profile was obtained by mass spectrometry. Surface imaging of intestinal mucus was performed at nanoscale by atomic force microscopy. WAS induced gut hyperpermeability and visceral hypersensitivity but did not modify either the number of intestinal goblet cells or Muc2 expression. In contrast, O-glycosylation of mucins was strongly affected, with the appearance of elongated polylactosaminic chain containing O-glycan structures, associated with flattening and loss of the mucus layer cohesive properties. L. farciminis bound to intestinal Muc2 and prevented WAS-induced functional alterations and changes in mucin O-glycosylation and mucus physical properties. WAS-induced functional changes were associated with mucus alterations resulting from a shift in O-glycosylation rather than from changes in mucin expression. L. farciminis treatment prevented these alterations, conferring epithelial and mucus barrier strengthening. [ABSTRACT FROM AUTHOR]

Objective:Intestinal proteases carry out a variety of functions in the gastrointestinal (GI) tract. Studies have reported that elevated enteric proteases in patients with GI disease can alter intestinal physiology, however the origin (human vs. microbial) of elevated proteases in patients with GI disease is unclear. Aim:The aim of this study was to investigate the association between protease activity and the microbiota in human fecal samples. Design:In order to capture a wide range of fecal protease (FP) activity stool samples were collected from 30 IBS patients and 24 healthy controls. The intestinal microbiota was characterized using 454 high throughput pyro-sequencing of the 16S rRNA gene. The composition and diversity of microbial communities were determined and compared using the Quantitative Insights Into Microbial Ecology (QIIME) pipeline. FP activity levels were determined using an ELISA-based method. FP activity was ranked and top and bottom quartiles (n=13 per quartile) were identified as having high and low FP activity, respectively. Results:The overall diversity of the intestinal microbiota displayed significant clustering separation (p = 0.001) between samples with high vs. low FP activity. The Lactobacillales, Lachnospiraceae, and Streptococcaceae groups were positively associated with FP activity across the entire study population, whilst the Ruminococcaceae family and an unclassified Coriobacteriales family were negatively associated with FP activity. Conclusions:These data demonstrate significant associations between specific intestinal bacterial groups and fecal protease activity and provide a basis for further causative studies investigating the role of enteric microbes and GI diseases. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Adipose tissue secretes various proteins referred to as adipokines, being involved in inflammation. It was recognized that mesenteric adipose tissue (MAT) is altered by inflammation, and pathologies such as inflammatory bowel disease (IBD). The aim of this study was to investigate the alterations of the mesenteric adipose tissue in two experimental colitis models in mice adapted to obtain moderate colonic inflammation. Main methods: Colonic inflammation was obtained using two models, either DSS dissolved in drinking water or intra-colonic instillation of DNBS. The expression of adipokines (leptin and adiponectin) and inflammatory markers (IL-6, MCP-1, F4/80) was studied by qRT-PCR in the MAT of treated and control mice. Key findings: Observations of the colon and IL-6 plasma level determination demonstrated that DNBS treatment led to stronger inflammation. Colitis induced a decrease of mRNA encoding to leptin and adiponectin in MAT. In contrast, colonic inflammation led to an increase of mRNA encoding to IL-6, MCP-1 and F4/80, a specific marker of macrophages. Significance: The mesenteric adipose tissue, in two models of moderate colitis, shows a loss of adipose profile and a strong increase of inflammatory pattern, close to the observations made in MAT of IBD patients. These data suggest that these pro-inflammatory modifications of MAT have to be taken into account in the pathophysiology of IBD. [Copyright &y& Elsevier]

Abstract: Since it is associated to the obesity epidemic, non alcoholic fatty liver disease (NAFLD) has become a major public health issue. NAFLD ranges from benign hepatic steatosis, i.e. abnormally elevated triglyceride accumulation, to non alcoholic steatohepatitis (NASH) that can lead to irreversible liver damages. The search for pharmacological and dietary approaches to treat or prevent NAFLD has pointed at nuclear receptors as sensible targets. Indeed, nuclear receptors are ligand-sensitive transcription factors that play a central role in hepatic lipid metabolism. Among nuclear receptors, the liver X receptor has been identified as an oxysterol receptor. It is involved in the control of various aspects of lipid metabolism that are reviewed in this manuscript. We highlight the role of LXR in the gut–liver axis and the studies that have provided a rationale for strategies specifically targeting the hepatic activity of LXR in NAFLD. [Copyright &y& Elsevier]

