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Hospital de Órbigo, Spain

Jimenez M.,Autonomous University of Barcelona | Jimenez M.,Institute Salud Carlos III | Clave P.,Institute Salud Carlos III | Clave P.,Autonomous University of Barcelona | And 3 more authors.
British Journal of Pharmacology

Nerve-mediated relaxation is necessary for the correct accomplishment of gastrointestinal (GI) motility. In the GI tract, NO and a purine are probably released by the same inhibitory motor neuron as inhibitory co-transmitters. The P2Y1 receptor has been recently identified as the receptor responsible for purinergic smooth muscle hyperpolarization and relaxation in the human gut. This finding has been confirmed in P2Y1-deficient mice where purinergic neurotransmission is absent and transit time impaired. However, the mechanisms responsible for nerve-mediated relaxation, including the identification of the purinergic neurotransmitter(s) itself, are still debatable. Possibly different mechanisms of nerve-mediated relaxation are present in the GI tract. Functional demonstration of purinergic neuromuscular transmission has not been correlated with structural studies. Labelling of purinergic neurons is still experimental and is not performed in routine pathology studies from human samples, even when possible neuromuscular impairment is suspected. Accordingly, the contribution of purinergic neurotransmission in neuromuscular diseases affecting GI motility is not known. In this review, we have focused on the physiological mechanisms responsible for nerve-mediated purinergic relaxation providing the functional basis for possible future clinical and pharmacological studies on GI motility targeting purine receptors. © 2014 The British Pharmacological Society. Source

Rofes L.,CIBER ISCIII | Clave P.,Gastrointestinal Physiology Laboratory | Ouyang A.,Penn State College of Medicine | Scharitzer M.,Medical University of Vienna | And 3 more authors.
Annals of the New York Academy of Sciences

Oropharyngeal dysphagia (OD) is a swallowing disorder caused by congenital abnormalities and structural damage and disease-associated damage of the oral cavity, pharynx, and upper esophageal sphincter. Patients with OD lack the protective mechanisms necessary for effective swallowing, exhibiting difficulty controlling food in the mouth and initiating a swallow, leading to choking, coughing, and nasal regurgitation. OD is a major risk factor for malnutrition, dehydration, and aspiration pneumonia. The following on OD includes commentaries on the application of simulation of oropharyngeal transient receptor potential vanilloid 1 (TRPV1) and maneuvers like the Shaker exercise to improve the safety and efficacy of swallow in OD patients; the prevalence of esophageal pathologies in OD patients and the need to evaluate the esophagus, esophagogastric junction, and stomach; and strategies for clinical screening to detect OD and aspiration among high-risk patients and to improve oral health care, maintain nutrition and hydration, and prevent aspiration pneumonia. © 2013 New York Academy of Sciences. Source

Serra-Prat M.,Research Unit | Serra-Prat M.,CIBER ISCIII | Palomera E.,Research Unit | Clave P.,Gastrointestinal Physiology Laboratory | Clave P.,Autonomous University of Barcelona
American Journal of Clinical Nutrition

Background: The relation between hunger, satiation, and integrated gastrointestinal motility and hormonal responses in morbidly obese patients after sleeve gastrectomy has not been determined. Objective: The objective was to assess the effects of sleeve gastrectomy on hunger, satiation, gastric and gallbladder motility, and gastrointestinal hormone response after a liquid meal test. Design: Three groups were studied: morbidly obese patients (n = 16), morbidly obese patients who had had sleeve gastrectomy (n = 8), and nonobese patients (n = 16). The participants fasted for 10 h and then consumed a 200-mL liquid meal (400 kcal + 1.5 g paracetamol). Fasting and postprandial hunger, satiation, hormone concentrations, and gastric and gallbladder emptying were measured several times over 4 h. Results: No differences were observed in hunger and satiation curves between morbidly obese and nonobese groups; however, sleeve gastrectomy patients were less hungry and more satiated than the other groups. Antrum area during fasting in morbidly obese patients was statistically significant larger than in the nonobese and sleeve gastrectomy groups. Gastric emptying was accelerated in the sleeve gastrectomy group compared with the other 2 groups (which had very similar results). Gallbladder emptying was similar in the 3 groups. Sleeve gastrectomy patients showed the lowest ghrelin concentrations and higher early postprandial cholecystokinin and glucagon-like peptide 1 peaks than did the other participants. This group also showed an improved insulin resistance pattern compared with morbidly obese patients. Conclusions: Sleeve gastrectomy seems to be associated with profound changes in gastrointestinal physiology that contribute to reducing hunger and increasing sensations of satiation. These changes include accelerated gastric emptying, enhanced postprandial cholecystokinin and glucagon-like peptide 1 concentrations, and reduced ghrelin release, which together may help patients lose weight and improve their glucose metabolism after surgery. © 2015 American Society for Nutrition. Source

