PAR-2-induced colonic inflammation does not depend upon paracellular permeability and lymphocyte infiltration

PAR-2-induced colonic inflammation does not depend upon paracellular permeability and lymphocyte infiltration. 10th United European Gastroenterology Wee

Probiotic Strains for Treating and/or Preventing Diarrhea

The present invention relates to a method of selecting or identifying probiotic strains capable of acting on the absorption of water in the colon, and use thereof as medicinal products in the treatment and/or prevention of diarrhea. The invention relates in particular to the strain of Bacillus subtilis CU1 for use in the treatment and/or prevention of diarrhea

Mechanism of action of probiotics

The modern diet doesn't provide the required amount of beneficial bacteria. Maintenance of a proper microbial ecology in the host is the main criteria to be met for a healthy growth. Probiotics are one such alternative that are supplemented to the host where by and large species of Lactobacillus, Bifidobacterium and Saccharomyces are considered as main probiotics. The field of probiotics has made stupendous strides though there is no major break through in the identification of their mechanism of action. They exert their activity primarily by strengthening the intestinal barrier and immunomodulation. The main objective of the study was to provide a deep insight into the effect of probiotics against the diseases, their applications and proposed mechanism of action

Memory deficits in a juvenile rat model of type 1 diabetes are due to excess 11β-HSD1 activity, which is upregulated by high glucose concentrations rather than insulin deficiency

Aims/hypothesis: Children with diabetes may display cognitive alterations although vascular disorders have not yet appeared. Variations in glucose levels together with relative insulin deficiency in treated type 1 diabetes have been reported to impact brain function indirectly through dysregulation of the hypothalamus-pituitary-adrenal axis. We have recently shown that enhancement of glucocorticoid levels in children with type 1 diabetes is dependent not only on glucocorticoid secretion but also on glucocorticoid tissue concentrations, which is linked to 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. Hypothalamus-pituitary-adrenal axis dysfunction and memory alteration were further dissected in a juvenile rat model of diabetes showing that excess 11β-HSD1 activity within the hippocampus is associated with hippocampal-dependent memory deficits. Here, to investigate the causal relationships between diabetes, 11β-HSD1 activity and hippocampus-dependent memory deficits, we evaluated the beneficial effect of 11β-HSD1 inhibition on hippocampal-related memory in juvenile diabetic rats. We also examined whether diabetes-associated enhancement of hippocampal 11β-HSD1 activity is due to an increase in brain glucose concentrations and/or a decrease in insulin signalling. Methods: Diabetes was induced in juvenile rats by daily i.p. injection of streptozotocin for 2 consecutive days. Inhibition of 11β-HSD1 was obtained by administrating the compound UE2316 twice daily by gavage for 3 weeks, after which hippocampal-dependent object location memory was assessed. Hippocampal 11β-HSD1 activity was estimated by the ratio of corticosterone/dehydrocorticosterone measured by LC/MS. Regulation of 11β-HSD1 activity in response to changes in glucose or insulin levels was determined ex vivo on acute brain hippocampal slices. The insulin regulation of 11β-HSD1 was further examined in vivo using virally mediated knockdown of insulin receptor expression specifically in the hippocampus. Results: Our data show that inhibiting 11β-HSD1 activity prevents hippocampal-related memory deficits in diabetic juvenile rats. A significant increase (53.0±9.9%) in hippocampal 11β-HSD1 activity was found in hippocampal slices incubated in high glucose conditions (13.9 mmol/l) vs normal glucose conditions (2.8 mmol/l) without insulin. However, 11β-HSD1 activity was not affected by variations in insulin concentration either in the hippocampal slices or after a decrease in hippocampal insulin receptor expression. Conclusions/interpretation: Together, these data demonstrate that an increase in 11β-HSD1 activity contributes to memory deficits observed in juvenile diabetic rats and that an excess of hippocampal 11β-HSD1 activity stems from high glucose levels rather than insulin deficiency. 11β-HSD1 might be a therapeutic target for treating cognitive impairments associated with diabetes

Postprandial hyperglycemia stimulates neuroglial plasticity in hypothalamic POMC neurons after a balanced meal

Mechanistic studies in rodents evidenced synaptic remodeling in neuronal circuits that control food intake. However, the physiological relevance of this process is not well defined. Here, we show that the firing activity of anorexigenic POMC neurons located in the hypothalamus is increased after a standard meal. Postprandial hyperactivity of POMC neurons relies on synaptic plasticity that engages pre-synaptic mechanisms, which does not involve structural remodeling of synapses but retraction of glial coverage. These functional and morphological neuroglial changes are triggered by postprandial hyperglycemia. Chemogenetically induced glial retraction on POMC neurons is sufficient to increase POMC activity and modify meal patterns. These findings indicate that synaptic plasticity within the melanocortin system happens at the timescale of meals and likely contributes to short-term control of food intake. Interestingly, these effects are lost with a high-fat meal, suggesting that neuroglial plasticity of POMC neurons is involved in the satietogenic properties of foods.Contrôle nerveux de la prise alimentaire et du métabolisme par une molécule neurale d'adhésion cellulaireISITE " BFCRéseau d'Innovation sur les Voies de Signalisation en Sciences de la Vi

