Perinatal exposure to a low dose of bisphenol A impaired systemic cellular immune response and predisposes young rats to intestinal parasitic infection.

Perinatal exposure to the food contaminant bisphenol A (BPA) in rats induces long lasting adverse effects on intestinal immune homeostasis. This study was aimed at examining the immune response to dietary antigens and the clearance of parasites in young rats at the end of perinatal exposure to a low dose of BPA. Female rats were fed with BPA [5 µg/kg of body weight/day] or vehicle from gestational day 15 to pup weaning.

A pilot study of fecal serine-protease activity: a pathophysiologic factor in diarrhea-predominant irritable bowel syndrome.

Background & Aims: The pathogenesis of irritable bowel syndrome (IBS) remains only partially understood, and no specific or universally effective patient management procedure has been developed to date. Our study was designed to evaluate if colonic luminal serine-proteases may be a relevant pathophysiologic marker of IBS.

Methods: Fecal samples of 38 IBS patients, 15 patients with ulcerative colitis (UC), and 15 healthy controls were studied.

Dexamethasone prevents visceral hyperalgesia but not colonic permeability increase induced by luminal protease-activated receptor-2 agonist in rats.

Background: Low-grade inflammation may play a role in the pathogenesis of irritable bowel syndrome (IBS). Although corticosteroids are potent inhibitors of inflammatory processes, only one study with corticosteroids in patients with postinfectious IBS exists, which suggests that prednisolone is not an effective treatment for IBS symptoms.

Aim: To evaluate whether dexamethasone treatment prevents protease-activated receptor-2 (PAR-2) activation-induced visceral hyperalgesia and increased permeability in rats, and to determine whether the effects involve colonic mast cells.

Colonic luminal proteases activate colonocyte proteinase-activated receptor-2 and regulate paracellular permeability in mice.

Luminal activation of protease-activated receptors-2 (PAR(2)) on colonocytes by trypsin or PAR(2)-activating peptide increases colonic paracellular permeability (CPP). The aim of this study was to evaluate the role of proteases from endogenous and bacterial origin in the modulation of CPP and colonocyte PAR(2) expression in mice. CPP was assessed with (51)Cr-EDTA after intracolonic administration of different protease inhibitors.

LPS-induced lung inflammation is linked to increased epithelial permeability: role of MLCK.

The respiratory system is directly exposed to low levels of lipopolysaccharide (LPS), present as a contaminant on airborne particles. In cystic fibrosis, the prevailing data identify structural changes of the airway epithelium, as well as tight junction dilatation. This study was aimed at determining the contribution of myosin light chain kinase to maintaining airway epithelium barrier integrity in the lung inflammatory response to LPS in rats.

PAR2 activation alters colonic paracellular permeability in mice via IFN-gamma-dependent and -independent pathways.

Activation of colonic proteinase-activated receptor-2 (PAR(2)) 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 PAR(2)-activating peptide, SLIGRL, on colonic paracellular permeability and inflammation at two different doses, 5 and 100 microg per mouse, in an attempt to discriminate between both PAR(2)-mediated effects.

Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism.

Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR2 agonists administered intracolonically in mice induce inflammation via a neurogenic mechanism. Pretreatment of mice with neurokinin-1 and calcitonin-gene-related peptide (CGRP) receptor antagonists or with capsaicin showed attenuated PAR2-agonist-induced colitis.

Stress-induced disruption of colonic epithelial barrier: role of interferon-gamma and myosin light chain kinase in mice.

Background & Aims: Stressful life events are supposed to be involved in various diseases such as inflammatory bowel diseases and irritable bowel syndrome. Impairment of the intestinal epithelial barrier function is a suspected consequence of stress, but the underlying mechanisms remain unclear. This study aimed to determine the mechanisms through which stress modulates the colonic epithelial barrier.

Protective effect of dietary nitrate on experimental gastritis in rats.