Espin F.,Gastrointestinal Physiology Laboratory | Rofes L.,CIBER ISCIII | Ortega O.,Gastrointestinal Physiology Laboratory | Clave P.,Gastrointestinal Physiology Laboratory | And 3 more authors.
Neurogastroenterology and Motility

Background: Neuro-transmission impairment could be associated to motility changes observed in patients with diverticular disease. Therefore, the objective was to characterize the inhibitory neuro-muscular transmission and gene expression changes of the enteric inhibitory pathways in patients with diverticulosis (DS). Methods: Circular muscle strips from sigmoid colon of patients with DS and controls were studied using the organ bath technique to evaluate spontaneous contractility and enteric motor neurons stimulated by electrical field and qRT-PCR to assess the expression of nNOS, iNOS, P2Y1R and PGP9.5. Key Results: Patients with DS presented decreased spontaneous rhythmic contractions (SRC) that were significantly enhanced after incubation with L-NNA (1 mM) and TTX (1 μM), and unaffected by the P2Y1 antagonist MRS2500 (1 μM). Stimulation on enteric motor neurons caused an increased duration of the latency of OFF-contractions in DS group (p < 0.001), antagonized by L-NNA and slightly affected by MRS2500 (1 μM). No differences in the IC50 between controls and DS patients were observed on inhibition of SRC for the NO-donor sodium nitroprusside (SNP) and the preferential P2Y agonist ADPβS. Moreover, nNOS relative expression was also up-regulated 2.3-fold in the DS group (p < 0.05) whereas there was no significant difference in relative expression of iNOS, P2Y1R and the neuronal marker PGP9.5 between groups. Conclusions & Inferences: Patients with DS presented an over-expression of nNOS with increased endogenously NO-mediated responses suggesting enhanced NO-release. Up-regulation in the nitrergic pathway in early stages of the disease might play a role in colonic motor disorders associated to diverticular disease. © 2014 John Wiley & Sons Ltd. Source

Rofes L.,CIBER ISCIII | Arreola V.,Gastrointestinal Physiology Laboratory | Lopez I.,CIBER ISCIII | Lopez I.,Gastrointestinal Physiology Laboratory | And 5 more authors.
Neurogastroenterology and Motility

Background: Chronic poststroke oropharyngeal dysfunction (OD) is a common condition, leading to severe complications, including death. Treatments for chronic poststroke OD are scarce. The aim of our study was to assess and compare the efficacy and safety of treatment with surface electrical stimulation (e-stim) at sensory and motor intensities in patients with chronic poststroke OD. Methods: Twenty chronic poststroke patients with OD were randomly assigned to (i) sensory e-stim (treatment intensity: 75% of motor threshold) or (ii) motor e-stim (treatment intensity: motor threshold). Patients were treated during 10 days, 1 h/day. Videofluoroscopy was performed at the beginning and end of the study to assess signs of impaired efficacy and safety of swallow and timing of swallow response. Key Results: Patients presented advanced age (74.95 ± 2.18), 75% were men. The mean days poststroke was 336.26 ± 89.6. After sensory stimulation, the number of unsafe swallows was reduced by 66.7% (p < 0.001), the laryngeal vestibule closure time by 22.94% (p = 0.027) and maximal vertical hyoid extension time by 18.6% (p = 0.036). After motor stimulation, the number of unsafe swallows was reduced by 62.5% (p = 0.002), the laryngeal vestibule closure time by 38.26% (p = 0.009) and maximal vertical hyoid extension time by 24.8% (p = 0.008). Moreover, the motor stimulus reduced the pharyngeal residue by 66.7% (p = 0.002), the upper esophageal sphincter opening time by 39.39% (p = 0.009), and increased bolus propulsion force by 211.1% (p = 0.008). No serious adverse events were detected during the treatment. Conclusions & Inferences: Surface e-stim is a safe and effective treatment for chronic poststroke dysphagic patients. Chronic post-stroke oropharyngeal dysfunction (OD) is a common condition, leading to severe complications, including death. Treatments for chronic post-stroke OD are scarce. Surface electrical stimulation is a safe and effective treatment for chronic post-stroke dysphagic patients. © 2013 John Wiley & Sons Ltd. Source

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