Francesco Torresan

Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation

Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinsons disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls.

Prucalopride exerts neuroprotection in human enteric neurons

Serotonin (5-hydroxytryptamine, 5-HT) and its transporters and receptors are involved in a wide array of digestive functions. In particular, 5-HT4 receptors are known to mediate intestinal peristalsis and recent data in experimental animals have shown their role in neuronal maintenance and neurogenesis. This study has been designed to test whether prucalopride, a well-known full 5-HT4 agonist, exerts protective effects on neurons, including enteric neurons, exposed to oxidative stress challenge. Sulforhodamine B assay was used to determine the survival of SH-SY5Y cells, human enteric neurospheres, and ex vivo submucosal neurons following H2O2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT4-mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated with prucalopride were protected from the injury elicited by H2O2 as shown by increased survival (73.5 ± 0.1% of neuronal survival vs. 33.3 ± 0.1%, respectively; P < 0.0001) and a significant reduction of proapoptotic caspase-3 and caspase-9 activation in all neurons tested. The protective effect of prucalopride was reversed by the specific 5-HT4 antagonist GR113808. Prucalopride promotes a significant neuroprotection against oxidative-mediated proapoptotic mechanisms. Our data pave the way for novel therapeutic implications of full 5-HT4 agonists in gut dysmotility characterized by neuronal degeneration, which go beyond the well-known enterokinetic effect.

INPP4B overexpression and c-KIT downregulation in human achalasia

Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia.

A new mechanism of gastroesophageal reflux in hiatal hernia documented by high-resolution impedance manometry: a case report.

Gastroesophageal reflux disease (GERD) is recognized to be a multifactorial disease and several mechanisms leading to reflux have been described, nevertheless its pathophysiology has not been fully clarified. Hiatus hernia is a known risk factor for GERD since it impairs the esophagogastric junction, leading to: reduction in lower esophageal sphincter pressure; increase in the frequency of the transient lower esophageal sphincter relaxation; and impairment of esophageal clearance. Last generation diagnostic techniques have improved the understanding of these mechanisms. A 72-year-old woman with hiatus hernia and GERD underwent a high resolution impedance manometry (HRIM) after a partial response to treatment with pantoprazole. None of the proposed pathophysiological mechanisms for GERD could explain the presence of reflux: HRIM showed normal lower esophageal sphincter (LES) pressure and contractile integral, complete bolus clearance in all test swallows, and absence of transient LES relaxation. However, after the end of each peristaltic wave, as the LES pressure returned to resting values, a gastroesophageal reflux was detected until the following swallow. We describe an interesting case of a patient with a sliding hiatus hernia, with symptoms suggestive of GERD, in which HRIM revealed a new possible mechanism through which hiatus hernia may lead to GERD.

XII AIST 2018 Conference: “The thousand faces of cough: clinical and therapeutic updates”

This paper summarizes the presentations submitted for publication of the 12th AIST National Congress (Associazione Italiana Studio Tosse/Italian Association for Cough Study) entitled “The thousand facets of cough. A clinical and therapeutic update”, which occurred last February 2nd-3rd, 2018 in Bologna (Italy). It summarizes the contributions from leading experts of the sector, who, as in the previous editions, also this year have analyzed a problem too often underestimated which still has many dark sides as regards both the diagnosis and the therapy of cough. The Scientific Committee has chosen topics that had less space in previous editions and these are topical subjects representing a concrete opportunity for learning and comparison of opinions, as well as indispensable elements for the correct management of the symptoms.Hereby we report the abstracts of the works submitted for publication in this Meeting report.The main topics have covered Cough relationship with nerve vagus, ATP, air pollution, GERD, imaging, COPD, pediatric and therapy. Of particular interest it is the preliminary data on cough hydration ratio that shows a highly significant correlation between dehydration and cough.

Sa1379 VIP Expression in the Submucosal Plexus in Patients With Parkinson Disease and Chronic Constipation

to rifaximin (400-mg thrice/d, 2-weeks) or placebo. Post-treatment stool forms, frequency, methane and CTT were recorded. Results: CC patients tended to be methane-producer more often (13/23 [56.5%] vs. 25/68 [36.5%]; p=0.07) and had greater area under curve (AUC) for methane (2415 [435-23580] vs. 1335 [0-6562.5], p=0.02) than non-constipating IBS. 8/13 (61.5%) methane-producers and 5/10 (50%) non-producers had abnormal CTT (marker retention: 36-h: 53 [0-60] vs. 19 [8-56], p=0.06; 60-h: 16 [0-57] vs. 13 [3-56], p=0.877). 6 (46.2%) and 7/13 (53.8%) methane-producers were randomized to rifaximin and placebo, respectively. Rifaximin reduced AUC for methane more (6697.5 [1777.523580] vs. 2617.5 [562.5-19867.5], p=0.005) than placebo (3945 [2415-12952.5] vs. 3720 [502.5-9210, p=0.118) at 1-month. CTT normalized in 4/6 (66.7%) on rifaximin (36-h retention: 54 [44-57] vs. 36 [23-60], p=0.05; 60-h: 45 [3-57] vs. 14 [11-51], p=0.09) but none on placebo (p=0.02) (36-h: 31 [0-60] vs. 25 [0-45], p=0.078; 60-h: 6 [0-54] vs. 12 [0-28], p=0.2). Weekly stool frequency (pre vs. post: 3 [1-9] and 7 [1-14], p=0.05) and forms tended to improve with rifaximin than with placebo. Conclusion: Rifaximin improves constipation by reducing breath methane and colon transit time. (Registration number in Clinical Trial Registry India: REF/2012/01/003216).