Effects of Inflammatory Mediators on Gut Sensititvity

Over the past decade, attention has been paid to the role of visceral sensitivity in the pathophysiology of functional bowel disorders, especially irritable bowel syndrome, and visceral hypersensitivity is the most widely accepted mechanism responsible for both motor alterations and abdominal pain. Inflammatory mediators sensitize primary afferents, especially C-fibre polymodal nociceptors, favouring the recruitment of silent nociceptors that give rise to secondary spinal sensitization. After local tissue injury, the release of chemical mediators such as potassium ions, ATP, bradykinin and prostaglandin E2 directly activate nerve endings and indirectly trigger the release of algesic mediators such as histamine, 5-hydroxytryptamine and nerve growth factor from other cells, which, in turn, stimulate proximal afferent nerve endings and silent nociceptors. Among the intermediary structures activated by inflammatory mediators and susceptible to the release of proalgesic substances, mast cells and platelets play a crucial role; however, immunocytes such as macrophages and neutrophils or sympathetic nerve terminals are also candidates. Moreover, events likely to activate synthesis of mediators by mast cells, such as stress and septic shock, also trigger colonic hypersensitivity. Prolonged visceral hyperalgesia may also depend on spinal sensitization. Anumber of substances are candidates to play a role at the spinal cord level in mediating painful and nonpainful sensations. Among them, substance P, dynorphins and glutamate play a pivotal role in postsynaptic sensitization, particularly during and after gut inflammation. Finally, despite the complexity of the relationship between inflammatory mediators and gut hypersensitivity, numerous results strongly suggest that alteration neuroimmune communications at the gut level may trigger a series of events that give rise to chronic changes in visceral sensitivity

ETUDE DES RELATIONS NEURO-IMMUNITAIRES DIGESTIVES AU COURS DE L'ALLERGIE ALIMENTAIRE CHEZ LE COBAYE ET LORS DES TROUBLES DE LA MOTRICITE ET DE L'INGESTION CHEZ LE RAT EN ETAT POST-INFECTIEUX

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Stress néonatal et conséquences sur la barrière intestinale et la viscérosensibilité

L'accumulation de nombreuses données fondamentales, cliniques et épidémiologiques a permis de caractériser et de mettre en évidence l'implication des facteurs environnementaux de la période néonatale dans l'apparition d'états pathologiques chez le jeune et l'adulte. Chez l'homme, les évènements traumatiques précoces sont connus pour être impliqués dans l'étiologie de pathologies digestives comme le syndrome de l'intestin irritable, caractérisé par des douleurs abdominales fréquemment associées à une augmentation de la perméabilité intestinale et à des troubles du transit intestinal. L'utilisation de modèles animaux a conforté ces données et a permis de montrer l'implication d'événements traumatiques précoces dans le développement de pathologies digestives chez le sujet adulte (ulcères gastriques et dysfonctionnements de la barrière épithéliale colique en réponse à un stress). Ainsi, un modèle expérimental présentant les mêmes caractéristiques physiopathologiques que celles du syndrome de l'intestin irritable a été mis au point. Ce modèle consiste à séparer les rats nouveau-nés de leur mère 3 heures par jour du deuxième au quatorzième jour de vie. Les rats ainsi néo-stressés développent à l'age adulte une hyperalgésie viscérale ainsi que des altérations du transit intestinal comparables à celles retrouvées dans le syndrome de l'intestin irritable. Le but de notre étude a été dans un premier temps, de caractériser les répercussions du stress néonatal sur la physiologie et sur le système immunitaire de la muqueuse intestinale. Dans un deuxième temps, nous avons cherché à déterminer en période néonatale les mécanismes impliqués dans ces altérations. Puis, dans une dernière étude nous avons recherché les médiateurs impliqués dans l'augmentation de la perméabilité intestinale induite par la séparation maternelle...Adverse events during childhood are considered as potent stressors often associated in humans with gastrointestinal diseases such as Crohn's disease or irritable bowel syndrome (IBS). The use of animal models of maternal deprivation has pointed out the importance of neonatal stress in favoring the occurrence of gastrointestinal diseases in adults. For example, early maternal separation has been found to predispose to gastric erosions, and colonic barrier dysfunction in response to a mild stress. As demonstrated with Ussing chambers, neonatal stress increases colonic ion transport but does not modify colonic permeability, at least in basal conditions and for the marker horseradish peroxidase. It has also been shown in rats that neonatal maternal deprivation triggers long-term hypersensitivity to rectal distension, which corresponds to the main pathophysiological characteristic of IBS in humans. Consequently, the present study aimed to establish whether maternal deprivation affects the integrity of colonic epithelial barrier and the immune status in adult rats. Secondly, we have investigated whether NGF was involved in the genesis of visceral hyperalgesia and immune alterations induced by neonatal maternal deprivation. Finally, we have determined whether mast cells, CRF and corticosterone were involved in maintaining elevated gut paracellular permeability observed in adult deprived rats...TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

ALTERATIONS DE LA MOTRICITE DIGESTIVE ASSOCIEES AUX PROCESSUS INFLAMMATOIRES INDUITS PAR LES RAYONNEMENTS IONISANTS CHEZ LE RAT

PARIS7-Bibliothèque centrale (751132105) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

1.2. Bases physiologiques de la satiété et de la digestion

La satiété L’arrêt de l’ingestion est lié à l’installation d’une sensation de satiété. Il ne faut pas confondre la satiété qui est l’état atteint lorsqu’on est rassasié, du rassasiement, processus qui conduit progressivement à cet état. L’arrêt du repas est le résultat de signaux biologiques qui sont dépendants en grande partie des qualités physiques et biochimiques des aliments ingérés. Ces qualités se traduisent sous forme de signaux provenant de la périphérie, intégrés au niveau de..