Summary: Background and aims: Intestinal barrier impairment is incriminated in the pathophysiology of intestinal gut disorders associated with psychiatric comorbidity. Increased intestinal permeability associated with upload of lipopolysaccharides (LPS) translocation induces depressive symptoms. Gut microbiota and probiotics alter behavior and brain neurochemistry. Since Lactobacillus farciminis suppresses stress-induced hyperpermeability, we examined whether (i) L. farciminis affects the HPA axis stress response, (ii) stress induces changes in LPS translocation and central cytokine expression which may be reversed by L. farciminis, (iii) the prevention of “leaky” gut and LPS upload are involved in these effects. Methods: At the end of the following treatments female rats were submitted to a partial restraint stress (PRS) or sham-PRS: (i) oral administration of L. farciminis during 2 weeks, (ii) intraperitoneal administration of ML-7 (a specific myosin light chain kinase inhibitor), (iii) antibiotic administration in drinking water during 12 days. After PRS or sham-PRS session, we evaluated LPS levels in portal blood, plasma corticosterone and adrenocorticotropic hormone (ACTH) levels, hypothalamic corticotropin releasing factor (CRF) and pro-inflammatory cytokine mRNA expression, and colonic paracellular permeability (CPP). Results: PRS increased plasma ACTH and corticosterone; hypothalamic CRF and pro-inflammatory cytokine expression; CPP and portal blood concentration of LPS. L. farciminis and ML-7 suppressed stress-induced hyperpermeability, endotoxemia and prevented HPA axis stress response and neuroinflammation. Antibiotic reduction of luminal LPS concentration prevented HPA axis stress response and increased hypothalamic expression of pro-inflammatory cytokines. Conclusion: The attenuation of the HPA axis response to stress by L. farciminis depends upon the prevention of intestinal barrier impairment and decrease of circulating LPS levels. [Copyright &y& Elsevier]

Abstract: Aims: Increased colonic paracellular permeability (CPP) is a key feature of gastro-intestinal disorders as irritable bowel syndrome and inflammatory bowel diseases. Stress stimulates exocrine pancreatic secretion through cholinergic pathways, and trypsin is known to increase CPP. Consequently we have investigated in this work whether trypsin released into the gut lumen following an acute stress may participate to the short-term increase in CPP. Main methods: Mice were treated with atropine or a non-selective CRF (corticotropin-releasing factor) receptor antagonist (α-helical CRF (9–41)), before being submitted to a 2-h stress session. Then, CPP and protease activity in colonic contents (total proteolytic, trypsin activity, and mouse mast cell protease (MMCP)-1 levels) were determined. The effects of colonic contents from sham-stressed or stressed animals on CPP were evaluated in mice colonic tissues mounted in Ussing chambers, in presence or not of soybean trypsin inhibitor (SBTI) or FSLLRY, a protease-activated receptor-2 (PAR2) antagonist. Key findings: Acute stress significantly increased CPP, proteolytic and trypsin activities, and MMCP-1 levels. Atropine inhibited stress-induced impairment of CPP and strongly diminished total proteolytic and trypsin activities in stressed animals, but not MMCP-1 levels. Colonic contents from stressed animals increased CPP in mice tissues, this effect being inhibited by SBTI and PAR2 antagonist. Significance: Acute stress activates cholinergic pathways, to trigger exocrine pancreatic secretion. Trypsin, released in these conditions, may be responsible for colonic barrier alterations through the activation of PAR2. [Copyright &y& Elsevier]

Abstract: ''The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health. [Copyright &y& Elsevier]

