Prucalopride in intestinal pseudo obstruction, paediatric experience and systematic review.

BACKGROUND: Intestinal pseudo obstruction both acute and chronic is an uncommon severe motility disorder that affect both children and adults, can lead to significant morbidity burden and have no standard management strategy. Prucalopride a highly selective serotonin receptor agonist is an effective laxative with reported extra colon action. We aim to report our experience in children with acute and chronic intestinal pseudo obstruction who responded to prucalopride and systemically review the use of prucalopride in intestinal pseudo obstruction. METHODS: A report of clinical experience and systemic review of the relevant medical databases to identify the outcome of usage of prucalopride in patients with acute and chronic intestinal pseudo obstruction. Studies meeting the selection criteria were reviewed including abstract only and case reports. RESULTS: All reported cases showed clinical response to prucalopride. There were three full text, two abstracts only and three case reports all reporting clinical improvement with prucalopride. CONCLUSION: Prucalopride appears to show promising results in children and adults with acute and chronic intestinal pseudo obstruction.

Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus.

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

In vivo NMDA/dopamine interaction resulting in Fos production in the limbic system and basal ganglia of the mouse brain.

Glutamatergic and dopaminergic effects on molecular processes have been extensively investigated in the basal ganglia. It has been demonstrated that NMDA and dopamine D(1) and D(2) receptors interact in the regulation of signal transduction and induction of transcription factors. In the present experiments, NMDA/dopamine interactions were investigated in the normosensitive caudate nucleus, hippocampus and amygdala by monitoring Fos production. We demonstrated that NMDA and the D(1) receptor agonist SKF 38393 triggered Fos levels in a distinct, non-overlapping and region-specific pattern. NMDA injected intraperitoneally (i.p.) elevated Fos levels in all hippocampal subfields and the central amygdala, whereas SKF 38393 triggered Fos production in basomedial, cortical, medial amygdala and caudate nucleus. The NMDA receptor antagonist CGS 19755 prevented NMDA- and SKF 38393-triggered Fos production in all investigated brain areas. Similarly, the D(1) receptor antagonist SCH 23390 inhibited the effects produced by SKF 38393 or NMDA. The D(2) receptor antagonist sulpiride exerted synergistic and antagonistic effects on NMDA- and SKF 38393-triggered Fos production, in a region specific manner. These data suggest that NMDA and dopamine receptors regulate Fos production within the limbic system and basal ganglia through regionally differentiated but interdependent actions.

Generalization of fear responses in C57BL/6N mice subjected to one-trial foreground contextual fear conditioning.

C57BL/6N mice were trained in a foreground contextual fear conditioning paradigm by a single exposure to a context (context 1) paired with an electric shock. Conditioned mice exhibited a strong fear response, indicated by increased freezing and low locomotor activity after subsequent re-exposure to context 1, which had been used for conditioning as well as in a novel context (context 2). The fear responses to contexts 1 or 2 required the temporal sequence of the conditioned (CS) and unconditioned (US) stimuli and did not differ significantly. The intensity of the fear response was maximal 24 h after conditioning, when long-term memory was fully established. The response to context 2 was interpreted as conditioned generalization, which was also observed in the elevated plus-maze representing an environment which differed in its spatial design significantly from contexts 1 and 2. Contextual discrimination of C57BL/6N mice was enhanced after extinction of the generalized fear. Strain studies employing C57BL/6J and Balb/c mice in addition to the C57BL/6N strain revealed that Balb/c and C57BL/6J mice acquired significantly weaker conditioned fear and generalized significantly less than C57BL/6N mice. It was concluded that the intensities of the context-specific and generalized fear responses were interlinked in a strain-specific manner.

Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice.

The performance of C57BL/6J (6J), C57BL/6N (6N), DBA/2J (2J) and DBA/2N (2N) mice in context- and tone-dependent fear conditioning was determined 24 h after fear conditioning to evaluate and compare different behavioral measures as indices of emotional learning. Freezing, the change in activity and the size of the explored area were evaluated as behavioral parameters indicating fear. Additionally, the heart rate (HR) increase elicited by tone presentation was evaluated as an autonomic indicator of fear. During the context-dependent memory test, freezing was high only in 6J and 6N mice, whereas a drop of activity and a reduced exploratory area was measured in all strains. During the tone-dependent memory test, high freezing, low activity, reduced exploratory area and a strong HR increase were demonstrated only in 6N and 6J mice, whereas behavioral and HR changes of 2J and 2N mice were always low. In extinction tests, context- and tone-dependent freezing of 6J mice decayed significantly faster than the freezing of 6N mice, whereas in both substrains the conditioned tachycardia to tone extinguished similarly in the home cage. The data demonstrate that monitoring of additional behavioral measures besides freezing and autonomic measures is necessary to interpret differences in associative learning performance of mouse strains that could be related to a differential expression of fear.

Relationship between fos production and classical fear conditioning: effects of novelty, latent inhibition, and unconditioned stimulus preexposure.

The relationship between FOS production in the sensory cortex and limbic system and the ability of C57BL/6N mice to acquire context- and tone-dependent freezing were investigated after fear conditioning, which was achieved by exposure of mice to context only or context and tone (10 kHz, 75 dB) as conditioned stimuli (Cs) paired with an electric footshock (0.7 mA, constant) as unconditioned stimulus (Us). The effect of preexposure to Cs or Cs paired with Us on FOS production and learning was also tested. It was demonstrated that high simultaneous FOS production in the parietal cortex, hippocampus, and amygdala paralleled the ability of mice to acquire strong freezing responses to novel Cs. After contextual preexposure (latent inhibition), FOS production could be elicited in the central amygdala only by shock and in the basolateral amygdala only by tone. Under these conditions, the ability of mice to acquire contextual freezing was almost abolished, whereas tone-dependent freezing was reduced. Lacking FOS production in the central amygdala after preexposure to context followed by shock (Us preexposure effect) paralleled the inability of mice to acquire tone-dependent freezing, although the tone elicited FOS production in the basolateral amygdala. On the basis of these findings it was concluded that synchronous Cs- and Us-induced FOS production in several defined forebrain areas was accompanied with associative learning of novel stimuli, and that a subsequent low level of FOS production might have been responsible or indicative for delayed conditioning to those stimuli.