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Maselli M.A.,Scientific Institute Of Gastroenterology S Of Bellis | Trisolini P.,Scientific Institute Of Gastroenterology S Of Bellis | Demma I.,Scientific Institute Of Gastroenterology S Of Bellis | Pezzolla F.,Scientific Institute Of Gastroenterology S Of Bellis | De Ponti F.,University of Bologna
Digestive Diseases and Sciences | Year: 2011

Background: Gender- and age-related differences in muscular and nerve-mediated responses in human colon are poorly characterized. We studied carbachol-induced motor responses and electrically evoked contractions in sigmoid circular muscle from adult and elderly patients of different gender. Methods: Sigmoid colon segments were obtained from 24 men and 16 women undergoing left hemicolectomy for colon cancer. Isometric tension was measured on muscle strips exposed to increasing carbachol concentrations. The effects of atropine, guanethidine, l-nitro arginine methyl ester (l-NAME), and tetrodotoxin on electrically evoked contractions were also studied. Results: Female patients showed higher maximal response to carbachol than male patients, elderly females being the most sensitive to carbachol among all patient groups. Electrically evoked contractions were linearly related to stimulation frequency and abolished by tetrodotoxin. Electrically evoked contractions were significantly more pronounced in elderly male patients; they were reduced by atropine and guanethidine and increased by l-nitro arginine methyl ester in the presence of atropine and guanethidine (P < 0.05). The effect of l-NAME was most marked in elderly male patients and least pronounced in elderly females. Conclusions: The response to carbachol and the role of nitrergic pathways differ according to age and gender; this may depend on muscarinic receptor upregulation or humoral factors affecting nitric oxide release, respectively. © 2010 Springer Science+Business Media, LLC.

Carabotti M.,University of Rome La Sapienza | Scirocco A.,University of Rome La Sapienza | Maselli M.A.,Scientific Institute Of Gastroenterology S Of Bellis | Severi C.,University of Rome La Sapienza
Annals of Gastroenterology | Year: 2015

The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions. This interaction between microbiota and GBA appears to be bidirectional, namely through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links. In this review we summarize the available evidence supporting the existence of these interactions, as well as the possible pathophysiological mechanisms involved. Most of the data have been acquired using technical strategies consisting in germ-free animal models, probiotics, antibiotics, and infection studies. In clinical practice, evidence of microbiota-GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e. autism, anxiety-depressive behaviors) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies. © 2015 Hellenic Society of Gastroenterology.

Maselli M.A.,Scientific Institute Of Gastroenterology S Of Bellis | Trisolini P.,Scientific Institute Of Gastroenterology S Of Bellis | Petitta C.,University of Rome La Sapienza | Lorusso D.,Scientific Institute Of Gastroenterology S Of Bellis | And 4 more authors.
Neurogastroenterology and Motility | Year: 2012

Background Differences in the actions of enteric neurotransmitters on colonic circular and longitudinal muscle layers have not been clearly determined, nor the possible existence of intrinsic myogenic phenotypes that might contribute to regional differences in human colon motor activity. The aim of this study was to analyze the direct pharmaco-mechanical coupling of carbachol (CCh) and vasoactive intestinal polypeptide (VIP) on human colonic smooth muscle strips and cells. Methods Circular and longitudinal muscle strips and cells were obtained from 15 human specimens of ascending and sigmoid colon. Both isometric tension on muscle strips and contraction and relaxation on cells were measured in response to increasing CCh and VIP concentrations. Key Results Circular muscle strips of ascending colon were more sensitive to the effect of CCh than that of sigmoid colon, EC50 values being, respectively, 4.15μmolL-1 and 8.47μmolL-1 (P<0.05), although there were no differences in maximal responses. No regional differences were observed in longitudinal muscle strips or in smooth muscle cells. Maximal responses to CCh were higher on circular than longitudinal muscle strips and cells throughout the colon. A greater sensitivity to VIP was observed in ascending colon compared with sigmoid colon, both in circular (EC50: 0.041 and 0.15μmolL-1, respectively, P<0.01) and longitudinal (EC50: 0.043 and 0.09μmolL-1, respectively, P<0.05) strips, and similar differences were observed in longitudinal smooth muscle cells (EC50: 44.85 and 75.24nmolL-1, respectively, P<0.05). Conclusions & Inferences Regional myogenic differences in pharmaco-mechanical coupling between the enteric neurotransmitters and smooth muscle contribute to the complex regional motor patterns of human colon. © 2012 Blackwell Publishing Ltd.

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