Nation-level Ecological Footprint accounts are currently produced for more than 150 nations, with multiple calculations available for some nations. The data sets that result from these national assessments typically serve as the basis for Footprint calculations at smaller scales, including those for regions, cities, businesses, and individuals. Global Footprint Network's National Footprint Accounts, supported and used by more than 70 major organizations worldwide, contain the most widely used national accounting methodology today. The National Footprint Accounts calculations are undergoing continuous improvement as better data becomes available and new methodologies are developed. In this paper, a community of active Ecological Footprint practitioners and users propose key research priorities for improving national Ecological Footprint accounting. For each of the proposed improvements, we briefly review relevant literature, summarize the current state of debate, and suggest approaches for further development. The research agenda will serve as a reference for a large scale, international research program devoted to furthering the development of national Ecological Footprint accounting methodology. [Copyright &y& Elsevier]

Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP) through mast cells and nerve growth factor (NGF), and modifies corticotrophin-releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast cells are involved in stress-induced mucosal barrier impairment. Consequently, this study aimed to specify whether corticosteronaemia and colonic expression of both preproCRF and CRF are modified by NMD, and to determine if altered expression may participate in the elevated GPP in connection with NGF and mast cells. Male Wistar rat pups were either separated from postnatal days 2–14, or left undisturbed with their dam. At 12 weeks of age, adult rats were treated with mifepristone (an antagonist of corticoid receptors), α-helical CRF(9-41) (a non-specific CRF receptor antagonist), or SSR-125543 (CRF-R1 receptor antagonist). We also determined corticosteronaemia and both colonic preproCRF and CRF expression. Then, control rats were treated by CRF, doxantrazole (mast cell stabilizer), BRX-537A (a mast cell activator) and anti-NGF antibody. NMD did not modify colonic CRF level but increased colonic preproCRF expression and corticosteronaemia. Peripheral CRF, via CRF-R1 receptor, but not corticosterone, was involved in the elevated GPP observed in these rats, through a mast-cell-mediated mechanism, since the increase of GPP induced by exogenous CRF was abolished by doxantrazole. Anti-NGF antibody treatment also reduced the elevated GPP induced by CRF or BRX-537A. CRF acts through CRF-R1 receptors to stimulate NGF release from mast cells, which participates in the elevated GPP observed in NMD adult rats. This suggests that early traumatic experience induced neuro-endocrine dysfunction, involved in alterations of gut mucosal barrier. [ABSTRACT FROM AUTHOR]

Activation of colonic proteinase-activated receptor-2 (PAR2) caused inflammation and increased mucosal permeability in mouse colon. The present study was aimed at characterizing the possible links between these two phenomena. We evaluated the effects of intracolonic infusion of PAR2-activating peptide, SLIGRL, on colonic paracellular permeability and inflammation at two different doses, 5 and 100 µg per mouse, in an attempt to discriminate between both PAR2-mediated effects. We further investigated the possible involvement of interferon γ (IFN-γ) and calmodulin-dependent activation of myosin light chain kinase (MLCK), and alterations of zonula occludens-1 (ZO-1) localization in PAR2-induced responses. Thus, at the lower dose, SLIGRL increased colonic permeability without causing inflammation. Western blotting showed phosphorylation of mucosal myosin light chain (MLC) expression after both doses of SLIGRL. Moreover, while the MLCK inhibitor, ML-7, abolished the permeability effects of the low dose of SLIGRL, it only partially inhibited that of the high dose. In IFN-γ-deficient mice (B6 ifng-/-), the increases in permeability were similar for both doses of SLIGRL and prevented by ML-7. In addition, MLCK immunoprecipitation revealed an increase of calmodulin binding to MLCK in the mucosa of mice treated with either dose of SLIGRL. Finally, we have shown that direct activation of PARE on enterocytes is responsible for increased permeability and ZO-1 disruption. Moreover, SLIGRL at a dose that does not produce inflammation increases permeability via calmodulin activation, which binds and activates MLCK. The resulting tight junction opening does not depend upon IFN-γ secretion, while the increased permeability in response to the high dose of PAR2 agonist involves IFN-γ secretion. [ABSTRACT FROM AUTHOR]

Presents a study that assessed the influence of weight loss on body composition, energy expenditure and protein turnover rate, and compared the effects on the parameters of two diets differing mainly in protein content. Experimental procedures; Results and discussion.