Nitrates have long been considered as harmful dietary components and judged responsible for deleterious effects on human health, leading to stringent regulations concerning their levels in food and water. However, recent studies demonstrate that dietary nitrate may have a major role in human health as a non-immune mechanism for host defence, through its metabolism to NO in the stomach. NO is a versatile molecule and although evidence exists showing that administration of low doses of exogenous NO protects against gastrointestinal inflammation, higher NO doses have been shown to exacerbate injury.

Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeability.

Activation of colonic proteinase-activated receptor-2 (PAR-2) provokes colonic inflammation and increases mucosal permeability in mice. The mechanism of inflammation is under debate and could be neurogenic and/or the consequence of tight-junction opening with passage of exogenous pathogens into the lamina propria. The present study aimed to further characterize the inflammatory effect of PAR-2 activation by investigating: 1) the role of NO, 2) the role of afferent neurons, and 3) a possible cause and effect relationship between colonic paracellular permeability changes and mucosal inflammation.

Stress-induced visceral hypersensitivity in female rats is estrogen-dependent and involves tachykinin NK1 receptors.

Hormonal cycling may be related to a higher incidence of pain syndrome in female. As tachykinins are pivotal in stress-induced colonic dysfunction, we investigated whether ovarian steroids influence stress-induced visceral hypersensitivity to rectal distension (RD) in female rats and further, whether this influence involves NK1 receptors. Female Wistar rats, either intact or ovariectomized (OVX), were equipped for abdominal muscle electromyography and submitted to 2-h partial restraint stress (PRS) or sham-PRS.

Alteration of CCK-induced satiety in post-Nippostrongylus brasiliensis-infected rats.

In rats, the nematode Nippostrongylus brasiliensis induces an intestinal inflammation, but after the inflammation had resolved and the worm burden eliminated, morphological alterations of the intestinal wall, mainly consisting of mast cell hyperplasia and enteric nerve remodeling, persist for several weeks. Intestinal signals reaching the brain through the vagus nerve and involving neuropeptides such as CCK, play a role in the control of food intake. Our hypothesis was that neuroimmune alterations of the intestine may alter this control.

Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2.

Proteinase-activated receptor (PAR)-2, a G-protein-coupled receptor for trypsin and mast cell tryptase, is highly expressed in the intestine. Luminal trypsin and tryptase are elevated in the colon of inflammatory bowel disease patients. We hypothesized that luminal proteinases activate PAR-2 and induce colonic inflammation.

Acute and chronic stress differently affect visceral sensitivity to rectal distension in female rats.

Stressful life events are frequently associated with outward signs of irritable bowel syndrome (IBS). Increasing evidence suggests that acute and chronic stress stimuli implicate different physiological mechanisms and neuroendocrine responses. Therefore, we investigated the influence of acute and chronic stress on visceral nociception in female rats and the involvement of colonic mast cells in this effect.

Enhanced intestinal motor response to cholecystokinin in post-Nippostrongylus brasiliensis-infected rats: modulation by CCK receptors and the vagus nerve.

The jejunal inflammation induced in rats by the nematode Nippostrongylus brasiliensis is followed by intestinal neuroimmune alterations including mast cell hyperplasia and nerve remodelling. On the other hand, cholecystokinin (CCK) plays a pivotal role in the regulation of intestinal motility. The aim of this study was to determine whether the intestinal motor response to CCK is altered 30 days after infection by N.

Absence of protective role of afferent nerves in early intestinal mucosal alterations induced by abdominal irradiation in rats.

Purpose: To assess the early effects of primary afferent nerve suppression by systemic treatment with the neurotoxin capsaicin in an acute model of abdominal irradiation in rats (10Gy, gamma).

Materials And Methods: Changes in myeloperoxidase (MPO) activity, calcitonin gene-related peptide (CGRP) tissue content, number of mast cells and apoptotic cells were determined in jejunum and ileum in four groups of rat male Wistar (vehicle sham-irradiated, vehicle irradiated, capsaicin sham-irradiated and capsaicin irradiated) at 1 and 3 days post-irradiation.

Results: In vehicle irradiated rats, CGRP was significantly increased from the first day after irradiation in jejunal mucosa; MPO activity increased in both segments at day 3 but not at day 1 after irradiation; the number of detectable mucosal mast cells dropped to nearly zero on days 1 and 3, while the apoptotic cells in the intestinal mucosa were significantly increased at day 1.

