Background: A previous study has suggested that Bifidobacterium animalis DN‐173 010 shortens the colonic transit time in women. Aim: To confirm this effect and to determine whether modifications of the faecal bacterial mass and/or faecal secondary bile salts may be the explanation. Methods: A double‐blind, cross‐over study was performed. Thirty‐six healthy women were studied in four consecutive 10‐day periods. During periods 2 and 4, they ingested three 125 g cups per day of a fermented milk which was either a product containing B. animalis DN‐173 010 or a control without bifidobacteria. Periods 1 and 3 were run‐in and washout periods, respectively. The total and segmental colonic transit times were assessed using a pellet method. In 12 subjects, all stools were collected and analysed for pH, faecal weight, bacterial mass and bile acids. Results: The total and sigmoid transit times were significantly shorter during dosing with B. animalis compared to the control period. The other transit times, faecal weight, pH, bacterial mass and bile acids were not significantly affected. Conclusions: B. animalis DN‐173 010 shortens the colonic transit time in healthy women. This effect is not explained by modifications of the faecal bacterial mass or secondary bile acids.

No abstract

AIT for respiratory allergy is safe, with a low number of SRs observed in real-life clinical practice. A personalized analysis of risk factors could be used to minimize SRs.

The ability of individual G protein-coupled receptors (GPCR) to engage multiple signaling pathways opens opportunities for the development of better drugs. This requires new knowledge and tools to determine the G protein subtypes and arrestins engaged by a given receptor. Here, we used a new BRET-based effector membrane translocation assay (EMTA) that monitors activation of each Gα protein through the recruitment of selective G protein effectors and βarrestins to the plasma membrane. Profiling of 100 therapeutically relevant GPCR revealed a great diversity of coupling profiles with some receptors displaying exquisite selectivity, whereas others promiscuitely engage all four G protein families. Comparison with existing datasets points to commonalities but also to critical differences between studies.Combining a biosensor subset allowed detecting activity of nearly all GPCR thus providing a new tool for safety screens and systems pharmacology. Overall, this work describes unique resources for studying GPCR function and drug discovery. KEYWORDSG protein-coupled receptor (GPCR), enhanced bystander bioluminescence resonance energy transfer (ebBRET), Biosensor, Effector membrane translocation assay (EMTA), Highthroughput assay, G protein activation, Functional selectivity, Systems pharmacology.

We failed to demonstrate any benefit of TENS on our primary end-point.

In a previous study, we established that leptin controls food intake and immune responses by acting on intestinal vagal chemosensitive mechanoreceptors via a functional link with interleukin‐1β (Il‐1β). Since the control of intestinal motility is one of the main roles of the vagal afferent fibres, we investigated the effects of leptin on intestinal electromyographic (EMG) activity which reflects intestinal motility. For this purpose, the effects of locally injected leptin on small intestine spontaneous EMG activity were studied in 23 anaesthetised cats. The EMG activity was recorded using bipolar electrodes implanted in the proximal small intestine. Leptin and Il‐1β (0.1, 1 and 10 μg), administered through the artery irrigating the upper part of the intestine 20 min after cholecystokinin (CCK, 10 μg, i.a.), had significant (P < 0.001) excitatory effects on intestinal EMG activity. The effects of both substances were blocked by the endogenous interleukin‐1β receptor antagonist (Il‐1ra, 250 μg, i.a.), by atropine (250 μg, i.a.) and by vagotomy. In the absence of CCK, leptin and Il‐1β had no effect on intestinal electrical activity. It can therefore be concluded that: (1) leptin is effective only after the previous intervention of CCK, (2) the enhancement of the electrical activity induced by leptin involves Il‐1β receptors and the cholinergic excitatory pathway, (3) the modes whereby the leptin‐induced enhancement of EMG activity occurs strongly suggest that these effects are due to a long‐loop reflex involving intestinal vagal afferent fibres and the parasympathetic nervous system.

The mechanism of action of SNS in patients with faecal incontinence almost certainly depends on the modulation of spinal and/or supraspinal afferent inputs. Further research on humans and animals will be required to gain a better understanding of the mechanisms of action of SNS.

Vagal afferent nerve fibres are involved in the transmission to the central nervous system of information relating to food intake and immune reactions. Leptin is involved in the control of food intake and has specific receptors in afferent vagal neurones. To investigate the role of these receptors, we studied the effects of leptin on single vagal afferent activities from intestinal mechanoreceptors in anaesthetized cats. The activity of 35 intestinal vagal mechanoreceptors was recorded by means of glass microelectrodes implanted in the nodose ganglion. Leptin (10 mg), administered into the artery irrigating the upper part of the intestine, induced activation in 17 units (P < 0.001), inhibition in 8 units (P < 0.05), and had no effect on 10 units. The excitatory effects of leptin were blocked by the endogenous interleukine-1b receptor antagonist, (Il-1ra, 250 mg, I.A.). Cholecystokinin (CCK, 10 mg, I.A.) induced an activatory response only in the two types of units which were responsive to leptin alone. When leptin was administered after CCK, its excitatory effects were enhanced and its inhibitory effects were blocked, whereas it had no effect on the units which were not affected by leptin alone. The interactions between leptin and CCK are specific ones, since other substances (phenylbiguanide, a serotoninergic agonist; substance P) known to activate the mechanoreceptors did not modify the effects of leptin. These results indicate that leptin appears to play a role in the control of immune responses and food intake via intestinal vagal afferent nerve fibres and that there is a functional link between leptin and Il-1b.