Development and sequels of intestinal inflammation in nematode-infected rats: role of mast cells and capsaicin-sensitive afferents.

Objectives: To determine whether intestinal mast cells and capsaicin-sensitive afferent nerves are involved in the development and sequels of Nippostrongylus brasiliensis-induced intestinal inflammation in rats.

Methods: Two series of experiments were performed. In the first series, six groups of 8 rats were used to study the effects of mast cell stabilization by ketotifen.

Alterations of intestinal motor responses to various stimuli after Nippostrongylus brasiliensis infection in rats: role of mast cells.

Nippostrongylus brasiliensis infection induces jejunal mastocytosis associated with enteric nerve remodelling in rats. The aim of this study was to evaluate the intestinal motility responses to meals and to neurotransmitters involved in the control of gut motility (acetylcholine (carbachol), substance P and neurokinin A) in both control and N. brasiliensis-infected rats 30 days post-infection.

Pathobiology of visceral pain: molecular mechanisms and therapeutic implications. III. Visceral afferent pathways: a source of new therapeutic targets for abdominal pain.

Visceral pain is the major cause of consulting in gastroenterology and the principal symptom of functional bowel disorders. This symptom is often associated with gut hypersensitivity to distension. The use of animal models has recently permitted the identification of some mediators supposed to play a pivotal role in the genesis of visceral hypersensitivity.

Reduction of the nociceptive response to gastric distension by nitrate ingestion in rats.

Background: Dietary nitrates are known to produce nitric oxide in the stomach, which may influence gastric function.

Aim: To investigate whether nitrate ingestion modifies gastric sensitivity to distension through a mechanism involving nitric oxide production.

Methods: Nociception, associated with gastric distension ranging from 10 to 40 mmHg, was assessed in anaesthetized rats by the amplitude of cardiovascular depressor responses.

Involvement of tachykinin receptors in sensitisation to cow's milk proteins in guinea pigs.

Background: There is growing evidence for a pivotal role for tachykinins in gut neuroimmune interactions.

Aims: To determine whether NK1, NK2, and NK3 tachykinin receptors are involved in milk protein induced allergic sensitisation.

Methods: Eight groups of 12 Dunkin-Hartley guinea pigs (250-300 g) were used.

Role of kinin B1 and B2 receptors and mast cells in post intestinal infection-induced hypersensitivity to distension.

Distension of the rat intestine causes a capsaicin-sensitive, pressure-dependent depressor response which is indicative of nociception. A hypersensitivity of jejunal distension which possibly involves tachykinin NK2 receptors and is restricted to areas with mast cell hyperplagia is observed in rats infected 30 days previously with Nippostrongylus brasiliensis. This study aimed to further investigate the role of mast cells, tachykinins and kinins in this intestinal hypersensitivity.

Effects of tachykinin receptor antagonists on the rat jejunal distension pain response.

Distension of the rat intestine causes a cardiovascular response which is indicative of nociception. Since tachykinins are involved in nociception, we tested the effect of neurokinin receptor antagonists against the distension-induced response. The jejunal distension-induced depressor responses were inhibited in a dose-dependent fashion by CP 99,994 (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine, tachykinin NK1 receptor antagonist, ED50 = 0.

Effects of nematode infection on sensitivity to intestinal distension: role of tachykinin NK2 receptors.

Distension of the rat intestine causes a depressor response which is predictive of nociception. This study investigated the effects of previous infection with Nippostrongylus (N.) brasiliensis on the sensitivity to intestinal distension and the role of tachykinin NK2 receptors.

Altered contractility of circular and longitudinal muscle in TNBS-inflamed guinea pig ileum.

Intestinal motility disorders are often associated with gut inflammation. We evaluated, in vitro under isometric conditions, changes in contractility of longitudinal and circular muscle layers from guinea pig ileum after 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis. TNBS treatment did not modify length-active tension relationships for both muscle layers, whereas a significant increase in passive tension was observed in the circular muscle response to stretching.